ToxicsPub Date : 2025-08-30DOI: 10.3390/toxics13090735
Amparo Mauricio-Gutiérrez, Didier D Ramírez-Gutiérrez, Omar Romero-Arenas, Carlos A Contreras-Paredes, Sandra Mora-Ravelo, Lilia Cedillo-Ramírez, José A Yáñez-Santos, María A Valencia de Ita
{"title":"Cytotoxic Effects and Micronuclei Frequency as a Biomarker of Genotoxicity in Farmers from the Municipality of Tehuacán, Puebla, Mexico.","authors":"Amparo Mauricio-Gutiérrez, Didier D Ramírez-Gutiérrez, Omar Romero-Arenas, Carlos A Contreras-Paredes, Sandra Mora-Ravelo, Lilia Cedillo-Ramírez, José A Yáñez-Santos, María A Valencia de Ita","doi":"10.3390/toxics13090735","DOIUrl":"10.3390/toxics13090735","url":null,"abstract":"<p><p>In Tehuacán, Puebla, Mexico, the agricultural sector is primarily dedicated to corn cultivation, which is reflected in the region's economy, culture, and diet. This sector follows an agro-industrial production model dependent on pesticides and chemical fertilizers, which impacts both soil health and the population's well-being. The objective of this study was to assess cytotoxic damage using the Buccal Micronucleus Cytome Assay (BMCA) in a population engaged in agricultural activities in San Diego Chalma, Tehuacán, Puebla, Mexico. Sociodemographic parameters were analyzed, along with the buccal micronucleus cytome assay, in a sample of 35 individuals composed of an agricultural group (18) and a control group (17). The agricultural group showed a significantly higher number of total micronucleated cells (Median = 714), which was 19.8 times greater than the non-agricultural group. Age, sex, basic education level, time of residence, and involvement in agricultural activities were key factors contributing to the development of buccal cell micronuclei, in addition to the use of pesticides as lambda-cyhalothrin, spinetoram, ethoprophos, carbofuran, methomyl, and chlorpyrifos ethyl without safety measures. There was an increased risk of developing micronucleated cells in males from the control group (OR = 2.386, 95% CI = 2.123-2.681) and in individuals aged 30-59 years (OR = 16.464, 95% CI = 14.315-18.935). The agricultural population for the 0-29 years presented a risk probability developing micronucleated cells of 99.8% in men and 99.9% in women, with a higher risk observed in women and in individuals who had lived their entire lives in San Diego Chalma, where they are continuously exposed to pesticides. Therefore, it is crucial to provide guidance, training, and improved public policies in the region of Puebla, Mexico.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxicsPub Date : 2025-08-30DOI: 10.3390/toxics13090732
William S Baldwin, Michael S Bloom, Katy W Chung, Subham Dasgupta, Marie E DeLorenzo, Kelly J Hunt, Peter B Key, John L Pearce, Kylie D Rock, Philip Tanabe, Morgan A Jacobellis, Melanie M Garcia, Lisa J Bain
{"title":"Toxicological, Chemical, Social, and Economic Challenges Associated with PFAS and Replacement Aqueous Film-Forming Foams (AFFF).","authors":"William S Baldwin, Michael S Bloom, Katy W Chung, Subham Dasgupta, Marie E DeLorenzo, Kelly J Hunt, Peter B Key, John L Pearce, Kylie D Rock, Philip Tanabe, Morgan A Jacobellis, Melanie M Garcia, Lisa J Bain","doi":"10.3390/toxics13090732","DOIUrl":"10.3390/toxics13090732","url":null,"abstract":"<p><p>Poly- and perfluorinated alkyl substances (PFAS) are a group of chemicals that are widely used, prevalent in the environment, associated with several toxic effects, and often have long half-lives. Their persistence and relevant toxicity are the primary causes of environmental and human health concerns, and they are referred to as \"forever chemicals\" because of their persistence. Environmental accumulation caused by slow natural biodegradation and subsequent long environmental half-lives leads to bioaccumulation and makes PFAS more likely to be chronically toxic with potential transgenerational effects. Ultimately, it is this persistence that causes the greatest concern because PFAS-contaminated sites need costly remediation techniques, or else the contaminated areas will not be available for proper economic development because of social and economic suppression. Non-PFAS, alternative Aqueous Film Forming Foams (AFFF) that are considered environmentally friendly, are being heavily considered or currently used for fire suppression instead of PFAS-based products. The bioaccumulation and toxicity of alternative AFFF are just starting to be studied. The purpose of this review is to discuss the basic environmental and human health effects of PFAS and alternative AFFF that propel regulatory changes, increase clean-up costs, reduce economic development, and drive the development of novel alternatives.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxicsPub Date : 2025-08-30DOI: 10.3390/toxics13090734
Michal Ordak, Wiktoria Gorecka, Pawel Konieczynski, Marek Wesolowski, Alina Plenis, Nasierowski Tadeusz, Bujalska-Zadrozny Magdalena
{"title":"Influence of Preparation Methods on the Concentrations of Lead and Cadmium in <i>Amanita muscaria</i> Products.","authors":"Michal Ordak, Wiktoria Gorecka, Pawel Konieczynski, Marek Wesolowski, Alina Plenis, Nasierowski Tadeusz, Bujalska-Zadrozny Magdalena","doi":"10.3390/toxics13090734","DOIUrl":"10.3390/toxics13090734","url":null,"abstract":"<p><p>In recent years, the consumption of <i>Amanita muscaria</i> has gained popularity as a perceived natural alternative to psychoactive substances, often promoted online for its supposed therapeutic properties. However, the safety of such preparations remains largely unverified, particularly with regard to toxic element content. The present study focused on evaluating how different preparation methods affect the concentrations of cadmium (Cd) and lead (Pb) in the most commonly consumed <i>Amanita muscaria</i> products. A total of 50 mushroom caps were collected in October 2024 from the Stąporków Forest District in central Poland. Seven types of preparations were analyzed: dried with skin, dried without skin, tincture (mineralized and direct), boiled, fermented, infusion, and decoction. Samples were analyzed using atomic absorption spectrometry (AAS); depending on the preparation type, some underwent acid digestion prior to measurement. Statistically significant differences in lead concentrations were observed between the various preparation types (<i>p</i> = 0.002; η<sup>2</sup> = 0.97). Lead levels in the direct tincture were significantly higher than those in the boiled (<i>p</i> = 0.001), infusion (<i>p</i> = 0.001), decoction (<i>p</i> = 0.009), and dried without skin (<i>p</i> = 0.04) forms. Significant differences in cadmium concentrations were also found (<i>p</i> = 0.006; η<sup>2</sup> = 0.94), with lower Cd levels in the decoction compared to the dried with skin (<i>p</i> = 0.009) and without skin (<i>p</i> = 0.001), as well as in the fermented form compared to the dried samples (<i>p</i> = 0.03 and <i>p</i> = 0.004, respectively). These findings demonstrate that the type of preparation significantly influences the levels of cadmium and lead in <i>Amanita muscaria</i> products. While aqueous and fermented preparations showed reduced metal concentrations, none can be considered entirely safe, as even lower levels of Cd and Pb may pose health risks with frequent or excessive consumption.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxicsPub Date : 2025-08-30DOI: 10.3390/toxics13090736
Peng Zhou, Jiankang Xuan, Weixiao Xu, Di An, Sining Meng, Hongchao Zhang, Miaoyang Hu, Wanqingyang Hui, Yifei Wang, Jie Cheng, Jianping Xiong, Jun Wang, Xufeng Chen
{"title":"Methamphetamine Exposure Induces Neuronal Programmed Necrosis by Permeabilizing Mitochondria via the RIPK1-RIPK3-MLKL Axis.","authors":"Peng Zhou, Jiankang Xuan, Weixiao Xu, Di An, Sining Meng, Hongchao Zhang, Miaoyang Hu, Wanqingyang Hui, Yifei Wang, Jie Cheng, Jianping Xiong, Jun Wang, Xufeng Chen","doi":"10.3390/toxics13090736","DOIUrl":"10.3390/toxics13090736","url":null,"abstract":"<p><p>Methamphetamine (Meth), a psychostimulant drug of the amphetamine type, is widely abused and highly neurotoxic. Meth exposure leads to neuronal necroptosis, and the mitochondrial dysfunction may be involved. However, the underlying mechanisms remain poorly understood. Here, we found that Meth significantly elicited the formation of the RIPK1-RIPK3-MLKL necrosome complex. Intriguingly, the activated MLKL (p-MLKL) translocated to the mitochondrial membrane and displayed pore-forming activity, manifesting as the penetration of MLKL in the cell membranes of the mitochondria, which caused decreased mitochondrial membrane potential, ATP generation, and mitochondrial DNA (mtDNA) and increased mitochondrial ROS (mtROS) generation, which finalized neuronal necroptosis. Notably, MLKL activation and translocation seem to depend on the RIPK1-RIPK3 axis since these adverse effects can be substantially ameliorated by disruption of the necrosome complex formation by the necroptotic inhibitor 1 (Nec-1), which also markedly impeded the MLKL mitochondrial membrane translocation. Finally, to delineate the effects of pore formation-associated ROS generation, specific blockage of mtROS retarded the Meth-induced neuronal necroptosis. In conclusion, our study reveals for the first time that MLKL mitochondrial membrane translocation may be involved in Meth-induced neuronal necroptosis. Therefore, impeding MLKL translocation might provide a novel therapeutic strategy for Meth-induced neurotoxicity.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Involvement of Surface Receptors in the Uptake and Cellular Responses Induced by Cationic Polyamine-Based Carbon Dots in Macrophages.","authors":"Agathe Cerland, Ezeddine Harmouch, Mickaël Rapp, Luc Lebeau, Françoise Pons, Carole Ronzani","doi":"10.3390/toxics13090731","DOIUrl":"10.3390/toxics13090731","url":null,"abstract":"<p><p>Cationic polyamine-based carbon dots (CDs) are increasingly being explored for biomedical applications. These ultrasmall (<10 nm) fluorescent nanoparticles, synthesized from organic precursors and functionalized with polyamines, possess a strong positive surface charge that enables efficient complexation and delivery of nucleic acids, making them promising candidates for gene therapy. However, the mechanisms by which the immune system, particularly macrophages, recognizes and responds to these nanomaterials remain poorly understood. In this study, we investigated the role of surface receptors in the uptake and biological effects of cationic polyamine-based CDs in macrophages. Our data showed that Fc receptors and the Toll-like receptor 4 (TLR4) were minimally involved in CD internalization and associated cellular responses in contrast to scavenger receptors (SRs). Indeed, SR inhibition reduced CD-induced cell viability loss, LDH release, and secretion of the pro-inflammatory cytokine IL-1β. Among SRs, SR-A1 was identified as a key receptor mediating CD recognition and toxicity, likely through activation of the MERTK signaling pathway. Importantly, these mechanisms occurred in the absence of serum, indicating that protein corona formation is not required for CD interaction with macrophage surface receptors. Overall, our findings highlight the prominent role of SRs, particularly SR-A1, as receptors recognizing cationic polyamine-based CDs on the surface of macrophages, and provide new insights into the cellular mechanisms underlying the immunotoxicity of these carbon-based nanomaterials.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxicsPub Date : 2025-08-29DOI: 10.3390/toxics13090729
Mengying Li, Lijuan Qi, Xinyi Xu, Rong Zhao, Xiaotong Wang, Yanhui Ha, Zhe Lin, Sujin Lu, Rong Chen, Junchao Zhao
{"title":"Characterization of the Chemical Composition, Cytotoxicity, and Metabolomic Effects of PM<sub>2.5</sub> in a Plateau City, China.","authors":"Mengying Li, Lijuan Qi, Xinyi Xu, Rong Zhao, Xiaotong Wang, Yanhui Ha, Zhe Lin, Sujin Lu, Rong Chen, Junchao Zhao","doi":"10.3390/toxics13090729","DOIUrl":"10.3390/toxics13090729","url":null,"abstract":"<p><p>The health impacts of atmospheric fine particulate matter (PM<sub>2.5</sub>) in plateau regions have attracted concerns, along with local population growth and rapid urbanization. This study collected PM<sub>2.5</sub> samples at summer and winter in Xining, a city located in the northeastern Tibetan Plateau. The chemical composition of PM<sub>2.5</sub> and its cytotoxicity on human lung epithelial cells (A549) are characterized, and composition-cytotoxicity correlation is discussed. The toxic mechanisms of PM<sub>2.5</sub> in different seasons were further investigated through metabolomic analysis using high-resolution mass spectrometry. The average PM<sub>2.5</sub> mass concentration in Xining during winter was 2.10 times higher than that during summer. The carbonaceous components in PM<sub>2.5</sub> were dominated by OC, while the main water-soluble ions were SO<sub>4</sub><sup>2-</sup>, NO<sub>3</sub><sup>-</sup>, and NH<sub>4</sub><sup>+</sup>, with Mg, Al, Fe, and Ca also present in high concentrations in metal elements. LDH and ROS emerged as the most PM<sub>2.5</sub>-affected toxicity indices in summer (34.59 ± 4.86 ng/L, 1.19× control) and winter (8.62 ± 1.25 ng/mL, 1.77× control), respectively. OC, Cl<sup>-</sup>, F<sup>-</sup>, Sn, Cr, SO<sub>4</sub><sup>2-</sup>, Pb, Zn, Mg, NO<sub>3</sub><sup>-</sup>, and NH<sub>4</sub><sup>+</sup> may synergistically exacerbate oxidative stress and inflammatory responses on A549 cells in Xining. Furthermore, glutathione metabolism, amino acid metabolism, and sphingolipid metabolism were identified as key pathways influencing cellular oxidation and inflammation. Thimonacic, 9-(2,3-dihydroxypropoxy)-9-oxononanoic acid, and hypoxanthine were common metabolites in both seasons. Our findings greatly enhance the understanding of health risks associated with PM<sub>2.5</sub> in the plateau city.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effectiveness and Remediation Mechanisms of Geo-Electrochemical Technology for Arsenic Removal in Paddy Soil from Northern Guangxi.","authors":"Yuxiong Jiang, Meilan Wen, Yao Sun, Panfeng Liu, Yunxue Ma, Caiyun Zhang, Xiaohan Zhang","doi":"10.3390/toxics13090728","DOIUrl":"10.3390/toxics13090728","url":null,"abstract":"<p><p>Arsenic pollution in paddy soil is a major environmental issue, and its remediation has become a subject of broad interest. Geo-electrochemical technology has been shown to have significant potential for remediating heavy metal-contaminated soils in recent years. Taking contaminated paddy soil from northern Guangxi as the research subject, this study aims to assess the effectiveness of geo-electrochemical technology for arsenic remediation. An orthogonal experimental design was used to identify the optimal combination of parameters, including power supply duration, voltage gradient, power supply mode, and electrolyte type. The arsenic removal efficiency was thoroughly assessed, and the underlying remediation mechanisms associated with geo-electrochemical technology combined with EDTA-2Na were extensively investigated. The findings revealed a substantial decrease in the residual arsenic fraction after treatment, accompanied by a substantial increase in the mobility and bioavailability of arsenic. The maximum removal rate of arsenic from the soil was determined to be 19.59%. Among the analyzed factors, electrolyte type exerted the most significant influence on the arsenic removal efficiency, followed by power supply duration and voltage gradient, while the impact of the power supply mode was less significant. The optimal remediation effect was achieved under the following conditions: a power supply duration of 108 h, a voltage gradient of 0.6 V/cm, continuous power supply mode, and the use of EDTA-2Na as the electrolyte. The multiple strong coordinating atoms in EDTA-2Na can form stable chelates with Fe<sup>3+</sup> and Al<sup>3+</sup> bound to arsenic in the soil, thereby causing the desorption of arsenic. The integration of geo-electrochemical technology with EDTA-2Na forms a synergistic multiphase electrochemical reaction mechanism, significantly improving the overall remediation efficiency in arsenic-contaminated soils.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxicsPub Date : 2025-08-29DOI: 10.3390/toxics13090726
Jinyu Li, Xiaomin Cao, Chengjuan Liu, Lin Cheng, Qiao Niu, Jisheng Nie
{"title":"Association of Prenatal Polycyclic Aromatic Hydrocarbons Exposure, DNA Hydroxymethylation, and Neurodevelopment at 0 and 2 Years of Age.","authors":"Jinyu Li, Xiaomin Cao, Chengjuan Liu, Lin Cheng, Qiao Niu, Jisheng Nie","doi":"10.3390/toxics13090726","DOIUrl":"10.3390/toxics13090726","url":null,"abstract":"<p><p>Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy may have effects on the offspring epigenome. And the change in onset epigenome may be associated with children's neurodevelopment. The current study investigated the relationship between 5-hydroxymethylcytosine (5-hmC) levels in cord blood and PAH metabolites in maternal urine at delivery and children's neurodevelopment at birth and at age 2. We enrolled 400 pregnant women and their newborns and collected their biological samples after obtaining written informed consent. Enzyme linked immunosorbent assay kits and Chromatin immunoprecipitation kits were used to assess the DNA hydroxymethylation level in cord blood. We observed that 1-hydroxypyrene (1-OHPyr) was inversely associated with gesell developmental scale scores, positively associated with global DNA 5-hmC levels, and associated with decreased 5-hmC levels of the brain-derived neurotrophic factor (<i>BDNF</i>) and methyl CpG binding protein 2 (<i>MeCP2</i>) gene promoter. In addition, the 5-hmC levels of the <i>BDNF</i> and <i>MeCP2</i> gene promoters were associated with motor scores. The global DNA 5-hmC was inversely associated with motor scores. Mediation analysis showed mediation effects between 1-OHPyr and motor scores by 5-hmC. The global DNA 5-hmC and <i>MeCP2</i> and <i>BDNF</i> gene promoter 5-hmC contributed 28.51%, 27.29%, and 18.98% of the effect on motor scores changes related to 1-OHPyr. The study results suggested that 5-hmC can be a potential mechanism between prenatal PAH exposure and children's neurodevelopment at age 2 and provide a better understanding of the role of hydroxymethylation in neurodevelopment.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxicsPub Date : 2025-08-29DOI: 10.3390/toxics13090727
Bridget R Knapp, Deborah L Hunter, Jeanene K Olin, Stephanie Padilla, Kimberly A Jarema
{"title":"Utilizing Multiple Behavioral Endpoints to Identify Negative Control Chemicals in a Larval Zebrafish Behavior Assay.","authors":"Bridget R Knapp, Deborah L Hunter, Jeanene K Olin, Stephanie Padilla, Kimberly A Jarema","doi":"10.3390/toxics13090727","DOIUrl":"10.3390/toxics13090727","url":null,"abstract":"<p><p>Identifying reliable negative control compounds is essential for determining the sensitivity and specificity of screening assays. However, well-characterized negative controls for developmental neurotoxicity behavioral assays in larval zebrafish (<i>Danio rerio</i>) are lacking. This study evaluated nine chemicals with no reported evidence of mammalian developmental neurotoxicity, and a positive control (fluoxetine) for developmental and neurodevelopmental (i.e., behavioral) toxicity in zebrafish. Embryos were exposed to each chemical (≤100 µM) during development, 0-5 days post-fertilization (dpf), then assessed as larvae (6 dpf) using a locomotor behavior light-dark transition test. Behavior was analyzed using two methods: (1) the traditional method, comparing the average total distance moved, and (2) a 13-endpoint approach analyzing 13 aspects of the locomotor profile. Results showed that ibuprofen, omeprazole, and fluoxetine induced developmental toxicity (teratogenesis), with fluoxetine also causing behavioral neurotoxicity. Behavioral effects of developmental exposure to selegiline hydrochloride depended on the analysis method. Exposure to the other six chemicals (D-mannitol, glycerol, L-ascorbic acid, metformin hydrochloride, saccharin, and sodium benzoate), as well as ibuprofen or omeprazole, did not produce behavioral effects using either analysis method. Identifying negative control chemicals is essential for evaluating behavioral alterations precipitated by unknown substances and will assist with screening new chemicals for neurodevelopmental toxicity.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}