Acute and Sub-acute Safety Studies of a Herbal Formulation for Urolithiasis in Laboratory Animals

Phloretin is a flavonoid, which is having strong antioxidant potentials and used in the treatment of numerous disorders. The aim of this study to evaluate the possible toxicological effect of Phloretin in Swiss albino mice. Methods: Single dose of Phloretin was administered stepwise in two groups by oral route and general behaviour, adverse effects and mortality were determined up to 14 days and compared to normal group. In sub-acute study, Phloretin was administered orally for 28 days to the four experimental groups and their body weight was measured each alternate day from the first day of dosing. The final body weight was recorded on 29th day and animals were euthanized by using thiopentone sodium, blood was collected and later haematological, lipid profile, biochemical parameter was evaluated and compared to normal group. Result: In acute toxicity study, no abnormal general behaviour, adverse effects were reported. The body weight, haematological, lipid profile and biochemical parameter also not recorded with any significant changes in sub-acute toxicity study. No significant mortality was reported in both the study. Histopathological examination revealed no alterations in clinical signs or organ weight at any dose. Conclusion: The result concludes that the oral administration of Phloretin did not produce any significant toxic effect in swiss albino mice. Hence, the test drug Phloretin is safe for therapeutic uses.

Evaluation of the acute and sub-acute toxicity of the ethanolic extract of Pericampylus glaucus (Lam.) Merr. in BALB/c mice

Aim Formononetin is a phytoestrogen which possess different pharmacological activities. The intraperitoneal route permits the identification of target organs involved in toxicity without compromising the molecule’s bioavailability. The current study investigated the safety profile of intraperitoneal formononetin in Swiss albino mice. Material and methods For acute toxicity study, formononetin administered intraperitoneally to mice at the doses of 5, 50, 100, 150, 200, and 300 mg/kg for 14 days. For the subacute toxicity study, mice were intraperitoneally administered with formononetin (12.5, 25, and 50 mg/kg) daily for 28 days. Results During the acute study, no deteriorating effect was observed on body weight, food and water intake, no behavioral changes were observed in animals. The lethal dose 50% (LD50) of formononetin was determined to be 103.6 mg/kg of BW, with a no observed adverse effect level (NOAEL) of 50 mg/kg of BW. Mortality was observed in the 300 mg/kg dose group and histopathological changes such as a mild degree of diffuse granular degeneration in the liver but for rest all doses did not have any adverse effect. In subacute study, no signs of adverse effects, mortality, no changes in body weight, food and water intake, and hematological and biochemical parameters were observed. Histopathology of subacute study indicates, formononetin did not have any noxious effect on organs. Conclusion Formononetin shows mortality at acute dose 300 mg/kg and LD50 at 103.6 mg/kg of BW, with a NOAEL of 50 mg/kg of BW, rest all doses for acute and sub-acute are safe when given intraperitoneally.

Toxicity data of 82 compounds, tested in both a sub-acute and a sub-chronic study, were evaluated to find out whether it is possible to substitute a sub-acute for a sub-chronic study without losing quantitative information. The no-effect level (NEL) and the minimal-effect level (MEL) were used as the basis for comparison. For each of the compounds, the sub-acute and sub-chronic studies were performed under similar conditions, with the same strain of rats and with a comparable range of dietary levels. It appeared that the NEL in the sub-acute study was equal to the NEL in the sub-chronic study for 56% of the compounds. For 44% of the compounds reviewed, the NEL in the sub-chronic test was lower than the NEL in the sub-acute test, indicating that a sub-chronic study cannot simply be replaced by a sub-acute study. However, it may be acceptable to use the NEL obtained in a sub-acute study as a basis for establishing acceptable daily intakes or permissible exposure levels for humans if an additional safety factor of 10 is applied. Furthermore, it was concluded that the conventional sub-acute study, including some selected haematological and biochemical parameters, seems extremely useful to obtain quick and reliable information on the toxicity of the numerous non-regulated chemicals which have to be investigated in the years to come.

Ocimum gratissimum is a medicinal plant that is widely used in the world, and has multiple uses in traditional medicine, including the treatment of epilepsy in children. The objective of this study was to evaluate the acute and subacute toxicity of decoction of Ocimum gratissimum leaves in Mus musculus mice. For the acute toxicity test, a single dose of 50, 300 and 2000 mg/kg of extract was administered orally to randomly selected to mice; then they were observed for 14 days. In the subacute study, the extract was administered orally daily to mice of both sexes at doses of 250, 500 and 1000 mg/kg body weight during the 28 days of the experiment. finally, Body weight was measured weekly, haematological, biochemical and histological analysis were performed. The aqueous extract of Ocimum gratissimum did not cause any mortality or significant changes in relative animal and organ weights during the acute and subacute tests at all doses. Few significant changes in food and water intake were observed at the dose of 1000 mg/kg. The highest dose of aqueous extract (2000 mg/kg) administered orally in the acute toxicity did not induce mortality. There were no significant changes in haematological parameters in the different batches treated. Therefore, the oral aqueous extract of Ocimum gratissimum did not produce any adverse side effects compared to the control group (distiller water) in the acute and subacute study. We can therefore conclude that Ocimum gratissimum can be considered safe in oral administration at the dose tested since it did not cause lethality or undesirable effects in general behaviour in white mice.

Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study

Potentilla fulgens Wall (Rosaceae), a well-known medicinal plant native to Asian regions has a rich history of traditional use for treating skin, gastrointestinal tract, and various metabolic disorders. Research has addressed that the plant is applied topically to treat conditions such as wounds, ulcers, and other skin ailments. Surprisingly, no prior investigation has explored the dermal toxicity of this plant. Therefore, the study was set to conduct the acute and sub-acute toxicity assessments on the ethyl acetate (EAPF) and methanol (MEPF) extracts of P. fulgenson Wistar rats. In the acute dermal toxicity study, rats received a single dose and were monitored for 14 days, while in the sub-acute study; they received a daily dose for 28 days. 2,000 and 5,000 mg/kg were tested by applying them to the shaved dorsal skin. Throughout the experiments, changes in physical appearance, behavior, and histological alterations were monitored. The results unequivocally revealed no abnormal physical or physiological changes, behavioral deviations, or mortality in any of the rats in both acute and sub-acute dermal toxicity assessments. Furthermore, there were no statistically significant differences (nsp > 0.05) in body weight, kidney, liver, spleen weights, hematological parameters, or blood biochemistry values between the treatment and control groups. These findings were further substantiated by the normal macroscopic and microscopic characteristics of the rats’ skin, kidneys, liver, and spleen. In conclusion, our study affirms that the application of EAPF and MEPF to the skin does not induce acute or sub-acute skin irritation nor elicit systemic toxic responses in rats.

Purpose: The aim of the investigation was to find out the degree of toxicity of the herbal composite for humans, animals, or the environment. Acute and 28 days repeated sub-acute oral toxicity study of herbal composite (Herbodil®) carried out as per the current OECD guidelines.Materials and Methods: 2000mg/kg of the herbal composite was orally administered to the animals to find out the acute toxicity. The treated animals were observed for toxic signs at thirty min, one, two and four hours and thereafter once a day for the next 14 days. In sub-acute study i.e.,28 days repeated dose oral study, the mice were segregated into four groups (two set for each sex) of six mice each. Group-1 mice served as a control (untreated). Group II mice consumed lower dose of herbal composite i.e., 100 mg/kg, Group III mice consumed middle/moderate dose i.e., 200 mg/kg and Group IV mice received high dose of 400 mg/kg (orally) once daily for 28 days respectively.Results: This experimental in vivo study confirm that neither the acute toxicity study of herbal composite at the dose level of 2000mg/kg nor the sub-acute 28 days oral toxicity study developed any toxic signs, behavioural changes, or mortality during the whole study. Haematological and biochemical parameters dose not changes during the sub-acute study. Relative body weight of the mice also not change after the study.Conclusion: Experimental results obtained from the current investigation suggest that LD50 of developed herbal composite was >2000 mg /kg and the herbal composite is completely safe and non-toxic for therapy.

α-l-Guluronic acid (ALG; G2013) has been previously introduced as a new anti-inflammatory agent with promising therapeutic effects. Thus, in the present study, we aimed to evaluate the acute and sub-acute toxicity of ALG through intravenous (i.v.) administration in Balb/C mice. ALG was administrated i.v. to the mice with doses of 300, 600, and 1000 mg/kg of body weight to investigate acute toxicity (single dose) and with doses of 25, 50, and 100 mg/kg of body weight to sub-acute toxicity study (daily injections for a period of 28 days). The mortality rate, food and water intake, behavior, body weight, gross necropsy, hematological and biochemical parameters as well as histopathological presentations of the vital organs (kidneys, liver, lungs, spleen, and heart) were examined in treated groups and compared to the healthy controls. The results of both acute and sub-acute studies showed that i.v. administrations of ALG did not affect the investigated parameters in both sexes, indicating that the LD50 of ALG was higher than 1000 mg/kg of body weight. As no difference was observed in toxicity profiles of investigated doses, no-observed-adverse-effect-level for i.v. administration of ALG in the sub-acute study was greater than 100 mg/kg body weight in both female and male mice. According to the finding, i.v. administration of ALG did not lead to any clinical sign in abovementioned doses, suggesting that ALG was well tolerated up to 1000 mg/kg. These pre-clinical findings support the application of ALG in the future clinical trials.

Background: 2?,3?,21?,23,28-penta hydroxyl 12-oleanene was isolated from roots of Laportea crenulata Gaud (Urticaceae) as a new triterpenoid and its antifungal activities was evaluated against a number of fungi where moderate antifungal activities were reported. However, no toxicological study has yet been carried out. Objective: The sub-acute toxicity of 2?,3?,21?,23,28-penta hydroxyl 12-oleanene was studied on albino mice. Methods: The triterpenoid was administered on intraperitoneal route at 300 ?g per mouse (20-27g) daily for 14 consecutive days. The studies included the determination of changes in body weight, hematological profiles (total count of red blood cell, white blood cell and platelet, differential count of white blood cell, erythrocyte sedimentation rate, and hemoglobin percentage), and biochemical parameters of blood (serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, serum bilirubin, creatinine, and urea) as well as histopathology of the liver, kidney, heart, and lung. Result: The changes in body weight, hematological, and biochemical parameters were statistically not significant when compared to control group mice. Histopathologically no abnormality was found on liver, kidney, heart, and lung of experimental group mice after treatment when compared to that of control group mice. Conclusion: In sub-acute toxicity studies, the triterpenoid was found to be nontoxic. We suggest further studies such as chronic toxicological studies as well as route selection experiments. Keywords: Biochemical parameters, body weight, hematological parameters, histopathological study, 2?,3?,21?,23,28-penta hydroxyl 12-oleanene

BackgroundRoundup Ready became the most cultivated genetically modified (GM) crop in the world. The aim of this study was to evaluate the effects of a diet containing GM soybean meal (RUR) on male and female Wistar rats. The body weights, food consumption, hematology, serum biochemistry, organ weight, and histopathological examination were compared between rats fed on GM soybean and those fed non-GM soybean after consumption of test diets for 18 weeks.MethodsSixty weaned Wistar albino rats (30 females and 30 males) were randomly assigned to three groups of ten rats for each group per each sex. All rats have been fed either a diet containing 0% GM soybean meal (control), 50% GM soybean meal (T1), and 100% GM soybean (T2). The body weights, food consumption, hematology, serum biochemistry, organ weight, and histopathological examination were compared between rats fed GM soybean and those fed non-GM Soybean after consumption of test diets for 18 weeks.ResultsExamined hematological parameters did not indicate a statistically significant difference between the GM soybean-fed groups (T1 and T2) and their respective controls, though the WBCs of the male of treated groups (T1 and T2), platelets count, and hemoglobin (HB) of the female of (T1) group were slightly elevated. The examined biochemical blood parameters showed that the level of triglycerides (TG) was statistically significantly higher in the female treated groups (T1 and T2) and lactate dehydrogenase (LDH) was significantly higher in treated groups compared to their respective controls. Elevated levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were observed in some of the treated groups. Histopathological examination of selected organs (liver, kidney, and pancreas) and testes or ovaries and female mammary gland revealed histological alterations among different treated groups (T1 and T2) with their respective controls.ConclusionThe obtained results indicate the necessity to revise the safety standards of consumption of diets containing GM soybean.

Passiflora edulis is traditionally used in folk lore medicine for the treatment of various ailments. To validate its use in traditional medicine, it is important to evaluate its toxicity in the animal system. Therefore, this study aimed to evaluate the toxicological effects of oral administration of aqueous leaf extract of P. edulis in Wistar albino rats. Acute toxicity tests were conducted by the oral administration of 200, 500, 1000 and 2000 mg/kg body weight of the animal. In subacute study, they were administered with various doses of aqueous extract of P. edulis (100, 200, 300, and 400 mg/kg body weight) to evaluate its toxicity for a period of 7 days. The effect of aqueous extract of P. edulis on organ weight, hematological, renal, and hepatic markers were analyzed. In acute toxicity study, no mortality was seen with in 24 h of the administration of P. edulis extract. No signs of neurological and behavioral changes were noticed with in 72 h. In the subacute study, the extract intake has not changed the hematological parameters such as RBC, WBC, and platelets and it was also found that the plasma level of amino transferases, ALP, urea, uric acid and, creatinine were also not altered by the administration of P. edulis extract throughout the study. The weight of organ was found to be unaltered in all the doses selected. The acute toxicity study reveals that the oral administration of the extract was found to be safe up to the dose level of 2000 mg/kg. The subacute study indicates that the extract is safe on the bone marrow function and it is neither hepatotoxic nor nephrotoxic. This supports the safety use of the aqueous extract of P. edulis in pharmacological studies.

Blood samples were collected from 220 adult and 78 subadult black bears (Ursus americanus) from fall 1977 through summer 1985 on the Kenai Peninsula, Alaska. The samples were analyzed for 24 biochemical and 2 hematological parameters. Discriminant analysis was used to select useful blood parameters for assessing the condition of black bears based upon the dynamic spring to fall physical condition change. Parameters found to be most useful for females were hemoglobin (Hb), alpha 1 globulin (A1G), and calcium (Ca). The parameters most useful for males were globulin (G), packed cell volume (PCV), albumin/globulin ratio (A/G), sodium (Na), calcium/phosphorus ratio (Ca/P), and Hb. We recommend using Hb and PCV to determine the condition of black bears in the field. Blood profile changes in denning bears were detected for nearly all parameters. The urea/creatinine (U/C) mean was 8.9 for denning bears (n = 48). J. WILDL. MANAGE. 52(1):63-70 Blood chemistry and hematology values have been used to apply the indicator animal concept (Franzmann 1970) to assess the nutritional status of herbivores (Franzmann 1985). LeResche et al. (1974) outlined the procedure for establishing nutrition-blood parameter relationships: (1) determine those characteristics that may potentially influence blood values (boundary conditions); (2) establish normal values within the boundary conditions; and (3) determine the nature and magnitude of changes in blood values resulting from known changes in food intake, nutrition, or related parameters. Hanks (1981) suggested adding a fourth criterion; assess the resilience of an animal population, or some measurement of its ability to withstand further perturbations. Most black bear blood studies have provided data for the identification of boundary condit ons (Eubanks et al. 1976, Bush et al. 1980, Beeman 1981). Sex, age, hibernation, and seasonal changes are sources of variation in blood values for black bears (Matula et al. 1980, Palumbo et al. 1983). This content downloaded from 207.46.13.112 on Mon, 03 Oct 2016 05:30:12 UTC All use subject to http://about.jstor.org/terms 64 BLOOD PROFILES OF BEARS * Franzmann and Schwartz J. Wildl. Manage. 52(1):1988 Table 1. Blood values that differed (P < 0.05) among seasons from subadult (536 months old) black bears on the Kenai Peninsula, Alaska, 1977-85. Blood parameter Unit Seasona f SD n Hemoglobin g/dL Summer A 16.7 2.3 27 Fall 19.7 2.1 7 Den 19.1 2.2 33 Packed cell volume % Summer A 41.5 6.7 26 Fall AB 45.7 3.1 7 Den B 48.9 5.5 33 Cholesterol mg/dL Summer 276.0 55.0 28 Fall 275.0 40.0 9 Den A 396.0 111.0 35 Lactic dehydrogenase IU/L Summer A 774.0 141.0 26 Fall 625.0 159.0 9

Low-level Mercury Exposure and Risk of Asthma in School-age Children.

This study evaluated the mutagenicity and acute toxicity of the juice extract of nutricultured Brassica napus containing vanadium (BECV). The BECV was prepared by nutriculture for 7 days in Jeju water containing vanadium. The mutagenic effects of BECV were investigated using the bacterial reverse mutation test, chromosome aberration test, and micronucleus test. Based on the results of the mutagenicity test, we propose that BECV is not a mutagenicity-inducing agent. In the acute oral toxicity study, male and female Sprague-Dawley rats were administered a single limiting dose of 0.014, 0.14, or 1.4 μg BECV/kg body weight; the rats were then observed for 7 days. No acute lethal effect was observed at the maximal dose of 1.4 μg BECV/kg body weight. In the subacute study, male and female rats were administered once daily, by oral gavage, a dose of 0.028, 0.14, and 0.7 μg/kg body weight of BECV for 28 days. No significant toxicity was observed not only hematological, biochemical, and pathological parameters but also the body and organ weights when compared to controls. The level of BECV with no observed adverse effects in male and female rats was 0.7 μg/kg body weight (concentration of vanadium in BECV) in the subacute toxicity study.