Development and Uses of Acute Reference Values

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Development and Uses of Acute Reference Values

• George Woodall, PhD
• National Center for Environmental Assessment
• Office of Research and Development
• US Environmental Protection Agency

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Acute Reference Values

• Reference Values Guidelines Standards
• Guidelines are recommendations
• Standards are legal limits
• Acute Exposure vs. Acute Effects

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Overview

• Brief Historical Background
• Purpose of Health Reference Values
• Categorizing Health Reference Values
• Deciphering the Alphabet Soup
• Ongoing EPA/NCEA Activities
• Comparisons Between Acute Reference Values

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Brief Historical Background

• Occupational Values predate others
• Early Public Health reference values focused on
  Chronic Effects
• Most emphasis on Cancer
• Non-cancer examples include RfCs and RfDs
• Acute Reference values for protecting the Public
  Health are more recent
• Incident in Bhopla, India (1984)
• RTK provisions of the Superfund program SARA
  (1986)
• Section 112(r) of Clean Air Act Amendments (1990)
• State initiatives

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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/continuous/repeated exposures,
• Duration, schedule, etc.
• Organizational Mandate

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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
• Public Health Protection
• All susceptible individuals (generally)
• More routine, repeated exposures

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Categories of Acute Health Standards and
Guideline Levels

• Occupational
• Occupational Safety and Health Administration
  (OSHA) - Under the Department of Labor
• National Institute for Occupational Safety and
  Health (NIOSH) - Part of the National Institutes
  of Health
• American Conference of Governmental Industrial
  Hygienists (ACGIH) - Independent organization

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Categories of Acute Health Standards and
Guideline Levels

• Emergency Response
• American Industrial Hygiene Association (AIHA) -
  Independent Association
• National Advisory Committee for Acute Exposure
  Guideline Levels (NAC/AEGL)
• National Academy of Sciences Committee for Acute
  Exposure Guideline Levels (NAS/AEGL)
• Office of Hazardous Materials Safety - Department
  of Transportation
• Department of Energy

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Categories of Acute Health Standards and
Guideline Levels

• Public Health Protection
• Agency for Toxic Substances and Disease Registry
  (ATSDR) - Part of the CDC
• Californias Office of Environmental Health and
  Hazard Assessment (OEHHA) - Part of the
  California EPA
• U.S. Environmental Protection Agency (EPA)

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Occupational Standards

• PELs (Permissible Exposure Limits)
• Developed by the Occupational Safety Health
  Administration (OSHA)
• The concentration of a substance to which most
  workers can be exposed without adverse effect
  averaged over a normal 8-h workday or a 40-h
  workweek.
• Expressed as a time-weighted average (TWA)
• PELs are enforceable.

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Occupational Standards

• OSHA Ceiling
• OSHAs permissible exposure limit ceiling value
• The concentration of a substance that should not
  be exceeded at any time.
• Enforceable limit

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Occupational Guidelines

• NIOSH REL (Recommended Exposure Limit)
• NIOSH-recommended exposure limit for an 8- or
  10-h TWA exposure and/or ceiling
• Recommendations that may be considered by OSHA
  for a PEL

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Occupational Guidelines

• IDLH (Immediately Dangerous to Life or Health)
• NIOSH recommended exposure limit to ensure that a
  worker can escape from an exposure condition that
  is likely to cause death or immediate or delayed
  permanent adverse health effects or prevent
  escape from the environment.
• Designed to allow exit from a toxic environment
  following respirator failure
• Up to 30 minutes

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Occupational Guidelines

• IDLH (continued)
• Determined for 387 substances in the mid-1970's
  (NIOSH and OSHA)
• Used in assigning proper respiratory protection
  equipment
• In the mid-1990s, NIOSH revisited and revised
  many of the original values
• Level of Concern (LOC) 0.1 x IDLH
• Used by EPA for initial 112(r) screening

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Occupational Guidelines

• NIOSH STEL (Short Term Exposure Limit)
• 15-minute TWA exposure which should not be
  exceeded at any time during a workday

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Occupational Guidelines

• TLV (Threshold Limit Value)
• TLV Committee was established by ACGIH in 1941
• The concentration of a substance to which most
  workers can be exposed without adverse effects.
• Usually an 8-hour TWA
• Ceiling values also exist for some chemicals

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Occupational Guidelines

• TLV-STEL (Threshold Limit Value Short Term
  Exposure Limit)
• Developed by ACGIH
• A 15-minute TWA exposure which should not be
  exceeded at any time during a workday.

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Emergency Response Guidelines

• AEGLs (Acute Exposure Guideline Levels)
• Values proposed by NAC/AEGL
• Reviewed and approved NAS/AEGL
• Values derived for 10- and 30-minutes, and 1-, 4-
  and 8-hours
• Usually applying Cn x T calculation
• Designed for use in rare, accidental releases

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AEGL Severity Categories
Courtesy of Ernest Falke, EPA
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Emergency Response Guidelines

• ERPGs (Emergency Response Planning Guidelines)
• Developed by AIHA
• Purpose is similar to the AEGLs
• Predates the AEGLs
• 3 severity categories, similar to AEGLs
• Based on a one-hour exposure

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Emergency Response Guidelines

• TEELs (Temporary Emergency Exposure Limits)
• Developed by DOE
• Values used where ERPGs do not exist
• Generated from other existent reference values
  (PELs, STELs, TLVs, etc.)
• Uses methodology cited in Craig et al., 1995
• Guideline Limits for Chemicals without ERPGs.
  Amer. Ind. Hyg. Assoc. J. 56, 919-925

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Emergency Response Guidelines

• ERG Emergency Response Guidebook
• Developed by DOT
• Designed for first responders during initial
  phase of response to a hazardous materials
  incident
• Specialized use defines evacuation zones
• Not readily comparable to any other reference
  values

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Public Health Protection Guidelines

• MRLs (Minimal Risk Levels)
• Developed by the ATSDR
• Acute (1-14 days)
• Intermediate (15-364 days)
• Chronic (gt365 days) exposures
• Designed for use in screening risks associated
  with Superfund sites

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Public Health Protection Guidelines

• California RELs (Reference Exposure Levels)
• Developed by OEHHA
• Designed for the most sensitive endpoint for the
  most sensitive individual
• One-hour value (may be up to 8-hour)

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Public Health Protection Guidelines

• Draft EPA Approach
• The Acute Reference Exposure (ARE) methodology
  was proposed in 1998
• Review by the Science Advisory Board (SAB) in
  1998 and EPAs Risk Assessment Forum (RAF) in
  2000 led to many recommendations
• Currently, a pilot study on a few selected
  chemicals is applying those recommendations

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Whats on the Horizon

• NCEA is in the process of developing a revised
  methodology for acute values
• May be included in IRIS in the future
• Incorporates use of categorical regression and
  benchmark dose, where feasible
• Applies Cn x T time-course calculations where
  appropriate
• Other less-than-lifetime reference values are
  also under consideration
• Draft documentation expected by 2005

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And now, for something completely different ...

• A comparison between various Acute Reference
  Values

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Comparisons of Reference Values

• Data set made available through Roy Smith (EPA)
• 2,275 reference values 854 chemicals
• 696 records had acute values for inhalation route
• 225 had enough information to allow comparisons
  based on similar units (mg/m3)
• 126 had more than one value to allow comparisons
  within chemicals

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Caveats to Analysis of Comparisons

• A work in progress
• Comparisons do not include all relevant variables
• Endpoint and Target Tissue
• Duration differences
• Exposure Scenario
• Only one-hour values were compared
• Additional data is being collected

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Correlations for Comparable Acute Reference Values
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Chronic
Acute
n
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Comparisons to Draft ARE Values

• Draft AREs developed for five chemicals
• Acrolein
• Ethylene Oxide
• Hexachlorocyclopentadiene
• Hydrogen Sulfide
• Phosgene

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Summary

• Acute Reference Values for the General Public are
  rather recent developments
• This topic is rife with acronyms
• Health Reference Values are developed for
  specific purposes and use outside those purposes
  should be done cautiously, 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
• Near Future Activities within EPA include
  developing an acute methodology

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Thank you for your attention