William Boyes_ US EPA - The University of Texas School of Public

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William Boyes_ US EPA - The University of Texas School of Public Powered By Docstoc
					 Air Toxics: Chronic Health
      Research Needs



              William K. Boyes
           Neurotoxicology Division
Office of Research and Development, US EPA
          Research Triangle Park, NC
          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
Dose metric is key
     Typical Dose Measures

    Basis               Peak                 Cumulative
External        Air concentration ( C )   C x t (Haber’s)
Exposure        (ppm, mg/m3)              Cn x t
                                          (ppm * yr, mg/m3 * yr)


Internal Dose   Tissue Concentration      Tissue AUC
                (mg/l)                    (mg/l * hr, mg/l * yr)
                                          Others?
      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)
Chronic Health Benchmarks
        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
Acute Health Benchmarks
 Epidemiology and Temporal Patterns

• Criteria Pollutants           • HAPs
   § PM                           § Little epidemiology
      • Hourly exposure peaks       regarding temporal
        linked to cardio-           exposure patterns
        pulmonary mortality
   § Ozone
      • Hourly/daily
        concentrations linked
        to reactive airway
        problems (asthma)
       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”
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
   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
Exposure-Dose-Response Model
Dose Metric for Neurotoxic VOCs
• Acute                        • Chronic
  § peak brain concentration     § Unknown
  § Use to extrapolate           § Likely cumulative in
     • across exposure             some way
       durations                     • AUC?
     • Across species                • Other
 Chronic Toluene Neurotoxicity




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




   As a function of ppm*yr
               What do we know?
         We Know                   We Don’t Know
Health benchmarks (RfC,        The other half
URE) for ~½ the HAPs
RfC: safe over a lifetime of   Risks above the RfC
exposure
URE: linear slope factors      Nonlinear mechanisms
Mean annual exposure           Temporal/spatial variations
estimates                      in exposure
Goal: BBDR models              Mode of action & dose
                               metrics

				
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posted:7/28/2013
language:English
pages:18