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

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.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2135351 ◽

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.

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Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

Journal of Toxicology ◽

10.1155/2019/3680757 ◽

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.

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

International Journal of Toxicology ◽

10.1177/109158180302200606 ◽

2003 ◽

Vol 22 (6) ◽

pp. 453-464 ◽

Cited By ~ 21

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.

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

Journal of Toxicology ◽

10.1155/2012/589520 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 2

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.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4748904 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 3

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.

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

International Journal of Toxicology ◽

10.1080/10915810802513379 ◽

2008 ◽

Vol 27 (3_suppl) ◽

pp. 11-27 ◽

Cited By ~ 7

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).

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Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril

10.21203/rs.3.rs-28217/v1 ◽

2020 ◽

Author(s):

Keyu Zhang ◽

Xiaoyang Wang ◽

Shuya Wei ◽

Chunmei Wang ◽

Mi Wang ◽

...

Keyword(s):

Clinical Pathology ◽

Dosage Level ◽

Toxicity Study ◽

Oral Toxicity ◽

Subchronic Toxicity ◽

Safety Database ◽

Beagle Dog ◽

Test Article ◽

Adverse Effect Level ◽

Effect Level

Abstract Background: Ethanamizuril is a novel triazine compound that exhibits remarkable anticoccidial activity in poultry. Due to its pharmacological properties, this study was to evaluate the 90-day subchronic toxicity of feeding ethanamizuril fed to beagle dog. Methods: The subchronic toxicity study was conducted in beagle dogs administered ethanamizuril by diet at doses of 12, 60 or 300 mg/kg/day for 90 days, respectively. Results: Ethanamizuril was well tolerated at low and middle dosages and there were no test article-related effects on survival, clinical observations, clinical pathology parameters, organs weight, macroscopic or microscopic evaluations. Test article-related changes were limited to effects on food consumption and histologic changes of kidneys in the 300 mg/kg/day group in both genders. However, the characteristic toxicities of ethanamizuril are recoverable in kidneys. Conclusions: Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 60 mg/kg/day, the middle dosage level tested. These results add to the safety database for ethanamizuril with potential for use as a novel coccidiostat.

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Subchronic Oral Toxicity of Sodium Tungstate in Sprague-Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581815585568 ◽

2015 ◽

Vol 34 (4) ◽

pp. 336-345 ◽

Cited By ~ 3

Author(s):

Wilfred C. McCain ◽

Lee C. B. Crouse ◽

Mathew A. Bazar ◽

Laurie E. Roszell ◽

Glenn J. Leach ◽

...

Keyword(s):

Food Consumption ◽

Male Rats ◽

High Dose ◽

Histopathological Changes ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

Male And Female ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Effect Level

The subchronic toxicity of sodium tungstate dihydrate aqueous solution in male and female Sprague-Dawley rats was evaluated by daily oral gavage of 0, 10, 75, 125, or 200 mg/kg/d for 90 days. Measured parameters included food consumption, body weight measurements, hematology, clinical chemistry, and histopathological changes. There was a significant decrease in food consumption and body weight gain in males at 200 mg/kg/d from days 77 to 90; however, there was no effect in food consumption and body weights in females. There were no changes in the hematological and clinical parameters studied. Histopathological changes were seen in kidney of male and female and epididymis of male rats. Histopathological changes were observed in the kidneys of male and female rats dosed at 125 or 200 mg/k/d consisting of mild to severe cortical tubule basophilia in 2 high-dose groups. Histological changes in epididymides included intraluminal hypospermia with cell debris in the 200 mg/kg/d dosed male rats. Histopathological changes were observed in the glandular stomach including inflammation and metaplasia in the high-dose groups (125 or 200 mg/kg/d) of both sexes of rats. Based on histopathology effects seen in the kidneys, the lowest observable adverse effect level was 125 mg/kg/d and the no observable adverse effect level was 75 mg/kg/d in both sexes of rats for oral subchronic toxicity.

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Safety Assessment of a Hydroethanolic Extract of Caralluma fimbriata

International Journal of Toxicology ◽

10.1177/1091581813492827 ◽

2013 ◽

Vol 32 (5) ◽

pp. 385-394 ◽

Cited By ~ 3

Author(s):

Antoinette Y. Odendaal ◽

Narendra S. Deshmukh ◽

Tennille K. Marx ◽

Alexander G. Schauss ◽

John R. Endres ◽

...

Keyword(s):

Developmental Toxicity ◽

Toxicity Study ◽

Developmental Study ◽

Sprague Dawley ◽

Oral Toxicity ◽

Toxicological Assessment ◽

Sprague Dawley Rats ◽

Chromosomal Aberration Test ◽

Hydroethanolic Extract

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 μg of extract/plate (Ames test) or 5000 μg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

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