[Evaluation of in vivo genotoxicity of chemicals--development and application of rodent micronucleus assay].

Abstract

Genotoxicity tests play an important role for the safety evaluation of chemicals. It is well known that there are in vitro and in vivo assay systems for evaluation of chemical genotoxicity on different endpoints. Bacterial gene mutation test and chromosomal aberrations test using mammalian cultured cells are representative examples. It is apparent that there are limitations of in vitro assay systems for chemical safety evaluation and risk assessment for human health and in vivo assay systems are becoming more important in the view point of weight of evidence. There are several in vivo assay systems have been developed and used for different endpoints. Among these, the rodent micronucleus test using hematopoietic cells has been most widely and frequently used to detect induction of chromosomal aberration. It is evident that there are chemicals that gave positive result in the in vitro chromosome aberration test but negative in the rodent micronucleus test. In such case, as a rule, the in vivo negativity is dominant to in vitro positivity. It is important and necessary to reduce animals without any loss of accuracy. In the micronucleus test, the development of the method using peripheral blood instead of bone marrow cells succeeded to reduce total number of animals for chromosomal aberration evaluation in vivo. Tiny amount of blood sampling can be done without killing animals, which is one of the most important advantages of the method, also permits to combine other assays for different endpoints that require different optimal sampling times. Based on this development, in vivo multiple endpoint assay system will be realized and lead more reduction of animals for evaluation of chemical genotoxicity. In this manuscript, We describe the history of development and applications of the peripheral blood micronucleus assay.