DIOXIN TOXIC EQUIVALENCY FACTORS--BATTELLE MEMORIAL INST

二恶英毒性当量因素--巴特尔纪念研究所

• 批准号: 2660935
• 负责人: MILTON HEJTMANCIK
• 金额: $ 13.77万
• 依托单位: BATTELLE MEMORIAL INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-25 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2660935
• 关键词: carcinogen testing; chemical carcinogen; chemical carcinogenesis; cytochrome P450; dioxins; dosage; environmental toxicology; halobiphenyl /halotriphenyl compound; laboratory rat; polychlorodibenzofuran

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.

该项目旨在测试以下假设： 美国环保局二恶英、二苯并呋喃和多氯联苯的临时毒性当量因子可 预测单一同系物的相对致癌效力， 雌性Sprague-Dawley大鼠 美国环保局临时TEFs 二恶英，二苯并呋喃，和平面PCBS可以预测相对 致癌潜力的环境相关的混合物 雌性Sprague-Dawley大鼠体内的这些化学物质。 的 二恶英的致癌性不会因二恶英的存在而改变。 非二恶英类PCB。 生物化学的相对效力 2年研究中的终点，如CYP 1A 1诱导， 当估计时，相当于致癌作用的相对效力 基于给药剂量。 的相对致癌效力 基于靶组织剂量的单个同系物相同 作为基于CYP 1A 1诱导的相对效价，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 组织剂量。 基于血清或全血的相对效价 血药浓度相当于给药剂量和目标浓度 组织剂量 为期两年的研究将在五个 单独的化合物（TCDD、PeCDF、PCB 126、PCB 118和 多氯联苯153）和两种混合物（混合物1：四氯二苯并对二恶英、五氯二苯并呋喃、多氯联苯126; 混合2：PCB 126和PCB 153）。 将进行的中期评价 第13、30和52周时将包括：甲状腺激素;肝脏 CYP 1A 1、CYP 1A 2和CYP 1B 1、UDP-GT、卟啉和视黄醇; 肺CYP 1A 1和CYP 1B 1;供试化学品的组织浓度 在肝、肺、血液和脂肪组织中;某些器官重量、细胞 肝脏增生和有限的组织病理学评价。 完整的组织病理学评估和测试的组织浓度 将在终末处死时进行化学品给药。