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

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.

Download Full-text

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.

Download Full-text

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.

Download Full-text

Subchronic and Genetic Safety Assessment of a New Medicinal Dendrobium Species: Dendrobium Taiseed Tosnobile in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/8950534 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11

Author(s):

Li-Chan Yang ◽

Jiunn-Wang Liao ◽

Chi-Luan Wen ◽

Wen-Chuan Lin

Keyword(s):

Histopathological Examination ◽

Micronucleus Test ◽

Clinical Signs ◽

Serum Biochemistry ◽

Female Rats ◽

Control Group ◽

Sprague Dawley ◽

Oral Toxicity ◽

Sd Rats

Dendrobium Taiseed Tosnobile is a new species of herba dendrobii (Shi-Hu) that was developed by crossbreeding D. tosaense and D. nobile. Its pharmacological activity and active component have been reported, but its subchronic toxicity and genetic safety have not yet been investigated. This study assessed the 90-day oral toxicity and genetic safety of the aqueous extracts of D. Taiseed Tosnobile (DTTE) in male and female Sprague-Dawley (SD) rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats. DTTE was given orally to rats at 800, 1600, or 2400 mg/kg for 90 consecutive days, and distilled water was used for the control group. Genotoxicity studies were performed using a bacterial reverse mutation assay and in vivo mammalian cell micronucleus test in ICR mice and analyzed using flow cytometry. Throughout the study period, no abnormal changes were observed in clinical signs and body weight or on ophthalmological examinations. Additionally, no significant differences were found in urinalysis, hematology, and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. Based on results, the no-observed-adverse-effect level of DTTE is greater than 2400 mg/kg in SD rats.

Download Full-text

Toxicological evaluation of the dried hydroethanolic extract of Amaranthus spinosus L. roots in Artemia salina larvae and Sprague Dawley rats

Clinical Phytoscience ◽

10.1186/s40816-021-00304-1 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Kokou Atchou ◽

Povi Lawson-Evi ◽

Aboudoulatif Diallo ◽

Kwashie Eklu-Gadegbeku

Keyword(s):

Body Weight ◽

Histopathological Examination ◽

Artemia Salina ◽

Female Rats ◽

Sprague Dawley ◽

Glucose Levels ◽

Amaranthus Spinosus ◽

Blood Glucose Levels ◽

Sprague Dawley Rats

Abstract Background Amaranthus spinosus is a medicinal plant used in traditional medicine to treat several diseases including diabetes and its complications. The aim of this study was to prove the safety of the plant in animal health. Methods The dry extract was obtained following the hydroethanolic extraction of A. spinosus roots. The cytotoxicity was evaluated in vitro by incubating Artemia salina larvae with the extract for 24 h. In vivo toxicity was assessed in Sprague Dawley rats. A single dose of 5000 mg/kg bw of extract was administered orally to female rats in acute toxicity and observed for 14 days for mortality and signs of toxicity. In subchronic toxicity, extract doses of 500 and 1000 mg/kg bw were administered orally to male and female rats for 28 consecutive days and observed for previous signs. Body weight was recorded daily and blood glucose levels every week. On day 29, blood was collected for biochemical and hematological studies. Organs were then exised for gross autopsy and histopathological examination. Results The in vitro study showed that the extract had a LC50 = 1.178 mg/mL in larvae and was considered to be non-cytotoxic. Oral administration of extract at a single dose of 5000 mg/kg bw did not cause any mortality or sign of toxicity in gross necropsy. In subchronic oral toxicity, repeated doses of 500 and 1000 mg/kg bw of extract, did not also cause any mortality or significant change in body weight, relative weight of vital organs. Furthermore, hematological and biochemical parameters and histopathological examination did not show any significant change. The observed decrease in blood glucose levels did not correlate with organ damage and supports the safety of the plant. However, the reduction of LDL-cholesterol has shown that the extract can prevent cardiovascular disease. Conclusions This finding demonstrated that A. spinosus root is non-toxic with a LD50 > 5000 mg/kg bw. Thus, the extract can be used for cutaneous and subchronic oral administration at doses ≤ 1000 mg/kg bw. However, further studies such as embryo/fetotoxicity, genotoxicity and neurotoxicity will be needed to prove the safety of chronic administration of the extract in patients and fetuses.

Download Full-text

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

Download Full-text

Potency of Murraya koenigii Leaves as Anti-Cancer Mammary in 7,12 dimethylbenz(α) anthracene (DMBA) induced-Sprague Dawley Rats

E3S Web of Conferences ◽

10.1051/e3sconf/202015101058 ◽

2020 ◽

Vol 151 ◽

pp. 01058

Author(s):

Siti Aisyah ◽

Ekowati Handharyani ◽

Nurliani Bermawie ◽

Agus Setiyono

Keyword(s):

Mammary Tumor ◽

Tumor Size ◽

Histopathological Examination ◽

Tumor Development ◽

Collagen Fibers ◽

Female Rats ◽

Sprague Dawley ◽

Murraya Koenigii ◽

Sprague Dawley Rat ◽

Sprague Dawley Rats

The purpose of the research was to study the potency of Murraya koenigii leaves extract to overcome the mammary tumor in Sprague Dawley rat. Thirty-five female rats were divided into seven groups: control (P1), tumor without therapy (P2), methotrexate group (P3), curative groups (P4 and P5) were given extract after the tumor was formed, and preventive groups (P6 and P7) were given extract before the tumor was formed with dose of 300 and 400 mg/kg, respectively. The induction of mammary tumor in rats were carried out using 7,12 dimethylbenz(α) anthracene (DMBA) subcutaneously. Bodyweight and tumor size were measured every week for 4 weeks. At the end of treatment, rats were euthanized and mammary glands were collected for histopathological examination. The result showed tumor size in P2 was significantly higher (p<0.05) than in other groups. On the other hand, tumor size in P4 and P6 were significantly smaller (p<0.05) compared to P5 and P7. Histopathological changes showed PMN cells, 1-3 layers of cuboid epithelial and solid collagen fibers proliferation in P2, while in P3 to P7 showed moderate collagen fibers proliferation. In conclusion, the administration of the extract at a dose of 300 mg/kg can decelerate tumor development in Sprague Dawley rat mammary gland.

Download Full-text

Subchronic Hepatotoxicity Evaluation of 1,2,4-Tribromobenzene in Sprague-Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581812437974 ◽

2012 ◽

Vol 31 (3) ◽

pp. 250-256 ◽

Cited By ~ 4

Author(s):

Darol E. Dodd ◽

Linda J. Pluta ◽

Mark A. Sochaski ◽

Kathleen A. Funk ◽

Russell S. Thomas

Keyword(s):

Adverse Effect ◽

Body Weight ◽

Exposure Time ◽

Clinical Signs ◽

Liver Weight ◽

Sprague Dawley ◽

Significant Incidence ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Effect Level

Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There were no TBB exposure-related clinical signs of toxicity or changes in body weight. Liver weight increases were dose and exposure time related and statistically significant at ≥10 mg/kg per d. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and time related. The 75 mg/kg per d group had minimally increased mitoses within hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was considered TBB exposure related at ≥25 mg/kg per d. Concentrations of blood TBB increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 µg/mL (2.5-75 mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for 13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg per d was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥10 mg/kg per d.

Download Full-text

SUBCHRONIC TOXICITY OF MALAYSIAN ACALYPHA INDICA: BIOCHEMISTRY AND HAEMATOLOGY ANALYSIS OF RAT

Jurnal Teknologi ◽

10.11113/jt.v78.8570 ◽

2016 ◽

Vol 78 (5-5) ◽

Author(s):

Norazlanshah Hazali ◽

Nurul Nadia Mohd Nazri ◽

Muhammad Ibrahim ◽

Mashita Masri

Keyword(s):

Body Weight ◽

Skin Diseases ◽

Female Rats ◽

Control Group ◽

Dosage Group ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

High Dosage Group ◽

Sprague Dawley Rats ◽

Acalypha Indica

Acalypha indica is one of the medicinal plants that have been used since ages to treat various diseases such as pneumoniae, asthma and skin diseases. This study aimed to explore the subchronic toxicity effect of Acalypha indica on Sprague Dawley rats based on haematological and biochemical parameters. The extract of Acalypha indica was prepared by aqueous extraction technique. 48 Sprague Dawley rats aged 7 weeks, weighing 150-200g were randomly divided into four groups, 6 animals per gender. A control group received water vehicle while three treated groups received the extract at dosage of 100 (low dosage group), 200 (medium dosage group) and 300 (high dosage group) mg/kg body weight. The sample was administered orally by using oral gavage daily for 90 days. No sign of toxicity and mortality was recorded in all groups throughout the study. There were no significant different (p>0.05) in body weight gain, food and water intake between control and treatment group. However, there was significant different in uric acid between control and high dosage group of male and female rats but the mean were in normal range. There were also reduced in mean of urea and creatinine in all dosage group of male and urea for all dosage group of female. Statistically significant reduced in urea was recorded between control and high dosage group of male only. Other parameters showed no significant different between control and treatment groups. Therefore, Acalypha indica is safe for human consumption and might be potential in reducing kidney damage problem.

Download Full-text

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.

Download Full-text

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.

Download Full-text