Toxicological assessment of Ricinus communis Linn root extracts

Ricinus communis Linn (Euphorbiaceae) plant parts are claimed to be used as carminative, asthma, bronchitis, leprosy, anti-inflammatory, cathartic, and aphrodisiac. The toxicological study was carried out in the root part of the plant. The collected root was extracted with methanol and water. The extracts were vacuum-dried to yield the respective aqueous (AE) and methanol (ME) extracts. Toxicological assessment sought to determine the safety of Ricinus communis root extracts. The extracts were evaluated in the acute toxicity study (OECD-423 guidelines) and 90 days repeated dose toxicological assessment in Wistar albino rats. The acute oral toxicity of the aqueous (AE) and methanol (ME) extracts did not produce any toxic symptoms or mortality at the dose level of 2000?mg/kg in rats. In the 90 days (sub-chronic toxicity) repeated dose toxicity study the extracts (AE and ME) were administered 1000?mg/kg daily through oral route. The sub-chronic toxicity study demonstrated no significant changes in body weight, food, and water intake. Hematology parameters RBC, WBC, DLC, Hb, blood clotting time, and the biochemical parameters glucose, blood urea nitrogen, creatinine, total cholesterol, total protein, total bilirubin AST, ALT, and ALP were estimated. Histopathology observation of the major vital organs (liver, kidney, heart, spleen, lungs, ovary, testis, and brain) were tested. The hematology, biochemical and histopathology evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the non-toxic nature of the root extracts AE and ME can be used for long-term usage in clinical practice.     

Safety assessment of a calcium-potassium salt of (−)-hydroxycitric acid

The safety of Garcinia cambogiaextract, its active ingredient (–)-hydroxycitric acid (HCA), and the marketed weight management formula, Super CitriMax^® (HCA-SX), is supported by numerous in vitro and animal experimental studies as well as several clinical studies. HCA-SX has been shown to reduce appetite, inhibit fat synthesis, and decrease body weight. A series of toxicological tests including acute, short-term, and sub-chronic studies as well as teratogenicity/reproduction and genotoxicity studies were performed on HCA-SX. In the acute oral toxicity study, administration of a single dose of 5,000?mg/kg of HCA-SX did not reveal any significant changes for all examined tissues. Following the high dose safety testing, there were no remarkable changes or differences observed in any of the experimental conditions monitored. There were no macroscopic abnormalities for any examined tissues at scheduled necropsies. On the basis of these findings, the consumption of HCA-SX at dose level of up to 4667?mg/day is considered safe.     

Acute and sub-chronic toxicity of Cajanus cajan leaf extracts

Context: The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse bioactivities, but little safety data are reported.

Objective: This study examines the toxicological profiles of C. cajan leaf extracts.

Materials and methods: The leaves were extracted by water or 90% ethanol to obtain water or ethanol extract (WEC or EEC). EEC was suspended in water and successively fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker compounds of the extracts were monitored by high-performance liquid chromatography (HPLC). Kunming mice were administered with a single maximum acceptable oral dose (15.0?g/kg for WEC, EEC and BEC and 11.3?g/kg for DEC) to determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity investigation, Sprague–Dawley rats were orally given WEC or EEC at 1.5, 3.0 or 6.0?g/kg doses for four weeks and observed for two weeks after dosing to determine toxicological symptoms, histopathology, biochemistry and haematology.

Results: Flavonoids and stilbenes in the extracts were assayed. In acute toxicity test, no mortality and noted alterations in weight and behavioural abnormality were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic toxicity study, no mortality and significant variances in haematological and biochemical parameters or organ histopathology were observed, but increased kidney weight in 3.0?g/kg WEC- or 3.0 and 6.0?g/kg EEC-treated female rats, and reduced testes and epididymis weight in EEC-treated male rats were recorded. These changes returned to the level of control after recovery period.

Conclusion: Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.     

Safety assessment of vitacoxib: Acute and 90-day sub-chronic oral toxicity studies

Vitacoxib, is a newly developed coxibs NSAID (selective inhibitors of cyclooxygenase-2). To date, no experimental data have been published concerning its safety for use as an additive in the human diet. In the present study, we assessed the acute and sub-chronic toxicity of vitacoxib administered by gavage. The acute toxicity tests in Sprague Dawley (SD) rats and ICR mice demonstrated that vitacoxib at a dose of 5000 mg/kg BW failed to alter any of the parameters studied. In the 90-day sub-chronic toxicity test, vitacoxib was administered to SD rats at the doses of 0 (control), 5, 10, 20, 30, and 60 mg/kg BW. The results demonstrated that there were no significant differences for most indexes of sub-chronic toxicity throughout the experiment at the dose of 5–20 mg/kg BW, indicating no apparent dose-dependent. However, there were significant histopathology changes in the liver and kidney, and alterations in some biochemical parameters in the 60 mg/kg BW group. Based on these findings, the gavage LD₅₀ was determined to be > 5000 mg/kg in SD rats and ICR mice, and the 90-day gavage no-observed-adverse-effect level (NOAEL) of vitacoxib was considered to be 20 mg/kg BW under the present study conditions.     

Safety evaluation of Monascus purpureus red mould rice in albino rats

Monascus purpureus MTCC 410-fermented rice (red mould rice) is one of the food supplements to lower blood–lipid levels and monacolins have been proven to be the main active constituents in red mould rice (RMR). In this study, we have assessed the safety of RMR by conducting toxicological studies in albino rats. Acute and sub-chronic toxicity studies were conducted on both sexes of albino rats. Feeding acute doses of RMR at 0.5, 1.0, 2.5 and 5.0 g/kg body weight to rats did not cause any symptoms of toxicity or mortality. Similarly, dietary feeding of RMR at 2.0%, 4.0%, 8.0% and 12.0% level (w/w) for 14 weeks did not produce any significant changes in food intake or gain in body weight of the experimental rats compared to control rats. There were no significant differences in the relative weight of vital organs, hematological parameters, macroscopic and microscopic changes in vital organs and serum clinical enzyme levels between the experimental and control groups. Moreover, the rats fed with RMR showed a significant reduction in cholesterol and triglyceride levels in both serum and liver. The results showed that toxicity studies with RMR of M. purpureus did not cause any toxic effects in albino rats.     

Sub-chronic toxicity study of the methanol root extract of Cnestis ferruginea

Context: Cnestis ferruginea (CF) Vahl ex DC (Connaraceae) is a shrub abundant in West Africa. Root preparations are used in traditional medicine to treat diverse conditions.

Objective: To evaluate the sub-chronic toxicological effects of the methanol root extract of CF.

Materials and methods: Groups of adult rats of both sexes were treated daily with distilled water (DW) and CF at doses of 80 (sub-therapeutic dose), 400 (therapeutic dose), and 1000 (supra-therapeutic dose) mg/kg orally for 90 days. Animals were weighed weekly and observed for behavioral and morphological changes. At the end, rats were sacrificed and blood samples collected for hematological and biochemical analysis. Vital organs were harvested, weighed, and assessed for in vivo antioxidants and histopathological changes. Sperm analysis and reversibility study were done, and mortality was recorded.

Results: CF at the therapeutic dose did not produce any significant irreversible deleterious effects on the weight of animals and vital organs, in vivo antioxidants, histopathological presentation, hematological, biochemical, and sperm parameters. Platelet anomaly was elicited as a delayed effect. Effects at the sub- and supra-therapeutic doses were similar but with delayed anemia in females and weight reduction and sterility in males as possible side effects. CF generally showed a potential to induce in vivo antioxidants.

Discussion and conclusion: Findings suggest that CF given over an extended period possess the potential to cause induction of in vivo antioxidants especially in the ovary. Possible side effects identified with CF, which necessitate caution, include delayed platelet anomaly and anemia in females, weight reduction, and sterility in males.     

Acute and subchronic dermal toxicity of Vitex negundo essential oil

Vitex negundo is a common herb in different herbal formulation. The potential acute and sub-chronic dermal toxicities were evaluated as per OECD (Organization for Economic Cooperation and Development) guidelines 402 and 411, respectively. Both sexes of Wistar rats were exposed to Vitex negundo oil of 2000?mg/kg body weight for acute dermal toxicity, whereas in the dermal sub-chronic toxicity study, rats were exposed to Vitex negundo oil 250, 500 and 1000?mg/kg body weight, respectively, for five times a week for 90?d. In acute and sub-chronic toxicity studies, all animals were normal without any behavioral, serum biochemistry, hematology, necroscopical and histopathological changes. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) of Vitex negundo oil were 250 and 1000?mg/kg/day, respectively. Vitex negundo oil is under the category 5 (Unclassified) according to the Globally Harmonized System, with an LD₅₀ value of over 2000?mg/kg.     

Acute and sub-chronic toxicity studies of honokiol microemulsion

The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD₅₀) was 50.5 mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication.     

Toxicological assessment of combined lead and cadmium: Acute and sub-chronic toxicity study in rats

The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90 day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD₅₀ value of Pb(NO₃)₂ and CdCl₂ mixture by the oral route was 2696.54 mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague–Dawley (SD) rats with dose–response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96 mg/(kg bw day) when administered orally for 90 consecutive days.     

Acute and sub-chronic toxicity studies of the extract of Thunberg Fritillary Bulb

The aim of this study was to investigate the acute and sub-chronic toxicity of extract of Thunberg Fritillary Bulb. For the acute toxicity tests, graded doses of the extract were administered orally to mice. The animals were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were orally administered the extract at doses of 1 and 3 mg/kg body weight (BW) for 26 weeks. After 26 weeks, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD₅₀) was 52.2 mg/kg body weight in the mice. In the sub-chronic toxicity tests, a dose of 1 mg/kg body weight presented no toxicity. Above the 1 mg/kg dose, the main adverse signs observed in male rats were body or head tremor and spontaneous motor activity reduction. There were no other significant changes observed in hematology, blood biochemistry, organ weight and organ histology. The overall findings of this study indicate that the extract of Thunberg Fritillary Bulb is non-toxic up to 1 mg/kg body weight, which can be considered a safe application dose.     

Toxicological assessment of a particulate yeast (1,3/1,6)-beta-D-glucan in rats.

This study investigates the toxicity of WGP 3-6, a yeast-derived beta-glucan ingredient, during single-dose acute and sub-chronic toxicity studies in rats. For the acute study, Fisher-344 rats were administered WGP 3-6 via gavage at a dose of 2000 mg/kg body weight, and any evidence of toxicity was monitored over a 14-day period. WGP 3-6 was well tolerated, indicating that the LD(50) value is greater than 2000 mg/kg body weight. For the sub-chronic study, Fisher-344 rats (10/sex/group) were randomly allocated to receive daily gavage treatment with WGP 3-6 at doses of 0, 2, 33.3, or 100 mg/kg body weight. Control and high-dose satellite recovery groups of each sex also were included. Full toxicological monitoring and endpoint investigations were performed throughout and upon completion of the study. No negative effects on animal weights or food consumption attributable to WGP 3-6 were evident at any dose. In addition, no mortality, clinical pathology, functional/behavioral, microscopic, or gross observations indicating toxicity were observed. Sporadic changes in some biochemical and hematological parameters were observed; however, since the effects were within the physiological ranges in historical controls, were not dose-responsive, or were not observed in both sexes, they were determined to be of no toxicological significance. In conclusion, no adverse or toxic effects were observed after subchronic oral administration of 2, 33.3, or 100mg/kg body weight/day of WGP 3-6 in Fisher-344 rats, and therefore, a no observed adverse effect level (NOAEL) of 100 mg/kg body weight/day, the highest dose tested, was determined.     

Toxicological studies on aqueous extract of Gmelina arborea in rodents

Context:?Gmelina arborea Roxb. (Verbenaceae) is an important medicinal plant in the traditional system of medicine of India. The plant is used in the treatment of snake-bites, fever, piles, and diabetes. However, there is little toxicological information available regarding its safety after exposure. The present study was designed to evaluate acute and repeated dose toxicity of the aqueous extract of Gmelina arborea stem bark.

Materials and methods:?In the acute toxicity test, Swiss albino mice were treated with aqueous extract (300, 2000, and 5000?mg/kg), orally. Animals were observed periodically during the first 24?h after administration of the extract, and daily thereafter for 14 days. In the repeated dose toxicity study, the aqueous extract of Gmelina arborea (300, 1000, and 2000?mg/kg per day) was administered orally for a period of 28 days in Wistar rats. The effects on body weight, food and water consumption, organ weight, hematology, clinical biochemistry, as well as histology, were studied.

Results and conclusion:?Aqueous extract did not produce mortality, changes in behavior or any other physiological activities in mice, for any of the selected doses. There were no significant differences in the body weight, organ weights and feeding habits between control and treated animals. Hematological and biochemical analysis showed no marked differences in any of the parameters examined in either the control or treated groups. Pathologically, neither gross abnormalities nor histopathological changes were observed. The aqueous extract of Gmelina arborea was found safe in acute and repeated dose toxicity studies when tested in rodents.     

Is folklore use of Euphorbia helioscopia devoid of toxic effects?

Objective: To evaluate acute toxic effects of Euphorbia helioscopia in order to assure the safety and usefulness of herbal remedy.

Materials and methods: The Organization for Economic Cooperation and Development (OECD) for chemical testing guidelines No. 425 for acute oral toxicity testing were followed in this study. Mice were divided into three groups (n?=?5). Group I served as control. Groups II and III were administered methanol extract of E. helioscopia leaves and latex orally at dose of 2000?mg/kg, respectively. Then, all the animals were observed for two weeks. Blood sampling was done by cardiac puncture after 14 days from each group for biochemical analysis. Histopathology was performed to find out any microscopic lesion in vital organs.

Results and discussion: LD₅₀ was found greater than 2000?mg/kg. There was decrease in cholesterol, triglycerides, LDL and VLDL levels of latex and leaves with methanol extract-treated animals, with respect to control indicating plant’s hypolipidemic effect. On macroscopic examination, no lesions were found on vital organs, such as liver, heart and kidney; and normal architecture was observed on microscopic examination.

Conclusion: On the basis of results, it was concluded that methanol extract of E. helioscopia leaves and latex were devoid of toxic effects in acute toxicity study.     

Screening of Panamanian Medicinal Plants for Brine Shrimp Toxicity,Crown Gall Tumor Inhibition,Cytotoxicity and DNA Intercalation

Crude extracts from 20 Panamanian plants used in traditional medicine have been screened for brine shrimp toxicity, tumor inhibition, DNA-intercalation and cytotoxicity tests in a clonogenic assay in V79 suspension culture gassed with air or nitrogen. Of the 20 plant extracts, 8 (40%) proved active in DNA intercalation. The most active were the methanol extracts of Bidens pilosa (root), Jatropha curcas (leaf), Pereskia bleo (whole plant), Isertia hypoleuca (leaf), Cyperus luzulae (root), Vernonia patens (leaf and stem), Alibertia edulis (stem) and Justicia graciliflora (aerial parts). Sixteen (80%) of the 20 methanol plant extracts were active in potato disc tumor inhibition assay; Cyperus luzulae (root), Justicia graciliflora (aerial parts), Pereskia bleo (whole plant) and Vernonia patens (leaf and stem) being the most active. Cytotoxicity in the clonogenic assay was observed only in three plant extracts: Cyperus luzulae, Piper auritum and Psychotria correae, whereas high brine shrimp toxicity (LC 50 <100 p.p.m.) was observed in 13(65%) of the 20 plant extracts tested. These results appear to show a good correlation between the three bioassays: brine shrimp toxicity, tumor inhibition and DNA intercalation. The latter bioassay is rapid, economical, and can be used in activity guided fractionation of plant extracts.     

Safety and toxicological evaluation of undenatured type II collagen

Previous research has shown that undenatured type II collagen is effective in the treatment of arthritis. The present study evaluated the broad-spectrum safety of UC-II by a variety of toxicological assays including acute oral, acute dermal, primary dermal irritation, and primary eye irritation toxicity. In addition, genotoxicity studies such as Ames bacterial reverse mutation assay and mouse lymphoma tests, as well as a dose-dependent 90-day sub-chronic toxicity study were conducted. Safety studies indicated that acute oral LD₅₀ of UC-II was greater than 5000?mg/kg in female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD₅₀ of UC-II was determined to be greater than 2000?mg/kg. Primary skin irritation tests conducted on New Zealand Albino rabbits classified UC-II as slightly irritating. Primary eye irritation tests conducted on rabbits indicated that UC-II was moderately irritating to the eye. UC-II did not induce mutagenicity in the bacterial reverse mutation test in five Salmonella typhimurium strains either with or without metabolic activation. Similarly, UC-II did not induce a mutagenic effect in the gene mutation test in mouse lymphoma cells either with or without metabolic activation. A dose-dependent 90-day sub-chronic toxicity study revealed no pathologically significant changes in selected organ weights individually or as percentages of body or brain weights. No significant changes were observed in hematology and clinical chemistry. Therefore, the results from the current study show a broad-spectrum safety profile of UC-II.     

Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): Acute and subchronic toxicity studies

Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days.     

银杏苁蓉配方急性毒性和亚慢性毒性实验研究

目的观察银杏苁蓉配方的毒性。方法按照《保健食品检验与评价技术规范》2003年版中的相关规定,进行银杏苁蓉片的急性毒性实验和90d喂养实验。结果银杏苁蓉配方的大鼠最大耐受剂量(MTD)大于15g·kg~(-1)·bw~(-1),属无毒级;将受试物掺入饲料中,自由摄取连续90d,大鼠体质量和食物利用率均无异常改变,各项血常规和生化指标均在本实验室正常指标值范围内,高剂量组和对照组动物各脏器的病理组织检查亦未见明显病变,未观察到有害作用(NOAEL),剂量为0.7g·kg~(-1)·bw~(-1)。结论可以判断银杏苁蓉配方为无毒物,未见急性毒性和亚慢性毒性。     

Safety investigation on total steroid saponins extracts from Dioscorea zingiberensis C.H. Wright: Sub-acute and chronic toxicity studies on dogs

Sub-acute and chronic toxic effects of total steroidal saponins (TSSN) extracts from Dioscorea zingiberensis C.H. Wright on various internal organs and biochemical indicators have never been studied before and this study is the first of its kind to demonstrate sub-acute and chronic toxicities of TSSN on dogs. Administration of TSSN extracts at doses up to 3000 mg/Kg daily for 14 days, no biochemical and organ changes were observed on the experimental groups of dogs. Further, chronic toxicity study through oral administration of TSSN extracts at the gradual doses of 50, 250 and 500 mg/Kg for 90 days followed by a 2-week recovery assay revealed absence of significant architectural and morphological changes in internal organs which were confirmed through histopathological examination and merely no significant alteration in the biochemical indicators including hematologic and urine analysis and electrocardiogram compared to the control dogs. This toxicological evaluation came across with the finding that the herbal preparation can be considered as nontoxic and animals could tolerate the extracts at doses up to 500 mg/Kg with LD₅₀ greater than 3000 mg/Kg. It may serve as a preliminary scientific evidence for further therapeutic investigations.     

Toxicological investigations on the methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats

Pre-clinical acute and sub-chronic toxicity studies of the methanol sub-fraction (MSF) of the seeds of Carica papaya, a putative male contraceptive, have been investigated in rats to evaluate safety of the test substance. A single oral dose of MSF at 2000 mg/kg body weight was studied over 14 days for acute toxicity, and daily oral doses of 50, 100, 250 and 500 mg/kg body weight were studied for 28- and 90-day periods for sub-chronic toxicity. Body weight, food and water intake and phenotypical toxicological symptoms were recorded daily. Sperm analysis, hematology, serum clinical biochemistry, libido and pathological examination of vital organs were recorded at the termination of the experimental periods. We observed no overt general toxicity in exposed animals. Food and water intake showed daily fluctuations within control limits. Sperm density showed a significant decrease in all 28- and 90-day repeated dose treated animals whereas total sperm motility inhibition was observed at 250 and 500 mg/kg dose levels at the 28-day time interval but in all dose groups at the 90-day interval. The preliminary results suggest the test substance may be a safe approach to male anti-fertility.     

Genotoxicity and sub-chronic toxicity of MYOLUTION® (branched chain keto acids)

MYOLUTION^®, which consists of a mixture of the branched chain keto acids, keto-leucine, keto-isoleucine and keto-valine, as their calcium salts, may potentially be used as a food ingredient based on the reported contributions of these compounds to muscle health and exercise performance. Tests on genotoxicity and sub-chronic toxicity were performed to evaluate the safety of branched chain keto acids. No genotoxic effects were observed in the bacterial mutation assay or the in vitro micronucleus assay in human lymphocytes. In the 28 day and 90 day repeated dose toxicity studies no test item related mortality or toxicological effects on clinical signs, body weight, food consumption, urine parameters, hematology, clinical biochemistry parameters, organ weight, gross pathological findings and histopathology were observed. Based on the studies described here, MYOLUTION^® does not exert a genotoxic effect, and a no-observed-adverse-effect-level of 3318.38 mg/kg bw/day in males and 3733.28 mg/kg bw/day in females was determined in the 90 day repeated dose toxicity study.