Comparative developmental toxicity of triethyltin using split‐litter and whole‐litter dosing

Abstract

Previous work suggested that toxicity resulting from acute postnatal administration of triethyltin (TET) was influenced by the treatment condition of rat littermates. To test this possibility, 2 dosing models were compared. For the split-litter model (20 litters/dose), 1 male and 1 female pup/litter received a single dose of 0 (saline), 3, 6 or 9 mg TET/kg on postnatal day 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 (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 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. Developmental toxicity produced by TET was not primarily determined by the dosing regimen.