1. 1 Risk Assessment for Air Toxics: The 4 Basic Steps NESCAUM Health Effects Workshop Bordentown, NJ July 30, 2008

2. 2 The Air Toxics Risk Assessment Process

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4. 4 Risk Assessment Risk Management Decision Statutory and legal Considerations Public Health Considerations Risk Management Options Social Factors Economic Factors Political Considerations 1. Exposure Assessment 4. Risk Characterization Toxicity Assessment 2. Hazard ID 3. Dose-Response Assessment The General Four Step Risk Assessment Process

5. 5 Planning and Scoping Toxicity Assessment Risk Characterization Exposure Assessment The General Air Toxics Risk Assessment Process How does the exposure occur? Is a chemical toxic? What is the likelihood that the exposure will result in an adverse health effect? What chemicals are they exposed to? Who is exposed? What is the relationship between the dose of a chemical and the response that results? How sure are we our answers are correct?

6. 6 Planning and Scoping Exposure Assessment Toxicity Assessment Risk Characterization Quantitative and Qualitative Expressions of Risk/Uncertainty POPULATION CHARACTERISTICS Measures of Exposure CHEMICAL CONCENTRATIONS Air, Soil, Water, Food (monitor/model) The Detailed Air Toxics Risk Assessment Process Dose/ Response Assessment Y X Chemical Release SOURCES FATE AND TRANSPORT ANALYSIS Hazard Identification EXPOSURE information DOSE/RESPONSE information SOURCE IDENTIFICATION

7. 7 Planning and Scoping Risk Characterization Exposure Assessment Toxicity Assessment Toxicity Assessment Focus 7 Dose/ Response Assessment Y X Hazard Identification

8. 8 Step A - Hazard Identification Is exposure to a chemical causally linked to particular health effects? Is the effect of practical significance? What is the nature and strength of the evidence of causation?

9. 9 Hazard ID can consider both…. Lethality (LD 50, LC 50 ) Impairment of normal biological function (e.g., liver damage) Heritable genetic change Increases/decreases in species population size or range Health/productivity of ecosystems Etc. Reduced visibility from airborne particulates Damage to historic structures by air pollutants Climate change from global warming Biological EffectsNon-Biological Effects

10. 10 Numerous Biologic Endpoints Mutations DNA damage Etc. Reproductive,developme ntal, neurological disorders Immunologic effects Acute effects (edema, CNS depression) Various other systemic effects (e.g., liver, kidney, lung damage) Non-Cancer Cancer  Multiple Adverse Endpoints  Uncontrolled Growth of Cells NASA Graphic Interaction with HAP

11. 11 Where do we get our information? Data on adverse biologic effects usually generated through… Epidemiological studies In-vitro assays (i.e., test tube) In vivo biologic assays Structure-activity relationships (SAR) Human Epidemiological Studies Hazard Identification Laboratory Animal Experiments

12. 12 Step B – Dose/Response Assessment Now that we’ve established that a chemical is toxic… We need to understand how much dose gives how much response (how potent is the chemical?) Some of our Hazard ID information may help us answer that question

13. 13 Dose-Response Curves Response patterns show how the compound affects exposed organisms Patterns can differ from one health endpoint to another Patterns can differ between populations (e.g. animals to humans, different life stages) R D R D

14. 14 EPA assumes… There is a threshold below which no observable adverse effect will occur (there is a toxicity threshold) We usually don’t know exactly where that point is from our lab animal data, so… We use our animal data, in conjunction with a series of uncertainty factors, to estimate a “safe” or “reference” exposure for humans Dose-Response - Noncancer

15. 15 Dose-Response - Noncancer = Observed Animal Data LOAELHuman RfC Apply Uncertainty Factors % Animals Responding Concentration NOAELNOEL Liver Toxicity (Critical Effect) Tremors Enzyme Change Weight Decrease

16. 16 Uncertainty Factor Criteria UF Extrapolating from animal data10, 3, or 1 Sensitive human populations10, 3, or 1 Subchronic NOAEL instead of chronic NOAEL10, 3, or 1 LOAEL used instead of NOAEL10, 3, or 1 Uncertainties in the database for10, 3, or 1 the chemical Inhalation RFC *HEC = human equivalent concentration **RfD (Oral) calculated similarly (usually in mg/kg-d) ***Some RfCs developed in the past may have employed a modifying factor (MF) to account for overall quality of the tox database

17. 17 Unless we have data that indicates otherwise, we assume … There is no exposure which is without cancer risk (a non-threshold response) Even very low doses are not risk free We know the lowest exposure from our lab animal experiments, but how do we extrapolate to the very low concentrations people are more likely to experience? Dose-Response - Cancer

18. 18 x Potency = the slope of the linear default line EC 10 LEC 10 Exposure Concentration Dose-Response - Cancer Empirical Range of Observation Range of Extrapolation x 0% 10% Response (Tumor or Nontumor Data) Linear Default Upper 95% Confidence Limit on Dose Central Estimate Environmental Exposure Levels Of Interest

19. 19 The IUR is the unitless upper bound estimate of the probability of tumor formation per unit concentration of chemical Measures of potency for ingestion are developed in a similar fashion, but are… In units of (risk per mg/kg-d) IUR (risk per ug/m3) = Slope of the line from the point of departure to zero Inhalation Unit Risk

20. 20 Nonthreshold (generally) Slope Factors Inhalation Unit Risk Oral Potency Factor Threshold (generally) Reference Values RfC (inhalation) RfD (oral) In Summary … Non-Cancer HazardCancer Risk

21. 21 There are many choices EPA IRIS database California Hotspots program ATSDR MRLs NCEA provisional values EPA HEAST Open literature Etc. Which value should we use? Sources of Toxicity Data

22. 22 Sources of Toxicity Data For air toxics risk assessments… OAQPS has developed and maintains a list of recommended chronic toxicity values for each of the HAPs Inhalation IURs and RfCs Oral slope factors and RfDs http://www.epa.gov/ttn/atw/toxsource/summary.html

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25. 25 The General Risk Assessment Process Let’s restate this 4-step process with a simple mathematical formula… RISK = f [(Measure of Exposure), (Measure of Toxicity)]

26. 26 The Risk Assessment Continuum: Tiered Approaches to the Process Complete study-specific data, no assumptions; higher cost, lower uncertainty No data, all assumptions; lower cost, high uncertainty Add uncertainty/variability analysis More refined exposure assessment More refined dispersion & exposure modeling Simple dispersion model Lookup Table SCREENING MORE REFINED

27. 27 The General Four Step Risk Assessment Process Risk Management Decision Public Health Considerations Statutory and legal Considerations Social Factors Economic Factors Political Considerations Risk Management Options 4. Risk Characterization Risk Assessment 1. Exposure Assessment Toxicity Assessment 2. Hazard ID 3. Dose-Response Assessment

28. 28 Questions? Contact Heidi Hales VT DEC/NESCAUM heidi.hales@state.vt.us 802-241-3848