Safety Assessment of a Wheat Bran Extract Containing Arabinoxylan-Oligosaccharides: Mutagenicity, Clastogenicity, and 90-Day Rat-Feeding Studies

2010 ◽  
Vol 29 (5) ◽  
pp. 479-495 ◽  
Author(s):  
Isabelle E. J. A. François ◽  
Olivier Lescroart ◽  
Wim S. Veraverbeke ◽  
Raluca Kubaszky ◽  
Judit Hargitai ◽  
...  
Keyword(s):  
Wheat Bran ◽  
Chinese Hamster ◽  
Safety Evaluation ◽  
Chromosome Aberration Assay ◽  
Average Intake ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Chinese Hamster Lung Fibroblast ◽  
Wheat Bran Extract

Wheat bran extract (WBE) is a food-grade preparation that is highly enriched in arabinoxylan-oligosaccharides. As part of the safety evaluation of WBE, its genotoxic potential was assessed in a bacterial reverse mutagenicity assay (Ames test) and a chromosome aberration assay on Chinese hamster lung fibroblast cells. These in vitro genotoxicity assays showed no evidence of mutagenic or clastogenic activity with WBE. The safety of WBE was furthermore evaluated in a subchronic toxicity study on rats that were fed a semisynthetic diet (AIN 93G) containing 0.3%, 1.5%, or 7.5% WBE for 13 weeks, corresponding to an average intake of 0.2, 0.9, and 4.4 g/kg body weight (bw) per day, with control groups receiving the unsupplemented AIN 93G, AIN 93G with 7.5% inulin, or AIN 93G with 7.5% wheat bran. Based on this rat-feeding study, the no-observed-adverse-effect level (NOAEL) for WBE was determined as 4.4 g/kg (bw)/d, the highest dose tested.

Safety Evaluation of a Proprietary Food-Grade, Dried Fermentate Preparation of Saccharomyces cerevisiae

2012 ◽  
Vol 31 (1) ◽  
pp. 34-45 ◽  
Author(s):  
Alexander G. Schauss ◽  
R. Glavits ◽  
John Endres ◽  
Gitte S. Jensen ◽  
Amy Clewell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Clinical Symptoms ◽  
Safety Evaluation ◽  
In Vivo Studies ◽  
Oral Toxicity ◽  
Toxicity Studies ◽  
Adverse Effect Level ◽  
Effect Level

A safety evaluation was performed for EpiCor, a product produced by a proprietary fermentation process using Saccharomyces cerevisiae. Studies included the following assays: bacterial reverse mutation, mouse lymphoma cell mutagenicity, mitogenicity assay in human peripheral lymphocytes, and a cytochrome P450 ([CYP] CYP1A2 and CYP3A4) induction assessment as well as 14-day acute, 90-day subchronic, and 1-year chronic oral toxicity studies in rats. No evidence of genotoxicity or mitogenicity was seen in any of the in vitro or in vivo studies. The CYP assessment showed no interactions or inductions. No toxic clinical symptoms or histopathological lesions were observed in the acute, subchronic, or chronic oral toxicity studies in the rat. Results of the studies performed indicate that EpiCor does not possess genotoxic activity and has a low order of toxicity that is well tolerated when administered orally. The no observable adverse effect level (NOAEL) was 1500 mg/kg body weight (bw)/d for the 90-day study and 800 mg/kg bw/d for the 1 year study, for the highest doses tested.

scholarly journals Safety assessment of nicotinamide riboside, a form of vitamin B3

2016 ◽  
Vol 35 (11) ◽  
pp. 1149-1160 ◽  
Author(s):  
DB Conze ◽  
J Crespo-Barreto ◽  
CL Kruger
Keyword(s):  
Adverse Effect ◽  
Micronucleus Assay ◽  
Positive Control ◽  
Vitamin B3 ◽  
Nicotinamide Riboside ◽  
Chromosome Aberration Assay ◽  
Adverse Effect Level ◽  
Effect Level

Nicotinamide riboside (NR) is a naturally occurring form of vitamin B3 present in trace amounts in some foods. Like niacin, it has been shown to be a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The safety of Niagen™, a synthetic form of NR, was determined using a bacterial reverse mutagenesis assay (Ames), an in vitro chromosome aberration assay, an in vivo micronucleus assay, and acute, 14-day and 90-day rat toxicology studies. NR was not genotoxic. There was no mortality at an oral dose of 5000 mg/kg. Based on the results of a 14-day study, a 90-day study was performed comparing NR at 300, 1000, and 3000 mg/kg/day to an equimolar dose of nicotinamide at 1260 mg/kg/day as a positive control. Results from the study show that NR had a similar toxicity profile to nicotinamide at the highest dose tested. Target organs of toxicity were liver, kidney, ovaries, and testes. The lowest observed adverse effect level for NR was 1000 mg/kg/day, and the no observed adverse effect level was 300 mg/kg/day.

Safety of a novel galacto-oligosaccharide: Genotoxicity and repeated oral dose studies

2009 ◽  
Vol 28 (10) ◽  
pp. 619-630 ◽  
Author(s):  
T. Kobayashi ◽  
N. Yasutake ◽  
K. Uchida ◽  
W. Ohyama ◽  
K. Kaneko ◽  
...  
Keyword(s):  
Oral Dose ◽  
Kluyveromyces Lactis ◽  
Clinical Signs ◽  
Chinese Hamster ◽  
Metabolic Activation ◽  
Blood Chemistry ◽  
Control Group ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Effect Level

A series of safety tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by a two-step enzymatic process involving Sporobolomyces singularis and Kluyveromyces lactis. Bacterial reverse mutation and chromosomal aberration tests, with or without metabolic activation, were performed. These tests showed no mutagenesis in the Ames assay or in Escherichia coli WP2uvrA, and no chromosomal aberrations in cultured fibroblast cells from Chinese hamster lungs (CHL/IU). Micronuclei were not induced in the reticulocytes of mouse peripheral blood following oral administration of GOS. In a 90-day repeated oral dose toxicity study in rats, GOS was administered at 0, 500, 1000 and 2000 mg/kg to male and female Sprague-Dawley rats. There were no GOS-related changes in clinical signs, body weight, water intake, feed intake, urinalysis, ophthalmology, haematology, blood chemistry, organ weights, gross pathology or histopathology in any of the treatment groups compared to the control group. The no observed adverse effect level (NOAEL) of GOS was at least 2000 mg/kg/day in both males and females.

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.

scholarly journals A 30-Day Preclinical Safety Evaluation Study of Recombinant Human Follicle-Stimulating Hormone in Female Rhesus Monkeys

2011 ◽  
Vol 30 (2) ◽  
pp. 153-161
Author(s):  
Yongming Cai ◽  
Zhengmin Chen ◽  
Zongpeng Zhang ◽  
Longsheng Zhang ◽  
Ming Li ◽  
...  
Keyword(s):  
Rhesus Monkeys ◽  
Follicle Stimulating Hormone ◽  
Recovery Period ◽  
Safety Evaluation ◽  
Evaluation Study ◽  
Chinese Origin ◽  
Female Rhesus ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Stimulating Hormone

The objective of this study was to identify potential target organs for toxicity of recombinant human follicle stimulating hormone (r-hFSH) in female rhesus monkeys and to establish a no observed adverse effect level (NOAEL). In all, 24 female rhesus monkeys (Chinese origin, weighing 3.4-5.2 kg, approximately 5 years of age) received repeated subcutaneous (sc) r-hFSH at doses of 10, 60, and 300 IU/kg per d or vehicle once daily for 30 days followed by a 15-day recovery period. Endometrial hyperplasia and dermal edema in the external genitals were found in some animals at 300 IU/kg per d. Pharmacologic-related multiple cystic follicles were found in all r-hFSH-treated groups. A weak, anti-FSH antibody response was detected at the end of treatment in animals administered 60 and 300 IU/kg per d. These results indicate that the primary effects of r-hFSH in female rhesus monkeys were related to its pharmacological activity on the reproductive system. The NOAEL was considered to be 60 IU/kg per d.

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.

Evaluation of genotoxicity and subchronic toxicity of standardized rose hip extract

2017 ◽  
Vol 37 (7) ◽  
pp. 725-741 ◽  
Author(s):  
A Nagatomo ◽  
M Oguri ◽  
N Nishida ◽  
M Ogawa ◽  
A Ichikawa ◽  
...  
Keyword(s):  
Oral Dose ◽  
Chinese Hamster ◽  
Gene Mutations ◽  
Ethanol Extract ◽  
Female Rats ◽  
Toxicity Studies ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Rose Hip

Rose hip is the fruit of the rose plant, which is widely used in food, cosmetics and as a traditional medicine. Therefore, rose hip is considered safe and has a sufficient history of consumption as food. However, few studies have reported on the safety of rose hip extracts in toxicological analyses. Thus, to evaluate the safety of rosehip polyphenol MJ (RHPMJ), an aqueous ethanol extract standardized with the trans-tiliroside content, we performed genotoxicity and 90-day repeated oral dose toxicity studies in compliance with the Organisation for Economic Co-operation and Development-Good Laboratory Practice. RHPMJ did not induce gene mutations in reverse mutation tests of Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA strains and did not induce chromosomal aberrations in cultured Chinese hamster lung (CHL/IU) cells. Moreover, micronucleus tests using rat bone marrow showed RHPMJ had no micronucleus-inducing potential. Finally, 90-day repeated oral dose toxicity studies (100–1000 mg/kg) in male and female rats showed no treatment-related toxicity in rats. These data indicate that the RHPMJ had no genotoxicity and a no-observed-adverse-effect level greater than 1000 mg/kg in rats.

Sign in / Sign up

Export Citation Format

Share Document