Developmental toxicology of trimethyltin in the rat

Pregnant rats were treated on either gestational day (GD) 7, 12, or 17 with single doses of trimethyltin chloride (TMT) ip at either 0, 5, 7, or 9 mg/kg. A significant effect of dose was manifest as decreased maternal weight at term, which persisted during lactation until postnatal day (PND) 15 in some groups. For all treatments combined, term weights of dams exposed on GDs 7 and 12 were greater than those treated on GD 17. Litter sizes were decreased for groups treated on GD 17 with 9 mg/kg TMT. Pups treated in utero and exhibiting treatment-induced decreases in weight at or near birth remained smaller than untreated animals into adulthood (PND 280). By PND 20, weights of pups treated on GD 7 greater than GD 12 greater than GD 17. Neuropathology of pups sacrificed on PND 1 was minimal in all animals with lesions only identified in animals treated on GDs 12 or 17 which consisted of subtle degenerative changes in the CA3 and CA4 regions of Ammon's horn of the hippocampus. Muscarinic cholinergic receptor binding in whole brains from pups on PND 1 did not show any significant changes compared to controls for any dose or day of exposure. These data indicate that prenatal TMT exposure results in postnatal toxicity in treated pups but only in the presence of maternal toxicity.