DIOXIN TOXIC EQUIVALENCY FACTORS--BATTELLE MEMORIAL INST

该项目旨在测试以下假设： 美国环保局对二恶英、二苯并呋喃和多氯联苯的临时TEF可以 预测单种同系物的相对致癌效力 雌性SD大鼠。美国环境保护局的临时TEF 二恶英、二苯并呋喃和平面多氯联苯可以预测相对 一种与环境相关的混合物的致癌效力 雌性SD大鼠体内的这些化学物质。这个 二恶英的致癌性不会因其存在而改变 非二恶英类电路板。生物化学的相对效价 在两年的研究中，终点，如CYP1A1诱导，是 相当于在估计时的致癌相对效力 根据给药剂量。的相对致癌能力 基于目标组织剂量的单个同系物是相同的 作为基于使用 相同的目标组织。相对致癌/生化 基于给药剂量的效力与基于 关于组织剂量。基于血清或整体的相对效力 血药浓度相当于给药剂量和靶点。 组织剂量。为期两年的研究将在五年内进行 单独化合物(TCDD、PeCDF、PCB126、PCB118和 PCB153)和两种混合物(混合物1：TCDD、PeCDF、PCB126；以及 混合2：PCB126和PCB153)。将进行的中期评价 13周、30周和52周将包括：甲状腺激素；肝脏 细胞色素P1A1、细胞色素P1A2和细胞色素P1B1、UDP-GT、卟啉和视黄醇； 肺组织细胞色素P1A1和细胞色素P1B1；测试化学物质的组织浓度(S) 在肝、肺、血液和脂肪组织中；某些器官重量，细胞 肝脏增生，有限的组织病理学评价。 完整的组织病理学评估和检测的组织浓度 化学(S)将在终极祭祀时表演。

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.