Munro I C
J Environ Pathol Toxicol. 1977 Nov-Dec;1(2):183-97.
Rodent bioassay systems are widely used to detect those environmental substances most likely to be carcinogenic. Experience with these systems has revealed several shortcomings of an operational nature which may complicate evaluation and interpretation of the results. Paramount among these are purity of the test chemical, dose selection, and experimental design. Special attention must be given to potential impurities in test substances which may be responsible wholly or in part for the production of toxic effects. Proposals for handling this problem are discussed. It is recommended that test chemicals be studied carefully in the proposed animal species using pharmacokinetic procedures, so that doses may be selected that will not jeopardize the outcome of the test nor overload metabolic detoxification systems. Whether or not a bigenerational exposure is required to adequately evaluate the carcinogenicity of the test substance will depend upon its use pattern and pharmacokinetic and metabolic behavior in the mother and fetus.
啮齿动物生物测定系统被广泛用于检测那些最有可能具有致癌性的环境物质。使用这些系统的经验揭示了一些操作性质的缺点，这些缺点可能会使结果的评估和解释变得复杂。其中最重要的是测试化学品的纯度、剂量选择和实验设计。必须特别注意测试物质中可能全部或部分导致毒性作用产生的潜在杂质。讨论了处理这个问题的建议。建议使用药代动力学程序在所提议的动物物种中仔细研究测试化学品，以便选择不会危及测试结果也不会使代谢解毒系统过载的剂量。是否需要两代暴露来充分评估测试物质的致癌性将取决于其使用模式以及在母体和胎儿中的药代动力学和代谢行为。
