Risk Of Toxicity Research Articles

Monitoring and management of adverse effects associated with trastuzumab deruxtecan: a UAE-specific consensus

Breast cancer is the most frequently diagnosed cancer in the UAE and a leading cause of cancer-related mortality. Although early diagnosis contributes to favorable prognoses, novel treatment modalities like antibody-drug conjugates (ADCs) have significantly broadened the therapeutic landscape for patients in metastatic settings. The recognition of “HER2-low” expression as a targetable category has caused a paradigm shift in the management of breast cancer. Although initially developed to target HER2-positive breast cancer, trastuzumab deruxtecan (T-DXd), an ADC, has now also been approved to treat metastatic or unresectable HER2-low breast cancers. Despite the inherent specificity of an ADC, the risk of off-site toxicity exists and is an essential component while assessing the risk-benefit ratio of the treatment. Developing strategies to balance efficacy and safety is crucial, especially for newly approved therapies like T-DXd. Regional perspectives, cultural beliefs, and demographic factors influence treatment decisions and outcomes. The objective of this paper is to establish a UAE-specific consensus among oncologists on practical T-DXd treatment considerations and management of associated side effects. Establishing a consensus on monitoring and managing T-DXd side effects among experts can promote informed decision-making.

Treatment of focal anaplastic Wilms tumor: A report from the Children's Oncology Group AREN0321 and AREN03B2 studies.

In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for stage II-IV FAWT. Four-year event-free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.9% and for stage IV FAWT were 61.4% and 71.6%, respectively. Therapy intensification for stage I and IV FAWT was evaluated as secondary objectives in AREN0321. Central review in the AREN03B2 Renal Tumors Classification, Biology, and Banking Study confirmed patient stage and tumor histology. Patients were then enrolled in AREN0321 and received DD4A with radiation for stage I-III FAWT and vincristine, doxorubicin, cyclophosphamide, carboplatin, and etoposide (UH-1/revised UH-1) with radiation for stage IV FAWT. Outcomes of patients with FAWT who were treated in AREN0321 (n=25) and in AREN03B2 (n=20) treated as per AREN0321 were analyzed. In the pooled data analysis from AREN0321 and AREN03B2, 4-year EFS and OS were both 100% for stage I-II FAWT (n=21), 82.4% (95% CI, 66.1%-100%) and 87.8% (95% CI, 73.4%-100%) for stage III FAWT (n=17), respectively, and both 85.7% (95% CI, 63.3%-100%) for stage IV FAWT (n=7). Four patients enrolled in AREN0321 had events: treatment failure occurred in three patients with stage III FAWT, and one treatment-related death was observed in a patient with stage IV FAWT following revised UH-1. No EFS or OS events occurred in patients with FAWT enrolled in AREN03B2 only. Patients with stage I and II FAWT have outstanding survival when treated with DD4A and radiation. Intensification of therapy may have improved survival for stage IV FAWT, albeit with an increased toxicity risk.

Safety of hyperbaric oxygen therapy in non-emergent patients with a history of seizures: A retrospective cohort study.

Hyperbaric oxygen therapy (HBOT) is well established as a treatment for various medical conditions. However, it poses a risk of oxygen toxicity, which can cause seizures particularly in individuals with pre-existing seizure disorders. Consequently, seizure disorders are considered a relative contraindication to HBOT. Despite this, the relative risk of HBOT-induced seizures in this patient population remains unclear. This retrospective cohort study aims to evaluate the safety of HBOT among patients with pre-existing seizure disorders. After obtaining approval from the Research Ethics Board, we retrospectively reviewed the patient charts of individuals with a history of seizures who were referred to the Rouge Valley Hyperbaric Medical Center and Toronto General Hyperbaric Medicine Unit for HBOT between January 2020 and December 2023. Relevant demographic information, past medical history, and HBOT session treatment protocols, such as the treatment pressure set in absolute atmospheric pressure (ATA) and number of air breaks, were recorded. The collected data was analyzed using descriptive statistics. A total of 43 patients were referred to HBOT during the study period, and 21 patients did not proceed with the treatments. In total, 634 HBOT sessions were administered to 22 patients in monoplace chambers with five-minute air breaks, and one patient experienced a seizure event. Each patient completed an average of 29 (range 3-60) sessions lasting 90-120 minutes at 1.8 ATA (n = 3), 2.0 ATA (n = 18), or 2.4 ATA (n = 1). Fifteen patients were on oral antiseizure medications during the HBOT course. The overall incidence of seizures was one in 634 treatments. While patients with a history of seizures may develop seizure activity during HBOT, the majority can safely undergo treatment when predetermined protocols are followed. With careful management and adherence to established protocols, HBOT can be a viable treatment option for those with seizure histories.

Individual Sensitivity for Radiotherapy-related Adverse Tissue Reactions in Patients Treated Twice for Metachronous Cancers.

The role of genetics in susceptibility to radiotherapy-induced toxicities is unclear. A strong impact of genetics should cause correlated toxicities in patients with metachronous double radiotherapy. We ascertained information about demographics, lifestyle, radiotherapy and early toxicities in irradiated tissues for a retrospective cohort of 98 patients from 2 hospitals who underwent two metachronous radiotherapeutic treatments (2007-2022) of different anatomical regions. European Organisation for Research and Treatment of Cancer/Radiation Therapy Oncology Group (EORTC/RTOG) toxicity scores per organ system were combined to a single mean score. We considered as genetic component the variation of toxicity not explained by radiation dose to the tumor, age at radiotherapy, sex, smoking status, and surgery. Variance components of toxicity were evaluated by ordinal logistic regression with random intercept. Common site combinations were breast/contralateral breast (N = 16), breast/endometrium (N = 6), and cervix/breast (N = 5). Mean toxicity over exposed tissues was 0.70 (range, 0-3). Prescribed radiation dose was significantly associated with mean toxicity, with a 5% (95% CI 3-8) increase of the odds for a higher toxicity level per Gy. Sex, surgery, age and smoking were not. There was no genetic contribution to risk of toxicities after adjustment. Toxicity levels were not more similar within patients than between patients, suggesting a negligible impact of genotype on radiotherapy-related toxicities.

Evaluation of Sanitary and Environmental Impact of Plant Protection Practices in Vineyards of Southwestern France: Organic and Conventional/Integrated Agriculture

The French wine industry is spread across the country and represents 789,000 ha (2023). Over 20% of the plant protection products (PPPs) sold in France are used in viticulture on less than 4% of the French UAA (Utilized Agricultural Area). The share of wine estates with organic farming certification has risen sharply, reaching 9% of French vineyards in 2016. The position occupied by the wine sector on both the national and international scale confirms the need to examine the impacts of different management practices in viticulture on human health and the environment. This study presents an approach to the assessment of plant protection practices in vineyards based on indicators of plant protection pressure and risk. It was carried out on wine-growing farms in the southwest of France, surveyed according to the two farming systems: conventional/integrated and organic. The main objective of this study was to compare the health and environmental impact of the PPPs used in these two farming systems. The impact assessment result of wine-growing plant protection practices shows that some pesticides and molecules used in organic farming, especially those based on copper and sulfur, are more harmful than products used in conventional/integrated farming, in particular to the environment. For this reason, all stakeholders involved in pesticide management should recognize the health and environmental impact of PPPs in order to reduce and to control their toxicity risks to public health and the natural environment.

The Safety Profile of Acne Supplements: Analysis of Active Ingredients

Introduction: Acne treatment options vary widely, with many patients using dietary supplements. Despite their popularity, these products pose safety concerns due to lack of FDA approval for safety or efficacy before release. The US Institute of Medicine sets Tolerable Upper Intake Levels (ULs) for nutrients, but there are no regulatory limits to prevent supplements from exceeding these ULs. Methods: On March 3, 2024, active ingredients from the top 50 best-selling acne supplements were collected from Amazon. Data were analyzed to identify ingredients and the frequency at which their dosages surpassed the ULs for different age groups. Results: The most prevalent active ingredients were zinc (40%), vitamin A (30%), diindolylmethane (DIM) (26%), vitamin E (26%), and selenium (24%). Thirty percent of all supplements contained at least one ingredient exceeding its UL for ages 9 to 13, 20% for ages 14-18, and 16% for ages 19 and older. Twenty-five percent of zinc-containing supplements and 33% of vitamin A-containing supplements exceeded the UL for any all groups. Discussion: Acne supplements frequently contain ingredients that surpass ULs, particularly zinc and vitamin A. Chronic toxicity from these nutrients can lead to significant health issues. Dermatologists should inquire about supplement use when prescribing treatments like isotretinoin to prevent toxicity risks.

Assessment of Scarcity, Toxicity, and Circularity Risks in the European Thermoelectric Market: A Focus on Tellurium, Antimony, Bismuth, and Lead

Assessment of Scarcity, Toxicity, and Circularity Risks in the European Thermoelectric Market: A Focus on Tellurium, Antimony, Bismuth, and Lead

Baclofinding solutions: Baclofen-induced encephalopathy in a peritoneal dialysis patient.

Baclofen is a gamma-aminobutyric acid agonist that is commonly and widely used for the treatment of muscle spasticity. Given its predominant kidney excretion, patients with reduced kidney function are at particular risk of drug accumulation and toxicity, with neurotoxicity in the form of drowsiness, encephalopathy, seizures, and coma being the most reported clinical features. In addition to the importance of early identification of baclofen toxicity and drug discontinuation, dialysis can effectively accelerate baclofen elimination given its small molecule weight, and the relatively low volume of distribution and weak protein binding. While several cases of baclofen-induced toxicity have been reported in hemodialysis patients, the literature on baclofen toxicity in individuals receiving peritoneal dialysis (PD) is limited. Here, we present a case of baclofen-induced encephalopathy in a PD patient following a single dose of baclofen. In this case, our patient was managed by continuous (24 h) automated PD, with complete recovery of neurological status within three days.

Disentangling the role of selenium in antagonizing the toxicity of arsenic and cadmium.

Cadmium (Cd) and inorganic arsenic (As) compounds are considered to be among the major public health hazards. This is due to both the high intrinsic toxicity of these substances and the often difficult to avoid exposure of the general population through contaminated water and food. One proposed method to reduce the toxic effects of As and Cd on animals and humans is the use of selenium (Se). As discussed in our previous article, laboratory studies show that this micronutrient can have a beneficial effect on the detoxification of As and Cd in the body through the formation of non-toxic complexes with these elements, as well as through the antioxidant effects of selenoproteins. New data that have emerged in recent years allow for a clearer description of the interaction between Se and As and Se and Cd. Human studies show that optimal levels of Se can have a beneficial effect in reducing the toxic effects associated with exposure to As or Cd. However, as Se levels in the body increase, the protective effects of Se may be reversed. Recent laboratory studies confirm the antagonistic effects of medium doses of Se toward Cd and As through the formation of nontoxic complexes, antioxidant, anti-inflammatory effects, and induction of pro-survival pathways in cells. In conclusion, Se has a complex effect on As and Cd toxicity, with both benefits and potential risks, depending on the form of Se and its dose as a supplement or the status (level) of this micronutrient in the body.

Micronutrient Seed Coatings of Layered Double Hydroxides Overcome Seedling Toxicity and Improve Micronutrient Uptake in Comparison with Soluble Micronutrient Coatings.

Zinc (Zn), boron (B), and molybdenum (Mo) are micronutrients, essential to crops, which can be efficiently applied to crops via seed coatings. However, fast micronutrient release from soluble seed coatings brings seedling toxicity risks. Hence, this study developed novel Zn-B-Mo slow-release seed coating compounds, i.e., nanostructured Zn2Al or Zn3Al-layered double hydroxides (LDHs) loaded with (poly)borate and molybdate. Assessment of the micronutrient release properties showed that both LDH compounds gradually dissolved at a pH of ∼ 4.5, releasing Zn, B, and Mo, while Zn3Al-B-Mo released Mo more slowly than Zn2Al-B-Mo through anion exchange (pH ∼ 7). Finally, in a seedling establishment trial with coated chickpea seeds, at elevated micronutrient doses, the Zn3Al-B-Mo LDH coating prevented adverse effects on seed emergence and seedling yield that were observed with a corresponding soluble coating due to seedling toxicity. Taken together, micronutrient LDHs prove to be promising compounds for controlling micronutrient supply from seed coatings.

DITTO: A Visual Digital Twin for Interventions and Temporal Treatment Outcomes in Head and Neck Cancer.

Digital twin models are of high interest to Head and Neck Cancer (HNC) oncologists, who have to navigate a series of complex treatment decisions that weigh the efficacy of tumor control against toxicity and mortality risks. Evaluating individual risk profiles necessitates a deeper understanding of the interplay between different factors such as patient health, spatial tumor location and spread, and risk of subsequent toxicities that can not be adequately captured through simple heuristics. To support clinicians in better understanding tradeoffs when deciding on treatment courses, we developed DITTO, a digital-twin and visual computing system that allows clinicians to analyze detailed risk profiles for each patient, and decide on a treatment plan. DITTO relies on a sequential Deep Reinforcement Learning digital twin (DT) to deliver personalized risk of both long-term and short-term disease outcome and toxicity risk for HNC patients. Based on a participatory collaborative design alongside oncologists, we also implement several visual explainability methods to promote clinical trust and encourage healthy skepticism when using our system. We evaluate the efficacy of DITTO through quantitative evaluation of performance and case studies with qualitative feedback. Finally, we discuss design lessons for developing clinical visual XAI applications for clinical end users.

Unapproved potassium phosphate products increase risk of aluminum toxicity in infants.

Unapproved potassium phosphate products increase risk of aluminum toxicity in infants.

Lower urinary tract sub-structures as predictors of late urinary toxicity in concurrent chemo-radiotherapy for anal cancer.

Late toxicity is substantial after chemotherapy for anal cancer. This study aimed to investigate the relationship between radiation dose to lower urinary tract sub-structures and the risk of late urinary toxicities, in patients with anal cancer treated with chemoradiotherapy or radiotherapy. From 2015 to 2021, 314 patients with localized anal cancer were included in a national prospective registration study. Urinary toxicity (CTCAE) was scored during treatment (acute toxicity) and at one- and three-years follow-up (late toxicity). Lower urinary tract sub-structures (bladder, bladder neck, bladder trigone, and urethra) were contoured post-hoc on the planning-CT and dosimetric variables extracted. Logistic regression was used to evaluate the association between clinical and dosimetric variables and registered toxicity. There was an increase in late toxicity from baseline of 15% for both urgency and frequency, and 25% for incontinence. The most common late toxicity was urinary frequency, with 40% of patients experiencing grade 1 and 2% experiencing grade 2 toxicity. A dose-effect relationship was found for late urinary urgency and increasing D0.1cm3 of the urethra (p=0.01). Increased late urinary frequency was correlated to increasing D2cm3 of the urethra (p=0.007), and bladder neck V30Gy (p=0.03). Patients with acute toxicity had up to three times increased risk of corresponding late toxicity. We found a significant dose-effect relationship between radiation dose to urethra and bladder neck and late urinary toxicity. These findings warrant more focus on these structures when optimizing radiotherapy for anal cancer. Furthermore, a strong association between having acute toxicity and developing late toxicity was shown.

Rapid Biomonitoring of Fluoropyrimidine-based Chemotherapy Drugs and their Biometabolites in Colorectal Cancer Patients’ Blood Samples using an In-syringe-based Fast Drug Extraction Technique followed by LC-MS/MS Analysis

Patients with dihydropyrimidine dehydrogenase (DPD) deficiency in peripheral mononuclear cells are at higher risk of severe toxicity due to the improper dose of fluorouracil-based chemotherapy drugs, which has become an essential aspect for consideration in clinical studies. 5-fluorouracil (5-FU) is a first-line and second-line chemotherapy drug in adjuvant, neoadjuvant, or palliative therapy settings to treat solid tumors and cancers. In this work, a novel in-syringe-based fast drug extraction (IS-FaDEx) technique followed by UHPLC-MS/MS detection was developed for rapid biomonitoring of 5-FU and its biometabolites in human blood samples. In this process, the 5-FU drug and its metabolites were extracted using 1 mL of extraction solvent, and then, the cleanup was performed with solid sorbents under an automated setup. Under optimized conditions, method validation results showed an excellent linearity range from 1∼1000 ng mL−1 with correlation coefficients >0.99. The detection limits varied between 0.4 and 2.0 ng mL−1, recoveries of 5-FU and its biometabolites ranged from 94.9–107.5%, and relative standard deviation were between 3.1-8.3%. The overall analytical GREEnness (AGREE) score for the proposed method was determined to be 0.83 using the AGREE metric approach, showing an excellent greenness profile. Therefore, the developed method proved efficient, robust, semi-automated, and rapid, which can considerably minimize solvent, salts, and sorbent usage following green and sustainable chemistry principles. The current approach showed effectiveness in drug monitoring investigations and can be beneficial for enhancing the efficacy and safety of 5-FU-based chemotherapy in colorectal cancer patients.

Optimisation of high-rate filamentous algal pond operating parameters for nutrient bioremediation of primary municipal wastewater

Effective management of operational parameters is crucial for optimising wastewater treatment in high-rate filamentous algal pond (HRFAP) systems. This study examined three key operational parameters - hydraulic retention time (HRT), stocking density, and harvest frequency - on the growth and nutrient bioremediation efficiency of Klebsormidium flaccidum cultivated in primary municipal wastewater in outdoor HRFAPs in summer and winter. Seasonal conditions significantly influenced biomass productivity, with productivity being 48.3 % higher in summer compared to winter across all experiments. The optimal HRT of 4 days for both seasons achieved the highest average reductions in total ammoniacal‑nitrogen (TAN) concentration (64.6 % day−1 ± 1.82 SE in summer, 32.3 % day−1 ± 1.82 SE in winter) and acceptable reductions in nitrate-N (66.6 % day−1 ± 3.54 SE in summer, 42.6 % day−1 ± 8.98 SE in winter) and dissolved reactive phosphorous (DRP, 19.8 % day−1 ± 1.01 SE in summer, 15 % day−1 ± 1.98 SE in winter). A stocking density of 0.25 g fresh weight (FW) L−1 was optimal in summer as it resulted in the highest reductions in TAN (75.9 % day−1 ± 2.49 SE), nitrate-N (43.8 % day−1 ± 3.31 SE), and DRP (21.6 % day−1 ± 1.37 SE). In winter, a stocking density of 0.5 g FW L−1 was optimal to mitigate the risk of primary wastewater toxicity during slower growth periods. Harvest frequency did not significantly affect nutrient removal rates across treatments and seasons; however, biomass productivity was significantly higher in summer with a 4-day harvest frequency (7.83 g dry weight (DW) m−2 day−1). Longer HRTs improved water quality variables, with the highest Escherichia coli (E. coli) reduction (99.9 %) observed with a stocking density of 0.25 g FW L−1 in winter. This study highlights the importance of seasonal optimisation of HRFAP operation to maximise biomass production and nutrient bioremediation for effective treatment of primary municipal wastewater.

Treatment of psoriasis with biologic and non-biologic targeted therapies in patients with latent tuberculosis infection or at risk for tuberculosis disease progression: Recommendations from a SPIN-FRT expert consensus.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.

ADSORPTION KINETICS AND ISOTHERM MODELS OF Cd(II), Zn(II), AND Cr(VI) BY GEORGIAN NATURAL AND MODIFIED FORMS OF MORDENITE

Environmental pollution with heavy metals is a problem of worldwide importance due to their toxicity and potential health risks. Among the heavy metals found in industrial waters are such toxic metals as Cd(II), Zn(II), and Cr(VI). In this study, the potential of Georgian natural and modified mordenite as a low-cost, eco-friendly adsorbent for the removal of cadmium (II), zinc (II), and chromium (IV) from aqueous solutions is studied. Langmuir and Freundlich isotherms are used to model adsorption data. Studies have shown that the correlation coefficient values (R2 ) were best fitted by the Langmuir isotherm. The maximum adsorption capacities are 0.84mg/g, 118.92mg/g and 2.25mg/g for cadmium(II), zinc(II) and chromium(IV) respectively as described by Langmuir isotherm

Seasonal variability and risk evaluation of emerging organic contaminants in European river: linking in silico and in vitro approaches to prioritize hazardous EOCs.

Emerging organic contaminants (EOCs) are a growing concern for aquatic ecosystems, underscoring the need for advanced risk assessment methodologies. This study employed an integrated approach to evaluate the risks associated with 563 EOCs across 13 monitoring sites along the Sava River in Croatia. Sampling was conducted during the winter and spring months, spanning February to May. The detected substances, totaling 551 compounds, included pharmaceuticals, illicit drugs, pesticides, industrial chemicals, hormones, artificial sweetener, and sunscreen chemical. We hypothesized that combining high-resolution chemical monitoring with bio-effect assessment tools could enhance the prioritization of high-risk EOCs and their mixtures. Persistent, bioaccumulative, and toxic (PBT) profiling and risk quotient (RQ) evaluations identified pesticides and industrial chemicals as key contributors to biological impacts, peaking in April due to agricultural activities. In vitro prioritization using exposure-activity ratios (EARs) derived from the ToxCast database revealed exacerbated biological effects during colder months (February and March), driven by elevated levels of pharmaceuticals, particularly synthetic glucocorticoids used for treatments of respiratory infections. By integrating PBT, RQ, and EAR assessments, eight EOCs, including methylprednisolone (a synthetic glucocorticoid), bisphenol A (an industrial chemical), nicotine (a stimulant), and five pesticides (temephos, disulfoton, pyridaben, bifenthrin, and chlorpyrifos-methyl), were prioritized for monitoring and regulatory attention. This multi-method framework advances next-generation risk assessment, offering critical insights for managing EOC pollution and safeguarding aquatic ecosystems and public health.

Deciphering physical and functional properties of chitosan-based particles for agriculture applications

Traditional methods for controlling plant pathogens rely on toxic chemicals, posing environmental and health risks. Developing sustainable, eco-friendly alternatives is crucial. Chitosan (CS)-based materials offer promising solutions for sustainable agriculture. We aimed to synthesize and characterize CS-based microparticles with varying properties and assess their antimicrobial performance to establish correlations between variations in physicochemical characteristics and their impact on performance within biological systems. We adjusted the synthesis parameters, producing particles labeled P1, P2, and P3, which have sizes of 0.19 ± 0.07 μm, 0.45 ± 0.32 μm, and 1.22 ± 0.32 μm, and zeta potentials of +7.6 ± 4.25 mV, +22 ± 3.51 mV, and + 12.9 ± 4.54 mV, respectively. Extensive toxicological screenings showed that these CS-based microparticles were non-toxic across cell cultures, mouse red blood cells, soil microbiota, nitrogen-cycling bacteria, and plant toxicity assays. Encouraged by these results, we evaluated their antimicrobial potential against economically important crop pathogens. The CS-based microparticles exhibited antimicrobial effects against the bacterium Pseudomonas syringae pv. tomato DC3000 and the fungus Fusarium solani f. sp. eumartii. Higher zeta potentials correlated with greater antimicrobial efficacy, evidenced by lower IC50 and minimum inhibitory concentration (MIC) values. These findings indicate that all three microparticles analyzed displayed antimicrobial activity against two economically significant crop pathogens, with P2 showing solid performance attributed to its physicochemical characteristics. Therefore, CS-based microparticles represent a promising, nontoxic, and environmentally friendly alternative for modern agriculture, with their biological activities potentially predictable through careful selection of physicochemical properties before the synthesis process.

Temperature-dependent toxicity and mechanisms of florfenicol on the embryonic development of marine medaka (Oryzias melastigma).

The extensive use of antibiotics and their persistence in the environment have seriously threatened marine ecosystems in recent years. The frequent occurrence of extreme weather due to climate change has also increased the uncertainty of effective toxicity identification and risk assessment of the chemicals of concern. This study aimed to investigate the toxic effects and potential mechanisms of florfenicol (0.5, 10, 100, 500 and 1000 μg/L) on the embryonic development of marine medaka (Oryzias melastigma) through 21-d experiment under three temperature exposure scenarios (20, 25, and 30 °C). Considering embryo development, the highest level of florfenicol at 1000 μg/L decreased the hatching success at 25 °C, whereas the total inhibition of hatching was observed at 20 °C regardless of florfenicol concentrations of concern. The ATP content was inhibited by the highest florfenicol dose at 20 °C, while stimulated ATP content at 20 °C and 30 °C, compared to 25 °C. Fluctuation of temperatures, especially at 20 ℃, induced oxidative stresses, including increased MDA contents and decreased CYP450 and HSP90 contents. For inflammatory response-related genes (nf-κb, nlrx1, pycard, caspase 1, and il-1β), an increase of florfenicol dose led to gene upregulation at 25 °C. Conversely, gene upregulation was also observed for all treatments at 30 °C, while predominantly downregulation was observed for all treatments at 20 °C. For genes related to DNA damage and apoptosis (pi3k, akt, foxo1, tp53, bcl-2, bax, apaf-1, caspase 9, and 3), alterations in gene expression were evident for all florfenicol treatments at both 20 °C and 30 °C. Therefore, this study suggests that the combined effects of florfenicol and temperature may disrupt the normal function of mitochondria, impacting ATP production, thereby inducing oxidative stress, inflammatory response, DNA damage, and apoptosis, ultimately resulting in decreased hatching rates and increased mortality. Furthermore, the key findings of this study reveal the complex interactions between florfenicol and temperature and emphasize the need to consider temperature when identifying toxicity and mechanisms, as well as the ecological risk assessment of florfenicol in marine environments.