The toxicity of dapsone was evaluated in Swiss mice treated orally by gavage with 50, 100, and 200 mg of dapsone/kg/day. Male mice (10/group) were dosed from study day 5 until the day prior to sacrifice on study day 25. Prior to dosing (study days 0-4), the male mice were cohabited with a group of female mice (20/dose group), hereafter referred to as females. The sperm-positive female (b) mice were dosed on days 6 through 15 of gestation and sacrificed on scheduled day 4 or 5 of lactation. A second group of female mice (20/dose group), hereafter referred to as females (a), were dosed from study day 0 (100 and 200 mg/kg/day dose groups) or study day 2 (50 mg/kg/day dose group) throughout mating on study days 9 to 13 until the day prior to sacrifice on day 18 of gestation. Adult mice were evaluated for clinical signs, body weight, hematology, gross necropsy, histopathology evaluations, and organ/body weights and sperm function (males only). Offspring were evaluated for viability, external anomalies, and weight.
Male, female (a), and female (b) mice developed drug-related elevations in methemoglobin levels and reticulocyte counts, and marginal decreases in RBC, HGB, and HCT values. The alterations in the clinical pathology parameters were accompanied by a drug-related splenomegaly that consisted microscopically of hematopoietic cell proliferation and hemosiderin pigmentation. Clinical observations of neurotoxicity such as body jerks and hyperactivity were detected in male and female mice treated with 100 and 200 mg/kg/day. The no-observable-adverse-effect-level for developmental toxicity was 100 mg/kg/day, as dosages of 200 mg/kg/day increased the average number of resorptions per litter and gross fetal alterations. Dosages of 200 mg/kg/day also decreased the percentage of pregnant mice per group, and decreased fetal body weights and pup body weights on day 0 postpartum.