SUBCHRONIC EFFECTS OF 2,3,7,8-TCDD OR PCBS ON THYROID-HORMONE METABOLISM - USE IN RISK ASSESSMENT

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pen tachlorobiphenyl (PCB 126), or 2,3,3',4,4',5-hexachlorobiphenyl (PCB 1 56) on thyroid hormone metabolism were studied in 13-week feeding stud ies in female Sprague-Dawley rats. The diets were supplemented with th e compounds tested at concentrations ranging from 0.2 to 20 mu g/kg di et for TCDD, 7 to 180 mu g/kg diet for PCB 126, or 1.2 to 12 mg/kg die t for PCB 156, respectively. Significant correlations were found for a ll three compounds between reductions in plasma total thyroxine (TT4) levels and inductions of the microsomal phase II enzyme UDP-glucuronos yltransferase by using T-4 as a substrate (T(4)UGT). Furthermore, the coinduction of certain phase I and II isozymes, i.c., cytochrome P450 1A1 (CYP1A1) and UGT1A1, by these compounds, clearly suggests the invo lvement of an Ah receptor-mediated mechanism in the disturbance of thy roid hormone metabolism by these polyhalogenated aromatic compounds. T hese results provide a mechanistic base for the use of certain effects on thyroid hormone metabolism by polyhalogenated aromatic compounds i n risk assessment. By using these effects, potencies of PCB 126 and PC B 156 relative to TCDD ranged from 0.008 to 0.1 for PCB 126, and from 0.00007 to 0.004 for PCB 156, respectively. These values correspond ve ry well with relative potencies of PCB 126 and PCB 156 by using some o ther well-known Ah receptor-mediated toxic and biochemical parameters.