title: Developmental exposure to brominated diphenyl ethers results in thyroid hormone disruption.
abstract: The objective of the current study was to characterize the effects of DE-71 (a commercial polybrominated diphenyl ether mixture containing mostly tetra- and penta-bromodiphenyl ethers) on thyroid hormones and hepatic enzyme activity in offspring, following perinatal maternal exposure. Primiparous Long-Evans rats were orally administered DE-71 (0, 1, 10, and 30 mg/kg/day) in corn oil from gestation day (GD) 6 to postnatal day (PND) 21. Serum and liver samples obtained from dams (GD 20 and PND 22), fetuses (GD 20), and offspring (PNDs 4, 14, 36, and 90) were analyzed for circulating total serum thyroxine (T(4)) and triiodothyronine (T(3)), or hepatic microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD), and uridine diphosphoglucuronosyl transferase (UDPGT) activity. There were no significant effects of treatment on maternal body weight gain, litter size, or sex ratio, nor were there any effects on any measures of offspring viability or growth. Serum T(4) was reduced in a dose-dependent manner in fetuses on GD 20 (at least 15%) and offspring on PND 4 and PND 14 (50 and 64% maximal in the 10 and 30 mg/kg/day groups, respectively), but recovered to control levels by PND 36. Reduction in serum T(4) was also noted in GD 20 dams (48% at highest dose), as well as PND 22 dams (44% at highest dose). There was no significant effect of DE 71 on T(3) concentrations at any time in the dams or the offspring. Increased liver to body weight ratios in offspring were consistent with induction of EROD (maximal 95-fold), PROD (maximal 26-fold) or UDPGT (maximal 4.7-fold). Induction of PROD was similar in both dams and offspring; however, EROD and UDPGT induction were much greater in offspring compared to dams (EROD = 3.8-fold; UDPGT = 0.5-fold). These data support the conclusion that DE-71 is an endocrine disrupter in rats during development.
authors.affiliation: Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Michele M
authors.initials: MM
authors.lastname: Taylor
authors.forename: Michael J
authors.initials: MJ
authors.lastname: DeVito
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Crofton
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000254:growth & development; D018811:Maternal Exposure / Q000009:adverse effects*; D008862:Microsomes, Liver / Q000378:metabolism; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010647:Phenyl Ethers / Q000633:toxicity*; D011075:Polybrominated Biphenyls; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D012098:Reproduction / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D013963:Thyroid Hormones; D014284:Triiodothyronine; C511295:2,2',4,4'-tetrabromodiphenyl ether; C086401:pentabromodiphenyl ether; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; C117189:thyroxine-UDP-glucuronosyltransferase; D014453:Glucuronosyltransferase; D013974:Thyroxine