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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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2026
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IF 10.6
Hao Hu,Yuxin Sun,Ruomiao Yang,Qian Hu,Bryan W. Brooks,Huizhen Li,Jing You
The tire-derived contaminant N -(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine quinone (6PPD-Q) is widespread in aquatic ecosystems and poses significant ecological risk. As a chiral compound, its enantiomers may exhibit differential toxicity, yet the underlying mechanisms remain limited. Here, we found that (+)-6PPD-Q was 2.4-fold more toxic to rainbow trout than (-)-6PPD-Q ( p < 0.05). In addition, in vitro metabolism assays using liver S9 fraction showed that (+)-6PPD-Q was metabolized 2.5-fold faster than (-)-6PPD-Q. Semi-quantitative nontarget analysis revealed that hydroxylated metabolites dominated the phase I metabolism. We identified metabolites with 3.5- and 1.5-fold lower toxicity than (+)-6PPD-Q and (-)-6PPD-Q, respectively, indicating that metabolism primarily serves as a detoxification pathway and does not explain enantioselective toxicity in vivo . To resolve this discrepancy, we systemically characterized the in vivo enantioselective toxicokinetics of 6PPD-Q enantiomers for the first time. (+)-6PPD-Q exhibited a significantly higher uptake rate and slower elimination rate, leading to 4–9-fold greater bioaccumulation. This predominant accumulation outweighed faster metabolism than (-)-6PPD-Q, resulting in substantially higher internal concentrations and ultimately greater toxicity of (+)-6PPD-Q. Neglecting enantiomer-specific bioaccumulation and elimination could substantially underestimate risks of chiral pollutants such as 6PPD-Q in aquatic systems. Our findings demonstrate that enantioselective toxicity of 6PPD-Q is governed by whole toxicokinetics rather than metabolism alone, highlighting the necessity of incorporating enantioselective toxicokinetic analysis into ecological risk assessment of chiral contaminants.
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2025
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IF 4.3
Chanlin Fang,Shanshan Di,Yuekai Zhang,Xinquan Wang,Yuanxiang Jin
N-(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD), a critical antioxidant in rubber manufacturing, has raised global concerns due to its environmental persistence and toxic transformation products. While its developmental toxicity is increasingly recognized, the mechanisms underlying melanogenesis disruption in fish remain poorly understood. In this study, we systematically investigated 6PPD's effects on melanin synthesis in zebrafish embryos and murine melanoma cells (B16F10). Larval zebrafish were exposed to 10 and 100 μg/L 6PPD exhibited dose-dependent reductions in melanin deposition, suppressed tyrosinase activity and downregulation of melanogenesis-related genes ( tyr , mitfa , trp1 , trp2 , and dct ). Notably, the inhibition of tyrosinase activity was closely linked to behavioral impairments, as larvae exposed to 100 μg/L 6PPD showed significantly decreased swimming distance and velocity under light-dark cycles. Molecular docking revealed strong binding affinities between 6PPD and the key melanogenic proteins (Dct, Tyr, Tyrp1a, and Tyrp1b), suggesting direct interference with enzymatic function. Parallel experiments in B16F10 cells confirmed cross-species melanin suppression, with reduced gene expression and melanin synthesis-related protein (Mitfa and Tyr) at subtoxic concentrations (0.5 and 2.5 mg/L), which was also verified by Masson-Fontana staining. These findings demonstrated that 6PPD disrupted conserved melanogenic pathways by targeting enzymatic activity, posing ecological risks to aquatic and terrestrial organisms.
研究领域:
毒理学
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发育生物学
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环境科学
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生物化学
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药理学
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分子生物学
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高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2026
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IF 5.4
Lei Miao,Wei Guo,Haitao Chen,Xiaozheng Sun
Understanding the interfacial adsorption pathways of tire‑derived contaminants on hybrid porous materials is critical for advancing colloid and interface science. Here, we design a hierarchically structured metal-organic framework (MOF)‑functionalized nanocellulose (MOF@NC) aerogel using dicarboxylic cellulose nanocrystal (DCN)‑mediated interfacial bridging, forming a chemically active and spatially interconnected adsorption network. The adsorption of 6PPD‑quinone was evaluated through kinetic, isotherm, and thermodynamic analyses, revealing rapid chemisorption consistent with a pseudo‑second‑order model and monolayer adsorption on energetically uniform sites following the Langmuir model, with a maximum adsorption capacity of 20.0 ± 0.5 mg g⁻¹ . The MOF@NC aerogel retained approximately 87.2 ± 2.4 % of its initial adsorption efficiency after five adsorption‑desorption cycles, demonstrating good interfacial stability and reusability. Spectroscopic analyses (FTIR, XPS, SEM‑EDS) identify multiple interfacial interactions, including amide‑bond formation, Lewis acid-base coordination with MOF Zr-oxo clusters, π–π stacking between aromatic domains, hydrogen bonding, and dispersive interactions. Complementary density functional theory (DFT) and reduced density gradient (RDG) reveal energetically favorable adsorption configurations, and pronounced electronic redistribution at the MOF-nanocellulose heterointerface. By integrating macroscopic adsorption behavior with molecular-level interfacial analysis, this work establishes a mechanism-oriented framework for interpreting adsorption at MOF-biopolymer hybrid interfaces, thereby advancing fundamental understanding of how hybrid colloidal interfaces govern the sequestration of aniline-derived contaminants beyond prior performance-focused studies.
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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
Chanlin Fang,Weijie Gu,You Weng,Shanshan Di,Xinquan Wang,Yuanxiang Jin
6PPD, a widely used antioxidant in tires, has emerged as an environmental contaminant linked to cardiotoxicity in aquatic organisms, yet the molecular mechanism underlying 6PPD-induced cardiac injury remains unclear. Here, the mechanisms of 6PPD induced cardiotoxicity were investigated utilizing a combination of in vivo zebrafish and in vitro cardiomyocyte models. We found that 6PPD exposure caused cardiac dysfunction, myocardial injury, and pathological remodeling, accompanied by impaired autophagic flux, mitochondrial damage, and cardiomyocyte apoptosis. Mechanistically, 6PPD markedly downregulated YKT6, a SNARE protein essential for autophagosome-lysosome fusion, in both heart of zebrafish and H9C2 cells. Molecular dynamics simulations predicted a potential xenobiotic-protein interaction between 6PPD and YKT6 that restricted its conformational flexibility. Moreover, loss of YKT6 disrupted autophagosome maturation and promoted P62 accumulation, whereas YKT6 overexpression restored autophagosome-lysosome fusion, alleviated mitochondrial injury, and rescued 6PPD-induced cardiomyocyte dysfunction. Consistently, overexpressing YKT6 in adult zebrafish hearts through pericardial injection can also reduce the accumulation of P62 and heart damage. Overall, our findings suggest that 6PPD-induced cardiotoxicity involves YKT6 suppression, which is associated with impaired autophagosome-lysosome fusion and mitochondrial dysfunction, contributing to cardiomyocyte apoptosis in zebrafish. Thus, it was possible that restoring YKT6 emerged as a promising strategy to mitigate 6PPD-associated cardiac injury.
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高影响因子
ACS Nano
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2026
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IF 17.3
Yilin Huang,Huan Ru,Chanlin Fang,Shanshan Di,You Weng,Mingrong Qian,Yuanxiang Jin
Abstract 6PPD, as an antioxidant in tire rubber, constitutes an emerging pollutant together with nanoplastics (NPs) widely present in the environment. This study explored the potential combined toxicity risk of 6PPD and 50 nm polystyrene nanoplastics (PS-NPs) to aquatic ecosystems. The study found that the presence of PS-NPs altered the physicochemical behavior of 6PPD and was associated with reduced cardiac accumulation of 6PPD and its oxidation product 6PPD-Q. The experiment showed that 6PPD activated the p53 signaling pathway by upregulating the expression of GRK5, thereby inhibiting the expression of SLC7A11 and GPX4, leading to increased ROS, iron overload, lipid peroxidation, and mitochondrial damage in zebrafish heart and rat cardiomyocytes (H9C2), thereby triggering ferroptosis. After coexposure of PS-NPs and 6PPD, physicochemical interactions between PS-NPs and 6PPD altered the colloidal state and environmental behavior of the mixture, while the cardiac levels of both 6PPD and 6PPD-Q were reduced, accompanied by weakened ferroptosis-related responses. This study revealed the cardiotoxic mechanism of 6PPD and the mitigation effect of PS-NPs after coexposure, providing a basis for environmental pollution risk assessment.
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高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2026
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IF 4.3
Mengzhu Lv,Zheng Lu,Xiaoyu Mao,Jiangtao Huang,Qianqian Zheng,Dashuang Mo,Liping Shu
N-(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD), a widespread tire-derived contaminant, has drawn increasing concern for its environmental persistence and toxicity. However, its specific effects on early liver development remain poorly understood. In this study, we investigated the hepatotoxicity of 6PPD using zebrafish larvae and human L02 hepatocyte models. A novel exposure strategy was employed, initiating 6PPD treatment at 48 h post-fertilization, after liver budding, to minimize interference from early-stage developmental defects. 6PPD exposure led to a marked reduction in liver size without obvious morphological abnormalities, alongside downregulation of hepatocyte marker genes. Importantly, liver growth gradually recovered after 6PPD removal, suggesting acute and reversible toxicity. Mechanistically, 6PPD induced DNA damage and apoptosis in hepatocytes, as evidenced by elevated γ-H2AX, baxa , and casp3a expression, while hepatocyte proliferation remained unaffected. Transcriptomic and qPCR analyses revealed activation of inflammatory pathways and increased macrophage infiltration. Co-treatment with the anti-inflammatory agent dexamethasone rescued liver size and reduced DNA damage, indicating inflammation as a key mediator of 6PPD-induced toxicity. Similarly, 6PPD exposure in human hepatocytes reduced viability and increased apoptotic markers, which were alleviated by dexamethasone. These results demonstrate that 6PPD causes acute, inflammation-mediated liver toxicity during embryogenesis, with conserved mechanisms across species.
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高影响因子
Environmental Chemistry and Ecotoxicology
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2026
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IF 12.3
Lu Tao,Yuhang Guo,Xue Liu,Haozhe He,Xiaoteng Fan
Parent 6PPD was detected in Weihe River at concentrations of 1.01–19.82 ng/L. • 6PPD treatment induced intestinal injury, oxidative-stress responses, and gut microbial changes in both fish species. • A correlative water–gut microbial framework was proposed for 6PPD ecotoxicity assessment. • Flavobacterium emerged as a potential microbial biomarker of 6PPD pollution. The tire antioxidant 6PPD is increasingly detected in traffic-impacted aquatic environments, yet its potential effects on native freshwater fish and associated microbial communities in inland river systems remain insufficiently understood. In this study, we combined field sampling at seven sites along the Weihe River, China, with 30-day semi-static laboratory exposure experiments to compare the responses of the native cyprinid Onychostoma macrolepis and the model species Danio rerio . Parent 6PPD was detected at all field sites at concentrations of 1.01–19.82 ng/L. Following exposure to nominal 6PPD concentrations of 1 and 10 μg/L, both fish species exhibited intestinal histopathological alterations, oxidative-stress responses, and treatment-associated restructuring of the gut microbial community. Genus-specific qPCR supported increased absolute abundance of Aeromonas in the 10 μg/L treatment group for both species, whereas Achromobacter abundance decreased in exposed O. macrolepis . In rearing water, Polynucleobacter showed a positive treatment-associated pattern, and SourceTracker analysis indicated greater compositional similarity between matched rearing-water and O. macrolepis gut communities in the 10 μg/L group. In natural river water, Flavobacterium showed the strongest positive site-level association with measured 6PPD concentration among the screened genera. This association remained significant after separate adjustment for multiple environmental covariates, supporting Flavobacterium as a potential microbial biomarker associated with 6PPD contamination. These findings support a correlative water–gut microbial framework and demonstrate the value of incorporating native fish into the ecological assessment of emerging tire-derived contaminants. Download: Download high-res image (152KB) Download: Download full-size image
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高影响因子
ENVIRONMENT INTERNATIONAL
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2026
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IF 10.2
Tingting Ding,Linghao Meng,Yahui Zhang,Zhuoya Dai,Shilin Du,Xuedong Wang,Jin Yan,Qiuhui Qian,Zejun Wang,Huili Wang
An in-silico strategy integrating product, ecological and health prediction was built. • The ecological risk thresholds of 6PPD transformation products are more sensitive. • CYP4F3 and HSD17B6 were identified as the molecular initiating events of 6PPD. • Zebrafish experiments validated the toxic mechanisms of 6PPD at the PNEC dose. With the rapid expansion in the diversity and production of chemical, the associated environmental pollution and health risks have become increasingly prominent, underscoring the urgent need for rapid identification of potential high-risk contaminants. In this study, we propose an integrated computational framework for the rapid hazard assessment of emerging contaminants. N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), a widely used rubber antioxidant, was selected as a case study. A total of 24 transformation products were obtained, including both previously reported compounds (e.g., 6PPD-quinone) and newly predicted ones. Following structural optimization via Gaussian-based quantum chemical calculations, frontier molecular orbital analysis was conducted to elucidate plausible biotransformation mechanisms of previously unreported metabolites. Quantitative structure–activity relationship models for ten aquatic species were developed to construct species sensitivity distributions, yielding a predicted no-effect concentration (PNEC) of 1550 ng/L. Several metabolites exhibited higher toxicity than the parent compound. Reverse molecular docking was performed against 23,391 human proteins and integrated with physiologically based toxicokinetic modeling. The results revealed a predominance of hepatic bioactivity and high-affinity binding to key metabolic enzymes (CYP4F3, CYP2J2, HSD17B6, and HSD17B2), suggesting potential molecular initiating events. The preliminary zebrafish experiments provided supportive evidence for these potential mechanisms, including oxidative stress, inflammatory responses, and hepatic dysfunction, while no significant effects were observed at PNEC-level concentrations. Overall, this study demonstrates a practical and generalizable framework for early hazard screening of emerging contaminants, providing a valuable tool for environmental risk assessment and management. Download: Download high-res image (133KB) Download: Download full-size image
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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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高影响因子
Emerging Contaminants
·
2026
·Vol. 12
·期 4
·100749
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IF 8.2
Hanghai Zhou,Zhou Wu,Zhongyong Yan,Zhendong Li,Lijia Jiang,Lihua Zou,Thilo Hofmann,Chunfang Zhang,Hua Li,Jiangwu Tang
N -(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD), a widely used tire antioxidant, can be transformed into the highly toxic oxidation product 6PPD-quinone (6PPD-Q). Although both compounds are increasingly detected in aquatic environments, their potential impacts on sediment microbial communities remain poorly understood. Here, sediment–water microcosms combined with amplicon sequencing, ecological network analysis, community assembly analysis, and metagenomics were used to investigate the attenuation of 6PPD and associated microbial responses at environmentally relevant concentrations. Both 6PPD and 6PPD-Q dissipated rapidly, with most of the added compounds attenuated within the first few days of incubation. Despite this rapid dissipation, transient 6PPD exposure was associated with shifts in microbial community succession, network characteristics, community assembly processes, and nutrient-related physicochemical properties, including increased NH 4 + and SO 4 2− concentrations. Metagenomic analyses indicated that carbon-cycling functional potential remained comparatively stable, whereas nitrogen- and sulfur-cycling functional potential exhibited greater variation across treatments and incubation periods. These microbial and functional responses remained detectable after substantial dissipation of both 6PPD and 6PPD-Q. Together, these findings suggest that transient exposure to tire-derived contaminants can influence sediment microbial community structure and functional potential after the dissipation of the parent compounds. This study highlights the importance of considering microbial ecological responses when evaluating the environmental implications of tire-derived contaminants in aquatic sediments. Download: Download high-res image (336KB) Download: Download full-size image
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高影响因子
危险品化学品经营许可证（带存储）