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Repeated dose toxicity and relative potency of 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for induction of CYP1A1, CYP1A2 and thymic atrophy in female Harlan Sprague-Dawley rats.
Toxicology ( IF 4.8 ) Pub Date : 2012-07-17 , DOI: 10.1016/j.tox.2012.07.005
Michelle J Hooth 1 , Abraham Nyska , Laurene M Fomby , Daphne Y Vasconcelos , Molly Vallant , Michael J DeVito , Nigel J Walker
Affiliation  

In this study we assessed the relative toxicity and potency of the chlorinated naphthalenes 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) and 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chemicals were administered in corn oil:acetone (99:1) by gavage to female Harlan Sprague-Dawley rats at dosages of 0 (vehicle), 500, 1500, 5000, 50,000 and 500,000 ng/kg (PCN 66 and PCN 67) and 1, 3, 10, 100, and 300 ng/kg (TCDD) for 2 weeks. Histopathologic changes were observed in the thymus, liver and lung of TCDD treated animals and in the liver and thymus of PCN treated animals. Significant increases in CYP1A1 and CYP1A2 associated enzyme activity were observed in all animals exposed to TCDD, PCN 66 and PCN 67. Dose response modeling of CYP1A1, CYP1A2 and thymic atrophy gave ranges of estimated relative potencies, as compared to TCDD, of 0.0015-0.0072, for PCN 66 and 0.00029-0.00067 for PCN 67. Given that PCN 66 and PCN 67 exposure resulted in biochemical and histopathologic changes similar to that seen with TCDD, this suggests that they should be included in the WHO toxic equivalency factor (TEF) scheme, although the estimated relative potencies indicate that these hexachlorinated naphthalenes should not contribute greatly to the overall human body burden of dioxin-like activity.

中文翻译:

1,2,3,4,6,7-六氯萘 (PCN 66) 1,2,3,5,6,7-六氯萘 (PCN 67) 与 2,3,7,8 的重复剂量毒性和相对效力-四氯二苯并对二恶英 (TCDD) 用于诱导雌性 Harlan Sprague-Dawley 大鼠的 CYP1A1、CYP1A2 和胸腺萎缩。

在本研究中,我们评估了氯化萘 1,2,3,4,6,7-六氯萘 (PCN 66) 和 1,2,3,5,6,7-六氯萘 (PCN 67) 的相对毒性和效力。 2,3,7,8-四氯二苯并对二恶英 (TCDD)。以 0(媒介物)、500、1500、5000、50,000 和 500,000 ng/kg(PCN 66 和 PCN 67)和1、3、10、100 和 300 ng/kg (TCDD) 2 周。在 TCDD 治疗动物的胸腺、肝脏和肺以及 PCN 治疗动物的肝脏和胸腺中观察到组织病理学变化。在暴露于 TCDD、PCN 66 和 PCN 67 的所有动物中观察到 CYP1A1 和 CYP1A2 相关酶活性显着增加。CYP1A1 的剂量反应模型,
更新日期:2019-11-01
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