Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Reprod Toxicol. 2011 May;31(4):392-401. doi: 10.1016/j.reprotox.2010.11.013. Epub 2010 Dec 3.
The multi-generation reproductive toxicity study (OECD TG 416 and USEPA 870.3800) has been extensively used internationally to assess the adverse effects of substances on reproduction. Recently the necessity of producing a second generation to assess the potential for human health risks has been questioned. The present standardized retrospective analysis of the impact of the second generation on overall study outcome combines earlier analyses and includes 498 rat multi-generation studies representing 438 different tested substances. Detailed assessment of study reports revealed no critical differences in sensitivities between the generations on the basis of a consideration of all endpoints evaluated. This analysis indicates that the second generation mating and offspring will very rarely provide critical information. These findings are consistent with the conclusions of previous retrospective analyses conducted by RIVM, USEPA and PMRA and support adoption of the proposed OECD extended one-generation reproductive toxicity study protocol in regulatory risk assessment testing strategies.
多代生殖毒性研究（OECD TG 416 和 USEPA 870.3800）已在国际上广泛用于评估物质对生殖的不良影响。最近，人们质疑是否有必要产生第二代物质来评估对人类健康的潜在风险。本研究对第二代物质对整体研究结果的影响进行了标准化的回顾性分析，该研究结合了早期的分析，并包括了 498 项大鼠多代研究，代表了 438 种不同的测试物质。详细评估研究报告显示，基于对所有评估终点的考虑，两代之间的敏感性没有显著差异。该分析表明，第二代交配和后代很少会提供关键信息。这些发现与先前由 RIVM、USEPA 和 PMRA 进行的回顾性分析的结论一致，并支持在监管风险评估测试策略中采用拟议的 OECD 扩展一代生殖毒性研究方案。
