New evidence links tire chemicals to chronic liver and brain toxicity

Emerging contaminants from rubber tires N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidation product     6PPD-quinone (6PPDQ)—are raising new red flags for aquatic ecosystems. A recent study reveals that prolonged exposure to these chemicals at environmentally realistic levels disrupts lipid and carbohydrate metabolism, causes liver injury, and alters behavioral patterns in zebrafish. The research shows that 6PPD primarily accumulates in the liver, while 6PPDQ targets the brain. Both compounds downregulate PPARγ, a key regulator of metabolic function, and elevate pro-inflammatory cytokines, triggering chronic toxicity. Notably, 6PPDQ proved more damaging than its precursor, suggesting that transformation products may pose even greater risks. The findings point to a pressing need for tighter regulation and environmental surveillance of tire-derived pollutants.

N-(1,3-Dimethylbutyl)-N’-phenyl-p-phenylenediamine (6PPD), an antioxidant widely used in vehicle tires, plays a critical role in preventing rubber degradation under stress. Yet, when released into the environment, it oxidizes into 6PPD-quinone (6PPDQ)—a compound now found globally in road runoff and surface waters. Prior research has linked both chemicals to developmental and systemic toxicity in aquatic organisms, but the mechanisms behind their long-term effects—particularly on liver function and neurobehavior—remain poorly defined. Zebrafish, due to their genetic similarity to humans and suitability for toxicological studies, provide a powerful model for tracing these effects. Given growing concerns, a deeper investigation into the bioaccumulation and chronic organ-specific toxicity of both 6PPD and 6PPDQ was urgently warranted.

In a study (DOI: 10.1016/j.ese.2025.100567) published April 29, 2025, in Environmental Science and Ecotechnology, researchers from South China Agricultural University and collaborators detailed how tire-derived compounds interfere with liver and neurological functions in zebrafish. By integrating toxicokinetic tracking, transcriptome profiling, and molecular interaction assays, the team compared the impacts of 6PPD and 6PPDQ. Their results revealed that while 6PPD accumulates more heavily in liver tissue, 6PPDQ induces more severe liver damage. These findings highlight distinct toxicity pathways, and suggest potential risks extend beyond fish to humans and other species exposed to tire-associated chemicals in aquatic environments.

In controlled three-month exposures, zebrafish showed clear differences in tissue accumulation and physiological damage. 6PPD localized primarily in the liver, whereas 6PPDQ was concentrated in the brain. Both compounds impaired growth and swimming behavior and caused visible liver abnormalities such as steatosis and cell degeneration. Enzyme assays revealed elevated levels of liver injury markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) and oxidative stress indicators (malondialdehyde, reactive oxygen species), alongside depleted antioxidant enzymes (superoxide dismutase, glutathione peroxidase-Px). Transcriptomic analysis confirmed widespread disruptions in metabolic pathways, especially genes related to lipid synthesis, glycolysis, and cholesterol regulation. Both chemicals suppressed Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) and upregulated inflammatory cytokines TNF-α and IL-6, with 6PPDQ exerting stronger molecular binding to PPARγ as shown by simulations and surface plasmon resonance tests. These effects collectively mirror the onset of nonalcoholic fatty liver disease, raising ecological and toxicological alarm.

“This study highlights the hidden threat posed by rubber-derived pollutants in urban runoff,” said Dr. Liangfu Wei, senior author of the study. “Our findings demonstrate that even low-level, long-term exposure to 6PPD and its oxidation product can severely disrupt liver metabolism and behavior in aquatic species. Notably, the transformation product 6PPDQ exhibits greater toxicity than its precursor, which has significant implications for regulatory monitoring and pollution control.” Dr. Wei emphasized the need for environmental risk assessments to include both parent compounds and their transformation products in regulatory evaluations.

These results offer crucial insights for environmental risk management and regulatory policy. The identification of PPARγ interference and metabolic disruption provides a molecular basis for chronic toxicity surveillance. Differentiating the toxic profiles of 6PPD and 6PPDQ highlights the importance of including chemical derivatives in hazard evaluations. The findings call for strengthened urban runoff control and the development of advanced water treatment systems to curb aquatic exposure. Given the conservation of metabolic pathways across vertebrates, the study also raises broader concerns about the long-term health effects of tire-derived contaminants on humans through contaminated water sources.

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References

DOI

10.1016/j.ese.2025.100567

Original Source URL

https://doi.org/10.1016/j.ese.2025.100567

Funding information

This work was financially supported by the China Postdoctoral Science Foundation (No. 2023M741216), Guangdong Province Basic and Applied Basic Research Fund - Provincial and Municipal Joint Fund (No. 2023A1515110978), Natural Science Foundation of Guangdong Province (No. 2024A1515012900), the National Natural Science Foundation of China (No. 32401410), Research Fund Program of Guangdong-Hong Kong Joint Laboratory for Water Security (No. GHJLWS-07), and Xiamen Key Laboratory of Intelligent Fishery (No. XMKLIF-OP-202304).

About Environmental Science and Ecotechnology

Environmental Science and Ecotechnology (ISSN 2666-4984) is an international, peer-reviewed, and open-access journal published by Elsevier. The journal publishes significant views and research across the full spectrum of ecology and environmental sciences, such as climate change, sustainability, biodiversity conservation, environment & health, green catalysis/processing for pollution control, and AI-driven environmental engineering. The latest impact factor of ESE is 14, according to the Journal Citation Report^TM 2024.