Interaction of dithane M-45 (mancozeb) and lead acetate during a teratogenicity test in rats

The teratogenic effects of lead acetate (Trial 1) and the possible teratoge nic effect of this compound administered in combination with a fungicide co ntaining 80% mancozeb (Trial 2) were studied in rats. The test substances w ere administered by gavage on Days 6-15 of gestation. In Trial 1, five grou ps were treated with lead acetate administered at doses of 0.1, 0.5, 1.0, 1 0.0 and 1000.0 mg/kg body weight (bwkg), respectively. In Trial 2, lead ace tate was applied at doses of 0.1, 10.0 and 1000.0 mg/bwkg, respectively. In the latter case the dose of the pesticide was 750 mg/bwkg in all treated g roups. Lead acetate was not teratogenic after a single administration. Comb ined administration of lead acetate and mancozeb gave rise to the following toxic effects: average maternal weight decreased during pregnancy, the rat io of live fetuses decreased after the two lowest doses, and fetal mortalit y increased in the lowest and in the highest dose groups. The ratio of feta l resorption was higher in all the treated groups than in the control group . A significant decrease occurred in average fetal and placental weight in each treated group as compared to the control. Maternal toxicity was expres sed in paralysis of the hindlimbs in the two lowest dose groups. Maternal m ortality was between 16.7 and 23.3% at the three dose levels. Phocomelia an d hernia cerebri occurred as characteristic fetal developmental anomalies i n all the treated groups. It is concluded that the joint administration of lead acetate and a mancozeb-containing fungicide can cause maternal toxicit y, embryotoxicity and characteristic teratogenic effects.