| Popis: |
This project is part of the Unilever R&D’s Aerosol Safety Programme and aimed at developing in vitro mono- and co-culture assays that can predict the fibrogenic potential of substances. The organic polymers S2218600, S2429901 and S2219200 (hereafter referred to as P1, P2 and P3, respectively) were used as model substances. The particles TiO2 and MinUsil (quartz) were used as negative and positive controls for fibrogenesis. All three polymers were found to cause fibrosis in male Wistar rats following intra-tracheal instillations. Animals treated with P1 and P3 developed fibrosing granuloma, and all polymers caused interstitial fibrosis. A strong initial inflammatory response was observed after use of all polymers. All polymers caused an increase in the size of alveolar macrophages, which was particularly pronounced after treatment with P2. The polymers’ ranking was P1 > P3 > P2 for their fibrogenic potential, and P3 > P1 > P2 for the initial inflammatory response. Several in vitro assays were used to assess different aspects of the fibrotic response using the rat lung fibroblast-like and alveolar epithelial type II cell lines RFL-6 and RLE-6TN. The cytotoxicity of the polymers as measured by the LDH assay was P3 >> P1 > P2. All polymers caused proliferation of both cell lines. The human fibroblast cell line HFL-1 was used to investigate changes in collagen production 24 h after treatment with the polymers. Collagen was increased compared to the untreated control in the order P1 > P3 > P2 for fibroblasts cultured alone or in co-culture with AE2 cells, but no changes in collagen expression were found in macrophages. The expression profiles of a fibroblast cell line and lungs treated with polymers did not show sufficient correlation to warrant it’s the use of whole genomic analysis as an alternative for animal testing. |
