Carcinogenicity of dapsone of mice and rats

Abstract

Dapsone (4,4'-diamino-diphenyl sulfone) has been tested for possible carcinogenicity in long-term animal experiments. BDIV rats and C₇ Bl mice received a 3.5% aqueous suspension of dapsone by intragastric intubation. Treatment was started in pregnant females during the last part of pregnancy, continued during lactation, then given to the offspring after weaning, five times a week for 104 weeks. The dose administered was 100 mg/kg to both rats and mice; total doses ranged from 10-16 g per rat and 1.2-1.4 g per mouse. Separate groups of animals received a combined treatment of dapsone with urethane or benzo (alpha) pyrene, to investigate the possible additive or synergistic action of dapsone with known carcinogens, as well as the possible inhibiting effect of dapsone on carcinogenesis. Unusual tumors, viz. spleen sarcomas (related to severe fibrosis of the spleen) were detected in male rats, and higher morbidity from C-cell thyroid carcinomas was observed in treated rats of both sexes than in control rats. There was no evidence that dapsone can modify the action of other chemical carcinogens. It was noted that: (1) although the increase in the incidence of tumours in dapsone-treated animals over that observed in untreated controls is statistically significant, the increase is relatively low; (2) the tumours appeared after lifetime treatment with maximum tolerated doses; (3) in rats, spleen sarcomas were observed mostly in males; this may indicate a possible hormone-dependence of the observed carcinogenic effect. The present results therefore provide only limited evidence of carcinogenicity of dapsone in rats.