Absorption, Distribution and Excretion
Following oral administration of radiolabeled sorbic acid, the total radioactive recovery rate was approximately 100% in both the low-dose and high-dose groups. The primary metabolic pathway of sorbic acid is via exhaled carbon dioxide; approximately 85% of the radioactive material is excreted as carbon dioxide within 4–10 hours after administration. Based on the rate and extent of this metabolism, it can be concluded that sorbic acid is rapidly and quantitatively absorbed in the gastrointestinal tract. Metabolism/Metabolites The metabolism of sorbic acid in rats is the same as that of normally occurring fatty acids. Under normal intake conditions, sorbic acid is almost completely oxidized to carbon dioxide and water. Trace amounts (0.1% dose) can be oxidized to trans-,trans-mucoconic acid. 1,4-Dinitro-2-methylpyrrole is a mutagenic product formed by the interaction of two common food additives, sorbic acid and sodium nitrite. It can be converted to 1-nitro-2-methyl-4-aminopyrrole by human fecal mixtures and various intestinal bacterial strains. Following oral administration of radiolabeled sorbic acid, the overall radioactivity recovery rate was approximately 100% for both low and high doses. The primary metabolic pathway of sorbic acid is via exhaled carbon dioxide, with approximately 85% of the administered radioactivity recovered as carbon dioxide within 4–10 hours. Based on the rate and extent of this metabolism, it can be concluded that sorbic acid is rapidly and quantitatively absorbed in the gastrointestinal tract.

Toxicity Summary
Identification and Uses: Sorbic acid is a white crystalline solid or powder. It is used as an intermediate in plasticizers and lubricants. Additionally, it is used as a preservative and antibacterial agent in food, cosmetics, and pharmaceuticals. It is used to improve the properties of drying oils. In alkyd coatings, it is used to increase gloss. It is used to improve the abrasive properties of cold glue. Human Exposure and Toxicity: Applying 150 mg of sorbic acid to human skin for 1 hour can cause severe irritation. In a reported study of 606 patients with suspected contact dermatitis, 5 underwent testing with sorbic acid (2.5% petrolatum solution) over a 3-year period, and all 5 patients developed allergic reactions. Allergic contact dermatitis caused by sorbic acid most commonly occurs after the use of topical medications containing this preservative (such as corticosteroid creams). Merck Ointment reported 25 cases of contact dermatitis, most of which were caused by sorbic acid. Sorbic acid can also cause stinging and non-immune contact urticaria reactions. Among 135 patients, 15% experienced eye irritation after using a hydrogel contact lens care system containing 0.10% sorbic acid. Genotoxicity studies using HeLa cells and plasmid DNA did not reveal mutagenicity or genotoxicity. Animal studies: Sorbic acid applied semi-occlusively to intact skin in three rabbits for 4 hours did not cause erythema or edema. At a concentration of 0.1 M, sorbic acid was non-irritating or non-sensitizing to guinea pig skin. However, applying 1 mg of sorbic acid to rabbit skin showed strong irritation. In tissue culture, 0.1% sorbic acid reduced the proliferation and survival rate of rabbit corneal epithelial cells. No adverse reactions were observed in rats fed diets containing 1%, 2%, 4%, and 8% sorbic acid for 90 days. Similarly, no adverse reactions were observed in puppies fed diets containing 4% sorbic acid for 90 days. Feeding male and female mice with diets containing 1%, 5%, or 10% sorbic acid for 80 weeks, and male and female rats with diets containing 0%, 1.5%, or 10% sorbic acid for 2 years, did not increase mortality or the incidence of spontaneous histological lesions (including tumors). However, mice fed a diet containing 15% sorbic acid for 88 weeks had a higher incidence of hepatocellular carcinoma. Hepatocellular carcinoma in mice fed a diet containing 15% sorbic acid is thought to be caused by chronic depletion of glutathione in the liver and the gradual production of various promutogens in the gut, which are absorbed and metabolically activated by the liver. No adverse effects on blood or visceral organs were observed after long-term feeding of rats, guinea pigs, rabbits, and dogs at doses ranging from 1 to 500 times the food intake. In rabbit developmental studies, no treatment-related maternal or developmental effects were observed at a dose of 300 mg/kg body weight/day. Maternal effects in the intermediate-dose group included increased respiratory rate, decreased weight gain, and rough spleen surface after administration. High-dose female maternal outcomes included increased respiratory rate, death, abortion, decreased body weight and weight gain, significantly reduced food intake, and post-mortem pathological findings (rough spleen surface and reduced spleen size). In the medium- and high-dose groups, statistically significant reductions in mean fetal and placental weight and fetal survival rate were observed. Sorbic acid showed no in vitro activity in Syrian hamster embryo (SHE) fibroblast micronucleus assays and SHE cell transformation assays. At oral doses up to 5000 mg/kg, sorbic acid increased the frequency of micronuclei in mice. Intraperitoneal injection of 75, 100, or 150 mg/kg sorbic acid significantly increased the frequency of sister chromatid exchange in mouse bone marrow cells, while this was not observed in the 25 or 50 mg/kg dose groups. After mice were fed a diet containing 15% sorbic acid for up to 6 months, the ether extract of mouse intestinal contents was not mutagenic to Salmonella typhimurium TA98, but the acidic component obtained by fractionation showed mild mutagenic activity upon addition of a metabolic activation system. These results indicate that the mutagen is gradually produced in the gut and metabolized in the liver for metabolic activation. Sorbic acid was negative in the Salmonella reverse mutation assay (Ames test) with or without metabolic activation. Sorbic acid was also negative in the Chinese hamster fibroblast chromosome aberration assay.
Interactions
The bactericidal activity of sorbic acid against Saccharomyces cerevisiae was increased 64-fold when combined with the half-minimum bactericidal concentration of polystyrene. This synergistic activity of polystyrene may stem from its ability to inhibit plasma membrane H+-ATPase. Sorbic acid possesses a conjugated double bond system, enabling it to undergo nucleophilic addition reactions with certain functional groups. This study quantitatively analyzed the interaction between sorbic acid and amine groups present in endogenous food components. The formation of novel products was confirmed using ethyl sorbate and various amine compounds, and their potential mechanisms were investigated. The products were separated and identified by analyzing the reaction mixture using HPLC, GC, GC-SM, and NMR. At 20°C, the addition reaction produces a linear monoadduct; while at 50°C and 80°C, cyclic derivatives formed by double addition are produced. Sorbic acid (E200) and its salts (potassium sorbate and calcium sorbate: E202 and E203) can be used as preservatives in various processed foods. Sorbic acid has a conjugated double bond system, making it susceptible to nucleophilic attack, sometimes resulting in mutagenic products. Under typical food processing conditions (50-80°C), we analyzed the cyclic derivatives formed by the double addition reactions of sorbic acid with various amines. Mutagenicity studies (including the Ames assay) and genotoxicity studies using HeLa cells and plasmid DNA showed that none of the studied products exhibited mutagenicity or genotoxicity. This study aimed to investigate whether pulsed electric field (PEF) treatment of two yeast strains—Dekkera bruxellensis and Saccharomyces cerevisiae—induced sublethal damage, and the relationship between sublethal damage and the inactivation effect of the combined action of PEF and sorbic acid. PEF induced sublethal damage in both yeasts: after 50 cycles of PEF treatment at 12 kV/cm in buffer solutions at pH 7.0 and 4.0, over 90% of the surviving cells of D. bruxellensis and 99% of the surviving cells of S. cerevisiae showed sublethal damage. The proportion of sublethal cells reached its maximum after 50 cycles of PEF treatment at 12.0 kV/cm (S. cerevisiae) or 16.5 kV/cm (D. bruxellensis), and thereafter remained stable or gradually decreased with increasing electric field strength and PEF treatment time. Sublethal PEF-damaged cells are sensitive to sorbic acid at a concentration of 2000 ppm. A synergistic inactivation effect was observed between PEF and sorbic acid. At pH 3.8, the presence of 2000 ppm sorbic acid gradually inactivated surviving yeast cells treated with pulsed electric field (PEF), and the combined treatment resulted in a cell death count exceeding 10⁵ logarithms under the studied conditions. This study demonstrates that PEF treatment causes sublethal damage to yeast, therefore, PEF inactivation of yeast is not an either-or process. The combined application of PEF and sorbic acid has proven to be an effective method for improving yeast inactivation rates. ...
For more complete data on interactions with sorbic acid (6 items in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in male rats >2000 mg/kg body weight
Oral LD50 in female rats >2000 mg/kg body weight
Oral LD50 in rats 10,500 mg/kg body weight
Oral LD50 in male rats 12,500 mg/kg body weight
For more complete non-human toxicity data for sorbic acid (9 in total), please visit the HSDB record page.

[1]. Growth and Inhibition of Microorganisms in the Presence of Sorbic Acid: A Review. J Food Prot. 1985 Apr;48(4):364-375.

Sorbic acid is a white powder or crystal with a melting point of 134.5℃. It has a slightly sour and astringent taste and a mild odor. Sorbic acid is a hexadienoic acid with double bonds at both C-2 and C-4 positions. It has four geometric isomers, including the trans isomer, which occurs naturally. It is a hexadienoic acid, a polyunsaturated fatty acid, a medium-chain fatty acid, and an α,β-unsaturated monocarboxylic acid. It is the conjugate acid of sorbate. Sorbic acid has been reported to exist in European plum (Prunus domestica) and Schisandra chinensis, and relevant data are available. (2E,4E)-2,4-hexadienoic acid is a preservative in many foods. It is usually used in potassium salt form, and less commonly in calcium salt form. (2E,4E)-2,4-hexadienoic acid is an antibacterial agent effective against a variety of microorganisms, especially yeasts and molds. (2E,4E)-2,4-hexadienoic acid is a preservative, particularly effective in acidic foods. Typical usage concentrations are 500-2000 ppm. (2E,4E)-2,4-hexadienoic acid belongs to the family of unsaturated fatty acids. These fatty acids contain at least one C=C double bond in their carbon chain. Sorbic acid is a metabolite of Saccharomyces cerevisiae. It is a mold and yeast inhibitor, used as an antimicrobial agent in foods, especially cheeses.

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Therapeutic Uses
Food Preservatives
Timolol's ocular bioavailability increases in sorbic acid solutions due to ion pair formation. Its octanol/water partition coefficient also increases, indicating the formation of a more lipophilic complex. The concentration of timolol in the aqueous humor was determined after instilling sorbic acid-containing timolol eye drops into rabbit eyes. When the molar ratio of sorbic acid to timolol is 2 or higher, the concentration of timolol in the aqueous humor is higher than when timolol is used alone. In the presence of sorbic acid, the maximum concentration and area under the curve of timolol in the aqueous humor are more than twice that of Timoptol maleate eye drops, and similar to those of TIMOPTIC-XE gel eye drops. To investigate the mechanism of absorption across the cornea, in vitro permeation curves of the drug on intact and deepithelialized corneas were analyzed based on a two-layer diffusion model. In the presence of sorbic acid, the partition coefficient of timolol in the corneal epithelium is approximately twice that of timolol alone, although its diffusion coefficient in the corneal epithelium remains unchanged. We conclude that the increased ocular bioavailability in the presence of sorbic acid is due to the increased partitioning of timolol in the corneal epithelium.

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Drug Warning
The use of topical medications and cosmetics containing sorbic acid should be avoided. There is currently no evidence that consuming foods containing sorbic acid causes eczema flare-ups.
Therefore, there is no need to avoid foods containing sorbic acid.

C6H8O2

112.13

112.052

110-44-1

Potassium sorbate;24634-61-5

643460

White to off-white solid powder

1.0±0.1 g/cm3

233.0±9.0 °C at 760 mmHg

132-135 °C(lit.)

139.9±9.6 °C

0.0±1.0 mmHg at 25°C

1.488

1.35

1

2

2

8

123

0

C/C=C/C=C/C(=O)O

WSWCOQWTEOXDQX-MQQKCMAXSA-N

InChI=1S/C6H8O2/c1-2-3-4-5-6(7)8/h2-5H,1H3,(H,7,8)/b3-2+,5-4+

(2E,4E)-hexa-2,4-dienoic acid

Hexadienoic acid; Sorbic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~445.91 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (22.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (22.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (22.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)