2. George M. Woodall, PhD NCEA Toxicologist Leland Urban Air Toxics Research Center October 18, 2005 EPA Reference Values: Regulatory Context

3. National Emission Standards for Hazardous Air Pollutants (NESHAP) Program Mandated in 1990 CAA Amendments Maximum Achievable Control Technology (MACT)  Assumption - Reducing emissions will reduce risk  However - No characterization of risk Residual Risk Assessments  Risk remaining after NESHAPs enactment – usually 8 years  Assessment of risk

4. Residual Risk Characterization of emissions  Annual  Hourly (generally, 10 x apportioned annual emissions) Modeling of emission dispersion  Emissions Current Reported MACT Limit  Meteorology Worst-case for Hourly 5-year Average for Cancer Worst year for Chronic Non-cancer Calculations of health-based risk  Using modeled receptors (often highest exposed receptor)  Both Cancer and Non-cancer Effects (acute and chronic durations)

5. What is a Reference Value? Reference Values = Guidelines & Standards Guidelines are recommendations for safe exposure levels  Integrated Risk Information System (IRIS) Reference Concentration (RfC) Standards are enforceable legal limits  National Ambient Air Quality Standards (NAAQS)

6. Risk Assessment Paradigm (NAS, 1994)

7. Purpose of Health Effects Reference Values Each reference value system has a specific reason for existence  Protection for specific populations Workers General population (Public Health) Susceptible sub-populations  Defined exposure scenarios Peak vs. Repeated vs. Continuous exposures Duration, schedule, etc.  Organizational Mandate

8. Reference Values and HAP Chemicals Two Durations Modeled in Residual Risk  Chronic Continuous (24-hour/day; 7-days/week; potentially for a lifetime) Low concentrations  Acute Short-term (<= 24-hour, single events; potentially repeated) High concentrations

9. Cancer Reference Values US EPA (http://www.epa.gov/iris/subst/index.html) -or- Cal EPA (http://www.oehha.ca.gov/air/cancer_guide/index.html)  Inhalation – Unit Risk (IUR)  Oral – Cancer Slope Factor (CSF) Chronic Exposure Durations Assumed

10. Chronic Non-Cancer Reference Values US EPA –Reference Concentration (Chronic RfC)  http://www.epa.gov/iris/subst/index.html ATSDR – Minimal Risk Level (Chronic MRL)  http://www.atsdr.cdc.gov/mrls.html California EPA – Reference Exposure Level (Chronic REL)  http://www.oehha.ca.gov/air/chronic_rels/index.html OAQPS Hierarchy: RfC > MRL > REL

11. Categories of Acute Health Standards and Guideline Levels Occupational  Healthy worker population  Exposures for average workday/workweek and short-term peaks Emergency Response  General population – not necessarily the “most susceptible”  Rare, short-term exposures  Adverse effects, not “safe” exposure levels (not re-entry) “Safe” Public Health Values  All susceptible subgroups (generally more conservative)  Longer-term, potentially repeated exposures

12. Reference ValueOrganizationLegal Standing Type ValueTWA (Yes/No) Exposure Duration PEL - Permissible Exposure Limit OSHAStandardOccupationalYes8-hour CeilingOSHAStandardOccupationalNoUp to10-minute REL - Recommended Exposure Limit NIOSHGuidelineOccupationalYes8-hour IDLH - Immediately Dangerous to Life and Health NIOSHGuidelineOccupationalNoUp to 30-minute STEL - Short Term Exposure Limit NIOSHGuidelineOccupationalYes15-minute TLV - Threshold Limit ValueACGIHGuidelineOccupationalYes8-hour TLV-STEL - TLV Short Term Exposure Limit ACGIHGuidelineOccupationalYes15-minute AEGL - Acute Exposure Guideline Level NAC/AEGL; NRC/AEGL GuidelineEmergency Response 10- and 30-minute; 1-, 4- and 8-hour ERPG – Emergency Response Planning Guideline AIHAGuidelineEmergency Response 1-hour TEEL – Temporary Emergency Exposure Level DOEGuidelineEmergency Response 1-hour ERG – Emergency Response Guidebook DOTGuidelineEmergency Response Specialized application MRL - Minimal Risk LevelATSDRGuidelinePublic Health1-14 days (acute); 15-364 days (intermed.); >365 days (chronic) REL - Reference Exposure Level Cal-EPA OEHHA GuidelinePublic Health1-8 hours EPA – Acute RfCUS EPADraft Guideline Public Health1-, 4-, 8-, and 24-hours Acute Reference Value Definitions (Woodall, 2005)

13. Acute Reference Values No hierarchy chosen  Arrays of all chemical-specific values used to determine “Safe” exposure level Occupational values NOT used in Residual Risk Comparisons to Chronic reference values also performed.

14. Occupational values below the AEGL-2 and ERPG-2 levels indicate a potential problem. The Draft Acute RfC is not yet ready for use in the regulatory setting. No Public Health nor low-level Emergency Response values available for Ethylene Oxide So, what do you use?

15. Analysis to Support Residual Risk Assessment Characterize the Acute Reference Values for HAPS  Best value to use in individual Residual Risk assessments Understand the basis for differences between values  Determine best course when critical Acute Reference Values are missing

16. Reference Values Database (Air Toxics Health Effects Database: http://www.epa.gov/ttn/atw/toxsource/summary.html ) Database 854 Chemicals (2,275 Values ) Acute Inhalation 243 Chemicals (696 values) Comparable Values 126 Chemicals

17. ChronicAcute n =

18. Comparison between Acute and Chronic Reference Values Determine which acute values may be more critical for Residual Risk Assessments Simple comparison (ratios) of acute to chronic values for single chemicals A Priori Assumption – Concern if Acute values (mostly 1-hr) within 3 orders of magnitude of their corresponding Chronic value

19. Ratio of Acute to Chronic Non-Cancer Inhalation Reference Values by HAP Chemical

20. *** ** *

21. Acute to Chronic Comparisons 92 chemicals had ratios calculated:  25 had a lowest ratio value ≤ 10  16 had a lowest ratio value > 10 and ≤ 100  19 had a lowest ratio value > 100 and ≤ 1000  32 had a lowest ratio value > 1000

22. Summary Health Reference Values are developed for specific purposes and use outside those purposes should be done judiciously, if at all Comparisons between Health Reference Values are more valid:  Within certain categories (occupational, emergency releases, public health protection) and  For comparable time frames Acute reference values for some chemicals may be more critical for residual risk analysis than their corresponding chronic values.

23. Acknowledgements Roy L. Smith, PhD (US EPA/OAQPS) Robert Hetes, PhD (US EPA/ORD) Mark Corrales, PhD (US EPA/OPEI)

24. References National Academies of Science (1994) Science and judgment in risk assessment. Washington, DC: National Academy Press Woodall, G.M. (2005) Acute health reference values: Overview, perspective, and current forecast of needs. Journal of Toxicology and Environmental Health, Part A, 68:901-926