scholarly journals A 4-Week Repeated Oral Dose Toxicity Study of Ssanghwa-Tang in Crl:CD Sprague Dawley Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Sae-Rom Yoo ◽  
Hyekyung Ha ◽  
Mee-Young Lee ◽  
Hyeun-kyoo Shin ◽  
Su-Cheol Han ◽  
...  
Keyword(s):  
Safety Information ◽  
Experimental Period ◽  
Serum Biochemistry ◽  
Toxicity Study ◽  
Herbal Formula ◽  
Sprague Dawley ◽  
Organ Weights ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Ssanghwa-tang (SHT), a traditional herbal formula, has been widely used to recover fatigue or consumptive disease after an illness. Along with much attention to herbal formula, the concerns about the safety and toxicity have arisen. To establish the safety information, SHT was administrated in Crl:CD Sprague Dawley rats at a daily dose of 0, 1000, 2000, and 5000 mg/kg for 4 weeks. During the test periods, we examined the mortality, clinical observation, body weight change, food consumption, organ weights, hematology, serum biochemistry, and urinalysis parameters. No changes of mortality and necropsy findings occurred in any of the groups during the experimental period. In either sex of rats treated with SHT at 5000 mg/kg/day, changes were observed in food intake, reticulocyte, total bilirubin, some urinalysis parameters, and relative organ weights. The results indicated that SHT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. This dosage was considered no observed adverse effect level (NOAEL) and was appropriate for a 13-week subchronic toxicity study.

scholarly journals Acute and Subchronic Oral Toxicity of Oil Palm Puree in Sprague–Dawley Rats

2020 ◽  
Vol 17 (10) ◽  
pp. 3404
Author(s):  
Zaida Zainal ◽  
Augustine Ong ◽  
Choo Yuen May ◽  
Sui Kiat Chang ◽  
Afiqah Abdul Rahim ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Pharmaceutical Formulations ◽  
Toxicity Study ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Subchronic Toxicity ◽  
Organ Weights ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Palm puree is rich in antioxidants and is produced via blending various proportions of mesocarp fibre and crude palm oil. The aim of this study was to assess the acute and subchronic toxicity of palm puree in male and female Sprague–Dawley rats. For the acute toxicity study, animals administered single palm-puree doses (2000 mg kg−1) by gavage were observed daily for 14 d. For the subchronic toxicity study, the rats were administered 500, 1000, or 2000 mg kg−1 palm puree daily for 28 d. We evaluated body and organ weights; performed haematological, biochemical, and histopathological analyses of blood and organ samples during and after treatment; and calculated the oral no-observed-adverse-effect level (NOAEL). The toxicity studies showed no signs of toxicity or mortality. The haematological, biochemical, and histopathological analyses and body and organ weights indicated no evidence of substantial toxicity at any dose of palm puree. The oral lethal dose and NOAEL for the palm puree were greater than 2000 mg kg−1 d−1 over 28 d. To the best of our knowledge, the present study is the first to confirm the safety of palm puree as a novel functional food. These encouraging results warrant further studies to elucidate its potential for pharmaceutical formulations.

Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague-Dawley Rats

2003 ◽  
Vol 22 (6) ◽  
pp. 453-464 ◽  
Author(s):  
Raymond G. York ◽  
Kathleen A. Funk ◽  
Michael F. Girard ◽  
David Mattie ◽  
Joan E. Strawson
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Developmental Toxicity ◽  
Thyroid Stimulating Hormone ◽  
Toxicity Study ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Maternal Thyroid

A developmental toxicity study was conducted with ammonium perchlorate (AP) in the drinking water at doses of 0.0, 0.01, 0.1, 1.0, and 30.0 mg/kg-day beginning 14 days before cohabitation and continuing through sacrifice. Twenty-four rats/group were cesarean-sectioned on day of gestation (DG) 21 and fetuses examined for visceral and skeletal alterations. An additional 16 litters/group were sacrificed on DG 21 for maternal and fetal serum TSH, T3, and T4 (thyroid-stimulating hormone, triiodothyronine, and thyroxine) levels and thyroid histopathology. Clinical and necropsy observations, body weights, feed and water consumption, and cesarean-sectioning parameters were comparable among the groups with only delays in ossification observed in the 30 mg/kg-day group. Maternal thyroid weights were increased in the 30.0 mg/kg-day group. Decreased colloid was present in male and female fetal thyroids in the 1.0 and 30.0 mg/kg-day groups. Maternal TSH was increased and T4 was decreased at all levels, and T3 was reduced at 30.0 mg/kg-day. Fetal TSH was increased at 1.0 and 30.0 mg/kg-day, T4 was reduced at 30.0 mg/kg-day, and T3 was decreased at all levels. The maternal no-observable-adverse-effect level (NOAEL) was 1.0 mg/kg-day; exposures of 30.0 mg/kg-day increased absolute and relative maternal thyroid weights and histopathology findings. The developmental NOAEL was 1.0 mg/kg-day; developmental delays in ossification occurred in the 30.0 mg/kg-day group. The colloid depletion in the thyroids and increased TSH and decreased T3 and T4 levels at lower exposures were considered adaptive and not adverse. No adverse effects on development at occurred levels that did not cause maternal toxicity. AP is not a selective developmental toxicant.

scholarly journals A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sae-Rom Yoo ◽  
Hyekyung Ha ◽  
Mee-Young Lee ◽  
Hyeun-Kyoo Shin ◽  
Su-Cheol Han ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Serum Biochemistry ◽  
Toxicity Study ◽  
Repeated Dose ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Organ Weights ◽  
Sprague Dawley Rats ◽  
Dose Oral

Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT), a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

scholarly journals Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-25
Author(s):  
Gajanan Deshmukh ◽  
Suresh B. Venkataramaiah ◽  
Chandrashekar M. Doreswamy ◽  
Mohan C. Umesh ◽  
Rajesh B. Subbanna ◽  
...  
Keyword(s):  
Biologically Active ◽  
High Dose ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Endogenous Antioxidant ◽  
In Vitro Genotoxicity

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

Subchronic Hepatotoxicity Evaluation of 1,2,4-Tribromobenzene in Sprague-Dawley Rats

2012 ◽  
Vol 31 (3) ◽  
pp. 250-256 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Kathleen A. Funk ◽  
Russell S. Thomas
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Exposure Time ◽  
Clinical Signs ◽  
Liver Weight ◽  
Sprague Dawley ◽  
Significant Incidence ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There were no TBB exposure-related clinical signs of toxicity or changes in body weight. Liver weight increases were dose and exposure time related and statistically significant at ≥10 mg/kg per d. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and time related. The 75 mg/kg per d group had minimally increased mitoses within hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was considered TBB exposure related at ≥25 mg/kg per d. Concentrations of blood TBB increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 µg/mL (2.5-75 mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for 13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg per d was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥10 mg/kg per d.

Comparative Toxicology Studies in Sprague-Dawley Rats, Rhesus Monkeys, and New Zealand White Rabbits to Determine a No Observed Adverse Effect Level for 1,1′-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] Dimethanesulfonate

2013 ◽  
Vol 32 (4_suppl) ◽  
pp. 59S-74S ◽  
Author(s):  
Merrill R. Osheroff ◽  
Dean J. Kobs ◽  
Matthew Buccellato ◽  
Claire R. Croutch ◽  
Laura E. Elcock ◽  
...  
Keyword(s):  
Adverse Effect ◽  
New Zealand ◽  
Rhesus Monkeys ◽  
Clinical Pathology ◽  
Intramuscular Administration ◽  
Sprague Dawley ◽  
Single Dose Study ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Studies were conducted in Sprague-Dawley rats, New Zealand White (NZW) rabbits, and rhesus monkeys to characterize the toxicity of 1,1′-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) following intramuscular administration. Rats received MMB4 DMS once daily for 7 days at 100, 200, 400, and 800 mg/kg/d; rabbits received a range of dose levels in 3 separate 7-day studies from 3 to 800 mg/kg/d and in a single-dose study from 50 to 200 mg/kg; and monkeys received MMB4 DMS at 150 to 600 mg/kg/d. Mortality was noted in rats and rabbits administered ≥200 mg/kg. All monkeys survived until scheduled termination. Adverse clinical observations were noted in the rats at ≥400 mg/kg/d and in rabbits administered ≥200 mg/kg; no adverse findings were noted in the monkeys. Clinical pathology changes were noted in the rabbit related to cardiac and renal function. In the rabbit and monkey, elevations in myoglobin, alanine aminotransferase/aspartate aminotransferase, platelets, creatine kinase, and coagulation factors were related to local inflammation at the intramuscular administration site. Light microscopic examination at the injection sites revealed acute skeletal muscle necrosis in vehicle control and treated groups. Target tissues in the rabbit studies were identified as kidney, heart, and lungs at ≥100 mg/kg/d. All changes noted in all the species demonstrated partial to complete recovery comparable to control values or to a clinically irrelevant level of effect. The NZW rabbit was the most sensitive species, and the no observed adverse effect level (NOAEL) was determined as 50 mg/kg/d; the NOAEL in the rat was 100 mg/kg/d; and the NOAEL in rhesus monkeys was >600 mg/kg/d.

scholarly journals Safety Assessment of Zigbir®: A Polyherbal Formulation in Sprague-Dawley Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Joseph Joshua Allan ◽  
Ranjit Madhukar Bhide ◽  
Amit Agarwal
Keyword(s):  
Body Weight Gain ◽  
Lethal Dose ◽  
Clinical Signs ◽  
Food Supplement ◽  
Toxicity Study ◽  
Sprague Dawley ◽  
Polyherbal Formulation ◽  
Sprague Dawley Rats ◽  
Repeated Dose Toxicity ◽  
Effect Level

The safety of Zigbir®, a polyherbal formulation intended for use as food supplement, was evaluated in Sprague-Dawley rats treated orally at the dose of 2000 mg/kg in acute and at 250, 500, and 1000 mg/kg for 90 days in subchronic toxicity study. The median lethal dose of Zigbir® was found to be more than 2000 mg/kg, and fourteen-day repeated dose toxicity study revealed it to be safe up to 1000 mg/kg. The subchronic study did not show any mortality or treatment-related adverse clinical signs. The treated animals exhibited normal feed intake and comparable body weight gain except for a decrease in females of 500 and 1000 mg/kg groups. Ocular examination revealed no abnormalities. Further, Zigbir® administration in rats did not induce any major changes in urinalysis, hematological, and biochemical evaluations except for minor alterations in few parameters at different dose levels. Gross and histopathological findings did not show any lesions attributable to Zigbir® administration. The no observed effect level of Zigbir® was found to be 500 and 250 mg/kg in male and female Sprague-Dawley rats.

Ninety-Day Toxicity Study of Alpha-Iso-Methylionone in Rats

2012 ◽  
Vol 31 (6) ◽  
pp. 595-601 ◽  
Author(s):  
Valerie T. Politano ◽  
Aurelia A. Lapczynski ◽  
Gretchen Ritacco ◽  
Anne Marie Api
Keyword(s):  
Blood Chemistry ◽  
Tubular Epithelium ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Renal Tubular Epithelium ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Liver And Kidney ◽  
Effect Level ◽  
Renal Tubular

Alpha-iso-methylionone (AIM), a fragrance ingredient, was evaluated for systemic toxicity in rats. Male and female Sprague Dawley rats were administered 0, 5, 30, or 500 mg/kg/d AIM via gavage for 90 days. Statistically significant changes in blood chemistry parameters (reduced aspartate aminotransferase [AST], and increased cholesterol, creatinine, and total protein) were observed in both sexes at 500 mg/kg/d. There were statistically significant increases in liver and kidney weights in both sexes and in spleen weights in males at 500 mg/kg/d. Adaptive hepatocyte enlargement was observed in both sexes at 500 mg/kg/d. Globular accumulations of eosinophilic material were observed in the renal tubular epithelium in males at ≥30 mg/kg/d. Thyroid and bone marrow histopathological changes were observed in males at 500 mg/kg/d. The no-observed-effect level was 5 mg/kg/d for males and 30 mg/kg/d for females. Based on histopathological changes in the kidney in males, the no-observed-adverse-effect level was 30 mg/kg/d.

Studies of the Toxicological Potential of Capsinoids: II. A 26-Week Daily Gavage Dosing Toxicity Study of CH-19 Sweet Extract in Rats

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 11-27 ◽  
Author(s):  
Terutaka Kodama ◽  
Eri Watanabe ◽  
Takeshi Masuyama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Toxicity Study ◽  
High Dose ◽  
Test Substance ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Test Article ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Dose Levels

A 26-week oral toxicity study of capsinoids-containing CH-19 Sweet extract was conducted in Sprague-Dawley rats (20 males and 20 females per group) at 6 weeks of age. The test substance was administered by gavage for 26 weeks at dose levels of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg/day. The concentration of capsinoids in the CH-19 Sweet extract employed was 71.25 to 73.15 mg/ml, resulting in dose levels of capsinoids of 89.06 to 91.44, 178.13 to 182.88, and 356.25 to 365.75 mg/kg, respectively. Adverse test article–related changes were only observed in males, not in females, and within the males, only at the high dose (5.0 ml/kg). Within that group (high-dose males), increases were observed in the numbers of segmented neutrophils, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, liver weights, and in the incidence and severity of hepatocellular focal necrosis. No test substance–related changes were detected in clinical signs, body weight, food consumption, water intake, ophthalmology, or urinalysis. No adverse test article–related changes were observed in low- or mid-dose males or in females at any dose. Based on the results of this chronic gavage study, the target organ was the liver and the no observed adverse effect level (NOAEL) for CH-19 Sweet extract in the rat was 2.5 ml/kg/day in males and 5.0 ml/kg/day in females (178.13 to 182.88 mg/kg and 356.25 to 365.75 mg/kg as capsinoids, respectively).

Developmental Toxicity of Thiodiglycol in Sprague-Dawley Rats

2007 ◽  
Vol 26 (4) ◽  
pp. 365-371 ◽  
Author(s):  
John T. Houpt ◽  
Lee C. B. Crouse ◽  
Richard A. Angerhofer ◽  
Glenn J. Leach ◽  
Gunda Reddy
Keyword(s):  
Adverse Effect ◽  
Developmental Toxicity ◽  
Female Rats ◽  
Main Study ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Dose Levels

Thiodiglycol (TG), a hydrolysis product of sulfur mustard (HD), is a potential contaminant of soil and water at certain military sites. To establish developmental toxicity criteria for TG, an oral developmental toxicity study was conducted in Sprague-Dawley rats. Neat thiodiglycol (99.9 %) was administered orally to mated female rats from gestation days (GDs) 5 through 19. The day of positive mating was considered day 0. A pilot study was conducted with TG at dose levels 250, 500, 1000, 2000, or 5000 mg/kg to select suitable doses for the main study. In the main study, three groups of rats (25/group) received TG by gavage at dose levels of 430, 1290, or 3870 mg/kg/day. A fourth group served as a sham control. On day 20 of gestation, all females were euthanized and a cesarean section performed. Litters were examined for soft tissue and skeletal alterations. Maternal toxicity was limited to dams receiving TG at 3870 mg/kg/day. At this dose, body weights and food consumption were reduced during certain periods of gestation. Fetuses derived from those dams exhibited a nonstatistically significant increased incidence of variations when compared to controls. Fetal body weights in the 3870 mg/kg/day group were significantly lower than controls. There was no increased incidence of anomalies when thiodiglycol-treated fetuses were compared to controls. It was concluded that TG did not produce terata. Developmental toxicity (decreased fetal weights and associated delays in development) occurred only at the maternally toxic dose of 3870 mg/kg. It appears that 1290 mg/kg/day could be considered no observed adverse effect level (NOAEL) for oral developmental toxicity. The lowest observed adverse effect level (LOAEL) was 3870 mg/kg for maternal toxicity.

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