Patulin and Human Health

In September 2021 Coca-Cola South Africa implemented a voluntary recall of Appletiser, a popular carbonated apple juice drink, with the manufacturer citing that the beverage was "outside of acceptable standards".  In the 10 days since we published this article, we have now seen another recall, this time an apple juice recall from Liquifruit.

So what is patulin?

Patulin, a mycotoxin found in fruits, is a chemical contaminant². It is produced by a variety of fungal species, including Aspergillus, Penicillium, and Byssochlamys.⁴, ⁶. The mould thrives on cereals, nuts, spices, dried fruits, apples, and coffee beans, frequently in warm, humid circumstances ¹⁰. Penicillium expansum, often known as the blue mould pathogen, is the primary producer of patulin in nature. It is frequently associated with mouldy food, notably apples and other deciduous fruits ¹¹.

What are mycotoxins?

Mycotoxins are secondary metabolites produced by filamentous fungi (moulds)³, they are biologically derived and so naturally occurring toxins. Patulin and other mycotoxins can cause disease in people and constitute a risk to livestock⁵. Mycotoxins contaminate raw agricultural commodities, processed foods as well as feeds³, posing substantial food safety risks to the food chain, even at very low concentrations, and have long been associated with incidents of poisoning in humans and animals³.  Three genera dominate the natural fungal flora related to food safety: Aspergillus, Fusarium, and Penicillium Aflatoxin A, patulin, and Alternaria toxins are mycotoxins commonly detected in fruits ^{6, 9} . The presence of these toxins in foodstuffs renders severe toxicity even at low levels, endangering human health and inflicting financial losses to fruit juice and related companies^{3, 9}. The absence of data on mycotoxin prevalence and levels in fruit products makes risk evaluation challenging ⁹. Ultimately food and feed safety, food security, and international trade are all affected^{3, 10}. Thus, to ensure consumer safety, national and international regulatory agencies must set limits for mycotoxin concentration in food and feed while considering the social and economic impacts of regulatory measures³.

What are sources of patulin?

Penicillium expansum is a saprophytic fungus that grows on apples (and other agricultural commodities) and is the principal source of patulin contamination in apple juices and related products ⁷. Patulin is a possible carcinogen found in commercial apple juice and other apple products, raising some public health concerns ¹³. Patulin formation has been observed in “apple” goods, most commonly in rotting apples.

Fruit injury promotes patulin production (bruises, insect damage, etc.)⁷. On damaged or mouldy fruits and vegetables, patulin-producing fungi are most commonly recovered ³. In other words, patulin is primarily formed in decaying fruit portions, with most patulin observed near the injured area. Thus, patulin content in apple products is often indicative of the quality of the apples used in production ¹⁵. Patulin's presence is, unsurprisingly, strictly regulated.

Patulin has been mostly observed in apple and apple-based goods including juices and ciders. Additionally, patulin has been detected in a variety of other foods, including spices, cereals, fruits, and vegetables. Although, on average, the patulin content of these goods remained significantly lower than that of products from the "apple" sector ⁷. Apricots, bananas, cherries, cereals (barley, wheat, corn), figs, grapes, grape juice, oranges, peaches, pears, plums, strawberries, shellfish, and wine are just a few of the other commodities ^{7, 3, 10, 11}.

How does this affect consumers?

Humans are exposed when they consume patulin-contaminated food ⁷. There are numerous vectors that transport the fungi and toxin causing danger, some of these vectors can be ambiguous including vegetation, water, soil, air, animals, and humans ⁷. P. expansum can be found in healthy fruit, but it only produces considerable levels of patulin when it forms a necrotic disc on the fruit⁷. Patulin is usually rapidly destroyed after it is absorbed through the gastrointestinal tract. Consumption of patulin-contaminated food, however, is still thought to be harmful to one's health ⁷.

Symptoms of patulin contamination

Weight loss, gastrointestinal disorders ⁽ulceration, distension, hemorrhage, and renal function disruption), intestinal disorders, vomiting, convulsions, agitation, edema, enzyme inhibition (particularly in the intestine and brain), organ damage (kidney and spleen), and DNA damage have all been observed in rat studies (in the brain, liver and kidneys) ^{7, 3}. Chronic exposure has also been shown to produce neurotoxic, immunotoxic, genotoxic, and teratogenic consequences ^{7, 3}. Patulin was also found to be harmful to male reproductive systems, reducing sperm count and morphology in rats ¹⁷. Additionally, it resulted in F1 litter abortions in rats and mice ¹⁶. Chick eggs were also found to be embryotoxic and teratogenic ¹⁶.

Examples of negative health effects range from acute poisoning to long-term consequences such as immunological weakening and cancer.  In a number of animal and even human trials, patulin was proven to be immunotoxic. Dietary relevant exposure, on the other hand, is unlikely to influence immune response. Patulin, while not a particularly strong toxin, is genotoxic. Some speculate that it is a carcinogen, although animal tests have been equivocal ⁷. In terms of patulin's ability to cause cancer in humans, the International Agency for Research on Cancer found that no assessment could be made because there is insufficient evidence regarding carcinogenicity. Despite patulin's genotoxicity reported by WHO based on varying genotoxicity data, it is classified as a group 3 carcinogen by the International Agency for Research on Cancer (IARC) due to inconclusive data.  However, patulin is thought to cause plasmatic membrane rupture, protein synthesis inhibition, and DNA and RNA synthesis inhibition at the cellular level ⁹.

Patulin has antibacterial effects against a variety of microorganisms. Patulin was once employed as an antibiotic against Gram-positive and Gram-negative bacteria, but it is no longer utilized for that purpose due to toxicity concerns ¹². Nancy Atkinson isolated it in 1943, and it was especially tested to be used against the common cold. It was studied in humans as an intranasal antibiotic for the common cold with few severe side effects but no benefit ¹². Nausea, gastrointestinal problems, and vomiting have been recorded in people ¹⁰. There are genotoxic, neurotoxic, immune-toxic, immunosuppressive, and teratogenic consequences among the chronic symptoms ³.

The nature of patulin

Patulin is an organic polyketide. It appears as a white powder that is soluble in acidic water and organic solvents ⁸. Patulin is also a thermostable lactone, which means it is unaffected by pasteurization or thermal denaturation ⁸. However, its stability is reduced after fermentation. Because alcoholic fermentation eliminates patulin, fermented goods such as cider are unaffected ^7,3. Patulin can, however, be found in fermented items to which apple juice was added after fermentation ⁷.

The apple-rotting fungus, P. expansum, is the major producer of patulin ⁷. P. expansum patulin production criteria include a temperature range of 0–24°C and a minimum water activity of 0.99 ⁹. When employed appropriately, the spores of patulin-producing mould are sensitive to the chemical disinfectants (for antifungal purposes) permitted in the food-processing sector ⁷. Fungal ascospores are extremely thermally resistant, withstanding pasteurisation at 90°C for 10 seconds ⁷. Patulin levels are also affected by changes in climate over the seasons and years ⁷.

Patulin is water-soluble and acid-stable, but loses activity in alkaline media ⁷. It is also thermally resistant, with a melting point of 110°C ⁷. Because it is adsorbed on plant cell walls ⁷, physical separation methods capable of removing damaged items are the only ones capable of removing a considerable fraction.

Allowed limits

Fruit appears to be the most important source of patulin exposure in adults, followed by compotes and cooked fruit ⁷. Compotes and cooked fruit, as well as non-alcoholic beverages, are the main sources of exposure in children ⁷. The decline in patulin exposure during the last decade can be explained in part by the implementation of rules on maximum levels of specific mycotoxins in food in 2006 ⁷. Patulin restrictions in apple products have been implemented in several countries, with several adjustments to regulatory limits for patulin in fruit juice ranging from 30 to 50 ppb ¹⁴. For instance, the Monitoring in Food Regulation (EC) No 1881/2006(8) establishes the maximum permitted amounts of patulin in foods intended for human consumption ⁷.  As of November 2003, the European Union stipulated that apple juice and other fruit drinks shall include no more than 50 micrograms per kilogram (ug/kg) and solid apple products contain no more than 25 ug/kg ⁷. This applies in South Africa also.

View the Codex Guidelines regarding limits of Patulin in Apple Juice

Risk management

Good agricultural techniques such as removing mould, cleaning, and not utilizing rotting or damaged apples can successfully manage patulin exposure. Recommendations to operators include implementing proper practices in storage, food production and preservation, sorting food to remove mouldy items (the most crucial stage for reducing patulin), as well as clarifying fruit juices may greatly reduce the patulin content ⁷. Since there is no efficient technique to totally detoxify patulin-contaminated food, preventing the hazard at the source is the most effective solution ⁷. Apples should be consumed within 24 hours of harvesting or held in cold storage (under 2°C) and used within four days; storing apples for more than three months requires the use of a controlled atmosphere ( under 1.8% oxygen); fruit with lesions larger than 10 cm² should be destroyed (cutting out the rotten parts is insufficient for eliminating the risk of patulin ingestion of patulin) ⁷. Furthermore, a range of techniques and sample preparation procedures, including thin layer chromatography (TLC), gas chromatography (GC), high-performance liquid chromatography (HPLC), and capillary electrophoresis, have been used to test for patulin contamination ¹⁵.

Food for thought

Patulin is less dangerous than other mycotoxins since it is production is accompanied by obvious rotting of the fruit, and so most of the toxin may be avoided by rejecting rotten fruits during selection and sorting ³. Nonetheless, patulin contents in foods are subject to regulatory restriction in some countries ³. The amount of patulin in the juices can be reduced once the rotting or damaged fruit is removed, but it cannot be entirely eliminated since the mycotoxin diffuses into the healthy sections of the fruit.

Patulin is found primarily in decaying apples and related products ¹⁰. In general, apple juice with a low patulin concentration will not cause acute intoxication ¹⁰. However, humans have reported nausea, gastrointestinal problems, and vomiting. While mycotoxin incidence cannot be totally avoided, several interventions can be applied to reduce mycotoxin levels and exposure throughout the food and feed chains³. These include pre-and post-harvest techniques, crop production, storage, and processing standards, the enforcement of advice and regulatory maximum limits for some mycotoxins, surveillance programs, and, lastly, dietary interventions³.

References

1. MyHACCP Hazard Factsheet  CATEGORY: Chemical  NAME: Patulin. (n.d.). Retrieved September 26, 2021, from https://view.officeapps.live.com/op/view.aspx?src=https%3A%2F%2Fmyhaccp.food.gov.uk%2Fsites%2Fdefault%2Ffiles%2Fresources%2Ffactsheet_patulin_0.docx&wdOrigin=BROWSELINK
2. Altomare, C., Logrieco, A. F., & Gallo, A. (2021). Mycotoxins and Mycotoxigenic Fungi: Risk and Management. A Challenge for Future Global Food Safety and Security. Encyclopedia of Mycology, 64–93. https://doi.org/10.1016/B978-0-12-819990-9.00032-9
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7. Sigma Aldrich. (n.d.). Patulin specification sheet. Sigma Aldrich. Retrieved September 26, 2021, from https://www.sigmaaldrich.com/specification-sheets/108/259/P1639-BULK________SIGMA____.pdf
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14. Zhong, L., Carere, J., Lu, Z., Lu, F., & Zhou, T. (2018). Patulin in Apples and Apple-Based Food Products: The Burdens and the Mitigation Strategies. Toxins 2018, Vol. 10, Page 475, 10(11), 475. https://doi.org/10.3390/TOXINS10110475
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16. Selmanoǧlu, G. (2006). Evaluation of the reproductive toxicity of patulin in growing male rats. Food and Chemical Toxicology, 44(12), 2019–2024. https://doi.org/10.1016/J.FCT.2006.06.022