Industrial and consumer goods contain diverse perfluoroalkyl substances (PFAS). These substances, like perfluorohexanoic acid (PFHxA) and perfluorohexanesulphonic acid (PFHxS), are under increased scrutiny due to their potential toxicity to aquatic organisms. However, our understanding of their biological impacts and mechanisms of action remains limited. The objectives of this review were to compare data for levels of PFHxA and PFHxS in aquatic environments and fish tissues, as well as toxicity mechanisms related to morphological, endocrine, metabolic, and behavioral endpoints. A computational assessment was also performed to identify putative mechanisms of toxicity and to characterize exposure biomarkers. Studies have shown that both PFHxA and PFHxS residues are present in diverse marine and freshwater fish tissues, suggesting the importance of monitoring these PFAS in aquatic organisms. In fish tissues, these chemicals have been reported to be as high as 37.5 ng/g for PFHxA and 1290 ng/g for PFHxS but their persistence in aquatic environments and degradation in tissues requires further study. In terms of mechanisms of toxicity, both oxidative stress and endocrine disruption have been reported. Based on evidence for endocrine disruption, we modeled interactions of estrogen and androgen receptors of several fish species with PFHxA and PFHxS. Molecular docking revealed that PFHxS has a stronger affinity for interacting with the estrogen and androgen receptors of fish compared to PFHxA and that estrogen and androgen receptors of fathead minnows, zebrafish, Atlantic salmon, and largemouth bass show comparable binding affinities for each chemical except for salmon Esr2b which appears to show lower affinity for PFHxA relative to Esr2a. While mechanistic data are lacking in fish, a computational assessment revealed that PFHxA can perturb the endocrine system, nervous system, and is linked to changes in kidney and liver weight. Proteins linked to PFHxA and PFHxS exposures in fish include those related to lipid and glucose regulation, reproductive proteins like KISS metastasis suppressor, and proteins associated with the immune system (specifically RAG1, RAG2), all of which are potential biomarkers of exposure. Taken together, we synthesize current knowledge regarding the environmental fate and ecotoxicology of PFHxA/PFHxS in fish species.

中文翻译：

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全氟己酸（PFHxA）和全氟己磺酸（PFHxS）对鱼类的毒性机制比较研究

工业和消费品含有多种全氟烷基物质 (PFAS)。这些物质，如全氟己酸 (PFHxA) 和全氟己烷磺酸 (PFHxS)，由于对水生生物具有潜在毒性而受到越来越严格的审查。然而，我们对其生物学影响和作用机制的了解仍然有限。本次综述的目的是比较水生环境和鱼类组织中 PFHxA 和 PFHxS 水平的数据，以及与形态、内分泌、代谢和行为终点相关的毒性机制。还进行了计算评估，以确定假定的毒性机制并表征暴露生物标志物。研究表明，多种海洋和淡水鱼组织中均存在 PFHxA 和 PFHxS 残留，这表明监测水生生物中这些 PFAS 的重要性。据报道，在鱼类组织中，这些化学物质的 PFHxA 含量高达 37.5 ng/g，PFHxS 含量高达 1290 ng/g，但它们在水生环境中的持久性和在组织中的降解需要进一步研究。就毒性机制而言，氧化应激和内分泌干扰都有报道。根据内分泌干扰的证据，我们模拟了几种鱼类的雌激素和雄激素受体与 PFHxA 和 PFHxS 的相互作用。分子对接显示，与 PFHxA 相比，PFHxS 与鱼类雌激素和雄激素受体相互作用的亲和力更强，并且黑头鲦鱼、斑马鱼、大西洋鲑鱼和大口黑鲈的雌激素和雄激素受体对除鲑鱼外的每种化学物质都显示出相当的结合亲和力相对于 Esr2a，Esr2b 对 PFHxA 的亲和力似乎较低。虽然缺乏鱼类的机制数据，但计算评估显示，PFHxA 会扰乱内分泌系统、神经系统，并与肾脏和肝脏重量的变化有关。鱼类中与 PFHxA 和 PFHxS 暴露相关的蛋白质包括与脂质和葡萄糖调节相关的蛋白质、KISS 转移抑制蛋白等生殖蛋白以及与免疫系统相关的蛋白质（特别是 RAG1、RAG2），所有这些都是潜在的暴露生物标志物。综上所述，我们综合了有关鱼类中 PFHxA/PFHxS 的环境归趋和生态毒理学的最新知识。