GENETIC TOXICITY TESTING IN RODENTS

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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 contact obtained under this solicitation would allow for the testing of approximately 15 chemicals per year 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.