Pharmaceutically active compounds

药物活性化合物
  • 文章类型: Journal Article
    微塑料(MP)污染是对海洋生物的潜在威胁。MPs和其他污染物的体外毒性,如药物活性化合物(PhAC)和溴化阻燃剂(BFR),已经被研究不足。本研究旨在研究不同粒径的聚苯乙烯微塑料(PS-MPs)对罗非鱼肝匀浆中乙氧基间苯二酚-O-脱乙基酶(EROD)和谷胱甘肽S-转移酶(GST)两种生物标志物的影响。该研究还检查了PS-MPs与各种环境污染物的综合作用,包括三个金属离子(Cu2+,Zn2+,Pb2+),三个BFR,六个PhAC在所选浓度下,单独的PS-MPs对两种生物标志物没有显著影响。然而,在大多数情况下,PS-MPs与其他污染物的结合显着影响了这两种生物标志物。对于EROD活动,PS+金属离子(除Zn2+1000μg/L),PS+BFR(十溴二苯醚(BDE-209)除外)或PS+甲氧苄啶(TMP)显著抑制活性值,而PS+4-对乙酰氨基酚(AMP)诱导EROD活性。对于商品及服务税,PS与大多数测试污染物(PS布洛芬(IBF)除外)一起大大降低了活性。因此,未来的研究应重点关注混合物的复合毒性,以制定更合理的环境安全评价标准。
    Microplastic (MP) pollution is a potential threat to marine organisms. In vitro toxicity of MPs and other pollutants, such as pharmaceutically active compounds (PhACs) and brominated flame retardants (BFRs), has been understudied. This study aimed to investigate the effects of polystyrene microplastics (PS-MPs) with different particle sizes on two biomarkers: ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) in tilapia liver homogenates. The study also examined the combined effects of PS-MPs with various environmental contaminants, including three metal ions (Cu2+, Zn2+, Pb2+), three BFRs, and six PhACs. PS-MPs alone had no remarkable effects on the two biomarkers at the selected concentrations. However, PS-MPs combined with other pollutants significantly affected the two biomarkers in most situations. For EROD activity, PS + metal ions (except Zn2+ at 1000 μg/L), PS + BFRs (except decabromodiphenyl oxide (BDE-209)) or PS+ trimethoprim (TMP) significantly inhibited activity values, whereas PS+ 4-acetaminophen (AMP) induced EROD activity. For GST, PS together with most tested pollutants (except PS+ ibuprofen (IBF)) greatly decreased the activities. Accordingly, future research should focus on combined toxicity of mixtures to set more reasonable environmental safety evaluation standards.
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  • 文章类型: Journal Article
    兽药不断被用于诊断,治疗,和预防牲畜疾病。然而,未经处理的兽药活性化合物无休止地排放到许多水体和陆地生态系统中,在生产过程中,空容器处理不当,未使用的药物或动物饲料,和治疗程序。这篇详尽的综述描述了兽药进入环境的不同途径,讨论农业实践的作用和不当的处置方法。详细阐述了兽药化合物对水生和陆地生态系统的有害影响,并举例说明了特定的兽药及其已知影响。这篇综述还旨在详细介绍微生物降解兽药化合物的机制,并重点介绍成功的案例研究和基于微生物的生物修复的最新进展。它还阐述了微生物电化学技术作为一种环保解决方案,用于从废水中去除药物污染物。最后,我们总结了在该领域的前景和进展下,大规模实施生物修复的潜在创新和挑战。
    Veterinary medications are constantly being used for the diagnosis, treatment, and prevention of diseases in livestock. However, untreated veterinary drug active compounds are interminably discharged into numerous water bodies and terrestrial ecosystems, during production procedures, improper disposal of empty containers, unused medication or animal feed, and treatment procedures. This exhaustive review describes the different pathways through which veterinary medications enter the environment, discussing the role of agricultural practices and improper disposal methods. The detrimental effects of veterinary drug compounds on aquatic and terrestrial ecosystems are elaborated with examples of specific veterinary drugs and their known impacts. This review also aims to detail the mechanisms by which microbes degrade veterinary drug compounds as well as highlighting successful case studies and recent advancements in microbe-based bioremediation. It also elaborates on microbial electrochemical technologies as an eco-friendly solution for removing pharmaceutical pollutants from wastewater. Lastly, we have summarized potential innovations and challenges in implementing bioremediation on a large scale under the section prospects and advancements in this field.
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  • 文章类型: Journal Article
    将药物活性药物排放到水和废水中已成为重大的环境威胁。传统方法无法有效去除废水中的这些化合物,因此有必要寻找更有效的方法。这项研究调查了MIL-101(Cr)-NH2作为从水溶液中吸附和去除药物活性化合物的优选且更有效的吸附剂的潜力。通过利用它的大孔隙度,高比表面积,和高稳定性,三种药物活性化合物萘普生(NAP)的结构和转运特性,双氯芬酸(DIC)和磺胺甲恶唑(SMX)的分子动力学模拟研究。结果表明,MIL-101(Cr)-NH2吸附剂适用于去除水溶液中的药物分子,萘普生的最大吸附容量为697.75mg/g,704.99mg/g双氯芬酸,磺胺甲恶唑为725.51mg/g。
    Discharging pharmaceutically active drugs into water and wastewater has become a significant environmental threat. Traditional methods are unable to effectively remove these compounds from wastewater, so it is necessary to search for more effective methods. This study investigates the potential of MIL-101(Cr)-NH2 as a preferable and more effective adsorbent for the adsorption and removal of pharmaceutically active compounds from aqueous solutions. By utilizing its large porosity, high specific surface area, and high stability, the structural and transport properties of three pharmaceutically active compounds naproxen (NAP), diclofenac (DIC) and sulfamethoxazole (SMX)) studied using molecular dynamics simulation. The results indicate that the MIL-101(Cr)-NH2 adsorbent is suitable for removing drug molecules from aqueous solutions, with maximum adsorption capacities of 697.75 mg/g for naproxen, 704.99 mg/g for diclofenac, and 725.51 mg/g for sulfamethoxazole.
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  • 文章类型: Journal Article
    药物活性化合物是一类重要的新兴污染物,它们在环境中的生物转化过程对于理解和评估迁移至关重要,改造,和新兴污染物的环境命运。细胞色素P450105酶家族已被证明在降解外源环境污染物中发挥重要作用。然而,其热稳定性和催化活性仍有待提高,以更好地适应复杂的环境条件。这项工作通过多种计算策略阐明了降解反应的关键机制和重要残基,建立一个突变库,并获得21个单点突变设计。实验验证表明,16个单一突变体的热稳定性增强,与R89F和L197Y突变体显示出最高的热稳定性增加135%和119%相对于野生型酶,分别。此外,由于D390Q的比活性较高,它被选择用于组合诱变,最终产生三个组合突变体(R89F/L197Y,R89F/D390Q,和R89F/L197Y/D390Q)具有增强的热稳定性和催化活性。本研究为通过半理性设计构建有效的酶变体提供了一种修饰方法,可以为新兴污染物的控制技术的发展做出贡献。
    Pharmaceutically active compounds are an important category of emerging pollutants, and their biological transformation processes in the environment are crucial for understanding and evaluating the migration, transformation, and environmental fate of emerging pollutants. The cytochrome P450 105 enzyme family has been proven to play an important role in the degradation of exogenous environmental pollutants. However, its thermostability and catalytic activity still need to be improved to better adapt to complex environmental conditions. This work elucidates the key mechanisms and important residues of the degradation reaction through multiple computational strategies, establishes a mutation library, and obtains 21 single-point mutation designs. Experimental verification showed that 16 single mutants had enhanced thermostability, with the R89F and L197Y mutants showing the highest increases in thermostability at 135 and 119% relative to the wild-type enzyme, respectively. Additionally, as a result of the higher specific activity of D390Q, it was selected for combination mutagenesis, ultimately resulting in three combination mutants (R89F/L197Y, R89F/D390Q, and R89F/L197Y/D390Q) with enhanced thermostability and catalytic activity. This study provides a modification approach for constructing efficient enzyme variants through semirational design and can contribute to the development of control technologies for emerging pollutants.
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  • 文章类型: Journal Article
    这项研究评估了新兴污染物(EC)的风险,目前在印度河流-恒河(6.5亿居民),亚穆纳(5700万居民),和Musi(7,500,000居民),总共13个EC,已用于风险评估研究。它们的浓度(例如,氟康唑:236950μg/l,环丙沙星:31000μg/l,咖啡因:21.57μg/l,等。)高于安全消费的阈值浓度(例如氟康唑允许水平为3.8μg/l,环丙沙星允许水平为0.51μg/l)。新兴污染物(EC)转移的三种不同途径(口服水摄入,口服鱼食,和皮肤水接触)已被考虑,并且该研究以2种方式进行:(i)确定性和(ii)概率方法(使用蒙特卡洛迭代法和10000次模拟)借助软件-Risk(7.5版)。风险值,危险商数(HQ)的量化值高于氟康唑等三条河流中几种化合物的允许限值1(HQ=18276.713),环丙沙星(HQ=278.675),伏立康唑(HQ=14.578),西替利嗪(总部=1006.917),莫西沙星(HQ=8.076),咖啡因(HQ=55.150),和布洛芬(HQ=9.503)。结果表明,氟康唑和咖啡因通过“口服途径”在河流中构成最大风险,该途径允许最大程度地转移河流中存在的ECs(占总风险的93%和82%)。风险值从美国环境保护局(USEPA)阈值限制为1的近25倍到19000倍(例如,咖啡因婴儿风险=25.990,氟康唑成人风险=18276.713)。最易受影响的年龄组,从这项研究中,是“成年人”(19-70岁),他们有可能经历与长期过度暴露于河流水域中存在的ECs相关的不良健康危害。Musi的污染物浓度最高,需要立即采取补救措施。Further,两种方法都表明,在所有三个研究领域中,近60-70%的人口都有与定期过度暴露于ECs相关的健康危害的风险。使这些地区适合居住。
    This study assesses the risk due to Emerging Contaminants (ECs), present in Indian rivers - Ganga (650 million inhabitants), Yamuna (57 million inhabitants), and Musi (7,500,000 inhabitants), 13 ECs in total, have been used for risk assessment studies. Their concentrations (e.g., Fluconazole: 236950 μg/l, Ciprofloxacin: 31000 μg/l, Caffeine: 21.57 μg/l, etc.) were higher than the threshold concentrations for safe consumption (e.g. Fluconazole allowable level is 3.8 μg/l, and Ciprofloxacin allowable level is 0.51 μg/l). Three different pathways of emerging contaminants (ECs) transfer (oral water ingestion, oral fish ingestion, and dermal water contact) have been considered and the study is carried out in 2 ways: (i) deterministic and (ii) probabilistic approaches (using Monte Carlo iterative methods with 10000 simulations) with the aid of a software - Risk (version 7.5). The risk value, quantified by Hazard Quotient (HQ) is higher than the allowable limit of 1 for several compounds in the three rivers like Fluconazole (HQ = 18276.713), Ciprofloxacin (HQ = 278.675), Voriconazole (HQ = 14.578), Cetirizine (HQ = 1006.917), Moxifloxacin (HQ = 8.076), Caffeine (HQ = 55.150), and Ibuprofen (HQ = 9.503). Results show that Fluconazole and Caffeine pose the maximum risk in the rivers via the \"oral pathway\" that allows maximum transfer of the ECs present in the river (93% and 82% contribution to total risk). The risk values vary from nearly 25 times to 19000 times the United States Environmental Protection Agency (USEPA) threshold limit of 1 (e.g., Caffeine Infant Risk = 25.990 and Fluconazole Adult Risk = 18276.713). The most susceptible age group, from this study, is \"Adults\" (19-70 years old), who stand the chance of experiencing the adverse health hazards associated with prolonged over-exposure to the ECs present in the river waters. Musi has the maximum concentration of pollutants and requires immediate remediation measures. Further, both methods indicate that nearly 60-70% of the population in all the three study areas are at risk of developing health hazards associated with over-exposure to ECs regularly, making the areas inhabitable.
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  • 文章类型: Journal Article
    水中药物活性化合物(PhAC)的存在是环保主义者的主要关注点,因为即使在极小的浓度下,它们也会对生物体产生有害影响。这篇综述的重点是PhAC,如镇痛药和抗炎化合物,它们在尿液中大量排泄,占药物污染的大部分。此外,其他PhAC,如抗癫痫药,讨论了β-受体阻滞剂和抗生素,因为它们也对水生环境中的药物污染有重要贡献。本综述分为两个部分。在第一部分,介绍了不同类别的PhACs及其在废水环境中的归宿。在第二部分,传统污水处理厂去除PhACs的最新进展,包括膜生物反应器(MBR),活性炭吸附和实验室规模研究涉及广泛的高级氧化过程(AOPs),为药物的完全矿化和降解提供实用和适当的策略,被审查。这篇综述表明,像双氯芬酸这样的药物,萘普生,扑热息痛和阿司匹林被常规系统有效去除。活性炭吸附适用于双氯芬酸和卡马西平的去除,而AOP是有效去除已审查的PhAC的主要水处理策略。
    The existence of pharmaceutically active compounds (PhACs) in the water is a major concern for environmentalists due to their deleterious effects on living organisms even at minuscule concentrations. This review focuses on PhACs such as analgesics and anti-inflammatory compounds, which are massively excreted in urine and account for the majority of pharmaceutical pollution. Furthermore, other PhACs such as anti-epileptics, beta-blockers and antibiotics are discussed because they also contribute significantly to pharmaceutical pollution in the aquatic environment. This review is divided into two parts. In the first part, different classes of PhACs and their fate in the wastewater environment are presented. In the second part, recent advances in the removal of PhACs by conventional wastewater treatment plants, including membrane bioreactors (MBRs), activated carbon adsorption and bench-scale studies concerning a broad range of advanced oxidation processes (AOPs) that render practical and appropriate strategies for the complete mineralization and degradation of pharmaceutical drugs, are reviewed. This review indicates that drugs like diclofenac, naproxen, paracetamol and aspirin are removed efficiently by conventional systems. Activated carbon adsorption is suitable for the removal of diclofenac and carbamazepine, whereas AOPs are leading water treatment strategies for the effective removal of reviewed PhACs.
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  • 文章类型: Journal Article
    真菌物种产生多种酶和代谢产物的能力,协同行动,使它们成为生物修复的宝贵工具,特别是在从污染环境中去除药物活性化合物(PhAC)中。PhACs是专门设计用于治疗或改变动物生理状况的化合物,包括抗生素,镇痛药,荷尔蒙,和类固醇。它们对所有生命形式的有害影响已成为公众强烈抗议的来源,因为它们具有持久性和不受控制地排放到各种废水中,医院流出物,和地表水。然而,研究表明,真菌具有在复杂环境中降解PhACs的必要代谢机制,比如土壤和水,此外,它们可用于生物反应器系统中以去除PhAC。在这方面,这篇综述强调了在PhACs生物降解中具有巨大潜力的真菌物种,它们的酶促武器库以及可能的生物降解机制。还强调了阻碍这种有前途的生物修复方法实时应用的挑战,以及改进的领域和未来的前景。总之,本文指出,研究人员认为,真菌生物修复是解决环境中日益严重的药物污染问题的一种有前途的策略,可以帮助减轻对生态系统和人类健康的负面影响。
    The ability of fungal species to produce a wide range of enzymes and metabolites, which act synergistically, makes them valuable tools in bioremediation, especially in the removal of pharmaceutically active compounds (PhACs) from contaminated environments. PhACs are compounds that have been specifically designed to treat or alter animal physiological conditions and they include antibiotics, analgesics, hormones, and steroids. Their detrimental effects on all life forms have become a source of public outcry due their persistent nature and their uncontrolled discharge into various wastewater effluents, hospital effluents, and surface waters. Studies have however shown that fungi have the necessary metabolic machinery to degrade PhACs in complex environments, such as soil and water, in addition they can be utilized in bioreactor systems to remove PhACs. In this regard, this review highlights fungal species with immense potential in the biodegradation of PhACs, their enzymatic arsenal as well as the probable mechanism of biodegradation. The challenges encumbering the real-time application of this promising bioremediative approach are also highlighted, as well as the areas of improvement and future perspective. In all, this paper points researchers to the fact that fungal bioremediation is a promising strategy for addressing the growing issue of pharmaceutical contamination in the environment and can help to mitigate the negative impacts on ecosystems and human health.
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  • 文章类型: Journal Article
    在本研究中,从武进地区的88种目标化合物中检测到60种新兴污染物(ECs),这是太湖盆地的西北地区,中国。其中,CF(咖啡因),一种PhAC(药物活性化合物),被检测为浓度最高的污染物。据观察,废水处理厂中PFASs(全氟/多氟烷基物质)的去除效率低于农药;此外,农药的含量低于PhACs。基于空间自相关模型估计的空间集聚,确定了28种污染物的可能来源。该模型提供了一个新的视角,有助于高精度地阐明源的位置。成功发现了6个PFAS和14个PhAC的点源;相比之下,农药的主要来源被确定为农业非点源。最后,本研究还评估了ECs的潜在风险,包括它们的水生生态风险和人类暴露风险。结论农药一般具有最高的生态风险,其次是PFAS和PhAC。为了评估农药的人群风险,扩展了基于废水的流行病学模型,以反算人均农药消费量,为0.22gd-1(103人均)-1。
    In the present study, 60 emerging contaminants (ECs) were detected from 88 target compounds in the district of Wujin, which is the northwest area of Tai Lake Basin, China. Among them, CF (caffeine), a type of PhAC (pharmaceutically active compound), was detected as the pollutant with the highest concentration. It was observed that the removal efficiencies of PFASs (per-/polyfluoroalkyl substances) in wastewater treatment plants were lower than those of pesticides; further, those of pesticides were lower than those of PhACs. Based on the spatial agglomeration estimated by the spatial autocorrelation model, the probable sources of 28 contaminants were identified. This model provided a new perspective that would help to clarify the location of sources with high accuracy. The point sources of 6 PFASs and 14 PhACs were successfully found; in contrast, the main source of pesticides was identified as an agricultural nonpoint source. Finally, the potential risks of the ECs were also assessed in this study, including their aquatic ecological risks and human exposure risks. It was concluded that pesticides generally had the highest ecological risk, followed by PFASs and PhACs. To evaluate the population risk of pesticides, the wastewater-based epidemiological model was extended to back-calculate the per capita pesticide consumption, which was 0.22 g d-1 (103capita)-1.
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  • 文章类型: Journal Article
    这项工作主要侧重于评估流经印度首都的多年生亚穆纳河(YR)中有机微污染物(OMPs)的患病率,德里。16次抽样活动(非季风,n=9;组织季风n=7)以了解季节变化,特别强调季风。我们在季风中发现了55种OMP;而在非季风中发现了47种。在亚穆纳河污染最严重的地区,有57项筛选和量化的OMP包括药物活性化合物,杀虫剂,内分泌干扰物,邻苯二甲酸酯,个人护理产品,脂肪酸,食品添加剂,荷尔蒙,以及医院废物中存在的微量有机物。在季风月份,浓度超过50μg/L的化合物为:腺嘌呤(64.6μg/L),邻苯二甲酸二乙酯(62.9μg/L),和八甲基三硅氧烷(56.9μg/L);非季风月份的情况相同,仅1-十二烷硫醇(52.3μg/L)。非季风月份OMP的平均浓度表明PhAC>PCP>农药>脂肪酸>医院废物>激素>农药>EDCs。在季风月份,由于地表径流和大量未经处理的废水排放,几乎没有检测到更多的OMPs浓度,其中主要包括PhACs(氯纤酸,双氯芬酸钠,吉非贝齐,酮洛芬),杀虫剂(艾氏剂,metribuzin,阿特拉津,simazine)。由于季风月份的稀释效应,3-乙酰氨基-5-溴苯甲酸(PhACs)的平均浓度从45.22μg/L降低到14.07μg/L,而一些EDC,如2,4-二叔戊基苯酚,3,5-二叔丁基-4-羟基苯甲醇,三苯基膦氧化物,在季风月份发现二苯甲酮的浓度要高得多。在季风月份检测到八甲基三硅氧烷(PCPs)的浓度高50倍。有趣的是,季风样品中约50%的OMP浓度高于非季风样品,这与季风诱导的稀释降低OMP浓度的一般理解相反。在RY水中双氯芬酸钠含量较高,布洛芬,酮洛芬,并且在欧洲和北美的河流中发现了氯纤酸。发现RY水中的雌三醇和雌酮等激素比美国河流中报道的最大浓度高70至100倍。最后,从多变量分析中可以明显看出,各种OMP对季风季节的反应不同。
    This work primarily emphases on evaluating the prevalence of organic micropollutants (OMPs) in the perennial Yamuna River (YR) that flow through the national capital of India, Delhi. Sixteen sampling campaigns (non-monsoon, n = 9; monsoon n = 7) were organized to understand the seasonal variations with special emphasis on monsoon. We have found fifty-five OMPs in the monsoon; while forty-seven were detected in non-monsoon. Fifty-seven screened and quantified OMPs in the most polluted stretch of River Yamuna included the pharmaceutically active compounds, pesticides, endocrine-disrupting chemicals, phthalates, personal care products, fatty acids, food additives, hormones, and trace organics present in hospital wastes. During monsoon months, compounds for which concentrations exceeded 50 μg/L were: adenine (64.6 μg/L), diethyl phthalate (62.9 μg/L), and octamethyltrisiloxane (56.9 μg/L); and the same for non-monsoon months was only for 1-dodecanethiol (52.3 μg/L). The average concentration of OMPs in non-monsoon months indicate PhACs>PCPs>Pesticides>Fatty acids>Hospital waste>Hormones>Pesticides>EDCs. In monsoon months due to surface runoff and high volume of untreated wastewater discharges few more OMPs concentrations were detected which mainly includes PhACs (clofibric acid, diclofenac sodium, gemfibrozil, ketoprofen), pesticides (aldrin, metribuzin, atrazine, simazine). Due to dilution effect in the monsoon months, average concentrations of 3-acetamido-5-bromobenzoic acid (PhACs) was reduced from 45.22 μg/L to 14.07 μg/L, whereas some EDCs such as 2,4- Di-tert-amylphenol, 3,5- di-tert-butyl-4-hydroxybenzyl alcohol, Triphenylphosphine oxide, Benzophenone were found in much higher concentrations in the monsoon months. Octamethyltrisiloxane (PCPs) was detected 50 times higher in concentration in the monsoon months. Interestingly, the concentration of about 50 % of the OMPs was more in the monsoon samples than in non-monsoon samples which is contrary to the general understanding that monsoon-induced dilution lowers the concentrations of OMPs. In RY water higher magnitude of diclofenac sodium, ibuprofen, ketoprofen, and clofibric acid was found than Europe and North America rivers. Hormones such as estriol and estrone in RY water are found 70 to 100 times higher than the maximum reported concentrations in the US streams. Finally, various OMPs responded differently to the monsoon season as evident from multivariate analyses.
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  • 文章类型: Journal Article
    The availability of pharmaceutically active compounds (PhACs) in surface waters and suspended solids/sediments presents an ecological hazard of chronic exposure to non-target organisms. Thus, water and sediment samples were collected from the Korle Lagoon in the west of Accra-Ghana city center to evaluate 35 medicinal drugs belonging to the main therapeutic classes and their toxicity to non-target organisms (i.e., fish, daphnid, and algae). High-performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS) was employed to analyze the levels of PhACs in the samples. PhACs levels in water samples were higher compared to PhACs levels in sediment samples. Acetaminophen, ibuprofen, tramadol, and Diclofenac were the PhACs that showed a higher frequency of detections and higher average concentrations. Diazepam, mefenamic acid, indomethacin, gemfibrozil, and glibenclamide exhibited a higher frequency of detections, but their average concentrations in both sample types were lower. The calculated risk index values for acetaminophen and ibuprofen suggested low ecological risks to fish, while tramadol showed medium to high ecological risks to daphnid. In contrast, acetaminophen and fenofibrate showed low ecological risks to daphnid. Additionally, the risk index values for fenofibrate suggested medium to high ecological risks to algae, while tramadol exhibited low ecological risks to algae. The other PhACs showed negligible ecological risks to non-target organisms. The calculated toxic unit values for each sampled site suggested a medium adverse ecological risk to non-target organisms. Based on the results obtained, the availability of PhACs in the studied area will have adverse effects on studied non-target organisms. The negative impacts of PhACs on non-target organisms may cause an imbalance in the food chain process, leading to a decrease in fish production and a reduction in fish quality. The result of this study is evidence of public health threat because the accumulation of PhACs in fish species may also cause some kinds of hormonal, chemical, and molecular changes within the various systems of the fishes to be toxic or unpleasant for humans\' consumption.
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