It Takes a Village to Raise a Child

1. It Takes a Village to Raise a Child Roberta L. Grant, Ph.D. Toxicology Section - Chief Engineer’s Office Texas Commission on Environmental Quality

2. Outline • Toxicity assessments • Chemicals with limited toxicity data • Chemicals with adequate toxicity data • Professional judgment • Interactive processes

3. Toxicity Assessment • The basic objective of a toxicity assessment is to identify what adverse health effects a chemical causes and how the appearance of these adverse effects depends on exposure level (dose)

4. Dose Response Assessment Hazard Identification Exposure Assessment Risk Characterization General Paradigm for Risk Assessment Risk Assessment U.S. Department of Health and Human Services

5. November 2006 Guidelines to Develop Effects Screening Levels, Reference Values, and Unit Risk Factors RG-442

6. Effects Screening Levels (ESLs) • Chemical-specific air concentrations set to protect human health and welfare. • Short-term ESLs are based on data concerning acute health effects [1-hr intermittent], odor/nuisance potential, and vegetative effects • Long-term ESLs [annual] are based on data concerning chronic non-carcinogenic and/or carcinogenic health effects and vegetative effects • This presentation will only discuss health-based ESLs

7. Reference Values (ReVs) and ESLs • Exposure to an air concentration at or below the ReV or ESL is not likely to cause adverse health effects in the general public, including sensitive subpopulations such as: • Children • Pregnant women • Elderly • Individuals with pre-existing conditions • ReVs and ESLs are screening values - not standards

8. ReVs and ESLsUnit Risk Factors • For acute and chronic health effects with a threshold health-based ESLs = 0.3 x ReV (cumulative and aggregate) • For chronic health effects without a threshold Derive a unit risk factor. Calculate a No Significant Risk Level of 1 in 100,000 excess risk

9. Texas Clean Air Act • Section 382.002 of the Texas Health and Safety Code empowers the TCEQ to regulate ambient air conditions to protect human health, general welfare, and physical property from impacts of air pollution in the ambient air. • The Texas Health and Safety Code is comprehensive. ESLs are developed for as many air contaminants as possible, even for chemicals with limited toxicity data.

10. Tiered Approach for Chemicals with Limited Toxicity Information

11. Threshold of Concern Approach

12. Threshold of Concern Approach • Obtain LC50 data and acute inhalation NOAELs from animal studies for 97 chemicals • Categorize chemicals into different acute inhalation toxicity potency classes using LC50 data and the Globally Harmonized System (GHS) of Classification and Labeling of Chemicals (United Nations 2005)

13. Threshold of Concern (TOC)

14. Calculate the 10th percentile of the cumulative percentage distribution of NOAELs in each category Cat 5 = 104 mg/m3 Cat 2 = 2 mg/m3 Cat 1 = 0.4 mg/m3 Cat 3&4 =12.6 mg/m3

15. Threshold of Concern (TOC) • Divide the 10th percentile NOAEL values by 100 to account for human variability and uncertainty of animal to human extrapolation Cat 1: 0.4 mg/m3 / 100 = 4 ug/m3 Cat 2: 2 mg/m3 / 100 = 20 ug/m3 Cat 3&4: 12.6 mg/m3 / 100 = 125 ug/m3 Cat 5: 104 mg/m3 / 100 = 1000 ug/m3 • Use the LC50 data of a chemical to categorize it into a GHS category. Use the TOC for that category as a generic ESL

16. Tier II Generic ESLsNOAEL to LC50 Ratio Approach

17. NOAEL-to-LC50 Ratio Calculate the ratio between acute inhalation NOAELs and LC50 Calculate the 10th percentile ratio 10th percentile ratio = 0.0083

18. NOAEL-to-LC50 Ratio • Divide the ratio of 0.0083 by 100 to account for human variability and uncertainty of animal to human extrapolation • Health-Protective Ratio = 0.000083 • LC50 data x 0.000083 = generic ESL

19. TOC or NOAEL-to- LC50 Ratio Approach? • Both approaches use LC50 data, although the TOC approach is generally more conservative than the NOAEL-to- LC50 Ratio approach • Use information on the chemical and a weight-of-evidence approach to decide which approach is most defensible • Choose the most conservative number if there is uncertainty in the quality of the LC50 data

20. Chemicals with Adequate Toxicity Data • Review essential data including physical/ chemical properties and select key studies • Conduct a Mode of Action (MOA) analysis (threshold or nonthreshold) • Choose the appropriate dose metric • Determine the Point of Departure (POD) for each key study • Conduct appropriate dosimetric modeling

21. Chemicals with Adequate Toxicity Data • Extrapolate from the adjusted POD to lower exposures based on MOA analysis and select critical effect • For health effects with thresholds • For health effects without a threshold (typically carcinogens)

22. THE FOUNDATION • Scientific data • Trained toxicologists and other scientists • Accepted scientifically-based procedures and guidelines • Professional judgment • Public comment

23. The Role of Professional Judgment • Judgment should be based on science and common sense • Difficult pill for society to swallow • Would you trust a bureaucrat to use judgment? Society as a whole Does Not! • With judgment comes responsibility

24. Professional Judgment and Balance “We must not only get the correct result, we must do so in a manner that promotes public acceptance of the result” Vincent Cogliano International Agency for Research on Cancers 2007 Toxicology and Risk Assessment Conference

25. Scientists Regulators and Risk Managers Academic researchers Consultants, specialists Industrial hygienists and scientists – the regulated community Interactive Processes Citizens and environmental groups

26. Interactive Processes Outlined in RG-442 ESL GuidelinesA Toxicity Value is Born • Chemicals for which we will develop ESLs will be posted on the TCEQ website • Draft Development Support Document (DSD) • The draft DSD becomes a proposed DSD

27. Interactive ProcessesThe Village - Public Comment Period • The proposed DSDs are posted on the TCEQ website for a 60- or 90-day public comment period • Public information meetings in Austin

28. Interactive ProcessesRaising the Child • Public comments are received • The final DSD and response to comments are posted on the TCEQ website • Transparency

29. Interactive Processes External Scientific Peer Reviews • External scientific peer reviews • RG-442 ESL Guidelines did undergo external scientific peer review and public comment • Occasionally, the TCEQ will conduct a peer review for an individual DSD (example: 1,3-butadiene)

30. Summary • The TCEQ conducts toxicity assessments to develop ESLs, ReVs, and URFs. ESLs and ReVs are health-protective screening levels whereas URFs are factors used to calculate air concentrations at the No Significant Risk Level of one in 100,000 excess risk

31. Summary • For chemicals with limited toxicity data, statistical or relative toxicity/potency approaches can be used to derive health-protective default or generic ESLs • Tier 1 – Threshold of Regulation • Tier II – Threshold of Concern and NOAEL-to-LC50 Ratio • Tier III – Relative Toxicity/Potency Approach

32. Summary • For chemicals with adequate toxicity data, the foundation of a sound toxicity assessment is toxicity data, scientifically- defensible procedures, professional judgment, balance, and interactive processes

33. Summary • It takes a community of scientists and specialists as well as the regulated community and concerned citizens engaged in a dynamic interactive process to produce a publicly acceptable toxicity assessment

34. ? ? ? QuestionsRoberta L. Grantrgrant@tceq.state.tx.us(512) 239-4115Toxicology Section Website:http://www.tceq.state.tx.us/implementation/tox/esl/guidelines/about.html ? ?