Environmental and Human Health Risks of 6PPD and 6PPDQ: Assessment and Implications

This review aims to synthesize current knowledge on the environmental contaminants N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone derivative (6PPDQ) derived from tire wear particles (TWPs), focusing on their environmental distribution, transformation, human exposure pathways, toxicological effects, and health risks to ecological and human health. A comprehensive literature review was conducted, compiling and analyzing data from environmental monitoring studies, toxicological assessments on aquatic and mammalian models, and emerging human biomonitoring research. Key findings on concentrations, toxicological endpoints (e.g., LC50, oxidative stress, genotoxicity), and exposure pathways were evaluated. 6PPD and its transformation product 6PPDQ are ubiquitous environmental pollutants found in air, water, soil, sediment, and dust. 6PPDQ is notably highly toxic to aquatic organisms, with an acute LC50 of 790 ng/L for coho salmon. Human exposure to these compounds occurs through inhalation, ingestion, and dermal contact, and their presence has been confirmed in human matrices including blood, urine, and cerebrospinal fluid. Toxicological studies, primarily on model organisms, indicate that 6PPD and 6PPDQ can induce oxidative stress, cause DNA damage, and disrupt metabolic and neurological functions. Adverse outcomes such as intestinal toxicity, reproductive impairment, neurobehavioral changes, and potential carcinogenicity have been observed. However, direct evidence of their health impacts on humans remains limited. 6PPD and 6PPDQ pose significant and widespread ecological risks, with 6PPDQ representing a particularly potent aquatic toxicant. While human exposure is confirmed, the full scope of human health implications is not yet well understood. The review highlights the need for longitudinal environmental tracking, mechanistic studies, and refined exposure models to inform regulatory actions and mitigate risks. Addressing these challenges is essential to mitigate the ecological and health burdens posed by 6PPD and 6PPDQ. This study underscores the global societal importance of addressing 6PPD-related pollution-a pervasive and transboundary environmental challenge stemming from universal tire wear.