Acute Toxicity Test Research Articles

Genotoxicity Of The Herbicide Picloram (TORDON ® 24K) on tadpoles of Boana pulchella (Amphibia, Anura, Hylidae)

Picloram (PIC) is an herbicide widely used in Uruguay to control weeds, especially in forest crops. In the present study, we evaluate the acute toxicity and genotoxicity of formulated 24.9% PIC-based Tordon®24K on Boana pulchella tadpoles under standard laboratory conditions. In the acute toxicity test we use mortality as the endpoint and we obtained a 48-h LC50 of 16.5 mg/L, LOEC 14.5 mg/L, and NOEC 12.5 mg/L. We determined genotoxicity in GS36 tadpoles exposed to sublethal concentrations of 8.5 (NOEC/1.5) and 12.5 mg/L (NOEC) PIC using micronucleus frequency (MN) and occurrence of nuclear abnormalities (AN) as endpoints. We noticed a significant increase in the frequency of MN and AN in all treatments tested at sublethal concentrations. Our findings demonstrate the genotoxic effects of this herbicide, which represent a danger to amphibians that inhabit agroecosystems. Based on the results obtained and considering that Boana pulchella is not a threatened species and has a wide distribution in the Uruguayan territory and the Pampa Biome, it could be considered a reference organism in environmental monitoring programs in the region.

Toxicity and safety profile evaluation of Shenfu injection in a murine sepsis model

AimThis study aimed to evaluate the preclinical safety of Shenfu injection for the treatment of sepsis. Tests were designed and conducted to determine the acute and long-term toxicity of Shenfu injection in rats, based on the recommended indications and dosage for human use. Materials and methodsRats were administered 22.5 g of raw drug/kg/day via tail vein injection. Toxicity symptoms were monitored for 14 days following the intravenous injection of Shenfu injection, and target organs affected by toxicity were analyzed. To assess long-term toxicity, rats were given 12, 9, or 6 g of raw drug/kg/day by intraperitoneal injection, equivalent to 12, 9, and 6 times the daily clinical dose for adult sepsis patients (3.3 mL of stock solution per 1 g of raw drug/kg/day), for 30 consecutive days. This was followed by a 28-day recovery period after withdrawal of the drug. During the administration and recovery periods, signs of toxicity were observed and compared with those in the control (stromal fluid) group. The aim was to predict potential clinical adverse reactions, including the nature and severity of these reactions, dose-response and time-response relationships, and the reversibility of the effects. Additionally, the study sought to identify the target organs or tissues potentially affected by repeated administration and suggest clinical indicators that should be monitored during the product's use. Furthermore, the safety of co-administration with commonly used chemical medications for the treatment of sepsis was investigated. ResultsIn the acute toxicity test, administration of the maximum dose of Shenfu injection (75 mL of stock solution/22.5 g of raw drug/kg/day) via tail vein injection resulted in transient symptoms, including piloerection (vertical hair response), weight loss, and reduced food intake. In the long-term toxicity experiments, rats received intraperitoneal injections of 0.3 g/mL (stock solution), 0.225 g/mL, and 0.15 g/mL Shenfu injection per day, which corresponded to 12, 9, and 6 times the daily clinical dose for adults with sepsis. The injections were administered twice daily for 30 days, followed by a 28-day drug withdrawal period for recovery. After 28 days, no significant toxicological changes were observed, apart from a hemodilution effect caused by the excessive volume of the drug and a slight increase in alkaline phosphatase and total bilirubin levels. The effects were reversible upon drug discontinuation. ConclusionsA single intravenous injection of 22.5 g of raw drug/kg/day and long-term intraperitoneal administration of up to 12 g of raw drug/kg/day are considered safe doses for rats.

In vivo immunomodulatory effect and safety of MSC-derived secretome

Background: Secretomes have been gaining interest in treating several diseases due to their pharmaceutical effects, such as the immunomodulatory effect. This study aimed to determine the immunomodulatory effect of secretomes derived from human umbilical cord mesenchymal stem cells (MSCs) and their safety. Methods: We conducted an in vivo immunomodulatory study using a carbon clearance assay. The safety of single-dose administration of secretome was done using fixed-dose methods of acute toxicity test. Results: The phagocytic index was higher in mice treated with secretome than in untreated mice. The acute toxicity study also showed that the administration of secretome derived from human umbilical cord MSCs did not change the mice’s body weight, physical examination results, organ weight, and gross anatomy examination. Conclusions: This study presents the potential of secretome derived from MSCs as a safe immunomodulatory agent.

Exposure to Cyantraniliprole Adversely Impacts Fitness of Harmonia axyridis: Acute Toxicity and Sublethal Effects on Development, Fecundity and Antioxidant Responses.

Extensive utilization of pesticides and their persistent residues inadvertently pose threats to the effectiveness and fitness of biocontrol agents in agroecosystems. However, these ecological consequences are generally disregarded when executing integrated pest management strategies (IPM). Cyantraniliprole (CNAP) serves as a wide-spectrum diamide insecticide and its sublethal effects have been well characterized on multiple insect pests, whereas its impacts on beneficial natural enemies remain unfathomed. Herein we exposed Harmonia axyridis, a predacious generalist, to lethal and sublethal concentrations of CNAP via dipping treatment (egg stage) and topical applications (1st-instar stage + adult stage). The acute toxicity tests revealed that LC50 of CNAP were 90.11, 86.11 and 240.50 mg/L against embryos, 1st instar nymphs and female adults, respectively, with safety factors ranging from 1.14 to 5.34, suggesting its medium toxicity for H. axyridis and larval stage was the most susceptible. The embryonic, larval and pupal durations of coccinellids ecdysed from CNAP-treated eggs and 1st instars were all elongated under sublethal concentrations, of which LC30 triggered more pronounced and significant retardations relative to control. Besides, exposed coccinellids displayed substantially diminished pupal mass and pupation rate, most notably for insects molted from the 1st-instar stage upon CNAP sublethal treatments. With respect to reproductive performance, LC10 and LC30 of CNAP all significantly suppressed female fecundity, as evidenced by reduced vitellin content, a prolonged pre-oviposition period (POP), mitigated laid eggs and the egg hatching rate. Specifically, there existed positive correlations between vitellin level (Vn) and number of eggs deposited by per female, indicative of CNAP affecting fecundity by regulation of Vn. In addition, the antioxidant system was also profoundly disrupted by CNAP, with compromised POD activity at different concentrations over time and induced hormesis of SOD/CAT activities post LC10 exposure. Activities of SOD and TAC were enhanced to exert protective functions during the first 48 h, while defense collapsed at 72 h following LC30 treatments that depleted all enzymatic activities. We speculated that fitness trade-offs may occur between reproductive capacity and antioxidant defenses to sustain physiological homeostasis in response to CNAP stress. Collectively, this study evaluated the ecological risk of CNAP and unmasked its adverse implications for overall fitness of H. axyridis, which highlighted rational application of agrochemicals to conserve biocontrol agents when implementing IPM strategies for sustainable pest control.

Subchronic Toxicity of Ethanol Extract of Mangosteen Rind (Garcinia Mangostana L.) on Kidney Function in Wistar Rats

Mangosteen (Garcinia mangostana L.) is a fruit that possesses antioxidant, antibacterial, antihistamine, anti-inflammatory, and antidiabetic properties. Before this, an acute toxicity test was conducted on the ethanol extract of mangosteen rind. However, further testing is required, specifically the subchronic toxicity test, to identify any hazardous effects that may not have been found in the previous study. The objective of this study is to evaluate the amount of toxicity based on the mortality rate, alterations in the relative weight of the kidneys, and changes in renal function as shown by levels of urea and creatinine. This study is an experimental investigation that employs the Post-test Only Control Group Design methodology, with a sample of 40 rats. The rats were categorized into two groups: the control group and the treatment group. The treatment group was divided into three subgroups, each receiving a dosage of 250 mg/kg body weight. The doses were 500 milligrams per kilogram and 1000 milligrams per kilogram of body weight, respectively. The control group received simply water and feed. The duration of the treatment was 28 days. Observations were conducted over 28 days, which involved monitoring animal mortality. On the 29th day, a surgical procedure was carried out to assess the comparative weight of the kidneys and collect blood samples for analyzing the levels of urea and creatinine. The findings demonstrated no mortality in the test subjects, although there was an elevation in the relative mass of the kidneys and an increase in urea concentrations. The increase in urea levels was observed in female rats using the Kruskal–Wallis test (P = 0.019). The study was further conducted using the post-hoc Mann–Whitney test. Control female rats exhibited notable disparities when administered dosages of 250 mg/kgBW and 500 mg/kgBW. The repeated administration of an ethanolic extract derived from the peel of the mangosteen fruit had a detrimental impact on the functioning of the kidneys, as evidenced by a rise in urea concentrations. Keywords: mangosteen, toxicity test, subchronic, kidney

Evaluating the Root Extract of Reynoutria ciliinervis (Nakai) Moldenke: An Analysis of Active Constituents, Antioxidant Potential, and Investigation of Hepatoprotective Effects in Rats

Reynoutria ciliinervis (Nakai) Moldenke (R. ciliinervis) root, a traditional Chinese medicine, was found to exhibit remarkable pharmacological properties through a series of comprehensive investigations. Our study commenced with a qualitative phytochemical analysis that identified 12 bioactive compounds within the plant. Subsequently, utilizing ultraviolet-visible spectrophotometry, the methanol extract emerged as the optimal solvent extract, which was abundant in diverse classes of compounds such as carbohydrates, phenolics, steroids, alkaloids, phenolic acids, and tannins. In vitro antioxidant assays underscored the exceptional free radical scavenging, metal ion chelation, hydrogen peroxide scavenging, singlet oxygen quenching, and β-carotene bleaching capabilities of the methanol extract, significantly outperforming other solvent extracts. Further ultra high-performance liquid chromatography–electrospray ionization–quadrupole time of flight–mass spectrometry analysis revealed the presence of 45 compounds, predominantly anthraquinones and phenolics, in the methanol extract. The extract demonstrated robust stability under various conditions, including high temperatures, varying pH levels, and simulated gastrointestinal digestion as well as efficacy in inhibiting the oxidation in edible oils. Acute toxicity tests in mice confirmed the safety of the methanol extract and provided a valuable dosage reference for future studies. Importantly, high-dose methanol extract exhibited a significant pre-protective effect against D-galactosamine-induced liver injury in rats, as evidenced by reduced alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, malondialdehyde levels, and elevated catalase and albumin levels. These findings suggest a potential role for the methanol extract of R. ciliinervis root in treating oxidative stress-related disorders, highlighting the plant’s immense medicinal potential. Our research offers a thorough evaluation of the bioactive components, antioxidant properties, stability, and liver-protecting effects of the methanol extract, setting the stage for deeper investigation and potential clinical applications.

A Comparison of European Union and Turkish Reports on the Statistics of Experimental Animal Use in Toxicity Testing.

The data on the number of animals used for experimental purposes, with a particular focus on regulatory toxicity studies, in Turkey and EU member states plus Norway (EU+), were compared for the period 2015 to 2020 (UK data after Brexit for 2020 were included too). The total number of listed vertebrates used for regulatory toxicity testing in the full 6-year reporting period in Turkey was 3.6% of that reported for the EU+. However, these numbers showed an increasing trend over the reporting period in Turkey, while the trend decreased in the EU+. In the top three most-used species for regulatory toxicology purposes in Turkey, 41% were fish (68,758 animals), followed by rats (29%; 49,975 animals), and then mice (20%; 33,292 animals). Turkey used low numbers of cats and dogs, while the corresponding number for the EU+ was more than 70-fold higher. Non-human primates were not used at all in Turkey, whereas about 34,000 were used in EU+ laboratories. The majority of toxicity tests (57%) performed in Turkey were categorised as 'Other' toxicity tests, and 27% were acute and sub-acute toxicity tests. Successful replacement alternatives (e.g. in vitro and in silico approaches) are already used in a wide range of research areas. However, although this new research and testing paradigm is underpinned by scientific evidence, the legislation and pace of acceptance of these new techniques in Turkey is considerably lagging behind other countries.

Apodanthera glaziovii (Cucurbitaceae) Shows Strong Anti-Inflammatory Activity in Murine Models of Acute Inflammation.

Background/objectives:Apodanthera glaziovii is an endemic species from the semi-arid Brazilian, which has limited toxicological and pharmacological studies. This species belongs to a well-studied family known for its bioactive compounds used in treating inflammatory. This study aimed to identify secondary metabolites in the stems from A. glaziovii, evaluate toxicity, and investigate the anti-inflammatory potential of the stem hydroalcoholic extract (SHE-Ag). Methods: qualitative and quantitative assays were employed to identify secondary metabolites, along with chromatographic analyses and 1H and 13C NMR. Toxicity was assessed through in vitro hemolytic toxicity, in vivo genotoxicity, and oral acute toxicity tests before the pharmacological assays were conducted. Results: phytochemical screening, HPLC and NMR analyses suggested the presence of saponins of the norcucurbitacin class. The SHE-Ag exhibited no hemolytic activity and no mutagenic potential. However, in vivo toxicity at a dose of 2000 mg/kg revealed hematological and biochemical alterations, while the 500 mg/kg dose was safe. In the anti-inflammatory assays, SHE-Ag at 100 mg/kg reduced paw edema by 55.8%, and leukocyte and neutrophil migration by 62% and 68% in the peritonitis model, respectively; inflammatory cell migration by 70% in the air pouch model, outperforming indomethacin, which showed a 54% reduction. Conclusions: these findings indicate that SHE-Ag is rich in saponins, confirmed through HPLC and 1H and 13C NMR analyses. The SHE-Ag also demonstrated low toxicity. The inflammation models used showed a reduction in inflammation, pro-inflammatory cells, and edema, highlighting the significant anti-inflammatory activity of hydroethanolic extract A. glaziovii stems.

Proteomic Profile of Blood Plasma of Mus Musculus in the Acute Toxicity Test of Single Black Garlic (Allium Sativum)

This study aims to obtain overall information about all proteins formed in body fluids, cells, or tissues at a certain time and to analyze the mechanism of cell responses to various types of stress and drugs. Single black garlic (SBG) has the potential to be a pharmacological agent. However, the safety of using single black garlic is still unknown, so a material toxicity test is needed. This research is a laboratory experimental research with a post-test-only control group design. An oral acute toxicity test was used. Observation time was 14 days and consisted of four treatments, negative control, SBG dose 2000 mg/kgbw (P1), 3000 mg/kgbw (P2), and 5000 mg/kgbw (P3). Post-treatment protein analysis was done using the SDS-PAGE electrophoresis method. Observations of clinical symptoms of SBG at doses of 2000 mg/kgbw, 3000 mg/kgbw, and 5000 mg/kgbw showed no clinical symptoms in mice, both motor activity and pupils were still normal, no convulsions (seizures), lacrimation, paralysis or death were seen in mice. Observations on plasma proteins showed differences in protein between the treatments at the SBG dose of 2000 mg/kgbw with the SBG dose of 3000 mg/kgbw and 5000 mg/kgbw, but the four treatments have the same type of protein in the protein band with a molecular weight of 25 kDa. So, it can be concluded that SBG doses of 2000 mg/kgbw, 3000 mg/kgbw, and 5000 mg/kgbw are not toxic to mice but can stimulate the expression of certain proteins. Keywords: Single Black garlic (SBG), oral acute toxicity test, proteomic analysis, SDS-PAGE

A novel pectin-like polysaccharide from Crocus sativus targets Galectin-3 to inhibit hepatic stellate cells activation and liver fibrosis

Liver fibrosis may lead to cirrhosis and even cancer without effective clinical medicine available. Previous studies demonstrated that galactan-containing pectins or pectin-like polysaccharides might target Galectin-3 (Gal-3) to impede fibrosis. This research aims to discover novel pectin-like galactan to interfere with fibrosis for potential new drug development. Thus, we purify a novel homogeneous Rhamnogalacturonan-I like polysaccharide with galactan input, XHH2, from the Crocus sativus flower. XHH2 (MW: 35.7 kDa) consists of rhamnose, galacturonic acid, galactose, and arabinose in ratios of 6.6: 6.1: 25.2: 12.1. The backbone of XHH2 comprises 1, 3, 6-Gal and 1, 3, 4-GalA, with branches at O-3 of 1, 3, 6-Gal and O-4 of 1, 3, 4-GalA. O-3 branches include 1, 3-Gal, 1, 4-Gal, 1, 6-Gal, T-Gal, and T-Glc, while O-4 branches consist of 1, 2, 4-Rha, 1, 4-GalA, 1, 5-Ara, T-Ara, T-Gal, and T-α-HexA. Surface plasmon resonance measurement shows that XHH2 binds to both Gal-3 and integrin β1 to block Gal-3/integrin β1 interaction. Mechanism studies further suggest that XHH2 inactivates hepatic stellate cells (HSCs) via disturbing the Gal-3/Integrin-β1/FAK pathway to alleviate liver injury and fibrosis in vitro &in vivo. XHH2 shows a favorable drug safety in the acute toxicity test of oral administration of XHH2 in mice. Overall, XHH2 is an active ingredient against liver fibrosis by targeting the interaction between Gal-3 and Integrin-β1.

A novel integrated testing strategy (ITS) for evaluating acute fish toxicity with new approach methodologies (NAMs)

Acute fish toxicity (AFT) tests are performed in aquatic risk assessments of chemical compounds globally. However, the specific endpoint of in vivo AFT is based on the lethal concentration 50 (LC50), which is a serious challenge in terms of animal welfare. To support the 3Rs principle of replacing, reducing, and refining use of animals, integrated testing strategies (ITS) have recently been developed for environmental risk assessment. ITS efficiently integrates multiple types of information, especially new approach methodologies (NAMs), and further supports regulatory decision-making. Currently, an effective ITS framework for evaluating aquatic toxicity is lacking. Therefore, we aimed to develop a promising ITS for AFT using in silico, in vitro, and in vivo data. We established the ITS via in silico (OECD QSAR Toolbox 4.6), fish cell line acute toxicity (FCT), and fish embryo acute toxicity (FET) tests and then validated the NAMs with AFT testing. The NAM data were derived from the European Chemicals Agency (ECHA) dossier, toxicology databases, peer-reviewed research articles, and this study. For the first step in the ITS process, we aimed to design a high-throughput screening tool to identify non-toxic and toxic chemicals. We found that results of in silico, FCT, and FET tests alone were strongly correlated with AFT. Among the models, the in silico model was most suitable for identifying toxicants due to its high sensitivity and minimal animal use. Next, considering regulatory purposes and flexibility, we determined the predictive LC50 of toxic chemicals by pursuing a preference-dependent strategy, sequential testing strategy, and sensitivity-dependent strategy. All the strategies demonstrated a predictive power equal to or greater than 73%. In addition, to meet user preferences, our ITS approach has high flexibility and supports animal welfare and environmental protection. We have therefore developed multiple powerful, flexible, and more humane ITS methods for acute fish toxicity assessment by integrating NAMs.

Antihyperglycemic activity of a novel polyherbal formula (HF344), a mixture of fifteen herb extracts, for the management of type 2 diabetes: Evidence from in vitro, ex vivo, and in vivo studies

Antihyperglycemic effects of a novel polyherbal formula (HF344), comprising fifteen Thai herbal extracts, were elucidated for pharmacological mechanisms and potential for managing type 2 diabetes mellitus, by employing in vitro, ex vivo, and in vivo approaches. LC/MS analysis of HF344 extract revealed several phytoconstituents, with piperine identified as the major active compound. HF344 extract significantly enhanced insulin secretion in RINm5F cells in vitro and inhibited glucose uptake into the everted sacs of the mouse small intestine ex vivo in a concentration-dependent manner compared to the control (p < 0.05). It exhibited potent α-glucosidase inhibition in vitro, with an IC50 of 96.74 μg/mL. Moreover, HF344 extract upregulated mRNA levels of GLUT1 in L6 skeletal myoblasts, suggesting increased glucose uptake into skeletal muscle. In addition, in vivo antihyperglycemic effects were assessed in streptozotocin (STZ)-nicotinamide (NA)-induced diabetic mice. Acute oral toxicity testing confirmed the HF344 extract's safety, with an LD50 exceeding 2000 mg/kg. Oral administration of HF344 extract (500 and 1000 mg/kg) in STZ-NA-induced diabetic mice significantly reduced the area under the fasting blood glucose (FBG)-time curve (AUC) in the oral glucose tolerance test (OGTT) model and treatment for 28-day reduced the FBG levels as compared with control (p < 0.05). This was accompanied by increased serum insulin levels and improved insulin resistance. HF344 extract also demonstrated a concentration-dependent inhibitory effect on malondialdehyde (MDA) production in vitro, with an IC50 of 7.24 μg/mL. Oral treatment with HF344 extract decreased MDA production in the homogenized muscle ex vivo collected from STZ-NA-induced mice. Furthermore, pretreatment with HF344 extract effectively restored the survival of RINm5F cells from STZ-induced damage. These findings suggest that HF344 is a promising polyherbal formula for managing blood glucose levels, enhancing insulin production, and providing antioxidant benefits in T2DM. Further research is required to evaluate the clinical efficacy and safety profiles of HF344.

Characterization of food color additives and evaluation of their acute toxicity in Wistar albino rats

Background and Aim: The use of food dyes can cause certain diseases, such as anemia and indigestion, along with other disorders, tumors, and even cancer. Therefore, this study aimed to determine the chemical nature and toxicity of some commercial dyes locally used in processed foods compared with standard food dyes. Materials and Methods: Three types of standard and commercial food color additives (Sunset Yellow, Tartrazine, and Carmoisine) were extensively examined. The chemical structures and functional groups of the dyes were evaluated by Fourier-transform infrared (FTIR) spectroscopy. The melting temperatures of the dyes were also determined by chemical thermal analysis. The acute toxicity test to evaluate the standard and commercial food color safety was estimated by a range-finding study using 150 Wistar albino rats. Sub-groups were administered one of the three colors under study at doses of 2, 3, 4, and 5 g/kg body weight (BW) orally for 7 days. When no mortality was observed, an additional 15 g/kg BW was administered. Concerning the median lethal dose 50 (LD50), 38 rats were exploited using the up-and-down method. Results: Commercial dyes had lower melting points than standard colors. Regarding the range-finding study, rats receiving different doses of the dyes exhibited no signs of toxicity, no deaths, and no clinical or gross pathological signs throughout the 7 days of the experiment. However, the animals that were dosed with 15 g/kg BW of each dye showed signs of loss of appetite, tachycardia, drowsiness, and eventual death. The LD50 values of the commercial food dyes, particularly Sunset Yellow and Carmoisine, were lower than those of the standard dyes. Conclusion: Commercial food colors were more toxic to rats than standard food colors. Differences were observed between the purity of the standard and commercial dyes, and the latter ones contained different percentages of salt, indicating the occurrence of fraud in commercial markets. Keywords: acute toxicity, food colors, Fourier-transform infrared spectroscopy, lethal dose 50, range-finding study.

Antitrypanosomal activities of ethanol extract of Harungana madagascariensis Lam. ex Poir against Trypanosoma brucei brucei - An in vivo model

African trypanosomiasis constitutes public health and veterinary challenges in sub-Saharan Africa. Development of vaccine for its prevention is beset with challenges. Hence, trypanosomiasis control is premised on vector control and treatment of identified cases. Effect of oral administration of ethanol extract of stem bark of H. madagascariensis on Trypanosoma brucei brucei (Federe strain) was investigated in experimentally-infected rat model. Harungana madagascariensis stem bark powder (300 g) was macerated in 1.5 l of 100 % n-hexane for 48 hours. The residue was dried and re-macerated in 1.5 l of 70 % ethanol for 48 hours. The filtrate was dried by evaporation on water bath at 60oC. Phytochemical screening revealed the presence of alkaloids, flavonoids, terpenoids, anthraquinones, saponins, phenols and tannins. Acute toxicity test revealed oral LD50 &gt; 5000 mg/kg body weight. Oral administration of the extract did not exert curative effect. Parasitaemia persisted in the extract treated rats (Group A-1250 mg/kg and Group B-2500 mg/kg body weight) till death. Rats administered 1250 mg/kg body weight outlived all inoculated rats by 2 days despite the significant (P &lt; 0.05) rise in parasitaemia. Anaemia was ameliorated in rats taking 1250 mg/kg body weight compared to groups B, C and D that were severely anaemic. Emaciation was ameliorated in both extract-treated groups A and B compared to groups C and D. Harunga madagascariensis demonstrated promising prospects as potential source of therapeutic agent for ameliorating the severity of anaemia and African trypanosomiasis.

Possible Causes of Extreme Variation of Benzo[a]pyrene Acute Toxicity Test on Daphnia magna.

There are enormous differences in benzo[a]pyrene (BaP) acute toxicity tests on Daphnia magna, according to previous publications. The explanations of the reasons for this extreme variation are necessary. In this context, the acute toxicity tests of different experiment conditions (light/dark, culture medium, and solvent) were conducted on Daphnia magna with BaP as the toxicant of concern. Based on the experiments above, molecular dynamics (MD) simulations were employed to investigate the mechanisms of action. According to our results, the significant influence of light exposure on the acute toxicity test of BaP (p < 0.05) on D. magna was recorded. On the basis of the MD simulations, it was possible that BaP may not affect the normal operation of Superoxide Dismutase and Catalase directly, and it could be quickly transferred from the body through Glutathione S-transferase and Cytochromes P450. Therefore, when exposed to light, the oxidative stress process intensifies, causing damage to Daphnia magna. Apparently, the ecotoxicity tests based on inhibition for D. magna cannot adequately reflect the toxic effects of BaP.

Toxicological profile of Balanites agyptiaca in albino Wistar rats

Background: Balanites aegyptiaca (BAE) is a thorny tree that grows in most arid and semi-arid areas of Africa, the Middle East and India. It is used in traditional medicine for its cardioprotective, deworming, antihelmintic, anti-infectious and antifungal properties. Excessive consumption of this plant's products can present risks of intoxication for consumers. Objective: The aim of this study was to assess the acute and subchronic oral toxicity of the aqueous extract of Balanites aegyptiaca leaves and roots, with a view to ensuring the safety of consumers of this plant. Method: Acute toxicity was carried out in accordance with the OECD experimental protocol. The plant extract tested was administered orally to female rats at a single dose of 2000 mg/kg. These animals were observed for 14 days. For the subchronic toxicity study, the aqueous extract was administered daily orally to male and female rats at different doses (250, 500 and 1000 mg/kg) for 30 days. After the treatment period, the animals were sacrificed for hematological, biochemical and histopathological analyses. Results: The results of the acute oral toxicity test showed that the aqueous extract of Balanites aegyptiaca leaves and roots was non-toxic at a dose of 2000 mg/kg. During the sub-chronic test period, observation of rat signs and behaviour revealed no abnormalities in the groups of animals treated with the extract compared with controls. A significant variation in relative heart and liver weights was observed at 1000 mg/kg. In addition, there was a significant reduction in concentrations of aspartate aminotransferase, total cholesterol, triglycerides and low-density lipoproteins in these rats. Compared with control groups. There was also a significant decrease in hemoglobin and mean corpuscular hemoglobin, with an increase in lymphocytes and white blood cells at the same dose of 1000mg/kg. Histological examinations of the kidneys and liver showed normal renal architecture, and the liver also showed normal hepatic architecture with slight degeneration at a dose of 1000mg/kg of the extract tested. Conclusion: Single administration of the 2000 mg/kg dose did not induce signs of significant toxicity in rats. However, in long-term oral treatment, safety measures must be taken. Thus, sub-chronic oral exposure of BAE to lower doses is recommended, while higher doses, of the order of 1000 mg/kg, should be avoided.

Mixed toxic effects of aluminium oxide nanoparticles with hexavalent chromium, tetracycline, and humic acid towards marine crustacean Artemia salina

ABSTRACT Aluminium oxide nanoparticles (Al2O3 NPs) are prevalent in natural water bodies due to their commercial applications, necessitating an evaluation of their toxicity to aquatic life. This study assessed the toxicity of Al2O3 NPs both alone and in combination with pollutants like chromium (Cr VI) and tetracycline (TC), as well as with organic matter such as humic acid (HA) on brine shrimp (Artemia salina). The addition of Cr (VI) enhanced the aggregation of Al2O3 NPs. Acute toxicity tests showed a concentration-dependent increase in A. salina mortality, primarily due to the early absorption of Al2O3 NPs. The presence of TC and HA reduced toxicity by binding to the nanoparticles. Additionally, HA influenced Al2O3 aggregation, while reactive oxygen species (ROS) production, protein concentration, and lipid peroxidation supported the toxicity findings. This research ultimately highlights the ecological implications of Al2O3 NPs on aquatic ecosystems.

Dermal Acute Toxicity Test

The aim of the dermal acute toxicity test is to identify the intrinsic toxicity of a product by assessing its hazard potential following acute skin exposure. This test also provides preliminary data that can be used to determine the appropriate dosage level and guide the design of subsequent toxicity studies, including determining the LD50 value and information about skin absorption. In this study, female rats (Rattus Nervegicus) are used as test subjects. The test material is prepared by diluting 15 ml of the sample to a final concentration of 994.9 mg/mL. The rats are exposed to the material for 24 hours. Post-exposure, microanatomical observations, and surgery in the abdominal and thoracic areas revealed no abnormalities.

Assessing the efficacy of Stemona collinsiae roots extract against third-stage larvae of Gnathostoma spinigerum and its safety profiles

Gnathostomiasis, caused by the advanced third-stage larvae of Gnathostoma spinigerum, demands novel treatment avenues. The ethanolic root extract of Stemona collinsiae has been postulated to have anthelminthic properties, suggesting its potential as an alternative remedy. In this study, S. collinsiae roots were collected, identified, and extracted with 95 % ethanol. The crude extracts were standardized using didehydrostemofoline as chemical marker. The efficacy of the S. collinsiae root extract against third-stage larvae of G. spinigerum and its toxicity to Wistar rats were evaluated. Both in vitro and in vivo tests were performed, where the in vitro tests assessed the anthelminthic potential of S. collinsiae extract against G. spinigerum larvae, while in vivo tests examined the extract's efficacy against G. spinigerum larvae in infected Wistar rats and the efficacy was compared with albendazole. Parallelly, Wistar rats underwent acute and sub-chronic toxicity tests to establish the safe dosage of the extract. The in vitro tests showcased significant anthelminthic activity, marked by discernible morphological alterations in the exposed larvae. Acute toxicity proved fatal at 2000 mg/kg body weight, while a dose of 300 mg/kg proved non-toxic. Using the Globally Harmonized Classification System, an LD50 of 500 mg/kg was determined. In vivo trials revealed a pronounced decline in G. spinigerum larvae among rats treated with the S. collinsiae extract. The larvae were also observed to be encysted post-treatment, while those treated with albendazole were not encysted. The S. collinsiae extract, with its noteworthy in vitro efficacy and favorable safety metrics in rodents, can be a potential anthelminthic agent. The diminished inflammatory response compared to albendazole hints at S. collinsiae being a safer gnathostomiasis treatment alternative. The promising results in these preliminary trials warrant a deeper investigation to determine the root extract's optimal dosing, suitable delivery methods, and its broader clinical implications.

Multiparameter analysis of Diuron and its metabolites (DCA and DCPMU) in different stages of zebrafish (Danio rerio) development

IntroductionDiuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a prominent herbicide in Brazilian agriculture, particularly in sugarcane farming. This herbicide persists in the environment and is transformed into potentially toxic metabolites, such as 3,4-dichloroaniline (DCA) and 3-(3,4-dichlorophenyl)-1-methylurea (DCPMU), raising concerns that encompass environmental contamination and One Health, which unites environmental and human health. Zebrafish are an appropriate experimental model to evaluate toxicity: they metabolically and genetically resemble humans and can be applied in ecotoxicology.MethodsIn this study, we have employed multiparameter evaluation to characterize the toxicity of environmentally relevant concentrations (0.5–100 μM) of Diuron, DCA, or DCPMU in Brazil, a developing country. In the early stages of zebrafish development, we performed the fish embryo toxicity test according to the guidelines established in OECD Protocol No. 236, extended to 144 h post fertilization (hpf). We also investigated the oxygen consumption rate in zebrafish embryos at 24 hpf, evaluated the acetylcholinesterase (AChE) enzymatic activity in zebrafish larvae at 96 hpf, and used the Comet Assay to assess DNA fragmentation in zebrafish larvae at 96 hpf. We subjected adult zebrafish to acute exposure for 96 h in accordance with OECD protocol no. 203 for the Acute Toxicity Test in Fish. Following this exposure, we analyzed mutagenicity by using the micronucleus test, which was complemented by quantification of nuclear anomalies (NA) in erythrocytes and further confirmed by histopathological investigations.Results and discussionExposure to any of the tested Diuron concentrations damaged DNA, and NA became significant beyond 10 μM Diuron. At 10 μM, DCA altered AChE activity, suggesting neuromuscular toxicity. Between 0.5 and 5 μM, DCA was potentially genotoxic, and 5–10 μM DCA induced nuclear pleomorphism. At all the tested concentrations, DCPMU damaged DNA, and NA emerged between 1 and 10 μM DCPMU. Adult zebrafish exposed to any of the tested Diuron, DCA, or DCPMU concentrations for 96 h did not exhibit significant histopathological alterations. Erythrocyte morphology analysis did not reveal mutagenicity. Although we observed non-mutagenic genotoxicity, chromosomal instability is of concern. The findings of this study contribute to our understanding of how Diuron and its metabolites affect zebrafish and highlights the need for multiparametric assessment to elucidate how herbicides and their metabolites impact the environment and human health. This endeavor informs regulatory measures for safely using Diuron and similar herbicides and reveals substantial implications for developing nations grappling with escalating water contamination due to pesticide use.