GENETIC TOXICITY TESTING IN RODENTS

该项目的目标是开发体内遗传 NTP环境毒理学计划（ETP）的毒性数据。 这项工作是通过内部研究计划和合同研究来实现的， 开发和测试程序。根据本合同获得的 招标将允许测试大约15种化学品， 对大鼠和/或小鼠体细胞遗传效应的5年耐受性。 要进行的测试将包括：骨骼中的染色体畸变（ABS） 骨髓和外周淋巴细胞;骨髓中的微核（MN）， 亚慢性研究（仅小鼠）的外周红细胞，以及其他 组织（例如，外周淋巴细胞，肺，脾）;着丝粒探针 各种组织的单细胞凝胶电泳分析; 以及转基因小鼠肝脏和其他组织中突变的测量 动物并非所有测试都将针对所有化学品进行。 测试的化学品将从那些已经过 亚慢性和慢性动物毒性和/或致癌性试验，或 建议进行此类测试，或NTP特别感兴趣。 从该合同中获得的结果将用于设置 长期动物试验的优先事项，并将提供信息， 作用机制，以支持解释长期动物 毒性结果。完成这些研究还将使 进一步开发ETP的遗传毒性数据库， 用于确定体内和体外之间的一致性水平 啮齿类动物遗传毒性试验及其体内结果的预测性 致癌作用

The objective of this project is the development of in vivo genetic toxicity data for the Environmental Toxicology Program (ETP) of the NTP. This work is achieved by in-house research programs and contract research, development, and testing programs. The contract obtained under this solicitation would allow for the testing of approximately 15 chemicals per bear for 5 years for somatic cell genetic effects in rats and/or mice. Tests to be performed will include: chromosome aberrations (ABS) in bone marrow and peripheral lymphocytes; micronuclei (MN) in bone marrow, peripheral erythrocytes from sub-chronic studies (mice only), and other tissues (e.g., peripheral lymphocytes, lung, spleen); centromeric probe analysis of MN; single-cell gel electrophoresis assays of various tissues; and measurement of mutations in liver and other tissues of transgenic animals. Not all tests will be performed on all chemicals. The chemicals tested will be selected from among those that have undergone subchronic and chronic animal toxicity and/or carcinogenicity testing, or that are proposed for such testing, or are of special interest to the NTP. The results obtained from this contract will be used for setting priorities for long-term animal testing, and will provide information on mechanisms of action to support the interpretations of long-term animal toxicity results. Completion of these studies will also allow for the further development of the ETP's genetic toxicity database which will be used to determine the level of agreement between in vivo and in vitro genetic toxicity tests and the predictivity of in vivo results for rodent carcinogenesis.