Assessment of the developmental and reproductive toxicity of diiodomethyl-p-tolylsulfone in rats and rabbits

Diiodomethyl-p-tolylsulfone (DIMPTS) was tested in developmental toxicity (DT) and reproductive toxicity studies. In the rat DT study, DIMPTS was administered at 0, 100, 300 or 1000 mg/kg/day. Maternal toxicity as evidenced by reductions in body weight gain or feed consumption at 1000 and, to a lesser extent, 300 mg/kg/day. The only developmental effect was umbilical hernia at 1000 mg/kg/day; therefore, NOELs for maternal and developmental toxicity were 100 and 300 mg/kg/day, respectively. In the rabbit DT study, NZW rabbits were gavaged with 0, 0.05, 0.5 and 2 mg/kg/day DIMPTS. The NOEL for maternal toxicity was 0.5 mg/kg/day, based on thyroid weight increase with histopathology. There were no observed developmental effects. In the two-generation study, CD rats were fed 0, 2.5, 10 or 40 mg/kg/day DIMPTS. Increased thyroid weight and histopathology were observed at all doses with associated pituitary findings in males. Reproductive toxicity at 40 mg/kg/day consisted of increased postimplantation loss, decreased gestation survival and two cases of dystocia, while litter size, pup survival/weight were affected at 10 and 40 mg/kg/day. The NOEL for parental toxicity could not be determined, while the NOEL for reproductive toxicity was 2.5 mg/kg/day. The maternal thyroid and reproductive effects in this study were consistent with iodine toxicity.

► DIMPTS tested in developmental toxicity (DT) and reproductive toxicity (RT) studies. ► Rat/rabbit DT: maternal NOEL 300/0.5 mkd; DT NOEL 1000 mkd/no effects. ► 2-Gen rat: parental NOEL: not determined, effects at all levels. ► RT: NOEL for reproductive toxicity was 2.5 mg/kg/day; dystocia and effects on survival. ► Maternal thyroid and reproductive effects consistent with iodine toxicity.