ToxSci Advance Access published online on May 28, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg131
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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1 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6
* To whom correspondence should be addressed. E-mail: bhales{at}pharma.mcgill.ca.
Tributyltin, an organotin, is ubiquitous in the environment. The consumption of contaminated marine species leads to human dietary exposure to this compound. Tributyltin is an endocrine disruptor in many wildlife species and inhibits aromatase in mammalian placental and granulosa-like tumor cell lines. We investigated the effects of tributyltin chloride exposure on pregnancy outcome in the Sprague-Dawley rat. Timed pregnant rats were gavaged either with vehicle (olive oil) or tributyltin chloride (0.25, 2.5, 10 or 20 mg/kg) from days 0-19 or 8-19 of gestation. On gestational day 20, dams were sacrificed and pregnancy outcome was determined. Tributyltin and its metabolites (dibutyltin, monobutyltin) were measured in maternal blood by gas chromatography. Both tributyltin and dibutyltin were present in maternal blood at approximately equal concentrations, whereas monobutyltin contributed minimally to total organotins. Organotin concentrations increased in a dose-dependent pattern in dams, independent of the window of exposure. Tributyltin chloride administration significantly reduced maternal weight gain only at the highest dose (20 mg/kg); a significant increase in post-implantation loss and decreased litter sizes, in addition to decreased fetal weights, were observed in this group. Tributyltin chloride exposure did not result in external malformations nor was there a change in sex ratios. However, exposure to 0.25, 2.5 or 10 mg/kg tributyltin chloride from gestation days 0-19 resulted in a significant increase in normalized anogenital distances in male fetuses; exposure from days 8-19 had no effect. There was a dramatic increase in the incidence of low weight (
© 2003 Society of Toxicology
Reproductive and Developmental Toxicology
Effects of in Utero Tributyltin Chloride Exposure in the Rat on Pregnancy Outcome
2 Food Research Division, Health Products and Food Branch, Health Canada, Tunney's Pasture, Ottawa, Ontario K1A 0L2; Departments of Cellular and Molecular Medicine, Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario
3 Toxicology Research Division, Health Products and Food Branch, Health Canada, Tunney's Pasture, Ottawa, Ontario K1A 0L2; Departments of Cellular and Molecular Medicine, Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario
4 INRS-Institut Armand-Frappier, Université du Québec, 245 Hymus Boul., Pointe Claire, QC, H9R 1G6
5 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6; Department of Pediatrics, McGill University, Montreal, Quebec H3G 1Y6; Department of Human Genetics, McGill University, Montreal, Quebec H3G 1Y6
6 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6; Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec H3G 1Y6
Abstract 
0.75 of the mean) fetuses after exposure to 20 mg/kg tributyltin chloride. Delayed ossification of the fetal skeleton was observed after in utero exposure to either 10 mg/kg or 20 mg/kg tributyltin chloride. Serum thyroxine and triiodothyronine levels were reduced significantly in dams exposed to 10 and 20 mg/kg tributyltin chloride throughout gestation; in dams treated with tributyltin from gestation days 8-19, serum thyroxine concentrations, but not triiodothyronine, were significantly decreased at both the 2.5 and 10 mg/kg exposures. Thus, maternal thyroid hormone homeostasis may be important in mediating the developmental toxicity of organotins.
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