This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO2), chrysotile, commercial crocidolite and amosite asbestos. Aerosol fiber distributions of the chrysotile, crocidolite and amosite were similar (fibers L > 20 μm/cm3: chrysotile-Low/High 29/72; crocidolite 24; amosite 47 fibers/cm3; WHO-fibers/cm3: chrysotile-Low/High 119/233; crocidolite 181; amosite 281 fibers/cm3). The number of particles/cm3 in the BD was similar to that in the chrysotile, crocidolite & amosite exposures (BD 470-715; chrysotile 495-614; crocidolite 415; amosite 417 particles/cm3). In the BD groups, few fibers L > 20 μm were observed in the lungs at the end of exposure and no fibers L > 20 μm at 90d post exposure. In the chrysotile groups, means of 204,000 and 290,000 fibers(L > 20 μm)/lung were measured at 89d. By 180d, means of 1 and 3.9 fibers were counted on the filter corresponding to 14,000 and 55,000 fibers(L > 20 μm)/lung. In the crocidolite and amosite groups mean lung concentrations were 9,055,000 and 11,645,000 fibers(L > 20 μm)/lung at 89d. At 180d the means remained similar with 8,026,000 and 11,591,000 fibers(L > 20 μm)/lung representing 10-13% of the total lung fibers. BAL determined the total number of macrophages, lymphocytes, neutrophils, eosinophils, epithelial-cells and IL-1 beta, TNF-alpha and TGF-beta. At the moderate aerosol concentrations used in this study, neutrophil counts increased ~5 fold in the amphibole asbestos exposure groups. All other groups and parameters showed no important differences at these exposure concentrations. The exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison to the TiO2 particle control and the chrysotile, crocidolite and amosite asbestos control groups. The BAL results provide an initial indication of the differential response. Part 2 presents the presentation and discussion of the histopathological and confocal microscopy findings in this study through 90 days post exposure.

中文翻译：

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在90天的定量吸入毒理学研究中，评估含温石棉刹车粉与TiO2，温石棉，青石棉或铁石棉的接触，剂量反应和命运，中期结果第1部分：实验设计，气雾剂暴露，肺部负担和BAL。

这项对老鼠的刹车粉尘（BD）（用温石棉制造的刹车片）进行的90天重复剂量吸入毒理学研究提供了对肺和胸膜的生物动力学和潜在毒理学的全面了解。暴露时间为6 h / d，5d / wk。，13wks，然后进行终生观察（〜20％存活率）。对照组包括颗粒对照组（TiO2），温石棉，商品青石棉和铁石棉。温石棉，青石棉和铁石棉的气溶胶纤维分布相似（纤维L> 20μm/ cm3：温石棉低/高29/72;青石棉24;铁石棉47纤维/ cm3; WHO纤维/ cm3：温石棉-低/高119/233；青石棉181；铁石棉281纤维/ cm3）。BD中的颗粒数/ cm3与温石棉，青石棉和铁石棉的暴露量相似（BD 470-715；温石棉495-614；青石棉415；amosite 417颗粒/ cm3）。在BD组中，暴露结束时在肺中观察不到L> 20μm的纤维，而暴露后90天在肺中未观察到L> 20μm的纤维。在温石棉组中，在89天时测得的平均肺纤维为204,000和290,000（L> 20μm）。到180d，在过滤器上计数到1和3.9根纤维的平均值，相当于14,000和55,000根纤维（L> 20μm）/肺。在青石棉和铁石棉组，平均肺浓度在89天时分别为9,055,000和11,645,000纤维（L> 20μm）/肺。在180天时，均值保持相似，分别为8,026,000和11,591,000根纤维（L> 20μm）/肺，占总肺纤维的10-13％。BAL确定了巨噬细胞，淋巴细胞，嗜中性粒细胞，嗜酸性粒细胞，上皮细胞和IL-1β，TNF-α和TGF-β的总数。在本研究中使用的中等浓度的气溶胶下，闪石石棉接触组中的中性粒细胞计数增加了约5倍。所有其他组和参数在这些暴露浓度下均未显示出重要差异。与TiO2颗粒对照组和温石棉，青石棉和铁石棉对照组相比，暴露和肺部负担的结果为评估刹车粉尘的潜在毒性提供了可靠的依据。BAL结果提供了差分响应的初始指示。第2部分介绍了本研究在暴露90天后的组织病理学和共聚焦显微镜检查结果的介绍和讨论。所有其他组和参数在这些暴露浓度下均未显示出重要差异。与TiO2颗粒对照组和温石棉，青石棉和铁石棉对照组相比，暴露和肺部负担的结果为评估刹车粉尘的潜在毒性提供了可靠的依据。BAL结果提供了差分响应的初始指示。第2部分介绍了本研究在暴露90天后的组织病理学和共聚焦显微镜检查结果的介绍和讨论。所有其他组和参数在这些暴露浓度下均未显示出重要差异。与TiO2颗粒对照组和温石棉，青石棉和铁石棉对照组相比，暴露和肺部负担的结果为评估刹车粉尘的潜在毒性提供了可靠的依据。BAL结果提供了差分响应的初始指示。第2部分介绍了本研究在暴露90天后的组织病理学和共聚焦显微镜检查结果的介绍和讨论。BAL结果提供了差分响应的初始指示。第2部分介绍了本研究在暴露90天后的组织病理学和共聚焦显微镜检查结果的介绍和讨论。BAL结果提供了差分响应的初始指示。第2部分介绍了本研究在暴露90天后的组织病理学和共聚焦显微镜检查结果的介绍和讨论。