Claxton L D, Houk V S, Monteith L G, Myers L E, Hughes T J
Genetic Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Mutat Res. 1991 Oct;253(2):137-47. doi: 10.1016/0165-1161(91)90127-t.
There has been an increasing need in genetic toxicology to progress from strictly qualitative tests to more quantitative tests. This, in turn, has increased the need to develop better quality assurance and comparative bioassay methods. In this paper, two laboratories tested 10 Salmonella mutagens in order to determine the usefulness of selected chemicals as potential reference materials to calibrate the Salmonella assay. If variance within a bioassay is sufficiently low and the rankings of the compounds are of acceptable consistency, the chemicals later could be evaluated for use as standard control compounds, as audit materials, and as standard reference materials for comparative bioassay efforts. The results demonstrated that the chosen chemicals (with the possible exception of dimethylcarbamylchloride) provide such consistent results in the Salmonella mutagenicity bioassay that they can be used for semi-quantitative calibration and as possible bioassay controls, special audit chemicals, and potentially as reference standards in comparative bioassay efforts. Reference standards, whether used as audit materials or in comparative bioassays, must be used concurrently with the test substances of interest; used without bias; used in a standardized, highly controlled bioassay; and be tested across an appropriate dose range. The study also shows that when these compounds are used as reference standards much care must be given to the number and spacing of doses if highly reproducible slope values are to be generated. We recommend use of a pilot test to establish a dose range for definitive tests and the placement of doses for the definitive tests within the first half of the linear dose-response curve. For appropriate comparisons, one should replicate the tests using the defined dose range and analyze the results in a non-biased statistical manner.
在遗传毒理学领域，从严格的定性测试向更定量的测试发展的需求日益增加。这反过来又增加了开发更高质量保证和比较生物测定方法的需求。在本文中，两个实验室测试了10种沙门氏菌诱变剂，以确定所选化学物质作为校准沙门氏菌测定的潜在参考材料的实用性。如果生物测定中的方差足够低，且化合物的排名具有可接受的一致性，则这些化学物质随后可被评估用作标准对照化合物、审核材料以及比较生物测定工作的标准参考材料。结果表明，所选化学物质（可能除二甲基甲酰氯外）在沙门氏菌致突变性生物测定中提供了如此一致的结果，以至于它们可用于半定量校准，并可作为可能的生物测定对照、特殊审核化学物质以及比较生物测定工作中潜在的参考标准。参考标准，无论是用作审核材料还是用于比较生物测定，都必须与感兴趣的测试物质同时使用；无偏使用；在标准化、高度受控的生物测定中使用；并在适当的剂量范围内进行测试。该研究还表明，当这些化合物用作参考标准时，如果要生成高度可重复的斜率值，必须非常注意剂量的数量和间隔。我们建议进行预试验以确定最终测试的剂量范围，并将最终测试的剂量置于线性剂量反应曲线的前半部分。为了进行适当的比较，应使用定义的剂量范围重复测试，并以无偏的统计方式分析结果。
