Subchronic Study of a White Kidney Bean (Phaseolus vulgaris) Extract with α-Amylase Inhibitory Activity

Common bean extract as a dietary supplement has received increased attention globally owing to its α-amylase inhibitory activity. The objective of this study was to evaluate the toxicity of a white kidney bean (Phaseolus vulgaris) extract by a repeated-dose 90-day subchronic oral toxicity study in Sprague-Dawley rats. In the subchronic toxicity study, 80 rats were orally administrated with white kidney bean extract at doses of 4, 2, and 1 g/kg body weight daily for 90 days. The results showed that the white kidney bean extract at doses up to 4 g/kg/day did not induce significant changes in body weight, organ weight, food consumption, hematology, serum biochemistry, and histopathology in rats, as compared to the control. The no-observed-adverse-effect level (NOAEL) of white kidney bean extract was determined to be >4 g/kg/day for both male and female rats, under the experimental conditions of this study.

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Oral Toxicity Evaluation of Thiodiglycol in Sprague-Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581814547541 ◽

2014 ◽

Vol 33 (5) ◽

pp. 393-402 ◽

Cited By ~ 3

Author(s):

Richard A. Angerhofer ◽

Mark W. Michie ◽

Glenn J. Leach ◽

Mark S. Johnson ◽

Gunda Reddy

Keyword(s):

Body Weight ◽

Food Consumption ◽

Sulfur Mustard ◽

Female Rats ◽

Male Rats ◽

Control Individual ◽

Sprague Dawley ◽

Oral Toxicity ◽

Male And Female Rats ◽

Sprague Dawley Rats

Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly. At termination of the experiment, urine, blood, and tissue samples were collected. Rats displayed significant decreased body weight with no effect on food consumption following administration of TDG at 5000 mg/kg/d. Both male and female rats showed significant increased kidney weights at 5000 mg/kg/d. The organ to body weight ratios increased significantly for liver, kidneys, testes, and brain in males and adrenals in females for 5000 mg/kg/d. At all doses of TDG, hematological and clinical parameters and tissue histopathology remained unaltered. The no observed adverse effect level (NOAEL) for oral subchronic toxicity was 500 mg/kg/d. Benchmark dose (BMD) was derived from the decreased gain in body weight that was seen in male rats. A BMD based on a 10% decrease in body weight was 1704 mg/kg/d, and the lower confidence limit on the dose BMD, the BMDL, was 372 mg/kg/d.

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Acute and subacute toxicity assessment of Madhulai Manappagu (Siddha herbal syrup formulation) in animal model

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2020-0327 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Meenakshi Sundaram Malayappan ◽

Gayathri Natarajan ◽

Logamanian Mockaiyathevar ◽

Meenakumari Ramasamy

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Oral Route ◽

Toxicity Assessment ◽

Toxicity Study ◽

Female Rats ◽

Albino Rats ◽

Oral Toxicity ◽

Gross Pathology ◽

Toxicity Studies

Abstract Objectives Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats. Methods The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses. Conclusions The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured.

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Toxicity Evaluation of a Traditional Polyherbal Unani Formulation Jawarish Shahi in Rats

The Journal of Phytopharmacology ◽

10.31254/phyto.2018.7502 ◽

2018 ◽

Vol 7 (5) ◽

pp. 412-418

Author(s):

Mohd Urooj ◽

◽

Mohammad Ahmed Khan ◽

G. Thejaswini ◽

Munawwar Husain Kazmi ◽

...

Keyword(s):

Body Weight ◽

Feed Intake ◽

Clinical Signs ◽

Female Rats ◽

Control Group ◽

Sprague Dawley ◽

Male And Female ◽

Salix Caprea ◽

Male And Female Rats ◽

Dose Levels

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight

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A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581816653375 ◽

2016 ◽

Vol 35 (5) ◽

pp. 568-583 ◽

Cited By ~ 7

Author(s):

Palma Ann Marone ◽

Jan Trampota ◽

Steven Weisman

Keyword(s):

Body Weight ◽

Body Weight Gain ◽

Antioxidant Properties ◽

Metabolic Activation ◽

Female Rats ◽

Systemic Absorption ◽

Test Substance ◽

Sprague Dawley ◽

Male And Female Rats ◽

Sprague Dawley Rats

l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation.

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Acute and Subchronic Toxicity Study ofEuphorbia hirtaL. Methanol Extract in Rats

BioMed Research International ◽

10.1155/2013/182064 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 31

Author(s):

Kwan Yuet Ping ◽

Ibrahim Darah ◽

Yeng Chen ◽

Subramaniam Sreeramanan ◽

Sreenivasan Sasidharan

Keyword(s):

Body Weight ◽

Toxicity Study ◽

Morphological Alteration ◽

Control Group ◽

Sprague Dawley ◽

Oral Toxicity ◽

Methanolic Extracts ◽

Sprague Dawley Rats ◽

Significant Difference

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.

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A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4748904 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Sae-Rom Yoo ◽

Hyekyung Ha ◽

Mee-Young Lee ◽

Hyeun-Kyoo Shin ◽

Su-Cheol Han ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Serum Biochemistry ◽

Toxicity Study ◽

Repeated Dose ◽

Sprague Dawley ◽

Oral Toxicity ◽

Organ Weights ◽

Sprague Dawley Rats ◽

Dose Oral

Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT), a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

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A 28-Day Repeated Dose Toxicological Study of an Aqueous Extract of Morus Alba L.

International Journal of Toxicology ◽

10.1177/1091581816670597 ◽

2016 ◽

Vol 35 (6) ◽

pp. 683-691 ◽

Cited By ~ 6

Author(s):

Tennille K. Marx ◽

Róbert Glávits ◽

John R. Endres ◽

Philip A. Palmer ◽

Amy E. Clewell ◽

...

Keyword(s):

Body Weight ◽

Animal Studies ◽

Clinical Pathology ◽

Morus Alba ◽

Water Soluble ◽

Female Rats ◽

Repeated Dose ◽

Oral Toxicity ◽

Male And Female ◽

Male And Female Rats

Morus alba L. (white mulberry) leaves are one of the oldest recognized traditional Chinese medicines. More recently, M alba leaves and their constituents, particularly iminosugars (or azasugars), have garnered attention for their ability to maintain normal blood glucose concentrations, an effect identified in both animal studies and human clinical trials. Reducose (Phynova Group Limited) is a commercial water-soluble extract of M alba leaves standardized to 5% 1-deoxynojirimycin (DNJ), an iminosugar with α-glucosidase inhibition properties. Although there is an extensive history of consumption of M alba leaves by humans and animals worldwide, suggesting that the leaves and their extracts have a relatively good safety profile, we are unaware of safety assessments on an extract containing a higher amount of DNJ than that occurs naturally. The current 28-day repeated dose oral toxicity study in rats, conducted according to Organisation for Economic Co-operation and Development guidelines, was carried out to assess the safety of Reducose. Male and female Hsd.Han Wistar rats (4 groups of 10 animals/sex) were administered Reducose via gavage at doses of 0, 1,000, 2,000 and 4,000 mg/kg body weight (bw)/d. No treatment-related mortality or adverse effects (per clinical observations, body weight/weight gain, food consumption, ophthalmoscopy, clinical pathology, gross pathology, organ weights, or histopathology) were observed, and no target organs were identified. The no observed adverse effect level was determined to be 4,000 mg/kg bw/d for both male and female rats, the highest dose tested.

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Nutritional and 13-Week Subchronic Toxicological Evaluation of Lignosus rhinocerotis Mycelium in Sprague-Dawley Rats

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18031271 ◽

2021 ◽

Vol 18 (3) ◽

pp. 1271

Author(s):

I-Chen Li ◽

Bi-Hua Yang ◽

Jing-Yi Lin ◽

Shan Lin ◽

Chin-Chu Chen

Keyword(s):

Body Weight ◽

Histopathological Examination ◽

Clinical Signs ◽

Female Rats ◽

Sprague Dawley ◽

Oral Toxicity ◽

Crude Lipid ◽

Sprague Dawley Rats ◽

Freeze Dried ◽

Lignosus Rhinocerotis

Lignosus rhinocerotis (Tiger’s Milk mushroom) is a novel mushroom with sclerotium belonging to the Polyporaceae family and has been reported widely to possess anti-cancer, anti-cough, antioxidant, gastro-protective, immuno-modulating, and neurite-stimulating properties. As numerous studies have proven the tremendous medicinal values of L. rhinocerotis, it is necessary to understand its nutrition as well as its safety for the recipient. Previous research on L. rhinocerotis has mainly focused on the naturally occurring sclerotium and may have overlooked mushroom mycelia from submerged liquid fermentation, which ensures a high uniform quantitative biomass production as well as a high biological value. Hence, this is the first report on the evaluation of nutrition and 13-week repeated oral toxicity of L. rhinocerotis mycelium (LRM). The LRM powder contained 9.0 ± 4.2% moisture, 1.9 ± 1.3% ash, 1.6 ± 2.2% crude lipid, 8.4 ± 5.3% crude protein, 79.3 ± 4.6% carbohydrate, and 364 kcal/100 g energy. The total free amino acid ranged from 349 to 5636 mg/100 g and the umami index of freeze-dried LRM powder was 0.37. For safety assessment, ninety-six rats were divided into four groups, each consisting of twelve male and twelve female rats. Test articles were administered by oral gavage to rats at 850, 1700, and 3400 mg/kg body weight/day for 13 weeks and reverse osmosis water was used as the control. All animals survived to the end of the study. During the experiment period, no abnormal changes were observed in clinical signs, body weight, or ophthalmological examinations. No adverse or test article-related differences were found in urinalysis, hematology, or serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. According to the above results, the no-observed-adverse-effect level (NOAEL) of L. rhinocerotis was identified to be greater than 3400 mg/kg body weight (BW)/day in Sprague–Dawley rats.

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Acute oral toxicity of squid and cuttlefish ink powder enzyme hydrolysates in Sprague-Dawley rats in accordance with the OECD Test Guideline 425

Food Research ◽

10.26656/fr.2017.5(5).219 ◽

2021 ◽

Vol 5 (5) ◽

pp. 259-264

Author(s):

Ayu Shazwani Z. ◽

Husnul Azan T. ◽

Wan Ezumi M.F. ◽

Rabeta M.S.

Keyword(s):

Body Weight ◽

Clinical Signs ◽

Normal Structure ◽

Female Rats ◽

Sprague Dawley ◽

Oral Toxicity ◽

Sprague Dawley Rats ◽

Behavioural Patterns ◽

Ld50 Value ◽

Enzyme Hydrolysate

The objectives of this study were to determine LD50 and establish the safety of ink squid and cuttlefish hydrolysates. In the acute toxicity study, three groups of female rats were randomly assigned. One group served as the control and two groups orally received a single limiting dose (2000 mg/kg body weight) of ink hydrolysates. There were no signs of adverse toxicity observed in behavioural patterns, clinical signs, and no significant differences (p>0.05) between the control and treated rats regarding their food and water consumption and body weight for up to 14 days. The histopathological evaluation revealed a normal structure and the absence of noticeable lesions in the vital organs of treated animals. It can be concluded that LD50 value is greater than 2000 mg/kg. The results showed that the squid ink powder enzyme hydrolysate (SIPEHs) and cuttlefish ink powder enzyme hydrolysate (CIPEHs) possess low toxicity, as indicated in the rat model. The preliminary results suggested that it should be further evaluated for long-term use and repeated dose effects to support the safe use of these hydrolysates.

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A comparative study of postpneumonectomy compensatory lung response in growing male and female rats

Journal of Applied Physiology ◽

10.1152/jappl.1992.73.2.446 ◽

1992 ◽

Vol 73 (2) ◽

pp. 446-451 ◽

Cited By ~ 19

Author(s):

H. S. Sekhon ◽

W. M. Thurlbeck

Keyword(s):

Body Weight ◽

Female Rats ◽

Normal Lung ◽

Sham Operation ◽

Sprague Dawley ◽

Lung Weight ◽

Male And Female ◽

Male And Female Rats ◽

Males And Females ◽

Lung Response

Postpneumonectomy compensatory lung response and normal lung growth in the early postnatal period were studied in male and female rats. Four-week-old litter-matched male and female Sprague-Dawley rats were subjected to left pneumonectomy or sham operation and followed for 3 wk. In both sexes after pneumonectomy, lung weight (WL), lung volume (VL), alveolar surface area (Sw), total alveolar number (N(at)), and the amount of DNA and protein increased significantly. In both males and females, WL, VL, and Sw matched those of both lungs of the sham-operated group, but N(at) and the amount of DNA and protein did not. Female pneumonectomy and sham-operated rats were smaller in body weight than males. Absolute WL, VL, Sw, N(at), and the amount of DNA and protein were significantly lower, but specific parameters (per unit body weight) were significantly greater in females than in males. After pneumonectomy, the postcaval lobe increased most in volume (70 and 73% in males and females, respectively). Mean linear intercept and mean chord length of alveoli increased, and the number of alveoli per unit volume decreased more in the postcaval and middle lobes than in upper and lower lobes in both sexes. Postpneumonectomy, loss of elastic lung recoil was observed in females. We conclude that, in certain aspects (WL, VL), compensatory growth matched both lungs of controls, but in others (biochemical, morphometric) it did not. There was evidence of alveolar multiplication, but the dominant effect was enlargement of air spaces.(ABSTRACT TRUNCATED AT 250 WORDS)

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