Safe Concentration Research Articles

Invasive Candidiasis: A Promising Approach Using Jatropha Dioica Extracts and Nanotechnology

AbstractCandida albicans, a common fungal organism, often lives harmlessly in the human body. However, under certain conditions, it can turn into a dangerous pathogen, causing infections that range from mild to life‐threatening. With rising resistance to antifungal treatments, understanding and controlling this opportunistic fungus has never been more crucial. This study highlights the potential of combining natural plant extracts, specifically the aqueous (JdextAq) and ethanolic (JdextEt) extracts of Jatropha dioica, with nanotechnology in the form of magnetite nanoparticles (MNPs) to combat this persistent pathogen. FTIR spectra revealed significant interactions between the metabolites and MNPs, specifically through binding to the Fe3+ and Fe2+ sites. The average size of the MNPs was 11±3 nm, and they are non‐toxic even at high concentration (500 μg/ml). The same effect is observed with JdextEt; however, JdextAq is cytotoxic at this concentration. The JdextAq‐MNPs hybrid is toxic even at very low concentrations (250–50 μg/ml). All materials demonstrated high inhibition against C. albicans. At safe concentrations for cell viability, MNPs (500 μg/ml) and JdextEt‐MNPs (500–50 μg/ml) achieved the highest inhibition rates of 97.13 % and 97.56 %, respectively. As antifungal resistance rises, these findings pave the way for innovative therapeutic strategies against this opportunistic pathogen.

The inhibitory effect of Hypericum japonicum on H9N2 avian influenza virus

The H9N2 subtype of avian influenza virus (AIV) causes severe immunosuppression and high mortality in view of its frequent co-infection with other pathogens, resulting in significant economic losses in the poultry industry. Current vaccines provide suboptimal immune protection against H9N2 AIV owing to antigenic variations, highlighting the urgent need for safe and effective antiviral drugs for the prevention and treatment of this virus. This study aimed to investigate the inhibitory effects of Hypericum japonicum extract on H9N2 AIV. Our findings revealed that the extract obtained through resin column separation using 60% ethanol (S06-60%) inhibited H9N2 AIV replication in Madin-Daby canine kidney cells in a dose-dependent manner. The maximum safe concentration of the water-soluble S06-60% extract was determined to be 0.05 mg/mL. Time-course experiments indicated that S06-60% primarily exerted its antiviral effects during the viral pretreatment and adsorption stages. Furthermore, in vivo experiments conducted on specific pathogen-free chickens confirmed the effectiveness of S06-60% in inhibiting H9N2 AIV infection and mitigating associated damage to tracheal and lung tissues. Overall, our study highlights the therapeutic potential of Hypericum japonicum extract S06-60% as a viable antiviral candidate against H9N2 AIV, offering promising implications for its application in poultry health management to reduce the economic impact on the poultry industry.

Anabasis setifera leaf extract from arid habitat: A treasure trove of bioactive phytochemicals with potent antimicrobial, anticancer, and antioxidant properties.

The main objective of this study was to evaluate the biological activities of Anabasis setifera extract, including its antimicrobial, anticancer, and antioxidant properties. In the current study, Anabasis setifera leaves extract was evaluated for antimicrobial, anticancer, antioxidant activities and phytochemical analyses. Ethyl acetate extract of Anabasis setifera (EA-AS) exhibited promising antimicrobial activity toward Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, Bacillus subtilis, Candida albicans, Aspergillus brasiliensis, Aspergillus fumigatus with MICs 62.5, 125, 62.5, 31.25, 62.5, 125 and 125 μg/mL respectively. Moreover, EA-AS showed anticancer activity at safe concentrations, where IC50 were 36.4 and 44 μg/mL toward Hep-G2 and MCF-7 cancerous cell lines. EA-AS was found to contain 55 significant compounds identified through gas chromatography mass spectrophotometry (GCMS). The most abundant compounds were 1,4-dimethoxy-6,7,8,9-tetrahydro-5-benzocycloheptenone (26.04%), hexa-2,4-diyn-1-ylbenzene (8.40%), dihydrobenzo[b]fluoranthene (6.10%), ethanone, 1-[2,3-dihydro-2-(1-methylethenyl)-5-benzofuranyl (6.10%), and valerenol (4.08%). GC mass analysis confirmed the antioxidant properties of AS by detecting several compounds with antioxidant activity, including hexa-2,4-diyn-1-ylbenzene, nerolidol, spathulenol, -naphthalenem ethanol, decahydro-4-trimethyl-8-methylene, hexadecenoic acid, tremetone, desmethoxyencecalin, heptadecyn-1-ol, thunbergol, hexadecanol, dotriacontane, taylorione, ligulatin, retinoic acid, and falcarinol. The analysis of EA-AS reveals that it is a rich source of valuable phytochemicals: total Phenolic Content: a promising 4,264 μg/mL /, suggesting substantial biological and pharmacological potential. Total tannin content: 391.17 μg/mL, indicating potential applications in industries like nutraceuticals, pharmaceuticals, and cosmetics. Total flavonoid content exceptionally high at 5,163 μg/mL, while the total alkaloid content measured 1,036.26 μg/mL. Additionally, EA-AS demonstrated antioxidant activity with an EC50 of 30.6 μg/mL. In conclusion, the comprehensive analysis of the EA-AS reveals its immense potential as a rich source of valuable phytochemicals with diverse bioactivities, warranting further in-depth studies to unlock its full pharmaceutical and commercial prospects. Our results suggest substantial biological and pharmacological prospects for EA-AS as a promising antimicrobial, anticancer, and potent antioxidant.

Effect of occupational exposure to ADCA on the incidence of allergic respiratory reactions - a literature review

1,1'-azodi(formamide) (ADCA) is widely used as a blowing agent, a chemical substance designed to induce foaming processes. In Poland, ADCA is manufactured by a company specializing in the production of polyethylene foam bags and laminates used in various industries including home appliances, electronics, construction, furniture, automotive, and sports and leisure. The mechanism of action of ADCA involves thermal decomposition, resulting in nitrogen, carbon monoxide, as well as ammonia and carbon dioxide as the main gaseous decomposition products. These penetrate the polymer matrix, contributing to expansion and foaming properties. Most studies evaluating the relationship between occupational exposure and the development of allergic respiratory diseases focus on workers involved in ADCA production or its use as a blowing agent in plastics. The objective is to assess the respiratory sensitizing effects of ADCA in humans due to occupational exposure, based on literature data. The presented data confirm that long-term occupational exposure to ADCA can lead to persistent bronchial hyperreactivity symptoms in workers. 1,1'-azodi(formamide) can induce occupational asthma, with initial symptoms including nasal congestion, conjunctivitis, wheezing, and cough. Subsequently, symptoms such as chest tightness, dyspnea, and nocturnal cough attacks may appear, with a latency period of several years observed before symptom onset. In some cases, symptom progression was noted with continued ADCA exposure, while in others, exposure was discontinued after initial symptoms, preventing observation of symptom exacerbation. Prior exposure to allergens, such as working in bakeries, appears to accelerate symptom onset. Improvement in allergy symptoms has been noted during weekend breaks from work. There is no safe concentration identified for ADCA that would not result in adverse health effects for workers. A concentration of 0.036 mg/m3 is considered the lowest observed adverse effect concentration, causing critical reduction in lung spirometric parameters. Med Pr Work Health Saf. 2024;75(5).

Scientific substantiation of the maximum permissible concentration of the pharmaceutical substance osimertinib mesylate in the air of the working area

Introduction. Osimertinib, a 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor, is currently the only drug registered for the treatment of metastatic non-small cell lung cancer in patients with a positive T790M mutation status. The production of osimertinib mesylate is planned on the territory of the Russian Federation, which necessitates research to substantiate the hygienic standard for the aerosol content of the substance in the air of the working area. Conducting research to substantiate the maximum permissible concentration of a substance requires significant material and time resources, while using the results of preclinical and clinical studies, mathematical modeling of processes, and risk assessment methodology allows for a comprehensive assessment of the substance, while significantly reducing the time and cost of work. The study aims to scientifically substantiate the maximum permissible concentration of the pharmaceutical substance osimertinib mesylate in the air of the working area using data from toxicological studies and mathematical modeling of the effects of the substance on humans in industrial conditions. Materials and methods. The materials used were domestic and international databases, reports, research protocols, scientific articles and monographs containing information on the physico-chemical and toxic properties, pharmacotherapeutic activity of osimertinib. Results. The specialists have conducted hygienic regulation of osimertinib, taking into account data on its toxicity, danger, pharmacotherapeutic activity, side effects, long-term consequences, pharmacokinetic studies and modeling. To substantiate the value of the maximum permissible concentration, the authors used the reference points: an inactive NOEL level of 1 mg/­kg/­day for general toxic effect, established in a 92-day experiment on rats with intragastric administration; the lowest observed level of adverse effects of LOAEL is 0.5 mg/kg/day for general toxic effect, established in a 180-day experiment on dogs with intragastric administration; the level that does not cause adverse effects of NOAEL is 10 mg/kg/day for general toxic effect, established in a 180-day experiment on mice with intragastric administration. Safe concentrations of osimertinib in the air of the work area were evaluated using reference points, including the pharmacological effect and the minimum daily therapeutic dose; toxicokinetic modeling of concentrations of a substance in the human body under production conditions and the level of minimal risk. Limitation. The study is limited to the review of open literature sources describing the toxicological/toxicokinetic characteristics of osimertinib mesylate. Conclusion. The most stringent indicators of safe exposure levels, established on the basis of pharmacological effect and toxicokinetic modeling in dogs, allowed us to recommend 0.005 mg/m3, aerosol, hazard class 1 as the maximum permissible concentration in the air of the working area for osimertinib mesylate. Ethics. This study did not require the conclusion of the Ethics Committee.

Determination of an Anti-Parasitic Active Pharmaceutical Ingredient in Wastewater Effluents Using Capillary Zone Electrophoresis.

Ireland has a successful pharmaceutical industry with over 100 pharmaceutical manufacturing sites across the island. Although this success has many benefits, the irreversible effects emissions from pharmaceutical manufacturing can have on the environment are a major drawback. Although known pollutants are regularly monitored with limits set out by the Environmental Protection Agency, one significant pollutant has been overlooked: pharmaceutical pollution. Detecting these pollutants and ensuring they are at a safe concentration for the environment is of utmost importance. In recent years, capillary electrophoresis is being recognised as a suitable alternative to high-performance liquid chromatography due to its many benefits such as faster analysis, water-based buffers and smaller sample volumes. In this paper, a capillary zone electrophoresis (CZE) method with a preconcentration step of solid-phase extraction was developed for an anti-parasitic active pharmaceutical ingredient (API) called ZB23. The API was successfully detected in a wastewater sample in less than 10min using the CZE parameters of 25mM borate buffer with a pH of 10.5, 15% MeOH, 10kV voltage, 25mbar for 5s injection size, an Lt of 40cm, an Ld of 31.5cm and a detection wavelength of 214nm.

Laboratory modeling of environmentally safe concentrations of fuel oil in the soils of Crimea

Laboratory modeling of environmentally safe concentrations of fuel oil in the soils of Crimea

Effect of water pollution by nickel on hepatic enzymes and oxidative enzymes in Cyprinus carpio (common carp)

Nickel (Ni) is considered a toxic heavy metal that causes serious diseases in humans and animals. Therefore, this study was conducted on common carp, which is considered an essential food item for humans. This study was designed to investigate the effect of nickel on the hepatic and antioxidant enzymes of Cyprinus carpio after 3 and 6 weeks of exposure to water contaminated with Ni. C. carpio fingerlings were purchased from a neighboring fish hatchery. The morphometric characteristics of the experimental fish were documented. All fish were stocked, regardless of gender. The fish were exposed to different concentrations (20, 40, 60, 80, and 100 mg/L) to obtain the LC50 for Ni during 96 hours, and the median lethal concentration of Ni was 80 mg/L through 96 hours. The fish were exposed to two safe concentrations, 1 ppm and 5 ppm. The results after 3 and 6 weeks were as follows: When compared to the control groups, all treated groups had significantly higher levels of liver function parameters (ALT and AST). Malondialdehyde (MDA) and catalase activity measurement (CAT) enzyme levels were considerably higher in all treated groups after 3 and 6 weeks as compared to control groups. These changes are trustworthy indications of the cellular and humoral immune responses in C. carpio.

Safety and efficacy of a feed additive consisting of an essential oil derived from the flowering tops of Lavandula angustifolia Mill. (lavender oil) for use in all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil from the fresh flowering tops of Lavandula angustifolia Mill. (lavender oil) when used as a sensory additive in feed and in water for drinking for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive under assessment is considered safe up to the maximum proposed use levels in complete feed of 30 mg/kg for dogs and ornamental fish. For the other target species, the calculated safe concentrations were 9 mg/kg for chickens for fattening, 13 mg/kg for laying hens, 12 mg/kg for turkeys for fattening, 19 mg/kg for pigs for fattening, 16 mg/kg for piglets, 23 mg/kg for sows, 39 mg/kg for veal calves (milk replacer) and salmonids, 35 mg/kg for cattle for fattening, sheep/goats and horses, 22 mg/kg for dairy cows, 14 mg/kg for rabbits and 7 mg/kg for cats. These conclusions were extrapolated to other physiologically related species. For any other species, the additive is safe at 7 mg/kg complete feed. The use of lavender oil in water for drinking was considered safe provided that the total daily intake does not exceed the daily amount considered safe when consumed via feed. The use of lavender oil in animal feed under the proposed conditions of use is safe for the consumer and the environment. Regarding user safety, the essential oil under assessment should be considered as an irritant to skin and eyes and as a dermal and respiratory sensitiser. Since the oil of the flowering tops of L. angustifolia is recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

Ambient air monitoring in Bishkek, Kyrgyz Republic for assessing the effectiveness of environment protection measures

The system of mobile monitoring of priority pollutants in the air of Bishkek, the capital of the Kyrgyz Republic, was improved and tested. The daytime dynamics of the content of nitrogen oxides (NO, NO2), carbon oxides (CO, CO2), formaldehyde (H2CO), and suspended microparticles (PM2.5) in the air on the central highways of the city were studied in winter. In 2023, significant concentrations of the components were identified. They exceeded the MAC standards several times and varied widely depending on the substance, the point and time of observation. A set of recommendations for reducing air pollution, including more environmentally friendly urban transport, types of fuel and its combustion technologies, were developed and partially implemented in 2022-2023. The results of monitoring of the content of the components were compared under similar conditions in 2023 and 2024. It was revealed that the recommendations of the Bishkek city administration contributed to reducing air pollution with harmful substances at most observation points to safe concentrations. The need for using the system of integrated mobile and automated monitoring of the atmospheric air in populated areas was justified.

Palmatine as a potent immunomodulator: Enhancing resistance to Micropterus salmoides rhabdovirus in largemouth bass through innate immune activation and viral suppression

Micropterus salmoides rhabdovirus (MSRV) poses a significant threat to aquaculture, causing substantial economic losses. In this study, we evaluated the antiviral efficacy and immunomodulatory potential of palmatine, a plant-derived monomer, against MSRV infection in largemouth bass. Our results demonstrated that palmatine significantly inhibited MSRV replication, with a reduction in viral nucleoprotein expression by 85 % at a safe concentration. Additionally, palmatine pre-treatment of EPC cells enhanced their antiviral capacity, with a maximum inhibition rate of 82 % following 24 h pre-incubation. Palmatine also effectively reduced MSRV-induced cytopathic effects, protecting cellular integrity and maintaining mitochondrial membrane potential. In vivo studies revealed that palmatine immersion at 80 mg/L was non-toxic and significantly suppressed MSRV replication in largemouth bass, increasing survival rates by 53 % over 15 d. Furthermore, palmatine pre-treatment enhanced the fish's resistance to MSRV, with a 78 % inhibition rate of viral replication and a 46 % increase in survival rate. Mechanistically, palmatine activated key immune genes, including IRF3, IRF7, and IFN, indicating its role in boosting innate immune responses. The compound also reduced horizontal transmission of MSRV in a cohabitation model, decreasing viral spread by up to 78 % over nine days. These findings highlight palmatine's potential as a small-molecule immunomodulator in aquaculture, offering a sustainable approach to disease management and enhancing fish health and welfare. Integrating palmatine into fish diets as an immunostimulant could provide a continuous, proactive defense against viral outbreaks, promoting more resilient and sustainable aquaculture practices.

Safe concentration, unsafe effects: Impact of BPA on antioxidant function in the hepatopancreas and ovarian gene expression in oriental river prawns (Macrobrachium nipponense)

This study investigated the effects of Bisphenol A (BPA), a common endocrine-disrupting chemical, on the antioxidant enzyme activities in the hepatopancreas and the expression of genes related to ovarian development in oriental river prawns (Macrobrachium nipponense). The 24hLC50 and 48hLC50 values for BPA were 80.59 mg/L and 63.90 mg/L, respectively, with a safe concentration of 12.06 mg/L. Prawns were exposed to low (4.85 mg/L), safe (12.06 mg/L), and high (30.00 mg/L) concentrations of BPA for 10 days to measure enzyme activities, and for 20 days followed by 7 days in BPA-free water to measure gene expression.Short-term exposure (12 h, 1d, 3d) to low concentration BPA did not significantly affect superoxide dismutase (SOD) activity in the hepatopancreas (P > 0.05), but long-term exposure (6d, 10d) significantly reduced SOD activity (P < 0.05). Catalase (CAT) activity showed no significant changes throughout the low concentration exposure period (P > 0.05). At safe and high concentrations, SOD and CAT activities significantly decreased after 12 h of exposure (P < 0.05).BPA affected heat shock protein 90 (HSP90) expression in the ovary, with low concentration BPA significantly upregulating HSP90 after 1 day (P < 0.05), but returning to normal levels after 10 and 20 days. At the safe concentration, HSP90 was significantly upregulated at all three sampling points (1d, 10d, 20d) (P < 0.05), while high concentration exposure led to significant upregulation only on day 10 (P < 0.05).Low concentration BPA had no significant effect on Cathepsin B (CB) and Cathepsin L (CL) gene expression in the ovaries (P > 0.05). However, safe concentration exposure promoted CB expression on days 1, 10, and 20 (P < 0.05), while high concentration exposure significantly increased CB expression on day 1 (P < 0.05), with levels returning to normal on days 10 and 20. CL expression significantly increased after 20 days of exposure to both safe and high concentrations (P < 0.05). Gene expression levels in the ovaries returned to normal after transfer to BPA-free water, with HSP90 and CB normalizing by day 1, and CL by day 7.These results indicate that even safe concentrations of BPA impose stress on the hepatopancreas and increase the expression of HSP90, CB, and CL genes in the ovaries, affecting ovarian development. And, these effects are reversible within a certain period after the removal of BPA.

Abamectin at environmentally relevant concentrations impairs bone development in zebrafish larvae

Abamectin (ABM) is a widely used pesticide in agriculture and veterinary medicine, which primarily acts by disrupting the neurological physiology of pests, leading to their paralysis and death. Its extensive application has resulted in contamination of many natural water bodies. While the adverse effects of ABM on the growth and development of non-target organisms are well documented, its impact on bone development remains inadequately studied. The present study aimed to investigate the effects of environmentally relevant concentrations of ABM (1, 5, 25 μg/L) on early bone development in zebrafish. Our results indicated that ABM significantly affected both cartilage and bone development of zebrafish larvae, accompanied by dose-dependent increase in deformity and mortality rates, as well as exacerbated apoptosis. ABM exposure led to deformities in the ceratobranchial (cb) and hyosymplectic (hs), accompanied by significant increases in the length of the palatoquadrate (pq). Furthermore, significant decreases in the CH-CH angle, Meckel's-Meckel's angle, and Meckel's-PQ angle were noted. Even at the safe concentration of 5 μg/L (1/10 of the 96 h LC50), ABM delayed the process of bone mineralization in zebrafish larvae. Real-time fluorescent quantitative PCR results demonstrated that ABM induced differential gene expression associated with cartilage and bone development in zebrafish. Thus, this study provides preliminary insights into the effects and molecular mechanisms underlying ABM's impact on the bone development of zebrafish larvae and offers new evidence for a better understanding of its toxicity.

Integrated battery thermal management and CO2 control in electric buses using recirculated air and waste heat recovery

In recent years, electric vehicles (EVs) have significantly progressed due to their environmental protection and energy-saving advantages. However, maintaining indoor thermal comfort and effective battery thermal management are critical considerations for EVs. Unlike conventional vehicles, EVs cannot use waste heat and depend on heat pump systems for winter heating and summer cooling. This research proposes a novel system to reduce the energy consumption of heat pump systems by using recirculated air while addressing the challenges of battery temperature management and maintaining safe CO2 concentrations in the cabin. The primary objectives of this research are threefold: first, to ensure passenger comfort through an integrated approach that includes cabin CO2 concentration safety; second, to recover heat from recirculated cabin air to save energy and control battery temperature; and third, to comprehensively analyze the performance of the Electric Vehicle Thermal Management System (EVTMS) using precise Computational Fluid Dynamics (CFD) analysis and mathematical modeling. This study will significantly enhance the understanding of energy consumption related to CO2 concentration control; an aspect previously overlooked in the literature. It will develop a battery temperature management strategy that leverages bus exhaust heat. These contributions will aid in achieving both passenger comfort and battery stability in electric buses, providing practical insights for the design and optimization of thermal management systems for future electric buses.

Efficacy of a novel oxygen scavenger mask in reducing local oxygen concentrations below the surgical fire risk threshold: an experimental proof-of-concept study

BackgroundThis study aims to evaluate the efficacy of an oxygen scavenging mask device in reducing local oxygen concentrations from nasal cannula ventilation compared to a standard open facial surgical field.MethodsThis is a controlled experiment using a custom-fabricated silicone midfacial oxygen scavenging device, SimMan airway management trainer manikin (Laerdal Medical, Stavanger, Norway), handheld oxygen detector (Forensics Detectors, Los Angeles, United States) and oxygen from a Datex Ohmeda Aisys Carestation anesthesia unit (GE HealthCare, Chicago, United States). Oxygen concentrations were measured at 18 facial landmarks (Fig. 1) with nasal cannula flow of 2, 4, and 6 L/min of 100% FiO2 in both masked and unmasked conditions (Fig. 2).ResultsThe mean oxygen concentration in the facial surgical field was 20.95% with the scavenger mask and 24.8% without (P < 0.001; two-tailed paired t-test). The unmasked condition was associated with suprathreshold oxygen concentration levels at 13 of 18 facial landmarks (Table 1). The device significantly reduced local oxygen concentration at 16 of 18 facial landmarks (Table 1). The device provided safe oxygen concentration levels at all three flow rates, and measured oxygen concentrations directly correlated with oxygen flow rate in the unmasked condition (Table 2).ConclusionsAn oxygen scavenger mask device reduced local oxygen concentrations from nasal cannula ventilation to below the 23% fire threshold in the entire facial surgical field external to the mask in these experiments. The device may reduce intraoperative fire risk in patients that require supplementary oxygen during surgery.

Effects of high-dose selenium-enriched Saccharomyces cerevisiae on growth performance, antioxidant status, tissue fat content and selenium concentration, and selenoenzyme mRNA expression in chicks

Selenium-enriched Saccharomyces cerevisiae (SSC) as organic selenium (Se) has been shown to have better advantages and is approved for use in animal feed rather than inorganic Se, however, there is little available data on the toxic effects of SSC on poultry. The present study was conducted to investigate the effects of high-dose SSC on growth performance, antioxidant status, tissue fat content and Se concentration, and selenoenzyme mRNA expression in chicks. A total of 500, 1-day-old SPF chicks were randomly divided into 5 groups with 10 replicates of 10 chicks each. Group 1 served as a control and was fed a basal diet supplemented with 0.15 mg/kg Se from sodium selenite (SS), group 2 was fed the basic diet supplemented with 1.5 mg/kg Se from SS, while groups 3, 4, and 5 were fed the basal diet supplemented with 1.5, 5 and 10 mg/kg Se from SSC, respectively. The results showed that SS and SSC supplementation significantly affected the average daily feed intake (ADFI), feed/gain ratio (FCR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, tissue fat content and Se concentration, and GPx1 and GPx4 mRNA levels compared with the control group (P < 0.05). Compared with group 2, group 3 exhibited higher GPx and SOD activities, tissue Se concentration, and lower MDA content on d 30, and higher Se concentration, GPx1 mRNA levels in liver and breast muscle and GPx4 mRNA levels in liver and thigh muscle, and lower MDA content on d 60 (P < 0.05). The results of correlation analysis showed that high-dose SSC supplementation was positively correlated with AFDI, FCR, MDA content, and tissue Se concentration, and negatively correlated with GPx and SOD activities, T-AOC, GPx1 and GPx4 mRNA levels in tissues. In conclusion, up to 1.5 mg/kg Se from SSC in diet may be a safe concentration for chicks that exhibited better biological effects than SS, the toxic effects of high-dose SSC supplementation mainly exhibited growth decrease, peroxidation and lipid metabolism disturbance, and became stronger with the increase of dietary Se levels.

Cytotoxicity and cell membrane interactions of choline-based ionic liquids: Comparing amino acids, acetate, and geranate anions

Ionic liquids (ILs) have found diverse applications in research and industry. Biocompatible ILs, a subset considered less toxic than traditional ILs, have expanded their applications into biomedical fields. However, there is limited understanding of the toxicity profiles, safe concentrations, and underlying factors driving their toxicity. In this study, we investigated the cytotoxicity of 13 choline-based ILs using four different cell lines: Human dermal fibroblasts (HDF), epidermoid carcinoma cells (A431), cervical cancer cells (HeLa), and gastric cancer cells (AGS). Additionally, we explored the haemolytic activity of these ILs. Our findings showed that the cytotoxic and haemolytic activities of ILs can be attributed to the hydrophobicity of the anions and the pH of the IL solutions. Furthermore, utilising quartz crystal microbalance with dissipation (QCM-D), we delved into the interaction of selected ILs, including choline acetate [Cho][Ac] and choline geranate [Cho][Ge], with model cell membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The QCM-D data showed that ILs with higher toxicities exhibited more pronounced interactions with membranes. Increased variations in frequency and dissipation reflected substantial changes in membrane fluidity and mass following the addition of the more toxic ILs. Furthermore, total internal reflection fluorescence microscopy study revealed that [Cho][Ac] could cause lipid rearrangements and pore formation in the membrane, while [Cho][Ge] disrupted the bilayer packing. This study advances our understanding of the cellular toxicities associated with choline-based ILs and provides valuable insights into their mechanisms of action concerning IL-membrane interactions. These findings have significant implications for the safe and informed utilisation of biocompatible ILs in the realm of drug delivery and biotechnology.

Non-conventional endpoints show higher sulfoxaflor toxicity to Chironomus riparius than conventional endpoints in a multistress environment

Evidence grows that standard toxicity testing might underestimate the environmental risk of neurotoxic insecticides. Behavioural endpoints such as locomotion and mobility have been suggested as sensitive and ecologically relevant additions to the standard tested endpoints. Possible interactive effects of chemicals and additional stressors are typically overlooked in standardised testing. Therefore, we aimed to investigate how concurrent exposure to environmental stressors (increased temperature and predation cues) and a nicotinic acetylcholine receptor (nAChR)-modulating insecticide (‘sulfoxaflor’) impact Chironomus riparius across a range of conventional and non-conventional endpoints. We used a multifactorial experimental design encompassing three stressors, sulfoxaflor (2.0–110 µg/L), predation risk (presence/absence of predatory cues), and elevated temperature (20 °C and 23 °C), yielding a total of 24 distinct treatment conditions. Additional stressors did not change the sensitivity of C. riparius to sulfoxaflor. To assess potential additive effects, we applied an Independent Action (IA) model to predict the impact on eight endpoints, including conventional endpoints (growth, survival, total emergence, and emergence time) and less conventional endpoints (the size of the adults, swimming abilities and exploration behaviour). For the conventional endpoints, observed effects were either lower than expected or well-predicted by the IA model. In contrast, we found greater than predicted effects of predation cues and temperature in combination with sulfoxaflor on adult size, larval exploration, and swimming behaviour. However, in contrast to the non-conventional endpoints, no conventional endpoints detected interactive effects of the neurotoxic insecticide and the environmental stressors. Acknowledging these interactions, increasing ecological context of ecotoxicological test systems may, therefore, advance environmental risk analysis and interpretation as the safe environmental concentrations of neurotoxic insecticides depend on the context of both the test organism and its environment.

A naturaly attenuated largemouth bass ranavirus strain provided protection for Micropterus salmoides by immersion immunization

Largemouth bass ranavirus (LMBV) causes disease outbreaks and high mortality at all stages of largemouth bass farming. Therefore, live vaccine development is critical for largemouth bass prevention against LMBV by immersion immunization. Herein, an attenuated LMBV strain with good immunogenicity, designated as LMBV-2007136, was screened from the natural LMBV strains bank through challenge assay and immersion immunization experiment. After determing the safe concentration range of LMBV-2007136, the minimum immunizing dose of immersion immunization was verified. When largemouth bass were vaccinated by immersion at the lowest concentration of 102.0 TCID50/mL, all of fish were survival post virulent LMBV challenge, and the relative percent survival (RPS) was 100 %. And the immune gene expression levels of IL-10, IL-12, IFN-γ, and IgM in the spleen and kidney post-vaccination were significantly up-regulated compared to the control group, but TNF-α expression showed no significant changes. The safety and efficacy of LMBV-2007136 at passages P8, P13, and P18 were futher assessed, and no death of largemouth bass was observed within 21 days post-immunization and RPS of three vaccination groups was 100 %, suggesting that the safety and efficacy of the attenuated strain at different passages was stable. Furthermore, in the virulence reversion test, the attenuated strain was propagated through 5 times in largemouth bass by intraperitoneal injection and no abnormality and mortality were observed, further proving the attenuated vaccine candidate LMBV-2007136 was safe. These results proved that LMBV-2007136 could be a promising candidate for a live vaccine to protect largemouth bass from LMBV disease.

Low concentrations of complex mixtures of pesticides and metabolites are toxic to common Carp brain cells (Cyprinus carpio carpio)

Pesticide use increases annually, and Brazil is the world’s largest consumer. However, unlike the European Union (EU), there is no established limit value for pesticide mixtures in drinking water, and therefore the concentration of pesticides can reach 3354 times the EU limit. Thus, determining the risk of exposure to pesticide mixtures and their main metabolites is challenging and requires the use of alternative methods. In the present study, the Common Carp Brain (CCB) cell line was used to evaluate the in vitro toxicity of relevant pesticide mixtures (glyphosate, 2,4-D, atrazine, and mancozeb) and their main metabolites after 72 h of exposure. The tested concentrations were based on the Acceptable Daily Intake (ADI) defined by Brazilian legislation. The results showed that cells exposed to lower concentrations of the pesticide mixtures and the pesticide + metabolite mixtures were affected by a decrease in cell confluence, resazurin metabolism, and wound healing capacity. The IBR index showed that lower concentrations had more severe effects, suggesting the absence of safe concentrations of these pesticide and metabolite mixtures for the CCB cell line within the tested concentration range. These findings raise concerns about the effects of exposure to these substances on animal and human health.