Effect biomonitoring in a controlled firefighting setting: an untargeted metabolomic pilot study

Exposure biomonitoring is limited to quantifying the internal dose of specific contaminants. However, it fails to capture the complex total biological burden comprising chemical mixtures (such as fire emissions) and physical and psychological stress. Effect biomonitoring, particularly using untargeted metabolomics, is required to comprehensively assess the systemic health effects of these complex exposures. This pilot study aimed to identify metabolic changes by analyzing urine samples collected from two individual firefighters before and after two controlled training scenarios. One scenario measured physical stress (using respiratory protection only), while the other measured additional smoke exposure (using a controlled fire). Samples were derived from an established exposure biomonitoring study which confirmed relevant additional exposure for 10 polycyclic aromatic hydrocarbons (PAHs) in the fire scenario despite protective gear. Urinary metabolites were extracted and analyzed using untargeted gas chromatography-mass spectrometry, followed by data analysis using MetaboAnalyst and R software. 79 human metabolites were identified. Principal component analysis showed a clear separation of the metabolic profiles. A t-test identified four metabolites specifically and significantly regulated by fire exposure: a decrease in catechol and 3-hydroxyphenylacetic acid, and an increase in 5-hydroxy-L-tryptophan and serotonin. Pathway analysis confirmed that the tryptophan and catecholamine pathways were primarily impacted. The observed metabolic changes indicate a significant systemic stress response and biological effect caused by fire exposure. Although metabolic changes indicate biological effects, the study conditions do not allow for distinguishing between toxicological and non-toxicological stressors (i.e. heat). The study demonstrates the potential of urinary metabolomics as a non-invasive method for supplementing effect biomonitoring for firefighters.