Journal of Advanced Research
·
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
·
神经科学
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
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
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Water Process Engineering
·
2025
·
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.
✓ 已验证
DOI
高影响因子
TOXICOLOGY
·
2025
·
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
·
环境健康
·
分子生物学
·
代谢学
·
微生物组学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
WATER RESEARCH
·
2024
·
IF 11.4
Wenyan Yu,Shaoyu Tang,Jonathan W.C. Wong,Zhujun Luo,Zongrui Li,Phong K. Thai,Minghan Zhu,Hua Yin,Junfeng Niu
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPD-Q) has been identified to induce acute toxicity to multifarious aquatic organisms at exceptionally low concentrations. The ubiquity and harmful effects of 6PPD-Q emphasize the critical need for its degradation from water ecosystems. Herein, we explored the transformation of 6PPD-Q by an ultraviolet-activated peroxymonosulfate (UV/PMS) system, focusing on mechanism, products and toxicity variation. Results showed that complete degradation of 6PPD-Q was achieved when the initial ratio of PMS and 6PPD-Q was 60:1. The quenching experiments and EPR tests indicated that SO 4 •− and •OH radicals were primarily responsible for 6PPD-Q removal. Twenty-one degradation products were determined through high-resolution orbitrap mass spectrometry, and it was postulated that hydroxylation, oxidative cleavage, quinone decomposition, ring oxidation, as well as rearrangement and deamination were the major transformation pathways of 6PPD-Q. Toxicity prediction revealed that all identified products exhibited lower acute and chronic toxicities to fish, daphnid and green algae compared to 6PPD-Q. Exposure experiments also uncovered that 6PPD-Q considerably reduced the community diversity and altered the community assembly and functional traits of the sediment microbiome. However, we discovered that the toxicity of 6PPD-Q degradation solutions was effectively decreased, suggesting the superior detoxifying capability of the UV/PMS system for 6PPD-Q. These findings highlight the underlying detrimental impacts of 6PPD-Q on aquatic ecosystems and enrich our understanding of the photochemical oxidation behavior of 6PPD-Q.
研究领域:
环境科学
·
生态毒理学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Qicai Zhang,Xianli Wang,Chengbin Liu,Huaxi Li,Zhongsheng Deng,Chunxia Yao,Yameng Li,Qinxiong Rao,Weiguo Song
Given the high toxicity of N-(1,3-dimethylbutyl)-N′-phenyl- p -phenylenediamine (6PPD) derivatives, such as 6PPD quinone (6PPDQ) to salmon, as well as their ubiquitous presence in the environment, the contaminant of aquatic food products has drawn significant attention. However, analytical methods for p -Phenylenediamines (PPDs) and their transformation products (TPs) in aquatic products remain underdeveloped. In particular, the degradation of some compounds and strong matrix effects complicate detection. In this study, we present a stable, rapid, and sensitive method combining salt-out assisted extraction, antioxidant protection, and multi-plug filtration clean-up (m-PFC) to detect two PPDs and five TPs in aquatic products. Crucially, the appropriate selection of antioxidants prevented the degradation of the easily oxidized target compounds. Further, the m-PFC method significantly enhanced the purification efficiency, achieving satisfactory recoveries (62.1–115 %), and method detection limits (MDLs) ranging from 0.00300 to 0.400 μg/kg. Subsequently, the method was applied to monitor PPDs and their TPs in aquatic products systematically, revealing the presence of 6PPD and N-isopropyl-N′-phenyl-1,4-phenylenediamine (IPPD) in white shrimp from aquafarms, whereas none of the seven target analytes were detected in fish and crab samples. These findings contribute to the detection of PPDs, their TPs and other unstable chemicals in aquatic products, thereby providing insights into their concentrations in these products.
研究领域:
分析化学
·
环境科学
·
食品安全
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
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
·
化学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）