Golub M S
Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Sacramento 94234-7320.
Reprod Toxicol. 1994 Jul-Aug;8(4):283-95. doi: 10.1016/0890-6238(94)90044-2.
Assessment of the potential developmental toxicity of arsenic in humans must be based entirely on the extensive animal literature; no appropriate human data are available. Hazard identification of developmental toxicity of arsenic in animal studies is complicated by the co-occurrence of maternal and developmental toxicity when the pregnant dam is exposed to the toxicant. Current regulatory guidance requires that, when maternal and developmental toxicity occur at the same or similar doses, detailed consideration needs to be given to whether developmental toxicity is secondary to maternal toxicity or whether it represents a distinct hazard. In this review, these principles were applied to the relatively large database of animal studies available for hazard identification of inorganic arsenic as a developmental toxicant. It is concluded that maternal and developmental toxicity occur in the same dose range for this potent cytotoxicant, although differential no observed adverse effect levels can be identified depending on the endpoints used. Various evidence from the basic science literature indicates that developmental toxicity is not secondary to maternal toxicity. Current regulatory guidance falls short of defining effective approaches to resolving the difficulties posed by co-occurrence of maternal and developmental toxicity.
对人类中砷潜在发育毒性的评估必须完全基于大量的动物文献；目前尚无合适的人类数据。当怀孕的母鼠接触毒物时，砷在动物研究中的发育毒性危害识别因母体毒性和发育毒性同时出现而变得复杂。当前的监管指南要求，当母体毒性和发育毒性在相同或相似剂量下出现时，需要详细考虑发育毒性是继发于母体毒性还是代表一种独特的危害。在本综述中，这些原则被应用于可用于将无机砷识别为发育毒物的相对大量的动物研究数据库。得出的结论是，对于这种强效细胞毒性剂，母体毒性和发育毒性在相同剂量范围内出现，尽管根据所使用的终点可以确定不同的未观察到不良反应水平。基础科学文献中的各种证据表明，发育毒性并非继发于母体毒性。当前的监管指南未能定义解决母体毒性和发育毒性同时出现所带来困难的有效方法。
