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A dose‐response study on urethane carcinogenesis in rats and mice
Author(s) -
Schmähl D.,
Port R.,
Wahrendorf J.
Publication year - 1977
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910190111
Subject(s) - medicine , cancer , physiology , toxicology , zoology , biology
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 μg/kg. The frequency of animals with malignancies increased steadily with increasing doses, beginning from 500 μg/kg/day for rats, and from 100 μg/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 μg/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 unobjectionable compound is called for.