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

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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.