Following a request from the European Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) of the European Food Safety Authority (EFSA) was asked to re-evaluate sorbic acid (E 200), potassium sorbate (E 202) and calcium sorbate (E 203) when used as food additives.
Sorbic acid (E 200), potassium sorbate (E 202) and calcium sorbate (E 203) are authorised as food additives in accordance with Annex II and Annex III of Regulation (EC) No 1333/2008 and were previously evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1974 and by the Scientific Committee on Food (SCF) in 1996.
JECFA evaluated sorbic acid and its salts in 1961, 1965 and, most recently, in 1973. A group Acceptable Daily Intake (ADI) of 25 mg/kg body weight (bw)/day expressed as sorbic acid was allocated, covering sorbic acid, sodium sorbate, potassium sorbate and calcium sorbate (JECFA, 1974). This ADI was based on a no observed adverse effect level (NOAEL) of 5 % in the diet of rats in a long-term study, equivalent to 2 500 mg/kg bw/day.
Based on studies originally evaluated by JECFA (1974), as well as more recent studies, the SCF endorsed the group ADI of 25 mg/kg bw/day for sorbic acid, potassium sorbate and calcium sorbate allocated by JECFA. The SCF noted that there were no toxicological studies on calcium sorbate, but nevertheless included this substance in the group ADI (SCF, 1996).
The Panel considered that data available on the absorption, distribution, metabolism and excretion of sorbic acid show that sorbic acid is absorbed and mainly excreted as expired carbon dioxide. As no data on bioavailability were available on potassium sorbate and calcium sorbate, the Panel considered that, owing to the ionisation properties of sorbic acid (pKa = 4.76), the unionised forms of these sorbates are absorbed by a diffusion process in the stomach. Potassium and calcium sorbate might dissociate into their constituents—potassium, calcium and sorbate ions—in the small intestine. Accordingly, sorbate from potassium or calcium sorbate should be bioavailable and absorbed in the same manner as from sorbic acid. The calcium and potassium ions are expected to enter normal homeostatic processes and are not expected to have an impact on the toxicity of the salts. Thus, the properties of the cations are not discussed further in the opinion.
Short-term and sub-chronic toxicity studies performed in rats and mice did not show any adverse effects at the concentrations tested (up to 9 200 mg/kg bw/day in rats).
Sorbic acid and potassium sorbate were investigated in in vitro and in vivo genotoxicity assays. Overall, the Panel considered that the database was sufficiently robust and that there was no evidence of genotoxic activity for sorbic acid or potassium sorbate. The Panel noted that no data on genotoxicity were available for calcium sorbate. The Panel considered that read-across from sorbic acid and potassium sorbate data on genotoxicity to calcium sorbate would be theoretically possible. However, given the available positive genotoxicity data on sodium sorbate (as reported by the SCF (1996)), the Panel considered that genotoxicity data on calcium sorbate are needed.
The Panel also noted that potential reaction products that may result from the interaction of sorbic acid with nitrites and with ascorbic acid in the presence of iron salts were demonstrated to be mutagenic in vitro and that there are certain food categories for which the use of these food additives (sorbic acid with ascorbic acid in the presence of iron salts or sorbic acid with nitrites) is permitted in parallel. However, these reaction products have been shown to be formed under optimal experimental conditions in an aqueous environment only and may not be formed to any major extent in food matrices.
The Panel also noted that the major reaction products resulting from the interaction of sorbic acid with different amines (e.g. methylamine, ethylamine, propylamine, butylamine and benzylamine) were not mutagenic in the bacterial reverse mutation assay.
Five long-term/carcinogenicity toxicity studies performed before 1976 were available, but more recent studies have not been identified in the literature. The Panel revisited all the relevant original reports and publications, except the Lang et al. (1967) study used to allocate the ADI by JECFA (1974), which was not available.
A two-generation reproductive toxicity study was performed in CD/Crl:CD rats in accordance with the Organisation for Economic Co-operation and Development (OECD) Guideline 416 and Good Laboratory Practice (GLP). Sorbic acid was administered by gavage at a dose of 0, 300, 1 000 or 3 000 mg/kg bw/day. Several adverse effects were described in pups, such as a decrease in mean litter body weight, milestones of physical development in F1 pups, a delay in functional development in F1 pups and a decrease in anogenital distance in male F2 pups in the mid- and high-dose groups. Considering the aforementioned observations, the Panel concluded that, by gavage, the NOAEL for developmental toxicity is 300 mg/kg bw/day. Furthermore, the Panel noted that, by gavage, the NOAEL for parental toxicity is 1 000 mg/kg bw/day based on effects on body weights of the parental male animals.
In a developmental toxicity study performed in rabbits in accordance with OECD Guideline 414 and GLP at doses of 0 (control), 300, 1 000 or 3 000 mg sorbic acid/kg bw/day by gavage from day 6 to 29 of gestation, maternal and fetal toxicity were observed in the mid- and high-dose groups. The Panel considered that the maternal NOAEL was 300 mg sorbic acid/kg bw/day and the NOAEL for the fetuses was also 300 mg sorbic acid/kg bw/day.
Given the lack of genotoxicity data on calcium sorbate and the available positive genotoxicity data on sodium sorbate, the Panel concluded that calcium sorbate should be excluded from the group ADI.
The Panel concluded that the present dataset on reproductive and developmental toxicity gives a reason to revise the group ADI of 25 mg/kg bw/day set by the SCF in 1996. The Panel considered that the NOAEL of 300 mg sorbic acid/kg bw/day from the two-generation reproductive toxicity study in rats can be used to allocate a temporary group ADI for sorbic acid and its potassium salt. By applying an uncertainty factor of 100, the Panel established a new temporary group ADI expressed as 3 mg sorbic acid/kg bw/day for sorbic acid (E 200) and potassium sorbate (E 202).
Exposure assessments to sorbic acid – sorbates (E 200, 202, 203) were carried out by the ANS Panel based on (1) maximum permitted levels (MPLs) set out in the European Union (EU) legislation (defined as the regulatory maximum level exposure assessment scenario) and (2) usage or analytical data (defined as the refined exposure assessment scenario).
Using the regulatory maximum level exposure assessment scenario, the Panel noted that this exposure estimate of sorbic acid – sorbates (E 200, 202, 203) exceeded the temporary group ADI of 3 mg/kg bw/day for all population groups at the mean and high levels. The main contributing food categories to the total mean exposure estimates for children, adolescents and adults in this scenario were bread and rolls, fine bakery wares and flavoured drinks. For the elderly, the main contributing food categories were bread and rolls and fine bakery wares, while, for toddlers, the main contributing food categories were bread and rolls, fine bakery wares and processed cheese.
From the refined estimated exposure scenario usingonly reported use levels, the Panel noted that the refined brand-loyal and non-brand-loyal exposure estimates exceeded the temporary group ADI of 3 mg/kg bw/day for all population groups at the mean and high levels. The main contributing food categories for all groups were bread and rolls and fine bakery wares.
From the refined estimated exposure scenario usingreported use levels and analytical data, the Panel noted that, for the refined brand-loyal exposure estimate, all population groups exceeded the temporary group ADI of 3 mg/kg bw/day at the mean and high levels (95th percentile), whilst, for the non-brand-loyal scenario, the temporary group ADI was exceeded in only toddler and children population groups in one country. The main contributing food categories for all groups were bread and rolls and fine bakery wares in the brand-loyal scenario and bread and rolls, fine bakery wares, flavoured drinks and sauces in the non-brand-loyal scenario.
The Panel noted that the most realistic approach using reported use levels and analytical data in the non-brand-loyal scenario did not exceed the temporary group ADI in any population group at the mean or in adolescents, adults and the elderly at the high level, except in the toddler and children population groups in one country. The Panel noted that, in these estimates, the main food contributors were bread and rolls, fine bakery wares and flavoured drinks.
The Panel also recommended that:
- genotoxicity studies on calcium sorbate need to be performed in order to consider including calcium sorbate in the group ADI;
- an extended one-generation reproductive toxicity study in rats including the second generation by diet needs to be performed in order to reconsider the temporary group ADI;
- if divalent transition metals are used as catalysts in the manufacturing process of sorbic acid, maximum residual levels of divalent transition metals should be included in the EC specifications for sorbic acid (E 200);
- the maximum limits for the impurities of toxic elements (lead, mercury and arsenic) in the EC specification for sorbic acid and its salts (E 200, 202, 203) should be revised in order to ascertain that sorbic acid – sorbates (E 200, 202, 203) as food additives will not be a significant source of exposure to those toxic elements in food;
- future research be performed on the occurrence of breakdown and reaction products of possible toxicological concern under realistic conditions of food processing and storage—especially when sorbic acid, potassium sorbate or calcium sorbate is used in parallel with ascorbic acid in the presence of iron salts or with nitrites.