ACUTE INHALATION STUDIES WITH METHYL ISOCYANATE VAPOR .2. RESPIRATORY-TRACT CHANGES IN GUINEA-PIGS, RATS, AND MICE

ACUTE INHALATION STUDIES WITH METHYL ISOCYANATE VAPOR .2. RESPIRATORY-TRACT CHANGES IN GUINEA-PIGS, RATS, AND MICE
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DOI:
10.1016/0272-0590(86)90188-0
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发表时间:
1986-05-01
期刊:
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子:
--
通讯作者:
DODD, DE
DODD, DE
中科院分区:
其他
文献类型:
--
作者:
FOWLER, EH;DODD, DE

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将Hartley豚鼠、fisher -344大鼠和B6C3F1小鼠暴露于不同浓度的异氰酸甲酯(MIC)蒸气中,大鼠和小鼠的最高浓度为20.4 ppm,豚鼠为10.5 ppm。每个物种的对照组只暴露于空气中。所有动物暴露时间均为6小时。幸存者在暴露14天后被处死。取下所有动物的呼吸道并用显微镜检查。豚鼠对MIC蒸气的敏感性高于大鼠,而大鼠对MIC蒸气的敏感性高于小鼠。在许多死亡的动物身上发现的大体病变包括鼻分泌物,通常带血,以及肺部变色。在接触后不久死亡的动物中,显微镜下的病变包括整个呼吸道上皮的急性坏死,并伴有充血、水肿和炎症。豚鼠特有的显微镜病变是闭塞性细支气管炎,坏死和炎症使细支气管完全封闭。在研究结束时(暴露后第14天)死亡或牺牲的一些动物中观察到的其他显微镜病变包括鼻腔呼吸上皮的鳞状化生,并延伸到喉部、气管,在某些情况下甚至延伸到支气管。此外,观察到整个气道上皮再生和气管、支气管和细支气管粘膜下纤维增生,后者主要局限于啮齿动物。没有动物暴露于2.4或1.0 ppm的MIC蒸气后死亡。在所有三个物种中,暴露于2.4 ppm的动物都有最小的显微镜损伤。只有在豚鼠中,这些1.0 ppm组的病变归因于MIC蒸气暴露。
Hartley guinea pigs, Fischer-344 rats, and B6C3F1 mice of both sexes were exposed to varying concentrations of methyl isocyanate (MIC) vapor with the highest concentrations being 20.4 ppm for rats and mice and 10.5 ppm for guinea pigs. A control group for each species was exposed to air only. All animals were exposed for a duration of 6 hr. and survivors were sacrificed 14 days following exposure. The respiratory tract was removed and examined microscopically from all animals. Guinea pigs were more sensitive to the MIC vapor than were rats which were in turn more sensitive than mice. Gross lesions encountered in many of the animals that died consisted of nasal discharge, often blood tinged, and discoloration of the lungs. Microscopic lesions included acute necrosis of epithelial lining throughout the respiratory tract in animals that died shortly after exposure coupled with congestion, edema, and inflammation. A microscopic lesion which appeared unique to guinea pigs was bronchiolitis obliterans where the necrosis and inflammation had completely closed the bronchioles. Additional microscopic lesions observed in some animals that died or were sacrificed at the end of study (postexposure Day 14) consisted of squamous metaplasia of respiratory epithelium in the nasal cavity, which extended into the larynx, trachea, and, in some cases, the bronchi. In addition, epithelial regeneration throughout the tract and submucosal fibroplasia in the trachea, bronchi, and bronchioles were observed, the latter lesion being primarily confined to rodents. No animals exposed to 2.4 or 1.0 ppm of MIC vapor died following exposure. There were minimal microscopic lesions at sacrifice in the 2.4 ppm-exposed animals from all three species. Only in guinea pigs were these lesions in the 1.0-ppm group attributed to MIC vapor exposure.