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Development of toxic equivalency factors for PCB congeners and the assessment of TCDD and PCB mixtures in rainbow trout

John L. Newsted·Paul D. Jones·John P. Giesy·Robert A. Crawford·Gerald T. Ankley·Donald E. Tillitt·Jay W. Gooch·Michael S. Denison
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Abstract

This study was undertaken to evaluate the relationship between mammalian and piscine 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) toxic equivalency factors (TEFs) for PCBs, based on induction of CYP1A enzyme activity, catalytic protein, and mRNA. Rainbow trout administered a single i.p. injection of TCDD had an average (±SD) ED50 of 0.91 ± 0.14 μg TCDD/kg for induction of ethoxyresorufin O -deethylase (EROD) activity. Ortho-substituted PCB congeners 2,3,3′,4,4′-pentachlorobiphenyl (PCB 105), 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118), 2,3,3′4,4′5-hexachlorobiphenyl (PCB !56), and 2,2′3,4,4′,5-hexachlorobiphenyl (PCB 138) did not induce CYP1A activity in rainbow trout. Only three non-ortho-substituted PCBs, i.e., 3,3′4,4′-tetrachlorobiphenyl (PCB 77), 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), and 3,3′4,4′5,5′-hexachlorobiphenyl (PCB 169) induced CYP1A enzyme activity, protein, and mRNA. The ED50s for induction of EROD activity were calculated as 134, 5.82, and 93.7 μg/kg for PCB 77, PCB 126, and PCB 169, respectively. The TCDD-TEFs based on EROD activity were 0.0006, 0.0014, and 0.0003 for PCB 77, PCB 126, and PCB 169, respectively. Binary mixtures of TCDD and three PCBs were also evaluated. Based on EROD activity and CYP1A protein, mixtures of TCDD and PCB 77 were slightly greater than additive. Mixtures of TCDD-PCB 156 and TCDD-PCB 126 were slightly less than additive. Results from these studies indicate that mammal-derived TEFs will underestimate the potency of planar chlorinated hydrocarbon mixtures to induce the CYP1A catalytic activity in rainbow trout. Also, while interactions among PCB congeners and TCDD were somewhat equivocal, they did not greatly differ from predicted additive responses.

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John L. Newsted, Paul D. Jones, John P. Giesy, Robert A. Crawford, Gerald T. Ankley, Donald E. Tillitt, Jay W. Gooch, Michael S. Denison. 1995-05-01. Development of toxic equivalency factors for PCB congeners and the assessment of TCDD and PCB mixtures in rainbow trout. https://doi.org/10.1002/etc.5620140518

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