Scientific Opinion on Flavouring Group Evaluation 06, Revision 4 (FGE.06Rev4): Straight‐ and branched‐chain aliphatic unsaturated primary alcohols, aldehydes, carboxylic acids and esters from chemical groups 1, 3 and 4

Abstract

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 56 flavouring substances in the Flavouring Group Evaluation 6, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision is made due to the inclusion of six additional flavouring substances, (-)-3,7-dimethyl-6-octen-1-ol .229], dec-4(cis)-enal .137], neral .170], trans-3,7-dimethylocta-2,6-dienal (geranial) .188], trans-3-hexenyl formate .562] and cis-3-hexenyl 2-methylbutanoate ]. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern and available data on metabolism and toxicity. The Panel concluded that the 56 substances 02.138, 02.152, 02.170, 02.175, 02.176, 02.195, 02.201, 02.222, 02.229, 02.234, 05.061, 05.082, 05.137, 05.143, 05.170, 05.174, 05.188, 05.203, 05.217, 05.218, 05.220, 05.226, 08.074, 08.100, 08.102, 09.341, 09.368, 09.377, 09.562, 09.567, 09.569, 09.572, 09.575, 09.612, 09.638, 09.640, 09.643, 09.672, 09.673, 09.674, 09.831, 09.838, 09.854, 09.855, 09.871, 09.872, 09.884, 09.885, 09.897, 09.898, 09.928, 09.937, 09.938, 09.939 and 09.950] do not give rise to safety concern at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Adequate specifications including complete purity criteria and identity for the materials of commerce have been provided for all 56 Forty-one of the flavouring substances in the present group have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the "Maximised Survey-derived Daily Intake" (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a "modified Theoretical Added Maximum Daily Intake" (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring subs...

Safety and efficacy of 26 compounds belonging to chemical group 3 (α,β‐unsaturated straight‐chain and branched‐chain aliphatic primary alcohols, aldehydes, acids and esters) when used as flavourings for all animal species and categories

“…The compounds of CG 3 under assessment in the present opinion are primary unsaturated alcohols, aldehydes (enals and dienals) and esters. In general, compounds belonging to CG 3 are rapidly absorbed, distributed, metabolised and excreted (WHO, 1997(WHO, , 1999(WHO, , 2004a(WHO, ,b, 2005(WHO, , 2006EFSA CEF Panel, 2010, 2013.…”

Safety and efficacy of α,β‐unsaturated straight‐chain and branched‐chain aliphatic primary alcohols, aldehydes, acids and esters belonging to chemical group 3 when used as flavourings for all animal species

“…In general, compounds belonging to CG 3 are rapidly absorbed, distributed, metabolised and excreted (WHO, 1999, EFSA CEF Panel, 2010b, 2013b.…”

“…The metabolic reactions involved in the biotransformation of straight-chain and branched-chain unsaturated primary aliphatic alcohols, aldehydes, carboxylic acids and esters (WHO, 1999;EFSA CEF Panel, 2010b, 2013b are: (i) hydrolysis of esters (Heymann, 1980); (ii) oxidation of linear and branched-chain alcohols and aldehydes to acids, by high capacity nicotinamide adenine dinucleotide (NAD+)/(nicotinamide adenine dinucleotide phosphate) NADP-dependent enzymes (Voet and Voet, 1990;Feron et al, 1991;Parkinson, 1996); (iii) reduction of aldehydes to alcohols by NAD(P)Hdependent reductases; (iv) conjugation with glucuronic acid of alcohols (a minor pathway for primary alcohols) and polar metabolites resulting from a combination of x,x-1 and b-oxidation (Diliberto et al, 1990); (v) metabolism of the resulting linear-or branched-chain unsaturated carboxylic acids to carbon dioxide in the tricarboxylic acid cyclic and fatty acid pathway (Voet and Voet, 1990), by b-oxidation (linear-and short-chain branched carboxylic acids) or x-oxidation (medium-and long-chain carboxylic acids, presence of ethyl or propyl side chains); (vi) isomerisation reactions by enoyl-CoA isomerase (shift of the double bond from delta 3 -to delta 2 -enoyl-CoA, when unsaturation begin at an oddnumbered carbon) and 3-hydroxyacyl-CoA epimerase (cis-to trans-isomerisation of delta 2 -enoyl-CoA); and (vii) saturation of unsaturated short-chain acids, to yield a substrate that may participate in the fatty acid pathway.…”

“…The first approach to the safety assessment for target species takes account of the intended use levels in animal feed relative to the maximum reported exposure of humans on the basis of the metabolic body weight. Human exposure in the EU to the individual compounds ranges from 0.0061 to 5,844 lg/person per day (EFSA, 2009b;EFSA CEF Panel, 2010a, 2013b. This corresponds to 0.0003-271 lg/kg 0.75 per day.…”

Safety and efficacy of non‐conjugated and accumulated unsaturated straight‐chain and branched‐chain, aliphatic primary alcohols, aldehydes, acids, acetals and esters belonging to chemical group 4 when used as flavourings for all animal species

“…The metabolic reactions involved in the biotransformation of straight-chain and branched-chain unsaturated primary aliphatic alcohols, aldehydes, carboxylic acids and esters (WHO, 1999b;EFSA (EFSA CEF Panel, 2010b, 2013b are: (i) hydrolysis of esters (Heymann, 1980); (ii) oxidation of linear and branched-chain alcohols and aldehydes to acids, by high capacity NAD+/NADP-dependent enzymes (Voet and Voet, 1990;Feron et al, 1991;Parkinson, 1996); (iii) reduction of aldehydes to alcohols by NAD(P)H-dependent reductases; (iv) conjugation with glucuronic acid of alcohols (a minor pathway for primary alcohols) and polar metabolites resulting from a combination of omega-, omega-1-and beta-oxidation (Diliberto et al, 1990); (v) metabolism of the resulting linear-or branched-chain unsaturated carboxylic acids to carbon dioxide in the tricarboxylic acid cyclic and fatty acid pathway (Voet and Voet, 1990), by b-oxidation (linear-and short-chain branched carboxylic acids) or x-oxidation (medium-and long-chain carboxylic acids, presence of ethyl or propyl side chains); (vi) isomerisation reactions by enoyl-CoA isomerase (shift of the double bond from delta 3 -to delta 2 -enoyl CoA, when unsaturation begins at an odd-numbered carbon) and 3-hydroxyacyl-CoA epimerase (cis to trans isomerisation of delta 2 -enoyl-CoA); (vii) saturation of unsaturated short-chain acids, to yield a substrate that may participate in the fatty acid pathway (Stryer, 1988;EFSA, 2010bEFSA, , 2013b.…”