In mice administered urethane in drinking water, lung inflammation occurred in males and females that received 1,100 ppm or greater. In the urethane in drinking water study, all males administered 3,300 ppm died by Week 4, and all females administered 3,300 ppm died by Week 5. All mice administered 10,000 ppm urethane in either vehicle died by Week 3. Cardiomyopathy occurred in males and females that received 1,100 or 3,300 ppm urethane in drinking water and in females that received 3,300 ppm urethane in ethanol. A concentration of 1,100 ppm urethane in either drinking water or ethanol effectively stopped estrous cycling.
Urethane is clearly genotoxic in vitro and in vivo .
In vitro , urethane induced mutations in Salmonella typhimurium strain TA1535 in the presence of liver S9 enzymes. However, no induction of chromosomal aberrations was observed in CHO cells treated with urethane, with or without S9. In vivo, urethane induced sex-linked recessive lethal mutations and reciprocal translocations in germ cells of adult male Drosophila melanogaster fed urethane. Significantly increased frequencies of micronucleated erythrocytes were observed in peripheral blood obtained from male and female mice after 45 days of exposure and in bone marrow and peripheral blood obtained after 13 weeks of exposure to urethane in drinking water. In summary, concentrations of 1,100 ppm urethane or greater in drinking water caused lymphoid and bone marrow cell depletion and hepatocellular lesions and increased the severity of nephropathy and cardiomyopathy in male and female rats.