Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA; Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
Blind Brook High School, Rye Brook, NY 10573, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2024 May;279:109874. doi: 10.1016/j.cbpc.2024.109874. Epub 2024 Feb 27.
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.
工业和消费品中含有多种全氟烷基物质（PFAS）。由于这些物质（如全氟己酸（PFHxA）和全氟己烷磺酸（PFHxS））对水生生物具有潜在毒性，因此受到了越来越多的关注。然而，我们对它们的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 的水平数据，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，以确定潜在的毒性机制，并描述暴露生物标志物。研究表明，PFHxA 和 PFHxS 残留都存在于各种海洋和淡水鱼类组织中，这表明监测水生生物中这些 PFAS 的重要性。在鱼类组织中，这些化学物质的含量高达 PFHxA 为 37.5ng/g，PFHxS 为 1290ng/g，但它们在水生环境中的持久性和在组织中的降解仍需进一步研究。在毒性机制方面，据报道既有氧化应激又有内分泌干扰。基于内分泌干扰的证据，我们对几种鱼类的雌激素和雄激素受体与 PFHxA 和 PFHxS 的相互作用进行了建模。分子对接显示，与 PFHxA 相比，PFHxS 与鱼类雌激素和雄激素受体的亲和力更强，并且食蚊鱼、斑马鱼、大西洋三文鱼和大口黑鲈的雌激素和雄激素受体对每种化学物质的结合亲和力相当，除了三文鱼 Esr2b，它被预测相对于 Esr2a 对 PFHxA 的亲和力较低。虽然一般来说鱼类缺乏这些化学物质的机制数据，但计算方法表明 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相关的蛋白质、KISS 转移抑制因子等生殖相关蛋白，以及与免疫系统相关的蛋白质（特别是 RAG1、RAG2），它们都是潜在的暴露生物标志物。综上所述，我们综合了目前关于鱼类中 PFHxA/PFHxS 的环境命运和生态毒理学的知识。
