Grant L D
Environ Health Perspect. 1976 Dec;18:85-94. doi: 10.1289/ehp.761885.
Several compelling aruguments have been advanced in support of expanding the use of "behavioral teratology" evaluations as routine components of toxicologic screening procedures. As a basis for development of effective behavioral teratology screening approaches, a conceptual framework is presented which interrelates: (1) changes in relative functional brain capacity with age, (2) possible times and durations of exposures to environmental insults, and (3) various types of toxicity testing procedures carried out at appropriate time points in relation to different exposure period. Within the context, several research strategies for behavioral teratology studies are concisely posed and evaluated. These include: (1) clinical hypothesis testing, where particular effect(s) of a given agent are evaluated based on hypotheses derived from clinical or epidemiological observations; (2) comprehensive screening approaches, where multifaceted, long-term longitudinal neurobehavioral evaluations are employed to assess whether any of a large number of possible deletarious effects are exerted by an agent and at what threshold exposure levels; (3) alternative screening heuristics, by which adequate assessments of neurobehavioral toxicity of various agents may be accomplished without completion of more exhaustive, but also more expensive and time-consuming comprehensive screening protocols.
已经提出了几个令人信服的论据来支持扩大“行为致畸学”评估的应用范围,使其成为毒理学筛查程序的常规组成部分。作为开发有效的行为致畸学筛查方法的基础,本文提出了一个概念框架,该框架将以下内容相互关联起来:(1)相对功能性脑容量随年龄的变化;(2)暴露于环境损害的可能时间和持续时间;(3)在与不同暴露期相关的适当时间点进行的各种毒性测试程序。在此背景下,简要提出并评估了行为致畸学研究的几种研究策略。这些策略包括:(1)临床假设检验,即根据从临床或流行病学观察得出的假设,评估特定药物的特定效应;(2)综合筛查方法,即采用多方面、长期的纵向神经行为评估,以评估一种药物是否会产生大量可能的有害效应以及在何种暴露阈值水平下产生这些效应;(3)替代筛查启发法,通过这种方法,可以在不完成更详尽但也更昂贵和耗时的综合筛查方案的情况下,对各种药物的神经行为毒性进行充分评估。