Abstract：
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 minnow, zebrafish, Atlantic salmon, and largemouth bass show comparable binding affinities for each chemical except for salmon Esr2b, which was predicted to have lower affinity for PFHxA relative to Esr2a. While mechanistic data are lacking in fish in general for these chemicals, a computational approach revealed that PFHxA can perturb the endocrine system, nervous system, and is linked to changes in kidney and liver weight. Proteins associated with 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.
摘要：
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）和全氟己磺酸（PFHxS），由于它们对水生生物的潜在毒性，正在受到越来越多的审查。然而,我们对其生物学影响和作用机制的理解仍然有限。本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，以及与形态学有关的毒性机制，内分泌，新陈代谢，和行为终点。还进行了计算评估以鉴定假定的毒性机制并表征暴露生物标志物。研究表明，PFHxA和PFHxS残基存在于不同的海洋和淡水鱼组织中，表明在水生生物中监测这些PFAS的重要性。在鱼组织中，据报道，这些化学物质对于PFHxA和PFHxS分别高达37.5ng/g和1290ng/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。在毒性机制方面，氧化应激和内分泌紊乱均有报道.根据内分泌紊乱的证据,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对与鱼的雌激素和雄激素受体相互作用具有更强的亲和力，斑马鱼,大西洋鲑鱼,大嘴鲈鱼对每种化学物质的结合亲和力相当，但鲑鱼Esr2b相对于Esr2a似乎对PFHxA的亲和力较低。虽然鱼类缺乏机械数据，计算评估表明PFHxA可以扰乱内分泌系统，神经系统,并与肾脏和肝脏重量的变化有关。与鱼类中PFHxA和PFHxS暴露相关的蛋白质包括与脂质和葡萄糖调节有关的蛋白质，生殖蛋白如KISS转移抑制因子，和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。一起来看,我们综合了有关鱼类中PFHxA/PFHxS的环境命运和生态毒理学的最新知识。
