Goldey E S, Tilson H A, Crofton K M
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Neurotoxicol Teratol. 1995 May-Jun;17(3):313-32. doi: 10.1016/0892-0362(94)00073-m.
Current screening strategies for developmental neurotoxicants emphasize extensive behavioral and histological examination of the nervous system of maternally exposed offspring. In an ongoing effort to identify more rapid screening techniques which accurately predict developmental neurotoxicity, we conducted a literature review to investigate the suggestion that the Chernoff/Kavlock assay may adequately identify developmental neurotoxicants as well as developmental toxicants (58). We included information on a broad range of chemical classes including: pesticides, heavy metals, solvents, antiproliferative agents, and neuroactive drugs. For each chemical/agent, we recorded evidence of developmental neurotoxicity, teratological malformations of the nervous system, and associated information on the effects of that chemical on birth weight, growth, fetal viability, and/or neonatal survival (neonatal endpoints included in the Chernoff/Kavlock assay). Although complete Chernoff/Kavlock data were not always available, our results indicate that only 65% of developmental neurotoxicants affected at least one of the neonatal endpoints in the assay. Based on these results, we believe that reliance on the Chernoff/Kavlock assay as a primary developmental neurotoxicity screen could lead to a number of "false negatives" in hazard identification studies, and this assay should not be used to replace more comprehensive developmental neurotoxicity screening procedures.
目前针对发育神经毒物的筛查策略着重于对母体暴露后代的神经系统进行广泛的行为学和组织学检查。为了持续努力寻找能够准确预测发育神经毒性的更快速筛查技术,我们进行了一项文献综述,以研究切尔诺夫/卡夫洛克试验是否能够充分识别发育神经毒物以及发育毒物的建议(58)。我们纳入了关于广泛化学类别的信息,包括:农药、重金属、溶剂、抗增殖剂和神经活性药物。对于每种化学物质/制剂,我们记录了发育神经毒性的证据、神经系统的致畸性畸形,以及该化学物质对出生体重、生长、胎儿活力和/或新生儿存活的影响的相关信息(切尔诺夫/卡夫洛克试验中包括的新生儿终点)。尽管并非总能获得完整的切尔诺夫/卡夫洛克数据,但我们的结果表明,只有65%的发育神经毒物在试验中影响了至少一个新生儿终点。基于这些结果,我们认为,将切尔诺夫/卡夫洛克试验作为主要的发育神经毒性筛查方法可能会在危害识别研究中导致许多“假阴性”,并且该试验不应被用于替代更全面的发育神经毒性筛查程序。