Developmental exposure to low-dose PBDE-99: tissue distribution and thyroid hormone levels.
Thyroid hormone concentrations, hepatic enzyme activities and tissue concentrations of 2,2',4,4',5-pentabromodiphenyl ether (PBDE-99) were evaluated in Wistar rats (dams and offspring) after treatment by gavage on gestation day (GD) 6 with a single low dose of either 60 or 300 microg PBDE-99/kg body weight (bw), respectively. Tissue concentration analysis confirmed that PBDE-99 is persistent in rodents as significant amounts of the parent compound were detected in adipose tissue 37 days after exposure. The dose of 300 microg PBDE-99/kg bw reduced thyroxin (T4) concentration in dams at the beginning of lactation (post-gestational day [PGD] 1), and caused a slight reduction in T4 on PGD 22, although not statistically significant. In offspring, reduced T4 was observed only at PND 22, probably due to cumulative effects of PBDE-99 during lactation. PBDEs have been shown to reduce T4 concentrations in several studies, but this is the first study demonstrating endocrine disruption at low doses. The adipose tissue concentration of PBDE-99 measured in this study was close to those reported for PBDE-99 in non-occupationally exposed humans. In addition, we have previously reported permanent changes in the reproductive systems and locomotor activity of male and female offspring using these same dosages.
Kuriyama
Sergio Noboru
SN
Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Charité University Medical School Berlin, Campus Benjamin Franklin, Berlin, Germany.
Wanner
Antonia
A
Fidalgo-Neto
Antonio Augusto
AA
Talsness
Chris E
CE
Koerner
Wolfgang
W
Chahoud
Ibrahim
I
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001822:Body Burden; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005865:Gestational Age; D014453:Glucuronosyltransferase / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010647:Phenyl Ethers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D011075:Polybrominated Biphenyls / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D013974:Thyroxine / Q000097:blood*; D014018:Tissue Distribution
D052244:Endocrine Disruptors; D055768:Halogenated Diphenyl Ethers; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C086401:pentabromodiphenyl ether; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase; D013974:Thyroxine