Establishing an In Vitro Model to Assess the Toxicity of 6PPD-Quinone and Other Tire Wear Transformation Products,Environmental Science & Technology Letters

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Establishing an In Vitro Model to Assess the Toxicity of 6PPD-Quinone and Other Tire Wear Transformation Products
Environmental Science & Technology Letters ( IF 8.9 ) Pub Date : 2023-05-02 , DOI: 10.1021/acs.estlett.3c00196
Justin B. Greer ₁ , Ellie M. Dalsky ₁ , Rachael F. Lane ₂ , John D. Hansen ₁

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The tire wear transformation product 6PPD-quinone (6PPDQ) has been implicated as the causative factor for broad scale mortality events for coho salmon in the Pacific Northwest. Highly variable sensitivity to 6PPDQ in closely related salmonids complicates efforts to evaluate the broader toxicological impacts to aquatic ecosystems. Our goals were to (1) validate the large range of in vivo species sensitivities reported for coho, Chinook, and sockeye salmon and (2) develop an in vitro platform for assessing 6PPDQ toxicity. In vivo studies confirmed the acute sensitivity of juvenile coho (12 h LC₅₀ = 80.4 ng/L) and demonstrated that sockeye salmon were not vulnerable to mortality. Chinook salmon were sensitive to 6PPDQ mortality at initial concentrations >25 μg/L, ∼10-fold greater than reported environmental measurements. In vitro, the coho salmon cell line CSE-119 was acutely sensitive to 6PPDQ (metabolic EC₅₀ = 7.9 μg/L, cytotoxicity EC₅₀ = 6.1 μg/L). Analogous Chinook (CHSE-214) and sockeye salmon (SSE-5) cell lines were nonresponsive in both assays, and rainbow trout RTG-2 cells began showing metabolic effects at 68 μg/L (EC₅). Recreation of species-specific 6PPDQ sensitivity in vitro implicates conserved modes of action in CSE-119 that could be utilized for mechanistic studies of 6PPDQ toxicity and screening of other PPD transformation products.

中文翻译：

建立体外模型以评估 6PPD-醌和其他轮胎磨损转化产物的毒性

轮胎磨损转化产物 6PPD-醌 (6PPDQ) 被认为是太平洋西北部银鲑大规模死亡事件的致病因素。在密切相关的鲑鱼中对 6PPDQ 的高度可变敏感性使评估对水生生态系统的更广泛毒理学影响的努力复杂化。我们的目标是 (1) 验证针对银鲑、奇努克鲑和红鲑所报告的大范围体内物种敏感性，以及 (2) 开发用于评估 6PPDQ 毒性的体外平台。体内研究证实了幼银的急性敏感性 (12 h LC ₅₀= 80.4 ng/L) 并证明红鲑不易死亡。奇努克鲑鱼对初始浓度 >25 μg/L 的 6PPDQ 死亡率敏感，比报告的环境测量值高 10 倍。在体外，银鲑细胞系 CSE-119 对 6PPDQ 非常敏感（代谢 EC ₅₀ = 7.9 μg/L，细胞毒性 EC ₅₀ = 6.1 μg/L）。类似的奇努克 (CHSE-214) 和红鲑 (SSE-5) 细胞系在两种测定中均无反应，虹鳟鱼 RTG-2 细胞在 68 μg/L (EC 5 ) 时开始显示代谢_效应。在体外重建物种特异性 6PPDQ 敏感性涉及 CSE-119 中的保守作用模式，可用于 6PPDQ 毒性的机理研究和其他 PPD 转化产物的筛选。

更新日期：2023-05-02

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