OCCUPATIONAL

DISEASES
OCCUPATIONAL DISEASES
 ОДЕСЬКИЙ ДЕРЖАВНИЙ
МЕДИЧНИЙ УНІВЕРСИТЕТ
THE ODESSA STATE
MEDICAL UNIVERSITY

Áiáëiîòåêà
ñòóäåíòà-ìåäèêà
Medical
Student’s Library
Започатковано 1999 р. на честь 100-річчя
Одеського державного медичного університету
(1900–2000 рр.)
Initiated in 1999 to mark the Centenary
of the Odessa State Medical University
(1900–2000)

1
OCCUPATIONAL
DISEASES
Recommended
by the Central Methodical Committee
for Higher Medical Education of the
Ministry of Health of Ukraine as a manual
for students of higher medical educational establishments
of the IV level of accreditation using English

Odessa
The Odessa State Medical University
2009
BBC 54.1,7я73
UDC 616-057(075.8)

Authors: O. M. Ignatyev, N. A. Matsegora, T. O. Yermolenko,

T. P. Oparina, K. A. Yarmula, Yu. M. Vorokhta

Reviewers: Professor G. A. Bondarenko, the head of the Department of

Occupational Diseases and Radiation Medicine of the Donetzk
Medical University named after M. Gorky, MD
Professor I. F. Kostyuk, the head of the Department of
Internal and Occupational Diseases of the Kharkiv State
Medical University, MD

This manual contains information about etiology, epidemiology, patho-

genesis of occupational diseases, classifications, new methods of exami-
nation, clinical forms and presentation, differential diagnosis, complica-
tions and treatment. It includes the questions of prophylaxis, modern trends
in treatment according to WHO adopted instructions, working capacity
expert exam.
The represented material is composed according to occupational dis-
eases study programme and it is recommended for the students of higher
medical educational establishments of the IV accreditation standard and
doctors of various specialities.

Рекомендовано Центральним методичним кабінетом

з вищої медичної освіти МОЗ України як навчальний посібник
для студентів вищих медичних навчальних закладів IV рівня акредитації,
які опановують навчальну дисципліну англiйською мовою
(Протокол № 4 від 24.12.2007 р. засідання
Комісії з медицини науково-методичної ради
Міністерства освіти і науки України)

© О. М. Ігнатьєв, Н. А. Мацегора,
Т. О. Єрмоленко, Т. П. Опаріна,
К. А. Ярмула, Ю. М. Ворохта, 2009
ISBN 978-966-7733-47-6 (серія) © Одеський державний медичний
ISBN 978-966-443-016-3 університет, 2009

4
 PREFACE

According to the best available estimates 100 million workers are in-
jured and 200,000 die each year in occupational accidents and 68–
157 million new cases of occupational disease are attributed to hazardous
exposures or workloads. Such high numbers of severe health outcomes
contribute to one of the most important impacts on the health of the world’s
population. Occupational injuries and diseases play an even more impor-
tant role in developing countries where 70% of the working population
of the world lives. By affecting the health of the working population, oc-
cupational injuries and diseases have profound effects on work produc-
tivity and on the economic and social well-being of workers, their fami-
lies and dependents.
According to recent estimates, the cost of work-related health loss and
associated productivity loss may amount to several per cent of the total
gross national product of the countries of the world.
The formal workforce constitutes on average 50–60% of a country’s
total population. If informal work and work at home are also taken into
account, the major part of the population is involved in work. This work
products all economic and material values all other societal activities thus
ensuring the socioeconomic development of countries.
The Constitution of the WHO, the WHO Global Strategy on Health
for All, plus the JLO Conventions on Occupational Safety and Health
and on Occupational Health Services stipulate among other issues the fun-
damental right of each worker to the highest attainable standard of health.
To access to occupational health services should be ensured for all work-
ers of the world irrespective of age, sex, nationality, occupation, type of
employment, or size or location of the workplace.
Although effective occupational health and safety programmes and
many structural changes have improved the conditions of work in some
sectors, several hazardous agents and factors such as physical, chemical,
5
biological as well as psychosocial stress in addition to occupational acci-
dents still threaten the health of workers in all countries continuing to
cause occupational and work-related diseases and injuries throughout the
world. In some economic sectors and in some countries occupational health
indicators show even worse trends than in the past.
Although the transfer of healthy and safe technologies has had a posi-
tive impact on development, the transfer of hazardous technologies, sub-
stances and materials to developing countries, which have insufficient
capacity to deal with such problems, constitute a threat both to the health
of workers and the environment.
New developments in work, the work environment and work organi-
zation, the introduction of new technologies, new chemical substances
and materials in all countries, and the growing mechanization and in-
dustrialization in developing countries can lead to new epidemics of oc-
cupational and work-related diseases and injuries. In addition, demographic
changes in working populations call for new strategies and programmes
for occupational health throughout the world.
The level of occupational health and safety, the socioeconomic devel-
opment of the country and the quality of life and well-being of working
people are closely linked with each other. This suggests that intellectual
and economic inputs in occupational health are not a burden but have a
positive and productive impact on the company and national economy.
Some industries and countries have demonstrated that it is technically fea-
sible and economically productive to prevent and minimize hazards at
work. Thus occupational health is an important factor for sustainable so-
cioeconomic development that enables workers to enjoy a healthy and
productive life both throughout their active working years and beyond
Way to a new healthy working life.
Governments should ensure the development of necessary infra-struc-
tures for effective implementation of occupational health programmes,
including occupational health services, research programmes, training and
education, information services and data banks. Networking of such in-
frastructures within and among the countries would substantially facili-
tate their efforts to implement national programmes.
It is a realistic long-term objective to organize well functioning and com-
petent occupational health services for all workers to ensure healthy and
safe workplaces as well as the required services for each individual work-
er. In order to be comprehensive such an occupational health service should
include first of all a multidisciplinaly preventive element, including sur-
veillance of the work environment and health of workers and, where ap-
propriate, relevant curative and health promotion elements.
6
 The focal point for practical occupational health activities is the work-
place. Employers are responsible for planning and designing a safe and
healthy work, workplace, work environment and work organization, as
well as for maintaining and constantly improving health and safety at work.
Workers in many countries are trained in occupational safety and health.
They have the right to know the potential hazards and risks in their work
and workplace, and they should, through appropriate mechanisms, par-
ticipate in planning and decision-making concerning occupational health
and other aspects of their own work, safety and health.

7
 Introduction
TO OCCUPATIONAL DISEASES

THE PLACE OF OCCUPATIONAL

DISEASES IN THE TRAINING
OF GENERAL PHYSICIANS
In the modern world a human being comes across with the greatest
majority of harmful factors which can unfavourably influence on his
health. The diseases caused by the influence on the human’s body unfa-
vourable factors of the industrial sphera are called occupational. A doc-
tor should be aquainted with this group of diseases because they have
special course and their social meaning is great as well. This group of
diseases is learnt in a special unit of inner medicine, a so called occupatio-
nal pathology.
Occupational pathology is a clinical discipline which studies the prob-
lems of etiology, pathogenesis, clinical course, diagnosis, treatment and
prophylaxis of occupational diseases. Occupational pathology is a part of
general clinical subjects and its meaning is closely connected with know-
ledge in other fields of medicine.
Occupational pathology is closely connected with hygienic subjects
and especially with labour hygiene, toxicology, pathological physiology
and other medical subjects. It goes without saying that the occupational
pathology is connected with social points, labour protection and safety
protection. The persons of different medical professions often come across
with the consequences of a harmful influence of industrial factors on the
human being’s organism. That is why they should have some knowledge
in the field of occupational pathology.
It refers to the general physicians as well as they should give medical
aid on the enterprises and together with the doctor of sanitary and epide-
miological stations to fulfil sanitary supervision, prevent harmful influ-
ence of industrial factors, treatment, reduction of general and occupational
morbidity.
Labor is one of the human being’s activity which has a favorable influ-
ence on his health and supplying the wellfare of the society. At the same

8
time some kinds of labor activity under certain conditions may lead to oc-
cupational diseases development. Insufficient and irregular technical equip-
ment of the industrial objects, non-observance of sanitary and hygienic nor-
mae necessary may lead to the development of occupational pathology.

HISTORIC STAGES OF OCCUPATIONAL

PATHOLOGY DEVELOPMENT
It was the labour activity of a human being which caused the idea about
occupational diseases development. One can point out several historical stag-
es in its development. We have very brief ideas about the ancient period of
its development from the works of separate doctors and philosophers. In
the ancient Greece and Roman literature in the works of Aristotel, Lucre-
tius, Ovidius and Plutarch one can find notions to the severe diseases and
high mortality rate among miners, slaves, working at the silver pits, leath-
ers, metallurgists. Hippocrates (460–377 BC) gave a more detailed descrip-
tion. He was the first who paid attention to the harmful properties of lead
dust and described the clinical picture of lead poisoning — “lead cramps”.

Classification of Occupational Hazards

and Dangers
I. Psychophysiologic factors
1.1. Static and dynamic overstrains of locomotor apparatus.
1.2. Hypodynamia.
1.3. Overstrain of circulatory, respiratory systems, vocal cords.
1.4. Neuropsychic overstrain.
II. Physical factors
2.1. Lowing or rising of temperature, moisture, atmospheric pressure.
2.2. A higher level of infrared, ultrasound, laser, ionizing, electro-
magnetic irradiation.
2.3. High level of dust content.
2.4. High level of noise, vibration, ultrasound.
2.5. Disturbance of illumination.
III. Chemical factors
3.1. Gases, steams, acids, alkali.
3.2. Dissolvents, varnishes, paints.
3.3. Pesticides.
IV. Biological factors
4.1. Micro- and macroorganisms.
4.2. Antibiotics, vitamins and other biologically active substances.
V. Danger of occupational trauma

9
 Classification of Occupational Diseases
(by Etiological Concept)
1. Diseases related to industrial dust exposure (pneumoconiosis, me-
chanic bronchitis, occupational bronchial asthma).
2. Diseases related to the exposure of physical factors of industrial
environment (vibrational disease, damages caused by different types of
irradiation, high or low temperature, etc.).
3. Diseases related to the exposure of chemical factors (acute and
chronic intoxications).
4. Diseases related to the exposure of biological factors (infectious,
parasitic and allergic diseases).
5. Occupational diseases caused by overstrain of separate organs and
systems (locomotor system, peripheric nerves and muscles, etc.).

Hygienic Classification of Labour

For hygienic estimation of labour conditions and character at the wor-
king places “The hygienic classification of labour” has been developed.
According to it they differentiate as follows:
A harmful industrial factor. This is a factor which influence on a
person working under certain conditions, may cause a disease or a stable
decrease of a working capacity.
A dangerous industrial factor. This is a factor which influence on a
person working under certain conditions, may cause a trauma or another
sudden acute worsening of health.
Heaviness of labour is a characteristic of labour process reflecting
primary load upon a locomotor apparatus and functional systems (cardio-
vascular, respiratory, etc.), providing its activity.
Strain of labour is a characteristics of a labour process reflecting a
primary load upon the central nervous system.

ESTIMATION OF LABOUR CONDITIONS

AND LABOUR CHARACTER
Principle of labour conditions and character differentiation is provid-
ed for the degree of industrial environment and labour process parame-
ters deviation from the existing hygienic standards and influence on the
functional state and health of the workers.
According to these indices they highlight three classes of labour con-
ditions and character.
10
 Class I — optimal labour conditions and character. An unfavourable
influence of dangerous and hazard occupational factors on the workers
are excluded. The requisites for high working capacity keeping are creat-
ed.
Class II — acceptable labour conditions and character when the level
of occupational dangers and hazards do not overpass the adopted hygie-
nic standards on the working places and possible functional labour-rela-
ted changes are recovered during regulated rest within the working day
or the rest at home by the beginning of the next shift. There is no unfa-
vourable influence on the condition of their health or health of their pos-
terity in the nearest and remote period.
Class III — hazard and dangerous labour conditions when because of
sanitary norm and rules violation the influence of occupational hazards
and dangers is possible in the limits overpassing hygienic standards and
psychophysiologic factors of labour activity and may cause functional
changes of an organism leading to the resistant decrease of the capacity
to the work and/or disturbances of health.
They highlight three degrees of dangerous and hazard labour conditions.
Degree I — labour conditions and character which cause functional
disturbances of reversible character if they are detected or stopped at ear-
ly stages.
Degree II — labour conditions and character which cause resistant
functional disturbances, leading to the morbidity rate increase and some-
times to the appearance of light signs and forms of occupational diseases.
Degree III — labour conditions and character with the higher danger
of occupatinal diseases development, higher morbidity rate.
The tasks of curable and prophylactic measures with occupational pa-
thology:
— rendering a qualified medical aid to the workers of the industrial
enterprises;
— regular medical examinations;
— prophylactic medical examinations;
— sanitary education;
— sanitative measures.

Prophylactic Medical Examination

The aim of prophylactic medical examination (PME) is to prevent dis-
eases (including non-occupational) by regular medical observation after
practically healthy persons and their labour conditions and way of life,
detection of the earliest stages of disease and timely treatment. PME in-
cludes four stages:

11
 1) definition of contingents for PME;
2) active indication of sick persons and correct organization of record-
keeping;
3) active systematic observation of the groups under PME;
4) organization of public prophylactic measures.
PME includes annual profound medical examination of all working
persons and conduction of a set scope of laboratory and instrumental in-
vestigations. This scope should include general blood analysis, examina-
tion of urine, determination of blood sugar and lipids, ECG and photofluoro-
graphy. Those who needs should be examined additionally with the use
of all modern methods. Simultaneously, risk-group persons should be de-
termined as well as the persons with the diseases on early stages. PME
provides for definition and individual estimation of health, working out
and condition of a complex of the necessary medical and social measures
and dynamic observation for the state of health of the persons working at
a certain enterprise.

12
 Chapter 1
DUST BRONCHITIS
AND OCCUPATIONAL
BRONCHIAL ASTHMA

DUST BRONCHITIS
Dust bronchitis and professional bronchial asthma are common dis-
eases. The tendency to their absolute ratio increase had been recently ob-
served. That is the result of the atmosphere pollution, frequent bronchitis
and the changes of the organisms reactivity. Late diagnosing, inadequate
therapy may cause invalidisation and complete professional disability, con-
vertion of the disease into its chronical form, complications, other severe
or even lethal diseases.
Long-term inspiration of the composite dust of medium agression rate
produces dust bronchitis. Smoking, infections and weather factors are the
additional factors adding to the main ethiological one — the dust itself.
In case of dust agression the nasal cavity suffers greatly. Primary irri-
tation converts into the hypertrophic catarrh, hypersecretion starts. These
changes cause poor nasal respiration to occur. Hypertrophy is followed
by atrophy. Ciliar epithelium gets replaced by the flat one, small glands
disappear. The nasal barrier function fails. Nasal irritation may cause the
attacks of spastic coughing.
The pathogenic stages of dust bronchitis are the following: primary
stage, inflammation stage, degeneration stage.
The clinical outline depends greatly on the inhaled dust type (mineral,
organic, silicate or carbon dust types). Coughing is the main symptom of
dust bronchitis. It’s usually dry, scarce sputum can be found. Usually the
onset term is long. The first symptoms appear after 5–10 years of con-
stant professional contact (table 1.1).
Basic therapy:
1. Isolation from dust.
2. Regeneration of the bronchial passage — removing of spasm, ede-
ma and hypersecretion:
— sympathomimetics (salbutamole, berotek, ephedrine);
— purine or xanthine derivates (euphilline, teophilline);

13
 Table 1.1. Classification of dust bronchitis
Form of bronchitis Clinical symptoms
Mild bronchitis 2–3 years of coughing (dry or scarce sputum). Dysp-
nea after excercise. Harsh breathing. Single dry rales.
Seldom attacks (1–2 times a year). Respiratory insuf-
ficiency (0–I)
Moderate bronchitis Constant coughing, sputum present. Dyspnea after usu-
al excercise, seldom attacks of choking. Harsh breath-
ing, dry rales. Seldom moist rales in lower segments
Attacks — 3–4 times a year. Respiratory insufficien-
cy (I–II). Changes of X-ray film. Emphysema, symp-
toms of cor pulmonale
Complicated forms. Constant coughing, excretion of sputum. Dyspnea at
Severe bronchitis patient state, choking. Long-term frequent attacks.
Combinations of pulmonary syndromes: asthmatic, in-
fectious-inflammatory, diffused obstructive emphyse-
ma. Respiratory insufficiency (III–IV). Hypoxemia.
X-ray — severe changes. Bronchial pneumosclerosis,
bronchoectases. Pneumonic infiltration symptoms are
found during the attacks. Severe emphysema. Cor pul-
monale (compensated or decompensated)

— cholinolytics (atropine);
— expectorants (bromhexine, mucolytine);
— mucolytics (acethylcysteine, mucosolvine, solvine);
— antibacterial drugs (sulphanilamides, hemi-synthetic penicillines,
cephalosporines);
— steroid glycosides;
— diuretics;
— oxygenation;
— physical therapy;
— respiratory training.
Medical Findings and Professional Abilities Examination
1st stage — poor clinical sympthoms, lungs functionally normal.
Professional abilities stay unchanged. Treatment and prophylaxis are
needed.
2nd stage — isolation from dust (the other job).
3rd stage — possible invalidisation (2nd group).
14
 Prophylaxis:
— mechanisation;
— anti-dust means (dust sedimentation);
— ventilation;
— individual protection means;
— medical examinations (at least once a year — obligate X-ray shot
of thorax).

OCCUPATIONAL
AND ENVIRONMENTAL ASTHMA
Dramatic advancements in the understanding of bronchial asthma have
taken place over the past decade, especially regarding the role of airway
inflammation in asthma. However, for a longer period of time, a better
cognition of asthma was evolving. There was stipulation of bronchial asth-
ma as a distinct pulmonary entity, and different from other common lung
conditions in 1688. In 1713, more than a quarter of a millennium ago,
Ramazzini chronicled occupational asthma when observing urticaria and
shortness of breath among grain sitters exposed to organic dusts. Over
the next 200 years, and until the beginning of the XX century, there was
a paucity of publications concerning occupational asthma. In 1911, there
was the recognition of asthma due to platinum salts among photographic
workers. There were recordings of asthma among workers producing oil
from castor beans in 1928. More interest in the association between the
workplace and asthma evolved in the late 1960s and 1970s. Clinical and
research interests in occupational asthma substantially heightened in the
1980s. In the 1990s, occupational asthma is the most common type of
occupational lung disease. The supporting data comes from information
on morbidity, disability, and the occurrence of the total number of cases.
Bronchial asthma affects approximately 5% of persons of all ages in
the general population. Asthma in the replace afflicts as many as 400,000
to 3 mln workers in the United States. These numbers may be an under-
estimation if we also consider workplace exacerbation of preexisting asth-
matic states. Moving into the XXI century we are gleaning new scien-
tific information to better explain asthma mechanisms and pathogene-
sis, especially the roles of bronchial mucosal injury and airway inflam-
mation.
When we consider occupational asthma on a clinical basis, a conclu-
sive diagnosis must be based on objective information that combines clin-
ical, physiologic, and laboratory findings. Prevention of occupational asth-
15
ma is paramount and involves a variety of strategies, most importantly
eliminating further workplace exposures of sensitized workers. A key so-
cioeconomic concern is the attempt to preserve the worker’s long-term
ability to be productive and financially provide for his/her family. An im-
portant goal is to try to return affected workers to their workplace in a
timely and prudent manner.

Definition of Occupational Asthma

Occupational asthma is an inflammatory disorder of the airways. There
is episodic airflow limitation, usually accompanied by nonspecific bron-
chial hyperresponsiveness. The initiation of occupational asthma occurs
after the inhalation of a substance or material that a worker may manu-
facture, use directly, or be exposed to incidentally at the work site. More
than 200 different agents cause allergic sensitization and specific airway
hyperresponsiveness. Nonallergic mechanisms also operate in the initia-
tion of asthma. Thus, irritant exposures may initiate asthma and the in-
duction of nonspecific airway hyperresponsiveness.
There has been difficulty formulating a precise definition of occupa-
tional asthma that is acceptable to the different groups and institutions
having different agendas and requirements.
A definition of use as a surveillance strategy and triggering public
health investigation or intervention is less restrictive than a definition ap-
propriate for workers’ compensation or legal purposes. Due to a diversity
of opinions, various definitions of occupational asthma are propounded.
A simple definition of occupational asthma is “variable airflow limi-
tation caused by a specific agent in the workplace”. A definition stress-
ing allergic pathogenesis is “variable airflow limitation caused by sensi-
tization to a specific agent encountered at work and excluding other oc-
cupational causes of variable airflow limitation not due to sensitization”.
The Industrial Injuries Advisory Council in Great Britain defines occu-
pational asthma as “asthma which develops after a variable period of symp-
tomless exposure to a sensitizing agent at work”. There are limits to the
consideration of what is an acceptable sensitizing agent when the defini-
tion is applied for compensation purposes. Smith formulated a medico-
legal definition of occupational asthma.
A definition of occupational asthma emphasizing a mechanism pro-
pounds that allergic occupational asthma is allergic/immunologic sensiti-
zation to a substance or material present in the work site. There is varia-
ble and work-related airflow limitation and the presence of both specific
and nonspecific airway hyperresponsiveness. For this type of occupational

16
asthma, a key clinical feature is that asthma develops after the passage of
a latent period, or a time span. During the latent period, exposure conti-
nues and allergy evolves. Eventually, there is the clinical manifestation
of work-related airflow limitation and specific and nonspecific airway hy-
perresponsiveness. The specific airway hyperresponsiveness relates to al-
lergic immunologic influences; the nonspecific airway hyperresponsive-
ness appears to be the sequela of bronchial mucosal injury and airway
inflammation.
Nonspecific airway hyperresponsiveness is such a characteristic fea-
ture of allergic and nonallergic occupational asthma that its absence brings
into question the very diagnosis of asthma. Nonetheless, there are cases
of allergic-type occupational asthma without nonspecific airway hyperre-
sponsiveness. There are also examples of allergic occupational asthma
where latency is not a feature, In such single-exposure cases, both aller-
gic and nonallergic mechanisms seem operative. Recurrent nocturnal at-
tacks of asthma are reported after a single exposure to Western red cedar
in a sensitized worker. Nonallergic occupational asthma occurs after a
high level, workplace irritant exposure and develops abruptly and with-
out a significant latent period. The exposure is characteristically singular
and intense. Asthma also occurs after lesser exposures and over a longer
(months to years) period of time. The absence of a latent perioid is a crit-
ical clinical feature, because it supports the contention that an allergic
mechanism is not operative.

Types of Occupational Asthma

There are two types of occupational asthma, depending on the pres-
ence or absence of a preceding latency period before asthma:
The first, occupational asthma with a latency period, encompasses in-
stances of occupational asthma for which an allergic/immunologic mech-
anism is identified.
The second, occupational asthma without a latency period, includes asth-
ma developing rather suddenly and is best illustrated by the reactive airways
dysfunction syndrome (RADS). Work-aggravated asthma, on the other hand,
is not considered occupational asthma but refers to the presence of concur-
rent asthma worsened by irritants or physical stimuli in the workplace.
The true prevalence of irritant-induced asthma (e.g., asthma without
latency) is unknown but is more common than previously perceived. In
one investigation, 6% of workers assessed for occupational asthma had
irritant-induced asthma (i.e., RADS) compared to 32% with allergic oc-
cupational asthma. Data from a community-based random sample of
17
3,606 adults, 40 to 69 years of age, residing in Beijing, China, examined
the relationship between occupational exposures to dusts and irritant gas-
es/fumes and physician’s diagnosis of asthma. After adjusting for sex, age,
education, residential areas, indoor coal combustion, and smoking status,
the attributable risks of dust-related asthma was 1.7%, while the risk for
asthma from irritant gases/fumes was 1.2%. Another study addressed seve-
ral hundred adult patients with bronchial asthma belonging to three ma-
jor races (Chinese, Malay, and Indian) and observed in five outpatient
primary care polyclinics. The risks of asthma were generally elevated for
service and manufacturing production workers, especially municipal clean-
ers and sweepers, textile workers, garment markers, electrical and elec-
tronic production workers, printers, and construction/renovation workers.
Nonspecific irritation effects are more common than sensitization as the
cause of work-related asthmatic symptoms in flour milling, baking, and
other flour-based industries. Nonspecific respiratory irritation was the
cause of asthma symptoms in 2.6% of workers, while sensitization was
responsible for symptoms in 0.3%.
The Sentinel Event Notification System for Occupational Risks
(SENSOR) Program, launched by the National Institute for Occupational
Safety and Health (NIOSH) in 1987, provides state-based surveillance and
intervention programs for occupational asthma. From 1988 through 1992,
328 cases met the SENSOR surveillance case definition for occupational
asthma. There were 128 cases classified as possible occupational asthma;
42 were RADS; and 37 cases were work-aggravated asthma. In Michi-
gan, more than 40% of the asthma case-patients worked in transportation
equipment manufacturing. In another investigation, the prevalence of oc-
cupational asthma in Michigan was estimated to be between 3% and
20.2%. In New Jersey, 15% of asthma case-patients worked in manufac-
turing of chemicals and allied products. The SENSOR data confirmed that
isocyanates are the most frequently reported asthma-causing agents (19.4%
of cases).
The prevalence of occupational asthma varies with the extent of expo-
sure and with occupation. For example, investigations note that approxi-
mately 4% of workers exposed to Western red cedar develop asthma (40);
the prevalence for Eastern red cedar is 3.8% to 7%. About 4% to 5% of
workers exposed to isocyanates develop occupational asthma. Asthma
from the proteolytic enzymes occurs in 10% to 45% of workers. Occu-
pational asthma caused by latex evolves in 2.5% of hospital employees.
Wheat flour allergy appears in 25% of bakers and pastry cooks. About
9% of the bakery workers show positive skin prick tests to fungal amyla-
se and 8% demonstrate elevated amylase-specific immunoglobulin E (IgE)
18
antibodies. About 41% of technicians report work-related symptoms pro-
voked by laboratory animals. The prevalence of work-related asthma
among factory employees manufacturing flux-cored solder containing col-
ophony is 21% in the highest exposure group and is 4% in the lower ex-
posure group. Malo and associates report that 23% of employees at a car-
pet-manufacturing plant that used guar gum to adhere the dye to the fiber
have a history suggestive of occupational asthma. An investigation of asth-
ma conducted on 619 cedar sawmill, 724 grain elevator, 399 pulp mill,
798 aluminum smelter, and 1,127 unexposed workers shows an overall
prevalence of physician-diagnosed asthma of 4.6%. The prevalence of
asthma is 3.9 times higher in cedar sawmill workers, 2.2 times higher in
pulp mill and aluminum smelter workers, and 1.7 times higher in grain
elevator workers compared with unexposed workers.

Risk Factors for the Development

of Occupational Asthma
Exposure Characteristics
A variety of exposure characteristics influence asthma development or
aggravate the disease once it is present. The chemical characteristic of an
allergen influences its antigenicity and its ability to cause asthma. Such rele-
vant characteristics as chemical type and reactivity, chemical sources, and
concentration of an exposure are pertinent. The intensity of an exposure is
critical. High levels are implicated in the pathogenesis of both types of occu-
pational asthma, with and without latency. Massive exposures occur with
RADS. Intermittent, high-level exposures are important in the pathogenesis
of toluene 2.4-diisocyanate (TDI)-induced asthma, but also asthma without
latency. Workers who are more frequently exposed to spills are more likely
to report asthma symptoms and show alterations in lung function testing.
An unmistakable dose-response relationship exists for an exposure and
the prevalence of allergic sensitization. This association is reported for
Western red cedar, Eastern red cedar, isocyanates, colophony, baking pro-
ducts, and acid anhydrides. Symptoms of work-related asthma in red ce-
dar workers are more common after 10 years of exposure, and levels of
pulmonary function are lower with higher wood dust exposures.
Cumulative exposure may be important, as exemplified by the inves-
tigation of Jones and associates for TDI. The duration of an exposure may
be influential as ascertained by the investigation of Di Stefano et al. In
the latter study, comparisons of lobar bronchial biopsies findings between
two TDI groups show that workers who develop asthma after a short-
term exposure (e.g., 2.4±0.4 years) show significantly higher numbers of
19
mast cells in the airway mucosa compared to the subjects who develop
asthma after long-term exposure to TDI (e.g., 21.6±3.1 years). Exposure
indices may also be tied to the type of asthmatic response noted. The pre-
sence of a late asthmatic-response is shown to have a linear relationship
to the logarithm of tetrachlorophthalic anhydride air exposure. The im-
mediate asthmatic response does not closely relate to tetrachlorophthalic
anhydride air exposure.
Poor working conditions are a good predictor for the development of
adverse pulmonary outcomes. For example, work activity in a small, poorly
regulated hemp mill, where there are routinely very high dust levels, is as-
sociated with reduced pulmonary function testing. An accelerated decline
in forced expiratory volume in 1 sec (FEV) is noted in women workers,
who are predominantly nonsmokers; this observation suggests an inde-
pendent effect of hemp on the airways.
Exposures may be monitored using biomarkers. Thus, bronchial re-
sponsiveness in aluminum pot-room workers with asthma appear related
to plasma levels of fluoride. Trimellitic anhydride (TMA) workers show-
ing late-occurring asthma or late respiratory systemic syndrome improve
after moving to lower exposure jobs. However, elevated IgE against TM-
HSA is considered to be a marker for a subpopulation of workers with
asthma and rhinitis that do not improve.
An industry factor is observed with TDI. Asthma is reported more of-
ten by workers employed in polyurethane processing than by employees
of TDI manufacturing.
A mill effect or plant effect is described to explain differences in the
frequency of byssinosis, and possibly of TDI asthma among workers with
similar exposure. Hexa-methylene diisocyanate (HDI) and TDI display
the same vapor pressures and are relatively volatile at room temperature;
MDI has a lower vapor pressure and is not volatile at room temperature.
MDI becomes volatile and is more likely to lead to asthma after heating
when its vapor pressure increases. This circumstance is observed in such
industrial processes as foundry work. The specific type of industrial proc-
ess may influence the development of asthma. For example, asthma ap-
pears in about 5% of workers exposed to isocyanates; 10% to 45% of
workers exposed to proteolytic enzymes; and 2% to 40% of workers ex-
posed to grain dust, including millers and bakers.

Geographic and Climatic Factors

Weather conditions such as wind direction and humidity may be in-
fluential. In Barcelona, Spain grain dusts released by unloading soybeans
caused asthma outbreaks. Apparently, the unloading of the soybeans gives
rise to sudden, massive release of soybean dust that reaches the urban
area owing to appropriate meteorological conditions and causes the epi-
20
demic. Asthma from red cedar is seen in the western United States. In the
Great Lakes area, grain dusts and flour frequently cause asthma. Chemi-
cals are indigenous to many areas, especially the industrial East and Mid-
west. Working in a cold environment may have an adverse effect on asth-
matics who exert themselves.

Atopy
The presence of the atopic status may influence how an individual
worker respond to a workplace allergen. The relationship between atopy
and allergic sensitization is best established for agents of higher molecu-
lar weight (>1,000 daltons). This includes the detergent enzymes, labora-
tory animal allergens, certain insect proteins, and products such as gum
acacia and flour. In a cross-sectional study, involving 178 bakery work-
ers, α-amylase exposure and atopy were the most important determinants
of α-amylase skin sensitization.
Atopy may also be important for certain low-molecular weight
(< 1,000 daltons) compounds such as platinum salts, ethylene diamine,
and dimethyl ethanolamine. Other low molecular weight agents, such as
TDI, Western red cedar, trimellitic anhydride, phthalic anhydride, and for-
maldehyde, do not seem to be influenced by the atopic state. The con-
flicting data on atopic sensitization and an agent’s molecular size suggest
that other factors are important in determining allergic sensitization.

Pathogenesis
Immunologic disorders are the basic initiators of the disease. The im-
munologic stage includes the interaction of allergene and the antibodies
binded to the cells of the sensibilized organism. Antibodies are immu-
noglobulines. The complexes of antibodies and antigenes are fixed to the
respiratory tract mucous coat labrocytes. The latter degranulate, excreting
histamine, serotonine, etc.
These compounds promote the bronchospasm, mucous coat edema, hyper-
secretion and the allergic inflammation. These factors produce choking
attack — the main symptom of bronchial asthma. The process is also influ-
enced by the neuro-regulative, endocrine and toxico-infectious mechanisms.
Symptoms:
1. Asthmoid bronchitis is a predecessor of asthma. It can pass without
turning into choking attacks. Quinke’s allergic edema and urticaria can
be considered to be pre-asthma too.
2. Mild asthma.
3. Moderate asthma.
4. Severe asthma.
21
 The symptoms of asthmoid bronchitis are dry coughing, harsh breath-
ing, emphysema, dry whistling rales.
Mild asthma is characterised by scarce attacks which can be easily
managed with broncholytics and anti-histamine drugs. The state of pa-
tients stays satisfactory. No complications are found at this period.
The isolation of patients from allergenes brings clinical reconvales-
cence.
Moderate asthma is characterised by frequent attacks of choking. These
attacks can be hardly managed with broncholytics. Coughing and dry rales
are found even at the remission period. Medium emphysema and cor pul-
monale symptoms appear. The isolation of patient from the allergenes
makes the choking attacks disappear, but dyspnea, coughing and dry rales
still occur.
Severe asthma is characterized by very frequent attacks of choking
which are hardly managed at all.
Status asthmaticus is a state of continuing asthmatic attacks (lasting for
hours or even days) which can’t be managed with usual means. Coughing,
dyspnea, dry rales and cor pulmonale accompanies the severe form. The
disease progresses. Isolation wouldn’t bring any positive progress at all.
The tests of bronchial passage (functional vital capacity, Tiffeneau’s
test, pneumotachometry) indicate bronchospasm.
X-ray data: emphysema, low diaphragm, poor respiratory excursion,
cor pulmonale.
Laboratory data: sputum — eosinophiles, Charcot — Leyden crys-
tals, Curschmann’s spirals. Blood: high alpha-2 and gamma globuline le-
vels, dysproteinemia.
Therapy
Ethiologic therapy: determination of allergene and its isolation.
Pathogenetic therapy: specific desensibilization (subcutaneous injec-
tions of allergene). Immunodepressors and steroids.The most popular ster-
oids are prednisolone, triamcinolone, dexamethasone and hydrocortisone.
Immunodepression: clone-blocking cytostatics (6-mercaptopurine; 4-
aminochinoline derivates — resochine, delagile).
Anti-histamin drugs: diasoline, diprasine, suprastine, tavegil.
Broncholytics and bronchodilatators: euphilline, asthmopent, alupent,
berotek.
Chiolinolytics — atropine, platyphilline.
Adrenaline and ephedrine for attacks management.
Status asthmaticus management: steroids (regeneration of the beta-recep-
tors sensivity), intravenous infusions (4% glucose, natrium bicarbonate, etc.)
Complex therapy — physical therapy, gymnastics, SPA.

22
 Prophylaxis and Professional Abilities Examination
Prophylaxis includes social and labour hygiene and improvement of
technologic processes.
Special protective clothes is the obligate mean of protection.
Removing of high and low temperatures, moisture and dust from the
technologic process improve the health prognosis.
Prophylactic examination and health control are needed. No contact
with sensibilising compounds or irritants is allowed to patients no matter
how good their state is.
Patients with mild asthma don’t lose their professional abilities.
The medium form is usually followed by significant decrease of the
professional abilities or their complete loss.
Severe asthma means complete loss of professional abilities (II and III
group invalidisation).

TESTS
1. A woman, aged 45, has been working for 20 years at the chemist-
pharmaceutical plant. She complains of asthma attacks, which occur
against a background of “full health”. Noisy, stridulous breathing, which
is heard at a distance. Herewith a patient takes a forced sitting position.
On examination the thorax is extended. The lips, nails’ loges, skin are
cyanotic. On percussion of the lungs — a band-box sound. Breathing is
difficult, with prolonged exhalation, a big amount of diffuse dry rales on
inhalation and exhalation are heard.
Make a probable diagnosis:
A. Chronic bronchitis.
B. Professional bronchial asthma.
C. Tuberculosis.
D. Acute pneumonia.
E. Tracheobronchitis.
2. A 32-year-old man has been working on the elevator for 10 years,
complains of constant cough for 2 years. Cough is dry, sometimes with
the small quantity of sputum. Heavy physical load causes dyspnea. Aus-
cultation: harsh breathing, single dry rales. 1–2 times a year the patient
notes exacerbation. X-ray revealed no changes. Signs of cardiac insuffi-
ciency are absent. A diagnosis was: dust bronchitis.
Define a degree of severity:
A. The I degree of severity.
B. The II degree of severity.
C. The III degree of severity.
23
 3. A woman, aged 35, has been working at the flax-spinning produc-
tion for over 5 years. During the preventive physical examination she com-
plained of strong pertussoid cough, which was terminated by the discharge
of a little amount of the viscous sputum, deterioration of condition du-
ring a week and during each day, attacks of asphyxia at the end of the
week. Objectively: expiratory dyspnea, dry rales in the thorax on auscul-
tation, reduction of FVCL, power of the exhalation,VCL, MVL.
What is the most probable cause of this condition?
A. Allergic alveolitis.
B. Dusty bronchitis.
C. Professional bronchial asthma.
D. Acute respiratory insufficiency.
E. Hypocapnia
4. A 35-year old man applied to the physician with complaints of the
constant cough, dyspnea, separation of a swampy mucous sputum, sea-
sonly appeared attacks of asphyxia last 6 months. In anamnesis — 10-
year experience of work at the lacquer-paint plant. He noticed that at-
tacks appear under overflowing of paints.
Objective: on the part of the respiratory system at the percussion — a
band-box sound on the base of the lungs; dry diffused rales are ausculta-
ted. Laboratory data: moderate eosinophilia. X-ray — a reinforcement of
a lung pattern and expansion of lungs’ roots.
What is the most possible reason of this condition?
A. Chronic toxic bronchitis at the stage of intensification.
B. Bronchial asthma, mild degree of severity.
C. Chronic toxic bronchitis complicated by bronchial asthma, moder-
ate degree of severity.
D. Bronchial asthma, moderate degree of severity.
E. Acute toxic alveolitis.
5. A woman, aged 50, has been working during 20 years at the chemi-
cal plant. She complains of attacks of asthma, appeared at work, noisy,
stridulous breathing, which is heard at a distance, dyspnea. At the exami-
nation — the thorax is extended. The lips, nails’ loges, skin are cyanotic.
At the percussion — a band-box sound. Breathing is harsh, with the pro-
longed expiration, a big amount of diffuse dry rales on the inhalation and
exhalation are auscultated.
What a pathology has this patient?
A. Chronic bronchitis.
B. Professional bronchial asthma.
C. Tuberculosis.
D. Acute pneumonia.
E. Tracheobronchitis.
24
 Chapter 2
PNEUMOCONIOSIS

Pneumoconiosis is a chronic disease of the lungs, which is connected

with long term inhalation and dust deposit in the lungs and characterized
by development of diffuse fibrosis. More specified formulation of the di-
sease today is a chronic diffuse pneumonitis, which connected with inha-
lation of occupational dust and developing of fibrosis in the lungs.
Three patterns are distinguished in the new classification of pneumo-
coniosis: etiologic, roentgenologic and clinical-functional (Table 2.1).
The first pattern includes 5 groups of pneumoconiosis: silicosis (dust
containing free dioxide of silicon), silicatosis (dust containing dioxide of
silicon in the linked state), carboconiosis (dust containing carbonicum),
metalconiosis (dust, containing primary metals possessing fybrogenum
action), hypersensible pneumoconiosis (aerosols of toxic-allergic metals;
organic dust of vegetable and animal origin; another toxic and allergic
inorganic dust), code and type of pneumoconiosis.
The second pattern includes basic X-ray signs of pneumoconiosis, type
of fibrosis, code of type, character of shadows, size, contours, degree of
manifestation and area of spreading, localization.
The third pattern includes clinical course, types of external breathing
violations of function (EBD) and developing of the disease.

Table 2.1. Classification of pneumoconiosis

Pattern 1. Etiologic
a) Taking into account composition of production dust (aerosol)
The type of
N The name of the group Code pneumoconiosis
1. Silicosis (dust containing free J. 62 1.1. Silicosis
dioxide of silicon) J. 62.8 1.2. Silicosilicatosis
Silicosiderosis
Silicoantracosis

25
 End of Pattern 1

N The name of the group Code The type of

pneumoconiosis
2. Silicatosis (dust containing J. 61 2.1. Asbestosis
dioxide of silicon in the J. 62.0 2.2. Caolinosis, olivinosis
linked state) 2.3. Talcosis
3. Carboconiosis (dust contain- J. 60 3.1. Antracosis
ing carbonicum) J. 63.3 3.2. Graphitosis, diamond
pneumoconiosis
4. Metalconiosis (dust, contain- J. 63.4 4.1. Siderosis, baritosis,
ing primary metals possessing J. 63 manganoconiosis
fibrogenum action) 4.2. Pneumoconiosis of
electric welders, polishers
5. Hypersensible pneumoconio- J. 63.2 5.1. Pneumoconiosis under
sis: J. 63.8 influence of beryllium,
— aerosols of toxic-allergic J. 63.0 chrome, nickel, platinum.
metals; 5.2. Bissinosis, papricosis,
— organic dust of vegetable exogenous allergic alveo-litis
and animal origin; (EAA)
— another toxic and allergic 5.3. Pneumoconiosis (pneu-
inorganic dust monitis) of plastic dust,
drugs

Pattern 2. Basic X-ray signs of pneumoconiosis

Character of Degree of mani-
Code shadows, size, festation and area Localisation
Type of fibrosis of type contours of spreading
Primary 0 Some strengthening Not sharply Mono-
pneumofibrosis of pulmonary pic- pronounced or bilateral
ture
Interstisial s Little shadows of Not sharply Bilateral
wrong form: pronounced (diffuse)
t — linear till 1.5 mmNot sharply
reticular shadows, pronounced
1.5–3.0 mm Moderatly
pronounced
lung picture
u — linear and ma- Moderatly
cular shadows, 3.0– pronounced
10.0 mm Sharply
pronounced
plenty shadows

26
 End of Pattern 2
Character of Degree of mani-
Code
Type of fibrosis shadows, size, festation and area Localisation
of type
contours of spreading
Nodular Small spheroid 1. Small amount Bilateral
shadows (nodulars) 2. Moderate
on the background amount
of interstitial fibro- 3. Big amount
sis:
p — size until
1.5 mm
q — size from 1.5
till 3mm
r — size from 3
till 10 mm
Nodular Big spheroid shad- 1. Area of expan- Bilateral or
ows (nodes) on the sion <50 mm; monolateral
background of 2. Expansion less
interstitial and than area of the
nodular fibrosis: right pulmonary
A — size 1–5 cm; superior lobe
B — size 5–10 cm; 3. Expansion more
C — size over 10 cm than area of the
right pulmonary
superior lobe

Pattern 3. Clinical picture and function

Types of
Stages external
of Clinical manifestations Stages of Clinical
breathing
pneumo- the disease course
dysfunction
coniosis (EBD)
I, II, 1. Without complications 1. Without 1. Acute (period — progredi-
III 2. Complicated: violations of work less ent
— bronchitis (nonob- EBD than 5 years) — slow
structive, obstructive) 2. With func- 2. Quick (period — stable
— pneumonia tional viola- of work less
tions: than 10 years) — regressive
— bronchial asthma
— restrictive 3. Slow
— bronchoectatic di
sease — obstruc- (period of work
tive over 10 years)
— tuberculosis
— diffusive 4. Late (5 years
— pulmonary bleeding and more after
— mixed
— rheumatoid pneumo- finished wor-
coniosis king with dust)

27
 SILICOSIS
Silicosis refers to a spectrum of pulmonary diseases attributed to the
inhalation of various forms of free crystalline silicon dioxide or silica. A
man-made disease, it is probably as old as human history and was known
to the ancient Egyptians and Greeks. Although the prevalence of silicosis
apparently peaked in the late XIX and early XX century when mecha-
nized industry was just beginning, even in developed countries today spo-
radic yet preventable cases of silicosis occur.
Silicon dioxide or silica is the most abundant mineral on earth. It is
formed from the elements silicon and oxygen under conditions of increased
heat and pressure. Silica exists in the crystalline and amorphous forms.
Crystalline forms are based on a tetrahedral structure in which the central
atom is silicon, and the corners are occupied by oxygen. The structure of
the crystal is such that two adjacent tetrahedrons share two oxygen
atoms. Examples of crystalline silica are quartz, cristobalite, and tridymi-
te. The most common form is quartz, a typical component of rocks. Some
of the common quartz-containing materials in industry are granite, slate,
and sandstone. Granite contains about 30% of free silica, slate — about
40%, and sandstone is almost pure silica. Crystobalite and tridymite oc-
cur naturally in lava and are formed when quartz or amorphous silica is
subjected to very high temperatures. They may also be formed in silica
bricks (refractory bricks) used in industrial furnaces.
Amorphous silica is noncrystalline and has relatively nontoxic pulmo-
nary properties. It occurs as diatomite (skeletons of prehistoric marine
organisms) or as vitreous silica (the result of carefully melting and then
quickly cooling crystalline silica). Heating diatomite with or without al-
kali (a process known as calcining) forms cristobalite, a material that has
the potential to be more toxic than quartz.
Crystalline silica that is not bound to other minerals is referred to as
“free”; when it is bound to other minerals it is referred to as “combined.”
The latter are also known as silicates. Examples of silicates that have been
widely used in industry include asbestos, talc [(Mg3Si4)O10 (OH)2], and
kaolinite (Al2O3SiO 2·H2O), a major component of china clay, or kaolin.

Workers at Risk for Silicosis

The knowledge that silicosis is associated with certain occupations is
rooted in antiquity. Hippocrates reported that miners developed dyspnea
with exertion. Ramazzini and Agricola were instrumental in recognizing
the relationship between rock dust exposure and the development of dys-
pnea in those who worked in this trade.
28
 The worst outbreak of silicosis in the United States occurred during
the construction of the Gauley Bridge tunnel in West Virginia in 1930
and 1931. In this unfortunate but preventable disaster, more than 400 men
of the estimated 2,000 engaged in rock drilling died, and about 1,500 con-
tracted silicosis and were eventually disabled.
Occupations known to carry increased risk for silicosis and the perti-
nent sources of exposure in these trades are enumerated in Table 2.2.
It is difficult to obtain precise estimates of the prevalence of silicosis
because of the many different occupations involved, the participation of
transient workers, and the variability of disease detection methods (e.g.,
autopsy versus compensation or screening data) and reporting practices
from place to place. In 1956 Trasko obtained estimates of silicosis preva-
lence by examining records of workers in 20 states who were compensat-
ed for silicosis. About 6,000 cases were identified. The largest numbers
of silicosis cases were found among metal miners (1,637) and foundry
workers (1,645). Because of the nature of case identifications, these num-
bers most likely underestimate the actual frequencies. Autopsy records
of 3,365 underground miners revealed the presence of classical silicotic
nodules in the lungs of 12.5% of the cases. In an investigation of worker
health at two silica flour mills, 16 (26%) of the 61 workers who were
exposed to micro-crystalline silica had radiographic evidence of simple
silicosis, and 7 (11%) had progressive massive fibrosis.

Table 2.2. Occupations of high risk for silicosis

Occupation Exposure hazard

Sandblaster Shipbuilding and iron-working industries
Miner or tunneler Underground miners are at risk during roof bolting, shot
firing, and drilling; surface coal mine drillers are at high
risk
Miller Finely milled silica for fillers and abrasives; “silica flour
workers”
Pottery workers Crushing flint and fettling are the major exposures
Glassmaker Sand used for polishing and enameling
Foundry worker Silica is essential during mold making; exposure is du-
ring fettling
Quarry worker Slate, sandstone, granite
Abrasives worker Finely ground particles

29
 Million workers outside of the mining industry are potentially exposed
to crystalline silica. Compared to working conditions of 20 years ago,
better methods of dust suppression and ventilation as well as respiratory
protection have diminished the attack rate among workers. However, new
cases of silicosis are still reported sporadically in both developed and
developing countries, and silicosis is still very much a disease of modern
days.

Pathology
On inspection, the silicotic lung is firm and blacker than normal. The
surface is coarse and nodular. The visceral pleura has areas of fibrosis
and may be covered by plaque like lesions. Peribronchial and hilar lymph
nodes are typically enlarged. On sectioning, these enlarged nodes show
concentrically arranged fibrous tissue. Cutting the lung reveals palpable
intrapulmonary nodules, especially in the upper lobes. In simple silicosis
these nodules are usually 2 to 6 mm in diameter. In conglomerate silico-
sis or progressive massive fibrosis, the lesions are typically 10 to 20 mm
diameter, a result of the coalescence of smaller nodules. Nodules vary in
color depending on the presence of other dusts. The extent of nodule cal-
cification is also variable.
The earliest parenchymal lesion in workers with relatively low-dose,
chronic exposure to free crystalline silica is a collection of dust-laden
macrophages and loose reticulin fibers in the peribronchial, perivascular,
and paraseptal or subpleural areas. Later, these lesions become more or-
ganized and may appear. The silicotic nodule, the pathologic hallmark of
silicosis, has a histologic appearance analogous to tornado. The central
zone, like the eye of the storm, shows little activity. It is hyalinized and
composed of concentrically arranged collagen fibers. The peripheral zone
is whorled and becomes less organized toward the edges. It contains macro-
phages, lymphocytes, and lesser amounts of loosely formed collagen.
Under polarized light microscopy, a few weakly birefringent particles may
be seen in the center of the nodule, likely the result of trapped crystalline
silica mixed with other dusts. In the periphery of the nodule, the amount
of dust and the degree of birefringence differ dramatically. Needle-shaped,
strongly birefringent material is easily seen intermingled with cells and
dust. The strongly birefringent crystals are silicates. This is the site of
active enlargement of the nodule and of ongoing inflammation. As the
disease progresses, the periphery of the silicotic nodule moves farther from
the hyalinized center, enmeshing small airways, pleura, and blood and
lymphatic vessels in the fibrotic process.

30
 Coalescence of silicotic nodules form the progressive massive fibrot-
ic (PMF) lesion, a mass of dense, hyalinized connective tissue with mini-
mal silica content, a small amount of anthracotic pigment, minimal cellu-
lar infiltrate, and negligible vascularization. Typically, the centers of these
conglomerate lesions cavitate, the result of mycobacterial infection or
ischemic necrosis when they exceed a certain size.
The histologic pattern of acute silicosis differs from that of chronic
silicosis. Silicotic nodules are rarely seen, and, if identified, are usually
poorly developed. The interstitium is thickened with inflammatory cells.
There is alveolar filling with proteinaceous material consisting largely of
phospholipids or surfactant (or surfactant-like material) which stain with
periodic acid-Schiff (PAS) reagent. Since the histologic appearance re-
sembles that of idiopathic alveolar preteinosis, this process occurring in
a clinical background of overwhelming silica exposure has also been called
silicoproteinosis. On electron microscopic examination the alveoli are lined
by prominent epithelial cells, the majority of which are hypertrophic type
II pneumocytes. The alveolar exudate is most likely the result of overpro-
duction of phospholipids and surfactant-associated proteins by these hyper-
trophic type II cells. In addition, desquamated pneumocytes, macropha-
ges, and silica particles are found in the alveolar spaces. Typically a min-
imal amount of pulmonary fibrosis is present. Therefore, although the term
silicoproteinosis may reflect one of the pathologic changes present, other
features of acute alveolar damage syndromes and even of desquamative
interstitial pneumonitis are a part of the recognized lung injury.

Pathogenesis
The majority of the existing information regarding the pulmonary cel-
lular and molecular responses to silica comes from experimental animal
models. Silicosis is induced in these models by tracheal instillation of
silica or by inhalational exposure of animals over a few weeks to months.
One therefore has to be concerned about correlates drawn between the
development of the silicotic nodules in experimental animals after only 6
or 8 months’ exposure to silica and the development of classic silicosis
over 20 or more years in humans. The applicability of this information to
humans is subject to speculation. Nevertheless, animal work has provi-
ded much insight into the pathogenesis of the illness.
The pathogenesis of silicosis begins with the inhalation of crystalline
silica particles that have favorable characteristics for deposition in the
alveolar spaces. The most important of these is size. Particles of a diame-
ter smaller than 3 mm and greater than 0.5 mm have the best chances of

31
entering and being retained in the pulmonary acini. The key event in the
genesis of silicosis is the interaction between the silica particle and the
alveolar macrophage, the main phagocytic cell in the alveolar space. Ear-
ly work on the pathogenesis of silica-induced lung injury focused on the
injury and cell death that occurred after ingestion of silica by alveolar
macrophages in vitro and in vivo. Lung injury was believed to be related
to the release of intracellular proteolytic enzymes following the disrup-
tion of the alveolar macrophage. Intracellular silica released in this proc-
ess was taken up by other macrophages. The recurrent cycle of macro-
phage phagocytosis, cell death, release of intracellular enzymes, and reup-
take of silica perpetuated the inflammatory process. More recent studies
suggest that cell injury may be a more crucial factor than cell death in the
pathogenesis of silicosis.
The fibrogenic effect of silica may be due to elaboration of several
inflammatory mediators by alveolar macrophages that have been activat-
ed by silica exposure or ingestion. The data supporting this come mainly
from experiments wherein alveolar macrophages are harvested by bron-
choalveolar lavage (BAL) from subjects or animals exposed to silica par-
ticles in vivo, or are collected directly after being exposed to silica par-
ticles in vitro. There are chemotaxis of neutrophils and macrophages when
these cells were exposed to BAL fluid supernatant of silica-exposed guinea
pigs. The recruitment of cells to the sites of particle deposition and cell
injury promotes the amplification of the inflammatory response. Enhanced
production of fibrogenic factors, specifically interleukin-1 (IL-1), tumor
necrosis factor (TNF), and transforming growth factor, by silica-activa-
ted alveolar macrophages has been shown.

Clinical Presentation and Diagnosis

The clinical diagnosis of silicosis has three requisites:
1. The recognition by the physician that silica exposure adequate to
cause this disease has occurred.
2. The presence of chest radiographic abnormalities consistent with
silicosis.
3. The absence of other illnesses that may mimic silicosis. For exam-
ple, miliary tuberculosis or pulmonary fungal infection may appear radi-
ographically identical to silicosis. In such cases, an extensive history and
microbiologic workup to identify infectious pathogens could help better
understand the cause of the radiographic abnormalities. Open lung biop-
sy is not needed to make the diagnosis of silicosis in the great majority of
cases. However, in cases where the exposures and clinical presentations

32
are atypical, biopsy, BAL, and scanning electron microscopy combined
with analytic techniques such as energy-dispersive x-ray analysis may be
needed for accurate diagnosis of the disease.
The presentation and severity of silicosis are influenced by multiple
factors, principally the concentration of free crystalline silica in the work-
place, the duration of exposure, and the physical characteristics and in-
nate fibrogenic properties of the respirable dust (i.e., the fraction of crys-
talline silica in the dust). Genetic factors, cigarette smoking, and addi-
tional complicating pulmonary diseases are among the host factors that
interact with the environment in an apparently complex and poorly un-
derstood fashion resulting in a spectrum of disease presentations. For these
reasons it is critical to recognize the features of classic silicosis, acute
silicosis, and accelerated silicosis.

Classic Silicosis
Classic silicosis is the most frequently recognized clinical presenta-
tion of silicosis. This results from low to moderate exposure to silica dust
for 20 years or more, although cases where the exposure occurred for
10 years or less have been reported. The extent of classic silicosis is de-
scribed by the degree of radiographic chest involvement. In the lesser ra-
diographic categories, silicosis does not typically cause impairment, al-
though patients may complain of cough, sputum production, and dyspnea
as a result of industrial bronchitis or concurrent cigarette smoking. Only
in the most advanced radiographic categories of classic silicosis without
progressive massive fibrosis is respiratory impairment attributable to sil-
ica exposure. The primary health concerns associated with mild classic
silicosis are a predisposition to mycobacterial infections and disabling
progressive massive fibrosis.
Progressive massive fibrosis typically causes respiratory impairment.
Large opacities develop in the upper lung zones, usually on an extensive
background of small, rounded nodules. The result is restriction of lung
volumes, decreased pulmonary compliance, and diminution of gas trans-
fer. Initially dyspnea occurs with exercise, but the condition progresses
to dyspnea at rest as more lung is involved. Cor pulmonale develops as
the illness progresses. Mycobacterial infection is always a concern. Deve-
lopment of such an infectious process in this clinical setting can radically
worsen chest symptoms, accelerate lung function decline, and alter the
chest radiograph.
The stiff lungs and basilar emphysema associated with progressive
massive fibrosis increase the risk of developing spontaneous pneumotho-

33
rax. This can result in a precipitous worsening of preexisting hypoxemia
and could be life threatening. The problem is exacerbated by the impaired
ability of the poorly compliant lung to reexpand. In complicated silicosis,
death is commonly attributable to progressive respiratory insufficiency.

Accelerated Silicosis
Accelerated silicosis results from exposure to higher concentrations
of silica over a period of 5 to 10 years. Progression is virtually certain,
even if the worker is removed from the workplace. Furthermore, antinuc-
lear antibodies and clinical autoimmune connective tissue diseases such
as scleroderma, rheumatoid arthritis, and systemic lupus erythematosus
are frequently associated with accelerated silicosis.

Acute Silicosis
Acute silicosis, the least frequent yet the most devastating form of this
disease, results from exposure to overwhelmingly excessive concentra-
tions of free crystalline silica for as little as a few years or even 1 year. It
was described in Britain by Middleton in 1929 as a syndrome of rapidly
progressing respiratory illness occurring after 2.5 to 4 years’ exposure to
silica dust. In 1930, MacDonald et al. reported on two young women in a
London factory who packed a kind of cleaning powder containing ground
silica. Both had also worked for brief periods in this industry and they
died from silica-induced respiratory failure. At autopsy the patients’ lungs
were noted to be heavy. Microscopic examination revealed that the alve-
oli were filled with desquamated cells and an “albuminous” exudate. The
authors proposed that the histologic changes resulted from the formation
of colloidal silica and insoluble silicates.
The invariable downhill clinical course of acute silicosis includes re-
lentless dyspnea, cor pulmonale, and pulmonary cachexia. Serial lung func-
tion tests show progressive restriction of lung volumes and impairment of
diffusing capacity. This form of silicosis is fatal, and death is typically at-
tributable to respiratory failure within several years of beginning exposure.

Radiology
The clinical presentation of silicosis (classic, accelerated, or acute) is
based on the time course necessary for the development of disease. The
type of chest radiographic lesions, however, does not seem to correlate
well with the duration of exposure. For example, conglomerate lesions
may be found in a worker exposed for only 5 years, whereas small roun-

34
ded opacities may be the only radiographic lesions in a worker who has
been exposed for more than 20 years.
The characteristic radiographic pattern of simple silicosis is the pre-
sence of rounded opacities that range in size from 1 to 10 mm. Using the
1980 convention described by the International Labour Organization’s
(ILO) International Classification of Radiographs of the Pneumoconioses,
these small rounded opacities are grouped into three diameter ranges
designated as p (up to 1.5 mm), q (exceeding 1.5 and up to 3 mm), and r
(exceeding 3 up to 10 mm). In the lower-profusion categories these opac-
ities are most often in the upper lung zones. In the more advanced stages
of the disease, the middle and lower lung zones typically are also involved.
In complicated or conglomerate silicosis, also described as progres-
sive massive fibrosis, smaller lesions coalesce into large ones and opaci-
ties exceeding 10 mm in diameter are recognized on the chest radiograph.
The 1980 ILO classification categorizes these as A (10 to 50 mm diame-
ter or several opacities greater than 10 mm but less than 50 mm aggregate
diameter), B (one or more opacities larger or more numerous than cate-
gory A but not exceeding the equivalent of the right upper zone), and
C (one or more large opacities whose combined area exceeds the equiva-
lent of the right upper zone). These large opacities tend to retract toward
the hilus, resulting in subpleural areas of air space enlargement. The clear
area between the lateral border of the opacity and the chest wall appears
as a bulla. Since coalescence of these nodules occurs in the upper zones,
the result is loss of upper zone volume, elevation of both hila, and the
development of basilar emphysematous changes. While cavitation of these
coalesced lesions may be explained by ischemia, tuberculosis or carcino-
ma with necrosis should also be considered in the differential diagnosis.
These distinctions are not always easy to make on a clinical basis.
Enlargement of hilar lymph nodes is common. In 5 to 10% of cases,
the hilar nodes calcify circumferentially, producing the so-called eggshell
pattern of calcification. This is not pathognomonic of silicosis, as it has
also been described in sarcoidosis, postirradiation Hodgkin’s disease, blas-
tomycosis, scleroderma, amyloidosis, and histoplasmosis. However, the
presence of eggshell hilar calcifications in the presence of typically dis-
tributed nodular parenchymal opacities reinforces the clinical impression
of silicosis when there is an appropriate exposure history.
Acute silicosis or silicoproteinosis presents radiographically with va-
rying degrees of air space filling. The radiographic differential diagnosis
includes pneumonias and other pulmonary infections, pulmonary edema,
alveolar hemorrhage, alveolar cell cancer, and idiopathic alveolar protei-
nosis. Several studies have examined the role of computed tomography
(CT) of the thorax in the diagnosis of silicosis.

35
 Pulmonary Function
It is difficult to make definite conclusions about the alterations in pul-
monary function in workers with silicosis, since considerable variability in
individual cases may be present, probably because of the multifactorial ef-
fects of concurrent cigarette smoking, the type of dusts involved in the ex-
posure (mixed versus pure), the dose of dust and duration of exposure, and
the presence of other pulmonary diseases such as tuberculosis.
In general, when the radiographs show only small rounded opacities
of low profusion, no significant impairment in ventilatory capacity is asso-
ciated. Abnormalities in spirometry can usually be explained by concur-
rent cigarette smoking or dust-induced bronchitis. Studies of different
groups of workers tend to support this generalization, especially when
care is taken to choose appropriate controls or to account for the effects
of coexisting factors such as those mentioned above. When these precau-
tions were taken, for example, no significant differences in forced vital
capacity (FVC) or forced expiratory volume in 1 sec (FEV 1) were de-
monstrated in South African gold miners who had radiographic evidence
of silicosis and those who did not. In a study of silicotic pottery workers
in Hong Kong, there was no statistically significant gradient in percen-
tage of predicted FEV1 among the radiographic categories of simple sili-
cosis in workers with and without symptoms of chronic bronchitis, al-
though FEV1 was lower in those with symptoms. FEV1 was significantly
lower as a percent predicted in those with conglomerate silicosis of B
and C types compared to those who had simple silicosis. These trends
were similar for those who had bronchitis and those who did not, though
values were significantly lower for the former group. In this study, as in
many others, significant impairment in total lung capacity, residual vo-
lume, and diffusion capacity tended to be associated with conglomerate
disease. A similar patterns of pulmonary function abnormality was also
shown in a study of silicotic sandblasters in Louisiana by Jones et al. Stu-
dies of lung mechanics in silicosis patients show abnormalities in lung
compliance, which tends to decrease as the severity of radiographic in-
volvement increases.
As a rule, rapid and progressive decline in pulmonary function accom-
panies acute silicosis. This is well illustrated in the case of a 34-year-old
surface coal mine driller, who presented with progressive dyspnea, cough,
weight loss, and bibasilar alveolar filling on the chest radiograph. His
initial FVC was 3.47 L (63% of predicted), and the single-breath transfer
factor was 6.32 ml/min/mm Hg (18% of predicted). After 10 months, the
36
FVC had further decreased to 1.77 L, and the patient was unable to per-
form the diffusing capacity test due to dyspnea. A radiographic picture of
progressive massive fibrosis had developed from the initial alveolar pat-
tern. This man died 26 months after his initial presentation.

Complications
Mycobacterial Infections
The association between silicosis and pulmonary tuberculosis is well
accepted. Epidemiologic studies suggest that the risk of pulmonary and
extrapulmonary tuberculosis is increased about threefold in workers who
have silicosis compared to those who do not. The incidence of tuberculo-
sis increases with the profusion of radiographic opacities. Only one study
revealed an increased incidence of pulmonary tuberculosis in foundry
workers who did not have radiographic evidence of silicosis but were em-
ployed in the industry longer than 25 years.
Mycobacterial infection should always be suspected when a silicosis
patient experiences worsening of respiratory symptoms or chest radiographs.
Yearly tuberculin tests are important in the follow-up of patients with sili-
cosis. A positive result on an intermediate purified protein derivative (PPD)
test or radiographic evidence of progression of the silicotic abnormalities
mandates a search for mycobacteria. If acid-fast smears are negative in the
presence of a positive tuberculin test, they recommend treatment with
300 mg of isoniazid daily for a year or a 4-month course of a mutlidrug
regimen. Poor compliance and the concern of isoniazid resistance has gene-
rated interest in shorter, multidrug chemoprophylaxis regimens, and recent
studies have highlighted the importance of directly observed therapy.
Smear or culture-positive silicotics should be treated with multiple
antituberculous drugs. Effective regimens generally contain isoniazid, ri-
fampin, and pyrazinamide. Older studies suggest that antituberculous
chemotherapy should be given for an extended period, ranging from more
than a year to a lifetime. Recent articles show successful outcomes and
acceptable relapse rates with shorter treatment regimens. One study sug-
gested that silicotics with tuberculosis do better when the usual multi-
drug regimen is given for 8 months. It is prudent, however, to guide ther-
apy by frequent clinical and radiographic examinations as well as smear
and culture responses.
Infections with atypical mycobacteria such as Mycobacterium kansa-
sii and Mycobacterium avium-intracellulare have also been reported. The
frequency at which these atypical mycobacterial infections are found is
probably related to the geographic distribution of the organisms.

37
 Immune-Mediated Complications
Associations between silicosis and progressive systemic sclerosis, scle-
roderma or rheumatoid arthritis are well described in the literature. Sero-
logic studies show a high prevalence of antinuclear antibodies, rheuma-
toid factor, and other markers of an activated humoral immune system
such as immune complexes and immunoglobulins. Whether and how these
factors, or the immune system in general, plays a direct role in the gene-
sis of silicotic lesions, and whether tissue injury related to silicosis pre-
disposes a person to autoimmune disease are matters of speculation.

Renal Complications
A variety of renal complications have been described in association
with silicosis. The clinical spectrum of silicon nephropathy includes glo-
merulonephritis, nephrotic syndrome, end-stage renal disease requiring
dialysis, and in one report a presentation mimicing Fabry’s disease. On
light microscopy, glomerular sclerosis, hypercellularity, crescents, cellu-
lar inflammatory infiltrates, and tubule damage have been seen. Electron
microscopic lesions include obliteration of foot processes, cytoplasmic
dense lysosomes, electron-dense deposits, and myelinlike bodies. Evidence
of immune system activation is frequently present in the glomeruli.

Cancer
Many animal and human epidemiologic studies have addressed the is-
sue of whether exposure to crystalline silica plays a role in the develop-
ment of pulmonary neoplasms. Animal studies have shown that rats giv-
en intrapleural silica develop malignant histiocytic lymphoma, and intra-
tracheal administration can result in respiratory neoplasms that resemble
human bronchogenic carcinoma. Older epidemiologic data reached con-
flicting conclusions regarding the association of silica exposure and lung
cancer. The discrepancies in conclusions from these studies were thought
to be related to sampling methods or to the fact that many of these studies
did not account for the effects of cigarette smoke or radon exposure in
underground mines.
The studies on refractory brick manufacturers in Genoa, Italy, and di-
atomaceous earth miners in California provide strong clues that exposure
to crystalline silica itself may be linked to excess deaths from respiratory
neoplasms.

38
 Treatment
The diagnosis of silicosis, especially if it is progressive, is always a
source of tremendous frustration for both clinician and patient, since there
is no proven effective therapy for this disease. Symptomatic airflow ob-
struction is treated with inhaled bronchodilators. Antibiotics are empiri-
cally given to patients with acute bronchitis. Oxygen is used to manage
hypoxemia and the associated pulmonary hypertension.
Numerous investigators have attempted to deal therapeutically with
the primary problem in silicosis, the presence of free crystalline silica in
the lung and the resulting inflammatory cascade, which is aggravated or
perpetuated by cells or the fibrogenic mediators they produce. In patients
with minimal disease, both lungs are lavaged sequentially in the same
session. Those with more severe disease have each lung lavaged in sepa-
rate sessions. Close auscultatory monitoring of the ventilated lung to pre-
vent and detect overflow from the lung being lavaged, as well as positive
pressure bag ventilation with 100% oxygen after infusion, are important
safety measures.
Corticosteroids and immunosuppressive agents have been used to treat
accelerated and acute silicosis. Although there is a suggestion that the
inflammatory process is at least lessened, whether this pharmacologic ap-
proach affects long-term outcome is not clear. If steroid therapy is insti-
tuted, tuberculosis prophylaxis with isoniazid is probably prudent until
cultures definitely show the absence of mycobacterial infection. In a
6-month trial of prednisolone for the treatment of chronic simple and com-
plicated silicosis in 34 patients in northern India, there were statistically
significant (although not clinically significant) improvements in lung vo-
lumes, diffusing capacity, and partial pressure of arterial oxygen (PaО2),
and a decrease in total cell count in BAL fluid.
Other therapies investigated in animal models and humans include in-
halation of aluminum, and inhalational or parenteral administration of a
polymer, polyvinyl pyridine N-oxide. Inhaled aluminum has not been
shown to be effective in human disease and in a sheep model of chronic
silicosis. While PVNO was shown to have some beneficial effects in some
experimental models, there is some concern that it could be carcinogenic.
More aggressive therapies have also been tried. A case of unilateral lung
transplantation in a 23-year-old man suffering from acute silicosis was
reported in 1972. The lung function and gas exchange improved and the
patient survived 10 months. With the current advances in transplantation
medicine, this option should therefore be considered seriously for indi-
viduals with far advanced silicosis.

39
 In Chinese traditional medicine hanfangji, an extract of the root of the
plant Stephania tetrandria, has been used to treat rheumatic diseases. The
principal active component of the extract is tetrandrine, a bisbenzyliso-
quinoline. Tetrandrine has been shown to inhibit and even reverse pul-
monary lesions in experimental silicosis. An open clinical trial showed
clinical and radiographic improvement in patients with pulmonary fibro-
sis from silica inhalation. While the exact mechanism of the antifibrotic
properties of tetrandrine is not established, it has in vitro antiphagocytic
and antioxidant properties and inhibits human neutrophil and monocyte
adherence. More recent work has demonstrated that tetrandrine is a po-
tent inhibitor of particle-stimulated oxygen consumption, superoxide re-
lease, and hydrogen peroxide production by rat alveolar macrophages. The
inhibition of these inflammatory mechanisms is strongly correlated with
tetrandrine’s binding affinity to alveolar macrophages.
Finally, the only reasonable way to deal with this man-made illness is
to prevent it. As a consequence of reduced dust standards and better in-
dustrial hygiene practices, silicosis afflicts far fewer people that it did
before.
Silicosis is preventable. The extent to which this can be realized de-
pends on education of employers and employees, strict enforcement of
industrial hygiene practices, and vigilance for circumstances where un-
acceptable exposures to respirable silica may happen. Further research
on the mechanism of lung injury in silicosis and its modulation by phar-
macologic agents will contribute to our therapeutic armamentarium for
this disease.

ASBESTOS-RELATED DISEASE
The term asbestos refers to a group of six naturally occurring, fibrous
hydrated silicates that share a common property of resistance to heat and
fire. Chrysotile, or white asbestos, is characterized by serpentine fibrils
and constitutes 90% of the asbestos that is employed in North America.
Amosite, crocidolite, anthophyllite, tremolite, and actinolite are employed
less often.
The health consequences of asbestos exposure are of great concern to
public health officials. Between 1940 and 1979, estimated 27,500,000 in-
dividuals were occupationally exposed to this substance in the United
States alone. This pattern of exposure and potential disease will continue
through this century as the asbestos in place deteriorates and requires re-
pair or removal. Exposure occurred most commonly in the occupations
of asbestos mining and manufacturing; shipbuilding, repair, and refitting;
40
general construction; automobile maintenance; and railroad engine repair.
In addition, an increased incidence of asbestos-related disease is found
among family members of asbestos workers and among workers employed
in the vicinity of asbestos workers (“bystander exposure”). Of note is that
a significant risk for disease has not been reported among populations
environmentally exposed to asbestos. It is unclear as to whether there is a
safe level (i.e., a threshold) for asbestos exposure below which there is
no increased risk for cancer. Extrapolation data suggest no minimal lev-
el; however, clinical studies indicate there may be a relatively safe level.
Low-dose, long-term exposures are showing an increased incidence in
asbestos-induced lung disease.
Asbestosis refers to parenchymal fibrosis and occurs in up to 78% of
heavily exposed insulation workers and up to 30% in moderate exposures.
Pathologically, asbestosis is characterized by the presence of interstitial
fibrosis and an increased number of asbestos ferruginous “bodies” and
uncoated asbestos fibers. The ferruginous body is an asbestos fiber coat-
ed with proteinaceous iron staining material; it is visible on light micros-
copy. Using lung digestion techniques, uncoated fibers may be identified
and counted; levels should be compared to those found in lungs of unex-
posed individuals to assess the significance of possible exposure in an
individual. The range is quite wide and does not appear to correlate well
with the type or degree of disease. The difference between environmen-
tal and occupational exposures, however, is clear.
Asbestosis usually begins subpleurally in the lung bases. If it progres-
ses, it may involve both lungs diffusely as a fine fibrosis. In the final stages,
the lungs may acquire a cystic honeycomb appearance (i.e., honeycomb
lung) and can be indistinguishable radiographically from other forms of
interstitial fibrosis. Recent experimental data suggest the fibrogenic re-
sponse to inhaled asbestos fibers begins within hours of exposure. It is
followed by macrophage-mediated immunologic, inflammatory, mechan-
ical, and chemical injury at the alveolar cellular level.
The clinical presentation of asbestosis is usually heralded by dyspnea.
End-inspiratory rales and clubbing often are present. A clinical diagnosis
of asbestosis requires an appropriate exposure history and a consistent
latency period (i.e., the number of years from the initial exposure). The
average minimal latency period for all forms of asbestos disease is ap-
proximately 20 years, but the latency may range from as low as 10–
15 years, and there is no upper limit. Chest X-ray analysis using the Inter-
national Labor Office system is useful to support a diagnosis; however,
the lack of distinct findings does not exclude a diagnosis. Several clinico-
pathologic studies have demonstrated significant asbestosis on lung biopsy
41
in 10–20% of patients with normal chest X-rays. High-resolution thin-
section computed tomography scans (HRCT) are valuable in providing
objective evidence of interstitial disease in the presence of normal, equiv-
ocal, or mild parenchymal abnormalities on a chest X-ray. The path-cor-
relate studies have clearly demonstrated a relationship between disease
on HRCT and lung tissue. There has been demonstrated correlation bet-
ween disease activity and gallium scans of the lung.
The laboratory is often helpful, although it occasionally demonstrates
enigmatic findings. Pulmonary function tests (PFTs) may disclose dimin-
ished lung volumes (i.e., forced vital capacity and total lung capacity)
and a decrease in carbon monoxide diffusing capacity. Such abnormali-
ties may be confounded by the countervailing effect of severe airways
disease, a condition that tends to raise total lung capacity and is found
among a high percentage of asbestos workers due to their heavy tobacco
exposure. The earliest PFT abnormality is a decline in compliance (i.e.,
increased stiffness). Exercise testing is useful in identifying clinically sig-
nificant pulmonary disease among dyspneic individuals with relatively
normal pulmonary function. The level of dyspnea often does not corre-
late with a single PFT value. The degree of impairment and disabili-
ty should be noted according to subjective and objective criteria estab-
lished by the American Thoracic Society and the American Medical As-
sociation.
Pleural disease or “pleural fibrosis” is the most common form of as-
bestos-related pulmonary injury. The incidence correlates primarily with
the disease latency. Pathologically, there are localized areas of pleural scar-
ring (the pleural plaque). Calcification may occur and appears to be pri-
marily related to the latency period. Calcification of diaphragmatic pleu-
ral plaques is a sine qua non of asbestos-related pleural disease. Pleural
plaques are usually bilateral and involve the middle and lower third of
the thoracic cage. Pleural plaques are generally found on the parietal pleu-
ral surface. Recent data from CT studies indicate that fissural and medi-
astinal visceral plaques also may be present. The usual pleural plaque does
not lead to an abnormal PFT; however, studies of groups of workers ex-
posed to asbestos have shown a significant decrement in forced vital ca-
pacity and forced expiratory volume in 1 sec with asbestos exposure, as-
bestos pleural plaques, and asbestosis and asbestos pleural disease. Ex-
tensive pleural plaques may lead to restrictive lung disease, particularly
if there is underlying parenchymal disease. Diffuse pleural thickening is
a distinct process that leads to thickening or fibrosis of the visceral and
parietal pleura. If extensive and severe enough, it results in lung entrap-
ment and may lead to severe impairment and ventilatory failure. The most
42
likely etiology of “benign” diffuse pleural thickening is an initial asbes-
tos-related pleural effusion. Subpleural fibrosis may also be present.
Rounded atelectasis is characterized by localized pleural thickening
and lung entrapment. Prior to advances in CT scanning, pleural biopsy
was necessary to distinguish this process from mesothelioma.
A variety of cancers are related to asbestos exposure. Lung cancer and
mesothelioma are discussed in other chapters. In addition, there is an in-
creased incidence of gastrointestinal cancers, particularly gastric, colon,
pharyngeal, and renal cancers, and lymphomas. There is a dramatic syn-
ergistic relationship between asbestos and the risk for cancers of the lung
excluding mesothelioma. Mesothelioma is reported with even minimal
asbestos exposure. There is no specific therapy for asbestos-related pleu-
ral or pulmonary disease. Common sense dictates the avoidance of any
further exposure once injury is recognized. Every effort should be made
to eliminate smoking. Other measures include early treatment of lung in-
fections, influenza and pneumonia vaccinations, careful surveillance, and
treatment of complications of respiratory failure (e.g., hypoxemia, con-
gestive heart failure).
Annual screening evaluations that include chest X-ray and PFTs are
important for selected patients. In view of the marked increased risk for
cancer, each patient should be fully evaluated for any change in cough
pattern, hemoptysis, or suggestive radiographic changes.

COAL WORKERS’ PNEUMOCONIOSIS

Coal workers’ pneumoconiosis (CWP), formerly called anthracosis or
anthracosilicosis, exists in two forms: simple and complicated, the latter
being known as progressive massive fibrosis (PMF). Simple CWP is di-
agnosed by a history of exposure to coal dust and chest radiographs show-
ing an increased profusion of small, round parenchymal densities (cate-
gories 0, 1, 2, and 3 as rated by the International Labor Office system for
grading radiographs for pneumoconiosis). The diagnosis of PMF requires
densities larger than 1 cm in diameter; some authorities require lesions
larger than 2 cm.
The basic pathologic lesion in simple CWP is the coal macule. This is
a collection of coal dust-laden macrophages, reticulin, and collagen lo-
cated within the walls of respiratory bronchioles and adjacent alveoli.
Macules range in size from 1–5 mm in diameter and are located predomi-
nantly in the upper lobes. As the number of macrophages grows, fibrosis
increases, creating micronodules (< 7 mm) and macronodules (7–20 mm).
A zone of focal emphysema is usually seen around macules and nodules,
43
possibly caused by mechanical traction on adjacent parenchyma or di-
gestion of alveolar walls by proteolytic enzymes released from macro-
phages. There is a tendency for nodules to cluster and eventually to coa-
lesce to produce PMF lesions.
The pathogenesis of CWP is unclear. Silica in coal dust was thought
to be the cause; it is now recognized that CWP is a pathologic entity dis-
tinct from silicosis, though the two conditions can coexist in the same
individual. Coal is composed predominantly of elemental carbon, toge-
ther with varying amounts of minerals, metals, and organic compounds.
Electrically charged surface radicals on coal dust damage biologic mem-
branes; however, coal dust is much less cytotoxic than silica. The pulmo-
nary macrophage plays a central role in the pathogenesis of CWP by re-
leasing inflammatory factors, recruiting polymorphonuclear leukocytes
into the lung, and stimulating fibroblast production of collagen.
A number of immunologic abnormalities have been found in miners
with CWP. Their etiologic role, if any, is not known, and their preva-
lence has varied in different studies. Miners with CWP have elevated
serum levels of IgA, IgG, C3, antinuclear antibodies, rheumatoid fac-
tor, and alpha1-proteinase inhibitor; similar findings are seen in other
forms of pneumoconiosis. There is no clear correlation between these
serologic factors and the risk or severity of CWP except for rheumatoid
pneumoconiosis (Caplan’s syndrome), which describes coal miners with
rheumatoid arthritis. The characteristic radiographic features of rheu-
matoid pneumoconiosis are rapidly enlarging, evenly distributed nod-
ules ranging in size from 0.3–5.0 cm in diameter, occurring in lungs
that otherwise show little evidence of pneumoconiosis. Microscopical-
ly, the active lesions are similar to subcutaneous rheumatoid nodules;
vasculitis is a common feature. Coal mining does not predispose to rheu-
matoid arthritis.
The risk of development and progression of CWP increases with greater
cumulative dust exposure.
Higher rank (hardness) coals are associated with increased risk of sim-
ple CWP and PMF. Anthracite is the highest rank, followed by bitumi-
nous coal and lignite. Experimentally, high-rank coals are cleared more
slowly from the lungs and are more cytotoxic. The attack rate for PMF
rises with increasing total lung dust; PMF usually occurs in the setting of
advanced simple CWP (categories 2 and 3). Increased silica content of
inhaled dust also increases the incidence of PMF. Historically, tuberculo-
sis has been considered as a risk factor for PMF; its role has diminished
in recent decades, though this organism should always be sought in a pa-
tient with expanding upper lobe lesions. Cavitation of PMF lesions is usu-
44
ally due to tissue necrosis, not tuberculosis. Coal miners do not have a
greater incidence of tuberculosis compared with the general population.
The issue of impairment and disability due to CWP has been contro-
versial. Most authorities agree that clinically significant pulmonary im-
pairment does not occur in nonsmoking patients with simple CWP, though
small reductions in spirometric values are common. Conversely, PMF is
associated with significant morbidity and premature death. Cough and
sputum production, often described as industrial bronchitis, usually have
little effect on lung function in the absence of smoking. Cigarette smo-
king, while responsible for the majority of pulmonary impairment among
coal miners, does not increase the incidence of simple CWP or the risk of
progression to PMF. The Federal Coal Mine Health and Safety Act and
Black Lung Benefits Program established guidelines for rating disability
based on reduction of the forced expiratory volume in 1 sec (FEV1) and
maximal voluntary ventilation (MVV); decrements in spirometric values
are based on a miner’s height, but not his age, and do not consider the
effects of smoking. Should a miner have either a normal ventilatory ca-
pacity or a slight decrement, he can still qualify for benefits if the PaO2
is reduced below a certain level with an alveolar-arterial oxygen gradient
greater than 45 mm Hg breathing room air at rest. Exercise testing is not
included in the rating system.
Today, the life expectancy of a coal miner is approximately that of the
general population. Excess deaths are seen for nonmalignant respiratory
disease, accidents, and stomach cancer. Approximately 4% of coal miner
deaths are directly attributable to pneumoconiosis, usually due to PMF;
most studies have not shown an excess mortality for simple CWP. These
excess deaths are counterbalanced by decreased mortalities from lung can-
cer and ischemic heart disease and by the “healthy worker effect.” Cor
pulmonale and right ventricular hypertrophy do not occur in the absence
of cigarette smoking or PMF. There is no specific treatment for CWP ex-
cept limiting dust exposure.

TESTS
1. A patient Y., 48 years old, has been working at the iron ore concen-
tration factory during 20 years. At the medical examination he presented
the following complaints: extended pains in the thorax in the manner of
pricking, dyspnea during insignificant physical load, cough (mainly on morn-
ings) with discharge of a small quantity of sputum. These complaints have
been observed during 5 months. Objective: a band-box sound in the lower
parts of the lungs, vague dry rale, at the interscapular space — a harsh brea-
45
thing. Excursion of the lower pulmonary margin on the middle axillar line
— 3 cm. X-ray investigation: in the lower parts of the lungs on the right
and on the left the pulmonary tissue is emphysematously changed, the
lung pattern is intensificated, deformed, roots are extended, compacted
and deformed. In the lower parts on the right and on the left there is a
greater amount of small (< 0.5 cm) nodular shadows.
Preliminary diagnosis:
A. Fibrinous pleurisy.
B. Silicosis, the 2nd stage.
C. Silicosiderosis, the 2nd stage.
D. Idiopathic fibrosing alveolitis.
E. Chronic bronchitis.
2. In the course of routine medical examination, which was conducted
among mining workers, it was chosen one of them, complained of dysp-
nea under the small physical load, pain in the thorax, dry cough. He has
worked for 14 years. Objective: a band-box sound at percussion on the lower
side areas of the lungs, reduction of the mobility of lower margins of the
lungs. Auscultation: a harsh breathing, pleura friction noise. Factors of func-
tions of the external respiration: reduction of vital capacity of the lungs
and minute volume of the lungs, increase of residual volume of the lungs.
Data of the roentgenologic examination: reinforcement and deformation of
a lung pattern, node shades by the size 3–5 mm. The roots of the lungs are
extended, compacted, of “cut” type. The pleura is slaked and deformed.
Probable diagnosis:
A. Silicosis, the 1st stage.
B. Silicosis, the 2nd stage.
C. Silicosis, the 3rd stage.
D. Dusty bronchitis.
E. Silicatosis.
3. A man, 40 years old, during 10 years has been working in the buil-
ding material production and has a contact with oxides of silicon.
What disease is it necessary to exclude during the periodic medical
examination?
A. Sarcoidosis of the lungs.
B. Syndrome of Hamman — Rich.
C. Tuberculosis.
D. Microlithiasis.
E. Pulmanory cancer.
4. A man, 42 years old, applied to the therapeutical department with
complaints of pricking pains in scapulas’ area, compression in the chest,
dyspnea at the physical load, sometimes cough with separation of a small
amount of the sputum. From anamnesis — during 10 years he has worked

46
in coal mining, has been ill for about 6 years; when these complaints ap-
peared for the first time, there wasn’t any therapy. Objective: at the per-
cussion — a band-box sound in the lower parts. Auscultation: a harsh
breathing. No heart pathology was revealed.
Possible diagnosis:
A. Pulmonary tuberculosis.
B. Silicosis.
C. Silicatosis.
D. Bronchiectatic disease.
E. Chronic bronchitis.
5. A man, 43 years old, has worked in coal industry over 10 years,
complains of the loss of the working capacity, dyspnea, strong cough with
a hard spitting sputum. Cough usually appears at the sharp changing of
the body position, under the physical load, breathing in a cool air and is
accompanied by asphyxia. Objective: auscultation — pleural dry and moist
rales; barrel chest, limited respiratory excursion of the lungs; at percus-
sion a band-box sound is defined. X-ray: an increase of transparency of
the lung pattern, plaining of the cupula of diaphragm, expansion of inter-
costal spaces.
What is the most probable diagnosis?
A. Silicosis.
B. Microlithiasis.
C. Tuberculosis.
D. Dusty bronchitis.
E. Silicatosis.
6. A patient, 46 years old, is applied with complaints of dyspnea under
insignificant physical load and sometimes at rest, appearance of cough, first
dry, afterwards with the plantiful sputum discharge, pains in the thorax,
which are vastly intensified during cough. During the examination: asthen-
ic habitus, dirty grey colour of the skin, with cyanotic colour of the face
and lips. There are distant rales in the lungs, the auxiliary musculature takes
part in the act of breathing, intercostal spaces are extended. From anamne-
sis: he has worked for 17 years at the Odessa Cement Plant as a packed-
man. Beginning with the age of 28 the patient has been on the dispensary
account in connection with the bronchial asthma, infectious-allergic form.
Establish diagnosis:
A. Bronchial asthma, an infectious-allergic form.
B. Bronchial asthma, an atopic form.
C. Chronic obstructive bronchitis.
D. Pneumoconiosis caused by cement dust, the 1st degree.
E. Pneumoconiosis coused by cement dust, the 2nd degree.

47
 Chapter 3
AGRICULTURAL DUST-INDUCED
LUNG DISEASE

Although not widely appreciated, the agricultural worker and possi-

bly those living in rural environments are at increased risk of developing
lung disease. The risk associated with progressive lung disease appears
to be more than threefold greater among those who are more heavily ex-
posed to dusts generated in the agricultural environment. Interestingly,
cigarette smoking does not appear to account for this excess risk, since
agricultural workers consistently have lower rates of cigarette smoking
than other occupations. These general epidemiologic observations are sup-
ported by an increasing number of exposure-specific studies in agricul-
tural workers, which are reviewed in this chapter. Lung disease caused
by agricultural aerosols affects a large population, with more than five
million agricultural workers in the United States and over 80% of the work
force in developing countries involved in agriculture. Unlike other occu-
pations, the agricultural worker usually lives in the same environment as
he/she works in, with exposures occurring throughout the week, and chil-
dren are commonly involved in agricultural work.
An agricultural worker and those living in a rural environment encoun-
ter a variety of inhaled organic dusts suspended in the atmosphere, in-
cluding molds and pollens in the air, dusts generated in silos and barns,
aeroalergens, silica from the soil, and general exposure to animal dan-
druf, grain dust, feed additives, and mite dust. While agricultural dusts
generally have a large fraction (approximately 30% to 40%) of particles
in the respirable range, these dusts differ tremendously in terms of their
individual constituents. Dusts generated in the production of animals are
obviously very different than dusts generated in the production and mar-
keting of grain products. In fact, within the animal confinement setting,
workers may be exposed to grain dust, gases (ammonia, hydrogen sulfide,
and carbon monoxide) generated from the manure pit, microorganisms
contaminating the manure, aerosolized fecal material, and animal proteins.

48
In all cases, these organic dusts are characterized by a complex mixture
of vegetable particles and fragments, microorganisms and their toxic prod-
ucts, insects and insect fragments, feed additives including fish meal and
antibiotics, avian and rodent proteins, pesticides, and adsorbed gases.
While the vegetable dust and exposures resulting from contamination with
microorganisms appear to be the primary respiratory pathogen, specific
methods involved in the cultivation and storage of these products influence
the type and degree of exposure. For example, irritant gases such as am-
monia and oxides of nitrogen are generated in storage silos and may con-
tribute to the respiratory symptoms experienced by these workers. Thus,
the agricultural aerosol is complex and contains a variable mix of agents
that may contribute to the development of lung disease.
This chapter discusses the clinical and occupational features of some of
the most common forms of lung disease associated with exposure to agricul-
tural dusts — asthma, chronic airway disease, and interstitial lung disease.

AGRICULTURAL ASTHMA
Asthma may either be caused or exacerbated by a specific exposure to
agents in the agricultural environment. In both cases, agricultural asthma is
characterized by variable and intermittent airflow obstruction initiated by
specific exposures in the agricultural environment. The objective signs of
airflow obstruction are often associated with symptoms of chest tightness,
wheezing, coughing, and dyspnea. Since immediate and delayed (up to
12 h) airway responses may occur following these exposures, the specific
agent causing the onset of airflow obstruction may not always be obvious.

Exposures to Plant-Derived Material

The largest and perhaps the most clinically relevant category of agents
known to cause asthma in the agricultural setting are the plant-derived
materials. Grain dust, cotton dust, and dusts generated from teas, tobac-
co, mushroom, chicory, and vegetable gums all represent a complex mix-
ture of vegetable particles and fragments, microorganisms and their prod-
ucts, insects and insect fragments, feed additives including fish meal and
antibiotics, avian and rodent proteins, and pesticides. The specific agents
most likely to cause or exacerbate asthma from these plant products are
the high molecular proteins that can act as allergens. However, other agents
in these dusts, such as tannins, mycotoxins, endotoxin, pollens, and in-
sect parts, may also contribute to the development of asthma in these in-
dividuals.

49
 Exposures to Animal-Derived Material
Animal-derived proteins can cause asthma in agricultural workers. This
form of asthma is much more common in atopic individuals who are ca-
pable of developing an immunoglobulin E (IgE) response to specific aero-
solized animal proteins. Animal handlers, especially in sale barns and con-
finement units, may be intermittently exposed to high concentrations of
animal-derived proteins, and are at particularly high risk of developing
asthma. Arthropod-derived material from grain mites, honeybees, barn
mites, and other arthropoda have been clearly shown to cause or exacer-
bate asthma in exposed populations. Since these are IgE-mediated respons-
es, a period of sensitization is needed and onset of wheezing is usually
immediate, often accompanied by rhinitis and other allergic symptoms.

Irritants
Low concentrations of irritants may result in airflow obstruction in
workers with underlying asthma but do not usually cause asthma. Thus,
chemicals common to the agricultural environment, including solvents,
ammonia vapors, welding fumes, pesticides, herbicides, and fertilizers,
may contribute to the exacerbation of airflow obstruction in individuals
with preexisting asthma. An extreme form of irritant-induced asthma may
occur following inhalation of high concentrations of fumes or vapors in
the agricultural setting. In particular, noxious vapors, such as ammonia,
may acutely cause extensive airway injury and result in recurrent episodes
of airflow obstruction. Characteristically, irritant-induced asthma occurs
only after an overwhelming exposure to irritating gases. The worker should
be able to report a specific event where he/she was exposed to a high con-
centration of fumes that resulted in an acute respiratory illness. These
exposures can acutely cause alveolar injury and result in pneumonia or
adult respiratory distress syndrome. Subsequent to the acute illness, the
worker may develop recurrent episodes of airflow obstruction that are
caused by a variety of irritants.

Pharmacologic Agents
Two agents that are thought to cause asthma through pharmacologic
mechanisms are organophosphate insecticides and vegetable dusts con-
taining histamine. Organophosphates inhibit acetylcholinesterase and re-
sult in overstimulation of cholinergic receptors. This is thought to induce
bronchospasm by increasing the concentration of guanosine 3′,5′-cyclic
monophosphate (cGMP). Although many factors may account for the de-

50
velopment of asthma in individuals exposed to cotton dust and other vege-
table dusts contain histamine, which may promote an allergic-like inflam-
matory process in the airway. The inflammatory response to inhaled his-
tamine may, in part, be responsible for the development of asthma fol-
lowing inhalation of vegetable dusts containing histamine.

Occurrence
The prevalence of asthma caused by exposure to agricultural dusts and
fumes is not known. Clearly, the prevalence of agricultural asthma de-
pends on the exposure and the setting. However, occupational asthma is
estimated to account for between 5% and 15% of the patients who are
diagnosed with asthma. Among farmers, 15% were found to have symp-
toms consistent with either asthma or allergic rhinitis. Interestingly, the
prevalence of asthma among grain workers is reported to be similar to a
comparative population of unexposed workers. This apparent disparity
may be explained by the factors that select workers into and out of the
grain industry. Despite these inconsistencies, a recent review indicates
that most studies in grain workers have shown approximately a twofold
excess risk of wheezing among grain workers when compared to un-
exposed workers. The prevalence of chronic wheezing apart from a cold
(37%) and in association with asthma exacerbations (11%) appears to be
higher in hog-confinement workers who are exposed to both organic dusts
and irritating fumes. Although data are sparse regarding the prevalence
of agricultural asthma, absolutely no data are available concerning the
incidence of asthma among agricultural workers and their family mem-
bers who are often exposed to similar bioaerosols. Importantly, the prev-
alence of asthma among agricultural workers is dose related and appears
to be influenced by host factors including preexisting asthma, airway hy-
perreactivity, and atopy. In addition to these factors, differences in spe-
cific products or processing may account for seasonal and geographic dif-
ferences in the prevalence of asthma among agricultural workers.

Pathogenesis
The pathogenesis of asthma induced or exacerbated by exposures in
the agricultural setting is highly variable and entirely dependent on the
specific nature and intensity of the exposure. Airway narrowing caused
by inflammation, edema, or hyperreactivity results in acute and reversible
decreases in airflow. Allergic and nonallergic mechanisms of inflammation
directly injure the airway epithelia. Recurrent episodes of inflammation
51
may result in chronic remodeling of the conducting airways and could be
responsible for the development of progressive airflow obstruction.
Classical allergic mechanisms of airway inflammation involving mast
cells, IgE, histamine, eosinophils, and lymphocytes may be responsible
for the development of asthma following exposure to animal-derived pro-
teins. In-patients with an IgE-mediated response, the symptoms and signs
of asthma occur in close temporal proximity to the exposure. Patients can
usually identify the specific agent responsible for their symptom, and these
individuals have an atopic history. IgE-antigen interactions result in mast
cell degranulation with the release of histamine. Importantly, histamine
can stimulate bronchial obstruction by enhancing vascular permeability,
increasing smooth muscle contraction and mucus secretion, and upregu-
lating the production of prostaglandins.
Noxious gases and irritants may directly injure the airway epithelia,
resulting in edema, inflammation, and cell death. In fact, the airway epi-
thelia may prove to be an important mediator of the inflammatory response
by producing and releasing chemotactic factors such as interleukin-8.
Sloughing of the airway epithelia and thickening of the subepithelial re-
gion is common in asthma and has been reported in asthma associated
with agricultural exposures. Thus, the airway epithelia may actually con-
tribute to the edema and inflammation following inhalation of particular-
ly irritating stimuli.
Direct pharmacologic effects of agents such as organophosphates and
vegetable dusts containing histamine may cause asthma by modulating
endogenous pathways associated with bronchial tone or airway inflam-
mation. For instance, cotton dust containing sufficient concentrations of
histamine, may have effects similar to endogenously produced histamine
and may substantially influence airway inflammation. Similarly, organo-
phosphate insecticides block acetylcholinesterase and can cause airflow
obstruction by increasing bronchial tone and decreasing the caliber of the
airways.

Clinical Features
The diagnosis of agricultural asthma is dependent on the demonstra-
tion of reversible airflow obstruction that occurs in conjunction with in-
halation of specific agents that have been reported to cause or exacerbate
asthma. Therefore, the physician should initially focus on the diagnosis
of asthma and secondarily determine if there is an occupational etiology.
Typical symptoms of asthma include recurrent episodes of a nonproductive
cough, chest tightness, wheezing, and dyspnea. These respiratory symp-
52
toms may occur immediately after specific exposures or may develop se-
veral hours after the toxic exposure. Often these symptoms worsen du-
ring the workweek and improve on weekends and vacations.
The diagnosis of asthma is based on the demonstration of reversible
airflow obstruction. Standard spirometry, reversible airflow obstruction
after bronchodilators, and inducible airflow obstruction with nonspecific
airway challenges are considered acceptable physiologic assessments of
reversible airflow obstruction. Demonstration of a forced expiratory vo-
lume in 1 sec (FEV 1) to forced vital capacity (FVC) ratio of less than
75% is considered diagnostic of airflow obstruction. A decrease in the
FEV1/FVC ratio is usually associated with a low FEV1 (less than 80%
predicted or in the bottom tail of the 90% confidence interval) or a low
forced expiratory flow after 25% to 75% of vital capacity has been ex-
pelled (FEF25-75) (less than 60% predicted). Variability in airflow ob-
struction is usually demonstrated by sequential spirometry but may be
documented by improvement in airflow with bronchodilators (at least a
12% improvement in FEV 1 is considered significant) or enhanced bron-
chodilator responsiveness following inhalation of either histamine or meth-
acholine. In many circumstances, spirometric measures of lung function
are normal. The demonstration of nonspecific bronchial reactivity is an
acceptable, objective measure of reversible airflow obstruction, which is
useful in supporting the diagnosis of asthma.
The diagnosis of agricultural asthma requires the demonstration of a
clear temporal relationship to specific exposures in the agricultural set-
ting that are known to cause asthma. The history is often helpful in iden-
tifying an occupational etiology and should incorporate the following
items:
— Presence of asthma-causing agents in the workplace
— New-onset asthma or worsening of previous asthma
— Exposure to an overwhelming concentration of ammonia or oxides
of nitrogen
— Worsening of symptoms during times of more intense exposure
— Improvement of symptoms when away from work or seasonally
Agricultural workers usually work and live in the same environment,
and some may work seven days a week. Thus, the temporal relationship
between exposures and symptoms may be difficult to determine. Physio-
logic testing, either by spirometry, peak flow measurements, or periodic
nonspecific bronchoprovocative challenges, can and should be used to
critically evaluate the temporal relationship between occupational expo-
sures and the development of airflow obstruction. For instance, demon-
stration of consistent decreases in FEV1 of 15% when exposed to a spe-
53
cific agent in the agricultural setting not only helps establish the diagno-
sis of agricultural asthma, but may assist in identifying the offending agent.
Although peak flow measures are dependent on patient cooperation
and are less reliable than traditional spirometric measures of airflow, peak
flow measurements are the most convenient and often the only feasible
approach to investigating work-induced asthma. Specific airway challenges
are a definitive method of making the diagnosis of occupational asthma,
however, these inhalation challenges are not entirely accurate, and very
few centers are equipped to perform these exposure-response studies in a
way that minimizes risk. On-site spirometric measures of airflow is the
preferable method to establish a temporal relationship between specific
exposures in the agricultural setting and the development of asthma.
Several immunologic tests have been proposed to evaluate patients with
suspected or proven occupational asthma; however, their clinical utility
is limited. Serologic or immunologic testing can assist in determining ato-
pic status with respect to environmental allergens. Reactions to specific
allergens are limited to the relatively few that have been completely puri-
fied such as extracts of flour and grain dusts, animal products, and cer-
tain chemicals. Serum IgG or IgE antibodies may be measured by radio-
immunoassay or enzyme-linked immunosorbent assay (ELISA) methods.
Unfortunately, these tests lack the sensitivity and specificity required for
making a definitive diagnosis, but when used in conjunction with other
testing methods and a careful patient history, these tests may help docu-
ment a specific etiology. In the most limited context, immunologic tests
may be helpful in farther documenting exposure and identifying the atop-
ic status of the patient.
Among patients with occupational asthma, the majority continue to
have asthma despite removal from the exposure. Remissions appear to be
related to the duration and intensity of the disease, with earlier and less
severe forms of asthma more likely to improve. Spontaneous recovery
has not been reported among workers who remain exposed to the agent
causing asthma. Thus, among agricultural workers, those with work-re-
lated asthma should be encouraged to modify their exposures by either
changing jobs or reducing the concentration of inhaled dust and fumes.
Although most agricultural workers will not change their occupation, sub-
stantial progress can be made by encouraging the use of a two-strap dust
mask or, in some cases, using an airstream respirator. In fact, one study
indicates that symptoms substantially improve by reducing the ambient
concentration of dust through the use of respirators.
The treatment of agricultural asthma is similar to other forms of asth-
ma and depends on the severity and frequency of symptoms. Antiinflam-
54
matory medications (preferably inhaled steroids) should be the mainstay
of treatment, and bronchodilators should be used as needed.
Importantly, the use of inhaled steroids should be continued for at least
6 months after the patient has been free of any respiratory symptoms. Im-
munologic testing should not be used to definitively diagnose agricultur-
al asthma.

CHRONIC AIRWAY DISEASE

Agricultural workers are at excess risk of developing chronic bronchi-
tis and chronic obstructive lung disease. Among agricultural workers, ac-
celerated declines in air-flow are significantly related to the concentra-
tion of dust and endotoxin in the bioaerosol, and the degree of airflow
obstruction across the work shift or after challenge with nonspecific in-
halants. Moreover, agricultural workers have a higher mortality from
chronic pulmonary diseases than workers from other industrial sectors.

Occurrence
Chronic exposure to agricultural dusts can cause irreversible and pro-
gressive airway disease. Epidemiologic studies performed in North Ame-
rica, the United Kingdom, Egypt, and South Africa all demonstrate that
workers chronically exposed to agricultural dust are at increased risk of
developing chronic cough, phlegm production, wheeze, and dyspnea, ir-
respective of smoking habits. Moreover, long-term follow-up studies have
shown that grain workers, as well as other agricultural workers, have ac-
celerated decline in airflow that is directly related to the concentration of
dust or duration of exposure. Although short-term experimental or occu-
pational exposure to grain dust results in reversible airway symptoms and
airflow obstruction, long-term occupational exposure to either grain dust
or cotton dust causes irreversible and progressive airway disease.
Epidemiologic studies have shown that the acute airway response to
grain dust and other organic dusts is predictive of the chronic airway re-
sponse to these agents. Several epidemiologic studies have shown that
the acute work-shift-related declines in airflow are independently associ-
ated with accelerated longitudinal declines in lung function among grain
handlers, cotton workers, and agricultural workers. Although the work-
shift response to organic dust may simply identify a cohort of individuals
with a high intrinsic risk of airway disease, it is equally possible that the
acute physiologic and biologic responses to inhaled organic dusts place
workers at higher risk of developing progressive airway disease. In a hu-
55
man autopsy report of three grain workers, the significant pathologic fin-
dings included peri-bronchiolar fibrosis without bronchiectasis, patchy
emphysema, and interstitial fibrosis; however, the smoking histories for
these individuals were not mentioned in the report. Among cotton wor-
kers, chronic pathologic findings attributable to cotton dust include bron-
chitis and bronchiolitis with mucus gland hyperplasia and goblet cell meta-
plasia. In aggregate, these findings indicate that agricultural workers chron-
ically exposed to organic dust are at risk for developing chronic airway
disease, involving progressive airflow obstruction, persistent airway and
alveolar inflammation, and remodeling of the airway architecture.

Pathogenesis
Animal inhalation studies demonstrate that inhalation of grain dust and
other organic dusts cause acute and chronic inflammatory lesions prima-
rily focusing on the airway and involving macrophages, neutrophils, and
specific proinflammatory cytokines. Inhalation studies in mice have shown
that following a single exposure to grain dust, neutrophils are rapidly re-
cruited to the lung and proinflammatory cytokines [IL-1, 2, 3, tumor necro-
sis factor-α (TNF-α), and IL-6], and chemokines [macrophage inflam-
matory (MIP)-2] are produced and released for up to 48 h. Swiss mice
exposed to grain dust for 16 weeks demonstrated increased neutrophils in
the walls and lumin of small bronchi and clusters of neutrophils and mac-
rophages in the ascini. Similarly, in rats exposed to grain dust for 8 weeks,
histologic changes included subepithelial neutrophils in the bronchi and
bronchioli, and dilated respiratory and alveolar ducts. In guinea pigs,
chronic exposure to cotton dust for 1 year resulted in airflow obstruction,
anatomic changes of the small airways consisting of hyperplasia of bron-
chiolar epithelium and type II cells, and thickening of the alveolar ducts
and alveolar septa. A recent study in hamsters showed that 6-week intra-
tracheal dosing with either cotton dust or endotoxin can cause mild cent-
rilobular emphysema. However, the pathogenic mechanisms that result
in chronic inflammation, irreversible airflow obstruction, and permanent
airway remodeling are unknown.

Clinical Features
The diagnosis of chronic obstructive lung disease (COPD) is based on
the physiologic assessment of air-flow. Patients with COPD have a re-
duced FEV 1 and a reduced FEV 1/FVC ratio. Although most of the pa-
tients with COPD may improve with bronchodilators, improvement in
FEV1 is usually less than 15% and the spirometric measures of airflow,
56
by definition, do not normalize. In addition, lung volumes may reveal air
trapping and the diffusing capacity may identify those patients with em-
physema.
The key, unanswered question is whether effective control of the acute
inflammatory response to inhaled agricultural dusts will prevent the de-
velopment of chronic airway disease. Studies have not been conducted to
address this question. However, there is increasing evidence in asthmat-
ics that control of the acute inflammatory response substantially improves
airflow and chronic airway inflammation. Prolonged treatment of newly
diagnosed mild asthmatics, chronic stable asthmatics, and severe asthma-
tics with inhaled corticosteroids resulted in significant improvement in
airflow. Our recommendations currently include reducing the concentration
of inhaled dust (better hygiene and use of a two-strap respirator) and
using inhaled corticosteroids in individuals with recurrent episodes of agri-
cultural dust-induced airflow obstruction.

INTERSTITIAL LUNG DISEASE

Agricultural workers are exposed to a wide variety of inorganic dusts,
depending on their occupation and local geography. Although there is some
evidence that asbestosis can be induced by inhalation of dust generated
by agriculture in asbestos-mining regions, agricultural dust-associated
pulmonary fibrosis is most closely associated with inhalation of inorgan-
ic silicate compounds. Most soils contain significant percentages of quartz
and other silica dusts. These dusts are aerosolized in processes that dis-
rupt the soil surface, such as tilling, sowing, and harvesting, particularly
of root vegetables. Harvesting can also secondarily aerosolize dusts pre-
viously deposited on leaves and growing plants in harvesting and process-
ing agricultural products such as grains and cotton. Workers who sort and
clean produce following harvest may be at particular risk from secondary
silica aerosolization. Farming activity causes significant particulate sus-
pension, which may be exacerbated by factors such as erosion, flooding,
and absent ground cover. The raising of livestock and other animals is
also associated with significant dust exposure, caused both by the soil
surface disruption and by contamination of livestock feed with inorganic
dusts. In addition, silicosis may result from inhalation of biogenic silica.
A number of plants are known to produce silica-containing fibers, inclu-
ding sugar cane and grains; ingestion of these plants is associated with
the development of esophageal carcinoma, but no studies have demonstra-
ted silicosis due to these fibers.

57
 While the relationship between many occupations and pulmonary fib-
rosis has been closely studied, the association between agricultural expo-
sure and pulmonary fibrosis has been less well examined. Although most
studies have focused on the contribution of silicates to pulmonary fibro-
sis in agricultural settings, asbestos and biotoxin inhalation can also lead
to fibrogenesis in the agricultural setting. Current exposure limits for sil-
ica have been set using mining and industrial exposures as benchmarks;
the relevance of these limits for agricultural workers has not been estab-
lished.

TESTS
1. A patient, 35 years old, an agriculturer, complains of a sharp sensa-
tion in the eyes, lacrimation, dryness and burning sensation in the nose at
cleaning, hoarseness of the voice, sensation of compression and stethal-
gia, dry cough; nasal bleeding, headache. It’s nessasary to prescribe for
the treatment:
A. Unithiol + Calcium tetacini + Ascorbic acid.
B. Penicillamine + Pentacinum.
C. Sodium sulfacetamide (Albucidum) — 2 % solution of Sodium hy-
drocarbonate + 1 % solution of Novocainum.
D. Nootropil + Aktovegine + Cerebrolysin.
E. Methylene dark blue + Glucose + Ascorbic acid.
2. A patient C., was delivered to CDH with the complaints of head-
ache, syncope, nausea, vomiting, abdominal pain. It was fixed that two
hours before hospitalization he processed a field by methylmercaptophos.
Objective: narrowing of the pupils, hyperhidrosis of the skin, bronchorrhea,
bradycardia, fibrillation of separate muscles. What organs and systems
suffer most of all as a result of this acute poisoning?
A. VNS.
B. Digestive organs.
C. Broncho-pulmonary system.
D. Locomotor system.
E. System of uropoiesis.
3. A patient A., 25 years old, works at the poultry factory during 5
years, complains of dry cough, dyspnea at the period of the working shift,
temperature above 39°C. Objective: percussion sound with a band-box
tone, weak vesicular breath, crepitation and fine bubbling rale on sepa-

58
rate areas of lungs. The type of the function of external breathing is re-
strictive. Blood test: Hb — 130,0 g/l; L — 90·109/l; ESR — 30 mm/h.
On X-Ray — diffuse enhancement and deformation of a lung pattern.
Establish diagnosis:
A. Croupous pneumonia.
B. Chronic bronchitis.
C. Exogenous allergic alveolitis.
D. Pneumoconiosis.
E. Bronchial asthma.

59
 Chapter 4
ACUTE TOXIC IRRITATIONS

RESPIRATORY TRACT IRRITANTS

Respiratory tract irritants are agents that result in an inflammatory re-
sponse or a physiologic response in the respiratory tract, because of
either their chemical reactivity or physical properties. Respiratory irri-
tants may be considered strong, weak, or relatively inert for the purposes
of this discussion, although this terminology is not standard.
Strong irritants, which are the major emphasis of this chapter, consist
of exposures that produce a stereotyped and acute pattern of damage in
the respiratory tract; recovery is often associated with major sequelae and
sometimes significant respiratory impairment. Strong irritants that are high-
ly reactive are more likely to produce an immediate and sometimes life-
threatening response. Examples of strong respiratory irritants, by any
standard, would include acrolein, ammonia, chlorine, chlorine dioxide,
phosphoric acid, and other chemical exposures described in the final sec-
tion of this chapter.
Weak irritants tend to act by inducing chronic symptoms over a pro-
longed period of time and often by aggravating existing disease such as
asthma and chronic bronchitis. It may be difficult to distinguish between
sensitization to an agent and airways irritation due to the agent; this is
sometimes a clinical problem with the isocyanates, for example. Exam-
ples of weak irritants include many common solvents (most potently the
xylenes), and alcohols.

The Mechanism of the Lung’s Response to Irritants

The lung is highly vulnerable to the effects of respiratory irritants. The
respiratory tract is protected by many layers of host defense, but they are
primarily effective against infectious agents. Chemical hazards may
bypass most of these in the upper airway and penetrate deeply to air-

60
ways and alveoli. When this occurs, the effect of the agent on the respira-
tory tract is governed primarily by the degree of penetration, the charac-
teristics of the agent, and the nature of the host defense mechanisms it
encounters at the level affected.
The respiratory tract is saturated with water beyond the carina and is
lined with a moist mucosa with a very large surface area. Inhaled gases
that are soluble in water to any appreciable extent tend to be dissolved
readily and removed from the airway very efficiently. Therefore, gases
penetrate the respiratory tract more deeply the less soluble they are in
water. Respiratory tract irritants that are chemically reactive but easily
neutralized, such as formaldehyde or acetic acid, may induce upper res-
piratory tract irritation, sinusitis, and sneezing but rarely cause problems
deeper in the respiratory tract. Relatively soluble gases, such as ammo-
nia, chlorine, and sulfur dioxide, penetrate poorly and usually cause pre-
dominantly airways irritation, which manifests itself as bronchospasm
or an acute bronchitis. Occasionally, the concentration at exposure is so
high that a soluble gas can penetrate in significant quantities to the al-
veolar level because of sheer mass, but this is very uncommon. Rela-
tively insoluble gases, such as phosgene, nitrogen dioxide, and ozone
penetrate very deeply, to the terminal bronchiolar and alveolar regions.
These gases are particularly dangerous because they can induce toxic pul-
monary edema, an often fatal outcome resembling adult respiratory di-
stress syndrome.
The response to respiratory irritants is highly variable, among the most
unpredictable of occupational health outcomes in the individual case. Im-
portant factors include the circumstances of exposure, the level of expo-
sure to the agent of interest, the constitutional susceptibility of the host
(especially if there is a history of atopy or airways reactivity), recent per-
sonal history (such as recent respiratory tract infections), smoking histo-
ry, and other recent exposures (including environmental tobacco smoke).
In a few cases, especially involving chronic cough, there may be a beha-
vioral component to the response and the cough itself may perpetuate the
response by causing further inflammation. Although documentation ap-
pears to be lacking, there is at least an anecdotal impression among some
clinicians that persons who smoked cigarettes and then quit are often more
susceptible to low-grade airways irritants than persons who never smoked
or who continue smoking. Empirical verification of this observation is
needed.
Another important aspect of respiratory irritants is that an irritant that
primarily affects deep structures often affects proximal structures on the
way down. For example, ozone is primarily associated with changes at
61
the level of the terminal bronchiole and alveoli, where it may alter breath-
ing reflexes in addition to a usually low-grade alveolitis. However, ozone
may also induce a cough and inflammation in the larger airways and na-
sal irritation.

CLINICAL MANIFESTATIONS
OF RESPIRATORY TRACT IRRITATION
The clinical effect produced depends on the level of penetration and
what happens when the agent encounters the predominant host defense
mechanisms at that level.
Gases that are very soluble and dusts that have a large aerodynamic
diameter tend to produce upper airways effects, such as sinusitis and na-
sal irritation. They often aggravate or mimic hay fever and may cause
symptoms to be pronounced in a previously quiescent atopic individual.
Such symptoms are likely to be one important category of the “sick build-
ing syndrome” and an important manifestation of indoor air quality. Since
approximately 15% of the adult population is atopic, it is clear why this
is a common problem. It is perhaps most commonly a result of airborne
dust alone. Such symptoms are also aggravated by low humidity, as oc-
curs in northern climates in winter and particularly indoors in climate-
control buildings.
Gases that are soluble and dusts that are somewhat larger than 10 µm
may have their primary effect on a larger airways of the lower respiratory
tract, causing cough or bronchoconstriction. In most cases, this effect tran-
sient or short-lived. Bronchoconstriction may be manifested as either acute
bronchospasm or aggravation of airways reactivity, with more frequent
and severe attacks in individuals with asthma. Occasionally, airways ob-
struction or cough may be pronounced in an individual without a history
of asthma but with a personal family history of atopy and especially hay
fever. In some situations, it is likely that the subclinical airways reactivi-
ty is enhanced by an inflammatory response to the irritant. This inflam-
matory response may be very low grade, unlikely to produce a response
in an individual who is not susceptible, and rarely resulting in wheezing
or productive cough. These responses are very variable depending on the
individual, the exposure situation, the season, since the person affected
may also responding to allergens.
Dusts of a diameter greater than 10 mm are very important in induc-
ing responses in the upper airway and larger airways of the lower respira-
tory tract, especially inducing bronchospasm in an individual with exist
reactive airways. Effects on small airways are usual silent because the
62
cross-sectional area at that level of respiratory tract is so large that there
is a huge functional reserve and no obstruction is clinically apparent. The
although there is evidence to suggest that some dusts induce fibrosis in
this region and low-grade small ways disease, this does not seem to be a
large effect. It is certainly a small response compared to induced by ciga-
rette smoking. However, it may be significant in contributing to chronic
obstructive pulmonary disease in the presence of other risk factors.
Particles that have a diameter less than 10 µm may penetrate the al-
veoli, deposit, and induce a pneumoconiosis. “Nuisance dusts,” which are
also called “particulates not otherwise classified/regulated” (PNOC), dusts
that are rarely associated with obvious clinical disease and for which no
separate regulatory standard exists in the United States. These dusts do not
result in exuberant fibrosis associated with the clinically important pneu-
moconioses, such as silicosis and asbestosis the dysfunctional immune re-
sponses of hypersensitivity pneumonitis or beryllium disease. However, all
such dusts may be associated with nonspecific responses at the alveolar
level that induce a low-grade response, small amounts of focal fibrosis.
Gases that penetrate deeply may induce a general pattern of diffuse
alveolar damage, which resemble: early pathology of adult respiratory dis-
tress syndrome. This response is very dangerous because it may lead to
toxic pulmonary edema, described in greater detail below. This is a re-
sponse to strong irritants and is clinically the most severe and most often
life-threatening effect of respiratory irritants.
Toxic inhalation is a serious pattern of respiratory injury that results
from diffuse alveolar damage and associated airway injury in an expo-
sure that involves deep penetration of strong respiratory irritants. The most
prominent feature of toxic inhalation is the risk of pulmonary edema. Pa-
renchymal lesions may result in honeycombing (interstitial fibrosis), re-
flecting abnormally proliferative fibrosis. Airways effects may be promi-
nent in toxic inhalation, among them acute bronchospasm, bronchiolitis
obliterans, and reactive airways dysfunction syndrome. Toxic inhalation
also involves substantial compromise of respiratory host defenses and a
risk of infection and complications.
Acute toxic inhalation by irritant, and particularly by oxidant, gases is
a complex process involving biochemical, morphologic, and functional
changes. The severity and special features of toxic inhalation depend on
the concentration inhaled, the duration of exposure, the redox potential
and chemical characteristics (especially solubility) of the individual gas,
and, as will be seen, other factors.
The pulmonary vascular endothelium is the primary target, and com-
promise of this tissue may lead to pulmonary edema. The pulmonary vas-
63
cular endothelium is a very active tissue that is susceptible to a variety of
toxic injuries but is capable of only limited response. A specific problem
of great complexity in oxidant gas injury is the behavior of fluid follow-
ing damage to the endothelial barrier. Among the most important func-
tions of the endothelium is the regulation of vascular tone by nitric oxide
(NO), which acts as a local hormone on adjacent arterial smooth muscle.
Its activity is kept strictly localized. This is an effective means of titra-
ting the vascular response and rapidly adjusting the vascular tone to chang-
ing hemodynamics.
The presence of this endogenous, nitrate-based messenger system for
vascular regulation robustly explains the therapeutic vasodilator action
of nitrates, the alterations in lung perfusion observed with inhalation of
nitrogen dioxide, and even the vasoconstriction response of the pulmonary
vascular bed during hypoxia, resulting as it does from decreased NO ac-
tivity. There is some evidence that vascular segments with impaired en-
dothelium may be more sensitive to nitrates and NO-induced vasodila-
tion than intact segments.
The apparent sensitivity of the pulmonary capillary endothelium may
be a multifactorial phenomenon. The lung is the organ at highest local
oxygen tension. The endothelium, despite its low turnover rate, is a very
active tissue metabolically. Current theory suggests that much of the cy-
totoxicity induced by agents such as oxidant gases, ionizing radiation, and
free radical-forming compounds (e.g., paraquat) is mediated by the su-
peroxide radical. The pulmonary capillary endothelium is thus at maxi-
mum risk. Furthermore, secondary phenomena of inflammation may re-
sult in very localized superoxide injury to the endothelium, an “innocent
bystander” effect, after stimulation of adjacent polymorphonuclear leu-
kocytes (PMNs) by activated complement, specifically C5a. The concept
is analogous to but distinct from the release of proteolytic enzymes by
phagocytic cells, a process that may set the stage for damage persisting
beyond the acute phase.
Another possible mechanism of injury is the release of vasoactive hu-
moral factors to which the endothelium is specifically responsive or pref-
erentially exposed by position. In the case of oxygen toxicity such meta-
bolic abnormalities occur before visible evidence of cellular injury. Al-
though humoral factors are undoubtedly involved, it is likely that the re-
lease of such factors, including bradykinin and the biogenic amines, con-
tributes to the expression of injury more than the injury itself.
The presence of specific receptors that increase vascular permeability
and induce pulmonary edema may be an important pharmacologic mech-
anism for the induction of pulmonary edema by toxic gases. This mecha-
64
nism provides an explanation for ontogenetic and phylogenetic differences
in susceptibility, the phenomenon of tolerance, the action of neurogenic
pathways, and the sympathetic appearance of edema in the contralateral
lung after unilateral embolism. To date, the theory lacks empirical vali-
dation.
The pulmonary vascular endothelium is not a highly complex struc-
ture, and its responses to injury are limited by physiologic constraints on
its function. Structural endothelial damage by toxic gases such as nitro-
gen dioxide or ozone or by irradiation include swelling, cytoplasmic chang-
es, proliferation of microvilli, and cell surface redundancy. Vesicles be-
come much more numerous and ultimately large vacuoles form. The cell
may retract or slough, even leaving behind denuded areas of basement
membrane. The functional results of this injury include loss of control of
solute transport across the endothelium, resulting in increased permeabil-
ity. This leads to interstitial and then alveolar edema.
Recent exposure to prior toxic inhalation, especially to phosgene, in-
creases relative resistance to a later lethal challenge with another gas. This
phenomenon of tolerance disappears within days but is remarkably strong
while it lasts. Tolerance to repeated exposure to toxic gases, particularly
the oxidant gases, is species-specific and inversely correlated with the
age of the animal documented. It is usually explained on the basis of the
regeneration of type I alveolar epithelial cells by the less susceptible type
II cell. However, the role of the endothelium may be more important in
the pathophysiology of toxic inhalation than previously realized.
The principal structural barrier to the passage of fluid is the alveolar
capillary membrane, which may be as thin as 0.5 mm. The lung is highly
vulnerable to flooding by plasma-derived fluid. Complex systems to con-
trol and contain the passage of fluid through the lungs act to protect it
from edema and resultant substantial changes in gas exchange. These
mechanisms that protect the lung include (a) the low pressure of the pul-
monary circulation, (b) the surfactant system (which reduces intraalveo-
lar surface tension), and (c) the lymphatic drainage system. The endothe-
lium is the first barrier component encountered on the capillary side. Plas-
ma water and smaller macromolecules are prevented from passing into
the interstitium by intact endothelial junctions. These can be disrupted
by circulatory overload, which stretches the intercellular junctions. Fluid
may then enter the interstitium, where there are no barriers, and fluid col-
lects as interstitial edema. At this point the barrier to further penetration
is the alveolar epithelium, in which the junctions are tighter, more comp-
lex, and less susceptible to alteration by mechanical stress. The final phase
of pulmonary edema, that of alveolar flooding, is thought to begin in the
65
corners of greatest curvature of the alveoli at a “critical configuration” of
volume and geometry in which inflation pressure no longer balances sur-
face tension and hydrostatic forces.
The pathways of resolution of toxic pulmonary edema have not been
systematically studied. Most of the work has been done on cardiogenic
(hydrostatic) edema and the capillary permeability type caused by sepsis
or inflammatory mechanisms. The degree to which an irritant gas inter-
feres with the process of resolution and repair may depend on its own
intrinsic toxicity to other anatomical elements, particularly to the alveolar
epithelium.

TESTS
1. A 35-year-old man applied to the physician with complaints of the
constant cough, dyspnea, separation of a swampy mucous sputum, sea-
sonly appearing attacks of asphyxia for the last 6 months. In anamnesis
— a 10-year experience of work on the lacquer-paint plant. He noticed
that attacks occur during exposure to paints.
Objective: on the part of respiratory system at the percussion — band-
box sound on the roots of the lungs; dry diffused rales. Laboratory data:
moderate eosinophilia. X-ray — amplification of the lung pattern and re-
traction of the roots of lungs.
What is the most possible reason of this condition?
A. Chronic toxic bronchitis at the stage of intensification.
B. Bronchial asthma, mild degree of severity.
C. Chronic toxic bronchitis complicated by bronchial asthma, moder-
ate degree of severity.
D. Bronchial asthma, moderate degree of severity.
E. Acute toxic alveolitis.
2. A woman, 50 years old, works at the chemical plant during 20 years,
complains of attacks of asthma, appeared at work, noisy breathing, heard
at a distance, dyspnea. At the examination — the thorax is extended. Lips,
nails’ loges, skin are cyanotic. At percussion — a band-box sound. Breath-
ing is harsh, with prolong exhalation, pronounced diffuse dry rales dur-
ing inhalation and exhalation are heard.
What a pathology has this patient?
A. Chronic bronchitis.
B. Professional bronchial asthma.
C. Tuberculosis.
D. Acute pneumonia.
E. Tracheobronchitis

66
 3. A 40-year old man K. works at the chemical plant on the production
of the sulfuric acid. Nitrogen dioxide escape took place as a result of in-
cident at the plant. Through 15 min a sick man has felt a general malaise,
which disappeared by itself after 1.5 h. In 10 hrs the condition of the pa-
tient sharply worsenned and he was hospitalized.
Objective: the condition is severe, cyanosis, bubbling breathing — 50
in 1 min, dyspnea, on auscultation — multiple dry and moist rales. Tones
of the heart are deaf. Heart rate — 120 bpm, BP — 110/70 mm Hg.
It’s possible to form the following diagnosis:
A. Acute poisoning with sulfuric acid.
B. Acute cardiovascular insufficiency.
C. Acute poisoning with ammonia.
D. Acute poisoning with nitrogases.
E. Cerebral haemorrhage.
4. A patient A., 32 years old, a worker of the Odessa sea port plant
during 2 years, applied to the local polyclinic to the physician with com-
plaints of headache, a tickling sensation in the throat, cough. At ausculta-
tion — dry rale in the lungs. Other changes are not revealed.
It’s possible to expect the following diagnosis in this case:
A. Pharyngitis.
B. Acute rhinitis.
C. Poisoning by ammonia.
D. Bronchitis.
E. Acute respiratory disease.
5. A patient P., 44 years old, was delivered to the hospital by an ambu-
lance with complaints of swoons, vomiting, pains in the epigastrium, a
sensation of mist before the eyes, noise in the ears, frequent rare stool, a
pain in the breastbone of compressing nature, a tickling sensation in the
throat, dry cough, general weakness. Under the objective examination:
pallor, hyperhydrosis, deaf tones of the heart, harsh breathing, dry rales.
Mucous membrane of the rhinopharynx is dry, white cover of the tongue,
the abdomen is inflated, palpation reveals a certain resistence in the epi-
gastrium. In the blood test: leucocytosis, increased ESR. Other changes
are not detected. Data from anamnesis: he worked with the process of
enriching by ammonium water, used a respirator not regularly.
It is possible to suppose in this patient:
A. Food toxicoinfection.
B. Poisoning by phosphoric organic substances.
C. Lead intoxication.
D. Acute intoxication by ammonium water.
E. Pesticides’ intoxication.

67
 Chapter 5
CARBON MONOXIDE,
METHEMOGLOBIN FORMERS,
HYDROGEN ARSENIDE
Various physico-chemical substances are used in national economy of
many countries of the world. They comprise nonorganic and organic com-
pounds. They may form toxic compounds by themselves or in combina-
tion with other substances. According to the classification of toxicity and
dangerous effect on the organism harmful substances may be divided into
four classes (Table 5.1).
Table 5.1. Classification of toxicity
Class of toxicity
Indication
1 2 3 4
Average toxic dose: <15 15–150 151–5,000 >5,000
ingestion (mg/kg)
Percutanic action (mg/kg) <100 100–500 501–1,500 >15,000
LC (mg/m3) 500 500–5,000 5000–50,000 >50,000

General Mechanism of Pathogenesis

of Acute Occupational Poisonings (AOP)
Acute poisonings may occur in accidents, violations of production proc-
ess technology. Depending on the properties of the toxic substance, acute
poisoning may occur at once (for example, in inhalation of carbon mon-
oxide of strong concentration) or after several exposures for a few hours
(methyl bromide).
Disturbances of activity of a number of regulator ferments catalyzing
porphyrin synthesis are very important for the course of AOP. Disturbance
of porphyrin biosynthesis is more often in poisoning with carbon mono-
xide.
AOPs also influence the condition of receptor metabolic processes in
the cell that effects the structure and function of the cellular membranes
and condition of the cellular metabolism. Among primary mechanisms of
membrane structure and function disturbance free radical oxidation is of
special importance.

68
 CARBON MONOXIDE
Sources and Exposure
Because of its many sources, carbon monoxide (CO) is a ubiquitous
air pollutant in the urban environment. It is produced during the combus-
tion of carbonaceous material, including gasoline, natural gas, oil, coal,
wood, and tobacco. The principal source of carbon monoxide in outdoor
air is motor vehicle emissions. In some areas of the country, wood burned
for heating may be an important contributor to ambient levels. The con-
centrations of carbon monoxide in ambient air vary much, owing to the
great spatial and temporal variability associated with its sources. Low
ambient levels (less than 1 mg/m3) are typically observed in outdoor set-
tings away from active roadways, such as some parks and recreation are-
as. Outdoor concentrations tend to increase with motor vehicle density
(e.g., downtown areas) and tend to be elevated in the air of the passenger
compartments of motor vehicles. Exposure to carbon monoxide is grea-
test during commuting and in proximity to operating motor vehicles. The
concentration in the passenger compartment of an automobile typically
averages 5 mg/m 3. Outdoor levels near roadways and parking areas ave-
rage 3 to 4 mg/m 3. Relatively higher levels may be encountered traveling
in heavy traffic: peak levels to 50 mg/m 3 may occur in a background of
approximately 10 mg/m 3. Because of the reliance on motor vehicles for
transportation in urban areas, automobile exhaust represents the single
greatest contributing source to total personal exposure.
In comparison to exposure during travel in automobiles, indoor levels
in residences and public buildings are generally low. In the absence of
unvented combustion appliances, indoor levels are usually equal to local
outdoor concentrations. The most commonly used unvented natural gas
appliance, the cooking range, is not a strong source, even if the residence
is poorly ventilated. Neither has tobacco smoke been found to be an im-
portant source of carbon monoxide exposure in homes. Carbon monox-
ide can accumulate because of the presence of stronger sources, includ-
ing improperly vented or malfunctioning furnaces, kerosene space heat-
ers, and charcoal fires for heating. In public buildings concentrations of 2
to 4 mg/m3 have been found to be typical. The fact that this level is slightly
higher than those in private residences is probably attributable to the ac-
tivity of motor vehicles in the areas immediately surrounding public build-
ings. Personal exposure to high levels of carbon monoxide in outdoor set-
tings may occur during the use of equipment and appliances powered by
small gasoline engines. Important sources include lawn mowers, edgers

69
and trimmers, chain saws, and snow blowers. These tools may be used
for prolonged sessions of work, and because they are handheld, the user
is close to the exhaust plume. Further, high concentrations of carbon mono-
xide may accumulate when such equipment is used in sheltered or par-
tially enclosed areas. High levels have also been measured in the air of
ice hockey rinks, which is contaminated by emissions from resurfacing
machines.

Health Effects
When inhaled, carbon monoxide diffuses across the lung epithelium
into the blood and reversibly binds to hemoglobin, taking over binding
sites for oxygen. Hemoglobin’s affinity for carbon monoxide is approxi-
mately 200 times greater than that for oxygen. Additionally, in the pre-
sence of carbon monoxide, allosteric changes take place on the hemo-
globin molecule, causing leftward shift of the oxyhemoglobin dissocia-
tion curve. Thus, inhalation of carbon monoxide decreases the oxygen-
carrying capacity of the blood and also the ability of tissues to extract
oxygen from the hemoglobin at low partial pressures. Tissues that are most
sensitive to low oxygen stress — the brain and the heart — are regarded
as particularly vulnerable to hypoxia induced by the presence of carbon
monoxide. Carbon monoxide may also interfere with intracellular oxy-
gen transport in muscle.
Sustained exposure to high concentrations of carbon monoxide, par-
ticularly indoors, may lead to poisoning, and ultimately death. A carbox-
yhemoglobin saturation level of 50% is generally regarded as sufficient
to cause coma and death. Analysis of death certificate data for 1977
through 1988 indicate that 11,547 deaths occurred nationally from car-
bon monoxide exposures that could not be attributed to suicide, homi-
cide, or house fire. Most of these deaths were associated with asphyxia-
tion by indoor exposures to exhaust from running autos, but 1,199 deaths
were attributed to the use of coal, kerosene, or wood in a heating appli-
ance (e.g., wood-burning stoves, kerosene space heaters), and another
1,047 deaths were attributed to carbon monoxide exposure from improp-
erly vented furnaces and heaters using natural gas fuels. Fortunately, there
appears to be a decreasing trend in the annual incidence rates of uninten-
tional carbon monoxide poisoning associated with nonvehicular sources.
The clinical manifestations of subacute poisoning (less than 50% satura-
tion) reflect the underlying hypoxic processes associated with high car-
boxyhemoglobin levels. They range from headache, fatigue, and flu-like
symptoms to chest pain, cardiac arrhythmia, and myocardial infarction.
70
The sequelae and diagnosis of subacute carbon monoxide poisoning are
well described elsewhere.
Most outdoor levels are too low to produce clinical symptoms but out-
door carbon monoxide does penetrate indoors and can contribute to ele-
vating carboxyhemoglobin saturation levels.
Low-level exposures have been the focus of most recent health effects
studies. In particular, these studies have tended to focus on subpopula-
tions whose cardiovascular or respiratory health is compromised. Suscep-
tible groups include people with ischemic heart disease (IHD), peripheral
vascular disease, and chronic obstructive pulmonary disease (COPD). For
each of these groups, exercise testing has been used to evaluate exercise
capacity after exposures to carbon monoxide sufficient to elevate carbo-
xyhemoglobin levels into the 2% to 6% range. Most of the studies em-
ployed double-blind crossover experimental designs, comparing exercise
performance after exposure to carbon monoxide to performance after ex-
posure to clean air. The responses evaluated in heart patients include the
interval to onset of angina pectoris and ST-segment depression on the
electrocardiogram (ECG), and in patients with intermittent claudication,
reduction in interval to leg pain. In the testing of COPD patients, the ma-
ximum distance walked during progressive treadmill exercise has been
used. In most studies, the subject selection criteria have involved testing
to demonstrate the reproducibility of the specific response during exer-
cise testing and have excluded current smokers.
In patients with exertional angina, earlier onset of angina pectoris and
ST-segment depression have been consistently observed at carboxyhemo-
globin levels of 2% to 4% by several investigative teams. In the largest of
these studies, the Health Effects Institute multicenter carbon monoxide study,
5% and 12% decreases in the time to onset of ST-segment depression were
observed at carboxyhemoglobin levels of 2% and 4%, respectively. Sig-
nificant decreases in time to onset of angina, 4% and 7%, were also dem-
onstrated at these respective carboxyhemoglobin levels. Findings for the
objective ECG end point and subjective end point of chest pain yielded
consistent results and are compatible with the hypothesis that an elevated
carboxyhemoglobin level impairs the response of the myocardium to in-
creased metabolic demands.
Another manifestation of myocardial ischemia is ventricular arrhyth-
mia. Myocardial hypoxia caused by carbon monoxide has been postulat-
ed to be a mechanism of sudden death. Animal models have provided
limited and mixed information on the arrhythmogenic potential of carbon
monoxide. The experimental design in these studies included induction
of myocardial infarction followed by exposure to produce carboxyhemo-
71
globin levels as high as 20%. Current evidence suggests no effect at car-
boxyhemoglobin levels up to 5% to 6% in patients with coronary artery
disease and no baseline ectopy at rest, but is inconclusive for patients
with baseline ectopy. Clinical studies have used carboxyhemoglobin lev-
els more typical of the urban exposure range. Sheps et al. investigated the
arrhythmogenic potential of carbon monoxide in a group of 41 men and
women with clinically established ischemic heart disease and a mixed his-
tory of ventricular ectopy. A 32% increase in the rates of ventricular ar-
rhythmia during cycle exercise was observed after chamber exposure to
200 mg/m3 carbon monoxide for 1 hr (mean carboxyhemoglobin 5.3%)
relative to filtered room air but not after exposure to 100 mg/m 3 for 1 hr.
At neither level of exposure was there a significant difference in the rate
of ventricular ectopy as measured by ambulatory ECG during the 6 hrs
after exposure and exercise.
Epidemiologic studies provide limited support for the hypothesis that
ambient carbon monoxide aggravates myocardial ischemia. Several stu-
dies have reported associations between ambient carbon monoxide levels
and hospital admissions for cardiorespiratory disease; however, causal
inferences cannot confidently be made. Most of the investigations have
relied on estimates of personal exposure derived from measurements made
at outdoor monitoring stations. Because correlations between central site
measurements and personal exposures are poor for carbon monoxide, sub-
stantial exposure misclassification probably occurred in these designs.
Furthermore, the study designs may have been confounded by unknown
or uncontrolled factors, including cigarette smoking and medications.
In an occupational study of tunnel and bridge workers in New York
City, employment records and historical monitoring records were used to
retrospectively classify exposure during the period 1952 to 1981. Expo-
sure classification was validated by personal monitoring of contemporary
workers. A standardized mortality ratio of 1.35 for cardiovascular causes
of death was observed for the high exposure group (tunnel workers) when
compared to the low exposure group (bridge workers). This statistical as-
sociation was supported by the observed decrease in mortality among
workers transferred from tunnels to bridges. The results of this study im-
ply that short-term repeated carbon monoxide exposure may be associa-
ted with excess mortality from heart disease.
Controlled clinical studies have also been conducted on patients with
COPD. Subjects with severe COPD are believed to be at risk for deve-
lopment of elevated carboxyhemoglobin levels because of reduced abili-
ty to eliminate carbon monoxide owing to decreased ventilatory capacity.
However, the evidence for effects of carbon monoxide on exercise per-
72
formance in this potentially susceptible subgroup is limited. Calverley and
co-workers observed a 7% reduction in the distance walked in 12 min-
utes after exposure to 200 mg/m3 carbon monoxide for 20 to 30 minutes;
however, because the order of exposure and testing was not randomized,
the effect could be attributed to fatigue.
Because of the sensitivity of the central nervous system to hypoxia,
several clinical studies have evaluated the impairment of vigilance, per-
ception, and the performance of complex tasks after exposure to low con-
centrations of carbon monoxide. The results of these investigations have
been inconsistent and are potentially attributable to methodologic differ-
ences in the neurobehavioral end-point measurements and differences in
carbon monoxide exposure protocols and measurement of carboxyhemo-
globin levels. Varying effects on visual perception, auditory perception,
manual dexterity, and vigilance have been reported, but in normal sub-
jects clinically important neurobehavioral deficits have not been observed
below 10% carboxyhemoglobin.
Finally, limited animal toxicology data have implicated carbon mon-
oxide as an agent that causes lower birth weight and increased fetal and
neonatal mortality. A case-control study of birth weight and maternal ex-
posure to ambient carbon monoxide during the last trimester of pregnan-
cy demonstrated an odds ratio of 1.5 at a mean neighborhood outdoor
level of at least 3 mg/m 3, compared to lower levels. The accuracy of this
finding is limited by failure to control for maternal smoking and potential
misclassification of personal exposure because outdoor monitoring data
were used.
The findings of controlled exposure studies, when viewed with the
evidence for widespread exposures to carbon monoxide in urban popula-
tions, suggest that several groups may be at risk for adverse, health ef-
fects. Although concentrations of carbon monoxide in the outdoor envi-
ronment are generally low, the prolonged exposure may nevertheless lead
to development of carboxyhemoglobin levels at which health effects have
been clinically demonstrated for susceptible persons. Because of the prev-
alence of cardiovascular disease, chronic respiratory disease, and preg-
nancy in the population, these adverse health effects assume public health
importance.
Carbon monoxide is a strong hemic poisoning by its toxic properties.
Carboxihemoglobin (COH) is formed under its influence that results in
hemoglobin blockade with transport disturbance of oxygen in blood caus-
ing hypoxemia and hypoxia. Connection of hemoglobin with carbon mon-
oxide is 300 times more than with oxygen. It promotes very fast forma-
tion of COH when carbon monoxide gets into the organism and trans-
73
portation of hemoglobin into inactive form which is not able to transport
oxygen into different tissues of the organism.
The cerebral tissue is the most sensitive to hypoxia and dies especial-
ly fast under such conditions. Carbon monoxide may exert pathologic ef-
fect on the peripheral nervous system.
There is increased permeability of the vascular walls, including capil-
laries which causes hemorrhage and dystrophicity up to necrosis in dif-
ferent organs and tissues — the brain, lungs, gastrointestinal tract.
Amido- and neurocompounds of benzene [methemoglobin formers
(MHFs)] also cause severe changes in blood, CNS and parenchymatous
organs. The processes of methemoglobin formation, oxygen deficiency,
affections of the CNS prevail in acute intoxications. MHFs are strong ox-
idizers. In getting into blood they oxidize hemoglobin to methemoglobin.
The latter is a rather stable compound, which is not dissociated.
Anoxemia and anoxia are the main pathologic signs which define most
of intoxications symptoms that the nervous system is very sensitive to.
The following parts are mostly affected: pyramidal ducts, striated body,
the cerebral cortex as well as fibers of the peripheral nerves.
Hydrogen arsenide is extremely toxic. It penetrates into the organism
through the respiratory organs without affection of the mucous membrane
of the upper respiratory tracts. It is a hemolytic poison whose effect is
manifested in 2.5–3 hrs after contract with it.
The results of active hemolysis are anemia, affection of the parenchy-
matous organs (kidneys, liver), nervous and cardiovascular systems. There
may be observed metabolic changes characteristic of toxic conditions: in-
creased amount of sugar and lactic acid in blood, hyperacetonuria, de-
crease of pool reservoirs of blood. Thus, development of anoxemia in in-
toxication of hemolytic character causes general hypoxia with its con-
comitant manifestations.
At the same time, severe dysfunction of the liver and kidneys can’t be
explained entirely by hemolysis. There are sings of toxic hepatitis in some
cases. In severe cases there may be progressing renal failure and devel-
opment of uremia. Changes in the cardiovascular system are to a great
extent by hydremia and anemia.
There may be observed enlargement of the heart, tachycardia, some
disturbances of conduction, arterial hypotension. The acute period of in-
toxication is characterized by headache, dizziness, something drowsiness
or condition of dramatic excitation. Late damages of the peripheral ner-
vous system should be emphasized, such as polyneuropathies with dra-
matic tenderness of the nervous trunks and parasthesias.

74
 Clinical Manifestations and Peculiarities
in Poisoning with Carbon Monoxide
Depending on the severity of the clinical manifestations there are three
stages of intoxication (Table 5.2): mild, moderate and severe. The severi-
ty of intoxication depends on carbon monoxide concentration in the air,
duration of exposure, individual sensitivity of the organism. Changes of
the CNS are the first to develop.
The duration of coma over 48 hrs is a prognostically bad symptom.
In favorable course, the patients coming out of coma have a condition
accompanied by motor excitation when they leap up, try to run, become
aggressive. There may be catarrhal laryngitis, sometimes edema of the
vocal fissure resulting in hoarseness and wheezing. There may be trophic
disturbances on the skin. Erythema is most frequent, it gets pigmented
later on. In some cases blisters develop on the background of erythema,
filled with exudates which resemble burns.

Table 5.2. Stages of poisoning with carbon monoxide

Stage of Symptoms
poisoning Subjective Objective
Mild Sensation of heaviness Flashes in the eyes, palpitation, vomiting,
in the head, throbbing trembling of the body, pink color of the
headache in the tem- mucous membranes and skin (caused
ples and forehead, tin- by accumulation of carbox; hemoglobin
nitus, weakness, nau- in blood), tachypnoe. HbCO levels of 10–
sea 30%
Moderate General weakness Confusion, absence of critical evaluation
of the situation, growing drowsiness. Re-
flexes are reduced. There is pathologic
Babinsky’s reflex. Rigidity of the occipi-
tal muscles. Ataxia.
HbCO levels of 40–50%
Severe — Loss of consciousness with coma and fi-
brillar twitching of some muscular groups.
There may be attacks of generalized con-
vulsions of clonic and tonic character.
The pupils are dilated, there is no reac-
tion to light. Severe bronchopneumonia
may develop on the 2nd–3rd day.
HbCO levels of 60–70%.
Death is likely at levels exceeding 70%

75
 Blood analysis is characterized by erythrocytosis and increased con-
tent of hemoglobin, sometimes neutrophilic to the left shift leukocytosis,
increased blood viscosity, decrease of ESR to 2–4 mm/hr. Carboxihemo-
globin appears in blood at the highest level of intoxication.
Not infrequently poor memory, emotional instability, dysfunction of
vision, smell, hearing and taste remain after acute poisoning. There may
be central paralyses in some cases. Motor, hearing and trophic disorders
may be observed as consequences of poisoning in the peripheral nervous
system. The patient may also have anemia, amnestic aphasia, apraxia, ag-
nosia, memory disturbances by Korsakov’s syndrome type. There may be
psychoses with hallucinations, phobias for several years after intoxi-
cation.

Treatment and Prophylaxis of Poisoning

with Carbon Monoxide
Treatment consists of intensive supportive care and providing high-
tissue oxygen levels to reduce cellular hypoxia and promote the elimina-
tion of CO. Under normobaric conditions, the elimination half-life of CO
while breathing room air is approximately 6 hrs. This is decreased to about
90 min when breathing 100% oxygen. While breathing 100% oxygen un-
der hyperbaric conditions at 3 atmospheres, the elimination half-life is
approximately 20 min.
a) Oxygen. All patients should receive 100% oxygen until the HbCO
level declines below 10%.
b) Endotracheal intubation is indicated for all patients with respirato-
ry distress, inability to protect their airway (i.e., comatose, or seizing pa-
tients), or ARDS.
c) Hyperbaric oxygen (HBO) therapy is indicated for patients with evi-
dence of end-organ toxicity, which includes significant neurologic defi-
cits (e.g., confusion, coma, seizures), myocardial ischemia or infarction,
and metabolic acidosis. In centers where neuropsychiatric testing is avail-
able, abnormal responses on the test battery can serve as an indication for
HBO therapy. The indications for HBO therapy based on HbCO levels
are less clear. Depending on the availability of an HBO chamber, persons
with the HbCO level of 20–30% should be considered for HBO therapy.
Pregnant women and patients at the extremes of age modify this value
downward. Hyperbaric oxygen in itself is teratogenic but probably less
so than the CO-induced hypoxia and inhibition of cellular respiration in
the fetus. When the chamber is a significant distance from the patient and
the patient is unstable, then the benefits versus risks must be considered.

76
 Discharge. Patients with mild manifestations of Co poisoning may be
discharged from the emergency department when the HbCO level has de-
clined to less than 10% and they are asymptomatic. Patients who have
major symptoms (usually association with HbCO levels >30%) or who
remain symptomatic require hospitalization.

POISONING
WITH METHEMOGLOBIN FORMERS
Amido- and nitrocompounds of benzene are widely used in industry
to make dyes, pharmaceutical preparation, explosives, etc. The most im-
portant among them are anilin, nitroanilin, nitrobenzene, dinitrobenzene.
Compounds of this group may cause both acute and chronic poisoning.
They penetrate into the organism through the respiratory organs and un-
damaged skin.
The maximum permissible concentration of anilin and benzene nitro-
compounds in the air of work premises is 3 mg/m3. Changes in the CNS
are the main ones in the clinical picture of acute intoxication. General
cerebral signs include headache, dizziness, nausea, vomiting, dramatic
weakness (the patients can hardly stand). Stupor with the following coma
develops in severe cases.
However, the most characteristic sign of acute poisoning with MHFs
is radial change of colour of the skin integument. On patient’s examina-
tion there are grey-blue colour of the mucous membranes and skin inte-
gument and cyanosis.
Severe cases of acute poisoning are characterized by hyperactivity of
knee-reflexes, development of clonuses and pathologic reflexes. The pu-
pils reaction to light is flaccid. Coming out of the comatous condition is
accompanied by motor excitation. During the first days after coma the
patient suffers from intense headache, weakness, dizziness. In some ca-
ses there may be narrowing of visual field margins. Sometimes these signs
may be accompanied by tenderness of the peripheral nerves, trigeminal
in particular.
There may be noted elevation of tonicity of the parasympathetic part
of the vegetative nervous system which is manifested by excessive swea-
ting, stable scarlet dermographism, bradycardia. Methemoglobin is de-
tected in blood. Depending on the severity, there are three stages of MHF
intoxication (Table 5.3).
Treatment and prophylaxis of poisoning with MHFs are presented in
table 5.4.
77
 Table 5.3. Degrees of intoxication with methemoglobin formers

Degree of Symptoms
intoxication Subjective Objective
Mild Headache, dizziness, Cyanosis of the mucous membranes and
weakness, drowsiness skin integument, ataxia, elevation of ten-
don reflexes, tachycardia with normal
ABP. About 20–25% of methemoglobin
in the blood.
Duration of the disease is 2–4 days
Moderate Intense headache, Cyanosis of the skin and mucous mem-
stunning condition, branes with peculiar grey-slate tint. Not
sometimes faint, infrequently enlarged, somewhat tender
marked muscular liver is palpated. There are slight dila-
weakness tation of the border, dull sounds and
tachycardia in the cardiovascular sys-
tem. The neurologic condition is char-
acterized by tenderness of the nervous
trunks, flaccid reaction of the pupils.
The blood is chocolate-brown. The labo-
ratory tests reveal 30–40 % methemo-
globin in it. Elevated blood viscosity,
reduced ESR, sometimes moderate neu-
trophilic leukocytosis. Hypoxia deve-
lops. The duration of clinical manifes-
tation is 5–8 days
Severe — Conscious disturbances as stupor and
even coma. Not infrequently there are
convulsions. The pupils are dilated, no
reaction to the light. There are no ref-
lexes. Dramatic cyanosis of the mucous
membrane and skin with slate tint.
Subicterus of the cornea. Dilatation of
the heart borders with dull sounds. Con-
siderable tachycardia and arterial hypo-
tension. The liver is enlarged and ten-
der. Elevated amount of direct bilirubin
in the blood. The blood is thick, visco-
tic, chocolate-brown with 60–70% of
methemoglobin, there are a lot of Heinz-
Erlich corpuscles. Test for paraamino-
phenol is negative

78
 Table 5.4. Measures in treatment
and prophylaxis of poisoning with MHFs

N Measures Aim
1. To take the man from the gas atmo- To prevent further penetration of the
sphere gas into the organism through the
respiratory organs
2. To take off the clothes and wash the To prevent further penetration of
skin with warm water MHFs through the skin
3. To use oxygenotherapy To struggle against respiratory and
hemic hypoxia
4. Intravenous dripping of solutions: — For disintoxication and diminution
physiologic 400.0–500.0 ml or he- of blood viscosity
modesis 500.0 ml or 5% glucose
400.0–500.0 ml
5. Intravenous stream introduction of To achieve demethemoglobin effect
20–30 ml of 40% glucose solution
6. Plasmapheresis For disintoxication
7. Cardiac drugs stimulating respiratory To improve condition and function
centres, neuropsychotropic drugs of the corresponding organs and
systems

POISONING WITH
HYDROGEN ARSENIDE
Hydrogen arsenide (HA) is a colourless gas, without smell but at
moderate temperature it is rapidly decomposed with a garlic smell.
It is very important to purify zinc, iron and some other metals from
arsenic. It is known that technician sulfuric and hydrochloric acids have
some amount of arsenic in their composition.
It accounts for accidents in getting hydrogen at the chemical laborato-
ries as well as production processes when interacted reaction, of mineral
acids with metals are used: in galvanoplastics, tinning, soldering, produc-
tion of anilin dyes, benzidine, acetylene, silver extraction from the zinc
dust, etching of the sheet iron for further covering with zinc or tin. There
may be cases of poisoning in cleansing of the tanks with sulfurous acid,
in submarines as a result of HA appearance in accumulator premises where
arsenic is in lead-antimonium alloy or in careless storage of arsenide prep-
arations, which are in insecticide groups.
The maximum permissible HA concentration in the air of work premis-
es is 0.3 mg/m3.

79
 There are cases of everyday poisoning with HA which is caused by
arsenic in blinds or oil dyes. HA is emitted into the air when moisture
and mould fungi appear on such surfaces.
The onset of acute poisoning is sudden as the contact with poison may
be imperceptible. This poisoning is complicated by the fact that charac-
teristic garlic smell appears only after decomposition with formation of
distilarsine when the patient already inhaled a toxic dose of poison.
The latent period depends on concentration of poison, duration of the
contact, individual reaction of the organism. It lasts from 10–20 min to
3–8 hrs (in some cases even to 24 hrs). Acute intoxication is differentiat-
ed by degree of severity (Table 5.5).

Table 5.5. Differentiated diagnosis of intoxication degree

with hydrogen arsenide
Degree of Symptoms
intoxication Subjective Objective
Mild Weakness, head- Subicterus of the cornea and skin. Bloody
ache, tiredness, urine. Jaundice and bilirubinemia in several
nausea, vomiting, days. Diminishing of erythrocyte number and
pain in the joints elevation of reticulocytes. Recovery is in a few
and back days, as a rule, not later than 1.5–2 weeks
Moderate Bad headache. In- Chillness, elevation of temperature to 38–39°C,
creasing pain in vomiting. Dark-brown urine. As a rule, jaundice
the joints and is in 6–12 hrs and has a bronze tint. Bilirubin
back, chest, upper increases to 0.2–0.025 g/l. The amount of re-
stomach, right ticulocytes increases to 100%, basophilic gran-
subcostal area. ular erythrocytes appear and leukocytosis with
Parasthesia increased amount of neutrophils and left shift.
Reverse development lasts 4–6 weeks
Severe Very intense head- Chill, fever to 38–39°C, vomiting, already du-
ache, pain in the ring the first hrs the urine becomes brown and
back, drowsiness contains a large amount of restored hemo-
globin. Protein is detected in 20–30%. In fu-
ture (on the 2nd day) progressive hemolysis
develops. The bilirubin number in blood in-
creases. There is a lot of urobilin in the urine.
At the end of 2–3 days there are symptoms
of hepatic affection, which become enlarged
and tender. In progressing course of the di-
sease, there develops renal failure with oligu-
ria and increased level of residual nitrogen to
1 g/1 and higher. In further progress there is
no excretion of urine, uremia develops and
the patient dies. Death is often at the end of
the 1st week

80
 Treatment and Prophylaxis of Poisoning
with Hydrogen Arsenide
The poisoned persons should be immediately hospitalized. They need
rest. They should have a lot of liquid. Transfusion of blood and blood
substitute should be made. Long-term inhalations of oxygen are adminis-
tered. Diuretics are used when there are no signs of severe affection of
the kidneys. When there is renal failure plasmapheresis and hemodialisis
are used. Parenteral intake of unitiol is necessary during the first hours.
Prophylaxis of HA poisoning in production consists of good control of
arsenic use as well as effective airing of the working places.

TESTS
1. What contents of HbCO arises in the blood at the carbon oxide acute
intoxication of moderate severity?
A. < 20–30%.
B. < 5%.
C. 35–40%.
D. 40–50%.
E. 10–20%.
2. What are the main preventive measures on warning of CO intoxi-
cation?
A. Special clothes.
B. Vaccination.
C. Encapsulating the processes connected with CO.
D. Ventilation.
E. Cessation of contact with the factor.
3. A patient M., 32 years old, occupied at production of viscous fi-
bers, complains of headache, syncope, sometimes vomiting. Objective:
shaky gait, tactile hallucinations.
What pathology is it necessary to think of?
A. Acute intoxication of carbon bisulfide, mild form.
B. Acute intoxication of carbon bisulfide, severe form.
C. Chronic intoxication, the 1st degree.
D. Chronic intoxication, the 2nd degree.
E. Chronic intoxication, the 3rd degree.

81
 Chapter 6
ORGANIC SOLVENTS

Solvents are simple organic substances that are (a) liquid at room tem-
perature and under standard atmospheric conditions, (b) relatively nonre-
active, and (c) able to dissolve a wide range of organic compounds (i.e.,
lipophilic). Most solvents are quite volatile. While exceptions to this de-
finition can be found, it is applicable to the majority of solvents used in
industry.
Solvents may be used for the selective dissolution of one substance
from a mixture (i.e., chemical extraction), for reduction of the viscosity
of another substance, or as feedstock for the production of synthetics. Some
solvents, such as certain alcohols as well as gasoline and other aliphatic
compounds, are used as fuels. A great variety of organic solvents are cur-
rently in use in industry. Commonly used organic solvents include the
aliphatic, cyclic, aromatic, halogenated, ketone, aldehyde, alcohol, and
ether classes. Solvents are constituents of, or are required in the produc-
tion of, a wide variety of products, including paints, varnishes and other
coatings, paint removers, fuels, glues, dyes and printing inks, degreasers
and dry cleaning agents, plastics, agricultural products, and pharmaceuti-
cals.
Solvents affect the nervous system, liver, kidneys, and skin. Several
are known human carcinogens; others are animal carcinogens suspected
of possessing carcinogenic activity in humans. The acute neurologic ef-
fects are related to the anesthetic property of solvents, manifesting as tran-
sient symptoms such as dizziness and light-headedness. A chronic, irre-
versible solvent syndrome that can include loss of intellectual function
has been described. Solvents have a wide range of potency for the induc-
tion of liver disease. Classically, the halogenated hydrocarbons are ca-
pable of inducing fatty changes and cirrhosis. The renal toxicity of sol-
vents includes both acute tubule necrosis and glomerulonephritis. Con-

82
tact dermatitis can occur in the setting of solvent exposure and is due
to defatting of skin that has been in contact with organic solvents. Se-
lected solvents have been related to cancer of the hematopoietic sys-
tem and the lungs.

EXPOSURE
Because solvents are found in a wide range of products and processes,
many workers are at risk of exposure. Solvent exposure is common among
painters and others involved in surface coating or finishing, degreasers,
printers, dry cleaners, petrochemical and refinery workers, and fiberglass
laminators. In Western Europe in 1980, 43% of all organic solvents were
used in paint and other surface coatings, 10% — for metal cleaning, 8.1%
— in household products, 6.7% — in adhesives, 6.1% in pharmaceutical
manufacturing, 3.9% — for dry cleaning, and 20% — for other uses. A
detailed evaluation of organic solvent different solvents were used in in-
dustry, most commonly ethanol, gasoline, toluene, isopropanol, and ace-
tone. In a related study, the highest exposures in Denmark were found to
occur in the printing and chemical industries. It is important to note that
many workers are at risk for solvent exposure, not just those in trades
with known widespread exposure. For example, an automobile mechanic
may be exposed intermittently to solvents if the work requires cleaning
parts in a solvent bath, a common procedure in mechanical repair.
Most occupational solvent exposure is to solvent mixtures. Indeed,
many solvents are provided as mixtures-paints, thinners, mineral spirits,
kerosene, jet fuel, gasoline, and white spirit, the common name for a sol-
vents mixture composed of aliphatics and aromatics. The frequent use of
solvents is problematic when estimating solvent exposure or attempting
to establish permissible limits.
Some authors distinguish two types of work activities, application and
process, in occupational exposure to solvents. Application work involves
the creation of an open surface from which solvents evaporate. It is usu-
ally associated with intermittent high-level exposure. Painting and degrea-
sing are examples. Solvent exposure in these settings can be highly varia-
ble and is related to both the work setting and ventilation, work in con-
fined spaces producing especially high and potentially acutely dangerous
levels. Process work is often found in the petrochemical and pharmaceu-
tical industries, where solvents typically are enclosed to reduce occupa-
tional exposure and prevent loss of product. In these settings solvent ex-
posure occurs during leaks or other failures of the enclosure system, pro-
duct transfer, or maintenance and repair.
83
 Estimation of occupational exposure to solvents is problematic because
(a) large variations in individual exposure can occur during the workday,
with periods of high exposure interspersed with periods of low exposure;
(b) much variability of exposure can exist between individuals, even those
performing the same tasks; (c) there is potential for multiple routes of
entry; (d) personal protective equipment may be used; (e) solvents are
commonly used mixtures. Several methods are available for estimating
occupational exposure to solvents, including environmental monitoring,
biologic monitoring, and semiquantitative retrospective exposure estima-
tion. The choice of methods depends on the exposure situation and the
goals of the exposure assessment activities.

ENVIRONMENTAL
BIOLOGIC MONITORING
Environmental monitoring involves measuring the concentration of
solvent vapor in ambient air available for respiratory uptake by workers.
Both direct reading and sampling methods are available. Direct reading
equipment includes indicator tubes, portable gas chromatographs, and
portable infrared analyzers, among others. This method of assessing ex-
posure is most useful when the composition of the airborne solvent con-
taminants is well known. Sampling methods include the use of grab sam-
ples, collection of time-weighted average samples, use of solid adsorbents,
and diffusion badges. Environmental measures of exposure can be ob-
tained from fixed locations at the work site and are called area samples.
Alternatively, breathing zone samples can be obtained by requiring the
worker to wear a portable device that samples air near the nose and mouth.
Breathing zone samples are considered more representative of individual
exposure than area samples. Environmental monitoring can be performed
for virtually any solvent in air.
Solvent uptake depends on several factors in addition to the concen-
tration of solvent in air, including both dermal uptake and work load. A
disadvantage of using environmental monitoring as the sole index of ex-
posure is that the contribution of these other factors to solvent uptake is
not measured, and therefore the actual dose may be poorly estimated.
Biologic monitoring is the evaluation of the internal exposure of the
organism to a chemical agent (i.e., the internal dose) by a biologic me-
thod. “In practice, this means measuring the substance itself or its metabo-
lites in various biologic media like blood, urine, expired air, hair, adipose

84
tissue, etc.” Biologic monitoring methods have been described for a variety
of industrial solvents, including benzene, toluene, xylene, styrene, trichlo-
rethylene, tetrachlorethylene, trichlorethane, and dimethylformamide. The
advantages of biologic monitoring are that (a) it accounts for all routes of
absorption, (b) nonoccupational exposures are also assessed, and (c) in-
dividual differences in the rate of uptake due to either use of personal
protection or differential uptake secondary to work load or other factors
are accounted for. The disadvantages of biologic monitoring include
(a) the need to obtain biologic media from workers, (b) limited under-
standing of the association between biologic exposure measures and work-
er health, and (c) the limited number of solvents for which biologic meas-
ures are available.
In epidemiologic study of the health effects of solvent exposure, it is
often the case that neither environmental nor biologic exposure informa-
tion is available. Frequently, exposure has occurred to a variety of sol-
vents under variable conditions of exposure. Furthermore, measures of
current exposure, environmental or biologic, may not represent past or
cumulative exposure. In this circumstance the duration of exposure is of-
ten used by investigators as a substitute for actual total exposure. Typi-
cally, this variable is closely correlated with age, and it may be a con-
founder in exposure-effect analyses. Recent attempts have been made to
develop a solvent exposure index for painters that utilizes information
obtained by questionnaire in combination with a weighting scheme for
factors that modify individual exposure, including respirator use, method
of paint application, and ventilation.
With the exception of styrene, it is common for workers to be exposed
to mixtures of solvents. This fact adds another level of complexity to the
assessment of solvent exposure, as different solvents have different toxic
potency. In an attempt to develop classification schemes for mixed solvent
exposure that are more accurate than simple solvent-years, some authors
have utilized a summary measure called the hygienic effect. The hygienic
effect is the sum, for all solvents present in a mixture, of the actual expo-
sure to each solvent divided by its maximum permissible exposure. The
assumption underlying this index is that the health effect at the maximal
permissible exposure level is equivalent for all solvents and that no syner-
gy of effect occurs. He concluded that the assumption of “additive effects
in the case of chemicals that share similar action in toxicity” was more ac-
curate than were assumptions of independent action, potentiation, or anta-
gonism, a conclusion that tends to support the hygienic effect concept.

85
 TOXICOKINETICS
Inhalation and percutaneous absorption of solvents are the two routes
of entry relevant to occupational medicine. Respiratory uptake of solvents
depends on solvent concentration in inhaled air, the blood-air partition
coefficient, alveolar ventilation, pulmonary perfusion, and the duration
of exposure. Because both alveolar ventilation and pulmonary perfusion
are functions of physical exertion or work load, manual labor can cause
substantial variation in solvent absorption. Pulmonary uptake occurs via
simple diffusion.
Dermal uptake is important only when liquid solvent is in contact with
the skin, and it may be the predominant route of entry for solvents of low
vapor pressure such as the glycol ethers. It is dependent on the surface
area of the skin in contact with solvent, skin thickness and physical charac-
teristics (cuts, abrasions, disease), and the duration of contact. Percuta-
neous absorption of solvent vapor is negligible.
The distribution of unchanged solvent in the body is a function the
solvent’s differential affinity for various target tissues, usually a function
of the lipid content and vascularity of the tissue or organ. Metabolism of
solvents occurs mainly in the liver and is typically mediated by the cyto-
chrome P-450 mixed-function oxidase system. A water-soluble conjugate
is produced that is subsequently excreted in the urine or bile. Biotrans-
formation usually results in a biologically less active metabolite; how-
ever, it can produce a metabolite of greater toxicity than the parent com-
pound, as in the case of metabolism of methyl-n-butyl ketone (MnBk) to
2.5-hexanedione, a peripheral neurotoxicant.
A great deal of recent research activity has concentrated on the devel-
opment of pharmacokinetic models of solvent exposure. In these models,
the body is represented as a set of compartments, and the interactions
between compartments are described with differential equations. Such
models may be useful for predicting the concentrations of solvents in va-
rious body tissues, and they also allow more precise estimation of dose-
effect relationships. Models of increasing complexity are required when
exposure to solvent mixtures is considered, when sources of variability
such as work load, body build, liver function, and renal function are con-
sidered, when chronic toxicity is the outcome of interest and tissue repair
processes mitigate the toxic effect of the solvent, or when bioactivation
or repair mechanisms can become saturated. Pharmacokinetic models re-
quire extensive validation prior to acceptance.
Solvents are eliminated by exhalation of the unchanged parent com-
pound or by urinary and biliary excretion of either the unchanged parent
compound or its metabolites.

86
 WORKER PROTECTION
A hierarchical approach is recommended for the reduction of work-
ers’ exposure to solvents. The initial step is to substitute less toxic sol-
vents for more toxic ones. Substitution of toluene for the carcinogen ben-
zene and of methylisobutyl ketone for the neurotoxicant MnBk are exam-
ples of this approach. In addition, changes in use in the paint industry
from solvent-based paints to both water-based paints and solventless pow-
der coatings represents substitution or elimination of potential solvent
exposure.
In addition to the substitution of safer solvents for more toxic ones,
effective ventilation and enclosure of solvent-based processes is useful
for reduction of solvent exposure. The spray booth found in many spray-
finishing facilities represents such a mechanism, both to isolate the spray-
finishing process from uninvolved workers and to establish an environ-
ment in which air flow directs solvent vapors away from the breathing
zone of the involved worker.
Respirators, either air-supply or air-purifying, are the least effective
means of reducing workers’ exposure to solvents. In addition, their use
requires a comprehensive respirator program, including worker education,
evaluation of worker fitness for use, fit testing, and regular maintenance.
Because some solvents are readily absorbed through the skin, an ef-
fective worker protection program must include measures to prevent skin
contact. Gloves are often used and can be effective. However, many are
permeable to a variety of solvents, so gloves must be selected carefully.
Barrier creams, the least effective method of reducing percutaneous ab-
sorption of solvents, are not recommended. In addition to gloves, reduc-
tion of percutaneous exposure includes washing areas of skin contact with
soap and water and removing solvent-contaminated clothing to prevent
prolonged skin contact.

EFFECTS ON THE NERVOUS SYSTEM

Neurotoxicity induced by exposure to organic solvents has emerged
as one of the most important issues in occupational health. Substantial
concern stems from the essential life functions performed by the nervous
system as well as the fact that damage to it may be irreversible. Although
much work has been done, substantial uncertainty still exists, particular-
ly with regard to the effects on the central nervous system of long-term,
low-level exposure to solvents.

87
 Solvents can cause depressant intoxication following acute exposure,
which appears to be related to physical or chemical interactions with mem-
branes or neurotransmitters. Long-term heavy exposure to solvents may also
cause persistent, potentially irreversible impairment in cognitive function
and affect, which may be associated with structural changes in neural
tissue.
Solvents may exert their primary effect on the central nervous system
(CNS), the peripheral nervous system (PNS), or both. CNS effects are
typically investigated with behavioral tests or electrophysiologic evalua-
tions. Information about the effects of occupational solvent exposure on
the PNS has come from studies that utilize clinical evaluation, electro-
physiologic examination, and histopathologic examination of biopsy spec-
imens. The effects of occupational solvent exposure on the PNS are more
clearly defined and easier to identify than those of the CNS, owing to the
relative simplicity of both the structure and function of the PNS.

Peripheral Nervous System

Widespread agreement exists that the solvents n-hexane, MnBK, and
carbon disulfide cause in humans peripheral neuropathy of the distal ax-
onal type. Other solvents suspected of having peripheral nerve effects in-
clude styrene and tetrachloroethylene. In this section discussion is restric-
ted to the peripheral nerve disorder induced by the hexacarbons n-hexane
and MnBK. An excellent review of hexacarbon-induced peripheral neu-
ropathy is provided by Schaumburg and co-workers.
The hexacarbon solvents n-hexane and MnBK have been used mainly
in thinners, glues, paints, and specialized printing materials. The occupa-
tional toxicity of the hexacarbons was first recognized in the 1960s when
an outbreak of peripheral neuropathy occurred in a shoe factory in Japan.
Occupational disease has usually occurred among workers who use glues
containing hexacarbons. Nonoccupational cases are mostly restricted to
the deliberate inhalational abuse of glues.
Exposure to n-hexane and MnBK cause changes in peripheral nerves
characterized initially by axonal swelling and focal demyelination in the
distal regions of the longer, larger axons. With progression, degeneration
of the entire axon occurs distal to the site of axonal swelling.
Both n-hexane and MnBK share a common metabolite, 2.5-hexanedione,
universally believed to be the peripheral neurotoxicant responsible for hexa-
carbon-induced peripheral neuropathy. This substance has been shown in
animals to produce in peripheral nerves pathologic changes that are virtu-
ally identical to those caused by administration of n-hexane and MnBK.

88
 In the occupational setting the onset of symptoms is usually gradual.
Deliberate inhalational abuse is associated with a more rapid onset of signs
and symptoms and can lead to disabling disease within 2 months. The
initial complaint is usually symmetric numbness of the fingers and toes.
Loss of cutaneous sensibility to light touch, vibration, pin prick, and tem-
perature are present on physical examination, as are proprioceptive ab-
normalities and loss of the Achilles tendon reflex. Severe disease can in-
clude motor weakness and atrophy.
Routine clinical laboratory test results are normal in patients with hex-
acarbon-induced peripheral neuropathy. Electrophysiologic evaluation
discovers symmetric distal electromyographic abnormalities consistent
with denervation as well as mild to moderate slowing of both motor and
sensory nerve conduction velocity.
A characteristic feature of hexacarbon-induced peripheral neuropathy
is the tendency for the disease to progress for up to 4 months following
cessation of exposure. There are no specific treatments, and the degree of
recovery is proportional to the severity of disease. Hexacarbon-induced
peripheral neuropathy is indistinguishable from other toxic and metabo-
lic neuropathies, so a careful occupational and social history is required
to identify the causative agent.
Central Nervous System
A great deal of controversy exists regarding the toxic effects of sol-
vents on the CNS. Much of the controversy is probably attributable to the
use of confusing terminology and inconsistent diagnostic criteria to de-
scribe CNS impairment. Fortunately, some movement toward standardi-
zation of terminology used to describe the effects of solvents on the CNS
has been made by the World Health Organization (WHO) and others. The
first basic distinction in the classification scheme proposed by the WHO
is acute versus chronic. Acute effects are graded as mild (acute intoxica-
tion) or severe (acute toxic encephalopathy). Chronic effects were classi-
fied as mild, consisting mainly of affective changes and loss of concen-
tration (organic affective syndrome); moderate, with some impairment of
neurobehavioral functioning (mild chronic toxic encephalopathy); or se-
vere, with significant loss of intellectual function (severe chronic toxic en-
cephalopathy). A second classification scheme is similar, except that spe-
cific names for the classifications are avoided (type 1, 2, and 3 are used
instead) and the mild chronic condition is subdivided into those having
primarily affective or primarily cognitive dysfunction.
Acute effects of exposure to solvents are pharmacologic and their in-
tensity is generally proportional to their concentration in the brain. There
89
may be initial euphoria and disinhibition. Higher intensity exposure may
result in prenarcosis symptoms such as dizziness, nausea and vomiting,
incoordination, paresthesia, increased salivation, and tachycardia. The
symptoms are generally transient, disappearing quickly after exposure is
terminated. Overexposure can lead to seizures, coma, and death in severe
cases. The likely mechanism is anoxia following depression of central
control of respiration.
Severe cases of overexposure to solvents are not common under nor-
mal working conditions. Poisoning by simple chlorinated solvents appears
more common than by aromatic solvents, and younger workers appear to
be at greater risk than older ones. About half of all reported cases (loss of
more than 3 days’ work) resulted in loss of consciousness, and fewer than
5% were fatal. There have been numerous case reports of accidental poi-
soning to a variety of alcohols, acetates, and ketone solvents, but such
cases are rare, perhaps owing to the respiratory irritant qualities of these
solvents.
Some cases of acute industrial poisoning may be the result of volatile
substance abuse (VSA), but the frequency of VSA among solvent-exposed
workers is unknown and presumed to be low. The overwhelming majori-
ty of VSA cases are teenagers abusing solvents recreationally. Adhesives
are the most abused products, and toluene is the solvent detected most
frequently in the blood. Voluntary inhalation of gasoline carries additio-
nal hazard, since it may contain tetraethyl lead and ω-hexane.
Subclinical effects of acute exposure to solvents in humans can be stu-
died in the laboratory under experimental control. It is not ethical to ex-
pose humans to agents or concentrations that are expected to produce se-
vere or lasting effects, so this type of study yields information only on
mild, transitory effects.
The most-studied solvents have been toluene, xylene, styrene, trichlo-
roethylene, perchloroethylene, and methylene chloride. These studies have
typically shown, at most, subtle effects of short-term exposure at the cur-
rent exposure limit values. The acute effects of most solvents are narcot-
ic; thus, performance decrements on tests of attention and reaction time
have been reported most often. In addition to cognitive tests, quantitative
measurement of postural stability may be a sensitive outcome for assess-
ment of acute effects of solvents on the nervous system.
The nonspecific effects of long-term exposure to solvents range from
a general negative affective state, to a subtle reduction in functional re-
serve capacity to perform well when fatigued or in a distracting environ-
ment, to mild slowing of psychomotor performance, to memory distur-
bance, and finally to severe intellectual deficits. The most severe condi-
90
tion, which has been called psychoorganic syndrome, presenile demen-
tia, and severe chronic toxic encephalopathy, is also the most controver-
sial. Although the existence of chronic solvent encephalopathy has been
questioned, experts now generally agree that it occurs but do not agree
on its prevalence. The extent to which these differences reflect differen-
ces in diagnostic criteria, past exposure, or other host factors is unknown.
A great number of epidemiologic investigations of CNS outcomes
among various solvent-exposed groups have been conducted. Several in-
ternational conferences have been held, and one critical review from a
conservative perspective has been published. It is beyond the scope of
this chapter to review all these studies. Rather, an orientation to the avail-
able literature and a discussion of the relevant issues are provided.
The epidemiologic studies have been either registry-based studies of
neuropsychiatric disability or cross-sectional studies comparing exposed
and unexposed groups for differences in prevalence of symptoms, neu-
robehavioral performance level, or prevalence of abnormality on neuro-
logic or neurobehavioral tests. The results have been almost as heteroge-
neous as the exposures and the methods used to assess outcome. The reader
is referred to a sample of well-conducted epidemiologic studies of multi-
ple neurologic outcomes among solvent-exposed workers.
Neuropsychiatric Disability
A number of studies based on pension or disability registries in rela-
tion to solvent exposure have been published. In general, risk of disabili-
ty award on the basis of neuropsychiatric illness was found to be elevat-
ed about twofold among solvent-exposed groups such as painters and floor
layers relative to comparison groups such as carpenters and electricians,
although there have been some exceptions to this trend. In addition to
registry based studies, case-control studies of the association between oc-
cupational solvent exposure and (a) psychiatric disorders requiring hos-
pitalization, (b) medical disability retirement resulting from chronic neu-
rologic and psychiatric disease, and (c) organic brain damage have been
published. Only in the study of organic brain damage was a significant
association with solvent exposure observed. Interestingly, an interaction
with alcohol consumption was observed, suggesting that alcohol consump-
tion may modify (increase) the adverse effect of occupational solvent ex-
posure on the central nervous system.
Symptoms
The rates of reporting of some symptoms were elevated above the rate
reported by comparison groups in the vast majority of published epide-
miologic studies of solvent-exposed workers. Those symptoms most of-
ten elevated were fatigue, irritability, depression, headaches, poor con-
91
centration, and forgetfulness. Terms such as neurasthenic syndrome and
organic affective syndrome have been used to label this constellation of
symptoms among solvent-exposed workers. Persistent expression of these
symptoms has led some investigators to speak of personality changes or
personality disturbances, which have been assessed with standardized per-
sonality tests.

Neurobehavioral Tests
Tests of neurobehavioral function are aimed at noninvasively assess-
ing the functional integrity of the CNS. Many standardized neurobehav-
ioral tests have been used to assess CNS function in solvent-exposed work-
ers. Because of the complexity of the human nervous system and the at-
tendant wide range of functions that can potentially be affected, sets, or
batteries, of tests are usually administered to the subjects in these stu-
dies. It is generally accepted that the tests administered should sample
from the perceptual, motor, psychomotor, learning-memory, attentional,
and affective functional domains.
In the last 15 years at least 16 epidemiologic studies of painters (car,
industrial, construction, and combinations of the three) and four studies
of paint-manufacturing workers exposed to mixed solvents have been pub-
lished. At least 11 studies of fiberglass fabrication workers exposed al-
most exclusively to styrene and at least four studies of printers exposed
primarily to toluene have been published. Many other epidemiologic stud-
ies of heterogeneous groups of solvent-exposed workers have been re-
ported. Neurobehavioral performance was reported to be poorer in the sol-
vent-exposed groups than in the referent groups in most of these studies.
The findings are far from consistent, however. Some studies have failed
to observe differences in neurobehavioral performance level between sol-
vent-exposed and referent groups, and even when differences between
exposure groups were observed, the pattern of differences was often in-
consistent across studies of presumably similar occupational groups. Dif-
ferent tests were administered in different studies, and tests intended to
measure the same functions, or even those bearing the same name, were
sometimes quite different in practice. Also, it should be noted that decre-
ments in performance on neurobehavioral tests are nonspecific; perform-
ance is affected by a number of factors not related to exposure (e.g., age,
education, native intellectual ability, and the motivation of the subject).
Furthermore, the functional significance of performance differences be-
tween exposure groups (e.g., a mean difference in reaction time of 20 mil-
liseconds) is not always apparent. Dose-response relationships have not
been observed in many investigations, probably owing to imprecise esti-
mation of exposure to the neurotoxic agents.

92
 Other Tests
Testing of three sensory systems — olfactory, auditory, and visual —
that may be early targets for solvent toxicity have received attention re-
cently. Although a Swedish study failed to show differences in smell iden-
tification between painters and referents, loss of hearing has been asso-
ciated with occupational exposure to solvents. In one study of self-reported
hearing difficulty, a significant association was observed with self-reported
occupational solvent exposure. Authors of another study, in which audi-
ometry was performed to characterize auditory function, observed a strong
effect of solvent exposure on hearing. In addition, a statistically signifi-
cant interaction between solvent exposure and noise exposure was ob-
served. Several reviews of the animal and human evidence in support of
this hypothesis are available. Deficits in performance of a simple color
vision test have been reported among several solvent-exposed groups;
however, these results have not been replicated in other investigations.
Changes in visual constrast sensitivity have also been reported for sol-
vent-exposed microelectronics workers and a series of solvent-exposed
patients.
Quantitative measurement of postural stability, or posturography, has
been employed as an index of highly integrated CNS and PNS activity
and findings have differed for solvent-exposed and referent groups.
Electrophysiologic outcomes such as electroencephalography and evoked
potentials have been shown to differ on a group basis between solvent-ex-
posed and referent groups. These methods are objective, but the findings
are nonspecific and their relevance to health is usually unknown.
Computed tomography (CT) has been used as an index of cerebral atro-
phy among solvent-exposed workers and patients, but the results of such
studies have been mixed. In addition to CT methods, several papers have
been published in which single photon emission computed tomography
(SPECT) was performed on solvent exposed subjects. Unfortunately, these
studies are of poor methodologic quality, which severely limits inferenc-
es that can be made from them.

Effects of Solvents
Acute tubule necrosis (ATN) is a potentially life-threatening renal dis-
order characterized by azotemia and oliguria. It is one cause of acute re-
nal failure. Short-term, high-level exposure to selected solvents is uni-
versally accepted as a cause of ATN. Solvents that have been described
as causing ATN include the halogenated hydrocarbons (especially carbon
tetrachloride), petroleum distillates, ethyiene glycol, ethylene glycol ethers,
93
diethylene glycol, dioxane, and toluene. ATN has been reported to follow
both intentional inhalational exposure (volatile substance abuse) and un-
intentional occupational inhalational exposure. In addition, ATN has been
described following dermal exposure (i.e., hand washing) to diesel fuel.
The mechanism of solvent-induced tubule damage is poorly understood.
Solvent-induced ATN is not associated with glomemlar disease.
When it occurs, ATN shortly follows solvent exposure, so the asso-
ciation with exposure is usually easy to establish. No studies are available
in which the risk of solvent-associated ATN is estimated. Some authors have
concluded that the risk of ATN associated with solvent exposure is low
because few reports of solvent-induced acute renal failure are available
despite the widespread use of solvents. Although in the past ATN was
universally fatal, recovery is common now that renal dialysis is readily
available. After the initial tubule changes associated with ATN have oc-
curred, tubules regenerate in approximately 3 weeks. While complete re-
covery is possible, renal insufficiency may persist.
Glomerulonephritis is a disorder characterized by, either individually
or in combination, hematuria, proteinuria, reduced glomerular filtration
rate, and hypertension. It is caused by alterations in the structure and func-
tional integrity of the glomerulus. Glomerulonephritis is the most com-
mon renal disease following long-term exposure to solvents.
Several comprehensive reviews of the literature relating solvent expo-
sure to glomerulonephritis are currently available. All include a discussion
of the many case reports of individual patients or series of patients with
glomerular disease who have a history of exposure to solvents. Agree-
ment exists that the results of these case series, while indicating the need
for additional research, are not conclusive. In addition, they review the
epidemiologic literature examining the association between glomeruloneph-
ritis and solvent exposure. Virtually all of the epidemiologic studies of
the relationship between overt glomerulonephritis and solvent exposure
have used a case-control design. One cross-sectional study of relevance
to this issue examined both serum antiglomerular basement membrane
and laminin antibody levels in relation to occupational solvent exposure.
The first comprehensive review included an evaluation of six studies
in which a case-control design was used to determine whether glomeru-
lar disease was associated with solvent exposure. In five of the six stu-
dies reviewed, a significantly larger proportion of subjects with disease
were exposed to solvents than were referents. In one study no association
was found; however, several weaknesses in design that had the potential
to bias the results of these studies have been noted: (a) inappropriate cont-
rols were used in three of the five positive studies, (b) blinding was a
94
concern in four, (c) recall bias was either possibly or probably present in
all, and (d) measures of exposure were either poorly defined or not ex-
plained in all. One study was judged to be of substantially higher quality
than the others; an odds ratio of 3.9 for the relationship between solvent
exposure and glomerulonephritis was observed in this study. Churchill
and colleagues concluded that additional studies were needed to clarify
the relationship between solvents and glomerular disease.
The most carefully performed case-control studies of the relationship
between glomerular disease and exposure to organic solvents controlled
the above-mentioned sources of bias by (a) requiring that all cases be con-
firmed by biopsy, (b) using appropriate control groups, and (c) ensuring
that interviewers were blinded to disease status of the subject. In addition,
semiquantitative measures of exposure based on interview information
obtained from subjects were incorporated into three studies. Of these five
studies, a significant association between solvent exposure and glomeru-
lar disease was observed in three. In the one cross-sectional study of cir-
culating antibodies considered to be potential preclinical indicators of
glomerulonephritis, significant associations were observed between these
indicators and occupational exposure to hydrocarbons and mixed solvents.
In summary, the body of research relating solvent exposure to glome-
rulonephritis is suggestive of an association, although not unequivocally.
However, several well-performed case-referent studies have found sig-
nificantly elevated odds ratios for exposure to solvents. Others have not,
although their statistical power was limited. No cohort studies of glome-
rular disease among solvent-exposed subjects have been published to date.
Given the low incidence of the outcome, such a study would be logisti-
cally difficult and require that a huge number of subjects be followed in
order for it to have adequate power to detect even a relatively large ef-
fect.
Several cross-sectional studies of urinary excretion of proteins and cells
in subjects occupationally exposed to organic solvents have been per-
formed. The aim of these studies was to detect renal tubule and glome-
rular dysfunction at an early or subclinical stage. Outcomes of interest
have included not only conventional clinical measures of renal function
such as proteinuria, albuminuria, and the presence of cells in urine but
also novel measures of renal function, such as excretion of low molecu-
lar weight enzymes and proteins, including I-acetylglucosaminidase, reti-
nol-binding protein, and α-microglobulin. The results of such studies have
been mixed, showing both mild tubule dysfunction and glomemlar effects.
Studies in which no effect was found on a variety of measures of re-
nal function have also been reported. In summary, some inconsistency
95
exists regarding the effects of solvents on measures of renal function
among working populations exposed to solvents. However, currently, a
preponderance of research findings suggest that mild tubular and glo-
memlar effects of unknown clinical significance are detectable in solvent-
exposed workers.
Carbon tetrachloride, tetrachlorethane, and chloroform are well-known
hepatotoxins, acutely causing hepatic necrosis and steatosis. In addition,
hepatic cirrhosis has been observed following long-term exposure to car-
bon tetrachloride. Use of these substances has diminished over the past
several decades, in large part because of their recognized hepatotoxicity
and the availability of less toxic substitutes.
Evidence on human exposure to other halogenated hydrocarbon sol-
vents such as methylene chloride, trichloroethylene, and trichloroethane
suggests that they are substantially less hepatotoxic than carbon tetrachlo-
ride and chloroform. A relative paucity of data from carefully performed
epidemiologic studies of exposed workers necessitates guarded conclu-
sions, however. Case reports of diffuse liver disease, including hepatic
necrosis and steatosis in workers exposed to trichloroethane and hepatic
necrosis with fibrosis in solvent abusers heavily exposed to trichloro-
ethylene, suggest that these chlorinated hydrocarbon solvents have hepa-
totoxic potential.
Few or no hepatotoxic effects have been observed in well-performed
cross-sectional epidemiologic studies of subjects exposed to nonhalogen-
ated solvents, including both aliphatics (kerosene, n-hexane, and others)
and aromatics (xylene, toluene, styrene, and others). These studies have
utilized conventional noninvasive laboratory methods, such as measure-
ment of serum hepatocellular enzymes, including aspartate aminotrans-
ferase (AST) and alanine aminotransferase (ALT), to identify the poten-
tial hepatotoxic effects.
Outbreaks of liver disease in the occupational setting, such as the ob-
servation of liver disease due to dimethyl-formamide at a coated-fabric
factory in the United States as well as in Taiwan and the case report of
two workers with fulminant hepatic failure following exposure to 2-nit-
ropropane, indicate that selected nonhalogenated hydrocarbon substanc-
es are capable of inducing acute and chronic liver disease in exposed pop-
ulations. These outbreaks underscore the need to identify solvents that
can induce hepatic disorders before they are made available for widespread
use.
Carbon tetrachloride and chloroform are well-recognized hepatoto-
xins. Other chlorinated hydrocarbon solvents such as trichloroethylene
and trichloroethane may also be hepatotoxic, although they appear to
96
be less potent. At this time the evidence for hepatotoxicity of these chlo-
rinated hydrocarbon solvents in humans is limited to case studies of ex-
posed workers and a few studies using relatively new methods of detect-
ing hepatic effects. Evidence from high-quality epidemiologic studies in-
corporating appropriate comparison groups indicates that the commonly
used nonhalogenated hydrocarbon solvents, including both aliphatic and
aromatic compounds, have few, if any, measurable effects on convention-
al measures of hepatic injury (i.e., serum transaminase and bilirubin lev-
els). Additional research is required to validate the newer methods that
are being used to detect hepatic effects of solvent exposure.
Because of their ability to dissolve grease and fat, cutaneous exposure
to solvents can deplete intact skin of lipids that are physiologically ne-
cessary for its functional integrity. This property of solvents results in an
irritant contact dermatitis characterized by dryness, scaling, and fissuring
of the skin, especially of the hands, in workers who have frequent dermal
contact with solvents. This occurs either because the work requires ma-
nual handling of materials wet with solvents, as in the case of manual
cleaning and degreasing, or in settings where solvents are used to wash
the hands to remove glues, plastics, or other materials from the skin. These
effects, which can be severe and require aggressive treatment with topi-
cal steroids, are reversible upon cessation of skin contact and are best
prevented by avoiding direct skin contact with solvents.
Solvents can be irritating to all mucous membranes. This results in
irritation of the eyes, nose, and respiratory tract for workers exposed un-
protected to solvent vapor. Airways irritation resulting in both bronchial
and tracheal irritation have been described among solvent-exposed groups.
The organic solvents benzene and the chloromethyl ethers, bischlo-
romethyl ether (BCME) and technical-grade chloromethyl methyl ether
(CMME), are well-established human carcinogens. Benzene is classi-
fied by the International Agency for Research on Cancer (IARC) as a
group 1 carcinogen. It causes leukemia and other malignant hematopoi-
etic disorders in humans. BCME is also classified by IARC as a group
1 carcinogen and is known to cause small cell carcinoma of the lung. It
is used as an alkylating agent and solvent during the manufacture of
polymers, ion-exchange resins, and waterproof coatings. Technical-grade
CMME contains 1% to 7% BCME. Epidemiologic studies demonstrat-
ing excess small cell lung cancer in working populations exposed to
BCME have come from the United States, the Federal Republic of Ger-
many, and Japan.
The IARC has classified the solvent epichlorohydrin as “probably car-
cinogenic to humans” (group 2A), noting that the human evidence of car-
97
cinogenicity was inadequate at the time of evaluation but that evidence to
declare it carcinogenic to animals was sufficient. Epichlorohydrin has been
used in varnish, paint, and nail polish.
The halogenated hydrocarbons have been shown to be carcinogenic in
animal systems; however, convincing human evidence is not available at
this time. Reports of increased cancer of selected sites are available for
many solvent-exposed cohorts: urologic malignancies and multiple mye-
loma in painters in New Zealand; esophageal and cervical cancers in dry
cleaners; cancers of the lymphatic and hematopoietic system, colorectal
cancer, and pancreatic cancer in commercial pressmen; lymphatic leuke-
mia in rubber industry workers exposed to carbon tetrachloride and car-
bon disulfide; and primary liver cancer in solvent-exposed workers.
The goals of the clinical evaluation of solvent-exposed patients are to
ascertain the presence of health effects attributable to solvent exposure,
determine whether preexisting or underlying disease complicates the ap-
proach to the patient, and provide guidance on exposure reduction and
periodic surveillance.
The evaluation of the symptomatic patient always begins with a re-
view of presenting complaints. When a solvent-exposed worker presents
for reasons other than current symptoms, such as periodic surveillance
examination, a review of neurologic and dermatologic symptoms should
be performed. Symptoms temporally related to exposure are a function of
the anesthetic property of solvents. Specifically, dizziness, light-headed-
ness, impaired concentration, and headache that have a temporal relation-
ship to solvent exposure are likely the result of the acute CNS effects. In
addition, unusual tiredness, sleep disturbance, appetite disturbance, mood
changes, and other vegetative signs may also be related to solvent expo-
sure, although in the absence of a close temporal association these very
nonspecific symptoms may be difficult to attribute to solvent exposure in
an individual case. Symptoms of dry, cracked, or itchy skin, especially of
the hands, should be sought. In addition to symptoms of neurologic and
dermatologic effects, symptoms of mucous membrane irritation manifes-
ting as discomfort of the eyes, nose, and throat, should be elicited expli-
citly.
Review of past diagnoses or symptoms of neurologic, renal, hepatic,
and dermatologic disease is required. The association between occupa-
tional solvent exposure and diagnosable conditions such as glomerulone-
phritis, contact dermatitis, cognitive impairment, and peripheral neuro-
pathy may have been overlooked by other clinicians. In addition, the pre-
sence of such conditions, even if they are unrelated to current solvent
exposure, may warrant more frequent medical surveillance or more aggres-
98
sive exposure reduction for individual patients. The use of alcohol or medi-
cations that can affect the target organ systems of solvents must be ascer-
tained, especially in light of increasing research evidence that toxicologi-
cally important interactions between these agents and solvents may occur.
The occupational circumstances under which the solvent exposure oc-
curred must be elicited from the patient. Clearly, this requires knowledge
not only of the job title but of daily occupational activities and the setting
in which solvent exposure occurs. Exposure from the activities of co-work-
ers should not be overlooked. An assessment of ventilation should be made,
if possible. Inquiries about enclosure of solvent-related processes, use of
hoods or other specialized ventilation, and specialty equipment such as
spray booths should be made. The specific constituents of the solvent-
containing materials used must be ascertained. This may necessitate re-
quests for material safety data sheets (MSDS) from employers, suppliers,
or manufacturers. Use and type of personal protective devices should be
determined, and an assessment of the effectiveness of the program evalu-
ated, if possible. Specific inquiry about the extent of skin contact and
measures taken to prevent its occurrence should be made. The occupa-
tional history should include a general assessment of the hygienic condi-
tions of the occupational setting, including the availability of separate
washing, changing, and eating facilities.
A complete physical examination, with emphasis on the skin and the
nervous system, should be performed. The skin, especially of the hands,
should be inspected for redness, drying, cracking, or fissuring. A mental
status examination that includes evaluation of alertness, orientation, cog-
nition, and short-term memory should be performed. Evaluation of pe-
ripheral nerve function by assessing proprioception, deep tendon refle-
xes, motor strength, postural stability (Romberg test), and cutaneous sen-
sibility to vibration, light touch, and pin prick should always be included
in the evaluation. Clinical assessment of liver size and tenderness should
be performed as it can be done quickly, although the clinician must rec-
ognize that it is not very sensitive.
Routine laboratory evaluation should be guided, in part, by the known
toxicity of the solvents. For example, liver function tests are more likely
to be of value in patients exposed to halogenated hydrocarbon solvents
than in those exposed to nonhalogenated solvents. The consumption of
alcohol must be considered when interpreting liver function test results.
Routine urinalysis and measures of renal function (blood urea nitrogen
and serum creatinine) are also reasonable for inclusion in the laboratory
evaluation of solvent-exposed workers, although, again, their utility is li-
mited by modest test sensitivity for early renal changes. The choice of
99
additional tests must be guided by the clinical presentation of the patient.
Those with complaints of persistent mood alteration or cognitive dysfunc-
tion, including memory loss, should be referred to a clinical neuropsy-
chologist for evaluation, and a complete dementia workup should be con-
sidered. Those with persistent neuritic complaints, such as numbness, tin-
gling, weakness, or pain, should be referred for neurologic consultation
or electrophysiologic evaluation of peripheral nerve function (nerve con-
duction measurement and electromyography).
The health effects of exposure to organic solvents are nonspecific.
Currently it is not known what proportion of neurologic, hepatic, renal,
and dermatologic disease in exposed populations is attributable to sol-
vents. Furthermore, the marked variety of exposures precludes sweeping
generalization. Prior to making a diagnosis of solvent-related disease, other
causes must be sought and their contribution to the current problem as-
sessed. Organic brain syndrome secondary to solvent exposure is a diag-
nosis of exclusion. Substantial difficulties in estimating attribution of end-
organ disease (e.g., peripheral neuropathy) due to solvent exposure occur
when other disorders (e.g., diabetes) present at the same time could cause
the same outcome.
Evaluation of the solvent-exposed worker provides an opportunity to
address the exposure situation for the purpose of reducing exposures and
preventing additional health effects for both the patient and co-workers.
Unfortunately, access to the workplace may be limited, and often neither
ambient nor biologic measures of exposure are available to allow quanti-
fication of the magnitude of exposure. In addition, patient confidentiality
requirements may make workplace intervention difficult or impossible.
Regardless, when the results of clinical evaluation suggest that biologi-
cally meaningful exposure is occurring, the clinician is obligated to ex-
plore avenues of exposure reduction within the confines of protection of
patient confidentiality.
Much remains unknown about the rational approach to the solvent-
exposed worker. Additional research is needed to clarify the clinical syn-
dromes caused by solvent exposure, to provide guidance for treatment,
and to attribute nonspecific outcomes to solvent exposure.

BENZENE
Benzene (С6Н 6) is the simplest and the prototypical aromatic hydro-
carbon. It is a known cause of aplastic anemia, leukemia, and lymphoma.
It is among the most widely used of all organic chemicals and has the
highest production volume of all known human carcinogens. Historical-
100
ly, benzene was produced as a by-product of coal gasification and coke
production. Today, however, it is produced principally by the petroche-
mical and petroleum-refining industries.
Benzene is a clear, colorless, noncorrosive, highly flammable liquid
with a strong and rather pleasant odor. Its low boiling point and high va-
por pressure cause rapid evaporation under ordinary atmospheric con-
ditions; the resulting vapors are nearly three times heavier than air.

Human Exposure
Benzene is used as a solvent, a degreasing agent, and as a fundamen-
tal building block in many processes in the synthetic chemical industry.
Occupational exposure occurs in the chemical, printing, rubber, paint, and
petroleum industries. Particularly heavy exposure occurs in maintenance,
clean-up, product sampling, and petroleum bulk transfer operations. Al-
though benzene’s use has recently declined in the United States and in
other industrially developed nations, data from developing countries sug-
gest that exposures there are widespread, especially in artisan work, shoe
manufacture, small chemical industries, and work involving children.
Environmental exposure to benzene is extensive, because benzene is a
constituent of both inhaled and environmental tobacco smoke. Also ben-
zene constitutes 1% to 2% of unleaded gasoline by weight, exposure oc-
curs during the pumping and handling of gasoline.
Occupational absorption of benzene occurs predominantly through in-
halation of benzene vapor. Experimental studies indicate that approximate-
ly 50% of inhaled benzene is absorbed into the body and the remainder is
exhaled. Ingested liquid benzene is rapidly absorbed through the gastroin-
testinal mucosa.
Benzene can also be absorbed through the skin. Dermal absorption is
substantially enhanced when the skin is cracked, blistered, or abraded, as
occurs in rubber workers engaged in tire building. It is estimated that a
rubber worker who produces 150 tires a day using benzene-containing
rubber solvent could absorb 6 mg of benzene through the skin; this com-
pares with an estimated 14 mg absorbed by inhalation per 8-hr day in an
atmosphere containing 1 mg/m 3 benzene vapor.

Metabolism and Mechanisms of Injury

Benzene is rapidly metabolized, principally in the liver. Its metabolic
products are excreted, mainly as water-soluble metabolites in urine, within
48 hrs of absorption. The oxidative products of benzene include phenol,
catechol, quinol, hydroxyquinol, and muconic acid.
101
 Metabolism of benzene is required for toxicity. This metabolism oc-
curs principally in the liver via the cytochrome P-450 and mixed-function
oxidase systems. Production of benzene metabolites in the liver is fol-
lowed by their transport to the bone marrow and other organs. Substan-
tial evidence indicates that benzene per se is not myelotoxic, and that its
toxicity is due to several of its metabolic products, particularly benzoqui-
none and muconaldehyde. These compounds have the ability to react with
DNA to form adducts. Benzene metabolism is quantitatively different at
different dose levels, and at low doses a relatively higher proportion of
benzene is converted to hydroquinones and other more highly toxic me-
tabolites than at higher doses; this finding suggests that linear extrapola-
tion of risk from high-dose studies may underestimate the true risk of low-
level benzene exposure.
Benzene itself is not mutagenic. However, various of its products are
mutagenic in bacterial species. Presumably, these active products such as
the quinones are involved in the causation of the chromosome damage,
with increased numbers of strand breaks, hyperploidy, and deletions ob-
served in humans and animal species exposed to benzene. It is hypothe-
sized that these chromosomal aberrations induced by benzene may lead
to inactivation of p53 or other tumor suppressor genes, and that these ge-
nomic events are involved in leukemogenesis. Recently, an association
has been suggested between benzene exposure and deletion of the long
arm of chromosome 5; this 5q-deletion is linked to myelodysplastic synd-
rome, a preleukemic condition, and the deletion is hypothesized to result
in inactivation of a leukemia tumor suppressor gene, possibly the gene
encoding pura, located at 5q31; the pura protein is involved in cell cycle
control of DNA replication. The principal screening tool for clinical as-
sessment of benzene toxicity is the complete blood count (CBC), includ-
ing a platelet count and a white cell differential count as well as a red
blood cell count, hemoglobin, hematocrit, and red blood cell indices. These
hematologic indices do not appear to be sufficiently sensitive to detect
toxic changes in workers whose exposures are within current exposure
standards. However, at high levels of exposure, benzene is associated with
significant decreases in white and red cell counts as well as in hemoglo-
bin levels. Therefore, periodic hematologic testing of benzene workers
may be useful to detect those who are exposed to higher-than-average am-
bient levels. Also, it is at least theoretically possible that periodic biologic
monitoring of workers exposed to benzene may detect any who are unusu-
ally sensitive, although such sensitivity has not been well documented.
Chromosome aberrations have been seen in several studies of workers
exposed to benzene, even at low levels. These changes consist of chro-
102
matid deletions and gaps as well as increased numbers of strand breaks
and micronuclei. The utility of these cytogenetic abnormalities as quanti-
tative screening tests for benzene exposure and toxicity is not yet estab-
lished and will require prospective epidemiologic follow-up of exposed
groups.
An important unmet need in benzene toxicology is for a stable biolo-
gic marker of exposure. There is need for a marker that better reflects
cumulative exposure over time than the measurement of evanescent lev-
els of benzene in exhaled breath or blood or the measurement of relative-
ly rapidly excreted phenol in urine.

Exposure Monitoring
Occupational exposure to benzene is assessed principally through per-
sonal (breathing zone) air sampling. Measurement of the blood benzene
level has traditionally been considered to be insensitive for occupational
exposure monitoring; however, recent studies with new high-resolution
gas chromatographic techniques suggest that blood sampling may be a
useful indicator of current benzene exposure.
Timing is very important in the determination of the blood level of
benzene because of the short half-life of the compound in blood. Mea-
surement of benzene in exhaled breath is another sensitive means of as-
sessing exposure. Approximately 50% of benzene is exhaled unmetabo-
lized; this measurement also is very time dependent.
Urinary phenol determination is a good biologic marker of recent in-
dustrial benzene exposure. Recent studies in China and Japan indicate that
there is a close quantitative relation between level of benzene vapor in work-
room air and urine phenol level. By contrast, urinary markers are not use-
ful as indicators of low-level benzene exposure in the general environment.

Toxicity
Immediate Effects
Central nervous system toxicity is the most important aspect of acute
high-dose exposure to benzene. Like many solvents, benzene is readily
soluble in lipids and rapidly crosses the blood-brain barrier to enter the
central nervous system. Low-level neurologic exposure causes headache
and nausea, whereas higher levels cause alteration of consciousness pro-
gressing to coma and respiratory arrest. Acute benzene exposure is toxic
to the liver and kidneys; elevations in the serum creatinine level as well
as in liver function enzymes and serum bilirubin can result. Benzene is

103
toxic to the skin. Direct contact may cause erythema and blistering. Long-
term direct contact removes lipids from the skin tissue and may result in
the development of a dry, scaly dermatitis. Benzene is poorly absorbed
through intact skin but is readily absorbed through cracked, dry, or fis-
sured skin. Immediate effects of ingestion of liquid benzene are local irrita-
tion of the mouth, throat, esophagus, and stomach. Subsequent absorption of
ingested benzene into the blood leads to the signs and symptoms of sys-
temic intoxication. High concentrations of benzene vapor are irritating to
the mucous membranes of the eyes, nose, and respiratory tract.

Long-Term Effects
Aplastic anemia is the classic cause of death in chronic benzene poi-
soning, and the association between benzene exposure and bone marrow
suppression has been recognized since 1897.
Leukemia in workers exposed occupationally to benzene was first re-
cognized in the 1920s. Additional case reports and case series published
from the 1920s to the 1960s repeatedly noted the association between
leukemia and exposure to benzene. All types of leukemia are observed in
reports of workers exposed to benzene. Myeloid and myelomonocytic
leukemias are the cell types most commonly seen, but also acute and chro-
nic lymphocytic leukemia are encountered. Additionally, benzene expo-
sure has been linked in clinical and epidemiologic studies to lymphoma,
including non-Hodgkin’s lymphoma and multiple myeloma.
Initial analyses of mortality in this population were primarily qualita-
tive, and they showed a significantly increased rate of deaths from leuke-
mia in workers exposed to benzene as well as a particularly striking in-
crease in leukemia mortality among workers employed for 5 or more years.
Then, in the most recent study in this series, an extensive effort was made
to examine quantitatively the dose-response relationship between benzene
and leukemia.
Benzene-induced leukemia may develop in some cases in persons who
previously have had aplastic anemia. In other cases, however, no prece-
ding aplastic anemia is seen; thus aplastic anemia does not appear to be a
necessary precursor to benzene-induced leukemia.
Prevention
The toxic effects of benzene are best prevented by replacing it with
less toxic compounds and thus eliminating exposure. There are many sol-
vents safer than benzene. If benzene cannot readily be replaced, for ex-
ample in the synthetic chemical industry where it is used widely as a

104
basic chemical reagent, it is essential to provide safety of workers. The
greatest risk of exposure in modern chemical factories is for maintenance
and cleanup workers. Also there may be substantial risk to workers en-
gaged in process sampling, laboratory analysis of process samples, and
bulk transfer operations. Protective efforts should therefore be targeted at
those specific job operations.
These early epidemiologic studies showed that occupational exposure
to benzene was statistically associated with excess numbers of deaths from
leukemia.
By merging industrial hygiene data with personnel records, cumula-
tive benzene exposures (ppm-years) were calculated for each member of
the work force. This approach provided a more directly quantitative in-
dex of exposure than analysis of length of employment and demonstrated
a strong dose-response relationship.

TESTS
1. A man, born in 1948, was hospitalized to the urological department
of regional hospital with profuse hematuria, which is accompanied with
weak pain in the overpubic area. Anamnesis data: he has been working
during 16 years at the dye-stuff production factory. Hystologically a tu-
mor is revealed in the field of the anatomical triangle of the urinary blad-
der, its construction — pupillary cancer. After additional tests — metas-
tases to regional lymph nodes. The most possible carcinogenic action of
the following factors:
A. 3, 4-benzipren.
B. Benzidine, R-naftilamine.
C. Ionizing radiation.
D. Aflatoxin.
E. Retrovirus, contained RNA.
2. A 40-year-old man works at a varnish plant, was delivered to the he-
matological department of the region hospital with complaints of fatigue,
bad headache, sickness, vomiting, weakness, imbalance, unconsciousness,
depression, pain in the thorax. Under the objective study there were re-
vealed: grey-blue colour of the skin integument and mucous membranes,
blood is chocolate-brown, disorders of coordination, seasonly — a daydream-
ing. Narrowing of the visual field. Under the laboratory exam: anemia, poi-
kilocytosis, anisocytosis, unconjugated bilirubine, leucocytosis with the left

105
shift. Increased viscosity of blood, increased amount of erythrocytes with
basophilic granules.
Which poisonous substance do these data determine?
A. Carbon oxide.
B. TEL.
C. Nitrate of mercury.
D. Amino- and nitrobenzene.
E. Phosphorus.
3. A worker of the artificial resin production, 35 years old, was hospi-
talized with complaints of a whining pain in the right hypochondrium,
weakness, fatigue, absence of the appetite, headache, sweating, pains in
joints and muscles, sickness.
Objective: bilious-brown colouration of the skin of hands, cyanosis of
the mucous membranes, painful liver at the palpation; blood test: hypo-
chromic anemia, appearance of Heinz — Ehrlich’s bodies till 3%.
What is the most possible reason of this condition?
A. Chronic intoxication by lead.
B. Chronic intoxication by nitro- and aminobenzene.
C. Chronic intoxication by metallic mercury.
D. Cancer of the liver.
E. Hepatic colic.
4. A workman of agriculture during a day inhered on the grape field,
where took part in the work on the struggle with vermins of vineyards. At
the end of a workday a man has felt a significant malaise, weakness, head-
ache, feeling of fear in the eyes. Afterwards sickness, then — vomiting,
hypersalivation, increased sweating joined. Then stomachache, diarrhea,
pain in the field of the heart appeared. Skin integument is pale, the pupils
of the eyes are dilated, spasm accomodation, weak pulsation. Pulse — 50
per min. There was observed a single fibrillar twitch of muscles of the
face, bones.
Preliminary diagnosis:
A. Nitrofenolic pesticides intoxication.
B. Urea intoxication.
C. Arsenious intoxication.
D. Chlorine-organic compound intoxication.
E. Hydrargium-organic compound intoxication.

106
 Chapter 7
INTOXICATION
BY CHEMICAL POISONS
IN AGRICULTURE

ACUTE AND CHRONIC INTOXICATIONS

WITH PESTICIDES
Pesticides are biocidal agents used to control a wide variety of organ-
isms that pose a threat to health or compete for food or other materials.
Selective toxicity is the principle of pesticide use, but because organisms
are similar at the cellular or subcellular level, adverse human health ef-
fects may occur.
The earliest pesticides included metals such as arsenic, mercury, and
lead. Other pesticides are inorganic chemicals, such as sulfur, and organ-
ic chemicals, such as nicotine derived from plants. After the discovery of
dichlorodiphenyltrichloroethane (DDT) in 1939, the world has witnessed
an unprecedented increase in the search for and production of synthetic
organic pesticides. Production of inorganic pesticides such as arsenicals
has steadily declined since the 1940s. The prolonged ecologic half-life
and lack of species selectivity of DDT and other organochlorine pesti-
cides was recognized in the 1960s. These pesticide characteristics and
concern about the effects of accumulation of organo-chlorines in human
adipose tissue caused the banning or severe restriction of most of these
agents. In their place, newer synthetic pesticides, predominantly organo-
phosphorus compounds, have been developed and are now widely used.
These agents cause less environmental damage through accumulation but
are more acutely toxic to humans and other animal species.
There are approximately 600 active pesticides ingredients, configured
in more than 45,000 formulations in use today. More ominously, toxic
organophosphates such as the nerve gas sarin have been used by terro-
rists to attack large numbers of people in cities in Japan.
Despite of temporary decrease of intensity of an agriculture, Ukraine
is still a developed agrarian country. Ripe fine crops of grain, vegetables
and fruit grow on our famous black earth. All this requires laborious work
107
and our hardworking people are ready to put the forces and soul in this
ground to yield high crops, but it appears unsufficiently.
For saving a crop it is necessary to conduct struggle with the wreckers
in agriculture. There are pesticides, used for this purpose, part of which
represent threat to health of the man if one neglects rules of work with them.
This circumstance also causes actuality of the given theme. A future
doctor should know a list of modern chemical poisons, which are applied
in agriculture, mechanism of their pathogenic influence on an organism
of a man, clinical pattern of acute and chronic poisoning, to be able to
treat injured and train the agriculture workers in methods of prophylaxis
of poisonings.
The development of a modern agriculture provides a wide use of ferti-
lizers, agents of struggle with weeds, wreckers of cultural plants.
The pesticides or agricultural chemical poisons include agents of strug-
gle with insects, originators of bacterial, fungic diseases of plants, with
rodents, chemical drugs for destruction of weeds.
The pesticides are used for pollination and plants spraying, for dry
and wet mordanting of seeds, for fumigation of ground, premises, sowing
material. Airplaines, tractor, automobile, satchel and manual sprayers and
pollinators are used for processing of plants. The mechanized methods of
pollination or spraying, in particular air, reduce an opportunity of getting
of chemical poisons on the skin, clothes and in organs of respiration of
workers. The wide circle of the people working in agriculture, workers of
depots, loaders, aviators, and also persons engaged in production of these
toxicants are exposed to immediate influence of pesticides.
The influence of chemical poisons on the nature and people is one of
the most actual problems of modernity.

Classification of Pesticides
1. Insecticides — for struggle with insects.
2. Fungicides — for treatment of plants for fungic diseases.
3. The insectofungicides — destroy both insects and originators of fun-
gic diseases.
4. The defoliants — destroy leaves of weeds.
5. Herbicides — only for destruction of weeds.
6. Bactericides — destruction of bacteria.
7. Acaricides — destruction of mites.
8. Ovicides — destruction of eggs of insects and mites.
The following pesticides are used in agriculture: chlorine-organic, phos-
phorus-organic, hydrargyrum-organic, arsenous, nitrophenol, derivants of
a carboline acid, drugs of copper and others.
108
 Occupational Exposure
Humans are exposed to pesticides in a variety of occupational settings,
including agriculture, structural pest control (e.g., buildings), public health
pest eradication programs, manufacture and formulation, transportation
industries such as railroads and trucking, the florist industry, and hazard-
ous waste treatment and cleanup. Many commercial products such as
paints, cotton, and wood products have fungicides added to prevent de-
generation. Herbicides are used heavily in maintaining roads and high-
ways in developed countries.
Assessing exposure to pesticides in an occupational setting is a com-
plex task. A worker may be exposed unknowingly to clothing saturated
with pesticides or by direct skin contact, but these amounts do not neces-
sarily predict the actual dose, or amount absorbed into the body. Absorp-
tion may occur through inhalation, ingestion, or direct absorption on der-
mal surfaces. Detailed information on rates of absorption and knowledge
of the pharmacokinetics of the compound in humans is often unavailable.
Relating the absorbed dose to human health effects is often difficult or
impossible. Work on biologic markers of pesticides may improve assess-
ment of exposure and dose.
Accurate data do not exist on the incidence of acute illnesses secondary
to pesticide poisoning, and even less is known about the chronic effects
of pesticide exposure. While most acute pesticide-related illnesses and
deaths in the past were caused by accidental agricultural exposure or at-
tempted suicides, toxicologists and clinicians today must be alert to the
illicit use of pesticides for criminal or militant activities. Health care pro-
viders must be able to recognize the immediate health effects of pesti-
cides to establish diagnosis quickly and to begin treatment early. World-
wide estimates for pesticide poisoning suggest the problem of acute to-
xicity and death is much greater in developing countries than in devel-
oped ones.
Biomagnification of organochlorine compounds in the food chain lead
to high residues, particularly in predaceous fish and birds. Elevated lev-
els of DDT (and to a lesser degree, dieldrin) in several species of birds of
prey lead to eggshell thinning and threatened species extinction. Because
organochlorine compounds are not species-specific, large populations of
animal species may be at risk of poisoning, which can lead to deleterious,
long-term changes in the diversity of ecosystems in nature. Furthermore,
pest species may develop increased tolerance or resistance to these spe-
cific pesticide compounds. Organochlorines have been largely replaced
by organophosphates and carbamate compounds that rapidly hydrolyze

109
in soil and by plants. Although organophosphates and carbamates do not
accumulate significantly in the environment, they remain extremely toxic
if used indiscriminately.
Environmental exposures to pesticides in humans most often result from
household or garden use. The World Health Organization (WHO) has es-
timated that more than 3 million cases of serious acute pesticide or insec-
ticide poisoning occur worldwide annually, the majority being caused by
organophosphates used for agriculture. There are an estimated 220,000
deaths annually from pesticides, and 99% of these are in developing count-
ries. This grim total occurs despite the fact that only 20% to 25% of the
global agrochemical use is in developing countries. The easy availability
of pesticides in many developing countries makes them a common means
of suicides.
Tolerance levels for pesticide residues in foods, the maximum residue
levels allowed when pesticides are used according to the directions on
the label, are set by the EPA. The levels are based on toxicologic studies
that attempt to balance the risks and benefits associated with the use of
pesticides on human foodstuffs.
Even though there is increasing public concern about pesticide resi-
dues in the food supply, residues detected in fresh and processed foods
are generally low. Only a small percentage are found to have levels above
tolerances, and most samples have no detectable residue. Results from
these analyses indicate that in general the dietary intake of pesticide
residues is within acceptable tolerance. When pesticides are used on
crops for which their use is not approved or are applied in an unap-
proved manner, however, outbreaks of food-borne pesticide illness may
occur.

Organophosphate Insecticides
Millions of pounds of organophosphate pesticides are used worldwide
in commercial farming, gardening, structural pest management, and vec-
tor control programs. The development of these agents derive from the
search for new chemical warfare or nerve gas agents in the 1930s. Al-
though the organophosphate nerve agents such as sarin, tabun, and VX
have not been used as insecticides, further research has shown that rela-
ted, less potent compounds can be used successfully as insecticides. The
worldwide use of these organophosphates compounds has increased over
the last 20 years, owing to increased use in the Third World and because
their use results in less severe environmental impacts than the organo-
chlorine insecticides. Because the organophosphate insecticides are less
110
detrimental to the environment, they have largely replaced the organo-
chlorine insecticides.
Examples of organophosphate insecticides include parathion, chlorfen-
vinphos, diazinon, fenmion, diamethoate, monocrotophos, and malathion.
These insecticides are commonly used in commercial farming, home gar-
dening, pest control (e.g., flies), environmental control of vectors (e.g.,
mosquitoes), and the control of ectoparasites (e.g., fleas, lice). They may
be combined with one or more other types of insecticides to potentiate
their insecticidal action.
Organophosphate insecticides are efficiently absorbed by inhalation,
ingestion, and skin penetration. Exposure by all three routes has been seen
in occupational poisonings. The degree of toxicity varies considerably,
depending on the route of exposure, and the exposure concentration and
dose. Organophosphate insecticides vary in potency. For example, the
median lethal dose (LD50) for parathion in humans is estimated to be
3 mg/kg while that of malathion is 1,375 mg/kg.
The toxic manifestations of organophosphate insecticides result from
the irreversible phosphorylation of the enzyme acetylcholinesterase (AchE)
found at the nerve-nerve synapse or nerve-muscle motor end plate where
anionic binding of acetylcholine normally occur. The loss of function of
this enzyme allows flooding of the postsynaptic receptors with acetyl-
choline, leading to a cholinergic crisis in severe cases.

Acute Signs and Symptoms

Patients acutely intoxicated with organophosphates often present with
a set of signs and symptoms. Recognition of these “toxidromes” helps
the astute clinician establish the chemical class of the toxicant quickly
and allow vital treatment to begin early. All too often, the clinician has
only a history of exposure or a toxidrome to suggest organophosphate
insecticide poisoning. The dramatic accounts of the Matsumoto sarin at-
tack in 1994 and the notorious Tokyo subway sarin attack in 1995 should
serve as valuable lessons to emergency room and hospital staff and prompt
simulated disaster drills to prepare health care providers.
The organophosphate insecticide toxidrome can develop during the
chemical exposure or be delayed some 4 to 12 hrs after exposure. The
key aspects of this toxidrome can be divided into muscarinic, nicotinic,
and central nervous system overstimulation.
Muscarinic overstimulation leads to hyperactivity of the parasympa-
thetic system, including miosis, bradycardia, and hypersecretion of sali-
vary, lacrimal, digestive, and bronchial glands. Accumulation of acetyl-
111
choline at the nicotinic synapses leads to blockade of nerve impulses in
the central nervous system, at the autonomic ganglia, and at the skele-
tal muscle-nerve junction. The latter effects lead to motor end plate dys-
function.
Nicotinic effects include muscle fasciculations that can be mistaken
for seizure, cramps, and generalized muscle weakness. Depression of respi-
ratory drive, delirium, loss of consciousness, and seizures are complica-
tions of central nervous system toxicity. The mnemonic DUMBELS (di-
arrhea, urination, miosis, bronchospasm, emesis, lacrimation, salivation)
describes the signs of cholinergic (muscarinic) excess seen with organo-
phosphate poisoning. A garlic odor may also be noted from the exposed
patient or from the container of the pesticide. Recent data have suggested
visual changes, pancreatitis, and psychiatric findings are seen with acute
organophosphate poisoning more commonly than previously recognized.
Establishing a diagnosis from acute or chronic low-dose exposure is
particularly difficult in children. The typical muscarinic and nicotinic signs
and symptoms of an acute organophosphate poisoning are often absent.
Patients may present with neurobehavorial changes, hypertonicity, and
even acute psychosis. To establish a preliminary diagnosis, clinicians
should be aware that reliable reference laboratories are capable of de-
tecting alkylphosphate metabolites of organophosphates in urine, but the
time necessary for this assay may limit its clinical usefulness.
Certain organophosphate insecticides have been associated with de-
layed and intermediate neurotoxicity syndromes. Characteristic manifes-
tations include weakness, paralysis, and paresthesias in the distal lower
extremities for the delayed syndrome, and weakness of proximal limb
muscles and muscles of respiration, and cranial nerve paralysis in the in-
termediate syndrome. Development of the delayed neuropathy is not as-
sociated with inhibition of neural or neuromuscular cholinesterases, as is
the acute toxicity. It has been correlated with initial phosphorylation or
inhibition of the neurotoxic esterase enzyme (NTE). Symptoms usually
occur within 2 to 3 weeks, with a denervation electromyographic pattern
and a progressively irreversible to slowly reversible course over 6 to
12 months. The intermediate syndrome associated with organophosphate
neurotoxicity was recently described in 10 patients.
The time of onset was between 1 and 4 days after significant organo-
phosphate insecticide poisoning, with proximal limb, neck, cranial, and
respiratory muscle involvement. The electromyogram (EMG) findings
were described as tetanic fade. Recovery took between 4 and 18 days;
seven often patients had respiratory difficulty and four often required me-
chanical ventilation. Most commonly, both delayed and intermediate neu-
112
rotoxicity have been seen in survivors of massive organophosphate in-
secticide poisonings coming from the Third World countries. Prolonged
effects of muscle blocker agents have been reported in patients poisoned
by organophosphate pesticides. Persistence of organophosphates meas-
ured in blood and in tissues at autopsy in humans has been demonstrated
particularly for the most lipid soluble agents such as penthion and me-
thidathion. The intermediate syndrome may represent delayed organophos-
phate absorption or prolonged tissue half-life.

Laboratory Findings
Confirmatory laboratory tests include measurements of plasma and red
blood cell (RBC) cholinesterase activities, which provide a measure of
the inhibition of two types of cholinesterase enzymes in vivo. However,
these studies may be available in a limited number of diagnostic labora-
tories in addition to regional poison control centers. At least six different
methods are available for measuring RBC and plasma cholinesterase le-
vels. Consequently, interlaboratory variability may be great and this va-
riability may complicate the interpretation of results.
Plasma cholinesterase (pseudocholinesterase) is produced by the li-
ver. It is a phase-reactant enzyme with baseline fluctuations due to many
variables. Falsely lowered activity may be due to chronic or acute liver
disease, chronic alcoholism, pregnancy, malnutrition, dermatomyositis, or
concomitant poisoning with carbon disulfide and organic mercury com-
pounds. Plasma cholinesterase levels decline and return faster than RBC
or “true” cholinesterase levels. The 3% of the population who are geneti-
cally deficient in this enzyme are particularly vulnerable to the neuromus-
cular blocker succinylcholine and may be hypersensitive to organophos-
phate insecticides. Regeneration of activity is normally related to synthe-
sis by the liver of new enzymes and may take 7 to 60 days to return to
levels found prior to organophosphate insecticide exposure. RBC choline-
sterase activity regenerates even more slowly because new RBCs must
be released from the bone marrow to replace those with inactivated cho-
linesterase enzyme. This slow rate of renewal (0.5% to 1% per day) can
take 60 to 90 days for RBC cholinesterase levels to return to nearly base-
line values.
Red blood cell cholinesterase is the preferred measurement for docu-
menting exposure and monitoring when exposed workers can return to
handling organophosphate insecticides. Generally, RBC cholinesterase
levels should be greater than 75% of baseline before workers are allowed
to return.
113
 Sensitive blood and urine screens for the parent organophosphate in-
secticide compounds and excreted metabolites exist but they are not rou-
tinely available and often require detailed knowledge of the specific par-
ent compound.
Symptoms of organophosphate insecticide toxicity are not usually seen
until 50% of baseline cholinesterase activity is inhibited, although this is
not a reliable threshold. The large variability in normal cholinesterase level
also makes its interpretation difficult. Cases of poisoning and even deaths
have been reported with depressions of less than 50%. Cholinesterase level
is useful in clinical evaluation, but it must be done in association with a
careful history and physical examination. Because baseline plasma cho-
linesterase levels are not usually available for an individual patient, seri-
al determinations are useful in acute exposures. No clearly reliable asso-
ciation has been established between the magnitude of serum cholineste-
rase decrease and the severity of poisoning; it is simply a marker of orga-
nophosphate intoxication or poisoning. Nevertheless, most authorities
consider mild exposure with minimal signs and symptoms to be associat-
ed with plasma cholinesterase levels 20% to 50% of baseline. Moderate
exposure, usually resulting in muscle fasiculations and miosis, is associ-
ated with plasma cholinesterase levels of 10% to 20% of baseline. Severe
poisoning with life-threatening symptoms is associated with plasma
cholinesterase levels of 0% to 10% of baseline. Some authors reported
that prolonged severe depression of plasma cholinesterase has been asso-
ciated with poor clinical outcomes after organophosphate poisoning.
However, survival has been reported with extremely low plasma cho-
linesterase levels, leading some investigators to suggest that serum cho-
linesterase levels have no prognostic value in acute organophosphate poi-
soning. Identifying high-risk patients based on this enzyme measurement
alone is not always reliable.
Leukocytosis with a leftward shift toward polymorphic neutrophils,
hyperglycemia, ketoacidosis, glycosuria, albuminuria, and acetonuria have
been reported with organophosphate poisoning, but these findings are not
specific or sensitive enough for diagnostic purposes. Hyperamylasemia
and other evidence of acute pancreatitis, such as computed tomographic
imaging of the pancreas, have been reported following organophosphate
poisoning. Recognition and appropriate therapy of acute pancreatitis when
evident may lead to a better prognosis.
Large, short-term doses of organophosphates insecticides have resulted
in prominent electroencephalographic (EEG) changes and convulsions in
humans and other primates. Studies have shown long-term (1 to 6 years)
spectral shifts in beta voltage in sarin-exposed primates or accidentally
114
exposed workers with serial EEG determinations. The usefulness, both
in terms of specificity and sensitivity, of these EEG findings in the dia-
gnosis of organophosphate poisoning has not been established. Cardiac
toxicity can manifest as intraventricular conduction abnormalities, atrial
dysrhythmias, and repetitive ventricular tachycardia such as torsades de
pointes.

Treatment
The decision to treat a possible organophosphate poisoning is often
based only on the history and physical examination findings. Initial ma-
nagement is directed at protecting and maintaining an open airway with
respiratory support, including airway suctioning, endotracheal intubation,
and mechanical ventilation with supplemental oxygen. Because organo-
phosphates insecticides can easily cross the skin barrier, they pose a par-
ticularly insidious threat of secondary contamination to unprotected health
care providers and emergency department personnel. Patients who arrive
at an emergency department without having had appropriate decontami-
nation should be decontaminated with large amounts of soap and water.
Removing clothing potentially saturated with organophosphates is parti-
cularly important for both patient and health care provider. Clothing and
other contaminated materials must be discarded as highly contaminated
waste. Even waste water from field or hospital decontamination must be
handled carefully. Gastric decontamination with lavage followed by re-
peated doses of activated charcoal is indicated for enteric exposure and
can reduce total and continued organophosphate exposure. Hemoperfusion
removes only minimal amounts of the organophosphate insecticides.
For acutely ill patients, atropine sulfate in doses sufficient to reverse
cholinergic (muscarinic) signs and symptoms is the primary pharmaco-
logic treatment. A specific dose limit or an arbitrary dose goal is not prac-
tical. Careful titration with atropine while monitoring reversal of exces-
sive parasympathetic stimulation is the standard of care. Initial doses of
0.4 to 2.0 mg atropine intravenously (IV) are given every 15 minutes un-
til evidence of “atropinization” or muscarinic blockade, such as flushing,
dry mouth, dilated pupils, and tachycardia, is seen. Repeated doses or con-
tinuous infusion of atropine to maintain partial muscarinic blockade is
needed. Evidence of cholinergic excess, including miosis, nausea, brady-
cardia, is used to govern atropine doses for several hours to days, depend-
ing on the severity of the organophosphate poisoning. Caution must be
exercised when treating children with large doses of pre-mixed atropine
sulfate because large amounts of preservatives (e.g., alcohols) used to in-

115
crease the shelf life of the drug can be toxic. Consultation with a pharma-
cist should allow formulation of a high-dose atropine sulfate solution that
is preservative-free. Other anticholinergic agents such as glycopyrrolate
have been shown to be as effective as atropine in the treatment of organo-
phosphate poisoning.

N-Methyl Carbamates Insecticides

The carbamates, like the organophosphates, are used in commercial
farming, home gardening, and control of domestic animal ectoparasites.
Aldicarb, oxamyl, and methomyl are highly toxic carbamate insecticides;
dioxacarb, carbaryl, and isoprocarb are less toxic. The carbamate insecti-
cides are often used in combination with an organophosphate or pyre-
throid insecticide.
Carbamate insecticides are readily absorbed by inhalation or inges-
tion through the skin. The N-methyl carbamate esters cause reversible in-
hibition of acetylcholinesterase. As in the case of organophosphates,
postsynaptic cholinergic receptors are flooded with acetylcholine, result-
ing in a characteristic toxidrome. Unlike the phosphorylated enzyme, the
carbamylated acetylcholinesterase enzyme can undergo spontaneous hy-
drolysis in vivo, which reactivates the enzyme. Less severe toxidromes of
shorter duration can be expected from carbamate poisoning because of
this hydrolysis.

Acute Signs and Symptoms

The diagnosis of carbamate poisoning is generally made by history
and clinical presentation of the patient. The clinical toxidrome of car-
bamate poisoning is similar to that of organophosphates. Symptoms typi-
cally develop within 15 min to 2 hrs after exposure and usually last less
than 24 hrs. Central nervous system toxicity is less predominant because
the carbamates do not penetrate the blood-brain barrier well. However,
carbamate poisoning in children was recently found to have a greater de-
pressant effect on the central nervous system when compared to organo-
phosphates. The cause of death is often acute respiratory failure from res-
piratory muscle fatigue, pulmonary edema, bronchorrhea, and bron-
chospasm. Central nervous system depression, seizures, and ventricular
arrhythmias also increase morbidity and mortality. Carbamate insecticide
poisoning has been responsible for causing trauma-related deaths and in-
juries. When dealing with farm injuries, the clinician must consider the
possibility of occult pesticide poisoning.

116
 Laboratory Findings
Plasma and RBC cholinesterase enzyme measurements are less useful in
cases of carbamate poisoning. Symptomatic patients whose blood samples
are drawn within a few hours of exposure and absorption can exhibit de-
pressed cholinesterase levels if the enzyme measurement is done rapidly.
Enzyme reactivation can occur in vitro as well as in vivo, causing a rise
in the enzyme activity before measurement, which makes clinical inter-
pretation extremely difficult. Urine and blood analyses for parent compounds
and metabolites have been described but are not often available. A radio-
immunoassay has been described for carbamate insecticides that may re-
solve these problems if the assay becomes commercially available.

Treatment
Symptomatic treatment of the patient poisoned by carbamate insecti-
cide includes aggressive respiratory support and atropine to reverse se-
vere muscarinic manifestations. Because of the shorter duration of effect
from in vivo hydrolysis, atropine treatment is usually required for less
than 24 hours. The most important difference in treatment for carbamate
and organophosphate poisoning involves 2-PAM. The use of 2-PAM is
relatively contraindicated in carbamate poisoning because it may enhance
acetylcholinesterase inactivation. After mixed or combined exposures in-
volving both organophosphates and carbamate insecticides or in severe
poisonings with an unidentified anticholinesterase agent, it is reasonable
to administer 2-PAM cautiously.

Organochlorine Insecticides
Most of the organochlorine pesticides have been banned in the United
States, principally because of their long ecologic half-lives. Organochlo-
rine insecticides can be classified by chemical structure.
Lindane (γ-hexachlorocyclohexane), currently the most commonly en-
countered organochlorine insecticide, will be used as the prototype com-
pound for discussing acute toxicity. It is available as a garden spray, struc-
tural and environmental pest control product, and as a scabicide (Kwell).
The mechanism of toxicity is related to the ability of the organochlorine
to alter ion fluxes, principally in nerve tissue. Although its use is decreas-
ing, it continues to be a source of human poisoning. Evidence suggests
that lindane produces antagonism of λ-aminobutyric acid-mediated inhi-
bition in the central nervous system.
Organochlorine insecticides are easily absorbed through the lungs,
gastrointestinal tract, and skin. As much as 10% of a topical dose of lin-
117
dane is systemically absorbed. Because of the relatively large surface area-
to-body weight ratio of infants, lindane poisoning has been reported to
result from repeated therapeutic doses of lindane scabicide shampoo. The
organochlorine insecticides are metabolized slowly and are excreted prin-
cipally in the feces. Lindane accumulates in organs, including fat and tis-
sue, but to a lesser extent than many of the other organochlorine insecti-
cide. Lindane excretion takes several days, whereas most other organo-
chlorine insecticides have much longer elimination half-lives. Lindane is
partially dechlorinated and oxidized, yielding a series of conjugated chlo-
rophenols and other oxidation products in the urine. Many of the organo-
chlorine insecticides, including lindane and mirex, are capable of induc-
ing liver microsomal enzymes, e.g., cytochrome P-450-dependent mono-
oxygenase system.

Immediate Signs and Symptoms

The neural excitation caused by the organochlorine insecticides leads
to their primary toxic manifestations. The toxidrome includes disturbances
of sensation, coordination, and mental status. Anorexia, malaise, head-
aches, myoclonic jerking, lethargy, tremor, hyperreflexia, motor hyperex-
citability, oral paresthesia after ingestion, and convulsions of organochlo-
rine pesticides have been associated with increased myocardial irritabili-
ty and cardiac arrhythmias. Lindane has been rarely associated with aplas-
tic anemia, agranulocytosis, disseminated intravascular coagulation, and
proximal myopathy with myoglobinuria. A singular case of self-poisoning
with 1.0 ml of intravenous thiodan resulted in refractory grand mal sei-
zures, increased liver enzyme levels, and acute rhabdomyolysis leading
to proximal myopathy and acute renal failure. Motor seizures were cont-
rolled with IV midazolam and thiopentone. Both liver and renal dys-
function resolved with supportive ICU care. Hemodialysis was not re-
quired. The patient experienced a full recovery.

Laboratory Findings
Blood, tissue, and urine determinations of organochlorine pesticides
and their metabolites are available from a limited number of laboratories.
These levels are rarely useful in the clinical management of acute poi-
soning. The relatively rapid metabolism of lindane compared to many of
the other organochlorine insecticides reduces the likelihood that the pa-
rent compound or metabolites will be detected in body fat, blood, urine,
or human milk. Other organochlorine pesticides and their metabolites, such
as DDT, dieldrin, mirex, and chlordecone, can remain in blood and tissue
118
(particularly fat) for weeks or months. Persons exposed to lindane long-
term at work have had fat-to-serum concentration ratios of 220:1. Wor-
kers exposed to lindane had whole blood lindane levels of 0.02 to
0.45 mg/m3. Symptoms are unlikely in patients with whole blood lindane
levels as high as 20 to 30 mg/m3. EEG abnormalities have been noted
after brief or long-term organochlorine exposure.

Treatment
Gastrointestinal decontamination with activated charcoal should be
used for acute oral poisoning with organochlorine pesticides. For any ex-
posure, skin decontamination and removal of contaminated clothing is
essential. Treatment of convulsions may require ventilatory support and
anticonvulsants such as diazepam, phenobarbital, or phenytoin. The orga-
nic solvents used to dispense organochlorine insecticides may result in
aspiration pneumonitis and even acute respiratory failure. Because of the
very long half-life of some organochlorine insecticides, e.g., chlordecone,
the resin cholestyramine (3 to 8 g four times daily) has been shown to
disrupt enterohepatic recirculation and significantly reduce the total body
half-life of these insecticides. Cholestyramine has been advocated in the
treatment of lindane poisoning. Repeated doses of activated charcoal over
days to weeks may have the same effect, but this approach remains un-
proven, specifically with organochlorine insecticides.

LONG-TERM HEALTH EFFECTS

OR POISONINGS WITH PESTICIDES
Most acute effects of pesticide toxicity are well characterized, and the
mechanisms of their pathogenesis have been established in many cases.
Studies on long-term effects, which develop or persist long after the ex-
posures that may have precipitated them, typically are less consistent in
their findings and often raise more questions than they answer. The abili-
ty of pesticides to cause cancer, neurotoxicity, and adverse reproductive
effects has been demonstrated in laboratory animals, but unambiguous
clinical or epidemiologic evidence of effects in humans exists for only a
few specific agents. For most pesticides, clinical or epidemiologic data
are lacking on long-term health effects or the data do not yet support clear
evidence of causality.
Epidemiologic studies have focused principally on pesticide formula-
tors and applicators as representing heavily exposed populations. Several
119
population-based investigations have studied both cancer and reproduc-
tive outcomes, although most of these have been limited by ecologic meth-
odology or poor estimates of pesticide exposure. In the remainder of this
chapter we focus on epidemiologic studies, including pertinent laborato-
ry and clinical results to clarify the effects of the various pesticides on
health outcomes.
Issues of causation, particularly from long-term exposures, ideally re-
quire a combination of laboratory, clinical, and epidemiologic data. Lab-
oratory studies may address the important question of biologic plausibili-
ty of associations observed in epidemiologic studies. The ability to as-
sess exposure quantitatively through biomarkers will greatly improve the
sensitivity and specificity of epidemiologic studies. Recognition of sub-
cellular initial lesions that contribute to eventual development of degene-
rative diseases also will open new avenues to epidemiology. Until such
studies are completed, prudent avoidance or minimization of exposure to
all xenobiotics is the safest course.

Cancer
While farmers mortality rates are lower than the general population’s
for all causes combined and for smoking-related cancers, numerous stud-
ies of farmers have demonstrated above average death rates from particu-
lar cancers, most not related to smoking. These studies, from several re-
gions in the United States as well as countries in Europe, have most com-
monly observed increases in leukemia, non-Hodgkin’s lymphoma (NHL),
and multiple myeloma. Fewer studies have observed increases in Hodg-
kin’s lymphoma and cancers of the brain, stomach, prostate, skin, and con-
nective tissue. While some of these studies have linked cancer rates to
pesticide use or other agricultural practices, all of the studies have seri-
ous problems of exposure misclassification. In addition, most farmers and
farm workers are exposed to numerous pesticides and other potentially
harmul substances, further complicating the conclusions from epidemio-
logic studies. The observed associations should be regarded provisional-
ly and sceptically. Despite these difficulties, hematopoietic and lymphat-
ic cancers consistently have been associated with farming, and in some
cases have been associated with geographic areas of higher pesticide
use or with specific agricultural activities, such as corn production, asso-
ciated with heavy pesticide use. More recently epidemiologic studies have
estimated exposure to specific pesticides (e.g., phenoxyl herbicides) and
evaluated their association with specific cancers (e.g., NHL).
A major epidemiologic approach to the question of pesticides and can-
cer has been to study occupational cohorts exposed to pesticides. Such
120
studies have included pesticide manufacturers, structural pest control ap-
plicators, and agricultural applicators. These studies lack exact measure-
ments of pesticide exposure in individuals, and multiple pesticide expo-
sures often occur, especially among applicators. They do, however, target
populations that experience relatively frequent, intense, and prolonged
exposures. Some show small increases in mortality due to cancer at va-
rious sites, although not always increasing with increasing exposure. An
increase in lung cancer mortality among arsenical manufacturers is consis-
tent with other epidemiologic data on the carcinogenicity of occupational
arsenic exposure. No excess risk, however, could be detected for former
users of lead arsenate (long since discontinued). Small increases in lung
cancer mortality have also been observed among chlordane and other or-
ganochlorine manufacturers and among structural and agricultural appli-
cators. Studies of these occupationally exposed cohorts generally have
not shown increases in lymphatic or hematopoietic cancer mortality rates.
Recent indications that chlorinated pesticides and their contaminants
may interact with hormone receptors (see Female Reproductive Effects,
below) have led to speculation about a possible role in the development
of cancer of the breast. This work was catalyzed by a case-control study
showing increased DDE (a metabolite of DDT) in the sera of patients
with breast cancer compared to controls. However, a larger nested case-
control study conducted within a prospective cohort found no evidence
of an association. The evidence remains contradictory and does not sup-
port a causal association.
In summary, there is consistent epidemiologic evidence for a small as-
sociation of lung cancer with exposure to pesticides no longer used in de-
veloped countries. This association is established for arsenicals and is sug-
gestive for the chlorinated hydrocarbons. Large prospective cohort studies
now in progress are attempting to reduce the uncertainty now prevalent.

Neurotoxicity
In most cases of acute neurotoxicity from pesticides, recovery is comp-
lete unless convulsions or other acute injuries occur. However, there is
evidence that long-term pesticide exposure may result in some chronic
neurologic effects. DDT and the other organochlorines are stored in fat
tissue, so cumulative exposure may occur. With DDT, symptoms of chronic
and of acute toxicity are similar — anorexia, weakness, anxiety, and hy-
perexcitability. Persistent neurologic sequelae are most likely to follow
acute organochlorine toxicity that is associated with convulsions. Polyneu-
ropathy has been associated with chronic exposure to some organochlo-
rine pesticides. Follow-up of adults and children years after chlordane
121
was sprayed around the apartment complex in which they lived indicated
impairment of balance, reaction time, and immediate recall, among other
test results.
The acute neurotoxic effects of the organophosphate and carbamate
insecticides, and the recently recognized intermediate syndrome, have been
discussed above. A delayed neuropathy has been observed in humans days
to weeks following acute organophosphate insecticide exposure. The syn-
drome is manifest by involvement of the longest nerve fibers, and presents
with progressive weakness, ataxia, and paralysis. Pathogenesis of this ir-
reversible syndrome appears to involve inhibition of the neurotoxic este-
rase enzyme (NTE) rather than of neural acetylcholinesterase, although
inhibition of acetylcholinesterase has been an inevitable concomitant. One
study of neurologic sequelae following organophosphate poisoning found
impaired visual attention and vibrotactile sensitivity among cases com-
pared to controls. While this finding is provocative, it needs to be repli-
cated with more complete follow-up and better estimates of exposure.
The possibility that pesticide exposure may contribute to development
of Parkinson’s disease has been suggested following observations that such
exposure is more common among Parkinson’s patients than among un-
affected people from the same region. A similar suggestion with respect
to Guillain — Barré syndrome has been reported only in the Chinese, in
an English abstract. Both of these observed associations require further
confirmation before they can be accepted as causal.
Studies of neuropsychologic effects in humans following acute organo-
phosphate insecticide poisoning have indicated a fairly consistent con-
stellation of subjective disturbance and subclinical deficits. Persistent
symptoms following acute toxicity include headache, dizziness, nausea,
visual disturbances, weakness, confusion, agitation, and insomnia. The
most consistent of positive measurable results has been elevation of the
threshold for vibratory sensation. These symptoms may last weeks to
months following cessation of exposure, persisting long after resolution
of cholinergic signs. Cholinesterase depression is only variably associa-
ted with these persistent symptoms.
A variety of neurobehavioral symptoms has been associated with chro-
nic low-dose exposure to organophosphate insecticides, but careful, rigo-
rous studies are generally lacking; some studies have failed to observe
these effects. Symptoms observed among workers exposed long-term to
organophosphate insecticides include fatigue, memory deficits, nervous-
ness, malaise, vision disturbances, and loss of concentration. There is sup-
portive evidence from animal studies for chronic neurologic effects of
organophosphate insecticide exposure, but more carefully controlled stu-
dies are necessary in humans.
122
 Reproductive Toxicity and Male Reproduction
Chlordecone (Kepone) was an insecticide and fungicide produced from
1958 to 1975, when production was stopped because of toxicity in pro-
duction workers. In animal studies chlordecone causes testicular atrophy.
Among the production workers in the Virginia Allied Chemical and Dye
Corporation plant, chlordecone caused oligospermia and reduced sperm
motility in several men, as well as neurotoxicity and several other clini-
cal effects.
The study of infertility among men exposed to pesticides and other
occupational agents is hindered by ignorance of the fundamental deter-
minants and modifiers of spermatogenesis, the large individual and in-
traperson variability in semen parameters, and difficulty in conducting
controlled epidemiologic investigations. Difficulties in obtaining accurate
estimates of pesticide exposures further hamper studies of their potential
adverse reproductive effects.
The possibility that environmental exposures including pesticides may
adversely impact sexual development of the male fetus has been discussed
seriously since publication of a study reporting decreasing semen quality
over a 50-year period. Data for the earlier 30 years of the study period
were sparse, and evaluation criteria may not have been comparable. Con-
firmatory and contradictory studies, including relatively strong evidence
from observations of wildlife in contaminated areas, have been reviewed
without reaching a firm conclusion. An important source of resistance to
the idea of environmental hormone disruption has been the low potency
of the implicated xenobiotics. An in vitro study on yeast genetically al-
tered to express a human estrogen receptor suggests synergistic effects of
combined exposures. The area of endocrine disruptors is one of current
intensive research.
Female Reproductive Effects
Few human studies directly address the effect of pesticides on female
reproductive outcomes. Most of the epidemiologic studies have been de-
scriptive or ecologic and do not provide direct support for causal associa-
tions with potential pesticide exposure. Furthermore, studies that have
evaluated associations between birth defects and agricultural activity or
pesticide use have generally been ecologic analyses and have been in-
consistent in their results. They thus have done little more than raise con-
cern about the effects of pesticides on female reproduction.

123
 Organochlorines, including DDT, have been implicated in a variety of
adverse reproductive outcomes. The mechanism is generally thought to
be interaction with estrogen receptors, either directly or indirectly by me-
tabolism to estrogen agonists. Abnormal menses and impaired fertility have
been suggested effects of the organochlorines. Epidemiologic evidence
has also suggested, but not definitely implicated, DDT exposure in pre-
mature delivery and spontaneous abortion.
One study of a small but intense outbreak of congenital abnormalities
provides persuasive evidence linking the event to consumption of fish treat-
ed for parasites with extraordinarily high doses of the organophosphates.
Two case reports of malformations associated with prenatal exposure to
organophosphates are anecdotal only, lacking any estimate of exposure
magnitude.

TESTS
1. A patient C., 34 y. o., complains of laboured breathing. The mucous
membrane of the nasopharynx is dry, tongue is white covered, the abdo-
men is inflated, at palpation some resistance in the epigastrium is defined,
dry rhonchi at auscultation are revealed. Blood analysis: leukocytosis, in-
creased ESR. He worked near aggregate of the enrichment by ammonium
hydroxide, used an oxygen breathing apparatus irregularly. It is possible
to suspect in this case:
A. An alimentary toxicoinfection.
B. Poisoning by POS.
C. Intoxication by lead.
D. Acute intoxication by ammonium hydroxide.
E. Intoxication by pesticides.
2. A patient C., 38 y. o., a horse breeder at the farm is delivered to
CDH with the complaints of a sharp weakness, headache, nausea, vomit-
ing, abdominal pain. It was fixed that 2 hrs before he was engaged in
weeding of the field processed by methylmercaptophos. Objective: nar-
rowing of the pupils, hyperhydrosis of the skin, miosis, bronchorrhea,
bradycardia, fibrillation of some muscles.
Preliminary diagnosis:
A. Acute intoxication by POC, a mild degree.
B. Acute intoxications by POC, a moderate degree.
C. Acute intoxication by POC, a severe degree.
D. Chronic intoxication by POC, a moderate degree.

124
 3. A patient H. works at the chemical industry on production of a phos-
phoric acid, complains of ostealgia.
What bones suffer most of all at chronic intoxication by phosphorus?
A. Bones of the backbone.
B. Bones of the arms.
C. Bones of the legs.
D. Pelvic bones.
E. Bones of the jaws.
4. A worker of the farm H. has applied for medical help because of an
acute poisoning by POC after processing sowings on the field. What term
should the cases of acute professional poisonings be investigated at?
A. 1 day.
B. A week.
C. 3 days.
D. 1 month.
E. 6 months.

125
 Chapter 8
OCCUPATIONAL EXPOSURE
TO VIBRATION

Probably since earliest time, when humans first took to the sea, the
debilitating and incapacitating effects of vibrating motion have been known.
With the beginning of the Industrial Revolution came vibrating hand tools
and automated machinery. Raynaud’s phenomenon first appeared in 1911
to 1918 in some workers who used vibrating hand tools. Post-World
War II, with the introduction of modern aircraft, ships, vehicles, etc.,
emerged a myriad of studies to determine how vibration affects the abili-
ty of human beings to function and perform work. It is now apparent that
occupational vibration affects the worker’s health and the ability to work
safely. Approximately 8 mln workers in the United States are exposed to
occupational vibration. Of these, 6.8 mln are principally associated with
vehicular operation (e.g., truck and bus driving, farming, construction)
there vibration impinges on the entire body. The remaining 1.2 mln
workers are users of gasoline powered tools (e.g., chain saws, brush cut-
ters, etc.), and users of pneumatic and electrical hand tools. Vibration im-
pinges locally and principally on the upper limbs when using the afore-
mentioned tools. The former vibration is referred to as whole-body vib-
ration (WBV), and is usually transmitted to the entire human body through
some supporting structure, such as a vehicle seat or a building floor; the
latter vibration is referred to as segmental or hand-arm vibration (HAV)
and usually is applied locally to specific body parts, for example the hands,
by a vibrating tool the generic term vibration refers to back-and-forth, up
and down, side to side linear motion that emanates from and returns to
some defined reference position. Rotational motion (pitch, yaw, and roll)
also occurs, but is rarely measured in occupational situations. Although
WBV and HAV are usually distinct, some workers may be exposed to
both types of vibration, depending on the job. For example, a worker
126
using a pneumatic jackhammer or road ripper tool with outstretched arms
receives principally HAV whereas if the worker operates the tool so that
it is placed in contact with the abdomen, the vibration reverts to WBV.
A person who works at the same job with vibration exposure for
20 hrs per week, 50 weeks per year, for 30 years, that person can receive
up to 30,000 hrs of cumulative vibration exposure. Thus it is imperative
to monitor and minimize both the acute and chronic effects of the vibra-
tion exposure on workers.

TERMINOLOGY
To understand vibration’s effects on humans it is important to be fa-
miliar with some terms. Vibration frequency, pronounced in Hertz (Hz),
describes the cyclic nature of vibration. For WBV the 1-Hz to 80-Hz band
(range) is of interest; for HAV the band is from 5 to 5,000 Hz. In the
occupational setting, usually more than one vibration frequency is simul-
taneously present, thus constituting a “vibration spectrum” that must be
analyzed. Vibration motion per second is characterized as a “vector quanti-
ty,” which consists of both a direction and a magnitude. Three mutually
perpendicular (linear) vectors at each vibrating point are usually meas-
ured. Each vector magnitude can be pronounced either as (a) vibration
displacement, which refers to the distance traversed between the normal
resting position of an object and its position at a given time in its vibrato-
ry cycle (in units of inches, feet, centimeters, millimeters, etc.); (b) ve-
locity (speed) of a moving object, which refers to the time rate of change
of displacement (in units of feet per second, meters per second, etc.); or
(c) a moving object’s speed, which usually changes over time; this time
rate of change of speed or velocity is acceleration and is pronounced in
gravitational units (g), or in meters per second per second (1g = 9.81 m/
sec/sec). Acceleration has been the most frequently used measure of vi-
bration intensity or magnitude, owing in part to its ease of measurement,
and from this one parameter both vibration velocity and displacement can
be mathematically derived. Resonance refers to the optimum condition
of maximum transfer (or coupling) of vibration energy from the vibrating
source to the receiver (e.g., the human body) accompanied by an actual
amplification of the incoming vibration by the human body per se; thus
in a resonant situation the body uncontrollably acts in concert with the
incoming vibration, exacerbating the effects.

127
 CLASSIFICATION
OF VIBRATION DISEASE
Whole-Body Vibration
I degree of severity:
1) syndrome of vascular dystonia (cerebral or peripheral);
2) vegetative-vestibular syndrome;
3) syndrome of sensory (vegetative-sensory) polyneuropathy of lower
extremities.
II degree of severity:
1) cerebral-peripheral syndrome of vascular dystonia;
2) syndrome of sensory (vegetative-sensory) polyneuropathy in com-
bination:
a) with polyradiculitis (syndrome of polyradiculoneuropathy);
b) with the second lumbar radicular syndrome (lumbar osteo-
chondrosis);
c) with dysfunction of nervous system (syndrome of neurasthenia).
III degree of severity:
1) syndrome of sensorimotoric polyneuropathy;
2) syndrome of discirculatory encephalopathy in combination with
peripheral neuropathy (syndrome of encephalopolyneuropathy).

Hand-Arm Vibration
I degree of severity:
1) syndrome of peripheral vascular dystonia of upper extremities,
including with the rare angiospasms of fingers;
2) syndrome of sensory (vegetative-sensory) polyneuropathy of up-
per extremities.
II degree of severity:
1) syndrome of peripheral vascular dystonia of upper extremities,
including with the frequent angiospasms of fingers;
2) syndrome of vegetative-sensory polyneuropathy of upper extremities:
a) with the frequent angiospasms of fingers;
b) with persistent vegetative-trophic disturbances on hands;
c) with trophic disturbances of vehicle of locomotor system of up-
per extremities and shoulder girdle (myofibrosis, periarthrosis, arthrosis);
d) with cervical and brachial plexopathy;
e) with syndrome of cerebral vascular dystonia.

128
 III degree of severity:
1) syndrome of sensorimotoric polyneuropathy of upper extremities;
2) syndrome of encephalopolyneuropathy;
3) syndrome of polyneuropathy with generalized akrovasoconstriction.

WHOLE BODY VIBRATION

Epidemiology and laboratory studies have shown that WBV is a form
of cumulative trauma; it can be regarded as a generalized stressor and
may affect multiple body parts and organs, depending on the vibration
stimuli characteristics. Thus vibration exposure time, direction, and in-
tensity are important, and the human resonance is especially important
since resonance represents the Achilles’ heel of human response to vi-
bration. When the vibration impinges vertically on the body, the princi-
pal WBV resonance occurs in the 4- to 8-Hz band (nominally 5 Hz). When
the vibration impinges horizontally or laterally, WBV resonance occurs
in the 1- to 2-Hz band. These resonances are due principally to the re-
sponse of the upper trunk and torso. The head-shoulder system can re-
sonate in the frequency range of 20 to 30 Hz, and the eyeballs can reso-
nate in the 60- to 90-Hz range. The hand-arm system appears to resonate
in the 150- to 200-Hz range. Other body parts can resonate at other fre-
quencies.
The significance of resonance can best be described by a simple
example. If a 5-Hz vibration magnitude of 1 g were applied to a human
subject’s buttocks, one could expect to measure as much as a 1.5 g vibra-
tory magnitude at the cranial level. Thus the body has intensified the ac-
tual acceleration applied by a factor of 1.5. The concern is that many ve-
hicles, for example, contain 5-Hz vibration components that reach the
body, as do higher-frequency tool components that reach the resonance
of the hand-arm system and can stimulate this response.
With regard to WBV medical effects, studies of human subjects have
shown that during WBV exposure oxygen consumption and pulmonary
ventilation increase. One study of 78 Russian concrete workers exposed
to WBV showed marked changes in bone structure involving spine de-
formations, intervertebral osteochondrosis, and calcification of the in-
tervertebral disks and Schmorl’s nodes. Hypoglycemia, hypocholes-tero-
lemia, and low blood ascorbic acid levels in concrete workers exposed to
WBV have also been reported. In an early study of agricultural and for-
estry workers, a rare clinical description of so-called WBV sickness is
found:
129
 “The first stage is marked by epigastralgia, distention, nausea, loss of
weight, drop in visual acuity, insomnia, disorders of the labyrinth, colo-
nic cramps, etc. The second stage is marked by more intense pain con-
centrated in the muscular and osteoarticular systems. Objective exami-
nations of the workers disclosed muscular atrophy and tropic skin lesions,
it is apparent that it is difficult to determine the critical moment at which
pathologic changes set in, especially due to differences in individual sen-
sitivity to vibration.”
The study of bus drivers revealed a statistically significant excess of
venous, bowel, respiratory, muscular, and back disorders in a population
of 1,448 interstate bus drivers exposed to WBV who were compared to
office workers and general population control groups. The study concluded
that the combined effects of WBV, body posture, postural fatigue, and
poor dietary habits contributed to the occurrence of these disorders. The
study of truck drivers examined 3,205 drivers and a control group of un-
exposed air traffic controllers. The study conclusions indicated that WBV,
forced body posture, cargo handling, and poor eating habits contributed
to significant excesses of back pain, spine deformities, strains, sprains,
and hemorrhoids among the truck drivers. The first study of heavy equip-
ment operators found that WBV-exposed workers had an excess of cer-
tain musculoskeletal diseases, including slipped disks, limb fractures, male
genital diseases (prostate), ischemic heart disease, and obesity of nonen-
docrine origin. A study of farm tractor drivers revealed that, in many cas-
es, the effects of WBV were exacerbated by poor seats, poor seating pos-
ture, and long working hours. A recent critical review of WBV epidemio-
logy studies with regard to the back concluded, “The most frequently re-
ported adverse effects (of WBV) are: low back pain, early degeneration
of the lumbar spinal system, and hemiated lumbar disks.... It must be con-
cluded that long-term exposure to WBV is harmful to the spinal system”.
Particularly disturbing are recent reports suggesting that WBV-exposed
female workers experience a high risk of menstrual disorders, abortion,
varicosities, and hyperemesis gravidarum.
Most whole body vibration researchers would agree that hard-tissue
(mostly lumbar) spinal disorders are the most frequently reported disor-
ders associated with occupational WBV exposures. But these lumbar spine
disorders must be tempered with the patient’s work history of lifting heavy
objects and related activities that can confound the diagnosis.
Finally, it is important to note that kinetosis can appear in the very
low WBV frequency vibration range of 0.1 to 1 Hz and rarely there carry
over effects on workers after the exposure ceases.

130
 Through the years there have been many human performance studies
of WBV. Most have used young, physically fit military personnel, such
as jet aircraft pilots, for short time periods (up to 30 min) in simulated
military situations. Studies of vibration have shown that the lowest sub-
jective discomfort-tolerance level occurs around the 5-Hz resonance fre-
quency. Manual tracking capability is also most seriously affected at
5 Hz. Visual acuity is severely impaired in the 1- to 25-Hz range. Per-
formance of tasks such as pattern recognition, reaction time, and moni-
toring appear not to be affected by WBV exposure. Laboratory studies
using simulated heavy equipment driving tasks that compared the effects
of a mixture of multiple vibratory frequencies (i.e., a limited spectrum)
showed that human subjects performed worse under the mixed-vibration
conditions containing a 5-Hz resonant frequency gradually improving as
the mixture was replaced by nonresonant single sinusoidal vibration.

HAND-ARM VIBRATION
Hand-arm vibration (HAV), or segmental vibration, unlike WBV, ap-
pears as locally applied cumulative trauma to the fingers and hands of
exposed workers using gasoline powered, pneumatic, or electrical hand
tools such as chain saws, chipping hammers, grinders, jack-hammers, jack-
leg type drills, etc. Extensive use of such tools (especially in cold envi-
ronments) has been causally linked to Raynaud’s phenomenon of occu-
pational origin, also variously called “dead hand” or “vibration white fin-
gers” (VWF) and most recently termed hand-arm vibration syndrome
(HAVS). This condition is characterized by tingling, numbness, and blan-
ching of the fingers with probable loss of muscle control and reduction
of sensitivity to heat and cold with accompanying pain on return of the
circulation.
Historically, the condition of blanching, numbness, and tingling in the
fingers of clinical patients was first reported in 1862 by the French phy-
sician Maurice Raynaud in his M.D. thesis, “Local Asphyxia and Sym-
metrical Gangrene of the Extremities”, which describes “a condition, a
local syncope, where persons, who are ordinary females, see under the
least stimulus one or more fingers becoming white and cold all at once.
The determining cause is often the impression of cold. The cutaneous sen-
sibility also becomes blunted and then annihilated.” This is primary Ray-
naud’s disease. Raynaud’s phenomenon affects up to 10% of the general
population and 5% or 6% of the working male population. These blanch-
ing attacks usually affect the fingers symmetrically and are relatively trivial
in the early stages of the disease. In later stages the attacks become se-
131
vere and painful, leading to blue, cold fingers wherein the skin becomes
atrophic, later ulcerated, and finally gangrenous. Raynaud also noted that
the number and severity of blanching attacks increased during times of
emotional stress.
In 1911 Loriga in Italy first described the initial association of vibra-
ting hand tools and Raynaud’s symptoms in the hands of miners who used
pneumatic hand tools. In 1918, the famous study of Dr. Alice Hamilton
was reported. She studied stone cutters using pneumatic hammers in the
Oolitic limestone quarries of Bedford, Indiana. She reported:
Among men who use the air hammer for cutting stone there appears
very commonly a disturbance in the circulation of the hands which con-
sists in spasmodic contraction of the blood vessels of certain fingers, ma-
king them blanched, shrunken, and numb. These attacks come on under
the influence of cold, and are most marked, not while the man is at work
with the hammer, but usually in the morning or after work. The fingers
affected are numb and clumsy when the vascular spasm persists. As it
passes over there may be decided discomfort and even pain, but the hands
soon become normal in appearance and as a usual thing the men do not
complain of discomfort between the attacks. ...The condition is undoub-
tedly caused by the use of the air hammer’ it is most marked in those
branches of stonework where the hammer is most continuously used and
it is absent only where the air hammer is used little or not at all. Stone-
cutters who do not use the air hammer do not have this condition of the
fingers. Men who have given up the use of the air hammer for many years
may still have their fingers turn white and numb in cold weather. The
trouble seems to be caused by three factors: long-continued muscular con-
traction of the fingers in holding the tool, the vibration of the tool, and
cold. It is increased by too continuous use of the air hammer, by grasping
the tool too tightly, by using a worn, loose hammer, and by cold in the
working place. If these factors can be eliminated the trouble can proba-
bly be decidedly lessened.
In the 1930s, reports by Seyring, who studied fettlers in iron found-
ries, by Telford and co-workers, who described men working with elect-
rically driven rotating tools in a warm environment, and by Hunt, who
studied riveters using pneumatic tools, all showed that VWF was on the
increase. In 1939, Leys reported diffuse scleroderma and Raynaud’s phe-
nomenon in a pneumatic hammer operator. In 1947, Agate and Druett ex-
amined 230 men who were grinding excess metal from small castings; of
this total, 163 (71%) had a history of white fingers, later to be called VWF.
With further research into VWF in the 1950s, signs and symptoms as-
sociated with vibrating tools were reported in other systems, such as the
132
peripheral nerves, bones, joints, and muscles. The association of VWF
with these disabilities became known later as hand-arm vibration syn-
drome.
In 1962 and 1964, Ashe and colleagues at Ohio State University in-
vestigated a small group of hard-rock drillers from Saskatchewan, seven
of whom were examined in the hospital. As part of these investigations,
arteriography and biopsy of the digital arteries were performed. Results
showed that, in the worst cases, extensive damage to the digital artery
intima with narrowing of the lumen had occurred as a result of the vibra-
tion exposure.
From 1964 on, a significant number of vibration syndrome cases ap-
peared in the United Kingdom, up to 90% in the logging and forestry
industries, where gasoline-powered chain saws had been in widespread
use for some 12 to 14 years. The clinical state of the hands of workers
using these chain saws was deteriorating to such an extent that the Brit-
ish Forestry Commission, in 1971, issued workers newly designed antivi-
bration (A/V) saws, which were based on the best available vibration cri-
teria of the time for 6 to 7 hrs per day, 5 days per week exposure.

Medical Assessment
It is important that primary Raynaud’s disease, as originally described
by Raynaud, be distinguished from secondary Raynaud’s phenomenon.
Secondary Raynaud’s may arise from (a) exposure to vibration; (b) trau-
ma, such as lacerations and fractures of the fingers and hands; (c) frost-
bite; (d) occlusive vascular disease, such as arteriosclerosis; (e) intoxica-
tion, as from ergot or nicotine; and (f) neurogenic causes such as polio-
myelitis. It is also necessary to exclude causes of reduced blood flow to
the fingers from compression of the main blood vessels at the outlet of
the thorax (e.g., cervical rib or “thoracic outlet” syndrome). In addition,
connective tissue disorders, such as scleroderma, polyarteritis nodosa, and
rheumatoid arthritis, may cause secondary Raynaud’s phenomenon. It is
recognized that it may not be possible to eliminate confounding condi-
tions during the diagnostic process, since on occasion scleroderma and
sclerodactyly with vibration induced Raynaud’s have occurred simulta-
neously in patients as have carpal tunnel syndrome (CTS) and primary
Raynaud’s.
Some years ago Taylor and Pelmear developed a white finger grading
system, which bears their names and became widely used in many coun-
tries. Their system tended to emphasize the vascular component of HAVS.

133
In 1986 a meeting was held in Stockholm, Sweden, at which a modified
Taylor — Pelmear system was adopted with the concurrence of Drs. Tay-
lor and Pelmear.
The modified system, called the Stockholm system, came about in rec-
ognition that although the majority of HAVS subjects have a combina-
tion of neurologic and vascular signs and symptoms, it became necessary
to separate these two components and stage or classify each independent-
ly, since it is possible that the neurologic component of the syndrome can
progress independently of the peripheral space vascular component in
some patients.
Given that the Taylor—Pelmear system has been used for many years
and that the literature is replete with studies that use it, and given the rela-
tive newness of the Stockholm system, both systems will be addressed here.
The Taylor—Pelmear system was developed for grading HAVS pa-
tients and uses the results of the physical examination, occupational health
history, history of social impairment (as a direct consequence of induced
white finger), and the degree of interference with hobbies; the HAVS pa-
tient is placed into one of the following categories. The initial symptoms
of HAVS are tingling or numbness after vibration exposure. In stage 1, as
vibration exposure time increases, finger blanching attacks begin and in-
crease in number, duration, and severity. They occur at first mainly in
cold temperatures, and especially during the early morning, either at home,
with chores, or en route to work as a result of exposure to the elements
(e.g., grasping a cold steering wheel, driving a motorcycle), or during
morning rest breaks. Workers who work outside in all weather conditions
(e.g., forestry workers) are most prone to early morning attacks. Workers
may report interference both at work and during hobby and leisure activi-
ties (e.g., gardening, fishing, woodworking, auto maintenance, etc.). All
such activities have one common factor: a reduced environmental tem-
perature, which triggers an HAVS attack. The latent period to finger
blanching is defined as the time interval from when the worker began
using the vibrating tool(s) to the appearance of the first white fingertip;
also note that thumbs generally do not blanch during an HAVS attack
(Table 8.1).
In stage 2 there is a limitation of hobby activities. In stage 3, there is a
definite cessation of hobby activities as well as interference with work,
particularly in outdoor jobs such as forestry, and especially in the winter;
difficulty with fine manual dexterity; difficulty in feeling and picking up
small coins; difficulty in buttoning/unbuttoning clothing; finger clumsi-
ness with increasing joint stiffness.

134
 Table 8.1. Exclusion criteria and differential diagnosis
for hand-arm vibration syndrome
Primary (Raynaud’s disease) Constitutional white finger
Secondary (Raynaud’s phenomenon)
Connective-tissue disease Scleroderma, systematic lupus erythematous,
dermatomyositis, polyarteritis nodosa, mixed
connective-tissue disease
Posttraumatic conditions Following injury, fracture, or operation; occu-
pational origin, vibration; frostbite and immer-
sion syndrome
Occlusive vascular disease Thoracic outlet syndrome (cervical rib, scalenus
anterior muscle), costoclavicular and hyperab-
duction syndromes. Thromboangiitis obliterans,
arteriosclerosis, embolism, thrombosis
Dysglobulinemia Cold hemagglutination syndrome; cryoglob-
ulinemia, macroglobulinemia
Intoxication Acro-osteolysis, ergot, nicotine
Neurogenic Poliomyelitis, hemiplegia, syringomyelia
Other Carpal tunnel syndrome

In stage 4, the severity of the HAVS and interference with work, so-
cial activities, and hobbies are so intense that the patient changes occu-
pation; tissue necrosis of the fingers can appear in rare instances with
increased vibration and cold exposure in this stage.
It is to be noted that the preceding sequence of increasing stages of
HAVS severity arises from the cumulative trauma effects of the imping-
ing vibration on the hands, usually from prolonged and regular use of
vibrating tools found in industry. The aforementioned latent interval is
related to the vibration (acceleration) intensity; the shorter the latent
interval, the more severe will be the HAVS if vibration exposure con-
tinues.
The Stockholm system is shown in Table 8.2 and requires the examin-
ing physician to do extensive work/hobby histories in order to estimate
the patient’s vibration dose. Vascular, neurologic, and musculoskeletal
objective tests must be performed in order to separately stage each hand
for neurologic and for vascular damage. The following tests for HAVS
are recommended:
135
 Table 8.2. Stockholm-revised vibration syndrome
classification system

Stage/Grade Description
Vascular component
1. Mild Occasional blanching attacks affecting tips of one
or more fingers
2. Moderate Occasional attacks in distal and middle phalanges
of one or more fingers
3. Severe Frequent attacks affecting all phalanges of most
fingers
4. Very severe As in stage 3 with trophic skin changes (tips)
Sensorineural component
0SN Vibration exposed — no symptoms
1SN Intermittent or persistent numbness with or with-
out tingling
2SN As in 1SN with reduced sensory perception
3SN As in 2SN with reduced tactile discrimination and
manipulative dexterity
The staging is made for each hand. The final grade of the disorder is indi-
cated by the stage and the number of affected fingers in each hand (e.g.,
stage/hand/no, of digits). This Stockholm Classification System is based on:
a) removal of the unquantifiable areas — difficulty at work, home, and
hobby activities;
b) discarding the seasonal component;
c) the syndrome to be separated into two major areas — vascular and sen-
sorineural;
d) separate staging of each hand.

Vascular component tests: cold provocation tests; Doppler artery de-

lineation; Alien and Louis — Prusik tests.
Neurologic component tests: two-point discrimination and depth sense
(aesthesiometry); vibrotactile threshold tests; light-touch, pain, and tem-
perature appreciation and dexterity tests; Moberg and pinch tests.
Musculoskeletal tests: dynamometer grip force and pinch tests.
Differential diagnosis (neuropathy and polyneuropathy): Tinel’s and
Phalen’s tests; nerve conduction velocity for median, ulnar, motor, and
sensory nerves of the Tinel and Phalen tests (which indicate the degree of
CTS symptoms).
136
 Hand-Arm Vibration Control
It is beyond the scope of this presentation to describe in detail the var-
ious methods for controlling HAVS in the workplace except to briefly
mention them. Totally controlling HAVS usually is multifaceted and in-
volves several measures.
The first line of control is better tool design (or tool redesign) that
incorporates the engineering principles of vibration damping and isola-
tion together with good ergonomic design. Currently there are many re-
duced vibration or so-called antivibration (A/V) gasoline-powered chain
saws and related forestry and professional landscaping tools available;
unfortunately, this is not the case for most pneumatic tools, except for a
single major Swedish company with virtually a complete line of effective
A/V tools. Although new A/V tools employing ergonomic principles are
beginning to appear on the market, most tool companies have a few
A/V tools at most in their complete lines.
The second line of control is A/V gloves, which use special viscoela-
sic materials to damp a broad spectrum of vibration. These gloves are
also intended to keep the hands warm and dry and prevent cuts and lace-
rations. The main design challenge is allowing sufficient sensory feed-
back and dexterity with a minimum grip strength (in order to reduce vib-
ration coupling into the hand).
The third line of control is hand-arm vibration standards. Although all
of these standards try to protect workers from the harmful effects of hand-
arm vibration, these standards emphasize (weight) the lower vibration fre-
quencies more than the high-frequency spectral components. As a result,
some of these standards are in the process of being revised accordingly.
The fourth and final line of control is work practices and medical sur-
veillance:
1. Any worker whose hands may be exposed to vibratory hand tools
should, prior to employment, be physically examined and questioned
about:
a) Signs and symptoms of primary Raynaud’s disease or Raynaud’s
phenomenon.
b) Detailed history of vibration exposure (which should be record-
ed); on the basis of present medical evidence, it is not advisable to allow
workers with primary Raynaud’s disease to use vibratory hand tools.
2. A/V tools should be used when and where possible; all tools should
be carefully maintained according to manufacturer’s recommendations.
Worn-out tools should be discarded and replaced with new ones, prefera-
bly A/V tools.

137
 3. Workers are advised as follows:
a) Use only full-finger A/V gloves at all times when using vibra-
ting hand-tools. A/V gloves with fingertip material removed ex-
pose the fingertips to vibration and thus do not adequately pro-
tect the finger-hand system despite the fact that finger dexterity
is improved.
b) Wear adequate clothing to keep the body core temperature at a
stable, acceptable level.
c) Keep the hands warm before and during work.
d) Do not allow the hands to become wet and chilled. Should this
happen, dry and warm the hands and put on a pair of dry, warm
A/V gloves. This may require carrying an extra pair of gloves.
e) Do not smoke while using vibrating hand tools. Nicotine acts as a
vasoconstrictor, reducing the blood supply to the fingers and hands.
f) Let the tool do the work, grasping it as lightly as it is safe to do
so, allowing the tool to rest on the workpiece where and when
possible.
g) Use only ergonomically designed A/V tools where and when pos-
sible.
h) Use the tool only when absolutely necessary, operating at re-
duced speed when possible.
i) Should signs of tingling, numbness, or white or blue fingers oc-
cur, see a physician promptly.
4. The hazard of HAVS can be reduced if continuous vibration exposure
over long time periods is avoided. Therefore, a 10-minute vibration-free rest
break for every hour of continuous vibration exposure is recommended.

TESTS
1. A woman, aged 50, a farmer, noted a headache during several weeks,
“a faint condition”. It was noted a vegetatic neuralgia of the upper limbs.
Diagnosis: vibration disease.
Determine a functional degree of the disease on the basis of these
symptoms:
A. І.
В. ІІ.
С. ІІI.
D. ІV.
E. V.

138
 2. A man, aged 40, a farmer, complains of the headache of constant
nature, a short faint condition. There were noted a vegetatic-sensitive
polyneuropathy of the limbs, the diencephalon syndrome.
A possible diagnosis and degree of the disease are following:
A.Vibration disease, the 1st degree.
B. Vibration disease, the 2nd degree.
C. Vibration disease, the 3rd degree.
D. Vibration disease, the 4th degree.
E. NCD.
3. A man, aged 40 y. o., works at the metallurgical industry. He ap-
plied to the physician with complaints of severe night aching pain in hands,
numbness of the fingers of the hands, general painfulness, extended head-
ache, strong pain in the heart area, palpitation.
What kind of the disease has this patient?
A. Vibration disease, local.
B. Vibration disease, general.
C. Raynaud’s syndrome.
D. Syringomyelia.
E. NCD.
4. A man, 35 y. o., has worked as a driller over 13 years. During a
preventive physical examination he complained of general sweating, head-
ache, which is accompanied by the noise and sonitus, memory impair-
ment, sleepiness, pain in the field of the heart. Objective: flutter of the
fingers and hands, oppressing of the pharynx, conjuctive and corneal re-
flexes, instability in the pose of Romberg, distal and general hyperhydro-
sis, bright steadfast dermographism.
What is the most possible reason of this condition?
A. Radiation disease.
B. Vibration disease.
C. Action of production noise.
D. Change of the atmospheric pressure.
E. Meniere’s disease.
5. A patient, 50 y. o., a mechanical engineer in the turbine shop of the
power plant, complains of the steady headache in the forehead area, in-
creased petulance. Besides, he notes a cold snap of limbs, pallor, season-
ly cyanosis, increased sweating of the palms and foots. During the exam-
ination — a reduction of the pulsation of dorsal arteries of feet on both
sides, bone power reduction.
139
 Establish diagnosis:
А. Raynauld’s disease.
В. Аthеrosclerosis of the lower limbs’ vessels.
С. Vibration disease action of the general vibrations.
D. Vibration disease caused by the action of the local vibrations.
E. Polyneuritis.

140
 Chapter 9
DYSBARISM

Dysbarism is the collective term used to describe the pathologic chan-

ges that occur when the human body is exposed to environmental pres-
sure changes (alternobaric exposure). Those altered pressures are trans-
lated into unphysiologic behavior of gases in organs and tissues. Failure
to adequately or timely adapt to those changes, can generate (depending
on a number of exposure and individual factors) the different clinical synd-
romes of dysbarism. Altemobaric exposure is a concern in a number of
occupational and recreational activities, such as diving, compressed air
work (as in tunnel construction and caisson work), as well as in aviation,
mountain climbing, and high-altitude flying.

HISTORICAL PERSPECTIVE
Diving has been an important human activity since antiquity and, as
such, the quest for increased depths and durations has been ongoing since
then. Although reports of dysbaric disorders began earlier, their experimen-
tal study was not possible until the XVII century, when diving bells were
introduced for salvage operations. In 1650, von Guericke developed the
air pump, which permitted simulation of high-altitude environments in
special gas chambers. Sir Robert Boyle (1627–1691) experimented with
live animals exposed to this gas chambers and noted bubbles floating in
the vitreous humor of their eyes. In 1667, Redi, an Italian naturalist, re-
ported on the death of animals when air was injected into neck veins. In
the XIX century, Augustus Siebe manufactured the first diving suit with
a surface air supply, and Ammussat observed that the speed of death of
air-injected animals was related to the size of the injured vein and the
relationship of this vein to the heart when air was injected. In 1818,
Bauchene reported the first case of fatal air embolism in a human. In the
141
1840s, decompression sickness (DCS) was first recognized in France in
men who were working in the compressed air environments of tunnels
and caissons. A French scientist, Paul Bert (1833–1886), was the first to
hypothesize that “caisson disease” resulted from the development of air
bubbles in body tissues and fluids after decompression from a hyperbaric
exposure. Bert also determined that the gas in those bubbles was nitro-
gen. In 1930, a Dutch physician named Jongbloed recognized that the joint
symptoms that he experienced after self-experimenting with hyperbaric
exposure were the same as those observed in men after rapid decompres-
sion from diving or caisson work. During World War II, Jacques Cous-
teau and Emile Gagnon developed a demand regulator that automatically
delivered breaths at any depth, the self-contained underwater breathing
apparatus (“scuba”). Hyperbaric chamber treatment techniques were also
refined during World War II because of the demands of submarine tech-
nology and higher flying aviation. At the same time, Behnke recognized
that the symptoms felt at high altitude were analogous to those associated
with caisson work, thus identifying a link between aviation and diving
hazards. By 1960, a classification scheme for decompression sickness
based on symptoms experienced by tunnel workers had been formulated.

ALTERNOBARIC EXPOSURES
Exposure to altered environmental pressures followed by a return to
atmospheric pressure occurs in a number of settings. When the rapidity
of the pressure changes exceeds that of the compensatory and adaptive
mechanisms of the human body, dysbaric disorders can result, depending
in part on interindividual differences in responses and susceptibility. This
chapter focuses on compressed air work and diving.
Compressed air work is carried out during tunnel construction and cais-
son work. A caisson is a watertight chamber used in construction work to
construct bridge and tunnel foundations under water. The chamber is
placed over the site of the proposed underwater foundation, and air is
pumped in at a pressure sufficient to displace the water and allow work
to be performed under dry conditions (Fig. 9.1). In the United States, work-
ing pressures for compressed air have varied from 3.1 to as high as 6.1
atmosphere absolute (ATA). Part of this work can now be done with me-
chanical devices.
There are three main diving methods, which have been sequentially
developed during man’s quest for deeper and more prolonged dives: breath-
hold diving, scuba diving, and saturation diving. Breath-hold diving is
the simplest and oldest of all. Once the diver holds his breath and de-

142
scends, the increased pressure that he is exposed to is applied to his en-
tire body. The duration of the dive is limited by that of the breath-hold,
and specifically the rate of PaCO 2 rise.
Scuba-diving allows descent deeper into the water for a considerable
longer duration than breath-hold diving Scubas provide a breathing mix-
ture (air, oxygen, helium-oxygen, helium-nitrogen-oxygen, hydrogen-ni-
trogen-oxigen) upon demand at the ambient pressure to which the diver
is exposed. This allows the maintenance of ambient pressure within the
respiratory tract. Dive computers calculate saturation and desaturation of
tissues. Their purpose is to maximize the time underwater by pushing dives
to the limit of a decompression model different from the more conserva-
tive one used to derive decompress tables. They therefore decrease safety
margins and increase in the probability of dysbarism. Recreation scuba
diving has gained immense popularity in many industrialized countries,
where it is by far more widespread
than commercial and military div- Material
ing. Recreation diving is currently Lock
restricted to depths of 39 m.
Saturation diving was devel-
oped to permit commercial divers, Man
especially in the oil industry, to per- Lock
form complex and economically
profitable tasks during prolonged
periods and at increased depths.
Saturation diving allows for an in-
crease in the ratio of time spent un- Water
derwater to the total diving time, Level
which is the sum of underwater
plus decompression time. In this
modality, divers descend in diving
bell where they are gradually com- River
pressed to pressure level encoun- Bed
tered at the depths where they are
released (which usually exceed 200
to 300 m). Breathing mixtures have
high partial pressures of inspired Pressurized
Working
oxygen, and an inert gas other than
Chamber
nitrogen (usually helium) is added.
The compression and descent phase
of this diving modality is long
enough for the diver’s tissue to be- Fig. 9.1. Scheme of a caisson

143
come fully saturated with the inert gas that is being breathed. Once satu-
rated, the diver can remain underwater for an indefinitely long period,
without further increasing his obligated decompression time. Stays of 1
to 14 days are usual, with decompressions of approximately the same du-
ration.
The technical refinements of scuba and saturation diving have allowed
increased human activity underway under hyperbaric conditions. With
these modalities, divers are exposed to breathing mixtures that are usual-
ly hyperbaric, hyperoxic, and have an increased gas density. Furthermore,
the surrounding environment can be hypothermic, physical activity can
be strenuous, and the specific tasks performed underwater may also ex-
pose commercial or technical divers to potentially injurious toxins and
physical agents. The compromises that are mad are felt to be “accepta-
ble,” although long-term, close follow-up is necessary to exclude unfore-
seen deleterious consequences.

PATHOPHYSIOLOGY
OF DYSBARISM
Whereas body tissues are nearly incompressible, the physical behav-
ior of gases is affected by three factors: pressure, volume, and tempera-
ture. The interrelationship between these factors is determined by Boyle’s,
Dalton’s, and Henry’s laws, three fundamental gas laws. Comprehension
of these concepts is essential to the understanding of dysbaric disorders,
which in this chapter are classified according to their pathophysiology.
Pressure is defined as force applied per unit area. Commonly used units
and equivalent pressures are 1 atmosphere (atm), 760 mm Hg, 10 m of
sea water. The sea of air under which we normally reside is defined (at
sea level) as 1 atmosphere (atm) of barometric pressure. Hyperbaric ex-
posures add to the ambient pressure and hypobaric exposures subtract from
it. Absolute pressure is the sum of ambient pressure plus any additionally
applied pressure. It is measured in atmosphere absolute (ATA) units. For
instance, under 10 m of sea water, 1 atm is added to the ambient pressure
and the absolute pressure is 2 ATA.
The Boyle’s law states that the volume (V) of a given mass of gas is
inversely proportional to its pressure (P): PV= K (a constant). In the hu-
man body, hyperbaric exposures (compression, diving descent) cause a
contraction in gas volume, and hypobaric exposures (decompression, as-
cent after diving) cause an expansion. A doubling of pressure to 2 ATA
results in the volume being halved; similarly, a decrease of pressure to
144
0.5 ATA is associated with a doubling of volume. The diameter of a
sphere or bubble is also affected by the pressure change but to a lesser
extent than volume. Whereas the volume change is more important in
predicting barotrauma, the bubble diameter change is the important factor
for restoring circulation to embolized areas during recompression the-
rapy.
The Dalton’s law states that the total pressure (P1) exerted by a mix-
ture of gases is the absolute sum of each individual gas: PT = P1 + P2 +
+ P3 + ... + P n. This law forms the physical principle of hyperbaric (rec-
ompression) therapy and the hypoxemia that occurs under hypobaric con-
ditions (Table 9.1; 9.2).

Table 9.1. Effects of gas laws on hypo-

and hyperbaric exposures

Distance from Ambient pressure PO2 Bubble Diameter

sea level, m (ATA) (PSI) (mm Hg) volume
+6,000 0.5 7.35 380 200% 126%
+2,000 0.8 11.76 608 125% 107%
0 1 14.70 760 100% 100%
–10,0 2 29.40 1,520 50% 79%
–20,0 3 44.1 2,280 33% 69%
–30,0 4 58.8 3,040 25% 63%
–40,0 5 73.5 3,800 20% 59%
–50,0 6 88.2 4,560 17% 55%

Table 9.2. Gas pressures under hypo-

and hyperbaric conditions
Distance from Pressure P0 2 PN PT
sea level, m (ATA) (mm Hg) (mm Hg) (mm Hg)
+8,000 0.388 62 233 295
+1,700 0.743 119 446 565
0 1.0 160 600 760
–10,0 2.0 320 1,200 1,520
–20,0 3.0 480 1,800 2,280
–30,0 4.0 640 2,400 3,040
–40,0 5.0 800 3,000 3,800
–50,0 6.0 960 3,600 4,560

145
 The Henry’s law provides the physiologic basis for understanding de-
compression sickness, nitrogen narcosis, and the formation of bubbles
when a bottle of champagne is uncorked. This law states that the amount
of gas that dissolves in a liquid at a given temperature is directly propor-
tional to the partial pressure of that gas. The Boyle’s, Dalton’s, and Hen-
ry’s law together describe the ideal gas law:
PV = nRT,
where P — pressure; V — volume; n — number of moles of gas; R —
universal gas constant, T — absolute temperature.
This law allows the prediction of the behavior of gases in response to
changes in environmental pressures.

Behavior of Gases During Compression

and Decompression
As predicted by the gas laws, the volume of gases within the body
change during hyperbaric and hypobaric exposures. If the gas volume
changes provoked exceed compensatory mechanisms of the body, the
major dysbaric disorders — decompression sickness (DCS) and barotrau-
ma — may result. In both conditions pathologic changes result from the
formation of gas bubbles. In barotrauma, changes in gas volumes within
air-filled anatomic structures are involved, and gas may be directly in-
jected into arteries. In DCS gas bubbles form within tissues and their vas-
culature, where they cause most of the damage.
Gases in the body under these circumstances takes into account the
phenomena of compression versus decompression, and gas behavior at
the level of tissues and of air-filled organs.
Compression in a hyperbaric environment causes tissue uptake and
saturation with gases. When ambient pressure rises, the partial pressure
of a given gas (e.g., nitrogen) in a tissue and the total pressure of gas in
an air-filled organ rise proportionally. Compression of gas in the latter is
the direct cause of barotrauma of descent. Compression also results in
the development of a gradient that causes a net flow of nitrogen from
pulmonary alveoli to the blood and subsequently into body tissues. The
rate of gas uptake is most rapid immediately following a pressure increase
and reaches a plateau as tissue saturation is approached. The time that it
takes to achieve equilibrium in gas uptake is a function of (a) the solubi-
lity of the gas in the tissue and (b) the rate at which the gas is delivered to
that tissue by blood. Tissue perfusion varies. Well-perfused tissues such
as the brain can achieve equilibrium with a gas within minutes; they are
relatively “fast” tissues. On the other hand, poorly perfused tissues such
146
as adipose tissue, joints, and tendons, which also have a high solubility
for gases, require more time to reach equilibrium and are called “slow”
tissues. Tissues acquire gases exponentially, and a range of half-times
(from 5 to 75 minutes) has been estimated to describe that process in dif-
ferent body tissues. Much longer half-times, however, are believed to oc-
cur for some tissues under specific circumstances. The latter is impor-
tant, because decompression tables are based on those half-time estimates.
Increased tissue perfusion, and thus gas uptake, as observed during exer-
cise, active heating, immersion, and supine position, may all increase the
risk for dysbarism (in particular DCS).
When ambient pressure is lowered during decompression, the rate of
escape of gas from tissue is believed to be similar to the rate of uptake,
but in reverse, as long as bubbles do not form. If the reduction of ambient
pressure to a level lower than the total gas pressure in tissues is too rapid,
formation of microbubbles within tissues is favored. These bubbles im-
mediately appear because the pressure of the dissolved gas cannot de-
crease fast enough by diffusion alone. Reversal of tissue supersaturation
with gas must therefore be controlled during ascent (decompression) in
order to minimize bubble formation and growth, the development of DCS,
gas expansion within air-filled organs, and barotrauma of ascent.
In the case of barotrauma of ascent, gas bubbles are formed from the
injection of rapidly expanding gas into the arteries. In the case of DCS,
the exact site of initial bubble formation and the microcirculatory events
related to intravascular bubbles following rapid decompression remain
unclear. Formation of bubbles primarily in the venous circulation, tissues
themselves, and/or arteries, have been hypothesized. Bubbles are thought
to originate on preformed bubble nuclei. The latter may exist in micro-
scopic hydrophobic spaces (e.g., between endothelial cells), or be genera-
ted by shear forces exerted on moving tissues. Once bubbles develop on
those nuclei, their size can increase as a function of several factors, in-
cluding exchange of gas with adjacent blood, presence of surfactant, and
coalescence or disintegration of bubbles resulting from collision. The high
fat content of the nervous tissue, combined with the high liposolubility of
nitrogen, may account for its vulnerability. Histologic studies on rapidly
decompressed animals demonstrated relative abundance of intravascular
gas bubbles in fat-rich tissues and organs. In the spinal cord, the white
matter, rather than the gray matter, is usually affected. A number of ob-
servations have established the presence of bubbles in almost all tissues,
intra- and extravascularly, and even intracellularly. Progressive stages of
bubble formation in fat tissue range from the enlargement of fat cells by
inclusions of microbubbles to the rupture of gas-filled cells generating
extracellular and extravascular pockets of gas in the tissue.
147
 Regardless of the origin of the gas bubbles three main interrelated mech-
anisms have been invoked to explain their pathologic effects in tissues: (a)
mechanical obstruction with reduced blood flow, (b) surface activity at the
gas-liquid interface of the bubbles, and (c) injury of vascular endothelia.
These three mechanisms can trigger local and systemic inflammatory ef-
fects. Bubbles have been shown to have surface activity due to the abnor-
mal gas-liquid interface. Denaturation and reorientation of globular plasma
proteins are believed to occur upon contact with that interface and be asso-
ciated with loss of function, aggregation of proteins, and coating of blood
cells that favor their aggregation. Those phenomena may explain several of
the observed changes in the blood during decompression, which include
sludging and rouleaux formation of red cells in small vessels, neutrophil
aggregation, platelet clumping, and a decrease in the number of circulating
red and white cells and platelets. In addition, and possibly through activa-
tion of kinin and complement pathways, several inflammatory phenomena
may result, such as increased capillary permeability and fluid extravasation.
All these alterations contribute to producing microcirculatory compromise,
endothelial damage, and local inflammatory tissue damage.
Some of the manifestations of DCS are similar to those of systemic in-
flammatory conditions characterized by complement activation. This led
some to hypothesize that complement activation may mediate DCS, per-
haps underlie intel-individual differences in susceptibility to it, and possi-
bly even explain its occasional recurrence after initially successful resolu-
tion with hyperbaric treatment. Complement activation may also mediate
some of the observed changes in blood elements and vascular endothelial
injury. In animal studies, air bubbles have been observed to activate com-
plement by the alternative pathway. In humans, activation of complement
by the alternative pathway has also been demonstrated in plasma samples
incubated with air and nitrogen bubbles, and in individuals subjected to
decompression. Furthermore, subjecting some of those individuals to a se-
ries of pressure profiles severe enough to cause bubble formation in blood
vessels revealed that complement-activation seemed to correlate with sus-
ceptibility to DCS. The functional and clinical relevance of decompression-
associated complement activation, however, remains to be determined.

Cardiovascular and Pulmonary Effects

of Gas Embolization
The physiologic consequences of gas embolization to the heart and
lungs is due to mechanical factors as well as secondary effects of released
mediators (as described above). Cardiovascular collapse may ensue due
to a combination of acute right heart failure and hypoxemia-related myo-

148
cardial infarction. If even a small amount (< 0.1 ml) of air enters a coro-
nary artery, ventricular fibrillation and infarct can result. Ultimately, poor
oxygen delivery results in multisystem organ failure and death.
Mechanical obstruction of the pulmonary arterial system and the right
heart may result from simple lodging of bubbles causing an “air-lock”
phenomenon. Vortex flow round a partially obstructing embolus is postu-
lated to cause a “whipping” type action that results in a blood-froth mix-
ture. The latter enhances platelet aggregation, fibrin formation, and coa-
lescence of intravascular fat. Proximal deposition of these fibrin strands
interspersed with conglomerations of red cells may play a major role in
the obstruction of the pulmonary vasculature. Transient pulmonary vaso-
constriction has also been detected in a canine model of venous gas em-
boli. These mechanisms resulted in a brisk rise in pulmonary vascular
resistance (PVR) prior to a fall in cardiac output when bubbles were in-
jected into the venous system of sheep. This sequence of events lends
further support to the hypothesis that vasoactive mediators may be in-
volved in the subsequent changes following gas emboli.
In the lungs, airways resistance (Raw) increases when gas emboli are
composed of air, oxygen, or nitrogen but not when they contain only car-
bon dioxide (CO 2) or the inert gases helium, neon, argon, or xenon. As a
result of the significant increases in Raw, lung water, and PVR, there is
maldistribution of ventilation relative to perfusion. The ventilation/per-
fusion (V/Q) ratio imbalances result in hypoxemia due to low V/Q areas
as well as areas of physiologic shunting (V/Q = 0). The V/Q maldistri-
bution that occurs during venous gas embolism also causes increased
areas of dead space (elevated V/Q ratios). This explains the finding of a
drop in end-tidal CO2 concentration (ET CO2) following venous gas em-
bolization as areas of high V/Q experience a “washout” of CO2 from the
poorly or nonperfused alveoli. The decrease in ETCO2 is exaggerated when
the cardiac output is also decreased.

Cardiopulmonary Effects of Diving

The physiologic effects of submersion have been studied in a head-
out immersion model during which the subject is submersed up to the
neck. This induces an asymmetric pressure on the subject’s body that is
proportional to the vertical distance that is immersed. Venous return is
augmented due to compression of the extremities by the relative high den-
sity of water and an increase in abdominal pressure relative to intratho-
racic pressure. Right atrial pressure rises, which stimulates release of atrial
natriuretic factor (ANF), which contributes to the diuresis and natriuresis
149
that usually accompanies head-out immersion. However, this shift can acute-
ly reduce circulating blood volume, which is further compromised by swea-
ting, the cold pressor response, and any associated alcohol intake.
The increase in intrathoracic pressure during head-out immersion ex-
periments induces several pulmonary changes, including:
a) a 70% decrease in expiratory reserve volume (ERV);
b) smaller reductions in vital capacity, since there is an increase in in-
spiratory capacity that partially compensates for the large decrease in ERV;
c) a small, but statistically significant, decrease in residual volume
caused by an increase in intrathoracic blood volume;
d) a 60% increase in the work of breathing partly due to an increase in
nonelastic airways resistance;
e) a form of “negative-pressure ventilation,” since the thorax and lungs
experience greater than 1 ATA while the oropharynx and nose are sur-
rounded by only 1 ATA (at sea level).
During breath-hold diving, the entire body is exposed to the increased
ambient pressure. Breath-hold diving is associated with decreased intratho-
racic pressure (relative to ambient pressure) and chest elastic recoil, and
increased work of breathing. Increased venous return to the heart also
results, which causes an increase in cardiac output that probably contrib-
utes to counteracting the pressure exerted on the thoracic cage. Distribu-
tion of pulmonary perfusion may also improve. At the end of a prolonged
dive, marked hypoxemia and hypercapnia occur, the latter being the usu-
al stimulus for resumption of ventilation. Ventilatory responses to hyper-
capnia and hypoxia have been shown to be altered in elite breath-hold
divers, Japanese pearl divers, and submarine escape training instructors.
Most studies have described a blunted response to hypercapnia with vari-
able tolerance to hypoxia. Whether these traits are genetic or adaptive
has not been determined, but they do contribute to the breath-hold diver’s
longer underwater performance. Hyperventilation before a dive produces
a larger depletion of the body CO2 reserves than increases in those of O2.
By retarding the hypercapnic stimulus, predive hyperventilation prolongs
the apnea time and favors the development of a more severe hypoxemia
than would result otherwise, thus increasing the risk of syncope and death.
By contrast, scubas maintain atmospheric pressure within the respira-
tory tract. They expose the lungs, however, to breathing mixtures that are
more dense, hyperbaric, and hyperoxic in comparison to atmospheric air.
The increased work of breathing, with decreased expiratory flow rates in
direct proportion to the ambient pressure, has been well documented by
several investigators in the past. Furthermore, mouthpieces, masks, and hel-
mets all add dead space (i.e., increased pulmonary ventilation/perfusion
150
ratio) to the total ventilation required for adequate respiratory gas ex-
change.
Different studies have documented pulmonary functional changes in
scuba divers and, more recently, in saturation divers. The results general-
ly suggest definite but mild degrees of overinflation and obstructive im-
pairment. Cross-sectional ventilatory functional studies in divers with pro-
longed exposure to hyperbaric environments demonstrated significant in-
creases in forced vital capacity (FVC) and forced expiratory volume in 1
second (FEV 1). Other studies detected decreases in air flow rates at low
lung volumes suggestive of obstructive impairment, and decreased diffu-
sion capacity uncorrected or corrected for alveolar volume (DL/VA).
Hyperoxia, hyperbaria, and venous gas microembolism appear to be in-
dependent contributors to the described pulmonary functional changes.
Although these changes may result (at least in part) from occupational
self-selection or from respiratory muscle training, they have also been sug-
gested to indicate small airways dysfunction.

NITROGEN NARCOSIS
AND HIGH-PRESSURE
NERVOUS SYNDROME (HPNS)
Nitrogen narcosis has been most commonly described in deep diving
while breathing compressed air. It has also been described in compressed
air workers. The resulting increased partial pressure of nitrogen in com-
pressed air generates a large additional nitrogen load, which (due to its
lipid solubility) easily saturates the brain tissue. This allows nitrogen to
exert narcotic effects, which have also been described for other “inert”
gases (e.g., hydrogen) in close correlation with their lipid solubility. The
term inert gas narcosis is sometimes used when referring to this condi-
tion, which sets clear limits on compressed air diving to depths of about
50 m.
The clinical syndrome of nitrogen narcosis is quite similar to alcohol
intoxication, and Cousteau coined the term “I’ivresse des grandes pro-
fondeurs” (or “rapture of the depths”) to describe it. It is characterized
by the development of abnormal behavior, euphoria, as well as impaired
judgment, intellectual functions, neuromuscular coordination, and perfor-
mance. The symptoms may begin at depths of 20 to 30 m. At depths greater
than 90 m (10 ATA) loss of consciousness can occur. The risk for drow-
ning accidents and death is very high, particularly because of the eupho-
ria and impaired judgment. Individual susceptibility to this condition va-

151
ries, and there is also some evidence for adaptation from frequent expo-
sures. The narcotic effect is believed to be exacerbated by cold water,
hypercarbia, fatigue, strenuous activity, and alcohol consumption. Upon
decompression (ascent), rapid and complete recovery occurs.
High-pressure neurologic syndrome (HPNS) was described when
breathing mixes of helium-oxygen began to be used to allow deep dives
(exceeding depths of 100 m) while avoiding the development of nitrogen
narcosis. Increased environmental pressure by itself causes HPNS, al-
though there are interindividual differences in susceptibility. HPNS is char-
acterized by hyperexcitability of the central nervous system. Clinically,
symptoms include opsoclonus, headache, vertigo, fatigue, euphoria, nau-
sea, and vomiting. Signs include decreased manual dexterity, tremors of
the hands and arms, myoclonus, dysmetria, and hyperreflexia.
The pathogenesis of HPNS is still unclear, but it involves a number of
disturbances in neural transmission, in particular enhanced subcortical release
of glutamate (with excitation of V-methyl-D-aspartate receptors) and decreased
serotoninergic activity. Electroencephalography reveals increased θ-activity.
At compressions of more than 30 ATA sleep disturbances are observed con-
sisting of awake periods, increased sleep stages I and II, and decreased REM
periods. Brain stem auditory evoked potential studies during saturation dives
have demonstrated increased neural transmission times, suggestive of en-
hanced synaptic excitability. A puzzling observation has been that the effects
of high environmental pressure (which explains HPNS) and anesthesia (which
nitrogen narcosis resembles) are mutually antagonistic.
Prevention of HPNS may be achieved by reducing the speed of com-
pression, and by adding nitrogen (5–10%) or hydrogen to the heliox breath-
ing mixture. Although anticonvulsants (especially barbiturates) have anti-
HPNS activity, they are of no practical use in diving. Serotonin receptor
antagonists may provide an additional approach to the prevention of HPNS.
Resolution without long-term sequelae seems to be the rule.

DECOMPRESSION SICKNESS
Decompression sickness (DCS) is probably the most frequent dysbar-
ic disorder. DCS occurs upon return from ahyperbaric (e.g., during a
diver’s ascent) or from a hypobaric exposure (hypobaric or altitude DCS,
e.g., in aviators). DCS is a probabilistic phenomenon with clear interindi-
vidual differences in susceptibility.
Decompression sickness symptoms are frequently concurrent, and
sometimes difficult to differentiate clinically from those of barotrauma of
ascent. This is not surprising, given that both conditions result from the

152
formation and the pathologic effects of gas bubbles. Furthermore, treat-
ment for the two conditions is essentially the same. The terms decom-
pression illness and decompression disorders are being increasingly used
to include both DCS and barotrauma. A descriptive clinical classification
has been recently proposed that does not attempt to differentiate between
these two entities or ascribe the observed clinical features to a given dis-
ease mechanism. This chapter, however, follows the traditional approach
of discussing these two entities separately.

Clinical Manifestations
Decompression sickness encompasses a broad spectrum of clinical dis-
orders, involving several organ systems with different degrees of severi-
ty. The diagnosis of DCS is a clinical one. Multiple organ involvement is
more frequent in DCS than in barotrauma of ascent, but the signs and
symptoms of both conditions can be quite similar and often occur con-
currently. Although symptoms of DCS usually occur within 6 hrs from
ascent, they are frequently not present immediately upon surfacing, and
delayed presentations (24 hrs) have been described. In contrast, symp-
toms of barotrauma and arterial gas embolism have a sudden and rapid
onset upon surfacing. In practice, any neurologic or cardiovascular symp-
tom or sign that occurs within 15 min of reaching the surface should be
assumed to be due to barotrauma and arterial gas embolism until proven
otherwise. Both conditions can relapse after initial successful hyperbaric
treatment, but this occurs slightly more frequently with DCS than with
barotrauma.
On the basis of severity of clinical presentation and the presence or
absence of neurologic involvement, decompression sickness has been tra-
ditionally classified into two types: type I (mild; peripheral limb and joint
pain, cutaneous involvement, no neurologic symptoms), and type II (se-
rious; primarily neurologic including vestibular, cerebral, and spinal in-
volvement, as well as other systemic symptoms). The symptoms of type I
disease may mask or antedate the more serious type II manifestations.
Although studies differ widely on the relative frequency of the two types
of disease, type II disease probably occurs in as many as 80% of DCS
patients.

Spinal Cord and Brain

Central nervous system (CNS) manifestations of decompression sick-
ness reflect potentially very ominous complications resulting in perma-
nent neurologic damage. The spinal cord, particularly the lower thoracic
and upper lumbar (T 12-L1) segments and its dorsal and lateral columns, is

153
by far the most frequently affected CNS structure. There is some evidence,
however, that cerebral damage may be more prevalent in DCS than was
once thought. The predilection for spinal cord in DCS remains unex-
plained, and it sharply contrasts with the predilection of barotrauma with
arterial gas embolism for the brain.
Morphologic studies in humans with DCS have been limited. Four sta-
ges of damage to the spinal cord have been described in humans: hyper-
acute, acute, subacute, and chronic. In the hyperacute phase, abrupt de-
creases in external pressure and formation of bubbles within tissues leads
to an explosive effect. If the pressure changes are less severe, gradual
accumulation of bubbles in the white matter may be seen instead. The
acute stage generally occurs 10 to 48 hrs following rapid decompression.
Infarcts are found in the lateral, ventral, and dorsal columns of the white
matter. Early myelin degeneration, and changes in the structure of neu-
rons in the gray matter are also observed at this stage, with associated
vascular injury and microthrombi. The subacute stage is characterized by
lipid phagocytosis, replacement of cells by astrocytes, and progressive
nerve fiber (wallerian) degeneration.
The chronic stage is marked by the progressive organization of white
matter infarcts.
The typical presentation of DCS in the CNS begins with transient back
pain radiated to the anterior chest or abdomen soon after rapid decom-
pression. Multifocal lesions probably explain the frequently observed com-
binations of sensory and motor deficits at multiple sites. Subsequently,
paresthesias and hyperesthesias develop in the legs. Without medical in-
tervention this situation progresses to urinary retention, lower extremity
paresis, and eventually paralysis. Detection of sub-clinical neurophysio-
logic abnormalities may be possible by using somatosensory evoked po-
tentials (SSEPs).
Although neurologic DCS has been regarded as predominantly a spi-
nal cord disease, on rare occasions it involves the brain. Clinically de-
tectable manifestations of brain damage include visual disturbances, hemi-
plegia, and unconsciousness. Patients with classic spinal cord manifesta-
tions have been reported to have concomitant cerebral perfusion defects.
A recent study using single photon emission tomography (SPET) repor-
ted statistically significant abnormal brain textures in divers who had ex-
perienced DCS in the past, compared to divers who had not. Overlapping
results between the two groups, however, were evident, and the signifi-
cance of these findings remains unclear.

154
 Pulmonary System
Under normal conditions the lungs work well in filtering out most gas
microbubbles. In most cases of DCS, no pulmonary symptoms occur, even
though bubbles may be detected in the venous circulation. However, the
relationship between degree of pulmonary embolization and pulmonary
symptoms remains unknown. Morphologic studies of the lungs’ response
to decompression showed no alteration in the bronchoscopic and histolog-
ic appearance of the airway mucosa. Pulmonary edema has been noted on
histologic examination of the lung parenchyma. In addition, small autopsy
series of patients who succumbed to acute decompression sickness frequently
demonstrated fat emboli to the lungs and peripheral organs.
The pulmonary syndrome, called “the chokes” by divers, develops in
2% to 8% of DCS patients and is characterized by paroxysmal cough,
substemal chest pain, and dyspnea. Early physical signs include respira-
tory distress, tachypnea, cyanosis, and in severe cases, hypotension and
shock.
Without appropriate therapeutic intervention (i.e., recompression) pa-
tients suffering from this syndrome may progress to noncardiogenic pul-
monary edema, circulatory collapse, and death. Recompression results in
essentially complete reversal of symptoms, usually within minutes. In a
case report, complete radiographic resolution of pulmonary edema was
documented to occur within a few hours of recompression treatment.

Osteoarticular System
It has been said that bone is the organ that limits human exposures to
compressed air. Indeed, involvement of bones in DCS occurs very frequently,
and includes an acute pain condition (known as the “bends”), and the late,
chronic complication of dysbaric osteonecrosis or aseptic bone necrosis.
The bends are one of the most frequent and typical manifestation of
decompression sickness. They consist of pain felt in the joints, or in both
muscles and bones. The pain has been described as dull, throbbing, grad-
ual in onset, variable in progression and severity, and occasionally pre-
ceded by paresthesias. The affected extremity is usually held in a se-
miflexed position, and less intense pains are referred to by divers as the
“niggles.” It is believed that the bends are caused by air embolism most
likely affecting the bone marrow, and to be related to later development
of chronic dysbaric osteonecrosis. The diagnosis of this condition is based
on its clinical features. Evaluation includes a search for involvement of
other organ systems, and treatment is the same as for all DCS (as dis-
cussed below).
155
 Dysbaric osteonecrosis (caisson disease) is a late and chronic compli-
cation of exposure to hyperbaric environments. Caisson disease was first
recognized at the beginning of the century in men who had worked in
caissons. It was later described in divers and, rarely, in aviators exposed
to hypobaric environments. Adherence to recognized decompression pro-
cedures does not completely prevent bone necrosis. The lack of early
symptoms (and few late ones) and its long latency (months or even years
after the initial exposure) also contribute to the persistence of this occu-
pational hazard.
Incidence and prevalence of dysbaric osteonecrosis among occupation-
ally exposed workers have varied over time. In divers, prevalence seems
to correlate with exposure dose (e.g., in terms of amount of pressure, and
number and duration of dives). Statistically significant correlations have
also been suggested between the presence of definite osteonecrotic le-
sions and number of episodes of decompression sickness, as well as body
weight. In the United Kingdom, the Medical Research Council De-
compression Sickness Registry, based on 10-year longitudinal data on
4,980 commercial divers, estimated the prevalence of dysbaric osteonecro-
sis at 4.2%, and the highest incidence at 6/1,000/year of diving experi-
ence. When the comparison has been possible, dysbaric osteonecrosis has
been found more frequently in compressed air workers than in divers.
Among compressed air workers the incidence of bone lesions also ap-
pears to be related to exposure dose (intensity of hyperbaric exposure and
number of hyperbaric experiences). No lesions have been reported in work-
ers exposed to less than 2.4 ATA, and osteonecrosis is most common when
the pressure exceeds 3.6 ATA. At least 50% of experienced compressed
air workers who have been exposed for many years have bone lesions.
Yet, there is evidence that even a single hyperbaric exposure can result in
osteonecrosis. Men without previous exposure to compressed air who suf-
fered at least one attack of the bends were more likely to have a bone
lesion than those who had not suffered such attacks. Conversely, not all
men with radiographic evidence of osteonecrosis were thought to have
experienced acute decompression sickness. Furthermore, in the absence of
any additional hyperbaric exposure, new lesions may develop in previous-
ly normal areas, and existing lesions may progress.
Dysbaric osteonecrosis usually develops only in portions of long bones
and in sites where fatty bone marrow is found in mature adults. The most
common sites are the distal end of the femur and the proximal end of the
humerus, tibia, and femur (Fig. 9.2). At each of these sites two types of
lesions can occur. Juxtaarticular (JA) lesions are situated adjacent to the
joint surface, more frequently in the femoral and humeral heads and sel-
156
 a b
Fig. 9.2. Distribution of bone lesions
in compressed air workers (a) and commercial divers (b)

dom near the articular surfaces of the knee or elbow joints. The head, neck,
or shaft (HNS) lesions, are situated in the remaining parts of the bone
that lie at a distance from the joint surface. HNS lesions most frequently
affect the medullary cavity of the lower femoral and upper tibial shaft,
but may involve the neck and head of the femur and humerus and are
often bilateral and symmetric. While HNS lesions usually remain symp-
157
tom free, JA lesions may cause pain and limitation of movement due to
damage to the adjacent joint surface. Structural failure of the joint may
result, and osteoarthritis may develop, causing marked disability. In divers,
joint damage was estimated to occur in 14.5% of previously identified
JA lesions.
While the characteristics of the osteonecrotic lesions that occur in di-
vers and compressed air workers are essentially indistinguishable, their
emphasis and distribution varies in the two groups. JA lesions have been
described to occur more commonly in compressed air workers than in
divers and have a predilection for the femoral head. In contrast, JA le-
sions in divers occur more frequently in the humeral head. When HNS
lesions occur, their location is more often in the humerus in compressed
air workers and in the lower femur in divers.
The precise cause of dysbaric osteonecrosis is not known. It is believed
to result from occlusion of multiple end arteries in the bones by intravas-
cular gas bubbles that develop during decompression; experimental evi-
dence, however, is insufficient. Alternatively, it has been hypothesized
that rapidly expanding nitrogen gas would cause bone marrow adipose
tissue damage with disruption of lipids and lipoproteins. The latter would
then lead to local release of intravascular procoagulant factors and the
blood changes discussed before.
No satisfactory experimental animal model exists for dysbaric os-
teonecrosis. Within just a few hours of arterial occlusion, the absence of
osteocytes from the bone lacunae can be recognized.
As repair of a necrotic area takes place, granulation tissue grows from
the living bone into the necrotic area and new bone is laid over the dead
trabeculae without prior resorption of latter. This formation of new bone
and failure of resorption creates an area of thickened trabeculae that is
separate from the dead bone and marrow. If the area of bone necrosis is
not too extensive, it may be completely repaired. This buildup of the
trabeculae takes at least 5 months after the ischemic episode to appear
and is the first point at which radiographic changes appear. As time pass-
es the changes become more pronounced, the dense areas growing larger.
Structural failure of the articular surface, easily detectable by radiography,
may eventually occur and can lead to secondary osteoarthritis. The time
from the first radiographic indication to the point of structural failure can
range from several months to a few years; the patient remains symptom
free until the articular surface is no longer intact. If bone death is not ex-
tensive and complete repair occurs, the radiographs return to normal.
Mesenchymal malignancies have very rarely been reported in asso-
ciation with preexisting osteonecrosis, regardless of the etiology. In the
158
majority of reported cases (including all of those associated with dysbaric
disorders), malignant fibrous hystiocytomas have been the histologic type.
Tumors have developed in the distal femur, femoral head, and distal tibia,
and all reported cases have been associated with HNS lesions, with long
(about 20-year period) latencies between last exposure and diagnosis.
Because the first changes leading to osteonecrosis are only slightly
different from the normal variation in the trabeculae, early radiographic
diagnosis requires high-quality radiographs and skilled interpretation.
Routine bone surveys should include the proximal ends of the humerus
and femur and the shafts of the femur and tibia. The most common radio-
graphic abnormalities (in order of descending frequency) are calcified
areas in the shaft of the bone, juxtaarticular dense areas and spherical
seg-mental opacities, and linear opacities. A generally accepted classifi-
cation developed by the British Medical Research Council Decompres-
sion Sickness Registry is used for clinical and surveillance purposes. It
first classifies the lesions according to their location (JA or HNS), and
then describes the patterns of altered bone density and structural failure.
On radiographs, some difficulty may be experienced in distinguishing
dense areas of aseptic bone necrosis from the bone islands that are com-
monly found in the normal skeleton. However, bone islands are usually
composed of uniformly dense compact bone and are ovoid or oblong. Le-
sions of aseptic osteonecrosis are usually irregular and have thickened
trabeculae running through them. Also, as mentioned previously, they are
often multiple and bilateral. Radiographic changes due to dysbaric os-
teonecrosis must also be differentiated from those of other conditions such
as Gaucher’s disease, sickle cell anemia, the arthropathy of steroid thera-
py, alcoholism, radiotherapy, some hemoglobinopathies, and osteoblastic
metastases. Most of these causes of bone necrosis are rare in relatively
young and healthy persons; therefore, when osteonecrosis occurs in a per-
son exposed to a hyperbaric environment, as long as the other causes are
ruled out, it can be attributed to work.
Additional imaging techniques may be useful in the diagnosis of dys-
baric osteonecrosis. These include computed tomography (CT), bone scin-
tigraphy, and magnetic resonance imaging (MRI). CT gives much better
definition than conventional radiography. In the early stages of osteonecro-
sis, CT allows clearer identification of the thickened trabeculae. Struc-
tural failure is also more easily identified with CT. Bone scintigraphy with
“technetium-labeled” diphosphonate seems more sensitive than traditional
radiographic methods. With bone scintigraphy the necrotic area of bone
produces a “cold” lesion resulting from decreased or absent uptake of radio-
isotope from the hypometabolic area. During revascularization, radioiso-
159
tope uptake increases, producing a “hot” lesion. While bone scintigraphy
is a powerful tool in that it can identify areas of osteonecrosis within sev-
eral weeks of ischemia, it is not without limitations. What bone scintigra-
phy possesses in sensitivity, it lacks in predictive value. Many bone dis-
eases show the characteristic hot spots that occur in osteonecrosis. More-
over, fewer than half the lesions shown by bone scintigraphy progress to
positive radiographic evidence of osteonecrosis. MRI has enhanced the
detection of osteonecrosis thanks to its ability to image in multiple planes
and to more clearly identify soft tissue and bone marrow. On MRI necrotic
areas appear as homogeneous areas of decreased signal intensity in the
JA area within just a few days. As revascularization occurs, so does an
increase in the signal intensity. MRI can be helpful in the detection of
early lesions. However, like bone scintigraphy, MRI lacks positive pre-
dictive value. Therefore, traditional radiography, in conjunction with CT,
still remains the easiest, most readily available method of diagnosing dys-
baric osteonecrosis. Bone scintigraphy may prove to be useful in early
detection and thus have a role in periodic surveillance. MRI may be use-
ful in clarifying equivocal radiographic appearances. Further work will
determine the role of bone scintigraphy and MRI in early detection.

Other Involved Systems

The skin is very frequently affected in DCS. Cutaneous pruritus, ery-
thema, nonspecific macular eruptions, and cutis marmorata are common
presentations of cutaneous DCS. Inner ear decompression sickness is more
common when helium-oxygen breathing mixtures are used for diving.
Symptoms usually begin during decompression (ascent) or shortly after
surfacing from a dive. Those symptoms include sensorineural hearing loss,
tinnitus, and/or vertigo during or shortly after decompression, which are
similar to those of inner ear barotrauma (discussed below). The latter,
however, usually occurs during compression or after a shallow dive, and
may be associated with middle ear barotrauma. Treatment is the opposite
for both conditions (recompression for inner ear DCS but not for baro-
trauma). Explosion of teeth, especially if they have been previously re-
paired, has been described after rapid decompression and it is more fre-
quently consider a form of barotrauma of ascent. Ocular signs and symp-
toms occur in about 7% of all DCS cases, and may include nystagmus,
diplopia, visual field defects, cortical blindness, convergence insufficien-
cy, central retinal artery occlusion, and optic neuropathy. Fluorescein an-
giography findings similar in appearance to those of choroidal ischemia
have been documented in divers, but their significance remains to be es-
160
tablished. The hematopoietic system is affected even beyond the intra-
vascular changes in blood components and plasma volume that have been
discussed above. Bone marrow infarction has been recognized as a com-
plication of decompression sickness. This is a consequence of bubble-
induced swelling of fat cells in the marrow rather than direct toxicity to
the hematopoietic series. Nephrotic syndrome due to minimal-change
glomerulonephritis was described in association with DCS in one case
report.

Treatment and Prognosis

Ideally, DCS should be prevented by decompression schedules that
estimate the degree and duration of safe decompression to be allowed for
gas equilibration during return to a normobaric environment. Those sched-
ules are developed and revised according to both empiric data and mathe-
matical models of gas elimination in the body. Not surprisingly, current
schedules, even when strictly followed, do not completely prevent DCS.
Furthermore, it may be impossible to eliminate the risk. Surveillance with
periodic radiographic examinations is necessary for persons at risk for
dysbaric osteonecrosis.
Decompression sickness is a true medical emergency, especially when
neurologic manifestations occur. The primary treatment for decompres-
sion sickness (as well as barotrauma) is to administer hyperbaric therapy
accompanied by 100% oxygen. The recompression pressure causes bub-
bles to become smaller, and breathing pure oxygen produces a gradient
by which inert gas in bubbles and tissues can diffuse out of the body.
Treatment protocols (decompression tables) usually consist of series of
timed exposures to increased atmospheric pressure with alternating 100%
oxygen and air breathing (to avoid oxygen toxicity). The use of helium-
oxygen mixes during recompression seems promising and may be used
more frequently in the future. Rapid transport of the victim to a recom-
pression facility is the single most important measure, and the probabili-
ty of recovery greatly decreases with delays. If transportation is by air,
either pressurized or low-flying unpressurized aircraft are preferred. Por-
table one-person recompression chambers have been devised to initiate
treatment immediately while transporting the patients, but are not widely
available. If transportation delays cannot be avoided, intermittent admi-
nistration of 100% oxygen and air is recommended. Additional suppor-
tive measures include the use of corticosteroids to reduce nerve tissue
edema and volume expansion (intravenous fluids). Their beneficial ef-
fects, however, have not yet been substantiated.
161
 Treatment can be extremely effective if begun early, when symptoms
are just developing, and tissue damage is only mild. Hyperbaric oxygen
therapy has achieved successful results in as many as 98% of cases of
neurologic DCS. If treatment is delayed, tissue damage increases; even if
all bubbles disappear with hyperbaric therapy, healing requires days to
weeks and may not be complete. By a still unknown mechanism, howev-
er, some patients (30–50%) relapse after having responded favorably to
recompression treatment, long after bubbles may have persisted. Repea-
ted recompression treatment is indicated in case of relapses, or until no
further clinical improvement is observed. Somatosensory evoked poten-
tial testing may provide a tool to monitor neurophysiologic improvement
during recompression treatment.
In most cases the aftereffects of decompression sickness resolve within
weeks of initial treatment, yet little is known of subsequent health com-
plications of this disorder. Permanent neurologic defects can result, even
with prompt and adequate recompression. In a study of U.S. Navy divers
that compared postdecompression sickness hospitalization rates with those
for a matched sample of divers who had no recorded diving accidents,
divers who had suffered from decompression sickness had significantly
higher rates than matched controls for total hospitalizations, symptoms
(vertigo, abnormal involuntary movement, limb or joint pain, chest pain,
abdominal pain, syncope, and headache), and disorders of the arteries and
veins (arterial embolism and thrombosis, phlebitis and thrombophlebitis,
occlusion of precerebral arteries, and aneurysm). Other manifestations may
not appear for many years. There is controversy, however, about the na-
ture, frequency, and extent of neurologic sequelae of neurologic DCS and
arterial gas embolism, which may be difficult to document objectively.
At the present time, there is still no consensus about recommendations
for divers who have had DCS. It is probably advisable that diving not be
resumed until 4 weeks after an episode of DCS and that it be discontin-
ued if long-term sequelae remain after treatment.
Treatment of dysbaric osteonecrosis is mainly symptomatic. Attempts
at repairing and revascularizing necrotic areas of bone in the femoral
and humeral heads have been largely unsuccessful. Patients with severe
structural failure frequently require prosthetic articular replacement.
Workers with definite JA osteonecrotic lesions should be advised to stop
their exposures, and should be followed even if they do. On the other
hand, data does not support a similar recommendation for workers with
definite HNS lesions. The probability of neoplastic transformation in
the site of bone infarction needs to be kept in mind during long-term
follow-up.
162
 BAROTRAUMA
Barotrauma is the second leading cause of death in scuba divers (drown-
ing is the first). Barotrauma may occur during descent or ascent when-
ever a gas-filled space, such as pulmonary alveoli, middle ear, paranasal
sinuses, stomach, or dental fillings, fails to equalize its internal pressure
relative to changes in ambient pressure. The most dramatic changes in
pressure and volume occur under hyperbaric conditions, but the hypobar-
ic environment of aviation and space flight can also predispose the avia-
tor to complications of barotrauma. Manifestations of barotrauma of des-
cent are usually referred to as “squeeze,” and those of barotrauma of as-
cent as “reverse squeeze.” Recreational divers refer to the pulmonary com-
plications of barotrauma as “bubble trouble.”

Barotrauma of Descent
The middle ear is commonly affected in divers and air travelers. As
the ambient pressure is altered by high altitude or diving, the tympanic
membrane (TM) is displaced outward or forced inward because of the
compressibility of middle ear air. If the pressure across the TM is equa-
lized by normally patent eustachian tubes, or by forcing air into the tubes
by a controlled Valsalva maneuver, there will be no net displacement of
the TM and no barotrauma. If the eustachian tube or sinus osmium is
blocked, it is not possible to restore gas pressure equilibrium across the
TM and intense pain and hemorrhage can result. Blockage is most fre-
quently due to mucosal edema from infections or allergies. Middle ear
barotrauma can be associated with usually transient peripheral facial nerve
paralysis due to compression of vasa nervorum and neurapraxia. If the
inner ear is affected, perforation of the oval window may result in symp-
toms of tinnitus, vertigo, hearing loss, and nystagmus. Temporal relation
with the characteristics of the dive help differentiate this inner ear baro-
trauma from inner ear DCS (see above), which is important in view of
their different treatments.
Together with the middle ear, the paranasal sinuses are the most com-
mon targets of barotrauma in divers, and the frontal sinuses are more fre-
quently affected. Symptoms of sinus barotrauma include severe pain over-
lying the sinus or adjacent teeth, sometimes associated with bloody nasal
discharge. Submucosal hemorrhage in the ear or paranasal sinuses may
be severe enough that surgical drainage is required. Prevention of these
conditions can be accomplished by the judicious use of systemic or nasal
decongestant and antiinflammatory steroid sprays. Unsatisfactory symp-

163
tom control and/or failure to equalize middle ear pressure by a Valsalva
maneuver contra-indicate a hyperbaric exposure.
During descent, facial barotrauma (face squeeze) can occur if the div-
er does not exhale through his nose into the mask. The latter allows equal-
ization of the gas pressure in the space between the mask and the face,
and the ambient pressure. The manifestations include facial mucocutane-
ous edema and/or ecchymosis, which does not require treatment. Dental
barotrauma, characterized by implosion of teeth (especially poorly filled
ones), can also occur during descent.

Barotrauma of Ascent
The ears are rarely affected on ascent because the eustachian tubes
normally function as one-way valves, allowing air to escape from the mid-
dle ear but not to enter it. Although less frequent than barotrauma of de-
scent, barotrauma of ascent is associated with the most serious and po-
tentially lethal complications: pulmonary barotrauma and arterial gas em-
bolism (AGE).
When transpulmonary (intratracheal minus alveolar) pressure exceeds
100 cm H 2O, gas can escape along perivascular sheaths and rupture into
the pulmonary interstitial tissue (interstitial emphysema), mediastinum
(pneumomediastinum), pleural spaces (pneumothorax), subcutaneous tis-
sues (subcutaneous emphysema), or the pulmonary veins or the left atri-
um (paradoxically through a patent foramen ovale) causing arterial gas
embolism. Excessive transpulmonary pressure gradients are most com-
mon under hyperbaric conditions, such as scuba diving, during which the
scuba apparatus allows the diver to maintain near-normal lung volumes
despite being exposed to hyperbaric intraalveolar pressures. According
to Boyle’s law, if a scuba diver ascends from a salt water dive of only
33 feet too rapidly or without exhaling, alveolar volume will double. This
differs from breath-hold diving during which the volume cannot exceed
total lung capacity at sea level. Less significant volume expansion occurs
at altitude. However, even small volume changes may cause barotrauma
if individual lung units have prolonged time constants (resistance × com-
pliance) due to obstruction or bronchospasm or if the diver fails to exhale
during ascent.
Short of rupturing, overdistention of the lung with resulting local in-
jury results in the relatively mild pulmonary overinflation syndrome. Pa-
tients may complain of hemoptysis, with or without chest pain. Chest ra-
diographs may reveal a small pleural effusion. Injury is localized to the
overdistended area and requires only symptomatic treatment.

164
 Symptoms of mediastinal emphysema include dysphagia, cough, dys-
pnea, and pleuritic chest pain that may radiate to the shoulders. Mediasti-
nal emphysema can only be detected radiographically, unless it extends
to the subcutaneous tissues of the neck (subcutaneous emphysema). A
pneumothorax, especially if under tension, is clinically detectable by a
characteristic physical examination: diminished ipsilateral breath sounds,
hyperresonance to percussion, and deviation of the trachea to the con-
tralateral side. Concomitant signs include tachypnea, tachycardia, hyper-
tension, and cyanosis. If a pneumo-pericardium is also present, a harsh
pericardial rub (Hamman’s “crunch”) may be auscultated. Treatment of a
pneumothorax involves administering high-flow oxygen and placement
of a chest tube. Concomitant injuries may require hyperbaric oxygen the-
rapy.
AGE is the most life-threatening syndrome of barotrauma. AGE and
decompression sickness share similar pathophysiology (formation of ar-
terial gas bubbles) and treatment (decompression). However, they differ
in the source of the gas bubbles, and in that DCS requires a transition to
an environment with lower ambient pressure, whereas AGE occurs iso-
barically. Although it is much less frequent than DCS, AGE accounts for
a disproportionately higher number of deaths from diving.
Clinically, there are two main presentations of AGE:
a) isolated CNS symptoms;
b) cardiovascular collapse. In divers, the CNS manifestations predomi-
nate (95% of reported cases of AGE). Cardiovascular collapse is thought
to be due to either acute myocardial ischemia after coronary artery em-
bolization or neurogenic-mediated hypertension and cardiac dysrhythmi-
as if the embolus lodges within the cerebral arterial circulation.
The neurologic manifestations of AGE are diverse. In contrast to DCS,
the brain is the most frequent target of AGE, and symptoms and signs are
noticed immediately upon surfacing, almost without exception. Simulta-
neous embolization of multiple brain arteries occurs, and this explains
the diversity of the neurologic clinical findings. Symptoms include verti-
go, a feeling of apprehension, confusion, and faintness. Signs progress
rapidly and range from sensory disturbances and aphasia to hemiplegia,
cortical blindness, hemianopias, confusion, coma, and seizures. Rare, but
classic, signs include marbling of the skin of the upper torso, gas in the
retinal arteries, and sharply demarcated areas of pallor on the tongue (Lei-
ber — Meister’s sign).
Five percent of individuals with AGE die almost immediately and 35%
stabilize or deteriorate. The majority (60%) improve within minutes be-
cause of redistribution of emboli to the venous circulation. Interestingly,
165
within 1 hour of initial embolization, approximately 15% of AGE cases
recover completely, but frequently relapse. Relapse may be due to the in-
teractions between air and blood elements, and triggering of the inflam-
matory mediator cascades discussed above.
Treatment is very similar to that of DCS. Despite the severity of AGE
manifestations, recompression in a hyperbaric chamber frequently reverses
them. Delays in transporting patients to a treatment facility is directly pro-
portional to mortality and frequency of long-term sequelae. A few issues
are relevant to the treatment of AGE. Patients are transported in a head-
down and left lateral decubitus position and that position is also main-
tained during hyperbaric treatment. The recommended starting compres-
sion is usually higher in AGE than in DCS, to ensure immediate bubble
size reduction. Relapse after an initial complete recompression treatment
is frequent (about 30%), although usually less so in AGE patients than in
those with DCS. Hyperbaric treatment is indicated for relapses, and is
continued daily until there is no evidence of further improvement. Al-
though administration of large doses of corticosteroids has been recom-
mended in the treatment of AGE, its therapeutic value is unclear. Cardiac
antiarrhythmic medication infusions are being increasingly used. Chest
radiograph to exclude tension pneumothorax and continuous ECG moni-
toring during hyperbaric treatment are also indicated.
As with DCS, there is no agreement on the nature, extent, and frequen-
cy of long-term neurologic sequelae from episodes of AGE. Long-term fol-
low-up should include careful neuropsychological assessments. All indi-
viduals who have suffered AGE should permanently refrain from diving.

Other Dysbaric Disorders

Oxygen-diving-induced middle ear underaeration is a condition of un-
known pathogenic mechanism, believed to be different from middle ear baro-
trauma. It occurs in divers in the morning hours after diving the previous
day with a pure oxygen breathing mixture. The pathogenesis is still unclear.
Middle ear negative pressure has been demonstrated by tympanography. Tran-
sient pain and hearing deficit are the usual complaints, and effusions can be
observed by otoscopic examination. The process is self-limited.

Medical Evaluation of Prospective Divers

Diving requires strenuous activity in an alien, hyperbaric environment.
The medical evaluation of individuals wishing to dive needs to focus on
conditions that either limit the ability to exercise, are exacerbated by exer-
cise, or can be provoked or worsened by alterations of ambient pressure,
166
volume, or temperature. Any contraindication for hyperbaric treatment
also contraindicates diving. Table 9.3 lists those conditions that are be-
lieved to be disqualifying for diving. The major diseases that require ex-
clusion are obstructive lung disease and cardiac conditions. The type of
diving (recreational versus commercial) influences the rigidity of the stand-
ards used to evaluate candidates.
The elderly should undergo appropriate cardiopulmonary exercise test-
ing prior to diving. The older diver should also be warned about an in-
creased risk of hypothermia.
Obstructive lung disease or previous pulmonary barotrauma place the
diver at risk because of hyperinflation, which may occur during ascent,
and because of limited exercise tolerance. Similarly, exercise-induced car-
diac dysrhythmias are a potential danger for divers. Intracardiac shunts
predispose to paradoxical venous emboli followed by arterial gas embol-
ization. Unfortunately, patent foramen ovale (demonstrated by echocar-
diography during a Valsalva maneuver) is a very common condition in
the general population. One study noted a prevalence of 24% in a group
of divers who had no symptoms of decompression sickness, compared to
two-thirds of divers who had.
Asthma poses a problem when an afflicted individual wants to dive.
Exercise or hyperventilation of cold, dry air may provoke airway con-
striction that can cause nonuniform ventilation distribution and localized
pulmonary hyperinflation. Even when asymptomatic and well controlled,
asthmatics show evidence of abnormal ventilation distribution as assessed
by frequency dependence of compliance testing. Hyperinflation and air
trapping theoretically predispose the diver to barotrauma during ascent.
Whether the hypothetical concerns of increased risk of barotrauma in asth-
matics translates into an increased number of diving accidents in asth-
matic divers has not been conclusively documented, and remains a con-
troversial issue. Until recently, most experts disqualified diving candi-
dates who had an asthma attack after the age of 12. Recently, various ar-
guments have questioned this dictum based on epidemiologic data. Of
100 scuba diving fatalities in New Zealand and Australia, 7% occurred in
asthmatics, whereas the incidence of asthma in those countries is 12% to
20%. However, there was a strong bias during the decade studied (1980–
1990) to exclude asthmatics from the dying population, which may ex-
plain the underrepresentation of asthmatics in mortality figures. In a ques-
tionnaire study of 10,400 certified divers, 8.3% had a history of asthma
and 3.3% currently had asthma at the time of the study. In studies of ac-
tive asthmatic divers, Farrell and Glanville reported no statistically in-
creased incidence of barotrauma compared to nonasthmatic divers.
167
 Table 9.3. Medical conditions
that may disqualify individuals from diving
Pulmonary disease (e. g. Obstructive lung disease)
Asthma (see text)
Bullous or cystic lung disease
Bronchiectasis
Cystic fibrosis
Chronic obstructive pulmonary disease
Predisposition to pulmonary barotrauma
Previous pneumothorax
Previous thoracic surgery
Eosinophilic granuloma
Pulmonary lymphangioleiomyomatosis
Pulmonary hemorrhage
Cardiac diseases
Intracardiac shunts, unrepaired
Coronary artery disease
Exercise-induced tachyarrhythmias
Dysmythmias, not controlled
Neurologic diseases
History of seizure disorder (except febrile seizures in infancy)
Recurrent episodes of syncope
Ophthalmologic and otolaryngologic conditions
Meniere’s disease
Middle ear prosthesis
Visual disturbance, severe
External ear canal obstruction
Unilateral vestibular organ damage
Failure to voluntarily equalize middle ear pressures (e.g., by Valsalva
maneuver)
Recent eye surgery
Presence of hollow orbital implant
Obstructed nasal and paranasal passages (e.g., upper respiratory
infections)
Miscellaneous
Previous episode AGE or sequelae from DCS
Poor physical conditioning
Psychological instability
Clinical dependency
Insulin-dependent diabetes mellitus
Sickle-cell disease or trait
Caries (including poorly filled ones)

168
 The estimated risk ratio for arterial gas embolism was 1.25 (95% con-
fidence interval 0.8–2.1) for asthmatic divers, and 1.65 (0.8–3.6) for cur-
rent asthmatics. However, a small sample size may have limited the abili-
ty to detect statistically significant risk ratios. Asthmatics would there-
fore face a less than twofold increase in risk of a very infrequent event.
Realizing that a significant number of recreational and commercial divers
have active or past history of asthma, the Undersea and Hyperbaric Medi-
cal Society recently sponsored a conference on asthmatic divers. Given the
fact that many asthmatics dive without experiencing the theoretically in-
creased risk of dysbarism, the experts focused on identifying which asth-
matics should be excluded from diving. The panel concluded that:
a) previous policies that excluded all asthmatics from diving may par-
adoxically increase the risk of dysbarism in asthmatic divers by discour-
aging them from obtaining an appropriate assessment of their fitness to
dive;
b) pulmonary function testing (PFT) is the best method of evaluating
an asthmatic’s fitness to dive;
c) asthma that is controlled (no symptoms, normal PFT), even if in-
haled (not systemic) steroids are required, does not preclude safe diving;
d) acute asthma, as evidenced by symptoms (dyspnea, chest tightness,
cough, nocturnal awakenings), signs (wheezing, coughing), or PFT ab-
normalities, would preclude diving until the symptoms have normalized
and returned to the individual’s baseline for a minimum of 3 weeks.
Airway hyperreactivity, a physiologic hallmark of asthma, may be best
assessed in divers by bronchoprovocation testing with exercise (which
simulates the activity of diving); inhalation of cold dry air, methacholine,
or histamine are other available methods.
Most experts discourage diving during pregnancy. Pregnant women
may incur difficulties when diving due to the physiologic changes that
they undergo. Congested mucous membranes may prevent equilibration
of the middle ear and sinuses. Abnormal temperature regulation may pre-
dispose to hypothermia. In addition, the increase in body fat may predis-
pose to decompression sickness. Of more concern is the fate of the fetus,
which can be adversely affected by a decrease in oxygen delivery. Sur-
veys of women who scuba dived during their pregnancies showed a fetal
complication rate similar to the general population but statistically in-
creased when compared to women divers who refrained from diving when
pregnant.
A previous history of dysbaric disorder is also a consideration. Divers
who have suffered DCS should refrain from any diving until 4 weeks af-
ter complete recovery. Divers who have sequelae from DCS or who have
experienced AGE (with or without sequelae) should not dive at all.

169
 TESTS
1. A man, 48 y. o., spent a holiday at the mountain health resort. After
good breakfast he climbed on the height of 800 m with a group of sports-
men at a rapid pace. At the end of the climbing nausea, giddiness ap-
peared, dyspnea, palpitation, and in some hours epistaxis appeared, the
pain sensations in joints and their tumescence increased. From anamne-
sis it is known that he has suffered from hypertension of 1st degree for 10
years. Establish diagnosis:
A. Alimentary toxicoinfection.
B. Hypertonic crisis
C. Rheumatic disease.
D. Mountain disease.
E. General cooling.
2. After skiing in the highlands a man of 40 years old felt fast fatigue,
weakness, dyspnea, palpitation, pain in joints, nasal bleeding, vomiting
with blood impurity. At slow descent down to the valley these signs de-
creased, and then disappeared absolutely.
Establish the diagnosis:
A. Disorder of the nervous system.
B. Hypobarism.
C. Coronary disease.
D. Rheumatoid attack.
E. Peptic ulcer.
3. A patient, 34 years old, a diver, complains of pain in the ears, “en-
flated abdomen”, sensation of cold, articular pain (knee and humeral),
skin itching (“caisson scabies”). Objective: the pain in nerve trunks, mus-
cles and joints are defined at palpation. The edema of periarticular tissue
is marked.
Put the diagnosis:
A. Acute caisson disease of moderate severity.
B. Acute caisson disease, a severe form.
C. Acute caisson disease, a mild form.
D. Chronic decompressive disease.
E. Intoxication with hydrogen sulfide.
4. A patient, 29 years old, a diver. While ascending from the depth, in
connection with breakage of the compressor he was compelled to increase
the rise. In 2 hours the complaints of sharp weakness, sansation of heavi-
ness and pains in the head appeared. Then sonitus, “fly flashing” before

170
eyes appeared. The vomiting, strong abdominal pains, often defecations
added. Objective: mydriatic pupils, reaction to light is reduced, horizon-
tal nystagmus, bradycardia, intense stomach, painful palpation.
What pathology is meant?
A. Ulcer of the stomach.
B. Acute compressed-air disease, a moderate form.
C. A poisoning with a respiratory admixture.
D. An acute compressed-air disease, a mild form.
E. Hypertensic crisis.
5. A man C., 46, a pilot with a 5-year experience on the preventive
examination marks, that in last 3 months in the flight, continued more
than 1 hr a desire to yawn, hypersalivation, nausea, sometimes swoon or
headaches, strong sweating have appeared. After the flight a malaise still
was not kept for a long time. Objective: BP — 140/95 mmHg, heart rate
— 80 bpm.
The preliminary diagnosis:
A. NCD, hypertonic type.
B. Vibration disease.
C. Altitude sickness.
D. Cochlear neuritis of a mild degree.
E. AH, the 1st degree.

171
 Chapter 10
OCCUPATIONAL
EXPOSURE TO NOISE

Damage to human hearing from exposure to noise can take two forms:
acute, which is secondary to a loud noise such as a blast, and chronic,
which is due to long-term exposure to hazardous noise levels. Noises haz-
ardous to human hearing are present in a variety of environments, includ-
ing military service, civilian occupations, especially manufacturing, and
leisure-time pursuits. Noise-induced hearing loss (NIHL) was recognized
as early as the publication of Bernardo Ramazini’s text on diseases of
workers in the XVIII century.
Recent estimates indicate that many people in the Ukraine work where
noise exposure levels of 80 dB or greater may present a hazard to hearing
and approximately 3.2% of people had some degree of hearing loss. The
proportion of those with hearing loss increased with age; within age
groups, rates were consistently greater for those who worked in indus-
tries defined as noisy.
Clearly, noise is a major occupational health risk. We recommended
the following measures to prevent hearing loss:
1. Develop new technology that leads to quieter processes.
2. Develop noise control strategies at the source of existing operations.
3. Develop hearing conservation programs and effective hearing pro-
tection devices.

NOISE AND HEALTH

In occupational medical practice, noise presents three fundamental risks
to health:
1. Acutely, through blasts, explosions, or other high-impulse noises
that lead to hearing deficits.
2. Chronically, through continued exposure to unsafe levels of noise
that lead to sensorineural hearing impairment.
3. Through extraauditory effects, including alterations in blood pres-
sure and adverse influences on existing illnesses such as hyperlipopro-
teinemia and diabetes.

172
 Acute Acoustic Trauma
Exposure to intense levels of noise can cause permanent damage to
the middle and inner ear. In one review of 52 cases of acute acoustic trau-
ma (AAT), the most common symptoms were hearing loss (95%) and tin-
nitus (70%). Most of the cases were thought to have been exposed to noise
levels in the range of 140 to 160 dB. Military service accounted for the
majority (45%); about one in four had bilateral damage.
Results of audiometric evaluation in AAT may reflect conductive hear-
ing loss secondary to traumatic rupture of the tympanic membrane, dis-
ruption of the ossicular chain, and mechanical damage to the oval win-
dow, as well as sensorineural loss from cochlear hair cell disruption. Higher-
frequency pure tone hearing loss is more common in AAT, with frequen-
cies between 4,000 and 8,000 Hz most affected. A period of weeks to
months may be required for hearing to stabilize; the pathologic process
resulting in progression of hearing loss from AAT appears not to extend
beyond a year unless other factors are present. Even if the audiometric
results return to normal, however, permanent damage may have occurred
to the sensory cells of the inner ear, and continued exposure to noise may
result in further deterioration of hearing. An interesting finding of evalu-
ations of AAT is that most people do not seek medical attention immedi-
ately following the blast explosion or traumatic event. It appears that tin-
nitus, rather than pain or decreased hearing acuity, was the symptom most
likely to prompt people to seek a medical evaluation.
Military operations present the greatest risks for suffering an acute in-
jury to the ear. A survey of World War II casualties indicated that aural
injuries accounted for 5.8% of the patients treated at a U.S. military hos-
pital in Paris. Relatively little information is available on the extent of
occupationally related acute hearing damage that progresses to the sen-
sorineural pattern typical of NIHL.
Unusual explosions have also occurred in certain settings, especially
in concert with terrorist activities. One such event in Belfast, Northern
Ireland was described. Nearly a year after an explosive blast in a restau-
rant, 30% of those present suffered from high-frequency sensorineural
hearing loss. (Hearing loss was defined as > 30 dB at 4,000 and 8,000 Hz
in one or both ears.)
In the Falkland Islands war, military personnel who operated heavier
weapons suffered greater hearing loss than those not so exposed. Soldiers
operating the heavier artillery, on average, had at least 5 dB loss in each
ear at certain frequencies. Blast injuries are particularly difficult to pre-
vent in military operations because of the reluctance of personnel to wear

173
hearing protection devices for fear that they will interfere with communi-
cations and place their lives at risk.
On physical examination the ear is usually normal unless the tympan-
ic membrane is ruptured, which occurs in approximately a third of cases
of AAT. Damage to the cochlea, vestibular system, and ossicles of the
inner ear can also occur. The diagnostic use of the auditory brain stem
response has been found to be effective in the clinical evaluation of a
blast injury to the ear. Note that it is not necessarily the ear exposed to
the blast that sustains the injury, since blast waves may bounce off walls
and surrounding objects to cause an injury in the ear not directly exposed
to the source.
Complications following such injuries include persistent perforation
of the tympanic membrane, permanent hearing loss, and cholesteatoma.
About 10% to 20% of tympanic membrane ruptures require surgical cor-
rection, with the remainder generally healing without intervention. The
patient with a persistent perforation should be advised to keep water, for-
eign bodies, and other potential contaminants out of the external auditory
meatus. Large perforations and those that appear not to be healing man-
date referral to an otolaryngologist.
Although prevention of AAT should be emphasized, these injuries can
rarely be predicted. Where prevention fails, proper treatment depends on
access to medical care. A number of treatment measures have been at-
tempted that are based on the premise that the blast has caused metabolic
disturbances in the sensory cells of the inner ear. Evaluation of the effec-
tiveness of medications, however, is impeded by the lack of preexposure
audiometric values.
In a review of medicinal therapy for AAT, no convincing evidence was
noted to support the use of vitamin A, B, or E, nicotinic acid, papaverine
hydrochloride, or a number of other substances. Dextran has been widely
used by the German military with variable results, which may have been
in part due to better pre-treatment thresholds in the treated subjects. Re-
ports suggest that following the injury, treatment must be given promptly
if the intervention is to be effective. More recent reports indicate a lack
of efficacy of dextran. The strength of these claims is difficult to evaluate
in light of the absence of clinically controlled double-blind evaluations.
A thorough understanding of the mechanisms of AAT would enhance
both prevention and treatment. Animal studies have suggested that cer-
tain pathologic features are consistent within species, especially the acute
mechanical failure associated with AAT. Consistent findings include sepa-
ration of the organ of Corti from the basilar membrane and disturbances
in function of the tympanic membrane and ossicles. In an attempt to un-
174
derstand the effect of various military operations on the hearing of troops,
the U. S. Army sponsored an evaluation of 67 sheep and pigs that were
exposed to military operations while they were positioned in an armored
vehicle. Tympanic membrane rupture was a consistent finding in the ani-
mals; the authors concluded, “The prevalence and severity of ear drum
injury is greater for large anti-armor artillery and that the injury correlat-
ed with increasing peak pressure” and therefore blast intensity.

Chronic Hearing Loss

Prolonged exposure to noise primarily damages the inner ear, espe-
cially the hair cells of the organ of Corti. Cochlear blood vessels, the stria
vascularis, and nerve endings associated with the hair cells can also be
damaged. Initially, the hair cells of the basal turn of the cochlea are af-
fected; this area is responsible for perception of higher-frequency sound.
Eventually, disruption of the medial and apical areas occurs as well.
Although the risk of suffering NIHL tends to increase with advancing
age as well as with length of employment, most noise-related effects oc-
cur within the early phases of exposure to noise. In fact, most of the dam-
age that occurs to the hearing mechanism tends to occur within the first
10 years. Presbycusis, the impairment of hearing due to advancing age,
results in diminished hearing ability usually beginning in the mid-40s and
continuing thereafter. People who suffer from sensorineural hearing loss,
however, do not usually recognize early changes in their ability to hear.
Nonetheless, early changes can usually be documented by audiometric
monitoring. A study of army helicopter pilots indicated that only one of
four who exhibit decrements on audiometric monitoring was aware of any
hearing deficit. Early symptoms of NIHL reflect a person’s ability to dis-
tinguish higher-pitched consonant sounds. Speech is recognized as less
intelligible as opposed to lower in volume. This latter point accounts for
the lack of efficacy of hearing amplification devices in the treatment of
people whose hearing is impaired due to noise.

Risk Factors
The major risk factor for suffering noise-induced hearing loss is pro-
longed unprotected exposure to levels of noise beyond 85 dB. A number
of other risk factors, however, have been proposed, including hyperlipo-
proteinemia, diabetes, solvents, cigarette smoking, eye color, and thyroid
abnormalities.
The contribution to hearing loss from lipid abnormalities remains un-
certain. A review of 100 patients with bilateral sensorineural deficit found
175
the prevalence of hyperlipoproteinemia to be lower than in the general
population. These results, however, differ from other, later results indi-
cating a significant correlation of elevated low-density-lipoprotein cho-
lesterol with noise-induced hearing loss.
A significant issue in occupational medicine is whether workers with
diabetes are at greater risk of NIHL. Non-insulin-dependent diabetes may
increase the risk of severe hearing loss in those with occupational expo-
sure to noise. Imprecise data, especially regarding the duration and se-
verity of disease, and small sample sizes of workers with insulin-depend-
ent diabetes mellitus (IDDM), have hampered attempts to draw a link be-
tween IDDM and NIHL. The cause of diabetes-induced hearing loss, how-
ever, is yet to be fully determined, but it appears to be due to metabolic
disturbances that affect nerve function. Despite the possibility of increased
risk of NIHL among diabetic patients, most occupational physicians do
not feel that scientific evidence warrants restricting people with this dis-
order from noisy work if appropriate measures for reducing noise expo-
sure are followed.
An investigation of more than 2,000 noise-exposed white males in an
aerospace company indicated that cigarette smokers have an approximately
40% greater risk of NIHL. In fact, the major risk factors for this cohort
were smoking, a noisy hobby such as guns, and number of years worked
at a noisy plant. These results give credence to the theory that suscepti-
bility to NIHL may be due to relative ischemia of the vasculature of the
inner ear. The contribution of ischemia, however, to the development of
NIHL is difficult to discern in light of conflicting scientific evidence, es-
pecially regarding people with diabetes. For example, patients with dia-
betic retinopathy had no greater prevalence of sensorineural hearing im-
pairment than controls. Other studies assessing the contribution of ciga-
rette smoking to the development of NIHL have shown mixed results.
Some evaluations have shown a strong association between smoking and
NIHL, others a dose-response relationship significant only at heavy smok-
ing levels, and still others demonstrate no association.
After noise, the exposure of most concern in the workplace setting is
industrial solvent exposure. Selective midfrequency hearing deficits have
been demonstrated in rats exposed to toluene, styrene, xylenes, and trichlo-
roethylene. Solvent abusers, with exposure primarily to toluene, have also
demonstrated balance disorders and hearing impairment. Epidemiologic
studies of hearing loss in solvent-exposed workers have been more va-
riable, possibly because of the role of other factors, such as workplace
noise, aging, and smoking, on the results. High-frequency hearing loss
has been described in workers exposed to mixed solvents and noise. Seve-
176
ral cohorts of workers exposed to solvents in the absence of noise have
also shown abnormalities on pure-tone audiometry or on evoked cortical
response audiometry, indicating an effect on more central pathways of
the auditory response.

Mechanisms of Noise-Induced Hearing Loss

How noise actually damages hearing has been the subject of a variety
of research efforts. Most investigations have been conducted on animals
and have attempted to determine the cellular and vascular damage secon-
dary to noise. The first detailed description of abnormalities in the inner
ear associated with sensorineural hearing loss was published in 1934. Since
then, research has indicated that the effects of noise tend to occur in the
organ of Corti, within the cochlea of the inner ear. This structure has three
outer rows and one inner row of hair cells, with the tectorial membrane
suspended above them. The hair cells contain cilia that project toward
the tectorial membrane. The energy transmitted from the tympanic mem-
brane via the ossicles to the cochlea vibrates the cilia and is then coded
into nerve impulses in the acoustic nerve. The hair cells are quite suscep-
tible to the trauma of loud noise. The cell bodies swell with repeated ex-
posure to loud noise and ultimately the hair cells are destroyed. Studies
have indicated that the vascular supply of the basilar membrane is dis-
rupted when high noise levels are applied. Capillary vasoconstriction in
response to loud noise may result in diminished oxygen tension and local
hypoxia within the cochlea.
A variety of animal investigations have been performed that confirm
the mechanisms described above. In a transmission electron microscopic
study, edema and swelling of the afferent nerve endings below the inner
hair cells were noted. Following an acute reaction, in which the hair cell
was distended, a cytoplasmic protrusion occurred that indicated cell da-
mage. These changes to the afferent nerve fibers were also noted in an
investigation of guinea pigs. In general, most investigators agree that a
combination of mechanical, metabolic, and vascular factors are involved
in the destructive changes that lead to NIHL. Eventually, the organ of
Corti breaks down with separation of segments of sensory cells from the
basilar membrane, leading to elimination of sensory structures and replace-
ment by a single flat cell layer.
In a study of rats, mean cochlear blood flow was much lower in noise-
exposed groups than in those not exposed to noise. In fact, an interesting
finding of potential clinical application was noted: rats that were sponta-
neously hypertensive tended to have a greater decrease in blood supply
177
than those that were not hypertensive. This finding may have some rele-
vance in evaluating the extraauditory health risks associated with noise,
such as hypertension. This observed reduction in cochlear blood flow could
lead to hypoxia, and ultimately disruption in inner ear metabolism. This
finding that hypertensive rats were at greater risk for NIHL was confirmed
by another study. It remains unclear, however, whether the decrease in
blood supply associated with impaired hearing is either a primary or sec-
ondary pathologic response. Another animal investigation noted vasocon-
striction of the cochlear blood vessels in response to exposure to high
noise levels. These authors also proposed impaired blood flow in the in-
ner ear capillary as the major mechanism leading to NIHL.
According to some authors, the pathologic abnormalities associated
with NIHL can be differentiated from those due to presbycusis. Certain
morphologic abnormalities, for example, appear to be different. Noise dis-
rupts the outer and inner hair cells of the organ of Corti; ultimately de-
generation of nerve fibers and ganglion cells occurs. Presbycusis, by con-
trast, causes abnormalities over the entire auditory system.

Extra-auditory Effects of Noise

The extraauditory effects of noise, most notably hypertension, remain
an area of active interest regarding health implications of noise. Investi-
gative results, however, have varied regarding the relationship to hyper-
tension of long-term noise exposure. The basis of the proposed relation-
ship between noise and hypertension is grounded in the stress response,
that is, as a result of noise, release of adrenocortical hormones and sym-
pathomimetic mediators leads to increased heart rate and eventually higher
blood pressure. Investigations have been hampered because the prevalence
of hypertension and presbycusis, as well as NIHL, tends to increase with
age.
A number of investigations have been conducted into the relationship
between noise and hypertension. One approach involves correlating noise
levels with blood pressure measurements, which has been attempted in
some cross-sectional evaluations. For example, the blood pressure of cer-
tain noise-exposed groups can be compared to a similarly matched group
of workers not exposed to loud noise. Another approach is to evaluate
the blood pressure of people with sensorineural hearing loss and com-
pare their measurements to those of matched controls without NIHL. An
investigation of nearly 200 workers in a quiet plant (less than 81 dB) in
comparison to others in a noisy plant (greater than 90 dB) observed no
difference in mean systolic or diastolic blood pressure. A strong relation-

178
ship, however, was noted between severe NIHL (defined as a hearing
threshold of 65 dB or more at 3,000, 4,000, 6,000, and 8,000 Hz) and
high blood pressure (defined as diastolic pressure more than 90 mm Hg
or a physician’s prescribing hypertensive medication). The rate of hyper-
tension among older workers with severe NIHL was twice as great as for
those without hearing loss. The authors noted the clinical difficulties in
distinguishing presbycusis from sensorineural hearing loss. They found
that subjects with NIHL were impaired in both ear — and bone-conduct-
ed sound and exhibited the traditional 4,000-Hz dip on audiometric eval-
uation. This study, however, was the first effort in which NIHL proved to
be a biologic marker for hypertension, even when traditional risk factors
were controlled. These results are consistent with other evaluations that
suggest that the duration of noise exposure required to cause hyperten-
sion is greater than that needed to cause NIHL.
A study of 245 retired metal assembly workers showed a significant
relationship between hypertension and NIHL (defined as more than
65 dB loss at 3,000, 4,000, or 6,000 Hz). Note that these definitions of
severe NIHL are not identical to standard threshold shifts that may be
detected in audiometric evaluations. The authors also suggested that a
threshold of occupational noise exposure may be necessary to increase
the risk of hypertension. High-frequency hearing loss has also been asso-
ciated with elevations in serum cholesterol, which may lead to impaired
blood supply to the inner ear. In fact, a model for an apparent interaction
between hypercholesterolemia and NIHL has been proposed.
An investigation of automotive workers, however, found no relation-
ship between mean blood pressure and hearing loss at 4,000 Hz among
white workers. Among the 119 blacks in the study a higher prevalence of
hypertension (32%) was noted than in the 150 whites (22%).
The authors noted other interesting findings. In particular, they found
no correlation between years of exposure and hearing loss; as a result of
this finding, they suggested that the exposure years may not accurately
reflect cumulative noise exposure. Moreover, because of blacks’ higher
risk of hypertension, the authors suggested they may also be more sus-
ceptible to sensorineural hearing loss. A study of nearly 500 people who
worked in a textile plant and were exposed to levels of noise beyond
100 dB revealed that approximately a third had hypertension. The authors
noted, however, that the relation of arterial hypertension to noise expo-
sure was not strong. Studies of human volunteers have tended to support
a relationship between noise and diastolic blood pressure elevations in
both normotensive and hypertensive volunteers.

179
 Fifteen healthy normotensive medical students exposed to 95 dB noise
for 20 min exhibited significant elevations in diastolic blood pressure.
This elevation in diastolic blood pressure secondary to noise is confirmed
by other investigations. The authors proposed that noise activates the sym-
pathetic nervous system and elevates blood pressure by increasing total
peripheral resistance. Animal studies support the concept that vasocon-
striction of the cochlear vessels plays an important role in causing NIHL.
An interesting aspect of this mechanism is that different strains of rats
have marked differences in susceptibility for contracting hypertension due
to noise. In a review of the animal literature, Pillsbury claimed a signifi-
cant relationship between hypertension, noise, hyperlipoproteinemia, and
hearing loss.
Various hormonal responses have also been described secondary to
noise; effects range from increased levels of urinary catecholamines to
increased concentration of 17-hydroxycorticoids. Increased postshift uri-
nary cortisol excretion has been noted in workers exposed to high ambi-
ent noise levels compared with those wearing hearing protection equip-
ment. These findings bolster the hypothesis that noise acts as a general
stressor in the setting of normal work demands.

Pregnancy and Noise

Exposure to noise has resulted in teratogenic effects on laboratory rats,
including reduced fertility and enlargement of the ovaries. In a case-con-
trol study in Finland, approximately 1,200 women were evaluated. Re-
sults showed no relationship between occupational noise exposure (greater
than 80 dB) and risk of either premature birth or low birth weight. Only
approximately 3% of the study group, however, reported any exposure to
noise at work during their pregnancy. Moreover, approximately two-thirds
of the noise-exposed women were on sick leave during their pregnancy.
It is unclear what effect exposure to noise during pregnancy may have
on the unborn child, in terms of increased rate of miscarriage, low birth
weight, or prematurity. Most evaluations have been conducted on wo-
men living in the vicinity of airports. Exposure to noise in utero may
affect hearing later in life. In a study of 131 offspring of Quebec wom-
en, there was a threefold increase in the risk of high-frequency hearing
loss in the children whose mothers were exposed in utero to noise in
the range of 85 to 95 dB, and a significant increase in the risk of hea-
ring loss at 4,000 Hz when there was a strong component of low-fre-
quency noise exposure.
180
 Clinical Evaluation of Hearing Impairment
Physicians who practice occupational medicine are likely to find them-
selves asked to assess hearing impairment, prevent further deterioration
of hearing, and recommend patients for further evaluation and treatment.
Human hearing has a remarkable capability for differentiating sounds ran-
ging from a rustling leaf to the blast of armaments. In fact, the ear can hear
frequencies as low as 20 Hz and as high as approximately 20,000 Hz.
The early symptoms of NIHL tend to be subtle and may not be readily
recognized by the patient. As NIHL progresses, the person’s ability to
distinguish softer sounds is usually disrupted first. For example, the sounds
of birds and other high-frequency sounds such as voices may be difficult
to discern. People with high-pitched voices, such as children and some
women, may speak in a way that presents difficulties for a person with
NIHL. In general, the amplitude of the sound is not affected as much as
its clarity. As noted earlier, people with NIHL initially have difficulty with
higher-pitched sibilant consonant sounds, such as distinguishing the word
fish from fist.
Since the primary effect of NIHL is on the inner ear, the astute physi-
cian must be aware of other symptoms of inner ear disease, especially
vertigo. Vertigo is often the first symptom of inner ear disorders. Both
vertigo and high-pitched tinnitus can be early signs of acoustic neuroma.
Its presence may also suggest Meniere’s disease.
Vertigo, however, is seldom associated with NIHL or presbycusis.
Nevertheless, NIHL rarely, if ever, produces profound deafness, but the
condition tends to be progressive. Hearing handicaps are usually noticed
when the threshold hearing level of important (speech frequencies such
as 500, 1,000, 2,000, and 3,000 Hz) averages more than 25 dB.
The diagnosis of NIHL is straightforward when the physician incor-
porates a clear occupational history of noise exposure with the results of
an audiometric evaluation. The audiometric results may indicate the need
for further evaluation with more detailed diagnostic studies. The major
pathologic entities in the differential diagnosis of NIHL are presbycusis
and ototoxicity, although more than 40 genetic and metabolic syndromes
can cause deafness. Physicians evaluating the contribution of workplace
noise to hearing loss should also consider nonoccupational causes such
as target shooting, motorcycle riding, hunting, loud music, and portable
radios. It has been shown, for example, that personal stereos with head-
phones can generate noise levels well beyond OSHA standards. The ma-
jor drugs associated with deafness include furosemide and aminoglyco-
side antibiotics (gentamicin, for example). Analgesics, such as salicylates
181
and antihistamines, as well as tricyclic antidepressants have been associ-
ated with ototoxicity. Salicylates, in particular, are well known to cause
reversible tinnitus.
In evaluating a hearing-impaired person, the physician is advised to
review the results of pure-tone audiometric testing, which assesses the
ability to hear various standardized frequencies. During the test, tone levels
are increased in volume until the person recognizes the sound. The deci-
bel reading at which the person first recognizes the sound at each fre-
quency is recorded; this value is termed the hearing threshold for that
frequency. Threshold levels above 25 dB are abnormal, and are especial-
ly important when the speech frequency ranges (500 to 4,000 Hz) are af-
fected.
Early impairment due to NIHL tends to occur at 4,000 Hz, with pres-
ervation of hearing at higher frequencies (8,000 Hz). These findings are
typical of NIHL, with this 4,000-Hz notch persisting and deepening with
increased hearing loss secondary to noise. With presbycusis, the audio-
metric pattern has a similar decrement in the 4,000-Hz range; however,
the loss tends to be greater still in the 8,000-Hz range, and no notch is
noted. The audiometric findings of hearing loss due to ototoxicity are simi-
lar to those of presbycusis.
Despite the differences described for audiometric results, differentiat-
ing NIHL from presbycusis can be a difficult exercise. Moreover, presby-
cusis and NIHL can act concurrently to affect hearing. People with NIHL,
however, tend to show high-frequency hearing deficits for both ear and
bone conduction of sound, reflecting the sensorineural character of the
hearing loss.
Other diagnostic and screening tools used to identify hearing impair-
ment and distinguish between differing etiologies have been described.
To assess the degree of hearing impairment among people over 65 years
of age, a handheld audioscope was combined with the Hearing Handicap
Inventory for the Elderly (HHIE), a self-administered ten-item question-
naire designed to assess emotional and social problems associated with
impaired hearing. The audioscope can be inserted into the ear and deliv-
ers a 40-dB tone at frequencies of 500, 1,000, 2,000, and 4,000 Hz. In
this evaluation of 178 patients, the audioscope proved to be a sensitive
and reliable test for the detection of hearing impairment in persons older
than 65 years. The same study, when coupled with the HHIE, was 83%
accurate in diagnosing NIHL.
After reviewing diagnostic studies, especially the audiometric evalua-
tion, the physician can formulate an opinion as to the cause of hearing
loss and whether therapy may be effective. Unfortunately, treatment mea-
182
sures for NIHL tend to be ineffective, since the primary problem is not
the amplification of sound but the distinguishing of various types of
sounds. Thus, amplification devices that correct other types of hearing
impairment by increasing transmission of sound in the middle ear are large-
ly ineffective. Nonetheless, the physician should be aware of the need for
otologic referral in evaluating hearing loss. Consultation with an otolaryn-
gologist may be necessary when reviewing audiometric monitoring tests
of a hearing conservation program or for clinical evaluation of individual
patients. Some points to remember in the evaluation of suspected NIHL
include the following:
1. Chronic NIHL is usually symmetric; other otologic disorders, espe-
cially the more serious, as well as treatable, types, are often asymmetric.
2. NIHL usually develops gradually; other otologic disorders may
progress rapidly.
3. NIHL usually causes high-frequency threshold shifts.
4. Regardless of the cause, a pure-tone threshold average in excess of
25 dB in either ear is likely to cause hearing difficulties.

Noise-Level Assessment
The first step in assessing the need for an HCP is to measure the am-
bient noise level. Assessments are customarily performed by an industri-
al hygienist or a similar professional. Measurements performed in the oc-
cupational setting usually consist of overall levels that are obtained
either through a sound-level meter or a noise dosimeter. Monitoring of cer-
tain areas of a facility that generate noise is required to identify employees
who need to be enrolled in the HCP or who require hearing protection.
These measurements can also be effective in determining the amount of
attenuation required of the hearing-protection devices may be used. More-
over, noise assessments help to acquaint employees and employers with
the level of noise in the facility. When area surveys are not appropriate,
individual measurements must be made with a personal dosimeter. This
particular approach, although capable of yielding more accurate results,
tends to be more time-consuming and complicated. Generally, an employee
wears the noise dosimeter on the shirt collar throughout a work shift. Ac-
curate measurements depend on reliable calibration of the monitoring de-
vice. In certain circumstances it is worthwhile to assess noise at the ear.
An approach to monitoring noise exposure in workers who wear commu-
nication headsets has also recently been introduced. This first step, as-
sessing the noise levels encountered in work, is one of the more critical
determinants in evaluating the need for an HCP. Once noise levels are
183
determined, they need to be reevaluated at intervals, especially if new
processes or plant equipment are introduced into an operation. The occu-
pational physician who is asked to participate in an audiometric monitor-
ing program should obtain results of noise level assessments, the date of
the measurements, and an assessment of whether they reflect normal op-
erations.
In work settings where noise levels exceed 90 dB, engineering controls
should be employed. Machinery design, enclosures, and noise-control pro-
ducts can be effective in reducing noise at its source. The importance of
noise-control measures cannot be overemphasized. One author, for example,
has claimed that “prevention of occupational deafness, if it is to be taken
seriously, requires a decisive shift to engineering noise control”.

Hearing Protection Devices

The fundamental approach to reducing the risk of NIHL is to control
noise at its source. In some cases, however, this approach is not feasible,
so it is essential to provide hearing-protection devices. These are of three
basis types: insert, which are devices inserted directly into the ear canal;
semiinsert, which are devices that cover entry into the ear canal; and muffs,
which completely encapsulate the ear itself. Hearing-protection devices
provide various levels of attenuation (noise reduction). No single type of
hearing protection can be considered the single best choice for all users;
different workers will choose different devices because of such factors as
personal comfort and variations in the anatomic structure of their ears.
Thus it is essential to offer employees a variety of hearing-protection de-
vices, to ensure that all can comfortably wear them. During the audio-
metric evaluation it is worthwhile to acquaint or reeducate the employee
in the proper use of the hearing-protection device. When such a device is
fitted at the time of the audiometric evaluation, the external canal can be
evaluated more thoroughly.
Most hearing-protection devices provide 15 — to 30-dB attenuation.
When insert plugs are combined with muffs, an additional 10 — to 15-dB
protection can be obtained, a result noted clinically in a study of army
helicopter pilots. A noise reduction rating (NRR), which reflects attenua-
tion of environmental noise, must be assigned by the manufacturer of the
hearing protection device. Efficacy of these devices in the workplace, how-
ever, is dependent on many variables, and attenuation of noise under ac-
tual working conditions may be 25% to 75% of the labeled NRR. For a
comprehensive review of hearing-protection devices, including selection,
fitting, and care, the best source remains Berger.

184
 Education and Training
Physicians may also participate in various educational and training pro-
grams designed to acquaint managers and employees with the health im-
plications of long-term exposure to high noise levels. Such educational
sessions can be of great benefit in motivating employers and supervisors,
and impressing on them the importance of noise control measures and
proper use of hearing-protection devices. Employees also need to be ap-
prised of the nature and consequences of NIHL, and of the importance of
wearing hearing-protection devices and participating in annual audiometric
monitoring programs.

TESTS
1. A man, 49 years old, has worked during 15 years as the tester of
engines. What complaints does the man have during a preventive medi-
cal examination?
A. Sweating.
B. Headache.
C. Memory impairment.
D. Sonitus.
E. Hearing impairment.
2. A man, 45 years old, visited a polyclinic with complaints of head-
ache, weakness, working ability and sleep disorder, unpleasant sensation in
the heart area, sonitus, palpitation, hearing impairment. From anamnesis it
is known that the patient during 15 years has worked as a technologist at
the water-pump station. Some months ago he had a lincomycine course, a
week ago he suffered from influenza. Objective: BP — 140/90 mm Hg.
The lability of the nervous system is found. The audiogram reveales an
increased level of sound perception.
Establish the diagnosis:
A. Idiopathic hypertension.
B. NCD
C. Infectious cochlear neuritis.
D. Hearing impairment owing to the use of lincomycine.
E. Hearing impairment owing to influence of industrial noise.
3. A man, 49 years old, has worked as a conductor during 20 years.
Last 2 months he hasn’t heard some music tones. There are a headache,
swoons periodically. General otoscopy revealed no changes. At the audio-

185
gram: rising of sensitivity level. Whispering speech he catches normally.
Roentgenogram of the skull bones isn’t changed.
Establish the diagnosis:
A. Cochlear neuritis, phase of adaptation.
B. Cochlear neuritis, phase of decompensation.
C. Latent encephalitis.
D. Otosclerosis.
E. Tumor of the brain.
4. A man, 29 years old, a professional DJ, complains of blunt head-
ache, feeling of heaviness and noise in the head, sonitus, hearing impair-
ment, swoons at change of the body position, acrimony, dicrease of atten-
tion, infringement of the sleep rhythm, unpleasant sensations in the heart
area, palpitation, change of pulse and BP.
Establish the preliminary diagnosis:
A. Neuroinfection.
B. Cochlear neuritis, the 2nd degree.
C. Transient impairment of the cerebral circulation.
D. Cochlear neuritis, the 1st degree.
E. Idiopathic hypertension.
5. A patient, 48 years old, has worked during 10 years at the Belyaev-
ka Water Distributing Station, in the turbine shop, complains on hearing
impairment, feeling of heaviness and noise in the head, occured at the end
of the duty; muscle weakness, increased sweating, pricking pain in the
heart area appeared also. Objective: tremor of fingers of the extended arms,
decrease of tendinous reflexes, BP — 140/70 mmHg, Heart rate —
78 bpm. Other tests: hearing loss on 4,000 Hz — 65 dB, perception of
whispering speech on 2 m. All kinds of sensitivity are preserved.
What pathology is it possible to think of?
A. Cochlear neuritis with 1st degree of the hearing impairment.
B. Vibration disease, the 2nd degree.
C. Acute otitis.
D. Sound vegetative polyneuropathy
E. Craniopharyngioma.

186
 Chapter 11
INTOXICATION WITH SALTS OF
HEAVY METALS (LEAD, MERCURY,
MANGANESE) AND THEIR COMPOUNDS

The materials having toxic properties are often applied at the industry.
Various chemical substances, inorganic and organic compounds, entering
an organism in small amounts belong to toxic substances, participate in
biochemical reactions in cells and tissues, break the normal processes of
metabolism and cause their dysfunction.
Such substances may be initial, intermediate and end products of the
chemical industry, different solvents, lacquers, paints, some dopes, com-
ponents used in engineering and exploitation of gears, as well as pesti-
cides, insecticides and other components used in agriculture.
Toxic ability is a property of chemical compounds to cause harmful
action. It is defined as size to absolute meaning of an average lethal doze
or concentration: 1/DL50 ; 1/CL50 . The first one indicates the doze pro-
voking the death of 50 % of laboratory animals, the second one deter-
mines the concentration of the substance. By the level of toxic ability all
chemical substances are divided into 5 classes.
The 1st class — extremely toxic substances. It is the most dangerous
industrial poisons and insecticides, forbidden to the usage in Ukraine. They
are derivative of cyanhydric acids, compounds of lead, mercury, arsenic,
etc. For the 1st class the maximally admitted concentration (MAC) of such
substances makes up less than 0.1 mg/m3 in the air of the working area.
The 2nd class — very toxic substances, e.g. methanol, carbon tetra-
chloride, etc.). MAC is from 0.1 to 1.0 mg/m 3.
The 3rd class — moderately toxic substances, e.g. aromatic hydro-
carbon. MAC — 1.1–10 mg/m 3.
The 4th class — low toxic substances, e.g. derivative of urea, etc.
MAC — over 10 mg/m3.
The basic route of exposure of industrial poisons are inhalatory (gas-
es, steams and aerosoles), through the skin and less often — through the
gastrointestinal tract. The inhalatory route of exposure to industrial poi-

187
sons in an organism is basic and the most dangerous (the area of alveolar
membranes exceeds 100 m2).
The toxic substances, well dissolving in fats and lipids, easily pene-
trate the unprotected skin: organic solvents, aromatic compounds, tetra-
ethyl lead etc.
Some poisons are soaked up already in the mouth cavity. Thus their
toxic ability grows. From the gastrointestinal tract through the portal vein
toxic substances fall in the liver where they are neutrolized. Therefore
MAC of many chemical agents at entering through the stomach can be
100–150 times higher than at inhalation route.
The distribution in an organism of industrial doses depends on their
physicochemical properties and can be irregular. For example, poisons
dissolving in lipoids are to greater extent are stored in subcutaneous-fat
layer. The salts of heavy metals accumulate in the osteal tissue.
The toxic substances accumulate basically in the liver, where they sub-
ject to oxidation reactions, reduction, deamination, acetylation, connec-
tion with other substances.
Some toxic substances have capacity to be stored in the tissues,
forming a deposit. The concentration of the drug in the blood is re-
duced, but the deposited compound is not decontaminated and under
certain conditions can act in the blood again, rendering a harmful ef-
fect.
The toxic substances are excreted both in changed and unchanged
way through the kidneys, the lungs, the gastrointestinal tract, the skin,
the salivary and mammary glands. The nature of toxic action of the
substance is determined by its physicochemical features determining
specificity of biochemical violations and organ damage. The sex, the
age, the personal sensitivity to a poison, the disease in the life history,
condition of target-organs are very important. The toxic influence of
industrial poisons can be increased by unfavourable factors of ma-
nufacturing surroundings, overheating, increase of humidity, physical
stress.

INTOXICATION WITH LEAD

AND ITS COMPAUNDS
Lead (Pb), a bluish gray metal, is distributed in the earth’s crust in a
large number of minerals. The most important of these, in terms of ex-
traction of lead, is galena (PbS), which consists of 85% lead metal. Two
other significant lead minerals are cerussite (PbCO3) and anglesite (PbSO4).
188
Galena is usually accompanied by sulfides of silver, antimony, copper,
bismuth, and tin. Lead is also found combined with zinc in sphalerite.
Lead is a member of group IVB in the periodic table and has a melting
point of 327°C. It has two oxidation states, Pb(II) and PB(IV) in addition
to its elemental stage Pb(0). The metal is extracted from the ore by con-
centration of the sulfide, heating (roasting), and reduction. The metal then
undergoes refining to remove other metal constituents in the ore. Because
of its widespread use, lead and some of its chemical compounds are near-
ly ubiquitous in the human environment and can be found in plants, oceans,
rivers, drinking water, soil, and in various food items. Lead is also present
in the air and attaches to dust particles. Consequently, the possibility of
human exposure to some form of lead is great. It can be said that the pres-
ence of lead in blood and other body fluids serves as an indicator of in-
dustrial development and activities; its presence always reflects environ-
mental pollution, whether it originates from the general or occupational
environment. Lead is one of the ancient metals, produced by humans and
used as early as 6,000 years ago in Asia Minor. Both its use and toxic
effects can be traced to the cradle of human civilization. The numerous
applications of lead throughout the ages have been as varied as the hu-
man mind can envision. To mention a few examples, the Egyptians used
leaden tools and vessels, and a leaden statuette in the British Museum in
London gives testimony to the fact that lead was also used by the Egyp-
tians in the arts and crafts around 3500 B.C. The Israelites made the can-
delabrum in the Second Temple of an alloy containing lead; in the Han-
ging Gardens of Babylon plants were kept in leaden pots to retain mois-
ture, while the Romans drank sapa, wines, and ciders sweetened and pre-
served with lead. The habit of drinking such beverages was prevalent among
the Roman aristocracy and, according to some historians, might have been
an important contributing factor to the fall of the Roman Empire.
Although lead may have had a major impact on society as early as two
millennia ago, it is only during the past two decades that drastic measures
have been taken in many industrialized countries to minimize human expo-
sure to lead. In this respect, the United States has been in the vanguard in
controlling both occupational and environmental lead exposure.
Some of the toxic effects of lead were probably known to both the
Greeks and the Romans. Hippocrates (circa 370 B.C.) describes a severe
attack of abdominal pain (possibly “lead colic”) in a man who extracted
metals, while Nicander, in the second century B.C., noted an association
between exposure to lead and symptoms such as pallor, constipation, co-
lic, and paralysis. Pliny (79 A.C.) mentions that lead-based paint was used
on ships and that lead poisoning occurred among shipbuilders in his time.
189
 The numerous epidemics of lead poisoning that occurred in the Mid-
dle Ages throughout Europe are of great historic and epidemiologic in-
terest. The ancient Roman practice of improving the taste of poor vinta-
ges with additives containing lead was common during the Middle Ages.
The many episodes of lead poisoning that occurred during this period were
in fact the result of this practice. This was primarily discovered by Eber-
hard Gockel, an alert physician in the German city of Ulm, who realized
that the severe clinical symptoms known as colica Pictonum (the colic of
Poitou) that occurred among monks in monasteries in Ulm were caused
by drinking wines treated with lead oxide (litharge). His findings were
published in 1697. Poitou was the region in France where the habit of
adding lead to wines was so prevalent that the colic of Poitou was synon-
ymous with lead colic.
Moreover, another probable cause of intoxication was drinking acidic
beverages that had either been stored in lead-glazed earthenware or been
contaminated with lead during manufacturing. Thus, Sir George Baker,
in his classic description of the Devonshire colic in 1767, traced the dis-
ease to cider that had been contaminated with lead. Subsequently, in this
episode, other lead-induced clinical effects (e.g., gout) were also associa-
ted with exposure.
In 1839 Tanquerel des Planches published a famous study of 1,217 ca-
ses of lead poisoning, and his clinical observations contributed much to
our current knowledge of the clinical signs and symptoms of this occupa-
tional disease, including effects on the central nervous system. He real-
ized that most cases of occupational lead poisoning were caused by inha-
lation of lead dust and fumes. He also suggested an association between
lead exposure and renal disease. In Great Britain, great efforts to control
occupational lead poisoning were introduced during the last decade of
the 19th century. The pioneering work by Sir Thomas Legge, the first
medical inspector of factories, resulted in strict legislation, including de-
claring lead poisoning a notifiable disease, in 1899.
The adverse clinical effects of lead were not confined to the European
continent but occurred in colonial America as well. Symptoms of lead
colic were caused by drinking rum distilled in leaden vessels, and in 1723
legislation was passed in Massachusetts “preventing abuses in distilling
of rum and other strong liquors with leaden heads or pipes”. Serious con-
cern over occupational lead poisoning in the United States began in 1910,
with the investigations of several lead-related industries by Alice Hamil-
ton, a pioneer in the field of American occupational medicine. Detailed
studies of the clinical and biochemical aspects of lead poisoning were
conducted during subsequent decades.
190
 Since lead does not serve any biologic function in the body, its pres-
ence has always been taken as a sign of environmental pollution. Despite
its known toxic effects and long history of lead-associated diseases, there
is evidence that compounds of this metal were used for medicinal pur-
poses, especially during the XVIII century in France. The surgeon Tho-
mas Goulard (circa 1784), a member of the famous medical faculty in
Montpellier, used extract of Saturn (a concoction of lead monoxide in
wine vinegar) externally to treat a number of conditions: inflammations,
sprains, joint stiffness, ligament injuries, and gunshot wounds. Although
Goulard did not recommend internal administration of lead, other medi-
cal authorities in the XVIII and XIX centuries advocated taking lead ace-
tate per os for epilepsy. It is interesting to note that these physicians were
indeed aware of the “side effects” of such treatment, which included ab-
dominal cramps (lead colic).
Although some sources of environmental lead pollution prevalent in
modern society are different from those of the Middle Ages, many of the
symptoms associated with excessive lead exposure remained consistent
over time. Control of lead exposure achieved by legislation and modern
technology has undoubtedly made acute lead poisoning a much rarer di-
sease; however, certain neurologic and gastrointestinal symptoms, known
for centuries to be lead related, are still common symptoms causing per-
sons exposed to lead to seek medical attention.
During the past two decades much concern has been voiced over the
potential health consequences of exposure to lead in both occupational
and general environments. During this period several investigators have
examined the effects of environmental lead exposure, particularly among
infants and young children, who are most sensitive to the effects of lead
in society. Through these studies it has become increasingly clear that
adverse health effects are seen at levels of exposure that during previous
decades were considered safe. Of greater concern is the fact that the le-
vels of environmental exposure at which adverse health effects can be
detected have become progressively lower and the magnitude of the lead-
related public health risk to children may be greater than was hitherto
estimated. Major efforts to reduce exposure to lead have been made or
are in progress in many industrialized countries.
Lead and its many compounds will be used in effecting some alloys,
accumulators, solders, chemical instrumentation, crystal, for manufactu-
ring of safety devices from irradiation, and also in effecting paints, gla-
zes etc. The contact is most dangerous to those by connections of lead,
which one well solve in biomediums of an organism. Basic of them are
shown in the table 11.1.
191
 Table 11.1. Toxic compounds of lead
Metallic lead — Pb
Lead acetate: (Lead sugar) — Pb (CH3COO)2 × 3H2O
Lead Acetate — Pb (CH 3COO)2
Basic lead carbonate (White lead) — PbCO3
Lead chloride — PbCl 2
Lead tetraethyl — Pb (C2H5)4

The route of lead and its compounds exposure depends on plant con-
ditions. It takes place basically through the respiratory tract by the way
of dust, aerosol or vapors. Less often — through the gastrointestinal tract
(by swallowing of spit or at random intoxication) and through the skin at
a contact to liposoluble compounds of lead.
The respiratory route is the most dangerous as it acts directly in the
blood. Here-in-after it circulates in connection with proteins of plasma,
being step-by-step deposited different organs, predominantly bones, dis-
placing calcium. The deposited lead under unfavorable conditions inten-
sively excretes again in the blood, that creates conditions for peaking to
intoxication, and quite often long after contact with it.
Sources and forms:
A. Oral ingestion
B. Inhalation
C. Dermal absorption
D. Intravenous route
Pharmacokinetics
A. Absorption
1. Oral exposure. About 300 mcg are ingested each day in the normal
adult diet, 10% of which are absorbed. Children absorb 50% of ingested
lead. However, absorption after ingestion of organolead, such as tetrae-
thyl lead in gasoline, may be as high as 75%.
2. Inhalation. Absorption is greater and more rapid by the pulmonary
route.
3. Dermal exposure. Absorption is poor except in the case of organic
lead.
4. Dietary deficiencies of calcium, iron, and zinc enhance lead absorp-
tion as well as its tissue storage.
B. Metabolism
1. Although poisoning is generally chronic (months to years), symp-
toms arise acutely. When exposure is by inhalation or intravenously, symp-
toms develop far more quickly than if the lead is ingested.
192
 2. Half-life: 32 years in the bones; 7 years in the kidneys.
3. Once absorbed from the digestive tract, lead is distributed to the
viscera, chiefly the kidneys and liver; it is then taken up by the skeletal
system and stored as the insoluble, biologically inert tertiary lead phos-
phate. Lead is also deposited in the bones, kidneys, and teeth.
4. Excretion of lead occurs by way of bile, urine, exfoliation of epi-
thelial tissue, and sweat.
5. Accumulation and toxicity occur if > 0.5 mg/day are absorbed.
6. A dose of 0.5 g of absorbed lead is estimated to represent a fatal dose.
Lead and its compounds fall into to poisons rendering polytropic action.

Pathogenesis of Lead Intoxication

1. Disturbance of biosynthesis of porphyrins and heme with develop-
ment of hypochromia, hypersyderemical anemia.
2. Damage of the nervous system (astenovegetative syndrome, poly-
neurites, encephalopathy).
3. Damage of the digestive tube (lead line on the gums, gastroduoden-
itis, lead colic).
4. Disturbance of lipid, carbohydrate and mineral metabolism, sex
glands.
One of the basic developments of intoxication by lead compounds is
the development of a peculiar “lead” anemia owing to disturbance of bio-
synthesis of porphyrins and heme.
As it is known, the process of synthesis of porphyrins passes a series
of stages. Initial products are glycine and succinic acid. Then as a result
of a series of enzymatic reactions the protoporphyrin IX will be derivat-
ed, which one after actuation in it divalent iron transforms to a heme.
Major intermediate products are aminolevulinolic acid and coproporphy-
rinogen. A feature of toxic action of lead is depressing activity of the
enzymes participating in the subsequent transformations of indicated in-
termediate connections at the expense of blocking of their sulfhydryl
groups. As a result of accumulation of the indicated products their con-
tents in urine is augmented. At the same time lack of formation of heme
leads to formation of a peculiar hypochromic anemia. Thus the contents
of iron in the blood is heightened, in erythrocytes is stored unused in syn-
thesis of heme protoporphyrins and iron. The lead also renders direct ef-
fect on erythrocytes, that results in a decrease of their elasticity, abbrevi-
ation of duration of their life and accelerated destruction. Outcome it is
the activating of erythrogenesis pronounced in reticulocytosis and appea-
rance of erythrocytes with a basophilic stippling.
193
 The pathogenesis of changes on the part of nervous system at a lead
intoxication is connected to disturbance of exchange because of enzy-
matic disturbance, and also direct operating of lead and its compounds
on nervous tissue. Already at early stages of lead intoxication acid-base
balance is disturbed. The processes of excitation dominate over inhi-
bition.

Clinical Manifestations
Disturbance of the blood and nervous system is most typical in clini-
cal picture of chronic lead intoxication.
Hematological signs of lead intoxication satumism are:
Hypochromic anemia, with the normal or heightened contents of iron
in serum, reticulocytosis, basophilic stippling of erythrocytes. Their de-
gree of manifestation as a whole corresponds to gravity of lead intoxi-
cation. The earliest and authentic sign of intoxication is the disturbance
of porphyrinic exchange manifested in increased allocation with urine ami-
nolevulinolic acid and coproporphyrin.
The changes on the part of the nervous system at effect of lead and its
compounds are shown by the asthenic syndrome, polyneuropathy and en-
cephalopathy. The most mild form is asthenic or asthenovegetative syn-
drome with its typical features (weakness, heightened fatigue, irritability,
headache, decrease of memory and capacity for work).
The polyneuritic syndrome manifests at early stage as sensory distres-
ses, then the condition deteriorates. The hands and feet, and characteris-
tically primary impairment of extensor muscles (e.g. wristdrop) are af-
fected to the greatest extent. The vegetative-vascular disturbances (cya-
nosis, sweating, decrease of dermal temperature) are frequent. With se-
vere forms of intoxication the mixed forms with considerable increase of
an affected zone prevail.
Encephalopathy is characterized by organic changes in the CNS. Cli-
nically the dysarthrias, hyperkinesis, ataxia, tremor, cramps, anisocoria,
nystagmus are clinically manifested.
On the part of the digestive organs the changes are observed in secre-
tory and motor disturbance of the gastrointestinal tract. The inclination
to hypersecretion of gastric juice, spasticoatonic phenomenon in the in-
testine, instability of stool, disturbance of taste are marked, etc. In the
most pronounced form all these phenomena manifest as lead colic. The
sign for the given intoxication is a leaden line. Its appearance is connec-
ted to deposit of lead sulphide which is generated due to hydrogen sul-
phite for people with paradontosis and caries of teeth.
194
 An often mark is dyskinesia of the bile duct. There are data about dis-
turbance of lipide, mineral and hormonal exchange.
According to the degree of manifestation the initial, mild and pro-
nounced forms are distinguished.
At the initial form only the laboratory signs of lead intoxication take
place: reticulocytosis up to 25%, basophilic stippling of erythrocytes up
to 4%, increase of excretion with a urine aminolevulinolic acid up to
15 mg, coproporphyrine up to 300 mcg by 1 g of creatinine.
At the mild form alongside with aggravation of laboratory para-
meters approximately 1.5–2.0 times as much as compared to previous,
mild anemia and initial neurologic symptomatology are already deter-
mined.
At the pronounced form all the clinical and laboratory symptomes are
sharply manifested.
The duration of lead intoxication depends on expressiveness and na-
ture of syndromes. The initial and mild forms usually have the favour-
able prognosis. After the termination of contact with lead and treatment
the parameters normalize. At the severe form the irreversible residual
changes are possible. It is important to remember that exacerbation of
lead intoxication could occur due to periodic entry of lead from deposit.
A. The gastrointestinal effects
1. Anorexia.
2. Abdominal pain, colic.
Leaden colic is the most frequent manifestation of lead poisoning in
adults. The patient is anorectic and constipated, and often has nausea and
vomiting. There is abdominal pain but no tenderness. Characteristically,
the patient presses on the abdomen to relieve the discomfort. Lead colic
generally accompanies lead encephalopathy in children.
3. Intermittent vomiting.
4. Constipation.
B. The CNS effects
1. Irritability.
2. Learning disability and regression.
3. Drowsiness.
4. Persistent vomiting.
5. Incoordination, weakness, paralysis.
6. Headache.
7. Peripheral neuropathy — rare in children, but foot drop characte-
ristic; in adults, wrist drop is characteristic.
Neuromuscular form. Slowing of motor nerve conduction velocity
is an early sign of lead poisoning in children; symptomatic neuropathy is

195
rare. In adults, however, symptomatic neuropathy is frequent in lead poi-
soning. Typically, lead neuropathy produces weakness, but paresthesias
and sensory changes may occur. Extensors are weakened before flexors,
and the most-used muscle groups (usually the extensors of the wrist) are
involved the first.
8. Stupor.
9. Convulsions.
10. Ataxia.
11. Papilledema, optic atrophy, or both.
12. Retinal pigmentation.
13. Cranial nerve paralysis.
Encephalopathy — more common in children than in adults. Lead en-
cephalopathy occurs in children who ingest large amounts of lead salts. It
occurs only rarely in adults and only in those exposed to tetraethyl lead,
which is lipid soluble and reaches high levels in the CNS. In children, it
is usually accompanied by pica, and it is most frequent between the ages
of 1 to 3 years. For unexplained reasons, lead encephalopathy is more
common in summer than in winter.
The usual symptoms of lead encephalopathy are personality change,
lethargy, and irritability progressing to somnolence and ataxia, and final-
ly, seizures, coma, and death. In children, acute episodes of lead enceph-
alopathy may recur, superimposed on a state of chronic lead intoxication.
The mortality of acute lead encephalopathy is less than 5% at the best,
but 40% of victims are left with permanent and significant residual neu-
rologic deficits, which may include dementia, ataxia, spasticity, and sei-
zures.
C. Acute and chronic ingestions
Lead ingestion can be divided into acute and chronic ingestions.
1. Chronic lead ingestion
a) signs and symptoms: nonspecific, vague aches and pains, wrist
and ankle drop, chronic nephritis;
b) history: environmental source, family history;
c) laboratory tests: anemia (Hgb < 100 g/l), basophilic stippling,
increased urinary ALA, blood level (0.3–0,6 mg/l), erythrocyte protopor-
phyrin less than 7 times normal;
d) radiography: lead lines, opacities on abdominal films.
2. Acute lead ingestion:
a) signs and symptoms: anorexia, constipation, abdominal pain, be-
havioral changes, vomiting, lethargy, hyperactivity, clumsiness, ataxia,
convulsions, coma;

196
 b) history: same as for chronic lead ingestion;
c) laboratory tests: same as for chronic lead ingestion; also increased
urinary coproporphyrins, blood lead level > 0.6 mg/l, erythrocyte protopor-
phyrin > 1.9 mg/l or > 7–10 times normal;
d) Roentgenography: the same as for chronic ingestion.
D. Less severe symptomatology
Less severe symptomatology may be exhibited in patients who have
blood lead levels below the “toxic” level.
E. Differential diagnosis
The differential diagnosis of lead poisoning includes encephalitis, por-
phyria, peripheral neuropathies (e.g., diabetes mellitus), brain abscess,
brain tumor, Reyes syndrome, meningitis (particularly tuberculous men-
ingitis), and other toxic ingestions (e.g., cadmium, zinc, salicylates).

Poisoning with Organic Lead Compounds

Tetraethyl lead was introduced commercially in 1923 and has been
used since the 1960s as a supplementary antiknock agent in gasoline. Dur-
ing combustion in the engine, the compound is broken down to inorganic
lead compounds such as carbonates, oxycarbonates, and oxides, which
constitute most important sources of lead pollution in the general envi-
ronment. However, some organic lead may also be present in automobile
exhaust fumes if the compound has not undergone combustion. The or-
ganic lead compounds are colorless liquids that are insoluble in water but
soluble in organic solvents. Exposure to these compounds occurs princi-
pally during synthesis, transport, and mixing with gasoline. Tetraethyl lead
is normally added to gasoline together with other organic halogen com-
pounds such as ethylene dibromide, the latter acting as a scavenger for
the removal of lead after combustion. Current world production is esti-
mated to be 300,000 tons per year.
The toxicity of organic lead compounds was recognized soon after they
were first employed, and in the 1920s several cases of severe poisoning
were described. Stricter industrial hygiene regulations were introduced
in 1926, and a considerable reduction in the number of cases with clini-
cal intoxication followed.
The toxicity of organic lead differs markedly from that of inorganic
lead compounds. Tetraethyl lead is fat soluble and easily absorbed through
the skin; in contrast to the inorganic lead compounds, the organic lead
substances can cause lead poisoning by absorption through the skin. It
should be noted that penetration of the skin usually occurs without caus-
ing local injury. Inhalation of vapor is another important route of entry

197
into the body for organic lead compounds. Tetraethyl lead is converted to
triethyl lead in the liver, and triethyl lead is the active toxic derivative.
Because of the solubility of organic lead in fat, accumulation occurs in
the central nervous system, and symptoms of intoxication are referable pri-
marily to this organ system. One of the early symptoms is insomnia, and it
can be accompanied by headache, anxiety, restlessness, and excitation of
the nervous system. In more severe cases, encephalopathy occurs with a
variety of symptoms, including hallucinations, convulsions, and acute psy-
chosis. The gastrointestinal symptoms are usually mild and include abdom-
inal discomfort and anorexia, but the abdominal cramps (colic), so typical
of inorganic lead poisoning, usually do not occur. Muscle, hepatic, and re-
nal damage has also been observed in cases of organic lead poisoning from
gasoline sniffing. A history of exposure to organic lead compounds and
subsequent development of encephalopathy suggest the diagnosis.
The blood lead level is slightly elevated, but the degree of elevation
usually does not correspond to the severity of clinical symptoms. Eryth-
rocyte protoporphyrin, urine aminolevulinic acid, and urine coproporphy-
rin levels may remain within normal range. A high level of lead in urine
supports the diagnosis.

Laboratory findings
A. Blood cells analysis
1. Anemia is not a common finding. Hemoglobin levels of < 100 g/l
due to lead toxicity are normochromic and normocytic in nature, result-
ing from interference with enzymes responsible for heme synthesis. Bone
marrow findings of erythroid hypoplasia and ringed sideroblasts have been
reported and are suggestive of interference of RBC synthesis. Lead at-
taches to RBC membranes, causing increased friability and decreased sur-
vival time. This phenomenon is believed to be due to interference with
the RBC membrane sodium-potassium pump. Patients with a predomi-
nantly hemolytic pattern are more likely to present with more severe ane-
mias than those with a predominantly hypoproliferative pattern, who usu-
ally develop only mild anemia.
2. Reticulocytosis results from early release of immature RBCs. Mye-
loid sources attempt to compensate for deceased RBC survival and de-
creased heme synthesis. Reticulocytosis is not present in iron deficiency
anemia and so is valuable for differentiating the two forms of anemia.
3. Basophilic stippling of erythrocytes on Wright stain of peripheral
blood has been observed to be a less frequent occurrence than anemia.
This finding is also nonspecific to lead poisoning and may be seen with
thalassemia and pyrimidine 5’-nucleotidase deficiency.

198
 4. Eosinophilia is a more common finding than basophilic stippling
but is also nonspecific. It has been shown not to be dose-related.
B. Serum lead level
1. Levels of 0.3–0.6 mg/l are regarded as significant for lead toxicity,
although levels of 0.6 mg/l in children and 0.8 mg/l in adults may be nec-
essary before clinical symptoms manifest. Atomic absorption spectrome-
try (AAS) is the most commonly utilized method for measuring blood
lead levels.
2. Levels below the toxic range do not rule out toxicity because 90%
of lead is stored in bone. Blood levels may be lower after a steady state
has been reached and recent exposure levels have been low. A toxic
lead level is a strong indication that toxic lead exposure has occurred
recently.
3. Unexpectedly high lead levels may be due to contamination of the
blood specimen with lead prior to laboratory analysis. Samples must be
taken with lead-free needles and vacutainers, and must be placed in lead-
free containers to avoid this problem. A second specimen must be ana-
lyzed to confirm the high blood lead levels.
C. Erythrocyte protoporphyrin (EPP)
1. This test is often referred to as FEP, or free erythrocyte protopor-
phyrin. Protoporphyrin accumulates as a result of the lead inhibition of
the enzyme ferrochelatase, which binds iron to protophyrin, forming he-
moglobin.
2. EPP is regarded as the foremost test for chronic lead poisoning, as
it reflects the soft-tissue lead levels and total body lead burden. EPP usu-
ally corresponds well with blood lead concentration after the first 2 months
of exposure. This lag is due to the time required for EPP to build up in
the erythrocytes after interference with hemoglobin synthesis.
3. EPP should be performed in conjunction with blood lead levels to
obtain a more accurate picture of total body burden. Iron deficiency ane-
mia also causes elevation of the EPP, but here blood lead levels are nor-
mal.
4. EPP is the most widely utilized screening test. A fingerstick speci-
men can be used with a fluorometer to perform the test. EPP analysis
with a fluorometer is a simpler technique than protoporphyrin analysis
using Delves cup AAS. The Centers for Disease Control (CDC) has rec-
ommended use of EPP to screen all children between the age of 9 months
and 6 years.
D. Delta-aminolevulinate dehydratase (ALA-D) activity
1. Lead decreases the activity of this enzyme, which is present in the
erythrocyte. This test is more sensitive than measurement of protopor-

199
phyrin levels. ALA-D activity is affected with blood lead levels of 0.5
mcmol/l; almost complete enzyme inhibition occurs at 2.0 mcmol/l, where-
as porphyrin levels remain low when blood levels are <1.5 mcmol/l.
2. Blood protoporphyrin measurements with a portable fluorometer are
recommended over ALA-D measurements for screening because the ALA-D
assay is more complicated to perform and requires a service laboratory.
E. Urinary ALA and coproporphyrin III
1. Urinary levels of ALA are increased owing to lead inhibiting the
enzyme delta-aminolevulinic acid dehydratase (ALA-D).
2. Lead inhibition of the enzyme coproporphyrinogen oxidase has been
proposed as a cause for increased coproporphyrin III.
3. Quantification of urinary ALA and coproporphyrin has been used
for surveillance of lead toxicity in exposed individuals. Blood fluoro-
metric erythrocyte protoporphyrin analysis has largely supplanted these
tests.
F. Calcium disodium versenate (CaNa2-EDTA) provocation test
1. CaNa2-EDTA is administered to evaluate chelatable lead stores.
Because serum lead levels may become elevated, it is not recommended
for patients who are symptomatic or have blood lead levels > 0.7 mg/l.
2. Patients with lead nephropathy may have falsely low results because
urinary lead is the measured parameter.
3. Procedure
a) administer CaNa2-EDTA 500 mg/m2 intramuscularly or dilute this
amount in 250 ml distilled water and administer intravenously over 1 hr;
b) copious fluids are encouraged;
c) urine is procured for lead analysis: an 8-hour specimen from chil-
dren and a 24-hour specimen from adults;
d) lead excretion ratio: urine lead (mcg) divided by CaNa2-EDTA
(mg):
— positive result in children: > 0.6;
— positive result in adults: > 1.0.
G. Indications for serologic evaluation
1. Erythrocyte protoporphyrin is recommended by the CDC for screen-
ing and is the primary test used for surveillance of lead toxicity.
2. ALA-D may also be used for screening, but the test costs more and
requires special instrumentation.
3. CBC and serum lead level must be determined for all patients who
are being evaluated for lead toxicity. Serum lead determinations help guide
subsequent management.

200
 4. Urinary ALA and coproporphyrin III may be used for surveillance
of continued lead exposure but have largely been replaced by erythrocyte
protoporphyrin.
5. CaNa2-EDTA provocation test is used to evaluate the patient for
chelatable lead stores and would be indicated for asymptomatic patients
with levels between 0.25 and 0.55 mg/l to determine if treatment is indi-
cated.
H. Roentgenography
1. Abdominal flat plate:
a) may show lead densities in the GI tract if the ingestion was with-
in the previous 36 hrs;
b) a negative film does not rule out lead toxicity.
c) a positive film showing densities in the GI tract gives additional
evidence for lead toxicity.
2. Long bone films:
a) lead lines are areas of increased density at the distal ends of grow-
ing bones, where rapid growth of bone occurs:
— lead lines are present only if there has been heavy chronic poi-
soning (minimum 4 weeks);
— the width and density of the lines increase with the duration of
the exposure;
— multiple lead lines indicate repeated episodes of toxicity;
— lead lines are most commonly seen between the ages of 2 and
5 years when bone is growing rapidly;
b) use as a screening test is poor because roentgenograms are usually
negative.
I. Hair and tooth lead
1. It is not useful for diagnosis and treatment of lead toxicity.
2. It is best used for population studies.
J. Additional testing
Additional testing should be directed to the specific organs that may
develop pathology as a direct result of lead toxicity.
1. Neurologic effects:
a) intelligence testing;
b) psychological testing;
c) motor strength;
d) lumbar puncture for opening pressure;
e) cerebrospinal fluid (CSF) for WBCs and protein;
f) peripheral motor nerve conduction velocity.

201
 2. Renal effects:
a) serum creatinine;
b) urinalysis;
c) 24-hour urine for creatinine, protein, and uric acid.
3. Reproductive and endocrine effects:
a) sperm counts;
b) serum testosterone;
c) metapyrone challenge test;
d) serum thyroxine;
e) thyroid-binding proteins.
4. GI effects:
a) SGOT;
b) SGPT.
Treatment is started from the termination of a contact with lead. For
removal of compounds of lead from an organism complexons are used.
Tetacinum-calcium is administered in the dosage under 20 ml with 10%
sol. daily within 3–4 days with an interval of 4–5 days, only 2–3 cycles.
Pentacinum is used in the dosage of 20 ml in 5% sol. after the same
scheme. D-Penicillaminum Skuprenil is also used by 150–300 mg 3 times
per day within 2–4 weeks. With the asthenoneurological syndrome vita-
minized drugs, adaptogenes, tranquilizers, soporific (under the indications)
are expedient. Vitamine medicines, and also balmeotherapy, massage, re-
sort therapy are applied with polyneurites.

Expertise of Capacity for Work

with the Initial Form of Lead Intoxication
The transfer to work outside the connection with lead for 1–2 months
with vigorous therapy (see above) in out-patient conditions is mandatory.
In subsequence probable returning to former activity. With the mild form
the treatment in the hospital is prescribed, for 1–2 months transfer to work
outside the contact with lead and only then (under condition of normali-
zation of parameters) they can return to former activity.
With the pronounced form all yardsticks are hardened — prolong treat-
ment without return to former activity. These people are provided with a
job or transferred to a group of physical inability. The preventive mainte-
nance actuates a complex of technical and sanitary-hygienic measures pre-
venting lead poisoning. The medical contraindications for activity with
lead including anemias, pathology of the central and peripheric nervous
system, disease of vessels and others are established.
202
 INTOXICATION WITH MERCURY
AND ITS INORGANIC COMPOUNDS
Mercury (Hg) is a metal and a natural component of the ocean and
earth’s crust. Compared to other elements, mercury is not a major com-
ponent of the biosphere. The weather and human industry release mercu-
ry into the air and water, resulting in its redistribution and increasing the
risk of human exposure.
When mercury becomes concentrated in the air, water, or foods as a re-
sult of human activity, it is considered to be a pollutant. Modern techniques
can detect mercury in parts per billion (mcg/m3) concentrations in the air
or water. Mankind has used mercury since history began, most recently as
a germicide and preservative, (e.g., in eye drops), for production of paper
pulp, in chemical processes such as alkaline-chlorine plants, and in the ma-
nufacturing of vinyl. Mercury is released from burning of fossil fuels and
waste materials. Monitoring of environmental contamination may employ
chemical analyses of sentinel animals or plant species that accumulate mer-
cury from air or water, as well as specimens taken directly from humans.
These monitoring strategies are discussed below.
Mercury exists in three forms: elemental (a liquid commonly known
as quicksilver), inorganic mercury compounds, and organic compounds.
Although all forms of mercury are toxic, the specific form of mercury
influences how mercury moves through the environment and within the
body. Both elemental and organic mercury are volatile and absorption by
inhalation is significant. The gastrointestinal tract accounts for the most
significant absorption of inorganic mercury salts, and for nonoccupatio-
nal exposures to organic mercury via the ingestion of foods.
The toxicity of mercury compounds is the result of their affinity for
sulfur and sulfhydryl groups; this affinity facilitates mercury binding with
proteins, which in turn results in cytotoxicity. Alkylmercurials, the most
toxic form of mercury, have a high absorbance from the gastrointestinal
tract and a slow rate of elimination from the body. These properties cause
alkylmercurials to accumulate in both soft and hard tissue with continued
exposure, even if the daily exposure is rather low. Details of the uptake,
binding, distribution, and metabolism of mercury have been well described.

Epidemiology
Occupational exposure represents a significant portion of mercury poi-
soning cases. Miners extracting gold from mercury, or extracting mercu-
ry ore (mercuric sulfide, cinnabar, is the most prevalent form) provided
early cases of occupational poisoning. Exposure is mostly by inhalation.
203
Respiratory problems dominate the effects of short-term inhalation expo-
sures. Longer-term exposures bring on signs of nervous system disorders
(see indices of exposure below). Miners may have neurobehavioral defi-
cits that persist for more than 10 years after the end of exposure.
The dental profession conveys higher risk of mercury poisoning be-
cause mercury-silver amalgams have been extensively used to fill dental
caries. Exposure is by inhalation and dermal routes. Procedures for hand-
ling mercury in dentistry have improved along with increasing awareness
of the health hazards of low-level exposure to mercury, and mercury amal-
gams are now used in only half of the dental restorations of Americans.
Dental personnel may have higher levels of mercury in their bodies and
may have higher incidence of nervous system impairment than employ-
ees of similar socioeconomic status who do not work with mercury. Fe-
male dental assistants whose work involved substantial use of mercury
amalgams and who practiced “poor mercury hygiene” were less fertile
than others who used less mercury in their work. Oddly, the women who
used small amounts of amalgam in their work were more fertile than the
control group who worked in dental offices that did not use amalgams.
These results illustrate that more research is needed before we can fully
understand the effects of low-level exposure to mercury.
Mercury is also used in the calibration of glass, in fluorescent lamps,
and in thermometers and electrical switches. Workers who had used ele-
mental mercury to calibrate glassware illustrate the onset and recovery
from mercury-induced tremor. Other current industrial uses are in paper
pulp processing and in alkaline-chlorine factories.

Mercury in the Food Chain

Ingestion of mercury in food is responsible for the largest number of
nonoccupational exposures. mercury is taken up by terrestrial and aquat-
ic plants, which become food for humans and other animals. Inorganic
mercury is converted to the more toxic organomercurial compounds, pri-
marily by methylation by anaerobic microorganisms in the sedimentary
layers of seas and lakes. As larger animal species feed on the plants or
smaller animals, the content of mercury in the tissues becomes concen-
trated, reaching its highest levels in large fish such as tuna, and other pred-
ators at the top of the food chain. The major portion of mercury in fish is
methylmercury. The risk from heavy consumption of these fish has caused
public authorities to regulate the marketing of seafood having > 1 mg/kg
mercury. Some seafoods contain significant amounts of selenium. Exper-
iments indicate that selenium binds some of the mercury and thus redu-
204
ces the toxicity that would occur with a given concentration of mercury
without selenium.
The most profound examples of people poisoned by environmental
mercury were in Iraq, where thousands of people were poisoned after
making bread from seed grain that had been treated with methylmercury
as a fungicide and in Minamata, Japan. The Japanese episode illustrated
the conversion of inorganic mercury to the more toxic organic forms, by
aquatic organisms. Mercury was discharged from a factory that used mer-
curic chloride in the manufacture of vinyl chloride. The effluent from the
factory drained into a bay. Seafood was a principal part of the diet of the
local people. The complex path of the runoff of inorganic mercury pollu-
tion from land to sea, its conversion to the highly toxic methylmercury,
accumulation in the food chain, and finally the delayed manifestations of
neurotoxicity among people made it difficult to trace the cause. The tra-
gedies in Iraq and Japan also illustrated the fetus’s higher vulnerability to
mercury, with the most severe cases becoming apparent at birth but oth-
ers displaying more subtle deficits later in the developmental process.
Attention has now shifted to children of fish-eating populations. Resi-
dents on islands (Seychelles, Faroes) where sea fish are the main compo-
nent of the diet have slightly higher concentrations of mercury in their
blood and hair than do other populations. These studies showed that moth-
ers can transmit mercury to their fetus through their blood supply, and to
their infant through maternal milk. Clear evidence of toxic effects is be-
ing sought for these relatively low exposures.

Mercury Exposure from Dental Amalgams

Metallic mercury accounts for about 50% of the material in most den-
tal fillings, and small amounts of mercury vapor are released from fill-
ings. The World Health Organization recently concluded that mercury-
silver amalgams, used in dentistry for about 150 years, offer several ad-
vantages over alternative materials for dental restorations; they provide a
desirably hard surface, and are inexpensive and long-lasting. Most den-
tists believe that amalgams present the patient with no more health risk
than that associated with alternative materials. However, people with mer-
cury amalgams exhale increased levels of mercury after brushing teeth or
chewing gum and have higher levels of mercury in their blood or mater-
nal milk than persons with few fillings. Mercury from amalgams may be
absorbed into the body through the buccal mucosa, the lung or the diges-
tive tract. Mercury appears in the nervous system and kidney of laborato-
ry animals after they were given dental amalgams. These data demonst-
205
rate the uptake of mercury from amalgams into the body, but do not indi-
cate whether the amount of mercury absorbed from amalgams contrib-
utes to health impairment.
Long-term exposure to mercury from dental amalgams can be quanti-
fied by the number of amalgam surfaces in the mouth. The level of mer-
cury in the urine represents primarily recent exposure, but urinary mer-
cury levels may be proportional to the number of amalgams. Mercury con-
tent of the blood and urine of adults with amalgam restorations is quite
low, but mercury is known to accumulate in the kidney and nervous sys-
tem, where it is less easily measured. Thus, there has been considerable
speculation that accumulated mercury from dental amalgams may con-
tribute to health problems (see “Chelation therapy” below).
There is little solid evidence of deleterious health effects that can be
traced unambiguously to amalgam. The largest body of research on health
effects of amalgams has been done in Sweden. Large epidemiologic stud-
ies of adults found no significant impairment of renal or immune systems
related to amalgams. One study reported no relationship between amal-
gams and children’s allergic problems. However, there is sufficient con-
cern about mercury from amalgams affecting the more vulnerable, juve-
nile population to cause the National Institute of Dental Research to be-
gin prospective clinical trials, the strongest experimental design for iden-
tifying health hazards from amalgams. At present, the large-scale replace-
ment of an individual’s amalgam fillings with nonmetallic materials seems
unjustified because the drilling releases mercury and thus worsens the
patient’s exposure. Occult religions and alternative medical practices lead
to some mercury poisonings. Santeria, a quasi-religious practice that has
been transplanted from the Caribbean islands, employs elemental mercu-
ry in potions that are thought capable of banishing evil forces from a per-
son or their home. It is not surprising that exuberant use of such potions
may result in accidental poisoning, but the extent of poisoning attributa-
ble to folk remedies is not known.

Indices of Exposure
Exposures to mercury in the workplace have become lower, and fewer
cases of mercury poisoning are reported after governmental regulation of
many organo-Hg compounds. Exposure to mercury in the ambient air can
be documented with personal monitoring devices.
Indices of human body burden are obtained by mercury content of hair,
blood, and urine. Most cases of mercury toxicity are associated with detec-

206
table mercury in the urine. Exposure to metallic mercury vapor and inor-
ganic mercury can be monitored in urinary mercury concentration, after
adjustment for creatinine content. Exposure to methyl mercury is best in-
dicated by the concentration of mercury in whole blood, where it is se-
questered in the red cells. Blood mercury concentration is a better index
of recent exposure to methylmercury than is urinary mercury. The elimi-
nation of mercury from blood and urine is much more rapid than from the
whole body. Thus, blood and urine mercury concentrations are most in-
fluenced by recent exposures (e.g., within a week) and provide less evi-
dence of past exposures.
A more extended chronology of past exposure to methyl mercury can
be determined from the analysis of the concentration gradient of mercury
along a strand of hair. Analysis of mercury in maternal hair may provide
good evidence of fetal exposure during the various gestational stages. The
hair and the finger nails are useful indicator media for two reasons: these
tissues are composed mostly of keratin, a protein that is formed from many
sulfhydryl groups that can bind mercury during the growth process, and
because cells of hair and nails survive for a relatively long time. Howev-
er, care is required to avoid contamination of hair and nails with mercury
external to the body, e.g., in dusts and cosmetic products.
Biologic specimens can be analyzed for total mercury content by atomic
absorption methods. Cold vapor atomic absorption spectrometry is the
most commonly used method to measure mercury in biologic samples.
Digestion of the specimen may be required to liberate ionic mercury from
the chemical matrix in which mercury is bound. Total mercury may be
further analyzed into its organic and inorganic components, if gas chro-
matography is combined with the atomic absorption method. Other meth-
ods and their suitability, depending on the expected concentration of mer-
cury in the specimen and the matrix in which mercury has been found,
have been reviewed frequently.
Many new methods are being assessed for their ability to detect mo-
lecular or cellular changes that can be shown to indicate exposure to, or
effects of, toxicants including mercury. Of particular relevance for mer-
cury is the suggestion that evidence of nervous system damage caused by
mercury may be seen in the peripheral blood, in the form of autoantibod-
ies produced in response to fragments of damaged nervous system cells.
N-acetyl-p-D-glucosaminidase (NAG) is one of a number of possible mark-
ers of renal changes in mercury-exposed workers. Elevation of urinary

207
porphyrins, one of the earliest indices of chronic exposure to mercury in
lab experiments, was also observed in dentists.
Traditional indices of mercury effects, involving measures of beha-
vioral and physiologic processes, are described below.
The clinical picture of a chronic mercury intoxication arises for work-
ing at a long-lived contact to mercury. The rates of growth and expres-
siveness depend on specific features of an organism, dose and time of
effect. The basic directivity — primary damage of the nervous system.
The list of the basic clinical signs is shown in table 11.2.
There are distinguished 3 stages of chronic mercury intoxication ac-
cording to the degree of manifestation.
The initial stage (the stage of “mercury nervosism”) is characterised
by fewer symptoms and fast reversibility. Alongside with asthenic phe-
nomena emotional instability, frightening dreams, dyspeptic distress (me-
tallic taste in the mouth, hypersalivation, diarrhea), tremor of the limbs
are observed. At well-timed relief from the contact with mercury and treat-
ment all the signs of disease completely disappear.
Stage of the moderately pronounced changes takes place at the long-
lived experience of activity with mercury, delayed recognition of initial
developments. Asthenovegetative disorders rise, the depression combines
with excitation and aggressiveness. Mercury eretism, psychopathologic
condition take place, as well as endocrine-vegetative dysfunctions, hyper-
thyroidism, goiter), tachycardia, arterial hypertension. The changes
strengthen on the part of the digestive channel and oral cavity, parodon-
tosis, colitis). The diencephalic crisises can take place.

Table 11.2. The basic clinical signs

of chronic mercury intoxication
1. Symptom-complex of irritable weakness (or “mercury nervosism”).
2. Asthenoneurotic or asthenovegetative syndrome, possible psy-
chopathologic distresses.
3. Tremor of fingers, sometimes heads, legs.
4. Increase of an excitability of sympathetic department of the vegeta-
tive nervous system (dermographism, sweating, hyperthermia).
5. Distress on the part of the endocrine glands.
6. Ulitis, stomatitis, gastritisþ
7. Trophic disturbance (loss of hair, brittleness of the nails).
8. Hematological violations (lymphocytosis, monocytosis, anemia).
9. Damage of the eyes.

208
 The convalescence in this stage also is possible at well-timed and steady
treatment, and also prevention from activity with mercury. The stage of
the pronounced changes is characterized by signs of toxic encephalopa-
thy, the memory and intellect is reduced, hallucinations are possible. The
tremor of fingers and arms becomes generalized. The microorganic symp-
tomatology, anizopria, flattening of the nasolabial fold, distinction in ten-
don reflexes, dysartheria, hypomimia, schizophrenical syndrome are pos-
sible.
The diagnosis is established taking into account clinical symptoma-
tology, data and sanitary-hygienic characteristic of working conditions.
Diagnosis is confirmed by the definition of mercury in urine (0.02–0.9 mg/l)
and in feces.

Chelation Therapy
Chelating agents have been used clinically as an antidote for severe
toxicity of mercury. However, there is limited evidence of the safety and
efficiency of chelating drugs to warrant their use for extended durations,
for less severe cases, or for prophylactic treatment. Most studies have
evaluated chelation outcome in terms of the metal’s concentration in blood
and other exposure indices; there is less evidence to indicate that che-
lation restores impaired function in the renal or nervous system toxicity
of mercury. Many of the neurobehavioral sequelae of mercury poisoning
appear to be irreversible, and the severity of neurotoxicity is influenced
by the duration of exposure as well as the magnitude of exposure. Thus,
chelation or rehabilitation therapies may be useful only if administered
in the early stages of intoxication, before irreversible changes occur. Nu-
merous clinical case reports tell of apparently irreversible neurotoxicity
of mercury that survives brief chelation treatment.
The most promising chelators are the dimercaprol derivatives, meso-
2,3-dimercaptsuccinic acid (DMSA, succimer) and dimercaptopropanesul-
fonate (DMPS, Dimaval). DMSA and DMPS have advantages over chelat-
ing agents used previously for the treatment of mercury toxicity, e.g., BAL
(British anti-Lewisite, dimercaprol), EDTA (ethylenediaminetetraacetic
acid), and D-penicillamine. DMSA and DMPS are water-soluble deriva-
tives of BAL and thus may be administered orally; they are less toxic
than most other chelators, and are effective in reducing metal concentra-
tions in experimental studies, and in reports of clinical efficacy. It is not
yet clear whether DMPS or DMSA may be the more effective. More evi-
dence is needed to determine if chelators are capable of reversing the toxic
effects of metals in the brain and kidney.
209
 The treatment of mercury intoxications should be complex, with al-
lowance for degrees of manifestation. For the ascent of mercury the anti-
dotes and symptomatic means (Table 11.3) will be used.
The expertise of capacity for work is carried out is differentiated de-
pending on the stage of the process (Table 11.4).

Table 11.3. Principles of treatment of chronic

mercury intoxication
1. Application of antidotes
— Unithiolum — 5 % sol., 5–10 ml intramuscularly, 1st day
2–4 times per day, then once within 6–7 days
— Natrium thiosulfuricum — 30% sol. i.v. slowly 5–10 ml daily
— Succimerum — at the highly severe forms of 0.3 g is dissolved in
6 ml with 5% sol. of soda: 1st day — 4 injections i. m., 2nd day —
3 injections, 3rd–7th days till 1–2 injections; in mild forms — tab. 0.5 ×
× 3 times per day within 7 days. — D-Penicillaminum ~ 0.15 ×
× 2–3 times a day — 1-st day
2nd day 0.15 × 1 time, then on alternate days by 0.15
2. Metabolic drugs neurotropic
— Aminalonum, Cerebrolysinum, Nootropilum
— Stugeronum, Cinnarizinum
— Vitamins of group B (B1, B12)
3. Tranquilizers, small doses of soporifics
4. Hydroprocedures (pine needle baths), MPE, psychotherapy

Table 11.4. Expertise of capacity for work

at chronic mercury intoxication
1. Initial stage
— Temporary break of contact with mercury
— Transfer to the other activity for the period of 1–2 months under
the labor medical certificate
— with improvement of health condition a worker can return to former
activity under a careful medical monitoring
2. Manifested stage
— The activity in conditions of mercury influence is contraindicated
— Transfer to the activity without any toxic substances
— The expertise of work ability is necessary
3. At toxic encephalopathy the patients are disabled

210
 The preventive actions are directed on replacement of mercury by less
harmful materials, creation of effective ventilation, equipment of opaque
surfaces for mercury, air cooling up to 10°C. Periodic medical examina-
tions of the people working with mercury in open condition (mining, smel-
ting of mercury, effecting of mercury paints, etc.) are carried out once
12 months; for working with mercury in a closed condition (devices, phar-
maceutical and cosmetic industry) — once 24 months. In realization of
physical examinations the participation of therapeutist and neuropatholo-
gist is necessary. All inspected carried out definition of the mercury con-
tents in urine.
The additional medical contraindications at employment in the con-
tact to mercury and its compounds include the chronic diseases of the
CNS (psychosises), peripheric and vegetative nervous system, diseases
of the digestive organs, skin, toxicomania. The indicated limitations al-
low avoiding of intoxications development in people of high risk group.

INTOXICATIONS WITH MANGANESE

Manganese (Mn) is a reddish-gray or silvery soft metal, a member of
group VII elements of the periodic table. Manganese minerals are widely
spread. Ores containing manganese (e.g. pyrolusite, braunite, manganite,
hauserite, manganesespat, tephroite, and rhodochrosite) could be found
on the bottom of the oceans. Most manganese is obtained from ores found
in Australia, Russia, Ukraine, India, and Brazil. Manganese is used to form
many important alloys. In steel, manganese improves rolling qualities, and
malleability, hardness, strength, and mild resistance. Manganese, with alu-
minum, antimony, and small amounts of copper, can form a highly ferro-
magnetic alloy. Manganese metal is reactive chemically and decomposes
cold water slowly. Many steel and iron manufacturing processes need the
addition of manganese to molten iron to reduce its iron oxide content by
the formation of manganese oxide. Manganese compounds are used in
the manufacture of dry cell batteries, and in paints, bleaching agents, and
disinfectants. Manganese is also used as a colorizer and coloring agent in
the manufacture of glass and ceramics. Potassium permanganate is a po-
werful oxidizing agent and is employed in quantitative chemical analysis
and in medicine as anticeptic. Manganese is an essential trace element,
and is required for the activity of the enzymes mitochondrial superoxide
dismutase, galactosyltransferase, and glutamate synthetase.
Manganese is very toxic, therefore in all industries, where the manga-
nese is applied, and also at its mining from ores there is a potential dan-
ger of originating of manganese intoxications.

211
 Manganese penetrates an organism through the lungs, to a lesser de-
gree — through the gastrointestinal tract and skin.
Manganese oxides are fast digested. In blood the manganese circu-
lates as a non-persistent complex with serum proteins. It deposites in
the bones, the brain, the parenchymatous organs by the way of slightly
soluble sodium phosphate. It excretes with feces and to a lesser degree
with urine. People exposed to manganese compounds for a long time, if
they are not keeping safety precautions could get chronic intoxication
with a primary damage to CNS. Manganese is haptene capable to in-
voke bronchial asthma, eczema. The combined exposure to manganese
and silicon dust can be observed. This condition is called manganoco-
niosis.

Pathogenesis
The manganese, being a trace element, participates in biological pro-
cesses. It enters the tissues structure, influences metabolism, e.g. oppresses
activity of cholinesterase, upsetting synaptic conduction, causes changes
in metabolism of serotonin.
With long and systematic exposure manganese causes direct damage
to the nervous tissue, and invokes vascular disturbance increasing perme-
ability of capillary tubes. There are data about direct influencing of man-
ganese on the processes of oxidative phosphorylation, excitability of
N-cholinergic and adrenergic systems. It changes activity of monoami-
noxidases of nerve cells, oppresses a biosynthesis of catecholamins, in-
creases an intensity of protein metabolism. The manganese is capable se-
lectively to strike the nervous system, predominantly its subcortical for-
mations. In initial stages of intoxication the disturbance of cortical acti-
vity, and hereinafter — distress of the motor analyzer develop.
Diffused excitation is spread to cortical zones. Simultaneous syner-
gists, excitation of antagonists muscles results in musculation rigidity. It
is established that the pathological locuses, developing in the subcortex,
invoke excitation in the cortical zone of the motor analyzer. In other words
chronic manganese poisoning causes pyramid insufficiency. But this agent
also influences the emotions.
Therefore, with chronic manganese intoxication along with struc-
tural changes the important role in its genesis is played by complex
neurodynamic shifts in majority of CNS’s parts stipulating a clinical
development of the disease. The manganese changes the functions of
the thyroid gland, the cardiovascular system, the gastrointestinal tract,
the liver, etc.

212
 Clinical Manifestations
The symptomatology of a chronic manganese intoxication develops
step-by-step, that invokes definite difficulties in diagnosis of its initial
forms.
The basic signs of intoxication are the functional disturbance of the
CNS, which has a progradient course and can turn to organic changes.
The damage of a striopallidal system is specific, that in the pronounced
stages shows akineticorigid (amiostatic) syndrome and phenomena of par-
kinsonism. Besides of neurologic symptomatology the disease is charac-
terised by hypertention and dyspeptic signs. Quite often even at early stag-
es of the disease the functional disturbance of the thyroid gland can be
marked. Chronic intoxication by manganese has three stages.
The initial stage is characterized by functional changes of the CNS:
fast fatigue, sleepiness, headache, which often occurs at the end of a la-
bour shift, decrease of functionability, weakness, loss of appetite. The sal-
ivation is sometimes increased, there are nausea and stomach aches as-
sociated with eating. Quite often already at this stage there are marked
paresthesia and pain in distal parts of the limbs. Patients, as a rule, do not
present much symptoms. The disease has a latent course. At further de-
velopment of intoxication it is possible to reveal functional disturbance
of the nervous system and phenomena of the polyneuritic syndrome; hy-
poalgesia, moderate decrease of muscular force, minor pain at a palpa-
tion of muscles of limbs ate typical. There are hypomyotonia, mild exo-
phthalm and “ophthalmic signs”, erectile dysfuncion, menstrual disorders.
There are marked fast appearance and fading of pilomotor jerk, poured
bright red dermographism, distal hyperhidrosis. The mechanical excita-
bility of muscles is increased. In peripheric blood in the onset of intoxi-
cation can be watched inclination to hyperglobulinemia, lymphocytosis
and monocytosis, left shift can be observed.
At development of the next stage of intoxication the initial phenome-
na of toxic encephalopathy develop. The positive signs of an oral autom-
atism (Marinesko’s and proboscis sign) are marked. The muscle tone is
increased. The transition of the 1st stage into the 2nd one sometimes passes
very fast. The cerebellar syndrome is characterised for the 2nd stage of chro-
nic manganese intoxication. There are observed inability to fulfil the
finger-nose test and instability in the Romberg’s test. The gait changes,
there can be disturbance of motions of arms at walking. Abdominal
reflexes are asymetric and exhaust fast. There is a generalized tremor
and more pronounced polyneuritic syndrome with development of trophic
dermal changes and considerable impairment of sensitivity. The crisises of

213
diencephalic nature are sometimes observed. The blood pressure is not
stable, the changes on the ECG of extracardial nature associated with de-
scribed neurologic symptomatology.
The third stage — manganese parkinsonism. A characteristic diffuse
damage to the brain with primary increase of extrapyramidal signs. In
this stage a masked face is observed, the motions are retarded and bound;
from time to time there is an emotional explosibility accompanying with
violent cry or by laugh. Intellect is reduced. The gait becomes disordered
(tiptoes), there is possible retro and propulsion; monotonic muffled speech.
The deep reflexes are high, there are marked clonuses of feet. Unlike to
postencephalic parkinsonism the manganese intoxication is not accom-
panied with pronounced hyperkinesias and cranial nerves dysfunction.
Besides of the indicated changes on the part of the CNS, which are
specific for chronic intoxication with manganese chronic gastritis with
dicreased gastral secretion, hepatomegaly and disturbance of protein-syn-
thesizing function and changes of carbohydrate and vitamin exchange.
Feature of clinical course of a chronic manganese intoxication is its
progredient development, independent on the termination of a contact with
metal. The aggravation of symptoms manifests in gait disorder increase.

Diagnosis
The special attention is payed to early diagnosis of chronic intoxica-
tion by manganese. Depending on working conditions, time of a contact
with manganese the risk of manganese intoxication could be determined.
Then detailed examination of the patient directed to specifying symptoma-
tology of damage to the nervous system and other signs is conducted for
establishing a diagnosis. If necessary, the health providers conduct pro-
longed dynamic medical supervision or even advanced clinical examina-
tion in the hospital.

Treatment
At mild stage of intoxication with manganese they are prescribed gen-
eral treatment directed on the increase of body resistance (gymnastics,
hydrotherapeutic procedures etc.), vitamins B1, B6, ascorbic acid and other
medications. In more advanced stages they apply central cholinolytics,
improving a metabolism and blood supply of the brain (Nootropil, Ami-
nolon, Scopolamin, Arpenal, etc.). If signs of parkinsonism occured, it is
necessary to prescribe cholinolytics (Norakin, Amedin, Tropacin, Corbella,
etc.).

214
 Expertise of Capacity for Work
If we suspect manganese intoxication, it is necessary to change tem-
porarily (for 1–2 months) the occupation into the one without exposure
to manganese. The decision on return to the previous job is made by an
expert comission.
At the advanced stages of disease patients are disabled. They can work
only in the special facilities. The expertise of work ability should be fo-
cused on the issues of medical and social-labor rehabilitation. They recom-
mend treatment in sanatoria and resorts, repeated courses of maintenance
therapy and dynamic surveillance of patients.

Preventive Maintenance
It is necessary to equip work places with mechanisation and reduce
the manganese dust concentration by hermetic sealing of equipment and
provision of exhausted ventilation. The preliminary and periodic medical
examinations should be conducted regularly.
The neuropathologist and therapeutist, otolaryngologist, dermatologist
participate in medical examinations. They assess the function of external
respiration, conduct electromyography of the skeletal muscles, a large pic-
ture frame photo roentgenophotography, blood count (Hb, RBC, WBC,
ESR).
Terms of periodic medical examinations depend on the occupation and
intensity of exposure to manganese. Thus, for example, workers employed
at the enterprises where manganese is provided would be examined 1 time
per 6 months, on an ore mining of manganese mixtures — 1 time per
12 months, on welding — 1 time per 24 months.
Contraindications to contact with manganese are following: chronic
diseases of the peripheral nervous system; mental disorders; pronounced
vegetative dysfunction; pronounced forms of chronic bronchitis, asthma,
chronic pneumonia, and other respiratory diseases.

TESTS
1. A woman came to the internist with complaints of dull spasmodic
stomach ache, constipation, moderate raising of blood pressure. Fatigue,
general weakness, increased petulance, headache. It’s known from anam-
nesis that the woman during 2 years had been working at the lacquer-
paint plant.

215
 Define the type of intoxication:
A. Oxides of carbon.
B. TEL.
C. Lead.
D. Mercury and its inorganic compounds.
E. Manganese.
2. A 52-year old man has been working during 12 years on assem-
bling the batteries at the factory. He presents complaints of the weakness,
quick fatigue, headaches, petulance, pains in the hands and legs, hyper-
hidrosis and disturbed movement of fingers; thirst, bad appetite, spasmoid
stomach aches. At the examination: skin is cool, humid, on the mucous
membranes of gums — a grey line. In the morning he had breakfast. In
blood test — reticulocytosis, Hb — 109 g/l, in coprogram — increased
amount of coproporphyrin before 500 mcg on 1 g of creatinine.
Your diagnosis:
A. Acute poisoning with mercury.
B. Food toxicoinfection.
C. Poisoning with sulfuric acid
D Chronic poisoning with lead.
E. Intensification of chronic gastritis.
3. A man, 43 years old, a driver of a cargo car, has done several gulps
of gasoline during transfusion from one car to another one. In several hours
he felt a strong headache, weakness, itching, feeling of hair in the mouth;
unexplained awe, salivation has appeared. He applied to the polyclinic,
where physician has found tremor of fingers, unstability in the Romberg’s
pose, nystagmus, dysarthria, ataxic unsteady gait, increased tendinous re-
flexes. ABP — 90/60 mmHg, temperature — 34.5°C, heart rate — 52 bpm.
Your diagnosis:
A. Poisoning with lead.
B. Poisoning with nitrochlorine benzene.
C. Poisoning with benzene.
D. Poisoning with TEL.
E. Poisoning with oxide of carbohydrate.
4. A patient, 52 years old, applied to the internist with complaints of
general weakness, quick fatigue, dizziness, weakness in the limbs, change
of a taste and reduction of vision. In the mouth — sensation of metallic
taste, bad appetite, periodic spasmoid stomach ache. From anamnesis —
he has worked during 20 years on the battery production. Laboratory tests:
reticulocytosis (> 40‰) increased amount of erythrocytes with basophilic

216
granulosity (> 60%), Hb — 125 g/l. In urine the contents of δ-aminole-
vulinic acid and coproporphyrin are increased.
Your diagnosis:
A. Hyperacidic gastritis.
B. Food toxicoinfection.
C. Chronic lead intoxication.
D. Poisoning with manganese.
E. Poisoning with mercury.
5. A patient during 20 years works at the battery production. He com-
plains of general weakness, petulance, swoons, muscular weakness and
pain in hands and legs, memory impairment and dicreased working ca-
pacity, increased sweating. Objective: tremor of fingers of stretching hands,
pains at the palpation on the length of nerves. Laboratory examinations:
anemia, reticulosis, erythrocytosis with basophilic granulosity.
Which compounds’ toxic action caused these clinic manifestations?
A. Mercury.
B. Manganese.
C. Lead.
D. Chromium.
E. Chlorine.

217
 Chapter 12
IONIZING RADIATION

Within weeks after Roentgen’s discovery of the X-ray in 1895, radia-

tion injuries began to be encountered in those working with the early ra-
diation equipment.
During the century since then, the study of such injuries has received con-
tinuing impetus from the expanding uses of radiation in medicine, science,
industry, and nuclear energy. In historical perspective, the effects of ion-
izing radiation have received more study than those of any other hazard-
ous environmental agent. As a result, our experience with radiation has
been strategically important in addressing other environmental and occu-
pational causes of the disease.

NATURE AND PROPERTIES

OF IONIZING RADIATION
Ionizing radiations are of two broad types: electromagnetic and par-
ticulate. The electromagnetic radiations include roentgen rays (or X-rays)
and gamma rays, which possess no mass or charge and which are charac-
terized by extremely short wave length and high frequency. The particu-
late radiations consist of electrons, protons, neutrons, alpha particles, neg-
ative pi-mesons, heavy charged ions, and other atomic particles varying
in mass and charge. Both types of ionizing radiation differ from other
forms of radiant energy in being able to disrupt the atoms and molecules
on which they impinge, thereby producing ions, free radicals, and, in turn,
biochemical lesions.
As ionizing radiation penetrates matter, it gives up its energy by colli-
ding with atoms and molecules in its path.
Such collisions are clustered so closely together along the path of an
alpha particle that the particle typically has only enough energy to traverse
a few cells, whereas the collisions are separated so far apart along the

218
path of an X-ray that the radiation can traverse the entire body. The ave-
rage rate at which energy is deposited per unit length of path, i.e., the
linear energy transfer (LET) of the radiation, is customarily pronounced
in kiloelectron volts per micrometer (keV/µm).
In general, the higher the LET of the radiation, the more likely it is to
deposit enough energy in a critical site within the cell, e.g., a deoxyribo-
nucleic acid (DNA) molecule or a chromosome, to cause an irreparable
molecular lesion. Alpha particles and other high-LET radiations are typi-
cally more potent, therefore, than low-LET radiations such as X-rays.
Within the body, the distribution and retention of each internally de-
posited radionuclide is governed by its physical and chemical properties,
i.e., the amount of radioactivity remaining in situ decreases with time
through both physical decay and biologic removal. The physical half-lives
of radionuclides vary from less than a second in the case of some radio-
nuclides to billions of years in the case of others. Biologic half-lives also
vary, tending to be longer for bone-seeking radionuclides (such as radi-
um, strontium, or plutonium) than for radionuclides that are deposited
predominantly in soft tissue (such as iodine, cesium, or tritium).

Quantities and Units of Measure

Following the recommendation of the International Commission on
Radiological Units and Measurements the International System (SI) of
units has come into increasingly wide use in place of the centimeter-gram-
second (cgs) system. The SI unit for expressing the dose of radiation that
is absorbed in tissue is the gray (Gy): 1 Gy = 1 joule per kilogram of
tissue. The corresponding cgs unit is the radiation absorbed dose (rad):
1 rad = 100 erg per gram of tissue = 0.01 Gy.
To enable doses of radiations of differing potencies to be normalized
in terms of risk, another unit, i.e., the equivalent dose, also is used in
radiologic protection. This unit is the sievert (Sv): 1 sievert is equivalent
to the dose in gray multiplied by an appropriate relative biological effec-
tiveness (RBE)-dependent quality factor (Q), so that, in principle, 1 Sv of
any given type of radiation represents the dose that is equivalent in bio-
logic effectiveness to 1 Gy of gamma rays. The corresponding cgs unit is
the rem: 1 rem = 0.01 Sv.
The unit for expressing the collective effective dose to a population
is the person-Sv; 1 sievert to each of 100 people = 100 person-Sv =
= 10,000 person-rem.
The unit for expressing the amount of radioactivity in a given sample
of matter is the becquerel (Bq); 1 Bq corresponds to that quantity of radio-

219
activity in which there is one atomic disintegration per second. The cgs
unit used for the same purpose is the curie (Ci); one Ci represents that
quantity of radioactivity in which there are 3.7 × 1010 atomic disintegra-
tions per second (1 Ci = 3.7 × 1010 Bq).
Historically, the unit used for measuring exposure to X-rays is the roent-
gen. One roentgen (R), defined loosely, is the amount of X-radiation that
produces one electrostatic unit of charge in 1 cubic centimeter of air un-
der standard conditions of temperature and pressure. Exposure of the sur-
face of the skin to 1 R of X-rays typically deposits a dose of slightly less
than 10 mGy (1 rad) in the underlying epidermis.

Sources and Levels of Ionizing Radiation

in the Environment
Ionizing radiation from natural, as well as artificial, sources is ubiqui-
tous in the human environment. Natural background radiation comes from
three main sources: cosmic rays, which originate in outer space; terrestri-
al radiation, which emanates from radium and other radioactive elements
in the earth’s crust; and internal radiation, which is emitted by potassi-
um-40 and other naturally occurring radionuclides normally present in
the body. The dose received from all three sources by a person living at
sea level in the United States averages about 0.94 mSv per year to all soft
tissues other than the lung. The intensity of cosmic radiation varies with
altitude by a factor of two or more, however, so that a person residing at
a high elevation (e.g., Denver) may receive twice as large a dose from
this source as one who resides at sea level. The radiation from the earth’s
crust also varies markedly from one geographic region to another, depend-
ing on local variations in the content of radioactive material in soil and
subterranean rock. The doses from these sources are far smaller in any
event than the average dose to the bronchial epithelium from radon in
indoor air; in heavy smokers, moreover, portions of the respiratory tract
may also receive as much as 200 mSv additional radiation per year from
the polonium that is normally present in tobacco smoke. Fertilizers and
building materials, atomic weapons fallout, nuclear power production, and
consumer products (color television sets, smoke detectors, luminescent
clock and instrument dials, etc.).
Workers in various occupations are exposed to additional ionizing ra-
diation, doses of which vary with the nature of the occupation, particular
work assignment, and working conditions. The annual dose equivalent
received occupationally in different countries averages less than 20 mSv
(200 mrem), and less than 0.1% of radiation workers exceed the maxi-
mum permissible dose limit (50 mSv) in any given year.

220
 Nature and Types of Radiation Injuries
For purposes of radiologic protection, it is customary to distinguish
between radiation injuries that have dose thresholds and those that are
assumed to lack dose thresholds. The former (so-called nonstochastic or
deterministic effects) include various acute and chronic tissue reactions
(e.g., erythema of the skin, depression of the blood count, oligospermia,
cataract of the lens) that result from the killing of large numbers of cells
in affected organs. Injuries of the latter type, on the other hand, include
mutagenic and carcinogenic effects, which are viewed as stochastic, or
probabilistic, effects that can result from radiation-induced changes in
single cells within affected organs.

Effects of Radiation at the Cellular Level Gene Mutation

Of the various molecules that radiation may damage within the cell,
DNA is the most critical, since damage to a single gene may irreparably
alter or kill the cell. A dose of radiation large enough to kill the average
dividing cell (1 or 2 Sv) suffices to cause dozens of lesions in its DNA,
most of which are reparable, depending on the effectiveness of the cell’s
DNA repair processes. In fact, thousands of such lesions are thought to
be produced each day in the DNA of every cell by natural background
radiation, oxidative metabolic reactions, and other causes.
Mutagenic effects of radiation have not yet been documented in human
germ cells, but they have been investigated extensively in human somatic
cells and in the germ cells of many other species, in which their frequency
approximates 105 to 106 per locus per Sv, depending on the locus in ques-
tion and the conditions of irradiation. The magnitude of the increase per
unit dose is so small that the absence of detectable mutagenic effects on the
children of the atomic bomb survivors is not surprising in view of the limit-
ed numbers of such children and the comparatively small average gonadal
dose received by their parents. On the basis of present knowledge, the dose
of ionizing radiation that would be required to double the frequency of heri-
table mutations in the human population is estimated to exceed 1 Sv, from
which it is inferred that less than 1% of the total burden of genetically re-
lated human diseases is attributable to natural background irradiation.

Chromosome Aberrations
By breaking chromosomes and/or interfering with their normal segre-
gation to daughter cells at the time of cell division, irradiation can alter
the number and structure of chromosomes in the cell. If two or more
chromosome breaks occur close enough together in space and time, the
221
broken ends from one break point may be joined incorrectly with those
from another, giving rise to translocations, inversions, rings, dicentrics,
and other types of chromosome rearrangements. With high-LET irradia-
tion, the frequency of such “two-event” aberrations increases steeply as a
linear function of the dose and is virtually independent of the dose rate,
whereas with low-LET irradiation it increases less abruptly, as a linear-
quadratic function of the dose, and is highly dependent on the dose rate,
i.e., the linear dose term predominates at low doses and low dose rates,
whereas the quadratic term predominates at high doses and high dose rates.
In human lymphocytes irradiated in culture, the frequency of two-event
chromosome aberrations approximates 0.1 aberration per cell per seivert in
the low-to-intermediate dose range. It is not astonishing, therefore, that the
frequency of such aberrations has been observed to be increased in radia-
tion workers and persons residing in areas of high natural background radi-
ation, as well as in persons exposed accidentally or therapeutically to large
doses of radiation, for whom it can serve as a crude biologic dosimeter.

Cytotoxic Effects
In general, the radiosensitivity of cells varies in proportion to their
rate of proliferation and inversely in relation to their degree of differenti-
ation, as noted early in this century by Bergonie and Tribondeau. Rela-
tively few types of cells (e.g., lymphocytes and oocytes) are radiosensi-
tive in a nonproliferative state. Although any cell can be killed by a large-
enough dose of radiation (hundreds or thousands of gray), a dose of only
1 to 2 Gy suffices to render most human clonogenic cells incapable of
proliferating.
The survival of cells, as measured by their ability to proliferate, tends
to decrease exponentially with increasing dose. With high-LET radiation,
the dose-survival curve is characteristically steeper than with low-LET
radiation and is relatively independent of the dose rate, whereas with low-
LET radiation the curve usually has an initial shoulder in the low-dose
region, which reappears between successive exposures as a result of re-
pair of radiation damage during the interim.

Effects on Tissues and Organs

Tissues in which cells proliferate rapidly are generally the first to man-
ifest injury. Mitotic inhibition is typically detectable within minutes after
intensive irradiation, in contrast to scarring, tissue breakdown, and other
degenerative changes, which may not appear until months or years later.
If a dose of radiation is absorbed gradually enough, its damaging effects
222
may be offset to varying degrees by the compensatory proliferation of
stem cells that escape injury, so that a larger dose of radiation can be to-
lerated if it is spread out in time than if it is absorbed in a single brief
exposure.
Because of the great multiplicity and diversity of ways in which irra-
diation can affect different organs, only those effects that are of particu-
lar relevance to occupational and accidental irradiation are described in
the following sections.

Skin
The earliest outward reaction of the skin is erythema, which results
from dilatation of blood capillaries by substances released from injured
cells in the overlying epidermis. The severity of the erythema increases
with the area as well as the depth of the skin that is irradiated. The thresh-
old dose for erythema in an area greater than 10 cm 2 varies from about 6
to 8 Gy delivered in a single, brief exposure to more than 30 Gy deliv-
ered in multiple exposures over a period of several weeks. After rapid
exposure to a dose of 6 Gy, the erythema may become evident within
hours, typically lasts only a few hours, and is followed 2 to 4 weeks later
by one or more waves of deeper and more persistent erythema.
For epilation, the threshold is lower: a dose of 3 to 5 Gy delivered in a
single, brief exposure suffices to cause temporary shedding of hair from
the scalp.

Blood-Forming Tissues
Hematopoietic cells are highly radiosensitive, undergoing degenera-
tive changes within minutes after a dose of 1 Sv, while mature leuko-
cytes, erythrocytes, and platelets are radioresistant. A dose of 3 to 5 Sv
acute whole-body irradiation suffices to kill enough hematopoietic cells
to cause profound depression of the white blood cells and platelet counts
within 3 to 5 weeks, whereas a dose of 0.5 to 1.0 Sv is not large enough
to depress the count severely. A dose of 10 Sv of whole-body irradiation,
which is lethal when received within minutes or days, can be tolerated
when accumulated gradually over a period of weeks or months or when
delivered to only a small fraction of the hematopoietic marrow.
Lymphocytes like hematopoietic cells, are highly radiosensitive. A dose
of 3 to 5 Sv of intensive whole-body irradiation suffices to cause prompt
lymphopenia, with profound depression of the immune response.
223
 Gastrointestinal Tract
Germinative cells in the epithelium of the small intestine can be killed
in sufficient numbers by intensive irradiation to cause denudation and ul-
ceration of the overlying mucosa. When a large part of the small intestine
is exposed acutely to a dose in excess of 10 Gy, a fulminating dysentery-
like reaction is produced, which may terminate fatally within several days.

Reproductive Organs
Immature spermatogonia are among the most radiosensitive cells in
the body. As a result, rapid exposure of both testes to a dose of only
0.15 Sv suffices to depress the sperm count temporarily, and permanent
sterility may result from a dose in excess of 4 Sv.
Oocytes also are radiosensitive. A dose of 1.5 to 2.0 Sv to both ova-
ries may cause temporary sterility, and a dose of 2.0 to 3.0 Sv — perma-
nent sterility, depending on the age at the time of irradiation.

Lens of the Eye

Irradiation of the lens can cause the formation of lens opacities within
a matter of months, depending on the dose. Although a posterior subcap-
sular opacity may become detectable microscopically after a dose of 0.6
to 1 Sv received in a single, brief exposure, the threshold for a vision-
impairing cataract is estimated to vary from about 2 to 3 Sv if received in
a few minutes to as much as 5.5 to 14 Sv if received over a period of
months. The occurrence of radiation cataracts in pioneer cyclotron physi-
cists provided the first evidence of the relatively high cataractogenic ef-
fectiveness of neutrons.

THE ACUTE RADIATION SYNDROME

Intensive irradiation of the major part of the hematopoietic system,
the gastrointestinal tract, the lung, or the brain can cause the acute radia-
tion syndrome. The prodromal symptoms — anorexia, nausea, and vom-
iting — typically begin within a few hours after irradiation. Except at
the highest doses, these symptoms usually subside by the end of the first
day and are followed by a symptom-free interval until the onset of the
main phase of the illness.
In the intestinal form of the syndrome, the main phase of the illness
characteristically begins 2 to 3 days after irradiation, with abdominal pain,
fever, and increasingly severe diarrhea, dehydration, prostration, and to-
xemia. The reaction progresses rapidly, culminating within several days
in a fatal, shocklike state.
224
 In the hematopoietic form of the syndrome, the main phase of the ill-
ness is related to leukopenia and thrombocytopenia, which typically do not
give rise to symptoms until the second to third week after irradiation. When
injury of the marrow is sufficiently extensive, death from infection or he-
morrhage may result during the fourth to sixth week after irradiation.
In the pulmonary form, an acute pneumonitis develops in the irradiat-
ed area within 1 to 3 months after a dose of 6 to 10 Sv to the lung. If
extensive, the process may terminate in respiratory failure, or it may lead
to pulmonary fibrosis and cor pulmonale months or years later.
A fourth form of radiation sickness, the cerebral form, can result from
acute exposure of the brain to a dose in excess of 50 Sv. In this reaction,
anorexia, nausea, and vomiting begin almost immediately after irradia-
tion, to be followed within minutes or hours by increasing drowsiness,
confusion, ataxia, convulsions, loss of consciousness, and death.

CARCINOGENIC EFFECTS
Irradiation has been observed to increase the incidence of cancers of
various types in radiotherapy patients, early radiologists, radium dial paint-
ers, underground hardrock miners, and atomic bomb survivors, depend-
ing on the conditions of exposure. Such cancers have not appeared until
years or decades after irradiation, however, and none has shown features
identifying it as having resulted from radiation specifically, as opposed
to some other cause. These findings, are complemented by extensive ex-
perimental data on radiation carcinogenesis in laboratory animals.
Excesses of many types of malignancy are evident in atomic bomb
survivors, in whom the overall incidence of cancer appears to have in-
creased in proportion to the radiation dose. However, the data do not suf-
fice to define precisely the shape of the dose-incidence curve in the low-
dose domain. Hence the carcinogenic risks of low-level irradiation can
be estimated only by extrapolation, based on assumptions about the rela-
tionship between incidence and dose. Of the available dose-incidence data
for the various cancers, the most extensive pertain to leukemia, cancer of
the female breast, and cancer of the thyroid gland.

Leukemia
All major forms of leukemia, except the chronic lymphocytic form,
have been observed to be increased in frequency after irradiation of the
whole body or a large part of the hematopoietic system. The increase has
typically appeared within 2 to 5 years after irradiation, has been dose de-

225
pendent, and has persisted 15 years or longer, depending on the hemato-
logic type of leukemia and the age at irradiation. In atomic bomb survi-
vors, patients treated with spinal irradiation for ankylosing spondylitis,
and women treated with pelvic irradiation for menorrhagia, the overall
excess of all forms of leukemia (other than the chronic lymphocytic form)
averaged over the first 25 years after irradiation has approximated 1 to
3 cases per 10,000 persons per year per sievert to the bone marrow. A
comparable excess has been observed in occupationally exposed workers,
based on combined analyses of the data from several different cohorts.
The data do not suffice to define the shape of the dose-incidence curve
unambiguously, but they appear to be most consistent with a linear-quad-
ratic dose-incidence relationship.
Leukemia has also been observed to be increased in frequency in Brit-
ish and American children who were exposed prenatally during radio-
graphic examination of their mothers, the excess corresponding roughly
to a 5% increase in the relative risk of childhood leukemia per millisiev-
ert, or to approximately 25 cases per 10,000 children at risk per sievert per
year during the first 10 years of life. Although no such increase was evi-
dent in Japanese children exposed prenatally to atomic bomb radiation, the
lack of an excess in this population is not incompatible with the increase
noted above, in view of the limited numbers of children in question.
The possibility that the excesses of leukemias and lymphomas in child-
ren residing in the vicinity of some of the nuclear plants in the United
Kingdom may have been caused by heritable oncogenic effects resulting
from the occupational irradiation of their fathers has been suggested by a
case-control study, but arguing against this hypothesis are:
a) the lack of any comparable excess in larger numbers of children
born outside of Seascale, England, to fathers who had received similar or
even larger doses of occupational radiation at the same facility;
b) the lack of similar excesses in French, Canadian, or Scottish child-
ren born to fathers with comparable occupational exposures;
c) the lack of an excess in the children of atomic bomb survivors;
d) the lack of excesses in U.S. counties containing nuclear plants.

Cancer of the Breast

A dose-dependent increase in the incidence of cancer of the breast has
been observed in women who survived atomic bomb irradiation, women
who were given radiation therapy to the breast for acute postpartum mas-
titis or other benign diseases, women who were examined repeatedly by
fluoroscopy of the chest during treatment for pulmonary tuberculosis with

226
artificial pneumothorax, and women who worked as radium dial painters.
In all four groups of women, the incidence of carcinoma of the breast
was observed to become elevated within 5 to 10 years after irradiation,
depending on the age at exposure, and to remain elevated for the duration
of follow-up. Averaged over all ages, the magnitude of the dose-depen-
dent excess is similar in each group, in spite of marked differences among
the groups in the rapidity with which the total doses were received. The
observation of comparably large carcinogenic effects in the women who
accumulated their doses in many small and widely separated increments
implies that successive exposures are additive in their cancer-causing ef-
fects on the breast and that there may be little or no threshold for such
effects.
Susceptibility appears to be highest in childhood and to decrease mark-
edly with the age at the time of irradiation, little if any cancer excess
being detectable in women exposed after the age 40. Furthermore, in atom-
ic bomb survivors of any given cohort whose tumors appeared relatively
early, the excess was larger than in those whose tumors appeared later,
suggesting that the former may have constituted a genetically susceptible
subgroup. In women irradiated during infancy or childhood, the excess
did not become evident until 30 to 40 years later, implying that expres-
sion of the carcinogenic effects of radiation on the breast depended on
their being promoted by age-related hormonal stimulation.

Thyroid Gland
Tumors of the thyroid gland have been observed to be increased in
frequency in atomic bomb survivors, patients given radiation therapy to
the neck in infancy for thymic enlargement and other non-neoplastic con-
ditions, patients given X-ray therapy to the scalp in childhood for treat-
ment of tinea capitis, Marshall islanders exposed to radioactive fallout
from a weapons test in 1954, children exposed to fallout from nuclear
weapons detonated at the Nevada test site, children exposed to radioac-
tivity released in the Chernobyl accident, and other populations exposed
to external irradiation of the thyroid. The induced neoplasms have con-
sisted chiefly of papillary adenomas and carcinomas, have caused a rela-
tively low rate of mortality, and have been preceded by latent periods of
10 to 25 years or longer. Susceptibility to the induction of such tumors
appears to be appreciably higher in females than in males, and to be
markedly higher in childhood than in adult life.
In persons who received X-ray therapy to the neck in infancy, the in-
cidence of thyroid cancer has been observed to be increased after a dose

227
as low as 65 mSv, and the observed dose-incidence relationship appears to
be consistent with a linear, nonthreshold function, corresponding to an ex-
cess of approximately 4 cancers per 10,000 person-yr-Sv. No excess has
been evident, however, in patients who have received as much as
0.5 Gy to the thyroid from iodine-131 administered for diagnostic purpos-
es, implying that such radiation is substantially less carcinogenic to the thy-
roid than external X- or gamma-radiation, possibly because of spatial and
temporal differences in the distribution of the radiation within the gland.

Radiation Accidents
In spite of elaborate precautions, some 285 nuclear reactor accidents
(excluding the Chernobyl accident) were reported between 1945 and 1987
in various countries, causing more than 1,350 persons to be irradiated, 33
of whom were injured fatally. The Chernobyl accident itself, owing to
inadequate containment of the reactor and other design and operating
flaws, released enough radioactivity to necessitate the evacuation of thou-
sands of people and farm animals from the surrounding area, and it caused
radiation sickness and burns in more than 200 emergency personnel and
firefighters, injuring 31 fatally. Accidents involving medical and indus-
trial gamma ray sources, which have been more numerous than reactor
accidents, also have also resulted in injuries and loss of life. In 1987, for
example, the improper disposal of a cesium-137 radiotherapy source in
Goiania, Brazil, led to the irradiation of dozens of unsuspecting victims,
four of whom were injured fatally as a result.
From the foregoing, it follows that in any situation where people may
be irradiated accidentally, plans for coping with such an accident should
be in place. The plans should include delineation of lines of authority for
managing an accident, knowledge of the local medical facilities capable
of evaluating and treating radiation accident victims, plans for handling
and transporting radioactive victims, and some instruction on the hazards
of radiation for those employed at the site.
In managing the radiation accident victim, sound medical judgment
should come first. Thus, even victims who are heavily irradiated or con-
taminated should be evaluated for other forms of injury, such as burns,
mechanical trauma, or smoke inhalation. In addition, persons who handle
or examine a potentially contaminated victim should wear gloves, mask,
and other protective clothing, to guard against self-contamination with
radioactivity. Detailed records should be kept of all examinations, meas-
urements, procedures, findings, personnel, and times involved.

228
 If radioactive contamination is detected, the victim should be isolated
and the contaminated area sealed off as soon as possible. Contaminated
clothing should be removed promptly, isolated in a plastic bag, and la-
beled to denote radioactivity. Contaminated parts of the body should be
isolated with paper or plastic, monitored for radioactivity, rinsed thor-
oughly, and monitored again. During the rinsing, care should be taken to
avoid abrading contaminated skin, and the rinse water should be isolated
as radioactive waste. If radioactive material may have been inhaled, the
victim should rinse the oral and nasal cavities with water, taking care not
to inhale or swallow more radioactivity in the process; the rinse water
and any other secretions should be collected in plastic bags, labeled, and
isolated for subsequent examination.
The management of radiation injuries themselves depends on the se-
verity of the injuries and the organs that are affected. Because the signs
and symptoms of radiation injury are nonspecific, pertinent information
from the victim’s exposure record, medical history, physical examination,
and laboratory data must be synthesized and integrated. Inasmuch as the
nature and severity of injury depend inevitably on the size and anatomic
distribution of the radiation dose, evaluation of the latter is paramount. In
the absence of physical dosimetry, cytogenetic analysis of circulating
lymphocytes can serve as a useful biologic dosimeter (Table 12.1).

Table 12.1. Responses to acute whole-body irradiation

Whole-body dose
Response
Sv rem
0.05–1.0 5–100 Asymptomatic. Minor depression of leukocytes and
platelets* in a few persons. Chromosome aberrations.
1.0–2.0 100–200 Mild anorexia, nausea, vomiting, and fatigue of <24 hrs’
duration in most persons. Depression of leukocytes and
platelets* in most persons, with lymphocytes declining
by about 50% within 48 hrs.
2.0–4.0 200–400 Symptomatic course with nausea and vomiting lasting 2-
4 days in most persons. Skin erythema and subsequent
epilation. Marked reduction in leukocytes and platelets.*
Some deaths within 60 days due to infection.
4.0–6.0 400–600 Serious illness with nausea and vomiting occurring within
a few hours and diarrhea.
Severe hematopoietic changes.* Approximately 50%
mortality, usually within 30 days (LD[50] = 450 rem).

229
 End of Table 12.1
Whole-body dose
Response
Sv rem
6.0–10.0 600–1000 Accelerated version of acute radiation syndrome with
severe nausea, vomiting, and diarrhea starting within a
few hours and culminating in gastrointestinal hemor-
rhage and severe fluid and electrolyte loss. Lymphocyte
depression to <500/mcl by 48 hrs. High mortality, usu-
ally within 14 days.
>10.0 >1000 Fulminant course with rapid onset of gastrointestinal,
CNS, and cardiovascular manifestations and complica-
tions. Lymphocytes decline to 0 within 48 hrs.
Mortality of 100%, usually within 72 hrs.
Note. * — maximum depression of lymphocytes usually occurs within 48 hrs, whereas
maximum depression of neutrophils and thrombocytes usually takes 3–4 weeks.

TESTS
1. Define an approximate dose of the radiation and degree of severity
of ARS, caused by external radiation.There were observed in a damaged
man at a period of primary reactions: single vomiting in 3 hrs after in-
jury, small general weakness, short headache, not changed consciousness;
skin and visible mucous membranes are not changed, temperature of the
body is 36.8°C. A term from the injury to primary reactions — 10 hrs.
Define the doze of radiation:
A. Dose of radiation 2–4 Gy, moderate degree of severity.
B. Dose of radiation 1–2 Gy, mild degree of severity.
C. Dose of radiation 4–6 Gy, severe degree.
D. Dose of radiation more than 6 Gy, extremely severe degree.
2. Define an approximate dose of the radiation and degree of severity
of ARS, caused by an external radiation. Among clinical manifestations
in a damaged man at a period of primary reactions there are following:
frequent vomiting, which has appeared in 2 hrs after the radiation, gen-
eral weakness, headache; consciousness is not changed, mild hyperemia
of the skin covers and mucous membranes, temperature of the body —
37.5°C. These changes were observed during the first day.
A. Dose of radiation more than 6 Gr, extremely heavy degree of se-
verity.
B. Dose of radiation 1–2 Gy, mild degree of severity.
C. Dose of radiation 2–4 Gy, moderate degree of severity.
D. Dose of radiation 4–6 Gy, severe degree.

230
 3. A patient, aged 32 years, 5 hrs after the Chornobyl disaster, where
he had been the operator during 2 years, was delivered to the rehabilita-
tion department. Objective: the confused consciousness, cramps, insta-
bility of BP, temperature of the body — 39°C. In the blood —leukopenia,
thrombocytopenia.
Establish the diagnosis:
A. Acute alcoholic poisoning.
B. Chronic radiation syndrome.
C. Acute radiation syndrome, the cerebral form.
D. Chronic radiation syndrome, the intestinal form.
E. Medicamental poisoning.
4. A man, aged 43 years old, at the examination presented the com-
plaints of weakness, headaches, dysability, decrease of memory and po-
tency, abaissement of hair, gums’ bleeding, sweating, often nasal bleed-
ings. Objective: on an internal surface of the femur and brachiums the
dermal petechias, positive pinch sign, stomatitis are observed. Changes
in the blood: leukopenia 0.2⋅10 9/l; thrombocytopenia — 120⋅103. Occu-
pational anamnesis: during 2 years he works as the driver on uranic mine.
The preliminary diagnosis:
A. Chronic radiation syndrome, 1st degree of severity.
B. An acute radiation syndrome.
C. The Werlhof’s disease.
D. Chronic radiation syndrome, 2nd degree of severity.
E. Scurvy.
5. A woman, aged 37 years, a researcher, complains of general weak-
ness, malaise, headache, fall of a working capacity, appetite and sleep
disorders, bleeding of gums, the dyspeptical phenomenon, infringement
of menstrual function, hypotonia, concussion, nasal bleedings.
The preliminary diagnosis:
A. Pregnancy.
B. Cancer.
C. Chronic radiation syndrome, 2nd degree of severity.
D. Vegetatovascular dystonia.
E. Toxicoinfection.

231
 Chapter 13
MUSCULOSKELETAL DISORDERS

Musculoskeletal disorders (MSDs) were recognized as having occu-

pational etiologic factors as early as the beginning of the 18th century.
However, it was not until the 1970s that occupational factors were exam-
ined using epidemiologic methods, and the work-relatedness of these con-
ditions began appearing regularly in the international scientific literature.
Since then the literature has increased dramatically; more than six thou-
sand scientific articles addressing ergonomics in the workplace have been
published. Yet, the relationship between MSDs and work-related factors
remains the subject of considerable debate.
The term musculoskeletal disorders (MSDs) refers to conditions that
involve the nerves, tendons, muscles, and supporting structures of the body.
Because the relationship between exposure to physical work factors and
the development and prognosis of a particular disorder may be modified
by psychosocial factors, the literature about psychosocial factors and the
presence of musculoskeletal symptoms or disorders is also reviewed.
Understanding these associations and relating them to the cause of di-
sease is critical for identifying exposures amenable to preventive and ther-
apeutic interventions. By the official data 32% of MSDs cases are the
result of overexertion or repetitive motion. In the OSHD survey amongst
367,424 injuries due to overexertion in lifting there were 65% cases af-
fected the back. Due to implementation of new technologies in the indus-
try the incidence rate of overexertion (in lifting) declined from 52.1 per
10,000 workers in 1992 to 41.1 in 1995; the incidence rate for repetitive
motion disorders declined from 11.8 per 10,000 workers in 1992 to 10.1
in 1995 in the developed countries. These declines are similar to those
seen for cases involving days away from work from all causes of injury
and illness. However, the prevalence and incidence of MSDs are still high.
Musculoskeletal disorders (MSDs) can affect the body’s muscles,
joints, tendons, ligaments and nerves. Most work-related MSDs develop

232
over time and are caused either by the work itself or by the employees’
working environment. They can also result from fractures sustained in an
accident. Typically, MSDs affect the back, neck, shoulders and upper
limbs; less often they affect the lower limbs.
Health problems range from discomfort, minor aches and pains, to more
serious medical conditions requiring time off work and even medical treat-
ment. In more chronic cases, treatment and recovery are often unsatisfac-
tory — the result could be permanent disability and loss of employment.
Many problems can be prevented or greatly reduced by complying with
existing safety and health law and following guidance on good practice.
Unfortunately, MSDs are an increasing problem. For the employee, they
cause personal suffering and loss of income; for the employer, they re-
duce business efficiency; and for government, they increase social secu-
rity costs. MSDs are a priority for the EU in its Community strategy. Re-
ducing the musculoskeletal load of work is part of the ‘Lisbon objective’,
which aims to create ‘quality jobs’ by:
— enabling workers to stay in employment; and
— ensuring that work and workplaces are suitable for a diverse popu-
lation.
A number of factors can influence a person’s response to risk factors
for MSDs in the workplace
The prevalence of MSDs increases as people enter their working years.
By the age of 35, most people have had their first episode of back pain.
Once in their working years (ages 25 to 65), however, the prevalence is
relatively consistent. Musculoskeletal impairments are among the most
prevalent and symptomatic health problems of middle and old age. None-
theless, age groups with the highest rates of compensable back pain and
strains are the 20–24 age group for men, and 30–34 age group for wom-
en. In addition to decreases in musculoskeletal function due to the devel-
opment of age-related degenerative disorders, loss of tissue strength with
age may increase the probability or severity of soft tissue damage from a
given insult.
Another problem is that advancing age and increasing number of years
on the job are usually highly correlated. Age is a true confounder with
years of employment, so that these factors must be adjusted for when de-
termining relationship to work. Many of the epidemiologic studies that
looked at populations with a wide age variance have controlled for age
by statistical methods. Several studies found age to be an important fac-
tor associated with MSDs, others have not. Although older workers have
been found to have less strength than younger workers, Mathiowetz et al.
demonstrated that hand strength did not decline with aging; average hand
233
pinch and grip scores remained relatively stable in their population with
a range of 29 to 59 years. Torell et al. found no correlation between age
and the prevalence of MSDs in a population of shipyard workers. They
found a strong relationship between workload (categorized as low, medi-
um, or heavy) and symptoms or diagnosis of MSDs.
Some studies have found a higher prevalence of some MSDs in wo-
men. A male to female ratio of 1:3 was described for carpal tunnel syn-
drome (CTS) in a population study in which occupation was not evalu-
ated.
The relationship of physical activity and MSDs is more complica-
ted than just “cause and effect.” Physical activity may cause injury.
However, the lack of physical activity may increase susceptibility to
injury, and after injury, the threshold for further injury is reduced. In
construction workers, more B-5 frequent leisure time was related to
healthy lower backs and severe low back pain was related to less lei-
sure time activity. On the other hand, some standard treatment regimes
have found that musculoskeletal symptoms are often relieved by physi-
cal activity.
Having good physical condition may not protect workers from risk of
MSDs. Persons with high aerobic capacity may be fit for jobs that re-
quire high oxygen uptake, but will not necessarily be fit for jobs that re-
quire high static and dynamic strengths and vice versa. When physical
fitness is examined as a risk factor for MSDs, results are mixed. For ex-
ample, some early case series reported an increased risk of MSDs associa-
ted with playing professional sports, or with physical fitness and exercise
while other studies indicate a protective effect and reduced risk. Boyce et
al. reported that only 7% of absenteeism could be explained by age, sex,
and physical fitness among 514 police officers 35 years or older. Cady et
al., on the other hand, found that physical capacity was related to muscu-
loskeletal fitness. Cady defined fitness for most physical activities as com-
binations of strength, endurance, flexibility, musculoskeletal timing and
coordination. Cady et al. evaluated male fire fighters and concluded that
physical fitness and conditioning had significant preventive effects on back
injuries (least fit 7.1% injured, moderately fit 3.2% injured and most fit
0.8% injured). However, the most fit group had the most severe back in-
juries. Low cardiovascular fitness level was a risk factor for disabling
back pain in a prospective longitudinal study among aerospace manufac-
turing workers by Battie et al. Good endurance of back muscles was found
to be associated with low occurrence of low back pain.
Few occupational epidemiologic studies have looked at non-work-re-
lated physical activity in the upper extremities. However, many of the
234
risk factors that are important in occupational studies occur in sports ac-
tivities — forceful, repetitive movements with awkward postures.
A combination of high exposure to load lifting and high exposure to
sports activities that engage the arm was a risk factor for shoulder tendin-
itis, as well as osteoarthritis of the acromioclavicular joint. Epicondylitis
in professional athletes has been well documented, and many of the bio-
mechanical and physiological studies of epicondylitis have been conducted
in professional tennis players and baseball pitchers. It is important to note
that professional sports activities usually provide players (i.e., workers)
with more substantial breaks for recovery and shorter durations for in-
tense tasks as compared with more traditional work settings in which work-
ers are required to perform repetitive, forceful work for 8 hours per day,
5 days per week.
Some epidemiologic support exists for the relationship between back
injury and a mismatch of physical strength and job tasks. Chaffin and
Park found a sharp increase in back injury rates in subjects performing
jobs requiring strength that was greater or equal to their isometric
strength-test values. The risk was three times greater in the weaker sub-
jects. In a second longitudinal study, Chaffin et al. evaluated the risk of
back injuries and strength and found the risk to be three times greater
in the weaker subjects. Keyserling et al. strength-tested subjects, bio-
mechanically analyzed jobs, and assigned subjects to either stressed or
non-stressed jobs. Following medical records for a year, they found that
job matching based on strength criteria appeared to be beneficial. In
another prospective study, Troup et al. found that reduced strength of
back flexor muscles was a consistent predictor of recurrent or persist-
ent back pain, but this association was not found for first time occur-
rence of back pain.
Dupuytren’s contracture (also known as Morbus Dupuytren or
Dupuytren’s disease, and sometimes misspelled as Dupuytren’s constric-
ture) is a fixed flexion contracture of the hand where the fingers bend
towards the palm and cannot be fully extended (straightened). It is named
after Baron Guillaume Dupuytren, the surgeon who described an opera-
tion to correct the affliction.The ring finger and little finger are the fin-
gers most commonly affected. The middle finger may be affected in ad-
vanced cases, but the index finger and the thumb are nearly always spared.
Dupuytren’s contracture progresses slowly and is usually painless. In pa-
tients with this condition, the tissues under the skin on the palm of the
hand thicken and shorten so that the tendons connected to the fingers can-
not move freely. The palmar aponeurosis becomes hyperplastic and un-
dergoes contracture.
235
 Incidence increases after the age of 40; at this age men are affected
more often than women. After the age of 80 the distribution is about even.
In Dupuytren’s disease, the tough connective tissue within one’s hand
becomes abnormally thick which can cause the fingers to curl and can
result in impaired function of the fingers, especially the small and ring
fingers. It usually has a gradual onset, often beginning as a tender lump
in the palm. Over time, pain associated with the condition tends to go
away, but tough bands of tissue may develop. These bands, which are the
source of the reduced mobility commonly associated with the condition,
are visible on the surface of the palm and may appear similar to a small
callus. It commonly develops in both hands and has no connection to dom-
inant or non-dominant hands, nor any correlation with right- or left-hand-
edness.
Dupuytren’s disease is a very specific affliction, and primarily affects:
— people of Scandinavian or Northern European ancestry; it has been
called the “Viking disease”, though it is also widespread in some Medi-
terranean countries (e.g. Spain and Bosnia) and in Japan;
— men rather than women (men are ten times as likely to develop the
condition);
— people over the age of 40;
— people with a family history (60 to 70% of those afflicted have a
genetic predisposition to Dupuytren’s contracture)
Some suspected, but unproven causes of Dupuytren’s contracture in-
clude trauma, diabetes, alcoholism, epilepsy and liver disease. There is
no proven evidence that hand injuries or specific occupational exposures
lead to a higher risk of developing Dupuytren’s disease although there is
some speculation that Dupuytren’s may be caused or at least the onset
may be triggered by physical trauma, such as manual labor or other over-
exertion of the hands.
De Quervain syndrome (also known as washerwoman’s sprain, Radial
styloid tenosynovitis, de Quervain disease, de Quervain’s tenosynovitis,
de Quervain’s stenosing tenosynovitis or mother’s wrist), is an inflam-
mation or a tendinosis of the sheath or tunnel that surrounds two tendons
that control movement of the thumb. These two tendons concerned are
the tendons of the extensor pollicis brevis and abductor pollicis longus
muscles. These two muscles, which run side by side, have almost the same
function: the movement of the thumb away from the hand in the plane of
the hand — so called radial abduction (as opposed to movement of the
thumb away from the hand, out of the plane of the hand (palmar abduc-
tion)). The tendons run, as do all of the tendons passing the wrist, in syno-
236
vial sheaths, which contain them and allow them to exercise their func-
tion whatever the position of the wrist. While de Quervain syndrome is
commonly believed to be an inflammatory condition or tendosynovitis,
evaluation of histological specimens shows no inflammatory changes —
rather a thickening and myxoid degeneration consistent with a chronic de-
generative process are seen. De Quervain seen in new mothers.de Quer-
vain syndrome is more common in women. A speculative rationale for this
is that women have a greater styloid process angle of the radius, but scien-
tific support for this theory is lacking.
The cause of de Quervain is not known. In medical terms, it remains
idiopathic. However, some authors claim that this diagnosis should be in-
cluded among overuse injuries and that repetitive movements of the thumb
are a contributing factor. More specifically, repetitive eccentric lowering
of the wrist into ulnar deviation especially with a load in the hand such as
a child or even a stack of dishes.
The clinical manifestations are presented by pain, tenderness, and
swelling over the thumb side of the wrist, and difficulty gripping.
Finkelstein’s test is used to diagnose de Quervain syndrome in people
who have wrist pain. To perform the test, the thumb is placed in the closed
fist and the hand is tilted towards the little finger — ulna deviation in
order to test for pain at the wrist below the thumb. Pain can occur in the
normal individual, but if severe, de Quervain’s syndrome is likely. Pain
will be located on the thumb side of the forearm about an inch below the
wrist.
The natural history of de Quervain’s syndrome is not well document-
ed. Nonetheless, there is enough observational experience to be fairly cer-
tain that it is a self-limited illness with no long-term consequence. Once
resolved it rarely recurs. The illness tends to last about 1 year on average.
There are no treatments that have been scientifically demonstrated to short-
en the duration of symptoms, principally because there are no controlled
scientific studies. Things that are tried, without support, and with incon-
sistent results include immobilization, round the clock anti-inflammatory
medications, ionophoresis, and corticosteroid injections. Case series of
patients receiving one of the most popular treatments (corticosteroid in-
jection) have claimed effectiveness even when the illness did not resolve
for months — clearly more study is needed. Operative release is the only
known way for predictably shortening the duration of symptoms, but is
elective. Surgery consists of opening the tunnels, or sheaths, that the ten-
dons pass through. The pain usually resolves in the time it takes the wound
to heal.
237
 While patients await disease resolution, the symptoms of de Quervain’s
syndrome can be managed with a spica splint that immobilises the wrist
and thumb, anti-inflammatory pain medications (or other non-narcotic pain
medications), and ice. While avoiding activities that cause pain will cer-
tainly decrease the overall amount of pain experienced, there is no evi-
dence that this will speed recovery, or that continuing to engage in these
activities will lead to any harm — the illness is in general a harmless
nuisance. Therefore, patients can safely choose their activity and pain level.
It is not dangerous or neglectful to remain active in spite of the pain. The
splint can be used as desired to improve function and quality of life du-
ring the illness.
Specialized hand therapists (both physical therapists and occupational
therapists) provide treatment in the form of splinting to immobilise and
rest the wrist and thumb. Therapists may recommend activity modifica-
tion to avoid repetitive eccentric lowering of the wrist into ulnar devia-
tion, but this is done in spite of the debate regarding the role of hand use
in etiology and risks “blaming the patient.” Some therapists also advo-
cate that, once pain free, therapeutic exercise (focusing on eccentric con-
trol) are encouraged to strengthen muscles and progressively overload the
tendons so that future episodes are avoided. This is also a highly debata-
ble theory. Recurrence of de Quervain’s syndrome is very uncommon.
Once it runs its course it rarely returns.
While splinting and activity modification are clearly palliative, there
is little scientific support for the efficacy of these treatments in shorten-
ing the duration of the illness.
In 1850 dr. A. Notta, an “interne” in Paris, described four adult pa-
tients between the ages of 20 and 60 who had a nodule on a flexor tendon
of a finger, thereby inhibiting its normal movement. In adult men and
women, the most common age for the triggering of digits is between 50
and 60 years. This condition took his name and is known as Notta’s syn-
drome.
Repeated minor trauma is probably the most likely cause of trigger
digit, but heavy manual labor with the direct palmar pressure of power
grasp may precipitate the symptoms at any adult age. Even ordinary use
of the hand is associated with a higher incidence of trigger digit in the
dominant right hand. The ring finger is most commonly affected; next in
involvement is the long finger, then the small finger, while the index fin-
ger is rarely involved. For some inexplicable reason, trigger thumb is far
more common in women.
238
 Tension myositis syndrome (TMS) is a name given by Dr. J. E. Sar-
no to a condition he describes as characterized by psychosomatic muscu-
loskeletal and nerve symptoms, most notably back pain. Sarno, a Profes-
sor of Clinical Rehabilitation Medicine at New York University School
of Medicine and Attending Physician at the Rusk Institute of Rehabilita-
tion Medicine at New York University Medical Center, has described TMS
in several books, and has stated that the condition may be involved in
other pain disorders as well. However, the TMS diagnosis and treatment
protocol are not accepted by the mainstream medical community. Some
authors include TMS in a list of conditions he considers to be possible
causes of back pain resulting in missed work days that increase the costs
of worker’s compensation programs.
Myalgia usually is a result of over-stretching of a muscle or group of
muscles. Myalgia without a traumatic history is often due to viral infec-
tions. Longer-term myalgias may be indicative of a metabolic myopathy,
some nutritional deficiencies or chronic fatigue syndrome.
The most common causes of myalgia are overuse, injury or stress.
However, myalgia can also be caused by diseases, disorders, medications,
as a response to vaccination and withdrawal syndromes.
Prevention and control. There are two approaches are widely accepted
for controlling workplace ergonomic hazards. Engineering control includes
measures taken to modify the forcefulness, repetitiveness, awkwardness,
vibration levels, physical pressures, or environmental extremes connect-
ed with a particular job. Engineering controls are the preferred approach
in preventing MSDs. Examples include modifications of:
1) the workstation layout;
2) selection and use of tools;
3) work materials;
4) work methods.
Administrative controls are management-directed work practices and
policies. Administrative control strategies include (1) changes in job rules
and procedures such as scheduling more rest breaks, (2) rotating workers
through jobs that are physically tiring, and (3) training workers to recog-
nize ergonomic risk factors and to learn techniques for reducing stress
and strain while performing their job.
Although engineering controls are preferred, administrative controls
can be helpful as temporary measures until engineering controls can be
implemented or when engineering controls are not technically feasible.
Since administrative controls do not eliminate hazards, the necessary pre-
cautions and safeguards must be followed.
239
 TESTS
1. A man, 40, a locksmith-polisher at the factory of radial tools. The
following symptoms have appeared: pain, swelling, crepitation of the fore-
arm. It was noted a reduction of functions of the hand and forearm, weak-
ness. Preliminary diagnosis:
A. De Quervain’s disease.
B. Bursitis.
C. Arthritis of the elbow joint.
D. Crepitative tendovaginitis of the forearm.
E. Epicondylitis.
2. A milkwoman complains of the pain in distal part of the forearm on
the part of the beam bone. The pain appears during a motion of the 1st
finger. Possible diagnosis:
A. Stenosed tendovaginitis.
B. Bursitis.
C. Crepitative tendovaginitis of the forearm.
D. Aseptic osteonecroses of the bone.
3. A woman, 35 y. o., has been working at the factory for 5 years. She
complains of irradiated pains in the metacarpophalangeal joints, irradiat-
ing to the bones. Around formation is found. Your diagnosis:
A. De Quervain’s disease.
B. Notta’s disease.
C. Bursitis.
D. Arthritis.
E. Tendovaginitis
4. A man C., 42 y. o., an engrover, complains of a painless tumor in
the elbow joint, which is not grown with the skin. On X-Ray — an oval
softtissued contours by nut-size. Your diagnosis:
A. Bursitis.
B. Epicondylitis.
C. De Quervain’s disease.
D. Notta’s disease.
E. Arthritis.

240
KEYS
Chapter 1 Chapter 8
1. B 1. B
2. A 2. C
3. C 3. A
4. C 4. B
5. B 5. C
Chapter 2
Chapter 9
1. C
1. D
2. B
2. B
3. C
3. C
4. B
4. B
5. E
5. C
6. E
Chapter 3 Chapter 10
1. C 1. E
2. C 2. E
3. C 3. A
4. B
Chapter 4 5. B
1. C
2. B Chapter 11
3. D 1. C
4. C 2. D
5. D 3. D
Chapter 5 4. C
1. D 5. C
2. C
3. A Chapter 12
1. B
Chapter 6 2. D
1. B 3. C
2. D 4. D
3. B 5. C
4. B
Chapter 7 Chapter 13
1. D 1. D
2. B 2. A
3. E 3. B
4. A 4. A

241
 REFERENCES

1. Артамонова В. Г. Профессиональные болезни : учебник —

3-е изд., перераб. и доп. / В. Г. Артамонова, Н. Н. Шаталов. —
М. : Медицина, 1996. — 432 с.
2. Вибрация, шум и здоровье человека / В. Г. Артамонова,
Н. Н. Шаталов ; под ред. Р. С. Орлова и В. Г. Артамоновой. —
Л., 1988.
3. Гольдельман А. Г. Силикотуберкулез как клиническая про-
блема / А. Г. Гольдельман, Д. М. Зислин. — Свердловск : Ураль-
ский ун-т, 1989. — 177 с.
4. Діагностика судинних порушень у хворих на вібраційну хво-
робу та їх лікування антагоністами кальцію : метод. рекомендації
/ упоряд. : І. Ф. Костюк, В. А. Капустник. — Харків, 1996. — 16 с.
5. Діагностика, лікування і профілактика структурно-функціо-
нальних змін кісткової тканини у робітників, що працюють при
підвищених вібраційних та статичних навантаженнях : метод.
рекомендації / упоряд. : О. М. Ігнатьєв, К. А. Ярмула ; Одес. держ.
мед. ун-т. — К. , 2006. — 37 с.
6. Пневмокониоз : патогенез и биологическая профилактика
/ Б. А. Капнельсон, О. Г. Алексеева, Л. И. Привалова, Е. В. Ползик.
— Екатеринбург : Ур.ОРАН, 1995. — 226 с.
7. Костюк І. Ф. Професійні хвороби : підручник. / І. Ф. Кос-
тюк, В. А. Капустник. — Харків : Основа, 1998. — 400 с.
8. Постанова Кабінету Міністрів України «Про затвердження
переліку професійних захворювань» від 08.11.00. № 1662
9. Профессиональные заболевания / под ред. Н. Ф. Измерова.
— М. : Медицина, 1996. — Т. 1. — 335 с.; Т. 2. — 480 с.
10. Профессиональные заболевания работников сельского хозяй-
ства / под ред. Ю. И. Кундиева, Е. П. Краснюк. — К. : Здоров’я,
1989. — 272 с.

242
 11. Кундієв Ю. І. Професійне здоров’я в Україні / Ю. І. Кундієв,
А. М. Нагорна. — К. : Авіценна, 2006. — 316 с.
12. Саакадзе В. П. Профессиональная бронхиальная астма
/ В. П. Саакадзе, С. А. Степанов. — Саратов : Саратовский ун-т,
1989. — 176 с.
13. Чернова С. Д. Хронический профессиональный бронхит
(пылевой, токсико-пылевой в сочетании с неблагоприятными
метеофакторами) : учеб. пособие / С. Д. Чернова. — Харьков :
Мед. академия последиплом. образования, 1999. — 13 с.
14. Moon R. E. The physiology of decompression illness / R. E. Moon,
R. D. Vann, P. B. Bennet // Sci. — 1995. — Vol. 273. — P. 70-77.
15. Jeyaratnam J. Acute pesticide poisoning: a major health prob-
lem / J. Jeyaratnam // World Health State Q. — 1990. — Vol. 43. —
P. 139-145.
16. Blain P. G. Aspects of pesticide toxicology / P. G. Blain // Ad-
verse Drug React Acute Poisoning Rev. — 1990. — Vol. 9. — P. 37-
68.
17. WHO (World Health Organization). Inorganic mercury. Envi-
ronmental Health Criteria 118. — Geneva, Switzerland : World Health
Organization, 1991.
18. Biological monitoring of environmental and occupational ex-
posure to mercury / S. Langworth, C. G. Elinder, C. J. Gothe, О. Ves-
terberg // Int. Arch. Occup. Environ. Health. — 1991. — Vol. 63. —
P. 161-167.
19. Task Force ACCP. Workshop on environmental and occupa-
tional asthma / K. Rosenman, M. Reilly, D. Kalinowsky // Chest. —
1990. — Vol. 98 (suppl). — 252 p.
20. Rosenman K. Silicosis in the 1990s / K. Rosenman, M. Reilly,
D. Kalinowsky // Chest. — 1997. — Vol. 11. — P. 779-786.
21. Silicosis and Silicate Disease Committee. Diseases associated
with exposure to silica and nonfibrous silicate minerals // Arch. Pathol.
Lat. Med. — 1988. — Vol. 112. — P. 673-720.
22. Tuberculosis / O. K. Asmolov, Yu. I. Bazhora, O. A. Baburina,
I. M. Smolska. — Odessa, 2005. — P. 190.
23. Taylor W. The vibration syndrome / W. Taylor. — L. : Aca-
demic, 1974.

243
 24. Goldman R. H. Lead poisoning in automobile radiator mecha-
nics / R. H. Goldman. // N Eng. J. Met. — 1987. — Vol. 317. —
P. 214-218.
25. Wallace L. Environmental exposure to benzene: an update
/ L. Wallace // Environ. Health Perspect. — 1996. — Vol. 104 (suppl 6).
— P. 1129-1136.
26. Snyder R. An overview of benzene metabolism / R. Snyder,
C. C. Hedii // Environ. Health Perspect. — 1996. — Vol. 104 (suppl 6).
— P. 1165-1171.
27. National Institute for Occupational Safety and Health. Crite-
ria for a recommended standard. Occupational noise exposure. Re-
vised criteria. — Washington : USDHHS, 1996.
28. Hanner P. Acute acoustic trauma. An emergency condition.
— ScandAudiol. — 1988. — Vol. 17. — P. 57-63.

244
 CONTENTS

PREFACE ................................................................................................ 5
INTRODUCTION TO OCCUPATIONAL DISEASES.......................... 8
The Place of Occupational Diseases
in the Training of General Physicians ...................................8
Historic Stages of Occupational Pathology Development.... 9
Classification of Occupational Hazards
and Dangers ...................................................................... 9
Classification of Occupational Diseases
(by etiological concept) .................................................. 10
Hygienic Classification of Labour .................................10
Estimation of Labour Conditions
and Labour Character .......................................................... 10
Prophylactic Medical Examination ................................ 11
Chapter 1. DUST BRONCHITIS AND OCCUPATIONAL
BRONCHIAL ASTHMA .................................................... 13
Dust Bronchitis.................................................................... 13
Occupational and Environmental Asthma .......................... 15
Definition of Occupational Asthma ...............................16
Types of Occupational Asthma ...................................... 17
Risk Factors for the Development
of Occupational Asthma .................................................19
Tests .......................................................................................23
Chapter 2. PNEUMOCONIOSIS.......................................................... 25
Silicosis ...............................................................................28
Workers at Risk for Silicosis .......................................... 28
Pathology ........................................................................ 30
Pathogenesis ...................................................................31
Radiology ........................................................................ 34
245
 Pulmonary Function........................................................ 36
Complications .................................................................37
Treatment ........................................................................ 39
Asbestos-Related Disease ...................................................40
Coal Workers’ Pneumoconiosis .......................................... 43
Tests .....................................................................................45
Chapter 3. AGRICULTURAL DUST-INDUCED
LUNG DISEASE .................................................................48
Agricultural Asthma ............................................................ 49
Exposures to Plant-Derived Material .............................49
Exposures to Animal-Derived Material .........................50
Irritants ............................................................................ 50
Pharmacologic Agents .................................................... 50
Occurrence ...................................................................... 51
Pathogenesis ...................................................................51
Clinical Features .............................................................52
Chronic Airway Disease .....................................................55
Occurrence ...................................................................... 55
Pathogenesis ...................................................................56
Clinical Features .............................................................56
Interstitial Lung Disease .....................................................57
Tests .....................................................................................58
Chapter 4. ACUTE TOXIC IRRITANTS.............................................60
Respiratory Tract Irritants ...................................................60
The Method of the Lung’s Response to Irritants ............ 60
Clinical Manifestations
of Respiratory Tract Irritation .............................................62
Tests .....................................................................................66
Chapter 5. CARBON MONOXIDE, METHEMOGLOBIN
FORMERS, HYDROGEN ARSENIDE .............................68
Carbon Monoxide ................................................................ 69
Sources and Exposure .....................................................69
Health Effects .................................................................70
Clinical Manifestations and Peculiarities
in Poisoning with Carbon Monoxide.............................. 75

246
 Treatment and Prophylaxis of Poisoning
with Carbon Monoxide ...................................................76
Poisoning with Methemoglobin Formers ............................ 77
Poisoning with Hydrogen Arsenide .................................... 79
Treatment and Prophylaxis of Poisoning
with Hydrogen Arsenide .................................................81
Tests .....................................................................................81
Chapter 6. ORGANIC SOLVENTS .....................................................82
Exposure .............................................................................. 83
Environmental Biologic Monitoring ...................................84
Toxicokinetics .....................................................................86
Worker Protection ...............................................................87
Effects on the Nervous System ...........................................87
Peripheral Nervous System ............................................ 88
Central Nervous System .................................................89
Neuropsychiatric Disability ............................................ 91
Benzene .............................................................................100
Human Exposure .......................................................... 101
Metabolism and Mechanisms of Injury ........................ 101
Exposure Monitoring .................................................... 103
Toxicity .........................................................................103
Tests ...................................................................................105
Chapter 7. INTOXICATION BY CHEMICAL POISONS
IN AGRICULTURE.......................................................... 107
Acute and Chronic Intoxications with Pesticides .............107
Classification of Pesticides ...........................................108
Occupational Exposure .................................................109
Organophosphate Insecticides ...................................... 110
N-Methyl Carbamates Insecticides ............................... 116
Organochlorine Insecticides ......................................... 117
Long-Term Health Effects or Poisonings
with Pesticides ................................................................... 119
Cancer ...........................................................................120
Neurotoxicity ................................................................ 121
Reproductive Toxicity and Male Reproduction ...........123
Female Reproductive Effects........................................ 123
Tests ...................................................................................124
247
Chapter 8. OCCUPATIONAL EXPOSURE
TO VIBRATION ...............................................................126
Terminology ...................................................................... 127
Classification of Vibration Disease ...................................128
Whole-Body Vibration .................................................128
Hand-Arm Vibration .....................................................128
Whole-Body Vibration ...................................................... 129
Hand-arm Vibration ...........................................................131
Medical Assessment .....................................................133
Hand-Arm Vibration Control........................................ 137
Tests ...................................................................................138
Chapter 9. DYSBARISM.................................................................... 141
Historical Perspective........................................................ 141
Alternobaric Exposures .....................................................142
Pathophysiology of Dysbarism .........................................144
Behavior of Gases During Compression
and Decompression .......................................................146
Cardiovascular and Pulmonary Effects
of Gas Embolization .....................................................148
Cardiopulmonary Effects of Diving .............................149
Nitrogen Narcosis
and High-Pressure Nervous Syndrome (HPNS) ...............151
Decompression Sickness ...................................................152
Clinical Manifestations.................................................153
Spinal Cord and Brain .................................................. 153
Pulmonary System ........................................................ 155
Osteoarticular System ...................................................155
Other Involved Systems ................................................ 160
Treatment and Prognosis .............................................. 161
Barotrauma ...................................................................... 163
Barotrauma of Descent ...............................................163
Barotrauma of Ascent .................................................164
Other Dysbaric Disorders ...........................................166
Medical Evaluation of Prospective Divers .................166
Tests .................................................................................170

248
Chapter 10. OCCUPATIONAL EXPOSURE TO NOISE .................. 172
Noise and Health .............................................................172
Acute Acoustic Trauma .............................................. 173
Chronic Hearing Loss .................................................175
Risk Factors ................................................................ 175
Mechanisms of Noise-Induced Hearing Loss ............ 177
Extra-auditory Effects of Noise .................................. 178
Pregnancy and Noise .................................................. 180
Clinical Evaluation of Hearing Impairment ...............181
Tests .................................................................................185
Chapter 11. INTOXICATION WITH SALTS
OF HEAVY METALS (LEAD, MERCURY,
MANGANESE) AND THEIR COMPOUNDS .............187
Intoxication with Lead and Its Compounds .................... 188
Pathogenesis of Lead Intoxication .............................193
Clinical Manifestations .............................................. 194
Poisoning with Organic Lead Compounds .................197
Intoxication with Mercury
and Its Inorganic Compounds.......................................... 203
Epidemiology.............................................................. 203
Mercury in the Food Chain ........................................ 204
Mercury Exposure from Dental Amalgams ...............205
Indices of Exposure .................................................... 206
Chelation Therapy ...................................................... 209
Intoxications with Manganese ........................................ 211
Pathogenesis ...............................................................212
Clinical Manifestations .............................................. 213
Diagnosis .................................................................... 214
Treatment .................................................................... 214
Expertise of Capacity for Work .................................. 215
Preventive Maintenance .............................................215
Tests .................................................................................216
Chapter 12. IONIZING RADIATION ................................................ 218
Nature and Properties of Ionizing Radiation .................. 218
Quantities and Units of Measure ................................ 219
Sources and Levels of Ionizing Radiation
in the Environment .....................................................220

249
 Nature and Types of Radiation Injuries .....................221
Effects of Radiation
at the Cellular Level Gene Mutation .......................... 221
The Acute Radiation Syndrome ...................................... 224
Carcinogenic Effects .......................................................225
Leukemia .................................................................... 225
Cancer of the Breast ...................................................226
Thyroid Gland .............................................................227
Radiation Accidents.................................................... 228
Tests .................................................................................230
Chapter 13. MUSCULOSKELETAL DISORDERS .......................... 232
Tests .................................................................................240
KEYS ...................................................................................................241
REFERENCES .................................................................................... 242

250
 Áiáëiîòåêà
ñòóäåíòà-ìåäèêà
Провідний редактор серії
В. М. Попов
Художнє оформлення серії
О. А. Шамшуріна

Навчальне видання

ІГНАТЬЄВ Олександр Михайлович

МАЦЕГОРА Ніна Анатоліївна
ЄРМОЛЕНКО Тетяна Олексіївна
ОПАРІНА Тамара Павлівна
ЯРМУЛА Костянтин Антонович
ВОРОХТА Юрій Миколайович

ПРОФЕСІЙНІ ХВОРОБИ
Навчальний посібник
Англійською мовою

Провідний редактор В. М. Попов

Редактор Р. В. Мерешко
Художній редактор О. А. Шамшуріна
Технічний редактор А. В. Попов
Коректор О. В. Титова
Поліграфічні роботи І. К. Каневський

Підп. до друку 27.03.2009. Формат 60х84/16.

Папір офсетний. Гарн. Таймс. Друк різографічний. Ум. друк. арк. 16,05.
Обл.-вид. арк. 24,00. Тираж 50. Зам. 1229.
Видано і надруковано Одеським державним медичним університетом.
65026, Одеса, Валіховський пров., 2.
Свідоцтво ДК № 668 від 13.11.2001.

251
 Ігнатьєв О. М. та ін.
Професійні хвороби : навч. посібник / О. М. Ігнатьєв,
Н. А. Мацегора, Т. О. Єрмоленко [та ін.]. — Одеса : Одес. держ.
мед. ун-т, 2008. — 252 с. — (Б-ка студента-медика). — Мова
англ.
ISBN 978-966-443-016-3

У навчальному посібнику викладено етіологію, епідеміологію,

патогенез професійних хвороб, класифікації, нові методи дослі-
дження, клінічні форми та прояви, диференційну діагностику, ус-
кладнення та лікування. Розглянуто питання профілактики, сучас-
ного лікування згідно з рекомендаціями Всесвітньої організації
охорони здоров’я, експертизи працездатності.
Викладений матеріал відповідає навчальній програмі з професій-
них хвороб для студентів медичних вузів IV рівня акредитації та ліка-
рів усіх фахів.
Рис. 2. Табл 18. Бібліогр. : 10 назв.
ББК 54.1,7я73

252