Bioavailability and half-life of decabromodiphenyl ether (BDE-209) in rat.

1. The absorption of the flame retardant decabromodiphenyl ether (BDE-209) has been shown by its detection in human plasma, but reported experimental data on its determined in rat, and qualitative analyses by GC/MS of metabolites in plasma were performed. The relative amount of phenolic metabolites was determined in a rat plasma sample obtained after administration of radiolabelled BDE-209. 2. The bioavailability of parent BDE-209 was calculated to be about 26% in rat. The concentrations of phenolic radioactivity in plasma 3 and 7 days after dosing were four times higher than those of the neutral compounds, i.e. parent compound, indicating absorption in rat are inconsistent. The bioavailability and half-life were therefore that total absorption was higher than 26%. 3. Thirteen phenolic metabolites were determined in the plasma and the major phenolic metabolites were characterized as a hydroxy-octaBDE, a hydroxy-nonaBDE and a hydroxy-methoxy-hexaBDE (guaiacol-type). The exposure to the phenolic metabolites seemed higher than the parent compound, BDE-209. 4. The initial elimination phase in plasma t1/2alpha for BDE-209 was 2 h, implying a rapid distribution of BDE-209 to well-perfused tissues. The distribution volume at steady state was 1.4 l kg-1, implying a low tendency for distribution to adipose tissue. The terminal t1/2 for BDE-209 in the intravenously dosed rat was calculated as 2.5 days (58 h).

Covalent binding of PCB metabolites to lipids: route of formation and characterization.

1. After an oral dose of (14)C-labelled 3,3',4,4'-tetrachlorobiphenyl (CB-77), the conventional germ-free and bile-duct cannulated male Sprague-Dawley rat excreted approximately 80% of the dose in faeces and/or bile within 3 days. 2. For the germ-free and conventional rat, 15% of the dose was excreted via the faeces as metabolites covalently bound to lipids. Bile-duct-cannulated rats excreted similar amounts of lipid-bound metabolites in the bile. The lipid-bound metabolites appear to be formed in the liver and excreted via the bile, and the microflora did not seem essential for the formation of lipid-bound metabolites. 3. The novel CB-77 metabolites had chemical and physical properties similar to those of lipids with regard to solubility and polarity, as determined by partition characteristics on various chromatographic systems. 4. In addition to identification of hydroxylated CB-77 metabolites, several fatty acid esters of hydroxy-chlorobiphenyls were indicated and one hydroxy-tetrachlorobiphenylol palmitoate was identified, but fatty acid esters were minor metabolites. 5. Approximately 70% of the lipid-bound metabolites were present in the fraction that contained phospholipids. The formation of lipid-bound CB-77 metabolites seems a spontaneous reaction rather than an enzymatically catalysed reaction, as indicated by the large number of different lipid-bound metabolites.

Identification of hydroxylated PCB metabolites and other phenolic halogenated pollutants in human blood plasma.

A growing number of studies have reported phenolic halogenated compounds (PHCs) that are retained in the blood of humans and wildlife. These PHCs may be industrial chemicals; metabolites thereof, as in the case with polychlorobiphenylols (OH-PCBs); or of natural origin. The present study was aimed to identify hitherto unknown PHCs in human plasma with chemical structures that are consistent to PHCs known to possess endocrine-disrupting activity. For this purpose, samples of blood plasma from 10 randomly selected male blood donors from Sweden were pooled and analyzed by GC/ECD and GC/MS. Brominated, bromochlorinated, and chlorinated methyl derivatives of phenols and OH-PCBs were synthesized to be used as authentic reference standards. More than 100 PHCs were indicated in the plasma, and among those a total of 9 monocyclic brominated or chlorinated phenol-, guaiacol-, and/or catechol-type compounds were identified as their methylated derivatives. The two major compounds were 2,4,6-tribromophenol and pentachlorophenol. Thirty-eight OH-PCB congeners were structurally identified on two GC columns of different polarity. The origin of the OH-PCB metabolites in the context of their parent PCB congeners are suggested. Other PHCs identified in the male plasma were Triclosan (5-chloro-2-[2,4-dichlorophenoxy] phenol), a common bactericide; 4-hydroxy-heptachlorostyrene, a metabolite of octachlorostyrene; and 3,5-dibromo-2-(2,4-dibromophenoxy)phenol, a natural compound and a potential metabolite of polybrominated diphenyl ethers.