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Oral exposure to tire rubber-derived contaminant 6PPD and 6PPD-quinone induce hepatotoxicity in mice

文献类型： 外文期刊

作者： Fang, Liya 1 ; Fang, Chanlin 1 ; Di, Shanshan 2 ; Yu, Yundong 1 ; Wang, Caihong 1 ; Wang, Xinquan 2 ; Jin, Yuanxiang 1 ;

作者机构： 1.Zhejiang Univ Technol, Coll Biotechnol & Bioengn, Hangzhou 310032, Peoples R China

2.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, State Key Lab Managing Biot & Chem Threats Qual &, Key Lab Detect Pesticide Residues & Control Zheji, Hangzhou 310021, Peoples R China

3.Desheng Middle Rd 298, Hangzhou 310021, Zhejiang, Peoples R China

4.Chaowang Rd 18, Hangzhou 310014, Zhejiang, Peoples R China

关键词： 6PPD; 6PPDQ; Male mice; Liver toxicity; Transcriptomic analysis

期刊名称：SCIENCE OF THE TOTAL ENVIRONMENT （ 影响因子：9.8； 五年影响因子：9.6 ）

ISSN： 0048-9697

年卷期： 2023 年 869 卷

页码：

收录情况： SCI

摘要： 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.

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