What is potassium sorbate

Potassium sorbate is the common name for potassium (2E,4E)-2,4-hexadienoate ¹⁾. The predominant use of potassium sorbate is as food additive (E 202) as mold and yeast inhibitor. Potassium sorbate (E 202) is used as a antimicrobial and fungistatic agent and preservative in foods, especially cheeses (unripened, ripened and whey cheese and cheese products), citrus fruits, chewing gum, processed potato products, potato gnocchi, meat pâté, processed meat, processed fish, processed eggs (dehydrated and concentrated frozen eggs), table-top sweeteners in liquid form, protein products, dietary foods for weight control, salads, fruit nectars, beer, wine, fruit wine and made wine, mead, aromatised wines and aromatised wine-based drinks and cocktails, potato-, cereal-, flour- or starch-based snacks, desserts and food supplements and processed nuts. Potassium sorbate has been also used as medication and in cosmetics and pharmaceuticals. Potassium sorbate is also approved as a biocidal active substance ²⁾.

Data on the potential for potassium sorbate to cause adverse effects in humans are limited to a few cases of skin irritation. Due to its long history as a food additive with no apparent toxic effects, and lack of toxic effects in laboratory animals fed low-to-moderate doses, the U.S. Food and Drug Administration considers potassium sorbate a “GRAS” (generally recognized as safe) food additive ³⁾. Therefore, it is not expected to cause any toxicity in humans at levels found in food. No irritation to eyes or skin was observed in laboratory animals following direct contact with potassium sorbate. Nasal irritation and lesions were observed in laboratory animals following repeated application of solutions containing low-to-moderate levels of potassium sorbate directly to the nasal mucosa. No birth defects developed in offspring of laboratory animals fed high doses of potassium sorbate. Data on the potential for potassium sorbate to cause reproductive effects were not available. No tumors were induced in laboratory animals following life-time exposure to moderate-to-high levels of potassium sorbate or its breakdown product sorbic acid. Increased liver tumors were observed in laboratory animals fed an extremely high dose of sorbic acid over time. The potential for potassium sorbate to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, or the U.S. National Toxicology Program 14th Report on Carcinogens.

Sorbic acid is absorbed and mainly excreted as expired carbon dioxide. The European Food Safety Authority Panel noted that there was no evidence of genotoxic activity for sorbic acid or potassium sorbate ⁴⁾. Sub-acute, sub-chronic and chronic toxicity studies did not show any adverse effects at concentrations up to 9,200 mg/kg body weigh per day in rats. The Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (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 per day expressed as sorbic acid was allocated, covering sorbic acid, sodium sorbate, potassium sorbate and calcium sorbate ⁵⁾. An acceptable daily intake (ADI) is the maximum amount considered safe to consume each day over the course of your lifetime. This acceptable daily intake (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 body weight per day. Based on studies originally evaluated by JECFA ⁶⁾, as well as more recent studies, the Scientific Committee for Food endorsed the group acceptable daily intake (ADI) of 25 mg/kg body weight per day for sorbic acid, potassium sorbate and calcium sorbate allocated by JECFA. The Scientific Committee for Food noted that there were no toxicological studies on calcium sorbate, but nevertheless included this substance in the group ADI ⁷⁾

The European Food Safety Authority Panel concluded that the present dataset on reproductive and developmental toxicity gives a reason to revise the group acceptable daily intake (ADI) of 25 mg/kg body weight per day set by the Scientific Committee on Food in 1996. The European Food Safety Authority Panel considered that the no observed adverse effect level of 300 mg sorbic acid/kg body weight per day from the two-generation reproductive toxicity study in rats can be used to allocate a temporary group acceptable daily intake (ADI) for sorbic acid and its potassium salt. By applying an uncertainty factor of 100, as a food additive, the European Food Safety Authority Panel established a new temporary group acceptable daily intake (ADI) expressed as 3 mg/kg body weight per day for sorbic acid and its potassium salt ⁸⁾. The European Food Safety Authority 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 acceptable daily intake (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.

Potassium sorbate is an important commercial chemical that is used as a preservative and antibacterial in food. The toxicological profile of potassium sorbate has been assessed at European Union level as a food additive and biocide ⁹⁾. As biocide ¹⁰⁾, the Rapporteur Member State Germany set an acceptable exposure level of 13.4 mg/kg body weight per day ¹¹⁾. Committee for Risk Assessment – European Chemical Agency ¹²⁾ proposed classification and labeling of potassium sorbate as eye irritant category 2. Under the current intended uses as a plant protection product in order to prevent any exposure to operators, workers, bystanders and residents authorization should be limited to indoor treatment of fruits with a closed drenching system.

Is potassium sorbate safe?

Human Toxicity Studies

The European Food Safety Authority 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 European Food Safety Authority Panel considered that, owing to the ionisation properties of sorbic acid, the unionized 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.

Sorbic acid is readily metabolized. Both man and rat appear to utilize identical metabolic mechanisms for oxidation of sorbate. The long-term studies suggest that the same no-effect level applies to the salts as to the free acid. Sorbic acid and potassium sorbate corresponding to the specifications do not cause tumors when administered orally or subcutaneously ¹³⁾. Level causing no toxicological effect in rats 50 000 ppm (5%) in the diet, equivalent to 2500 mg/kg body weight per day. Estimate of acceptable daily intake for man 0-25 mg/kg body weight as sum of sorbic acid and calcium, potassium and sodium sorbate (expressed as sorbic acid).

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 body weight per day in rats).

Sorbic acid and potassium sorbate were investigated in in vitro and in vivo genotoxicity assays. Overall, the European Food Safety Authority Panel considered that the database was sufficiently robust and that there was no evidence of genotoxic activity for sorbic acid or potassium sorbate ¹⁴⁾. The Panel noted that no data on genotoxicity were available for calcium sorbate. The European Food Safety Authority 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 ¹⁵⁾, the European Food Safety Authority Panel considered that genotoxicity data on calcium sorbate are needed ¹⁶⁾.

The European Food Safety Authority 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 ¹⁷⁾.

The European Food Safety Authority 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 ¹⁸⁾.

Five long-term/carcinogenicity toxicity studies performed before 1976 were available, but more recent studies have not been identified in the literature. The European Food Safety Authority Panel revisited all the relevant original reports and publications used to allocate the ADI by JECFA ¹⁹⁾.

A two-generation reproductive toxicity study was performed in CD/Crl:CD rats in accordance with the Organization 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 body weight 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 (no-observed-adverse-effect) for developmental toxicity is 300 mg/kg body weight per day. Furthermore, the Panel noted that, by gavage, the NOAEL (no-observed-adverse-effect) for parental toxicity is 1,000 mg/kg body weight per 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 body weight per day by gavage from day 6 to 29 of gestation, maternal and fetal toxicity were observed in the mid- and high-dose groups. The European Food Safety Authority Panel considered that the maternal NOAEL was 300 mg sorbic acid/kg body weight per day and the NOAEL for the fetuses was also 300 mg sorbic acid/kg body weight per day.

Given the lack of genotoxicity data on calcium sorbate and the available positive genotoxicity data on sodium sorbate, the European Food Safety Authority Panel concluded that calcium sorbate should be excluded from the group acceptable daily intake (ADI).

The European Food Safety Authority Panel concluded that the present dataset on reproductive and developmental toxicity gives a reason to revise the group acceptable daily intake (ADI) of 25 mg/kg body weight per day set by the Scientific Committee on Food in 1996. The European Food Safety Authority Panel considered that the NOAEL of 300 mg sorbic acid/kg body weight per 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 European Food Safety Authority Panel established a new temporary group ADI expressed as 3 mg sorbic acid/kg body weight per day for sorbic acid (E 200) and potassium sorbate (E 202).

Using the regulatory maximum level exposure assessment scenario, the European Food Safety Authority Panel noted that this exposure estimate of sorbic acid – sorbates [sorbic acid (E 200) and its salts [potassium sorbate (E 202) and calcium sorbate (E 203)] exceeded the temporary group acceptable daily intake (ADI) of 3 mg/kg body weight per 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 flavored 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 using only reported use levels, the European Food Safety Authority Panel noted that the refined brand-loyal and non-brand-loyal exposure estimates exceeded the temporary group acceptable daily intake (ADI) of 3 mg/kg body weight per 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.

The European Food Safety Authority 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 acceptable daily intake (ADI) of 3 mg/kg body weight per day 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 European Food Safety Authority Panel noted that, in these estimates, the main food contributors were bread and rolls, fine bakery wares and flavored drinks.

Genotoxicity studies

Potassium sorbate, sodium benzoate and potassium nitrate have been tested for their genotoxic, cytostatic and cytotoxic potential in human peripheral blood cells in vitro ²⁰⁾. Potassium nitrate has shown no activity in the test system. When potassium sorbate and sodium benzoate were used at concentrations of 2.0, 0.2 and 0.02 mM no cytostatic activity was detected ²¹⁾. However, concentrations of 4 and 8 mM have shown a weak cytostaticity. Additionally, a genotoxic activity using the sister chromatid exchanges (SCE) methodology has been observed at 8 mM of sodium benzoate and at 4 and 8 mM of potassium sorbate. No cytotoxic activity has been induced by the three preservatives. Data demonstrate that the preservatives at low concentrations can be considered as non genotoxic under conditions tested ²²⁾.

The genotoxic potential of sorbic acid and potassium sorbate was investigated in vivo and in vitro. Oral administration of sorbic acid (up to 5000 mg/kg body weight) did not induce sister chromatid exchanges or the formation of micronuclei in bone marrow cells of mice ²³⁾. Intraperitoneal treatment of rats with 400-1200 mg potassium sorbate/kg body weight did not alter the elution profile of DNA from isolated liver cells in the in vivo alkaline elution assay. Sorbic acid did not induce DNA repair in cultured human A549 cells in the unscheduled DNA synthesis (UDS) assay. In vitro incubation of the cells with 1-1000 ug potassium sorbate/mL, in the absence or presence of rat liver homogenate, did not result in the formation of DNA single-strand breaks in the alkaline elution assay. These results demonstrate that sorbic acid and its potassium salt are not genotoxic in vivo or in vitro. In contrast to sorbic acid and potassium sorbate, sodium sorbate is very sensitive to oxidative degradation; the main oxidation product was identified to be 4,5-oxohexenoate, which was mutagenic in the Ames test ²⁴⁾.

Human skin studies

In three repeat insult patch tests using a total of 478 subjects, sorbic acid had overall sensitization rates of 0, 0.33, and 0.8%. All the subjects sensitized were inducted with 20% sorbic acid and challenged with 5% sorbic acid. Formulations containing up to 0.5% sorbic acid or 0.15% potassium sorbate were not cumulative irritants or were very mild cumulative irritants ²⁵⁾. They were not primary irritants and were not sensitizers ²⁶⁾.

A RIPT (Repeat Insult Patch Test) to determine irritation and sensitization potential of potassium sorbate was conducted using 56 panelists and a facial scrub containing 0.1% potassium sorbate ²⁷⁾. The formulation was diluted 1 :I00 by weight with distilled water for the study. Eight 24 hr semiocclusive induction patches were applied over a 2 week period to the lateral upper arm of each subject. Reactions were scored at patch removal. After an approximately 2 week rest period, a 24 hr semiocclusive challenge patch was applied to a previously untreated site. Reactions to the challenge patch were graded at patch removal and 24 and 48 hr later. Two slight, transient, questionable erythema reactions were observed during induction ²⁸⁾. No other reactions were observed during induction or challenge. The facial scrub did not induce dermal irritation or sensitization.

The skin irritation and sensitization potential of a facial scrub containing 0.1% potassium sorbate was evaluated in a RIPT (Repeat Insult Patch Test) to determine irritation and sensitization potential of potassium sorbate with 47 panelists ²⁹⁾. The formulation was diluted 1 :I00 in distilled water. Eight 24 hr semiocclusive induction patches were applied to the lateral aspect of the upper arms of the subjects over a 2 week period, and reactions were scored on a scale of O-5 at patch removal. After a 2 week rest period, a 24 hour semiocclusive challenge patch was applied, and reactions were scored at patch removal and 24 and 48 hour later. No reactions greater than 2 (moderate erythema) were observed during the induction period, and no reactions at challenge were indicative of sensitization ³⁰⁾.

In vitro tests

The objective of this study was to measure the influence of topical steroids and the preservative potassium sorbate on the ciliary beat frequency of human nasal mucosa in vitro ³¹⁾. In vitro study of cultured ciliated cells of human nasal mucosa. Human nasal mucosa was removed endoscopically and cultured for 10 days. Cell cultures with ciliated cells grown on an object slide were exposed to benzalkonium chloride and topical steroids in an exposure chamber. The ciliary beat frequency was measured with a photometer. The preservative potassium sorbate did not influence ciliary beat frequency in different concentrations. The glucocorticoid budesonide spray containing potassium sorbate did not affect ciliary beat frequency at 10% dilution and showed moderate reversible decrease of ciliary beat frequency at 50% dilution. The glucocorticoid sprays fluticasone propionate and mometasone fuorate containing the preservative benzalkonium chloride caused a reversible decrease of ciliary beat frequency at 10% dilution and a complete irreversible standstill at 50% dilution. In vitro, the steroid sprays containing fluticasone or mometasone, both with benzalkonium chloride, caused slowing or standstill of ciliary beat frequency depending on the concentration. The isolated preservative potassium sorbate and the budesonide nasal spray containing this preservative did not have negative influence on ciliary beat frequency in vitro. Potassium sorbate can therefore be considered harmless to the motility of ciliated cells ³²⁾.

Other toxicity information

In humans, a few cases of idiosyncratic intolerances have been reported (non-immunological contact urticaria and pseudo-allergy) ³³⁾. The frequency appears low but there are too few reported data for an accurate assessment of the true incidence. In extreme conditions (high concentrations and temperature) sorbic acid may react with nitrite to form mutagenic products but these mutagens are not detectable under normal conditions of use, even in curing brines ³⁴⁾.

Based on these considerations the FDA’s Select Committee on GRAS Substances (SCOGS) concludes that:

“There is no evidence in the available information on sorbic acid and its sodium, potassium and calcium salts that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future” ³⁵⁾.

• Potassium sorbate used as a chemical preservative in food for human consumption is generally recognized as safe when used in accordance with good manufacturing practice ³⁶⁾.

• Potassium sorbate used as a chemical preservative in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice ³⁷⁾.

• Substances migrating to food from paper and paperboard products used in food packaging that are generally recognized as safe for their intended use, within section 409 of the Act. Potassium sorbate is included on this list ³⁸⁾.

The European Food Safety Authority Panel recommended that:

• genotoxicity studies on calcium sorbate need to be performed in order to consider including calcium sorbate in the group acceptable daily intake (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 acceptable daily intake (ADI) 3 mg/kg body weight per day for sorbic acid and its potassium salt;
• 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 (E 200) and its salts [potassium sorbate (E 202) and calcium sorbate (E 203)] should be revised in order to ascertain that sorbic acid – sorbates [sorbic acid (E 200) and its salts [potassium sorbate (E 202) and calcium sorbate (E 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.

Potassium sorbate side effects

Hypersensitivity, allergenicity and intolerance

Out of 20 children exposed to mayonnaise dressing preserved with potassium sorbate (0.11 %), 18 developed perioral urticaria, which was considered as a contact dermatitis induced by sorbates in the oral mucosa. The authors considered that this reaction was not of immunological origin ³⁹⁾. In 90 persons, there were concentration-dependent reactions to sorbic acid solutions after a closed patch test. At the lowest dose (0.1 %), there was a reaction in 20 % of the participants; at a dose of 1 %, there was a reaction in 62 % of the participants; and, at the highest dose (5 %), there was a reaction in 65 % of the test persons. The skin reaction could not be reproduced on the oral mucosal surface after application of 5 or 10 % sorbic acid in water ⁴⁰⁾.