げっ歯類を用いる小核試験の基礎研究ならびにその行政面への応用

Abstract

Genotoxicity is an important consideration in the safety evaluation of chemicals. It is well known that there are in vitro and in vivo assay systems with different endpoints for evaluating chemical genotoxicity. 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 from the viewpoint of weight of evidence. There are several in vivo assay systems that have been developed and which are based on various 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 a positive result in the in vitro chromosome aberration test but were negative in the rodent micronucleus test. In such case, as a rule, the in vivo negativity is considered dominant to the in vitro positivity.It is important and necessary to reduce use of test animals without any loss of evaluation accuracy. In the micronucleus test, development of the method using peripheral blood instead of bone marrow cells succeeded in reducing the total number of animals required for chromosomal aberration evaluation in vivo. Sampling of very small amounts of blood can be done without killing animals, which is one of the most important advantages of the method; it also permits combining with other assays for different endpoints that require different optimal sampling times. Based on this development, in vivo multiple endpoint assay systems will be realized and will lead to further reduction of animal use for the evaluation of chemical genotoxicity. In this manuscript, I describe the history of development and applications of the peripheral blood micronucleus assay.