The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Scientific Panel is asked to evaluate the 47 flavouring substances in this Flavouring Group Evaluation 6, Revision 1 (FGE.06Rev1), using the procedure as referred to in the Commission Regulation EC No 1565/2000. These 47 flavouring substances belong to chemical groups 1 and 4 of Annex I of the Commission Regulation (EC) No 1565/2000.

Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC) on a request from the Commission, Flavouring Group Evaluation 22: Ring-substituted phenolic substances from chemical groups 21 and 25: Question No EFSA-Q-2003-165

In vitro genotoxicity testing needs to include tests in both bacterial and mammalian cells, and be able to detect gene mutations, chromosomal damage and aneuploidy. This may be achieved by a combination of the Ames test (detects gene mutations) and the in vitro micronucleus test (MNvit), since the latter detects both chromosomal aberrations and aneuploidy. In this paper we therefore present an analysis of an existing database of rodent carcinogens and a new database of in vivo genotoxins in terms of the in vitro genotoxicity tests needed to detect their in vivo activity. Published in vitro data from at least one test system (most were from the Ames test) were available for 557 carcinogens and 405 in vivo genotoxins. Because there are fewer publications on the MNvit than for other mammalian cell tests, and because the concordance between the MNvit and the in vitro chromosomal aberration (CAvit) test is so high for clastogenic activity, positive results in the CAvit test were taken as indicative of a positive result in the MNvit where there were no, or only inadequate data for the latter. Also, because Hprt and Tk loci both detect gene-mutation activity, a positive Hprt test was taken as indicative of a mouse-lymphoma Tk assay (MLA)-positive, where there were no data for the latter. Almost all of the 962 rodent carcinogens and in vivo genotoxins were detected by an in vitro battery comprising Ames+MNvit. An additional 11 carcinogens and six in vivo genotoxins would apparently be detected by the MLA, but many of these had not been tested in the MNvit or CAvit tests. Only four chemicals emerge as potentially being more readily detected in MLA than in Ames+MNvit--benzyl acetate, toluene, morphine and thiabendazole--and none of these are convincing cases to argue for the inclusion of the MLA in addition to Ames+MNvit. Thus, there is no convincing evidence that any genotoxic rodent carcinogens or in vivo genotoxins would remain undetected in an in vitro test battery consisting of Ames+MNvit.

A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins.

Studies on the genotoxicity of chromium: from the test tube to the cell

On the transformation and enterohepatic circulation of cholic acid in the rat: bile acids and steroids 68.

Reactions of carbonyl compounds with (monohalo) methyleniminium salts (vilsmeier reagents)

Mutagenicity of quinoline derivatives and analogs-quinoxaline 1,4-dioxide is a potent mutagen.

The metabolism of cholic acid by Arthrobacter simplex was investigated. This organism effected both ring a cleavage and elimination of the hydroxyl groups at C-7 and C-12 and gave a new metabolite, (4R)-4-[4α-(2-carboxyethyl)-3aα-hexahydro-7aβ-methyl-5-oxoindan-1β-yl]valeric acid, which was isolated and identified through its partial synthesis. A degradative pathway of cholic acid into this metabolite is tentatively proposed, and the possibility that the proposed pathway could be extended to the cholic acid degradation by other microorganisms besides A. simplex is discussed. The possibility that the observed reactions in vitro could occur during the metabolism of bile acids in vivo is considered.

/pdf/microbiological-degradation-of-bile-acids-ring-a-cleavage-3ou4nkk6f9.pdf

Microbiological degradation of bile acids. Ring a cleavage and 7α,12α-dehydroxylation of cholic acid by Arthrobacter simplex

FOR the microbiological oxidation of cholic acid, two possible pathways different from that found in A. faecalis1 or E. coli2 can be suggested.

Microbiological Degradation of Cholic Acid

Polycyclic N-hetero compounds. XX: Synthesis of 11,13,15-triazasteroid with an alkyl group in the D-ring and an investigation of its antidepressive activity

Shohei Hayakawa

Papers

Mutagenicity of quinoline derivatives and analogs-quinoxaline 1,4-dioxide is a potent mutagen.

Microbiological degradation of bile acids. Ring a cleavage and 7α,12α-dehydroxylation of cholic acid by Arthrobacter simplex

Microbiological Degradation of Cholic Acid

Polycyclic N-hetero compounds. XX: Synthesis of 11,13,15-triazasteroid with an alkyl group in the D-ring and an investigation of its antidepressive activity

A versatile novel synthesis of benzofuran and related compounds. II: The Vilsmeier reaction of α-phenoxyacetophenones