Linking sources to early effects by profiling urine metabolome of residents living near oil refineries and coal-fired power plants.

BACKGROUND: This study aims at identifying metabolic changes linking external exposure to industrial air toxics with oxidative stress biomarkers. METHODS: We classified 252 study subjects as 111 high vs. 141 low exposure subjects by the distance from their homes to the two main emission sources, oil refineries and coal-fired power plants. We estimated individual's external exposure to heavy metals and polycyclic aromatic hydrocarbons (PAHs) by dispersion and kriging models, respectively. We measured urinary levels of heavy metals and 1-hydroxypyrene (1-OHP) as biomarkers of internal exposure, and 8-OHdG, HNE-MA, 8-isoPGF2α, and 8-NO2Gua as biomarkers of early health effects. We used two-dimensional gas chromatography time-of-flight mass spectrometry to identify urine metabolomics. We applied "meet-in-the-middle" approach to identify potential metabolites as putative intermediate biomarkers linking multiple air toxics exposures to oxidative stress with plausible exposures-related pathways. RESULTS: High exposure subjects showed elevated ambient concentrations of vanadium and PAHs, increased urine concentrations of 1-OHP, vanadium, nickel, copper, arsenic, strontium, cadmium, mercury, and thallium, and higher urine concentrations of all four urine oxidative stress biomarkers compared to low exposure subjects. We identified a profile of putative intermediate biomarkers that were associated with both exposures and oxidative stress biomarkers in participants. Urine metabolomics identified age-dependent biological pathways, including tryptophan metabolism and phenylalanine metabolism in children subjects (aged 9-11), and glycine, serine, and threonine metabolism in elderly subjects (aged>55), that could associate multiple exposures with oxidative stress. CONCLUSION: By profiling urine biomarkers and metabolomics in children and elderly residents living near a petrochemical complex, we can link their internal exposure to oxidative stress biomarkers through biological pathways associated with common complex chronic diseases and allergic respiratory diseases. The internal exposure may possibly be traced to multiple air toxics emitted from specific sources of oil refineries and coal-fired power plants.