Comparative teratogenicity of di-n-butyltin diacetate with n-butyltin trichloride in rats

Abstract

Teratological tests were conducted on di-n-butyltin diacetate (DBTA), and n-butyltin trichloride (MBTC). Pregnant Wistar rats were treated orally with DBTA at doses of 0, 1.7, 5.0, 10.0, and 15.0 mg/kg/day or with MBTC at doses of 0, 50, 100, 200, and 400 mg/kg/day during days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. Thymic atrophy of the pregnant rats was observed in a dose-dependent manner by DBTA treatment. The incidence of dead or resorbed fetuses and total resorption fetuses increased at the highest dose of DBTA. The incidence of fetuses with external malformations, such as cleft mandible, cleft lower lip, ankyloglossia (tongue-tie) and schistoglossia (cleft tongue), increased in a dose-dependent manner by DBTA treatment. The incidence of fetuses with skeletal malformations such as anomaly of mandibular fixation, fused ribs, fused cervical vertebral arches and fused thoracic vertebral arches also increased at 10.0 and 15.0 mg/kg. However, MBTC, one of the main metabolites of di-n-butyltin, failed to show any evidence of tetatogenic activity at any doses tested. The results indicate that DBTA has potent teratogenic effects on rat fetuses, and DBTA is different from MBTC with respect to teratogenic effects.

Maternal and Fetal Toxicity of Dimethyltin in Rats.

“…23) However, the severity of thymic atrophy caused by DMTC treatment was less than that caused by di-n-butyltin. The lowest doses exhibiting thymic atrophy were 15 mg/kg/day (68 µmol/kg/day) for DMTC and 5 mg/kg/day (14 µmol/kg/day) for di-n-butyltin.…”

“…The lowest doses exhibiting thymic atrophy were 15 mg/kg/day (68 µmol/kg/day) for DMTC and 5 mg/kg/day (14 µmol/kg/day) for di-n-butyltin. 23) Signs of neural damage or cerebral edema have been reported in rats treated with trimethyltin or triethyltin compounds, but not in DMTC-treatment rats. 31) In my preliminary study, however, more than seven consecutive treatments of DMTC caused tremor and aggression at a relatively high dose (30 mg/kg/day).…”

“…In these studies, oral dosing of DMTC resulted in thymic atrophy which was one of the most sensitive criterion for toxicity of di-n-butyltin, 23) tri-nbutyltin 29) and di-n-octyltin 30) but not mono-nbutyltin. 23) However, the severity of thymic atrophy caused by DMTC treatment was less than that caused by di-n-butyltin.…”

“…[21][22][23][24] However, it nevertheless remains important to evaluate the teratological effects of other disubstituted organotins such as dimethyltin. Noland et al 25) reported that dimethyltin dichloride (DMTC) administered orally to pregnant SpragueDawley rats was absorbed from the intestine and transferred across the placenta to the fetus.…”

n‐Butylzinnverbindungen [MAK Value Documentation in German language, 2008]

“…Trächtigkeitstag von bis zu 400 mg MBTC/kg KG und Tag keine signifikanten maternaltoxischen oder entwicklungstoxischen Wirkungen beobachtet (Noda et al 1992 . Es wurden keine vermehrten Missbildungen beobachtet.…”