Li Xuejing, Xu Li, Wan Yanjian, Li Juxiao, Qian Xi, Xia Wei, He Zhenyu, Zheng Tongzhang, Xu Shunqing, Li Yuanyuan
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Institute of Environmental Health, Wuhan Centers for Disease Control & Prevention, Wuhan, Hubei 430024, PR China.
Sci Total Environ. 2022 Dec 15;852:158375. doi: 10.1016/j.scitotenv.2022.158375. Epub 2022 Aug 29.
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.
N - 乙酰 - 4 - 氨基酚（NA4AP，对乙酰氨基酚）是一种广泛使用的药物，在普通人群的尿液样本中普遍存在，这引发了对人类健康风险的担忧；氧化应激被认为是其毒性作用的一种机制。N - 乙酰 - 2 - 氨基酚（NA2AP）是NA4AP的异构体；到目前为止，很少有研究描述孕妇体内NA4AP和NA2AP的暴露特征。在这项研究中，测量了在三个不同孕期收集的尿液样本（n = 2124）中NA4AP和NA2AP的浓度，以检查中国孕妇（n = 708）体内它们的负荷情况以及它们与三种氧化应激生物标志物（OSB，8 - OHG、8 - OHdG和HNE - MA）的关联。在100%的尿液样本中检测到了NA4AP（中位浓度：7.96 ng/mL）；在94.9%的样本中检测到了NA2AP（中位值：3.05 ng/mL）。它们在三个孕期的浓度的组内相关系数较差（<0.4）；NA4AP和NA2AP之间的相关性较弱（r：0.15 - 0.23）。家庭收入较高或夏季提供尿液样本（与冬季相比）的孕妇，其NA4AP浓度较高。具有大学及以上学历（与高中以下学历相比）的孕妇，其NA2AP浓度较高，但夏季提供尿液样本（与冬季相比）的孕妇，其NA2AP浓度较低。基于三个孕期平均浓度估计的NA4AP第95百分位数每日摄入量（2331 ng/kg - bw/d）比NA4AP的参考剂量（RfD）低40倍（2.33 与93 μg/kg - bw/d）。尿液中NA4AP和NA2AP的浓度与所选OSB的较高水平相关。例如，NA4AP四分位数间距增加与8 - OHG增加26.5%（95%CI：23.6 - 29.6%）、8 - OHdG增加27.5%（95%CI：23.8 - 31.3%）以及HNE - MA增加33.4%（95%CI：24.7 - 42.7%）相关（p < 0.05）。这是第一项在三个孕期反复测量它们的浓度、检查它们的暴露特征并揭示它们与孕妇所选OSB关联的研究。需要进一步研究以确定NA4AP、NA2AP及其另一种异构体（即N - 乙酰 - 3 - 氨基酚）的非故意暴露源，以及与它们暴露相关的更多健康风险。
