Consultant in Toxicology, Geneva, Switzerland.
CiToxLab, Szabadságpuszta, Hungary.
Toxicol Appl Pharmacol. 2018 Jul 15;351:74-92. doi: 10.1016/j.taap.2018.04.033. Epub 2018 Apr 27.
This study provides an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake-dust (brakes manufactured with chrysotile). The design included a 28-day repeated multi-dose inhalation exposure (6 h/d, 5 d/wk, 4 wks) followed by 28-days without exposure. Fiber control groups included a similar grade chrysotile as used in the brakes and a commercial crocidolite asbestos. Aerosol fiber distributions of the chrysotile and crocidolite were similar (fiber-length > 20 μm/cm: Chrysotile-low/high 42/62; Crocidolite-low/high 36/55; WHO-fibers/cm: Chrysotile-low/high 192/219; Crocidolite-low/high 211/255). The total number of aerosol particles/cm in the brake-dust was similar to that in the chrysotile (Brake-dust 710-1065; Chrysotile 532-1442). Brake-dust at particle exposure levels equal to or greater than chrysotile or crocidolite caused no indication of microgranulomas, epithelial hyperplasia, or fibrosis (Wagner score < 1.7) or changes in bronchoalveolar lavage (BAL) indices from the air control. Chrysotile BAL indices did not differ from the air control. Pathologically, there was low level of inflammation and epithelial hyperplasia, but no fibrosis (Wagner score ≤ 3). Crocidolite induced elevated neutrophils and cell damage (BAL), persistent inflammation, microgranulomas, and fibrosis (Wagner scores 4) which persisted through the post exposure period. Confocal microscopy of snap-frozen chestwalls showed no difference between control, brake-dust and chrysotile-HD groups or in thickness of visceral or parietal pleural. The crocidolite exposure resulted in extensive inflammatory response, collagen development and adhesions between the visceral and parietal surfaces with double the surface thickness. These results provide essential information for the design of a subsequent subchronic study.
本研究旨在了解吸入刹车尘（由温石棉制成的刹车片）后肺部和胸膜中的生物动力学和潜在毒理学。该设计包括 28 天重复的多剂量吸入暴露（每天 6 小时，每周 5 天，共 4 周），随后进行 28 天无暴露。纤维对照组包括与刹车片相同等级的温石棉和商业青石棉。温石棉和青石棉的气溶胶纤维分布相似（纤维长度>20μm/cm：温石棉低/高 42/62；青石棉低/高 36/55；WHO 纤维/cm：温石棉低/高 192/219；青石棉低/高 211/255）。刹车尘中的气溶胶粒子总数/cm 与温石棉相似（刹车尘 710-1065；温石棉 532-1442）。在等于或大于温石棉或青石棉的粒子暴露水平下，刹车尘不会引起微肉芽肿、上皮增生或纤维化（Wagner 评分<1.7），也不会引起支气管肺泡灌洗（BAL）指数的变化与空气对照相比。温石棉 BAL 指数与空气对照无差异。病理学上，炎症和上皮增生程度较低，但无纤维化（Wagner 评分≤3）。青石棉引起中性粒细胞和细胞损伤（BAL）升高、持续炎症、微肉芽肿和纤维化（Wagner 评分 4），这些在暴露后仍持续存在。对冷冻胸部的共聚焦显微镜检查显示，对照组、刹车尘组和温石棉-HD 组之间或内脏胸膜和壁胸膜的厚度无差异。青石棉暴露导致广泛的炎症反应、胶原形成和内脏与壁面之间的粘连，使表面厚度增加一倍。这些结果为随后的亚慢性研究设计提供了重要信息。
