URINE MUTAGENICITY AND BIOCHEMICAL EFFECTS OF THE DRINKING-WATER MUTAGEN, CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2[5H]-FURANONE (MX), FOLLOWING REPEATED ORAL-ADMINISTRATION TO MICE AND RATS

Mutagenicity analysis of urine from rats treated by oral gavage with M X at a dose of 64 mg/kg for 14 days revealed that only 0.3% of the adm inistered compound was excreted in a genotoxically active form. At low er doses, mutagenicity was not detectable. No evidence of micronucleus induction in peripheral blood erythrocytes was observed in mice treat ed similarly. These findings indicate that MX is extensively detoxifie d in vivo and is unlikely to cause genetic damage in systemic tissues except at relatively high doses where detoxification pathways become s aturated. In a separate experiment, significant depressions were obser ved in D-glucaric acid and thioether excretion and in levels of severa l liver enzymes involved in xenobiotic metabolism, The mechanism for t hese metabolic alterations and their relevance to the in vivo metaboli sm of tine compound require further investigation.