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Nonlinearity of dose-response functions for carcinogenicity.

机译:致癌性的剂量反应函数的非线性。

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摘要

Carcinogenesis data for 315 chemicals were obtained from the National Cancer Institute-National Toxicology Program (NCI-NTP) bioassay programs and were analyzed to examine the shape of carcinogenesis dose-response curves. Tumor site data were more often consistent with a quadratic response than with a linear response, suggesting that the routine use of linear dose-response models will often overestimate risk. Information from in vivo short-term mutagenicity and genotoxicity assays was also obtained for most of these rodent bioassays. It was found that there were no clear relationships between the shape of the carcinogenesis dose-response curve and the result of the short-term test. These observations argue against the concept that carcinogens that are positive in a short-term assay be regulated using a linear dose-response curve and those that are negative be regulated using a sublinear dose-response curve or a safety factor approach.
机译:从美国国家癌症研究所-国家毒理学计划(NCI-NTP)生物测定程序中获得了315种化学物质的致癌数据,并对其进行了分析,以检查致癌剂量响应曲线的形状。肿瘤部位数据通常与二次反应相符,而不与线性反应相符,这表明线性剂量反应模型的常规使用通常会高估风险。对于大多数这些啮齿动物生物测定,还从体内短期诱变和遗传毒性测定中获得了信息。发现致癌剂量-反应曲线的形状与短期试验结果之间没有明确的关系。这些观察结果与以下观点背道而驰:在短期测定中呈阳性的致癌物应使用线性剂量反应曲线进行调节,而在阴性分析中则应使用亚线性剂量反应曲线或安全系数方法进行调节。

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