PCB methyl sulphones in rat liver after exposure to PCB (Clophen A50): analysis and radiosynthesis of selected methylsulphonyl-PCBs

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.