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F344大鼠和B6C3F1小鼠反复吸入暴露后溴甲烷的毒理学与病理学研究

Toxicology and pathology of methyl bromide in F344 rats and B6C3F1 mice following repeated inhalation exposure.

作者信息

Eustis S L, Haber S B, Drew R T, Yang R S

机构信息

National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.

出版信息

Fundam Appl Toxicol. 1988 Nov;11(4):594-610. doi: 10.1016/0272-0590(88)90124-8.

DOI:10.1016/0272-0590(88)90124-8
PMID:3229585
Abstract

The toxicity of methyl bromide was studied in male and female F344 rats and B6C3F1 mice exposed by inhalation to 160 ppm methyl bromide or air 6 hr/day, 5 days/week for up to 6 weeks. The animals were killed after 3, 10, or 30 exposure days, or when 50% mortality was observed in any group. Only female rats survived the entire 30 exposure days at 160 ppm methyl bromide with less than 50% mortality. There were clear species- and sex-related differences in susceptibility of specific organs to methyl bromide. Primary target organs were the brain, kidney, nasal cavity, heart, adrenal gland, liver, and testis. In rats, neuronal necrosis occurred in the cerebral cortex, hippocampus, and thalamus of the brain whereas in mice neuronal necrosis occurred primarily in the internal granular layer of the cerebellum. Nephrosis occurred in all exposed mice, but not rats, and was likely a major cause of moribundity and death. Necrosis of the olfactory epithelium was more severe and extensive in rats than mice. Myocardial degeneration occurred in male and female rats and to a lesser degree in male mice. There was atrophy of the inner zone of the adrenal cortex in female mice and cytoplasmic vacuolation of the adrenal cortex in rats. Testicular degeneration occurred in rats and mice. The target organ specificity of methyl bromide is similar to that of methyl chloride, suggesting that the two monohalomethanes may have a common mechanism of action.

摘要

对雄性和雌性F344大鼠以及B6C3F1小鼠进行了溴甲烷毒性研究,通过吸入方式使其暴露于160 ppm溴甲烷或空气中,每天6小时,每周5天,持续长达6周。在暴露3天、10天或30天后,或者在任何一组观察到50%死亡率时,将动物处死。只有雌性大鼠在160 ppm溴甲烷浓度下存活了整个30天的暴露期,死亡率低于50%。特定器官对溴甲烷的易感性存在明显的物种和性别差异。主要靶器官是脑、肾、鼻腔、心脏、肾上腺、肝脏和睾丸。在大鼠中,大脑的大脑皮质、海马体和丘脑发生神经元坏死,而在小鼠中,神经元坏死主要发生在小脑的内颗粒层。所有暴露的小鼠均发生肾病,但大鼠未发生,肾病可能是濒死和死亡的主要原因。大鼠嗅上皮的坏死比小鼠更严重且更广泛。雄性和雌性大鼠均发生心肌变性,雄性小鼠的心肌变性程度较轻。雌性小鼠肾上腺皮质内区萎缩,大鼠肾上腺皮质出现细胞质空泡化。大鼠和小鼠均发生睾丸变性。溴甲烷的靶器官特异性与氯甲烷相似,表明这两种一卤代甲烷可能具有共同的作用机制。

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