Exposure Markers of Nitrated Aromatic Compounds and the Association with Nitrative Stress

Nitrated aromatic compounds (NACs) belong to a groupof ubiquitousenvironmental contaminants, and lacking exposure markers has restrictedthe accurate assessment of their exposure and subsequent health effects.Hence, based on gas chromatography and tandem mass spectrometry coupledwith an electron capture ion source, we established a novel nontargetedexposomic approach to achieve highly sensitive and standard-independentdetection for urinary NACs. Applying this technique to urine samplesfrom a panel of 26 international travelers, we detected 184 NACs,of which 151 were inferred molecular formulas by accurate mass, and25 were verified by reference standards. The isomeric profiles ofthe identified NACs suggested their direct excretion without functionalizationmetabolism after environmental absorption, which was corroboratedby in vitro metabolism assays. Levels of 121 NACs,including nitrophenols, hydroxy-nitrobenzoic acids, and nitronaphthols,were increased from 1.3 to 21.1-fold after traveling from Los Angelesto Beijing, in association with ambient NO2 levels. MostNACs were significantly associated with the marker of nitrative stress,with stronger associations observed in Beijing. This study providedan advanced analytical approach for exposure markers of NACs and preliminaryevidence of their potential to trigger nitrative stress, an importantbut poorly understood response that may relate to adverse health effects.