A review of inhalation toxicology studies with Para-aramid fibrils

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The paper summarizes the results of inhalation toxicology studies associated with para-aramid (p-aramid) fibrils. The review is subdivided into two categories: the results of inhalation toxicity studies and mechanistic inhalation studies. Keratin-associated lesions were observed in the lungs of female rats following chronic exposure to high concentrations of p-aramid. These lesions were originally interpreted as cystic keratinizing squamous cell carcinomas (CKSCC). In recent years, this keratinizing lesion has been observed in the lungs of rats with greater regularity in numerous chronic inhalation studies following exposures to a variety of dusts. In an attempt to reach a consensus on an appropriate diagnosis for this lesion, an international panel of pathologists was convened to evaluate the morphological aspects of this lesion. The panel considered that the most appropriate diagnosis for this lesion was ‘proliferative keratin cyst’ (PKC). the biological potential of the PKC remains controversial, but it appears to be unique to the rat species and has little relevance for humans. Mechanistic studies with p-aramid have demonstrated that acute inhalation of high concentrations of fibrils produces a potent but transient pulmonary inflammatory and cell labelling response. The inhaled fibrils have low durability in the lungs of rats as evidenced by a progressive decrease in median fibre lengths with increasing residence time in the lung. In contrast, in a comparative study, size-separated chrysotile asbestos produced a sustained increase over controls in cellular proliferation responses of terminal airways, parenchyma, subpleural and mesothelial regions. In addition, while the short fibres were cleared at a normal or rapid rate, the long (i.e. > 5 μm) chrysotile fibres were retained in the lung or cleared at a slow rate, suggesting that this subpopulation of fibres is durable in the lungs of exposed rats. These results point out the differences in the lung responses between p-aramid fibrils when compared to chrysotile asbestos fibres, namely, that chrysotile produced enhanced and sustained cell proliferation responses, and that the long chrysotile fibres were retained in the lungs of exposed rats.