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

Nitrated aromatic compounds (NACs) belong to a group
of ubiquitous
environmental contaminants, and lacking exposure markers has restricted
the accurate assessment of their exposure and subsequent health effects.
Hence, based on gas chromatography and tandem mass spectrometry coupled
with an electron capture ion source, we established a novel nontargeted
exposomic approach to achieve highly sensitive and standard-independent
detection for urinary NACs. Applying this technique to urine samples
from a panel of 26 international travelers, we detected 184 NACs,
of which 151 were inferred molecular formulas by accurate mass, and
25 were verified by reference standards. The isomeric profiles of
the identified NACs suggested their direct excretion without functionalization
metabolism after environmental absorption, which was corroborated
by 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 Angeles
to Beijing, in association with ambient NO2 levels. Most
NACs were significantly associated with the marker of nitrative stress,
with stronger associations observed in Beijing. This study provided
an advanced analytical approach for exposure markers of NACs and preliminary
evidence of their potential to trigger nitrative stress, an important
but poorly understood response that may relate to adverse health effects.