Small-molecule intercalation induces defective generation of bromine-doped bismuth oxychloride to enhance photocatalytic degradation and detoxification of tetracycline.

Photocatalysts are one of the effective methods to degrade antibiotic contamination, but the efficiency is low and the toxicity is not well recognized. Deep lattice doping to induce defect generation is an effective way to improve the performance of photocatalysts. Here, defect-rich bromine-doped BiOCl-XBr photocatalysts were constructed with the help of small molecules inserted into the interlayer. The photocatalytic degradation performance of BiOCl-XBr was significantly enhanced, and its degradation rate was up to about 12 times that of BiOCl monomer. The main reasons for the stronger photocatalytic performance of BiOCl-XBr include Br doping to enhance visible light absorption, surface defects, and Bi valence changes to improve charge transport. The degradation of tetracycline (TC) produced more toxic intermediates, and the biotoxicity experiments also confirmed that the toxicity showed a trend of increasing and then decreasing, indicating that the more toxic intermediates were also mineralized during the degradation process. However, the mortality and hatching rate of zebrafish in the exposed group after degradation recovered but changed their activity pattern under light and dark conditions. This further warns us to focus on the toxicity changes after antibiotic degradation. Finally, based on the free radical analysis, the mechanism of photocatalytic degradation and detoxification of TC by BiOCl-XBr was proposed.

Adverse Outcome Pathways Mechanistically Describing Hepatotoxicity.

Adverse outcome pathways (AOPs) describe toxicological processes from a dynamic perspective by linking a molecular initiating event to a specific adverse outcome via a series of key events and key event relationships. In the field of computational toxicology, AOPs can potentially facilitate the design and development of in silico prediction models for hazard identification. Various AOPs have been introduced for several types of hepatotoxicity, such as steatosis, cholestasis, fibrosis, and liver cancer. This chapter provides an overview of AOPs on hepatotoxicity, including their development, assessment, and applications in toxicology.

Toxicity Potential of Nutraceuticals.

During the past few decades and especially during and after the COVID-19 pandemic, the use of nutraceuticals has become increasingly popular in both humans and animals due to their easy access, cost-effectiveness, and tolerability with a wide margin of safety. While some nutraceuticals are safe, others have an inherent toxic potential. For a large number of nutraceuticals, no toxicity/safety data are available due to a lack of pharmacological/toxicological studies. The safety of some nutraceuticals can be compromised via contamination with toxic plants, metals, mycotoxins, pesticides, fertilizers, drugs of abuse, etc. Knowledge of pharmacokinetic/toxicokinetic studies and biomarkers of exposure, effect, and susceptibility appears to play a pivotal role in the safety and toxicity assessment of nutraceuticals. Interaction studies are essential to determine efficacy, safety, and toxicity when nutraceuticals and therapeutic drugs are used concomitantly or when polypharmacy is involved. This chapter describes various aspects of nutraceuticals, particularly their toxic potential, and the factors that influence their safety.

Recent Advances in Nanodrug Delivery Systems Production, Efficacy, Safety, and Toxicity.

In the last three decades, the development of nanoparticles or nano-formulations as drug delivery systems has emerged as a promising tool to overcome the limitations of conventional delivery, potentially to improve the stability and solubility of active molecules, promote their transport across the biological membranes, and prolong circulation times to increase efficacy of a therapy. Despite several nano-formulations having applications in drug delivery, some issues concerning their safety and toxicity are still debated. This chapter describes the recent available information regarding safety, toxicity, and efficacy of nano-formulations for drug delivery. Several key factors can influence the behavior of nanoparticles in a biological environment, and their evaluation is crucial to design non-toxic and effective nano-formulations. Among them, we have focused our attention on materials and methods for their preparation (including the innovative microfluidic technique), mechanisms of interactions with biological systems, purification of nanoparticles, manufacture impurities, and nano-stability. This chapter places emphasis on the utilization of in silico, in vitro, and in vivo models for the assessment and prediction of toxicity associated with these nano-formulations. Furthermore, the chapter includes specific examples of in vitro and in vivo studies conducted on nanoparticles, illustrating their application in this field.

Carbonyl-amine condensation coupled ozonolysis of dipropylamine and styrene: Decay kinetics, reaction mechanism, secondary organic aerosol formation and cytotoxicity.

Oxidation of organic amines (OAs) or aromatic hydrocarbons (AHs) produces carbonyls, which further react with OAs to form carbonyl-amine condensation products, threatening environmental quality and human health. However, there is still a lack of systematic understanding of the carbonyl-amine condensation reaction processes of OAs or between OAs and AHs, and subsequent environmental health impact. This work systematically investigated the carbonyl-amine condensation coupled ozonolysis kinetics, reaction mechanism, secondary organic aerosol (SOA) formation and cytotoxicity from the mixture of dipropylamine (DPA) and styrene (STY) by a combined method of product mass spectrometry identification, particle property analysis and cell exposure evaluation. The results from ozonolysis of DPA and STY mixture revealed that STY inhibited the ozonolysis of DPA to different degrees to accelerate its own decay rate. The barycenter of carbonyl-amine condensation reactions was shifted from inside of DPA to between DPA and STY, which accelerated STY ozonolysis, but slowed down DPA ozonolysis. For the first time, ozonolysis of DPA and STY mixture to complex carbonyl-amine condensation products through the reactions of DPA with its carbonyl products, DPA with STY's carbonyl products and DPA's bond breakage product with STY's carbonyl products was confirmed. These condensation products significantly contributed to the formation and growth of SOA. The SOA containing particulate carbonyl-amine condensation products showed definite cytotoxicity. These findings are helpful to deeply and comprehensively understand the transformation, fate and environmental health effects of mixed organics in atmospheric environment.

Assessment of acute, subacute genetic toxicities and immunomodulatory activity of palm (Trachycarpus fortunei) buds.

ETHNOPHARMACOLOGY RELEVANCE: Palm buds are a natural green resource of the forest, which are not only rich in nutrients but contain a large number of phenolic acids and flavonoids, among other components. It has a variety of biological activities such as antioxidant and uterine smooth muscle stimulation. AIM OF THE STUDY: To evaluate the safety of palm buds for use as a nutraceutical product and food by evaluating the toxicity, subacute toxicity and genotoxicity of the young palm buds. Also studied for its immune-enhancing activity. MATERIALS AND METHODS: Acute toxicity tests were performed in mice using the maximum tolerance method, and the manifestations of toxicity and deaths were recorded after administration of 10,000 mg/mL for 14 consecutive d (days) of observations. To assess subacute toxicity, mice were treated with palm buds (750, 1500, or 3000 mg/mL) daily for 28 days. The teratogenicity of palm buds was assessed by the Ames test, the mouse bone marrow cell micronucleus test, and the mouse spermatozoa malformation test. In addition, we evaluated the immune-enhancing ability of palm buds by the mouse carbon profile test, delayed-type metamorphosis reaction, and serum hemolysin assay. RESULTS: In the acute toxicity study, the Median Lethal Dose (LD50) was greater than 10,000 mg/kg bw in both male and female rats. There were also no deaths or serious toxicities in the subacute study. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw. However, the mice's food intake decreased after one week. The medium and high dose groups had a reducing effect on body weight in mice of both sexes. In addition, the changes in organ coefficients of the liver, kidney and stomach in male mice were significantly higher in the high-dose group (3.23 ± 0.35, 0.75 ± 0.05, 0.57 ± 0.05 g) than in the control group (2.94 ± 0.18, 0.58 ± 0.05, 0.50 ± 0.02 g). Hematological analyses showed that all the indices of the rats in each palm sprout dose group were within the normal range. The results of blood biochemical indicators showed that there was a significant reduction in TP in the blood of male mice in the high-dose group (44.6 ± 7.8 g/L) compared to the control group (58.3 ± 15.1 g/L). In histopathological analysis, none of the significant histopathological changes were observed. The results of the immunological experiment in mice showed that the liver coefficient and thymus coefficient of the high-dose group (8400 mg/kg) were significantly lower than the control group. There was no remarkable difference in auricle swelling between each dose palm bud group (1400, 2800, or 8400 mg/kg) and the control group. The anti-volume number of the high-dose group was significantly increased. CONCLUSION: Palm buds have non-toxic effects in vivo and have little effect on non-specific and cellular immunity in the test mice within the dose range of this experiment. The immunoenhancement in mice is mainly achieved through humoral immunity. In conclusion, our results suggest that palm buds are safe for use as healthcare products and food.

Approaching Pharmacological Space: Events and Components.

The pharmacological space comprises all the dynamic events that determine the bioactivity (and/or the metabolism and toxicity) of a given ligand. The pharmacological space accounts for the structural flexibility and property variability of the two interacting molecules as well as for the mutual adaptability characterizing their molecular recognition process. The dynamic behavior of all these events can be described by a set of possible states (e.g., conformations, binding modes, isomeric forms) that the simulated systems can assume. For each monitored state, a set of state-dependent ligand- and structure-based descriptors can be calculated. Instead of considering only the most probable state (as routinely done), the pharmacological space proposes to consider all the monitored states. For each state-dependent descriptor, the corresponding space can be evaluated by calculating various dynamic parameters such as mean and range values.The reviewed examples emphasize that the pharmacological space can find fruitful applications in structure-based virtual screening as well as in toxicity prediction. In detail, in all reported examples, the inclusion of the pharmacological space parameters enhances the resulting performances. Beneficial effects are obtained by combining both different binding modes to account for ligand mobility and different target structures to account for protein flexibility/adaptability.The proposed computational workflow that combines docking simulations and rescoring analyses to enrich the arsenal of docking-based descriptors revealed a general applicability regardless of the considered target and utilized docking engine. Finally, the EFO approach that generates consensus models by linearly combining various descriptors yielded highly performing models in all discussed virtual screening campaigns.

Photochemical properties and toxicity of fluoroquinolone antibiotics impacted by complexation with metal ions in different pH solutions.

Acid-base dissociable antibiotic-metal complexes are known to be emerging contaminants in the aquatic environments. However, little information is available on the photochemical properties and toxicity of these complex forms. This study investigated the spectral properties of three fluoroquinolones (FQs) with and without metal ions Fe(III), Cu(II), and Al(III) in solutions under different pH conditions, as well as evaluated the changes in toxicity due to the complex with these metal ions using luminescent bacteria (vibrio fischeri). FQs showed a higher tendency to coordinate metal ions under alkaline conditions compared to neutral and acidic conditions, and the formation of complexes weakened the ultraviolet-absorbing ability of FQs. At pH = 7.0, Cu(II) quenched the fluorescence intensity of FQs. Moreover, their Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy were explored, revealing that the coordination sites of Cu(II) in three FQs were situated in a bidentate manner through the oxygen atom of the deprotonated carboxyl group and cyclic carbonyl oxygen atom. This conclusion was further verified by the theory of molecular surface electrostatic potential. In addition, except for complexes of ciprofloxacin-metals, enhanced toxicity of FQs upon coordination with Fe(III) was observed, while reduced toxicity was found for coordination with Cu(II) and Al(III). These results are important for accurately evaluating the photochemical behavior and risk of these antibiotics in aquatic environments contaminated with metal ions.

Computational Toxicology Methods in Chemical Library Design and High-Throughput Screening Hit Validation.

The discovery of molecular toxicity in a clinical drug candidate can have a significant impact on both the cost and timeline of the drug discovery process. Early identification of potentially toxic compounds during screening library preparation or, alternatively, during the hit validation process is critical to ensure that valuable time and resources are not spent pursuing compounds that may possess a high propensity for human toxicity. This report focuses on the application of computational molecular filters, applied either pre- or post-screening, to identify and remove known reactive and/or potentially toxic compounds from consideration in drug discovery campaigns.

In Vitro Cell-Based MTT and Crystal Violet Assays for Drug Toxicity Screening.

The development of novel drug candidates is a current challenge in pharmacology where therapeutic benefits must exceed side effects. Toxicology testing is therefore a fundamental step in drug discovery research. Herein, we describe the first line of toxicology testing program, consisting in cell-based high-throughput screening assays, which have the advantage of being easy, rapid, cheap, and reproducible while providing quantitative information. We illustrate MTT and Crystal Violet assays, two common colorimetric tests able to assess both cytostatic and cytotoxic effects, respectively, of a drug candidate. MTT assay allows evaluation of cellular metabolic activity, by which cell viability can be inferred; Crystal Violet staining is directly correlated with attached viable cells, thus allowing direct assessment of cell survival and death. Therefore, combination of the two methodologies represents a useful tool for predicting drug sensitivity and efficacy, the first milestones in pre-clinical toxicology workflow.

TIRESIA and TISBE: Explainable Artificial Intelligence Based Web Platforms for the Transparent Assessment of the Developmental Toxicity of Chemicals and Drugs.

Developmental toxicity is key human health endpoint, especially relevant for safeguarding maternal and child well-being. It is an object of increasing attention from international regulatory bodies such as the US EPA (US Environmental Protection Agency) and ECHA (European CHemicals Agency). In this challenging scenario, non-test methods employing explainable artificial intelligence based techniques can provide a significant help to derive transparent predictive models whose results can be easily interpreted to assess the developmental toxicity of new chemicals at very early stages. To accomplish this task, we have developed web platforms such as TIRESIA and TISBE.Based on a benchmark dataset, TIRESIA employs an explainable artificial intelligence approach combined with SHAP analysis to unveil the molecular features responsible for calculating the developmental toxicity. Descending from TIRESIA, TISBE employs a larger dataset, an explainable artificial intelligence framework based on a fragment-based fingerprint encoding, a consensus classifier, and a new double top-down applicability domain. We report here some practical examples for getting started with TIRESIA and TISBE.

Dissolved carbon in biochar: Exploring its chemistry, iron complexing capability, toxicity in natural redox environment.

Dissolved black carbon (DBC) plays a crucial role in the migration and bioavailability of iron in water. However, the properties of DBC releasing under diverse pyrolysis conditions and dissolving processes have not been systematically studied. Here, the compositions of DBC released from biochar through redox processes dominated by bacteria and light were thoroughly studied. It was found that the DBC released from straw biochar possess more oxygen-containing functional groups and aromatic substances. The content of phenolic and carboxylic groups in DBC was increased under influence of microorganisms and light, respectively. The concentration of phenolic hydroxyl groups increased from 10.0∼57.5 mmol/gC to 6.6 ∼65.2 mmol/gC, and the concentration of carboxyl groups increased from 49.7∼97.5 mmol/gC to 62.1 ∼113.3 mmol/gC. Then the impacts of DBC on pyrite dissolution and microalgae growth were also investigated. The complexing Fe3+ was proved to play a predominant role in the dissolution of ferrous mineral in DBC solution. Due to complexing between iron ion and DBC, the amount of dissolved Fe in aquatic water may rise as a result of elevated number of aromatic components with oxygen containing groups and low molecular weight generated under light conditions. Fe-DBC complexations in solution significantly promoted microalga growth, which might be attributed to the stimulating effect of dissolved Fe on the chlorophyll synthesis. The results of study will deepen our understanding of the behavior and ultimate destiny of DBC released into an iron-rich environment under redox conditions.

Ozonolysis of ketoprofen in polluted water: Reaction pathways, kinetics, removal efficiency, and health effects.

Ketoprofen (KET), as a non-steroidal anti-inflammatory drug frequently detected in aqueous environments, is a threat to human health due to its accumulation and low biodegradability, which requires the transformation and degradation of KET in aqueous environments. In this paper, the reaction process of ozone-initiated KET degradation in water was investigated using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The detailed reaction path of KET ozonation is proposed. The thermodynamic results show that ozone-initiated KET degradation is feasible. Under ultraviolet irradiation, the reaction of ozone with water can also produce OH radicals (HO·) that can react with KET. The degradation reaction of KET caused by HO· was further studied. The kinetic calculation illustrates that the reaction rate (1.99 × 10-1 (mol/L)-1 sec-1) of KET ozonation is relatively slow, but the reaction rate of HO· reaction is relatively high, which can further improve the degradation efficiency. On this basis, the effects of pollutant concentration, ozone concentration, natural organic matter, and pH value on degradation efficiency under UV/O3 process were analyzed. The ozonolysis reaction of KET is not sensitive to pH and is basically unaffected. Finally, the toxicity prediction of oxidation compounds produced by degradation reaction indicates that most of the degradation products are harmless, and a few products containing benzene rings are still toxic and have to be concerned. This study serves as a theoretical basis for analyzing the migration and transformation process of anti-inflammatory compounds in the water environment.

A systematic review of herbicide safener toxicity.

Herbicide safeners are agrochemicals added to herbicide formulations to protect crops from herbicide damage without reducing the effectiveness of the herbicide against weeds. While safeners are typically structurally similar to their co-formulated herbicides, they are classified as "inert" in the United States, meaning they are not held to the same regulatory standards as the herbicides. This review systematically examines the toxicity of safeners, which is important given their large-scale global use and potential for exposure to wildlife, livestock, and humans. A systematic review of peer-reviewed literature identified only seven studies examining safener toxicity. Regulatory toxicity data, compiled from the European Chemicals Agency (ECHA) database, included data for 9 of the 18 commercial safeners. Most safeners have low acute ecotoxicity and mammalian toxicity; however, chronic effects and the underlying mechanism are less clear. Benoxacor showed enantioselective metabolism and depletion by drug-metabolizing enzymes. In conclusion, despite the widespread use of safeners, significant knowledge gaps exist regarding their toxicity. More research is needed to fully characterize the potential risks of safeners to human health and the environment. Regulatory agencies should consider reclassifying safeners as active ingredients to ensure adequate toxicity testing and risk assessment.

Detection and Prediction of Toxic Aluminum Concentrations in High-Priority Salmon Rivers in Nova Scotia.

Elevated concentrations of toxic cationic aluminum (Ali) are symptomatic of terrestrial and freshwater acidification and are particularly toxic to salmonid fish species such as Atlantic salmon (Salmo salar). Speciated metal samples are rarely included in standard water monitoring protocols, and therefore the processes affecting Ali dynamics in freshwater remain poorly understood. Previous analysis of Ali concentrations in Nova Scotia (Canada) rivers found that the majority of study rivers had concentrations exceeding the threshold for aquatic health, but a wide-scale survey of Ali in Nova Scotia has not taken place since 2006 (Dennis, I. F., & Clair, T. A., 2012, Canadian Journal of Fisheries and Aquatic Sciences, 69(7), 1174-1183). The observed levels of dissolved aluminum in Atlantic salmon (Salmo salar) rivers of Atlantic Canada have potential serious and harmful effects for aquatic populations. We present the findings of the first large-scale assessment of the Ali status of Nova Scotia rivers in 17 years; we measured Ali concentrations and other water chemistry parameters at 150 sites throughout the Southern Uplands region of Nova Scotia from 2015 to 2022. We found that Ali concentrations exceeded toxic thresholds at least once during the study period at 80% of the study sites and that Ali concentrations increased during the study period at all four large-sample study sites. Modeling of relationships between Ali concentrations and other water chemistry parameters showed that the most important predictors of Ali are concentrations of the dissolved fractions of Al, iron, titanium, and calcium, as well as dissolved organic carbon and fluoride. We developed a fully Bayesian linear mixed model to predict Ali concentrations from a test data set within 15 µg/L. This model may be a valuable tool to predict Ali concentrations in rivers and to prioritize areas where Ali should be monitored. Environ Toxicol Chem 2024;00:1-12. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Safety assessment of novel oxadiazole derivatives in acute and sub-acute toxicity studies.

1,3,4-Oxadiazole is a fascinating heterocyclic compound with a unique five-membered ring structure containing nitrogen and oxygen atoms. It has garnered significant attention for its interactions and activities within biological systems. This versatility has led to the production of several ligands using this compound as a pharmacophore. This study evaluates the acute toxicity of three oxadiazole derivatives (1,3,4-Bromo, Chloro, and Iodo) followed by a 28 days sub-acute study involving four different doses of each derivative. The study followed the guideline, the Organization for Economic Cooperation and Development (OECD) outlined, specifically OECD Guidelines 425 for the acute toxicity study and OECD Guidelines 407 for the sub-acute study. In the acute toxicity study, a high dose of 2000 mg/kg was administered to male and female rats to establish lethal dose 50 (LD50) values, and the rats were closely monitored for 14 days. The subsequent sub-acute study involved the administration of four different doses (1.25, 2.5, 5, and 10 mg/kg) of each derivative to male and female rats for 28 days. Throughout both studies, careful monitoring for signs of toxicity and comprehensive hematological, biochemical, and histological analysis were carried out thoroughly. The results of the acute toxicity study indicated that all three derivatives had LD50 values exceeding 2000 mg/kg, and the rats did not display significant signs of toxicity. Similarly, no organ or systemic toxicity was observed in the repeated dose sub-acute study for any of the three derivatives. In conclusion, based on the findings of these studies, it was determined that the derivatives are safe for further investigation of their pharmacological activity.

Morphological, physiological, and transcriptomic analyses indicate that cell wall properties and antioxidant processes are potential targets for improving the aluminium tolerance of broad beans.

Aluminium (Al) stress is the second-leading abiotic stress on crops. An improved understanding of the response mechanisms of plants to Al stress will provide scientific guidance for enhancing the crops' tolerance to Al stress. In this study, Al stress (50-200 µM AlCl3) caused visible damage to broad bean (Vicia faba L.) roots rather than shoots, which was attributed to Al accumulation and distribution in different tissues. Root transcriptomic analysis revealed that Al stress altered cell wall properties by downregulating lignin synthesis and several xyloglucan endotransglucosylase/hydrolase-, expansin- and peroxidase (POD)-encoding genes, which likely weakened cell extensibility to inhibit root growth. Additionally, Al stress impeded reactive oxygen species scavenging pathways involving POD activity and flavonoid biosynthesis, leading to oxidative damage characterised by malondialdehyde accumulation. These results indicate that optimising cell wall properties and/or enhancing antioxidant processes are crucial for alleviating Al toxicity to broad beans. Interestingly, exogenous application (500 and 1000 µM) of the flavonoid apigenin effectively alleviated Al toxicity in broad bean roots by partially improving the total antioxidant capacity of the roots. This study contributes to understanding the interaction between plants and Al and provides new strategies to alleviate Al toxicity in crops.

Aspirin reduces Ponatinib-induced cardiovascular toxic phenotypes and death in zebrafish.

BACKGROUND: Ponatinib (Iclusig) is an oral tyrosine kinase BCR-ABL inhibitor for treating patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) who are resistant to the therapies with other tyrosine kinase inhibitors. However, adverse cardiovascular events caused by Ponatinib are a serious issue that affects patients' survival rates. Thus, it is necessary to search for candidate drugs to reduce the cardiovascular toxicity of Ponatinib. PURPOSE: To investigate the effects of Aspirin on Ponatinib-induced cardiovascular toxicity in zebrafish. METHODS: AB strain of wild type zebrafish (Danio rerio), Tg (cmlc2: GFP) transgenic zebrafish, and Tg (gata1: dsRed) transgenic zebrafish were used as in vivo models to assess survival, blood flow, cardiac morphology, and function. Thrombus formation was detected using O-dianisidine staining. The transcriptome of zebrafish larvae treated with Ponatinib was assessed using RNA sequencing. RESULTS: Ponatinib not only reduced survival rate but also caused cardiovascular toxic events such as pericardial edema, abnormal heart structure, low heart rate, and thrombosis. In addition, whole-body transcriptome analysis showed that Ponatinib up-regulated the expression of cyclooxygenase-1 (COX-1). Compared with other antithrombotic drugs, a COX-1 inhibitor Aspirin more effectively reduced ponatinib-induced cardiovascular toxicity events and improved the survival rate of zebrafish larvae. CONCLUSION: Our findings suggest that Aspirin exhibits the potential to reduce Ponatinib-induced cardiovascular toxicity.

Comprehensive eco-geno-toxicity and environmental risk of common antiviral drugs in aquatic environments post-pandemic.

The eco-geno-toxicological impacts of the most widely used antiviral drugs against SARS-CoV2 - ribavirin, ritonavir, nirmatrelvir and tenofovir - were investigated in freshwater organisms. Ribavirin and tenofovir exhibited the highest acute toxicity in the rotifer Brachionus calyciflorus at concentrations of a few mg/L while ritonavir and nirmatrelvir showed similar effects at tens of mg/L; acute toxicity of ribavirin was also observed in the crustacean Ceriodaphnia dubia at similar concentrations. In contrast, the crustacean Thamnocephalus platyurus showed the lowest sensitivity to the antiviral drugs tested with no sublethal effects. Chronic toxicity tests revelead that these antivirals induced effects in consumers at concentrations of environmental concern (ng-µg/L). Ribavirin showed the highest toxicity to the alga Raphidocelis subcapitata, while ritonavir showed the highest toxicity to B. calyciflorus and C. dubia. DNA damage and oxidative stress were observed in C. dubia at 0.001 µg/L and 0.1 µg/L when exposed to ritonavir and nirmatrelvir respectively, and at 1 µg/L when exposed to ribavirin and tenofovir. Toxic and genotoxic environmental risks were assessed with risk quotients for ritonavir, tenofovir and ribavirin exceeding the threshold of 1, indicating significant environmental concern.