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催化裂化澄清油的亚慢性皮肤暴露所致全身毒性、化学表征及皮肤渗透

Systemic toxicity from subchronic dermal exposure, chemical characterization, and dermal penetration of catalytically cracked clarified slurry oil.

作者信息

Cruzan G, Low L K, Cox G E, Meeks J R, Mackerer C R, Craig P H, Singer E J, Mehlman M A

出版信息

Toxicol Ind Health. 1986 Dec;2(4):429-44. doi: 10.1177/074823378600200406.

DOI:10.1177/074823378600200406
PMID:3590198
Abstract

Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).

摘要

澄清浆状油(CSO),即流化催化裂化装置的重质残渣馏分,每周5天,以8、30、125或500毫克/千克/天的剂量,连续13周涂抹于每组10只雄性和10只雌性斯普拉格-道利大鼠剃毛的背部,另一组以2000毫克/千克/天的剂量处理2周。给大鼠戴上硬纸板伊丽莎白项圈,以尽量减少受试材料的摄入,受试材料未稀释涂抹,且皮肤未覆盖。一组相似的大鼠作为对照;除未给它们的皮肤涂抹CSO外,处理方式相同。以30毫克/千克/天或更高剂量的CSO处理的大鼠出现了与剂量相关的死亡率和体重增加抑制;以2000毫克/千克/天给药的大鼠无一存活超过2周。CSO毒性的主要靶器官是肝脏、胸腺和骨髓。对肝脏的影响包括重量增加(500毫克/千克/天时增加250%)、胆小管炎、弥漫性肝细胞变性和肥大、坏死、纤维化、血糖降低、碱性磷酸酶、天冬氨酸氨基转移酶、丙氨酸氨基转移酶、胆红素和甘油三酯水平升高。发现胸腺小,显微镜检查显示萎缩或发育不全。在以30毫克/千克/天给药的一些大鼠的骨髓中发现了红系发育不全,且随着剂量增加严重程度增加。红系发育不全伴有与剂量相关的贫血。即使在以8毫克/千克/天给药的大鼠中,肝脏显微镜检查也观察到胆管有非常轻微的异常。色谱分离和分析表明,CSO含有约58%的3至5环多环芳烃(PAHs)和约8 - 10%的咔唑衍生物。体外和体内皮肤渗透研究表明,咔唑物质在相当程度上可穿透皮肤(约44%);2或3环(8 - 13%)或5环PAHs的穿透较少(3%)。

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