Tilson H A
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Drug Metab Rev. 1996 Feb-May;28(1-2):121-39. doi: 10.3109/03602539608993995.
The U.S. EPA neurotoxicity risk assessment guidelines define neurotoxicity as the capacity of chemical, biological, or physical agents to cause an adverse functional or structural change in the peripheral or central nervous system. Chemical-induced changes in the structure or persistent changes in behavior, neurochemistry, or neurophysiology of the nervous system are regarded as neurotoxic effects. Reversible effects occurring at doses that could endanger performance in the workplace, are associated with a known neurotoxicological mechanism of action, covary with a known neurotoxicological effect, or are latent effects uncovered by pharmacological or environmental challenge, could be considered to be neurotoxic effects. It should also be noted that even if a chemical-induced change in neurobiological function or structure does not meet the criteria established for a neurotoxic effect, the alteration could still be considered as adverse and used in a regulatory decision. Adverse effects detected by neurobiological procedures should not, however, necessarily lead to the conclusion that the chemical is a neurotoxicant. At the present time,the default RfD uncertainty factor approach is used for neurotoxicological data. A number of other safety factor approaches and quantitation dose-response models have been proposed for evaluating neurotoxicological data. However, a very limited number of comparisons have been made between the RfD approach and alternatives. In summary, neurotoxicity is one of several noncancer and points currently being used by regulatory agencies. The effective utilization of neurobiological measures to assess chemical-induced changes in the structure and function of the nervous system depends on properly designed studies and elimination of potential confounding variables that obscure interpretation of data from toxicological studies.
美国环境保护局（EPA）的神经毒性风险评估指南将神经毒性定义为化学、生物或物理制剂导致外周或中枢神经系统出现不良功能或结构变化的能力。化学物质引起的神经系统结构变化或行为、神经化学或神经生理学的持续变化被视为神经毒性效应。在可能危及工作场所表现的剂量下出现的可逆效应，与已知的神经毒理学作用机制相关，与已知的神经毒理学效应共变，或通过药理学或环境挑战揭示的潜在效应，都可被视为神经毒性效应。还应注意的是，即使化学物质引起的神经生物学功能或结构变化不符合神经毒性效应的既定标准，这种改变仍可被视为不良效应并用于监管决策。然而，通过神经生物学程序检测到的不良效应不一定会得出该化学物质是神经毒物的结论。目前，默认的参考剂量（RfD）不确定性因子方法用于神经毒理学数据。已经提出了许多其他安全因子方法和定量剂量反应模型来评估神经毒理学数据。然而，在RfD方法与其他方法之间进行的比较非常有限。总之，神经毒性是监管机构目前使用的几种非癌症关注点之一。有效利用神经生物学措施来评估化学物质引起的神经系统结构和功能变化，取决于设计合理的研究以及消除可能混淆毒理学研究数据解释的潜在混杂变量。
