Mean Lethal Dose Research Articles

Ethanol crude leaf extract of weeping fig (Ficus benjamina) causes mild hepatotoxicity in Sprague dawley rats

Weeping fig (Ficus benjaminaeaf extract has diverse medicinal properties but little is reported about its hepatotoxicity. This study determined the mean lethal dose (LD50) and investigated the effects of F. benjamina ethanol crude leaf extract on biochemical parameters and liver histology of Sprague Dawley rats. Twenty-nineemale rats weighing 133-204 g were used. The LD50 was determined with nine rats based on Lorke’s method. The experimental groups consisted of twenty rats, divided into four groups of five. Each group received treatment as follows: Control (feed and water only) and low, medium, and high doses (500, 1000, 1500 mg/kg respectively) of the extract orally for 21 days. All animals were weighed and sacrificed using Ketamine intra-peritoneal injection. Blood samples were collected for biochemical parameters of total bilirubin, conjugated bilirubin, aspartate aminotransferase (AST) alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Liver tissues were removed and processed by the formalin-fixed-paraffin wax-embedding method. The tissue blocks were sectioned and subjected to Hematoxylin/Eosin and Masson trichrome staining. The extract’s LD50 was >5000 mg/kg. The rats’ body weights did not change statistically (p=0.985). Total bilirubin (p=0.003), conjugated bilirubin, AST, ALT, and ALP values (p=0.001) increased significantly. The AST high-doseroup had the highest fold increase (4.8). The liver histology showed mild sinusoidal dilation at 500 mg/kg. There was marked hemorrhage and fibrosis at medium and high doses. Although the extract had relatively low acute toxicity, 1000 and 1500 mg/kg doses were associated with mild hepatotoxicity characterized by veno-occlusion disease. The 500 mg/kg dose is safer for medicinal purposes.

Experimental Investigations of Assessment of Acute Toxicity of Drilling Mud.

At present, the main technological stages of oil production related to drilling operations require the use of a wide variety of drilling mud, which has a complex, multicomponent chemical composition. The drilling mud used and the resulting drilling waste must be safe for human health and the environment. The toxicity and hazard of drilling mud at this point in time remain poorly understood scientific problems and require detailing and studying in toxicological terms. The real degree of hazard and toxicity of drilling mud can only be determined by an experimental method, since its composition, which changes depending on the nature of the technological process and its degree of depletion, is not constant, which can change the toxicological properties. In an experiment conducted on adult male rats, under conditions of a single intragastric injection of drilling mud, new data were obtained regarding the parameters of its toxicity and hazard. The use of a wide variety of methods for determining lethal doses of drilling mud, including the probit analysis method, made it possible not only to substantiate the mean lethal dose of drilling mud but also other parameters of toxicity and survival of animals in the experimental groups. Features of eating behavior and body weight dynamics and the nature of the behavioral reactions revealed by the number and duration of stands and frequency and duration of grooming also indicate the presence of dose-dependent effects.

Effects of Ionizing Radiation on Intestinal Bile Acid Metabolism: Mechanism of the Radioprotective Effect of Glycoursodeoxycholic Acid

Radioactive intestinal injury is a common complication during radiotherapy of tumors. The aim of this study is to observe the effect of ionizing radiation on short-term changes in intestinal bile acids and to investigate the radioprotective effect of bile acids on intestinal cells. A rat model of small intestinal injury was constructed by exposing the abdomen of the rats to daily irradiation at 2 Gy for 4 d in succession. The bile acids were quantified using metabolomics analysis. IEC-6 cells, a small intestinal epithelial cell line, were divided into a dimethyl sulfoxide (DMSO) control group receiving DMSO and 0 Gy irradiation, a glycoursodeoxycholic acid (GUDCA) experimental group receiving GUDCA and 0 Gy irradiation, a DMSO irradiation group receiving DMSO and 10 Gy irradiation, and a GUDCA irradiation group receiving GUDCA and 10 Gy irradiation. Cell viability and cytotoxicity was assessed by CCK-8 assay test. The apoptosis rate of cells was determined by flow cytometry. The colony formation rate and the radiosensitivity of the cells were determined by colony formation assay on solid media. The expression levels of proteins associated with cell death were determined using Western blot. After exposure to irradiation, the small intestine tissues of the rats showed typical radioactive intestinal injury. In addition, various bile acids showed fluctuation before and after irradiation. Among the bile acids, GUDCA increased significantly at 3 d after irradiation, but returned to the pre-irradiation level at 7 d after irradiation. Compared with the control group, after GUDCA treatment at 20 μmol/L for 24 h, the cell viability rate after irradiation was significantly higher than that of the DMSO group (P<0.05); the expression levels of the proteins, including PARP, caspase-3, RIP, and GSDMD, were significantly lower than those in the control group (P<0.05). After GUDCA treatment at 20 μmol/L for 24 h and 48 h, the cell apoptosis rate of the cells after irradiation was lower than that of the DMSO group (P<0.05). Compared with the DMSO control group, the colony formation ability of the GUDCA experimental group was stronger than that of the DMSO group after irradiation at 0, 2, 4, and 6 Gy (P<0.05). D0, or the mean lethal dose, of the GUDCA group was 6.374, while that of the DMSO group was 4.572. Compared with the DMSO control group, the D0 value of the GUDCA treatment group increased, and the sensitization enhancement ratio (SER) was 0.717. After exposing the abdomen of rats to irradiation, the intestinal bile acid metabolism of the rats will change significantly, and GUDCA can produce radioprotective effects on intestinal cells to a certain extent.

Isolation, Identification, and Characterisation of a Novel ST2378 Aeromonas hydrophila Strain from Naturally Diseased Frogs, Rana dybowskii.

In 2023, Rana dybowskii exhibiting characteristic skin ulcers were found on a farm in northeastern China. Subsequently, two dominant bacteria, Aeromonas hydrophila Rd001 and Acinetobacter johnsonii Rd002, were isolated from naturally infected R. dybowskii. Experimental infection confirmed that Rd001 was the primary pathogen responsible for the disease in R. dybowskii, with a mean lethal dose (LD50) of 6.25 × 102 CFU/g. The virulence genotype of Rd001 was identified as ser+/aha+/lip+/nuc+/hlyA+/aer+/alt+/ast+/act+. Antimicrobial susceptibility testing indicated that Rd001 was sensitive to enrofloxacin, flumequine, and neomycin. MLST analysis showed that Rd001 belonged to a new sequence type of A. hydrophila, named ST2378. This study offered the first comprehensive investigation into the pathogenicity, virulence genotypes, antimicrobial resistance, and genetic traits of A. hydrophila isolated from R. dybowskii, providing a theoretical foundation for preventing and controlling A. hydrophila infections.

Exploring the Role of Metal in the Biointeraction of Metallacarboranes with C. elegans Embryos.

Cobaltabis(dicarbollides), ferrabis(dicarbollide), and their halogenated derivatives are the most studied metallacarboranes with great medical potential. These versatile compounds and their iodinated derivatives can be used in chemotherapy, radiotherapy, particle therapy, and bioimaging when isotopes are used. These metallacarboranes have been evaluated in vitro and recently in vivo with complex animal models. Lately, these studies have been complemented using the invertebrate Caenorhabditis elegans (C. elegans), a nematode largely used in toxicology. When evaluated at the L4 stage, cobaltabis(dicarbollides), ([o-COSAN]- and [8,8'-I2 -o-COSAN]- ), exhibited a higher mean lethal dose (LD50 ) than ferrabis(dicarbollides) ([o-FESAN]- and [8,8'-I2 -o-FESAN]- ). In this work, we used the C. elegans embryos since they are a complex biological barrier with concentric layers of polysaccharides and proteins that protect them from the environment. We assessed if the metal atom changes their biointeraction with the C. elegans embryos. First, we assessed the effects on embryo development for metallacarboranes and their di-iodinated derivatives. We observed changes in color and in their surface structure. An exhaustive physicochemical characterization was performed to understand better this interaction, revealing a stronger interaction of ferrabis(dicarbollide) compounds with C. elegans embryos than the cobaltabis(dicarbollide) molecules. Unveiling the biological interaction of these compounds is of great interest for their future biomedical applications.

Phytochemicals, acute toxicities and actual median lethal doses (actual LD50) of Zingiber officinale and Allium sativum given singly and in combination via mice models

Phytochemicals are substances produced mainly by plants which are very important due to their biological and pharmacological activities. The pharmacological effects of these components range from the treatment of bacterial and fungal infections to the treatment of chronic-degenerative diseases such as diabetes and cancer. Mice were used for assessing the acute toxicities; studies usually conducted to evaluate the effects of a single substance. Each animal receives a single dose of the test substance but repeated doses may be administered provide all doses are administered within 24 hours. This study is aimed at assessing the phytochemical components, acute toxicities and actual Mean Lethal Doses (actual LD50) of Zingiber officinale and Allium sativum when administered separately and in combination. Both the phytochemical analysis and acute toxicity testing were done using standard methods with slight modification of the acute toxicity method which led to obtaining the actual LD50 for the tested samples and minimizing the number of study animals used. The phytoconstituents of Zingiber officinale were alkaloids, tannins, flavonoids, steroids and terpenoids and those of Allium sativum were alkaloids, saponins, flavonoids, and glycosides. The actual lethal doses of Zingiber officinale, Allium sativum and combination of the two were 8,660, 4,472, and 5,477 mg/kg body weight respectively. In conclusion, Zingiber officinale was practically none toxic while Allium sativum had slight toxicity which was ameliorated when the two herbs were administered together. Thus, rendering the combination of the two herbs safe, as evident in the actual LD50 being raised to 5,477 mg/kg body weight.

Estimation of the relative biological effectiveness (RBE) of the 177Lu − DOTA − iPSMA radiopharmaceutical

Relative biological effectiveness is a radiobiological parameter relevant in radiotherapy planning and useful in evaluating the physiological impact of radiation in different tissues. Targeted radionuclide therapy allows the selective and specific deposition of higher radiation doses in a noninvasive way and without collateral effects through the administration of radiopharmaceuticals. Lu−DOTA−177(hydrazinylnicotinoyl−Lys−(Nal)−NH−CO−NH−Glu) also called Lu−iPSMA177 is a third generation radiopharmaceutical composed by a peptide that recognizes the prostate-specific membrane antigen (PSMA), a membrane protein overexpressed in several types of cancer and that mediates the radiopharmaceutical's recognition of cancer cells. The present study reports radiobiological parameters of Lu−iPSMA177 and demonstrates the superiority of targeted radiopharmaceuticals over external radiotherapy treatment options in terms of their relative biological effectiveness. The relative biological effectiveness value of 1.020±0.003 for the LINAC, estimated by fitting the linear-quadratic model equation to the resulting survival curves, was like those of 1.25±0.04,1.060±0.005and1.00±0.04 obtained by an alternative method in relation to the mean lethal doses at 90, 80 or 60 survival percent respectively. While the relative biological effectiveness values of 5.65±0.13,4.72±0.27and2.87±0.19 estimated for Lu−iPSMA177 were significantly higher than those for the LINAC. The results confirm that the biological effect produced by the deposition of a radiation absorbed dose delivered by the LINAC can be induced with a quarter of that dose using Lu−iPSMA177 due to the energy distribution, dose-rate and energy fluence.

Measuring the Mean Lethal Dose (LD50) of 6 MV X-rays in Wistar Rats

Introduction: There is a risk of genetic mutations and damage to the bodies of the patients and employees who are exposed to ionizing radiation. Utilizing substances that neutralize the produced free radicals by ionizing radiation is one solution to overcome this problem. To study the radioprotective role of these compounds, the mean lethal dose that kills 50% of animals exposed to radiation within 30 days (LD50/30) should be determined. This value is the basis for studying radioprotectors effects on animals. The present study aimed to evaluate the survival or death rate in irradiated rats with different doses of X-rays to determine the mean lethal dose of 6 MV X-rays. Method: A total of 42 male and female Wistar rats with an approximate weight of 160 ± 10 g were examined. The animals were kept in the pet house at a temperature of 25°C and a light-dark cycle of 12 hours, and water and food were provided freely. The animals were randomly divided into seven groups. Six groups received X-rays with doses of 6.4, 6.5, 6.6, 6.7, 6.8, and 6.9 Gy, respectively. The seventh group (control group) received no radiation dose. The rats were examined for 60 days, and their mortality results were recorded. Results: Based on the obtained results, LD50/30 was 6.641 Gy for Wistar rats weighing 160 ± 10 g and 16 weeks’ old calculated by Probit Analysis. Conclusion: This finding can be used to investigate the protective effects of natural substances and chemical drugs on the effects of X-rays on the body.

A Study of the Chemical Composition, Antioxidant Potential, and Acute Toxicity of Bulgarian Tanacetum vulgare L. Essential Oil.

Common tansy (Tanacetum vulgare L.) is a plant with medicinal properties that has traditionally been used in folk medicine for its anthelmintic, antispasmodic, and choleretic effects, for the treatment of diarrhea and digestive problems, and externally, as an insecticide in veterinary practices. In the current study, we investigated, for the first time, the chemical profile and antioxidant activity of essential oil from a wild population of T. vulgare L. growing in Bulgaria. Common tansy essential oil (EO), which is rich in bicyclic monoterpenes, was obtained using hydrodistillation and characterized by using gas chromatography-mass spectrometry (GC-MS). Thirty-seven compounds were identified in Bulgarian tansy EO. Among the major constituents were oxygenated monoterpenes, including compounds such as camphor (25.24%), trans-chrysantenyl acetate (18.35%), cis-verbenol (10.58%), thujone (6.06%), eucaliptol (5.99%), and α-campholenal (5.98%). The analysis results identified the essential oil from T. vulgare L. grown in the western Rhodope Mountains of Bulgaria as the camphor chemotype. Furthermore, its antioxidant activity was analyzed using the oxygen radical absorbance capacity (ORAC) method and was found to be 605.4 ± 49.3 µmol TE/mL. The essential oil was also tested for single-dose acute toxicity on Wistar rats and was found to be non-toxic by oral administration. The mean lethal dose by intraperitoneal administration was LD50 i.p. = 14.9 g/kg body weight. The results of the conducted study can serve as a basis for the evaluation and subsequent exploration of other pharmacotherapeutic effects of the essential oil obtained from the inflorescences of the Bulgarian species T. vulgare L.

A Study of the Chemical Composition, Acute and Subacute Toxicity of Bulgarian Tanacetum parthenium Essential Oil.

Tanacetum parthenium (L.) Sch.Bip. (T. parthenium) is an aromatic perennial plant belonging to the Asteraceae family, also known as feverfew. It is widely distributed in various regions of Europe and other parts of the world. The plant has a rich background in the traditional medicine of many nations and has been used as a remedy for fever, pain, inflammation, asthma, rheumatism, menstrual disorders, etc. Methods: GC-MS analysis was conducted to determine the chemical composition of the isolated essential oil (EO). Using the method proposed by Litchfield and Wilcoxon, the average lethal dose (LD50) of the EO on Wistar rats was determined for two routes of administration: oral (p.o.) and intraperitoneal (i.p.). The subacute toxicity of the EO was also tested by oral administration of a daily dose of 1.0 g/kg body weight (BW) for 28 days. The toxicity of the EO was evaluated by observing and evaluating changes in behavior, body weight, basic hematological and serum biochemical parameters, and histopathological changes of the internal organs. Thirty-seven volatile organic compounds representing 94.58% of the total oil composition were tentatively detected in the obtained T. parthenium EO. The dominant compounds were camphor (45.47%), trans-chrisantenyl acetate (21.65%), camphene (9.48%), and cis-isogeraniol (5.42%). The results showed that the EO was not toxic when administered in acute oral doses. The acute mean lethal dose for intraperitoneal administration was LD50 i.p. = 2.13 g/kg BW. In the subacute study involving administration of an oral dose of EO for 28 days, there were a number of changes in the hematological and serum biochemical parameters of the blood compared with the control group of animals. However, no symptoms of toxicity, changes in the body weight of the rats, death, or pathological changes in the histological indicators of the examined organs-brain, heart, stomach, liver, spleen and kidney-were found. Extrapolating the results obtained from the rat experiments, we can state that the EO is safe for use in doses below 1 g/kgBW for a period not exceeding one month.

Gamma irradiation-induced genetic variability and its effects on the phenotypic and agronomic traits of groundnut (Arachis hypogaeaL.).

In order to increase genetic variability for the improvement of groundnut, two varieties, namely Kp29 and Fleur11, were treated with six different gamma irradiation doses. A significant effect of mutagenesis was distinctly observed in the stem lengths, roots, and survival percentage in both varieties. The radio-sensitivity test showed a mean lethal dose of 436.51Gy for Kp29 and 501.18Gy for Fleur11. Furthermore, this study revealed putative mutants with variable agro-morphological traits. Seven chlorophyll mutants and various seed shape and color mutants were obtained. This study demonstrates the potency of gamma irradiation to induce high genetic variability that led to the emergence of certain mutations of economic importance.

A comparison of the chemo- and radiotoxicity of thorium and uranium at different enrichment grades

Uranium and thorium are heavy metals, and all of their isotopes are radioactive, so it is impossible to study chemical effects entirely independent of the radiation effects. In the present study, we tried to compare the chemo- and radiotoxicity of both metals, taking into account deterministic radiation damages reflected by acute radiation sickness and stochastic radiation damages leading to long-term health impairments (e.g., tumor induction). We made at first a literature search on acute median lethal doses that may be expected to be caused by chemical effects, as even acute radiation sickness as a manifestation of acute radiotoxicity occurs with latency. By simulations based on the biokinetic models of the International Commission on Radiological Protection and using the Integrated Modules for Bioassay Analysis software, we determined the amounts of uranium at different enrichment grades and thorium-232 leading to a short-term red bone marrow equivalent dose of 3.5 Sv considered to cause 50% lethality in humans. Different intake pathways for incorporation were considered, and values were compared to the mean lethal doses by chemotoxicity. To assess stochastic radiotoxicity, we calculated the uranium and thorium amounts leading to a committed effective dose of 200 mSv that is often considered critical. Mean lethal values for uranium and thorium are in the same order of magnitude so that the data do not give evidence for substantial differences in acute chemical toxicity. When comparing radiotoxicity, the reference units (activity in Bq or weight in g) must always be taken into account. The mean lethal equivalent dose to the red bone marrow of 3.5 Sv is reached by lower activities of thorium compared to uranium in soluble compounds. However, for uranium as well as thorium-232, acute radiation sickness is expected only after incorporation of amounts exceeding the mean lethal doses by chemotoxicity. Thus, acute radiation sickness is not a relevant clinical issue for either metal. Concerning stochastic radiation damages, thorium-232 is more radiotoxic than uranium if incorporating the same activities. Using weight units for comparison show that for soluble compounds, thorium-232 is more radiotoxic than low-enriched uranium in the case of ingestion but even more toxic than high-enriched uranium after inhalation or intravenous administration. For insoluble compounds, the situation differs as the stochastic radiotoxicity of thorium-232 ranges between depleted and natural uranium. For acute effects, the chemotoxicity of uranium, even at high enrichment grades, as well as thorium-232 exceeds deterministic radiotoxicity. Simulations show that thorium-232 is more radiotoxic than uranium expressed in activity units. If the comparison is based on weight units, the rankings depend on the uranium enrichment grades and the route of intake.

Investigating the Antibacterial Effects of Synthetic Gamma-Lactam Heterocycles on Methicillin-Resistant Staphylococcus aureus Strains and Assessing the Safety and Effectiveness of Lead Compound MFM514.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be one of the main causes of hospital-acquired infections in all regions of the world, while linezolid is one of the only commercially available oral antibiotics available against this dangerous gram-positive pathogen. In this study, the antibacterial activity from 32 analogues of synthetic gamma-lactam heterocycles against MRSA was determined. Amongst screened analogues for the minimum inhibitory concentration (MIC) assay, compound MFM514 displayed good inhibitory activity with MIC values of 7.8-15.6 µg/mL against 30 MRSA and 12 methicillin-sensitive S. aureus (MSSA) clinical isolates, while cytotoxicity evaluations displayed a mean inhibitory concentration (IC50) value of > 625 µg/mL, displaying a potential to becoming as a lead compound. In subsequent animal studies for MFM514, a single-dose oral acute toxicity test revealed an estimated mean lethal dose (LD50) value of <5000 mg/kg, while in the mice infection test, a mean effective dose (ED50) value of 29.39 mg/kg was obtained via oral administration. These results suggest that gamma-lactam carbon skeleton, particularly MFM514, is highly recommended to be evaluated further as a new safe and efficacious orally delivered antibacterial agent against MRSA.

The study of the cytotoxic effect of disinfectants

The toxicity of individual disinfectants has been studied in vitro using human cell cultures (HT-29 (epithelial-like cells of colon adenocarcinoma), HEK 293 (human embryonic kidney cells)) to create a model for assessing the toxicity of residual amounts of disinfectants that can enter milk for a person. Standard tests have been used to assess cell viability and amount: methyl tetrazolium (MTT) test, neutral red cell staining (NRP), and sulforhodamine B (SRB) test. Disinfectants have a dose- and time-dependent cytotoxic effect on human cell cultures. IC50avg (concentration of the drug that suppresses a certain cell function by 50%) of disinfectants based on the effect on cell cultures (average value) is Biodez – 117.29 ±14 μl/l, Blanidas – 389.25 ±20.83 μl/l, Virkon-S – 343.04 ±28.04 μl/l, Neochlor – 473.82 ±30.16 μl/l, Phan – 56.71 ±7.05 μl/l, Chlorination – 343.28 ±27.26 μl/l, Chlorinated lime – 117.35 ±9.44 μl/l. Mean toxic doses for cell cultures are lower than the mean lethal dose (based on literature data) for rats and mice by gastric administration. The novelty is that determining the cytotoxicity of disinfectants in vitro using human cell cultures can significantly reduce the number of animals for establishing LD50 during the registration procedure of new agents, making it possible to make preliminary conclusions about the toxicity of substances at the stage of chemical screening, preliminary hygienic regulation, identify target organs of toxic influence.

In-vitro and In-vivo Neutralization Activity of Methanol Extract of Adansonia digitata Fruit Pulp against Naja nigricollis Venom

Background: Adansonia digitata has been used as a traditional medicine to treat various diseases including snakebite envenomation. Objective: In this study, the protective and ameliorative potentials of crude methanol extract of Adansonia digitata fruit pulp against crude venom of Naja nigricollis in-vitro and in-vivo were investigated. Method: The dose-dependent inhibitory studies, pharmacological, histopathological and in vivo studies were conducted using standard methods. Result: The mean lethal dose of the crude methanolic extract of Adansonia digitata fruit pulp in Wistar rats was &gt; 5,000 mg/kg, while Naja nigricollis venom was 0.89 mg/kg. The anti-lethality effective concentration of the fruit pulp on Naja nigricollis venom was 92.52 mg/ml. Treatment significantly (&lt; 0.05) inhibited the activities of Naja nigricollis phospholipase A2 and dose-dependently reduced Naja nigricollis venom-induced paw oedema at 1-4 hours post-envenomation. In-vivo, treatment with 250 and 500 mg/kg of Adansonia digitata fruit pulp was protective against the clinical signs and mortality. Serum acetylcholinesterase activities were maintained in the group treated with normal saline and the ameliorative groups but decreased significantly (p &lt; 0.05) in other groups. Brain acetylcholinesterase was high in all the groups by day 1 but was reduced with increasing dose by day 2 in the ameliorative groups only. Adansonia digitata fruit pulp also preserved the histoarchitecture of the brain, heart, liver and spleen from venom-induced pathologies. Conclusion: Crude methanolic extract of Adansonia digitata fruit pulp possesses good protective and ameliorative neutralization effects on Naja nigricollis venom and could be promising in the management of snakebite envenomation.

Nematicidal lipopeptides from Bacillus paralicheniformis and Bacillus subtilis: A comparative study.

The aim of this work was to develop a comparative study between Bacillus paralicheniformis TB197 and B. subtilis ATCC 21332 strains in terms of growth, cyclic lipopeptide production, nematicidal activity, and active lipopeptide characteristics. Crude lipopeptide extracts (CLEs) from their fermentation broths were obtained, and their nematicidal activity (NA) was estimated as the mean lethal dose (LD50), employing Caenorhabditis elegans. Using a bioguided approach, CLE components were fractionated by semipreparative thin layer chromatography, and active lipopeptides were characterized by mass spectrometry. Both strains produced similar concentrations of CLEs (p ≥ 0.05) (0.99 ± 0.11 and 1.14 ± 0.15mg/mL by TB197 and ATCC 21332, respectively). The estimated LD50 values of CLEs from the TB197 and ATCC 21332 strains were 3.88 and 8.15mg/mL, respectively, showing that the NA of the TB197 strain CLE was 2.1-fold higher (p ≤ 0.05). Mass spectrometry revealed that strain TB197 synthesizes several families of lipopeptides, namely, fengycin A (C14-C17), fengycin B (C16-C17), surfactin (C15-C17), and lichenysin (C12, C13, C14, and C16), from which fengycins and lichenysins possess the highest NA (100 and 60% mortality in C. elegans larvae, respectively), while the ATCC 21332 strain produces mainly surfactin (C13-C17) (NA 63% mortality). The main differences found in this study were that the TB197 strain has a higher tolerance to inhibition by the product, and the lipopeptides they synthesize have a higher nematicidal activity due to the diversity of families compared to ATCC 21332. Likewise, it was shown that more polar lipopeptides (fengycins) are more effective at causing mortality in C. elegans larvae. KEY POINTS: • The nematicidal activity of lipopeptides from TB197 is higher than from ATCC 21332 • TB197 produces surfactin, lichenysin, and fengycin, while ATCC 21332 mainly produces surfactin • The most polar lipopeptides (fengycins) cause more mortality in C. elegans L2.

Acute and developmental toxicity of embelin isolated from Embelia schimperi Vatke fruit: In vivo and in silico studies.

Embelin is a hydroxybenzoquinone constituent of the Embelia species that has anti-disease properties. However, its toxicity, particularly the in silico, acute, and developmental toxicity profiles, has yet to be thoroughly investigated. Hence, this study aims to assess these toxicity profiles. In silico and in vivo experimental studies were conducted on embelin isolated from the fruits of Embelia schimperi Vatke. In silico toxicity predictions were computed using the ProTox model. The in vivo experiment was done by administering 5000mg/kg of embelin to a single female albino Wistar rat, followed by three female rats in the absence of death, to determine the mean lethal dose (LD50). Afterwards, three groups of pregnant rats were treated with embelin at doses of 250mg/kg, 500mg/kg, and 1000mg/kg for the developmental toxicity test. Vehicle and ad libitum control groups were used to compare the acute and developmental toxicity variables. In silico toxicity predicted that embelin is free from hepatotoxic, carcinogenic, mutagenic, and cytotoxic effects. No inhibitory effect on hERG channels was observed. It has an immunotoxic property and an inhibitory effect on the CYP2D6 enzyme. Since mortality and signs of toxicities were not observed after treatment with 5000mg/kg, the mean lethal dose (LD50) is determined to be >5000mg/kg. There was no significant difference in the morphological scores or number of somites among experimental animals. None of the embryonic systems possessed developmental delays. Nevertheless, the crown-rump length of the high-dose group became significantly shorter. Maternal food intake and weight gain exhibited significant dose-dependent differences between embelin-treated animals and controls. The number of implantations was significantly low in the treatment group, accompanied by a higher frequency of prior resorption. Embelin is predicted to have a high probability of immunotoxicity potential and affect drug metabolism by inhibiting CYP2D6. In addition, it affects food intake, weight gain, and the number of implantations in pregnant rats. Therefore, it is highly recommended not to take embelin and embelin-rich plants during pregnancy. Further in vitro and in vivo studies need to be conducted to understand the mechanism behind the toxicity of embelin.

Characterization of bacterial diversity and capacity to remove lead of a consortium from mining soil.

At present, the presence of lead (Pb2+) continues to be a problem in water bodies due to its continuous use and high toxicity. The aim of this study was to investigate the bacterial diversity of a potential consortium used as a biosorbent for the removal of lead in an aqueous solution. The minimum inhibitory concentration and the mean lethal dose of the consortium were determined, and then the optimal variables of pH and temperature for the removal process were obtained. With the optimal conditions, the kinetic behavior was evaluated, and adjustments were made to different mathematical models. A Fourier transform infrared spectroscopy analysis was performed to determine the functional groups of the biomass participating in the removal process, and the diversity of the bacterial consortium was evaluated during Pb2+ removal by an Ion Torrent Personal Genome Machine System. It was found that the intraparticle diffusion model was the one that described the adsorption kinetics showing a higher rate constant with a higher concentration of Pb2+, while the Langmuir model was that explained the isotherm at 35°C, defining a maximum adsorption load for the consortium of 54mg/g. In addition, it was found that Pb2+ modified the diversity and abundance of the bacterial consortium, detecting genera such as Pseudomonas, Enterobacter, Citrobacter, among others. Thus, it can be concluded that the bacterial consortium from mining soil was a biosorbent with the ability to tolerate high concentrations of Pb2+ exposure. The population dynamics during adsorption showed enrichment of Proteobacteria phyla, with a wide range of bacterial families and genera capable of resisting and removing Pb2+ in solution.

On the issue of substantiating a high degree of one-time marginal probability of detecting pentasodium salt of diethylenetriaminepentaacetic acid in the working area

Introduction. Pentasodium salt of diethylenetriaminepentaacetic acid, which is widely used in the chemical industry as an initiator of polymerization processes, has a wide range of toxic properties. However, the normative hygienic standard for the working area in the whole wide world has not yet been established. Purpose of the study. Experimental substantiation of a large number of one-time MPC of pentasodium salt of diethylenetriaminepentaacetic acid in the environment. Materials and methods. Pentasodium salt of diethylenetriaminepentaacetic acid, CAS No. 140-01-2, outbred male rats weighing 200-240 g. Research in the field of the protection of animals used for scientific purposes (ETS N 123) is aimed at studying the protection of animals used for scientific purposes. Examinations of experimental studies on animals using generally accepted and unified methods. Statistical processing of research materials was carried out using standard application programs Statistica 10.0. Results. The mean lethal dose of diethylenetriaminepentaacetic acid pentasodium salt (DL50) for male white rats is 1702.8±228mg/kg, the acute inhalation action threshold (Limac) is the concentration of 4.62±0.4mg/m3, the irritant action threshold (Limir) - concentration 2.5±0.2 mg/m3, irritating zone (Zir) equals 2.9. Conclusion. A high one-time maximum allowable concentration of the pentasodium salt of diethylenetriaminepentaacetic acid in the environment, equal to 0.7 mg/m3, has been scientifically substantiated and experimentally found. Hazard class 2, limiting indicator of harmfulness - irritant effect. Restrictions. The authors transfer the editors of the exclusive right to natural disasters (publications), other use of the materials of the articles without citing the authors for a specific publication is strictly prohibited. Ethics. The material of the article was approved by the ethics committee at the Federal Budgetary Institution "Novosibirsk Research Institute of Hygiene" of Rospotrebnadzor (No. 2 of January 14, 2022).

Toxic and hygienic evaluation of the pyridine derivative — 2-ethyl-4-nitropyridine N-oxide

Introduction. The toxic and hygienic assessment of both the final product and intermediate synthesis products remains the key preventive measure to avoid intoxication of workers’ body by industrial xenobiotics in the chemical and pharmaceutical industry and in the context of a constant increase in the range of used compounds. In recent years, nitrogen-containing heterocyclic compounds of the pyridine group have been widely used in various industries. One of these substances is the anti-tuberculosis drug ethionamide, the intermediate product in the synthesis of which is 2-ethyl-4-nitropyridine N-oxide. Materials and methods. In experiments, the toxic properties of 2-ethyl-4-nitropyridine N-oxide were studied. The investigations were carried out on outbred rats and mice, rabbits and guinea pigs. The effect of the substance on experimental animals was assessed using standard physiological, biochemical, hematological and morphological indices. Intermediate toxicity was studied with different methods of substance administration (oral, percutaneous and inhalation) both in single and repeated experiments. The obtained results were processed using the Statistic 10.0 software package. Results. Mean lethal doses of 2-ethyl-4-nitropyridine N-oxide for female rats and male mice were 1250 mg/kg (976.6÷1600.0 mg/kg) and 430 mg/kg (355.4÷520.3mg/kg), respectively; for female mice - 675 mg/kg. The ability of the substance to accumulate was average: the cumulation coefficient was 4.0. There were no significant differences in the effect of the substance on animals of different species and gender. The substance didn’t show a local irritating effect on the skin, skin-resorptive and allergic effects, but a pronounced irritating effect on the mucous membranes of the eyes was revealed. In the subacute experiment, 2-ethyl-4-nitropyridine N-oxide showed a toxic effect mainly on the blood system. A specific damaging effect was revealed, which was expressed in an imbalance of the content of oxyhemoglobin and methemoglobin with a significant increase in the latter. The threshold index of acute inhalation effect was 76.7 mg/m3. The tentative safe exposure level in the air of the working area for the substance was calculated at the level of 0.5 mg/m3. Limitations. The investigation is limited to the study of the toxicological characteristics of 2-ethyl-4-nitropyridine N-oxide. In accordance with the directive documents on the protection of experimental animals, the limited number of in vivo experiments is connected with the dangers for animals and with public ethical views on in vivo experiments. Conclusion. The proposed tentative safe level of exposure to 2-ethyl-4-nitropyridine N-oxide in the air of the working area at the level of 0.5 mg/m3 makes it possible to attribute the xenobiotic to hazard class II. Under the conditions of compliance with the specified standard, the dose absorbed by the worker under the production conditions will be no more than 5-10 mg per work shift, which guarantees safety for health and minimizes the risk to the health of workers. Information on the toxicity of 2-ethyl-4-nitropyridine N-oxide can be useful for solving a wide range of tasks fixed in the control and supervisory activities of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing, hygienic rationing and monitoring, and will contribute to the prevention and reduction of incidence rate associated with the exposure to harmful factors of the production environment.