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Effects of in utero tributyltin chloride exposure in the rat on pregnancy outcome.
- Source :
-
Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2003 Aug; Vol. 74 (2), pp. 407-15. Date of Electronic Publication: 2003 May 28. - Publication Year :
- 2003
-
Abstract
- 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, was 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 (GD) 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 (< or =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 GD 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.
- Subjects :
- Administration, Oral
Anal Canal abnormalities
Anal Canal drug effects
Animals
Dose-Response Relationship, Drug
Embryo Implantation drug effects
Embryonic and Fetal Development drug effects
Environmental Pollutants administration & dosage
Environmental Pollutants pharmacokinetics
Female
Genitalia, Male abnormalities
Genitalia, Male drug effects
Litter Size drug effects
Male
Pregnancy blood
Rats
Rats, Sprague-Dawley
Sex Characteristics
Sternum abnormalities
Sternum drug effects
Thyroxine blood
Trialkyltin Compounds administration & dosage
Trialkyltin Compounds blood
Trialkyltin Compounds pharmacokinetics
Triiodothyronine blood
Weight Gain drug effects
Environmental Pollutants toxicity
Maternal Exposure adverse effects
Reproduction drug effects
Trialkyltin Compounds toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1096-6080
- Volume :
- 74
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicological sciences : an official journal of the Society of Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 12773765
- Full Text :
- https://doi.org/10.1093/toxsci/kfg131