ENVIRONMENT INTERNATIONAL
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2025
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IF 9.7
Jiaqi Shi,Yan Li,Qi Wei,Xin Zhu,Shaohua Cao,Wenyi Xie,Yang Guo,Jing Wei,Zekai Li,Tao Long
The widely used rubber antioxidant N-(1,3-Dimethylbutyl)-N’-phenyl-p-phenylenediamine (6PPD) and its ozonated product, 6PPD-quinone (6PPD-Q), are highly toxic to aquatic life, yet understanding on their environmental behaviors is limited. This study comprehensively investigated their adsorption and transformation processes on natural Fe-Mn nodules (NFMN), which commonly exist in sediments and soils through a combination of diverse experimental and computational methods. The maximum adsorption capacity of 6PPD-Q (719.2 μg·g −1 ) is significantly higher than that of 6PPD (133.8 μg·g −1 ) at 293 K, and it is more difficult to desorb. They follow different kinetic and isothermal adsorption models, and environmental conditions (including temperature, pH, and anions) exert distinct influences on the adsorption of the two substances. Adsorption mechanisms involving electrostatic attraction, charge transfer, hydrogen bonding, and Lewis acid-base complexation were unveiled. For 6PPD, electrostatic adsorption and Lewis acid-base complexation contribute significantly to its adsorption. Conversely, for 6PPD-Q, the contribution of Lewis acid-base complexation outweighs that of hydrogen bonding, while the effect of electrostatic adsorption is relatively negligible. The stronger electrostatic attraction, more efficient charge transfer, and a greater number of binding sites for hydrogen bonding and Lewis acid-base complexation with NFMN results in more robust adsorption of 6PPD-Q. Furthermore, 6PPD can transform into 6PPD-Q on NFMN, facilitated by dissolved Mn(III). This study advances understanding of the adsorption behavior and mechanism of 6PPD and 6PPD-Q, and highlights a new pathway for 6PPD-Q formation, which provides valuable reference for assessing the water body exposure risks and formulating environmental remediation strategies for such pollutants. Environmental Implication This study offers the first comprehensive insight into the interactions between 6PPD/6PPD-Q and NFMN, illuminating their environmental behavior in water and soil systems. It reveals the adsorption discrepancy between 6PPD and 6PPD-Q, and elucidates the mechanisms underlying the difference in adsorption. Additionally, it uncovers a novel pathway for 6PPD-Q formation, offering valuable implications for risk assessment and environmental remediation strategies.
研究领域:
环境科学
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化学
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DOI
PubMed
高影响因子
Journal of Environmental Sciences
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2024
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IF 5.9
Shike Zhang,Xinyi Su,Jiada Zhang,Tingting He,Lei Tang,Zepei Zhao,Linying Cao
N-phenyl-N′-(1,3-dimethylbutyl)-p-phenylenediamine (6PPD) is a tire rubber antioxidant that can be oxidized to form derivative 6PPD-quinone (6PPD-Q). 6PPD and 6PPD-Q have been detected in human urine with concentrations reaching nanomolar levels. However, their human adverse effects and toxic mechanism are not explicit. This study elucidated their lipid metabolism disruption effects on hepatic cells (HepG2) and revealed a potential molecular mechanism via estrogen-related receptor γ (ERRγ) pathway. The results of fluorescence competitive binding assay showed that 6PPD and 6PPD-Q could bind to ERRγ with an IC 50 (the concentration of a ligand competing 50% probe from ERRγ) of 9 nmol/L and 6 nmol/L, respectively. The reporter gene assay indicated that 6PPD-Q activated ERRγ in a concentration-dependent mode with the lowest observable effective concentration (LOEC) of 100 nmol/L and the maximum induction rate of 320%, while 6PPD displayed weak ERRγ activity. The molecular docking showed that the binding energies of 6PPD/6PPD-Q with agonistic ERRγ were much lower than those with antagonistic ERRγ, implying that 6PPD/6PPD-Q tended to display ERRγ agonistic binding mode. The BODIPY fluorescence staining and triglyceride (TG) assay revealed that 6PPD and 6PPD-Q promoted lipid accumulation and TG production in HepG2 cells with LOEC of 10 nmol/L and 100 nmol/L, respectively. The ERRγ antagonist (GSK5182) co-exposure reversed the lipid induction effects of 6PPD/6PPD-Q, which confirmed the regulatory roles of ERRγ. Overall, our study revealed a novel endocrine disruption mechanism of 6PPD and 6PPD-Q via ERRγ and their hepatic lipid inducing risks, providing novel information for their health hazard evaluation.
研究领域:
毒理学
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细胞生物学
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分子生物学
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DOI
高影响因子
ENVIRONMENTAL RESEARCH
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2024
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IF 7.7
Xingyao Ye,Xiaojun Niu,Ling Li,Mengyu Lv,Dongqing Zhang,Deye Chen,Yu Line,Zhiquan Yang
N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is an antioxidant commonly used in tire manufacturing, and its release into the environment has significantly increased due to rapid urbanization. When subjected to ozonation, 6PPD converts into the harmful pollutant 6PPD quinone (6PPDQ). These substances enter wastewater treatment plants (WWTPs) via stormwater runoff and pipelines, posing significant risks to the functional microorganisms. Anammox, a strictly controlled and sensitive microbial nitrogen removal process, is especially susceptible to the effects of the pollutants. This study investigates the comprehensive impact of 6PPD-Q and 6PPD on anammox communities based on characterization analysis and metagenomics. At environmental concentrations, 6PPD-Q at 200 ng/L-1000 ng/L led to the disintegration of anammox granules. Extended exposure to both 6PPD-Q and 6PPD significantly reduces the population of anammox bacteria (AnAOB). By utilizing organic matter from dead cells and incoming carbonate as a carbon source, the system evolved into a nitrogen metabolism network primarily focused on denitrification and dissimilatory nitrate reduction to ammonium (DNRA). This transformation was accompanied by a reshuffling of the microbial community and associated genes, resulting in an accumulation of NH 4 + -N. These findings underscore the toxicity of 6PPD-Q and 6PPD to anammox and stress the importance of incorporating 6PPD into regulatory and preventive strategies.
研究领域:
环境科学
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微生物学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Chunyu Liu,Xingchen Zhao,Liqiong Guo,Qilin Yu,Weifei Zhang,Zijuan Peng,Yan Gao,Xiaoyun Gong,Penghui Li,Hui Jiao,Tao Zhou,Qinghe Zhang,Shanjun Song,Guibin Jiang
With increasing concerns about N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-quinone (6PPD-Q), relevant environmental investigations and toxicological research have sprung up in recent years. However, limited information could be found for human body burden assessment. This work collected and analyzed 200 samples consisting of paired urine and plasma samples from participants (50 male and 50 female) in Tianjin, China. Low detection frequencies (DF, <15 %) were found except for urinary 6PPD-Q (86 %), which suggested the poor residue tendency of 6PPD and 6PPD-Q in blood. The low DFs also lead to no substantial association between two chemicals. Data analysis based on urinary 6PPD-Q showed a significant difference between males and females ( p < 0.05). No significant correlation was found for other demographic factors (Body Mass Index (BMI), age, drinking, and smoking). The mean values of daily excretion (ng/kg bw/day) calculated using urinary 6PPD-Q for females and males were 7.381 ng/kg bw/day (female) and 3.360 ng/kg bw/day (male), and apparently female suffered higher daily exposure. Further analysis with daily excretion and ALT (alanine aminotransferase)/TSH (thyroid stimulating hormone)/ blood cell analysis indicators found a potential correlation with 6PPD-Q daily excretion and liver/immune functions. Considering this preliminary assessment, systematic research targeting the potential organs at relevant concentrations is required.
研究领域:
环境科学
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毒理学
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PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2025
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IF 11.3
Ningbo Geng,Shijiao Hou,Shuai Sun,Rong Cao,Haijun Zhang,Xianbo Lu,Shusheng Zhang,Jiping Chen,Yanhao Zhang
N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) has been identified as the cause of the “urban runoff mortality syndrome.” Thus, the ecological risks of substituted p-phenylenediamines (PPDs) and their quinone derivatives (PPD-Qs) in water have gained global attention. However, large-scale observation of their pollution characteristics in surface water is still lacking. Herein, a nationwide investigation revealed the pervasive occurrence of PPDs and PPD-Qs in riverine waters across China, with the mean concentration of ∑5PPD-Qs being 4.9 times higher than their parent ∑5PPDs. Notably, the 6PPD-Q concentrations at eight sampling sites exceeded the median lethal concentration for coho salmon. National annual riverine fluxes were estimated at 113.1 and 276.2 tonnes/year for PPDs and PPD-Qs, respectively, with the Yangtze River contributing more than one-third of the total fluxes. The transformation of PPDs to PPD-Qs was dependent on atmospheric hydroxylation rates and the half-lives of PPDs. A combined multimedia exposure assessment revealed that water exposure accounted for 82.5% of human exposure to PPDs and PPD-Qs, surpassing the contributions from dust and air exposure. This study provides a comprehensive spatial picture of PPDs and PPD-Qs in China. The national atlas highlights their potential ecological risks and implies that targeted actions should be taken to mitigate potential exposure to PPDs and PPD-Qs.
研究领域:
环境科学
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毒理学
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生态学
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Nan Jiang,Xuexin Hao,Zichen Wang,Minzhen Li,Dong Zhang,Rong Cao,Ruiqin Zhang,Haijun Zhang,Jiping Chen,Ningbo Geng
The extensive utilization of rubber-related products can lead to a substantial release of p -phenylenediamine (PPD) antioxidants into the environment. In recent years, studies mainly focus on the pollution characteristics and health risks of PM 2.5 -bound PPDs. This study presents long-time scale data of PPDs and N-(1,3-dimethylbutyl)-N′-phenyl- p -phenylenediamine quinone (6PPD-Q) in PM 2.5 and proposes the innovative use of PPDs as new markers for vehicular emissions in the Positive Matrix Factorization (PMF) source apportionment . The results indicate that PPDs and 6PPD-Q were detectable in 100 % of the winter PM 2.5 samples, and the concentration ranges of PPDs and 6PPD-Q are 15.6–2.92 × 10 3 pg·m −3 and 3.90–27.4 pg·m −3 , respectively, in which 6PPD and DNPD are the main compounds. Moreover, a competitive formation mechanism between sulfate, nitrate, ammonium (SNA) and 6PPD-Q was observed. The source apportionment results show that the incorporation of PPDs in PMF reduced the contribution of traffic source to PM 2.5 from 13.5 % to 9.5 %. In the traffic source factor profiles, the load of IPPD, CPPD, DPPD , DNPD and 6PPD reaches 91.8 %, 91.6 %, 92.9 %, 80.6 % and 87.2 %, respectively. It`s amazing that traditional markers of traffic source, which often overlap with coal burning and industrial sources, over-estimated the contribution of vehicles by one third or more. The discovery of PPDs as specific markers for vehicular emissions holds significant utility, particularly considering the growing proportion of new energy vehicles in the future. The results may prove more accurate policy implications for pollution control . Synopsis PPDs are excellent indicators of vehicle emissions, and PMF without PPDs over-estimated the contribution of traffic source to PM 2.5 .
研究领域:
环境科学
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大气污染研究
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2026
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IF 10.6
Yu Lei,Xiaopeng Yan,Shengwen Zhao,Qian Zhang,Luo Liu,Qian Sun
The tire-derived antioxidant 6PPD and its highly toxic transformation product (TP) 6PPD-Q represent an emerging threat to aquatic ecosystems. For example, 6PPD-Q is identified as the cause of acute mortality in coho salmon . This study investigates the phytoremediation potential of riverine plants in natural wetlands (e.g. Typha minima ( T. minima )) to remove 6PPD and 6PPD-Q. T. minima accelerated the removal of 6PPD and 6PPD-Q from the medium compared to the unplanted controls, with a half-life of 21.31 min and 23.97 h respectively. Total 80 TPs were identified in roots and leaves. Multiple novel pathways were proposed to elucidate the biotransformation processes. The formation of hydrophilic TPs demonstrated the potential of T. minima in detoxifying 6PPD and 6PPD-Q. The occurrence of TPs was related to the activities of detoxification enzymes, such as cytochrome P450 monooxygenase. Although 6PPD and 6PPD-Q resulted in oxidative stress symptoms in T. minima , these stresses could be mitigated by their antioxidant defense system. The findings of the present study provide insights into the metabolic fate of 6PPD and 6PPD-Q in T. minima . This offers a foundation for natural wetlands in mitigating the ecological risks of tire-derived micropollutants in river basin management.
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PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2026
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IF 7.3
Yuhang Zhou,Zhenjie Zang,Xingzu Wang,Yunhao Feng,Zhenqing Wang,Ziyao Li,Tongxiang Diao,Qiang Fu,Hui Zhang
N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPD-Q) is an oxidation product of the tire rubber antioxidant 6PPD. Recent studies have detected 6PPD-Q in various environmental media, including water, air, and soil, and in human biospecimens such as urine, breast milk, blood and cerebrospinal fluid. These findings highlight its widespread presence in the environment and the potential for multi-route human exposure. Although previous research has demonstrated that 6PPD-Q induces multi-organ toxicity, particularly in the liver and nervous system, its effects on the male reproductive system and the associated molecular mechanisms remain unexplored. We developed a chronic exposure model in male mice to systematically assess the toxic effects of 6PPD-Q on the testes and its potential mechanisms. Our results indicate that 6PPD-Q accumulates in testicular tissue and induces histological damage, which is characterized by reduced serum testosterone levels, impaired sperm quality, sloughing of the spermatogenic epithelium, and disruption of the blood-testis barrier. Mechanistic investigations suggest that these effects are associated with impaired autophagy, elevated oxidative stress, and increased apoptosis in testicular tissue. Through integrated network toxicology and transcriptomics analyses, we identified TRPM2 (transient receptor potential cation channel subfamily M member 2)-mediated autophagy dysfunction as a critical event in 6PPD-Q-induced testicular injury. This study systematically unveils the toxic effects of 6PPD-Q on the male mouse reproductive system and elucidates the underlying molecular mechanisms. It elucidates that TRPM2-mediated autophagy plays a crucial role in the testicular injury induced by 6PPD-Q. This research provides essential evidence for understanding the reproductive health risks posed by emerging environmental pollutants and for developing prevention strategies.
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2026
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IF 10.6
Xia-Wen Qiu,Jiajun Chen,Jiayan Wang,Yujie Li,Xiaoyan Qi,Xianchang Zeng,Huajun Feng,Xianghui Kong
Respiratory viral infections contribute substantially to global disease burden and mortality. N -(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine quinone (6PPD-Q) has garnered significant attention due to its marked ecotoxicity. However, it remains unclear how this prevalent environmental pollutant impacts host immune defense against respiratory viral infections. This study established a murine model involving 14-day consecutive intranasal administration of environmentally relevant doses of 6PPD-Q coupled with intranasal instillation of influenza A virus (IAV) or tail vein injection of vesicular stomatitis virus (VSV). Our findings revealed that mice pre-exposed to 6PPD-Q exhibited higher mortality during viral infection. Notably, 6PPD-Q exposure resulted in extensive viral dissemination, severe pulmonary pathology, and markedly dysregulated inflammation, characterized by excessive increases in IL-6, TNF-α, IL-1β, and IL-10. Immune profiling demonstrated that 6PPD-Q exposure induced the selective accumulation of neutrophils, monocytes, and monocyte-derived macrophages (MDMs) in the lungs during IAV infection. Interestingly, macrophage depletion unequivocally abolished the differences of survival, viral loads, and cytokine levels between the vehicle- and 6PPD-Q-treated mice. Mechanistically, 6PPD-Q activated NF-κB signaling in pulmonary MDMs, driving excessive inflammatory responses. Our findings confirm that 6PPD-Q significantly increases host susceptibility to viral pneumonia. This underscores the critical significance of environmental health management in the prevention and control of respiratory infectious diseases.
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2026
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IF 10.6
Lu Zhang,Huizhen Li,Zhong Zheng,Ruomiao Yang,Qian Hu,Xiaolei Zhang,Jing You
2-((4-Methylpentan-2-yl)amino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione (6PPD-Q), a ubiquitous transformation product of tire rubber antioxidants, has emerged as an aquatic pollutant of high ecotoxicological concern due to its extremely high acute toxicity to sensitive salmonid species. While recent toxicological studies have identified several pathways associated with acute toxicity, systemic lipid dysregulation in sensitive salmonids remains poorly characterized. Semi-quantitative untargeted lipidomics was employed to characterize lipidomic perturbations in surviving rainbow trout ( Oncorhynchus mykiss ), a species highly sensitive to 6PPD-Q, following acute exposure and to explore how these perturbations may contribute to adverse effects. Following a 24 h acute exposure to 6PPD-Q at environmentally relevant concentrations (0.45, 0.9, and 1.8 μg/L), significant oxidative stress was observed, evidenced by elevated reactive oxygen species, malondialdehyde levels, and increased antioxidant enzyme activities. Lipidomic analysis revealed extensive dysregulation of the lipid profile. This disruption was characterized by the accumulation of triglycerides (TG) and oxidized triglycerides (OxTG), alongside a selective decrease in diacylglycerols (DG) and phospholipids (PL) containing polyunsaturated fatty acids. Docosahexaenoic acid (DHA) and arachidonic acid (AA) were identified as the most affected species (DHA-PL and AA-PL). Furthermore, a significant reduction in mitochondria-associated lipids, specifically cardiolipin (CL) and coenzyme Q10 (CoQ10), was noted, which was consistent with previously reported mitochondrial impairment. These perturbations suggested that 6PPD-Q may be associated with suppressed fatty acid β-oxidation, resulting in TG accumulation. This study provides new insights into lipidomic perturbations associated with acute 6PPD-Q exposure and identifies specific OxTG species as candidate biomarkers for environmental monitoring and ecological risk assessment.
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PubMed
高影响因子
FOOD CHEMISTRY
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2026
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IF 10.4
Wenhao Li,Jiaqi Zhao,Qian Sun,Manman Wang,Yu He
A novel ratiometric fluorescence molecularly imprinted probe was developed. • High-affinity imprinted sites granted the sensor superior specificity. • The aggregation-induced emission effect boosted the response sensitivity. • Smartphone-assist device offered a precise visual and on-site detection. • The YOLOv5 algorithm achieved a prediction accuracy of 99.6%. N-(1,3-Dimethylbutyl)- N ′-phenyl-p-benzoquinone (6PPD-Q) is ubiquitous in aquatic environments and poses big threats to food safety and public health. Therefore, there is an urgent need to develop timely and effective methods to detect 6PPD-Q. In this work, the Zn-doped silicon quantum dots and Au nanoclusters were embedded in the molecularly imprinted polymers to form ratiometric fluorescence sensor for the detection of 6PPD-Q in the concentration ranging from 0.0099 to 1.0 μg·mL −1 with the detection limit of 3.0 ng·mL −1 . The imprinting factor was calculated as 2.56. Then, a 3D-printing device was developed to capture fluorescence for images digital image colorimetry of 6PPD-Q while YOLOv5 algorithm was employed to achieve a prediction accuracy of 99.6%. The recovery rates for real sample analysis ranged from 95.5% to 108.0%. This method offers a simple and rapid strategy for detecting 6PPD-Q in food samples.
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2026
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IF 6.6
Haitao Zhang,Chaofeng Chen,Dayu Wang,Yiwei Huang,Yang Liu,Zhiyuan Wang,Furui Fu,Hongyu Wang,Senjie Shi,Yijin Li,Jianchun Zeng,Caiping Shen,Chudan Zhong,Xiaozhou Liu,Jinlun Chen,Jie Li,Shufen Liu,Jin Huang,Yirong Zeng,Wenjun Feng
As an emerging environmental contaminant, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) poses a potential threat to public health. However, the potential link between 6PPD-Q exposure and bone health remains largely unexplored. This study aims to systematically investigate the toxic effects of 6PPD-Q on bone metabolism and elucidate the underlying mechanisms by integrating transcriptomic sequencing, network toxicology, single-cell RNA, Molecular docking, molecular dynamics with both in vivo and in vitro experiments. Integrative analysis converged on mitophagy as a central mechanism in 6PPD-Q-induced osteoporosis, with single-cell sequencing identifying bone marrow-derived mesenchymal stem cells (BMSCs) as the key cell type and revealing CX43, MMP2, PDGFRB, and FYN as the principal targets. Molecular docking and MD simulations confirmed the targeted binding of 6PPD-Q to CX43. RNA-seq analysis of rat tibiae validated the differential expression of CX43 and the critical role of mitophagy. Both in vivo and in vitro experiments demonstrated that 6PPD-Q-induced bone loss was associated with the downregulation of CX43 and concomitant mitophagy dysregulation. In conclusion, this study elucidates that 6PPD-Q induces bone loss was associated with the downregulation of CX43 and concomitant mitophagy dysregulation. Our work establishes a comprehensive mechanistic framework for 6PPD-Q-induced bone damage and offers novel insights for future research into its bone toxicity. The 1 or 10 mg/kg dose used in this study, although higher than the typical environmental exposure level, is consistent with the effects observed in cadmium exposure and is close to the 8 mg/kg dose used in studies on mouse bone toxicity. Additionally, the 5 ng/mL concentration of 6PPD-Q used in the in vitro experiments is comparable to the concentration detected in freshwater, indicating its environmental relevance.
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高影响因子
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