scholarly journals Fermotein Does Not Exert Genotoxic Effects in Bacterial Reverse Mutation and in Vitro Mammalian Cell Micronucleus Tests

2021 ◽  
pp. 113-123
Author(s):  
Marjolein Van Der Spiegel ◽  
José J. Van Den Driessche ◽  
Elisa Leune ◽  
Kirsten Knobel ◽  
Wim De Laat
Keyword(s):  
Mammalian Cell ◽  
Micronucleus Test ◽  
Dose Range ◽  
The Body ◽  
Cell Protein ◽  
Human Consumption ◽  
Genotoxic Effects ◽  
Reverse Mutation ◽  
Range Finding

Aim: Fermotein is an innovative single-cell protein obtained from fermentation of the filamentous fungus Rhizomucor pusillus. Like other filamentous fungi, a lack of information on this species exists to assess its safety for human consumption. The capability to induce gene mutations or structural and numerical chromosomal aberrations of this fungus and derived products has never been studied before. The objective of the current study was to investigate the genotoxic effects of Fermotein using a bacterial reverse mutation test and an in vitro mammalian cell micronucleus test. Methodology: The bacterial reverse mutation test and in vitro mammalian cell micronucleus test were performed in accordance with GLP and concurrent OECD guidelines. Dose-range finding tests were used to select appropriate doses of Fermotein Dry. The highest doses in the genotoxicity experiments were determined by the solubility of the mycoprotein. Results: The bacterial reverse mutation test and in vitro mammalian cell micronucleus test were performed in accordance with GLP and concurrent OECD guidelines. Dose-range finding tests were used to select appropriate doses of Fermotein Dry. The highest doses in the genotoxicity experiments were determined by the solubility of the mycoprotein. Conclusion: No safety concerns regarding genotoxicity were identified for Fermotein and no further in vivo genotoxicity testing is required. Information from the current study contributes to the body of evidence for a novel food authorisation of Fermotein in the EU and a GRAS notification in the US.

Genotoxicity Studies on Sel-Plex®, a Standardized, Registered High-Selenium Yeast

2006 ◽  
Vol 25 (6) ◽  
pp. 477-485 ◽  
Author(s):  
James C. Griffiths ◽  
Ray A. Matulka ◽  
Ronan Power
Keyword(s):  
Chromosome Aberration ◽  
Micronucleus Test ◽  
Mutagenic Activity ◽  
Human Lymphocytes ◽  
Selenium Yeast ◽  
Yeast Saccharomyces Cerevisiae ◽  
Reverse Mutation ◽  
High Selenium ◽  
Chromosome Aberration Test

Selenium, recognized as an essential nutrient for human health, is a component of proteins and enzymes required for various biological functions and is currently being used as a feed supplement for livestock in geographical areas that are naturally low in selenium. Selenium is structurally similar to sulfur, replacing the sulfur atom in stoichiometric amounts and thus functions through an association with proteins, termed selenoproteins. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast ( Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). A unique, standardized, registered high selenium food-grade baker’s yeast ( S. cerevisiae; Sel-Plex®), was tested in the following battery of Genotoxicity assays; (1) a bacterial reverse mutation test (Ames test); (2) an in vitro mammalian chromosome aberration test; and (3) a mouse micronucleus test. Under the conditions of this assay, Sel-Plex® showed no evidence of mutagenic activity in Salmonella typhimurium, in the bacterial reverse mutation test. Sel-Plex® did not induce significant chromosomal aberrations in cultured human lymphocytes in the in vitro mammalian chromosome aberration test. Sel-Plex® did not statistically increase the frequency or proportion of micronucleated immature erythrocytes in the mouse micronucleus test. Thus, from the studies presented here, the authors conclude that Sel-Plex® is nongenotoxic.

scholarly journals Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

2014 ◽  
Vol 50 (2) ◽  
pp. 251-256
Author(s):  
Igor Vivian de Almeida ◽  
Giovana Domingues ◽  
Lilian Capelari Soares ◽  
Elisângela Düsman ◽  
Veronica Elisa Pimenta Vicentini
Keyword(s):  
Rattus Norvegicus ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Term Treatment ◽  
Genotoxic Effects ◽  
Short Term ◽  
Short Term Treatment ◽  
Chromosomal Aberration Test

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

Two Procedures for the Prediction of Acute Toxicity (LD50) from Cytotoxicity Data

1992 ◽  
Vol 20 (1) ◽  
pp. 40-49 ◽  
Author(s):  
Willi Halle ◽  
Horst Spielmann
Keyword(s):  
Linear Regression ◽  
Acute Toxicity ◽  
Correlation Coefficient ◽  
Mammalian Cell ◽  
Wide Spectrum ◽  
Dose Range ◽  
Linear Regression Analysis ◽  
Range Finding ◽  
Mammalian Cell Lines ◽  
Ic50 Values

Single linear regression analysis was used to characterise the relationship between cytotoxicity in a variety of mammalian cell culture systems and acute oral toxicity (LD50) in experimental animals. The following results were obtained. Firstly, in a cytotoxicity assay using the calf aortic endothelial cell line BKEz-7, IC50 values determined for 44 chemicals in culture showed significant correlation with the oral LD50 values for rat and mouse (computed correlation coefficient r=0.546). After eliminating three chemicals that were characterised by extreme lethality indices (LI = IC50/LD50), the correlation coefficient of the remaining 41 chemicals increased to a value of r=0.728. By using the linear regression model for these 41 chemicals, the oral LD50 for rat and mouse can be predicted correctly from the IC50 values for 83% of substances from a variety of chemical substance classes within a range of approximately one order of magnitude of dosage unit of LD50 for rat and mouse. Secondly, the mean IC50 values (IC50x¯) determined as the geometrical mean of two or more IC50 values per substance, which were generated in a wide spectrum of mammalian cell lines and collected in a “Registry of Cytotoxicity” (RC), gave similar results (r=0.644). Likewise, with the aid of this method, the oral LD50 for rat and mouse can be predicted for 74% of non-selected chemicals from structurally-different classes in the same dosage range, e.g., 1–25 millimoles per kg body weight. The prediction of LD50 values from in vitro cytotoxicity data may permit the calculation of a more precise dose range-finding and offers a new way for reducing the number of animals in acute toxicity testing.

Nicotine derived genotoxic effects in human primary parotid gland cells as assessed in vitro by comet assay, cytokinesis-block micronucleus test and chromosome aberrations test

2014 ◽  
Vol 28 (5) ◽  
pp. 838-846 ◽  
Author(s):  
Christian Ginzkey ◽  
Gudrun Steussloff ◽  
Christian Koehler ◽  
Marc Burghartz ◽  
Agmal Scherzed ◽  
...  
Keyword(s):  
Comet Assay ◽  
Parotid Gland ◽  
Chromosome Aberrations ◽  
Micronucleus Test ◽  
Genotoxic Effects ◽  
Gland Cells

scholarly journals Safety and Toxicological Evaluation of a Novel Citrus Sudachi Extract Powder

2016 ◽  
Vol 6 (10) ◽  
pp. 677
Author(s):  
Debasis Bagchi ◽  
Yasuhiro Shikishima ◽  
Orie Yoshinari ◽  
Yoshiaki Shiojima ◽  
Hiroyoshi Moriyama ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Mammalian Cell ◽  
Skin Irritation ◽  
Female Rats ◽  
Eye Irritation ◽  
Reverse Mutation ◽  
Male And Female Rats ◽  
Mutation Assay ◽  
Cell Gene

Background: Citrus sudachi, an evergreen tree found primarily in the prefecture of Tokushima, Japan, is a widely used popular citrus fruit used in cooking and also consumed as a juice. Citrus sudachi peels are rich in flavonoids including sudachitin (5,7,4’-trihydroxy-6,8,3’-trimethoxyflavone), and exhibit potent antioxidant, antimicrobial and anti-diabetic properties, while several limonoids and their glucosides are found in its seeds. We examined the broad spectrum safety of a novel light yellow to golden yellow Citrus sudachi Extract Powder (organic, nutritive) from the dried fruit rind (25:1 herbs to extract ratio) containing no less than 1% sudachitin in various toxicology models in GLP-approved laboratories.Methods: The acute oral toxicity study was conducted in female Sprague-Dawley rats by up and down procedure. The single dose acute dermal LD50 of Citrus sudachi Extract Powder was assessed in both male and female rats. The primary skin irritation toxicity of Citrus sudachi Extract Powder was assessed in female New Zealand Albino rabbits to determine the potential for Citrus sudachi Extract Powder to produce irritation after a single topical application, while primary eye irritation index of Citrus sudachi Extract Powder was conducted in female New Zealand Albino rabbits. Ames’ bacterial reverse mutation assay was conducted to determine the ability of Citrus sudachi Extract Powder to induce reverse mutation at selected histidine loci in five tester strains of Salmonella typhimurium viz. TA1535, TA97a, TA98, TA100, and TA102 in the presence and absence of a metabolic activation system (S9) at the doses of 5000, 1500, 500, 150 and 50 mg/plate. Mutagenic potential of Citrus sudachi Extract Powder was also evaluated in vitro mammalian cell gene mutation test using the thymidine kinase gene of L5178 Tk+/- 3.7.2C mouse lymphoma cell line.Results: The acute oral LD50 of Citrus sudachi Extract Powder was found to be greater than 5000 mg/kg body weight. The single dose acute dermal LD50 of Citrus sudachi Extract Powder was found to be greater than 2000 mg/kg body weight in both male and female rats. In primary skin irritation test, Citrus sudachi Extract Powder was found to be slightly irritating to the skin. The primary dermal irritation index (PDII) calculated for Citrus sudachi Extract Powder was found to be 0.8. In primary eye irritation test, the maximum mean total score (MMTS) of Citrus sudachi Extract Powder was found to be 2.7 and thus, Citrus sudachi Extract Powder was classified as minimally irritating to the eye. In both Ames’ bacterial reverse mutation assay and in vitro mammalian cell gene mutation test, no mutagenicity was observed.Conclusion: Overall, these toxicological evaluations demonstrate the broad spectrum safety of Citrus sudachi extract powder.Keywords: Citrus sudachi Extract Powder; acute oral toxicity; acute dermal toxicity; primary dermal irritation; primary eye irritation; Ames’ bacterial reverse mutation assay; in vitro mammalian cell gene mutation assay

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