scholarly journals Preclinical Safety of the Root Extract ofPolygala tenuifoliaWilldenow in Sprague-Dawley Rats and Beagle Dogs

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Ki Young Shin ◽  
Beom Young Won ◽  
Hyun Jee Ha ◽  
Yeo Sang Yun ◽  
Hyung Gun Lee
Keyword(s):  
Clinical Signs ◽  
Female Group ◽  
Test Substance ◽  
Root Extract ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Subchronic Toxicity ◽  
Polygala Tenuifolia ◽  
Preclinical Safety

The root ofPolygala tenuifoliaWilldenow has been used for the treatment of insomnia, depression, and amnesia. However, the toxicological properties of the herb have been overlooked, because it has been used for a long time for various purposes. In this study, we evaluated the preclinical safety of the root extract in rats and beagle dogs. First, the acute oral toxicity was tested in both rats and dogs. In the rats, only one female of 2 g/kg died, but no treatment-related death or clinical and gross findings were observed after the administration. No toxicological changes or mortalities related to the test substance were also observed after the administration in the dogs. Although vomiting, discoloration, or hemorrhage was found in some dogs, there were no serious abnormalities. Second, the subchronic toxicity was investigated in the rats. Two animals were found dead in the female group of 1,000 mg/kg/day, but there were no abnormal findings associated with the test substance. There also were no adverse effects on the clinical signs, body weight, and hematological and biochemical findings. Therefore, our results showed that the acute or subchronic toxicity of the root extract ofPolygala tenuifoliamight not be toxic to rats and dogs.

scholarly journals Safety Assessment of Acer tegmentosum Maxim. Water Extract: General Toxicity Studies in Sprague–Dawley Rats and Beagle Dogs With Re-evaluation of Genotoxic Potentials

2021 ◽  
Vol 12 ◽  
Author(s):  
Jin-Sung Park ◽  
Euna Kwon ◽  
Yun-Soon Kim ◽  
Sang-Moo Kim ◽  
Dae-Sun Kim ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Clinical Signs ◽  
Water Extract ◽  
Deciduous Tree ◽  
Human Consumption ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Oral Toxicity

Acer tegmentosum Maxim., commonly known as Manchurian stripe maple, is a deciduous tree belonging to the family of Aceraceae and has been traditionally used in folk medicine for its remedial effects in liver diseases and traumatic bleedings. With a growing body of experimental evidence for its pharmacological efficacies, such as neuroprotective, hepatoprotective, antioxidant, and anti-inflammatory activities, A. tegmentosum has gradually gained popularity as a health supplement and functional food. However, the large part of essential toxicity information still remained lacking despite the possibility of mutagenic potentials as previously suggested, posing safety concerns for human consumption. In this study, we evaluated 90-day repeated oral toxicity of A. tegmentosum Maxim. water extract (ATWE) in SD rats with acute toxicity assessment in beagle dogs, and reevaluated genotoxicity using a combination of in vitro and in vivo assays. During the oral study period, ATWE did not cause toxicity-related clinical signs and mortality in rodents without adverse effects observed in the analysis of hematology, serum biochemistry, and histopathology, establishing >5,000 mg/kg BW as the NOAEL. In addition, doses up to 5,000 mg/kg BW did not cause acute toxicity in beagle dogs. When assessed for genotoxicity using bacterial reverse mutation, chromosome aberration, and micronucleus formation, ATWE showed lack of mutagenicity and clastogenicity. These results demonstrated that AWTE was safe in the present preclinical study for systemic toxicity and genotoxicity at the tested doses, providing a guideline for safe use in humans.

Studies of the Toxicological Potential of Capsinoids: II. A 26-Week Daily Gavage Dosing Toxicity Study of CH-19 Sweet Extract in Rats

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 11-27 ◽  
Author(s):  
Terutaka Kodama ◽  
Eri Watanabe ◽  
Takeshi Masuyama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Toxicity Study ◽  
High Dose ◽  
Test Substance ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Test Article ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Dose Levels

A 26-week oral toxicity study of capsinoids-containing CH-19 Sweet extract was conducted in Sprague-Dawley rats (20 males and 20 females per group) at 6 weeks of age. The test substance was administered by gavage for 26 weeks at dose levels of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg/day. The concentration of capsinoids in the CH-19 Sweet extract employed was 71.25 to 73.15 mg/ml, resulting in dose levels of capsinoids of 89.06 to 91.44, 178.13 to 182.88, and 356.25 to 365.75 mg/kg, respectively. Adverse test article–related changes were only observed in males, not in females, and within the males, only at the high dose (5.0 ml/kg). Within that group (high-dose males), increases were observed in the numbers of segmented neutrophils, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, liver weights, and in the incidence and severity of hepatocellular focal necrosis. No test substance–related changes were detected in clinical signs, body weight, food consumption, water intake, ophthalmology, or urinalysis. No adverse test article–related changes were observed in low- or mid-dose males or in females at any dose. Based on the results of this chronic gavage study, the target organ was the liver and the no observed adverse effect level (NOAEL) for CH-19 Sweet extract in the rat was 2.5 ml/kg/day in males and 5.0 ml/kg/day in females (178.13 to 182.88 mg/kg and 356.25 to 365.75 mg/kg as capsinoids, respectively).

scholarly journals Acute and Subchronic Oral Toxicity Evaluation of Aqueous Root Extract ofDicoma anomalaSond. in Wistar Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Fatai Oladunni Balogun ◽  
Anofi Omotayo Tom Ashafa
Keyword(s):  
Clinical Signs ◽  
Toxicity Testing ◽  
Blood Chemistry ◽  
Root Extract ◽  
Toxicity Evaluation ◽  
Oral Toxicity ◽  
Subchronic Toxicity ◽  
Toxicity Studies ◽  
Significant Difference ◽  
Aqueous Root Extract

The present study evaluated the safety of aqueous root extract ofDicoma anomala(AQRED) through acute and subchronic toxicity studies. Single oral dose of AQRED at the concentration of 0, 5, 300, and 2000 mg/kg as well as 125, 250, and 500 mg/kg/day was administered to rats for 14-day acute and 90-day subchronic oral toxicity studies. The results revealed no mortalities or observed clinical signs of toxicity in all the rats during both investigation periods. In subchronic toxicity testing, administration of AQRED also did not cause any changes in body weight as well as food and water consumption patterns. The haematological parameters and blood chemistry revealed no significant difference (p>0.05) between the treatment and the control except in platelet count, alkaline phosphatase, and sodium levels where there was a significant increase (p<0.05), although there was also a significant reduction (p<0.05) in alanine transaminase, aspartate transaminase, and creatinine when compared to control. However, these changes were not reflecting the results from histology. Conclusively, the obtained results suggested that the LD50of AQRED is in excess of 2000 mg/kg and its oral administration for 90 days revealed that it is unlikely to be toxic, hence, safe.

scholarly journals Thirteen-Week Oral Toxicity Study of HVC1 in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Kyungjin Lee ◽  
Ho-Young Choi
Keyword(s):  
Hematological Parameters ◽  
Clinical Signs ◽  
Ethanol Extract ◽  
New Drugs ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Weight Changes ◽  
Oral Toxicity ◽  
Blood Biochemical

Studies on the safety of herbal medicine are essential for the development of new drugs. The aim of this study was to evaluate the no-observed-adverse-effect-level (NOAEL) of HVC1 (Gamisamhwangsasim-tang, a 30% ethanol extract of a mixture of Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma) and identify its target organs after oral administration to Sprague-Dawley (SD) rats repeatedly for 13 weeks. Three test groups were treated with HVC1 at a dose of either 500 (low-dose), 1,000 (middle-dose), or 2,000 (high-dose) mg/kg/day. Another group received high-dose HVC1 and was observed for 4 weeks following treatment to examine recovery from the effects of the extract. All treatment groups were compared to a vehicle control group. During the study, mortality, clinical signs, body weight changes, food consumption, abnormal lesions in the eye, urinary parameters, hematological parameters, blood coagulation time, blood biochemical parameters, changes in organ weight, gross findings, and histopathological changes were examined. No systemic toxicity related to HVC1 was observed in any group, and it was concluded that the NOAEL of HVC1 was 2,000 mg/kg/day. No target organ was identified.

Subchronic Toxicity Study of Lactitol in Dogs

1992 ◽  
Vol 11 (2) ◽  
pp. 219-232 ◽  
Author(s):  
H.P. Til ◽  
M.C. Bosland ◽  
V.M.H. Hollanders ◽  
A. Bär
Keyword(s):  
Comparison Group ◽  
Urine Analysis ◽  
Hematological Parameters ◽  
Test Substance ◽  
Oral Toxicity ◽  
Hemoglobin Content ◽  
Subchronic Toxicity ◽  
Treatment Groups ◽  
Cell Counts ◽  
High Doses

The subchronic oral toxicity of lactitol was examined by feeding the test substance at dietary levels of 0, 5, 10, and 15% to groups of 6 male and 6 female dogs for 26 weeks. A comparison group received a diet containing 15% lactose. Although the dogs gradually were adapted to the high doses of the test compounds, diarrhea was observed in the dogs fed 10 and 15% lactitol, and 15% lactose. The diarrhea in the lactose group was less severe than in the 10% lactitol group. Body weight did not show treatment-related differences between the groups. Food intake was slightly higher in the lactitol groups than in the controls. Hemoglobin content (Hb), packed cell volume (PCV), and red blood cell counts (RBC) were slightly lower in dogs of the 15% lactitol group and the 15% lactose group. No other hematological parameters exhibited differences between the various treatment groups. Plasma glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), protein, albumin, glucose, and urea showed no treatment-related differences. However, plasma alkaline phosphatase (AP) tended to be lower in the females of all lactitol groups from day 0 to the end of the study. Transient decreases in plasma calcium and potassium levels were seen in lactitol- and lactose-fed female dogs. Semiquantitative urine analysis did not reveal any abnormalities. There was no impairment of the function of the liver or kidneys in any of the groups. The absolute and relative weights of the cecum, filled as well as empty, were relatively high in males of all lactitol groups and in females of the 10 and 15% dose groups. The weight of the colon and the small intestines, which were determined in males only, were increased in the 5 and 15% lactitol groups. Gross and microscopic examination did not reveal any pathological change that could be attributed to the feeding of lactitol or lactose. It is concluded that under the conditions of the study, daily doses of up to 4.2–6.8 g/kg b.w. are tolerated without obvious signs of toxicity.

scholarly journals Clinical and Morphological Aspects in Assessing the Safety of OSPL-502 with Repeated Dose Administration

2018 ◽  
Vol 6 (9) ◽  
pp. 1581-1587
Author(s):  
Sergey A. Zhuchkov ◽  
Alexandr S. Kinzirsky ◽  
Irina V. Koroleva ◽  
Yuriy B. Vicharev
Keyword(s):  
Toxic Effect ◽  
Adrenal Glands ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Repeated Administration ◽  
Test Substance ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Pharmacological Substance ◽  
Effect Level

BACKGROUND: OSPL-502 is a new potential medicinal drug which stimulates a cognitive function. It is necessary to reveal clinical manifestations of its general toxic effect and determine organs that are most heavily affected by this pharmacological substance. AIMS: To describe and estimate clinical and histopathological changes in the organism of experimental animals in response to the repeated administration of pharmacological substance OSPL-502. MATERIAL AND METHODS: The study was conducted by the OECD Guidelines (Test No. 407) on Sprague-Dawley rats. The drug was administered at the dose of 20, 60 and 180 mg/kg. RESULTS: The repeated doses of OSPL-502 have not caused any toxic effects on the growth of body weight, food and water consumption of the tested animals, or affected the musculoskeletal system and exploratory behaviour of the rats in the doses of 20 and 60 mg/kg. The dose of 180 mg/kg (1800 times larger than the therapeutic dose) has shown clinical signs of toxicity in females but has not resulted in the death of the animals. Due to morphological methods, we have found histostructural changes in the liver, kidneys and adrenal glands of the rats that were treated with the test substance in the maximum dose. These changes are reversible and reduce within 14 days after the admission of the studied substances is cancelled. CONCLUSION: OSPL-502 at the dose of 180 mg/kg has a weakly pronounced toxic effect, the dose of 60 mg/kg is the threshold, and that of 20 mg/kg is no-observable-adverse-effect-level (NOAEL); the liver, kidneys and adrenal glands can be considered target-organs for the tested substance.

scholarly journals A 90-Day Oral Toxicity Study of the Ethanol Extract from Eupatorium japonicum Thunb and Foeniculum vulgare in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Guangcheng Dai ◽  
Chenglu Wang ◽  
Wei Tang ◽  
Jiangyun Liu ◽  
Boxin Xue
Keyword(s):  
Body Weight ◽  
Safety Information ◽  
Clinical Signs ◽  
Ethanol Extract ◽  
Male Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Foeniculum Vulgare ◽  
Hematological Indices ◽  
Eupatorium Japonicum

Eupatorium japonicum Thunb and Foeniculum vulgare are two of the most widely used folk herbs and constituents in many traditional Chinese herbal formulas. Nonetheless, little toxicological and safety information associated with following daily repeated exposure is obtained according to previous research. The present study was performed to assess the toxicity of ethanol extract from Eupatorium japonicum Thunb and Foeniculum vulgare (EFE) in male rats administered by dietary oral gavage at target doses of 0.39, 0.78, and 1.56 g/kg body weight/day for 90 days. There were no significant adverse effects on clinical signs, body weight, food conversion efficiency, and vital hematological indices. However, some hematology and biochemical indices such as WCV, MCH, MCHC, LY, MPV, T-CHO, as well as TG revealed significant changes in Sprague–Dawley rats and organ weights in lung and spleen showed diminished in male rats. Necropsy and histopathology findings suggested that no significant differences in absolute weights were found in all organs except lung and spleen, and no treatment-related alteration was identified in any organs. All results obtained in the present study indicated that the proper use of EFE in traditional medicine at oral dosages up to 1.56 g/kg/day body weight may harbor no prolonged toxicity to rats. However, further studies of EFE are still necessary to assess its oral safety in patients.

Absence of Mutagenicity, Genotoxicity, and Subchronic Oral Toxicity of Touchi Extract

2007 ◽  
Vol 26 (5) ◽  
pp. 465-473 ◽  
Author(s):  
Hiroyuki Fujita ◽  
Tomohide Yamagami
Keyword(s):  
Micronucleus Test ◽  
Clinical Signs ◽  
Water Extract ◽  
Human Consumption ◽  
Mouse Bone Marrow ◽  
Oral Toxicity ◽  
Subchronic Toxicity ◽  
Toxicological Studies ◽  
Chinese Food

Touchi, a traditional Chinese food used mainly for seasoning is obtained by first steaming soybeans followed by fermentation with Aspergillus oryzae (koji). A series of toxicological studies was conducted to evaluate the mutagenic and genotoxic potential and subchronic toxicity of a water extract of Touchi, a known inhibitor of α-glucosidase activity. Touchi extract (TE) did not induce reverse mutations in Salmonella typhimurium strains TA98, TA1537, TA100, TA1535, and Escherichia coli WP2uvrA at concentrations up to 5000 μg/plate, in either the absence or presence of exogenous metabolic activation. No deaths occurred and no abnormal clinical signs were observed in any animal in any group in an in vivo micronucleus test, and TE was devoid of clastogenic activity when administered orally to mice at doses up to 2000 mg/kg/day. Thus, TE was evaluated as negative in the bacterial reverse mutation and mouse bone marrow micronucleus tests under the conditions of these assays. To evaluate its subchronic toxicity, SPF rats were administered TE at doses of 0,250,1000, and 2500 mg/kg/day via oral gastric intubation. No treatment-related toxic changes were seen in clinical signs, body weight, food consumption, urinalysis, hematology, blood chemistry, necropsy, organ weight, or histopathology. The no observed adverse effect level for TE was thus considered to be more than 2500 mg/kg/day in both males and females. These results are consistent with Touchi’s status as a traditional Chinese food derived from fermented soybeans and its purported long history of use. Specifically, these data are consistent with the expected safety of human consumption of TE up to at least 5 g/day.

Studies of the Toxicological Potential of Capsinoids: IV. Teratology Studies of CH-19 Sweet Extract in Rats and Rabbits

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 41-57 ◽  
Author(s):  
Bruce K. Bernard ◽  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Body Weight ◽  
Sex Ratio ◽  
Food Consumption ◽  
Clinical Signs ◽  
Pathological Finding ◽  
High Dose ◽  
Corpora Lutea ◽  
Test Substance ◽  
Sprague Dawley ◽  
Adverse Effect Level

In order to evaluate the safety of CH-19 Sweet extract that contains capsinoids, teratology studies were conducted in pregnant Sprague-Dawley rats (20 rats per group) and pregnant New Zealand white rabbits (17 to 22 animals per group). The test substance was administered to rats by gavage for 11 days on gestation days 7 to 17 at doses of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg and to rabbits for 13 days on gestation days 6 to 18 at doses of 0 (vehicle), 0.25, 0.5, and 1.0 ml/kg. As the concentration of capsinoids in CH-19 Sweet extract was 72.2 to 75.05 mg/ml, the resulting dose of capsinoids administered to rats was 90.25, 180.5, and 361 mg/kg, and to rabbits was 18.76, 37.53, and 75.05 mg/kg in the vehicle, low-, mid-, and high-dose groups, respectively. In the rat study, no deaths occurred in any group and there were no test substance–related changes or abnormalities in clinical signs, body weight, food consumption, or gross pathological findings. There were no test substance–related changes in the number of corpora lutea, number or index of implantations, index of embryofetal deaths, number of live fetuses, sex ratio, fetal body weight at the end of the gestation period, or abnormalities in the placenta of live fetuses. There were no test substance–related abnormalities or variations in the external, skeletal, or visceral examinations of live fetuses. It was concluded that the test article caused neither teratogenic effects nor abnormalities in the progression of ossification. In the rabbit study, there were no test substance–related effects on clinical signs, body weight, food consumption, or necropsy findings. There were neither test substance–related abortions nor test substance–related effects on the number of corpora lutea, or number or index of implantations. There were no test substance–related effects on the number of dead embryos/fetuses, the number of live fetuses, sex ratio, body weight of live fetuses, or gross pathological finding in the placentas. There were no test substance–related external abnormalities or incidences of visceral or skeletal abnormalities or variations, and there were no test substance–related effects on the progress of ossification in any group. The authors concluded the no observed adverse effect level (NOAEL) of CH-19 Sweet extract containing capsinoids on pregnant animals and fetal development/growth was >5.0 ml/kg/day (>361 mg/kg/day as capsinoids) in rats and >1.0 ml/kg/day (>75.05 mg/kg/day as capsinoids) in rabbits.

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

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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