scholarly journals Acute and Subchronic Oral Toxicity Study of Gardenia Yellow E500 in Sprague-Dawley Rats

2020 ◽  
Vol 17 (2) ◽  
pp. 531
Author(s):  
Xiaoqiao Tang ◽  
Yangfeng Wang ◽  
Wenxiang Yang ◽  
Yanhua Zheng ◽  
Chunxia Liu ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Recovery Period ◽  
Lethal Dose ◽  
Body Weight Loss ◽  
The Body ◽  
High Dose ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Natural Colorant ◽  
Liver And Kidney

Objective: This study was conducted to evaluate the acute and subchronic toxicity of gardenia yellow, a natural colorant widely used in China and other Asian countries. An acute toxicity test was performed in S-D rats of both genders and the lethal dose (LD50) of per oral gardenia yellow was estimated to be more than 15.0 g/kg·bw. In the subchronic study, gardenia yellow was orally administered to rats by gavage at doses of 0, 0.50, 1.50 and 4.50 g/kg·bw/day for 90 days followed by a recovery period of 28 days. No appreciable toxic-related changes were observed in the 0.50 g/kg·bw/day group. When the animals received gardenia yellow at 1.50 g/kg·bw/day or more, body weight loss was observed, and pigments began to deposit in several vital organs, resulting in significant changes of several hematological and biochemical indicators related to the nutritional status of the body, liver and kidney function, more severe in the high dose group. In the recovery period, the alterations of the clinical symptoms and parameters were relieved a lot. Based on the results of the current study, the no observed adverse effect level (NOAEL) of gardenia yellow E500 in rats was set to be 0.50 g/kg·bw/day.

scholarly journals Acute and Chronic Oral Toxicity of a Partially Purified Plaunotol Extract fromCroton stellatopilosusOhba

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chatchai Chaotham ◽  
Songpol Chivapat ◽  
Anan Chaikitwattana ◽  
Wanchai De-Eknamkul
Keyword(s):  
Chronic Toxicity ◽  
Clinical Symptoms ◽  
Lethal Dose ◽  
Blood Platelet ◽  
Oral Toxicity ◽  
Liver And Kidney ◽  
High Doses ◽  
Altered Liver ◽  
Further Development

Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves ofCroton stellatopilosusOhba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluatedin vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD50=10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11–1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550–1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans.

scholarly journals Toxicity Assessment of Thiodiglycol

2005 ◽  
Vol 24 (6) ◽  
pp. 435-442 ◽  
Author(s):  
Gunda Reddy ◽  
Michael A. Major ◽  
Glenn J. Leach
Keyword(s):  
Sulfur Mustard ◽  
Clinical Chemistry ◽  
Developmental Toxicity ◽  
Chinese Hamster ◽  
The Body ◽  
High Dose ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Toxicological Studies

Sulfur mustard (HD) undergoes hydrolysis to form various products such as thiodiglycol (TG) in biological and environmental systems. TG is a precursor in the production of HD and it is also considered as a “Schedule 2” compound (dual-use chemicals with low to moderate commercial use and high-risk precursors). Several toxicological studies on TG were conducted to assess environmental and health effects. The oral LD50 values were >5000 mg/kg in rats. It was a mild skin and moderate ocular irritant and was not a skin sensitizer in animals. It was not mutagenic in Ames Salmonella, Escherichia coli, mouse lymphoma, and in vivo mouse micronucleus assays, but it induced chromosomal aberrations in Chinese hamster ovarian (CHO) cells. A 90-day oral subchronic toxicity study with neat TG at doses of 0, 50, 500, and 5000 mg/kg/day (5 days/week) in Sprague-Dawley rats results show that there are no treatment-related changes in food consumption, hematology, and clinical chemistry in rats of either sex. The body weights of both sexes were significantly lower than controls at 5000 mg/kg/day. Significant changes were also noted in both sexes in absolute weights of kidneys, kidney to body weight ratios, and kidney to brain weight ratios, in the high-dose group. The no-observed-adverse-effect level (NOAEL) for oral toxicity was 500 mg/kg/day. The developmental toxicity conducted at 0, 430, 1290, and 3870 mg/kg by oral gavage showed maternal toxicity in dams receiving 3870 mg/kg. TG was not a developmental toxicant. The NOAEL for the developmental toxicity in rats was 1290 mg/kg. The provisional oral reference dose (RfD) of 0.4 mg/kg/day was calculated for health risk assessments. The fate of TG in the environment and soil showed biological formation of thiodiglycalic acid with formation of an intermediate ((2-hydroxyethyl)thio)acetic acid. It was slowly biodegraded under anaerobic conditions. It was not toxic to bluegill sunfish at 1000 mg/L and its metabolism and environmental and biochemical effects are summarized.

One-generation reproduction toxicity study of Dithane M-45 (mancozeb) and lead acetate

2002 ◽  
Vol 50 (3) ◽  
pp. 365-371 ◽  
Author(s):  
L. Várnagy ◽  
P. Budai ◽  
E. Molnár ◽  
Keyword(s):  
Body Weight ◽  
Lead Acetate ◽  
Clinical Symptoms ◽  
Reproductive Toxicity ◽  
The Body ◽  
High Dose ◽  
Lactation Period ◽  
Treatment Groups ◽  
Body Weight Increase ◽  
Dose Levels

The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of diet. The three treatment groups received, in addition to the above doses of lead acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals decreased significantly before the pregnancy period. This tendency was also seen in males after the combination treatment. At the two high dose levels a remarkable body weight increase was seen in the female animals during the lactation period. As a result of treatment, decreased body weight of offspring was measured during the lactation period. No gross pathological changes were seen. Histological examination showed general tubulonephrosis in the experimental animals. It can be established that the administration of Dithane M-45 did not enhance the reproductive toxicity of lead acetate.

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 Prophylactic effect of vitamin E against hepatotoxicity, nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

2009 ◽  
Vol 55 (3) ◽  
pp. 219-226 ◽  
Author(s):  
Nahla S. El-Shenawy ◽  
Rasha A. Al-Eisa ◽  
Fawzia El-Salmy ◽  
Omema Salah
Keyword(s):  
Body Weight ◽  
Vitamin E ◽  
Kidney Function ◽  
Kidney Tissue ◽  
The Body ◽  
High Dose ◽  
Protective Effects ◽  
Histopathological Changes ◽  
Liver And Kidney ◽  
Haematological Indices

Abstract Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E (100 mg/kg body weight) on mice (25 - 30 mg) treated with diazinon (32.5 or 16.25 mg/kg body weight) organophosphate insecticide for 14 days. Subchronic DZN exposure and the protective effects of vitamins E (vitE) were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase (ALT), aspartate aminotaransferase (AST), alkaline phosphatise (AIP), and some parameters of kidney function (urea and creatinine) in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon (DZNH) decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significantly. Moreover, there was a statistically significant decrease in haemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE + DZN treated groups. According to the present study, we conclude that vitE can reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function.

Strain difference in thermoregulation of rats surviving extreme heat

1982 ◽  
Vol 52 (2) ◽  
pp. 410-415 ◽  
Author(s):  
F. Furuyama
Keyword(s):  
Body Temperature ◽  
Heat Tolerance ◽  
Strain Difference ◽  
Body Weight Loss ◽  
The Body ◽  
Sprague Dawley ◽  
Survival Times ◽  
Sprague Dawley Rats ◽  
Thermoregulatory System ◽  
Different Strains

The survival times of unanesthetized rats in 42.5 degree C. 48% rh were studied in 12 different strains. In males, Sprague-Dawley rats (P less than 0.01) and Fisher 344/MK (P less than 0.05) showed significantly higher heat tolerance than the other 9 strains. Among Sprague-Dawley rats, females tolerated heat longer than males (P less than 0.05). There was no difference in lethal body temperature according to strains and exposure temperatures (38.5–48.5 degree C). Maximum survivable body temperature was 43.1 degree C in males and 43.3 degree C in females. The body weight loss in heat was greater in Sprague-Dawley, Fisher 344/MK, and JCL:Wistar strains. The degree of saliva spreading during the equilibrium period just below the maximum survivable body temperature correlated significantly with heat tolerance and was found to be the index of strain difference in heat tolerance. These findings demonstrated that the thermoregulatory system of rats is controlled genetically, though survival times of individuals in different strains sometimes overlap.

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 Subchronic Oral Toxicity Study of Decitabine in Combination With Tetrahydrouridine in CD-1 Mice

2014 ◽  
Vol 33 (2) ◽  
pp. 75-85 ◽  
Author(s):  
Pramod Terse ◽  
Kory Engelke ◽  
Kenneth Chan ◽  
Yonghua Ling ◽  
Douglas Sharpnack ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Combination Therapy ◽  
Food Consumption ◽  
Blood Cells ◽  
Recovery Period ◽  
White Blood Cells ◽  
Clinical Pathology ◽  
High Dose ◽  
Severe Toxicity ◽  
Oral Toxicity

Decitabine (5-aza-2′-deoxycytidine; DAC) in combination with tetrahydrouridine (THU) is a potential oral therapy for sickle cell disease and β-thalassemia. A study was conducted in mice to assess safety of this combination therapy using oral gavage of DAC and THU administered 1 hour prior to DAC on 2 consecutive days/week for up to 9 weeks followed by a 28-day recovery to support its clinical trials up to 9-week duration. Tetrahydrouridine, a competitive inhibitor of cytidine deaminase, was used in the combination to improve oral bioavailability of DAC. Doses were 167 mg/kg THU followed by 0, 0.2, 0.4, or 1.0 mg/kg DAC; THU vehicle followed by 1.0 mg/kg DAC; or vehicle alone. End points evaluated were clinical observations, body weights, food consumption, clinical pathology, gross/histopathology, bone marrow micronuclei, and toxicokinetics. There were no treatment-related effects noticed on body weight, food consumption, serum chemistry, or urinalysis parameters. Dose- and gender-dependent changes in plasma DAC levels were observed with a Cmax within 1 hour. At the 1 mg/kg dose tested, THU increased DAC plasma concentration (∼10-fold) as compared to DAC alone. Severe toxicity occurred in females receiving high-dose 1 mg/kg DAC + THU, requiring treatment discontinuation at week 5. Severity and incidence of microscopic findings increased in a dose-dependent fashion; findings included bone marrow hypocellularity (with corresponding hematologic changes and decreases in white blood cells, red blood cells, hemoglobin, hematocrit, reticulocytes, neutrophils, and lymphocytes), thymic/lymphoid depletion, intestinal epithelial apoptosis, and testicular degeneration. Bone marrow micronucleus analysis confirmed bone marrow cytotoxicity, suppression of erythropoiesis, and genotoxicity. Following the recovery period, a complete or trend toward resolution of these effects was observed. In conclusion, the combination therapy resulted in an increased sensitivity to DAC toxicity correlating with DAC plasma levels, and females are more sensitive compared to their male counterparts.

scholarly journals Does Oral Ingestion ofPiper sarmentosumCause Toxicity in Experimental Animals?

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Maizura Mohd Zainudin ◽  
Zaiton Zakaria ◽  
Nor Anita Megat Mohd Nordin ◽  
Faizah Othman
Keyword(s):  
Safety Information ◽  
The Body ◽  
Control Group ◽  
Sprague Dawley ◽  
Internal Organs ◽  
Haematological Profile ◽  
Daily Dose ◽  
Liver And Kidney ◽  
Prevalence Of Diabetes Mellitus ◽  
Herbal Plant

The prevalence of diabetes mellitus has reached epidemic proportion in Malaysia and worldwide. Scientific studies have shown that herbal plantPiper sarmentosumexhibits an antidiabetic property. Despite the extensive usage and studies of this herb as alternative medicine, there is paucity of the literature on the safety information of this plant. Thus, the present study aimed to observe the subacute toxic effects ofPiper sarmentosumaqueous extract (PSAE) on the haematological profile, liver, and kidney in rats. The extract was administered by oral gavage to 6 male and femaleSprague Dawleyrats in daily dose of 50 mg/kg, 300 mg/kg, and 2000 mg/kg for 28 consecutive days. The control group received normal saline. General behavior of the rats, adverse effects, and mortality were observed for 28 days. The haematological and biochemical parameters were determined at baseline and after the treatment. PSAE did not show abnormality on the body weight and gross observation of internal organs. The haematological, biochemical and histopathological profiles showed minimal changes and variation within normal clinical range except for significant increase in serum potassium level that suggests the need of regular monitoring. Nevertheless, these findings suggested that PSAE up to 2000 mg/kg/day did not show subacute toxicity inSprague Dawleyrats.

scholarly journals Toxicological Features ofCatha edulis(Khat) on Livers and Kidneys of Male and Female Sprague-Dawley Rats: A Subchronic Study

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Abdulsamad Alsalahi ◽  
Mahmood Ameen Abdulla ◽  
Mohammed Al-Mamary ◽  
Mohamed Ibrahim Noordin ◽  
Siddig Ibrahim Abdelwahab ◽  
...  
Keyword(s):  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Catha Edulis ◽  
Male And Female ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
Serum Aspartate Aminotransferase ◽  
Liver And Kidney ◽  
Kg Medium

Hepato- and nephrotoxicity of Khat consumption (Catha edulisForskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100–120 g) were distributed randomly into four groups of males and female (n=12). Normal controls (NCs) received distilled water, whereas test groups received 500 mg/kg (low dose (LD)), 1000 mg/kg (medium dose (MD)), or 2000 mg/kg (high dose (HD)) of crude extract ofCatha edulisorally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats.

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