Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells DOI Creative Commons
Jong Geol Lee, Seon Min Lee, Moonjung Hyun

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 290, P. 117744 - 117744

Published: Jan. 1, 2025

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a synthetic additive widely used in the rubber industry, and its oxidized product 6PPD-quinone (6PPDQ), have garnered widespread attention as an emerging hazardous chemicals owing to their potential detrimental effects on aquatic ecosystem human health. The of 6PPD 6PPDq female reproductive tract, especially embryo implantation, remain unknown were investigated this study. We spheroid attachment outgrowth models BeWo trophoblastic spheroids Ishikawa cells surrogates for blastocyst endometrial epithelium, respectively. Treatment with up 48 h decreased viability dose- cell line-dependent manner (20-100 μM 10-100 6PPDQ both lines). At noncytotoxic concentration, exposure 1 10 reduced further inhibited invasion epithelial monolayer. A similar result was observed 6PPDQ-exposed groups. Gene expression profiling 6PPD- revealed that differentially regulated panel transcript markers toward overall downregulation receptivity invasion. study provides first proof adverse trophoblast during window warranting need vivo clinical studies.

Language: Английский

Analysis, environmental occurrence, fate and potential toxicity of tire wear compounds 6PPD and 6PPD-quinone DOI
Xiaoli Chen, Tao He, Xinlu Yang

et al.

Journal of Hazardous Materials, Journal Year: 2023, Volume and Issue: 452, P. 131245 - 131245

Published: March 21, 2023

Language: Английский

Citations

99
Environmental Occurrence and Toxicity of 6PPD Quinone, an Emerging Tire Rubber-Derived Chemical: A Review DOI
Khaled Zoroufchi Benis, Ali Behnami, Shahab Minaei

et al.

Environmental Science & Technology Letters, Journal Year: 2023, Volume and Issue: 10(10), P. 815 - 823

Published: Sept. 1, 2023

N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is a chemical added to tires prevent their oxidative degradation. 6PPD highly reactive with ozone and oxygen, leading the formation of transformation products such as quinone (6PPDQ) on tire surfaces and, subsequently, in road wear particles. 6PPDQ toxicant that has been found roadway runoff receiving water systems. Its presence municipal stormwater led acute mortality coho salmon during migration urban creeks reproduce, generating global interest studying its occurrence toxicity environment. This review aims provide critical overview current state knowledge 6PPDQ, assisting researchers policymakers understanding potential impacts this emerging environment human health. As there are many unanswered questions surrounding further research needed. highlights importance including regulations for 6PPD, well all synthetic chemicals concern.

Language: Английский

Citations

57
Urine Excretion, Organ Distribution, and Placental Transfer of 6PPD and 6PPD-Quinone in Mice and Potential Developmental Toxicity through Nuclear Receptor Pathways DOI
Haoqi Zhao, Sydney P. Thomas, Mark J. Zylka

et al.

Environmental Science & Technology, Journal Year: 2023, Volume and Issue: 57(36), P. 13429 - 13438

Published: Aug. 29, 2023

The rubber antioxidant 6PPD has gained significant attention due to its highly toxic transformation product, 6PPD-quinone (6PPDQ). Despite their detection in urines of pregnant women, the placental transfer and developmental toxicity 6PPDQ are unknown. Here, we treated C57Bl/6 mice with 4 mg/kg or investigate urine excretion transfer. Female male exhibited sex difference profiles 6PPDQ. Urine concentrations were one order magnitude lower than those 6PPD, suggesting higher bioaccumulation In from embryonic day 11.5 15.5, showed ∼1.5–8 times placenta, embryo body, brain, Using vitro dual-luciferase reporter assays, revealed that activated human retinoic acid receptor α (RARα) retinoid X (RXRα) at as low 0.3 μM, which was ∼10-fold detected urines. RXRα 1.2 μM. These results demonstrate exposure risks during pregnancy emphasize need for further toxicological epidemiological investigations.

Language: Английский

Citations

50
Uptake and Biotransformation of the Tire Rubber-derived Contaminants 6-PPD and 6-PPD Quinone in the Zebrafish Embryo (Danio rerio) DOI Creative Commons
Nico Grasse, Bettina Seiwert, Riccardo Massei

et al.

Environmental Science & Technology, Journal Year: 2023, Volume and Issue: 57(41), P. 15598 - 15607

Published: Oct. 2, 2023

N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6-PPD) is a widely used antioxidant in tire rubber known to enter the aquatic environment via road runoff. The associated transformation product (TP) 6-PPD quinone (6-PPDQ) causes extreme acute toxicity some fish species (e.g., coho salmon). To interpret species-specific toxicity, information about biotransformation products of 6-PPDQ would be relevant. This study investigated toxicokinetics and zebrafish embryo (ZFE) model. Over 96 h exposure, accumulated ZFE with concentration factors ranging from 140 2500 for 70 220 6-PPDQ. A total 22 TPs 12 were tentatively identified using liquid chromatography coupled high-resolution mass spectrometry. After exposure 6-PPD, comprised 47% peak area (TPA), 4-hydroxydiphenylamine being most prominent ZFE. Upon >95% taken up was biotransformed, + O glucuronide dominating (>80% TPA). Among other reactive N-phenyl-p-benzoquinone imine found. knowledge this may support studies organisms.

Language: Английский

Citations

50
Widespread occurrence of two typical N, N’-substituted p-phenylenediamines and their quinones in humans: Association with oxidative stress and liver damage DOI
Shiming Song, Yanxia Gao,

Shuai Feng

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 468, P. 133835 - 133835

Published: Feb. 19, 2024

Language: Английский

Citations

37
Association between 6PPD-quinone exposure and BMI, influenza, and diarrhea in children DOI
Zhuxia Zhang, Xijin Xu,

Ziyi Qian

et al.

Environmental Research, Journal Year: 2024, Volume and Issue: 247, P. 118201 - 118201

Published: Jan. 21, 2024

Language: Английский

Citations

23
Chronic exposure to tire rubber-derived contaminant 6PPD-quinone impairs sperm quality and induces the damage of reproductive capacity in male mice DOI
Kezhen Yao,

Quanmin Kang,

Wenbo Liu

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 470, P. 134165 - 134165

Published: March 28, 2024

Language: Английский

Citations

21
Environmental profiles, hazard identification, and toxicological hallmarks of emerging tire rubber-related contaminants 6PPD and 6PPD-quinone DOI Creative Commons

Yang Jiang,

Chunzhi Wang,

Ling Ma

et al.

Environment International, Journal Year: 2024, Volume and Issue: 187, P. 108677 - 108677

Published: April 21, 2024

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is commonly used in rubber compounds as antioxidants to protect against degradation from heat, oxygen, and ozone exposure. This practice extends the lifespan of products, including tires, by preventing cracking, aging, deterioration. However, environmental consequences waste generated during product use, particularly formation 6PPD-quinone (6PPD-Q) through reaction 6PPD with ozone, have raised significant concerns due their detrimental effects on ecosystems. Extensive research has revealed widespread occurrence its derivate 6PPD-Q various compartments, air, water, soil. The emerging substance been shown pose acute mortality long-term hazards aquatic terrestrial organisms at concentrations below environmentally relevant levels. Studies demonstrated toxic a range organisms, zebrafish, nematodes, mammals. These include neurobehavioral changes, reproductive dysfunction, digestive damage exposure pathways. Mechanistic insights suggest that mitochondrial stress, DNA adduct formation, disruption lipid metabolism contribute toxicity induced 6PPD-Q. Recent findings human samples, such blood, urine, cerebrospinal fluid, underscore importance further public health toxicological implications these compounds. distribution, fate, biological effects, underlying mechanisms environment highlight urgent need for additional understand address impacts

Language: Английский

Citations

21
In Vitro and In Vivo Biotransformation Profiling of 6PPD-Quinone toward Their Detection in Human Urine DOI

Man Deng,

Xiaotong Ji,

Bo Peng

et al.

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(21), P. 9113 - 9124

Published: May 14, 2024

The antioxidant N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its oxidized quinone product 6PPD-quinone (6PPD-Q) in rubber have attracted attention due to the ecological risk that they pose. Both 6PPD 6PPD-Q been detected various environments humans cohabit. However, date, a clear understanding of biotransformation potential biomarker for exposure are lacking. To address this issue, study presents comprehensive analysis extensive across species, encompassing both vitro vivo models. We tentatively identified 17 metabolites vitro, 15 mice vivo, confirmed presence two human urine samples. Interestingly, different patterns were observed species. Through semiquantitative based on peak areas, we found almost all underwent within 24 h mice, primarily via hydroxylation subsequent glucuronidation. This suggests rapid metabolic processing mammals, underscoring importance identifying effective biomarkers exposure. Notably, monohydroxy 6PPD-Q-O-glucuronide consistently most predominant our studies, highlighting as key epidemiological research. These findings represent first data set mammalian systems, offering insights into pathways involved possible biomarkers.

Language: Английский

Citations

17
Potential human health risk of the emerging environmental contaminant 6-PPD quinone DOI
Wan Xin, Geyu Liang, Dayong Wang

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 949, P. 175057 - 175057

Published: July 26, 2024

Language: Английский

Citations

16