Re-evaluating dioxin: Science Advisory Board's review of EPA's reassessment of dioxin and dioxin-like compounds

Original publisher: [Washington, D.C.] : U.S. Environmental Protection Agency, Science Advisory Board, [1995] OCLC Number: (OCoLC)40383750 Subject: Dioxins. Excerpt: ... by its reliance on the standard EPA default assumption of a linear non-threshold model for carcinogenic risk. The Committee suggests that EPA consider, in future revisions, alternative risk models, allowing for minimal response at low environmental levels of exposure, and which would be consistent with the body of available physiological ( and, with the opportunities now arising, pharmaco-kinetic ) modeling of factors such as deposition, tissue dose, and excretion, as well as the epidemiological, and bioassay data. Vis-a-vis cancer, the Committee notes that all of the evidence available argues strongly that TCDD exerts its carcinogenic effect primarily through its effectiveness as a promoting agent stimulating cell replication in a reversible manner, and inhibiting apoptosis, both mechanisms presumably mediated through the Ah receptor and associated transduction mechanisms. TCDD is thus not a complete carcinogen, and, to avoid confusion should not be designated as such in the EPA document. Almost all Members of the Committee do concur with EPA's judgment that 2,3,7,8-TCDD, under some conditions of exposure, is likely to increase human 2 cancer incidence. The conclusion with respect to dioxin-like compounds is less firm. The Committee notes that the assignment of the dioxins, the PCBs, or PBBs to one of a mutually exclusive and collectively exhaustive set of carcinogenicity categories grossly oversimplifies the state of the science in most instances, excepting those compounds for which there is an abundance of uniformly consistent evidence, but that EPA must make such an assignment. Under the 1986 EPA cancer guidelines, levels of carcinogenic evidence, with mutually exclusive descriptive terms are provided. These choices include Group A--human carcinogen; B--probable human carcinogen on the 1 b...