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

• Published in: Toxicology and applied pharmacology Vol. 387; p. 114847
• Main Authors: Bernstein, D.M., Toth, B., Rogers, R.A., Kling, D.E., Kunzendorf, P., Phillips, J.I., Ernst, H.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15-01-2020
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2019.114847

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.
•Evaluated brake dust from brake pads manufactured with chrysotile in 90-day study.•Included comparative TiO2, chrysotile, crocidolite & amosite asbestos exposure grps.•No significant pathology observed at any time point in the brake-dust groups.•Chrysotile produced low level of inflammation in the lungs, no effect in pleura.•Crocidolite and amosite produced pathological response (fibrosis) in lung & pleura.