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

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 33 flavouring substances in the Flavouring Group Evaluation 24, Revision 1 (FGE.24Rev1), using the procedure as referred to in the Commission Regulation (EC) No 1565/2000. These 33 flavouring substances belong to chemical group 28 of Annex I of the Commission Regulation (EC) No 1565/2000.

Pyridine, pyrrole, indole and quinoline derivatives from chemical group 28 Flavouring Group Evaluation 24, Revision 1 Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC)

We tested the 10 known or suspected spindle poisons (colchicine, econazole nitrate, chloral hydrate, hydroquinone, diazepam, thiabendazole, cadmium chloride, thimerosal, pyrimethamine and vinblastine) of the coordinated EEC programme for induction of aneuploidy with the in vitro porcine brain tubulin assembly assay. The influence of the compounds on different parameters [lag-phase, polymerization velocity, endabsorption (steady-state level), reversibility, influence on disassembly at 4 degrees C] was evaluated. Colchicine [IC30 (30% inhibition concentration): 0.002 mM), vinblastine (IC30: 0.002 mM), thimerosal (IC30: 0.03 mM), thiabendazole (IC30: 0.5 mM) and chloral hydrate (IC30: 60 mM) led to an inhibition of tubulin assembly in vitro. No influence on the steady-state level was obtained with econazole nitrate (up to 0.1 mM), diazepam (up to 2.5 mM), cadmium chloride (up to 1 mM), pyrimethamine (up to 1 mM) and hydroquinone (up to 25 mM), the highest dose tested being limited either by precipitation or by reaching the maximal solubility of the compound in the solvent used. Diazepam enhanced the lag-phase and slightly reduced the polymerization velocity dose-dependently; however, all the treated test mixtures reached the same end absorption levels as the control. The influence on the disassembly process was studied at 4 degrees C. Microtubules treated with colchicine, econazole nitrate, diazepam, thiabendazole, cadmium chloride, thimerosal and pyrimethamine reached the same end absorption level after disassembly as the untreated control. Chloral hydrate reduced the disassembly rate but the end absorption of the control was not reached, the 30% reduction concentration being 0.25 mM. Hydroquinone at very high doses (greater than 10 mM) stimulated the disassembly process.(ABSTRACT TRUNCATED AT 250 WORDS)

/pdf/effects-of-10-known-or-suspected-spindle-poisons-in-the-in-52150y614n.pdf

Effects of 10 known or suspected spindle poisons in the in vitro porcine brain tubulin assembly assay.

The diploid yeast strain D61.M was used to study induction of mitotic chromosome loss. The test relies upon the uncovering and expression of multiple recessive markers reflecting the presumptive loss of the chromosome VII homologue carrying the corresponding wild-type alleles. The underlying 'loss event' is probably complex since the predicted centromere-linked lethal tetrad segregations for chromosome VII are not recovered. Instead, the homologue bearing the multiple recessive markers is patently homozygous. An interlaboratory study was performed in which 16 chemicals were tested under code in 2 laboratories. The results generated by the Berkeley and Darmstadt laboratories were in close agreement. Acetonitrile, ethyl acetate, 4-acetylpyridine, propionitrile and nocodazole were identified as potent inducers of mitotic chromosome loss. Acetone, dimethyl sulfoxide and 2-methoxyethyl acetate either elicited weak responses or yielded ambiguous results. Water, carbon tetrachloride, 4-fluoro-D,L-phenylalanine, amphotericin B, griseofulvin, cadmium chloride, ethyl methanesulfonate and methylmercury(II) chloride failed to induce chromosome loss. These data suggest that the system described herein represents a reliable assay for chemically induced chromosome loss in yeast.

Detection of induced mitotic chromosome loss in Saccharomyces cerevisiae--an interlaboratory study.

The fundamental problems that face us in the development of suitable assay systems for the detection of potentially aneugenic (aneuploidy-inducing) chemicals include: (a) the diversity of cellular targets and mechanisms where perturbations of structure and function may give rise to changes in chromosome number, and (b) the phylogenetic differences that exist between species in their mechanism and kinetics of cell division and their metabolic profiles. A diverse range of assay systems have been developed, which have been shown to have potential for use in the detection of either changes in chromosome number or of perturbations of the events which may be causal in the induction of aneuploidy. Chromosome number changes may be detected cytologically by karyotypic analysis, or by the use of specialised strains in which aneuploid progeny may be observed due to phenotypic differences with aneuploid parental cells or whole organisms. Techniques for the detection of cellular target modifications range from in vitro studies of tubulin polymerisation to observations of the behaviour of various cellular organelles and their fidelity of action during the division cycle. The diversity of mechanisms which may give rise to aneuploidy and the qualitative relevance of events observed in experimental organisms compared to man make it unlikely that the detection and risk assessment of the aneugenic activity of chemicals will be possible using a single assay system. Optimal screening and assessment procedures will thus be dependent upon the selection of an appropriate battery of predictive tests for the measurement of the potentially damaging effects of aneuploidy induction.

Comparisons of tests for aneuploidy.

A series of pyridine derivatives, 2-methyl-, 2-chloro-, 2-acetyl-, 3-acetyl-, 4-acetyl-, 2-phenyl-, 2,4-dimethyl-, 2,6-dimethyl- and 2-methyl-5-ethyl-pyridine, were shown to induce mitotic aneuploidy in strain D61.M of Saccharomyces cerevisiae . Induction of mitotic recombination was also observed with 3- and 4-acetylpyridine and 2-phenylpyridine in strain D61.M. 4-Acetylpyridine and 2-phenylpyridine were found to induce mitotic gene conversion and 2-phenyl-pyridine also induced reverse mutation in strain D7 of Saccharomyces cerevisiae . These two agents also inhibited the GTP-mediated assembly of porcine brain tubulin in vitro.

Genetic and anti-tubulin effects induced by pyridine derivatives

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Genetic and anti-tubulin effects induced by pyridine derivatives