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

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.

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.

scholarly journals Subacute Oral Toxicity of Yukmijiwhang-Tang in Crl:CD Sprague-Dawley Rats and Its Cytotoxicity

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Soo-Jin Jeong ◽  
Chang-Seob Seo ◽  
Jung-Im Huh ◽  
Hyeun-Kyoo Shin
Keyword(s):  
Food Intake ◽  
Scientific Evidence ◽  
Safety Information ◽  
Clinical Signs ◽  
Serum Biochemistry ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Adverse Effect Level

Background. The traditional herbal formula Yukmijiwhang-tang (YMJ) consists of six medicinal herbs and has been used to treat dysuria, diabetic mellitus, and neurosis in Korea, China, and Japan. Here we report safety information on its subacute toxicity and the cytotoxicity.Methods. YMJ extract was administered to SD rats at various dosages for 4 weeks. We monitored clinical signs, mortality, body and organ weights, food intake, and hematological and serum biochemistry factors. For cytotoxicity testing, each cell line was treated with various concentrations of YMJ for 24 h.Results. YMJ treatment had no significant effects on changes in clinical signs, body weight, or food intake in male or female rats. In male rats, YMJ treatment decreased the absolute weights of the epididymides and serum Na levels. In female rats, YMJ significantly reduced the prothrombin time (PT) and serum creatine level. However, the changes were not severe and were considered to be in the normal physiological range for rats. The no-observed-adverse-effect-level (NOAEL) was estimated to be 2000 mg/kg/day. YMJ extract did not exert any cytotoxicity against 23 tested cell lines.Conclusions. Our data provide scientific evidence on the safety of YMJ for potential development as a prescription drug.

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

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

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.

scholarly journals Toxicological Investigations of Aristolochia longa Root Extracts

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Nasreddine El Omari ◽  
Omar El Blidi ◽  
Abdelhakim Bouyahya ◽  
Karima Sayah ◽  
Saad Bakrim ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Global Analysis ◽  
Clinical Signs ◽  
Experimental Period ◽  
High Dose ◽  
Herbaceous Plant ◽  
Oral Toxicity ◽  
Toxicity Potential ◽  
Liver And Kidney

Aristolochia longa L. (Aristolochiaceae) is an herbaceous plant recognized in alternative medicine for its many therapeutic virtues. The aim of this study was to determine the pharmacotoxicological effects of this plant in order to ensure safe clinical use. The oral toxicity of the aqueous extract of A. longa roots was performed in vivo on Wistar rats at doses of 0.8, 1.25, 2, 2.5, and 5 g/kg/day for 21 days. Clinical signs were observed throughout the experimental period, followed by measurement of body weight change, while selected biochemical parameters, as well as relative organ weights and the histology of liver, kidney, and intestinal tissues, were evaluated after 6, 11, and 16 days and then at the end of 21 days of daily administration. At repeated doses for 21 days, the extract contributed to significant weight gain, in both control and treated rats. The global analysis of hepatic and renal biomarkers showed a significant increase between control and different doses of the extract, from the first to the third week of treatment, indicating the likely toxic effect of the extract on liver and kidney function. Organ toxicity was confirmed by histopathological examination, which revealed greater renal and hepatic parenchymal changes in animals treated with a high dose beyond the 16th day. At the end of the treatment, relatively small size of intestinal villi was also observed. It was concluded that ALAE has a low toxicity potential in nonprolonged oral administrations. However, at high chronic oral doses, A. longa appears to have significant toxicity on the organs tested.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
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.

scholarly journals ACUTE DERMAL TOXICITY STUDY OF ARECA CATECHU LINN. EXTRACT IN SPRAGUE-DAWLEY RATS

2016 ◽  
Vol 9 (9) ◽  
pp. 209
Author(s):  
Liza Meutia Sari ◽  
Frans D Suyatna ◽  
Gus Permana Subita ◽  
Elza Ibrahim Auerkar
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Lethal Dose ◽  
Clinical Signs ◽  
Treated Group ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Dermal Toxicity ◽  
Areca Catechu

ABSTRACTObjective: Areca catechu Linn. or biji pinang is one of the most widely used psychoactive substance with several hundred million users worldwide,predominantly in Southern Asia. However, details of the dermal toxicity of A. catechu L. are still undiscovered. The objective of this study is toinvestigate the in vivo acute dermal toxicity of aqueous extract of A. catechu L. at dose 15,000 mg/kg body weight in Sprague-Dawley rats.Methods: The acute dermal toxicity of A. catechu L. nut extract was investigated in rats, as per OECD Guidelines 402 for acute toxicity protocols. Thebody weight, possibility of death, general signs, and behavior activity parameters were measured for 14 days to ascertain the median lethal dose(LD50) of the extract. At the end of the study, all the animals in all the treated group were sacrificed.Results: The LD50 was found to be >15,000 mg/kg body weight. There was significant weight increase (p<0.05) in treated group when comparedto control group. No mortality was observed during whole 14 days study period. A single dose of 15,000 mg/kg of body weight did not producetreatment-related signs of toxicity in any of animal tested.Conclusion: A single dermal dose to A. catechu L. aqueous extract had no toxic effects on mortality, clinical signs, body weight changes, and grossfindings in female rats at a dose of 15,000 mg/kg of body weight. Subsequently, the concentrate can be employed for pharmaceuticals nutrient plants.Keywords: A. catechu L., Acute dermal toxicity, LD50.

Effects of Postnatal Exposure to a Mixture of Polychlorinated Biphenyls, p,p′-dichlorodiphenyltrichloroethane, and p-p′-dichlorodiphenyldichloroethene in Prepubertal and Adult Female Sprague-Dawley Rats

2005 ◽  
Vol 24 (2) ◽  
pp. 111-127 ◽  
Author(s):  
Daniel Desaulniers ◽  
Gerard M. Cooke ◽  
Karen Leingartner ◽  
Korian Soumano ◽  
Jonathan Cole ◽  
...  
Keyword(s):  
Polychlorinated Biphenyls ◽  
Hepatic Metabolism ◽  
Female Rats ◽  
Proliferation Index ◽  
Control Group ◽  
Exposure Level ◽  
Postnatal Exposure ◽  
Sprague Dawley

The postnatal period is a critical phase of development and a time during which humans are exposed to higher levels of persistent organic pollutants (POPs), than during subsequent periods of life. There is a paucity of information describing effects of postnatal exposure to environmentally relevant mixtures of POPs, such as polychlorinated biphenyls (PCBs), p,p′-dichlorodiphenyltrichloroethane (DDT), and p,p′-dichlorodiphenyldichloroethene (DDE). To provide data useful for the risk assessment of postnatal exposure to POPs, mixtures containing 19 PCBs, DDT, and DDE were prepared according to their concentrations previously measured in the milk of Canadian women, and dose-response effects were tested on the proliferation of MCF7-E3 cells in vitro, and in vivo experiments. Female neonates were exposed by gavage at postnatal days (PNDs) 1, 5, 10, 15, and 20 with dosages equivalent to 10, 100, and 1000 times the estimated human exposure level over the first 24 days of life. The MCF7-E3 cells showed a 227% increase in the AlamarBlue proliferation index, suggesting estrogen-like properties of the mixture, but this was not confirmed in vivo, given the absence of uterotrophic effects at PND21. An increase (511%) in hepatic ethoxyresorufin- o-deethylase activity at the dose 100 × was the most sensitive endpoint among those measured at PND21 (organ weight, mammary gland and ovarian morphometry, hepatic enzyme inductions, serum thyroxine and pituitary hormones). In liver samples from older female rats (previously involved in a mammary tumor study [Desaulniers et al., Toxicol. Sci. 75:468–480, 2001]), hepatic metabolism of 14C-estradiol-17 β (E2) at PND55 to PND62 was significantly higher in the 1000 × compared to the control group, but hepatic detoxification enzyme activities had already returned to control values. The production of hepatic 2-hydroxy-E2 decreased, whereas that of estrone increased with age. In conclusion, the smallest dose of the mixture to induce significant effects was 100×, and mixture-induced changes in the hepatic metabolism of estrogens might be a sensitive indicator of persistent effects.

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.

Genetic Toxicity Studies of the Ketogenic Ester Bis Hexanoyl (R)-1,3-Butanediol

2021 ◽  
pp. 109158182199177
Author(s):  
Brianna J. Stubbs ◽  
Andrey I. Nikiforov ◽  
Marisa O. Rihner ◽  
Sari Weston ◽  
Nancy Higley ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Mutagenic Activity ◽  
Metabolic Activation ◽  
Coli Strain ◽  
Control Group ◽  
Sprague Dawley ◽  
Genetic Toxicity ◽  
Polychromatic Erythrocytes

A series of studies was conducted to assess the genetic toxicity of a novel ketone ester, bis hexanoyl (R)-1,3-butanediol (herein referred to as BH-BD), according to Organization for Economic Co-operation and Development testing guidelines under the standards of Good Laboratory Practices. In bacterial reverse mutation tests, there was no evidence of mutagenic activity in any of the Salmonella typhimurium strains tested or in Escherichia coli strain WP2 uvrA, at dose levels up to 5,000 μg/plate in the presence or absence of Aroclor 1254-induced rat liver (S9 mix) for metabolic activation. In the in vitro micronucleus test using human TK6 cells, BH-BD did not show a statistically significant increase in the number of cells containing micronuclei when compared with concurrent control cultures at all time points and at any of the concentrations analyzed (up to 100 μg/mL, final concentration in culture medium), with and without S9 mix activation. In the in vivo micronucleus test using Sprague Dawley rats, BH-BD did not show a statistically significant increase in the incidence of micronucleated polychromatic erythrocytes relative to the vehicle control group. Therefore, BH-BD was concluded to be negative in all 3 tests. These results support the safety assessment of BH-BD for potential use in food.

Sign in / Sign up

Export Citation Format

Share Document