REDUCTION OF THYROID-HORMONE LEVELS BY METHYLSULFONYL METABOLITES OF POLYCHLORINATED BIPHENYL CONGENERS IN RATS

Male Sprague-Dawley rats received four consecutive intraperitoneal dos es of four kinds of methylsulfonyl (MeSO2) metabolites of polychlorina ted biphenyl (PCB) congeners: 3-MeSO2-2,2',3',4',5,6-hexachlorobipheny l (3-MeSO2-CB132), 3-MeSO2-2,2',3',4', 5,5'-hexachlorobiphenyl (3-MeSO 2-CB141); 3-MeSO2-2,2',4',5,5',6-hexachlorobiphenyl (3-MeSO2-CB149) an d 4-MeSO2-2,2',4',5,5',6-hexachlorobiphenyl (4-MeSO2-CB149). The conge ners were major MeSO2-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO2 metabolites (20 mu mol/kg once daily for 4 days) reduced serum total thyroxine levels by 22-44% at a much lowe r dose than phenobarbital (PB; 431 mu mol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine leve ls were reduced 37% by treatment with 4-MeSO2-CB149 at day 7. A 30% in crease in thyroid weight was produced by 3-MeSO2-CB141 treatment. Tota l cytochrome P450 content was increased by 3-MeSO2-CB132, 3-MeSO2-CB14 1 and 3-MeSO2-CB149, but not by 4-MeSO2-CB149. Thus, it is likely that the 3-MeSO2-hexachlorobiphenyls and 4-MeSO2-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results sho w that tested 3- and 4-MeSO2 metabolites of PCB congeners reduce thyro id hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters.