Sfide scientifiche e gestionali per una società resiliente ai rischi ambientali in un clima che cambia

Asbestos is a generic term used to identify six silicate minerals of commercial and economic value. The most critical route of exposure is inhalation, leading to the development of Lung Carcinoma (LC) and Malignant Pleural Mesothelioma (MPM) (Schulte et al., 2011). In Italy, the use and production of asbestos were banned in 1992. However, this is still a relevant problem because many contaminated sites are still present and the malignancies associated to asbestos exposure have a long latency period, and so exposed subjects are still at risk of developing a neoplastic disease. Another problem is posed by Natural Occurring Asbestos (NOA), to which bans and regulations cannot be applied. In recent years other types of Elongated Mineral Particles (EMPs), such as erionite and antigorite, have also drawn attention, as they share similar geometry with asbestos fibres and have been linked to high incidence of LC and MPM (Ballirano et al., 2018). NOA and naturally occurring non-asbestos classified asbestiform mineral (NONA) are widespread in many areas of Italy and represent a source of potentially inhalable fibres (Belluso et al., 2020). Although the mechanisms of asbestos-induced carcinogenesis are still poorly understood, three main parameters determining fibre toxicity have been identified: (i) morphology, (ii) biodurability, and (iii) chemical reactivity (Schulte et al., 2011). These characteristics can be affected by the interaction of fibres with the biological environment, with consequent impact on fibres toxic potential. Different Simulated Lung Fluids (SLFs) have been used to study the modifications of EMPs in the biological surroundings: although useful, these fluids represent an oversimplification since they lack specific molecules of the respiratory tract that may affect the dissolution mechanisms and biological activity of inhaled fibres (Zangari et al., 2023; Innes et al., 2021). A possible way to overcome this issue is using Biological Fluids (BFs), which are more complex and better represent the biological environment, and therefore could be more reliable for modelling the fibres behaviour in the human body. At present, there are no studies addressing the interaction between EMPs and BFs. Here, we present an innovative approach that combines mineralogy and biology, with the aim of unveiling the mechanisms of EMPs-induced carcinogenesis. The general goal of this project is to gain valuable knowledge about the interaction of hazardous and potentially hazardous mineral fibres with biological fluids of the lung and pleural compartments, in particular Bronchoalveolar Lavage Fluids (BALFs) and Pleural Effusions (PEs). This will be achieved by investigating the fibres properties (biodurability, mineralogy, chemical reactivity, ability of protein adsorption) and how they change after incubation with complex biological fluids. The systematic investigation of possible EMPs modifications occurring in BFs more accurately reflects the in vivo behaviour of the material under investigation, increasing the knowledge about how the biological environment affects the properties of inhaled EMPs, since until now most studies have been focused on the effects caused by EMPs to the human body (Ghio et al., 2008). In these experimental settings, the study of fibres of well-known carcinogenicity can help predict the toxicity and pathogenicity of unclassified fibres. The relevance of this project also lies in the fact that it includes EMP samples from different Italian regions: by identifying the conditions for potential health hazards caused by these fibres, we can contribute to the assessment of the environmental hazards posed by natural mineral outcrops throughout the territory.