Urinary paracetamol (4-acetaminophenol) and its isomer 2-acetaminophenol of Chinese pregnant women: Exposure characteristics and association with oxidative stress biomarkers

Abstract

N-Acetyl-4-aminophenol (NA4AP, paracetamol/acetaminophen), a widely used pharmaceutical, is ubiquitous in urine samples of general population, raising concern about human health risks; oxidative stress is considered to be a mechanism for its toxicities. N-Acetyl-2-aminophenol (NA2AP) is an isomer of NA4AP; until now, few studies characterized exposure characteristics of NA4AP and NA2AP in pregnant women. In this work, NA4AP and NA2AP concentrations in urine samples (n = 2124) collected at three different trimesters were measured to examine their internal body burden among Chinese pregnant women (n = 708) and their associations with three oxidative stress biomarkers (OSBs, 8-OHG, 8-OHdG, and HNE-MA). NA4AP was detected in 100% of the urine samples (median concentration: 7.96 ng/mL); NA2AP was detected in 94.9% of them (median: 3.05 ng/mL). The intraclass correlation coefficients of their concentrations across three trimesters were poor (<0.4); correlations of NA4AP and NA2AP were weak (r: 0.15–0.23). Pregnant women who had higher household income or urine samples provided in summer (vs. winter) had higher concentrations of NA4AP. Pregnant women who had a college degree or above (vs. less than a high school education) had higher concentrations of NA2AP but urine samples provided in summer (vs. winter) had lower concentrations of NA2AP. The 95th percentile estimated daily intake of NA4AP (2,331 ng/kg-bw/d) based on averaged concentrations of the three trimesters was 40 times lower than the cRfD for NA4AP (2.33 vs. 93 μg/kg-bw/d). Urinary concentrations of NA4AP and NA2AP were associated with higher levels of the selected OSBs. For example, an interquartile range increase in NA4AP was associated with a 26.5% (95% CI: 23.6–29.6%) increase in 8-OHG, a 27.5% (95% CI: 23.8–31.3%) increase in 8-OHdG, and a 33.4% (95% CI: 24.7–42.7%) increase in HNE-MA (p < 0.05). This is the first study to measure their concentrations repeatedly over three trimesters, examine their exposure characteristics, and reveal their associations with the selected OSBs in pregnant women. Further studies are needed to identify non-intentional exposure sources of NA4AP, NA2AP, and another isomer of them (i.e., N-acetyl-3-aminophenol), as well as more health risks related to their exposure.