Multiview behavior and neurotransmitter analysis of zebrafish dyskinesia induced by 6PPD and its metabolites

Ji, Jiawen; Huang, Jinze; Cao, Niannian; Hao, Xiaolong; Wu, Yanhua; Ma, Yongqiang; An, Dong; Pang, Sen; Li, Xuefeng

doi:10.1016/j.scitotenv.2022.156013

Cited by 38 publications

(18 citation statements)

References 59 publications

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“…Aside from environmental ubiquity, emerging evidence also suggested some significant toxicities of 6PPD and 6PPD-Q. ,− For example, 6PPD has been shown to induce toxicity in fathead minnow ( Pimephales promelas ) and freshwater mussel ( Lampsilis siliquoidea ). , In addition to being highly toxic to coho salmon as reported by Tian et al, , 6PPD-Q was also demonstrated to be toxic to zebrafish larvae with a 24 h LC 50 of 308.67 μg/L . More recently, 6PPD and 6PPD-Q were found to cause anxiety-like behaviors and unbalance in zebrafish . Although the aquatic toxicities of 6PPD and 6PPD-Q are becoming clearer, their adverse effects on mammals and humans remain largely unknown.…”

Section: Introductionmentioning

confidence: 92%

“…22 More recently, 6PPD and 6PPD-Q were found to cause anxiety-like behaviors and unbalance in zebrafish. 24 Although the aquatic toxicities of 6PPD and 6PPD-Q are becoming clearer, their adverse effects on mammals and humans remain largely unknown. In particular, internal exposure to 6PPD and 6PPD-Q may pose potential health risks to humans.…”

Section: ■ Introductionmentioning

confidence: 99%

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First Report on the Occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as Pervasive Pollutants in Human Urine from South China

Liang

et al. 2022

Environ. Sci. Technol. Lett.

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-N′-phenyl-p-phenylenediamine (6PPD) and its quinone derivative, 6PPD-quinone (6PPD-Q), have been found to be prevalent in the environment, but there are currently no data on their presence in humans. Herein, we conducted the first human biomonitoring study of 6PPD and 6PPD-Q by measuring 150 urine samples collected from three different populations (general adults, children, and pregnant women) in South China. Both 6PPD and 6PPD-Q were detected in the urine samples, with detection frequencies between 60% and 100%. Urinary 6PPD-Q concentrations were significantly higher than those of 6PPD and correlated well with those of 6PPD (p < 0.01), indicating coexposure to 6PPD and 6PPD-Q in humans. In vitro metabolic experiments demonstrated rapid depletion of 6PPD by human liver microsomes, which should be responsible for the lower concentrations of 6PPD in human urine. Additionally, pregnant women exhibited apparently higher concentrations of 6PPD and 6PPD-Q (median 0.068 and 2.91 ng/mL, respectively) than did adults (0.018 and 0.40 ng/mL) and children (0.015 and 0.076 ng/mL). The high daily urinary excretion of 6PPD-Q in pregnant women was estimated to be 273 (ng/kg bw)/day. Considering that 6PPD-Q was a lethal toxicant to multiple aquatic species, the potential human health risks posed by its long-term exposure require urgent attention.

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Section: Introductionmentioning

confidence: 92%

Section: ■ Introductionmentioning

confidence: 99%

First Report on the Occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as Pervasive Pollutants in Human Urine from South China

Liang

et al. 2022

Environ. Sci. Technol. Lett.

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“…It has been indicated that this observed mortality was associated with a concentration of 6-PPDQ in the environment . Acute exposure to 6-PPDQ at concentrations of 500–1000 μg/L caused abnormal locomotion behaviors in zebrafish . Acute exposure to 6-PPDQ could further cause mitochondrial dysfunction in some adherent cell lines .…”

Section: Introductionmentioning

confidence: 99%

“…7 Acute exposure to 6-PPDQ at concentrations of 500− 1000 μg/L caused abnormal locomotion behaviors in zebrafish. 14 Acute exposure to 6-PPDQ could further cause mitochondrial dysfunction in some adherent cell lines. 15 However, the information on the effects of long-term exposure to 6-PPDQ on organisms is still limited.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Environmental pollutants could enter and be accumulated in organisms and human body through the food chain, which causes hazardous health risks . The 6-PPDQ could be detected in various species, such as snakehead, weever, and Spanish mackerel fish . Acute mortality of coho salmon (Oncorhynchus kisutch) after 6-PPDQ exposure was observed in the stormwater in the Pacific Northwest of the United States .…”

Section: Introductionmentioning

confidence: 99%

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Exposure to 6-PPD Quinone at Environmentally Relevant Concentrations Causes Abnormal Locomotion Behaviors and Neurodegeneration in Caenorhabditis elegans

Hua

Feng

Liang

et al. 2023

Environ. Sci. Technol.

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6-PPD quinone (6-PPDQ) can be transformed from 6-PPD through ozonation. Nevertheless, the potential neurotoxicity of 6-PPDQ after long-term exposure and the underlying mechanism are largely unclear. In Caenorhabditis elegans, we here observed that 0.1–10 μg/L of 6-PPDQ caused several forms of abnormal locomotion behaviors. Meanwhile, the neurodegeneration of D-type motor neurons was observed in 10 μg/L of 6-PPDQ-exposed nematodes. The observed neurodegeneration was associated with the activation of the Ca2+ channel DEG-3-mediated signaling cascade. In this signaling cascade, expressions of deg-3, unc-68, itr-1, crt-1, clp-1, and tra-3 were increased by 10 μg/L of 6-PPDQ. Moreover, among genes encoding neuronal signals required for the control of stress response, expressions of jnk-1 and dbl-1 were decreased by 0.1–10 μg/L of 6-PPDQ, and expressions of daf-7 and glb-10 were decreased by 10 μg/L of 6-PPDQ. RNAi of jnk-1, dbl-1, daf-7, and glb-10 resulted in the susceptibility to 6-PPDQ toxicity in decreasing locomotory ability and in inducing neurodegeneration, suggesting that JNK-1, DBL-1, DAF-7, and GLB-10 were also required for the induction of 6-PPDQ neurotoxicity. Molecular docking analysis further demonstrated the binding potential of 6-PPDQ to DEG-3, JNK-1, DBL-1, DAF-7, and GLB-10. Together, our data suggested the exposure risk of 6-PPDQ at environmentally relevant concentrations in causing neurotoxicity in organisms.

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Acute Toxicity Testing of Pink Salmon (Oncorhynchus gorbuscha) with the Tire Rubber–Derived Chemical 6PPD‐Quinone

Foldvik,

Kryuchkov,

Ulvan

et al. 2024

Enviro Toxic and Chemistry

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N‐(1,3‐dimethylbutyl)‐N′‐phenyl‐p‐phenylenediamine‐quinone (6PPD‐quinone) is a widespread contaminant of emerging concern resulting from oxidation of 6PPD, which is an antidegradant substance added to tires. The recent identification of 6PPD‐quinone as the cause of acute mortality in coho salmon has quickly motivated studies on 6PPD‐quinone toxicity to other species. Subsequent findings have shown that 6PPD‐quinone toxicity is highly species specific. Closely related species can differ widely in response to 6PPD‐quinone from extremely sensitive to tolerant. Hence toxicity testing is currently the only way to establish whether a species exhibits 6PPD‐quinone toxicity. We investigated the acute toxicity of 6PPD‐quinone in pink salmon alevins (sac fry). This species has is the only Pacific salmon that so far has not been tested for 6PPD‐quinone sensitivity. Fish were exposed in static water in eight treatments with initial concentrations ranging from 0.1 to 12.8 μg/L. Fish were observed for 48 h, and changes in concentrations of 6PPD‐quinone were monitored throughout the experiment. No mortalities or substantial changes in behavior were recorded. Environ Toxicol Chem 2024;00:1–7. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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Multiview behavior and neurotransmitter analysis of zebrafish dyskinesia induced by 6PPD and its metabolites

Cited by 38 publications

References 59 publications

First Report on the Occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as Pervasive Pollutants in Human Urine from South China

First Report on the Occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as Pervasive Pollutants in Human Urine from South China

Exposure to 6-PPD Quinone at Environmentally Relevant Concentrations Causes Abnormal Locomotion Behaviors and Neurodegeneration in Caenorhabditis elegans

Acute Toxicity Testing of Pink Salmon (Oncorhynchus gorbuscha) with the Tire Rubber–Derived Chemical 6PPD‐Quinone

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