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.

scholarly journals Toxicological assessment of Euglena gracilis strain Eu029 shows no adverse effects in vivo and in vitro

2018 ◽  
Vol 2 ◽  
pp. 239784731876167
Author(s):  
Jennifer M Symonds ◽  
Nicole Beauchamp ◽  
Takuto Takeuchi ◽  
Koji Yamada ◽  
Kohei Atsuji ◽  
...  
Keyword(s):  
Euglena Gracilis ◽  
Metabolic Pathways ◽  
Micronucleus Assay ◽  
Food Ingredient ◽  
Toxicological Assessment ◽  
Acute Toxicity Study ◽  
Adverse Effect Level ◽  
Effect Level

Euglena gracilis is a single-celled organism capable of photosynthesis and heterotrophy. Euglena sp. have long been studied in the laboratory for its metabolic pathways, cell motility, and ease of culture. The safety of E. gracilis strain eu029 (EG029) for use as a food ingredient was assessed in a bacterial reverse mutagenesis assay (Ames), rec assay, in vivo micronucleus assay, acute toxicity study in mice, 13-week toxicology in rats, and a teratology study in mice and rats. EG029 was not genotoxic. The No Observed Adverse Effect Level (NOAEL) in the 13-week study was greater than 1000 mg/kg/day, the highest dose tested. Teratogenicity studies did not find any defects in fetal development or effects to maternal health in rats at 1000 mg/kg/day, 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 Bioelution, Bioavailability, and Toxicity of Cobalt Compounds Correlate

2020 ◽  
Vol 174 (2) ◽  
pp. 311-325 ◽  
Author(s):  
Ruth Danzeisen ◽  
David Lee Williams ◽  
Vanessa Viegas ◽  
Michael Dourson ◽  
Steven Verberckmoes ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
In Vivo Toxicity ◽  
Invaluable Tool ◽  
Adverse Effect Level ◽  
In Vitro Bioaccessibility ◽  
The Difference

Abstract Based on the wide use of cobalt substances in a range of important technologies, it has become important to predict the toxicological properties of new or lesser-studied substances as accurately as possible. We studied a group of 6 cobalt substances with inorganic ligands, which were tested for their bioaccessibility (surrogate measure of bioavailability) through in vitro bioelution in simulated gastric and intestinal fluids. Representatives of the group also underwent in vivo blood kinetics and mass balance tests, and both oral acute and repeated dose toxicity (RDT) testing. We were able to show a good correlation between high in vitro bioaccessibility with high in vivo bioavailability and subsequent high in vivo toxicity; consequently, low in vitro bioaccessibility correlated well with low in vivo bioavailability and low in vivo toxicity. In vitro bioelution in simulated gastric fluid was the most precise predictor of the difference in the oral RDT lowest observed adverse effect levels of 2 compounds representing the highly and poorly bioaccessible subset of substances. The 2 compounds cobalt dichloride hexahydrate and tricobalt tetraoxide differed by a factor of 440 in their in vitro bioaccessibility and by a factor of 310 in their RDT lowest observed adverse effect level. In summary, this set of studies shows that solubility, specifically in vitro bioelution in simulated gastric fluid, is a good, yet conservative, predictor of in vivo bioavailability and oral systemic toxicity of inorganic cobalt substances. Bioelution data are therefore an invaluable tool for grouping and read across of cobalt substances for hazard and risk assessment.

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.

scholarly journals In Vivo Toxicity and the Antioxidant Activity of the Hot Water Extract of Glechoma Hederacea

2020 ◽  
Author(s):  
Yun-Chin Chung ◽  
Jiunn-Wang Liao ◽  
Kuo-Yuan Li ◽  
Jyun-Kai Jhan ◽  
Su-Tze Chou
Keyword(s):  
Adverse Effect ◽  
Water Extract ◽  
Hot Water ◽  
Oral Toxicity ◽  
Subacute Toxicity ◽  
Hot Water Extract ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Glechoma Hederacea

Abstract Background Glechoma hederacea belongs to the Labiatae family and has many biological effects. Our previously in vitro studies, hot water extract of G. hederacea (HWG) possessed antioxidant and anti-inflammatory activities. Also, the Ames test indicated that HWG had no mutagenicity. However, the in vivo toxicity and antioxidant capacity have not been clearly demonstrated. Thus, this study was aimed to evaluate the antioxidant properties and the safety level of HWG by using animal models. Methods The genotoxicity were performed by micronucleus assays in mice. Acute oral toxicity and 28-day repeated feeding toxicity tests were performed via the oral gavage method for Sprague-Dawley (SD) rats. Furthermore, the effect of HWG on the oxidation–antioxidation equilibrium of male rats was also evaluated. Results HWG did not induce an increase in micronucleus ratios in vivo, no acute lethal effect at a maximum tested dose of 5.0 g HWG /kg bw was observed in rats. The 28-day oral toxicity study revealed the no observed adverse effect level (NOAEL) of HWG in rats was 1.0 g/kg bw. The HWG-treatment significantly elevated the vitamin C level and the SOD activity in heart, and increased the vitamin E concentrations in brain. The HWG-treatment maintained the balance of the glutathione level and the activities of catalase and glutathione peroxidase. Besides, the level of lipid peroxidation and plasma of total antioxidant status (TAS) showed that HWG-treated rats were not significantly changed compared with the control group. Conclusions HWG had no genotoxicity, and did not induce acute or subacute toxicity in SD rat. The level of no observed adverse effect level (NOAEL) of HWG rats was 1.0 g/kg bw for subacute toxicity study. HWG possessed antioxidant potential and reduced oxidative stress by improving the antioxidant system in animal.

scholarly journals Assessment of the Genotoxic Potential of Cizolirtine a Substance-P and Calcitonin Gene-Related Peptide Release Modulator

Drug Research ◽  
2020 ◽  
Author(s):  
AntonioR. Fernández de Henestrosa ◽  
Ana-Paz Marín ◽  
Araceli Tortajada ◽  
Cristina Vila ◽  
Antonio Guzmán
Keyword(s):  
Chromosome Aberrations ◽  
Micronucleus Assay ◽  
Weight Of Evidence ◽  
Mouse Bone Marrow ◽  
In Vivo Assays ◽  
Genotoxic Potential ◽  
Negative Results ◽  
Chromosome Aberration Assay

AbstractThe analysis of the genotoxic potential of cizolirtine, a compound being developed as a drug for analgesia and for urinary incontinence, was carried out using a battery of in vitro and in vivo assays as recommended in the guidelines for medicinal products. Negative results were obtained in an Ames test (up to 5000 µg/plate), in a Mouse Lymphoma assay (up to 2000 µg/ml) and in a single dose mouse bone marrow micronucleus assay (up to 300 mg/kg). In a human lymphocyte chromosome aberration assay, a slight statistical increase in the frequency of cells with chromosome aberrations including gaps was reported for the concentrations of 200 and 1600 μg/ml at the 24-h sampling time. This minor increase in chromosome aberrations was considered of questionable biological relevance since it was moderate, was within the laboratory historical control values, did no show a dose-dependent effect and was not observed at similar concentrations in a repeat assay. Taking into considerations the results obtained in the different in vitro and in vivo assays and a weight-of-evidence analysis, it suggests that cizolirtine would not pose a genotoxic risk when administered to humans.

Safety Assessment of Bacillus licheniformis Me1 Isolated from Milk for Probiotic Application

2012 ◽  
Vol 31 (3) ◽  
pp. 228-237 ◽  
Author(s):  
Vadakedath Nithya ◽  
Serva P. Muthukumar ◽  
Prakash M. Halami
Keyword(s):  
Bacillus Licheniformis ◽  
Safety Assessment ◽  
Micronucleus Assay ◽  
Toxicity Study ◽  
Oral Toxicity ◽  
Ocular Lesions ◽  
Industry Applications ◽  
Adverse Effect Level ◽  
Effect Level

In this study, an in vivo toxicological safety assessment of Bacillus licheniformis Me1, a native isolate from milk, was performed. An acute toxicity study in male albino Wistar rats demonstrated no treatment-related illness or mortality. A 90-day subchronic oral toxicity study using 2 doses (1.1 × 1010 and 1.1 × 1011 colony-forming unit [CFU]/kg body weight [BW], respectively) failed to show dose-dependent illness or mortality. Moreover, neither significant differences in serum biochemical and hematological analyses nor histopathological changes in organs or tissues were found when compared to the control groups. The no-observed-adverse-effect level (NOAEL) was found to be greater than 1.1 × 1011 CFU/kg BW. The in vivo micronucleus assay in mice did not reveal any signs of genotoxic effect at any of the doses tested. Furthermore, dermal and acute eye irritation tests conducted in rabbits showed no edema or erythema and ocular lesions. These results suggest that B licheniformis Me1 can be considered safe for food industry applications.

scholarly journals In VitroandIn VivoBiological Effects of Novel Arylimidamide Derivatives against Trypanosoma cruzi

2014 ◽  
Vol 58 (7) ◽  
pp. 3720-3726 ◽  
Author(s):  
Bruno Lisboa Timm ◽  
Patrícia Bernadino da Silva ◽  
Marcos Meuser Batista ◽  
Francisca Hildemagna Guedes da Silva ◽  
Cristiane França da Silva ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Latin American ◽  
Public Health Problem ◽  
Experimental Models ◽  
Reference Drug ◽  
Content Type ◽  
Adverse Effect Level ◽  
Effect Level

ABSTRACTChagas disease (CD), a neglected tropical disease caused byTrypanosoma cruzi, remains a serious public health problem in several Latin American countries. The available chemotherapies for CD have limited efficacy and exhibit undesirable side effects. Aromatic diamidines and arylimidamides (AIAs) have shown broad-spectrum activity against intracellular parasites, includingT. cruzi. Therefore, our aim was to evaluate the biological activity of eight novel AIAs (16DAP002, 16SAB079, 18SAB075, 23SMB022, 23SMB026, 23SMB054, 26SMB070, and 27SMB009) against experimental models ofT. cruziinfectionin vitroandin vivo. Our data show that none of the compounds induced a loss of cellular viability up to 32 μM. Two AIAs, 18SAB075 and 16DAP002, exhibited goodin vitroactivity against different parasite strains (Y and Tulahuen) and against the two relevant forms of the parasite for mammalian hosts. Due to the excellent selective indexes of 18SAB075, this AIA was moved toin vivotests for acute toxicity and parasite efficacy; nontoxic doses (no-observed-adverse-effect level [NOAEL], 50 mg/kg) were employed in the tests for parasite efficacy. In experimental models of acuteT. cruziinfection, 18SAB075 reduced parasitemia levels only up to 50% and led to 40% protection against mortality (at 5 mg/kg of body weight), being less effective than the reference drug, benznidazole.

scholarly journals Toxicological assessment of β-galactosidase shows no adverse effects in vivo and in vitro

2020 ◽  
Vol 4 ◽  
pp. 239784732090877
Author(s):  
Jennifer M Symonds ◽  
Tomohiro Fujita ◽  
Shouhei Aoki ◽  
Kazuma Shiota ◽  
Claire L Kruger
Keyword(s):  
Adverse Effects ◽  
Chromosome Aberration ◽  
Micronucleus Assay ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Ames Assay ◽  
Toxicological Assessment ◽  
Chromosome Aberration Assay

A safety assessment for β-galactosidase derived from Aspergillus oryzae (GODO-FAL) was performed. The test article was a concentrated, purified β-galactosidase diluted in glycerin and water with an activity of 10,000 U/mL. A series of genotoxicology tests including micronucleus assay, chromosome aberration assay, and reverse mutagenesis (Ames) assay confirmed that GODO-FAL was not clastogenic or mutagenic at any of the concentrations used, up to 2000 µg/mL for the chromosome aberration assay and 5000 mg per plate in the Ames assay. GODO-FAL was not toxic in acute, repeated oral toxicity, and sub-chronic toxicity assays in Sprague–Dawley rats at any dose used, up to 2000 mg/kg/day. Based on results from the subchronic toxicology assay, the no observed adverse effects level for GODO-FAL was at least 2000 mg/kg/day.

In Vitro and In Vivo Neutralizing Activity of Uvaria chamae Leaves Fractions on the Venom of Naja nigricollis in Albino Rat and Bovine Blood

2020 ◽  
Vol 14 (4) ◽  
pp. 295-311
Author(s):  
Ada Gabriel ◽  
Mamman Mohammed ◽  
Mohammed G. Magaji ◽  
Yusuf P. Ofemile ◽  
Ameh P. Matthew ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Neglected Tropical Diseases ◽  
Lethal Dose ◽  
Positive Control ◽  
Haemolytic Activity ◽  
Cytotoxic Activities ◽  
Albino Rat ◽  
Aqueous Residue

Background: Snakebite envenomation is a global priority ranked top among other neglected tropical diseases. There is a folkloric claim that Uvaria chamae is beneficial for the management of snakebite and wounds in African ethnobotanical surveys. Besides, there are many registered patents asserting the health benefits of U. chamae. Objective: This study aimed to investigate U. chamae’s potentials and identify candidates for the development of tools for the treatment and management of N. nigricollis envenomation. Methods: Freshly collected U. chamae leaves were air-dried, powdered, and extracted in methanol. The median lethal dose of the extract was determined and further fractionated with n-hexane, n-butanol and ethyl acetate. Each fraction was tested for neutralizing effect against venom-induced haemolytic, fibrinolytic, hemorrhagic, and cytotoxic activities. Results: U. chamae fractions significantly (p<0.05) neutralized the haemolytic activity of N. nigricollis venom in n-butanol; 31.40%, n-hexane; 33%, aqueous residue; 39.60% and ethyl acetate; 40.70% at the concentration of 100mg/ml of each fraction against 10mg/ml of the snake venom when compared to the positive control. The fibrinolytic activity of N. nigricollis venom was significantly (p<0.05) neutralized in n-hexane at 73.88%, n-butanol; 72.22% and aqueous residue; 72.22% by the fractions of U. chamae. In addition, haemorrhagic activity of N. nigricollis venom was significantly (p<0.05) neutralized by U. chamae fractions at the concentrations of 100mg/ml, 200mg/ml and 400mg/ml except for n-butanol and aqueous residues at 400 mg/ml. Conclusion: U. chamae leaves fractions possess a high level of protection against N. nigricollis venoms-induced lethality and thus validate the pharmacological rationale for its usage in the management of N. nigricollis envenomation.

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