Chernoff N, Rogers J M, Kavlock R J
Health Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC 27711.
Toxicology. 1989 Dec 1;59(2):111-25. doi: 10.1016/0300-483x(89)90050-4.
The objective of testing xenobiotics for potential developmental toxicity is to extrapolate laboratory animal information to the human species, thereby deriving biologically rational regulatory policies. One of the problems that significantly contributes to the difficulty of this task is the possibility that general effects on the maternal organism could affect the developing conceptus. Published data have indicated that factors intrinsic to the maternal organism affect developmental outcome. This overview examines factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process. Standard teratology testing protocols often call for dose levels that induce overt maternal toxicity, and the developmental effects of this toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems there have been both research and literature review efforts dealing with the relationship of maternal and developmental toxicity. Relevant studies are reviewed here, and suggestions for avenues of future research are offered including the identification of any syndromes of developmental effects occurring at maternally toxic levels irrespective of the causative agent, and experimental approaches for the characterization of maternal toxicity.
检测外源性物质潜在发育毒性的目的是将实验动物信息外推至人类，从而制定出符合生物学原理的监管政策。这项任务面临诸多困难，其中一个显著问题是母体机体的一般效应可能会影响发育中的胚胎。已发表的数据表明，母体机体的内在因素会影响发育结局。本综述探讨了可能直接或间接影响发育结局的因素，重点关注那些与危害评估过程最为相关的因素。标准的致畸试验方案通常要求设定能引发明显母体毒性的剂量水平，而这种毒性对发育的影响（单独以及与同时发生的胚胎/胎儿损伤共同作用时），仍给监管机构带来了相当大的解释难题。针对这些问题，人们开展了研究并进行了文献综述，以探讨母体毒性与发育毒性之间的关系。本文对相关研究进行了综述，并提出了未来研究方向的建议，包括识别在母体毒性水平下出现的任何发育效应综合征（无论致病因素是什么），以及表征母体毒性的实验方法。
