Stanton M E, Spear L P
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Neurotoxicol Teratol. 1990 May-Jun;12(3):261-7. doi: 10.1016/0892-0362(90)90097-v.
Assessment measures used in developmental neurotoxicology are reviewed for their comparability in humans and laboratory animals, and their ability to detect comparable adverse effects across species. Compounds used for these comparisons include: substances of abuse, anticonvulsant drugs, ethanol, methylmercury, lead, PCBs, and ionizing radiation. At the level of functional category (sensory, motivational, cognitive and motor function, and social behavior), close agreement was found across species for all neurotoxic agents reviewed, particularly at high exposure levels. This was true even though the specific end points used to assess these functions often varied substantially across species. In addition, it was found that: 1) the U.S. EPA Developmental Neurotoxicology Test Battery presented at the Workshop would have identified the hazard to humans of exposure to the above compounds, although it may have underestimated human risk in some cases; 2) assessment of developmental neurotoxicity should involve evaluation of all categories of function; 3) for most compounds reviewed, the neurotoxic effects of prenatal exposure cannot be attributed to maternal toxicity, and exposure at or just below the threshold for such toxicity is an appropriate upper level for developmental neurotoxicity testing; 4) maternal exposure during the postnatal period poses a number of serious methodological problems; and 5) animal studies would better parallel human studies if more emphasis was placed on evaluation during development.
对发育神经毒理学中使用的评估方法进行了审查,以评估其在人类和实验动物中的可比性,以及检测不同物种间可比不良反应的能力。用于这些比较的化合物包括:滥用物质、抗惊厥药物、乙醇、甲基汞、铅、多氯联苯和电离辐射。在功能类别(感觉、动机、认知和运动功能以及社会行为)层面,在所审查的所有神经毒剂中,不同物种间都存在密切一致性,尤其是在高暴露水平下。即便用于评估这些功能的具体终点在不同物种间往往差异很大,情况也是如此。此外,研究发现:1)研讨会上介绍的美国环境保护局发育神经毒理学测试组合本可识别出人类接触上述化合物的危害,尽管在某些情况下可能低估了人类风险;2)发育神经毒性评估应涉及对所有功能类别的评估;3)对于所审查的大多数化合物,产前接触的神经毒性作用不能归因于母体毒性,处于或略低于此类毒性阈值的暴露水平是发育神经毒性测试的合适上限;4)产后母体接触会带来一些严重的方法学问题;5)如果在发育过程中更加强调评估,动物研究将能更好地与人体研究相平行。