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water. Tumor specific incidence data are reported by Port (1985). Male and female NMRI mice and
Sprague-Dawley rats (40/sex/group) were exposed to urethane in drinking water from 8 weeks of age
for their lifetime such that the daily dose rate was 0, 0.1, 0.5, 2.5, or 12.5 mg/kg body weight. Animals
were given the appropriate dose in 20 ml drinking water. Animals were observed until their natural
death. Among mice, significant increases in tumor incidence (p < 0.1 by Fisher’s exact test) were found
for pulmonary adenoma in males (6/40, 9/40, 14/40 in the 0.5, 2.5, and 12.5 mg/kg dose groups,
respectively vs. 0/40 controls), and pulmonary adenoma (12/40 treated with 12.5 mg/kg urethane vs.
5/40 controls), pulmonary carcinoma (5/40 treated with 12.5 mg/kg urethane vs. 0/40 controls),
angiosarcoma of the liver (4/40 treated with 12.5 mg/kg urethane vs. 0/40 controls), and mammary
carcinoma (4/40 treated with 12.5 mg/kg urethane vs. 0/40 controls) in females. For each of these
tumor types, the trend toward increased incidence was found to be dose-related (p < 0.01 by Mantel-
Haenszel trend test). Among female rats, a significant increase in the incidence of mammary carcinoma
(1/40, 2/40, 9/40 in the 0.5, 2.5, and 12.5 mg/kg urethane dose groups, respectively vs. 0/40 in the 0.1
mg/kg urethane dose group, p = 0.0011) and the combined incidence of mammary adenoma and
carcinoma was found (2/40, 3/40, 4/40, 13/40 in the 0.1, 0.5, 2.5, and 12,5 mg/kg urethane dose
groups, respectively vs. 2/40 in the 0.1 mg/kg urethane dose group, p = 0.0016 by Fisher’s exact test).
The incidence data for the untreated control animals were lost. The trend was found to be dose-related
(p < 10 -4 by Mantel-Haenszel trend test).
Klein et al. (1962) treated 7-8 day old B6AF 1 /J mice (C57BL/6 female × A/J male) with 2.8 or 5.5
mg urethane in 0.05 ml 0.1% dioctylester of sodium sulfosuccinic acid by oral gavage 3 times per week
for 5 weeks. Control groups for the low-dose group included both males receiving vehicle only and
males receiving no treatment. Males and females receiving no treatment served as a control for the
high-dose group. Survivors of the treatment period comprised the study group and ranged from 39 to
57 animals. Survival in the treated groups was significantly lower than in controls. Among animals
receiving the higher dose of urethane, treated males had a higher incidence of leukemias (32/42 treated
vs. 0/38 vehicle controls, p = 10 -13 ; Fisher’s exact test), lung adenomas (42/42 treated vs. 10/38 vehicle
controls, p = 10 -12 ) and hepatoma (4/42 treated vs. 0/38 vehicle controls, p = 0.07) than animals
receiving vehicle alone. Among animals receiving the lower dose of urethane, males showed a higher
incidence of lung adenomas (40/41 treated vs. 3/40 untreated controls, p = 10 -17 ), hepatoma (23/41
treated vs. 0/40 untreated controls, p = 10 -8 ), and leukemias (19/41 treated vs. 0/40 untreated controls,
p = 10 -6 ) relative to untreated control animals. In the same dose group, females showed a higher
incidence of leukemias (16/40 treated vs. 1/57 controls, p = 10 -6 ) , lung adenomas (39/40 treated vs.
9/57 controls, p = 10 -6 ), hepatomas (5/40 treated vs. 0/57 controls, p = 0.01), and forestomach
papillomas (3/40 treated vs. 0/57 controls, p = 0.07) relative to untreated control animals.
Della Porta et al.(1963a) exposed 5 groups of male and female CTM mice to drinking water containing
0.4% urethane in several exposure scenarios ranging from a total exposure time of 5 to 15 days.
Effective group size was the number of survivors at 25 weeks for treated animals (range: 30-83 mice)
and survivors at 45 weeks for controls (88 males and 99 females). Among all exposed animals there
was a significant increase in the incidence of lung adenomas over control animals (p < 10 -8 ; Fisher’s
exact test). Among all exposed female mice, the incidence of lymphosarcoma was increased over
controls (p < 0.05). Among all exposed male mice, the incidence of reticulosarcoma was increased
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