Median Effective Concentration Research Articles

Understanding the Role of Low-Dose Polystyrene Microplastic in Copper Toxicity to Rice Seed (Oryza sativa L.).

There is still much to learn with respect to the potential for microplastics (MPs) to interact with environmental toxins and biota. In the present study, we investigated the effect of MPs on the toxicity of copper (Cu) to rice seeds (Oryza sativa L.). The 7-day median effective concentration (EC50) value of MPs on rice seed germination was 864 mg/L (95% confidence interval [CI] 839 to 897 mg/L). We found that MPs slightly reduced Cu toxicity to rice seeds. The 7-day EC50 of Cu on rice seed germination increased from 7.29 mg/L (95% CI 7.10-7.52 mg/L) to 7.93 mg/L (95% CI 7.58-8.08 mg/L) in the presence of 20 mg/L MPs. We examined this toxicity reduction phenomenon by investigating the role of MPs in the process of Cu transport, Cu accumulation, and metabolic responses. Further investigation found that the MPs used in the present study hardly adsorbed Cu, but these MPs accumulated on the coats of rice seeds and significantly reduced Cu accumulation in rice seedlings. When Cu concentration was 10 mg/L, the presence of MPs reduced the accumulation of Cu in rice seedlings by 34%. We also found that, compared with only Cu present, the addition of MPs resulted in lower reactive oxygen species accumulation and higher catalase activity and glutathione levels in rice seedlings, which also contributed to Cu toxicity reduction. Collectively, the present study shows that polystyrene MPs have the potential to form associations with plant structures which can ultimately impact heavy metal bioaccessibility and therefore toxicity. Environ Toxicol Chem 2024;00:1-10. © 2024 SETAC.

Synthesis, fungicidal activity and molecular docking of novel pyrazole-carboxamides bearing a branched alkyl ether moiety

Succinate dehydrogenase inhibitors are essential fungicides used in agriculture. To explore new pyrazole-carboxamides with high fungicidal activity, a series of N-substitutedphenyl-3-di/trifluoromethyl-1-methyl-1H-pyrazole-4-carboxamides bearing a branched alkyl ether moiety were designed and synthesized. The in vitro bioassay indicated that some target compounds displayed appreciable fungicidal activity. For example, compounds 5d and 5e showed high efficacy against S. sclerotiorum with EC50 values of 3.26 and 1.52 μg/mL respectively, and also exhibited excellent efficacy against R. solani with EC50 values of 0.27 and 0.06 μg/mL respectively, which were comparable or superior to penflufen. The further in vivo bioassay on cucumber leaves demonstrated that 5e provided strong protective activity of 94.3 % against S. sclerotiorum at 100 μg/mL, comparable to penflufen (99.1 %). Cytotoxicity assessment against human renal cell lines (239A cell) revealed that 5e had low cytotoxicity within the median effective concentrations. Docking study of 5e with succinate dehydrogenase illustrated that R-5e formed one hydrogen bond and two π-π stacking interactions with amino acid residues of target enzyme, while S-5e formed only one π-π stacking interaction with amino acid residue. This study provides a valuable reference for the design of new succinate dehydrogenase inhibitor.

Assessment of the effects of 2,4-D-dichlorophenoxyacetic acid-based herbicide exposure in eggs and embryos of golden apple snails using OCT

This study aimed to evaluate the effects of herbicide 2, 4-D-dichlorophenoxy acetic acid on golden apple snail eggs and embryos. Additionally, the study assessed the applicability of optical coherence tomography (OCT), a non-invasive depth cross-sectional microscopic imaging technique, as a novel method, to the best of our knowledge, for studying morphological changes in golden apple snail eggs and embryos, in comparison to the conventional approach of using white light microscopy. The study revealed that the herbicide 2,4-D-dichlorophenoxy acetic acid affected the hatchery rate and morphological changes of the eggs and embryos. The lethal concentration (LC50), representing the concentration of a substance that is expected to cause death in half of the population being studied, of the golden apple eggs and embryos increased with longer exposure time and higher concentrations. The estimated median effective concentration (EC50), which denotes the concentration producing the desired effect in 50% of the exposed golden apple embryos, exhibited a similar trend of change as the LC50. When compared to the microscopic study, it was observed that OCT could be employed to investigate morphological changes of golden apple snail eggs and embryos, enabling evaluation of alterations in both 2D and 3D structures.

Design, synthesis, antifungal evaluation and mechanism study of novel norbornene derivatives as potential laccase inhibitors.

To discover novel fungicide candidates, five series of novel norbornene hydrazide, bishydrazide, oxadiazole, carboxamide and acylthiourea derivatives (2a-2t, 3a-3f, 4a-4f, 5a-5f and 7a-7f) were designed, synthesized and assayed for their antifungal activity toward seven representative plant fungal pathogens. In the in vitro antifungal assay, some title norbornene derivatives presented good antifungal activity against Botryosphaeria dothidea, Sclerotinia sclerotiorum and Fusarium graminearum. Especially, compound 2b exhibited the best inhibitory activity toward B. dothidea with the median effective concentration (EC50) of 0.17 mg L-1, substantially stronger than those of the reference fungicides boscalid and carbendazim. The in vivo antifungal assay on apples revealed that 2b had significant curative and protective effects, both of which were superior to boscalid. In the preliminary antifungal mechanism study, 2b was able to injure the surface morphology of hyphae, destroy the cell membrane integrity and increase the intracellular reactive oxygen species (ROS) level of B. dothidea. In addition, 2b could considerably inhibit the laccase activity with the median inhibitory concentration (IC50) of 1.02 μM, much stronger than that of positive control cysteine (IC50 = 35.50 μM). The binding affinity and interaction mode of 2b with laccase were also confirmed by molecular docking. This study presented a promising lead compound for the study of novel laccase inhibitors as fungicidal agrochemicals, which demonstrate significant anti-B. dothidea activity and laccase inhibitory activity. © 2024 Society of Chemical Industry.

Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections.

Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC50, CC50) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (Cmax)/EC50, were used to predict the potential in vivo efficacy. The 20 drugs with the highest ratios were retested in human Calu-3 and Caco-2 cells, and their CC50 was determined in an expanded panel of cell lines. Many of the 20 drugs with the highest ratios were inactive in human Calu-3 and Caco-2 cells. Antivirals effective in controlled clinical trials had unbound Cmax/EC50 ≥ 6.8 in Calu-3 or Caco-2 cells. EC50 of nucleoside analogs were cell dependent. This approach and earlier availability of more relevant cultures could have reduced the number of unwarranted clinical trials.

Prediction of acute toxicity for Chlorella vulgaris caused by tire wear particle-derived compounds using quantitative structure-activity relationship models

Tire wear particles (TWPs) enter aquatic ecosystems through various pathways, such as rainwater and urban runoff. Additives in TWPs can harm aquatic organisms in these ecosystems. Therefore, it is essential to investigate their toxicity to aquatic organisms. In our study, we initially recorded the median effective concentrations of 21 TWP-derived compounds on Chlorella vulgaris growth, ranging from 0.04 to 8.60 mg/L. Subsequently, through an extensive review of the literature, we incorporated 112 compounds with specific toxicity endpoints to construct the QSAR model using genetic algorithm and multiple linear regression techniques, followed by the construction of the consensus model and the quantitative read-across structure-activity relationship (q-RASAR) model. Meanwhile, we employed rigorous internal and external validation measures to assess the performance of the model. The results indicated that the developed q-RASAR model exhibited strong adaptation, robustness, and reliable prediction, with q-RASAR indicators of Q2LOO = 0.7673, R2tr = 0.8079, R2test = 0.8610, Q2Fn = 0.8285−0.8614, and CCCtest = 0.9222. Based on an external dataset containing 128 emerging TWP-derived compounds, the model's applicability domain coverage was 90.6 %. The q-RASAR model predicted that the structure of diphenylamine was associated with higher toxicity, possibly liked to the SpMax2_Bhm and LogBCF descriptors. The established model reliably provides prediction and fills a critical data gap. These findings highlight the potential risks posed by emerging TWP-derived compounds to aquatic organisms.

Toxicity of individual and mixture of organic compounds to P. Phosphoreum and S. Capricornutum using interpretable simple structural parameters

Human and environmental ecosystem beings are exposed to multicomponent compound mixtures but the toxicity nature of compound mixtures is not alike to the individual chemicals. This work introduces four models for the prediction of the negative logarithm of median effective concentration (pEC50) of individual chemicals to marine bacteria Photobacterium Phosphoreum (P. Phosphoreum) and algal test species Selenastrum Capricornutum (S. Capricornutum) as well as their mixtures to P. Phosphoreum, and S. Capricornutum. These models provide the simplest approaches for the forecast of pEC50 of some classes of organic compounds from their interpretable structural parameters. Due to the lack of adequate toxicity data for chemical mixtures, the largest available experimental data of individual chemicals (55 data) and their mixtures (99 data) are used to derive the new correlations. The models of individual chemicals are based on two simple structural parameters but chemical mixture models require further interaction terms. The new model's results are compared with the outputs of the best accessible quantitative structure–activity relationships (QSARs) models. Various statistical parameters are done on the new and comparative complex QSAR models, which confirm the higher reliability and simplicity of the new correlations.

Chronic toxic effects of erythromycin and its photodegradation products on microalgae Chlorella pyrenoidosa

The photodegradation products (PDPs) of antibiotics in the aquatic environment received increasing concern, but their chronic effects on microalgae remain unclear. This study initially focused on examining the acute effects of erythromycin (ERY), then explored the chronic impacts of ERY PDPs on Chlorella pyrenoidosa. ERY of 4.0 − 32 mg/L ERY notably inhibited the cell growth and chlorophyll synthesis. The determined 96 h median effective concentration of ERY to C. pyrenoidosa was 11.78 mg/L. Higher concentrations of ERY induced more serious oxidative damage, antioxidant enzymes alleviated the oxidative stress. 6 PDPs (PDP749, PDP747, PDP719, PDP715, PDP701 and PDP557) were identified in the photodegradation process of ERY. The predicted combined toxicity of PDPs increased in the first 3 h, then decreased. Chronic exposure showed a gradual decreasing inhibition on microalgae growth and chlorophyll content. The acute effect of ERY PDPs manifested as growth stimulation, but the chronic effect manifested as growth inhibition. The malonaldehyde contents decreased with the degradation time of ERY at 7, 14 and 21 d. However, the malonaldehyde contents of ERY PDPs treatments were elevated compared to those in the control group after 21 d. Risk assessment still need to consider the potential toxicity of degradation products under long-term exposure.

Generation and characterization of a nanobody against the avian influenza virus H7 subtype

Avian influenza virus (AIV) H7N9 diseases have been recently reported, raising concerns about a potential pandemic. Thus, there is an urgent need for effective therapeutics for AIV H7N9 infections. Herein, camelid immunization and yeast two-hybrid techniques were used to identify potent neutralizing nanobodies (Nbs) targeting the H7 subtype hemagglutinin. First, we evaluated the binding specificity and hemagglutination inhibition activity of the screened Nbs against the H7 subtype hemagglutinin. Nb-Z77, with high hemagglutination inhibition activity was selected from the screened Nbs to optimize the yeast expression conditions and construct oligomeric forms of Nb-Z77 using various ligation methods. The oligomers Nb-Z77-DiGS, Nb-Z77-TriGS, Nb-Z77-Fc and Nb-Z77-Foldon were successfully constructed and expressed. Nb-Z77-DiGS and Nb-Z77-Foldon exhibited considerably greater activity than did Nb-Z77 against H7 subtype hemagglutinin, with median effective concentrations of 384.7 and 27.33 pM and binding affinity values of 213 and 5.21 pM, respectively. Nb-Z77-DiGS and Nb-Z77-Foldon completely inhibited the hemagglutination activity of the inactivated virus H7-Re1 at the lowest concentration of 0.938 μg/mL. This study screened a strain of Nb with high hemagglutination inhibition activity and enhanced its antiviral activity through oligomerization, which may have great potential for developing effective agents for the prevention, diagnosis, and treatment of AIV H7 subtype infection.

Chronic Effects of an Insect Growth Regulator (teflubenzuron) on the Life Cycle and Population Growth Rate of Folsomia candida.

Current standard toxicity tests on nontarget soil invertebrates mainly focus on the endpoints survival and reproduction. Such results are likely insufficient to predict effects at higher organizational levels, for example, the population level. We assessed the effects of exposure to the pesticide teflubenzuron on the collembolan Folsomia candida, by performing a full life-cycle experiment exposing single individuals via contaminated food (uncontaminated control and 0.2, 0.32, 0.48, 0.72, 1.08, and 1.6 mg/kg dry yeast). Several life-history traits were considered by following the growth and development of newly hatched individuals over a period of 65 days. We assessed survival, body length, time to first oviposition, cumulative egg production, and hatchability of eggs. A two-stage model was applied to calculate the population growth rate (λ) combined with elasticity analysis to reveal the relative sensitivity of λ to the effects of teflubenzuron on each life-history parameter. Body length was the least sensitive life-history parameter (median effective concentration = 1.10 mg teflubenzuron/kg dry yeast) followed by time to first oviposition (0.96 mg/kg), survival (median lethal concentration = 0.87 mg/kg), cumulative egg production (0.32 mg/kg), and egg hatchability (0.27 mg/kg). Population growth decreased with increasing concentrations of teflubenzuron (λ = 1.162/day in control to 1.005/day in 0.72 mg/kg dry yeast, with populations going extinct at 1.08 and 1.6 mg/kg dry yeast). Elasticity analysis showed that changes in juvenile survival had a greater impact on the population growth rate compared with the other life-history traits. Our study provides a comprehensive overview of individual-level effects of long-term exposure to teflubenzuron and integrates these effects to assess the potential risk to collembolan populations. Environ Toxicol Chem 2024;43:1173-1183. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Identification the Pathogen Cause a New Apple Leaf Blight in China and Determination the Controlling Efficacy for Five Botanical Fungicides.

Alternaria leaf blight has recently been described as an emerging fungal disease of apple trees which is causing the significant damage in the apple-growing areas of Tianshui and Jingning, Gansu, China. In the present study, the pathogen species involved in apple leaf blight and its biological characteristics were identified, and the inhibitory activity of different botanical fungicides against the pathogen was evaluated in vitro. Four strains were isolated from the symptomatic areas of necrotic apple leaves, and initially healthy leaves showed similar symptoms to those observed in orchards after inoculation with the ABL2 isolate. The ABL2 isolate was identified as Alternaria tenuissima based on the morphological characteristics of its colonies, conidiophores, and conidia, and this was also confirmed by multi-gene sequence (ITS, OPA10-2, Alta-1, and endoPG) analysis and phylogenic analysis. The optimum temperature, pH, carbon source, and nitrogen source for the growth of A. tenuissima mycelia were 28 °C, 6-7, soluble starch, and soy flour, respectively. In addition, the botanical fungicide eugenol exhibited the highest inhibitory effect on the mycelial growth and conidia germination of A. tenuissima, and the median effective concentration (EC50) values were 0.826 and 0.755 μg/mL, respectively. The protective and curative efficacy of eugenol were 86.85% and 76.94% after inoculation in detached apple leaves at a concentration of 4 μg/mL. Our research provides new insights into the control of apple leaf blight disease by applying botanical fungicides.

Design, synthesis and antifungal activity of indole derivatives containing 1,3,4-oxadiazole

In this study, 21 indole derivatives containing 1,3,4-oxadiazole were designed and synthesized, the results of the biological activity test showed that the target compounds had certain antifungal activity against 12 plant pathogenic fungi in vitro, among which. E1 showed excellent bioactivity against Botrytis cinerea (B.c.), Tomato Botrytis cinerea (F.M.) and Phomopsis sp (P.s.), with median effective concentration (EC50) values of 2.8, 5.1 and 5.2 µg/mL, which are higher than those of the control drug azoxystrobin (Az) at 15.2, 31.2 and 15.2 µg/mL. In vivo tests on blueberry leaves, tomato leaves and kiwifruit showed that E1 at 200 µg/mL offered stronger protective effect against B.c. (91.9 %) than Az (83.8 %) in blueberry leaves, F.M. (83.3 %) than Az (72.9 %) in tomato leaves and P.s. (89.3 %) than Az (86.9 %) in kiwifruit. Scanning electron microscope (SEM) experiments showed that B.c. hyphae treated with E1 had abnormal shrinkage and obvious morphological changes. The results of the mechanism study showed that E1 could change the integrity of the cell wall and cell membrane of pathogen B.c., which led to the increase in malondialdehyde (MDA), cell leakage and permeability and the rupture of the cell membrane. Because of their strong antifungal effects on plant fungus, indole derivatives containing 1,3,4-oxadiazole were predicted to develop into novel fungicides.

Interactions of monolayer molybdenum disulfide sheets with metalloid antimony in aquatic environment: Adsorption, transformation, and joint toxicity

The tremendous application potentiality of transitional metal dichalcogenides (TMDs), such as molybdenum disulfide (MoS2) nanosheets, will unavoidably lead to increasing release into the environment, which could influence the fate and toxicity of co-existed contaminants. The present study discovered that 59.8 % of trivalent antimony [Sb(III)] was transformed by MoS2 to pentavalent Sb [Sb(V)] in aqueous solutions under light illumination, which was due to hole oxidation on the nanosheet surfaces. A synergistic toxicity between MoS2 and Sb(III, V) to algae (Chlorella vulgaris) was observed, as demonstrated by the lower median-effect concentrations of MoS2 + Sb(III)/Sb(V) (13.1 and 20.9 mg/L, respectively) than Sb(III)/Sb(V) (38.8 and 92.5 mg/L, respectively) alone. Particularly, MoS2 at noncytotoxic doses notably increased the bioaccumulation of Sb(III, V) in algae, causing aggravated oxidative damage, photosynthetic inhibition, and structural alterations. Metabolomics indicated that oxidative stress and membrane permeabilization were primarily associated with down-regulated amino acids involved in glutathione biosynthesis and unsaturated fatty acids. MoS2 co-exposure remarkably decreased the levels of thiol antidotes (glutathione and phytochelatins) and aggravated the inhibition on energy metabolism and ATP synthesis, compromising the Sb(III, V) detoxification and efflux. Additionally, extracellular P was captured by the nanosheets, also contributing to the uptake of Sb(V). Our findings emphasized the nonignorability of TMDs even at environmental levels in affecting the ecological hazard of metalloids, providing insight into comprehensive safety assessment of TMDs.

Integrated physio-biochemical and transcriptomic analysis reveals the joint toxicity mechanisms of two typical antidepressants fluoxetine and sertraline on Microcystis aeruginosa

Selective serotonin reuptake inhibitor (SSRI) antidepressants are of increasing concern worldwide due to their ubiquitous occurrence and detrimental effects on aquatic organisms. However, little is known regarding their effects on the dominant bloom-forming cyanobacterium, Microcystis aeruginosa. Here, we investigated the individual and joint effects of two typical SSRIs fluoxetine (FLX) and sertraline (SER) on M. aeruginosa at physio-biochemical and molecular levels. Results showed that FLX and SER had strong growth inhibitory effects on M. aeruginosa with the 96-h median effect concentrations (EC50s) of 362 and 225 μg/L, respectively. Besides, the mixtures showed an additive effect on microalgal growth. Meanwhile, both individual SSRIs and their mixtures can inhibit photosynthetic pigment synthesis, cause oxidative damage, destroy cell membrane, and promote microcystin−leucine−arginine (MC-LR) synthesis and release. Moreover, the mixtures enhanced the damage to photosynthesis, antioxidant system, and cell membrane and facilitated MC-LR synthesis and release compared to individuals. Furthermore, transcriptomic analysis revealed that the dysregulation of the key genes related to transport, photosystem, protein synthesis, and non-ribosomal peptide structures was the fundamental molecular mechanism underlying the physio-biochemical responses of M. aeruginosa. These findings provide a better understanding of the toxicity mechanisms of SSRIs to microalgae and their risks to aquatic ecosystems.

Assessment of Mitochondrial Function in the AmE-711 Honey Bee Cell Line: Boscalid and Pyraclostrobin Effects.

There is a growing concern that chronic exposure to fungicides contributes to negative effects on honey bee development, life span, and behavior. Field and caged-bee studies have helped to characterize the adverse outcomes (AOs) of environmentally relevant exposures, but linking AOs to molecular/cellular mechanisms of toxicity would benefit from the use of readily controllable, simplified host platforms like cell lines. Our objective was to develop and optimize an in vitro-based mitochondrial toxicity assay suite using the honey bee as a model pollinator, and the electron transport chain (ETC) modulators boscalid and pyraclostrobin as model fungicides. We measured the effects of short (~30 min) and extended exposures (16-24 h) to boscalid and pyraclostrobin on AmE-711 honey bee cell viability and mitochondrial function. Short exposure to pyraclostrobin did not affect cell viability, but extended exposure reduced viability in a concentration-dependent manner (median lethal concentration = 4175 µg/L; ppb). Mitochondrial membrane potential (MMP) was affected by pyraclostrobin in both short (median effect concentration [EC50] = 515 µg/L) and extended exposure (EC50 = 982 µg/L) scenarios. Short exposure to 10 and 1000 µg/L pyraclostrobin resulted in a rapid decrease in the oxygen consumption rate (OCR), approximately 24% reduction by 10 µg/L relative to the baseline OCR, and 64% by 1000 µg/L. Extended exposure to 1000 µg/L pyraclostrobin reduced all respiratory parameters (e.g., spare capacity, coupling efficiency), whereas 1- and 10-µg/L treatments had no significant effects. The viability of AmE-711 cells, as well as the MMP and cellular respiration were unaffected by short and extended exposures to boscalid. The present study demonstrates that the AmE-711-based assessment of viability, MMP, and ETC functionality can provide a time- and cost-effective platform for mitochondrial toxicity screening relevant to bees. Environ Toxicol Chem 2024;43:976-987. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Characteristics of fluopicolide-resistance mutants in Phytophthora nicotianae, the pathogen causing black shank disease in tobacco

Black shank, a devastating disease in tobacco production worldwide, is caused by the oomycete plant pathogen Phytophthora nicotianae. Fluopicolide is a pyridinylmethyl-benzamides fungicide with a unique mechanism of action and has been widely used for controlling a variety of oomycetes such as Plasmopara viticola, Phytophthora infestans, Pseudoperonospora cubensis, P. nicotianae and Bremia lactucae. However, the fluopicolide-resistance risk and molecular basis in P. nicotianae have not been reported. In this study, the sensitivity profile of 141 P. nicotianae strains to fluopicolide was determined, with a mean median effective concentration (EC50) value of 0.12 ± 0.06μg/mL. Five stable fluopicolide-resistant mutants of P. nicotianae were obtained by fungicide adaptation, and the compound fitness index of these resistant mutants were lower than that of their parental isolates. Additionally, cross-resistance tests indicated that the sensitivity of fluopicolide did not correlate with other oomycete fungicides, apart from fluopimomide. DNA sequencing revealed two point mutations, G765E and N769Y, in the PpVHA-a protein in the fluopicolide-resistant mutants. Transformation and expression of PpVHA-a genes carrying G765E and N769Y in the sensitive wild-type isolate confirmed that it was responsible for fluopicolide resistance. These results suggest that P. nicotianae has a low to medium resistance risk to fluopicolide in laboratory and that point mutations, G765E and N769Y, in PpVHA-a are associated with the observed fluopicolide resistance.

Antiparasitic efficacy of flavonoids identified from Psoralea corylifolia against Tetrahymena piriformis in guppy (Poecilia reticulate)

Tetrahymena piriformis belongs to the ciliated protists (ciliates), causing severe economic losses in aquaculture. Chemical drugs currently used usually have toxic side effects, and there is no specific drug against Tetrahymena. Therefore, it is an urgent need to identify new antiparasitic lead compounds. In the present study, the in vitro parasiticidal activity of ethyl acetate (EtOAc) extracts and water extracts from 22 selected traditional Chinese medicines (TCMs) were evaluated against T. piriformis. The EtOAc extract of P. corylifolia turned out to be the most active with the minimum parasiticidal concentration of 100 mg/L within 3 h. Thus, it was separated into 12 fractions by the first-dimensional (D1) normal phase liquid chromatography (NPLC), meanwhile combining with in vitro antiparasitic tests for activity tracking. Subsequently, 8 flavonoids were identified in the active fractions by the second-dimensional (D2) reverse phase liquid chromatography (RPLC) tandem high-resolution mass spectrometry. According to the results, 5 flavonoids were selected for in vitro antiparasitic test, of which isobavachalcone showed the minimum parasiticidal concentration of 3.125 mg/L in 2 h. Bathing treatment of infected guppies with isobavachalcone could significantly reduce the burden of T. piriformis, obtaining a 24-h median effective concentration (24-h EC50) value of 1.916 mg/L. And the concentration of isobavachalcone causing guppies to die within 24 h is 39 times than that of 24-h EC50. The results demonstrated that isobavachalcone has the potential to be developed into a novel commercial fish drug against T. piriformis.

Toxicity of commercial and pure forms of three nonsteroidal anti-inflammatory drugs in Xenopus laevis embryos before and after ozonation

In this study, the toxic and teratogenic effects of three commercial drugs and their active ingredients on Xenopus laevis embryos before and after ozonation were evaluated using the Frog Embryos Teratogenesis Assay–Xenopus (FETAX). First, the median lethal concentration (LC50) and, if data were available, the median effective concentration, teratogenic index and minimum growth inhibitory concentration were determined for each drug substance without ozonation. Then, the active substance amounts of three selected nominal concentrations (LC50/2, LC50, and LC50×2) of each test substance before ozonation were measured by HPLC analysis and the toxicity of these substances was evaluated after 2, 3, 4, and 5 h of ozonation. In addition, degradation products that may occur during ozonation were evaluated by LC-MS analysis. The 96-h LC50s of Dolphin–diflunisal, Dichloron–diclofenac sodium, and Apranax–naproxen drug–active substance pairs were determined to be 22.3 and 11.1, 25.7 and 18.7, and 47.8 mg active substance/L and 45.3 mg/L, respectively. According to the FETAX test results, the Dolphin–diflunisal drug–active ingredient pair did not cause growth retardation in exposed embryos. Dichloron–diclofenac sodium and Apranax–naproxen drug–active ingredient pairs were both teratogenic and growth inhibitory. In the second stage of the study, in which the effectiveness of ozonation in eliminating the toxic effects of drugs is evaluated, it is seen that ozonation is partially successful in eliminating the toxic effects of Dolphin–diflunisal and Dichloron–diclofenac sodium pairs, but insufficient for eliminating the effects of the Apranax–naproxen pair.

Effects of benzophenone-3 and its metabolites on the marine diatom Chaetoceros neogracilis: Underlying mechanisms and environmental implications

The wide application of benzophenones (BPs), such as benzophenone-3 (BP3), as an ingredient in sunscreens, cosmetics, coatings, and plastics, has led to their global contamination in aquatic environments. Using the marine diatom Chaetoceros neogracilis as a model, this study assessed the toxic effects and mechanisms of BP3 and its two major metabolites (BP8 and BP1). The results showed that BP3 exhibited higher toxicity on C. neogracilis than BP8 and BP1, with their 72-h median effective concentrations being 0.4, 0.8 and 4 mg/L, respectively. Photosynthesis efficiencies were significantly reduced after exposure to environmentally relevant concentrations of the three benzophenones, while cell viability, membrane integrity, membrane potential, and metabolic activities could be further impaired at their higher concentrations. Comparative transcriptomic analysis, followed by gene ontology and KEGG pathway enrichment analyses unraveled that all the three tested benzophenones disrupted photosynthesis and nitrogen metabolism of the diatom through alteration of similar pathways. The toxic effect of BP3 was also attributable to its unique inhibitory effects on eukaryotic ribosome biosynthesis and DNA replication. Taken together, our findings underscore that benzophenones may pose a significant threat to photosynthesis, oxygen production, primary productivity, carbon fixation, and the nitrogen cycle of diatom in coastal waters worldwide.

Novel Reproduction Toxicity Test Method for Hyalella azteca Using Sexually Mature Amphipods Provides More Robust Data Than Standard Methods in Exposures to Imidacloprid.

Hyalella azteca is an epibenthic crustacean used in ecotoxicology, but there are challenges associated with standard methods using reproduction as an endpoint. A novel, 28-day reproduction toxicity test method for H. azteca was created to address these issues by initiating tests with sexually mature amphipods to eliminate the confounding effects of growth, using a sex ratio of seven females to three males to reduce reproductive variability, and conducting tests in water-only conditions to make recovery of juveniles easier and expand testing capabilities to water-soluble compounds. In the present study, we evaluated the 28-day novel method by comparing it with the 42-day standard test method in duplicate and parallel water-only, static-renewal exposures to sublethal concentrations of imidacloprid (0.5-8 µg/L). Both methods showed similar effects on survival, with survival approaching 50% in the highest test concentration (8 µg/L). However, the 42-day median effect concentrations (EC50s) for growth were more sensitive in the standard method (1.5-3.2 µg/L) compared with the 28-day EC50s generated by the novel method (>8 µg/L). Reproduction endpoints (juveniles/female) produced similar EC50s between methods, but the data were less variable in novel tests (smaller coefficients of variation); therefore, fewer replicates would be required to detect effects on reproduction compared with the standard method. In addition, novel tests generated 28 days of reproduction data compared with 14 days using standard tests and allowed survival and growth of sexes to be assessed independently. Thus, the novel method shows promise to improve the use of reproduction as an endpoint in water-only toxicity tests with H. azteca. Environ Toxicol Chem 2024;43:723-735. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.