ENVIRONMENTAL RESEARCH
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2025
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IF 7.7
Zhe Wang,Mingjun Zhu,Yao Hu,Jiaxi Liu,Xiaoyu Ma,Hong Zhou
The antioxidant 6PPD and its oxidized product 6PPD-Quinone (6PPDQ) have attracted considerable attention due to their various acute toxicities to aquatic organisms. However, the chronic toxicity of two compounds in aquatic animals is still unknown. Here, adult zebrafish were exposed to 6PPD and 6PPDQ at environmentally relevant concentrations (20 μg/L) for 28 days, and histological analysis showed that 6PPD caused more severe hepatic vacuolization than 6PPDQ. Meanwhile, 6PPD induced more serious lipid accumulation and a higher increase in triglyceride and total cholesterol levels than 6PPDQ, suggesting higher hepatotoxicity of 6PPD. Furthermore, transcriptomic analysis revealed that both compounds disturbed glucolipid metabolism to different degrees by altering the expression of different peroxisome proliferator-activated receptors (PPARs), in which 6PPD inhibited gene expressions in glucolipid metabolism possibly by PPARα, PPARβ and RXR, while 6PPDQ disrupted the expressions of partial genes in similar pathways probably via PPARγ. Additionally, 6PPD but not 6PPDQ increased Fe 2+ content, decreased the protein levels of ferroportin 1, ferritin and glutathione peroxidase 4, accompanied with the increase of malondialdehyde level and the decrease of glutathione content, suggesting ferroptotic response by 6PPD. Overall, our data deepened the understanding of 6PPD- and 6PPDQ-induced hepatotoxicity association with glucolipid metabolism disorders and ferroptotic responses.
研究领域:
环境毒理学
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分子生物学
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PubMed
高影响因子
WATER RESEARCH
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2026
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IF 12.8
Jingqi Ruan,Teng Zhang,Peizeng Yang,Xinping Yang,Bin Gao,Junhe Lu,Deyang Kong
The widespread occurrence of 6PPD-quinone (6PPD-Q), a highly toxic transformation product of the tire-derived antioxidant 6PPD, poses serious threat to salmon fisheries. Here, we provide the first quantitative evaluation of 6PPD phototransformation in ice under UV irradiation, a condition directly relevant to salmon habitats. Freezing markedly accelerated both 6PPD photodegradation and its conversion to 6PPD-Q, with a molar yield of 4% in ice versus 1.7% in liquid water. This enhancement arises from the freeze-concentration effect, which enriches 6PPD and oxygen molecules within the quasi-liquid boundary region, selectively amplifying singlet oxygen ( 1 O 2 ) production. In ice, 1 O 2 accounted for 45.9% of 6PPD degradation and 70.2% of 6PPD-Q formation, compared to 4.1% and 35.0%, respectively, in liquid water, where • OH dominated 6PPD-Q formation. These findings highlight ice as an active photochemical medium and identify ice-covered urban waters as potentially overlooked hotspots for 6PPD-Q formation, with direct implications for salmon-bearing ecosystems in cold regions.
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2023
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IF 13.6
Chenguang Li,Yanlei Zhang,Shiqi Yin,Qin Wang,Yuanyuan Li,Qiang Liu,Liuqingqing Liu,Xianxiang Luo,Lingyun Chen,Hao Zheng,Fengmin Li
p -Phenylenediamines (PPDs), an important type of rubber antioxidants, have received little study on their environmental fate , particularly for their vital photodegradation process in water environment. Accordingly, N -(1,3-dimethylbutyl)- N′ -phenyl-1,4-phenylenediamine (6PPD), as a representative of PPDs, was investigated experimentally and theoretically for its photodegradation in water. Rapid photodegradation occurred when 6PPD was exposed to illumination especially UV region irradiation. Under acidic conditions, the photodegradation of 6PPD accelerated mainly due to the increased absorption of long wavelength irradiation by ionized 6PPD. Nine photodegradation products (e.g., 6PPD - quinone (6PPDQ)) of 6PPD were identified by an ultra-performance liquid chromatography QTOF mass spectrometry . Molar yields of photoproducts such as 6PPDQ, aniline, 4-aminodiphenylamine, and 4-hydroxydiphenylamine were 0.03 ± 0.00, 0.10 ± 0.01, 0.03 ± 0.02, and 0.08 ± 0.01, respectively. Mechanisms involved in 6PPD photodegradation include photoexcitation , direct photolysis, self-sensitized photodegradation, and 1 O 2 oxidation , as demonstrated by electron paramagnetic resonance (EPR) analysis, scavenging experiments, and the time-dependent density functional theory (TD-DFT). Notably, the toxicity of the reaction solution formed during the photodegradation of 6PPD was increased by the formation of highly toxic products (e.g., 6PPDQ). This study provides the first explanation for photodegradation mechanisms of 6PPD and confirms the pathway of 6PPDQ produced by the photoreaction in water environment.
研究领域:
环境科学
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化学
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毒理学
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PubMed
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
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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高影响因子
Journal of Water Process Engineering
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2025
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IF 6.7
Yiyang Lin,Tao Lin,Han Chen,Junding Yin
The effect of N , N -bis(carboxymethyl)glutamic acid (GLDA) on the removal of organic pollutants by Fe(II)-mediated periodate (PI) advanced oxidation process at neutral pH was investigated, in which N-(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine quinone (6PPD-Q) was used as the model pollutant. The results showed that the Fe(II)-GLDA complex formed by mixing GLDA with Fe(II) in a 1:1 ratio reacted with PI can degrade 6PPD-Q effectively. The presence of GLDA alters the redox potential of Fe(II)/Fe(III), which allows for a better utilization of Fe(II) under the synergistic effect of ultraviolet (UV) irradiation. Based on quenching experiments, sulfoxide probe transformation and electron spin resonance (ESR) signals, the reactive species that play a major role in this process are Fe IV O and IO 3 . The degradation products of 6PPD-Q were detected by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) and two possible degradation pathways were proposed based on density functional theory (DFT) calculations. The toxicity of 6PPD-Q was found to be effectively reduced after degradation by Ecological Structure Activity Relationships (ECOSAR) software analysis and zebrafish experiments. This study provides some fundamental insights for the removal of organic pollutants by GLDA-enhanced Fe(II)/PI system under neutral conditions.
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高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2023
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IF 9.8
Liya Fang,Chanlin Fang,Shanshan Di,Yundong Yu,Caihong Wang,Xinquan Wang,Yuanxiang Jin
N-(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD) is a widely used additive for protecting various rubber products, and its product of oxidation N-(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine-quinone (6PPDQ) has attracted extensive attention in aquatic toxicity. However, the toxicity of 6PPD and 6PPDQ in mammals has not been reported yet. In this study, the effects of 6PPD and 6PPDQ on the liver of C57BL/6 mice were assessed by orally administering different doses of 6PPD and 6PPDQ (10, 30, and 100 mg/kg) in mice for 6 weeks. 6PPD and 6PPDQ were found to bioaccumulate in the liver in a dose-dependent manner. Moreover, a high dose of 6PPD and 6PPDQ exposure increased not only the liver weights but also liver triglyceride levels, indicating that 6PPD and 6PPDQ exposure induced hepatotoxicity in mice. Furthermore, transcriptomic analysis revealed that 6PPD and 6PPDQ induced differential expression of genes mainly enriched in glycolipid metabolism, immune-related, and glutathione metabolism pathways. Therefore, 6PPD and 6PPDQ altered hepatic metabolism in mice. Furthermore, 6PPDQ could induce an immune response by upregulating the transcription of immune-related genes and promoting macrophage infiltration in the liver. In conclusion, our study revealed the toxic effects of 6PPD and 6PPDQ exposure on multi-endpoints in the liver of mice and improve our understanding of the health risks of 6PPD and 6PPDQ to mammals. The findings of our study may help formulate better safety regulations for the use and disposal of rubber products.
研究领域:
毒理学
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分子生物学
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环境科学
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药理学
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DOI
PubMed
高影响因子
TOXICOLOGY
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2025
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IF 4.6
Liya Fang,Jinhua Xu,Chanlin Fang,Yuanxiang Jin
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is a commonly used rubber protectant that continuously enters the environment via groundwater. Its oxidation product, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPDQ), has garnered significant concern due to its reported toxicity in animals. This study aims to evaluate the intestinal toxicity and potential metabolic impact of 6PPD and 6PPDQ in mice following oral exposure to various doses. Our results demonstrate that both compounds compromise the intestinal barrier, as evidenced by significant increases in the expression of tight junction proteins (claudin-1 and occludin) and mucin protein (MUC2). These changes suggest an impairment of both the physical and chemical barriers of the intestine. Following exposure, there was a marked increase in pro-inflammatory cytokines (IL-6, IL-22, and NOD-1), indicating an inflammatory response associated with the disruption of lipid metabolism and macrophage polarization. Specifically, the shift from M2 to M1 macrophage polarization correlates with increased expression of M1 markers despite no change in the M1/M2 ratio over prolonged exposure. Furthermore, 6PPD exposure significantly reduced gut microbiota richness and evenness, with more pronounced changes observed in the 6PPDQ-treated group. Correlation analysis suggested that these microbial shifts may influence host carnitine and lipid metabolism pathways. Ultimately, both 6PPD and 6PPDQ exposure led to elevated levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) in the bloodstream, attributed to decreased TC esterification. These findings highlight the potential long-term health risks associated with environmental exposure to 6PPD and 6PPDQ, particularly concerning gut integrity and metabolic dysregulation. Synopsis This study investigates the toxicity of 6PPD and its transformation product 6PPDQ, revealing their detrimental effects on intestinal health, disruption of gut microbiota, and alterations in lipid metabolism, highlighting significant implications for both environmental and human health.
研究领域:
毒理学
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环境健康
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分子生物学
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代谢学
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微生物组学
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免疫学
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药理学
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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
Hanghai Zhou,Zhendong Li,Zhou Wu,Lihua Zou,Hong Sun,Hua Li,Xin Wang,Yuan Wang,Junwei Jin,Thilo Hofmann,Jiangwu Tang
Tire and road wear particles introduce complex mixtures of metals and organic additives into soils, yet the primary drivers of their combined toxicity remain poorly resolved. Here, we investigated the individual and combined effects of zinc oxide (ZnO), a major inorganic tire additive, and 6PPD-quinone (6PPD-Q), a toxic transformation product of the tire antioxidant 6PPD, using a soil invertebrate exposure model. A gradient of ZnO concentrations was tested alone and in combination with an environmentally relevant level of 6PPD-Q to simulate co-contaminated soils. While single exposures induced oxidative stress, metabolic perturbation, and gut microbiome alteration, co-exposure under high Zn conditions resulted in increased mortality and growth inhibition relative to single treatments. Chemical analysis revealed enhanced Zn accumulation in organisms under co-exposure, whereas 6PPD-Q bioaccumulation declined at elevated Zn levels, indicating that internal Zn burden was more consistently associated with organism-level impairment than measured internal 6PPD-Q concentration under the tested conditions. Integrated biochemical, histological, and multi-omics analyses showed that co-exposure was associated with enhanced oxidative stress, altered energy metabolism, impaired neuroimmune function, and destabilized gut microbial structure and predicted metabolic potential. Complementary multi-omics analyses revealed coordinated alterations in antioxidant defense, detoxification capacity, and mitochondrial metabolism under high-Zn co-exposure, consistent with a reduced physiological tolerance to chemical stress. Together, these findings support the interpretation that zinc accumulation likely represents a primary contributor to co-exposure toxicity, while 6PPD-quinone may amplify adverse outcomes by constraining organismal stress-buffering capacity. These results highlight the need to consider metal–organic interactions and differential toxic contributions in mixture-based environmental risk assessment of tire-derived contaminants.
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PubMed
高影响因子
Journal of Advanced Research
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2025
·
IF 13
Qu-Nan Wang,Chunzhi Wang,Yán Wāng
Introduction The extensive use of 6PPD in tire rubber has led to its increase in atmospheric tire wear particles. 6PPD reacts with ozone to form 6PPD-quinone (6PPD-Q), a respiratory toxicant enriched in tire and road wear particles. Objectives The aim of this study is to decipher the potential sensitive target organs and toxic actions by inhalation exposure to atmospheric 6PPD-Q. Methods This study employed a mouse inhalation exposure model to simulate environmental levels of 6PPD-Q at three concentrations of 0, 0.14, and 14 mg/m 3 . Using a 28-day exposure period followed by an equivalent recovery phase, we systematically evaluated the toxicological targets and effects of subacute exposure. Results The findings revealed that, compared to pulmonary, cardiovascular, and metabolic organ damage, 6PPD-Q-induced neurotoxicity was more persistent and irreversible, particularly characterized by prolonged anxiety-like behaviors. Histopathological analyses of the basolateral amygdala, using Nissl staining and markers of neuronal aging, indicated substantial neuronal degeneration linked to elevated oxidative stress, identifying this region as a critical target of 6PPD-Q neurotoxicity. Transcriptomic analysis uncovered that the expression of Egr1 , a transcription factor crucial for neuronal plasticity, was markedly dysregulated. Findings of significant downregulation at the gene level and an upward trend in protein expression suggest that Egr1 expression is influenced by translational efficiency, epigenetic modifications, and post-translational regulatory mechanisms. Egr1 dysregulation disrupted downstream networks involving solute carrier proteins and calcium-binding proteins, contributing to aberrant neurobehavioral outcomes. Notably, the elevation of Egr1 protein levels in the basolateral amygdala but not in the cerebral cortex highlights the region-specific nature of 6PPD-Q’s neurotoxic effects. Conclusion This study provides the first insights into the neurotoxicity and irreversibility of inhaled 6PPD-Q exposure, paving the way for future research into the long-term neurological consequences and regulatory mechanisms of 6PPD-Q.
研究领域:
毒理学
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神经科学
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环境健康
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Yuying Zhang,Lei Yan,Longxing Wang,Haijun Zhang,Jiping Chen,Ningbo Geng
N , N ′-substituted p -phenylenediamines (PPDs) are widely used antioxidants in rubber tires, which could be released and accumulated in road dusts with rubber tires wear. As ozonation product of N -(1,3-dimethylbutyl)- N′ -phenyl- p -phenylenediamine (6PPD), 6PPD-quinone (6PPD-Q) exhibited higher toxicity to coho salmon. However, studies on their environmental behaviors are still limited. Road dust is the major medium PPDs exist, which significantly affects the levels of PPDs in other mediums, especially surface water and particulate matter. In this study, road dust samples were collected in 55 major cities of China to explore the distribution characteristics of PPDs and 6PPD-Q. The concentrations of total PPDs (ΣPPDs) and 6PPD-Q in urban trunk road dust samples were in the ranges of 7.90–727 and 3.00–349 ng/g, with median concentrations of 68 and 49 ng/g, respectively. 6PPD and 6PPD-Q are the dominant components in most road dusts. The functional region-dependent pollution characteristics of PPDs and 6PPD-Q give the first finding that urban tunnel road was the highly polluted region, followed by urban trunk roads. Suburban road dusts had a lower pollution level. Moreover, the estimated daily intake (EDI) of PPDs and 6PPD-Q for children was much higher than adults.
研究领域:
环境科学
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毒理学
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DOI
PubMed
高影响因子
Journal of Environmental Sciences
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2026
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IF 6.5
Jingqi Ruan,Teng Zhang,Peizeng Yang,Xinping Yang,Jing Chen,Yuefei Ji,Junhe Lu
Quantitatively analyzed 6PPD degradation and 6PPD-Q formation in UV/NOM. • • OH dominated 6PPD photodegradation, followed by 3 NOM* and 1 O 2 . • 3 NOM* and 1 O 2 mainly contributed to 6PPD-Q formation, while • OH played less. • 6PPD-Q molar yields followed the trend: 1 O 2 > 3 NOM* > • OH > direct photolysis. Photochemical transformation of the tire-derived antioxidant N -(1,3-dimethylbutyl)- N' -phenyl- p -phenylenediamine (6PPD) in sunlit waters has been recognized as an important source of 6PPD-quinone (6PPD-Q), a product with reported acute toxicity to coho salmon. However, the relative contributions of transient reactive species to 6PPD photodegradation and 6PPD-Q formation remain poorly understood. Here, we quantitatively evaluated the photochemical transformation mediated by natural organic matter (NOM), which serves as an important photosensitizer and significantly accelerates both 6PPD degradation and 6PPD-Q generation. Through radical scavenging and kinetic solvent isotopic effect experiments, we identified the excited triplet state NOM ( 3 NOM*), singlet oxygen ( 1 O 2 ), and hydroxyl radical ( • OH) as the key reactive species driving these processes. At 3 mg C /L NOM, their contributions to 6PPD degradation follow descending order: • OH (30.9 %) > 3 NOM* (27.4 %) > 1 O 2 (18.5 %) > direct photolysis (17.6 %). Interestingly, kinetic modeling revealed a shift in dominance for 6PPD-Q formation, with 3 NOM* and 1 O 2 contributing 38.7 % and 30.2 %, respectively, followed by • OH (26.1 %) and direct photolysis (4.7 %). This shift is due to the higher molar yields of 6PPD-Q from 1 O 2 (10.8 %) and 3 NOM* (9.4 %), compared to • OH (5.6 %) and direct photolysis (1.8 %). This quantitative understanding is essential for predicting the environmental fate of 6PPD and informing strategies to mitigate its ecological risks. Download: Download high-res image (347KB) 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）