TOXICOLOGY

Group 1:

Chan, Aylmer Jason

Cheng, Leonard
Dimaano, Ron Michael
Hilario, Apolonio, Jr.
Pescones, Kristofil

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Introduction

• The study of the adverse effects of chemicals on living

organisms

• Concerned mainly with the toxic or poisonous properties

of chemical substances

• Among the most multidisciplinary of sciences

• The science of poisons

• Assesses the probability of hazards

• Deal with adverse effects ranging from acute to long-

term
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Factors that contribute to toxicity:

• Route of entry

• Dosage level

• Physiological state of the receiver

• Environmental conditions

• Physical properties of the chemical

• Chemical properties of the chemical

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Toxicology

• Acute and chronic effects

• Air-contaminate exposure

• Neoplasms

• Permissible exposure limits

• Threshold limit values

• Biological exposure indices

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Route of Entry

•Inhalation

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Inhalation

• The upper respiratory

tract is the first
passageway of air.
• Removes half of
particles that are 2
micrometers in
diamater; half are
removed by the
alveolar air spaces.

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Inhalation

• Alveolar sacs 
capillary walls 
tissue cells
• Due to higher
concentration of
oxygen in alveolar
sacs than from the
blood coming to the
lungs from right
ventricle.

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Inhalation

• Artery (w/ oxygen) 

capillary tissue cells

• Tissue cells  vein

(Carbon dioxide)

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Inhalation

Type and quantity of

chemical depend on:
• Concentration in air
• Exposure duration
• Pulmonary ventilation
volumes
• Lower water solubility
and higher fat
solubility

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Absorption through the skin

Outcomes
• Skin may block entry
into body
• Causes skin irritation
• Produce skin
sensitization
• Penetrate the skin and
enter the bloodstream.

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Absorption through the skin

• Epidermis – 0.5-4 mm
• Dermis – 15 to 40
times thicker than
epidermis.
• Blood vessels, nerve
fibers, hair follicles and
sweat glands are located
in the dermis.
• Subcutaneous layer –
contains fatty elements
that serves as cushion
and insulator.

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Absorption through the skin

• Skin regulates body

temperature through
sweating.
• High humidity = low
evaporation rates of
sweat
• Skin absorption rate is
proportional to
temperature and
perspiration rate.

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Aids in absorption of
chemicals

Abrasion

Laceration

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Absorption through the skin

 Comparison between a
laceration and a
puncture

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Factors considered in the ability to be
absorbed

• Aqueous and lipid solubilities

• Extent of ionization of water
• Soze of the molecule
• pH of the skin
• Concentration of the hair follicles in the skin

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Ingestion

• It is less frequent to
happen than
contamination
through skin
absorption or
inhalation.
• Contaminates via
hand-to-mouth
contact

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Ingestion

• One should never eat

lunch in the
contaminated areas!
• Saliva or respiratory
tract mucus from
another person who
inhaled chemicals can
contaminate an
individual when
swallowed.

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Injection

• Very rare in workplace

• Sometimes used in
laboratory animal
studies for far cheaper
cost.
• It bypasses the
protections that
prevent chemicals from
entering the body

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Dose-response Relationship

• Difference between Concentration and Dose

– Concentration – the quantity of a substance that
is exposed externally to a biological system.
– Dose – the quantity of a substance that enters
into the biological system.
• Dose-response relationship
• How do they test?

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Dose-response Relationship

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Dose-response Relationship

• Linear
• Not all exposures (low-level) to most chemicals are
harmful
• Length of exposure time is also considered:
– HIGH concentration, LOW time period = LOW
concentration, HIGH time period

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Dose-response Relationship

• Response (Animal organs)

– Liver: ingested chemicals; they are processed,
transformed/stored, then to the bloodstream
– Kidney: inhalation, skin absorption, and
injection: excrete (separate then eliminate)
– Bones: toxic chemicals like lead and strontium

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Dose-response Relationship

• Poison: Rate of intake > Rate of detoxification

– Bigger doses at on time
– Smaller doses at multiple times (BETTER!!!)
• Inhalation exposures of airborne chemicals are
expressed in Lethal Concentration (LC)
• Unit: ppm (Parts per million)

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Toxicodynamics

• Effects of poison to the body

• Classification
– Exposure
•Acute
•Chronic
– Physiological

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Acute Effects

• Short-term exposure
• Large dose
• More severe
• Reversible

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Chronic Effects

• Long-term exposure
• Small dose
• Less severe
• Irreversible

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Physiological Effects

• Irritant
– Causes inflammation
of the skin and
mucous membranes
(skin, eyes, nose, or
respiratory system).

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Physiological Effects

• Corrosive
– A material that can
destroy human tissue.
Includes both acids
and bases and may be
a solid liquid or gas.

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Physiological Effects

• Asphyxiant
– A material that deprives
tissue of oxygen and causes
suffocation by displacing
oxygen or interfering
chemically with oxygen
absorption, transport or
utilization.

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Physiological Effects

• Narcotics
– Depresses the
response of the
nervous system
– Some examples
are alcohol

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Physiological Effects

• Hepatotoxin
– Substances that causes liver damage

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Physiological Effects

• Nephrotoxin
– Substances that cause damage to the kidneys

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Physiological Effects

• Carcinogen
– A material which can
cause cancer. Example:
asbestos, Bis-
chloromethyl ether,
benzene, acrylonitrile

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Permissible Exposure Limits

• Adopted by OSHA (1970), Occupational Safety

and Health Administration, for industrial
chemical exposure
• Based upon the Threshold Limit Values of the
American Conference of Governmental
Industrial Hygienists (ACGIH).
– Data based mainly on industrial experience
and animal inhalation studies

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Permissible Exposure Limits

• OSHA requires the employer to initiate certain

safety provisions if the action level is
exceeded.
– One half of PEL
• Examples would be:
– Employee exposure measurement
– Employee training
– Medical surveillance
• Minimum expense and protection

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Permissible Exposure Limits

• Laboratory animal studies are important in

determining chemical toxicity
• But acute toxicity data is not very reliable
because
– Certain animal species are more sensitive to
a chemical than others.
– Animal response may not be necessarily
parallel the human response as the dosage
level is varied.

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Permissible Exposure Limits

• ACGIH uses all toxicity information sources

available in setting TLVs.
• Many common chemicals have sufficient
historic human exposure data.
• OSHA responds quickly to TLV changes by the
ACGIH.
• Adjusts PEL to reflect TLV change.

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THRESHOLD LIMIT VALUES

• The TLV of a chemical substance defines the

reasonable level to which a worker can be exposed
without adverse health effects.
• The volume occupied by a given weight of a gas
depends upon the gas’s molecular weight.

mg ppm(molwt )
=
m ^3 24.5
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THRESHOLD LIMIT VALUES

• Three TLV categories

• 1. Threshold limit value, time-weighted average
(TLV-TWA)
– Time-weighted average concentration for a
normal 8-hour workday and a 40-hour work
week.
– Nearly all workers may be repeatedly exposed

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THRESHOLD LIMIT VALUES

∑ tiCi
TLV − TWA = i −1
n

∑ ti
i =1
Where
TLV-TWA = threshold value, time-weighted average
(ppm)
ti = exposure time at concentration i (h)
Ci = concentration of chemical (ppm)
n = total time periods

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THRESHOLD LIMIT VALUES

• 2. Threshold limit value, short-term-exposure limit

(TLV-STEL)

– Concentration to which workers can be exposed

continuously for a short period of time without
experiencing negative effects, and without
exceeding TLV-TWA.

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THRESHOLD LIMIT VALUES

• STEL – defined as a 15-minute TWA exposure

that should not be exceeded at anytime during a
workday. Less than 4 times/day

∑ tiCi
TLV − STEL = i −1

0.25
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THRESHOLD LIMIT VALUES

• 3. Threshold limit value, ceiling (TLV-C)

– Concentration should not be exceeded during
any part of the working exposure.

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THRESHOLD LIMIT VALUES

• TLV-TWA and TLV-C are more commonly used than TLV-

STEL
• TLV serves as guidelines to assist in the control of health
hazards.
• Should not be used as precise legal standards, but can
be useful in developing health and safety programs.
• OSHA has placed considerable reliance on the TLVs.

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THRESHOLD LIMIT VALUES

• Notice of Intended Changes by ACGIH

• TLV allows higher concentration levels provided
that elevated levels are offset by periods of lower
concentration.
• TLVs are measured in the workplace (breathing
zone)
– Contaminations of air as well as changing
conditions of work environment are avoided.

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THRESHOLD LIMIT VALUES

• Combined effect must be considered.

n
Ci
TLVmix = ∑
i = 1 TLVi
• Where
Ci = observed ambient concentration (ppm)
TLVi = corresponding threshold limit (ppm)
If the sum exceeds unity, the mixture threshold limit of the mixture has
been exceeded.

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THRESHOLD LIMIT VALUES
• Odor Thresholds for Chemical substances that are greater than the Chemical TLV
(*ACGIH intends to reduce further)
Chemical Odor Threshold (ppm) Inhalation TLV-TWA (ppm)

Benzene 100 10*

Carbon monoxide - 25

Carbon tetrachloride 79 5 skin

Chlorine 5 0.5

Chlorobromomethane 400 200

Chloroform 200 10

Epichlorohydrin 10 2* skin

Ethylene oxide 300 1

Isopropyl amine 10 5

Methanol 2000 200 skin

Methylene chloride 300 50

Nitromethane 200 20

Propylene oxide 200 20

Toluene-2, 4-disocyanate 0.4 0.005

Turpentine 200 100

Vinyl chloride 4100 5

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THRESHOLD LIMIT VALUES

• There are assumed no synergistic or antagonistic

effects of the combination of substances present.
• Heat, ultraviolet light, ionizing radiation, elevated
pressure, and high altitudes may cause additional
body stress and could alter the effects of chemical
exposure.

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THRESHOLD LIMIT VALUES

• Analysis of biological samples from humans who

have been exposed to toxic agents is useful in
assessing occupational exposure to hazardous
substance.
• Amount of toxin can be determined from blood,
urine and breath samples.
Urine – heavy metals
Blood – heavy metals and carbon dioxide
Breath - organics

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THRESHOLD LIMIT VALUES

• Observed effects may not occur for extended periods

of time.
• Substances can be stored in target organs for
extended periods of time before an equilibrium is
established within body systems.
• Body converts many toxic organic compounds to less
harmful metabolites.
• Inhaled gases and vapors are not converted but
exhaled from the body.

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Prevention

• Safety provisions
– Employee exposure measurement
– Employee training
– Medical surveillance

• Laboratory animal studies

• Threshold limit values

• Analysis of biological samples

• Biological exposure indices

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Preventive measures

• implementing a work/rest regimen matched to the severity of

the workers' heat exposure

• making drinking water and salt readily available to replace the

water and salt lost by sweating

• making protective clothing available to workers as appropriate

• reducing environmental heat by engineering controls

• monitoring environmental heat at the job site

• performing preemployment and periodic medical examinations

to define those at increased risk
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References

• Craigmill, Arthur L., “Extension Toxicologist Cooperative Extension

University of California Environmental Toxicology Newsletter

• Farcett, H.H, Hazardous and Toxic Materials, Wiley New York, 1984

• Gallant, R. W., “Highly Toxic Liquids: Teaching Operators to Handle

Them,” Chemical Engineering, April 1990, pp. 116-120.

• Grossel, S. S., “Highly Toxic Liquids: Moving tThem Around the Plant,”
Chemical Engineering, April 1990, pp. 110-115.

• Ottoboni, M. A., The Dose Makes the Poison, Vincente Books, Berkeley,
Calif., 1984.

• Osha, Occupational Exposures to Hazardous Chemicals in Laboratories,

Federal Register, 55, no. 21 (30 January, 1990): 3300-3335. Microfiche.

• Plog, B. A., et al., Fundamentals of Industrial Hygiene, National Safety

Council, Itasca, Ill., 1988.