Comparative developmental toxicity of triethyltin using split-litter and whole-litter dosing.

Previous work in our laboratory suggested that toxicity resulting from acute postnatal administration of triethyltin (TET) was influenced by the treatment condition of littermates. To test this possibility, two dosing models were compared. For the split-litter model (N = 20 litters/dose), 1 male and 1 female pup per litter received a single dose of O (saline), 3, 6, or 9 mg TET/kg on postnatal d 5; the remaining 6 littermates were not injected. In the whole-litter model, all 8 littermates received 0, 3, 6, or 9 mg TET/kg (N = 5 litters/dose). Differences between dosing models were found for preweaning body weight and adult figure-eight maze activity. Body weights were reduced in all TET-dosed pups; for 3-mg/kg animals, the reduction in preweaning growth was more persistent for pups in the split-litter group. Motor activity in a figure-eight maze was increased in both 6- and 9-mg/kg animals; for the high dose, the increase in activity was greater for animals in the split-litter group. There were no differences between dosing models in mortality, brain weight, or postweaning body weight. Approximately 50% of the 9-mg/kg animals died; there was no treatment related mortality at lower doses. Adult body weight also remained decreased only in the 9-mg/kg animals. Brain weight was reduced for all TET dose groups. These results indicate that developmental toxicity produced by TET is not primarily determined by the dosing regimen.