title: Exposure to an environmentally relevant mixture of brominated flame retardants affects fetal development in Sprague-Dawley rats.
abstract: Brominated flame retardants are incorporated into a wide variety of consumer products and are known to enter into the surrounding environment, leading to human exposure. There is accumulating evidence that these compounds have adverse effects on reproduction and development in humans and animal models. Animal studies have generally characterized the outcome of exposure to a single technical mixture or congener. Here, we determined the impact of exposure of rats prior to mating and during gestation to a mixture representative of congener levels found in North American household dust. Adult female Sprague-Dawley rats were fed a diet containing 0, 0.75, 250 or 750mg/kg of a mixture of flame retardants (polybrominated diphenyl ethers, hexabromocyclododecane) from two weeks prior to mating to gestation day 20. This formulation delivered nominal doses of 0, 0.06, 20 and 60mg/kg body weight/day. The lowest dose approximates high human exposures based on house dust levels and the dust ingestion rates of toddlers. Litter size and resorption sites were counted and fetal development evaluated. No effects on maternal health, litter size, fetal viability, weights, crown rump lengths or sex ratios were detected. The proportion of litters with fetuses with anomalies of the digits (soft tissue syndactyly or malposition of the distal phalanges) was increased significantly in the low (0.06mg/kg/day) dose group. Skeletal analysis revealed a decreased ossification of the sixth sternebra at all exposure levels. Thus, exposure to an environmentally relevant mixture of brominated flame retardants results in developmental abnormalities in the absence of apparent maternal toxicity. The relevance of these findings for predicting human risk is yet to be determined.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada H3G 1Y6.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Berger
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada H3G 1Y6.
authors.forename: Pavine L C
authors.initials: PL
authors.lastname: Lefèvre
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada H3G 1Y6.
authors.forename: Sheila R
authors.initials: SR
authors.lastname: Ernest
authors.affiliation: Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada K1A 0K9.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Wade
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada H3G 1Y6.
authors.forename: Yi-Qian
authors.initials: YQ
authors.lastname: Ma
authors.affiliation: Food Research Division, Bureau of Chemical Safety, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada K1A OL2.
authors.forename: Dorothea F K
authors.initials: DF
authors.lastname: Rawn
authors.affiliation: Food Research Division, Bureau of Chemical Safety, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada K1A OL2.
authors.forename: Dean W
authors.initials: DW
authors.lastname: Gaertner
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada H3G 1Y6; Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada H3G 1Y6.
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaire
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada H3G 1Y6. Electronic address: barbara.hales@mcgill.ca.
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Hales
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000473:pathology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004391:Dust; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000008:administration & dosage / Q000633:toxicity*; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000633:toxicity*; D008098:Litter Size; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004391:Dust; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; C089796:hexabromocyclododecane
keywords: Environmental contaminant; House dust; In utero; Mixture; Polybrominated diphenyl ethers; Skeletal development