Phd in CHEMICAL SCIENCES

Thesis title: Biological monitoring for the assessment of exposure to hazards and health surveillance

Occupational exposure to hazards remains a major global health concern, with over 2.7 million work-related deaths recorded annually, nearly 1 million of which are attributed to exposure to chemicals. Despite the existence of comprehensive regulatory frameworks, current chemical risk assessment strategies rely largely on environmental monitoring and modeling techniques. These conventional approaches often fail to accurately reflect internal exposure due to few limitations. Biological monitoring offers a more direct and individualized assessment of exposure by measuring chemicals or their metabolites in biological matrices. However, its widespread application is hindered by the limited number of substances with defined biological limit values (BLVs): actually, only one substance has a legislated BLV (lead in blood), highlighting a significant regulatory gap. In this context, this PhD research focuses on the applicability and effectiveness of NMR-based metabolomics as an innovative tool for exposure assessment in occupational settings. In part I, a complete and reproducible metabolomics workflow was optimized and applied to five biomonitoring settings in different complex exposure scenarios. NMR profiling revealed significant alterations in multiple metabolic pathways, including energy metabolism, amino acid turnover and redox balancing, suggesting early, subclinical biochemical responses to occupational stressors. Multiplatform approaches are also presented for two scenarios combining NMR with gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS) enabling broader metabolome coverage and deeper mechanistic insights. In part II, the same metabolomics approach was applied to assess the biological effects of airborne particulate matter exposure using Drosophila melanogaster as a novel in vivo model. Both in laboratory and in situ exposures conditions tested demonstrated the model’s sensitivity and relevance for toxicological studies in occupational field. Overall, the findings of this work highlight the potential of NMR-based metabolomics as a complementary tool in occupational health frameworks with the aim to enable improved risk assessment, exposure monitoring, and the development of preventive strategies.