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EFFECTS OF LOW DOSE MIXTURES OF PCB126 AND PERCHLORATE ON THE HYPTHALAMIC-PITUITARY-THYROID (HPT) AXIS IN THE MALE RAT.
Citation:
MCLANAHAN, E., J. CAMPBELL, J. M. HEDGE, J. V. BRUCKNER, K. M. CROFTON, M. MUMTAZ, D. FERGUSON, AND J. FISHER. EFFECTS OF LOW DOSE MIXTURES OF PCB126 AND PERCHLORATE ON THE HYPTHALAMIC-PITUITARY-THYROID (HPT) AXIS IN THE MALE RAT. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Perchlorate (ClO4) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) are environmental contaminants known to disturb thyroid hormone homeostasis by well defined modes of action that lead to hypothyroidism in the rat. PCB126 increases phase II conjugation of T4 (T4-glucuronide) by inducing hepatic glucuronosyl transferases and ClO4 blocks thyroidal uptake of iodide. In this binary mixture study, adult male Sprague-Dawley rats were administered an oral bolus dose of 0, 0.075, 0.75, or 7.5 g PCB126/kg-bw in corn oil on Day 0. On Day 1, ClO4 was administered via drinking water (DW) (0 or 0.01 mg ClO4/kg-bw per day) until tissues were collected on Days 2 and 5. Surprisingly, rats that received ClO4 in DW for 4 days had modestly elevated serum total T4 concentrations, however a less than additive response was observed when pretreated with PCB126. Dose and time dependent induction of hepatic EROD activity, a marker for CYP1A1, was observed over the 5 day period for all but the lowest dose of PCB126. The binary mixture resulted in a greater than additive effect on Day 2 but a less than additive effect on Day 5 for EROD and total cytochrome P450 activities. Hepatic T4-glucuronide production was elevated for the 7.5 g PCB126/kg-bw dose group on Days 2 and 5; there was no significant effect due to ClO4. Thyroidal iodide (127I) stores were not altered by these chemicals and ranged from 10-15 ug (both lobes) for control and treatment groups. Physiological models of the HPT axis, perchlorate and PCB 126 are under development to interpret the nonlinear HPT axis disturbances that apparently involve both stimulation and inhibition. This abstract does not reflect USEPA policy. Funding was provided by ATSDR #U61/ATU472105-01, US EPA, and NSF fellowship (DGE0229577).