Effects of short-term in vivo exposure to polybrominated diphenyl ethers on thyroid hormones and hepatic enzyme activities in weanling rats.
Polybrominated diphenyl ethers (PBDEs), used as flame retardants, are ubiquitous environmental contaminants. PBDEs act as endocrine disruptors via alterations in thyroid hormone homeostasis. We examined thyroid hormone concentrations and hepatic enzyme activity in weanling rats exposed to three commercial PBDE mixtures: DE-71, DE-79, and DE-83R. Female Long-Evans rats, 28 days old, were orally administered various doses of DE-71, DE-79, or DE-83R for 4 days. Serum and liver samples were collected 24 h after the last dose and analyzed for serum total thyroxine (T(4)), triiodothyronine (T(3)), thyroid-stimulating hormone (TSH), hepatic microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD), and uridinediphosphate-glucuronosyltransferase (UDPGT) activities. The PBDE-treated groups did not exhibit significant changes in body weight; however, increased liver weights, as well as 10- to 20-fold induction in EROD and 30- to 40-fold induction in PROD were found in the DE-71-- and DE-79--treated animals. DE-71 and DE-79 caused dose-dependent depletion of T(4), accompanied by up to 3- to 4-fold induction in UDPGT activities. Serum total T(4) was decreased a maximum of 80% for DE-71 and 70% for DE-79 in the highest dose, with benchmark doses (BMDs) of approximately 12.74 mg/kg/day for DE-71 and 9.25 mg/kg/day for DE-79. Dose-related effects in serum T(3) levels were less apparent, with maximal reductions of 25-30% at the highest dose for both DE-71 and DE-79. The two mixtures showed no effect on serum TSH levels. Benchmark dose analysis revealed that the two mixtures were comparable in altering thyroid hormone levels and hepatic enzyme activity. DE-83R was not effective in altering any of the measured parameters. The present study suggests that short-term exposure to some commercial PBDE mixtures interferes with the thyroid hormone system via upregulation of UDPGTS:
Zhou
T
T
Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA.
Ross
D G
DG
DeVito
M J
MJ
Crofton
K M
KM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002845:Chromatography; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D007455:Iodine / Q000737:chemistry; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010647:Phenyl Ethers / Q000494:pharmacology*; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D020318:Rats, Long-Evans; D013972:Thyrotropin / Q000032:analysis* / Q000097:blood / Q000187:drug effects*; D013974:Thyroxine / Q000032:analysis* / Q000097:blood / Q000187:drug effects*; D013997:Time Factors; D014284:Triiodothyronine / Q000032:analysis* / Q000097:blood / Q000187:drug effects*
D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D007457:Iodine Radioisotopes; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D014284:Triiodothyronine; C086401:pentabromodiphenyl ether; D013972:Thyrotropin; D007455:Iodine; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D014453:Glucuronosyltransferase; D013974:Thyroxine