Dose‐Response Carcinogenicity in Rats on Low‐dose Levels of N‐Ethyl‐N‐nitrosourethane

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Abstract
A dose‐response study on the carcinogenicity of N‐ethyl‐N‐nitrosourethane (ENUR) was undertaken to examine its effect at low doses. Six‐week‐old female F344 rats were divided into 5 groups, each consisting of 40 animals. ENUR was dissolved in distilled water at dose levels of 0 (control), 0.15, 0.6, 2.5 and 10 ppm, and rats were given these solutions ad libitum for 2 years. Significant increase of the total tumor incidences and shortening of the mean survival times were observed in groups given 2.5 and 10 ppm ENUR. In groups given 0.6 ppm or more ENUR, digestive tract tumors were induced dose‐dependently. They were restricted to the upper digestive tract from the oral cavity to the forestomach, and were histologically squamous cell papillomas or carcinomas. Dose‐related differences in the location and incidence of these tumors were found. The virtually safe doses (VSDs) calculated by using the Weibull, Logit and Probit models were 0.365 × 10‐2, 0.110 × 10‐1 and 0.779 × 10‐1 ppm, respectively. The VSDs estimated in the present study are discussed in comparison with those of other carcinogens.