Simulated gastric hydrolysis and developmental toxicity of dibutyltin bis(2‐ethylhexyl thioglycolate) in rats.

Previously, dibutyltin dichloride (DBTC) was the putative toxophore for dibutyltin bis‐alkyl and bis‐thio esters. Recent chemical and toxicological data on dioctyltin bis(2‐ethylhexyl thioglycolate) suggest the thioglycolate esters of alkyltins do not generate the dichloride toxophore. Our results, using 119Sn‐nuclear magnetic resonance (NMR) spectroscopy, demonstrated that dibutyltin bis(2‐ethylhexyl thioglycolate) (DBTE) is hydrolyzed to dibutyltin chloro‐(2‐ethylhexyl thioglycolate) (DBTEC) under simulated gastric conditions. No DBTC was detected. DBTE was administered orally to presumed‐pregnant Sprague–Dawley rats in a corn oil vehicle at 2.5, 8.5, and 25.0 mg/kg/day (Gestation Day 5 [GD5] through GD19). There were no maternal deaths, no treatment‐related statistically significant reductions in feed consumption, maternal body weight or weight gain, or adverse gestational outcomes. Maternal thymus weight was significantly reduced in rats at 25 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. Based on the obtained experimental data, it is concluded here that DBTE forms DBTEC, not DBTC, in the stomach, and DBTE was not teratogenic nor fetotoxic in rats, a species sensitive to DBTC. The maternal no‐observed‐adverse‐effect level (NOAEL) was 8.5 mg/kg/day, and the developmental NOAEL was 25 mg/kg/day, the high dose. The maternal LOAEL was 25 mg/kg/day based on reduced maternal thymus weight. Dibutyltin bis(2‐ethylhexyl thioglycolate) (DBTE) forms dibutyltin chloro‐(2‐ethylhexyl thioglycolate) (DBTEC) in gastric milieu, not dibutyltin dichloride (DBTC). Daily oral DBTE doses (2.5, 8.5, and 25.0 mg/kg/day [GD5–GD19]) reduced maternal thymus weight 25 mg/kg but produced no adverse gestational outcomes. We conclude DBTE metabolizes to DBTEC, not DBTC, in the stomach, and DBTE was not developmentally toxic in rats. Read‐across of DBTC developmental effects to DBTE is not justified. The maternal and developmental NOAEL for DBTE were 8.5 and 25 mg/kg/day, respectively. [ABSTRACT FROM AUTHOR]