Viluksela M, Stahl B U, Rozman K K
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Chemosphere. 1994 Nov-Dec;29(9-11):2381-93. doi: 10.1016/0045-6535(94)90407-3.
A 13-week oral toxicity study with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) was performed in Sprague-Dawley rats. Rats received HpCDD at five different dose levels or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at one dose level. The doses were divided into 4 daily loading doses and 6 biweekly maintenance doses. At the end of the 13-week dosing period half of the rats were scheduled for necropsy and the other half after another 13-week off-dose period. This preliminary report contains only data from male rats during the 13-week main study period. At the two highest doses of HpCDD and in the TCDD dosage group the body weight or body weight gain was reduced. Mortality was 15, 50 and 5%, respectively. Wasting syndrome was the primary cause of death, but some rats died of hemorrhage without wasting, which may be related to the dose-dependent decrease in platelet counts. Phosphoenolpyruvate carboxykinase (PEPCK), the rate limiting enzyme of gluconeogenesis, was decreased only at the two highest dose levels of HpCDD and in the TCDD group, all of which also showed mortality. Ethoxyresorufin O-deetylase (EROD) was induced dose-dependently in all treated groups. Serum total thyroxine (T4) concentrations were decreased beginning at the middle dose of HpCDD. The study demonstrates that the toxicity observed after subchronic exposure to HpCDD is very similar to that of TCDD. Most importantly, most of the effects after subchronic and acute dose exposure are identical, confirming the validity of 0.007 as the toxic equivalency factor for HpCDD.
对斯普拉格-道利大鼠进行了一项为期13周的1,2,3,4,6,7,8-七氯二苯并-对-二恶英（HpCDD）口服毒性研究。大鼠接受了五个不同剂量水平的HpCDD或一个剂量水平的2,3,7,8-四氯二苯并-对-二恶英（TCDD）。剂量分为4个每日负荷剂量和6个每两周一次的维持剂量。在13周给药期结束时，一半的大鼠安排进行尸检，另一半在另外13周的停药期后进行。本初步报告仅包含13周主要研究期内雄性大鼠的数据。在两个最高剂量的HpCDD组和TCDD剂量组中，体重或体重增加减少。死亡率分别为15%、50%和5%。消瘦综合征是主要死因，但一些大鼠死于出血而无消瘦，这可能与血小板计数的剂量依赖性减少有关。磷酸烯醇丙酮酸羧激酶（PEPCK），糖异生的限速酶，仅在两个最高剂量水平的HpCDD组和TCDD组中降低，所有这些组也都出现了死亡。乙氧基异吩唑酮O-脱乙基酶（EROD）在所有治疗组中均呈剂量依赖性诱导。血清总甲状腺素（T4）浓度从HpCDD的中剂量开始降低。该研究表明，亚慢性暴露于HpCDD后观察到的毒性与TCDD非常相似。最重要的是，亚慢性和急性剂量暴露后的大多数影响是相同的，证实了0.007作为HpCDD毒性当量因子的有效性。
