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

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 ESLs Unit 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. Obtain LC 50 data and acute inhalation NOAELs from animal studies for 97 chemicals Categorize chemicals into different acute inhalation toxicity potency classes using LC 50 data and the Globally Harmonized System (GHS) of Classification and Labeling of Chemicals (United Nations 2005)

13. Threshold of Concern (TOC) Table 3-3. Threshold of Concern Approach for Determining Tier II Generic Short-Term ESLs Globally Harmonized System of Classification and Labeling of Chemicals (GHS) Category 1Category 2Category 3Category 4Category 5 Skin IrritationCorrosiveIrritantMild Irritant Eye IrritationCauses serious eye damage Causes serious eye irritation Causes mild to moderate eye irritation d Oral LD 50 mg/kg 0 to < 5 a > 5 to < 50 a > 50 to < 300 a > 300 to < 2000 a > 2,000 a LC 50 gas ppm v 0 to < 100> 100 to < 500> 500 to < 2500> 2500 to < 5000> 5,000 LC 50 dust & mists b mg/m 3 0 to < 50> 50 to < 500> 500 to < 1000> 1000 to < 5000> 5,000 LC 50 vapors c mg/m 3 0 to < 500> 500 to < 2000 > 2000 to < 10,000> 10,000 to < 20,000> 20,000 Generic Short-Term ESL 4 µg/m 3 20 µg/m 3 125 µg/m 3 1000 µg/m 3

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

15. Threshold of Concern (TOC) Divide the 10 th percentile NOAEL values by 100 to account for human variability and uncertainty of animal to human extrapolation Cat 1: 0.4 mg/m 3 / 100 = 4 ug/m 3 Cat 2: 2 mg/m 3 / 100 = 20 ug/m 3 Cat 3&4: 12.6 mg/m 3 / 100 = 125 ug/m 3 Cat 5: 104 mg/m 3 / 100 = 1000 ug/m 3 Use the LC 50 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 ESLs NOAEL to LC 50 Ratio Approach

17. NOAEL-to-LC 50 Ratio 10 th percentile ratio = 0.0083 Calculate the ratio between acute inhalation NOAELs and LC50 Calculate the 10th percentile ratio

18. NOAEL-to-LC 50 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 LC 50 data x 0.000083 = generic ESL

19. TOC or NOAEL-to- LC 50 Ratio Approach? Both approaches use LC 50 data, although the TOC approach is generally more conservative than the NOAEL-to- LC 50 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 LC 50 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) (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 with thresholds For health effects without a threshold 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. Interactive Processes Scientists Industrial hygienists and scientists – the regulated community Academic researchers Citizens and environmental groups Regulators and Risk Managers Consultants, specialists

26. Interactive Processes Outlined in RG-442 ESL Guidelines A 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 Processes The 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 Processes Raising 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-LC 50 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. Questions Roberta L. Grant rgrant@tceq.state.tx.us (512) 239-4115 Toxicology Section Website: http://www.tceq.state.tx.us/implementation/tox/esl/guidelines/ about.html @tceq.state.tx.us ? ? ? ? ?