Repeated measurements of 21 urinary metabolites of volatile organic compounds and their associations with three selected oxidative stress biomarkers in 0-7-year-old healthy children from south and central China

Abstract

Human beings are extensively and concurrently exposed to multiple volatile organic compounds (VOCs, including some Class I human carcinogens), which may induce oxidative stress in human body. Data on urinary metabolites of VOCs (mVOCs) among young children are limited. No studies have examined their inter-day variability of mVOCs and their associations with oxidative stress biomarkers (OSBs) using repeated urine samples from children. In this study, we measured twenty one mVOCs and three OSBs [8-hydroxy-2'-deoxyguanosine (8-OHdG; for DNA), 8-hydroxyguanosine (8-OHG; for RNA], and 4-hydroxy nonenal mercapturic acid (HNEMA; for lipid)] in 390 urine samples of 130 children (three samples on three consecutive days provided by each participant) aged 0-7 years from September 2018 to January 2019 in Shenzhen, south China, and Wuhan, central China. HPMMA (3-hydroxypropyl-1-methyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine), 3HPMA (3-hydroxypropyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl)-l-cysteine), and ATCA (2-aminothiazoline-4-carboxylic acid) had higher specific gravity-adjusted median concentrations (1 383, 286, and 273 μg/L, respectively) than the others. Intraclass correlation coefficients of mVOCs ranged from 0.29 to 0.71. After false-discovery rate (FDR, defined as FDR q-value < 0.05) adjustment, linear mixed-effects models revealed that 14 mVOCs were positively associated with 8-OHdG (β range: 0.09-0.37), 11 mVOCs were positively associated with 8-OHG (β range: 0.08-0.30), and 11 mVOCs were positively associated with HNEMA (β range: 0.21-0.70) in urine. Considering the weight of the mVOC index accounted for the associations, based on the weighted quantile sum regression model, parent compounds of DHBMA (3,4-dihydroxybutyl mercapturic acid/N-Acetyl-S-(3,4-dihydroxybutyl)-l-cysteine) and t,t-MA (trans,trans-muconic acid) should be listed as priority VOCs for management to mitigate health risks. For the first time, this study characterized the inter-day variability of urinary mVOCs and their associations with selected OSBs (8-OHdG, 8-OHG, and NHEMA) in young, healthy Chinese children.

Keywords: Co-exposure; Human biomonitoring; Inter-day variability; Oxidative stress biomarkers; UPLC-MS/MS; Volatile organic compounds.