Presence of N, N′-Substituted p-Phenylenediamine-Derived Quinones in Human Urine

Human exposure to various N,N'-substituted p-phenylenediamine-derived quinones (PPDQs) has been of increasing concern. Recent studies have examined N-phenyl-N'-(1,3-dimethylbutyl)-p-phenylenediamine-derived quinone (6PPDQ) in human urine to evaluate human exposure. However, other PPDQs in human urine have not been thoroughly investigated. This study analyzed six PPDQs in urine collected from 149 healthy individuals in Taizhou, China. All target PPDQs were detected, with 6PPDQ (mean 2.4 ng/mL, <limit of detection (LOD)-19 ng/mL) and 2-(cyclohexylamino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione (CPPDQ; 2.1 ng/mL, <LOD-24 ng/mL) being the most prevalent. Human urinary concentrations of 2,5-bis((5-methylhexan-2-yl)amino)cyclohexa-2,5-diene-1,4-dione (77PDQ; mean 1.5 vs. 0.87 ng/mL; <i>p</i> = 0.013) and 2,5-bis(o-tolylamino)cyclohexa-2,5-diene-1,4-dione (mean 1.1 vs. 0.62 ng/mL; <i>p</i> = 0.027) were significantly higher in females compared to males. For CPPDQ (<i>p</i> < 0.01) and 6PPDQ (<i>p</i> < 0.01), a decrease was observed in urinary concentrations as participants aged. The daily excretion (DE) of PPDQs through urine was estimated for Chinese adults. The highest average DE was recorded for 6PPDQ at 81 ng/kg-bw/day, with a range from <0.5 to 475 ng/kg-bw/day. Following this, CPPDQ had a mean DE of 68 ng/kg-bw/day (range <0.5-516 ng/kg-bw/day), and 77PDQ had a mean DE of 30 ng/kg-bw/day (<0.5-481 ng/kg-bw/day). This study is the first to explore the presence of various PPDQs in human urinary samples, which is essential for assessing the potential health risks associated with these substances.