Yun-Hao Ding, Wen-Xiong Wang
The tire-wear transformation product 6PPD-quinone (6PPD-Q) is a primary driver of "Urban Runoff Mortality Syndrome" by inducing acute and species-specific mortality in salmonids, yet the underlying toxicokinetic mechanisms remain poorly understood. In this study, we investigated the multi-tissue biokinetics of 6PPD-Q in sensitive rainbow trout (Oncorhynchus mykiss) and relatively tolerant masu salmon (Oncorhynchus masou) using novel damage-coupled biokinetic models. Surprisingly, results revealed a non-linear, accelerating accumulation trajectory across all tissues, with the brain and liver serving as the predominant toxicant sinks. These accumulation profiles were strongly affected by exposure concentration and exposure period, whereas species-related effects were tissue-specific and expressed through interaction terms rather than as a uniform species difference. Simulated parameters indicated that the acute sensitivity of rainbow trout was driven by a high initial brain uptake rate constant (k1) and vulnerability to physiological damage in peripheral tissues. Specifically, the composite damage-sensitivity index in the muscle and gills of rainbow trout was 25- to 213-fold higher than that of masu salmon. This toxicant-induced physiological damage triggered a lethal "positive feedback accumulation" loop, where compromised physiological damage exponentially increased tissue absorption, leading to a rapid influx of 6PPD-Q. Conversely, masu salmon maintained its tolerance via superior physiological resilience and robust clearance mechanisms. This study quantitatively showed that kinetic instability, precipitated by toxicant-induced physiological damage, governed 6PPD-Q species-specific acute toxicity. The findings challenge traditional steady-state risk assessments paradigms and provide a dynamic predictive framework for evaluating the physiological damaging of emerging contaminants in aquatic ecosystems.