title: Oral (gavage), in utero and postnatal exposure of Sprague-Dawley rats to low doses of tributyltin chloride. Part 1: Toxicology, histopathology and clinical chemistry.
abstract: Tributyltin (TBT) is a biocide that contaminates foods, especially shellfish. TBT is an endocrine disrupter in several marine species and is neurotoxic and immunotoxic in mammals. We have examined the effects of exposure to low doses of tributyltin chloride (TBTC) from day 8 of gestation until adulthood. Pregnant rats were gavaged daily with 0, 0.025, 0.25 or 2.5 mg TBTC/kg body weight from day 8 of gestation until weaning. Stomach contents of suckling pups contained undetectable levels of TBT and dibutyltin (DBT) levels were detectable only in the highest TBTC dose used, indicating negligible lactational transfer to pups. Post weaning, pups were gavaged daily with the same dose of TBTC administered to their mothers and sacrificed on post-natal days (PND) 30 (males and females), 60 (females) and 90 (males). TBTC had no effects on dams' body weights, food consumption, litter size, sex ratio or survival of pups to weaning. However, all doses of TBTC significantly affected parameters of the growth profile of the pups (mean body weights, average slope, curvature) and the ratio of weekly food consumption to weekly body weight gain indicated enhanced food conversion to body mass in females but a decreased conversion in males. Liver, spleen and thymus weights were also affected by TBTC. In male pups dosed at 2.5 mg/kg/day, reduced serum thyroxine levels were evident, indicating that the thyroid is a target for TBTC toxicity. No histopathological lesions were seen in the liver but elevated serum alanine aminotransferase, gamma-glutamyl transferase and amylase indicated hepatotoxicity. Significant decreases in liver weights in female pups exposed to 0.025 mg/kg/day TBTC were observed at PND 60. Decreases in spleen and thymus weights also pointed towards toxic effects of TBTC on the immune system. The 0.025 mg/kg/day TBTC should have been a no affect dose and yet this dose caused significant effects on growth profiles, decreased liver weights and elevated serum GGT levels in females.
authors.affiliation: Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, Tunney's Pasture, Ottawa, Ontario K1A 0L2, Canada. gerard_cooke@hc-sc.gc.ca
authors.forename: G M
authors.initials: GM
authors.lastname: Cooke
authors.forename: H
authors.initials: H
authors.lastname: Tryphonas
authors.forename: O
authors.initials: O
authors.lastname: Pulido
authors.forename: D
authors.initials: D
authors.lastname: Caldwell
authors.forename: G S
authors.initials: GS
authors.lastname: Bondy
authors.forename: D
authors.initials: D
authors.lastname: Forsyth
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005506:Food Contamination; D007441:Intubation, Gastrointestinal; D008098:Litter Size / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014220:Trialkyltin Compounds; C011559:tributyltin