ABSTRACT
Ubidecarenone (coenzyme Q10) has been widely used as a complementary therapy in heart failure and as a dietary supplement for over two decades. Ubidecarenone is manufactured by organic synthesis, yeast (non-Saccharomyces cerevisiae) fermentation, or bacteria fermentation. There are many reports on the safety of ubidecarenone. However, genotoxicity of ubidecarenone manufactured by bacteria fermentation has not been reported. We carried out genotoxicity evaluation of ubidecarenone manufactured by bacteria fermentation through the bacterial reverse mutation test (Ames test) and in vitro chromosome aberration test in compliance with the Japanese guidelines on genotoxicity testing of pharmaceuticals and the Organization for Economic Co-operation and Development (OECD) guidelines for testing chemicals. The results indicate neither increase of revertant colonies nor chromosome aberration, suggesting that the ubidecarenone manufactured by bacteria fermentation has no genotoxic activities under the condition of this study.
Subject(s)
Fermentation , Mutagenicity Tests , Ubiquinone/analogs & derivatives , Animals , Bacteria/metabolism , Cell Line , Cricetinae , Cricetulus , Dose-Response Relationship, Drug , Female , Male , Mutagenicity Tests/methods , Rats , Rats, Sprague-Dawley , Ubiquinone/biosynthesis , Ubiquinone/toxicityABSTRACT
Although phosphatidylinositol (PI) is an important component in all plants and animals, there is no toxicity report when purified PI is orally administrated to animals. As a safety evaluation of PI, acute, subchronic and genotoxicity studies were conducted with purified PI from soy lecithin (Asahi Kasei PI). Up to 2,000 mg/kg of Asahi Kasei PI was administrated once orally to male and female rats. There were no deaths or any clinical sign in any group throughout the observation period. Then, Asahi Kasei PI was repeatedly administered orally to male and female rats at daily doses of 100, 300 and 1,000 mg/kg for 13 weeks. Neither death nor any toxicological signs during the administration period and no changes related to the test substance administered were observed in any group with regard to body weight, food consumption, ophthalmoscopy, hematology, blood biochemistry, necropsy, organ weights or histopathology. Based on these results, the no-observed-adverse effect level (NOAEL) of Asahi Kasei PI was considered to be 1,000 mg/kg/day for male and female rats. Genotoxicity evaluation of Asahi Kasei PI was also carried out by the bacterial reverse mutation test (Ames test) and in vitro chromosome aberration test in compliance with the Japanese guidelines on genotoxicity testing of pharmaceuticals, the OECD guidelines for testing chemicals and guidelines for designation of food additives and for revision of standards for use of food additives. The results indicate neither increases of revertant colonies nor chromosome aberration, suggesting that Asahi Kasei PI has high safety in genotoxicity.
Subject(s)
Glycine max/chemistry , Lecithins/chemistry , Mutagens/toxicity , Phosphatidylinositols/toxicity , Administration, Oral , Animals , Body Weight/drug effects , Cells, Cultured , Chromosome Aberrations , Clinical Chemistry Tests , Cricetinae , Cricetulus , Eating/drug effects , Female , Hematologic Tests , Male , Mutagens/classification , No-Observed-Adverse-Effect Level , Phosphatidylinositols/classification , Plant Extracts/toxicity , Rats , Rats, Sprague-Dawley , Salmonella typhimurium/drug effects , Salmonella typhimurium/geneticsABSTRACT
As part of a safety evaluation of Coenzyme Q10, a subchronic toxicology study was conducted. Coenzyme Q10 was repeatedly administered orally to male and female Crl:CD(SD) rats at daily dose levels of 300, 600 and 1200 mg/kg for 13 weeks. Neither death nor any toxicological signs were observed in any group during the administration period. No change related to the test substance administered was observed in any group with regard to body weight, food consumption, ophthalmoscopy, hematology, blood biochemistry, necropsy, organ weights or histopathology. Based on these results, the non-observed-adverse-effect level (NOAEL) of Coenzyme Q10 was considered to be 1200 mg/kg/day for male and female rats under these study conditions.
Subject(s)
Dietary Supplements/toxicity , Toxicity Tests, Chronic , Ubiquinone/analogs & derivatives , Administration, Oral , Animals , Body Weight/drug effects , Coenzymes/administration & dosage , Coenzymes/toxicity , Feeding Behavior/drug effects , Female , Male , No-Observed-Adverse-Effect Level , Organ Size/drug effects , Organ Specificity , Rats , Rats, Sprague-Dawley , Ubiquinone/administration & dosage , Ubiquinone/toxicityABSTRACT
In a screening campaign to isolate strains with the ability to remove the bad smell associated with animal faeces, strain MA001(T) was isolated from a soil sample obtained from Shizuoka prefecture, Japan. The isolate grew at pH 6-9 but not at pH 10. Cells were Gram-positive, straight rods with peritrichous flagella and produced ellipsoidal spores. The isolate was positive for catalase and oxidase tests but negative for indole production, deamination of phenylalanine and H(2)S production. The isolate did not produce acid from any carbohydrates tested and could not grow in more than 2 % NaCl. The DNA G+C content was 39.4 mol%. The cellular fatty acids profile consisted of significant amount of C(15) branched-chain fatty acids, iso-C(15 : 0) and anteiso-C(15 : 0). Phylogenetic analysis based on 16S rRNA gene sequencing indicated that strain MA001(T) was closely related to Bacillus simplex and Bacillus psychrosaccharolyticus. DNA-DNA hybridization revealed a low relatedness of the isolate to several phylogenetically close neighbours (less than 9 %). On the basis of the phenotypic characteristics observed, phylogenetic data based on 16S rRNA gene sequencing and DNA-DNA relatedness data, it is concluded that the isolate should be classified as representing a novel species, for which the name Bacillus asahii is proposed. The type strain is MA001(T) (=JCM 12112(T)=NCIMB 13969(T)).
