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.

该项目旨在检验以下假设： 用于二恶英，二苯并呋喃和PCB的USEPA临时TEF可以 预测单个同类物在 雌性Sprague-Dawley老鼠。 USEPA临时TEF 二恶英，Dibenzofurans和Planar PCB可以预测相对 环境相关混合物的致癌效力 这些化学物质在雌性Sprague-Dawley大鼠中。 这 二恶英的致癌性不会因存在的存在而改变 非二氧蛋白喜欢PCB。 生化的相对功能 在为期两年的研究中，终点（例如CYP1A1诱导）是 相当于估计的癌变的相对效力 基于管理剂量。 相对的致癌效力 基于目标组织剂量的单个同类物是相同的 作为基于CYP1A1诱导的相对效力 相同的目标组织。 相对致癌/生化 基于管理剂量的能力与基于剂量的剂量相同 在薄剂量上。 基于血清或整体的相对效果 血液浓度等效于施用的剂量和靶标 施工剂量。 为期两年的研究将与五个 各个化合物（TCDD，PECDF，PCB126，PCB118和 PCB153）和两种混合物（混合1：TCDD，PECDF，PCB126； 混合2：PCB126和PCB153）。 要进行的临时评估 13、30和52周将包括：甲状腺激素；肝 CYP1A1，CYP1A2和CYP1B1，UDP-GT，卟啉和视黄醇； 肺CYP1A1和CYP1B1;测试化学的组织浓度 在肝脏，肺，血液和脂肪组织中；某些器官重量，细胞 肝脏的增殖，组织病理学评估有限。 完整的组织病理学评估和组织浓度 化学物质将在末端牺牲时进行。