Nair Pranav, Sun Jianxian, Xie Linna, Kennedy Lisa, Kozakiewicz Derek, Kleywegt Sonya M, Hao Chunyan, Byun Hannah, Barrett Holly, Baker Joshua, Monaghan Joseph, Krogh Erik T, Song Datong, Peng Hui
Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
Environmental Sciences and Standards Division, Ontario Ministry of the Environment, Conservation and Parks, Toronto, Ontario M9P 3 V6, Canada.
Environ Sci Technol. 2025 Apr 22;59(15):7485-7494. doi: 10.1021/acs.est.4c12220. Epub 2025 Apr 8.
-(1,3-Dimethylbutyl)--phenyl--phenylenediamine-quinone (6PPD-Q), the tire rubber-derived transformation product of 6PPD, was recently discovered to cause the acute mortality of coho salmon (). Aiming to identify potential replacement antiozonants for 6PPD that do not produce toxic quinones, seven PPD-quinones with distinct side chains were synthesized to investigate their structure-related toxicities using rainbow trout (). While 6PPD-Q exerted high toxicity (96 h LC = 0.35 μg/L), toxicity was not observed for six other PPD-quinones despite their similar structures. The fish tissue concentrations of 6PPD-Q after sublethal exposure (0.29 μg/L) were comparable to the other PPD-quinones, which indicated that bioaccumulation levels were not the reason for the selective toxicity of 6PPD-Q. Hydroxylated PPD-quinones were detected as the predominant metabolites in fish tissue. Interestingly, a single major aromatic hydroxylation metabolite was detected for the alternate PPD-quinones, but two abundant OH-6PPD-Q isomers were detected for 6PPD-Q. MS spectra confirmed that hydroxylation occurred on the alkyl side chain for one isomer. The structurally selective toxicity of 6PPD-Q was also observed in a coho salmon (CSE-119) cell line, which further supports its intrinsic toxicity. This study reported the selective toxicity of 6PPD-Q and pinpointed the possibility for other PPDs to be applied as potential substitutes of 6PPD.
6-苯基-1,3-二甲基丁基对苯二胺醌（6PPD-Q）是6PPD的轮胎橡胶衍生转化产物，最近被发现会导致银大麻哈鱼急性死亡。为了确定不会产生有毒醌类的6PPD潜在替代抗臭氧剂，合成了七种具有不同侧链的对苯二胺醌，以研究它们对虹鳟鱼的结构相关毒性。虽然6PPD-Q具有高毒性（96小时半数致死浓度=0.35μg/L），但其他六种对苯二胺醌尽管结构相似却未观察到毒性。亚致死暴露（0.29μg/L）后鱼组织中6PPD-Q的浓度与其他对苯二胺醌相当，这表明生物累积水平不是6PPD-Q选择性毒性的原因。羟基化对苯二胺醌被检测为鱼组织中的主要代谢产物。有趣的是，其他对苯二胺醌检测到一种主要的芳香族羟基化代谢产物，但6PPD-Q检测到两种大量的OH-6PPD-Q异构体。质谱证实其中一种异构体的羟基化发生在烷基侧链上。在银大麻哈鱼（CSE-119）细胞系中也观察到了6PPD-Q的结构选择性毒性，这进一步支持了其内在毒性。本研究报道了6PPD-Q的选择性毒性，并指出其他对苯二胺有可能作为6PPD的潜在替代品应用。
