Today, many research groups in the world are struggling to fully understand the mechanisms leading to the carcinogenesis of hazardous mineral fibres, like asbestos, in view of devising predictive toxicology models. Our work attempts the completion of a model aimed at evaluating how, and to what extent, physical-crystal-chemical and morphological parameters of mineral fibres prompt adverse effects leading to carcinogenesis. In vitro toxicology tests on the 10 key characteristics (KC) of carcinogens adopted by the International Association for Research on Cancer (IARC) have been performed for a commercial chrysotile divided in two size-separated fractions (> and ≤ m length), standard UICC crocidolite and the non-carcinogenic wollastonite. The analysis of the in vitro data allowed to assess the major fibre parameters for each mineral fibre, and the intensity of their effect, responsible for alterations of major IARC KCs (1). Our model shows that, although similar toxicological responses of major IARC KCs are observed for the two carcinogens chrysotile and crocidolite, due their different physical-chemical features the fibre parameters contributing to carcinogenicity seem to be specific for each fibre. For chrysotile, the major fibre parameters contributing to the IARC KC cellular alterations are the surface area and the dissolution rate with the related velocity of release of metals (namely iron). For crocidolite, they are fibre length, iron, ferrous ion and transition metals content, and zeta potential. Conversely, among the 10 KCs analysed in vitro, the altered pathways discriminating between the non-carcinogenic and the carcinogenic fibres were: 2.Genotoxicity, 3.Altered DNA repair, 4.Epigenetic alterations, 5.Oxidative stress, 6.Chronic inflammation, 9.Immortalization. In conclusion, we propose the use of an algorithm for a mineral fibre predictive toxicology model by combining the fibre parameters with selected discriminating KCs, possibly leading to prevention strategies as long as the nature of the fibre of the exposed patient is known.
A comprehensive model for predicting the toxicology of mineral fibres by connecting the fibre parameters to the key characteristics of carcinogens.
Serena Mirata;Vanessa Almonti;Mario Passalacqua;Stefania Vernazza;Anna Maria Bassi;Sonia Scarfì
2026-01-01
Abstract
Today, many research groups in the world are struggling to fully understand the mechanisms leading to the carcinogenesis of hazardous mineral fibres, like asbestos, in view of devising predictive toxicology models. Our work attempts the completion of a model aimed at evaluating how, and to what extent, physical-crystal-chemical and morphological parameters of mineral fibres prompt adverse effects leading to carcinogenesis. In vitro toxicology tests on the 10 key characteristics (KC) of carcinogens adopted by the International Association for Research on Cancer (IARC) have been performed for a commercial chrysotile divided in two size-separated fractions (> and ≤ m length), standard UICC crocidolite and the non-carcinogenic wollastonite. The analysis of the in vitro data allowed to assess the major fibre parameters for each mineral fibre, and the intensity of their effect, responsible for alterations of major IARC KCs (1). Our model shows that, although similar toxicological responses of major IARC KCs are observed for the two carcinogens chrysotile and crocidolite, due their different physical-chemical features the fibre parameters contributing to carcinogenicity seem to be specific for each fibre. For chrysotile, the major fibre parameters contributing to the IARC KC cellular alterations are the surface area and the dissolution rate with the related velocity of release of metals (namely iron). For crocidolite, they are fibre length, iron, ferrous ion and transition metals content, and zeta potential. Conversely, among the 10 KCs analysed in vitro, the altered pathways discriminating between the non-carcinogenic and the carcinogenic fibres were: 2.Genotoxicity, 3.Altered DNA repair, 4.Epigenetic alterations, 5.Oxidative stress, 6.Chronic inflammation, 9.Immortalization. In conclusion, we propose the use of an algorithm for a mineral fibre predictive toxicology model by combining the fibre parameters with selected discriminating KCs, possibly leading to prevention strategies as long as the nature of the fibre of the exposed patient is known.
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