Bioassay of pivalolactone for possible carcinogenicity.

The bioassay of pivalolactone for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. Pivalolactone in water was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species. The high and low dosages of pivalolactone utilized were, respectively, 300 and 150 mg/kg/day for rats and 150 and 75 mg/kg/day for mice. After a 103-week period of compound administration for rats and a 102-week period of compound administration for mice, rats were observed for 2 additional weeks and mice for 1 additional week. Twenty animals of each sex and species were placed on test as vehicle controls. There was no significant positive association between dosage and mortality for either rats or mice, and in both species, adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. Compound-related mean body weight depression was not observed in either sex of either species. In addition, no adverse clinical signs were observed among dosed mice. This evidence, plus the relatively fast decomposition of pivalolactone in water, suggests the possibility that the animals, and in particular the mice, may have been able to tolerate a higher dose. Statistically significant incidences of squamous-cell papillomas and squamous-cell carcinomas of the forestomach were observed in rats but not in mice. No other rare or unusual tumors were observed in either species. Under the conditions of this bioassay, pivalolactone was found to be carcinogenic to both male and female Fischer 344 rats, producing squamous-cell carcinomas and squamous-cell papillomas of the forestomach. This study provided no evidence for the carcinogenicity of pivalolactone in B6C3F1 mice of either sex.