Mantovani A, Ricciardi C, Macrì C, Stazi A V
Laboratorio di Tossicologia Comparata ed Ecotossicologia, Istituto Superiore di Sanità, Rome, Italy.
Ann Ist Super Sanita. 1993;29(1):47-55.
Hundreds of environmental chemicals affect prenatal development in experimental animals. However, only methylmercury and PCBs have been connected with such effects in humans during localized outbreaks of high exposure. In addition growth and development might also be affected by long-term intake of lead, fluorides or PCBs. Several factors may explain the discrepancy between human and animal data: the actual exposure of the population is below threshold levels, unspecific or delayed effects can be difficult to identify, etc. When experimental data are used to assess the hazards for the conceptus, due consideration should be given to actual ability of the study to detect effects. Thus, the limitations in statistical power, the relevance of the parameters considered and low-dose extrapolation should be taken into account. Finally, understanding toxicokinetics and biological mechanisms is needed to perform interspecies comparisons. Three examples of environmental chemicals showing different prenatal hazards are presented: thiabendazole, a benzimidazole compound with a moderate teratogenic potential, but which could represent a good model for biological extrapolation; nitrofen, a diphenyl ether herbicide which may pose a significant hazard, because of its high potential, toxicokinetics, and specific, hormone-like, teratogenic mechanisms; PCBs, well-known, global, cumulative pollutants which are not teratogenic in the laboratory animals, but may affect the human conceptus at high intake levels.
数百种环境化学物质会影响实验动物的产前发育。然而，在高暴露的局部疫情期间，只有甲基汞和多氯联苯与人类的此类影响有关。此外，长期摄入铅、氟化物或多氯联苯也可能影响生长发育。有几个因素可以解释人类和动物数据之间的差异：人群的实际暴露低于阈值水平、非特异性或延迟效应可能难以识别等。当使用实验数据评估对胎儿的危害时，应适当考虑研究检测效应的实际能力。因此，应考虑统计功效的局限性、所考虑参数的相关性以及低剂量外推。最后，进行种间比较需要了解毒代动力学和生物学机制。本文介绍了三种显示不同产前危害的环境化学物质的例子：噻苯达唑，一种具有中等致畸潜力的苯并咪唑化合物，但它可能是生物学外推的良好模型；除草醚，一种二苯醚除草剂，由于其高潜力、毒代动力学以及特定的、类似激素的致畸机制，可能构成重大危害；多氯联苯，一种众所周知的全球性累积污染物，在实验动物中不具有致畸性，但在高摄入量时可能会影响人类胎儿。
