Health Effects of Air Toxics

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Health Effects of Air Toxics

• MIT Air Toxics Symposium
• August 4, 2004
• Judith A. Graham, Ph.D., Fellow ATS
• Long-Range Research Initiative
• American Chemistry Council
• Judy_Graham_at_americanchemistry.com
• www.uslri.org

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Presentation Topics

• Health Effects and Assessment Issues
• Air Toxics Program of the ACCs Long-Range
  Research Initiative

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GPRA Goals (source EPA Air Toxics Research
Strategy draft 2002)

• By 2010, reduce air toxics emissions by 75 from
  1993 levels.
• By 2020, eliminate unacceptable risks of cancer
  and other significant health problems from air
  toxics emissions for at least 95 of the
  population, with particular attention to children
  and other sensitive subpopulations

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Risk Assessment/Risk Management Framework
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Foundation for Decision-Making
MACT Stds Residual Risk Stds Urban
Area Source Stds Community Initiatives
Utility Determination Actions Mobile Source
Stds Combustion Stds NATA
HEALTH RISK INFORMATION Is it sufficient?
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The Conundrum

• Individual Air Toxics
• 188 CAA
• 34 NATA
• 21 Mobile Source
• 18 Indoor Air

Facility
SOURCE 1
SOURCE 2
SOURCE 3
8-9 Yr after MACT Residual Risk? Ample margin of
safety test.
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Sources of Air Toxics
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RfC Linear Multistage
Model

• Lifetime continuous exposure
• Adverse effects unlikely in sensitive groups
• NOAEL/BMD (human adj)/UFs NOAEL, interspecies,
  intraspecies, chronic, database

• Lifetime continuous exposure
• Upper bound excess lifetime cancer risk
• Risk unlikely to exceed upper bound
• Risk likely to be somewhere between 0 and upper
  bound

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Far More Advanced Assessment Methods Available,
if Database Rich

• Noncancer
• Expert judgment (e.g., EPA ozone)
• Advanced BMD and Bayesian analyses (e.g., EPA Mn)
• Probabilistic UFs (e.g., pubs, mostly for RfDs)
• 1999/2003 EPAs Draft Revised Cancer Guidelines
• Mode of action
• Biologically-based dose-response modeling
• Margin of exposure
• 2003 supplement for early-life exposure

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Research Causes Evolution of Formaldehyde Cancer
Assessment

• Early 80s, nasal cancers in rodents, gt6ppm
• Later
• rat-human nasal dose models
• mode of action (DPX CRCP)
• 2-stage clonal growth model link of DPX CRCP
  with tumors

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Current and Future Needs

• Use available health information in
  state-of-the-science assessments, in time for
  regulatory use
• Prioritize and fill chemical-specific health data
  gaps in context of the risk wheel
• Expand research on complex mixtures of air toxics
• Improve risk assessment methodologies
• harmonization of cancer and noncancer methods
• reduced reliance on generic defaults,
• consideration of real-world exposures (e.g.,
  dose-rate, intermittent)

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The ACCs Long-Range Research Initiative (LRI)

• Goal Provide fundamental research essential to
  improving chemical testing and risk assessment
  practices and policies
• Research independence
• PIs select chemicals
• PIs own data and publish in peer-reviewed
  literature without ACC approval
• Research conducted according to
• MOU with CIIT Centers for Health Research
• Competitive RfP program, often with other federal
  agencies

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LRI Air Toxics Program

• Human Exposure Studies
• Atmospheric formation of air toxics mixtures,
  with identification of toxic components (UNC)
• Measurement of indoor, outdoor, and personal
  exposures to VOCs in several areas of Boston and
  Detroit (Harvard,U.MI)
• Improve air toxics exposure models (EOHSI with
  EPA/NERL OAQPS)

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LRI Air Toxics Program

• Dose Studies
• Respiratory tract dosimetry modeling, reactive
  gases and particles (CIIT)
• Animal-to-human extrapolation
• Human age models
• Age-dependent pharmacokinetic modeling for
  systemically acting chemicals (CIIT, ENVIRON)
• Chlorine dosimetry (CIIT)

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LRI Air Toxics Program

• Health Effects and Assessment Studies
• Chlorine dose-response modeling (CIIT)
• Mechanisms of acute lung injury (CIIT)
• Lung biomarkers (CIIT)
• Methods for developmental effects (EPA, Cornell,
  TNO, CIIT)
• Chloroform computational modeling (CIIT)
• Functional genomics (CIIT)
• BB-DR modeling (CIIT, Colorado State, Gradient)

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For more information on LRI www.uslri.org