Comparison of Calidria chrysotile asbestos to pure tremolite: Inhalation biopersistence and histopathology following short-term exposure

Comparison of Calidria chrysotile asbestos to pure tremolite: Inhalation biopersistence and histopathology following short-term exposure
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DOI:
10.1080/08958370390248888
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发表时间:
2003-12-01
影响因子:
2.1
通讯作者:
Smith, P
Smith, P
中科院分区:
医学4区
文献类型:
--
作者:
Bernstein, DM;Chevalier, J;Smith, P

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温石棉(一种蛇纹石矿物)和角闪孔石棉之间的差异一直存在广泛的争论。许多研究表明,温石棉比角闪石从肺中清除得更快。为了量化温石棉和角闪孔石棉透闪石的相对清除率,根据欧盟委员会推荐的指导方针,在一项吸入生物持久性研究中对两种纤维进行了评估。此外,对短期暴露后肺部的组织病理学反应进行了评估。本文介绍了在停止接触后90天内的研究结果。研究结束后,后续文章将提供停止暴露后12个月的完整结果。为了量化这些纤维从肺中去除的动态和速率,研究了来自加利福尼亚州新伊德里亚Coalinga矿的商业级温石棉样品的生物持久性,Calidria RG144型和长纤维透沸石。对于合成玻璃体纤维,已发现长度超过20微米的纤维的生物持久性与其致病的可能性直接相关。本研究旨在确定肺清除率(生物持久性)和组织病理学反应。由于长纤维已被证明具有最大的致病性,因此设计了气溶胶产生技术,以最大限度地增加长可呼吸纤维的数量。温石棉样品被特别选择,在暴露气溶胶中有200根纤维/厘米(3)长度超过20微米。这些较长的纤维被发现主要由多个较短的原纤维组成。所选择的透闪石样品在暴露气溶胶中有100根纤维/厘米(3),长度超过20微米。加州温石棉纤维比任何其他商业纤维(包括合成玻璃体纤维)更快地从肺中清除(T-1/2,T-纤维lbbb20 (mum) = 7小时)。有了如此迅速的纤维清除,5天的暴露预计不会导致肺部出现任何病理变化,吸入温石棉的动物的肺部没有出现炎症或病理迹象,与呼吸过滤空气的动物的肺部没有什么不同。暴露于透闪石5天后,一旦沉积在肺实质中的透闪石纤维不清除,几乎立即导致肺部炎症和病理反应。在第一个检查时间点,停止暴露后1天,观察到炎症并已形成肉芽肿。暴露后14天,这些微肉芽肿变成纤维化,暴露后90天,胶原沉积的严重程度增加,其中一只大鼠观察到间质纤维化。这些发现为证实温石棉与角闪石之间的动力学和病理学差异提供了重要的基础。由于温石棉已被证实不含透闪石纤维,目前的研究结果以及毒理学和流行病学研究的结果表明,这种纤维与肺部疾病无关。
The differences between chrysotile asbestos, a serpentine mineral, and amphibole asbestos have been debated extensively. Many studies have shown that chrysotile is cleared from the lung more rapidly than amphibole. In order to quantify the comparative clearance of chrysotile and the amphibole asbestos tremolite, both fibers were evaluated in an inhalation biopersistence study that followed the European Commission recommended guidelines. In addition, the histopathological response in the lung was evaluated following the short-term exposure. This article presents the results of this study through 90 days after cessation of exposure. Following the termination of the study, a subsequent article will provide the complete results through 12 mo after cessation of exposure. In order to quantify the dynamics and rate by which these fibers are removed from the lung, the biopersistence of a sample of commercial grade chrysotile from the Coalinga mine in New Idria, CA, of the type Calidria RG144 and of a long-fiber tremolite were studied. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 mum has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance ( biopersistence) and the histopathological response. As the long fibers have been shown to have the greatest potential for pathogenicity, the aerosol generation technique was designed to maximize the number of long respirable fibers. The chrysotile samples were specifically chosen to have 200 fibers/cm(3) longer than 20 mum in length present in the exposure aerosol. These longer fibers were found to be largely composed of multiple shorter fibrils. The tremolite samples were chosen to have 100 fibers/cm(3) longer than 20 mum in length present in the exposure aerosol. Calidria chrysotile fibers clear from the lung more rapidly (T-1/2,T- fibers L> 20 (mum) = 7 h) than any other commercial fiber tested including synthetic vitreous fibers. With such rapidly clearing fibers, the 5-day exposure would not be expected to result in any pathological change in the lung, and the lungs of animals that inhaled Calidria chrysotile showed no sign of inflammation or pathology and were no different than the lungs of those animals that breathed filtered air. Following this 5-day exposure to tremolite, the tremolite fibers once deposited in the lung parenchyma do not clear and almost immediately result in inflammation and a pathological response in the lung. At the first time point examined, 1 day after cessation of exposure, inflammation was observed and granulomas were already formed. By 14 days postexposure these microgranulomas had turned fibrotic, and by 90 days postexposure the severity of the collagen deposits had increased and interstitial fibrosis was observed in one of the rats. These findings provide an important basis for substantiating both kinetically and pathologically the differences between chrysotile and the amphibole tremolite. As Calidria chrysotile has been certified to have no tremolite fiber, the results of the current study together with the results from toxicological and epidemiological studies indicate that this fiber is not associated with lung disease.