It Takes a Village to Raise a Child

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It Takes a Village to Raise a Child

• Roberta L. Grant, Ph.D.
• Toxicology Section - Chief Engineers Office
• Texas Commission on Environmental Quality

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Outline

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

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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)

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General Paradigm for Risk Assessment
Risk Assessment
U.S. Department of Health and Human Services
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November 2006 Guidelines to Develop Effects
Screening Levels, Reference Values, and Unit Risk
Factors RG-442
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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

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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

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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

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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.

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Tiered Approach for Chemicals with Limited
Toxicity Information
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Threshold of Concern Approach
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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)

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Threshold of Concern (TOC)
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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 34 12.6 mg/m3
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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 34 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

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Tier II Generic ESLsNOAEL to LC50 Ratio Approach
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NOAEL-to-LC50 Ratio
Calculate the ratio between acute inhalation
NOAELs and LC50 Calculate the 10th percentile
ratio
10th percentile ratio 0.0083
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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

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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

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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

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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)

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THE FOUNDATION

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

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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

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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
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Interactive Processes
Citizens and environmental groups
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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

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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

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Interactive ProcessesRaising the Child

• Public comments are received
• The final DSD and response to comments are posted
  on the TCEQ website
• Transparency

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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)

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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

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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

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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

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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

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QuestionsRoberta L. Grantrgrant_at_tceq.state.tx.u
s(512) 239-4115 Toxicology Section
Websitehttp//www.tceq.state.tx.us/implementatio
n/tox/esl/guidelines/about.html
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