Twenty-Eight-Day Repeated-Dose Inhalation Exposure of Rats to Diethylene Glycol Monoethyl Ether

C.J. Hardy , D.W. Coombs , D.J. Lewis , H.J. Klimisch
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Abstract

This study was carried out to provide information on the effects of inhalation of diethylene glycol monoethyl ether, a substance used in industry which may be accidentally inhaled by man. Sprague–Dawley CD rats were exposed by inhalation to a test atmosphere containing diethylene glycol monoethyl ether in a nose-only exposure system for 6 hr a day, 5 days a week for 28 days. Mean exposure levels were 0.09, 0.27, and 1.1 mg/liter. At the two lowest exposure levels the test substance was present entirely as vapor, but at the highest exposure level the test atmosphere was approximately equally divided by mass into respirable droplets (aerosol) and vapor. A comprehensive battery of toxicological evaluations including food consumption, body weight, clinical signs, hematology, and biochemistry revealed no evidence of a systemic effect of exposure. Histopathological examination showed changes indicative of mild nonspecific irritation in the upper respiratory tract of rats exposed at the two highest exposure levels. These changes consisted of foci of necrosis in the ventral cartilage of the larynx of rats exposed at 0.27 or 1.1 mg/liter and an increase in eosinophilic inclusions in the olfactory epithelium of the nasal mucosa of rats exposed at 1.1 mg/liter. The no observed adverse effect level for systemic effects was 1.1 mg/liter and the no observed adverse effect level for signs indicative of mild nonspecific irritation of the upper respiratory tract was 0.09 mg/liter.

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大鼠对二甘醇单乙醚28天重复吸入暴露
进行这项研究是为了提供关于吸入二甘醇单乙醚的影响的信息,二甘醇单乙醚是一种在工业中使用的物质,可能被人意外吸入。将Sprague-Dawley CD大鼠吸入含二甘醇单乙醚的试验环境中,每周5天,每天6小时,持续28天。平均暴露水平分别为0.09、0.27和1.1毫克/升。在两个最低暴露水平下,测试物质完全以蒸汽的形式存在,但在最高暴露水平下,测试大气按质量大致等分分为可呼吸的液滴(气溶胶)和蒸汽。包括食物摄入量、体重、临床症状、血液学和生物化学在内的一系列综合毒理学评估显示,没有证据表明暴露会产生系统性影响。组织病理学检查显示,暴露于两个最高暴露水平的大鼠上呼吸道出现轻度非特异性刺激的变化。这些变化包括暴露在0.27或1.1 mg/l剂量下的大鼠喉部腹侧软骨出现坏死灶,以及暴露在1.1 mg/l剂量下大鼠鼻黏膜嗅上皮嗜酸性包裹体增加。未观察到的系统性不良反应水平为1.1 mg/l,未观察到的上呼吸道轻度非特异性刺激迹象的不良反应水平为0.09 mg/l。
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