Safety Evaluation of Standardized Extract of Curcuma longa (NR-INF-02): A 90-Day Subchronic Oral Toxicity Study in Rats

NR-INF-02 is a standardized extract containing turmerosaccharides from Curcuma longa that has anti-inflammatory, analgesic, and chondroprotective potential. In view of its potential uses, NR-INF-02 was evaluated for its safety in Wistar rats at an oral dose of 250, 500, and 1000 mg/kg in a 90-day repeated dose subchronic toxicity study. NR-INF-02 administered at 250, 500, and 1000 mg/kg for 90 days did not show any mortality or clinical signs of toxicity. Body weight gain, food consumption, ocular and neurological examination, and hematological, blood biochemical, hormone, and urine analysis revealed no evidence of toxicity of NR-INF-02 treatment in rats. Absolute and relative organ weights were comparable to control rats. The study did not reveal any major treatment related gross pathological and histopathological alterations in the tissues or organs examined. Thus, based on study observations, the no-observed adverse effect level (NOAEL) was found to be 1000 mg/kg body weight in albino Wistar rats.

Download Full-text

Safety evaluation of fructooligosaccharide (FOSSENCETM): Acute, 14-day, and subchronic oral toxicity study in Wistar rats

Toxicology Research and Application ◽

10.1177/2397847318787750 ◽

2018 ◽

Vol 2 ◽

pp. 239784731878775 ◽

Cited By ~ 1

Author(s):

Manish Jain ◽

Manoj Gote ◽

Ashok Kumar Dubey ◽

S Narayanan ◽

H. Krishnappa ◽

...

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Clinical Chemistry ◽

Clinical Signs ◽

Safety Evaluation ◽

Toxicity Study ◽

Feed Consumption ◽

Oral Toxicity ◽

Trophic Effect ◽

Neurological Effects

Fructooligosaccharide (FOS) has been used in infant formula and conventional foods as prebiotics. Short chain FOS (FOSSENCETM) is produced by a patented process of biotransformation of sucrose by the action of enzyme from live microbial cells, hence toxicology studies were initiated to assess its safety. The objective of the present study was to determine safety of FOSSENCETM in acute, 14-day, and subchronic (90-day) toxicity studies. In acute and 14-day studies, administration of the FOSSENCETM to Wistar rats did not cause any mortality or clinical signs and changes in body weights, feed consumption, and gross pathology at the doses of 2000, 5000, and 9000 mg/kg body weight. In the subchronic (90-day) toxicity study, FOSSENCETM was administered by oral gavage to Wistar rats at the doses of 0, 2000, 5000, and 9000 mg/kg/day for 90 days. No treatment-related clinical signs or mortalities were observed. Similarly, no treatment-related toxicologically or biologically significant changes in body weight, feed consumption, ophthalmological findings, neurological effects, hematology, clinical chemistry, urinalysis, and gross pathological findings were noticed. However, statistically significant increase in weight of cecum (without correlative microscopic change) was noted at all the test item-treated groups in males and females and was considered to be a trophic effect and not a toxic effect in rats.

Download Full-text

A 90-Day Oral Toxicity Study of an Ethanolic Root Extract of Caesalpinia bonduc (L.) Roxb. in Wistar Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6620026 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Mariette Sindete ◽

Adam Gbankoto ◽

Razack Osseni ◽

Nounagnon Darius Tossavi ◽

Simon Azonbakin ◽

...

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Body Weight Gain ◽

Clinical Signs ◽

Relative Weight ◽

Drug Effects ◽

Root Extract ◽

Weight Changes ◽

Oral Toxicity ◽

Urinary Parameters

Background. Plant medicine is the oldest form of health care known to mankind; hence, studies on their safety for use are essential for the control of adverse drug effects. In Benin, Caesalpinia bonduc is one of many medicinal plants used as aphrodisiac, and for treatment of various ailments including prostatic hyperplasia. Despite its numerous ethnomedicinal benefits, toxicological information associated with its chronic use is currently limited. Objective. The present study therefore assessed the toxicity of an ethanolic root extract of Caesalpinia bonduc in Wistar rats. Methods. Caesalpinia bonduc root extract was administered by oral gavage at doses of 31.25, 125, and 500 mg/kg/day for 90 days to male Wistar rats, after which body weight changes, food consumption, urinary parameters, hematological and blood biochemical parameters, organ weights changes, gross pathology, and histopathology of vital organs were assessed. Results. There were no death or abnormal clinical signs, no significant changes in body weight gain or urinary parameters, and no changes in necropsy and histopathology findings of vital organs associated with extract treatment. However, some indices such as erythrocytes, total cholesterol, and aspartate amino transferase increased in rats treated with high doses of the extract, as well as relative weight of testes, followed by a decrease in food intake and prostate relative weight. Conclusion. The results indicate that an ethanolic root extract of Caesalpinia bonduc does not cause significant adverse effects and suggest its tolerability up to 500 mg/kg for daily administration of 90 days.

Download Full-text

Acute and 28-Day Subchronic Oral Toxicity of an Ethanol Extract ofZingiber zerumbet(L.) Smith in Rodents

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/608284 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Chia Ju Chang ◽

Thing-Fong Tzeng ◽

Shorong-Shii Liou ◽

Yuan-Shiun Chang ◽

I-Min Liu

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Histopathological Examination ◽

Body Weight Gain ◽

Lethal Dose ◽

Ethanol Extract ◽

Oral Route ◽

The Body ◽

Toxicity Study ◽

Oral Toxicity

The objective of this study was to evaluate the acute and subacute toxicity (28 days) of the ethanol extract ofZ. zerumbetrhizomes (EEZZ) via the oral route in Wistar rats of both sexes. In the acute toxicity study, Wistar rats were administered a single dose of 15 g kg−1of body weight by gavage, and were monitored for 14 days. EEZZ did not produce any toxic signs or deaths; the 50% lethal dose must be higher than 15 g kg−1. In the subchronic toxicity study, EEZZ was administered by gavage at doses of 1000, 2000 and 3000 mg/kg daily for 4 weeks to Wistar rats. The subacute treatment with EEZZ did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse-effect level for EEZZ is 3000 mg kg−1for rats under the conditions of this study. Hence, consumption of EEZZ for various medicinal purposes is safe.

Download Full-text

Acute, Subacute, and Genotoxicity Assessments of a Proprietary Blend of Garcinia mangostana Fruit Rind and Cinnamomum tamala Leaf Extracts (CinDura®)

Journal of Toxicology ◽

10.1155/2020/1435891 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Sundararaju Dodda ◽

Venkata Krishnaraju Alluri ◽

Trimurtulu Golakoti ◽

Krishanu Sengupta

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Lethal Dose ◽

Toxicity Study ◽

Mouse Bone Marrow ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Garcinia Mangostana ◽

Cinnamomum Tamala ◽

Fruit Rind

The present communication describes a battery of toxicity studies that include an acute oral toxicity, a subacute twenty-eight-day repeated oral dose toxicity, and genotoxicity studies on a herbal formulation CinDura® (GMCT). This proprietary herbal composition contains the extracts of the Garcinia mangostana fruit rind (GM) and the Cinnamomum tamala leaf (CT). The toxicological evaluations were performed following the Organization for Economic Cooperation and Development (OECD) guidelines. The acute oral toxicity study in Wistar rats suggests that the median lethal dose of CinDura® is at least 2000 mg/kg body weight. Acute dermal and eye irritation tests in New Zealand white rabbits indicate that the test item is nonirritant to the skin and eyes. A twenty-eight-day repeated dose oral toxicity study was conducted in male and female Wistar rats using daily doses of 250, 500, and 1000 mg/kg body weight, followed by a fourteen-day reversal period for two satellite groups. The CinDura®-supplemented animals did not show any sign of toxicity on their body weights, organ weights, and on the hematobiochemical parameters. The gross pathology and histopathological examinations indicated no treatment-related changes in the experimental animals. Overall, the no-observed-adverse-effect level (NOAEL) of the herbal blend is 1000 mg/kg body weight, the highest tested dose. Also, the results of the bacterial reverse mutation test and the erythrocyte micronucleus assay in mouse bone marrow suggest that CinDura® (GMCT) is neither mutagenic nor clastogenic.

Download Full-text

Prenatal Oral (Gavage) Developmental Toxicity Study of Decabromodiphenyl Oxide in Rats

International Journal of Toxicology ◽

10.1080/10915810252866051 ◽

2002 ◽

Vol 21 (2) ◽

pp. 83-91 ◽

Cited By ~ 30

Author(s):

M. L. Hardy ◽

R. Schroeder ◽

J. Biesemeier ◽

O. Manor

Keyword(s):

Body Weight ◽

Flame Retardant ◽

Corn Oil ◽

Body Weight Gain ◽

Developmental Toxicity ◽

Clinical Signs ◽

Toxicity Study ◽

Wide Range ◽

Effect Level ◽

Effect Of Treatment

Decabromodiphenyl oxide (DBDPO) is a highly effective flame retardant that is primarily used in electrical and electronic equipment with a secondary, but important, application in upholstery textiles. DBDPO, the second largest volume brominated flame retardant in use today, has undergone a wide range of toxicology tests in mammalian species with the results indicating a no-adverse-effect level of ∼1000 mg/kg/day in oral repeated-dose studies. An oral prenatal developmental toxicity study of the commercial DBDPO product (97% purity) was performed under current EPA OPPTS and OECD guidelines. Female Sprague-Dawley rats (25 mated females/group) received 0, 100, 300 or 1000 mg DBPDO/kg/day via gavage in corn oil during gestation days 0 through 19. All females survived until scheduled sacrifice. No clinical signs of toxicity were observed. Pregnancy rates in the control and treated groups ranged from 96% to 100% and provided 23 or more litters in each group for evaluation on gestation day 20. No effect of treatment was seen in maternal gestational parameters (body weight, body weight gain, and food consumption), uterine implantation data, liver weight, or necropsy findings. Likewise, no effect of treatment was seen in fetal body weights, fetal sex distribution, or during the fetal external, visceral, or skeletal examinations. The NOEL (noobservable-effect level) for maternal and developmental toxicity was 1000 mg DBPDO/kg/day, the highest dose level administered on gestation days 0 to 19.

Download Full-text

Oral Toxicity Studies, Histopathology and Anti-Diabetic activity of Polyherbal Extract in STZ induced diabetes in Rats

Current Biotechnology ◽

10.2174/2211550111666211220165802 ◽

2021 ◽

Vol 11 ◽

Author(s):

Pranay Wal ◽

Nikita Saraswat ◽

Ankita Wal ◽

Rashmi Saxena Pal ◽

Deepa Maurya

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Standard Dose ◽

Ethanolic Extract ◽

Toxicity Study ◽

Antidiabetic Activity ◽

Asparagus Racemosus ◽

Oral Toxicity ◽

Saraca Asoca ◽

Toxicity Studies

Background: Diabetes mellitus is a disease and endocrine disorder and it's a growing health problem in various countries. The prevalence of diabetes rises worldwide including South Africa 5.4% in 2025 increases as expected. The World Health Organization (WHO) estimated the diabetes mellitus problem in adults 173 million in developing counties. In this research observation of glucose levels indicated the diabetic state in Wistar rats by resulting from Streptozotocin administration and using a Metformin as a standard dose. This study demonstrated the acute oral toxicity and subacute oral toxicity of ethanolic extract of Saraca asoca leaves and Asparagus racemosus roots and showed the antidiabetic activity. Objective: To perform acute toxicity studies and sub-acute toxicity of the polyherbal ethanolic extract on the vital organ and isolated organ and record and noticed the visible changes on organs of each group of Wistar rats. Explore the hypoglycaemic action of the polyherbal extract of Saraca asoca and Asparagus racemosus. Methods: Wistar rats were divided into required groups for toxicity study first is acute oral toxicity 5,50, 300,2000 mg/kg body weight. Subacute oral toxicity studies were performed by administering a 250, 500, 1000mg/kg body weight. For demonstrating the antidiabetic activity the animals divided into 5 groups 1 normal control given saline group 2 standard dose Metformin compulsory dose groups 3 Streptozotocin-Induced diabetic 150mg/kg body weight body weight, groups 4 ethanolic extracts at a 100mg/kg groups 5 ethanolic extract 200mg/kg. On the last day of all the dosing period examined the Blood glucose levels and body weights of rat and histopathology studied were done by animal sacrifice and cut organs such as tissue pancreas, spleen, heart, lungs, liver, and kidney, placed on the slide and done a microscopic examination. Data selection has been complete by research papers from many databases such as NCBI, Web of science and Science direct and PubMed from year 1989 to 2020 by utilize research. skeywords such as “Antidiabetic”, “Saraca indica”, “Asparagus racemosus”, “ethanolic polyherbal extract”, “oral toxicity study”, “histopathology”, “Streptozotocin. Results : The polyherbal ethanolic extract of Saraca asoca and Asparagus racemosus at a dose of 100mg/kg and 200mg/kg was showed better effects against Streptozotocin-Induced diabetic 150mg/kg body weight body weight. All the extracts showed significantly (P <0.05) and it is safe and non-toxic nature by performed a toxicity study acute and subacute oral toxicity and the bodyweight are also improved, no inflammation and erosion are seen on any organs of Wistar rat by demonstrated a histopathology analysis. Conclusions: The polyherbal ethanolic extract of Saraca asoca and Asparagus racemosus showed hypoglycaemic activity against STZ-induced diabetes in experimental Wistar rats in Wistar rats. The results are shown beneficial effects of these ethanolic extract it helps in improving the changes in lipid metabolism, and protect the organs of Wistar rat liver, kidney, spleen, pancreas, lungs, heart against due to impairment of blood glucose and also in body weight. All organs were weighted and cut the tissue of organs and stained from eosin dye and changes observed by microscopy photos. no signs of inflammation and erosion.

Download Full-text

Safety Evaluation ofYukmijihwang-tang: Assessment of Acute and Subchronic Toxicity in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/672136 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Hyekyung Ha ◽

Jun Kyoung Lee ◽

Ho Young Lee ◽

Woo Suk Koh ◽

Chang Seob Seo ◽

...

Keyword(s):

Body Weight ◽

Single Dose ◽

Safety Information ◽

Clinical Signs ◽

Safety Evaluation ◽

Sprague Dawley ◽

Weight Changes ◽

Oral Toxicity ◽

Renal Disorder ◽

Body Weights

Yukmijihwang-tang(YMJ;Liu wei di huang tang(China),Rokumigan(Japan)) has been used in the treatment of diseases including renal disorder, cognitive vitality, and diabetes mellitus. However, there is very little information regarding the toxicity of YMJ to give an assurance of safety for clinical treatment. To provide safety information for YMJ, we evaluated its acute and sub-chronic toxicity in rats. The single-dose toxicity of YMJ was examined using Sprague-Dawley rats. Rats were treated with YMJ extract orally at 0, 500, 1000, or 2000 mg/kg body weight. After a single administration, clinical signs were observed every day for two weeks, and body weights were measured five times, including an initial measurement on day 1 (the day of administration). In the sub-chronic oral toxicity study, YMJ was administered to rats at 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. Mortalities, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. We found no mortality and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute and sub-chronic studies following oral administration in the rat at up to 2000 mg/kg/day YMJ. YMJ may not have any single-dose toxicity; the LD50of YMJ was over 2000 mg/kg, and it is safe for rats. The no-observed-adverse-effect-level (NOAEL) was considered to be 2000 mg/kg/day.

Download Full-text

Acute and Subacute Oral Toxicity Assessment of European Cranberrybush (Viburnum opulus L). Fruit Extract

Current Developments in Nutrition ◽

10.1093/cdn/nzab037_065 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 355-355

Author(s):

Gizem Ozan ◽

Alev Cumbul ◽

Engin Sümer ◽

Dilara Baban ◽

Ahmet Aydın ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Histopathological Examination ◽

Clinical Signs ◽

Toxicity Study ◽

High Dose ◽

Oral Toxicity ◽

Viburnum Opulus ◽

Fruit Extract ◽

Subacute Toxicity

Abstract Objectives The intake of the high dose of polyphenols might cause adverse health effects on humans, in such cases, toxicological testing may be required to ensure safe levels of intake. In the present study, acute and subacute oral toxicity studies of polyphenol-rich European cranberrybush (Viburnum opulus L.) (ECB) fruit extract were evaluated to ensure the safe use of this extract. Methods In acute toxicity, freshly prepared ECB extract dissolved in distilled water was administrated to Sprague-Dawley rats by oral gavage at a single dose of 2000 mg/kg and signs of toxicity and mortality was observed. In subacute toxicity, Balb-c mice were administrated orally at 500 (low dose) and 2000 mg/kg (high dose) of ECB extract for 28 days and their mortality, clinical signs and, body weight were recorded on a daily and weekly basis, respectively. At the end of 28 days, while blood samples from each animal were taken for hematological and biochemical analysis, vital organs were taken for histopathological examination. Results In acute toxicity study, ECB extract showed no toxicological signs observed on behavioral change and body weight of rats after 14 days indicating that the lethal dose (LD50) of the ECB fruit extract might be higher than 2000 mg/kg. No death and no abnormal clinical signs were also recorded in subacute toxicity study. However, the increment in body weight of administrated high dose of ECB extract animals were significantly lower than control (P > 0.05). High dose of ECB fruit extract induced the level of in some hematological parameters. Even amylase and lipase values were lower than normal ranges at high dose animals, other biochemical parameters results were not significantly different from the controls. In histopathological examination, the total histopathological scores ECB extract administrated mice at both doses were showed normal histological features in many tissues compared to control. However, administrated with a high dose of ECB extract showed significant changes in kidney, liver, and adipose tissue that were alterations (edema, infiltration, and bleeding) compared to control. Conclusions These findings indicated that polyphenol-rich ECB extract might show a toxic effect at a high dose (2000 mg/kg) and no observed adverse effect level (NOAEL) of ECB extract was 500 mg/kg ECB fruit juice. Funding Sources This study was supported by Yeditepe University.

Download Full-text

Single dose oral toxicity study of ethanolic extract from inflorescence of Casuarina equisetifolia in Wistar rats

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i6-s.2075 ◽

2018 ◽

Vol 8 (6-s) ◽

pp. 44-47

Author(s):

O. Umamaheswar Rao ◽

M. Chinna Eswaraiah

Keyword(s):

Body Weight ◽

Single Dose ◽

Wistar Rats ◽

Ethanolic Extract ◽

Toxicity Study ◽

Casuarina Equisetifolia ◽

Oral Toxicity ◽

Dose Oral ◽

Test Guideline ◽

Oecd Test Guideline

The purpose of the study was to evaluate the single dose oral toxicity of the ethanolic extract from inflorescence of Casuarina equisetifolia, Family: Casuarinaceae in female Wistar Rats. The acute toxicity study was carried out based on Organization for Economic Co-operation and Development (OECD) Test Guideline 423. However, this plant safety evaluation data was not available so, selected the starting dose from 300 mg/kg body weight. The animals were orally administered a single dose of 300 mg/kg body weight and followed by 2000 mg/kg body weight in next step. Signs of toxicity and mortality were observed after 30 min, 1, 2, 4 and 24h of administration of the extract and once daily for 14 days. There was no mortality in the tested animals and no abnormal clinical signs were observed related to test item. No abnormalities were detected in gross pathology observations in all the rats at both the dose levels. Based on observations of the present study, it can be concluded that the LD50 of ethanolic extract from inflorescence of Casuarina equisetifolia is greater than 2000mg/kg body weight and can be classified as Category 5; however, further studies are needed to confirm long term toxicities. Keywords: Acute oral toxicity, ethanolic extract from inflorescence of Casuarina equisetifolia, LD50, OECD Test Guideline, Wistar Rat.

Download Full-text

An Assessment of the Genotoxicity and Subchronic Toxicity of a Supercritical Fluid Extract of the Aerial Parts of Hemp

Journal of Toxicology ◽

10.1155/2018/8143582 ◽

2018 ◽

Vol 2018 ◽

pp. 1-26 ◽

Cited By ~ 11

Author(s):

Tennille K. Marx ◽

Robin Reddeman ◽

Amy E. Clewell ◽

John R. Endres ◽

Erzsébet Béres ◽

...

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Cannabis Sativa ◽

Body Weight Gain ◽

Dose Range ◽

Recovery Period ◽

Oral Toxicity ◽

Range Finding ◽

Aerial Parts ◽

Toxicological Studies

A battery of toxicological studies was conducted on a supercritical CO2 extract of the aerial parts of the Cannabis sativa plant, containing approximately 25% cannabinoids. No evidence of genotoxicity was found in a bacterial reverse mutation test (Ames), in an in vitro mammalian chromosomal aberration test, or in an in vivo mouse micronucleus study. A 14-day repeated oral dose-range finding study conducted in Wistar rats at 1000, 2000, and 4000 mg/kg bw/day resulted in effects where a NOAEL could not be concluded. Based on those results, a 90-day repeated dose oral toxicity study was performed in rats using doses of 100, 360, and 720 mg/kg bw/day, followed by a 28-day recovery period for two satellite groups. Significant decreases in body weight, body weight gain, and differences in various organ weights compared to controls were observed. At the end of the recovery period, many of the findings were trending toward normal; thus, the changes appeared to be reversible. The NOAEL for the hemp extract in Hsd.Han Wistar rats was considered to be 100 mg/kg bw/day for males and 360 mg/kg bw/day for females.

Download Full-text