In 2009 the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) has adopted a scientific opinion on the re-evaluation of Sunset Yellow FCF (E 110) as a food additive in the EU. In its opinion, the ANS Panel established a temporary acceptable daily intake (tADI) of 1 mg/kg bw/day and requested a 28-day study with Sunset Yellow FCF to be performed in accordance with OECD guidelines and with well-defined material, in order to clarify the histopathological changes in the testes and the changes in the blood lipid profile observed by Mathur el al. (2005a, 2005b) in rats, after 90-day dietary exposure to Sunset Yellow FCF at dose levels equivalent to 250 and 1 500 mg/kg bw/day.
Following a request from the European Commission, the ANS Panel was asked to deliver a scientific opinion on the data generated from a 28-day study conducted as a result of the recommendations contained in the 2009 opinion and whether, on the grounds of these new data, the ADI should be reconsidered.
Furthermore, following the conclusions of the 2009 opinion as regards exposure to Sunset Yellow FCF (E 110), EFSA was requested to carry out a refined exposure assessment for this food additive. In that opinion, the ANS Panel had evaluated the exposure to Sunset Yellow FCF (E 110) on the basis of the uses and use levels authorised in the legislation and the reported use levels as provided by industry, and concluded that at the maximum reported levels of use of Sunset Yellow FCF, refined intake estimates were generally below the temporary ADI of 1 mg/kg bw/day. However, in 1- to 10-year old children, the mean and the high percentiles of exposure could be higher than this temporary ADI, at the upper end of the range.
The ANS Panel noted that since the publication of its scientific opinion on the re-evaluation of Sunset Yellow FCF for use as a food additive in 2009, an updated evaluation has been completed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2011 (JECFA, 2011). In its latest evaluation, JECFA concluded that the ADI for Sunset Yellow FCF should be increased from 2.5 mg/kg bw/day to 4 mg/kg bw/day. Thus, the ANS Panel considered that, in order to fulfil the current mandate, the latest evaluation performed by JECFA in 2011 was also to be taken into account for the setting of an ADI for this food colour, alongside any other relevant publications that might have become available since the publication of the previous scientific opinion.
The ANS Panel considered the results from a dietary 28-day study in male Hsd:SD® rats performed by Product Safety Labs (2012) using levels of Sunset Yellow FCF up to 18 000 mg/kg diet (equivalent to 1 475 mg/kg bw/day), and performed according to the current OECD guidelines, and concluded that the findings reported by Mathur et al. (2005a, 2005b) on lipid profile and testes histopathology were not confirmed. The Panel agreed with the authors of the 28-day study that the NOAEL of this study was 18 000 mg/kg diet (equivalent to 1 475 mg/kg bw/day), the highest dose level tested. The Panel noted that the material tested in this 28-day study met the EU specifications for Sunset Yellow FCF as a food additive. The Panel, based on the data described in its 2009 opinion and the results from this new 28-day study, concluded that the findings of the Mathur studies (2005a, 2005b) should be disregarded for the risk assessment of Sunset Yellow FCF.
The ANS Panel also evaluated one unpublished long-term feeding study in mice and two studies in rats provided by the United States Food and Drug Administration (FDA), which had also been considered by JECFA in its latest evaluation from 2011. In the light of the data from these long-term feeding studies, the ANS Panel concluded that no carcinogenic potential of Sunset Yellow FCF was observed in mice and rats. Based on the occurrence of the adverse effect on pup body weight gain, observed during the last part of the lactation in a long-term rat study in the group fed 1.5 % FD&C Yellow No. 6 (Sunset Yellow FCF) in the diet, and described in the full reports provided by the FDA, the Panel agreed with JECFA that the NOAEL for this study was 0.75 % (equivalent to 375 mg/kg bw/day). The Panel considered that, this NOAEL being obtained from a long-term study including an in utero phase, an uncertainty factor of 100 can be applied for the derivation of a new ADI of 4 mg/kg bw/day.
Lastly, the results of an extensive literature search performed on three electronic databases (PubMed, Web of Science and Toxnet) and covering the time span between approximately one year before the adoption of the opinion on the re-evaluation of Sunset Yellow FCF (i.e. from 1 November 2008) until 31 December 2013, aiming to retrieve any additional relevant toxicological data, was reviewed by the ANS Panel.
The safety of Sunset Yellow FCF, with particular respect to the data on its metabolism, genotoxicity and carcinogenicity, had already been reviewed by the ANS Panel in the context of the recent assessment of Allura Red AC and other structurally related sulphonated mono azo dyes (EFSA ANS Panel, 2013). The additional extensive literature search did not reveal any new data in addition to those already considered in this statement.
A study was carried out to investigate the effect of oral administration of Amaranth, Sunset Yellow FCF and Curcumin on immunological responses (Hashem et al., 2010). Sunset Yellow FCF (315 mg/kg bw/day) was administered by gavage to female Sprague Dawley albino rats for 4 weeks. The authors stated that Sunset Yellow used at dose of 315 mg/kg bw/day exerted a depressing effect on the cellular, but not humoral, immune response. The Panel noted that this study was conducted with locally sourced uncharacterised material of unknown purity and did not consider this study suitable for risk assessment.
Oestrogenic activity of Sunset Yellow FCF was demonstrated in an in vitro model system (Axon et al., 2012). According to EFSA’s Scientific Opinion on the hazard assessment of endocrine disruptors (EFSA SC, 2013) “the fact that a substance in an in vitro assay is binding to an endocrine receptor, then interfering with the intracellular messenger system connecting receptor to target or resulting in an endocrine-related response in a target cell, must be taken as strong indication for endocrine activity. If a suitable animal model provides further indication for an endocrine-related adverse effect, this substance should be considered an endocrine disruptor”. However, in long-term studies including an in utero phase in mice and rats, no effects on endocrine and reproductive organs were observed. Therefore, the results of this in vitro study were not further considered in the risk assessment.
In conclusion, the newly submitted data from the 28-day toxicity study and the overall available toxicological database on Sunset Yellow, including long-term studies, provides a basis to revise the established temporary ADI. Based on the NOAEL of 375 mg/kg bw/day from the long-term feeding study in rats and an uncertainty factor of 100, a new ADI for Sunset Yellow FCF of 4 mg/kg bw/day was established.
A refined exposure assessment for Sunset Yellow FCF (E 110) has been performed taking into consideration the Maximum Permitted Levels (MPLs) of use currently authorised in Annex II of Regulation (EC) No 1333/2008.
Overall, exposure estimates for Sunset Yellow FCF (E 110) based on the currently authorised MPLs of use in foods are well below the new ADI of 4 mg/kg bw/day established by the ANS Panel, for all population groups. This is due both to the fact that MPLs for Sunset Yellow FCF were largely decreased, following the amendment of the legislation in 2013, and to a more refined exposure assessment being performed, taking into account the restrictions/exceptions listed in Annex II of Regulation (EC) No 1333/2008 and the use of the EFSA Comprehensive Database (FoodEx) system.
It should be noted that in 2012, further to the amendment of Annex II of Regulation (EC) No 1333/2008 as regards the conditions of use and the use levels for Sunset Yellow FCF (E 110) , MPLs were either withdrawn or decreased by a factor of 2 to 30. Updated information on the actual use levels of Sunset Yellow FCF in foods was made available by the industry for few of the food categories in which this food additive is authorised. In addition, concentration data on Sunset Yellow FCF in foods were provided by Member States. These data were in their majority collected before June 2013. Nevertheless, in the absence of more recent data, these data were also considered for the refined exposure assessment scenario, provided that the values were below the currently authorised MPLs of use of Sunset Yellow FCF.
The Panel noted that the results of the present exposure estimates for Sunset Yellow FCF based both on the currently authorised MPLs and reported use levels are well below the new ADI of 4 mg/kg bw/day for all population groups. The exposure results are much lower compared to the ones from the exposure assessment performed by the ANS Panel in 2009 (EFSA ANS Panel, 2009) for all population groups. For children and toddlers, the present results are of the same magnitude when compared with the exposure estimates obtained in the refined exposure assessment of Sunset Yellow FCF (E 110) performed by EFSA in 2011.
Overall, the Panel concluded that using data provided by the food industry and Member states, the reported uses and use levels of Sunset Yellow FCF (E 110) would not be of safety concern.