title: Effects of chronic exposure to an environmentally relevant mixture of brominated flame retardants on the reproductive and thyroid system in adult male rats.
abstract: Brominated flame retardants (BFRs) are incorporated into a wide variety of consumer products, are readily released into home and work environments, and are present in house dust. Studies using animal models have revealed that exposure to polybrominated diphenyl ethers (PBDEs) may impair adult male reproductive function and thyroid hormone physiology. Such studies have generally characterized the outcome of acute or chronic exposure to a single BFR technical mixture or congener but not the impact of environmentally relevant BFR mixtures. We tested whether exposure to the BFRs found in house dust would have an adverse impact on the adult male rat reproductive system and thyroid function. Adult male Sprague Dawley rats were exposed to a complex BFR mixture composed of three commercial brominated diphenyl ethers (52.1% DE-71, 0.4% DE-79, and 44.2% decaBDE-209) and hexabromocyclododecane (3.3%), formulated to mimic the relative congener levels in house dust. BFRs were delivered in the diet at target doses of 0, 0.02, 0.2, 2, or 20 mg/kg/day for 70 days. Compared with controls, males exposed to the highest dose of BFRs displayed a significant increase in the weights of the kidneys and liver, which was accompanied by induction of CYP1A and CYP2B P450 hepatic drug-metabolizing enzymes. BFR exposure did not affect reproductive organ weights, serum testosterone levels, testicular function, or sperm DNA integrity. The highest dose caused thyroid toxicity as indicated by decreased serum thyroxine (T4) and hypertrophy of the thyroid gland epithelium. At lower doses, the thickness of the thyroid gland epithelium was reduced, but no changes in hormone levels (T4 and thyroid-stimulating hormone) were observed. Thus, exposure to BFRs affected liver and thyroid physiology but not male reproductive parameters.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: Sheila R
authors.initials: SR
authors.lastname: Ernest
authors.forename: Michael G
authors.initials: MG
authors.lastname: Wade
authors.forename: Claudia
authors.initials: C
authors.lastname: Lalancette
authors.forename: Yi-Qian
authors.initials: YQ
authors.lastname: Ma
authors.forename: Robert G
authors.initials: RG
authors.lastname: Berger
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaire
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Hales
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D006984:Hypertrophy; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment; D012737:Sex Factors; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D036401:Toxicity Tests, Chronic
chemical_list: D004785:Environmental Pollutants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D013739:Testosterone; C089796:hexabromocyclododecane; C086401:pentabromodiphenyl ether; D019363:Cytochrome P-450 CYP1A1; D013974:Thyroxine