Another flaw in the linearized multistage model upper bounds on human cancer potency.
The statistical methodology used by the EPA and other federal agencies to characterize human cancer potencies based on animal experiments greatly exaggerates the estimates and bounds for human cancer risks in some instances. The current methodology incorporates simplified assumptions and approximations that fail to properly assess the impact of quantitative differences in human and experimental animal background transition rates from stage to stage in the multistage carcinogenic process. Because the majority of tumorigenic responses in rats and mice occur in organs with a high background tumor incidence and, hence, high background stage transition rates, the current simplified methodology often significantly overstates human risk. This newly recognized flaw in conjunction with the several previously recognized flaws in the current characterizations of human cancer potencies argues strongly for a change away from the current characterizations based solely on a default screening methodology to a more comprehensive, biologically based risk assessment methodology.
Sielken
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Sielken, Inc., Bryan, Texas 77802.
Stevenson
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D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015233:Models, Statistical; D012307:Risk Factors
D002273:Carcinogens