毒理性
识别和使用：二乙胺（DEN）是一种无色液体，具有鱼腥味和类似氨的气味。它用于石油工业、浮选剂、染料、药品。它还用作从油、脂肪和蜡中去除杂质的选择性溶剂，以及在铁、钢和金属工业中作为腐蚀抑制剂。人类暴露和毒性：成年志愿者在气候室中暴露于25 ppm（75 mg/m³）的二乙胺15分钟，以研究急性鼻部反应，相当于当前的阈限值-短期暴露限值。暴露于从0增加到12 ppm的浓度，持续60分钟，平均浓度为10 ppm（30 mg/m³）。观察到中等至强烈的嗅觉反应和明显的鼻腔和眼睛刺激。二乙胺蒸气引起的角膜上皮水肿，通常不伴有疼痛，导致在灯光周围看到彩色光环。角膜上皮的水肿，主要是视力障碍的原因，第二天自行消退，但在极强烈的暴露后，水肿和模糊需要几天才能清除，并伴有光过敏和角膜表面粗糙不适。动物研究：兔暴露于50和100 ppm的DEN蒸气，每天7小时，每周5天，持续6周。所有兔子在暴露后存活，体重正常，没有显示出对化学物质的任何外部反应。在100 ppm时，肺部含有细胞浸润和支气管肺炎；肝脏出现实质变性，有细胞再生迹象；肾脏显示肾炎。在50 ppm时也产生了相同的变化，但程度较轻。在吸入50 ppm的兔子中看到了轻微的心肌变性迹象，但在100 ppm时没有明显迹象。雄性和雌性大鼠暴露于0、25或250 ppm的二乙胺（DEA）蒸气，每天6.5小时，每周5天，持续24周，以评估心脏和其他器官系统的毒性。在暴露的前2周，暴露于250 ppm DEA的大鼠体重没有增加。然而，2周后，这些大鼠的体重增加速度超过了对照组。然而，在整个研究过程中，暴露于250 ppm DEA的雄性和雌性大鼠的平均体重与对照组相比仍然下降。在暴露于250 ppm DEA的大鼠中观察到打喷嚏、流泪和鼻子发红。组织病理学检查显示，暴露于250 ppm DEA的大鼠鼻黏膜有损伤。这些呼吸道上皮的病变包括鳞状化生、化脓性鼻炎和淋巴组织增生。除血尿素氮外，没有观察到对器官重量、血液学或临床化学指标有显著的治疗相关影响，血尿素氮是在暴露于250 ppm DEA的雄性和雌性大鼠24周后评估的。与高剂量动物相比，在25 ppm DEA间歇暴露24周的动物中没有观察到治疗相关影响。在暴露于DEA浓度达24周的雄性和雌性大鼠中没有观察到心脏毒性。在鼠伤寒沙门氏菌/微粒体预培养试验中评估了二乙胺的致突变性。二乙胺在四个鼠伤寒沙门氏菌菌株（TA98、TA100、TA1535和TA1537）中进行测试，剂量为0、10、33、100、333、1000和3333 μg/板，有或没有代谢活化。二乙胺在这些测试中呈阴性。在两个独立的细菌致突变性试验中，每个试验都有或没有外源代谢活化酶，二乙胺没有致突变性。测试的细菌菌株包括鼠伤寒沙门氏菌菌株TA98、TA100、TA1535和TA1537以及大肠杆菌菌株WP2 uvrA/pKM101。除了两个细菌试验的阴性结果外，在雄性和雌性小鼠的外周血液中没有观察到微核红细胞频率的显著增加。NTP对大鼠和小鼠进行了为期2年的吸入研究。没有证据表明二乙胺在暴露于31、62.5或125 ppm的雄性和雌性大鼠中具有致癌活性。没有证据表明二乙胺在暴露于16、31或62.5 ppm的雄性和雌性小鼠中具有致癌活性。暴露于二乙胺导致雄性和雌性大鼠和小鼠的鼻腔非肿瘤性病变、雄性大鼠的角膜、雌性大鼠的胸膜和肺的发病率增加。
IDENTIFICATION AND USE: Diethylamine (DEN) is a colorless liquid with fishy, ammonia-like odor. It is used in petroleum industry, in flotation agents, dyes, pharmaceuticals. It also used as a selective solvent for the removal of impurities from oils, fats, and waxes, and as a corrosion inhibitor in iron, steel, and metal industries. HUMAN EXPOSURE AND TOXICITY: Adult volunteers were exposed to 25 ppm (75 mg/cu m) diethylamine in a climate chamber for 15 min in order to study the acute nasal reactions to an exposure equivalent to the present threshold limit value-short-term exposure limit. Exposure to a concentration increasing from 0 to 12 ppm took place for 60 min, equal to an average concentration of 10 ppm (30 mg/cu m). A moderate to strong olfactory response and distinct nasal and eye irritation were observed. Edema of the epithelium of the cornea, generally without pain, has been produced by diethylamine vapors, causing colored halos to be seen around lights. The edema of the corneal epithelium, which is principally responsible for the disturbance of vision, clears spontaneously by the next day, but after exceptionally intense exposures the edema and blurring have taken several days to clear and have been accompanied by photophobia and discomfort from roughness of the corneal surface. ANIMAL STUDIES: Rabbits were exposed to DEN vapors at 50 and 100 ppm, 7 hours/day, 5 days/week for 6 weeks. All rabbits survived the exposures and had normal body weights without demonstrating any outward signs of response to the chemical. At 100 ppm, lungs contained cellular infiltration and bronchopneumonia; livers had parenchymatous degeneration with evidence of cell regeneration; and kidneys showed nephritis. The same changes, but to a lesser degree, were produced at 50 ppm. A suggestion of very slight cardiac muscle degeneration was seen in rabbits inhaling 50 ppm but was not evident at 100 ppm. Male and female rats were exposed at 0,25 or 250 ppm diethylamine (DEA) vapor, 6.5 hr per day, 5 days per week, for 24 weeks in order to assess cardiac and other organ system toxicity. During the first 2 weeks of exposure, the rats exposed at 250 ppm DEA did not gain weight. After 2 weeks, however, the rate of weight gain of these rats was greater than that of controls. Nevertheless, mean body weights for both sexes of rats exposed at 250 ppm DEA remained depressed compared to controls throughout the study. Sneezing, tearing, and reddened noses were seen in rats exposed at 250 ppm DEA. Histopathologic examinations revealed lesions of the nasal mucosa of rats exposed at 250 ppm DEA. These lesions of the respiratory epithelium consisted of squamous metaplasia, suppurative rhinitis, and lymphoid hyperplasia. There were no pronounced treatment-related effects on organ weights, hematology, or clinical chemistry indices except for blood urea nitrogen which was evaluated in rats of both sexes exposed at 250 ppm DEA for 24 weeks. In contrast to the high-dose animals, no treatment-related effects were observed in rats intermittently exposed at 25 ppm DEA for up to 24 weeks. No evidence of cardiotoxicity was seen in rats exposed to either DEA concentration for up to 24 weeks. Diethylamine was evaluated for mutagenicity in the Salmonella/microsome preincubation assay. Diethylamine was tested at doses of 0, 10, 33, 100, 333, 1000, and 3333 ug/plate in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) with or without metabolic activation. Diethylamine was negative in these tests. Diethylamine was not mutagenic in either of two independent bacterial mutagenicity assays, each conducted with and without exogenous metabolic activation enzymes. Bacterial strains tested included Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2 uvrA/pKM101. In addition to the negative results in the two bacterial assays, no significant increases in the frequencies of micronucleated erythrocytes were seen in peripheral blood of male or female mice from the 3-month study. NTP conducted 2 year inhalation studies in rats and mice. There was no evidence of carcinogenic activity of diethylamine in male or female rats exposed to 31, 62.5, or 125 ppm. There was no evidence of carcinogenic activity of diethylamine in male or female mice exposed to 16, 31, or 62.5 ppm. Exposure to diethylamine resulted in increased incidences of nonneoplastic lesions of the nose in male and female rats and mice, of the cornea in male rats, and of the pleura and lung in female rats.
来源:Hazardous Substances Data Bank (HSDB)
