PCB methyl sulphones in rat liver after exposure to PCB (Clophen A50): analysis and radiosynthesis of selected methylsulphonyl-PCBs.
1. The hepatic metabolism of polychlorinated biphenyls (PCBs) and formation of PCB methyl sulphone metabolites (MeSO2-PCBs) was determined in the male Sprague Dawley rat 1, 2, 4 or 8 weeks after dosage with Clophen A50 (a commercial PCB mixture). 2. The total concentration of the PCB congeners examined (sigmaPCB) decreased during the experimental period, from 40 microg g(-1) lipid (l.w.) after 1 week to 4 microg g(-1) l.w. after 8 weeks. A 50% decrease of PCB in the liver were estimated to be 28, 13 and 11 days for 2,2',4,4',5,5'-hexachlorobiphenyl (CB153), 2,2',3,3',4,4',5-heptaCB (CB170) and 2,2'3,4',5,5',6-heptaCB (CB187), respectively. 3. The total MeSO2-PCB (sigmaMeSO2-PCB) concentration increased from 800 to 1,020 ng g(-1) l.w. during the first 2 weeks of treatment and thereafter a decrease to 120 ng g(-1) l.w. after 8 weeks. The relative concentration of both 3'-MeSO2-2,2',4,4',5-pentaCB (3'-MeSO2-CB101) and 3'-MeSO2-2,2',3,4,5'-pentaCB (3'-MeSO2-CB87) in rat liver showed significant increases during the 8 weeks. In contrast, the relative concentrations of 4-MeSO2-2,4',5,5-tetraCB (4-MeSO2-CB64), 3-MeSO2-2,3',4',5-tetraCB (3-MeSO2-CB70) and 4-MeSO2-2,2',3,4,5',6'-hexaCB (4'-MeSO2-CB132) decreased significantly. 4. A route for the synthesis of radiolabelled MeSO2-PCBs was developed employing the 'Pummerer reaction' to convert methylthio-PCBs (MeS-PCBs) to the corresponding mercapto-PCBs (SH-PCB). The SH-PCBs were methylated with radiolabelled methyl iodide and the resulting sulphides oxidized to yield the corresponding MeSO2-PCBs. Using this approach, 3-[14C]-MeSO2-2,2',4',5,5',6-hexaCB (3-[14C]-MeSO2-CB149), 4-[14C]-MeSO2-2,2',4',5,5',6-hexaCB (4-[14C]-MeSO,-CB149), 3'-[14C]-MeSO2-CB101, 4'-[14C]-MeSO2-2,2',4,5,5'-pentaCB (4'-[14C]-MeSO2-CB101) and 4'-[3H]-MeSO2-CB101 were synthesized in quantitative radiochemical yields.
Larsson
C
C
Department of Environmental Chemistry, Stockholm University, Sweden.
Bergman
A
A
D000818:Animals; D002625:Chemistry, Organic / Q000379:methods*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
C025647:clophen A50; D011078:Polychlorinated Biphenyls