Patulin

Last updated
Patulin [1]
Patulin.png
Patulin 3d structure.png
Names
IUPAC name
4-hydroxy-4H-furo[3,2-c]pyran-2(6H)-one
Other names
2-Hydroxy-3,7-dioxabicyclo[4.3.0]nona-5,9-dien-8-one
Clairformin
Claviform
Expansine
Clavacin
Clavatin
Expansin
Gigantin
Leucopin
Patuline
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.215 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 205-735-2
KEGG
PubChem CID
UNII
  • InChI=1S/C7H6O4/c8-6-3-4-5(11-6)1-2-10-7(4)9/h1,3,7,9H,2H2 Yes check.svgY
    Key: ZRWPUFFVAOMMNM-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C7H6O4/c8-6-3-4-5(11-6)1-2-10-7(4)9/h1,3,7,9H,2H2
    Key: ZRWPUFFVAOMMNM-UHFFFAOYAU
  • O=C\1O/C2=C/COC(O)C2=C/1
Properties
C7H6O4
Molar mass 154.12 g/mol
AppearanceCompact prisms
Density 1.52 g/ml
Melting point 110 °C (230 °F; 383 K)
Soluble
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Patulin is an organic compound classified as a polyketide. It is named after the fungus from which it was isolated, Penicillium patulum . It is a white powder soluble in acidic water and in organic solvents. It is a lactone that is heat-stable, so it is not destroyed by pasteurization or thermal denaturation. [2] However, stability following fermentation is lessened. [3] It is a mycotoxin produced by a variety of molds, in particular, Aspergillus and Penicillium and Byssochlamys . Most commonly found in rotting apples, the amount of patulin in apple products is generally viewed as a measure of the quality of the apples used in production. In addition, patulin has been found in other foods such as grains, fruits, and vegetables. Its presence is highly regulated.

Contents

Biosynthesis, synthesis, and reactivity

Patulin is biosynthesized from 6-methylsalicylic acid via multiple chemical transformations. [4]

Isoepoxydon dehydrogenase (IDH) is an important enzyme in the multi-step biosynthesis of patulin. Its gene is present in other fungi that may potentially produce the toxin. [5] It is reactive with sulfur dioxide, so antioxidant and antimicrobial agents may be useful to destroy it. [6] Levels of nitrogen, manganese, and pH as well as abundance of necessary enzymes regulate the biosynthetic pathway of patulin. [5]

Uses

Patulin was originally used as an antibiotic against Gram-positive and Gram-negative bacteria, but after several toxicity reports, it is no longer used for that purpose. [7] Isolated by Nancy Atkinson in 1943, it was specifically trialed to be used against the common cold. [7] Patulin is used as a potassium-uptake inhibitor in laboratory applications. [2] Kashif Jilani and co-workers reported that patulin stimulates suicidal erythrocyte death under physiological concentrations. [8]

Sources of exposure

Frequently, patulin is found in apples and apple products such as juices, jams, and ciders. It has also been detected in other fruits including cherries, blueberries, plums, bananas, strawberries, and grapes. [6] Fungal growth leading to patulin production is most common on damaged fruits. [9] Patulin has also been detected in grains like barley, wheat, corn and their processed products as well as in shellfish. [6] [10] [ full citation needed ] Dietary intake of patulin from apple juice has been estimated at between 0.03 and 0.26 μg/kg bw/day in various age groups and populations. [11] Content of patulin in apple juice is estimated to be less than 10–15μg/L. [11] A number of studies have looked into comparisons of organic vs conventional harvest of apples and levels of patulin contamination. [12] [13] [14] For example, one study showed 0.9% of children drinking organic apple juice exceeded the tolerable daily intake (TDI) for patulin. [15] [ full citation needed ] A recent article described detection of patulin in marine strains of Penicillium, indicating a potential risk in shellfish consumption. [10]

Toxicity

A subacute rodent NOAEL of 43 μg/kg body weight as well as genotoxicity studies were primarily the cause for setting limits for patulin exposure, although a range of other types of toxicity also exist. [3]

While not a particularly potent toxin, patulin is genotoxic. Some theorize that it may be a carcinogen, although animal studies have remained inconclusive. [16] Patulin has shown antimicrobial properties against some microorganisms. [1] Several countries have instituted patulin restrictions in apple products. The World Health Organization recommends a maximum concentration of 50 µg/L in apple juice. [17] In the European Union, the limit is also set at 50 micrograms per kilogram (µg/kg) in apple juice and cider, at 25 µg/kg in solid apple products, and at 10 µg/kg in products for infants and young children. These limits came into force on 1 November 2003. [18] [ full citation needed ]

Acute

Patulin is toxic primarily through affinity to sulfhydryl groups (SH), which results in inhibition of enzymes. Oral LD50 in rodent models have ranged between 20 and 100 mg/kg. [3] In poultry, the oral LD50 range was reported between 50 and 170 mg/kg. [5] Other routes of exposure are more toxic, yet less likely to occur. Major acute toxicity findings include gastrointestinal problems, neurotoxicity (i.e. convulsions), pulmonary congestion, and edema. [3]

Subacute

Studies in rats showed decreased weight, and gastric, intestinal, and renal function changes, while repetitive doses lead to neurotoxicity. Reproductive toxicity in males was also reported. [5] A NOAEL in rodents was observed at 43μg/kg bw. [3]

Genotoxicity

WHO concluded that patulin is genotoxic based on variable genotoxicity data, however it is considered a group 3 carcinogen by the International Agency for Research on Cancer (IARC) since data was inconclusive. [3]

Reproduction studies

Patulin decreased sperm count and altered sperm morphology in the rat. [19] Also, it resulted in abortion of F1 litters in rats and mice after i.p. injection. [5] Embryotoxicity and teratogenicity were also reported in chick eggs. [5]

Immunotoxicity

Patulin was found to be immunotoxic in a number of animal and even human studies. Reduced cytokine secretion, oxidative burst in macrophages, increased splenic T lymphocytes, and increased neutrophil numbers are a few endpoints noticed. [5] However, dietary relevant exposure would not be likely to alter immune response. [6]

Human health

Although there are only very few reported cases and epidemiological data, the FDA has set an action limit of 50 ppb in cider due to its potential carcinogenicity and other reported adverse effects. [3] In humans, it was tested as an antiviral intranasally for use against the common cold with few significant adverse effects, yet also had negligible or no beneficial effect. [7]

Risk management and regulations

Patulin exposure can be successfully managed by following good agricultural practices such as removing mold, washing, and not using rotten or damaged apples for baking, canning, or juice production. [3] [9]

US

The provisional tolerable daily intake (PTDI) for patulin was set at 0.43 µg/kg bw by the FDA [3] based on a NOAEL of 0.3 mg/kg bw per week. [3] Monte Carlo analysis was done on apple juice to compare exposure and the PTDI. Without controls or an action limit, the 90th percentile of consumers would not be above the PTDI. However, the concentration in children 1–2 years old would be three times as high as the PDTI, hence an action limit of 50 µg/kg. [3]

WHO

The World Health Organization recommends a maximum concentration of 50 µg/L in apple juice. [17]

EU

The European Union (EU) has set a maximum limit of 50μg/kg on fruit juices and drinks, while solid apple products have a limit of 25μg/kg. For certain foods intended for infants, an even lower limit of 10μg/kg is observed.

To test for patulin contamination, a variety of methods and sample preparation methods have been employed, including thin layer chromatography (TLC), gas chromatography (GC), high-performance liquid chromatography (HPLC), and capillary electrophoresis. [20]

Related Research Articles

<span class="mw-page-title-main">Aflatoxin</span> Group of poisons produced by moulds

Aflatoxins are various poisonous carcinogens and mutagens that are produced by certain molds, particularly Aspergillus species. The fungi grow in soil, decaying vegetation and various staple foodstuffs and commodities such as hay, sweetcorn, wheat, millet, sorghum, cassava, rice, chili peppers, cottonseed, peanuts, tree nuts, sesame seeds, sunflower seeds, and various spices. In short, the relevant fungi grow on almost any crop or food. When such contaminated food is processed or consumed, the aflatoxins enter the general food supply. They have been found in both pet and human foods, as well as in feedstocks for agricultural animals. Animals fed contaminated food can pass aflatoxin transformation products into eggs, milk products, and meat. For example, contaminated poultry feed is the suspected source of aflatoxin-contaminated chicken meat and eggs in Pakistan.

A mycotoxin is a toxic secondary metabolite produced by fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually reserved for the toxic chemical products produced by fungi that readily colonize crops.

<span class="mw-page-title-main">T-2 mycotoxin</span> Chemical compound

T-2 mycotoxin is a trichothecene mycotoxin. It is a naturally occurring mold byproduct of Fusarium spp. fungus which is toxic to humans and animals. The clinical condition it causes is alimentary toxic aleukia and a host of symptoms related to organs as diverse as the skin, airway, and stomach. Ingestion may come from consumption of moldy whole grains. T-2 can be absorbed through human skin. Although no significant systemic effects are expected after dermal contact in normal agricultural or residential environments, local skin effects can not be excluded. Hence, skin contact with T-2 should be limited.

<span class="mw-page-title-main">Fumonisin B1</span> Chemical compound

Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by multiple species of Fusarium molds, such as Fusarium verticillioides, which occur mainly in maize (corn), wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.

<span class="mw-page-title-main">Ochratoxin</span> Group of chemical compounds

Ochratoxins are a group of mycotoxins produced by some Aspergillus species and some Penicillium species, especially P. verrucosum. Ochratoxin A is the most prevalent and relevant fungal toxin of this group, while ochratoxins B and C are of lesser importance.

<span class="mw-page-title-main">Ochratoxin A</span> Chemical compound

Ochratoxin A—a toxin produced by different Aspergillus and Penicillium species — is one of the most-abundant food-contaminating mycotoxins. It is also a frequent contaminant of water-damaged houses and of heating ducts. Human exposure can occur through consumption of contaminated food products, particularly contaminated grain and pork products, as well as coffee, wine grapes, and dried grapes. The toxin has been found in the tissues and organs of animals, including human blood and breast milk. Ochratoxin A, like most toxic substances, has large species- and sex-specific toxicological differences.

<span class="mw-page-title-main">Citrinin</span> Chemical compound

Citrinin is a mycotoxin which is often found in food. It is a secondary metabolite produced by fungi that contaminates long-stored food and it causes different toxic effects, like nephrotoxic, hepatotoxic and cytotoxic effects. Citrinin is mainly found in stored grains, but sometimes also in fruits and other plant products.

Mycotoxicology is the branch of mycology that focuses on analyzing and studying the toxins produced by fungi, known as mycotoxins. In the food industry it is important to adopt measures that keep mycotoxin levels as low as practicable, especially those that are heat-stable. These chemical compounds are the result of secondary metabolism initiated in response to specific developmental or environmental signals. This includes biological stress from the environment, such as lower nutrients or competition for those available. Under this secondary path the fungus produces a wide array of compounds in order to gain some level of advantage, such as incrementing the efficiency of metabolic processes to gain more energy from less food, or attacking other microorganisms and being able to use their remains as a food source.

<span class="mw-page-title-main">Sterigmatocystin</span> Chemical compound

Sterigmatocystin is a polyketide mycotoxin produced by certain species of Aspergillus. The toxin is naturally found in some cheeses.

<i>Penicillium expansum</i> Species of fungus

Penicillium expansum is a psychrophilic blue mold that is common throughout the world in soil. It causes Blue Mold of apples, one of the most prevalent and economically damaging post-harvest diseases of apples.

Mycoestrogens are xenoestrogens produced by fungi. They are sometimes referred to as mycotoxins. Among important mycoestrogens are zearalenone, zearalenol and zearalanol. Although all of these can be produced by various Fusarium species, zearalenol and zearalanol may also be produced endogenously in ruminants that have ingested zearalenone. Alpha-zearalanol is also produced semisynthetically, for veterinary use; such use is prohibited in the European Union.

<span class="mw-page-title-main">3-MCPD</span> Chemical compound

3-MCPD (3-monochloropropane-1,2-diol or 3-chloropropane-1,2-diol) is an organic chemical compound with the formula HOCH2CH(OH)CH2Cl. It is a colorless liquid. It is a versatile multifunctional building block. The compound has attracted attention as the most common member of chemical food contaminants known as chloropropanols. It is suspected to be carcinogenic in humans.

<span class="mw-page-title-main">Methiocarb</span> Chemical compound

Methiocarb is a carbamate pesticide which is used as an insecticide, bird repellent, acaricide and molluscicide since the 1960s. Methiocarb has contact and stomach action on mites and neurotoxic effects on molluscs. Seeds treated with methiocarb also affect birds. Other names for methiocarb are mesurol and mercaptodimethur.

<span class="mw-page-title-main">Roquefortine C</span> Chemical compound

Roquefortine C is a mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines produced by various fungi, particularly species from the genus Penicillium. It was first isolated from a strain of Penicillium roqueforti, a species commercially used as a source of proteolytic and lipolytic enzymes during maturation of the blue-veined cheeses, Roquefort, Danish Blue, Stilton and Gorgonzola.

Aflatoxin B<sub>1</sub> Chemical compound

Aflatoxin B1 is an aflatoxin produced by Aspergillus flavus and A. parasiticus. It is a very potent carcinogen with a TD50 3.2 μg/kg/day in rats. This carcinogenic potency varies across species with some, such as rats and monkeys, seemingly much more susceptible than others. Aflatoxin B1 is a common contaminant in a variety of foods including peanuts, cottonseed meal, corn, and other grains; as well as animal feeds. Aflatoxin B1 is considered the most toxic aflatoxin and it is highly implicated in hepatocellular carcinoma (HCC) in humans. In animals, aflatoxin B1 has also been shown to be mutagenic, teratogenic, and to cause immunosuppression. Several sampling and analytical methods including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), mass spectrometry, and enzyme-linked immunosorbent assay (ELISA), among others, have been used to test for aflatoxin B1 contamination in foods. According to the Food and Agriculture Organization (FAO), a division of the United Nations, the worldwide maximum tolerated levels of aflatoxin B1 was reported to be in the range of 1–20 μg/kg (or .001 ppm - 1 part-per-billion) in food, and 5–50 μg/kg (.005 ppm) in dietary cattle feed in 2003.

<span class="mw-page-title-main">Yessotoxin</span> Chemical compound

Yessotoxins are a group of lipophilic, sulfur bearing polyether toxins that are related to ciguatoxins. They are produced by a variety of dinoflagellates, most notably Lingulodinium polyedrum and Gonyaulax spinifera.

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<span class="mw-page-title-main">Nivalenol</span> Type of mycotoxin

Nivalenol (NIV) is a mycotoxin of the trichothecene group. In nature it is mainly found in fungi of the Fusarium species. The Fusarium species belongs to the most prevalent mycotoxin producing fungi in the temperate regions of the northern hemisphere, therefore making them a considerable risk for the food crop production industry.

Aflatoxin M<sub>1</sub> Chemical compound

Aflatoxin M1 is a chemical compound of the aflatoxin class, a group of mycotoxins produced by three species of Aspergillus – Aspergillus flavus, Aspergillus parasiticus, and the rare Aspergillus nomius – which contaminate plant and plant products.

References

  1. 1 2 Merck Index, 11th Edition, 7002
  2. 1 2 Patulin sigmaaldrich.com
  3. 1 2 3 4 5 6 7 8 9 10 11 "Patulin in Apple Juice, Apple Juice Concentrates and Apple Juice Products". www.fda.gov. Archived from the original on 2013-08-15.
  4. ↑ Puel, Olivier; Galtier, Pierre; Oswald, Isabelle (2010). "Biosynthesis and Toxicological Effects of Patulin". Toxins. 2 (4): 613–631. doi: 10.3390/toxins2040613 . PMC   3153204 . PMID   22069602.
  5. 1 2 3 4 5 6 7 Puel, Olivier; Galtier, Pierre; Oswald, Isabelle P. (5 April 2010). "Biosynthesis and Toxicological Effects of Patulin". Toxins. 2 (4): 613–631. doi: 10.3390/toxins2040613 . PMC   3153204 . PMID   22069602.
  6. 1 2 3 4 Llewellyn, G.C; McCay, J.A; Brown, R.D; Musgrove, D.L; Butterworth, L.F; Munson, A.E; White, K.L (1998). "Immunological evaluation of the mycotoxin patulin in female b6C3F1 mice". Food and Chemical Toxicology. 36 (12): 1107–1115. doi:10.1016/s0278-6915(98)00084-2. PMID   9862653.
  7. 1 2 3 Medical Research Council. Clinical trial of patulin in the common cold. Lancet1944; ii: 373-5.
  8. ↑ Lupescu, A; Jilani, K; Zbidah, M; Lang, F (2013). "Patulin-induced suicidal erythrocyte death". Cellular Physiology and Biochemistry. 32 (2): 291–9. doi: 10.1159/000354437 . PMID   23942252.
  9. 1 2 "Patulin". Archived from the original on 2013-10-18. Retrieved 2013-11-25.
  10. 1 2 Pouchous et al. Shellfish
  11. 1 2 Wouters, FA, and Speijers, GJA. JECFA Monograph on Patulin. World Health Organization Food Additives Series 35 (http://www.inchem.org/documents/jecfa/jecmono/v26je10.htm)
  12. ↑ Pique, E., et al. Occurrence of patulin in organic and conventional apple juice. Risk Assessment. Recent Advances in Pharmaceutical Sciences, III, 2013: 131–144.
  13. ↑ Piemontese, L.; Solfrizzo, M.; Visconti, A. (2005-05-01). "Occurrence of patulin in conventional and organic fruit products in Italy and subsequent exposure assessment". Food Additives and Contaminants. 22 (5): 437–442. doi:10.1080/02652030500073550. ISSN   0265-203X. PMID   16019815. S2CID   31155096.
  14. ↑ Piqué, E; Vargas-Murga, L; Gómez-Catalán, J; Lapuente, Jd; Llobet, JM (October 2013). "Occurrence of patulin in organic and conventional apple-based food marketed in Catalonia and exposure assessment". Food and Chemical Toxicology. 60: 199–204. doi:10.1016/j.fct.2013.07.052. PMID   23900007.
  15. ↑ Beark et al 2007
  16. ↑ "Patulin: a Mycotoxin in Apples". Perishables Handling Quarterly (91): 5. August 1997
  17. 1 2 "Foodborne hazards (World Health Organization". Retrieved 2007-01-22.
  18. ↑ Patulin information leaf from Fermentek
  19. ↑ Selmanoglu, G (2006). "Evaluation of the reproductive toxicity of patulin in growing male rats". Food Chem. Toxicol. 44 (12): 2019–2024. doi:10.1016/j.fct.2006.06.022. PMID   16905234.
  20. ↑ Baert, Katleen; De Meulenaer, Bruno; Verdonck, Frederik; Huybrechts, Inge; De Henauw, Stefaan; Vanrolleghem, Peter A.; Debevere, Johan; Devlieghere, Frank (2007). "Variability and uncertainty assessment of patulin exposure for preschool children in Flanders". Food and Chemical Toxicology. 45 (9): 1745–1751. doi:10.1016/j.fct.2007.03.008. PMID   17459555.
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