DISPOSITION OF HALOGENATED DIBENZOFURANS

氯化二苯并二恶英(CDDS)和二苯并呋喃(CDF)是 在世界范围内被发现为环境污染物。以前的研究 我们实验室的研究表明，新陈代谢是一种 排毒的先决条件和解毒过程。 坚持与新陈代谢不足有关，但也可能是 受身体成分的调节。这些化合物很好 口服后吸收，尽管2，3，4，7，8-五CDF(4- PeCDF)和2，3，7，8-四CDF(TCDF)在 不是老鼠就是猴子。这些化学物质，以及2，3，7，8- 四氯二苯并对二恶英(TCDD)和1，2，3，7，8-五氯二恶英(1- PeCDF)只能从皮肤吸收很少(相当于20% 所应用的剂量)。在大鼠体内，新陈代谢遵循以下规律 顺序：TCDF大于1-PeCDF大于TCDD 大于4-PeCDF。这与持续性成反比 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 人类种群，对猴子的毒性几乎与TCDD一样。 我们还检查了它的处置和毒性。 八氯二苯二恶英(OCDD)。口服后吸收不良 暴露(吸光度低于10%)。然而，被吸收的是 在肝脏中浓缩并持续存在。重复暴露结果 强迫症在肝脏和脂肪组织中呈线性堆积。 大鼠的全身半衰期在3-5个月之间， 这表明稳态条件永远不会实现 在持续、低水平暴露的情况下。我们让老鼠暴露在 每周5天，每周13周，以确定是否 亚慢性接触会导致任何毒性影响。事实上, 强迫症引起的中毒综合征与急性 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，一种轻微的，非 再生性贫血，胆汁酸增加。因此，强迫症， 虽然只有0.01-.001X有效，但在其行动上与TCDD相似 反复曝光。

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.