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Integrated Monitoring of Water Quality, Metal Ions, and Antibiotic Residues, with Isolation and Optimization of Enrofloxacin-Degrading Bacteria in American Shad (Alosa sapidissima) Aquaculture Systems. 美国沙鱼养殖系统水质、金属离子和抗生素残留的综合监测及恩诺沙星降解菌的分离与优化
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-22 DOI: 10.3390/jox15060174
Yao Zheng, Jiajia Li, Ampeire Yona, Xiaofei Wang, Xue Li, Julin Yuan, Gangchun Xu

This study investigated water quality, metal ion concentrations, and antibiotic residues specifically enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP), across six American shad (Alosa sapidissima) aquaculture sites over a one-year period. Water and sediment samples were analyzed to determine contamination levels, and ENR-degrading bacteria were isolated from the culture environment to explore their potential use in bioremediation. Findings showed that NH3-N and total suspended solids (TSS) exceeded recommended standards at all sampling sites. Elevated levels of Li, Na (except S1), Fe, Ni (except S2 and S4), Sr, and Cu were found at site S3. Site S5 recorded the highest concentrations of Al, As, and Pb, while Cd was most abundant at S6. In sediments, S5 showed higher levels of Mg, K (except S3), Ca, Cr, Mn, Fe, Ni, As, Pb, Cu, and Zn (except S3). ENR and CIP were detected in all water and sediment samples, with a 100% detection rate. The highest ENR (16.68-3215.95 mg·kg-1) and CIP (3.90-459.60 mg·kg-1) concentrations in water occurred at site S6, following a seasonal pattern of autumn > winter > summer > spring. In sediments, the maximum ENR (41.43-133.67 mg·kg-1) and CIP (12.36-23.71 mg·kg-1) levels were observed in spring. Two ENR-degrading bacterial strains were successfully isolated and identified as Enterococcus and Bacillus. Optimal degradation was achieved at 30 °C, pH 8.0, 6% inoculum, and 3000 Lux, resulting in a 64.2% reduction in ENR after 72 h. Under slightly different conditions (25 °C, pH 10), degradation reached 58.5%. This study provides an efficient strain resource for the bioremediation of ENR pollution in the aquaculture water of American shad.

本研究调查了6个美国沙鱼养殖场的水质、金属离子浓度和抗生素残留,特别是恩诺沙星(ENR)及其代谢物环丙沙星(CIP)。对水和沉积物样品进行分析以确定污染水平,并从培养环境中分离出enr降解细菌,以探索其在生物修复中的潜在用途。结果表明,各采样点NH3-N和总悬浮固体(TSS)均超过推荐标准。S3部位Li、Na(除S1)、Fe、Ni(除S2和S4)、Sr和Cu水平升高。S5位点的Al、As和Pb含量最高,S6位点的Cd含量最高。S5沉积物中Mg、K(除S3外)、Ca、Cr、Mn、Fe、Ni、As、Pb、Cu和Zn(除S3外)含量较高。所有水和沉积物样品均检测到ENR和CIP,检出率为100%。水中ENR (16.68 ~ 3215.95 mg·kg-1)和CIP (3.90 ~ 459.60 mg·kg-1)浓度在S6站点最高,呈现秋季bb0冬季bb1夏季bb2春季的季节格局。沉积物中ENR (41.43 ~ 133.67 mg·kg-1)和CIP (12.36 ~ 23.71 mg·kg-1)在春季最高。成功分离出两株enr降解菌,鉴定为肠球菌和芽孢杆菌。在30°C、pH 8.0、6%接种量和3000 Lux条件下,降解效果最佳,72 h后ENR降低64.2%。在稍微不同的条件下(25°C、pH 10),降解效果达到58.5%。本研究为美国鲥鱼养殖水体ENR污染的生物修复提供了有效的菌种资源。
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引用次数: 0
Insights into Hepatic, Neuronal, and hERG Channel Safety of Plant-Derived Active Compounds. 植物源性活性化合物的肝脏、神经元和hERG通道安全性研究
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-22 DOI: 10.3390/jox15060175
Yosita Kasemnitichok, Sion Lee, Oh Bin Kwon, Tullayakorn Plengsuriyakarn, Kesara Na-Bangchang

Curcumin (CUR), atractylodin (ATD), α-mangostin (αMG), ethyl-p-methoxycinnamate (EPMC), ligustilide (LIG), and β-eudesmol (BEU) are commonly used in Thai traditional medicine formulations. This study evaluated the cytotoxic effects of these compounds in HepG2 liver cancer cells and ReNcell VM neural progenitor cells using the resazurin assay, as well as their potential for hERG inhibition in hERG-overexpressing HEK293 cells, utilizing the automated patch-clamp technique. αMG and CUR significantly reduced HepG2 cell viability (IC50 = 5.5 and 21 µM, respectively). In undifferentiated ReNcell VM cells, αMG was the most potent inhibitor of cell viability (IC50 = 2.1 µM), followed by CUR (IC50 = 21.1 µM), while in differentiated ReNcell VM cells, only αMG exhibited significant neurotoxicity (IC50 = 6.0 µM). Other compounds showed no significant effects on these cells. ATD, BEU, LIG, and EPMC demonstrated low inhibition of hERG channels (IC50 = 26.4, 33.4, 37.3, and 53 µM, respectively), while CUR and αMG displayed weak inhibitory effects (IC50 > 100 µM). αMG may have cytotoxic effects on hepatocytes and neurons at concentrations much higher than when used as medicine or food supplements. At regular clinical doses, αMG, ATD, BEU, EPMC, LIG, and CUR are unlikely to cause significant side effects. However, if these compounds are considered for drug development, their potential effects on hERG channels should be carefully assessed to avoid possible cardiotoxicity. Pharmacokinetics, both preclinical and clinical studies, are necessary to understand the relationship between the plasma concentration profile of EPMC and its potential risks for hepatotoxicity, neurotoxicity, cardiotoxicity, and drug interactions.

姜黄素(CUR)、苍术素(ATD)、α-山竹素(αMG)、对甲氧基肉桂酸乙酯(EPMC)、藁本内酯(LIG)和β-桉树酚(BEU)是泰国传统药物配方中常用的几种成分。本研究利用resazurin实验评估了这些化合物在HepG2肝癌细胞和ReNcell VM神经祖细胞中的细胞毒性作用,以及它们在hERG过表达的HEK293细胞中抑制hERG的潜力,利用自动膜片钳技术。αMG和CUR显著降低HepG2细胞活力(IC50分别为5.5和21µM)。在未分化的ReNcell VM细胞中,αMG是最有效的细胞活性抑制剂(IC50 = 2.1µM),其次是CUR (IC50 = 21.1µM),而在已分化的ReNcell VM细胞中,只有αMG表现出显著的神经毒性(IC50 = 6.0µM)。其他化合物对这些细胞没有明显的影响。ATD、BEU、LIG和EPMC对hERG通道的抑制作用较弱(IC50分别为26.4、33.4、37.3和53µM),而CUR和αMG对hERG通道的抑制作用较弱(IC50为100µM)。α - mg对肝细胞和神经元的细胞毒作用浓度远高于作为药物或食物补充剂时的浓度。在常规临床剂量下,αMG、ATD、BEU、EPMC、LIG和CUR不太可能引起明显的副作用。然而,如果考虑将这些化合物用于药物开发,则应仔细评估其对hERG通道的潜在影响,以避免可能的心脏毒性。临床前和临床研究的药代动力学对于了解EPMC血浆浓度谱与其肝毒性、神经毒性、心脏毒性和药物相互作用的潜在风险之间的关系是必要的。
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引用次数: 0
Association Between Antibiotic Exposure and the Risk of Male Infertility: A Case-Control Study. 抗生素暴露与男性不育风险之间的关系:一项病例对照研究。
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-21 DOI: 10.3390/jox15050172
Friday E Okonofua, Lorretta Favour C Ntoimo, Titus A M Msagati, Oladiran Ayodeji, Michael Aziken, Akhere Omonkhua, Victor Ohenhen, Celestina Olafusi, Moses O Alfred

Irregular use of antibiotics is widespread in Nigeria, which has been reported to be associated with the prevalence of antibiotic resistance. As antibiotics have been reported to be associated with declining male infertility in animal models, we investigated the association between exposure to antibiotics and sperm quality. The study was a prospective case-control study involving 136 infertile men and 154 fertile men recruited from five hospitals in southern Nigeria. Semen analysis was carried out, while Liquid Chromatography Mass Spectrometry was used to assay for various antibiotics in urinary samples. Three antibiotics showed an independent association with sperm quality in the regression analysis. Urinary ampicillin was associated with more than a 3 mL decline in sperm count in the cases, with no significant effects shown in the control group. Similarly, a significant association of urinary chloramphenicol with sperm motility and sperm morphology was shown in cases of infertility. In contrast, an independent association of urinary tetracycline with increased sperm motility in men with infertility was found, but no significant association was shown in fertile men. We conclude that urinary antibiotics-ampicillin, tetracycline, and chloramphenicol-may be associated with varying sperm characteristics and sperm quality in Nigerian men.

在尼日利亚,不规律使用抗生素的情况很普遍,据报道,这与抗生素耐药性的流行有关。据报道,在动物模型中,抗生素与男性不孕症的下降有关,因此我们研究了抗生素暴露与精子质量之间的关系。该研究是一项前瞻性病例对照研究,从尼日利亚南部的五家医院招募了136名不育男性和154名有生育能力的男性。进行精液分析,采用液相色谱-质谱法测定尿液样品中的各种抗生素。回归分析显示,三种抗生素与精子质量有独立的相关性。在这些病例中,尿氨苄西林与精子数量下降超过3ml有关,而在对照组中没有显示出明显的影响。同样,尿氯霉素与精子活力和精子形态的显著关联显示在不孕症的情况下。相比之下,发现尿四环素与不育男性精子活力增加有独立的联系,但在有生育能力的男性中没有明显的联系。我们得出结论,尿用抗生素——氨苄西林、四环素和氯霉素——可能与尼日利亚男性不同的精子特征和精子质量有关。
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引用次数: 0
Scientific and Regulatory Perspectives on Chemical Risk Assessment of Pesticides in the European Union. 欧盟农药化学风险评估的科学和监管观点。
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-21 DOI: 10.3390/jox15050173
Fabio Buonsenso

People are exposed to pesticides daily through food, drinking water, and the environment, both in urban and rural settings. These chemicals, while offering economic and agricultural benefits through pest control and increased productivity, may pose a growing risk to human health and ecosystem biodiversity. While the European regulatory framework offers a robust foundation for risk assessment, significant limitations persist, especially in addressing cumulative exposure, low-dose effects, and chemical mixtures. This review focuses on selected scientific and regulatory challenges by reviewing recent European Food Safety Authority (EFSA) conclusions, Organization for Economic Co-operation and Development (OECD) test guidelines updates, and current European legislative approaches. Particular attention is given to the regulation of endocrine-disrupting and reprotoxic substances, highlighting progress and remaining gaps in implementation. A brief mention will also be made of immuno-toxic substances, for which no specific hazard class has yet been established. Building on official reports and peer-reviewed literature, this review provides a structured evaluation of the scientific and regulatory landscape, including underexplored issues like the transition to animal-free toxicology and integration of biomonitoring with health data. The goal is to propose realistic, evidence-based improvements to current frameworks using integrated, interdisciplinary approaches that connect toxicology, policy, and implementation science. A shift to a holistic, systems-based, and precautionary paradigm is vital to address emerging challenges and ensure strong protection of health and environment, as well as supporting the needs of the agricultural sector.

无论是在城市还是农村,人们每天都通过食物、饮用水和环境接触农药。这些化学品虽然通过防治病虫害和提高生产力提供经济和农业效益,但可能对人类健康和生态系统生物多样性构成越来越大的风险。虽然欧洲监管框架为风险评估提供了坚实的基础,但仍然存在重大局限性,特别是在处理累积暴露、低剂量效应和化学混合物方面。本综述通过回顾最近欧洲食品安全局(EFSA)的结论、经济合作与发展组织(OECD)测试指南的更新和当前欧洲立法方法,重点关注选定的科学和监管挑战。特别注意内分泌干扰物和生殖毒性物质的管制,突出了执行方面的进展和仍然存在的差距。还将简要提到免疫毒性物质,目前尚未确定其具体的危害类别。在官方报告和同行评议文献的基础上,本综述对科学和监管前景进行了结构化评估,包括向无动物毒理学过渡以及将生物监测与健康数据相结合等未被充分探讨的问题。目标是利用将毒理学、政策和实施科学联系起来的综合跨学科方法,对现有框架提出现实的、基于证据的改进。要应对新出现的挑战,确保对健康和环境的有力保护,并支持农业部门的需求,向以系统为基础的整体预防模式转变至关重要。
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引用次数: 0
Four-Year Monitoring Survey of Pesticide Residues in Tomato Samples: Human Health and Environmental Risk Assessment. 番茄样品中农药残留四年监测调查:人体健康与环境风险评价。
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-20 DOI: 10.3390/jox15050171
Alessandro Atzei, Hamza Bouakline, Francesco Corrias, Alberto Angioni

A four-year survey was conducted to monitor the presence of multiple pesticide residues contaminating tomatoes, with the aim of evaluating the potential health and environmental risks. A multiresidue liquid chromatography-triple mass spectrometry with a multiple reaction monitoring (LC-MS/MS-MRM) method was fully validated and used to test 252 pesticides in 360 samples analysed. According to SANTE guidelines, the proposed method was considered suitable for the purpose. Dietary risk assessment was conducted using the Hazard Quotient (HQ) approach and the European Food Safety Authority (EFSA) Pesticide Residue Intake Model; meanwhile, the cumulative environmental risk assessment was conducted using the Concentration Addition (CA) and Independent Action (IA) methods. Data obtained revealed multiple contaminations in most fields examined over the years. Twenty-two pesticide residues were identified, comprising 68.2% fungicides, 27.3% insecticides, and the remaining 4.5% acaricides. Higher levels were detected for Boscalid in 2022 in three fields, with an average value of 0.42 mg/kg. Multi-residue contamination occurred each year; the lowest abundance was detected in 2023 (3.9%), and the highest in 2022 (12.3%), with 5 pesticide residues as the maximum number of compounds detected in one sample in 2022. The consumer risk assessment identified no potential health concerns for adults or toddlers, and the combined risk was considered acceptable. The environmental assessment showed maximum cumulative ratio (MCR) values that were always ≥1, indicating a contribution to the toxicity of the mixture, only slightly higher than that of the single compound with the highest toxicity. The results of this study highlight the critical need to include cumulative dietary exposure assessments in pesticide risk evaluations, especially for food products that are susceptible to contamination by multiple residues.

进行了一项为期四年的调查,以监测多种农药残留污染番茄的情况,目的是评估潜在的健康和环境风险。建立了多残留液相色谱-三重质谱联用多反应监测(LC-MS/MS-MRM)方法,并对360份样品中的252种农药进行了检测。根据SANTE指南,建议的方法被认为适合于目的。采用危害商(HQ)法和欧洲食品安全局(EFSA)农药残留摄入模型进行膳食风险评估;同时,采用浓度加法法(CA)和独立行动法(IA)进行累积环境风险评价。获得的数据显示,多年来检查的大多数田地都存在多重污染。鉴定出22种农药残留,其中杀菌剂占68.2%,杀虫剂占27.3%,杀螨剂占4.5%。2022年在三个地区检测到较高的Boscalid水平,平均值为0.42 mg/kg。每年都发生多残留污染;丰度最低的年份是2023年(3.9%),最高的年份是2022年(12.3%),单个样品最多检出5种农药残留。消费者风险评估没有发现对成人或幼儿的潜在健康问题,综合风险被认为是可以接受的。环境评价显示,最大累积比(MCR)值始终≥1,表明混合物的毒性贡献,仅略高于毒性最高的单一化合物。这项研究的结果强调了在农药风险评估中纳入累积饮食暴露评估的迫切需要,特别是对于易受多种残留物污染的食品。
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引用次数: 0
Estrogen Degradation Metabolites: Some Effects on Heart Mitochondria. 雌激素降解代谢物对心脏线粒体的影响。
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-18 DOI: 10.3390/jox15050170
Cristina Uribe-Alvarez, Elizabeth Lira-Silva, Lilia Morales-García, Natalia Chiquete-Felix, Francisco Javier Roldán-Gómez, Jesús Vargas-Barrón, José J García-Trejo, Alejandro Silva-Palacios, Salvador Uribe-Carvajal, Natalia Pavón

Mitochondria play crucial roles in various cellular functions, including ATP production, apoptosis, and calcium homeostasis. Signaling pathways and hormones such as estrogens regulate the mitochondrial network through genetic, epigenetic, and metabolic processes. Estrogens increase the efficiency of mitochondrial oxidative phosphorylation by preventing uncoupling. Upon reaching menopause, when estrogen levels decrease, impaired mitochondrial function (uncoupled oxidative phosphorylation, lower ATP yields) is observed. Like all hormones in the body, estrogens undergo metabolic processing, resulting in estrogenic degradation metabolites (EDMs). These metabolites can form adducts with genomic and mitochondrial DNA and are of particular interest due to their potential role as carcinogens. Given that estradiol influences mitochondrial function, it is possible that EDMs may have an impact on heart mitochondria. To investigate this, we used isolated heart mitochondria from control and oophorectomized (mimicking menopausal stage) female Wistar rats of the same age. We found that mitochondria exposed to EDMs exhibited reduced coupling of oxidative phosphorylation and diminished ATP production, while increasing reactive oxygen species generation. Furthermore, these effects were significantly stronger in mitochondria from oophorectomized rats than in mitochondria from control (intact) rats. In addition, mitochondrial oxidative phosphorylation complex activities were differentially affected: complex I and ATPase activities decreased, while complex IV remained unaffected. We propose that exposure to EDMs promotes mitochondrial dysfunction in rats and that these effects are exacerbated by oophorectomy, a procedure commonly used to model the effects of menopause in women.

线粒体在多种细胞功能中起着至关重要的作用,包括ATP的产生、细胞凋亡和钙稳态。信号通路和激素如雌激素通过遗传、表观遗传和代谢过程调节线粒体网络。雌激素通过防止解偶联来提高线粒体氧化磷酸化的效率。绝经后,当雌激素水平下降时,线粒体功能受损(非偶联氧化磷酸化,ATP产量降低)。与体内所有激素一样,雌激素也会经历代谢过程,产生雌激素降解代谢物(EDMs)。这些代谢物可以与基因组和线粒体DNA形成加合物,由于它们作为致癌物的潜在作用而受到特别关注。鉴于雌二醇影响线粒体功能,edm可能对心脏线粒体有影响。为了研究这一点,我们使用了来自对照组和卵巢切除(模拟绝经期)的同龄雌性Wistar大鼠的分离心脏线粒体。我们发现,暴露于edm的线粒体表现出氧化磷酸化和ATP产生减少的偶联,同时增加活性氧的产生。此外,这些影响在卵巢切除大鼠的线粒体中明显强于对照(完整)大鼠的线粒体。此外,线粒体氧化磷酸化复合物活性受到不同程度的影响:复合物I和atp酶活性下降,而复合物IV未受影响。我们提出,暴露于edm会促进大鼠的线粒体功能障碍,而这些影响会因卵巢切除术而加剧,这是一种通常用于模拟女性更年期影响的手术。
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引用次数: 0
Heavy Metals Affect the Antioxidant Defences in the Soil Ciliate Rigidohymena tetracirrata. 重金属对土壤纤毛虫僵膜虫抗氧化防御的影响
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-17 DOI: 10.3390/jox15050169
Govindhasamay R Varatharajan, Antonio Calisi, Santosh Kumar, Daizy Bharti, Arnab Ghosh, Shikha Singh, Amit C Kharkwal, Martina Coletta, Francesco Dondero, Antonietta La Terza

In this study, we evaluated the cytotoxicity and antioxidant activity of the soil ciliate Rigidohymena tetracirrata (Gellért, 1942) Berger 2011, exposed to single and bimetallic mixtures of heavy metals (HMs) for 24 h. Ecotoxicological tests showed LC20 values of 0.16, 19.86 and 0.68 mg L-1 to Copper (Cu), Zinc (Zn), and Cadmium (Cd), respectively, and LC50 values of 0.25, 44.12 and 1.12 mg L-1, respectively. Furthermore, it was observed that the mixture of Cd and Zn exhibited antagonism in comparison to other mixtures, (Cd + Cu and Cu + Zn). In the total phenolic content (TPC) assay, a higher phenolic content was observed for the LC20 of extracellular Cu (p ≤ 0.01) and the LC20 of intracellular Cd (p ≤ 0.001). The LC50 values for Cd and Zn in both extracellular and intracellular contents demonstrated increased α,α-diphenyl-β-picrylhydrazyl (DPPH) scavenging activity with significant values of p ≤ 0.05, respectively. Regarding hydroxyl scavenging activity (HRSA), the LC50 of extracellular Cd (p ≤ 0.001) and LC50 of intracellular Cu (p ≤ 0.001) exhibited higher antioxidant activity. Therefore, the present study suggests that R. tetracirrata holds considerable potential as bioindicators and could be used as a model organism in ecotoxicological studies of soil polluted by HMs.

在本研究中,我们评估了土壤毛虫刚性膜(Rigidohymena tetracirrata, gell, 1942) Berger 2011,暴露于单一和双金属重金属混合物(HMs) 24小时的细胞毒性和抗氧化活性。生态毒理学测试显示,铜(Cu),锌(Zn)和镉(Cd)的LC20值分别为0.16,19.86和0.68 mg L-1, LC50值分别为0.25,44.12和1.12 mg L-1。此外,与Cd + Cu和Cu + Zn的混合物相比,Cd和Zn的混合物表现出拮抗作用。在总酚含量(TPC)测定中,胞外Cu LC20和胞内Cd LC20的酚含量均较高(p≤0.01)。细胞外和细胞内含量对Cd和Zn的LC50值均表现出α、α-二苯基-β-苦酰肼(DPPH)清除能力增强,且显著值分别为p≤0.05。在羟基清除活性(HRSA)方面,胞外Cd LC50 (p≤0.001)和胞内Cu LC50 (p≤0.001)表现出较高的抗氧化活性。因此,本研究表明,四爪鼠具有相当大的生物指示潜力,可以作为模式生物用于农药污染土壤的生态毒理学研究。
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引用次数: 0
DNA Damage and Bisphenol Levels in Chronic Kidney Disease Patients Undergoing Hemodialysis. 接受血液透析的慢性肾病患者的DNA损伤和双酚水平
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-17 DOI: 10.3390/jox15050167
Cesar Emilio Ruiz, Lourdes Vela, Martí Nadal, Neus González, Ricard Marcos, Alba Hernández, Susana Pastor, Elisabeth Coll

Bisphenol (BP) compounds are widely present in the environment, primarily due to their use as plastic additives. These substances involve health risks, particularly as endocrine disruptors. While the general population is chronically exposed, patients with end-stage chronic kidney disease undergoing hemodialysis (HD-CKD) represent a particularly vulnerable group. This is due to both impaired renal clearance of circulating BPs and potential contamination from plastic-containing dialyzers used in extracorporeal blood circulation. In this longitudinal study, from the 35 HD-CKD patients initially selected, 25 changed their conventional dialyzers to BPA-free dialyzers for 6 months. Blood serum samples were collected, at baseline and after the intervention, to quantify levels of five BP analogues: Bisphenol A (BPA), Bisphenol AF (BPAF), Bisphenol F (BPF), Bisphenol B (BPB), and Bisphenol S (BPS). Genotoxicity was assessed using the comet assay and the micronucleus test on peripheral white blood cells. Among the analyzed BPs, only BPAF showed a statistically significant reduction when using BPA-free dialyzers. In terms of genotoxicity, a significant decrease was observed only in primary DNA damage (mainly DNA strand breaks), with no notable changes in chromosomal damage. This is the first study to detect multiple BP analogues in HD-CKD patients, beyond BPA, and to associate human exposure to BPs with DNA damage biomarkers. The observed reduction in DNA damage in parallel with decreased BPAF levels highlights the importance of monitoring and minimizing BP exposure of this high-risk population.

双酚(BP)化合物广泛存在于环境中,主要是由于它们被用作塑料添加剂。这些物质涉及健康风险,特别是作为内分泌干扰物。虽然一般人群长期暴露,但接受血液透析的终末期慢性肾病(HD-CKD)患者是一个特别脆弱的群体。这是由于循环bp的肾脏清除受损和体外血液循环中使用的含塑料透析器的潜在污染。在这项纵向研究中,从最初选择的35名HD-CKD患者中,25名患者在6个月的时间里将传统的透析器改为不含bpa的透析器。在基线和干预后采集血清样本,量化五种BP类似物的水平:双酚A (BPA)、双酚AF (BPAF)、双酚F (BPF)、双酚B (BPB)和双酚S (BPS)。采用彗星试验和外周白细胞微核试验评估遗传毒性。在分析的bp中,使用不含bpa的透析器时,只有BPAF有统计学意义的降低。在遗传毒性方面,仅在原发性DNA损伤(主要是DNA链断裂)中观察到显着降低,而在染色体损伤方面没有显着变化。这是第一个在HD-CKD患者中检测除BPA之外的多种BP类似物,并将人类暴露于BP与DNA损伤生物标志物联系起来的研究。观察到DNA损伤的减少与BPAF水平的降低同时发生,这突出了监测和尽量减少这一高危人群BP暴露的重要性。
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引用次数: 0
Two-Step Air/Water Oxidation Process for the Long-Lasting Photoluminescence and Biological Viability (MTT Assay) of Porous Silicon Particles. 两步空气/水氧化法用于多孔硅颗粒的持久光致发光和生物活力(MTT)测定。
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-17 DOI: 10.3390/jox15050168
Claudia Castillo Calvente, María F Gilsanz-Muñoz, Javier Pérez-Piñeiro, Arisbel Cerpa-Naranjo, Rodrigo Blasco, Elvira Bragado-García, María S Fernández-Alfonso, Darío Gallach-Pérez

Due to their visible photoluminescence (PL) at room temperature, porous silicon particles (PSps) have gained interest for their potential biomedical applications, making them promising biological markers for in vivo or in vitro use. This study explores the PL evolution and stabilization of PSps following a two-step oxidation process involving air annealing and chemical oxidation in deionized water. PS layers were fabricated by electrochemical etching of p+-Si wafers and then annealed in air at 300 °C and 600 °C for five minutes. The layers were then stored in deionized water and sonicated to produce PSps. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to analyze the morphology and composition of the particles, and spectrofluorimetry was used to monitor the PL over several weeks. Samples annealed at 300 °C exhibited a transition from nearly complete PL quenching to strong yellow-red emission. In contrast, the 600 °C sample showed no PL emission. The cytotoxicity of the PSps was evaluated using an MTT assay on human endothelial cells (EA.Hy926) with PSps and polyethylene glycol (PEG)-coated PSps at concentrations of (3.5-125 µg/mL) in both serum-free and fetal bovine serum (FBS)-containing media over 24, 48, and 72 h. Cell viability was significantly affected by both exposure time and particle concentration; however, this effect was prevented under conditions mimicking the physiological plasma environment.

由于其在室温下的可见光致发光(PL),多孔硅颗粒(psp)因其潜在的生物医学应用而引起了人们的兴趣,使其成为体内或体外使用的有前途的生物标志物。本研究探讨了PSps在空气退火和去离子水化学氧化两步氧化过程后的PL演化和稳定性。通过电化学刻蚀p+-Si晶片制备PS层,然后在300℃和600℃的空气中退火5分钟。然后将这些层储存在去离子水中,并通过超声波产生psp。使用扫描电子显微镜(SEM)和能量色散x射线光谱(EDX)分析颗粒的形态和组成,并使用荧光光谱法监测几周内的PL。在300℃退火的样品表现出从几乎完全的PL淬火到强黄红发射的转变。相比之下,600°C的样品没有PL发射。PSps和聚乙二醇(PEG)包被的PSps在无血清和含胎牛血清(FBS)的培养基中浓度为(3.5-125µg/mL),在24、48和72小时内对人内皮细胞(EA.Hy926)的细胞毒性进行了MTT试验评估。细胞活力受到暴露时间和颗粒浓度的显著影响;然而,在模拟生理等离子体环境的条件下,这种效应被阻止。
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引用次数: 0
QSAR Models for Predicting Oral Bioavailability and Volume of Distribution and Their Application in Mapping the TK Space of Endocrine Disruptors. 预测口服生物利用度和分布体积的QSAR模型及其在内分泌干扰物TK空间绘制中的应用。
IF 4.4 Q1 TOXICOLOGY Pub Date : 2025-10-15 DOI: 10.3390/jox15050166
Guillaume Ollitrault, Marco Marzo, Alessandra Roncaglioni, Emilio Benfenati, Olivier Taboureau, Enrico Mombelli

Toxicokinetic (TK) properties are essential in the framework of chemical risk assessment and drug discovery. Specifically, a TK profile provides information about the fate of chemicals in the human body. In this context, Quantitative Structure-Activity Relationship (QSAR) models are convenient computational tools for predicting TK properties. Here, we developed QSAR models to predict two TK properties: oral bioavailability and volume of distribution at steady state (VDss). We collected and curated two large sets of 1712 and 1591 chemicals for oral bioavailability and VDss, respectively, and compared regression and classification (binary and multiclass) models with the application of several machine learning algorithms. The best predictive performance of the models for regression (R) prediction was characterized by a Q2F3 of 0.34 with the R-CatBoost model for oral bioavailability and a geometric mean fold error (GMFE) of 2.35 with the R-RF model for VDss. The models were then applied to a list of potential endocrine-disrupting chemicals (EDCs), highlighting chemicals with a high probability of posing a risk to human health due to their TK profiles. Based on the results obtained, insights into the structural determinants of TK properties for EDCs are further discussed.

毒性动力学特性在化学品风险评估和药物发现的框架中是必不可少的。具体来说,TK档案提供了有关化学物质在人体内的命运的信息。在这种情况下,定量构效关系(QSAR)模型是预测TK性质的方便计算工具。在这里,我们建立了QSAR模型来预测TK的两个特性:口服生物利用度和稳态分布体积(VDss)。我们分别收集和整理了1712和1591两大组化学物质的口服生物利用度和VDss,并将回归和分类(二元和多类)模型与几种机器学习算法的应用进行了比较。R- catboost模型预测口服生物利用度的Q2F3为0.34,R- rf模型预测VDss的几何平均折叠误差(GMFE)为2.35。然后将这些模型应用于潜在的内分泌干扰化学物质(EDCs)列表,突出显示由于其TK特征而极有可能对人类健康构成风险的化学物质。基于所获得的结果,进一步讨论了EDCs的TK性质的结构决定因素。
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引用次数: 0
期刊
Journal of Xenobiotics
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