scholarly journals Dose and time-dependent acute and subchronic oral toxicity study of propoxazepam in mice and rats

2020 ◽  
Vol 8 (1) ◽  
pp. 1 ◽  
Author(s):  
Nikolay Yakovlevich Golovenko ◽  
Valentina Nikolayevna Kovalenko ◽  
Vitalii Borisovich Larionov ◽  
Аnatoliy Semenovich Reder

Propoxazepam, 7-bromo-5 - (o-chlorophenyl)-3-propoxy - 1,2-dihydro - 3H-1,4-benzodiazepin-2-one, in the models of nociceptive and neuropathic pain showed significant analgesic activity. In order to explore clinical potential of propoxazepam for long term human consumption, toxicology testing in laboratory animals using well-accepted international guidelines is required. Acute toxicity tests were conducted by the oral administration of 2500; 3500; 4000; 4500 and 5000 mg/kg body weight to male and female mice and rats for a period of 3, 7 and 14 day. In subacute study, male rats were administered with various doses of propoxazepam (0.9, 4.5, and 9.0 mg/kg) to evaluate its toxicity for a period of 90 days. The effect of propoxazepam on body weight gain and organ weights, food and water consumptions were analyzed. From the present study, it can be concluded that the acute (3, 7 and 14 days) and subchronic (90 days) oral administrations of propoxazepam did not produce any clinical signs of toxicity or mortality of the male and female mice and rats. These results revealed that the LD50 of propoxazepam is greater than 5000 mg/kg and it therefore, belongs to the category V of relatively non-toxic substances according to the GHS. In the acute toxicity study, neither mortality no significant change in the body weight and the relative organ weights were recorded in all treated mice and rats. Present data set revealed that there wasn`t a strong correlation between body weight with food and water consumptions. The result indicates that the oral administration of propoxazepam did not produce any significant toxic effect in mice and rats and the substance can be safely used for therapeutic use in pharmaceutical formulations.  

2007 ◽  
Vol 26 (3) ◽  
pp. 247-251 ◽  
Author(s):  
T. Ramesh ◽  
K. Lee ◽  
H. W. Lee ◽  
S. J. Kim

Acute oral toxicity of methanol extract of Asiasari radix was evaluated in ICR mice of both sexes. In this study, mice were administrated orally with dosages of 1000, 3000, and 5000 mg/kg body weight of Asiasari radix extract. Mortality, signs of toxicity, body weight, food consumption, and gross findings were observed for 14 days post treatment of Asiasari radix extract. No mortality, signs of toxicity, and abnormalities in gross findings were observed. In addition, no significant differences were noticed in the body and organ weights between the control and treated groups of both sexes. These results show that the methanol extract of Asiasari radix is toxicologically safe by oral administration.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Loubna Kharchoufa ◽  
Mohamed Bouhrim ◽  
Noureddine Bencheikh ◽  
Soufiane El Assri ◽  
Asmae Amirou ◽  
...  

Ethnopharmacological Relevance. Haloxylon scoparium Pomel is a herbal medicine traditionally used for treating scorpions and snakebite, diabetes, and stomachache as well as several other diseases. No systematic study of the potential toxicity of the plant has been described. Aim of the Study. The current study is aimed at assessing the potential toxicity of Haloxylon scoparium Pomel through the acute and subacute toxicity tests. Materials and Methods. Acute toxicity test was performed on Swiss albino mice at a single oral dose of 1-10 g/kg for 14 consecutive days. General behavioral adverse effects, mortality, and latency of mortality were determined. In the subacute study, the Haloxylon scoparium Pomel extract was administered orally at doses of 500, 1000, and 2000 mg/kg daily for 30 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined at the end of the experiment. Sections of livers and kidneys were removed for histological studies. Results. Acute toxicity study showed that the oral LD50 value of Haloxylon scoparium Pomel extract was 5000 mg/kg. The subacute toxicity study of Haloxylon scoparium Pomel extract at doses 500, 1000, and 2000 mg/kg did not produce any observable symptoms of toxicity and no significant variation in body weight, organ weights, food, and water consumption or mortality in all treated rats. However, the administration of the Haloxylon scoparium Pomel extract to rats at 500 mg/kg and 1000 mg/kg showed a significant decrease in platelets. Moreover, only at the highest dose (2000 mg/kg), the extract caused a significant increase in red blood cells and hemoglobin. Our results showed that subacute treatments with Haloxylon scoparium Pomel extract at doses of 1000 mg/kg and 2000 mg/kg significantly elevated alkaline phosphatase and triglycerides. Histological studies showed that the subacute treatments of rats with Haloxylon scoparium Pomel extracts, at the doses 1000 and 2000 mg/kg, induced some histopathological changes in the livers but a slight changing in kidneys. Conclusion. Our results indicated low acute toxicity of the aqueous extract of Haloxylon scoparium Pomel. Furthermore, daily oral administration of Haloxylon scoparium Pomel extract caused some damages to the livers of rats treated with high doses, expressed by an increase in some enzyme activities such as ALP. Regarding the renal function, we did not find remarkable toxicity in the subacute treatment with Haloxylon scoparium Pomel extracts at doses 1000 and 2000 mg/kg. However, further toxicity assessments should be done to ascertain the safety or the toxicity of this valuable plant species “Haloxylon scoparium pomel” in subchronic treatments.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Seewaboon Sireeratawong ◽  
Supaporn Vannasiri ◽  
Urarat Nanna ◽  
Tipaya Singhalak ◽  
Kanjana Jaijoy

We studied an acute and chronic oral toxicity of the extract from Ziziphus attopensis (ZA) in male and female SD rats according to the OECD guidelines. After a single oral administration of ZA 5 g/kg body weight, measurement of the body and organs, necropsy, and health monitoring were performed. The body and organ weights and behavior were not changed relative to the control rats indicating that ZA does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with ZA at the doses of 1, 2, 4, and 8 g/kg body weight for 180 days. Body weight changes, hematological and biochemical parameters, organ weights, gross finding, and histopathology examination were monitored during the experimental period. The results did not show any differences from the control groups. Analyses of these results with the information of signs, behavior, and health monitoring can lead to a conclusion that the long-term oral administration of ZA for 180 days does not cause chronic toxicity.


Author(s):  
Michel Archange Tagne Fokam ◽  
Paul Aimé Noubissi ◽  
René Kamgang

Euphorbia scordifolia is used in Cameroon as galactagogue and in the treatment of gastrointestinal disorders. This work was undertaken to evaluate the acute and subchronic toxicities of ethanol/water extract of Euphorbia scordifolia (EWEs). Acute toxicity study was carried out by oral administration of 1, 2, 3, 4 and 5 g/kg body weight of EWEs to mice in the respective groups. Subchronic toxicity study was conducted by oral administration of the extract at daily doses of 50, 75 and 100 mg/kg body weight to another group of rats for 28 days, while rats in the control group received 10 mL/kg body weight of distilled water. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, EWEs was found to be non-toxic at a dose of 5000 mg/kg body weight. The subchronic treatment with EWEs did not alter either the body weight gain or the food and water consumption. Biochemical analysis did not show any significant differences in any of the parameters examined in males or females. Hematological analysis showed a significant decrease (P<0.01) in white blood cells and red blood cells in males treated with 100 mg/kg bw and a significant (P<0.01) decrease in hemoglobin and hemoglobin hematocrit in all treated females. Necropsy and histopathological examination revealed some slight hepatic necrosis with the dose 100 mg/kg bw. It would be necessary to use the ethanol/water extract for short periods (<4 weeks). Thus, the plant, at least its ethanol/water extract, could be considered with a wide margin of safety for short-term oral use.


2020 ◽  
Vol 14 (1) ◽  
pp. 64-69
Author(s):  
Ekaterina V. Lagereva ◽  
Vladislav E. Abramov

The purpose of the research is to evaluate the acute toxicity of Altric-Extra when introduced into the stomach to mice and rats. Materials and methods. The studies were conducted in the vivarium of the All-Russian Research Institute of Fundamental and Applied Parasitology of Animals and Plants. The acute toxicity of Altric-Extra was determined on 20 white outbred male mice weighing 19.3–23.3 g, 10 animals in a group and on 30 white outbred male rats weighing 150–196 g, 6 animals in a group. Altric-Extra was administered to mice of the experimental group once into the stomach in the form of a suspension in a dose of 5,986 mg/kg at the rate of 0.2 ml/10 g of body weight. Altric-Extra rats were also administered once into the stomach in the form of a suspension at the rate of 2.0 ml/100 g body weight. As a carrier in the preparation of the suspension, 1% starch gel was used. The experimental rats of groups 1, 2, 3 and 4 were given Altric-Extra at doses of 4,580.2 mg/kg, 3,846.2; 3,088.8 and 1,577.9 mg/ kg respectively. Mice and rats of the control groups were administered once with 1% starch gel. For 14 days, the behavior and condition of the animals was monitored. The body weight of the experimental animals was measured on the 1st, 3rd, 7th, 9th and 14th days of the experiment. Results and discussion. Medium lethal doses of LD50 have been established for oral administration to laboratory animals. For mice, the LD50 was more than 5 986 mg/kg, i.e., according to the generally accepted hygienic classification, Altrick-Extra belongs to hazard class 4 (low-hazard substances). On rats, the LD50 was 3 103.1±48.5 mg/kg (2,354.6÷3,851.5 mg/kg). Therefore, Altrik-Extra belongs to hazard class 3 (substances are moderately hazardous).


2021 ◽  
Vol 148 (12) ◽  
pp. 58-67
Author(s):  
Pham Thi Van Anh ◽  
Nguyen Van Dam ◽  
Nguyen Van Dat ◽  
Pham Thanh Ky ◽  
Nguyen Trong Thong ◽  
...  

Assessment of toxicities of DA.AMLODEPON HVD hard capsule on experimental animals. The acute toxicity of DA.AMLODEPON HVD was assessed on Swiss mice according to World Health Organization Guidance, and LD50 determination according to the method of Litchfield – Wilcoxon. The sub-chronic toxicity study of DA.AMLODEPON HVD at two doses (0.42 g/kg/day and 1.26g/kg/day) was conducted in rats for four consecutive weeks. After administration, general conditions and the body weight of rats were evaluated. Blood samples were collected for analyzing serum parameters before treatment (T0), second week (T1), and fourth week (T2). Histopathological analysis of livers and kidneys was observed at the end of the experiment. The results revealed that mice were taken up to a maximum dose of 39.15 g/kg with no symptoms of acute toxicity, LD50 of DA.AMLODEPON HVD has not been determined. The sub-chronic toxicity study at two doses did not change the body weight of rats, general conditions. The parameters for structures and functions of livers and kidneys and microscopic of the livers and kidneys are in a normal range during the study period.


Author(s):  
Nadine Joissy Epoh ◽  
Olivette Laure Matafack Dongmo ◽  
Herve Tchoumbou Tadjoua ◽  
Félicité Mbiapo Tchouanguep ◽  
Phelix Bruno Telefo

Aim: The fruit of Solanum indicum Linn have been reported traditionally to have anti-hypertensive and diuretic properties. This study was undertaken to evaluate the toxicological potential of S. indicum fruits aqueous extract through the acute and sub-acute toxicity tests in rats. Methodology: For acute toxicity evaluation, a single oral dose of 5000 mg/kg of the plant extract was administrated in 60 days old female albino Wistar rats. Then, the animals were observed for 14 days. Sub-acute toxicity studies were conducted with 50 adult rats of both gender that orally received during 28 days, increasing doses of the plant extract. Their body weight and food intake were weekly collected. At the end of the experiment, biochemical and hematological parameters as well as histological analysis of organs (liver, kidneys and spleen) were undertaken. Results: Single oral administration of 5000 mg/kg dose of the fruit plant aqueous extract produced no mortality or signs of toxicity. During sub-acute test, no variations in body weight and food intake of both animals gender were observed. An important decrease in male’s rat liver weight were obtained at the dose 25 mg/kg; serum urea, total cholesterol, TAG, ALP and AST levels were significantly lowered in male especially at the dose 50 mg/kg, but this decrease was noticed only in serum urea, ALP and ALT in female rats. Furthermore, a significant decrease in platelets number, serum PCT, MPV and PDW levels were recorded in all treated male rats except those receiving the highest extract dose. No structural changes in treated animal organs section histology were observed when compared to controls. Conclusion: The fruits aqueous extracts of S. indicum is safe when administered acutely and for 28 days in rats. However, alterations on their hematological and biochemical parameters were not closely related with the dose, implying caution on its use.


2021 ◽  
Vol 17 (40) ◽  
pp. 178
Author(s):  
Kablan Kassi Jean Jacques ◽  
Blahi Adelaïde Nadia, ◽  
Kouakou Koffi Roger ◽  
Diby Yao Seraphin ◽  
Siapo Yao Martin ◽  
...  

The present study is part of a vast program of the valorization of the medicinal flora and to help the populations to make a real profit from the use of plants in order to avoid any problem of poisoning. Petroselinum crispum Mill. (Apiaceae) is a plant, whose therapeutic virtues are diverse. The toxicological aspect of the aqueous extract of Petroselinum crispum leaves in male and female rats was investigated. The acute toxicity study with the single dose of 5000 mg/Kg body weight shows that the aqueous extract from the leaves of Petroselinum crispum is not toxic orally. According to Organisation for Economic Cooperation and Development (OECD) Guideline 423, the oral LD50 for this extract is greater than 5000 mg/kg body weight. In addition, the sub-acute toxicity study (OECD 407) showed that the aqueous extract from the leaves of Petroselinum crispum did not show any toxic effects at doses 50,100 and 200 mg/kg body weight and would have an orexigenic effect after 28 days of treatment. The different histological sections showed that the aqueous extract of Petroselinum crispum is not toxic on the vital organs and appears to be hepatoprotective.


Author(s):  
Roman Dotsenko ◽  
Yevheniia Vashchyk ◽  
Andriy Zakhariev ◽  
Andrii Zemlianskyi ◽  
Ekaterina Dotsenko ◽  
...  

The aim: to determine the parameters of acute toxicity of the preparative form of an antiemeric agent based on maduramycin and nicarbazine for white mice, white rats and guinea pigs with a single oral administration. Materials and methods. Determination of acute toxicity of the formulation by oral administration was performed on 48 adult male mice, 48 adult nonlinear male rats, 48 adult male guinea pigs. To conduct an experiment on the principle analogues were formed seven experimental and one control group, 6 animal each. The dose of the formulation was calculated individually based on body weight values. It should be noted that the total volume of the emulsion of the formulation administered orally is not exceeded 1.0 cm3per 100 gram b. w. Results. Toxicometric parameters of the formulation were calculated by the method of least squares for probit analysis of mortality curves. It was found that the LD50 of the preparative form of antiemeric agent for white mice for a single oral administration is 238.05±28.08 mg/kg, LD16 – 128.71 mg/kg, LD84 – 347.39 mg/kg, LD100 - 402, 06 mg/kg body weight, respectively. LD50 of the preparative form of antiemeric agent for white rats with a single oral administration is 260.51±28.83 mg/kg, LD16 – 148.39 mg/kg, LD84 – 372.65 mg/kg, LD100 – 428.71 mg/kg body weight, respectively. LD50 of the preparative form of antiemeric agent for guinea pigs for a single oral administration is 275±21.12 mg/kg, LD16 – 201.74 mg/kg, LD84 – 348.25 mg/kg, LD100 – 384.88 mg/kg body weight body respectively. Conclusions. According to SOU 85.2-37-736: 2011 "Veterinary drugs. Determination of acute toxicity” preparative form of a complex antiemeric agent based on maduramycin and nicarbazine on the degree of toxicity can be attributed to moderately dangerous substances (3rd hazard class)


1995 ◽  
Vol 11 (2) ◽  
pp. 151-165 ◽  
Author(s):  
Joseph D. Cirvello ◽  
Ann Radovsky ◽  
James E. Heath ◽  
Daniel R. Farnell ◽  
Charles Lindamood

t-Butyl alcohol (TBA) was administered in drinking water to F344/N rats and B6C3F1 mice for two years using 60 animals/dose/sex/species. Male rats received doses of 0, 1.25, 2.5, or 5 mg/ml and females received 0, 2.5, 5, or 10 mg/ml, resulting in average daily doses of approximately 85, 195, or 420 mg TBA/kg body weight for males and 175, 330, or 650 mg/kg for females. Ten rats per group were evaluated after 15 months. Male and female mice received doses of 0, 5, 10, or 20 mg/ml, resulting in average daily doses of approximately 535, 1,035, or 2,065 mg TBA/kg body weight for males and 510, 1,015, or 2,105 mg/kg for females. Survival was significantly reduced in male rats receiving 5 mg/ml, female rats receiving 10 mg/ml, and male mice receiving 20 mg/ml. Long-term exposure to TBA produced increased incidences of renal tubule adenoma and carcinoma in male rats; transitional epithelial hyperplasia of the kidney in male and female rats; follicular cell adenoma of the thyroid in female mice; and follicular cell hyperplasia of the thyroid and inflammation and hyperplasia of the urinary bladder in male and female mice. In addition, a slight increase in follicular cell adenoma or carcinoma of the thyroid (combined) in male mice may have been related to the administration of TBA.


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