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F344大鼠和B6C3F(1)小鼠吸入氯丁二烯(2-氯-1,3-丁二烯)的毒性

Toxicity of inhaled chloroprene (2-chloro-1,3-butadiene) in F344 rats and B6C3F(1) mice.

作者信息

Melnick R L, Elwell M R, Roycroft J H, Chou B J, Ragan H A, Miller R A

机构信息

National Institute of Environmental Health Services, Research Triangle Park, NC 27709, USA.

出版信息

Toxicology. 1996 Apr 15;108(1-2):79-91. doi: 10.1016/0300-483x(95)03286-o.

Abstract

Chloroprene (2-chloro-1,3-butadiene) is a high production chemical used almost exclusively in the production of polychloroprene (neoprene) elastomer. Because of its structural similarity to isoprene (2-methyl-1,3-butadiene) and to 1,3-butadiene, a potent trans-species carcinogen, inhalation studies were performed on chloroprene to characterize its toxicological potential and to provide a basis for selecting exposure concentrations for chronic toxicity and carcinogenicity studies. Thirteen-week inhalation toxicology studies were conducted in male and female F344 rats and B6C3F(1) mice at exposure concentrations of 0, 5, 12, 32 or 80 ppm (6 h/day; 5 days/week). A 200 ppm exposure group was also included for rats only, because a previous study showed that this concentration of chloroprene is lethal to mice. In mice, exposure to 80 ppm chloroprene caused a marginal decrease in body weight gain in males and epithelial hyperplasia of the forestomach in males and females. This lesion has been observed in mice exposed to isoprene or 1,3-butadiene. In rats, exposure to 80 ppm chloroprene or higher concentrations caused degeneration and metaplasia of the olfactory epithelium and exposure to 200 ppm caused anemia, hepatocellular necrosis and reduced sperm motility. These lesions have not been observed in rats exposed to isoprene or 1,3-butadiene. The profile of toxic effects of chloroprene is considerably different from that of isoprene or 1,3-butadiene; this may be due to differences in exposure concentrations that were used in toxicology studies of these compounds and /or to the influence of the chlorine substitution on the toxicokinetics of these compounds, on their biotransformation, or on the reactivity of metabolic intermediates with tissue macromolecules.

摘要

氯丁二烯(2-氯-1,3-丁二烯)是一种高产量化学品,几乎专门用于生产聚氯丁二烯(氯丁橡胶)弹性体。由于其结构与异戊二烯(2-甲基-1,3-丁二烯)以及一种强效的跨物种致癌物1,3-丁二烯相似,因此对氯丁二烯进行了吸入研究,以表征其毒理学潜力,并为选择慢性毒性和致癌性研究的暴露浓度提供依据。在雄性和雌性F344大鼠以及B6C3F(1)小鼠中进行了为期13周的吸入毒理学研究,暴露浓度分别为0、5、12、32或80 ppm(每天6小时;每周5天)。仅在大鼠中还设置了一个200 ppm的暴露组,因为先前的一项研究表明,这种浓度的氯丁二烯对小鼠具有致死性。在小鼠中,暴露于80 ppm氯丁二烯会导致雄性体重增加略有下降,以及雄性和雌性前胃上皮增生。在暴露于异戊二烯或1,3-丁二烯的小鼠中也观察到了这种病变。在大鼠中,暴露于80 ppm氯丁二烯或更高浓度会导致嗅觉上皮变性和化生,暴露于200 ppm会导致贫血、肝细胞坏死和精子活力降低。在暴露于异戊二烯或1,3-丁二烯的大鼠中未观察到这些病变。氯丁二烯的毒作用谱与异戊二烯或1,3-丁二烯有很大不同;这可能是由于这些化合物毒理学研究中使用的暴露浓度不同和/或氯取代对这些化合物的毒代动力学、生物转化或代谢中间体与组织大分子反应性的影响。

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