A dose-response study on urethane carcinogenesis in rats and mice.
Sprague-Dawley rats and NMRI mice were treated with urethane in the drinking water for 2 years. In both species the daily doses were: 100, 500, 2,500, and 12,500 mug/kg. The frequency of animals with malignancies increased steadily with increasing doses, beginning from 500 mug/kg/day for rats, and from 100 mug/kg/day for mice. To evaluate the possible cancer risk for man due to urethane in beverages, the observed response rates were used to extrapolate responses at lower doses. At a daily dose of 0.14 mug/kg/day (corresponding to daily consumption of a beverage with 10 ppb urethane by a 70-kg man) the upper risk limits were estimated to be 3.2 in 100,000 for rats, and 470 in 100,000 for mice (modified Mantel-Bryan procedure). Problems in calculating a possible cancer risk for man on the basis of animal observations are discussed. Since treatment of beverages with diethyldicarbonate leads to the formation of urethane, and since a cancer risk to man from urethane cannot be excluded, replacement of diethyldicarbonate by a toxicologically unobjectionale compound is called for.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000401:mortality; D051381:Rats; D012737:Sex Factors; D014520:Urethane / Q000008:administration & dosage
D014520:Urethane