Middaugh Lawrence D, Dow-Edwards Diana, Li Abby A, Sandler J David, Seed Jennifer, Sheets Larry P, Shuey Dana L, Slikker William, Weisenburger Walter P, Wise L David, Selwyn Murray R
Department of Psychiatry and Behavioral Science, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Toxicol Sci. 2003 Dec;76(2):250-61. doi: 10.1093/toxsci/kfg211. Epub 2003 Aug 12.
This report describes the results of a survey designed to evaluate the contribution of F1 neurobehavioral testing to hazard identification and characterization in safety assessment studies. (To review the details of the distributed survey, please see the supplementary data for this article on the journal's Web site.) The survey provided information about studies completed in industrial laboratories in the United States, Europe, and Japan since 1990 on 174 compounds. The types of compounds included were pharmaceutical (81%), agricultural (7%), industrial (1%), or were undefined (10%). Information collected included the intended use of the test agent, general study design and methodology, the types and characteristics of F1 behavioral evaluations, and the frequency with which agents affected neurobehavioral parameters in comparison to other F0 and F1 generation parameters. F1 general toxicology parameters such as mortality, pre- and postweaning body weight, and food intake were assessed in most studies and were affected more frequently than other parameters by the test agents. F1 behavioral parameters were assessed less consistently across studies, and were less frequently affected by the agents tested. Although affected by agents less often than general toxicology parameters, F1 behavioral parameters along with other parameters defined the no-observed-effect level (NOEL) in 17/113 (15%) of studies and solely defined the NOEL in 3/113 (2.6%) of studies. Thus, F1 behavioral parameters sometimes improved on the standard toxicological measures of hazard identification. While not detecting agent effects as readily as some measures, the F1 behavioral parameters provide information about agent effects on specialized functions of developing offspring not provided by other standard measures of toxicity. The survey results emphasize the need for further research into the methods of behavioral assessment as well as the mechanisms underlying the neurobehavioral alterations.
本报告描述了一项调查结果，该调查旨在评估F1神经行为测试在安全评估研究中对危害识别和特征描述的贡献。（如需查看分布式调查的详细信息，请参阅该期刊网站上本文的补充数据。）该调查提供了自1990年以来在美国、欧洲和日本的工业实验室中完成的关于174种化合物的研究信息。所包括的化合物类型有药物类（81%）、农业类（7%）、工业类（1%）或未明确分类的（10%）。收集的信息包括受试物的预期用途、一般研究设计和方法、F1行为评估的类型和特征，以及与其他F0和F1代参数相比，受试物影响神经行为参数的频率。在大多数研究中评估了F1一般毒理学参数，如死亡率、断奶前后体重和食物摄入量，且这些参数比其他参数更频繁地受到受试物影响。F1行为参数在各研究中的评估一致性较差，且较少受到受试物影响。尽管F1行为参数受受试物影响的频率低于一般毒理学参数，但在113项研究中的17项（15%）中，F1行为参数与其他参数共同确定了未观察到效应水平（NOEL），在113项研究中的3项（2.6%）中，F1行为参数单独确定了NOEL。因此，F1行为参数有时能改进危害识别的标准毒理学测量方法。虽然F1行为参数不像某些测量方法那样容易检测到受试物的影响，但它能提供关于受试物对发育中后代特殊功能影响的信息，而这是其他标准毒性测量方法所不能提供的。调查结果强调需要进一步研究行为评估方法以及神经行为改变的潜在机制。
