Following a request from the European Commission, the European Food Safety Authority (EFSA) Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) was asked to deliver a scientific opinion on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel was requested to evaluate three flavouring substances in the Flavouring Group Evaluation 35, Revision 1 (FGE.35Rev1), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These three flavouring substances belong to chemical group 30 of Annex I of the Commission Regulation (EC) No 1565/2000.
Compared with FGE.35 consisting of three candidate substances, all being salts of quinine from the priority list, FGE.35 Revision 1 includes specification data on quinine sulphate [FL-no: 14.152] and quinine monohydrochloride dihydrate [FL-no: 14.155], new intake data on all three candidate substances and toxicological and genotoxicity data on quinine hydrochloride [FL-no: 14.011] and two structurally related quinine salts.
The quinine component is the (−)-isomer, which has (8S,9R)-configuration.
All three substances are classified into structural class III and do not naturally occur in food.
Because the three candidate substances are water-soluble salts of the same flavouring component, quinine, and because they are expected to replace each other, the Panel decided to carry out the safety assessment on the basis of exposure to quinine equivalents.
In its evaluation, the Panel, as a default, used the “Maximised Survey-derived Daily Intake” (MSDI) approach to estimate the per capitaintakes 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 substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases, the Panel requires more precise data on use and use levels.
On the basis of the genotoxicity data available on the quinine salts the Panel concluded that there is no concern for genotoxicity for the candidate substances, when used as flavouring substances.
The Panel considered a well conducted 21-day study in humans, with much higher levels of exposure to quinine than those resulting from its use as flavouring substance at levels reported in this FGE.35Rev1 (i.e. MSDI of 745 µg per capita per day (expressed as quinine equivalents) or a highest mTAMDI of 29100 µg quinine equivalents per person per day for [FL-no: 14.011]), providing a no observed adverse effect level (NOAEL) of 72 mg quinine equivalents/person/day. Because of the availability of this study and the knowledge of quinine toxicity following its use as an anti-malarial agent, the Panel decided that the Procedure for the evaluation of flavouring substances, as laid down in Commission Regulation (EC) No 1565/2000, is not applicable. The Panel considered the use of quinine at levels of exposures as indicated by the mTAMDI not of safety concern. The mTAMDI is expected to reliably reflect the use of quinine because its consumption is limited to only two food categories: alcoholic and non-alcoholic beverages.
These exposure levels are equivalent to a daily consumption of approximately 300 ml of non-alcoholic beverages containing quinine at the maximum permitted level of 100 mg/l. The margin of safety is approximately 100 for the MSDI and 2.5 for the mTAMDI.
The Panel noted that a very high intake (e.g. more than 1 litre) of non-alcoholic beverages containing quinine or its salts at the maximum permitted level could result in adverse health effects in human.
In order to determine whether the conclusion for the candidate substances can be applied to the material of commerce, it is necessary to consider the available specifications. Specifications, including purity criteria and identity for the materials of commerce, have been provided for all three candidate substances.
Accordingly, the three flavouring substances, quinine hydrochloride [FL-no: 14.011], quinine sulphate [FL-no: 14.152] and quinine monohydrochloride dihydrate [FL-no: 14.155], would present no safety concern at the levels of intake estimated on the basis of the MSDI or mTAMDI approach. The Panel addressed in this evaluation only those food categories (14.1 and 14.2) in which the use of quinine is permitted according to Annex I of regulation 1334/2008. Therefore, this evaluation is applicable for the use of quinine hydrochloride [FL-no: 14.011], quinine sulphate [FL-no: 14.152] and quinine monohydrochloride dihydrate [FL-no: 14.155] in alcoholic and non-alcoholic beverages.
Considering the occurrence of hypersensitivity against quinine in the human population, the Panel would support continuation of the legal requirement for labelling of quinine-flavoured foods.