Lang Tran Institute of Occupational Medicine Edinburgh, UK

Transcription

1 RISK ASSESSMENT OF ENGINEERED NANOMATERIELS Lang Tran Institute of Occupational Medicine Edinburgh, UK NanoSafety and NanoCode Project Outputs, Prague 1 st November 2011

2 STRUCTURE OF THE TALK Exposure Assessment approaches Hazard Assessment approaches Risk Assessment Approach Derivation of Control Limit Risk Management Strategy

3 EXPOSURE IN RISK ANALYSIS

4 EXPOSURE Emission Extent Duration Background Mode of Exposure Inhalation Ingestion Dermal Intravenous injection

5 EXPOSURE PATHWAYS RS Report Nanoscience and nanotechnologies (2004)

6 LIFE CYCLE OF ENP

7 METRICS FOR EXPOSURE-DOSE-RESPONSE

8 PARTICLE CAUSE LUNG DISEASE Coal Quartz, asbestos Asbestos

9 TARGET ORGANS FOR NANOPARTICLES EFFECTS Lungs In air Gut Cleared from lungs In foods and drinks Skin Present in cosmetics Deposition from air Lungs, endothelium, RES Medical nanoparticles

10 FROM EXPOSURE TO INTERNAL DOSE Hypothetical Toxico-kinetics of Nanoparticles N a n o p a r t i c l e s Brain Nose Lung Skin gut blood spleen endothelium liver heart atherogenic plaques

11 From Internal Dose to Response Role of inflammation and oxidative stress in disease Combustion-derived nanoparticles Free radicals / oxidative stress This also represents the dominant hypothesis for new nanoparticles Inflammation Cardiovascular disease Asthma COPD Scarring Cancer lungs

12 Pathogenesis of atherothrombosis Plaque rupture and Thrombosis Unstable angina Myocardial infarction INFLAMMATION CV death Endothelium Atherosclerosis Adapted from Libby P. Circulation. 2001;104:

13 Nanoparticles-brain and blood.

14 mg C 13 /gram organ Translocation of inhaled nanoparticles to the brain Rats exposed to radioactive nanoparticles of carbon Days after Exposure Lung Olfactory Cerebrum Cerebellum Oberdorster, G., E. Oberdorster, and J. Oberdorster Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 113:

15 Why be concerned about exposure to nanotubes? Asbestos/ fibres? Nanotubes? Nanoparticles Multi-walled carbon nanotubes 50mm x <100nm Asbestos

16 ASBESTOS RELATED DISEASES 16

17 FIBRE PATHOGENICITY PARADIGM 17

18 AERODYNAMICS OF LONG FIBRES 18

19 PANEL OF FIBRES AND MWCNT 19

20 PLEURAL INFLAMMATION ONLY LONG CNT ARE INFLAMMOGENIC IN PLEURAL SPACE OF MICE 20

21 PERSISTENT INFLAMMATION IN PLEURAL SPACE BY LONG CNT 21

22 SIMILAR RESPONSES IN PLEURAL AND PERITONEAL CAVITIES TO INSTILLED CNT PANEL 22

23 FURTHER VERIFICATION 23

24 MECHANISMS FOR MWCNT TOXICITY 24

25 UNCERTAINTY ANALYSIS

26 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) of 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.

27 THE PARADIGM OF RISK MANAGEMENT Fundamental to the Strategy for Occupational Health and Safety with Nanotechnology is the Risk Management Paradigm

28 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/m 3 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 of nanomaterials can drive the toxicity and design new industrially useful nanomaterials without these features