title: Organotin speciation and tissue distribution in rat dams, fetuses, and neonates following oral administration of tributyltin chloride.
abstract: Tributyltin (TBT) is a biocide that contaminates human foodstuffs, especially shellfish. TBT is an endocrine disrupter, producing imposex in several marine gastropods. Previous studies showed that oral dosing of rat dams with TBT chloride leads to abnormal fetal and postnatal development. In this study, the tissue distribution and speciation of organotins in tissues were examined in dams, fetuses, and neonates following dosing of rat dams commencing on gestational day (GD) 8 by oral gavage with TBT in olive oil at 0, 0.25, 2.5, or 10 mg/kg body weight (BW)/d. Dams' body weights were significantly reduced by the 10-mg/kg BW/d TBT treatment. At GD20, there were no significant effects of any TBT treatment on pup weights, litter size, sex ratio, or tissue weights. However, at postnatal day (PND) 6 and 12, neonatal pup weights were reduced by the 10-mg/kg BW/d TBT treatment but tissue weights were unaffected, except for the liver weight of female pups, which was reduced by the 10-mg/kg BW/d TBT treatment. Tissues harvested on GD20 and PND6 and PND12 were extracted for determination of organotins by gas chromatography-atomic emission detection (GC-AED). In most tissues, TBT and its metabolite dibutyltin (DBT) were evident but monobutyltin (MBT) was rarely measured above the detection limit. The livers and brains of fetuses contained TBT and DBT at levels that were approximately 50% of the equivalent tissues in the dams. Furthermore, these tissues appeared to preferentially absorb/retain organotins, since the concentrations were greater than were found for the total loading in whole pups. The placenta also contained relatively large quantities of TBT and DBT. Postnatally, the TBT levels in pups decreased markedly, a probable consequence of the extremely low levels of organotins in rat milk. However, DBT levels in pups livers and brains were maintained, probably due to metabolism of TBT to DBT. Similarly, while dams' spleens contained significant quantities of organotins, the pups' spleens contained smaller quantities, and these decreased rapidly between PND6 and PND12. These results show that organotins cross the placenta and accumulate in fetal tissues but that during lactation, the pups would receive minimal organotins through the milk and during this period, the levels of TBT in pups' tissues decreases rapidly. Consequently, fetuses would be at greater risk of the adverse effects of TBT, but due to the lack of transfer through milk, the risk would be reduced during the lactational period.
authors.affiliation: Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada. Gerard_Cooke@hc-sc.gc.ca
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Cooke
authors.forename: Don S
authors.initials: DS
authors.lastname: Forsyth
authors.forename: Genevieve S
authors.initials: GS
authors.lastname: Bondy
authors.forename: Romain
authors.initials: R
authors.lastname: Tachon
authors.forename: Brett
authors.initials: B
authors.lastname: Tague
authors.forename: Laurie
authors.initials: L
authors.lastname: Coady
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D008297:Male; D008892:Milk / Q000737:chemistry; D009947:Organotin Compounds / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D010920:Placenta; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014018:Tissue Distribution; D014220:Trialkyltin Compounds / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism* / Q000633:toxicity
chemical_list: D004785:Environmental Pollutants; D009947:Organotin Compounds; D014220:Trialkyltin Compounds; C011559:tributyltin