The heterozygous p53 knockout mouse model was used to assess whether vascular
tumors noted in a 2-year carcinogenicity study in CD-1 mice with
carbaryl were induced through a genotoxic mechanism. This knockout mouse model was selected for
carbaryl because of the high sensitivity of this model to genotoxic events and its low spontaneous incidence of
tumors until 9-12 months of age.
Carbaryl was administered continuously via the diet to groups of 20 male heterozygous p53 knockout mice at concentrations of 0, 10, 30, 100, 300, 1000 and 4000 ppm for 180 days. Histopathological examinations revealed no evidence of
carbaryl-induced
neoplasms of any type. In particular, no neoplastic or preneoplastic changes were noted in the vascular tissue of any of the organs examined. Only
neoplasms, recognized as those that occur spontaneously in untreated mice of this strain, were sporadically observed in a few animals from the intermediate dose groups with no evidence of a dose- or treatment-related effect. Therefore, under the conditions of this study, the no-observed-effect level (NOEL) of
carbaryl for neoplastic changes in male mice was 4000 ppm (around 716 mg/kg
body weight/day). We conclude: (1)
carbaryl does not appear to be a genotoxic
carcinogen at least in male mice; (2) if the vascular
tumors observed in the CD-1 mice are treatment-related, they could have been induced by a non-genotoxic mechanism; (3) the response in transgenic animals may provide useful complementary results to better assess
carbaryl's potential genotoxic hazard to humans.