DISPOSITION OF HALOGENATED DIBENZOFURANS

卤代二苯并呋喃的处置

• 批准号: 3941460
• 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/3941460
• 关键词: body composition; chemical structure function; dioxins; embryo /fetus toxicology; environmental contamination; environmental toxicology; gastrointestinal toxin absorption; genetic strain; halobiphenyl /halotriphenyl compound; halogenation; isomer; polychlorodibenzofuran; toxicant screening; toxin metabolism

Chlorinated dibenzodioxins (CDDs) and dibenzofurans (CDFs) are found world-wide as environmental pollutants. Previous studies from our laboratory have indicated that metabolism is a prerequisite for elimination and is a detoxification process. Persistence is related to lack of metabolism, but can also be modulated by body composition. These compounds are well absorbed after oral exposure, although 2,3,4,7,8-pentaCDF (4- PeCDF) is not absorbed as well as 2,3,7,8-tetraCDF (TCDF) in either the rat or the monkey. These chemicals, as well as 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,7,8-pentaCDF (1- PeCDF) are only poorly absorbed from the skin (equivalent to 20% of an applied dose). In the rat, metabolism follows the following order: TCDF is greater than 1-PeCDF is greater than TCDD is greater than 4-PeCDF. This is inversely relate to the persistence of these compounds with 4-PeCDF having the longest whole-body half-life. 4-PeCDF, which has been shown to be present in the human population, is nearly as toxic as TCDD in the monkey. We have also examine the disposition and toxicity of octachlorodibenzodioxin (OCDD). It is poorly absorbed after oral exposure (less than 10% absorption). However, what is absorbed concentrates and persists in the liver. Repeated exposure results in a linear accumulation of OCDD In the liver and adipose tissue. The whole body half-life is between 3-5 months in the rat, suggesting that steady-state conditions would never be achieved upon continuous, low-level exposure. We exposed rats for as long as 13 weeks, 5 days per week, to OCDD to determine if subchronic exposure would result in any toxic effects. In fact, OCDD caused the same toxic syndrome as that seen upon acute exposure to TCDD: induction of specific hepatic monoxygenases, fatty changes and vacuolization of the liver, a mild, non- regenerative anemia, and increases in bile acids. Thus, OCDD, while only .01-.001X as potent, is TCDD-like in its actions upon repeated exposure.

氯化二苯并二恶英（CDD）和二苯并呋喃（CDF）是 作为环境污染物在世界范围内被发现。 以前的研究 从我们的实验室已经表明，新陈代谢是一个 这是一个消除的先决条件，也是一个解毒的过程。 持久性与缺乏新陈代谢有关，但也可能是 由身体成分调节。 这些化合物很好地 虽然2，3，4，7，8-pentaCDF（4- PeCDF）的吸收不如2，3，7，8-tetraCDF（TCDF）， 老鼠或者猴子。 这些化学物质，以及2，3，7，8- 四氯二苯并对二恶英（TCDD）和1，2，3，7，8-pentaCDF（1- PeCDF）仅从皮肤吸收不良（相当于20% 剂量）。 在大鼠中，代谢遵循以下过程 顺序：TCDF大于1-PeCDF大于TCDD 大于4-PeCDF。 这与持久性成反比 在这些化合物中，4-PeCDF具有最长的全身 半衰期 4-PeCDF，已被证明存在于 在人类中的毒性几乎与TCDD在猴子中的毒性相同。 我们还研究了 八氯二苯并二恶英。 口服后吸收不良 暴露（小于10%吸收）。 然而，吸收的是 集中并持续存在于肝脏中。 重复暴露结果 在肝脏和脂肪组织中呈线性积累。 在大鼠中的全身半衰期为3-5个月， 这意味着稳态条件永远不会达到 持续的低强度暴露 我们让老鼠暴露在 13周，每周5天，OCDD确定是否 亚慢性接触会产生任何毒性效应。 事实上， OCDD引起的毒性综合征与急性 暴露于TCDD：诱导特异性肝单加氧酶， 肝脏的脂肪变化和空泡化，轻度，非- 再生性贫血和胆汁酸增加 因此，OCDD， 虽然只有0.01 - 0.001倍的效力，但其作用类似于TCDD， 反复暴露。