Following a request from the European Commission (EC) to the European Food Safety Authority (EFSA), the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) delivered a scientific opinion reevaluating the safety of β-apo-8′-carotenal (E 160e) when used as a food colour (EFSA ANS Panel, 2012). In this re-evaluation, the ANS Panel used a 13-week study in rats to establish an acceptable daily intake (ADI) of 0.05 mg/kg body weight (bw)/day for β-apo-8′-carotenal (E 160e).
After the publication of the EFSA opinion, the European Commission received new information concerning the interpretation of kidney data from this 13-week study in rats and considered that EFSA implemented new methodology in its exposure assessment. Therefore, the European Commission requested EFSA to reconsider the established ADI and to refine the exposure assessment of its previous opinion.
The Panel was provided with supplementary information on the evaluation of the significance of kidney changes (Hard, 2012), previously observed by Edwards et al (2007) and Perry and Shearer (2008). The Panel evaluated the new report (Hard, 2012) reviewing the significance of eosinophilic droplets in the kidneys of rats of both sexes observed at all dose levels of β-apo-8’-carotenal active ingredient/kg bw/day. The material was most prominent in the cortical tubules of female rats exposed to 100 mg/kg bw/day. Hard (2012) suggested that it was very likely that the eosinophilic material represented accumulation of the test compound or a derivative during normal renal processing. The persistence of a reduced amount of the accumulating material in proximal convoluted tubule cells of the kidneys at the end of the 4-week recovery period indicated that the material was eliminated, but at a relatively slow rate (Hard, 2012). At the high dose of 100 mg/kg bw/day, a rare condition of cell detachments was suspected, accompanied by very occasional mitotic figures, which suggested that the normal ability of the proximal tubule to repair proximal convoluted tubule cells affected by the accumulated material might have marginally been exceeded at this dose. Based on these observations, the author concluded that 30 mg/kg bw/day represented a no observed adverse effect level (NOAEL), since no microscopic evidence of tubule injury was observed at this dose. The Panel agreed with this conclusion.
The Panel concluded that based on the NOAEL of 30 mg/kg bw/day from the 13-week study in rats, in which tubular cell injury was observed at 100 mg/kg bw/day, and using an uncertainty factor of 100, an ADI for β-apo-8’-carotenal of 0.3 mg/kg bw/day was established. The Panel considered an uncertainty factor of 100 as sufficient, not needing an extra adjusting factor due to the pivotal study being a subchronic study (and not a chronic study), given the fact that tubular injury was not observed in the two-year study at 40 mg/kg bw/day, the single dose tested.
Scenarios used for the exposure assessment based on the MPLs or use levels in reported food categories combined with the MPLs for other categories led to an exceedance of the ADI up to 10-20 fold in all population groups, both at mean and high level exposure.
However, a further refined exposure scenario was based only on the limited number of categories where industry reported use levels and analytical data. Exposure estimates using this scenario were below the ADI at the mean level for all population groups. At high level of exposure, the ADI was exceeded for toddlers and children, and the exposure for adolescents was at about the ADI. The Panel considered that this high level exposure estimate was still conservative and concluded that these exceedances are unlikely to occur. The Panel concluded that the uses and use levels of β-apo-8’-carotenal (E 160e), as reported by the food industry, would not be of safety concern.