Aggregate exposure pathways for 6PPD-quinone: A source-to-target site continuum integrating exposure and human health

N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPD-Q), a transformation product of the tire additive 6PPD, has been increasingly detected in environmental compartments, yet its cumulative risk remains poorly characterized. This study developed an Aggregate Exposure Pathway (AEP) framework to assess the mechanistic transport of 6PPD-Q from environmental sources to neuronal mitochondria in humans, focusing on the Pearl River Delta. A Weight of Evidence assessment identified key exposure states (KES) across air, road dust, surface runoff, surface water, and biota, highlighting critical data gaps in mass flux estimates, partitioning coefficients, and uptake rates. The study identified significant data gaps in atmospheric deposition, sludge-soil partitioning, groundwater leaching, oral and respiratory bioaccessibility and bioavailabity, and blood-cerebrospinal fluid permeability of 6PPD-Q. A Weight of Evidence assessment revealed significant gaps in the empirical support and quantitative understanding in 60 % of the key transitional relationships, particularly in intermediate media, external exposure and internal exposure. The findings emphasize the need for quantitative models incorporating mass fluxes and phase transfer dynamics to refine exposure predictions. Future research should focus on experimentally determining partitioning coefficients, uptake and accumulation rates, and the flux of 6PPD-Q in environmental and biological systems to enhance quantitative AEP modeling. By systematically integrating mechanistic exposure data, AEPs provide a structured approach for improving cumulative risk assessment and guiding targeted mitigation strategies.