4-2) Quantitative evaluation on the genotoxic potency of chemicals

Two in vitro tests with different genetic end points, gene mutation and chromosomal damage, and an in vivo test, preferably the micronucleus test in mice, were recommended as a battery system for the primary assessment of genotoxic effects of chemicals. From our comparative studies on the mutagenic potency of chemicals, it was pointed out that results should be evaluated quantitatively rather than qualitatively, since the potency varies extensively, at range of 1O fold, among different chemicals, and the in vitro genotoxins relatively weak tend to be negative in in vivo mutagenicity tests as well as in carcinogenicity tests in rodents. New Salmonella tester strains, called YG-series, were established, which showed a high nitroreductase or acetyltransferase activity and specifically sensitive to nitroarens or aromatic anmines in the reverse mutation assays (Ames test). These strains could detect a small amount of mutagenic aromatic amines containing in the urine of cigarette smokers. A new technique in the micronucleus test using peripheral blood erythrocytes was introduced. A cumurative genotoxic effect of benzene, for an example, was detected in the peripheral blood even several weeks after treatment every week by gavage. A cyto-flowmetric analysis can be also applied to monitoring of such effects.