抄録
Hydroxylated polybrominated diphenyl ethers (OH-PBDEs), which have been detected in wildlife and humans, are of concern due to their greater toxicities relative to synthetic PBDEs. There is evidence suggesting that OH-PBDE’s are products of PBDE metabolism. However, laboratory exposure studies during which test animals were administered synthetic PBDEs (ug/g body weight) revealed formation of only trace amounts of OH-PBDEs (<0.01-1 % of PBDEs). We have demonstrated that Methoxylated PBDEs (MeO-PBDEs), which have been shown to be of natural origin, and not synthetic PBDE’s, appear to be the primary metabolic precursors of OH-PBDE’s. A LC-MS/MS method was developed to simultaneously quantify MeO-BDE and OH-PBDEs as well as potentially affected hormones (estrogens). The mechanism(s) of OH-PBDE formation was determined in hepatic microsomes. Phase I enzymes, notably CYP1A1 and CYP1A2, are at least partially responsible for conversion of MeO-PBDE’s to OH-PBDEs. To further elucidate this mechanism of action, pregnane-X-receptor (PXR) and aryl-hydrocarbon receptor (AhR) knock-down cell lines were developed to investigate the role of biotransformation enzymes under the control of each receptor. Because OH-PBDEs have been reported to affect concentrations of steroid and thyroid hormones, associations between concentrations of OH-PBDEs and the hormones E2, T3 and T4 in blood of Korean women as well as their foetuses were examined. Indeed. most of the OH-PBDEs measured in blood of Korean women was of natural origin. The naturally occurring 6-OH-BDE-47 was the only hydroxylated BDE detected. In addition, 6-OH-PBDE-47 was found to cross the placental barrier with concentrations being significantly greater in cord serum. The transport protein, transthyretin (TTR), may be responsible for the observed accumulation of OH-PBDEs in the developing foetus. There were no significant associations between concentrations of OH-PBDEs and hormone concentrations. Based on the results of controlled laboratory studies with animals, current concentrations of OH-PBDE-47 in blood of Korean women is approximately 4-fold less than the threshold for effects.
