Preventing Adverse Health Effects From Nanotechnology CDC
Preventing Adverse Health Effects From Nanotechnology CDC
Preventing Adverse Health Effects From Nanotechnology CDC
m
1
m
GOLD
Each side=1 M
Mass43,000 lb
Surface Area (SA)=6 m
2
8 ft x 8 ft room
Each side=1/4 M
Mass43,000 lb
SA=24 m
2
Each side=1 nM
Mass43,000 lb
SA=6 billion m
2
2500 miles
2
State of Delaware= 2490 miles
2
10
What Could a Nanoparticle Be?
Dr. A . Maynard: Woodrow Wilson International Center for Scholars
11
Same CompositionDifferent Shape
Zinc Oxide Nanoparticles
Materials Today J une 2004. Zhong Lin Wang, Georgia Institute of Technology
12
13
What is nanotechnology
Applications of nanotechnology
Concern about health and safety effects of nanoparticles
NANOTECHNOLOGY:
THE THI RD I NDUSTRI AL REVOLUTI ON
Why is Nanotechnology of Great Interest?
Imparts useful properties to materials
Stronger
Lighter
More durable
Different melting temperatures
Enhanced electrical conductivity
More transistors on integrated chip
Enhanced chemical reactivity
14
All of these point to the possibility of creating
new and very powerful applications
Potential Revolution in Manufacturing
See and manipulate
one atom at a time
building molecular
tools
Using 35 Xenon atoms
to spell out a logo
Copy nature mimic
self replication
15
Source: IBM Research
Applications of Nanotechnology
Agriculture More efficient, targeted delivery of plant nutrients, pesticides
Automotive Lighter, stronger, self-healing materials
Biomedical
Targeted therapeutics, enhanced detection, new structural
materials
Energy More efficient fuel cells, solar collectors
Environmental New pollution control and remediation tools, sensors
Food New safety sensors, food preservatives, nutrient additives
Materials
Self-cleaning glass, stain resistant, stronger materials, body
armor
Water New purification approaches
16
Early Nano-enabled Consumer Products
Are on the Market Now
Wilson Double
Core tennis balls
Eddie Bauer
Ruston Fit Nano-
Care khakis
3M Adper Single
Bond Plus
dental adhesive
Mercedes
CLS-class
Samsung Nano
SilverSeal Refrigerator
Wyeth Rapamune
immuno-suppressant
Provided by Larry Gibbs, Stanford University, 2006
17
Nanoparticulate fuel additives
= 10% better fuel economy
Nanocomposite body moldings
= 20% lighter
Nanoscale
catalysts
= 20%
reduction in
emissions
Gibbs,
18
Source: Burnham Institute
Nanotechnology and Health:
Turning Fiction to Reality
Potential for
Disease sensing
Diagnosis
Targeted therapy
Science Fact Cancer Treatment
19
20
What is nanotechnology
Applications of nanotechnology
Concern about health and safety effects of nanoparticles
NANOTECHNOLOGY:
THE THI RD I NDUSTRI AL REVOLUTI ON
Basis for Concern about Health and Safety Effects of
Nanoparticles
Findings from air pollution epidemiology
Particles < 2.5 m associated with respiratory and cardiovascular
effects
Studies of industrial fumes (e.g., welding fumes) and
combustion (e.g., diesel) products
Wide range of effects: pulmonary and eye irritation, fever, lung cancer
Initial animal inhalation studies of engineered
nanomaterials
Pulmonary fibrosis, granulomas, and inflammation
Lung cancer, mesothelioma-like effects
Cardiovascular effects: oxidative stress, plaque
21
Nanomaterials have been shown to
Translocate from nose to brain
Translocate from lungs to most organ systems
Have potential for skin penetration
Basis for Concern about Health and
Safety Effects of Nanoparticles
(cont)
22
Major Knowledge Gaps Related to Nanotechnology
Health and Safety
Risk Management
Develop procedures to minimize exposures
Risk Characterization
Is substance hazardous and will there be exposure?
Exposure Assessment
Will there be exposure in real-world conditions?
Hazard Identification
Is there reason to believe this could be harmful?
Approaches to Safe Nanotechnology (DHHS (NIOSH) Publication 2009-125)
23
24
http://www.cdc.gov/niosh/topics/nanotech
Hazard Identification Gaps
What are the hazards of the major types of nanoparticles?
NIOSH: Identified pulmonary fibrosis and atherosclerosis
What are the mechanisms of action?
NIOSH: Demonstrated that the formation of highly reactive oxygen
compounds cause tissue damage
25
Exposure Assessment Gaps
What exposures are occurring now?
To workers, consumers, and the environment
How should exposure be measured and what metrics
(mass, surface area, particle count) should be used?
NIOSH has conducted field assessments at 26
worksites and demonstrated exposure to nanoparticles
26
Risk Characterization Gaps
Can animal data accurately predict human risk?
Value of short-term tests
NIOSH: Conducted risk assessments on titanium dioxide and
carbon nanotubes
27
What are the risks for
various population
exposed to
nanomaterials?
Identify cohorts at risk
Value of exposure registries
Risk Management Gaps
What are the limits of controls?
NIOSH: Defined exposure limits to
titanium dioxide
What exposure limits can be
recommended for individual and
categories of nanoparticles?
What medical surveillance is
appropriate for people exposed
to nanomaterials?
NIOSH: Developed various guidance
documents
28
29
Women cotton thread workers, circa 1890
Potential: Great Societal Benefit
Challenge: Responsible Development
PUBLI C HEALTH APPLI CATI ONS OF
NANOTECHNOLOGY
30
Mark D. Hoover, PhD, CHP, CIH
Senior Research Scientist
National Institute for Occupational Safety and Health
Applications span a broad spectrum
Prevention of disease or injury
Medical diagnosis and treatment
Reducing environmental and energy impact
A compendium of nanotechnology products and
applications can be found at
http://www.nanotechproject.org/inventories
31
PUBLI C HEALTH APPLI CATI ONS OF
NANOTECHNOLOGY
Personal water purification
32
Prevention of Disease or Injury
Industrial water purification
Lifestraw Lifesaver water bottle
Liquid
condoms
Prevention of STDs
Nano-enabled
systems
Contamination control
Anti-microbial
surface
treatments
33
Medical Diagnosis and Treatment
Laboratory diagnostic testing
Home diagnostic testing
Nano chip technologies
Magnetic nanoparticle cell sorters Gold nanoparticle protein binding
Micro-array diagnostics
Bone
repair
media
Nano
scaffolds
Functional coatings
34
Reducing Environmental and Energy Impact
Energy conservation
Electronics
Nano-formulated
insulation
Light-emitting diodes
Inert or
activated
surfaces
Self-cleaning glass
Nano-enhanced UV and rain actions
An Instructive Applications Example:
Nanotechnology in the Food Industry
35
Weiss et al., J Food Science, 71(9): R107-R116, 2006.
Applications span a broad spectrum
Prevention of disease or injury
Medical diagnosis and treatment
Reducing environmental and energy impact
Opportunities
Understand the scope of potential applications
Foster the matching of priority public health concerns with
development and application of efficient and cost-effective
nano-enhanced solutions
36
Enhancing the Future for Public Health
Applications of Nanotechnology
Sally S. Tinkle, Ph.D.
Senior Science Advisor
National Institute of Environmental Health Sciences
National Institutes of Health
NI H: HARNESSI NG THE POWER OF
NANOTECHNOLOGY FOR HUMAN HEALTH
37
Science in Pursuit of
Fundamental knowledge about the nature and
behavior of living systems
Application of that knowledge to prevent, detect,
diagnose, and treat disease and disability
= Extramural only
NEI
NCI
NHLBI
NLM
NINDS
NIMH
NIAMS
NINR
NCCAM
CIT
CC
NHGRI
NIA
NIAAA
NIAID
NICHD
NIDCD
NIDCR
NIDDK
NIDA
OD
NIGMS
NCRR
NIBIB
NCMHD
FIC
CSR
National Institutes of Health
NIEHS
38
Nanotechnology Enables New Biomedical Solutions
Therapeutics
Intervention
Cellular and
Organ System Function
Diagnosis Early
Detection
39
M
i
l
l
i
o
n
s
o
f
D
o
l
l
a
r
s
FY 2001 2002 2003 2004 2005 2006 2007 2008 2009
$M 4.4 7.9 7.3 11.9 16.3 17.2 19.5 31.1
SBIR/STTR
Actual
NNI
Begins
NIH Nanotechnology Funding
ARRA
Slide courtesy of J effery Schloss, NHGRI, NIH
NNI, National Nanotechnology Initiative
40
NIEHS Nanotechnology Health and Safety Initiative
Goal
Determine of the relationship between the physical and chemical
properties of engineered nanomaterials and biological response
Identify nanomaterial design principles that maximize benefit and
minimize risk to humans and the environment
Research Components
Material characterization
Physiological response
Pathobiological response
Informatics / predictive models
Training
41
Challenge: Develop reliable and reproducible methods to assess
exposure and biological response/toxicological endpoints
Challenge: Understand more precisely how chemical composition
and structural arrangements of dictate biological interaction
NIEHS Extramural Research Programs
42
NIBIBNIEHSNCINanoInformaticsCollaboration
Need: Create publically available ontology and
interoperability framework between existing nanomaterials
databases
Mechanism: Four year contract
NIEHS-NCI NanoStructural Biology Collaboration
Need: Create database of structural attributes of
nanomaterials and their relationship to biology
Mechanism: Task order, annual renewal
NIBIB-NIEHS-NCI NanoInformatics Collaboration
NCI
NIBIB
NIEHS
NCI
NIEHS
43
Inter-Institute Collaborations
NIBIB, National Institute of Biomedical Imaging and Bioengineering
NIEHS, National Institute of Environmental Health Sciences
NCI, National Cancer Institute
National Toxicology Program
Cadmium based quantum dots
Role of skin integrity on pharmacokinetic studies after
dermal exposure
Titanium dioxides: Dermal pharmacokinetics
Impact of coatings and crystal state
Carbon based fullerenes: Pulmonary and oral toxicity
Impact of size of C60 aggregates
Multiwalled carbon nanotubes
Influence of length and diameter on pulmonary toxicity
Ceric oxide
Role of particle size on pulmonary toxicity
Nanosilver
Role of particle size and shape on PK and toxicity
44
Expand the applications of nanotechnology to solve
critical biomedical research questions
Extend NIH presence in the global nanotechnology
research community
Enlarge the health and safety portfolio to identify the
basic design principles to engineer nanomaterials
for maximum benefit to society with minimal risk of
unintended consequences
Next Steps for NIH
45
46
HAZARD ASSESSMENT OF NANOMATERI ALS:
WHY I S I T SO CHALLENGI NG?
Vincent Castranova, PhD
Branch Chief
Pathology and Physiology Research Branch
Health Effects Laboratory Division
National Institute for Occupational Safety and Health
47
Nanoparticles exhibit unique physiochemical properties
distinct from fine (micrometer size) particles of the
same composition
Unique properties
Yield unique applications
Make unique bioactivity likely
Yet, nanoparticles are currently regulated by
OSHA and EPA under standards for the fine analogue
Example: Carbon nanotubes are currently regulated as fine graphite
Hazard Assessment (Evaluation of Bioactivity) Is
Essential for Nanoparticles
EPA, Environmental Protection Agency
National Nanotechnology Initiative
http://www.nano.gov
48
NNI Research Priorities for
Nanomaterials and Their Effects on Human Health
Develop and validate animal models to
Quantify dose-response
Determine the relationship between physical and chemical
properties of nanoparticles and their bioactivity
Develop high throughput, predictive, in vitro tests to
evaluate nanoparticle bioactivity
Ultimately, extrapolate data to responses of humans
to nanoparticle exposure
49
50
1. Hazard Assessment Issues:
Animal Models
Determine responses to nanoparticles via different routes
of exposure (pulmonary, dermal, oral, intravenous)
Evaluate responses at site of exposure and distal sites
Evaluate the relationship between responses to
short-term vs long-term exposures
Evaluate responses to well-characterized sets of
nanoparticles
Characterize nanoparticles both as produced and as
delivered to the test system
Example: Issue of agglomeration in physiological saline and that
agglomeration decreases the bioactivity of nanoparticles
2. Hazard Assessment Issues:
In Vitro Tests
Use appropriate in vitro tests
Must know mechanisms of action for each nanoparticle
Damage resulting from generation of reactive products
Altered cell division resulting in abnormal (mutated) cells
Use doses relevant to those used in animal models
(g/surface area of exposed cells)
Technical challenges
Interference of nanoparticles with assay indicator chemicals
Adsorption of nutrients from the assay medium
51
3. Hazard Assessment Issues:
Extrapolation to Humans
Use doses relevant to human exposures
Need human exposure data
Translate exposure dose to surface area of target tissue in
humans (an example for lung exposure: g/alveolar surface area)
Use structure sizes relevant to human exposures
Identify nanoparticle structure size distribution in workplace air
Nanoparticles agglomerate in physiological saline
Need to develop biocompatible dispersants, which do not mask
surface reactivity (diluted alveolar lining fluid), to obtain
appropriate structure size distributions
52
NIOSH Hazard Assessment Research Priorities
Studying carbon black, single-walled carbon nanotubes
(SWCNT), multi-walled carbon nanotubes (MWCNT),
TiO
2
spheres and wires, silicon nanowires, silver, nickel,
quantum dots, ZnO, WC-Co, etc
Evaluating
Exposure routes: pulmonary and dermal
Biological endpoints: pulmonary, cardiovascular, CNS, and dermal
Determining the relationship between given
physicochemical properties of a nanoparticle and its
bioactivity
Developing in vitro screening tests for rapid prediction
of the bioactivity of a given nanoparticle
53
TiO2, titanium dioxide
ZnO, zinc oxide
WC-Co, tungsten carbide/cobalt
NIOSH Hazard Assessment Research
Key Accomplishments
Pulmonary exposure to
Carbon nanotubes cause rapid and persistent fibrosis in mice
Certain nanoparticles (SWCNT or TiO
2
) can cause cardiovascular
dysfunction
MWCNT or TiO
2
nanowires can induce inflammatory mediators in
certain regions of the brain
Carbon nanotubes
Multi-walled nanotubes can reach the intrapleural space
(site of mesotheliomia)
Single-walled nanotubes can interfere with cell division
54
SWCNT, single-walled carbon nanotubes
MWCNT, multi-walled carbon nanotubes
TiO
2
, titanium dioxide
NANOTECHNOLOGY AT GEORGI A TECH:
FORGI NG THE SMALL
William D. Hunt, PhD
Professor
School of Electrical and Computer Engineering
Georgia Institute of Technology
DISCLOSURE: Professor W. D. Hunt is the Chief Technical Officer
and has 1/3 ownership in Zen Sensing, LLC
56
Develop new types of devices and systems with
nanotechnology components
Collaborate with Emory Medical School and CDC
Vital importance of complementary set of skills and practical and
translation of science to practice
Move the technology developments to the marketplace
Guide students and post-docs to a career in
nanotechnology
Importance of student education related to ethics and safety
Overarching Nanotechnology Goals
at Georgia Tech
Nanotechnology Research Centers at Georgia Tech
Georgia Tech is a NNIN member
Housed in the Marcus Nanotechnology
Research Center
The Nanotechnology Center for
Personalized and Predictive
Oncology
Lead S. Nie; Funding NCI/NIH
The Nanomedicine Development
Center
Lead G. Bao; Funding NIH Roadmap
Initiative in Nanomedicine
The Program of Excellence in
Nanotechnology
Lead G. Bao; Funding NHLBI/NIH
NNIN, National Nanotechnology Infrastructure Network
NCI, National Cancer Institute, NIH
NHLB, National Heart, Lung and Blood Institute, NIH
Nanomedicine Research Projects at Georgia Tech
Bioconjugated nanoparticle probes for molecular
and cellular imaging (S. Nie)
Blood analysis by nanophontonic near infrared
spectroscopy (A. Adibi)
Fluorescent RNA probes (Molecular Beacons) for in
vivo analysis (G. Bao)
ZnO nanobelts for energy harvesting for implants
(Z.L. Wang)
Nanofluidics for sample handling for DNA analysis
(P. Kohl)
Biohazard Water Analyzer and Detector Using
Carbon Nanofiber Arrays
Principle
Carbon nanofiber-DNA conjugates and billions of nanofibers on a chip
Application Biohazard water analyzer
Measures the total and viable cell concentrations
Detects common and rare pathogens associated with waterborne
illnesses - E. coli O157:H7, Cryptosporidium and Giardia species
Bruce Gale, University of Utah, Alan Cassell, NASA Ames Research Center
Neil Gordon, Early Warning Inc., Devin Brown, Georgia Tech
Biosensor chip Biohazard analyzer system Carbon nanofiber
Biomolecular Recognition Using a Digital Radio
Professor William D. Hunt, School of Electrical and Computer Engineering
Georgia Institute of Technology
Principle
Detecting conformational change,
a critical aspect of almost all
biomolecular interactions,
in vapor phase using a nanoscale
hydrogel
Differentiation between
close chemical analogs,
indistinguishable by mass
spectrometry: small
molecules(~300 Daltons), lipids,
proteins, DNA, cells
Application Real-time analysis of exhaled breath
Detection of methylated DNA, phosphorylated proteins
Background Photo
Courtesy of National Science Foundation
Roberta Berry, JD, PhD
Assoc. Prof. of Public Policy
Principal Investigator
Kathy Kinlaw, MDiv
Assoc. Dir., Emory Center for
Ethics Principal Investigator
Wendy Newstetter, PhD
Dir. of Learning Sciences
Research, Dept. of Biomedical
Engineering Co-Principal
Investigator
Robert Kirkman, PhD
Assoc. Prof. of Public Policy
Dir., Center for Ethics &
TechnologyCo-Principal
Investigator
Edward Queen, PhD, JD
Dir., Ethics and Servant Leadership
Emory Center for Ethics
Co-Principal Investigator
Gillian Hue, PhD
Fellow, Emory Center for Ethics,
Program in Science and Society
Senior Personnel
Leslie Wolf, JD, MPH
Assoc. Prof. of Law
Principal Investigator
Martha Elks, MD, PhD
Assoc. Dean for Med. Ed.
Prof. and Chair of Med. Ed.
Principal Investigator
Ethically Contentious
Research and Innovation:
62
GLOBAL EFFORTS TO PREVENT
OCCUPATI ONAL HAZARDS FROM
NANOTECHNOLOGY
Kristen M. Kulinowski, PhD
Executive Director, Center for Biological and Environmental
Nanotechnology
Director, International Council on Nanotechnology
Faculty Fellow in Chemistry
Rice University
IMAGE CREDITS: Rice University, NIOSH
63
Gaps
Greater knowledge base on hazard than exposure
Occupationally-relevant research is almost non-existent
No quantitative exposure limits to inform occupational practice
GLOBAL EFFORTS TO PREVENT HUMAN
HEALTH HAZARDS FROM
NANOTECHNOLOGY
RESULT
Research knowledge base
has little practical application to human health
64
Progress to Bridge the Gaps
Government: Guidance documents and first regulatory decisions
International bodies: Standards and outreach to emerging economies
Grassroots and consortia: Research protocols and practical tool
GLOBAL EFFORTS TO PREVENT HUMAN
HEALTH HAZARDS FROM
NANOTECHNOLOGY
RESULT
Lots of activity, little high level coordination
Bringing It All Together
Occupationally Relevant Research is Lagging
65
SOURCE: ICON Virtual J ournal of Nano Environment, Health and Safety http://icon.rice.edu/research.cfm
All , All published research relating to the potential environmental, health and safety effects of nanomaterials
Occupational Health , e.g., efficacy of gloves, respirators; workplace exposure assessment
Less than 6% of all nano impacts research is of high occupational relevance
0
100
200
300
400
500
600
700
800
2001 2002 2003 2004 2005 2006 2007 2008 2009
Peer Reviewed Nano Environment, Health and Safety Journal
Articles
Exposure Hazard All Occupational
Stakeholders Seek Information
about Good Practice
Surveyed organizations reported that they
believe there are special risks related to the
nanomaterials they work withand that they
are actively seeking additional
information on how to best handle
nanomaterials.
Comprehensive, international survey
of handling practices in the
nanotech workplace
66
SOURCE: http://tinyurl.com/iconsurvey
Survey respondents were nanomaterial manufacturers, users and researchers in industry, academia and
independent and government labs from North America, Europe, Asia and Australia.
Government Guidance Documents
67
NIOSH
IRSST
BAuA
UK HSE
METI
JNIOSH
Safe Work
Australia
IRSST, Institut de recherche Robert-Sauv en sant et en scurit du travail
BAuA, (German) Federal Institute for Occupational Safety and Health
HSE, Health and Safety Executive
METI, Ministry of Economy, Trade and Industry (J apan)
NIOSH, J apan National Institute for Occupational Safety and Health
Regulatory Developments of Note in
the United States
Toxic Substances Control Act (TSCA)
Manufacturers have registered dozens of nanoscale materials under
TSCA
Special rules issued for carbon nanotubes
Recognize nanotubes as new substances
Require use of protective measures in the workplace
Federal Insecticide, Fungicide and Rodenticide Act
(FIFRA)
Companies fined for failing to register nanoscale products making
antimicrobial claims
68
Regulatory Developments of Note in Europe
69
REACH = Registration, Evaluation, Authorization and
Restriction of Chemical Substances
Low-volume registration thresholds
Manufacturers required to provide toxicity information
Extends to existing as well as new chemicals
European Parliament
Calling for nano label to inform consumers about nano ingredients
Global Activities of Established International Bodies
Organization for Economic Cooperation and Development
INTERGOVERNMENTAL GROUP
Safety testing on representative set of nanomaterials; development of test
guidelines for assessing nanomaterial toxicity
Primarily government officials
ISO/TC 229 Nanotechnologies: VOLUNTARY STANDARDS
Developing consensus standards for terminology, characterization, and
health & safety
technical Report on health & safety practices in occupational settings
Multi-stakeholder: government, industry, legal, academic, non-governmental
World Health Organization: NON-GOVERNMENTAL
Collaborating Centers developing information on hazards, risks, and controls
Doing outreach to emerging countries on safe handling of nanomaterials
Non-governmental but partners with government
70
Grassroots Groups and Consortia
GoodNanoGuide*:
http://www.goodnanoguide.org
Online resource for developing and sharing safe handling protocols
International Alliance for NanoEHS Harmonization*
http://www.nanoehsalliance.org
Grassroots effort by research scientists to develop validated toxicity protocols
NanoImpactNet* (EU)
http://www.nanoimpactnet.eu
Coordinating test strategies, screening tools and risk assessment methodologies
NanoRisk Framework
http://www.nanoriskframework.com
Risk management framework developed by DuPont and Environmental Defense Fund
71
*Significant NIOSH participation or sponsorship
International Council on Nanotechnology
INCLUSIVE: Multi-stakeholder cooperation GLOBAL: International perspective
PROACTIVE: Stewards for sustainability TECHNICAL: Grounded in science
Developing and communicating information regarding
potential environmental and health risks of nanotechnology
to foster risk reduction and maximize societal benefit.
http://icon.rice.edu
72
Survey Reports Backgrounders
Knowledge Base
ICON is a Valuable Source of Credible Information
73
http://icon.rice.edu
Bringing It All Together
National
nanotech
partnership
Manufacturers
and users
Researchers
Health and
safety
practitioners
74
Focused research of high
occupational relevance
Risk control strategies able
to be implemented now
Outreach and training for workers, researchers, and occupational professionals
Howard and Murashov, J Nano Particle Res (2009) 11:16731683
75 75
PUBLI C HEALTH GRAND ROUNDS
Apr i l 15, 2010