Statement on Allura Red AC and other sulphonated mono azo dyes authorised as food and feed additives

Abstract

The ANS Panel has been asked by EFSA to assess the new scientific information that has become available since the adoption of the opinion on the re-evaluation of the food colouring agent Allura Red AC in 2009, in particular the positive findings from an in vivo comet assay in mice. The findings from this study have been interpreted in conjunction with all the available relevant data from genotoxicity testing, metabolism and carcinogenicity, and in consideration of possible species differences between mouse and rat. These new data have been considered in the context of the overall relevant data available not only for Allura Red AC but also for a number of other structurally related sulphonated mono azo dyes authorised as food additives, namely: Amaranth, Ponceau 4R, Sunset Yellow FCF, Tartrazine and Azorubine/Carmoisine. The Panel concluded that the new data by themselves were insufficient at this time to change the conclusions of the 2009 opinion on the safety of Allura Red AC and that there is currently no reason to revise the ADI. The read-across exercise has highlighted a shared pattern of effects for this class of substances that would warrant further investigation The Panel therefore recommended a repetition of the in vivo comet assay in mice, to be performed in compliance with the most recent and internationally validated experimental protocol, using whole cells and examining a wide range of tissues. These recommendations apply to all the sulphonated mono azo dyes included in this review. This request originates from an opinion adopted by the FEEDAP Panel in April 2012 on the reevaluation of the substance for use in feedingstuffs for cats and dogs. In its opinion, the FEEDAP Panel had concluded that the genotoxic potential of Allura Red AC could not be excluded and that the data available were insufficient to demonstrate the safety of the substance for its proposed use.In the context of the re-evaluation of Allura Red AC for use as a food additive, a first positive in vivo comet assay in mice by Tsuda et al. (2001) The ANS Panel critically reviewed the study by Shimada et al. (2010) and noted that these results were observed by a single group of researchers using an in-house developed protocol that uses isolated nuclei from homogenised tissues. Although this protocol was considered to meet the minimum criteria for acceptance of the in vivo comet assay (EFSA, 2012), the Panel noted that such protocol had not been included in the international validation exercise. Under the same experimental conditions, no effect could be observed in the rat. The Panel noted that the same findings observed for Allura Red AC were also reported by Shimada et al. (2010) for the two other authorised food dyes tested in this study, Amaranth and Ponceau 4R.The Panel acknowledged the role of the comet assay as an indicator test for the detection of DNA lesions and/or DNA repair activity and concluded that the findings reported cannot be considered conclusive evidence of mutagenicity, i.e. of induced permanent genetic cha...

Modern methodologies and tools for human hazard assessment of chemicals

“…The hazard characterization step should, where possible, include an assessment of dose-response and an evaluation of uncertainties (WHO, 2009). The apical point occurs at lower dose than other effects and is the basis to identify a Reference Point (RP) such as No-Observed-Adverse-Effect Level (NOAEL), Lowest-Observed-Adverse-Effect-Level (LOAEL) or the lower confidence limit of the Benchmark Dose (BMDL) (EFSA, 2009a(EFSA, , 2013. For a given chemical, the apical endpoint is identified on the dose-response relationship from the pivotal toxicity study in test species (rat, mouse, rabbit, dog).…”

“…It also provides a basis to develop in vitro to in vivo extrapolations (IVIVE) and to predict potential interactions between compounds, which gives a basis to take into account TK interactions for hazard characterisation of multiple compounds (chemical mixtures) (Coecke et al, 2006;Chen et al, 2011;Jayaraman et al, 2011;Kumar et al, 2011;Abass et al, 2013;EFSA, 2013). It also provides a basis to develop in vitro to in vivo extrapolations (IVIVE) and to predict potential interactions between compounds, which gives a basis to take into account TK interactions for hazard characterisation of multiple compounds (chemical mixtures) (Coecke et al, 2006;Chen et al, 2011;Jayaraman et al, 2011;Kumar et al, 2011;Abass et al, 2013;EFSA, 2013).…”

“…Each compartment can also have several sub-compartments consisting of a vascular section, an interstitial space, and a cellular space (Gerlowski and Jain, 1983;EFSA, 2013). The number of compartments varies from model to model, i.e.…”

Safety of Allura Red AC in feed for cats and dogs

“…In the more recent ANS opinion (EFSA ANS Panel, 2013), the new findings were interpreted in conjunction with all the available relevant data from genotoxicity testing, metabolism and carcinogenicity, and in consideration of possible species differences between mouse and rat. These new data were considered in the context of the overall relevant data available not only for Allura Red AC, but also for a number of other structurally related sulphonated mono azo dyes authorised as food additives.…”

“…Instead, the FEEDAP Panel derived safe dietary levels for target animals using a no observed adverse effect level (NOAEL) obtained in toxicity studies with laboratory animals and a default value for body weight to estimate for feed intake (FEEDAP Panel guidance for additives already authorised for use in food (EFSA FEEDAP Panel, 2012c). This NOAEL was derived from studies in rats resulting in a NOAEL of 695 mg/kg body weight per day for growth suppression in pups in a reproduction study and a NOAEL of 701 mg/kg body weight per day for males in a developmental toxicity study (EFSA ANS Panel, 2009, 2013. Applying a safety factor of 100, the highest safe dietary concentration of Allura Red AC was calculated for dogs (default value 15 kg bw and 250 g dry matter intake/day) with 370 mg/kg complete feed and for cats (default value 3 kg bw and 60 g dry matter intake/day) with 308 mg/kg complete feed.…”