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 provide a scientific opinion re-evaluating the safety of Sunset Yellow FCF (E 110) when used as a food colouring substance.
Sunset Yellow FCF (E 110) is an azo dye allowed as a food additive in the EU and previously evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1982 and the EU Scientific Committee for Food (SCF) in 1984. Both committees established an ADI of 0-2.5 mg/kg bw/day.
The Panel noted that the specifications on the purity of Sunset Yellow FCF permit concentrations of unidentified unsulphonated aromatic amines to be present in concentrations of up to 100 mg/kg Sunset Yellow FCF. Although some aromatic amines may be associated with genotoxicity or even carcinogenicity, the Panel noted that Sunset Yellow FCF was negative in in vitro genotoxicity as well as in long-term carcinogenicity studies.
It is concluded that Sunset Yellow FCF is absorbed from the gastrointestinal tract to only a small extent and thus most of an orally administered dose is excreted via the faeces. As little of the colour was retrieved from the faeces as intact dye, Sunset Yellow FCF is likely to be broken down by intestinal azo-reduction. The urine also predominantly contains azo-reduction products (sulphanilic acid, 1-amino-2-naphtol-6-sulphonic acid, and the N-acetylated forms). Following this observation it is noted that systemic exposure to free sulphonated aromatic amines may occur.
The SCF, JECFA and TemaNord evaluations concluded, based on in vivo and in vitro studies available at that time, that Sunset Yellow FCF did not show any genotoxic activity.
In the Sasaki et al. 2002 publication, an in vivo Comet assay in mice was used to measure DNA damage in various tissues after gavage of Sunset Yellow FCF at a dose of 0, or 2000 mg/kg bw. At 3 hours and 24 hours after Sunset Yellow FCF administration no DNA damage was noted.
The Panel concluded that the potential genotoxicity of Sunset Yellow FCF has been thoroughly researched both in vitro and in vivo, and there are no indications of any genotoxic potential of Sunset Yellow FCF or its metabolites.
Eleven studies considering chronic toxicity and carcinogenicity of Sunset Yellow FCF were included in the JECFA 1982 evaluation. The later evaluations from the SCF and TemaNord do not present additional studies on long-term toxicity and no additional long-term studies were conducted since these previous evaluations were published. Altogether it was concluded by SCF, JECFA and the authors of the TemaNord report that there was no evidence for carcinogenicity of Sunset Yellow FCF.
A study by McCann et al. concluded that exposure in the diet to two mixtures of four synthetic colours plus the preservative sodium benzoate, Mix A and Mix B, both containing Sunset Yellow FCF, resulted in increased hyperactivity in 3-year old and 8- to 9-year old children in the general population. Recently, the EFSA Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) 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 activity and attention in children selected from the general population excluding children medicated for Attention-Deficit/Hyperactivity 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.
Since the previous evaluations of Sunset Yellow FCF by JECFA in 1982 and the SCF in 1984 some new toxicity studies have been reported.
Mathur et al. reported results of a 90 day study on Sunset Yellow FCF in rats at dose levels equivalent to 250 and 1500 mg Sunset Yellow FCF/kg bw/day. There were significant effects on the testes for both dose groups and the Panel concluded that the lowest dose tested is a Lowest Observed Adverse Effect Level (LOAEL). In another paper, Mathur et al. reported significant and dose-related elevations in total lipid and various lipid fractions in rats exposed for 90 days to 250 mg and 1500 mg Sunset Yellow FCF/kg bw/day. These results also revealed a LOAEL of 250 mg/kg bw/day. A LOAEL of 250 mg/kg bw/day is lower than the No Observed Adverse Effect Level (NOAEL) of 500 mg/kg bw from the rat and dog study previously used by JECFA to derive the Acceptable Daily Intake (ADI). The Panel noted however that the Sunset Yellow FCF administered in the studies of Mathur et al. was obtained at the local market in India and that the specifications or purity of this preparation were not defined. The Panel also noted that the 90-day rat study reported by Gaunt and Gangolli and used by JECFA to derive the ADI also reported effects on testes weight. Although in the rat study reported by Gaunt and Gangolli the effects on testes weight were reported to occur without accompanying histological changes, the parameters investigated did not include sperm morphology and sperm mobility. The Panel concluded that all together these findings do give reason for re-definition of the ADI. In the light of the uncertainties the Panel decided to reduce the ADI for Sunset Yellow FCF, by an extra uncertainty factor of 2.5, to 1.0 mg/kg bw/day and make the ADI temporary for 2 years. Within this period clarification of the effects of Sunset Yellow FCF on the testis, sperm morphology and sperm mobility should be provided, based on a 28 day study performed according to the recently updated OECD test guideline 407, including characterisation of testes histopathology, sperm morphology and sperm mobility.
The Panel concluded that while some sensitivity reactions after Sunset Yellow FCF intake have been reported, mostly when Sunset Yellow FCF is taken within mixtures of other synthetic colours, no conclusion on the induction of sensitivity by Sunset Yellow FCF could be drawn from the limited scientific evidence available. The Panel also noted that sensitive individuals may react at dose levels within the ADI.
The dietary exposure to Sunset Yellow FCF was estimated by the Panel based on the Maximum Permitted Levels (MPLs) of use, by applying the Budget method (Tier 1) with the assumptions described in the report of the 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 both for the children and 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 Sunset Yellow FCF, as identified by the Panel from the data made available 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 the children population (aged 1-10 years), estimates have been calculated 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 EU consumers for Sunset Yellow FCF intake estimates.
When considering MPLs (Tier 2), the mean dietary exposure to Sunset Yellow FCF 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 Sunset Yellow FCF of 0.5 mg/kg bw/day to 1.1 mg/kg bw/day for the high level (97.5th percentile) consumers of soft drinks.
When considering the maximum reported use levels (Tier 3), the mean dietary exposure to Sunset Yellow FCF for European children (aged 1-10 years) ranged from 0.2 mg/kg bw/day to 2.1 mg/kg bw/day and from 0.6 mg/kg bw/day to 5.8 mg/kg bw/day at the 95th percentile. Estimates reported for the UK adult population give a mean dietary exposure to Sunset Yellow FCF of 0.3 mg/kg bw/day and of 0.9 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 Sunset Yellow FCF, refined (Tier 3) intake estimates are generally below the temporary ADI of 1 mg/kg bw/day. However, in 1- to 10-year old children the mean and the high percentile of exposure (95th/97.5th) can be 0.2 -2.1 and 0.6-5.8 mg/kg bw/day, respectively, and thus higher than the temporary ADI at the upper end of the range.
The Panel notes that the specifications of Sunset Yellow FCF need to be updated with respect to the level of identified sulphonated subsidiary dyes including the illegal dye Orange II, the level of Sudan I and 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.