Using PBPK modeling and comprehensive realism methodology for the quantitative cancer risk assessment of butadiene.
The National Academy of Sciences and many others have noted the need for quantitative health risk assessment methodology that goes beyond a simple screening analysis based on upper bounds on risk. The Academy recommended adoption of methodologies which provide a higher-tier analysis based on realistic estimates of risk which reflect more of the available biological information. In recent years, scientists have challenged the assumption of low-dose linearity and other default assumptions in cancer risk assessment. These challenges have stimulated the continued evolution of quantitative risk assessment methodologies, because effective risk management requires accurate characterizations of uncertainty and greater utilization of cost-benefit analyses for decision making. "Comprehensive Realism" is an emerging quantitative weight-of-evidence based risk assessment methodology for both cancer and noncancer health effects which utilizes probability distributions and decision analysis techniques to reflect more of the available human and animal dose-response data. The current state of knowledge about the relative plausibility of alternative dose-response analyses is also addressed in this approach. The framework discussed here should lead to a higher-tier assessment of butadiene.
Sielken, Inc., Bryan, TX 77802, USA.
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D002070:Butadienes / Q000493:pharmacokinetics / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D018570:Risk Assessment
D002070:Butadienes; D002273:Carcinogens; C031763:1,3-butadiene