Scientific Opinion on the re-evaluation of propionic acid (E 280), sodium propionate (E 281), calcium propionate (E 282) and potassium propionate (E 283) as food additives

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 deliver a scientific opinion re-evaluating propionic acid (E 280), sodium propionate (E 281), calcium propionate (E 282) and potassium propionate (E 283) when used as food additives.

Propionic acid (E 280), sodium propionate (E 281), potassium propionate (E 282) and calcium propionate (E 283) are authorised food additive in accordance with Annex II of Regulation (EC) No 1333/2008 and have been previously evaluated by the EU Scientific Committee for Food (SCF) in 1974 and 1990, and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1973.

The JECFA allocated an acceptable daily intake (ADI) “not limited” for propionic acid and its sodium, potassium and calcium salts considering that propionate is a normal intermediary metabolite and a normal constituent of foods (JECFA, 1974).

In 1974, the SCF concluded that potassium propionate could be added to the list of preservatives permitted to be used in food (SCF, 1975). In 1990, the SCF concluded that there were no adverse health consequences to man from the present uses of propionic acid as a food additive (SCF, 1992). However, the SCF expressed the need to assess comparative studies with other short chain fatty acids and their salts. The SCF established an ADI “not specified”.

Currently, propionic acid - propionates (E 280- 283) are authorised food additives in the EU with maximal permitted levels (MPLs) ranging from 1000 to 3000 mg/kg in foods.

Propionates are naturally occurring substances in the normal diet. Propionic acid is produced by certain bacteria and occurs in various food and feed stuffs as a result of microbial production.

The absorption of short chain fatty acids, including propionate, by the gastrointestinal has been studied both in rats and in humans. The absorption has been described to occur rapidly through the mammalian gastrointestinal tract. The Panel noted that sodium propionate, calcium propionate and potassium propionate will be dissociated in the gastrointestinal tract into propionate and their relevant cations. Therefore, the Panel considered that when assessing systemic (and genotoxic) endpoints, a group evaluation based on the propionate ion was appropriate for propionic acid and its salts. Overall, the ADME data of propionate indicated that oral exposure results in significant absorption. The distribution of the unchanged molecule is unknown whereas radioactivity from orally administered ¹⁴C-sodium propionate is distributed in all organs. Propionate is extensively metabolised with approximately 80 % being oxidised to carbon dioxide and excreted by exhalation.

Investigations on in vivo toxicity of the propionates have shown that acute toxicity is low with oral LD₅₀ values of 351-4290 mg/kg bw in rats. In repeated doses toxicity studies, propionic acid induced acanthosis and hyperkeratosis of the forestomach mucosa of rats at concentrations of 0.62 %. These lesions were not observed after the recovery period. From a 90-day study in dogs, the Panel identified a no observed adverse effect level (NOAEL) of 0.3 % propionic acid in the diet based on epithelial hyperplasia in the oesophagus in the 1% group that had resolved after a recovery period.

The Panel considered that although the number of reliable genotoxicity studies was limited, there was no concern with respect to genotoxicity for propionic acid, calcium propionate and sodium propionate. No genotoxicity data were available for potassium propionate. However, using a read-across approach, the Panel considered that this conclusion was also applicable to potassium propionate.

In long-term studies, forestomach lesions were reported. However, the Panel considered that forestomach hyperplasia in rodents is not a relevant toxicological endpoint for humans because humans lack this organ and there is an absence of a correlation between forestomach in rats and oesophageal lesions in humans. The Panel concluded that the long-term toxicity studies indicated that propionic acid and propionates were not of concern with respect to carcinogenicity.

Studies on reproductive toxicity of propionic acid and its salts were not available, however, in the 90-day studies in dogs and in rats histopathological investigations of the reproductive organs did not reveal any abnormalities. Developmental toxicity was not observed in rodents up to dose levels of 300 or 400 mg/kg bw/day, the highest dose levels tested. At the highest dose tested no maternal toxicity was observed.
For estimates derived using the MPL, mean exposure to propionic acid - propionates from their use as food additives ranged from 0.7-18.9 mg/kg bw/day in toddlers, 1.7-21.1 mg/kg bw/day in children, 1.4-10.9 mg/kg bw/day in adolescents, 1.3-7.8 mg/kg bw/day in adults and 0.8-8.3 mg/kg bw/day in the elderly. The high exposure to propionic acid - propionates using the MPL ranged from 3.6-36.3 mg/kg bw/day in toddlers, 5.5-40.8 mg/kg bw/day in children, 4.6-22.3 mg/kg bw/day in adolescents, 3.8-16.2 mg/kg bw/day in adults and 2.7-16 mg/kg bw/day in the elderly. The Panel noted that exposure estimates using reported use levels were similar to those from the use of MPLs due to the fact that no major differences were reported for food uses by industry.

The Panel estimated the exposure to propionic acid - propionates from others sources as natural food occurrence based on the levels in food reviewed from literature sources and for flavourings substances based on the data reported by JECFA (JECFA, 1998).

Total combined high exposure to propionic acid - propionates from all sources (food additive, flavouring and natural sources) across the five population groups ranged from 3.0 mg/kg bw/day in the elderly to 41.5 mg/kg bw/day in children. The Panel noted that their use as food additives is the major contributor to exposure.

The Panel noted that considering the differences in their respective molecular weights, it would be justified to establish different MPLs for propionic acid and for propionates.

The Panel concluded that the available toxicity database did not allow allocation of an ADI. The Panel considered that the overall exposure and toxicity data available were sufficient to base a risk assessment on a comparison of exposure and concentrations causing site of contact irritation. The Panel noted that in the 90-day study in dogs, 0.3 % propionic acid in the diet, did not provoke site of contact irritancy and this concentration was equal to the highest maximum permitted level of propionic acid - propionates (3000 mg/kg) in food, in the category of bread and rolls. The Panel noted that the concentration provoking site of contact effect in the 90-day study in dogs (1 % propionic acid in the diet) is a factor of three higher than the concentration of propionic acid - propionates in food at the highest permitted level.

Overall, taking into account of all these considerations including the natural occurrence in food, the Panel concluded that for food as consumed, there would not be a safety concern from the maximum concentrations of propionic acid - propionates [propionic acid (E 280), sodium propionate (E 281), calcium propionate (E 282) and potassium propionate (E 283)] at their currently authorised uses and use levels as food additives.

Furthermore, the Panel noted that the specifications for lead are different for propionic acid and its salts and there are specifications for iron and fluoride for the propionic salts but not for the propionic acid. In addition, the Panel further noted that boron trifluoride is used as a catalyst in the manufacturing process of propionic acid and residual amounts of the catalyst could be present in the final product. Therefore, the Panel considered that limits for fluoride and boron should be included in the specifications of propionic acid. The Panel also noted that the pH of a 10 % solution of calcium propionate in the EU specifications (range 6.0 to 9.0) and the JECFA specifications (range 7.5 to 10.5) are different, and the JECFA specifications is in agreement with the one reported in the Food Chemical Codex.