GENOTOXICITY STUDIES WITH CHLOROETHANE

In a recent 2-year inhalation study with F344 rats and B6C3F1 mice con ducted as part of the U.S. National Toxicology Program (NTP, 1989), ch loroethane (ECl) at an exposure concentration of 15 000 ppm induced a high incidence of endometrial uterine carcinomas only in female mice b ut not in rats, leading to the conclusion of ''clear evidence of carci nogenicity'' for the mouse. In order to elucidate whether a genotoxic effect may be a critical factor for the carcinogenicity of ECl in the mouse, we have performed three genotoxicity tests: (1) in vitro HPRT t est with CHO cells according to a specially developed gas protocol, (2 ) in vivo/in vitro UDS with female B6C3F1 mice at an exposure concentr ation of 25000 ppm (6 h/day, 3 days), (3) in vivo micronucleus assay w ith male and female B6C3F1 mice exposed to 25000 ppm ECl according to the same schedule. In the in vitro HPRT test a mutagenic potential of ECl was detected in the presence as well as in the absence of S9 mix. In contrast, both in vivo test systems failed to detect any indication s of genotoxicity of chloroethane at an exposure concentration even hi gher than that of the NTP study. It is suggested that in vivo the geno toxic potential of ECl is so low that an assumed genotoxic damage is b elow the detection limit of the test systems used. This leads to the c onclusion that genotoxicity may not be a key factor in the induction o f the uterine carcinomas in the B6C3F1 mouse.