Tire Chemicals Found to Cause Liver Damage and Brain Toxicity

A common chemical used in tires and its breakdown product accumulate in different organs and disrupt vital metabolic processes, according to new research that raises concerns about their environmental impact. The study reveals that even at concentrations typically found in urban runoff, these compounds can cause significant liver damage and behavioral changes in fish over time.

The research, published in Environmental Science and Ecotechnology, tracked how 6PPD (a rubber preservative found in virtually all tires) and its derivative 6PPD-quinone (6PPDQ) affect zebrafish during long-term exposure. Scientists discovered distinctly different patterns of accumulation and damage between the two compounds, with 6PPDQ proving more toxic despite lower concentrations in liver tissue.

What happens when chemicals that protect our tires from wear eventually wash into streams and rivers? The implications extend beyond aquatic ecosystems, as these same compounds have been detected in various seafood species consumed by humans.

Chemical Fingerprints in Different Organs

The study revealed a striking pattern of how these tire-derived chemicals distribute themselves in the body. The parent compound 6PPD preferentially accumulated in the liver and reproductive organs, while its breakdown product 6PPDQ concentrated primarily in the brain, where levels were over five times higher than those of 6PPD.

This targeting of different organs helps explain the diverse toxic effects observed. The brain accumulation of 6PPDQ appears particularly concerning for neurological function, while both chemicals ultimately caused liver damage resembling early-stage fatty liver disease.

“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.”

Key Findings About Tire Chemical Toxicity

• 6PPD accumulated primarily in the liver, while 6PPDQ targeted the brain
• Both chemicals caused growth impairment and altered swimming behavior
• Exposure led to liver inflammation, fat accumulation, and cell damage
• 6PPDQ proved more toxic than its parent compound despite lower liver concentrations
• Both compounds disrupted lipid and carbohydrate metabolism
• The chemicals suppressed an important metabolic regulator (PPARγ) and increased inflammatory markers

Signs of Liver Disease in Exposed Fish

After three months of exposure to environmentally relevant concentrations (2-8 μg/L) of these chemicals, zebrafish displayed clear signs of liver damage. Examination of liver tissue revealed significant fat accumulation and cellular changes consistent with non-alcoholic fatty liver disease.

Blood tests confirmed liver injury, with elevated levels of enzymes like ALT, AST, and ALP that typically indicate liver damage. The researchers also found increased markers of oxidative stress and inflammation in the liver tissue, alongside depleted antioxidant enzymes that normally protect cells from damage.

Genetic analysis revealed widespread disruption of metabolic pathways, particularly those involved in lipid synthesis, glucose metabolism, and cholesterol regulation. The pattern of changes closely resembled metabolic dysfunction seen in early-stage liver disease.

Behavioral Changes Signal Neurological Effects

Beyond liver damage, the researchers observed significant behavioral changes in exposed fish. Zebrafish swimming in water containing either 6PPD or 6PPDQ showed reduced swimming distance, increased time spent in dark areas of the tank, and longer periods of immobility – all indicators of potential anxiety-like behavior and neurological impact.

These behavioral changes appeared dose-dependent, with fish exposed to higher concentrations showing more severe effects. Interestingly, the behavioral changes aligned with reduced energy production in the liver, suggesting the chemicals may disrupt the body’s ability to generate the energy needed for normal activity.

The specific accumulation of 6PPDQ in brain tissue provides a potential explanation for these behavioral effects, raising questions about how this chemical might impact the nervous system over time.

From Fish to Humans: Potential Implications

While this study focused on zebrafish, the findings have potential implications for human health. Zebrafish are widely used as model organisms in toxicology because they share many genetic and physiological similarities with humans, particularly in metabolism and liver function.

The researchers noted that 6PPD and 6PPDQ have been detected in various aquatic species consumed by humans, including snakehead, weever, and Spanish mackerel. Environmental monitoring has found these compounds in urban runoff water worldwide at concentrations similar to those tested in this study (0.21 to 2.71 μg/L).

The identification of PPARγ as a target for these chemicals is particularly significant, as this protein plays a crucial role in metabolic regulation across vertebrate species. Disruption of PPARγ has been linked to metabolic disorders and liver disease in humans.

Future Research and Regulatory Considerations

This research highlights the importance of considering both parent compounds and their breakdown products when evaluating environmental pollutants. In this case, the transformation product (6PPDQ) proved more toxic than the original compound, despite being less concentrated in liver tissue.

The findings suggest current regulatory approaches that focus primarily on parent compounds may underestimate environmental and health risks. The researchers emphasize the need for improved urban runoff control and advanced water treatment systems to reduce exposure to these compounds.

Dr. Wei emphasized the need for environmental risk assessments to include both parent compounds and their transformation products in regulatory evaluations. Given the conservation of metabolic pathways across vertebrates, these findings raise broader concerns about potential long-term health effects of tire-derived contaminants on humans through contaminated water sources.