Final results from a 90-day quantitative inhalation toxicology study evaluating the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos: Histopathological examination, confocal microscopy and collagen quantification of the lung and pleural cavity

• Published in: Toxicology and applied pharmacology 2021-08, Vol.424, p.115598, Article 115598
• Main Authors: Bernstein, David M., Toth, Balazs, Rogers, Rick A., Kunzendorf, Peter, Phillips, James I., Schaudien, Dirk
• Format: Article
• Language: English
• Subjects: Amphibole; Asbestos; Brake dust; Chrysotile; Inhalation; Pathology; Tumors
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2021.115598

The final results from this multi-dose, 90-day inhalation toxicology study in the rat with life-time post-exposure observation have shown a significant fundamental difference in pathological response and tumorgenicity between brake dust generated from brake pads manufactured with chrysotile or from chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. The groups exposed to brake dust showed no significant pathological or tumorigenic response in the respiratory track compared to the air control group at exposure concentrations and deposited doses well above those at which humans have been exposed. Slight alveolar/interstitial macrophage accumulation of particles was noted. Wagner grades were 1–2 (1 = control group), similar to the TiO2 particle control group. Chrysotile was not biopersistent, exhibiting in the lung a deterioration of its matrix which results in breakage into particles and short fibers which can be cleared by alveolar macrophages and which can continue to dissolve. Particle-laden macrophage accumulation was observed, leading to a very-slight interstitial inflammatory response (Wagner grade 1–3). There was no peribronchiolar inflammation, occasional very-slight interstitial fibrosis (Wagner grade 4), and no exposure-related tumorigenic response. The pathological response of crocidolite and amosite compared to the brake dust and chrysotile was clearly differentiated by the histopathology and the confocal analysis. Crocidolite and amosite induced persistent inflammation, microgranulomas, persistent fibrosis (Wagner grades 4), and a dose-related lung tumor response. Confocal microscopy quantified extensive inflammatory response and collagen development in the lung, visceral and parietal pleura as well as pleural adhesions. These results provide a clear foundation for differentiating the innocuous effects of brake dust exposure from the adverse effects following amphibole asbestos exposure. •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/tumors observed at any time point in the brake-dust grps.•Chrysotile produced low level inflammation in lungs, no tumors, no effect in pleura.•Crocidolite & amosite produced lung tumor dose-response & lung & pleural fibrosis.