Toxicology and carcinogensis. Studies of urethane, ethanol, and urethane/ethanol (urethane, CAS No. 51-79-6; ethanol, CAS No. 64-17-5) in B6C3F1 mice (drinking water studies).
BACKGROUND
Urethane occurs naturally as a by-product of fermentation. The main exposure of humans to urethane is from drinking alcoholic beverages. The International Agency for Research on Cancer has determined that consumption of alcoholic beverages is clearly linked to certain cancers in humans. We studied mixtures of urethane and ethanol (alcohol) to determine if urethane, alone or in combination with ethanol, caused cancer in mice.


METHODS
We gave groups of 48 male and female mice drinking water containing combinations of urethane (0, 10, 30, or 90) and other ethanol (0%, 2.5%, or 5%) for two years. Tissues from more than 40 sites were examined for every animal.


RESULTS
Ther were more deaths and lower body weights in groups of animals exposed to higher concentrations of urethane. Higher concentrations of urethane increased the rates of cancer of the liver, lung, harderian gland, and of hemangiosarcomas in both male and female mice. Urethane also increased the rates of cancer of the skin and forestomach in male mice and of the mammary gland and ovary in female mice. There were also small increases in the occurrence of hemangiosarcoma in the spleen in male mice and in the uterus and skin of female mice.


CONCLUSIONS
We conclude that urethane caused cancer at several sites in male and female mice. It was not possible to determine from this study whether ethanol alone caused cancer in mice, and there was weak evidence that ethanol may have affected the carcinogenicity of urethane, slightly lowering the incidence of lung and harderian gland tumors in male mice and increasing the incidence of heart and lung tumors in female mice.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D018736:DNA Adducts / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D012997:Solvents / Q000633:toxicity*; D016019:Survival Analysis; D014520:Urethane / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply
D002273:Carcinogens; D018736:DNA Adducts; D012997:Solvents; D014874:Water Pollutants, Chemical; D014520:Urethane; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System