Department of Environmental Science and Engineering, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
SKL-ESPC and College of Environmental Sciences and Engineering, Center for Environment and Health, Peking University, Beijing 100871, China.
Environ Sci Technol. 2024 May 28;58(21):9113-9124. doi: 10.1021/acs.est.4c01106. Epub 2024 May 14.
The antioxidant -(1,3-Dimethylbutyl)-'-phenyl--phenylenediamine (6PPD) and its oxidized quinone product 6PPD-quinone (6PPD-Q) in rubber have attracted attention due to the ecological risk that they pose. Both 6PPD and 6PPD-Q have been detected in various environments that humans cohabit. However, to date, a clear understanding of the biotransformation of 6PPD-Q and a potential biomarker for exposure in humans are lacking. To address this issue, this study presents a comprehensive analysis of the extensive biotransformation of 6PPD-Q across species, encompassing both and models. We have tentatively identified 17 biotransformation metabolites , 15 in mice , and confirmed the presence of two metabolites in human urine samples. Interestingly, different biotransformation patterns were observed across species. Through semiquantitative analysis based on peak areas, we found that almost all 6PPD-Q underwent biotransformation within 24 h of exposure in mice, primarily via hydroxylation and subsequent glucuronidation. This suggests a rapid metabolic processing of 6PPD-Q in mammals, underscoring the importance of identifying effective biomarkers for exposure. Notably, monohydroxy 6PPD-Q and 6PPD-Q-O-glucuronide were consistently the most predominant metabolites across our studies, highlighting monohydroxy 6PPD-Q as a potential key biomarker for epidemiological research. These findings represent the first comprehensive data set on 6PPD-Q biotransformation in mammalian systems, offering insights into the metabolic pathways involved and possible exposure biomarkers.
抗氧化剂-(1,3-二甲基丁基)-'-苯基--苯二胺（6PPD）及其氧化醌产物 6PPD-醌（6PPD-Q）在橡胶中引起了关注，因为它们具有生态风险。6PPD 和 6PPD-Q 都已在人类共同居住的各种环境中检测到。然而，迄今为止，对于 6PPD-Q 的生物转化及其在人体中的潜在暴露标志物仍缺乏清晰的认识。为了解决这个问题，本研究对 6PPD-Q 在不同物种中的广泛生物转化进行了全面分析，包括 和 模型。我们暂定鉴定了 17 种 6PPD-Q 的生物转化代谢物，其中 15 种在小鼠中，同时在人类尿液样本中确认了两种代谢物的存在。有趣的是，不同物种观察到了不同的生物转化模式。通过基于峰面积的半定量分析，我们发现 6PPD-Q 在暴露于小鼠体内的 24 小时内几乎全部发生了生物转化，主要通过羟化和随后的葡萄糖醛酸化。这表明 6PPD-Q 在哺乳动物体内的代谢处理非常迅速，突显了确定有效暴露标志物的重要性。值得注意的是，单羟基 6PPD-Q 和 6PPD-Q-O-葡萄糖醛酸苷是我们研究中始终最主要的代谢物，突出了单羟基 6PPD-Q 作为流行病学研究潜在关键标志物的地位。这些发现代表了哺乳动物系统中 6PPD-Q 生物转化的首个全面数据集，为涉及的代谢途径和可能的暴露标志物提供了深入了解。
