Advanced Breathomics Reveals Human Absorption of Exogenous Volatile Organic Compounds

Human exhaled volatile organic compounds (VOCs) exhibit diverse profiles influenced by environmental exposures, yet the physiological processes governing their inhalation retention and exhalation dynamics remain unclear. This study introduces the inhalation retention index (IRI), a metric for quantifying the uptake of ambient VOCs in humans. Using GC × GC-TOF MS/FID, we analyzed exhaled breath samples from 103 individuals alongside corresponding ambient air samples, identifying 107 common VOCs. Applying the alveolar gradient (AG) method, we identified compounds with population-level exogenous dominance and calculated their corresponding IRI values. Our results indicate that exogenous-advantaged VOCs found in subjects primarily consist of alkanes, aromatics, and aldehydes, with body absorption proportion ranging from 27.05 to 70.53%, offering valuable quantitative insights into the incomplete absorption of ambient air pollutants by the human body. Furthermore, VOC molecular weight, occupation, and environmental levels significantly influence IRI (<i>p</i> < 0.001), displaying linear or logarithmic relationships for specific substances, highlighting the complexity of VOC disposition. Monte Carlo simulations estimated the average daily dose (ADD) of VOC exposure, while a physiologically based pharmacokinetic (PBPK) model simulated the absorption and distribution of styrene, emphasizing the pivotal role of IRI in capturing realistic chemical behavior within the body. The proposed IRI method offers a novel framework for evaluating the uptake and systemic persistence of environmental pollutants, addressing critical gaps in existing data. This approach advances our understanding of VOC exposure dynamics and provides new insights into public health and safety.