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The Evolution of In Vitro Toxicity Assessment Methods for Oral Cavity Tissues—From 2D Cell Cultures to Organ-on-a-Chip
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Emission Characteristics of Volatile Organic Compounds from Material Extrusion Printers Using Acrylonitrile–Butadiene–Styrene and Polylactic Acid Filaments in Printing Environments and Their Toxicological Concerns
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Progestin Footprint in the European Douro River Estuary
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Per- and Poly-Fluoroalkyl Substances, and Organophosphate Flame Retardants in the Upper Yangtze River: Occurrence, Spatiotemporal Distribution, and Risk Assessment
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Air, Skin, and Biological Monitoring of French Fire Instructors’ Exposure to Particles/PAHs During Controlled Fire and Mitigation Strategies
Journal Description
Toxics
Toxics
is an international, peer-reviewed, open access journal on all aspects of the toxic chemicals and materials, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, AGRIS, and other databases.
- Journal Rank: JCR - Q1 (Toxicology) / CiteScore - Q2 (Chemical Health and Safety)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.3 days after submission; acceptance to publication is undertaken in 2.3 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
3.9 (2023);
5-Year Impact Factor:
4.2 (2023)
Latest Articles
Suppression of NOX2-Derived Reactive Oxygen Species (ROS) Reduces Epithelial-to-MesEnchymal Transition Through Blocking SiO2-Regulated JNK Activation
Toxics 2025, 13(5), 365; https://doi.org/10.3390/toxics13050365 (registering DOI) - 30 Apr 2025
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(1) Background: Silicosis, a chronic lung fibrosis disorder triggered by the accumulation of silica dust in the deep lung regions, is characterized by intricate molecular mechanisms. Among these, the NOX2 (NADPH oxidase 2) and JNK (C-Jun N-terminal kinase) signaling pathways play pivotal roles
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(1) Background: Silicosis, a chronic lung fibrosis disorder triggered by the accumulation of silica dust in the deep lung regions, is characterized by intricate molecular mechanisms. Among these, the NOX2 (NADPH oxidase 2) and JNK (C-Jun N-terminal kinase) signaling pathways play pivotal roles in the progression of pulmonary fibrosis. Despite their significance, the precise mechanisms underlying the crosstalk between these pathways remain largely unexplored. (2) Methods: To unravel these interactions, we examined the interplay between JNK and NOX2 in human epithelial cells subjected to silica dust exposure through in vivo assays, followed by validation using single-cell sequencing. Our findings consistently revealed elevated expression levels of key components from both the JNK signaling pathway and NOX2 in the lungs of silicosis-induced mice and silica-treated human epithelial cells. (3) Results: Notably, the activation of these pathways was linked to increased ROS (reactive oxygen species) production, elevated levels of profibrogenic factors, and diminished cell proliferation in silica-exposed human lung epithelial cells. Further mechanistic analyses demonstrated that JNK signaling amplifies NOX2 expression and ROS production induced by silica exposure, while treatment with the JNK inhibitor SP600125 mitigates these effects. Conversely, overexpression of NOX2 enhanced silica-induced JNK activation and the expression of epithelial–mesenchymal transition (EMT)-related factors, whereas NOX2 knockdown exerted the opposite effect. These results suggest a positive feedback loop between JNK and NOX2 signaling, which may drive EMT in lung epithelial cells following silica exposure. (4) Conclusions: This reciprocal interaction appears to play a critical role in lung epithelial cell damage and the pathogenesis of silicosis, shedding light on the molecular mechanisms underlying profibrogenic disease and offering potential avenues for therapeutic intervention.
Full article
Open AccessReview
A Review of Biogenic Volatile Organic Compounds from Plants: Research Progress and Future Prospects
by
Rongrong Luo, Xiaoxiu Lun, Rui Gao, Le Wang, Yuan Yang, Xingqian Su, Md Habibullah-Al-Mamun, Xiaohang Xu, Hong Li and Jinjuan Li
Toxics 2025, 13(5), 364; https://doi.org/10.3390/toxics13050364 (registering DOI) - 30 Apr 2025
Abstract
Biogenic volatile organic compounds (BVOCs) emitted by plants contribute to secondary air pollution through photochemical reactions in sunlight. Due to the influence of multiple factors, accurately characterizing and quantifying the emission of BVOCs from plant sources is challenging, which poses significant obstacles to
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Biogenic volatile organic compounds (BVOCs) emitted by plants contribute to secondary air pollution through photochemical reactions in sunlight. Due to the influence of multiple factors, accurately characterizing and quantifying the emission of BVOCs from plant sources is challenging, which poses significant obstacles to the effective management and control of BVOCs. Therefore, this paper summarizes the emission mechanisms of BVOCs from plants, explores the primary factors influencing variations in the emission rates of these compounds, and evaluates the advantages and limitations of contemporary “measurement-modeling” methods for characterizing BVOC emissions. It is concluded that current measurement techniques still need to be further developed to meet the criteria of simplicity, affordability, and high precision simultaneously, and in terms of modeling and prediction studies, there is a lack of in-depth research on the atmospheric chemistry of BVOCs and the synergistic effects of multiple factors. Finally, it is suggested to leverage interdisciplinary strengths to develop advanced measurement technologies and high-resolution models for monitoring volatile compounds. Additionally, strategically selecting low-BVOC tree species in pollution-vulnerable urban areas—contingent on rigorous ecological assessments—combined with stringent controls on anthropogenic precursors (e.g., anthropogenic volatile organic compounds (AVOCs)) could serve as a complementary measure to mitigate secondary pollution.
Full article
(This article belongs to the Special Issue Source and Components Analysis of Aerosols in Air Pollution)
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Immobilization of Inorganic Phosphorus on Soils by Zinc Oxide Engineered Nanoparticles
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Jonathan Suazo-Hernández, Rawan Mlih, Marion Bustamante, Carmen Castro-Castillo, María de la Luz Mora, María de los Ángeles Sepúlveda-Parada, Catalina Mella, Pablo Cornejo and Antonieta Ruiz
Toxics 2025, 13(5), 363; https://doi.org/10.3390/toxics13050363 (registering DOI) - 30 Apr 2025
Abstract
The overuse of inorganic phosphate fertilizers in soils has led to the transfer of inorganic phosphorus (Pi) to aquatic ecosystems, resulting in eutrophication. Adsorption–desorption studies in batch systems were used to evaluate the effect of adding 1% zinc oxide (ZnO) engineered nanoparticles (ENPs)
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The overuse of inorganic phosphate fertilizers in soils has led to the transfer of inorganic phosphorus (Pi) to aquatic ecosystems, resulting in eutrophication. Adsorption–desorption studies in batch systems were used to evaluate the effect of adding 1% zinc oxide (ZnO) engineered nanoparticles (ENPs) on Pi retention in Ultisol, and Mollisol soils. The 1% ZnO–ENPs showed increased chemical properties such as pH, electrical conductivity, and organic matter content, and reduce nutrient bioavailability (P, N, and Zn), and physical properties such as surface area and pore size of the two soils. The kinetic data of Pi adsorption on Ultisol, Mollisol, Ultisol + 1% ZnO–ENP, and Mollisol + 1% ZnO–ENP systems fitted well to the pseudo-second-order model (r2 ≥ 0.942, and χ2 ≤ 61), and the Elovich model (r2 ≥ 0.951, and χ2 ≤ 32). Pi adsorption isotherms for the Ultisol soil adequately fitted to the Freundlich model (r2 = 0.976, and χ2 = 16), and for the Mollisol soil, the Langmuir model (r2 = 0.991, and χ2 = 3) had a better fit to the data. With 1% ZnO–ENPs, the linear, Langmuir, and Freundlich models correctly described the Pi adsorption data. Pi desorption was reduced in the Ultisol compared to the Mollisol soil, and with 1% ZnO–ENPs further decreased Pi desorption in both soils. Therefore, ENPs can be used as a new alternative material for Pi fixation in agricultural soils and contribute to mitigating eutrophication issues of aqueous systems.
Full article
(This article belongs to the Special Issue Metal Oxide-Based Nanomaterial Remediation of Contaminated Soil and Water)
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Open AccessArticle
N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish
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Niki Tagkalidou, Júlia Goyenechea-Cunillera, Irene Romero-Alfano, Maria Olivella Martí, Juliette Bedrossiantz, Eva Prats, Cristian Gomez-Canela and Demetrio Raldúa
Toxics 2025, 13(5), 362; https://doi.org/10.3390/toxics13050362 (registering DOI) - 30 Apr 2025
Abstract
Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeutic efficacy of N-acetylcysteine-amide (AD4), a blood–brain
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Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeutic efficacy of N-acetylcysteine-amide (AD4), a blood–brain barrier (BBB)-permeable derivative of N-acetylcysteine, in a novel severe acute ACR neurotoxicity model in adult zebrafish. Adult zebrafish received a single intraperitoneal (i.p.) injection of ACR (800 μg/g), followed by AD4 (400 μg/g i.p.) or PBS 24 h later. ACR exposure reduced brain GSH levels by 51% reduction at 48 h, an effect fully reversed by AD4 treatment. Behavioral analyses showed that AD4 rescued ACR-induced deficits in short-term habituation of the acoustic startle response (ASR). Surprisingly, ACR exposure did not alter the neurochemical profile of key neurotransmitters or the expression of genes related to redox homeostasis, synaptic vesicle recycling, regeneration, or myelination. These results demonstrate AD4’s neuroprotective effects against acute ACR-induced brain toxicity, highlighting its therapeutic potential and validating adult zebrafish as a translational model for studying neurotoxic mechanisms and neuroprotective interventions.
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(This article belongs to the Special Issue Toxicological Studies Using Zebrafish Models)
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Open AccessArticle
Oxidative Stress Response of Liver Cell Culture in Atlantic Salmon Challenged Under Two Antibiotics: Oxytetracycline and Florfenicol
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Luis Vargas-Chacoff, Francisco Dann, Ricardo Oyarzún-Salazar, Daniela Nualart and José Luis P. Muñoz
Toxics 2025, 13(5), 361; https://doi.org/10.3390/toxics13050361 (registering DOI) - 30 Apr 2025
Abstract
Aquaculture is currently the fastest-growing sector in animal production, with an average annual growth rate of 7.5% since 1970. In Chile, the industry is largely driven by salmonid farming, with Salmo salar (Atlantic salmon) accounting for over 65% of national production. This species
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Aquaculture is currently the fastest-growing sector in animal production, with an average annual growth rate of 7.5% since 1970. In Chile, the industry is largely driven by salmonid farming, with Salmo salar (Atlantic salmon) accounting for over 65% of national production. This species has shown the most significant growth within the sector. This growth is achieved by having high-density farming, which results in high levels of stress due to overcrowding and the appearance of pathogens such as the Infectious Salmon Anemia (ISA) virus, Bacterial Kidney Disease (BKD), Caligus sea lice (Caligus rogercresseyi), and Piscirickettsiosis (SRS) caused by Piscirickettsia salmonis, among others. This study evaluated the toxicity of the two most commonly used antibiotics in the salmon industry—oxytetracycline and florfenicol—at four concentrations each, using primary liver cell cultures of Atlantic salmon (Salmo salar). Oxidative stress was assessed through enzymatic activity and gene expression of oxidative markers, including cytochrome P450, catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx). Samples were analyzed at 1, 3, 6, 12, and 48 h post-exposure. These findings reveal time- and dose-dependent oxidative responses in salmon liver cells to OTC and FLO, providing critical insights into the sublethal cellular effects of antibiotics commonly used in aquaculture, which indicates the presence of a high amount of free radicals in the liver cells, indicating toxicity of both antibiotics.
Full article
(This article belongs to the Special Issue Pharmaceutical Pollutants: Environmental Fate, Risk Assessment and Sustainable Solutions)
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Open AccessArticle
Screening of Profitable Chrysanthemums for the Phytoremediation of Cadmium-Contaminated Soils
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Xinzhe Lu, Yanfang Chen, Jinqiu Song, Jiayu Bao, Chunzheng Dai, Rui Sun, Jiacheng Liu, Chenjiang Jin, Nanchong Zhong, Chunlei Huang and Kokyo Oh
Toxics 2025, 13(5), 360; https://doi.org/10.3390/toxics13050360 - 30 Apr 2025
Abstract
To explore the phytoremediation effect of ornamental chrysanthemums on cadmium (Cd)-contaminated farmland soil, a 2-year field trial was conducted on 23 chrysanthemum cultivars in Cd-contaminated soil in Zhejiang Province, China. The biomass yields, Cd content of the plants, Cd enrichment coefficient, and remediation
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To explore the phytoremediation effect of ornamental chrysanthemums on cadmium (Cd)-contaminated farmland soil, a 2-year field trial was conducted on 23 chrysanthemum cultivars in Cd-contaminated soil in Zhejiang Province, China. The biomass yields, Cd content of the plants, Cd enrichment coefficient, and remediation efficiency were evaluated. The aboveground biomass of the tested chrysanthemums was 67.10–166.08 g/plant, the aboveground Cd content was 1.97–5.92 mg kg−1, and the Cd enrichment coefficient was 2.98–9.84. In a screening test of twenty-three chrysanthemum cultivars, six cultivars, such as marigolds, were characterized by high cadmium accumulation, with the average cadmium accumulation of chrysanthemums exceeding 0.6 mg per plant, and the remediation of rhizosphere-contaminated soils took only 4–5 years. Fourteen chrysanthemum cultivars have good multiple-cropping characteristics, and five multiple-cropping chrysanthemum cultivars, such as QX-yz, have high heavy metal tolerance. The multiple-cropping JL-yg cultivars with higher Cd accumulation could be recommended for the remediation of Cd-contaminated farmland. The application of bamboo vinegar to the chrysanthemum rhizosphere effectively promoted Cd absorption. After estimating the economic benefits of artificially planting five dominant varieties of chrysanthemums for polluted farmland remediation, it is concluded that the annual income of a worker can be slightly higher than the average annual income level of local residents.
Full article
(This article belongs to the Special Issue Safe Utilization and Ecological Restoration of Heavy Metal Polluted Farmland)
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Correlation Analysis Between Physical–Chemical and Biological Conditions in the River and the Incidence of Diseases in the City of Piracicaba, Brazil
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Alexander Ossanes de Souza, Deoclecio Jardim Amorim and Ernani Pinto
Toxics 2025, 13(5), 359; https://doi.org/10.3390/toxics13050359 - 30 Apr 2025
Abstract
The Piracicaba River basin, in the State of São Paulo, Brazil, covers approximately 12,400 km2 and plays a crucial economic role in São Paulo’s agribusiness corridor. However, it faces recurrent episodes of pollution, impacting water quality and public health, especially in urban
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The Piracicaba River basin, in the State of São Paulo, Brazil, covers approximately 12,400 km2 and plays a crucial economic role in São Paulo’s agribusiness corridor. However, it faces recurrent episodes of pollution, impacting water quality and public health, especially in urban areas exposed to contamination. Despite this, few studies have investigated the ecological and epidemiological consequences of this environmental degradation. Therefore, this study analyzed the correlation between physicochemical and biological variables of the Piracicaba River and the incidence of diseases in the city of Piracicaba between January 2019 and September 2024. Data on hospital admissions for respiratory, neurological, and liver symptoms were used, as well as environmental and water quality information, such as dissolved oxygen, turbidity, conductivity, and the presence of cyanobacteria, obtained from public databases. The results showed seasonal patterns and long-term trends, highlighting the health risks associated with the river’s pollution. Parameters such as phosphorus, pH, cyanobacteria concentration and climatic factors (temperature and humidity) showed an influence on the occurrence of respiratory, digestive, and neurological diseases. The study reinforces the need for continuous monitoring of water quality and public policies to mitigate impacts on the population’s health.
Full article
(This article belongs to the Special Issue Alien Species in Aquatic Toxicology)
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Assessment of Potential Toxic Effects of Fungicide Fludioxonil on Human Cells and Aquatic Microorganisms
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Maria Antonopoulou, Anna Tzamaria, Sotiris Papas, Ioanna Efthimiou and Dimitris Vlastos
Toxics 2025, 13(5), 358; https://doi.org/10.3390/toxics13050358 - 30 Apr 2025
Abstract
Fludioxonil is a widely used fungicide that is frequently used to combat fungal plant diseases. Consequently, excessive concentrations of fludioxonil may enter and accumulate over time in aquatic systems, harming (micro) organisms in several ways. Thus, it is of great importance to evaluate
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Fludioxonil is a widely used fungicide that is frequently used to combat fungal plant diseases. Consequently, excessive concentrations of fludioxonil may enter and accumulate over time in aquatic systems, harming (micro) organisms in several ways. Thus, it is of great importance to evaluate the potential toxic effects of fludioxonil using bioassays. In the present study, various in vitro assays were used to assess the possible effects of fludioxonil in human cells and aquatic microorganisms. For the investigation of the toxic effects of fludioxonil on freshwater microalgae, Scenedesmus rubescens and Dunaliella tertiolecta were exposed to various environmentally relevant concentrations of the fungicide for a period of 96 h. Fludioxonil at 50–200 μg L−1 significantly limited the growth of both microalgae, especially in the first 24 h of the exposure, where inhibitions up to 82.34% were calculated. The toxicity of fludioxonil was further evaluated via the Microtox test, and the studied fungicide was found to be less toxic for the bacteria Aliivibrio fischeri. Regarding human cells, the fludioxonil’s toxic and cyto-genotoxic effects were assessed using the Trypan blue exclusion test and the Cytokinesis Block MicroNucleus (CBMN) assay. Cell viability in all fludioxonil-treated concentrations was similar to control values according to the results of the Trypan blue exclusion test. However, the CBMN assay was used and revealed that fludioxonil had genotoxic potential in higher concentrations and exerted cytotoxic activity against human lymphocytes. Specifically, only the highest dose of fludioxonil, i.e., 10 μg mL−1, exerted genotoxic effects against human lymphocytes, whereas treatment with 0.5, 1, and 5 μg mL−1 did not lead to statistically significant induction of micronuclei (MN) frequencies compared with the control culture. However, fludioxonil-mediated cytotoxicity was statistically significant, which was demonstrated by the decreased CBPI (cytokinesis block proliferation index) values in all cases except for the lowest dose, i.e., 0.5 μg mL−1.
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(This article belongs to the Special Issue From Low-Tier to Individual Effects of Emerging Pollutants: Integrative Approaches to Ecotoxicological Assessments—2nd Edition)
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Environmental DNA-Based Ecological Risk Assessment of PAHs in Aged Petroleum-Contaminated Soils
by
Jinrong Huang, Chang Zhou, Fanyong Song, Tianyuan Li, Jianing Wang and Xiaowen Fu
Toxics 2025, 13(5), 357; https://doi.org/10.3390/toxics13050357 - 29 Apr 2025
Abstract
(1) Background: Polycyclic aromatic hydrocarbons (PAHs) are important components of petroleum and pose a serious threat to the soil environment of oil production well sites. Therefore, scientific risk thresholds and ecological risk assessment methods must be established for PAHs in petroleum-contaminated soils. (2)
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(1) Background: Polycyclic aromatic hydrocarbons (PAHs) are important components of petroleum and pose a serious threat to the soil environment of oil production well sites. Therefore, scientific risk thresholds and ecological risk assessment methods must be established for PAHs in petroleum-contaminated soils. (2) Methods: In this study, based on the environmental DNA (eDNA) method, the soil bacterial community was considered as a receptor to assess the ecological risks of PAH contamination in aged petroleum-polluted soils. A combination of the risk quotient and the equivalent toxicity factor was used to assess the ecological risk of PAHs. (3) Results: A dose–response curve was plotted to determine the 50% effective concentration (EC50) of the total equivalent toxicity for 16 PAHs (∑TEQBaP) in petroleum-contaminated soils. Following the plot of the species sensitivity distribution (SSD) curve, the hazardous concentration for protecting 95% species values (HC5) of petroleum hydrocarbons (TPHs), electrical conductivity (EC), and total equivalent toxicity of PAHs were calculated to be 892.1 μs·cm−1, 149.9 mg·kg−1, and 0.2601 mg·kg−1, respectively. The regression models of the distribution factor (DF) and aging factor (AF) were defined as DF = −1.132 SOM + 0.033PAHs + 9.968 and AF = 242.518 SOM + 1256.029 lgpH + 0.024 EC − 1415.447. Following calibrations of the DF and AF, the value of HC5 was determined as 0.1956 mg·kg−1, which could be considered the risk threshold of the total toxicity of PAHs. The calibrated toxicity data distribution was consistent with that of the normal cumulative probability distribution model. The results showed that 50% of the aged petroleum-contaminated soils showed high-risk levels of bacterial communities exposed to PAHs. (4) Conclusions: This study provides a reference for deriving the ecological risk threshold of soil pollutants and explores alternative methods for the ecological risk assessment of PAHs at specific sites.
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(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)
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Identification and Time Series Analysis of PM2.5 and O3 Associated Health Risk Prevention and Control Areas
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Xinyu Huang, Bin Zou and Shenxin Li
Toxics 2025, 13(5), 356; https://doi.org/10.3390/toxics13050356 - 29 Apr 2025
Abstract
Air pollution of PM2.5 and O3 is a global health concern. Traditional approaches for identifying air pollution control areas mainly relied on pollutant concentrations, neglecting population distribution and exposure. This study proposes a method to divide these areas from a health
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Air pollution of PM2.5 and O3 is a global health concern. Traditional approaches for identifying air pollution control areas mainly relied on pollutant concentrations, neglecting population distribution and exposure. This study proposes a method to divide these areas from a health risk perspective, comparing their objectivity and rationality with the government-defined key regions. The results show that for PM2.5, the health risk population and average risk rates in the prevention and control areas were 0.993 million (0.1286%), 1.030 million (0.1283%), and 1.023 million (0.1202%) in 2010, 2015, and 2020, significantly higher than in the key areas: 0.778 million (0.1252%), 0.834 million (0.1278%), and 0.825 million (0.1212%). Similarly, for O3, the figures in the prevention and control areas were 0.096 million (0.01228%), 0.095 million (0.01243%), and 0.110 million (0.01316%), also higher than in the key areas: 0.0757 million (0.01218%), 0.078 million (0.01189%), and 0.090 million (0.01315%). Additionally, the Gini coefficients for PM2.5, O3, and overall health risks in the prevention and control areas were lower (0.182, 0.203, 0.284) compared to those in the key areas (0.207, 0.216, 0.292). This study provides a method for defining air pollution control regions based on health risks, offering significant insights for pollution zoning and prevention strategies
Full article
(This article belongs to the Special Issue Atmospheric Emissions Characteristics and Its Impact on Human Health)
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Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via PI3K/Akt/mTOR-Mediated Autophagy
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Amina A. Farag, Mahmoud Mostafa, Reham M. Abdelfatah, Alshimaa Ezzat ELdahshan, Samar Fawzy Gad, Shimaa K. Mohamed, Mona K. Alawam, Aya Aly Elzeer, Nesma S. Ismail, Sally Elsharkawey, Haneen A. Al-Mazroua, Hatun A. Alomar, Wedad S. Sarawi and Heba S. Youssef
Toxics 2025, 13(5), 355; https://doi.org/10.3390/toxics13050355 - 29 Apr 2025
Abstract
Imidacloprid (IMI) is a widely used insecticide known for its high selectivity toward insects. Ellagic acid (EA) is a plant-derived polyphenolic compound recognized for its therapeutic potential and favorable safety profile in the treatment of various diseases. This study aimed to evaluate the
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Imidacloprid (IMI) is a widely used insecticide known for its high selectivity toward insects. Ellagic acid (EA) is a plant-derived polyphenolic compound recognized for its therapeutic potential and favorable safety profile in the treatment of various diseases. This study aimed to evaluate the therapeutic effects of EA, formulated as novasomes (NOV), against IMI-induced thyroid dysfunction and to investigate the underlying mechanisms. Rats were divided into four equal groups: control, EA-NOV, IMI, and IMI + EA-NOV. Thyroid function was assessed by measuring free triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) levels. Thyroid tissues were examined to evaluate histopathological alterations, as well as to assess the oxidative/antioxidant pathway (Nrf2, SOD, TAC, MDA), inflammatory pathway (IL-1β, TNF-α, NF-κB), apoptotic pathway (Bcl, BAX), and autophagy pathway (PI3K/Akt/mTOR, P53, Beclin-1). Exposure to IMI resulted in impaired thyroid function, the upregulated gene expression of the PI3K/Akt/mTOR pathway, and downregulated P53 expression. Additionally, immunohistochemical staining revealed Beclin-1-mediated autophagy, alongside increased apoptosis, oxidative stress, and elevated levels of inflammatory cytokines. Conversely, EA improved thyroid function and ameliorated histopathological alterations by enhancing autophagy-inducing pathways. Additionally, the alleviation of oxidative stress was evidenced by the increased immunohistochemical staining of Nrf2, which promoted the synthesis and activity of antioxidant enzymes and reduced apoptotic and inflammatory markers. This study proposes the use of EA as a potential protective, naturally occurring phytoceutical against IMI-induced thyroid dysfunction, primarily through the modulation of PI3K/Akt/mTOR-mediated autophagy.
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(This article belongs to the Special Issue Exposure to Endocrine Disruptors and Risk of Metabolic Diseases)
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Potential Health Risk of Microplastic Exposures from Skin-Cleansing Products
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Raluca Maria Bucur (Popa), Cristiana Radulescu, Ioana Daniela Dulama, Raluca Maria Stirbescu, Ioan Alin Bucurica, Andreea Laura Banica and Sorina Geanina Stanescu
Toxics 2025, 13(5), 354; https://doi.org/10.3390/toxics13050354 - 29 Apr 2025
Abstract
This research aims to investigate and quantify the possible presence of microplastics (MPs) in usual skin-cleansing products (i.e., liquid soap, micellar water, and micellar cleansing oil), the most popular from the market in terms of brand and customer confidence. Therefore, optical microscopy and
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This research aims to investigate and quantify the possible presence of microplastics (MPs) in usual skin-cleansing products (i.e., liquid soap, micellar water, and micellar cleansing oil), the most popular from the market in terms of brand and customer confidence. Therefore, optical microscopy and micro-Fourier transform infrared spectroscopy (micro-FTIR) were used to determine the MPs’ number, color, shape, size, and chemical composition. For the first time, the results were correlated with the possible exposure paths (i.e., inhalation, ingestion, or adsorption) to assess the human health risk of the analyzed micellar-based cleansers in terms of chronic total exposure dose to microplastics. Finally, a statistical analysis was added to this study for source prediction of MPs in skin-cleansing samples in terms of morphology, chemical composition, and other factors (i.e., brand, packaging, etc.). The various exposures and toxicities of MPs were assessed in terms of potential health risk, knowing that their toxic effect depends on the polymeric structure strongly linked with the size, shape, and concentration in the products.
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(This article belongs to the Special Issue Health Effects and Toxicology Studies of Emerging Contaminants)
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Long-Term Exposure to Microplastics Promotes Early-Stage Hepatocarcinogenesis Induced by Diethylnitrosamine in Rats by Modulation of Their Gut Microbiota
by
Huina Guo, Jianan Wang, Shaowen Huang, Suren Rao Sooranna, Fangyi Shu and Genliang Li
Toxics 2025, 13(5), 353; https://doi.org/10.3390/toxics13050353 - 29 Apr 2025
Abstract
Hepatocarcinogenesis is linked to environmental factors, with microplastics (MPs) emerging as a global environmental concern that may contribute to liver injury. However, the impact of MPs on the early stages of hepatocarcinogenesis has been largely ignored. Here we investigated the impact of long-term
[...] Read more.
Hepatocarcinogenesis is linked to environmental factors, with microplastics (MPs) emerging as a global environmental concern that may contribute to liver injury. However, the impact of MPs on the early stages of hepatocarcinogenesis has been largely ignored. Here we investigated the impact of long-term MP exposure on the formation of preneoplastic lesions during hepatocarcinogenesis induced by diethylnitrosamine (DEN) in rats. Rats were injected with DEN to induce preneoplastic lesions, and then they were orally administered with 1 µm MPs 0.5 mg/kg body weight per day for 20 weeks. The results revealed that long-term exposure to MPs did not induce the formation of glutathione S-transferase placental form (GST-P)-positive foci as preneoplastic lesions during hepatocarcinogenesis in these animals, thereby indicating non-carcinogenicity. However, MP exposure resulted in a 1-fold increase in both the number and size of GST-P-positive foci in rats initiated with DEN compared to those treated with DEN alone. Accordingly, MP exposure led to a 0.61-fold increase in the index of proliferating cell nuclear antigen (PCNA)-positive cells in DEN-initiated rats when compared to DEN treatment alone. In addition, the composition of the gut microbiota was significantly altered, accompanied by various levels of short-chain fatty acids. Our results suggest that long-term MP exposure can promote pre-neoplastic lesion formation in DEN-induced rats by increased cell proliferation as well as alterations in the gut microbiota and short-chain fatty acid levels. This highlights the potential health risks associated with hepatocarcinogenesis linked to long-term exposure to MPs.
Full article
(This article belongs to the Special Issue Impact of Micro- and Nanoplastics and Protective Dietary Nutrients for Human Health)
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Determination of Multiple Fluorescent Brighteners in Human Plasma Using Captiva EMR-Lipid Clean-Up and LC-MS/MS Analysis
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Yubing Yan, Bowen Liang, Jiawen Yang, Qing Deng, Xiaoying Liang, Hui Chen, Bibai Du and Lixi Zeng
Toxics 2025, 13(5), 352; https://doi.org/10.3390/toxics13050352 - 28 Apr 2025
Abstract
Fluorescent brighteners (FBs) are a class of chemicals extensively used in industrial and consumer products. Their environmental occurrences and potential health risks have raised significant concerns. However, the lack of analytical methods for FBs in human samples has hindered the accurate assessment of
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Fluorescent brighteners (FBs) are a class of chemicals extensively used in industrial and consumer products. Their environmental occurrences and potential health risks have raised significant concerns. However, the lack of analytical methods for FBs in human samples has hindered the accurate assessment of internal exposure levels. Addressing this gap, this study developed and validated a novel method for the simultaneous determination of 13 FBs at trace levels in human plasma using solid-phase extraction combined with HPLC-MS/MS. The method employed EMR-Lipid SPE columns, which can selectively adsorb phospholipids for plasma sample pre-treatment. Detection was achieved through positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) modes. The results showed that all 13 FBs exhibited good linearity within their respective ranges, with correlation coefficients (R2) greater than 0.992. The method quantitation limits (MQLs) of the FBs ranged from 0.012 to 0.348 ng/mL, and the spiked recovery rates ranged from 61% to 98%. The method was successfully applied to analyze 10 adult plasma samples, detecting 10 FBs with total concentrations ranging from 0.221 to 0.684 ng/mL. This study provides a reliable analytical method for determining FBs in human plasma, providing a basis for further research on human internal exposure to FBs and associated health risk assessments.
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(This article belongs to the Special Issue Health Risk Assessment of Exposure to Emerging Contaminants)
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Evaluation of Potential Toxic Elements in Soils from Three Urban Areas Surrounding a Steel Industrial Zone
by
Georgios Charvalas, Aikaterini Molla, Alexios Lolas, Elpiniki Skoufogianni, Savvas Papadopoulos, Evaggelia Chatzikirou, Christina Emmanouil and Olga Christopoulou
Toxics 2025, 13(5), 351; https://doi.org/10.3390/toxics13050351 - 28 Apr 2025
Abstract
The urban zone around the city of Volos, a Greek city with a historically industrialized profile, faces threats arising from Potential Toxic Element (PTE) contamination. The scope of this study is to determine the contamination levels of 10 PTEs in three urban areas
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The urban zone around the city of Volos, a Greek city with a historically industrialized profile, faces threats arising from Potential Toxic Element (PTE) contamination. The scope of this study is to determine the contamination levels of 10 PTEs in three urban areas which are located near the industrial zone in the city of Volos. For this purpose, a total of 30 soil samples from parks, playgrounds and roadsides were collected from the Agios Georgios, Velestino and Rizomilos areas (Magnesia, Central Greece). The sampling was conducted in June 2022 and the concentrations of chromium (Cr), nickel (Ni), copper (Cu), arsenic (As), cadmium (Cd), lead (Pb), iron (Fe), manganese (Mn), cobalt (Co) and zinc (Zn) were measured through inductively coupled plasma mass spectrometry (ICP-MS). The Contamination Factor (CF), Pollution Load Index (PLI) and Geo-accumulation Index (Igeo) revealed moderate pollution in most cases, whereas in some sites the contamination was significant for Ni or for As. Principal Component Analysis showed concomitant changes for some PTEs in Component 1 and for others in Component 2, explaining approximately 67% of the variation. K-means Cluster Analysis showed two distinct groups of PTE-impacted sites within these urban areas. It can be postulated that industrial activities may have a carry-over effect on the soil in residential areas. Frequent monitoring of areas deemed as “contaminated” and time-series data are needed to examine in depth the soil pollution in cities and its possible shifts in relation to the changes in industrialization status in the extended urban areas.
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(This article belongs to the Special Issue Soil Heavy Metal Pollution and Human Health)
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Oral Supplementation with Modified Natural Clinoptilolite Protects Against Cadmium Toxicity in ICR (CD-1) Mice
by
Michaela Beltcheva, Yana Tzvetanova, Peter Ostoich, Iliana Aleksieva, Tsenka Chassovnikarova, Liliya Tsvetanova and Rusi Rusew
Toxics 2025, 13(5), 350; https://doi.org/10.3390/toxics13050350 - 27 Apr 2025
Abstract
For the first time, this study investigates in vivo the potential of Na-modified natural clinoptilolite to mitigate cadmium toxicity in ICR mice, a model relevant to human health. We enhanced natural clinoptilolite to improve its cadmium (Cd) exchange capacity. Mice were exposed to
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For the first time, this study investigates in vivo the potential of Na-modified natural clinoptilolite to mitigate cadmium toxicity in ICR mice, a model relevant to human health. We enhanced natural clinoptilolite to improve its cadmium (Cd) exchange capacity. Mice were exposed to environmentally realistic cadmium nitrate Cd(NO3)2 doses in their drinking water. The detoxification efficacy of the mineral was evaluated over 45 days in four groups: control (no supplementation), Cd(NO3)2 only, clinoptilolite only, and a combination of Cd(NO3)2 and clinoptilolite. We assessed Cd bioaccumulation in the liver and kidneys, genotoxicity (micronucleus assay), hematological parameters, and oxidative stress markers. Cd exposure resulted in significant bioaccumulation, reduced growth, changes in erythrograms, DNA damage, and oxidative stress. Mice receiving clinoptilolite alone showed a significant increase in body mass. Modified clinoptilolite led to a nearly 48% reduction in Cd accumulation and a 30% increase in Cd excretion in the Cd-plus-clinoptilolite group compared to the Cd-only group. Erythrogram and leukogram parameters returned to near-normal levels, with reductions in malondialdehyde (MDA) and increases in glutathione (GSH) observed by the end of the experiment. No elevated levels of micronuclei were found following clinoptilolite supplementation. These results suggest that modified clinoptilolite may be a cost-effective detoxifier in Cd-polluted regions.
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(This article belongs to the Section Metals and Radioactive Substances)
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A Deep Learning Algorithm for Multi-Source Data Fusion to Predict Effluent Quality of Wastewater Treatment Plant
by
Shitao Zhang, Jiafei Cao, Yang Gao, Fangfang Sun and Yong Yang
Toxics 2025, 13(5), 349; https://doi.org/10.3390/toxics13050349 - 27 Apr 2025
Abstract
The operational complexity of wastewater treatment systems mainly stems from the diversity of influent characteristics and the nonlinear nature of the treatment process. Together, these factors make the control of effluent quality in wastewater treatment plants (WWTPs) difficult to manage effectively. To address
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The operational complexity of wastewater treatment systems mainly stems from the diversity of influent characteristics and the nonlinear nature of the treatment process. Together, these factors make the control of effluent quality in wastewater treatment plants (WWTPs) difficult to manage effectively. To address this challenge, constructing accurate effluent quality models for WWTPs can not only mitigate these complexities, but also provide critical decision support for operational management. In this research, we introduce a deep learning method that fuses multi-source data. This method utilises various indicators to comprehensively analyse and predict the quality of effluent water: water quantity data, process data, energy consumption data, and water quality data. To assess the efficacy of this method, a case study was carried out at an industrial effluent treatment plant (IETP) in Anhui Province, China. Deep learning algorithms including long short-term memory (LSTM) and gated recurrent unit (GRU) were found to have a favourable prediction performance by comparing with traditional machine learning algorithms (random forest, RF) and multi-layer perceptron (MLP). The results show that the R2 of LSTM and GRU is 1.36%~31.82% higher than that of MLP and 9.10%~47.75% higher than that of traditional machine learning algorithms. Finally, the RReliefF approach was used to identify the key parameters affecting the water quality behaviour of IETP effluent, and it was found that, by optimising the multi-source feature structure, not only the monitoring and management strategies can be optimised, but also the modelling efficiency of the model can be further improved.
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(This article belongs to the Special Issue Monitoring and Risk Assessment of Emerging Chemical Contaminants in the Aquatic Environment)
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Solutions to the Dilemma of Antibiotics Use in Livestock and Poultry Farming: Regulation Policy and Alternatives
by
Shimei Zheng, Yongchao Li, Cuihong Chen, Naiyu Wang and Fengxia Yang
Toxics 2025, 13(5), 348; https://doi.org/10.3390/toxics13050348 - 27 Apr 2025
Abstract
While the application of antibiotics in livestock production has undeniably propelled the rapid growth of animal husbandry, the escalating crisis of antimicrobial resistance stemming from antibiotic use poses significant threats to global public health and sustainable agricultural development. To address this critical challenge,
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While the application of antibiotics in livestock production has undeniably propelled the rapid growth of animal husbandry, the escalating crisis of antimicrobial resistance stemming from antibiotic use poses significant threats to global public health and sustainable agricultural development. To address this critical challenge, multifaceted strategies have been implemented through coordinated policy interventions and scientific innovations. This review systematically examines two pivotal dimensions: (1) evolving regulatory frameworks governing antibiotic usage and (2) emerging non-antibiotic alternatives, with a particular focus on their implementation mechanisms and technological maturation. The analysis of transnational antibiotic governance encompasses comparative policy evolution in the European Union, the United States, and China. These regulatory paradigms address critical control points including registration management policies, usage monitoring systems, and integrated surveillance programs. Concerning technological alternatives, six categories of antibiotic substitutes are critically evaluated: Chinese herbal formulations, plant-derived essential oils, antimicrobial peptides, microecological agents, acidifiers, and enzyme preparations. These solutions are functionally categorized into prophylactic agents (enhancing disease resilience) and zootechnical additives (optimizing feed efficiency). These antibiotic alternatives demonstrate certain efficacy in alleviating the challenges of antibiotic overuse, yet they still face multiple implementation barriers. Further investigations are warranted to establish standardized efficacy evaluation protocols and conduct technoeconomic feasibility assessments under commercial-scale production conditions. Ultimately, resolving the antibiotic dilemma requires synergistic collaboration between regulatory bodies, pharmaceutical innovators, and academic researchers. This work emphasizes the crucial interplay between evidence-based policymaking and technological advancement in shaping sustainable livestock production systems.
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(This article belongs to the Special Issue Antibiotics and Resistance Genes in Environment)
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Response to Oxidative Stress Induced by Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine in Differentiated PC12 Cells
by
Cunzhi Li, Xiaoqiang Lv, Zhiyong Liu, Hui Deng, Ting Gao, Huan Li, Xinying Peng, Airong Qian, Junhong Gao and Lifang Hu
Toxics 2025, 13(5), 347; https://doi.org/10.3390/toxics13050347 - 27 Apr 2025
Abstract
Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is a globally recognized energetic material that widely used in industrial, mining, and military fields. Like hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and other nitramine compounds, HMX has also been reported to exhibit neurotoxicity. However, the molecular mechanisms underlying the toxic effects of HMX remain
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Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is a globally recognized energetic material that widely used in industrial, mining, and military fields. Like hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and other nitramine compounds, HMX has also been reported to exhibit neurotoxicity. However, the molecular mechanisms underlying the toxic effects of HMX remain poorly understood. Therefore, this study aims to investigate the neurotoxicity induced by HMX by adopting PC12 cells. The results show that HMX treatment decreased cell viability and upregulated the intracellular free calcium ions (Ca2+) in PC12 cells. Furthermore, HMX caused aggravated oxidative stress in PC12 cells, as evidenced by the upregulations of reactive oxygen species (ROS) and malondialdehyde (MDA). Intracellular biochemical assays demonstrated that HMX induced loss of mitochondrial membrane potential in PC12 cells. Notably, altered expression of brain-derived neurotrophic factor (BDNF) and ionotropic glutamate receptors (iGluRs), as well as an abnormal transcription profile, were also observed in PC12 cells treated by HMX. These findings suggest that HMX exerts toxic effects on PC12 cells, involved in oxidative stress, and disturbances in Ca2+ and BDNF, accompanied by aberrant iGluRs. Overall, the present study helps us better understand the health hazards associated with HMX and provides valuable insights for developing the health protection standards related to HMX exposure.
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(This article belongs to the Section Neurotoxicity)
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Safety and Sublethal Effects of Acaricides on Stethorus punctillum, a Neglected Key Natural Enemy of Phytophagous Mites
by
Huan Guo, Dawei Zhang, Haoyu Wang, Xiaoling He, Senshan Wang and Yanhui Lu
Toxics 2025, 13(5), 346; https://doi.org/10.3390/toxics13050346 - 26 Apr 2025
Abstract
Stethorus punctillum Weise, a predatory beetle attacking phytophagous mites in northwest China, remains underutilized for biological control. Current over-reliance on synthetic acaricides necessitates evaluation of their non-target effects on this predator, particularly their safety and sublethal impacts. Here, we assessed the acute toxicity
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Stethorus punctillum Weise, a predatory beetle attacking phytophagous mites in northwest China, remains underutilized for biological control. Current over-reliance on synthetic acaricides necessitates evaluation of their non-target effects on this predator, particularly their safety and sublethal impacts. Here, we assessed the acute toxicity of four acaricides to S. punctillum in laboratory bioassays and then focused on sublethal impacts of abamectin on adult predation efficiency and lifespan. Based on the LC50 values, the acute toxicities of the four acaricides tested against S. punctillum larvae and adults both ranked as follows (from greatest to least): abamectin > pyridaben > spirotetramat > petroleum oil. All acaricides exhibited selective toxicity (STR: 2.16–182.49) with moderate to low risk (SF: 0.46–8.71). Notably, petroleum oil, despite showing the lowest acute toxicity to S. punctillum, posed the highest risk to larvae (SF: 0.46–0.77). Abamectin exposures at LC20 or LC50 significantly compromised S. punctillum adults, prolonging prey handling time (females: 33–100%; males: 40%), reducing maximum daily predation (females: 25–50%; males: 29%), and shortening adult lifespan (females: 2.34–3.17 days; males: 3.95–5.08 days). This study assessed the safety of four commonly used acaricides for S. punctillum, revealing abamectin-induced impairments to key biological traits. Our findings offer critical insights for risk-aware acaricide selection and integrated spider mite management strategies in agroecosystems in northwest China.
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(This article belongs to the Section Agrochemicals and Food Toxicology)
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