DIOXIN TOXIC EQUIVALENCY FACTORS--BATTELLE MEMORIAL INST

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This project has been designed to test the following hypotheses: The USEPA interim TEFs for dioxins, dibenzofurans and PCBs can predict the relative carcinogenic potency of single congeners in female Sprague-Dawley rats. The USEPA interim TEFs for dioxins, dibenzofurans, and planar PCBS can predict the relative carcinogenic potency of an environmentally relevant mixture of these chemicals in the female Sprague-Dawley rat. The carcinogenicity of a dioxin is not altered by the presence of a nondioxin like PCB. The relative potencies for biochemical endpoints, such as CYP1A1 induction, in the two-year studies are equivalent to the relative potency for carcinogenesis when estimated based on administered dose. The relative carcinogenic potencies of the individual congeners, based on target tissue dose, are the same as the relative potencies based on CYP1A1 induction using the same target tissues. The relative carcinogenic/biochemical potencies based on administered dose are the same as those based on tissue dose. The relative potencies based on serum or whole blood concentrations are equivalent to administered dose and target tissue dose. Two-year studies are to be performed with five individual compounds (TCDD, PeCDF, PCB126, PCB118 and PCB153) and two mixtures (Mix 1: TCDD, PeCDF, PCB126; and Mix 2: PCB126 and PCB153). Interim evaluations to be performed at 13, 30 and 52 weeks will include: Thyroid hormones; liver CYP1A1, CYP1A2 and CYP1B1, UDP-GT, porphyrins and retinol; lung CYP1A1 and CYP1B1; tissue concentration of test chemical(s) in liver, lung, blood and adipose tissue; certain organ weights, cell proliferation of liver, and limited histopathologic evaluation. Complete histopathologic evaluation and tissue concentration of test chemical(s) will be performed at terminal sacrifice.