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Air Toxics: Chronic Health Research Needs

William K. Boyes Neurotoxicology Division Office of Research and Development, US EPA Research Triangle Park, NC. Air Toxics: Chronic Health Research Needs. What is the Goal?. Biologically-based dose response model

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Air Toxics: Chronic Health Research Needs

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  1. William K. Boyes Neurotoxicology Division Office of Research and Development, US EPA Research Triangle Park, NC Air Toxics: Chronic Health Research Needs

  2. What is the Goal? • Biologically-based dose response model • “predictive tool used to estimate potential human health risks by describing and quantifying the key steps in the cellular, tissue and organismal responses as a result of chemical exposure” • The preferred approach, e.g. • EPA new Cancer Risk Assessment Guidelines • NAS research priorities for particulate matter

  3. Dose metric is key

  4. Typical Dose Measures

  5. Reference Concentration (RfC) NOAEL * [HEC] RfC = ------------------------- UF RfC A concentration to which lifetime exposure will be without appreciable risk (w/in order of magnitude) NOAEL*[HEC] NOAEL, or equivalent adjusted for human dosimetry UF Uncertainty factors (up to 3000 total)

  6. Chronic Health Benchmarks

  7. Uncertainty Factors of HAP RfCs • Uncertainty factors: • LOAEL to NOAEL (up to) 10 • Short duration to long 10 • Animal to human 10 • Human variability 10 • Inadequate database 10 • Maximum total 3000

  8. Acute Health Benchmarks

  9. Criteria Pollutants PM Hourly exposure peaks linked to cardio-pulmonary mortality Ozone Hourly/daily concentrations linked to reactive airway problems (asthma) HAPs Little epidemiology regarding temporal exposure patterns Epidemiology and Temporal Patterns

  10. Exposure Patterns • Risk assessment for chronic exposures considers only mean annual exposure levels • Yet HAP exposures vary greatly from time to time • Human activity patterns • Changing weather • Emission patterns and/or “upsets”

  11. Recent Studies of Upset Emissions • Public Citizen (Austin TX, 2005) • In some cases, upset releases exceeded annual releases several thousand fold • 7,533 upset events to Texas in 2004 • Some facilities report upset events on average every other day

  12. Concentration-Driven Health Outcomes • Respiratory Irritants • Concentration more important than C x t • Acute CNS effects of VOCs • Peak brain concentration determines outcome and not AUC • Development • Short critical periods of development (hrs/days) • Short term exposure episodes lead to life long alterations

  13. Exposure-Dose-Response Model

  14. Acute peak brain concentration Use to extrapolate across exposure durations Across species Chronic Unknown Likely cumulative in some way AUC? Other Dose Metric for Neurotoxic VOCs

  15. Chronic Toluene Neurotoxicity As a function of ppm As a function of ppm*yr

  16. Toluene Neurotoxicity Rat vs Human As a function of ppm*yr

  17. What do we know?

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