Chen Hanfeng, Jin Hangbiao, Ren Fangfang, Guo Ruyue, Zhu Jianqiang, Huang Kaiyuan
Department of Neurology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 324000, PR China.
Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China.
Environ Pollut. 2025 Aug 1;378:126489. doi: 10.1016/j.envpol.2025.126489. Epub 2025 May 19.
Human exposure to of N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine (6PPD) has raised global concerns due to its documented toxic effects, including hepatotoxicity, metabolic disruption, and potential contributions to organ damage. 6PPD-quinone (6PPD-Q), a ubiquitous transformation product of 6PPD, has been identified as a major toxicant linked to acute mortality in aquatic species, underscoring its ecological and human health risks. While these compounds exist as enantiomers with demonstrated differences in environmental behavior and toxicity, their enantiomer-specific distribution and excretion patterns in humans remain unknown limiting accurate risk assessments. This study analyzed 6PPD and 6PPD-Q in 109 pairs of whole blood and urine from general Chinese adults at the enantiomer-specific level. Results showed that 6PPD (range < LOD-0.60 ng/mL) and 6PPD-Q (<LOD-0.74 ng/mL) were detected in 39 % and 43 % of human whole blood samples, respectively. Calculated mean enantiomer fraction (EF) values of 6PPD and 6PPD-Q in human whole blood were 0.45 ± 0.061 (n = 32) and 0.41 ± 0.049 (n = 37), respectively. Mean levels of 6PPD and 6PPD-Q in human urine were 0.52 ng/mL (range < LOD-2.3 ng/mL) and 0.81 ng/mL (<LOD-2.9 ng/mL), respectively. Mean EF values for 6PPD and 6PPD-Q were 0.38 ± 0.044 and 0.31 ± 0.059, respectively, in human urine samples. In addition, Rectus-6PPD (mean 73 mL/day/kg) and Rectus-6PPD-Q (65 mL/day/kg) showed much lower (p < 0.05) mean daily renal clearance values than Sinister-6PPD (90 mL/day/kg) and Sinister-6PPD-Q (94 mL/day/kg), respectively. To our awareness, the present study reports the first data on the enantiomer-specific distribution and levels of 6PPD and 6PPD-Q in adult blood and urine, and their enantioselectivity in the human urinary excretion process. These findings underscore the necessity of incorporating enantiomer-specific data into risk assessments. Future studies should prioritize enantiomer-specific toxicokinetics and environmental monitoring to refine exposure and hazard evaluations.
人类接触 N-(1,3-二甲基丁基)-N'-苯基-1,4-苯二胺（6PPD）已引发全球关注，因为其具有已记录的毒性作用，包括肝毒性、代谢紊乱以及对器官损伤的潜在影响。6PPD-醌（6PPD-Q）是 6PPD 普遍存在的转化产物，已被确定为与水生物种急性死亡相关的主要毒物，凸显了其生态和人类健康风险。虽然这些化合物以对映体形式存在，且在环境行为和毒性方面存在差异，但其在人体中的对映体特异性分布和排泄模式仍不清楚，这限制了准确的风险评估。本研究在对映体特异性水平上分析了 109 对中国普通成年人的全血和尿液中的 6PPD 和 6PPD-Q。结果显示，分别在 39%和 43%的人体全血样本中检测到了 6PPD（范围<检测限-0.60 ng/mL）和 6PPD-Q（<检测限-0.74 ng/mL）。计算得出人体全血中 6PPD 和 6PPD-Q 的平均对映体分数（EF）值分别为 0.45±0.061（n = 32）和 0.41±0.049（n = 37）。人体尿液中 6PPD 和 6PPD-Q 的平均水平分别为 0.52 ng/mL（范围<检测限-2.3 ng/mL）和 0.8 ng/mL（<检测限-2.9 ng/mL）。人体尿液样本中 6PPD 和 6PPD-Q 的平均 EF 值分别为 0.3±0.044 和 0.31±0.059。此外，右旋-6PPD（平均 73 mL/天/千克）和右旋-6PPD-Q（65 mL/天/千克）的平均每日肾脏清除率值分别比左旋-6PPD（90 mL/天/千克）和左旋-6PPD-Q（94 mL/天/千克）低得多（p<0.05）。据我们所知，本研究首次报告了 6PPD 和 6PPD-Q 在成人血液和尿液中的对映体特异性分布和水平，以及它们在人体尿液排泄过程中的对映体选择性。这些发现强调了将对映体特异性数据纳入风险评估的必要性。未来的研究应优先进行对映体特异性毒代动力学和环境监测，以完善暴露和危害评估。
