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STRUCTURE OF THE TALK
- Exposure Assessment approaches
- Hazard Assessment approaches
- Risk Assessment Approach
– Derivation of Control Limit
- Risk Management Strategy
Lang Tran Institute of Occupational Medicine Edinburgh, UK - - PowerPoint PPT Presentation
Lang Tran Institute of Occupational Medicine Edinburgh, UK - - PowerPoint PPT Presentation
RISK ASSESSMENT OF ENGINEERED NANOMATERIELS Lang Tran Institute of Occupational Medicine Edinburgh, UK NanoSafety and NanoCode Project Outputs, Prague 1 st November 2011 STRUCTURE OF THE TALK Exposure Assessment approaches Hazard
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EXPOSURE IN RISK ANALYSIS
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EXPOSURE
- Emission
– Extent – Duration – Background
- Mode of Exposure
– Inhalation – Ingestion – Dermal – Intravenous injection
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EXPOSURE PATHWAYS
RS Report Nanoscience and nanotechnologies (2004)
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LIFE CYCLE OF ENP
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METRICS FOR EXPOSURE-DOSE-RESPONSE
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PARTICLE CAUSE LUNG DISEASE
Coal Asbestos Quartz, asbestos
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TARGET ORGANS FOR NANOPARTICLES EFFECTS
Skin Present in cosmetics Deposition from air Gut Cleared from lungs In foods and drinks Lungs In air Lungs, endothelium , RES Medical nanoparticles
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Brain N a n o p a r t i c l e s Skin gut atherogenic plaques Lung Nose endothelium liver blood spleen heart
Hypothetical T
- xico-kinetics of Nanoparticles
FROM EXPOSURE TO INTERNAL DOSE
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From Internal Dose to Response Role of inflammation and oxidative stress in disease Asthma Inflammation Combustion-derived nanoparticles Free radicals / oxidative stress Cardiovascular disease Cancer Scarring COPD lungs This also represents the dominant hypothesis for new nanoparticles
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Atherosclerosis Unstable angina Myocardial infarction CV death
Plaque rupture and Thrombosis
Adapted from Libby P. Circulation. 2001;104:365-372.
Pathogenesis of atherothrombosis
INFLAMMATION
Endothelium
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Nanoparticles-brain and blood
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mg C13/gram organ
1 2 3 4 5 6 7
0.0 0.5 1.0 1.5
Days after Exposure
Lung Cerebrum Olfactory Cerebellum
Translocation of inhaled nanoparticles to the brain
Oberdorster, G., E. Oberdorster, and J. Oberdorster. 2005. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 113:823-839.
Rats exposed to radioactive nanoparticles of carbon
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Why be concerned about exposure to nanotubes? Nanotubes Asbestos/ fibres ? Nanoparticles ?
Multi-walled carbon nanotubes 50mm x <100nm
Asbestos
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ASBESTOS RELATED DISEASES
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FIBRE PATHOGENICITY PARADIGM
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AERODYNAMICS OF LONG FIBRES
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PANEL OF FIBRES AND MWCNT
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PLEURAL INFLAMMATION
ONLY LONG CNT ARE INFLAMMOGENIC IN PLEURAL SPACE OF MICE
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PERSISTENT INFLAMMATION IN PLEURAL SPACE BY LONG CNT
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SIMILAR RESPONSES IN PLEURAL AND PERITONEAL CAVITIES TO INSTILLED CNT PANEL
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FURTHER VERIFICATION
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MECHANISMS FOR MWCNT TOXICITY
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UNCERTAINTY ANALYSIS
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RISK ASSESSMENT
- Monte Carlo (MC) Method to simulate the cumulative exposure and obtain
a frequency distribution of Exposure values.
- For the hazard of ENP, we will estimate the Derived No Effect Level (DNEL)
- f exposure based on the most sensitive target organ.
- Due to uncertainty, we will not obtain a single point estimate of a DNEL but
a frequency distribution of DNEL values.
- A Risk Index (RI) such as the ratio of Exposure to DNEL will be calculated.
From the distribution of the RI values, informative parameters, like the ‘expected RI’ or the probability that RI is greater than 1 can be derived. These parameters are important to risk managers.
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THE PARADIGM OF RISK MANAGEMENT
Fundamental to the Strategy for Occupational Health and Safety with Nanotechnology is the Risk Management Paradigm
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CONCLUSIONS
- Control limit for exposure to Engineered Nanomaterials is
essential for Risk Assessment
- Nanomaterials have high surface to volume ratio and this will lead
to low mass based control limit
- e.g 7 µg/m3 for carbon nanotube
- Can the workplace exposure be controlled at such low (mass
based) level of exposure?
- If this is not feasible then we must look forward to a new
generation of engineered nanomaterials that are:
- SAFE BY DESIGN
- i.e. We must understand which physico-chemical characteristics
- f nanomaterials can drive the toxicity and design new