Abstract
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 (ΣPCB) decreased during the experimental period, from 40 μg g−1 lipid (l.w.) after 1 week to 4 μg 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 (ΣMeSO2-PCB) concentration increased from 800 to 1020 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, 4-[14C]-MeSO2-2′,4′,5,5′,6-hexaCB (3-[14C]-MeSO2-CB149), 4-[14C]-MeSO2-2,2′,4′,5,5′,6-hexaCB (4-[14C]-MeSO2-CB149), 3′-[14C]-MeSO2-CB101,4′-[14C]-MeSO2-2,2′,4,5,5′-pentaCB (4′-[14C]-MeSO2-CB101) and 4′-[3C]-MeSO2-CB101 were synthesized in quantitative radiochemical yields.