Acute and Subchronic (28-day) Oral Toxicity Studies on the Film Formulation of k-Carrageenan and Konjac Glucomannan for Soft Capsule Application

The aim of this study was to investigate the acute and subchronic toxicity of a film formulation that combines κ-Carrageenan and konjac glucomannan for soft capsule application. For the acute toxicity study, a dose of 2000 mg/kg body weight (bw) of the film suspension was administered orally to rats. The animals were observed for toxic symptoms and mortality daily for 14 days. In a subchronic toxicity study, the film suspension, at doses of 10, 30 and 75 mg/kg bw for 28 days, were orally administered to rats. After 28 days, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity study, neither signs of toxicity nor death among the rats were observed for up to 14 days of the experimental period. The results of the subchronic toxicity study show that there were no significant changes observed in the hematology and organ histology. Some alterations to the relative organ weight and blood biochemistry were observed, but they were considered to be temporary effects and not an indication of toxic effects. The overall findings of this study indicate that the film formulation of κ-Carrageenan and konjac glucomannan is non-toxic up to a dose of 75 mg/kg bw, which could be considered a safe dose for soft capsule application.

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Absence of Detectable Toxicity in Rats Fed Partially Hydrolyzed Guar Gum (K-13) for 13 Weeks

International Journal of Toxicology ◽

10.1080/109158197226928 ◽

1997 ◽

Vol 16 (6) ◽

pp. 611-623 ◽

Cited By ~ 5

Author(s):

Takatoshi Koujitani ◽

Hidetoshi Oishi ◽

Yuji Kubo ◽

Toshihiro Maeda ◽

Keiji Sekiya ◽

...

Keyword(s):

Acute Toxicity ◽

Guar Gum ◽

Toxicity Study ◽

Oral Toxicity ◽

Subchronic Toxicity ◽

Mutagenic Potential ◽

Reverse Mutation ◽

Acute Toxicity Study ◽

K 13 ◽

Partially Hydrolyzed Guar Gum

Toxicity studies were conducted to evaluate acute and subchronic oral toxicity and mutagenicity of partially hydrolyzed guar gum (K-13). In an acute toxicity study, mice and rats were treated with K-13 at a dose of 6000 mg/ kg. There were no deaths, so the LD50s were >6000 mg/ kg in both species. In a subchronic toxicity study, K-13 was given to rats as a dietary admixture at concentrations of 0.2. 1.0 and 5.0% for 13 weeks. There were no effects attributable to K-13 in any examinations. K-13 proved to have no mutagenic potential in a reverse mutation test using bacteria.

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Acute Toxicity Study of Porang (Amorphophallus oncophyllus) Flour Macerated with Strobilanthes crispus in Wistar Rats

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2021.6813 ◽

2021 ◽

Vol 9 (A) ◽

pp. 976-981

Author(s):

Rizka Qurrota A’yun ◽

Uswatun Hasanah ◽

Hamam Hadi ◽

Mustofa Mustofa ◽

Eva Nurinda ◽

...

Keyword(s):

Acute Toxicity ◽

Bioactive Compound ◽

Urinary Protein ◽

Toxicity Study ◽

Fixed Dose ◽

Oral Toxicity ◽

Biochemical Tests ◽

Serum Glutamic Oxaloacetic Transaminase ◽

Acute Toxicity Study ◽

Strobilanthes Crispus

BACKGROUND: Porang (Amorphophallus oncophyllus) is a local tuber food that high in bioactive compound glucomannan. It uses are limited due to oxalate acid content which poses health risks. Strobilanthes crispus leaves could reduce the level of calcium oxalate in porang. However, there is still no study to prove its safety. AIM: This study aimed to investigate the acute oral toxicity study of porang (A. oncophyllus) macerated with S. crispus based on observation of mortality rate (LD50), the changes in behavior during 72 h, renal and hepatic function such as urinary protein, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT) levels of Wistar rat (Rattus norvegicus) METHODS: An acute toxicity test was conducted based on the Organization of Economic Co-Operation and Development 420 Fixed-Dose Procedure Guideline that consists of preliminary and main studies. For the preliminary study, rats were divided into control and five treatment groups with the dosage of 50, 300, 2000, and 5000 mg/kg body weight (BW) for each natural porang flour (NPF) and S. crispus-macerated porang flour (SPF). For the main study, rats were divided into four groups, those were NPF and SPF with the dosage of 2000 and 5000 mg/kg BW. Levels of urinary protein and blood serum SGOT and SGPT levels were measured at 0, 24, and 72 after treatment. RESULTS: The acute toxicity study showed that porang and porang macerated with S. crispus were not toxic until the highest dose of 5000 mg/kg BW. It was proved by the absence of LD50, no change in behavior, no weight losses, and also the results of biochemical tests, such as urinary protein, SGOT, and SGPT which were still in the normal range. CONCLUSIONS: Porang flour and SPF were concluded as non-toxic food based on acute toxicity study.

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Acute Oral Toxicity of Pinnatoxin G in Mice

Toxins ◽

10.3390/toxins12020087 ◽

2020 ◽

Vol 12 (2) ◽

pp. 87 ◽

Cited By ~ 3

Author(s):

Silvio Sosa ◽

Marco Pelin ◽

Federica Cavion ◽

Fabienne Hervé ◽

Philipp Hess ◽

...

Keyword(s):

Acute Toxicity ◽

Nicotinic Acetylcholine Receptors ◽

Morphological Changes ◽

Clinical Signs ◽

Rapid Onset ◽

Toxicity Study ◽

Oral Exposure ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Acute Toxicity Study

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8–450 µg kg−1). At the dose of 220 µg kg−1 and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 µg kg−1, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD50 for PnTx-G equal to 208 μg kg−1 (95% confidence limits: 155–281 µg kg−1) and to estimate a provisional NOEL of 120 µg kg−1.

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Withania frutescens. L Extract: Phytochemical Characterization and Acute and Repeated Dose 28-Day Oral Toxicity Studies in Mice

BioMed Research International ◽

10.1155/2020/1976298 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Abdelfattah EL Moussaoui ◽

Mohammed Bourhia ◽

Fatima Zahra Jawhari ◽

Imane Es-safi ◽

Syed Saeed Ali ◽

...

Keyword(s):

Acute Toxicity ◽

Oral Administration ◽

Biochemical Parameters ◽

Clinical Symptoms ◽

Toxicity Study ◽

Control Group ◽

Oral Toxicity ◽

Traditional Use ◽

Subacute Toxicity ◽

Acute Toxicity Study

Background. Withania frutescens. L (W. frutescens) is a perennial woody medicinal plant belonging to family Solanaceae largely used by the indigenous population to Morocco for the treatment of disease. Objective. The purpose of this study was to investigate the chemical composition, acute, and subacute toxicity of W. frutescens extract in mice. Materials and Methods. The phytochemical composition of W. frutescens extract was determined using a gas chromatograph (GC/MS). Acute toxicity study was carried out in mice through oral administration of single doses 500 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was performed with oral administration of repeated doses 500 and 2000 mg/kg/day for 28 days. Biochemical parameters (alanine aminotransferase, aspartate aminotransferase, urea, and creatinine), as well as histopathological changes potentially occurred in organs, (liver, kidney, and spleen) were evaluated. Results. The results of chromatographic analysis showed the richness of W. frutescens extract in interesting phytochemical compounds majorly constituted of bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-(C10H16). Regarding acute toxicity study, the results showed no clinical symptoms occurred in treated mice compared to the control group and no histological changes detected in analyzed organs of treated mice with dose put to 2000 mg/kg nor adverse effect on biochemical parameters. Conclusion. The outcome of this work showed no toxic effect of W. frutescens in mice up to dose 2000 mg/kg bodyweight. Therefore, this study could scientifically validate further traditional use with safety in the range of tested doses.

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Oral Toxicological Studies ofPuerariaFlower Extract: Acute Toxicity Study in Mice and Subchronic Toxicity Study in Rats

Journal of Food Science ◽

10.1111/1750-3841.12263 ◽

2013 ◽

Vol 78 (11) ◽

pp. T1814-T1821 ◽

Cited By ~ 4

Author(s):

Akira Takano ◽

Tomoyasu Kamiya ◽

Masahito Tsubata ◽

Motoya Ikeguchi ◽

Kinya Takagaki ◽

...

Keyword(s):

Acute Toxicity ◽

Toxicity Study ◽

Subchronic Toxicity ◽

Acute Toxicity Study ◽

Toxicological Studies

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Safety assessment of subtilisin QK in rats

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00506-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shuai Xiao ◽

Dingbang Hu ◽

Ya Gao ◽

Yang Ai ◽

Sang Luo ◽

...

Keyword(s):

Acute Toxicity ◽

Adverse Effects ◽

Oral Dose ◽

Fibrinolytic Activity ◽

Toxicity Study ◽

Subchronic Toxicity ◽

Safety Pharmacology ◽

Sd Rats ◽

Acute Toxicity Study ◽

Safety Pharmacology Study

Abstract Background Subtilisin QK is a serine protease in the subtilisin family, and is fermented by Bacillus subtilis QK02. The fibrinolytic activity of subtilisin QK was measured by detecting low molecular weight degradation products using a spectrophotometric method developed by Japan Bio Science Laboratory Co., Ltd. Subtilisin QK powder can maintain its fibrinolytic activity for more than 24 months when it is stored at room temperature and protected from light. Our previous results showed that subtlisin QK directly degraded cross-linked fibrins in the fibrin plate assay and effectively inhibited thrombosis in the mouse thrombus model. The aim of this study was to determine the acute toxicity, potential subchronic toxicity, and safety pharmacology of subtilisin QK in Sprague–Dawley (SD) rats. Methods In the acute toxicity study, a single oral dose of 100,000 FU/kg was administered to 10 female and 10 male SD rats. In the 28-day subchronic toxicity, 60 female and 60 male SD rats were randomly assigned to four experimental groups (daily oral dose of 0, 2500, 7500 and 25,000 FU/kg). In the safety pharmacology study, 20 female and 20 male SD rats were randomly assigned to four experimental groups (single oral dose of 0, 500, 1500 and 5000 FU/kg). Results No death occurred and no adverse effects were observed in the acute toxicity study at a dose of 100,000 FU/kg. In the 28-day subchronic toxicity study, several hematological and blood biochemical parameters showed increases or decreases; however, due to the lack of a dose–response relationship, these differences were considered unrelated to treatment. In the safety pharmacology study, no adverse effects were observed on the central nervous of SD rats post-administration up to a dose of 5000 FU/kg subtilisin QK. Conclusion The results showed that oral consumption of subtilisin QK is of low toxicological concern. No adverse effects were observed at doses of 2500, 7500, and 25,000 FU/kg in the 28-day subchronic toxicity, and the no-observed-adverse-effect level (NOAEL) of subtilisin QK was 25,000 FU/kg.

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Hepatoprotective effect of Helicanthus elastica

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i2.26149 ◽

2016 ◽

Vol 11 (2) ◽

pp. 525 ◽

Cited By ~ 1

Author(s):

K.N. Sunil Kumar ◽

R. Rajakrishnan ◽

J. Thomas ◽

G. Aadinaath Reddy

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Dose Level ◽

Video Clip ◽

Ethanolic Extract ◽

Ethanol Extract ◽

Toxicity Study ◽

Oral Toxicity ◽

Acute Toxicity Study ◽

Whole Plant

Search for medicinal plants to treat liver disorders is an important research topic on herbs. Acute toxicity study is a prerequisite for safety and dose fixation for further pharmacological actions. In the present study, aqueous and 95% ethanolic extract of whole plant of Helicanthus elastica were subjected to acute oral toxicity. The aqueous and ethanolic extract revealed no observable changes in the rats up to the dose level of 2,000 mg /kg body weight. The extracts were then screened for paracetamol-induced hepatic injury at dose levels of 200 and 400 mg/kg body weight (1/10 and 1/5 LD50 based on toxicity study). The aqueous extract of whole plant of H. elastica was found to produce significant (p<0.05) reversal of the paracetamol-induced changes in the measured biochemical and histopathological parameters at lower dose of 200 mg/kg which was found to be better than ethanol extract at the same dose level.Video Clip:<a href="https://www.youtube.com/v/cO6HI1Kikxs">Acute toxicity study and others:</a> 5 min 38 sec

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PHARMACOGNOSTIC, ANTIOXIDANT AND ACUTE TOXICITY STUDY OF Ficus sycomorus (Linn) (Moraceae) ROOT AND STEM BARK

FUDMA Journal of Sciences ◽

10.33003/fjs-2020-0402-244 ◽

2020 ◽

Vol 4 (2) ◽

pp. 605-614

Author(s):

Murtala M. Namadina ◽

H. Haruna ◽

U. Sanusi

Keyword(s):

Acute Toxicity ◽

Radical Scavenging ◽

Stem Bark ◽

The Body ◽

Toxicity Study ◽

Bark Extract ◽

Root Extract ◽

Acute Toxicity Study ◽

Radical Scavenging Ability ◽

Phytochemical Components

Most of biochemical reactions in the body generates Reactive Oxygen Species (ROS), which are involved in the pathogenesis of oxidative stress-related disorders like diabetes, nephrotoxicity, cancer, cardiovascular disorders, inflammation and neurological disorders when they attack biochemical molecules like proteins, lipids and nucleic acid. Antioxidants are used to protect the cells or tissues against potential attack by ROS. Most medicinal plants possess a rich source of antioxidants such as flavonoids, phenols, tannins, alkaloids among others. These phytochemicals are currently pursued as an alternative and complimentary drug. In this study, phytochemical components, antioxidant and acute toxicity study of the methanol extract of stem bark and root of F. sycomorus were carried out using standard methods. Findings from this study revealed the presence of some diagnostic microscopical features such as calcium oxalate, starch, gum/mucilage, lignin, Aleurone grain, suberized/Cuticular cell wall and inulin but calcium carbonate was absent in stem bark but present in the powdered root. Quantitative physical constants include moisture contents (6.40% and 7.82%), ash value (7.20% and 9.30 %) in stem bark and root respectively. Carbohydrates, alkaloid, flavonoids, saponins, tannins, glycoside, steroid, triterpenes and phenols were present in all the extracts. They were found to exhibit potent 1,1,-diphenyl 2-picryl hydrazyl (DPPH) free scavenging activity. The DPPH radical scavenging ability of the extracts showed the following trend Ascorbic acid < stem bark extract˃ root extract. The LD50 of the methanolic stem bark and root extracts were found to be greater than 5000 mg /kg and is considered safe for use. Nonetheless, further

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In-vitro and in-vivo evaluation of antidiabetic activity of Withania coagulans extract

The Natural Products Journal ◽

10.2174/2210315509666190416155757 ◽

2019 ◽

Vol 09 ◽

Author(s):

Tejas Patel ◽

B.N. Suhagia

Keyword(s):

Blood Glucose ◽

Acute Toxicity ◽

Aqueous Extract ◽

Pancreatic Beta Cell ◽

Toxicity Study ◽

Acute Toxicity Study ◽

Withania Coagulans ◽

Study Results

Background: Diabetes mellitus is major issue to public health as its prevalence is rising day by day. Synthetic agents available for the diabetic treatment are expensive or produce undesirable side effect on chronic use and some of them are not suitable during pregnancy. Herbal medicines accepted widely due to side effects and low cost. Objective: The aim of present study was to evaluate the activity of Withania coagulans extract using In-vitro and In-vivo model. Methods: Different three types of Withania coagulans extract were prepared using aqueous (W1), Alcohol (W2) and hydro-alcoholic (50:50) mixture (W3). In-vitro Anti-diabetic activity of the all three extracts evaluated using RINm5F Pancreatic beta cells.Further, n-vivo anti-diabetic evaluation performed by administering 50 mg/kg (p.o) aqueous extract for 7 days in Streptozotocin (STZ)-induced mice. Body weight of the animals was also determined to perform acute toxicity study. Results: The results of in –vitro cell based study indicated that among all three extract, aqueous extract (W1) of Withania coagulans showed potential increase in inulin release. The EC50 of the W1 (249.6 µg/L) which is compared with standard (Glibenclamide) EC50. From the results of In-vitro study, W1 subjected for acute toxicity study and the acute toxicity study results indicated LD50 of 50mg/kg. Diabetic rats treated with W1 extract at oral dose of 50 mg/kg for 7 days showed 34.17% reduction in blood glucose in comparison to untreated diabetic (STZ-induced) rats. Blood glucose levels of Standard treated (Glibenclamide) and control untreated. Conclusion: In conclusion, results of pancreatic beta cell based study showed increase in insulin release by administration of extract. Further aqueous extract (W1) was potentially reduced blood glucose level in STZ induced diabetic mice.

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Safety Evaluation of Eucalyptus globulus Essential Oils through Acute and Sub-acute Toxicity and Skin Irritation in Mice and Rats

Current Chemical Biology ◽

10.2174/2212796814999200818095036 ◽

2020 ◽

Vol 14 (3) ◽

pp. 187-195

Author(s):

Berhan Mengiste ◽

Tizazu Zenebe ◽

Kassahun Dires ◽

Ermias Lulekal ◽

Awol Mekonnen ◽

...

Keyword(s):

Acute Toxicity ◽

Essential Oil ◽

Eucalyptus Globulus ◽

Biochemical Parameters ◽

Skin Irritation ◽

Toxicity Study ◽

Subacute Toxicity ◽

Acute Toxicity Study ◽

Limit Test ◽

Ointment Formulation

Background: The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats. Methods: The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects. Results: The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction. Discussion: In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application. Conclusion: This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.

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