title: Toxicologic and immunologic effects of perinatal exposure to the brominated diphenyl ether (BDE) mixture DE-71 in the Sprague-Dawley rat.
abstract: Brominated diphenyl ethers (BDEs) are persistent environmental contaminants found in human blood, tissues, and milk. To assess the impact of the commercial BDE mixture DE-71 on the developing immune system in relation to hepatic and thyroid changes, adult (F0) rats were exposed to DE-71 by gavage at doses of 0, 0.5, 5, or 25 mg/kg body weight (bw)/d for 21 weeks. F0 rats were bred and exposure continued through gestation, lactation and postweaning. F1 pups were weaned and exposed to DE-71 by gavage from postnatal day (PND) 22 to 42. On PND 42, half of the F1 rats were assessed for toxicologic changes. The remaining F1 rats were challenged with the T-dependent antigen keyhole limpet hemocyanin (KLH) and immune function was assessed on PND 56. Dose-dependent increases in total BDE concentrations were detected in the liver and adipose of all F0 and F1 rats. In F0 rats, increased liver weight, hepatocellular hypertrophy, and decreased serum thyroxine (T4) were characteristic of DE-71 exposure. In F1 rats perinatal DE-71 exposure caused a nondose-dependent increase in body weight and dose-dependent increases in liver weight and hepatocellular hypertrophy. Serum T3 and T4 levels were decreased. In spleen from DE-71 exposed rats the area occupied by B cells declined while the area occupied by T cells increased; however, cellular and humoral immune responses to KLH challenge were not altered. Thus hepatic and thyroid changes in rats exposed perinatally to DE-71 were associated with altered splenic lymphocyte populations, an effect which has been linked to hypothyroidism.
authors.affiliation: Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada, K1A 0K9. genevieve.bondy@hc-sc.gc.ca
authors.forename: Genevieve S
authors.initials: GS
authors.lastname: Bondy
authors.forename: David E
authors.initials: DE
authors.lastname: Lefebvre
authors.forename: Syed
authors.initials: S
authors.lastname: Aziz
authors.forename: Wendy
authors.initials: W
authors.lastname: Cherry
authors.forename: Laurie
authors.initials: L
authors.lastname: Coady
authors.forename: Ellen
authors.initials: E
authors.lastname: Maclellan
authors.forename: Cheryl
authors.initials: C
authors.lastname: Armstrong
authors.forename: Michael
authors.initials: M
authors.lastname: Barker
authors.forename: Gerard
authors.initials: G
authors.lastname: Cooke
authors.forename: Dean
authors.initials: D
authors.lastname: Gaertner
authors.forename: Doug L
authors.initials: DL
authors.lastname: Arnold
authors.forename: Rekha
authors.initials: R
authors.lastname: Mehta
authors.forename: Paul R
authors.initials: PR
authors.lastname: Rowsell
mesh_terms: D000328:Adult; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004785:Environmental Pollutants / Q000032:analysis / Q000276:immunology / Q000633:toxicity*; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000032:analysis / Q000276:immunology / Q000633:toxicity*; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D007774:Lactation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008892:Milk / Q000737:chemistry; D009929:Organ Size / Q000187:drug effects; D018812:Paternal Exposure / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D013997:Time Factors; D014018:Tissue Distribution; D014886:Weaning
chemical_list: D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D013963:Thyroid Hormones; C086401:pentabromodiphenyl ether