scholarly journals A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats

2021 ◽  
Vol 58 ◽  
pp. 004695802110560
Author(s):  
Min Hong ◽  
Min Lu ◽  
Yimin Qian ◽  
Liping Wei ◽  
Yaqun Zhang ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Recovery Period ◽  
Safety Evaluation ◽  
Toxicity Assessment ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Renal Tubular Cells ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Renal Tubular

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

scholarly journals Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sittichai Koontongkaew ◽  
Orapan Poachanukoon ◽  
Seewaboon Sireeratawong ◽  
Thaweephol Dechatiwongse Na Ayudhya ◽  
Parirat Khonsung ◽  
...  
Keyword(s):  
Body Weight ◽  
Clinical Chemistry ◽  
Hematological Parameters ◽  
Safety Evaluation ◽  
Chronic Administration ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Zingiber Cassumunar

Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P<0.05). The weights of lung and kidney of treated females were increased (P<0.05). Treated males were increased in spleen and epididymis weights (P<0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females.

Epidermal growth factor accelerates renal tissue repair in a model of gentamicin nephrotoxicity in rats

1992 ◽  
Vol 263 (5) ◽  
pp. F806-F811 ◽  
Author(s):  
N. J. Morin ◽  
G. Laurent ◽  
D. Nonclercq ◽  
G. Toubeau ◽  
J. A. Heuson-Stiennon ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Binding Sites ◽  
Renal Tissue ◽  
Sprague Dawley ◽  
Renal Tubular Cells ◽  
Sprague Dawley Rats ◽  
Epidermal Growth ◽  
Renal Tubular ◽  
Cessation Of Treatment

Epidermal growth factor (EGF) is a potent mitogen for renal tubular cells that possess specific high-affinity binding sites for this polypeptide. However, actual function of EGF within the kidney remains to be elucidated. We evaluated the effect of exogenous EGF administration on the rate of tubular regeneration in an experimental model of gentamicin (GT) nephrotoxicity. Female Sprague-Dawley rats were anesthetized, and a miniosmotic pump filled with mouse EGF or saline was implanted subcutaneously. Twenty-four hours later, GT (40 mg.kg-1 x 12 h-1 ip) was given for 4 and 8 days. Groups of treated animals and controls were killed either the day after cessation of treatment (days 5 and 9) or 4 and 8 days after the end of 8-day GT administration (days 12 and 16). Cortical GT levels of groups killed at days 5, 9, 12, and 16 were similar in animals infused with saline or EGF. Serum creatinine levels were significantly higher in GT-treated animals infused with EGF or saline and killed at days 9 and 12 compared with saline-treated animals infused with EGF or saline alone (P < 0.01). Blood urea nitrogen (BUN) also increased as a result of GT administration. However, in animals receiving GT and EGF and killed at day 16, mean BUN level was significantly lower (P < 0.01) compared with rats dosed with GT alone. In treated rats, the extent of tubular regeneration, evaluated by the rate of [3H]thymidine incorporation into renal cortical DNA or by the frequency of S-phase cells (histoautoradiography), was increased in a dose- and time-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirteen-Week Oral Toxicity Study of l-Glutamine in Rats

2004 ◽  
Vol 23 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Shoji Tsubuku ◽  
Kazuhisa Hatayama ◽  
Kazunori Mawatari ◽  
Miro Smriga ◽  
Takeshi Kimura
Keyword(s):  
Ketone Bodies ◽  
Recovery Period ◽  
Control Group ◽  
Standard Diet ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Urine Ph ◽  
Toxicological Effects ◽  
Adverse Effect Level ◽  
Hematology Parameters

l-Glutamine (Gln) is a semiessential amino acid used in enteral feeding in critically ill patients, and is contained in numerous dietary supplements available to the general public. This study evaluated toxicological effects of Gln in male and female Sprague-Dawley rats. Gln produced by Ajinomoto Co. (Tokyo, Japan) was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/ w), respectivelly. A control group of rats received only a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. Throughout the administration and recovery periods, no deaths were observed, and no changes in diet consumption, ophthalmologic findings, gross pathology, and histopathology were detected. Several changes in urine parameters (total protein, urine pH, and a positive incidence (±) of ketone bodies) were observed in the 2.5% and 5.0% groups at the end of the administration period. Minor increases were found in hematology parameters for the 5.0% group (platelet count, γ-globulin, lactate dehydrogenase [LDH]), but all changes were within physiological range. No effects of administration were observed in the 1.25% group. The no-observed-adverse-effect level (NOAEL) for Gln was estimated at 1.25% for both genders (males 0.83 ± 0.01 g/kg/day; females, 0.96 ± 0.06 g/kg/day).

scholarly journals Juvenile toxicity study of Gossence™ (galactooligosaccharides) in Sprague Dawley rats

2020 ◽  
Vol 4 ◽  
pp. 239784732091321
Author(s):  
Manish Jain ◽  
Moninder Kaur ◽  
Deepika Pandey Tiwari ◽  
Chandrashekara Vishwanath ◽  
Nataraju Javaregowda ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Pediatric Population ◽  
Recovery Period ◽  
Clinical Signs ◽  
Weighted Average ◽  
Organ Weight ◽  
High Dose ◽  
Average Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Gossence™ (galactooligosaccharide; GOS) is a prebiotics and used as one of the major constituents in infant milk formulas that act as a functional food. Gossence is manufactured by Tata Chemicals Ltd, India, through a patented process of biotransformation of lactose. A toxicology study in juvenile rats was carried out to assess the safety profile of Gossence intended for pediatric population. The objective of this study is to assess the potential systemic toxicity of Gossence when administered through gavage at dose levels of 1000, 2000, or 5000/3000 mg/kg/day (equivalent to 1347, 2694, and 6735/4041 mg/kg/day of GOS, respectively) to juvenile Sprague Dawley rats from postnatal day (PND) 4 to PND 52 (i.e. total 49 days of dosing period). A separate group of animals were treated with vehicle (purified Milli Q water) for a similar duration. The following parameters were evaluated during the study period: morbidity/mortality check, clinical signs, body weights, body weight changes, food consumption, functional observational battery, motor activity, postnatal developmental observations, hematology, clinical chemistry, urinalysis, organ weight, gross pathology, and histopathology. During dosing phase, the high-dose group, 5000 mg/kg/day, was reduced to 3000 mg/kg/day (equivalent to 4041 mg/kg/day dose of GOS) from day 16 (PND 19) onward, due to clinical signs of watery feces and yellow color stains at urogenital region and mortality in two animals on day 15 (PND 18) of the study. Time-weighted average dose for 5000 mg/kg/day was equivalent to 3600 mg/kg/day. No further deaths or clinical signs were noticed in animals at 3000 mg/kg/day from day 18 (PND 21) of dosing phase to until terminal euthanization. At the terminal euthanization, there were no test item-related gross changes observed in all surviving rats except for, an increased cecum size in some of the rats at 5000/3000 mg/kg/day, which correlated with the increased weights of cecum with contents during organ weight recording, but this had no correlating light microscopic changes during histological examination. The cecal enlargement was completely recovered following the 14-day recovery period. The no-observedadverse-effect level is 3000 mg/kg/day for Gossence, which is equivalent to 4041 mg/kg/day of GOS in both sexes.

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.

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.

Single- and Repeated-Dose Oral Toxicity Studies of Citicoline Free-Base (Choline Cytidine 5′-Pyrophosphate) in Sprague-Dawley Rats

2009 ◽  
Vol 28 (6) ◽  
pp. 479-487 ◽  
Author(s):  
A. G. Schauss ◽  
S. Somfai-Relle ◽  
I. Financsek ◽  
R. Glavits ◽  
S. C. Parent ◽  
...  
Keyword(s):  
Urine Volume ◽  
Free Base ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Sprague Dawley Rats ◽  
Dose Oral ◽  
Absolute Lymphocyte Counts ◽  
Renal Tubular ◽  
High Level ◽  
Phosphorus Intake

The dietary supplement Citicoline free-base (choline cytidine 5′-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.

scholarly journals Subchronic Toxicity Studies of 2,4,6-Trichlorophenol in Sprague-Dawley Rats

1990 ◽  
Vol 9 (5) ◽  
pp. 497-506 ◽  
Author(s):  
J. Peter Bercz ◽  
Merrel Robinson ◽  
Lillian Jones ◽  
Norbert P. Page ◽  
Michael J. Parnell ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Adrenal Glands ◽  
Corn Oil ◽  
Clinical Chemistry ◽  
Sprague Dawley ◽  
Weight Changes ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

2,4,6-Trichlorophenol (TCP) has been found in drinking water as a result of its use as a fungicide and due to its inadvertent production in the water purification process. This study was conducted since information on the toxicity from repeated ingestion was inadequate. Male and female Sprague-Dawley rats were gavaged with TCP administered in corn oil (2 ml/kg body weight) for 90 consecutive days at dose levels of 0, 80, 240, and 720 mg/kg per day. Treatment-related effects were observed at the highest dose (720 mg/kg/day) and consisted of salivation, urine stains on the fur, increase in absolute and relative weights of the kidneys, liver, adrenal glands, and testes. At this dose, increases were seen in serum protein, albumin, and alanine aminotransferase (ALT), with a decrease in urinary pH. Some effects observed at 240 mg/kg per day were an increase in the absolute and relative weights of the liver and adrenal glands in females, relative liver weights in males, and an increase in serum albumin in males. No treatment-related effects were observed at 80 mg/kg per day. No mortality or significant effects were observed at any dose level for body weight, food consumption, ophthalmic lesions, hematology, gross pathology, or histopathology. Based on clinical chemistry and organ weight changes, it appears that the liver, kidney, and adrenal glands were target organs for systemic toxicity to TCP in this study, although this was not correlated with histopathology lesions. It was concluded that 240 mg/kg/day represents a lowest observed adverse effect level (LOAEL), although the toxic effects were minimal. The no observed adverse effect level (NOAEL) for subchronic exposure to TCP by the oral route was 80 mg/kg per day.

scholarly journals Safety evaluation of galacto-oligosaccharides

2017 ◽  
Vol 1 ◽  
pp. 239784731771586
Author(s):  
Yuting Zhou ◽  
Claire Kruger ◽  
GS Ravi ◽  
DP Santhosh Kumar ◽  
SK Vijayasarathi ◽  
...  
Keyword(s):  
Body Weight ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Safety Evaluation ◽  
Feed Consumption ◽  
Sprague Dawley ◽  
Entire Treatment Period ◽  
Toxic Response ◽  
Sprague Dawley Rats ◽  
Conventional Foods

Galacto-oligosaccharides (GOS) have been added to infant formulas and conventional foods as prebiotics all over the world. The present study was conducted to assess the subchronic toxicity of a GOS syrup (VITAGOS™) when administered orally by gavage daily at 0, 1020, 2041, and 4082 mg GOS syrup/kg/day to male and female Sprague-Dawley rats to deliver doses of 0, 500, 1000, and 2000 mg GOS/kg/day for 90 days. Throughout the entire treatment period, no abnormal clinical signs or mortalities were observed. Similarly, no test article-related toxicologically adverse findings were seen in body weight, feed consumption, ophthalmological findings, hematology, coagulation, clinical chemistry, urinalysis, organ weights, and gross pathology or histopathology. Significant increases in the cecum weight of males and females treated with 2000 mg GOS/kg/day were associated with mucosal hypertrophy/hyperplasia; no changes in the cecum were noted at lower doses. The organ weight and histopathological changes noted in the cecum are consistent with findings in rats administered other poorly digestible and fermentable substances; thus, this is considered to be an adaptive rather than toxic response. The No-Observed-Adverse-Effect-Levels for VITAGOS™ is 4082 mg GOS syrup/kg body weight/day or 2000 mg GOS/kg body weight/day.

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