title: Bioassay of dapsone for possible carcinogenicity.
abstract: A bioassay of dapsone, 4,4'-sulfonyldianiline, for possible carcinogenicity was conducted by administering the test material in feed to Fischer 344 rats and B6C3F1 mice. Groups of 35 rats and 35 mice of each sex were administered dapsone at one of two doses, either 600 or 1,200 ppm for rats and either 500 or 1,000 ppm for mice. The rats and mice were treated for 78 weeks; the rats were then observed for 26-28 weeks, the mice for 28-30 weeks. Matched controls consisted of groups of 15 untreated rats and 14 untreated mice of each sex, pooled controls, used for statistical evaluation, consisted of the matched controls combined with 30 male and 30 female untreated rats and 29 male and 29 female untreated mice from similarly performed bioassays of two other test chemicals. All surviving rats were killed at 104-106 weeks, all surviving mice at 106-108 weeks. Treated rats and mice had lower mean body weights than the corresponding controls; when treatment was discontinued at week 78, both species showed some increase in body weight. Survival among rats was unaffected by treatment with dapsone; adequate numbers of animals survived for meaningful statistical analyses of the incidences of tumors. Dapsone did not adversely affect the survival of mice, as shown by the test for positive dose-related trend. Suppurative bronchopneumonia was found in some mice in all matched-control and treated groups. Several control males died early in the study, while survival of the other groups of mice was not affected until week 75. Among rats, mesenchymal tumors of the abdominal organs or peritoneal tissues occurred in 13/35 low-dose males and 22/33 high-dose males. None occurred among control males or among control or treated females. The most commonly occurring tumors were fibroma, fibrosarcoma, or sarcoma, NOS (not otherwise specified), of the spleen and the peritoneum. In male rats, these mesenchymal tumors of the spleen occurred in a statistically significant incidence in both treated groups (low-dose 6/34, P=0.006; high-dose 14/32, P<0.001) when compared with pooled controls. In the peritoneum, the incidences of these mesenchymal tumors were significant in both treated groups (low-dose 5/35, P=0.014; high-dose 6/33, P=0.005) when compared with the pooled controls. No tumors related to treatment were found in female rats. Among the mice, there were no tumors that could clearly be related to treatment. It is concluded that under the conditions of this bioassay, dapsone was not carcinogenic for female Fischer 344 rats or B6C3F1 mice of either sex. Dapsone was carcinogenic (sarcomagenic) for male Fischer 344 rats, causing mesenchymal tumors in the spleen and the peritoneum.