Yang R S, Rauckman E J
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Toxicology. 1987 Dec 1;47(1-2):15-34. doi: 10.1016/0300-483x(87)90158-2.
In cooperation with the Agency for Toxic Substances and Disease Registry, the National Toxicology Program is participating in a Public Health Service activity related to the Comprehensive Environmental Response, Compensation and Liability Act (Superfund Act) by conducting toxicology studies on chemicals found in high-priority hazardous waste sites and for which adequate toxicological data are not available. As part of this effort, a project on the toxicology of chemical mixtures of groundwater contaminants was initiated. The first study, centered on the health effects of groundwater contaminants, is at the contractual stage. Nineteen organic and six inorganic chemicals, selected from more than 1000 known groundwater contaminants, will be given in drinking water to Fischer 344 rats and B6C3F1 mice for 3 or 6 months. Controls and five dose levels, based on average concentrations (i.e., baseline level) of individual component chemicals, or 0.1-, 10-, or 1000-fold of the baseline level, will be used. Toxicological end points include mortality, clinical signs, water and food consumption, body and organ weights, clinical pathology analytes (e.g., hematology, clinical chemistry, and urinalysis), gross and histopathology, neurobehavioral tests, sperm morphology and vaginal cytology evaluations (SMVCE), and cytogenetics. This paper summarizes the rationale behind our experimental design and the factors one must consider when designing studies of complex chemical mixtures.
国家毒理学计划与有毒物质和疾病登记署合作，正通过对在高优先级危险废物场地发现且缺乏充分毒理学数据的化学物质进行毒理学研究，参与一项与《综合环境反应、赔偿和责任法》（超级基金法）相关的公共卫生服务活动。作为这项工作的一部分，启动了一个关于地下水污染物化学混合物毒理学的项目。第一项以地下水污染物健康影响为核心的研究正处于合同签订阶段。从1000多种已知的地下水污染物中挑选出的19种有机化学物质和6种无机化学物质，将以饮用水的形式给予Fischer 344大鼠和B6C3F1小鼠，为期3或6个月。将设置对照组以及基于各成分化学物质平均浓度（即基线水平）或基线水平的0.1倍、10倍或1000倍的五个剂量水平。毒理学终点包括死亡率、临床症状、水和食物消耗、体重和器官重量、临床病理学分析物（如血液学、临床化学和尿液分析）、大体和组织病理学、神经行为测试、精子形态和阴道细胞学评估（SMVCE）以及细胞遗传学。本文总结了我们实验设计背后的基本原理以及在设计复杂化学混合物研究时必须考虑的因素。
