George M. Woodall, PhD

NCEA Toxicologist

Leland Urban Air Toxics Research Center

October 18, 2005

EPA Reference Values:Regulatory Context

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

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)

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)

Risk Assessment Paradigm (NAS, 1994)

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

Reference Valuesand 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

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

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

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

Reference Value Organization Legal Standing

Type Value TWA (Yes/No)

Exposure Duration

PEL - Permissible Exposure Limit

OSHA Standard Occupational Yes 8-hour

Ceiling OSHA Standard Occupational No Up to10-minute

REL - Recommended Exposure Limit

NIOSH Guideline Occupational Yes 8-hour

IDLH - Immediately Dangerous to Life and Health

NIOSH Guideline Occupational No Up to 30-minute

STEL - Short Term Exposure Limit

NIOSH Guideline Occupational Yes 15-minute

TLV - Threshold Limit Value ACGIH Guideline Occupational Yes 8-hour

TLV-STEL - TLV Short Term Exposure Limit

ACGIH Guideline Occupational Yes 15-minute

AEGL - Acute Exposure Guideline Level

NAC/AEGL; NRC/AEGL

Guideline Emergency Response

10- and 30-minute; 1-, 4- and 8-hour

ERPG – Emergency Response Planning Guideline

AIHA Guideline Emergency Response

1-hour

TEEL – Temporary Emergency Exposure Level

DOE Guideline Emergency Response

1-hour

ERG – Emergency Response Guidebook

DOT Guideline Emergency Response

Specialized application

MRL - Minimal Risk Level ATSDR Guideline Public Health 1-14 days (acute); 15-364 days (intermed.); >365 days (chronic)

REL - Reference Exposure Level

Cal-EPA OEHHA

Guideline Public Health 1-8 hours

EPA – Acute RfC US EPA Draft Guideline

Public Health 1-, 4-, 8-, and 24-hours

Acute Reference Value Definitions (Woodall, 2005)

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.

Ethylene Oxide Acute Reference Values

0.01

0.1

1

10

100

1000

0 60 120 180 240 300 360 420 480 540

Minutes

pp

m -

EtO

AEGL-3 (Interim)

AEGL-2 (Interim)

ERPG-3

ERPG-2

NIOSH REL

OSHA PEL

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?

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

Reference Values Database(Air Toxics Health Effects Database:

http://www.epa.gov/ttn/atw/toxsource/summary.html)

Database854 Chemicals(2,275 Values )

Acute Inhalation 243 Chemicals (696 values)

Comparable Values126 Chemicals

ChronicAcute

n =

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

Ratio of Acute to Chronic Non-CancerInhalation Reference Values by HAP Chemical

***

**

*

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

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.

Acknowledgements

• Roy L. Smith, PhD (US EPA/OAQPS)

• Robert Hetes, PhD (US EPA/ORD)

• Mark Corrales, PhD(US EPA/OPEI)

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