Bernstein David M, Rogers Rick, Smith Paul
Inhal Toxicol. 2004 Oct-Nov;16(11-12):745-61. doi: 10.1080/08958370490490176.
With the initial understanding of the relationship of asbestos to disease, little information was available on whether the two different groups of minerals that are called asbestos were of similar or different potency in causing disease. Asbestos was often described as a durable fiber that if inhaled would remain in the lung and cause disease. It has been only more recently, with the development of a standardized protocol for evaluating the biopersistence of mineral fibers in the lung, that the clearance kinetics of the serpentine chrysotile have been shown to be dramatically different from those of amphibole asbestos, with chrysotile clearing rapidly from the lung. In addition, recent epidemiology studies also differentiate chrysotile from amphibole asbestos. The biopersistence studies mentioned have indicated that chrysotile from Canada and California clear rapidly from the lung once inhaled. However, variations in chrysotile mineralogy have been reported depending upon the region. This is most likely associated with variations in the forces which created the chrysotile fibers centuries ago. In the present study, the dynamics and rate of clearance of chrysotile from the Cana Brava mine in central Brazil was evaluated in a comparable inhalation biopersistence study in the rat. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 microm has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance (biopersistence) and translocation and distribution within the lung. As the long fibers have been shown to have the greatest potential for pathogenicity, the chrysotile samples were specifically chosen to have more than 450 fibers/cm(3) longer than 20 microm in length present in the exposure aerosol. For the fiber clearance study (lung digestions), at 1 day, 2 days, 7 days, 2 wk, 1 mo, 3 mo, 6 mo, and 12 mo following a 5-day (6 h/day) inhalation exposure, the lungs from groups of animals were digested by low-temperature plasma ashing and subsequently analyzed by transmission electron microscopy (at the GSA Corp.) for total chrysotile fiber number in the lungs and chrysotile fiber size (length and diameter) distribution in the lungs. This lung digestion procedure digests the entire lung with no possibility of identifying where in the lung the fibers are located. A fiber distribution study (with confocal microscopy) was included in order to identify where in the lung the fibers were located. At 2 days, 2 wk, 3 mo, 6 mo, and 12 mo postexposure, the lungs from groups of animals were analyzed by confocal microscopy to determine the anatomic fate, orientation, and distribution of the retained chrysotile fibrils deposited on airways and those fibers translocated to the broncho-associated lymphoid tissue (BALT) subjacent to bronchioles in rat lungs. While the translocation of fibers to the BALT and lymphatic tissue is considered important as in cases of human's with asbestos-related disease, there has been no report in the literature of pathological changes in the BALT and lymphatic tissue stemming from asbestos. Thus, if the fibers are removed to these tissues, they are effectively neutralized in the lung. Chrysotile was found to be rapidly removed from the lung. Fibers longer than 20 microm were cleared with a half-time of 1.3 days, most likely by dissolution and breakage into shorter fibers. Shorter fibers were also rapidly cleared from the lung with fibers 5-20 microm clearing even more rapidly (T1/2 = 2.4 days) than those < 5 microm in length (T1/2 weighted = 23. days). Breaking of the longer fibers would be expected to increase the short fiber pool and therefore could account for this difference in clearance rates. The short fibers were never found clumped together but appeared as separate, fine fibrils, occasionally unwound at one end. Short free fibers appeared in the corners of alveolar septa, and fibers or their fragments were found within alveolar macrophages. The same was true of fibers in lymphatics, as they appeared free or within phagocytic lymphocytes. These results support the evidence presented by McDonald and McDonald (1997) that the chrysotile fibers are rapidly cleared from the lung in marked contrast to amphibole fibers which persist.
随着对石棉与疾病关系的初步认识,关于被称为石棉的两类不同矿物在致病方面的效力是相似还是不同,几乎没有可用信息。石棉常被描述为一种耐用纤维,若被吸入会留在肺部并引发疾病。直到最近,随着评估矿物纤维在肺部生物持久性的标准化方案的发展,才发现蛇纹石温石棉的清除动力学与闪石石棉的显著不同,温石棉能迅速从肺部清除。此外,近期的流行病学研究也将温石棉与闪石石棉区分开来。上述生物持久性研究表明,来自加拿大和加利福尼亚的温石棉一旦被吸入,会迅速从肺部清除。然而,据报道温石棉矿物学存在因地区而异的情况。这很可能与几个世纪前形成温石棉纤维的力量差异有关。在本研究中,在大鼠的一项可比吸入生物持久性研究中,评估了来自巴西中部卡纳布拉瓦矿的温石棉从肺部清除的动态和速率。对于合成玻璃纤维,已发现长度超过20微米的纤维的生物持久性与它们致病的可能性直接相关。本研究旨在确定肺部清除(生物持久性)以及在肺部的转运和分布。由于长纤维已被证明具有最大的致病潜力,温石棉样品被特意选取,使其暴露气溶胶中长度超过20微米的纤维含量超过450根/立方厘米。对于纤维清除研究(肺部消化),在为期5天(每天6小时)的吸入暴露后的第1天、2天、7天、2周、1个月、3个月、6个月和12个月,通过低温等离子体灰化消化动物组的肺部,随后通过透射电子显微镜(在GSA公司)分析肺部温石棉纤维总数以及肺部温石棉纤维尺寸(长度和直径)分布。这种肺部消化程序会消化整个肺部,无法确定纤维在肺部的位置。为了确定纤维在肺部的位置,纳入了一项纤维分布研究(使用共聚焦显微镜)。在暴露后第2天、2周、3个月、6个月和12个月,通过共聚焦显微镜分析动物组的肺部,以确定沉积在气道上的残留温石棉原纤维以及转运至大鼠肺部细支气管下方支气管相关淋巴组织(BALT)的那些纤维的解剖归宿、取向和分布。虽然纤维向BALT和淋巴组织的转运被认为很重要,如同在患有石棉相关疾病的人类病例中那样,但文献中尚无关于石棉导致BALT和淋巴组织病理变化的报道。因此,如果纤维被转运至这些组织,它们在肺部会被有效中和。已发现温石棉能迅速从肺部清除。长度超过20微米的纤维以1.3天的半衰期清除,很可能是通过溶解和断裂成较短纤维。较短纤维也能迅速从肺部清除,5 - 20微米的纤维清除速度甚至比长度小于5微米的纤维(加权半衰期 = 23天)更快(半衰期 = 2.4天)。较长纤维的断裂预计会增加短纤维池,因此可以解释清除率的这种差异。短纤维从未被发现聚集在一起,而是呈现为单独的细原纤维,偶尔一端会展开。短游离纤维出现在肺泡间隔的角落,并且在肺泡巨噬细胞内发现纤维或其片段。淋巴管中的纤维情况也是如此,它们呈现为游离状态或在吞噬性淋巴细胞内。这些结果支持了麦克唐纳和麦克唐纳(1997年)提出的证据,即温石棉纤维与持续存在的闪石纤维形成鲜明对比,能迅速从肺部清除。