DISPOSITION OF HALOGENATED DIBENZOFURANS

卤代二苯并呋喃的处置

• 批准号: 3840981
• 负责人: L S BIRNBAUM
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3840981
• 关键词: adipose tissue; aging; bile circulation; biotransformation; detoxification; dioxins; dosage; drug administration routes; environmental contamination; environmental toxicology; excretion; feces; feces analysis; gastrointestinal toxin absorption; halobiphenyl /halotriphenyl compound; laboratory rat; liver metabolism; occupational hazard; polychlorodibenzofuran; skin absorption; toxicant screening; toxin metabolism

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are toxic environmental and industrial contaminants. Dermal absorption constitutes a major route of exposure to these chemicals with maximal absorption of a low dose ranging from 40% (TCDD) to 65% (TCDF). Absorption through the skin occurs very slowly yet appears to be more rapid during the first 24 to 48 hours after contact. Our results with TCDD and TCDF suggest that physicochemical properties may govern the rate of absorption of these chemicals. Absorption of a low dose of TCDD through the skin of very young animals is increased compared to absorption through the skin of adult animals. Our results suggest that the potential for systemic exposure might be less in adults compared to children. Polybrominated dibenzo-p-dioxins (PBDDs) and dibenzofurans (PCDFs) are potential environmental contaminants due to their formation from thermolysis or pyrolysis of certain brominated flame retardants. The disposition of TBDD was studied in male F-344 rats following oral or intravenous administration. TBDD exhibited non-linear absorption kinetics with maximal oral absorption (about 80%) occurring at doses <0.01 umol/kg. Distribution to the liver and adipose, the major tissue depots, was dose- dependent, with preferential accumulation in the liver versus the adipose at higher doses. Feces was the major route of elimination and excretion was dose-dependent. The apparent terminal whole body half-life of TBDD was estimated to be 18 days. Within 6 hours, about 6% of the dose was excreted into the bile in metabolized form; pretreatment did not appear to enhance biliary excretion. The overall disposition of TBDD appears similar to that observed for TCDD. The dose-dependent tissue distribution and excretion kinetics suggest important considerations for high to low dose extrapolations.

多氯二苯并二恶英（PCDDs）和二苯并呋喃（PCDFs）是 有毒的环境和工业污染物。 皮肤吸收 构成了接触这些化学品的主要途径， 低剂量的吸收范围为40%（TCDD）至65%（TCDF）。 吸收 通过皮肤发生非常缓慢，但似乎更迅速， 接触后24至48小时内。 我们对TCDD和TCDF的研究结果表明， 物理化学性质可能决定这些物质的吸收速率， 化学品 幼儿皮肤对低剂量TCDD的吸收 与成人皮肤吸收相比， 动物 我们的研究结果表明，全身暴露的可能性 与儿童相比，成年人可能更少。 多溴二苯并二恶英（PBDD）和二苯并呋喃（PCDF）是 潜在的环境污染物，因为它们的形成， 某些溴化阻燃剂的热分解或热解。 的 在雄性F-344大鼠中研究了TBDD的处置， 静脉给药。 TBDD的吸收动力学呈非线性 最大口服吸收（约80%）发生在剂量<0.01 μ mol/kg时。 分布到肝脏和脂肪，主要的组织仓库，是剂量- 依赖性，与脂肪相比，优先在肝脏中蓄积 在更高的剂量。 粪便是主要的排泄途径 呈剂量依赖性。 TBDD的表观终末全身半衰期为 预计18天。 在6小时内，约6%的剂量被排出体外 以代谢形式进入胆汁;预处理似乎没有增强 胆汁排泄 TBDD的总体处置似乎类似于 观察TCDD。 剂量依赖性组织分布和排泄 动力学表明对于高剂量到低剂量 外推