{{redirect|Claviform|the botany and zoology term|Glossary of entomology terms#clavate}} {{Chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 462273608 | Reference = <ref name="merck">Merck Index, 11th Edition, 7002</ref> | ImageFileL1 = Patulin.png | ImageFileR1 = Patulin_3d_structure.png | IUPACName = 4-hydroxy-4''H''-furo[3,2-''c'']pyran-2(6''H'')-one | OtherNames = 2-Hydroxy-3,7-dioxabicyclo[4.3.0]nona-5,9-dien-8-one<br /> Clairformin<br />Claviform<br />Expansine<br />Clavacin<br />Clavatin<br />Expansin<br />Gigantin<br />Leucopin<br />Patuline |Section1={{Chembox Identifiers | Abbreviations = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4534 | InChI = 1/C7H6O4/c8-6-3-4-5(11-6)1-2-10-7(4)9/h1,3,7,9H,2H2 | InChIKey = ZRWPUFFVAOMMNM-UHFFFAOYAU | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 294018 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C7H6O4/c8-6-3-4-5(11-6)1-2-10-7(4)9/h1,3,7,9H,2H2 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = ZRWPUFFVAOMMNM-UHFFFAOYSA-N | CASNo_Ref = {{cascite|correct|CAS}} | CASNo = 149-29-1 | EINECS = 205-735-2 | PubChem = 4696 | KEGG_Ref = {{keggcite|changed|kegg}} | KEGG = C16748 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 95X2BV4W8R | SMILES = O=C\1O/C2=C/COC(O)C2=C/1 | RTECS = | MeSHName = | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 74926 }} |Section2={{Chembox Properties | C=7 | H=6 | O=4 | MolarMass = 154.12 g/mol | Appearance = Compact prisms | Density = 1.52 g/mL | MeltingPtC = 110 | MeltingPt_notes = | BoilingPtC = | BoilingPt_notes = | Solubility = Soluble | SolubleOther = | Solvent = | pKa = | pKb = }} |Section7={{Chembox Hazards | MainHazards = | NFPA-H = | NFPA-F = | NFPA-R = | NFPA-S = | HPhrases = | PPhrases = | GHS_ref = | FlashPt = | AutoignitionPt = | ExploLimits = | PEL = }} }}

'''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.<ref name="sigma">[http://www.sigmaaldrich.com/catalog/product/sigma/p1639?lang=en&region=US Patulin] sigmaaldrich.com</ref> However, stability following fermentation is lessened.<ref name="ucm212520">{{cite web |url=https://www.fda.gov/food/foodborneillnesscontaminants/naturaltoxins/ucm212520.htm |title=Patulin in Apple Juice, Apple Juice Concentrates and Apple Juice Products |website=www.fda.gov |url-status=dead |archive-url=https://web.archive.org/web/20130815072813/http://www.fda.gov/Food/FoodborneIllnessContaminants/NaturalToxins/ucm212520.htm |archive-date=2013-08-15}}</ref> 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.

==Biosynthesis, synthesis, and reactivity== Patulin is biosynthesized from 6-methylsalicylic acid via multiple chemical transformations.<ref>{{cite journal | doi = 10.3390/toxins2040613 | doi-access = free | title = Biosynthesis and Toxicological Effects of Patulin | date = 2010 | last1 = Puel | first1 = Olivier | last2 = Galtier | first2 = Pierre | last3 = Oswald | first3 = Isabelle | journal = Toxins | volume = 2 | issue = 4 | pages = 613–631 | pmid = 22069602 | pmc = 3153204 }}</ref>

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.<ref name="Puel">{{cite journal|last1=Puel|first1=Olivier|last2=Galtier|first2=Pierre|last3 =Oswald|first3=Isabelle P.|title=Biosynthesis and Toxicological Effects of Patulin|journal=Toxins|date=5 April 2010|volume=2|issue=4|pages=613–631|doi=10.3390/toxins2040613|pmid=22069602|pmc=3153204|doi-access=free}}</ref> It is reactive with sulfur dioxide, so antioxidant and antimicrobial agents may be useful to destroy it.<ref name="Llewellyn">{{Cite journal | doi = 10.1016/s0278-6915(98)00084-2 | title = Immunological evaluation of the mycotoxin patulin in female b6C3F1 mice | date = 1998 | last1 = Llewellyn | first1 = G.C | last2 = McCay | first2 = J.A | last3 = Brown | first3 = R.D | last4 = Musgrove | first4 = D.L | last5 = Butterworth | first5 = L.F | last6 = Munson | first6 = A.E | last7 = White | first7 = K.L | journal = Food and Chemical Toxicology | volume = 36 | issue = 12 | pages = 1107–1115 | pmid = 9862653 }}</ref> Levels of nitrogen, manganese, and pH as well as abundance of necessary enzymes regulate the biosynthetic pathway of patulin.<ref name="Puel" />

== 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.<ref name="MRC">Medical Research Council. Clinical trial of patulin in the common cold. ''Lancet''1944; ii: 373-5.</ref> Isolated by Nancy Atkinson in 1943, it was specifically trialed to be used against the common cold.<ref name="MRC" /> Patulin is used as a potassium-uptake inhibitor in laboratory applications.<ref name="sigma" /> Kashif Jilani and co-workers reported that patulin stimulates suicidal erythrocyte death under physiological concentrations.<ref>{{cite journal|last=Lupescu|first=A|author2=Jilani, K |author3=Zbidah, M |author4= Lang, F |title=Patulin-induced suicidal erythrocyte death.|journal=Cellular Physiology and Biochemistry|date=2013|volume=32|issue=2|pages=291–9|pmid=23942252 |doi=10.1159/000354437|doi-access=free}}</ref>

== 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.<ref name="Llewellyn" /> Fungal growth leading to patulin production is most common on damaged fruits.<ref name="pippin">{{cite web |url=http://www.orangepippin.com/resources/general/patulin |title=Patulin |access-date=2013-11-25 |url-status=dead |archive-url=https://web.archive.org/web/20131018034231/http://www.orangepippin.com/resources/general/patulin |archive-date=2013-10-18 }}</ref> Patulin has also been detected in grains like barley, wheat, corn and their processed products as well as in shellfish.<ref name="Llewellyn" /><ref name="Pouchous">Pouchous et al. Shellfish</ref>{{full|date=January 2024}} Dietary intake of patulin from apple juice has been estimated at between 0.03 and 0.26 μg per kg body weight per day in various age groups and populations.<ref name="wouters">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)</ref> Content of patulin in apple juice is estimated to be less than 10–15&nbsp;μg/L.<ref name="wouters" /> A number of studies have looked into comparisons of organic vs conventional harvest of apples and levels of patulin contamination.<ref>Pique, E., et al. Occurrence of patulin in organic and conventional apple juice. Risk Assessment. Recent Advances in Pharmaceutical Sciences, III, 2013: 131–144.</ref><ref>{{Cite journal|last1=Piemontese|first1=L.|last2=Solfrizzo|first2=M.|last3=Visconti|first3=A.|date=2005-05-01|title=Occurrence of patulin in conventional and organic fruit products in Italy and subsequent exposure assessment|journal=Food Additives and Contaminants|volume=22|issue=5|pages=437–442|doi=10.1080/02652030500073550|issn=0265-203X|pmid=16019815|s2cid=31155096}}</ref><ref>{{cite journal|last1=Piqué|first1=E|last2=Vargas-Murga|first2=L|last3=Gómez-Catalán|first3=J|last4=Lapuente|first4=Jd|last5=Llobet|first5=JM|title=Occurrence of patulin in organic and conventional apple-based food marketed in Catalonia and exposure assessment.|journal=Food and Chemical Toxicology |date=October 2013|volume=60|pages=199–204|doi=10.1016/j.fct.2013.07.052|pmid=23900007}}</ref> For example, one study showed 0.9% of children drinking organic apple juice exceeded the tolerable daily intake (TDI) for patulin.<ref>Beark et al 2007</ref>{{full|date=January 2024}} A recent article described detection of patulin in marine strains of Penicillium, indicating a potential risk in shellfish consumption.<ref name="Pouchous" />

== 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.<ref name="ucm212520" />

While not a particularly potent toxin, patulin is genotoxic. Some theorize that it may be a carcinogen, although animal studies have remained inconclusive.<ref>"Patulin: a Mycotoxin in Apples". Perishables Handling Quarterly (91): 5. August 1997</ref> Patulin has shown antimicrobial properties against some microorganisms.<ref name="merck" /> Several countries have instituted patulin restrictions in apple products. The World Health Organization recommends a maximum concentration of 50&nbsp;μg/L in apple juice.<ref name="FHWHO">"Foodborne hazards (World Health Organization". Retrieved 2007-01-22.</ref> In the European Union, the limit is also set at 50 micrograms per kilogram (μg/kg) in apple juice and cider, at 25&nbsp;μg/kg in solid apple products, and at 10&nbsp;μg/kg in products for infants and young children. These limits came into force on 1 November 2003.<ref>Patulin information leaf from Fermentek</ref>{{full|date=January 2024}}

=== Acute === Patulin is toxic primarily through affinity to sulfhydryl groups (SH), which results in inhibition of enzymes. Oral LD<sub>50</sub> in rodent models have ranged between 20 and 100&nbsp;mg/kg.<ref name="ucm212520" /> In poultry, the oral LD<sub>50</sub> range was reported between 50 and 170&nbsp;mg/kg.<ref name="Puel" /> 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.<ref name="ucm212520" />

=== 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.<ref name="Puel" /> A NOAEL in rodents was observed at 43&nbsp;μg/kg body weight.<ref name="ucm212520" />

=== 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.<ref name="ucm212520" />

=== Reproduction studies === Patulin decreased sperm count and altered sperm morphology in the rat.<ref>{{cite journal | last1 = Selmanoglu | first1 = G | title = Evaluation of the reproductive toxicity of patulin in growing male rats | doi = 10.1016/j.fct.2006.06.022 | journal = Food Chem. Toxicol. | year = 2006 | volume = 44| issue = 12 | pages = 2019–2024 | pmid = 16905234 }}</ref> Also, it resulted in abortion of F1 litters in rats and mice after i.p. injection.<ref name="Puel" /> Embryotoxicity and teratogenicity were also reported in chick eggs.<ref name="Puel" />

=== 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.<ref name="Puel" /> However, dietary relevant exposure would not be likely to alter immune response.<ref name="Llewellyn" />

=== 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.<ref name="ucm212520" /> 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.<ref name="MRC" />

== 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.<ref name="ucm212520" /><ref name="pippin" />

'''US'''

The provisional tolerable daily intake (PTDI) for patulin was set at 0.43&nbsp;μg/kg body weight by the FDA<ref name="ucm212520" /> based on a NOAEL of 0.3&nbsp;mg/kg body weight per week.<ref name="ucm212520" /> 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&nbsp;μg/kg.<ref name="ucm212520" />

'''WHO'''

The World Health Organization recommends a maximum concentration of 50&nbsp;μg/L in apple juice.<ref name="FHWHO" />

'''EU'''

The European Union (EU) has set a maximum limit of 50&nbsp;μg/kg on fruit juices and drinks, while solid apple products have a limit of 25&nbsp;μg/kg. For certain foods intended for infants, an even lower limit of 10&nbsp;μg/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.<ref>{{cite journal | doi = 10.1016/j.fct.2007.03.008 | title = Variability and uncertainty assessment of patulin exposure for preschool children in Flanders | date = 2007 | last1 = Baert | first1 = Katleen | last2 = De Meulenaer | first2 = Bruno | last3 = Verdonck | first3 = Frederik | last4 = Huybrechts | first4 = Inge | last5 = De Henauw | first5 = Stefaan | last6 = Vanrolleghem | first6 = Peter A. | last7 = Debevere | first7 = Johan | last8 = Devlieghere | first8 = Frank | journal = Food and Chemical Toxicology | volume = 45 | issue = 9 | pages = 1745–1751 | pmid = 17459555 }}</ref>

==References== {{Reflist|2}}

== External links == * [http://www.foodsafetywatch.org/factsheets/patulin/ Patulin] {{Webarchive|url=https://web.archive.org/web/20171219144226/http://www.foodsafetywatch.org/factsheets/patulin/ |date=2017-12-19 }}, Food Safety Watch

Category:Mycotoxins Category:Furanones