Acute Oral Toxicity Study Research Articles

Retraction Note: Understanding mechanical characteristics of pH-responsive PEG 4000-based polymeric network for colorectal carcinoma: its acute oral toxicity study

Retraction Note: Understanding mechanical characteristics of pH-responsive PEG 4000-based polymeric network for colorectal carcinoma: its acute oral toxicity study

A 90-day preclinical toxicological evaluation in rats of a highly purified and concentrated mulberry leaf extract.

Mulberry (genus Morus) leaves have long been used as a human food, especially in Asia, and animal feed. More recently, mulberry leaf extracts have been introduced as a convenient way to consume mulberry for non-nutritional functional effects. Reducose® 5% is an Morus alba leaf extract that has been highly purified and standardized to a content of 5 ± 0.5% 1-deoxynojirimycin, a naturally present polyhydroxylated piperidine alkaloid analog of D-glucose. This extract has previously been evaluated in acute and subacute (28-day) oral toxicity studies in which no adverse effects of the test item were observed in mice or rats, respectively. Due to continued and growing interest in the extract in multinational markets, we have now further investigated potential toxic effects in subchronic (90-day) oral toxicity study in male and female Han:WIST rats. The test item was administered at doses of 850, 1700, and 2550 mg/kg bw/day, and did not cause adverse effects in clinical signs, body weight development, clinical pathology, gross pathology, or histopathology in comparison to the vehicle-control group. The no-observed-adverse-effect-level was determined to be 2550 mg/kg bw/day. These results add to the existing body of both preclinical and clinical work relevant to the safety of the extract and of interest to regulators in various global markets.

Phytochemical and pharmacological profiling of extracts of Pterygota alata (Roxb.) R. Br. leaves deciphered therapeutic potentialities against pain, hyperglycemia and diarrhea via in vivo approaches

Background and aimPterygota alata (Roxb.) R. Br. is a large, broad-leaved evergreen plant in the family Malvaceae (formerly Sterculiaceae). The present study aimed to investigate the phytochemical and pharmacological properties of methanolic extract of the leaves (200 mg/kg bw and 400 mg/kg bw) of P. alata focusing on analgesic, hypoglycemic, and anti-diarrheal potentials on the Swiss Albino mice model. MethodsGas chromatography and mass spectrometry (GC-MS) technique was employed to identify the bioactive compounds from the plant species. The tail flicking procedure and acetic acid-induced writhing inhibition were carried out to estimate central and peripheral analgesic properties. The anti-diarrheal property of the herbaceous extractive was assessed employing the castor oil-induced antidiarrheal approach, while the hypoglycemia was estimated employing the tail-tipping method. ResultsThe study reported a total of thirty-seven phytoconstituents by using GC-MS analysis, where erucamide (25.5 %), 8,11,14-Docosatrienoic acid, methyl ester (14.58 %), methyl linoleate (12.67 %), and methyl palmitate (9.23 %) were most abundant in the plant species. In evaluating central analgesia, the leaf extract of P. alata exerted significant central analgesic (200 mg/kg bw and 400 mg/kg bw) efficacy. The acetic acid-induced writhing was inhibited by 45.84 % and 66.67 % at both doses, demonstrating a promising peripheral analgesic effect compared to diclofenac sodium (75.00 %). On the contrary, hypoglycemic actions remained dosage and time-dependent. In the antidiarrheal activity assay, the number of diarrheal feces was reduced significantly by 40.00 % (200 mg/kg) and 68.00 % (400 mg/kg), correspondingly, which was comparable to the positive control loperamide (72.00 %). In addition, the study of acute oral toxicity revealed that the extracts of the plant species were found to be safe, with a median lethal dose (LD50) value greater than 1000 mg/kg. ConclusionThe current study supports the assertion that the P. alata plant species is rich in numerous phytoconstituents and has the potential for traditional application in managing pain, hyperglycemia, and diarrhea. Nonetheless, additional investigation is necessary to extract and identify the bioactive compounds from the plant, which is crucial for advancing the discovery of novel medicinal compounds aimed at addressing a range of health conditions.

Ameliorated in vitro anti-cancer efficacy of methotrexate loaded zinc oxide nanoparticles in breast cancer cell lines MCF-7 & MDA-MB-231 and its acute toxicity study

Traditional therapies often struggle with specificity and resistance in case of cancer treatments. It is therefore important to investigate new approaches for cancer treatment based on nanotechnology. Zinc oxide nanoparticles (ZnONPs) are known to exhibit anti-cancer properties by inducing oxidative stress, apoptosis, and cell cycle arrest. Methotrexate (MTX) a known anti-folate shows specificity to folate receptors and interrupts healthy functioning of cells. This study proposes the use of previously characterized biocompatible Methotrexate loaded Zinc oxide nanoparticles (MTX-ZnONPs) as a dual action therapeutic strategy against breast cancer cell lines, MCF-7 (MTX-sensitive) and MDA-MB-231 (MTX-resistant). To elucidate the cytotoxicity mechanism of MTX-ZnONPs an in depth In vitro study was carried out. In vitro assays, including cell cycle analysis, apoptosis assay, and western blot analysis to study the protein expression were performed. Results of these assays, further supported the anti-cancer activity of MTX-ZnONPs showing apoptotic and necrotic activity in MCF-7 and MDA-MB-231 cell line respectively. In vivo acute oral toxicity study to identify the LD50 in animals revealed no signs of toxicity and mortality up to 550 mg kg−1 body weight of animal, significantly higher LD50 values than anticipated therapeutic levels and safety of the synthesized nanosystem. The study concludes that MTX-ZnONPs exhibit anti-cancer potential against breast cancer cells offering a promising strategy for overcoming resistance.

Bioproduction of yeast single cell oil with acute oral toxicity study intended for edible oil application.

Human nutrition and health rely on edible oils. Global demand for edible oils is expanding, necessitating the discovery of new natural oil sources subjected to adequate quality and safety evaluation. However, in contrast to other agricultural products, India's edible oil supply is surprisingly dependent on imports. The microbial oil is generated by fermentation of oleaginous yeast Rhodotorula mucilaginosa IIPL32 MTCC 25056 using biodiesel plant byproduct crude glycerol as a fermentable carbon source. Enriched with monounsaturated fatty acid, nutritional indices mapping based on the fatty acid composition of the yeast SCO, suggested its plausible use as an edible oil blend. In the present study, acute toxicity evaluation of the yeast SCO in C57BL/6 mice has been performed by randomly dividing the animals into 5 groups with 50, 300, 2000, and 5000mg/Kg yeast SCO dosage, respectively, and predicted the median lethal dose (LD50). Detailed blood biochemistry and kidney and liver histopathology analyses were also reported. The functions of the liver enzymes were also evaluated to check and confirm the anticipated toxicity. To determine cell viability and in vitro biocompatibility, the 3T3-L1 cell line and haemolysis tests were performed. The results suggested the plausible use of yeast SCO as an edible oil blend due to its non-toxic nature in mice models.

Bioactive Components Analysis and Pharmacological Properties of Extracts and Metabolites of Lichen Umbilicaria crustulosa

Lichens, a diverse group of organisms, have a unique structure consisting of fungal filaments and photosynthetic partner cells. This research conducted a comprehensive chemical analysis and evaluation of the anti-inflammatory and antioxidant properties of methanolic and acetone extracts from Umbilicaria crustulosa lichen, along with its isolated metabolites. The process involved separating atranorin and chloratranorin fractions, physodic acid, and gyrophoric acid. Secondary metabolites were identified using chromatographic and spectroscopic data. The total polyphenols content was determined spectrophotometrically. This study examined the antioxidant activity of extracts of the lichen U. crustulosa and the isolated fractions using three methods: DPPH scavenging activity, ABTS scavenging activity, and reducing power. This study also evaluated the acute oral toxicity and the anti-inflammatory activity of the extracts in Wistar albino rats. A higher content of the total phenolic compounds was found in the acetone extract, but antioxidant and anti-inflammatory activities were more prominent in the methanolic extract. The isolated atranorin and chloratranorin fractions and compound physodic acid showed the highest antioxidant activity. No toxic effects were noted in the acute oral toxicity study. This study highlights the potential of the investigated lichen as a valuable source of novel biological agents.

Cell based and In vivo systematic evaluation of some Egyptian plant extracts targeting breast cancer

The prevalence of breast cancer as a significant public health concern necessitates continued exploration of natural resources for novel anti-cancer agents is crucial. Material and methodsAnticancer activity of plant extracts on monolayer breast cancer cell line (MCF7) with lower levels of toxicity towards normal (RPE1) underwent further assessment using a three-dimensional model (3D). The extract's effects were investigated through multiple assays including apoptosis induction using quantifying cleaved cytokeratin-18 (CK18) and DNA fragmentation. Additionally, the expression of Bcl-2 and Bax was quantitative using real-time PCR. The median lethal dose (LD50) was determined by the acute oral toxicity, while biomarkers associated with tumorigenesis, metastasis, and cell death were quantified by ELISA. ResultsLimoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts. They demonstrated potent cytotoxicity against MCF7 with no significant effect on hTERT RPE-1, with an IC50 of 100 μM. The extract demonstrated effectiveness in killing cancer cells within 3D tumor-like structures, induced apoptosis through caspase-3 activation and cleavage of cytokeratin-18, up-regulated the tumor suppressor p53, down-regulated the anti-apoptotic Bcl-2 gene, and caused DNA fragmentation. Acute oral toxicity studies in mice indicated low toxicity, and in a syngeneic mouse tumor model, the extract significantly inhibited tumor growth, suggesting its potential for further development. ConclusionLimoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts.

ACUTE AND SUB-ACUTE TOXICOLOGICAL STUDY OF VANGA BHASMA

Introduction: Vanga is a dhatu, that has been used externally since the Samhita period. During the rasa shastra era, vanga was utilized internally for Prameha, (urinary disorder ) Medoroga(diseases of medadhatu – fat tis-sue), Kapha Vikaras(diseases of kapha-bodily constitution ), and other purposes after Bhasmikara-na.(preaparation of Bhasma - medicine ) Objective: Evaluate Acute and Sub-acute toxicity of Vanga Bhasma. Materials &Methods: The acute and sub-acute toxicity studies of Vanga Bhasma were carried out on Wistar Albino rats using 425 and 407 OECD guidelines, respectively. Acute oral toxicity study of the test drug was car-ried out at the limit dose of 2000 mg/kg orally in rats. In a sub-acute toxicity study, Vanga bhasma was adminis-tered to rats for 28 consecutive days at doses of 22.5(TED-therapeutic equivalent dose), 112.5(TEDX5), and 225 mg/kg(TEDX10). The effects of the drug were assessed on haematological, biochemical, histological, and pon-deral parameters. Results: Acute toxicity: the study showed the LD 50 value of Vanga Bhasma is greater than 2000mg/kg. Sub-acute toxicity: this study did not produce any signs or symptoms of toxicity at TED, TEDX5, and TEDX10. Conclusion: The single dose of 2000mg/kg body weight evaluated by acute toxicity study is proved to be non-toxic. Overall analysis reveals that test drug vanga bhasma is very well tolerated at rat human therapeutic equivalent dose and multiples of it. Therefore, Vanga bhasma, prepared and administered in accord-ance with customary protocols, is safe to consume at therapeutic dose levels.

Safety and efficacy evaluation of halicin as an effective drug for inhibiting intestinal infections.

Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and Clostridium perfringens (C. perfringens). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD50 of 2018.3mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated in vivo. Our study found that halicin had a good therapeutic effect on intestinal infection model of C. perfringens. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.

TOXICOLOGICAL EVALUATION OF OLEANOLIC ACID (PENTACYCLIC TRITERPENOID) EXTRACTED FROM LANTANA CAMARA ROOTS FOLLOWING ORAL EXPOSURE IN WISTAR RATS

Objective: The aim of the present study was to perform an acute toxicity study to obtain information on the possible adverse effects from a single oral administration of Oleanolic acid in Wistar rats as the onset of toxicity, and to determine the range of exposure (to the LD50 cut-off criteria). Following a sub-chronic 90-days Repeated toxicity study by oral route to determine any potential indication of its dose response relationship and determine no observed effect level (NOEL)/ no-observed adverse effect level (NOAEL)/ low observed effect level (LOEL)/ low observed adverse effect level (LOAEL). Methods: A dose level of 2000mg/kg body weight was employed as step one for single acute study. Based on the survival pattern of the previously dosed animals after 48 hours, same dose 2000 mg/kg body weight) was repeated for Step 2 as a confirmatory test. For the 90-day toxicity study, the highest dose was determined as 1000mg/kg Body weight, and the middle and lower doses were 500 and 250mg/kg Body weight respectively. The rat group was held for a 14-day recovery period after the last dose administration, to observe for any persistence or reversal of toxic effects. Results: Results of the acute toxicity study showed no mortality on the dose level of 2000mg/kg body weight with no significant clinical and body weight changes. During the 90-day Repeated dose oral sub-chronic toxicity study, no rats died. There were no significant clinical changes related to the test item in terms of functional evaluation, body weight, food and water consumption, ophthalmological tests, urine analysis, necropsy findings, or organ weight, Hematology, and biochemistry at the highest dose level of 1000 mg/kg bwt. Conclusion: It is concluded that LD50 Cut-off Value of “Oleanolic acid” in from acute oral toxicity study in Wistar Rats is 2000 mg/kg b.wt. In addition, 90 days study have showed no significant changes with respect to any hematological or blood chemical analyses in 1000, 500 and 250 mg/kg bwt groups. Based on histopathological findings, clinical signs and other parameters, it may be concluded that upon repeated once oral administration for consecutive 90 days, the Oleanolic acid (Pentacyclic Triterpenoid) extracted from Lantana camara roots at the dose level of 1000 mg/kg body weight have caused no adverse effect in both sexes of Wistar Rats.

Prospects for the use of medicinal plants extracts (Mallotus oppositifolius and Kalanchoe crenata) as antimicrobials against salmonellosis in poultry

This study is a contribution to the search for alternatives to combat antibiotic resistance in Salmonella strains in poultry farming. The objective of this work is to highlight the main phytochemical compounds of 2 Ivorian medicinal plants (Mallotus oppositifolius and Kalanchoe crenata) and to evaluate their acute oral toxicity with a view to their use in the poultry sector, to fight against certain avian pathologies, including Salmonellosis. The phytochemical compounds of the different extracts of the plants used in this study were highlighted by colouring and precipitation methods. Acute oral toxicity was adapted to broilers according to the guideline OECD 425, 2008. This experimental study, which is the very first adapted to broiler chickens, was carried out with the agreement of the National Ethics Committee for Life and Health Sciences. The phytochemical screening carried out showed that each of these three antibacterial extracts possesses at least the major phytochemical groups sought. At the end of the acute oral toxicity study, no mortality was observed and the biochemical analysis of the subjects' blood showed creatinine values ​​≤ 10 mg/L.; aspartate aminotransferase (ASAT) ≤ 275 IU/L; alanine aminotransferase (ALT) ≤ 50 IU/L, urea=0.01g/L, CRP≤6 mg/L; and blood sugar was between 2 and 5 g/L in subjects from different batches. Ultimately, the aqueous and ethanolic extracts of Mallotus oppositifolius and the ethanolic extract of Kalanchoe crenata can be used as an antibacterial in broiler farming.

Synthesis, in vitro Anti-HIV-1RT evaluation, molecular modeling, DFT and acute oral toxicity studies of some benzotriazole derivatives

This study synthesized and evaluated a series of benzotriazole derivatives denoted 3(a-j) and 6(a-j) for their anti-HIV-1 RT activities compared to the standard drug efavirenz. Notably, compound 3 h, followed closely by 6 h, exhibited significant anti-HIV-1 RT efficacy relative to the standard drug. In vivo oral toxicity studies were conducted for the most active compound 3 h, confirming its nontoxic nature to ascertain the safety profile. By employing molecular docking techniques, we explored the potential interactions between the synthesized compounds (ligands) and a target biomolecule (protein)(PDB ID 1RT2) at the molecular level. We undertook the molecular dynamics study of 3 h, the most active compound, within the active binding pocket of the cocrystallized structure of HIV-1 RT (PDB ID 1RT2). We aimed to learn more about how biomolecular systems behave, interact, and change at the atomic or molecular level over time. Finally, the DFT-derived HOMO and LUMO orbitals, as well as analysis of the molecular electrostatic potential map, aid in discerning the reactivity characteristics of our molecule.

Oral acute toxicity study and in vivo antimalarial activity of Strychnos lucida R. Br. tablet

Ethnopharmacological relevanceMalaria eradication has been a major goal of the Indonesian government since 2020. Medicinal plants, such as Strychnos lucida R. Br., are empirically used to treat malaria through traditional preparation methods. However, the safety and efficacy of these plants have not yet been confirmed. Therefore, further investigations are necessary to confirm the safety and efficacy of S. lucida as an antimalarial agent. Aims of the studyTo quantify the concentration of brucine in the S. lucida extract, determine the acute oral toxicity of the standardized extract, and evaluate the in vivo antimalarial potency of S. lucida tablet (SLT). Materials and methodsAcute oral toxicity of S.lucida extract was determined using the Organization for Economic Co-operation and Development 420 procedure, and the analytical method for brucine quantification was validated using high-performance liquid chromatography. In addition, antimalarial activity was determined using the Peter's four-day suppressive method. ResultsAcute toxicity analysis revealed S. lucida as a low-toxicity compound with a cut-off median lethal dose of 2000–5000 mg/kg body weight [BW], which was supported by the hematological and biochemical profiles of the kidneys, liver, and pancreas (p > 0.05). Extract standardization revealed that S. lucida contained 3.91 ± 0.074% w/w brucine, adhering to the limit specified in the Indonesian Herbal Pharmacopeia. Antimalarial test revealed that SLT inhibited the growth of Plasmodium berghei by 27.74–45.27%. Moreover, SLT improved the hemoglobin and hematocrit levels. White blood cell and lymphocyte counts were lower in the SLT-treated group than in the K (+) group (p < 0.05). ConclusionHistopathological and biochemical evaluations revealed that S. lucida extract was safe at a dose of 2000 mg/kg BW with low toxicity. SLT inhibited Plasmodium growth and improved the hemoglobin, hematocrit, and red blood cell profiles. Additionally, SLT reduced the lymphocyte and WBC counts and increased the monocyte and thrombocyte counts as part of the immune system response against Plasmodium infection.

Evaluation of in silico model predictions for mammalian acute oral toxicity and regulatory application in pesticide hazard and risk assessment

The United States Environmental Protection Agency (USEPA) uses the lethal dose 50% (LD50) value from in vivo rat acute oral toxicity studies for pesticide product label precautionary statements and environmental risk assessment (RA). The Collaborative Acute Toxicity Modeling Suite (CATMoS) is a quantitative structure-activity relationship (QSAR)-based in silico approach to predict rat acute oral toxicity that has the potential to reduce animal use when registering a new pesticide technical grade active ingredient (TGAI). This analysis compared LD50 values predicted by CATMoS to empirical values from in vivo studies for the TGAIs of 177 conventional pesticides. The accuracy and reliability of the model predictions were assessed relative to the empirical data in terms of USEPA acute oral toxicity categories and discrete LD50 values for each chemical. CATMoS was most reliable at placing pesticide TGAIs in acute toxicity categories III (>500–5000 mg/kg) and IV (>5000 mg/kg), with 88% categorical concordance for 165 chemicals with empirical in vivo LD50 values ≥ 500 mg/kg. When considering an LD50 for RA, CATMoS predictions of 2000 mg/kg and higher were found to agree with empirical values from limit tests (i.e., single, high-dose tests) or definitive results over 2000 mg/kg with few exceptions.

Safety profile of Naga Bhasma prepared by two classical methods

Abstract Background: Naga Bhasma (NB) (incinerated lead) has been indicated as a remedy for the treatment of a wide range of diseases including Prameha (diabetes), Kasa (cough), Raktapradara (menorrhagia), Shukradosha (defects in semen), etc., However, improperly prepared NB can cause harmful effects on the human body. In modern science also, lead consumption has been accepted to produce toxicity. Aim: The present study was undertaken to elucidate and compare the toxicity profile of two samples of NB prepared by two different methods to ascertain the safety aspects. Materials and methods: In the first method, NB was prepared by using Parada (mercury), Gandhaka (sulfur), and Nimbu Swarasa (juice of Citrus medica var acida of Watt). In the second method, NB was prepared by using Ashwattha-Twaka-Churna (Ficus religiosa L.), Manahshila (realgar) (Ariloha), and Nimbu Swarasa. In both methods, 30 calcination cycles were given. Charles foster albino rats were used for the pharmacological study. Acute oral toxicity study was carried out as per organization for economic cooperation and development (OECD) 425 and chronic oral toxicity study was carried out as per OECD 408 (90-day oral repeated dose toxicity study). Acute oral toxicity study was conducted at five dose levels, namely 100, 250, 500, 1000, and 2000 mg/kg body weight. Chronic toxicity was carried out at a dose level of 62.5 mg/kg body weight. Animals were sacrificed on the 91st day by cervical dislocation. Blood was collected from the jugular vein and sent for hematological and biochemical investigations were done. Organs were used for histopathological studies. The data were analyzed by unpaired t-test. Results: No mortality was observed in the acute toxicity study. Chronic toxicity study shows that both the test drugs do not produce significant toxicity, but both were not completely free from adverse effects at the dose level studied. Conclusion: The study shows that both the test drugs do not produce significant toxicity, but they are not completely free from adverse effects at the dose level studied.

Leaching of unexpected cyazofamid degradation products into groundwater demonstrates gaps in current pesticide risk assessment

To investigate the formation and leaching potential of degradation products N,N-dimethylsulfamide (DMS) and dimethylsulfamic acid (DMSA) from cyazofamid under real-world agricultural conditions, the fungicide cyazofamid was applied in a potato crop as part of the Danish Pesticide Leaching Assessment Programme (PLAP). Leaching of DMS, DMSA, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (CCIM), and 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carboxylicacid (CTCA) was monitored in water from the variably saturated zone (suction cups) and groundwater for more than two years following the applications. In total, 424 samples were analyzed for the content of the four degradation products. An additional laboratory study was executed in parallel with the field monitoring study. Here, cyazofamid was applied to soil columns and leaching of the four degradation products was studied under controlled conditions.In the EFSA conclusion on cyazofamid, CCIM and CTCA are mentioned as major relevant metabolites; DMS is not mentioned in the risk assessment and DMSA is only included in acute oral toxicity studies and an in vitro bacterial mutation assay. In contrast to the EFSA conclusion on cyazofamid, our studies showed no leaching of the two major metabolites, CTCA and CCIM, but instead, major leaching of DMS and DMSA in both the field and laboratory studies was observed. That is, both DMS and DMSA leached to the groundwater in concentrations >0.1 μg/L for more than half a year. Based on this, we suggest improvements to the current pesticide risk assessment.

&lt;i&gt;In Vivo&lt;/i&gt; Hepatoprotective Activity of Hydroalcohol Extract of &lt;i&gt;Gyrocarpus asiaticus&lt;/i&gt; Willd and &lt;i&gt;Lactuca runcinata&lt;/i&gt; DC

Objective: Investigation of hepatoprotective activity of Gyrocarpus asiaticus Willd (GA) and Lactuca runcinata DC (LR) prepared by hydroalcohol extraction. Methodology: Albino rats were used for the in vivo experiments for the determination of oral acute toxicity study. For these experiments, 6 groups were created of which 5 groups were for each plant extract and 1 group for control. A total of 11 groups were made for the toxicity study. Each group required 2 albino mice. Different doses of 0.025, 0.2, 0.5, 2, and 5 gm/kg body weight were administered orally for each plant extract. For the control group, these were administered with distilled water. For hepatoprotective activity, albino rats were randomly divided into 5 (control, toxic, standard, 2 samples) groups, and 4 animals were randomly divided into each group. For 2 plants, a total of 7 groups were made. 5% gum acacia was used as the vehicle. For induced hepatotoxicity CCl4 and as a standard drug silymarin was used. Result and Discussion: Plant extracts did not show any toxicity, and no histopathological changes were seen in the liver, kidney, or lungs due to toxicity. In the study of GA Willd and LR DC extract prepared by hydroalcohol solution, there was evidence of protection against CCl4-induced hepatotoxicity in the Histopathological study of the liver of albino rats. Conclusion: Hydroalcohol extract of LR DC and GA Willd shows no oral acute toxicity and LR DC shows no significant hepatoprotective activity but GA Willd shows significant hepatoprotective activity

Characterization of the antioxidant activity, identified free radical-relieving components by LC/QTOF/MS and acute oral toxicity studies of Tri-Tharn-Thip tea

This study assessed the antioxidant activities and bioactive maker of Tri-Than-Thip tea (Tri-TTa) to provide database support for the use of Tri-Than Thip remedy according to the Thai Pharmaceutical Textbook and aims to develop herbal medicine or food from natural products. Tri-TTa and herbal components were tested for antioxidant scavenging activity (DPPH assay, ABTS assay), chain-breaking/iron ion chelating activity (Metal Chelating Activity; MAC, the ferric-reducing antioxidant power activity; FRAP), superoxide anion radical scavenging activity (NBT assay), oxygen radical antioxidant capacity (ORAC assay), total content of Phenolic (TCP) and flavonoid (TCP) substance. The chemical components were separated and investigated by LC/QTOF/MS for safe dosages due to acute oral toxicity in rats. The Tri-TTa showed the strongest inhibition of antioxidant activity with the DPPH, ABTS, and MCA assay, with IC50 values of 0.087 ± 0.003, 0.025 ± 0.000, and 0.012 ± 0.000 mg/mL, respectively. In addition, Tri-TTa can also inhibit superoxide anion radicals, with IC50 values of 158 ± 0.009 mg/mL, and the oxygen radical was 3.47 ± 0.03 μM of TE/g extract. TCP, TCF, and FRAP values of Tri-TTa were 154.123 ± 1.326, 80.233 ± 14.268 mg equivalent/g of extract, and 1092.457 ± 106.024 mM FeSO4/mg, respectively. Additionally, Tri-TTa contains important substances in the phenolic and flavonoid groups that have good antioxidant abilities and were confirmed to be safe through acute oral toxicity testing in rats, which revealed no toxicity-related effects at high doses. Tri-TTa is a strong candidate for use as a natural product with antioxidant activity, suggesting that plant polyphenol content may promote antioxidant activity. These results support further research on Thai folk remedy infusions as promising antioxidant agents that can be developed for food, tea, or tonic drugs from natural.

Oral acute toxicity study of ethanol extract of Mobe leaves (Artocarpus lacucha Buch-Ham) in Wistar rats

Many medicinal plants are now being chosen because the treatment is safer and cheaper. Artocarpus lacucha Buch-Ham is a plant with many pharmacological activities and is efficacious; its safety has not been studied. Acute oral toxicity evaluation followed Organization for Economic Co-operation and Development guidelines using the fixed dose method. The evaluation began with a preliminary test, then a primary test with three groups: a 2000 mg/Kg BW dose test group, a 5000 mg/Kg BW dose test group, and a control group. The results of visual observations, haematological and clinical examinations, and histological examination of organs (liver, spleen, kidneys, lungs and heart) showed no toxicity in the animals, and they did not die during testing. The findings of this study support the safety of Artocarpus lacucha Buch-Ham leaf ethanol extract, which did not produce harmful results in acute toxicity tests.

In Silico Prediction of Oral Acute Rodent Toxicity Using Consensus Machine Learning.

Acute oral toxicity (AOT) is required for the classification and labeling of chemicals according to the global harmonized system (GHS). Acute oral toxicity studies are optimized to minimize the use of animals. However, with the advent of the three Rs principles and machine learning in toxicology, alternative in silico methods became a reasonable alternative approach for addressing the AOT of new chemical matter. Here, we describe the compilation of AOT data from a commercial database and the development of a consensus classification model after evaluating different combinations of molecular representations and machine learning algorithms. The model shows significantly better performance compared to publicly available AOT models. Its performance was evaluated on an external validation data set, which was compiled from the literature, and an applicability domain was deduced.