“Simulated gastric hydrolysis and developmental toxicity of dioctyltin bis(2-Ethylhexylthioglycolate) [DOTE] in rabbits and mice”

Abstract

Based on previous studies, dioctyltin dichloride [DOTC] was a putative toxophore for dioctyltin thioesters. Our results, generated with the use of 119Sn-NMR spectroscopy demonstrated that dioctyltin bis(2-ethylhexyl thioglycolate) [DOTE] hydrolyzed to form dioctyltin chloro-(2-ethylhexyl thioglycolate) [DOTCE] under simulated gastric conditions, but no DOTC was formed. DOTE was administered orally at 4, 20, and 80 mg/kg/day [GD6-GD28; rabbits] or at 15, 30, and 60 mg/kg/day [GD5-GD17; mice]. There were no maternal deaths, treatment-related statistically significant reductions in maternal body weight or weight gain, or adverse gestational outcomes in either species. Maternal thymus weight was significantly reduced in mice at 30 and 60 mg/kg. There were no effects on fetal growth, no dose-dependent pattern of external, visceral or skeletal malformations and no increase in anatomical variations in either species. We conclude that DOTE likely forms DOTCE, not DOTC, in the stomach and DOTE was not teratogenic or fetotoxic in rabbits or mice. The rabbit maternal NOAEL was 80 mg/kg/day. The rabbit developmental NOAEL was 80 mg/kg/day. The mouse maternal LOAEL was 30 mg/kg/day based on reduced thymus weight and a dose-dependent effect on maternal weight at 60 mg/kg. The mouse developmental NOAEL was 60 mg/kg bw/day, the high dose.