Toxicity Assessment Research Articles

A Comprehensive Study of the Degradation of Veterinary Antibiotics by Non-Thermal Plasma: Computational, Experimental, and Biotoxicity Assessments

Water quality is threatened by numerous pollutants, among which antibiotics are of great concern due to their widespread use and unaltered excretion, leading to water contamination and fostering antibiotic resistance. To comprehensively address sustainable water remediation, herein, the susceptibility to non-thermal plasma degradation of two veterinary antibiotics (Oxytetracycline (OTC) and Lincomycin (LNC)) are compared in an integral approach, including computational analyses, plasma irradiation assays, and a byproduct toxicity assessment. The computational assessment was performed by evaluating the ionization potential (IP) obtained from Density Functional Theory calculations and determining the antibiotics’ susceptible sites for radical attack. Plasma irradiation achieved nearly complete degradation (~100%) of both compounds with the initial concentration of 1 mg L−1, while 60% degradation was observed when the starting concentration was 10 mg L−1. The mineralization rates were 21% and 31% for OTC and LNC, respectively. The degradation profiles followed similar trends, as expected from their comparable IP values. After treatment, the solution exhibited lower biotoxicity compared to the original antibiotics. Therefore, this work represents a step forward in addressing one of the key environmental challenges of our time and encourages further extending the analysis towards the remediation of water polluted with many other organic compounds.

Assessment of myco-fabricated Al2O3 NPs toxicity on cancer cells and pathogenic microbes by suppression of bacterial metabolic key enzymes.

There has been a recent change in global attention towards addressing antimicrobial resistance (AMR) as a result of the concerning increase in mortality rates. Nanomaterials have become highly favorable options for a wide range of industrial and biological uses. The objective of this study was to produce aluminum oxide nanoparticles (Al2O3 NPs) using a crude extract from the fungus Aspergillus sp. WAH23, and then analyze the nanoparticles using UV-analysis, electron microscopy (TEM and SEM), and (FT-IR) and X-ray diffraction (XRD). Results revealed that formed nanoparticles are spherical with an average size of 8.5 nm. XRD analysis confirmed the crystalline nature of the synthesized Al2O3 NPs. The Al2O3 nanoparticles exhibited antibacterial properties against a wide range of pathogenic microbes. The antibacterial efficacy of these nanoparticles on the examined bacterial strains was exhibited through their ability to hinder several metabolic processes, including phosphofructokinase (PFK), enolase, and glutamine synthetase. Additionally, the nanoparticles increased the activity of NADH-oxidase, the content of MDA, and the formation of H2O2. The study also examined the anticancer properties of Al2O3 nanoparticles on various types of cancer cells.

Toxicity assessment following conventional radiation therapy and pulsed low dose rate radiation therapy: an in vivo animal study.

Pulsed low dose rate radiotherapy (PLDR) is a new radiation delivery method, in which the fractional dose is divided into sub-fractional doses with periodical time breaks in between. The goal of our study is to assess the toxicity on healthy tissues resulting from PLDR as compared to conventional radiotherapy (CRT) using the same physical X-ray dose. We analyzed the weight and survival time for CRT and PLDR groups and studied the inflammatory cytokine transforming Growth Factor-β (TGF-β), usually released following irradiation. Histopathological and immunohistochemical analyses were conducted for intestinal and bone marrow tissues from rats subjected to 8Gy whole- body irradiation using CRT and PLDR techniques. We investigated genotoxicity by performing a comet assay (CA) in splenic tissues. Our findings showed an improvement in survival time with PLDR versus CRT by 82%.The mean survival time for CRT rats' group was 6.3days, while it was 35.9days for PLDR group.The weight of CRT group decreased gradually by 3.7%, while weight of PLDR group increased gradually by 2.4%.CRT resulted in more cellular atrophy in bone marrow and intestinal tissues than in PLDR treatments as shown by hematoxylin and eosin staining analysis. In addition, the transforming growth factor-β (TGF-β) expression in bone marrow and intestinal tissues of CRT was higher than those expressed in tissues from PLDR as demonstrated by the Immuno reactive score (IRS). It was10(0.53) and 9.8(0.55) for BM and intestinal tissues, respectively from CRT group and 5.8(0.63) for PLDR for both tissues. The measured CA parameters were larger with CRT compared to PLDR, where the Tail Length (TL), Tail DNA % (TD%) and Tail Moment (TM) measurements were 25.4(3.4), 56.5(7.6)% and 20.5(3.5) for CRT, 7.3(1.9), 30.0(7.2)% and 5.7(1.8) for PLDR, with P value 0.000064, 0.0004 and 0.00017, respectively. This study indicates that PLDR can reduce the toxicity on normal tissues compared to CRT.

Progress in the study of toxic effects of drugs on the male reproductive system

This paper provides a comprehensive summary of the toxic effects of drugs on the male reproductive system, with a special focus on the mechanisms of testicular and sperm damage caused by chemotherapeutic agents, antibiotics, and immunosuppressants. Drug-induced reproductive toxicity usually manifests through multiple pathways including direct injury, interference with hormone regulation, oxidative stress, and DNA damage. These mechanisms can lead to impaired spermatogenesis, decreased testicular function, and long-term infertility, thereby seriously affecting male reproductive health. Specifically, chemotherapeutic drugs, such as cisplatin and cyclophosphamide, have been widely documented to cause direct damage to the testes, leading to significant decreases in sperm quantity and quality. Antibiotics and nonsteroidal anti-inflammatory drugs also negatively affect reproductive function by affecting mitochondrial function and inducing oxidative stress in the testicular cells. Although important advances have been made in recent years in the study of drug-induced reproductive toxicity, further exploration is needed to assess the variability of individual responses to drugs and develop long-term protective measures. Future research should focus on developing accurate toxicity assessment methods, customized therapeutic regimens, and enhanced fertility protection strategies, such as the use of antioxidants and methods for the cryopreservation of testes and sperm. Interdisciplinary collaboration will provide new solutions for balancing disease treatment and fertility preservation, especially in the use of high-risk drugs, such as anticancer therapies, where achieving both efficacy and reproductive health will be an important clinical challenge.

Toxicity assessment and bioimaging potential of carbon dots synthesized from banana peel in zebrafish model

Zebrafish serve as a pivotal model for bioimaging and toxicity assessments; however, the toxicity of banana peel-derived carbon dots in zebrafish has not been previously reported. The aim of this study was to assess the toxicity of carbon dots derived from banana peel in zebrafish, focusing on two types prepared through hydrothermal and pyrolysis methods. Banana peels were synthesized using hydrothermal and pyrolysis techniques and then compared for characteristics, bioimaging ability, and toxicity in zebrafish as an animal model. Pyrolysis-derived banana peel and hydrothermal-derived banana peel showed blue emission under ultraviolet light, indicating excitation-dependent behavior. To test their potential application for bioimaging, a soaking method was used using zebrafish that showed fluorescence intensity in the eyes, abdomen, and tail of zebrafish. Toxicity comparison showed that pyrolysis-derived banana peel had lower toxicity with 50% lethal concentrations (LC50) of 1707.3 ppm than hydrothermal-derived banana peel (LC50 993 ppm) in zebrafish. Both types of carbon dots showed significant differences (p<0.05) in hatching rates at 96 and 120 hours of exposure. Of the two methods for carbon dot synthesis from banana peel, the pyrolysis method had a higher toxicity threshold than the hydrothermal method, as indicated by the LC50 value and the number of zebrafish embryos that died, hatched delayed, and experienced malformation during their development.

Long-term outcomes and prognostic factors of short-course radiotherapy (SCRT) in rectal cancer: a monocentric retrospective study.

To evaluate efficacy and tolerance of short-course radiotherapy (SCRT) prior to possible chemotherapy (CHT) and surgery in 64 patients with locally advanced rectal cancer, in terms of acute and early late toxicity and survival outcomes with prognostic factors. Sixty-four patients affected by rectal tumor were treated from 2008 to 2023 radiation therapy, with a total dose of 25Gy in 5 fractions. The Kaplan-Meier method was used to estimate the rates of overall survival (OS), cancer specific survival (CSS), local control (LC), disease free survival (DFS) and metastasis free survival (MFS). Univariate analysis for prognostic factors was performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios. Toxicity assessment has been considered in acute and in early late for gastrointestinal (GI), genitourinary (GU) districts. Median follow-up was 49.6months. The median OS was 65months with 1-year, 2-year and 5-year OS at 90.6%, 77.7% and 60% respectively. CSS at the 1-year, 2-year and 5-year was 98.3%, 96.2% and 86.2% respectively. LC at 1-year, 2-year and 5-year was 93.4%, 89.4% and 87.2% respectively. DFS at the 1-year, 2-year and 5-year was 93.4%, 89% and 87% respectively. The status of lymph nodes at diagnosis was a prognostic factor in term of LC and DFS. Acute GI toxicity was G1 in 10 (15.6%) patients. Five (7.8%) patients had a G1 acute GU toxicity. Fifteen (23.4%) patients developed chronic GI toxicities. SCRT is an effective treatment in patients with rectal cancer and provides good outcomes with very low rates of toxicity profile.

In vivo assessment of topically applied silver nanoparticles on entire cornea: comprehensive FTIR study

Silver nanoparticles (AgNPs) have gained attention in medicine for their potent antibacterial, antiviral, and anti-inflammatory properties. The use of silver nanoparticles in ophthalmic solutions raises concerns regarding potential toxicity of nanoparticles to ocular tissues, such as the cornea, conjunctiva, and retina, which necessitates further toxicity assessments aiding in the development of safer ophthalmic solutions. This study investigates the impact of AgNPs on corneal tissue using ophthalmic investigations, Fourier transform infrared (FTIR) spectroscopy, and chemometric analyses. Three concentrations of AgNPs (0.48 µg/mL, 7.2 µg/mL, and 15.5 µg/mL) were topically applied twice daily for 10 days, synthesized biologically by reducing silver nitrate with almond kernels water extract. Corneas, obtained by cutting 2–3 mm below the ora serrata, were analyzed with FTIR spectroscopy and subjected to chemometric analyses. Results reveal AgNPs’ influence on constituents with OH and NH groups, affecting corneal lipids and reducing the lipid saturation index. AgNPs alter both bulk and interfacial water, leading to changes in corneal hydration thus modifying corneal physico-chemical properties. The influence extends to the water environment around proteins and lipids, releasing bound water from phospholipids and disrupting hydrogen bonding networks around proteins. In conclusion, the applied AgNPs concentrations can be linked to dry eye onset.

Computer prediction of toxicity of new S-alkyl derivatives of 1,2,4-triazole

1,2,4-Triazole derivatives are of researchers’ significant interest due to their diverse biological properties, such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. The integration of a 2-bromo-4-fluorophenyl fragment into the triazole structure can significantly enhance these activities. However, the evaluation of the toxicity of such compounds remains a critically important aspect for their practical application. To reduce the time and cost of experimental studies, QSAR (Quantitative Structure-Activity Relationship) methods are actively used, allowing the prediction of toxicity based on the molecular structure of compounds. Aim of the study. To assess the toxicity of new S-derivatives of 5-(2-bromo-4-fluorophenyl)-4-R-1,2,4-triazol-3-thiols using the QSAR method, specifically to predict acute toxicity parameters (LD50), and to determine the influence of different (length) radicals on the toxicity of these compounds. Materials and methods. The objects of the virtual study were derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazol-3-thiols. They were evaluated at the Department of Toxicological and Inorganic Chemistry of the Zaporizhzhia State Medical and Pharmaceutical University. The toxicity assessment was conducted using the nearest neighbor method via the Toxicity Estimation Software Tool (TEST). The prediction of the lethal dose (LD50) for rats was based on the structural similarity of the studied compounds with known substances, for which experimental toxicity data are available. Results. The conducted QSAR analysis demonstrated that structural changes in S-derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazol-3-thiols significantly affect the predicted toxicity. The primary factor influencing the changes in LD50 values is the variation of radicals at the 5th position of the triazole ring. Conclusions. The results of the study showed, that the toxicity of new S-alkyl derivatives of triazol-3-thiols depends on the type of alkyl substituent. Compounds with propyl to heptyl fragments exhibit increased toxicity, while derivatives with thiol, octyl, nonyl, and decyl residues are characterized by lower toxicity.

Cell Painting and Chemical Structure Read-Across Can Complement Each Other for Rat Acute Oral Toxicity Prediction in Chemical Early Derisking.

Early derisking decisions in the development of new chemical compounds enable the identification of novel chemical candidates with improved safety profiles. In vivo studies are traditionally conducted in the early assessment of acute oral toxicity of crop protection products to avoid compounds, which are considered "very acutely toxic", with an in vivo lethal dose of 50% (LD50) ≤ 60 mg/kg body weight. Those studies are lengthy and costly and raise ethical concerns, catalyzing the use of nonanimal alternatives. The objective of our analysis was to assess the predictive efficacy of read-across approaches for acute oral toxicity in rats, comparing the use of chemical structure information, in vitro biological data derived from the Cell Painting profiling assay on U2OS cells, or the combination of both. Our findings indicate that the classification of compounds as very acute oral toxic (LD50 ≤ 60 mg/kg) or not is possible using a read-across approach, with chemical structure information, morphological profiles, or a combination of both. When classifying compounds structurally similar to those in the training set, the chemical structure was more predictive (balanced accuracy of 0.82). Conversely, when the compounds to be classified were structurally different from those in the training set, the morphological profiles were more predictive (balanced accuracy of 0.72). Combining the two models allowed for the classification of compounds structurally similar to those in the training set to slightly improve the predictions (balanced accuracy of 0.85).

Electrochemical degradation of aromatic organophosphate esters: Mechanisms, toxicity changes, and ecological risk assessment

Aromatic organophosphate esters (AOPEs), including triphenyl phosphate (TPHP), tricresyl phosphate (TCP), and 2-ethylhexyl diphenyl phosphate (EHDPP), pose significant health and ecological risks. Electrochemical advanced oxidation process (EAOP) is effective in removing refractory pollutants. In this study, the degradation performance and detoxication ability of AOPEs by EAOP were investigated. Hydroxylation, oxidation, and bond cleavage products were identified as major degradation products (DPs) due to the reaction with ·OH and O₂·-. Toxicity assessments using ecological structure activity relationship (ECOSAR) model and flow cytometry (FCM) revealed the cytotoxicity and aquatic toxicity for DPs were significantly decreased. 16S rRNA gene sequencing of sediment exposure to AOPEs and DPs were applied to assess ecological toxicity, and results showed reduced bacterial richness and diversity with EHDPP and TCP, while TPHP slightly enhanced richness. AOPEs and DPs altered bacterial genera involved in carbon, nitrogen, sulfur cycling and organic compound degradation. Bacterial community assembly suggested elevated stochastic processes and reduced ecotoxicity, confirming AOPEs can be effectively detoxified by 10-min EAOP treatment. Molecular ecological network analysis indicated increased complexity and stability of bacterial communities with DPs. These findings comprehensively revealed the toxicity of AOPEs and their DPs and provided the first evidence of effective degradation and detoxification by EAOP from ecotoxicological perspective.

An assessment of radiological risks and chemical toxicity due to naturally occurring radionuclides in surface waters of a semiarid region in Brazil

Santa Quitéria, a city in northeastern Brazil, faces significant challenges in ensuring the availability of potable water due to its semi-arid climate and limited water resources. This study investigates the radiological quality of surface waters commonly used by the population for drinking and by animals for hydration. Water samples were collected from six different locations over a 25-month period, and the concentrations of naturally occurring radionuclides were measured using spectrophotometric analysis, total alpha, and gross beta counting. The mean activity concentrations of Unat, 226Ra, 210Pb, 232Th, and 228Ra were determined to be 9.89∙10−2, 5.35∙10−2, 5.86∙10−2, 6.89∙10−3, and 2.81∙10−3 Bq∙L−1, respectively. Statistical methods, such as cluster and factor analysis, were applied to understand the distribution patterns of these radionuclides. The study also estimated dose rates from radionuclide intake, with a maximum value of 108.5 µSv·y−1, and compared the results against dose limits set by relevant organizations. Furthermore, the risks of morbidity and mortality from radionuclide intake were assessed, revealing the need for optimization at one sampling point where the health risks exceeded intervention thresholds.

Acute Oral Toxicity Assessment of Repchol in Wistar Rats: A Liver-protective Herbal Premix for Poultry

The present study was conducted for the assessment of acute oral toxicity and safety analysis of Repchol Premix (M/s Ayurvet Limited) according to OECD-423 guidelines. Six adult Wistar rats, weighing 113-134 g, were used for the study. After oral administration of Repchol@ 300 and 2000mg/kg body weight, the animals were observed for manifestation of toxic effect and death upto14 days. Evaluation of safety analysis and toxicity was assessed on the basis of presence of mortality or toxicity symptoms. Every animal in group served as its own control. At the end of experiment blood biochemical parameters and histopathological changes in heart, liver, kidney and lung were studied. The results showed that Repchol did not produce toxic effects or mortality during the experimental period. The body weight changes observed for two weeks were in the normal range. In Repchol treated rats biochemical parameters like AST, ALT, ALP and creatinine were observed within normal range and in histopathological examination no significant microscopic alterations were observed. Thus, the observations indicated that Repchol Premix did not produce toxic effect or acute oral toxicity and the LD50 of compound is beyond 2000mg/kg.

A hybrid system based on the combination of adsorption, electrocoagulation, and wetland treatment for the effective remediation of industrial wastewater from underground coal gasification (UCG)

The study verified the effectiveness of treating post-process underground coal gasification (UCG) wastewater, containing high loads of inorganic and organic pollutants, using constructed wetlands (CW) enhanced by hybrid adsorption and electrocoagulation (EC) techniques. Four different system configurations were tested: wetland, EC/wetland, adsorbent/wetland, and EC/adsorbent/wetland. Each experiment lasted 60 days. The feed and effluents from each treatment step were analysed for their basic physicochemical parameters such as metals and trace elements, phenols, sulphides, cyanides, total organic carbon (TOC), chemical oxygen demand (COD), biological oxygen demand (BOD), benzene, toluene, ethylene, xylene (BTEX), and polyaromatic hydrocarbons (PAHs).Systems with electrocoagulation proved to be effective in the case of metal removal. The best results were obtained for Fe, Ni, Sb and As (up to 96%, 98%, 94% and 82% respectively). The systems were ineffective in removing Mn. All tested systems showed the greatest effectiveness in the treatment of wastewater from phenols, BTEX and CN (almost 100% removal). CWs without preliminary electrocoagulation showed practically 100% effectiveness in removing BTEX after 14 days of treatment. Electrocoagulation was particularly effective in reduction of large quantity of PAH compounds (from 1228 μg/l to below 0.050 μg/l). Effective toxicity reduction from V class to II class after 60 days in comparison with meeting the requirements contained in the Best Available Techniques (BAT) document, showed that all tested systems were favorable in terms of UCG wastewater treatment. A significant decrease in toxicity was observed in just 14 days (around 90% reduction of toxicity measured in TU values for systems without adsorbent and around 75% for systems with adsorbent). The wastewater were still toxic due to the formation of degradation intermediates of organic compounds (BTEX, PAHs, phenol compounds), despite a significant decrease in the concentration of contaminants, therefore toxicity assessment should be one of the evaluation criteria for industrial wastewater treatment.

Sonophotocatalytic degradation of rhodamine B dye using Zr doped ZnO nanoparticles: Kinetic study and toxicity assessment

This study investigates sonophotocatalysis for the oxidation of Rhodamine B (RhB) dye using Zr doped ZnO nanoparticles. The synthesized nanoparticles were characterized by scanning electron microscope, Fourier-transform infrared, X-ray diffraction, Brunauer Emmett-Teller, thermogravimetric analysis, and photoluminescence. The hybrid sonophotocatalysis system achieved 98.73 ± 1.25% degradation of RhB under the conditions: RhB dye concentration = 10 ppm, 4 wt% of Zr doped ZnO = 0.1 g, reaction temperature = 30 °C, time = 60 min, pH = 7. A kinetic model was developed to predict the efficiency of RhB degradation through intrinsic elementary chemical reactions. The high coefficient of determination (R2 = 0.96) indicates the model's prediction accuracy in describing the degradation kinetics of RhB within sonophotocatalysis system. The electrical energy per order (EEO) analysis demonstrated that US + UVC + 4 wt% of Zr doped ZnO significantly reduced EEO (1055 kWh m−3 order−1). The synergy index for this combination was approximately 1.60, demonstrating a significant synergistic effect. Density Functional Theory (DFT) studies were utilized to propose the most probable degradation pathway, identifying reactive sites and potential byproducts. The simulations revealed the central carbon atom (1C site) as highly susceptible to radical attacks, indicating potential decolorization pathways such as N-de-ethylation, chromophore cleavage, and ring opening. Toxicity assessments of both the parent dye and its intermediates were conducted using ECOSAR (Ecological Structure Activity Relationship) to evaluate their ecological impacts. The combination of experimental results and kinetic modeling and simulations offers a deep understanding of RhB degradation complexities, driving advancements in sustainable water treatment technologies.

Automated acute skin toxicity scoring in a mouse model through deep learning.

This study presents a novel approach to skin toxicity assessment in preclinical radiotherapy trials through an advanced imaging setup and deep learning. Skin reactions, commonly associated with undesirable side effects in radiotherapy, were meticulously evaluated in 160 mice across four studies. A comprehensive dataset containing 7542 images was derived from proton/electron trials with matched manual scoring of the acute toxicity on the right hind leg, which was the target area irradiated in the trials. This dataset was the foundation for the subsequent model training. The two-step deep learning framework incorporated an object detection model for hind leg detection and a classification model for toxicity classification. An observer study involving five experts and the deep learning model, was conducted to analyze the retrospective capabilities and inter-observer variations. The results revealed that the hind leg object detection model exhibited a robust performance, achieving an accuracy of almost 99%. Subsequently, the classification model demonstrated an overall accuracy of about 85%, revealing nuanced challenges in specific toxicity grades. The observer study highlighted high inter-observer agreement and showcased the model's superiority in accuracy and misclassification distance. In conclusion, this study signifies an advancement in objective and reproducible skin toxicity assessment. The imaging and deep learning system not only allows for retrospective toxicity scoring, but also presents a potential for minimizing inter-observer variation and evaluation times, addressing critical gaps in manual scoring methodologies. Future recommendations include refining the system through an expanded training dataset, paving the way for its deployment in preclinical research and radiotherapy trials.

Bridging organ transcriptomics for advancing multiple organ toxicity assessment with a generative AI approach

Translational research in toxicology has significantly benefited from transcriptomic profiling, particularly in drug safety. However, its application has predominantly focused on limited organs, notably the liver, due to resource constraints. This paper presents TransTox, an innovative AI model using a generative adversarial network (GAN) method to facilitate the bidirectional translation of transcriptomic profiles between the liver and kidney under drug treatment. TransTox demonstrates robust performance, validated across independent datasets and laboratories. First, the concordance between real experimental data and synthetic data generated by TransTox was demonstrated in characterizing toxicity mechanisms compared to real experimental settings. Second, TransTox proved valuable in gene expression predictive models, where synthetic data could be used to develop gene expression predictive models or serve as “digital twins” for diagnostic applications. The TransTox approach holds the potential for multi-organ toxicity assessment with AI and advancing the field of precision toxicology.

Balancing Fertility Preservation and Treatment Efficacy in (Neo)adjuvant Therapy for Adolescent and Young Adult Breast Cancer Patients: a Narrative Review.

Adolescent and young adult (AYA) breast cancer survivors face a significant risk of infertility due to the gonadotoxic effects of (neo)adjuvant therapy, which complicates their ability to conceive post-treatment. While (neo)adjuvant therapy primarily aims to improve recurrence-free and overall survival, fertility preservation strategies should also be considered for young patients. This narrative review explores recent advancements in fertility preservation techniques, such as oocyte, embryo, and ovarian tissue cryopreservation, and evaluates the feasibility of modifying breast cancer (neo)adjuvant therapy to preserve fertility without compromising survival outcomes. Our review highlights that clinical trials with co-primary endpoints of oncological safety and fertility preservation are limited, and substituting standard treatment regimens solely for fertility preservation is currently not recommended. Nevertheless, new clinical studies have emerged that either exclude highly ovarian-toxic agents, such as cyclophosphamide, or omit adjuvant therapy altogether, even if fertility preservation is not their primary endpoint. Unfortunately, many of these trials have not evaluated ovarian toxicity. Notably, since 2020, major oncology organizations, including the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO) have advocated for the routine assessment of ovarian toxicity in all clinical trials. The review underscores the importance of incorporating ovarian toxicity as a standard endpoint in future trials involving premenopausal breast cancer patients to identify treatment regimens that can effectively balance fertility preservation with treatment efficacy.

Unveiling the interspecies correlation and sensitivity factor analysis of rat and mouse acute oral toxicity of antimicrobial agents: first QSTR and QTTR Modeling report

Abstract This study aims to identify toxic potential and environmental hazardousness of antimicrobials. In this regard, the available experimental toxicity data with rat and mouse acute oral toxicity have been gathered from ChemID Plus database (n = 202) and subjected to data curation. Upon the data curation 51 and 68 compounds were left for the rat and mouse respectively for the modeling. The quantitative structure toxicity relationship (QSTR) and interspecies correlation analysis by quantitative toxicity-toxicity relationship (QTTR) modeling was approached in this study. The models were developed from 2D descriptors under OECD guidelines by using multiple linear regressions (MLR) with genetic algorithm (GA) for feature selection as a chemometric tool. The developed models were robust (Q2LOO = 0.600–0.679) and predictive enough (Q2Fn = 0.626–0.958, CCCExt = 0.840–0.893). The leverage approach of applicability domain (ad) analysis assures the model’s reliability. The antimicrobials without experimental toxicity values were classified as high, moderate and low toxic based on prediction and ad. The occurrence of the same classification from QSTR and QTTR models revealed the reliability of QTTR models.Finally, the applied “sensitivity factor analysis” typifies the sensitivity of chemicals toward each species. Overall, the first report will be helpful in the toxicity assessment of upcoming antimicrobials in rodents.

Microbial degradation mechanisms of the neonicotinoids acetamiprid and flonicamid and the associated toxicity assessments

Extensive use of the neonicotinoid insecticides acetamiprid (ACE) and flonicamid (FLO) in agriculture poses severe environmental and ecological risks. Microbial remediation is considered a feasible approach to address these issues. Many ACE-and FLO-degrading microorganisms have been isolated and characterized, but few reviews have concentrated on the underlying degradation mechanisms. In this review, we describe the microbial degradation pathways of ACE and FLO and assess the toxicity of ACE, FLO and their metabolites. Especially, we focus on the enzymes involved in degradation of ACE and FLO, including cytochrome P450s, nitrile hydratases, amidases, and nitrilases. Those studies reviewed here further our understanding of the enzymatic mechanisms of microbial degradation of ACE and FLO, and aid in the application of microbes to remediate environmental ACE and FLO contamination.

PEPITA: Parallelized High-Throughput Quantification of Ototoxicity and Otoprotection in Zebrafish Larvae.

Drug-induced hearing injury (ototoxicity) is a common, debilitating side effect of many antibiotic regimens that can be worsened by adverse drug interactions. Such adverse drug interactions are often not detected until after drugs are already on the market because of the difficulty of measuring all possible drug combinations. While in vivo mammalian assays to screen for ototoxic damage exist, they are currently time-consuming, costly, and limited in throughput, which limits their utility in assessing drug interaction outcomes. To facilitate more rapid quantification of ototoxicity and assessment of adverse drug interactions that impact ototoxicity, we have developed a high-throughput workflow we call parallelized evaluation of protection and injury for toxicity assessment (PEPITA). PEPITA uses zebrafish larvae to quantify ototoxic damage and protection. Previous work has shown that hair cells (HCs) in the zebrafish lateral line are very similar to human inner ear HCs, meaning zebrafish are a viable model to test drug-induced ototoxicity. In PEPITA, we expose zebrafish larvae to different combinations of drugs, fluorescently label the HCs, and subsequently use microscopy to quantify the brightness of the fluorescently labeled HCs as an assay for ototoxic damage and hair-cell viability. PEPITA is a reproducible, low-cost, technically accessible, and high-throughput assay. These advantages allow many experiments to be conducted in parallel, paving the way for systematic evaluation of drug-induced hearing injury and other multidrug interactions. Key features • Analysis of drug-induced hair cell damage associated with ototoxicity using Danio rerio • Ototoxicity assessment performed in vivo • Uses microscopy to generate images to assay ototoxicity quantitatively. • Enables testing of various combinations of drugs at various doses to determine toxicity-associated drug-drug interaction outcomes (synergy, antagonism).