title: Carcinogenesis Bioassay of Bisphenol A (CAS No. 80-05-7) in F344 Rats and B6C3F1 Mice (Feed Study).
abstract: A carcinogenesis bioassay of bisphenol A, an intermediate used in the manufacture of epoxy, polycarbonate, and polyester-styrene resins, was conducted by feeding diets containing 1,000 or 2,000 ppm of the test chemical to groups of 50 F344 rats of either sex, 1,000 or 5,000 ppm to groups of 50 male B6C3F1 mice, and 5,000 or 10,000 ppm to groups of 50 female B6C3F1 mice for 103 weeks. Groups of 50 rats and 50 mice of either sex served as controls. Mean body weights of rats of either sex and of high-and low-dose female mice and high-dose male mice were lower than those of the controls throughout the study. Since food consumption of dosed female rats was only 70% to 80% that of the controls throughout most of this study, reduced body weight gain was probably due to reduced food consumption. Food consumption by dosed male rats was 90% that of controls. Food consumption among all groups of mice appear to be similar. Leukemias occurred at increased incidences in dosed rats of both sexes. In male rats, the dose-related (13/50, 12/50, 23/50) trend was statistically significant (P=0.021) by a Cochran-Armitage test, but neither the trend nor the increase in the high-dose group was significant by life table analyses, which adjust for survival differences among groups. The increased incidences in dosed female rats were also not statistically significant (7/50, 13/50, 12/50). Interstitial-cell tumors of the testes occurred at statistically significant incidences in low- and high-dose male rats; however, since this lesion normally occurs at a high incidence in aging F344 male rats, the increased incidence observed in this study was not considered compound related (35/49, 48/50, 46/49). In male mice, there was an increased incidence of leukemias or lymphomas (2/49, 9/50, 5/50), but this increase was not statistically significant. A compound-related increased incidence of multinucleated giant hepatocytes was observed in male mice (1/49, 41/49, 41/50), but there was no increase of liver tumors in male mice. The marginally significant increase in leukemias in male rats, along with an increase (not statistically significant) in leukemias in female rats and a marginally significant increase in the combined incidence of lymphomas and leukemias in male mice, suggests that exposure to bisphenol A may be associated with increased cancers of the hematopoietic system. A statistically significant increase in interstitial-cell tumors of the testes in male rats was also suggestive of carcinogenesis, but was not considered to be convincing evidence of a compound-related effect because this lesion normally occurs at a high incidence in aging F344 rats. Under the conditions of this bioassay, there was no convincing evidence that bisphenol A was carcinogenic for F344 rats or B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Equivocal Female Rats: Equivocal Male Mice: Equivocal Female Mice: Negative Synonym: 4,4'-isopropylidenediphenol