Makris Susan L, Vorhees Charles V
U.S. Environmental Protection Agency, National Center for Environmental Assessment, 1200 Pennsylvania Ave., NW (8623P), Washington, DC 20460, United States.
Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, United States.
Neurotoxicol Teratol. 2015 Nov-Dec;52(Pt A):62-7. doi: 10.1016/j.ntt.2015.05.010. Epub 2015 Jun 3.
There are a variety of chemicals, including pharmaceuticals, that alter neurobehavior following developmental exposure and guidelines for the conduct of studies to detect such effects by statute in the United States and Europe. Guidelines for Developmental Neurotoxicity Testing (DNT) studies issued by the U.S. Environmental Protection Agency (EPA) under prevailing law and European Organization for Economic Cooperation and Development (OECD) recommendations to member countries provide that such studies include a series of neurobehavioral and neuropathological assessments. Among these are assessment of cognitive function, specifically learning and memory. After reviewing 69 DNT studies submitted to the EPA, tests of learning and memory were noted to have detected the lowest observed adverse effect level (LOAELs) less frequently than behavioral tests of locomotor activity and acoustic/auditory startle, but slightly more than for the developmental Functional Observational Battery (devFOB; which is less extensive than the full FOB), but the reasons for the lower LOAEL detection rate for learning and memory assessment could not be determined. A major concern identified in the review, however, was the adequacy of the methods employed in these studies rather than on the importance of learning and memory to the proper assessment of brain function. Accordingly, a symposium was conducted to consider how the guidelines for tests of learning and memory might be improved. Four laboratories with established histories investigating the effects of chemical exposures during development on learning, memory, and attention, were invited to review the topic and offer recommendations, both theoretical and practical, on approaches to improve the assessment of these vital CNS functions. Reviewers were asked to recommend methods that are grounded in functional importance to CNS integrity, well-validated, reliable, and amenable to the context of regulatory studies as well as to basic research on the underlying processes they measure. This Introduction sets the stage for the reviews by providing the background and regulatory context for improved tests for learning and memory in DNT and other regulatory studies, such as single- or multi-generational studies where similar methods are incorporated.
有多种化学物质，包括药物，在发育过程中接触后会改变神经行为，在美国和欧洲有相关法规规定了检测此类影响的研究开展指南。美国环境保护局（EPA）根据现行法律发布的发育神经毒性测试（DNT）研究指南以及经济合作与发展组织（OECD）向成员国提出的建议规定，此类研究应包括一系列神经行为和神经病理学评估。其中包括认知功能评估，特别是学习和记忆评估。在审查提交给EPA的69项DNT研究后发现，学习和记忆测试检测到最低观察到的有害作用水平（LOAELs）的频率低于运动活动和听觉惊吓行为测试，但略高于发育功能观察组合（devFOB；其范围比完整的FOB小），但无法确定学习和记忆评估中LOAEL检测率较低的原因。然而，审查中确定的一个主要问题是这些研究中所采用方法的充分性，而非学习和记忆对正确评估脑功能的重要性。因此，举办了一次研讨会来考虑如何改进学习和记忆测试指南。邀请了四个在研究发育过程中化学暴露对学习、记忆和注意力影响方面有着悠久历史的实验室来审查该主题，并就改进这些重要中枢神经系统功能评估的方法提出理论和实践建议。要求评审人员推荐基于对中枢神经系统完整性的功能重要性、经过充分验证、可靠且适用于监管研究背景以及对其所测量的潜在过程的基础研究背景的方法。本引言通过提供DNT及其他监管研究（如纳入类似方法的单代或多代研究）中改进学习和记忆测试的背景及监管背景，为这些综述奠定了基础。
