Reduction of serum thyroxine concentrations by methylsulfonyl metabolites of tetra-, penta- and hexachlorinated biphenyls in male sprague-dawley rats

Male Sprague-Dawley rats received four consecutive intraperitoneal doses of nine methylsulfonyl (MeSO2) metabolites of tetra-, penta- and hexachlorina ted biphenyls (tetra-, penta- and hexaCBs) to determine their effects on th yroid hormone levels. Nine MeSO2 metabolites, major MeS02-PCBs detected in human milk, liver and adipose tissue, were 3-MeSO2-2,2',4',5-tetraCB (3-MeS O2-CB49), 3-MeSO2-2,3',4',5-tetraCB (3-MeSO2-CB70), 3-MeSO2-2,2',3',4',5-pe ntaCB (3-MeSO2-CB87), 3-MeSO2-2,2',4',5,5'-pentaCB (3-MeSO2-CB101), 4-MeSO2 -2,2',4',5,5'-pentaCB (4-MeSO2-CB101), 3-MeSO2-2,2',3',4',5,6-hexaCB (3-MeS O2-CB132), 3-MeSO2-2,2',3',4',5,5'-hexaCB (3-MeSO2-CB141), 3-MeSO2-2,2',4', 5,5',6-hexaCB (3-MeSO2-CB149) and 4-MeSO2-2,2',4',5,5',6-hexaCB (4-MeSO2-CB 149). All nine MeSO2 metabolites (20 mu mol/kg once daily for four days) re duced serum total thyroxine levels (16-44%) at a much lower dose than pheno barbital (431 mu mol/kg once daily for four days) on days 2, 3, 4 and 7 aft er the last dosage. Total triiodothyronine level was reduced 37% by treatme nts with 3-MeSO2-CB49 and 3-MeSO2-CB149 at day 7, but increased 35% and 38% by 3-MeSO2-CB70 and 4-MeSO2-CB101 at days 3 and 4, respectively. The reduc tions in thyroxine levels led to an increase in thyroid-stimulating hormone levels by 3-MeS02-CB49, 3-MeSO2-CB87, 3-MeSO2-CB101, 3-MeSO2-CB132, 3-MeSO 2-CB141, 3-MeSO2-CB149 and 4-MeSO2-CB149. A 30% increase in thyroid weight was produced by 3-MeSO2-CB101 and 3-MeSO2-CB141 treatments. Total cytochrom e P450 content and the activity of 7-pentoxyrosorufin O-dealkylase were inc reased by all seven 3-MeSO2-PCBs. 3-MeSO2-CB49, 3-MeSO2-CB87, 3-MeSO2-CB101 and 3-MeSO2-CB132 also increased the activity of 7-ethoxyresorufin O-dealk ylase. Thus, it is likely that all nine tested MeSO2 metabolites could infl uence thyroid hormone metabolism. The results show that tested 3- and 4-MeS O2 metabolites of tetra-, penta- and hexaCBs reduce thyroid hormone levels in rats, suggesting that the metabolites may act as endocrine-disrupters. ( C) 2000 Elsevier Science Ltd. All rights reserved.