Drosophila melanogaster as model organism to assess brake dust toxicity by a multi-platform approach

Exposure to brake dust, a component of non-exhaust contribution by vehicular traffic, poses a significant global health threat due to its high content of potentially toxic elements (PTEs). This study employed an innovative approach using untargeted metabolomics on the model organism Drosophila melanogaster adults following larval exposure to brake dust. We exposed or not (control) D. melanogaster larvae in laboratory conditions to brake dust in the food medium at two concentrations: 75 and 750 mg/L. In adult individuals, we assessed both elemental accumulation via ICP-MS analysis (25 elements) as an exposure marker and metabolomic alterations via NMR analysis as an effect marker. Larval brake dust exposure resulted in the significant accumulation of several PTEs (i.e. Bi, Cu, Fe, Sb, Sn, W) in adults and induced a developmental delay at the highest dose (750 mg/L). Metabolomic analysis revealed a distinct stress signature: a generalized decrease in free amino acids (suggesting hyperactive protein synthesis for detoxification/damage repair, including metallothioneins) and a contrasting increase in Glutamine (bolstering glutathione-mediated antioxidant defence). Further signs of metabolic distress included Krebs Cycle disruption and suggested gut microbiota alterations. Overall, our findings demonstrate that larval brake dust exposure causes persistent, system-wide metabolic shifts in adults. The proposed metallomics-metabolomics multi-platform approach using D. melanogaster may represent a powerful tool for advancing toxicological science related to particulate matter health assessment. • Brake dust exposure caused PTEs accumulation and developmental delay in adults; • NMR analysis showed reduced free amino acids and increased glutamine levels; • Multi-platform analysis linked BD-derived PTEs to specific metabolic alterations; • Early-life BD exposure induced persistent, metal-dependent metabolic effects; • D. melanogaster metabolomics proved effective for PM health impact assessment.