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  1. Requirements for a biologically realistic cancer risk assessment for inorganic arsenic.

    Article - En anglais

    A remarkable feature of the carcinogenicity of inorganic arsenic (Asi) is the observation that human exposures to Asi have been strongly associated with increases in skin, lung, and internal cancers, but Asi does not typically cause tumors in standard laboratory animal test protocols.

    Considerable controversy has centered on whether there is epidemiological evidence of a « threshold » for the carcinogenic effects of Asi, or at least of a highly nonlinear dose-response.

    Saturation of metabolism in the dose-range associated with tumors does not appear to be adequate to produce a major impact on the dose-response for carcinogenicity.

    If there is a strong nonlinearity, it results from the nature of the carcinogenic mechanism (s) of Asi.

    However, no single hypothesis for the mechanism of Asi carcinogenicity has widespread support.

    A biologically realistic cancer risk assessment for Asi would require a quantitative description of the dose of active arsenic species in target tissues, the interactions between active arsenic and tissue constituents, and the manner in which these interactions result in tumor formation in multiple organs in humans, but not in experimental animals.

    Although Asi has only infrequently been associated with tumors in animal studies, it has repeatedly been shown to act as a comutagen in vitro and as a cocarcinogen in vivo.

    Asi is clastogenic, producing chromatid aberrations, but does not produce point mutations at single gene loci. (...)

    Mots-clés Pascal : Arsenic, Carcinogène, Toxicité, Article synthèse, Homme, Relation dose réponse, DNA, Promoteur tumeur, Mutagène, Relation homme environnement, Polluant, Evaluation, Risque

    Mots-clés Pascal anglais : Arsenic, Carcinogen, Toxicity, Review, Human, Dose activity relation, DNA, Tumor promotor, Mutagen, Man environment interface, Pollutant, Evaluation, Risk

    Logo du centre Notice produite par :
    Inist-CNRS - Institut de l'Information Scientifique et Technique

    Cote : 99-0197490

    Code Inist : 002B03M01. Création : 16/11/1999.