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Scientific Opinion on the re-evaluation of Azorubine/Carmoisine (E 122) as a food additive

EFSA Journal 2009; 7(11):1332 [40 pp.]. doi:10.2903/j.efsa.2009.1332
  EFSA Panel on Food Additives and Nutrient Sources added to food (ANS) Panel Members F. Aguilar, U.R. Charrondiere, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, S. Grilli, R. Guertler, J. Koenig, C. Lambré, J-C. Larsen, J-C. Leblanc, A. Mortensen, D. Parent-Massin, I. Pratt, I.M.C.M. Rietjens, I. Stankovic, P. Tobback, T. Verguieva, R.A. Woutersen Acknowledgment The Panel wishes to thank the members of the Working Group B on Food Additives and Nutrient Sources for the preparation of this opinion: D. Boskou, R. Charrondiere, B. Dusemund, D. Gott, T. Hallas-Møller, K.F.A.M. Hulshof, J. König, D. Parent-Massin, I.M.C.M. Rietjens, G.J.A. Speijers, P. Tobback, T. Verguieva, R.A. Woutersen. Contact Unit-ANS@efsa.europa.eu
Type: Opinion of the Scientific Committee/Scientific Panel On request from: European Commission Question number: EFSA-Q-2008-226 Adopted: 24 September 2009 Published: 12 November 2009 Last updated: 24 November 2009. This version replaces the previous one/s. Affiliation: European Food Safety Authority (EFSA), Parma, Italy
Abstract

The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion re-evaluating the safety of Azorubine/Carmoisine (E 122). Azorubine/Carmoisine has previously been evaluated by JECFA in 1983 and the SCF in 1984. Both committees established an Acceptable Daily Intake (ADI) of 0-4 mg/kg bw/day. The Panel was not provided with a newly submitted dossier and based its evaluation on previous evaluations, additional literature that became available since then and the data available following a public call for data. New studies included a study reporting alterations in the morphology of somatic chromosomes in Secale cereale (rye), and a study by McCann et al. that concluded that exposure to mixtures including Azorubine/Carmoisine, resulted in increased hyperactivity in 3-years old and 8- to 9-years old children. The Panel notes that the study in rye was not a standard genotoxicity assay, and concluded, given that all other genotoxicity tests were negative and that Azorubine/Carmoisine does not contain a structural alert, that there is no concern with respect to genotoxicity. The Panel also concurs with the conclusion from a previous EFSA opinion on the McCann et al. study that the findings of the study cannot be used as a basis for altering the ADI. The Panel concludes that the present database does not give reason to revise the ADI of 4 mg/kg bw/day. The Panel also concludes that at the maximum reported levels of use, refined intake estimates are below the ADI, although in 1- to 10-year old children the high percentile of exposure (95th) can be slightly higher than the ADI at the upper end of the range.

© European Food Safety Authority, 2009

Summary

Following a request from the European Commission to the European Food Safety Authority (EFSA), the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on Azorubine/Carmoisine (E 122) when used as a food colouring substance.

Azorubine/Carmoisine (E 122) is an azo dye allowed as a food additive in the EU and has previously been evaluated by the Joint FAO/WHO Joint Expert Committee on Food Additives (JECFA) in 1983 and the EU Scientific Committee for Food (SCF) in 1984. Both committees established an Acceptable Daily Intake (ADI) of 0-4 mg/kg bw/day.

The Panel noted that the specifications on the purity of Azorubine/Carmoisine permit concentrations of unidentified unsulphonated aromatic amines to be present in concentrations of up to 100 mg/kg Azorubine/Carmoisine. Although some aromatic amines may be associated with genotoxicity or even carcinogenicity, the Panel notes that Azorubine/Carmoisine was negative in vitro genotoxicity studies and an in vivo genotoxicity study as well as in long-term carcinogenicity studies.

The Panel concurs with the view expressed in previous evaluations by JECFA and TemaNord that the absorption of Azorubine/Carmoisine is limited, but that after reduction in the gastrointestinal tract, free sulphonated aromatic amines may reach the systemic circulation.

The SCF and also the JECFA and TemaNord evaluations concluded, based on in vivo and in vitro studies available at that time, that Azorubine/Carmoisine does not show any genotoxic activity.

In a more recent study, Zaharia and Pavel have tested four colourings, Tartrazine (E 102), Azorubine/Carmoisine (E 122), Patent Blue (E 131) and Acid Green 50 (E 142), on the frequency of divisional cells, mitotic index, mutagenic process, and the potential of these synthetic colourings to induce chromosomal modifications. Using cytogenetic analysis, the researchers claim to have proven that important alterations in the morphology of somatic chromosomes occur in Secale cereale (= rye) in the presence of Azorubine/Carmoisine. The Panel notes that this was not a standard genotoxicity assay, and concluded, given that all other genotoxicity tests were negative and that Azorubine/Carmoisine does not contain a structural alert, that there is no concern with respect to genotoxicity of Azorubine/Carmoisine.

There are no indications that Azorubine/Carmoisine induces tumour formation. Various non-neoplastic lesions have been observed after feeding of Azorubine/Carmoisine to mice and rats, but these findings have in the past been disregarded mainly based on the fact that high incidences were also seen in historical controls. The 1982 National Toxicology Program studies on carcinogenicity in rats and mice indicated that Azorubine/Carmoisine was not associated with the incidence of any type of tumour.

Based on the same dataset for long-term toxicity/carcinogenicity, previous evaluations by JECFA, the SCF and TemaNord also concluded that based on the data available there is no concern with respect to carcinogenicity or genotoxicity.

A study by McCann et al. has concluded that exposure to two mixtures of four synthetic colours plus the preservative sodium benzoate in the diet, both of them, Mix A and Mix B, containing Azorubine/Carmoisine, were reported to result in increased hyperactivity in 3- and 8- to 9-year old children in the general population. Recently, the European Food Safety Authority (EFSA) published an opinion on this McCann et al. study.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials (AFC) concluded that:

  • the McCann et al. study provides limited evidence that the two different mixtures of synthetic colours and sodium benzoate tested had a small and statistically significant effect on the activity and attention in children selected from the general population, excluding children medicated for the Attention Deficit Hypersensitivity Disorder (ADHD), although the effects were not statistically significant for the two mixtures in both age groups;
  • since mixtures, and not individual additives were tested in the study by McCann et al., it is not possible to ascribe the observed effects to any of the individual compounds; and,
  • in the context of the overall weight of evidence and in view of the considerable uncertainties, such as the lack of consistency and relative weakness of the effect, and the absence of information on the clinical significance of the behavioural changes observed, the findings of the study cannot be used as a basis for altering the ADI of the respective food colours or sodium benzoate.

The Scientific Panel on Food Additives and Nutrient Sources added to Food concurs with these conclusions. Altogether, the Panel concludes that the present database does not give reason for revision of the ADI of 0-4 mg/kg bw/day.

The Panel concluded that while some sensitivity reactions after Azorubine/Carmoisine intake have been reported, mostly when Azorubine/Carmoisine is taken within mixtures of other synthetic colours, no conclusion on the induction of sensitivity by Azorubine/Carmoisine could be drawn from the limited scientific evidence available. The Panel also notes that sensitive individuals may react at dose levels within the ADI.

The dietary exposure to Azorubine/Carmoisine from the MPLs of use was estimated by the Panel using the Budget method (Tier 1) with the assumptions described in the report of the Scientific Cooperation (SCOOP) Task 4.2. The Panel calculated a theoretical maximum daily exposure of 8.1 mg/kg bw/day both for adults and for a typical 3 year-old child.

Refined exposure estimates have been performed for both children and the adult population according to the Tier 2 and Tier 3 approaches described in the SCOOP Task 4.2, which combines, respectively detailed individual food consumption information from the population with the MPLs of use as specified in the Directive 94/36/EC on food colours (Tier 2), and with the maximum reported use levels of Azorubine/Carmoisine listed in Table 3, as identified by the Panel from the data by the UK Food Standards Agency, the Food Safety Authority of Ireland, the Agence Française de Sécurité Sanitaire des Aliments, the Union of European Beverage Associations, the European Spirits Organisation, the Federation of European Food Additives, Food Enzymes and Food Culture Industries and the Confederation of the Food and Drink Industries of the EU (Tier 3). For children (1-10 years old), estimates have been performed for nine European countries (Belgium, France, the Netherlands, Spain, UK, Czech Republic, Italy, Finland and Germany). For the adult population, the Panel has selected the UK population as representative of the EU consumers for Azorubine/Carmoisine intake estimates.

When considering MPLs (Tier 2), the mean dietary exposure to Azorubine/Carmoisine for European children (aged 1-10 years), ranged from 0.3 mg/kg bw/day to 2.5 mg/kg bw/day, and from 0.7 mg/kg bw/day to 6.7 mg/kg bw/day at the 95th percentile. Estimates reported for the UK adult population give a mean dietary exposure to Azorubine/Carmoisine of 0.5 mg/kg bw/day and of 1.1 mg/kg bw/day for high level (97.5th percentile) consumers of soft drinks.

When considering the maximum reported use levels, the mean dietary exposure to Azorubine/Carmoisine for European children (aged 1-10 years), ranged from 0.25 mg/kg bw/day to 2.4 mg/kg bw/day and from 0.6 mg/kg bw/day to 6.5 mg/kg bw/day at the 95th percentile. Estimates reported for the UK adult population give a mean dietary exposure of 0.4 mg/kg bw/day and of 1.0 mg/kg bw/day for high level (97.5th percentile) consumers of soft drinks.

The Panel concludes that at the maximum reported levels of use of Azorubine/Carmoisine, refined intake estimates are below the ADI, although in 1- to 10-year old children the high percentile of exposure (95th) can be slightly higher than the ADI at the upper end of the range.

The Panel further notes that the specifications of Azorubine/Carmoisine need to be updated with respect to the percentage of material not accounted for that may represent sodium chloride and/or sodium sulphate as the principal uncoloured components. The Panel notes that the JECFA specification for lead is ≤ 2 mg/kg whereas the EC specification is ≤ 10 mg/kg.

The Panel notes that the aluminium lake of the colour could add to the daily intake of aluminium for which a Tolerable Weekly Intake of 1 mg aluminium/kg bw/week has been established and that therefore specifications for the maximum level of aluminium in the lakes may be required.

Keywords

Azorubine, Carmoisine, E 122, CAS 3567-69-9, CI Acid Red 14, CI Food Red 3, food colouring substance, EINECS number 222-657-4