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Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 2: Histopathological examination, Confocal microscopy and collagen quantification of the lung and pleural cavity.
Toxicology and Applied Pharmacology ( IF 3.8 ) Pub Date : 2019-12-09 , DOI: 10.1016/j.taap.2019.114847
D M Bernstein 1 , B Toth 2 , R A Rogers 3 , D E Kling 3 , P Kunzendorf 4 , J I Phillips 5 , H Ernst 6
Affiliation  

The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

中文翻译:

在90天的定量吸入毒理学研究中评估含温石棉刹车粉与TiO2,温石棉,青石棉或铁石棉的肺和胸膜的剂量反应和命运-中期结果第2部分:组织病理学检查,共聚焦显微镜和肺和胸腔的胶原蛋白定量。

这项为期90天的多剂量吸入毒理学研究与暴露后的终生观察得出的中期结果表明,用温石棉TiO2制造的刹车片产生的刹车粉尘在肺部的持久性和病理反应方面存在重要的根本差异。与闪石,青石棉和铁石棉相比,单独使用温石棉或温石棉。在刹车粉尘暴露组中,任何时候都没有观察到明显的病理反应。注意到颗粒有少量的巨噬细胞积累。瓦格纳分数为1至2(1 =空气控制组),与TiO2组相似。温石棉具有生物可降解性,显示其基质变弱,并分解成短纤维和颗粒,可以被肺泡巨噬细胞清除并持续溶解。在温石棉暴露组中,观察到颗粒载有巨噬细胞的积累导致轻微的间质性炎症反应(Wagner评分1-3)。没有支气管周围发炎,偶尔有非常轻微的间质纤维化。组织病理学和共聚焦分析清楚地将角闪石棉,青石棉和铁石棉的病理反应与制动粉尘和温石棉的病理反应区分开。青石棉和铁石棉均引起持续的炎症,微肉芽肿和纤维化(Wagner评分4),并持续至暴露后。肺和速冻胸壁的共聚焦显微镜检查定量了肺以及内脏和顶叶表面广泛的炎症反应和胶原蛋白的发育。此处报告了中期结果,为区分刹车粉暴露与闪石石棉暴露后的影响提供了明确的依据。整个生命周期后期的后续结果将随之而来。
更新日期:2019-12-11
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