Teratogenic evaluation of 1,1,3,3-tetrabutylurea in the rat following dermal exposure.

The teratogenic potential of 1,1,3,3-tetrabutylurea (TBU) was evaluated in the Crl:CD(SD)BR rat. Doses of 25, 50 or 100 mg TBU/rat/day in 0.5 ml dimethyl phthalate were applied to the shaven dorsal skin on days 6-15 of gestation, the day on which a sperm-positive vaginal smear was present being designated day 1. The rats were killed 1 day before natural delivery and the foetuses were examined for external development, structure and integrity of internal tissues and organs, and skeletal development. No maternal effects were seen in rats exposed to 25 mg TBU, but skin irritation and a reduction in maternal body-weight gains were seen in rats treated with either 50 or 100 mg/day, the effects being more pronounced in the 100-mg/day group. In the latter group, the number of pregnancies maintained was reduced and the number of resorptions per litter, calculated only on the litters with resorptions, was increased. Foetuses derived from the females treated with 100 mg/day were slightly smaller than the controls but were structurally normal. The outcome of pregnancy was unaltered in rats given either 25 or 50 mg TBU/day. No increase in malformed foetuses was observed in any of the test groups. Under the conditions of this study, TBU was not teratogenic when applied dermally to rats at doses up to 100 mg/day.