Subchronic inhalation studies of styrene in CD rats and CD-1 mice.
Subchronic inhalation studies of styrene in CD rats and CD-1 mice.
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CD 大鼠和 CD-1 小鼠中苯乙烯的亚慢性吸入研究。
DOI：
10.1093/toxsci/35.2.152
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
Pamela A. Mullins
中科院分区：
文献类型：
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作者：
G. Cruzan;JANETTE R. Cushman;LARRY S. Andrews;GEOFFREY C. Granville;ROLAND R. Miller;COLIN J. Hardy;D. W. Coombs;Pamela A. Mullins
每组10只雄性和10只雌性Charles River(CRL)大鼠暴露于0、200、500、1000或1500ppm的苯乙烯蒸气中，每周5天，每天6小时，持续13周。苯乙烯对存活率、血液学或临床化学均无影响。13周后，1500ppm的雄性体重减轻了10%，1000ppm和1500ppm的雄性和雌性摄入的水分比对照组多。组织病理学改变局限于鼻粘膜的嗅觉上皮。将20只雄性和20只雌性CRL CD-1和B6C3F1小鼠暴露在苯乙烯蒸气中，暴露于0、15、60、250或500ppm的蒸汽中，每天6小时，每周5天，持续2周。在CD-1和B6C3F1小鼠中都观察到了暴露于250或500ppm的死亡；雌性小鼠因暴露于250ppm而死亡，但雄性小鼠没有死于500ppm。将10只雄性和10只雌性CRL CD-1小鼠暴露在苯乙烯蒸气中，每周5天，每天6小时，每次50,100,150或200ppm，持续13周。两只暴露在200ppm的雌性在第一周死亡。在200ppm的死者和一些女性幸存者身上，肝脏毒性很明显。在暴露于100、150或200ppm的小鼠的肺部和所有治疗组的鼻腔中观察到了变化，那些暴露于50ppm的小鼠受影响较小。15只雄性大鼠和30只雄性小鼠组成的卫星组按上述方法暴露2、5或13周，以测量细胞增殖(BrdU标记)。大鼠和小鼠肝脏及大鼠肺细支气管区和肺泡区的细胞未见细胞增殖增加。小鼠肺中II型肺泡细胞的标记指数未见增加，而在150和200ppm的浓度下，Clara细胞的标记指数在2周后增加，偶尔在5周后增加。动物之间的标记指数差异很大，强调了大群体规模的必要性。对于鼻道效应，CD-1小鼠没有发现NOAEL，但CD大鼠的NOAEL为200ppm。至于其他影响，大鼠的NOAEL为500ppm，小鼠为50ppm。
Groups of 10 male and 10 female Charles River (CRL) CD (Sprague-Dawley-derived) rats were exposed to styrene vapor at 0, 200, 500, 1000, or 1500 ppm 6 hr per day 5 days per week for 13 weeks. Styrene had no effect on survival, hematology, or clinical chemistry. Males at 1500 ppm weighed 10% less after 13 weeks and males and females at 1000 and 1500 ppm consumed more water than controls. Histopathologic changes were confined to the olfactory epithelium of the nasal mucosa. Groups of 20 male and 20 female CRL CD-1 and B6C3F1 mice were exposed to styrene vapor at 0, 15, 60, 250, or 500 ppm 6 hr per day 5 days per week for 2 weeks. Mortality was observed in both CD-1 and B6C3F1 mice exposed to 250 or 500 ppm; more female mice, but not males, died from exposure to 250 ppm than from 500 ppm. Groups of 10 male and 10 female CRL CD-1 mice were exposed to styrene vapors at 0, 50, 100, 150, or 200 ppm 6 hr per day 5 days per week for 13 weeks. Two females exposed to 200 ppm died during the first week. Liver toxicity was evident in the decedents and in some female survivors at 200 ppm. Changes were observed in the lungs of mice exposed to 100, 150, or 200 ppm and in the nasal passages of all treatment groups, those exposed to 50 ppm being less affected. Satellite groups of 15 male rats and 30 male mice were exposed as described above for 2, 5, or 13 weeks for measurement of cell proliferation (BrdU labeling). No increase in cell proliferation was found in liver of rats or mice or in cells of the bronchiolar or alveolar region of the lung of rats. No increase in labeling index of type II pneumocytes was seen in mouse lungs, while at 150 and 200 ppm, an increased labeling index of Clara cells was seen after 2 weeks and in occasional mice after 5 weeks. Large variations in the labeling index among animals emphasize the need for large group sizes. For nasal tract effects, a NOAEL was not found in CD-1 mice, but in CD rats, the NOAEL was 200 ppm. For other effects, the NOAEL was 500 ppm in rats and 50 ppm in mice.