Editing Aflatoxin

{{Short description|Group of poisons produced by moulds}}
{{distinguish|Alpha toxin (disambiguation){{!}}Alpha toxin}}
[[File:(–)-Aflatoxin B1 Structural Formulae V.1.svg|thumb|right|Chemical structure of [[Aflatoxin B1|aflatoxin B<sub>1</sub>]]]]

'''Aflatoxins''' are various [[toxicity|poisonous]] [[carcinogen]]s and [[mutagen]]s that are produced by certain [[Mold (fungus)|mold]]s, especially ''[[Aspergillus]]'' species such as ''[[Aspergillus flavus]]'' and ''[[Aspergillus parasiticus]]''. According to the [[USDA]], "They are probably the best known and most intensively researched [[mycotoxins]] in the world."<ref>{{Cite web |title=Molds on Food: Are They Dangerous? |url=https://www.fsis.usda.gov/food-safety/safe-food-handling-and-preparation/food-safety-basics/molds-food-are-they-dangerous |website=www.fsis.usda.gov}}</ref> The fungi grow in soil, decaying vegetation and various [[staple food|staple foodstuffs and commodities]] such as hay, [[maize]] (corn), [[peanut]]s, [[coffee]], [[wheat]], [[millet]], [[sorghum]], [[cassava]], [[rice]], [[chili pepper]]s, [[cottonseed]], [[tree nuts]], [[sesame seeds]], [[sunflower seeds]], and various cereal grains and oil seeds. 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 milk, milk products, and meat.<ref name="Fratamicopm" /> For example, contaminated poultry feed is the suspected source of aflatoxin-contaminated chicken meat and eggs in Pakistan.<ref name="Iqbal" />

Children are particularly vulnerable to aflatoxin exposure, which is linked to [[Immunosuppression|immune suppression]], [[stunted growth]],<ref>{{cite journal | vauthors = Khlangwiset P, Shephard GS, Wu F | title = Aflatoxins and growth impairment: a review | journal = Critical Reviews in Toxicology | volume = 41 | issue = 9 | pages = 740–55 | date = October 2011 | pmid = 21711088 | doi = 10.3109/10408444.2011.575766 | s2cid = 19262759 }}</ref> delayed development,<ref name=hamed2005/> aflatoxicosis,<ref>{{cite web | url=https://www.business.qld.gov.au/industries/farms-fishing-forestry/agriculture/biosecurity/animals/diseases/guide/aflatoxicosis#:~:text=Aflatoxicosis%20is%20a%20fungal%20toxicosis,without%20adequate%20drying%20and%20aeration | title=Aflatoxicosis | date=30 September 2014 }}</ref> and [[liver cancer]]. Some studies have reported an association between childhood stunting and aflatoxin exposure, although this link has not been consistently detected in all studies.<ref>{{cite journal | vauthors = Voth-Gaeddert LE, Stoker M, Torres O, Oerther DB | title = Association of aflatoxin exposure and height-for-age among young children in Guatemala | journal = International Journal of Environmental Health Research | volume = 28 | issue = 3 | pages = 280–292 | date = April 2018 | pmid = 29706087 | doi = 10.1080/09603123.2018.1468424 | bibcode = 2018IJEHR..28..280V | s2cid = 23510545 }}</ref><ref>{{cite journal | vauthors = Turner PC, Collinson AC, Cheung YB, Gong Y, Hall AJ, Prentice AM, Wild CP | title = Aflatoxin exposure in utero causes growth faltering in Gambian infants | journal = International Journal of Epidemiology | volume = 36 | issue = 5 | pages = 1119–25 | date = October 2007 | pmid = 17576701 | doi = 10.1093/ije/dym122 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Mitchell NJ, Hsu HH, Chandyo RK, Shrestha B, Bodhidatta L, Tu YK, Gong YY, Egner PA, Ulak M, Groopman JD, Wu F | title = Aflatoxin exposure during the first 36 months of life was not associated with impaired growth in Nepalese children: An extension of the MAL-ED study | journal = PLOS ONE | volume = 12 | issue = 2 | pages = e0172124 | date = 2017 | pmid = 28212415 | pmc = 5315312 | doi = 10.1371/journal.pone.0172124 | bibcode = 2017PLoSO..1272124M | doi-access = free }}</ref><ref>{{cite journal | vauthors = Chen C, Mitchell NJ, Gratz J, Houpt ER, Gong Y, Egner PA, Groopman JD, Riley RT, Showker JL, Svensen E, Mduma ER, Patil CL, Wu F | title = Exposure to aflatoxin and fumonisin in children at risk for growth impairment in rural Tanzania | journal = Environment International | volume = 115 | pages = 29–37 | date = March 2018 | pmid = 29544138 | pmc = 5989662 | doi = 10.1016/j.envint.2018.03.001 | bibcode = 2018EnInt.115...29C }}</ref> Furthermore, a causal relationship between childhood stunting and aflatoxin exposure has yet to be conclusively shown by epidemiological studies, though such investigations are underway.<ref>{{cite journal | vauthors = Smith LE, Prendergast AJ, Turner PC, Mbuya MN, Mutasa K, Kembo G, Stoltzfus RJ | title = The Potential Role of Mycotoxins as a Contributor to Stunting in the SHINE Trial | journal = Clinical Infectious Diseases | volume = 61 | issue = Suppl 7 | pages = S733–7 | date = December 2015 | pmid = 26602301 | pmc = 4657594 | doi = 10.1093/cid/civ849 }}</ref><ref>{{cite journal |last1=Hoffmann |first1=V. |last2=Jones |first2=K. |last3=Leroy |first3=J. L. |date=2018 |title=The impact of reducing dietary aflatoxin exposure on child linear growth: a cluster randomised controlled trial in Kenya |journal=BMJ Global Health |volume=3 |issue=6 |pages=e000983 | pmid=30588341 | doi=10.1136/bmjgh-2018-000983|pmc=6278920 | doi-access=free}}</ref><ref>{{cite journal | vauthors = Hoffmann V, Jones K, Leroy J | title = Mitigating aflatoxin exposure to improve child growth in Eastern Kenya: study protocol for a randomized controlled trial | journal = Trials | volume = 16 | pages = 552 | date = December 2015 | pmid = 26634701 | pmc = 4669614 | doi = 10.1186/s13063-015-1064-8 | doi-access = free }}</ref> Adults have a higher tolerance to exposure, but are also at risk. No animal species is known to be immune. Aflatoxins are among the most [[carcinogen]]ic substances known.<ref name=hudler/> After entering the body, aflatoxins may be metabolized by the liver to a reactive [[epoxide]] intermediate or hydroxylated to become the less harmful aflatoxin M<sub>1</sub>.

Aflatoxin poisoning most commonly results from ingestion, but the most toxic aflatoxin compound, B<sub>1</sub>, can permeate through the skin.<ref name=boonen/>

The [[United States Food and Drug Administration]] (FDA) action levels for aflatoxin present in food or [[mycotoxins in animal feed|feed]] is 20 to 300&nbsp;[[parts-per notation#ppb|ppb]].<ref name=fda2000/> The FDA has had occasion to declare both human and pet food recalls as a precautionary measure to prevent exposure.

The term "aflatoxin" is derived from the name of the species ''Aspergillus flavus'', in which some of the compounds first were discovered. A new disease was identified with unknown characteristics in England during the 1950s and 1960s, which increased turkey mortality. Later, aflatoxin was recognized in 1960 in England as a causative agent of the mysterious [[Turkey X disease]] that causes excessive mortality in turkey poults.<ref name=wannop/> Aflatoxins form one of the major groupings of [[mycotoxins]], and apart from ''Aspergillus flavus'' various members of the group of compounds occur in species such as ''Aspergillus parasiticus'', ''Aspergillus pseudocaelatus'', ''Aspergillus pseudonomius'', and ''Aspergillus nomius''.<ref>J. Varga, J.C. Frisvad, R.A. Samson: "Two new aflatoxin producing species, and an overview of Aspergillus section Flavi", Stud Mycol. 2011 Jun 30; 69(1): 57–80. doi: 10.3114/sim.2011.69.05</ref>

== Major types and their metabolites ==

[[Aflatoxin B1|Aflatoxin B<sub>1</sub>]] is considered the most toxic and is produced by both ''[[Aspergillus flavus]]'' and ''[[Aspergillus parasiticus]]''. [[Aflatoxin M1|Aflatoxin M<sub>1</sub>]] is present in the fermentation broth of ''Aspergillus parasiticus'', but it and aflatoxin M<sub>2</sub> are also produced when an infected liver metabolizes aflatoxin B<sub>1</sub> and B<sub>2</sub>.

* Aflatoxin B<sub>1</sub> and B<sub>2</sub> (AFB), produced by ''A.&nbsp;flavus'' and ''A.&nbsp;parasiticus''
* Aflatoxin G<sub>1</sub> and G<sub>2</sub> (AFG), produced by some Group II ''A.&nbsp;flavus'' and ''Aspergillus parasiticus''<ref>{{cite journal | vauthors = Geiser DM, Dorner JW, Horn BW, Taylor JW | title = The phylogenetics of mycotoxin and sclerotium production in Aspergillus flavus and Aspergillus oryzae | journal = Fungal Genetics and Biology | volume = 31 | issue = 3 | pages = 169–79 | date = December 2000 | pmid = 11273679 | doi = 10.1006/fgbi.2000.1215 | url = https://naldc-legacy.nal.usda.gov/naldc/download.xhtml?id=35468&content=PDF | access-date = 2018-12-29 | archive-date = 2021-01-26 | archive-url = https://web.archive.org/web/20210126201540/https://naldc-legacy.nal.usda.gov/naldc/download.xhtml?id=35468&content=PDF | url-status = dead }}</ref>
* Aflatoxin M<sub>1</sub> (AFM<sub>1</sub>), metabolite of aflatoxin B<sub>1</sub> in humans and animals (exposure in [[nanogram|ng]] levels may come from a mother's milk)
* Aflatoxin M<sub>2</sub>, metabolite of aflatoxin B<sub>2</sub> in milk of cattle fed on contaminated foods<ref name=fermetek/>
* Aflatoxicol (AFL): metabolite produced by breaking down the lactone ring
* Aflatoxin Q<sub>1</sub> (AFQ<sub>1</sub>), major metabolite of AFB<sub>1</sub> in ''[[in vitro]]'' liver preparations of other higher vertebrates<ref name=smith/>

AFM, AFQ, and AFL retain the possibility to become an epoxide. Nevertheless, they appear much less capable of causing [[mutagenesis]] than the unmetabolized ABM.<ref>{{cite journal | vauthors = Neal GE, Eaton DL, Judah DJ, Verma A | title = Metabolism and toxicity of aflatoxins M1 and B1 in human-derived in vitro systems | journal = Toxicology and Applied Pharmacology | volume = 151 | issue = 1 | pages = 152–8 | date = July 1998 | pmid = 9705898 | doi = 10.1006/taap.1998.8440 }}</ref>

== Contamination conditions ==

Aflatoxins are produced by both ''[[Aspergillus flavus]]'' and ''[[Aspergillus parasiticus]]'', which are common forms of 'weedy' molds widespread in nature. The presence of those molds does not always indicate that harmful levels of aflatoxin are present, but does indicate a significant risk. The molds can colonize and contaminate food before harvest or during storage, especially following prolonged exposure to a high-humidity environment, or to stressful conditions such as drought. Aflatoxin contamination is increasing in crops such as [[maize]] as a result of [[climate change]] creating better conditions for these molds.<ref>{{cite journal |last1=Yu |first1=Jina |last2=Hennessy |first2=David A |last3=Tack |first3=Jesse |last4=Wu |first4=Felicia |title=Climate change will increase aflatoxin presence in US Corn |journal=Environmental Research Letters |date=1 May 2022 |volume=17 |issue=5 |pages=054017 |doi=10.1088/1748-9326/ac6435|bibcode=2022ERL....17e4017Y |doi-access=free }}</ref><ref>{{cite journal |last1=Battilani |first1=P. |last2=Toscano |first2=P. |last3=Van der Fels-Klerx |first3=H. J. |last4=Moretti |first4=A. |last5=Camardo Leggieri |first5=M. |last6=Brera |first6=C. |last7=Rortais |first7=A. |last8=Goumperis |first8=T. |last9=Robinson |first9=T. |title=Aflatoxin B1 contamination in maize in Europe increases due to climate change |journal=Scientific Reports |date=July 2016 |volume=6 |issue=1 |pages=24328 |doi=10.1038/srep24328|pmid=27066906 |pmc=4828719 |bibcode=2016NatSR...624328B |doi-access=free }}</ref>

The native habitat of ''Aspergillus'' is in soil, decaying vegetation, [[hay]], and grains undergoing microbiological deterioration, but it invades all types of organic substrates whenever conditions are favorable for its growth. Favorable conditions for production of aflatoxins include high [[moisture content]] (at least 7%) and temperatures from {{convert|55|to|104|°F|°C|abbr=on}} [optimum {{convert|27|to|30|C|F}}].<ref>{{Cite web|title=Risk of aflatoxin contamination increases with hot and dry growing conditions {{!}} Integrated Crop Management|url=https://crops.extension.iastate.edu/encyclopedia/risk-aflatoxin-contamination-increases-hot-and-dry-growing-conditions|access-date=2021-06-13|website=crops.extension.iastate.edu}}</ref><ref>{{Cite web|title=Storing nuts at a low temperature (refrigeration) reduces aflatoxin levels and mold and yeast counts for 3–6 months {{!}} News {{!}} Postharvest – Fruits, Vegetables and Ornamentals|url=https://www.postharvest.biz/en/news/storing-nuts-at-a-low-temperature-refrigeration-reduces-aflatoxin-levels-and-mold-and-yeast-counts-for-3-6-months/_id:80408/|access-date=2021-06-13|website=www.postharvest.biz}}</ref> Aflatoxins have been isolated from all major cereal crops, and from sources as diverse as peanut butter and cannabis. The staple commodities regularly contaminated with aflatoxins include cassava, chilies, corn, cotton seed, millet, peanuts, rice, sorghum, sunflower seeds, tree nuts, wheat, and a variety of spices intended for human or animal consumption. Aflatoxin transformation products are sometimes found in eggs, milk products, and meat when animals are fed contaminated grains.<ref name= Fratamicopm/><ref>{{cite journal |last1=Pradeepkiran |first1=Jangampalli Adi | name-list-style = vanc |title=Analysis of aflatoxin B1 in contaminated feed, media, and serum samples of Cyprinus carpio L. by high-performance liquid chromatography |journal=Food Quality and Safety |date=December 2018 |volume=2 |issue=4 |pages=199–204 |doi=10.1093/fqsafe/fyy013|doi-access=free }}</ref>

A study conducted in [[Kenya]] and [[Mali]] found that the predominant practices for drying and storage of maize were inadequate in minimizing exposure to aflatoxins.<ref name=aflacontrol/>

[[File:Aflatossina_su_frutta_secca.jpg|thumb|Shine emitted by aflatoxins under ultraviolet light at right. At left, the same fruit under natural light.]]

==Prevention==

A primary means of limiting risk from aflatoxins in the food supply is [[food hygiene]] in the commercial commodity supply chain, such as rejecting moldy grain for use in [[food processing]] plants and testing of batches of ingredients for aflatoxin levels before adding them to the mix. Regulatory agencies such as the FDA set limits on acceptable levels. [[Grain drying]] itself, which is [[grain drying#History|necessary for viable combine harvesting in many regions]], lays the fundamentals for this effort by preventing stored grain from being too damp in the first place.

There is very limited evidence to show that agricultural and nutritional education can reduce exposure to aflatoxin in low to middle income countries.<ref>{{cite journal | vauthors = Visser ME, Schoonees A, Ezekiel CN, Randall NP, Naude CE | title = Agricultural and nutritional education interventions for reducing aflatoxin exposure to improve infant and child growth in low- and middle-income countries | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | pages = CD013376 | date = April 2020 | issue = 4 | pmid = 32270495 | pmc = 7141997 | doi = 10.1002/14651858.cd013376.pub2}}</ref>

==Pathology==

No animal species is known to be immune to the [[acute toxicity|acute toxic]] effects of aflatoxins. Adult humans have a high tolerance for aflatoxin exposure and rarely succumb to acute aflatoxicosis,<ref name=williams/> but children are particularly affected, and their exposure can lead to stunted growth and delayed development, in addition to all the symptoms mentioned below.<ref name=hamed2005/>

High-level aflatoxin exposure produces an acute [[liver|hepatic]] [[necrosis]] (acute aflatoxicosis), resulting later in [[cirrhosis]] or [[liver cancer|carcinoma of the liver]]. Acute liver failure is made manifest by [[hemorrhage|bleeding]], [[edema]], alteration in digestion, changes to the absorption and/or metabolism of nutrients, and mental changes and/or [[coma]].<ref name=williams/>

Chronic, [[asymptomatic|subclinical]] exposure does not lead to symptoms so dramatic as acute aflatoxicosis. Chronic exposure increases the risk of developing liver and gallbladder cancer,<ref>{{cite journal | vauthors = Nogueira L, Foerster C, Groopman J, Egner P, [[Jill Koshiol|Koshiol J]], Ferreccio C | title = Association of aflatoxin with gallbladder cancer in Chile | journal = JAMA | volume = 313 | issue = 20 | pages = 2075–7 | date = May 2015 | pmid = 26010638 | doi = 10.1001/jama.2015.4559 | pmc = 7169945 | doi-access = free }}</ref> as aflatoxin metabolites may [[intercalation (biochemistry)|intercalate]] into DNA and [[alkylation|alkylate]] the bases through its epoxide [[Moiety (chemistry)|moiety]]. This is thought to cause mutations in the ''[[p53]]'' gene, an important gene in preventing cell cycle progression when there are DNA mutations, or signaling [[apoptosis]] (programmed cell death). These mutations seem to affect some base pair locations more than others, for example, the third base of codon 249 of the p53 gene appears to be more susceptible to aflatoxin-mediated mutations than nearby bases.<ref>{{cite journal | vauthors = Aguilar F, Hussain SP, Cerutti P | title = Aflatoxin B1 induces the transversion of G→T in codon 249 of the p53 tumor suppressor gene in human hepatocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 18 | pages = 8586–90 | date = September 1993 | pmid = 8397412 | pmc = 47402 | doi = 10.1073/pnas.90.18.8586 | bibcode = 1993PNAS...90.8586A | doi-access = free }}</ref> As with other DNA-alkylating agents, Aflatoxin B<sub>1</sub> can cause immune suppression, and exposure to it is associated with an increased [[viral load]] in [[HIV]] positive individuals.<ref name=jolly/><ref name=jolly2/>

The expression of aflatoxin-related diseases is influenced by factors such as species, age, nutrition, sex, and the possibility of concurrent exposure to other toxins. The main target organ in mammals is the liver, so aflatoxicosis primarily is a hepatic disease. Conditions increasing the likelihood of aflatoxicosis in humans include limited availability of food, environmental conditions that favour mould growth on foodstuffs, and lack of regulatory systems for aflatoxin monitoring and control.<ref name= MachidaMGomiK/>

A regular diet including [[Apiaceae|apiaceous vegetables]], such as [[carrot]]s, [[parsnip]]s, [[celery]], and [[parsley]] may reduce the [[carcinogenic]] effects of aflatoxin.<ref name=petersen/>

There is no specific antidote for aflatoxicosis. Symptomatic and supportive care tailored to the severity of the liver disease may include intravenous fluids with dextrose, active vitamin K, B vitamins, and a restricted, but high-quality protein diet with adequate carbohydrate content.

=== In other animals ===
In dogs, aflatoxin has potential to lead to liver disease. Low levels of aflatoxin exposure require continuous consumption for several weeks to months in order for signs of liver dysfunction to appear.<ref name=bingham/> Some articles have suggested the toxic level in dog food is 100–300&nbsp;ppb and requires continuous exposure or consumption for a few weeks to months to develop aflatoxicosis.<ref name=bastianello/> No information is available to suggest that recovered dogs will later succumb to an aflatoxin-induced disease.

Turkeys are extremely susceptible to aflatoxicosis. Recent studies have revealed that this is due to the efficient [[cytochrome P450]] mediated metabolism of aflatoxin B<sub>1</sub> in the liver of turkeys and deficient [[glutathione-S-transferase]] mediated detoxification.<ref name=rawal1/><ref name=rawal2/>

Some studies on pregnant hamsters showed a significant relationship between exposure of aflatoxin B<sub>1</sub> (4&nbsp;mg/kg, single dose) and the appearance of [[teratology|developmental anomalies]] in their offspring.<ref name=goldblatt/>

In 2005, Diamond Pet Foods discovered aflatoxin in a product manufactured at their facility in [[Gaston, South Carolina]].<ref>[https://www.fda.gov/AboutFDA/CentersOffices/ORA/ORAElectronicReadingRoom/ucm061767.htm FDA Inspection Report-Diamond Gaston SC Plant 12/21/2005-1/19/2006].</ref><ref>[https://www.fda.gov/Safety/Recalls/ArchiveRecalls/2005/ucm111929.htm 2005 Recall], FDA</ref> In 23 states, Diamond voluntarily recalled 19 products formulated with corn and manufactured in the Gaston facility. Testing of more than 2,700 finished product samples conducted by laboratories confirmed that only two date codes of two adult dog formulas had the potential to be toxic.<ref>AKC Standard Article Contaminated Diamond Pet Food Products and 'Best By' Dates Narrowed {{usurped|1=[https://web.archive.org/web/20110707101136/http://www.akcstandard.com/article/contaminated-dog-food-1-06.html/ Akcstandard.com]}}</ref>

In December 2020 and January 2021, Midwestern Pet Foods recalled dog food that contained fatal levels of aflatoxin.<ref>{{Cite journal|last=Medicine|first=Center for Veterinary|date=2021-01-12|title=FDA Alert: Certain Lots of Sportmix Pet Food Recalled for Potentially Fatal Levels of Aflatoxin|url=https://www.fda.gov/animal-veterinary/outbreaks-and-advisories/fda-alert-certain-lots-sportmix-pet-food-recalled-potentially-fatal-levels-aflatoxin|journal=FDA|language=en}}</ref> As many as 70 dogs had died from aflatoxin poisoning by January 12, 2021.<ref>{{Cite web|last=Tyko|first=Kelly|title=Dog food recall expands: More than 70 dogs have died and 80 pets sick after eating Sportsmix pet food|url=https://www.usatoday.com/story/money/shopping/2021/01/12/recall-alert-midwestern-pet-foods-sportsmix-recalled-aflatoxin-risk/6642035002/|access-date=2021-01-13|website=USA TODAY|language=en-US}}</ref>
[[File:41598_2018_35246_Fig1_HTML.png|thumb|Schematic summarizing the major AFB1 and AFM1 contamination/exposure routes and adverse health effects to human]]

== Detection in humans ==
There are two principal techniques that have been used most often to detect levels of aflatoxin in humans.

The first method is measuring the AFB<sub>1</sub>-[[guanine]] [[adduct]] in the urine of subjects. The presence of this breakdown product indicates exposure to aflatoxin B<sub>1</sub> during the past 24 hours. This technique measures only recent exposure, however. Due to the [[half-life]] of this metabolite, the level of AFB<sub>1</sub>-guanine measured may vary from day to day, based on diet, it is not ideal for assessing long-term exposure.

Another technique that has been used is a measurement of the AFB<sub>1</sub>-[[serum albumin|albumin]] adduct level in the blood serum. This approach provides a more integrated measure of exposure over several weeks or months.

==List of outbreaks==
{{expand section|date=December 2014}}
International sources of commercial [[peanut butter]], [[cooking oils]] (e.g. [[olive oil|olive]], [[Peanut oil|peanut]] and [[sesame oil]]), and [[cosmetics]] have been identified as contaminated with aflatoxin.<ref name=bao/><ref name="peanut"/><ref name=analytical/> In some instances, [[Liquid chromatography–mass spectrometry|liquid chromatography]]–[[tandem mass spectrometry]] (LC–MS/MS), and other analytical methods, revealed a range from 48% to 80% of selected product samples as containing detectable quantities of aflatoxin. In many of these contaminated food products, the aflatoxin exceeded the safe limits of the U.S. [[Food and Drug Administration]] (FDA), or other regulatory agency.<ref name="peanut"/><ref name=analytical/><ref name=leong/>
* 1960: Outbreak of Turkey 'X' disease in England and aflatoxin discovery<ref>{{cite journal |pmid=34205163 |date=2021 |last1=Pickova |first1=D. |last2=Ostry |first2=V. |last3=Toman |first3=J. |last4=Malir |first4=F. |title=Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation |journal=Toxins |volume=13 |issue=6 |page=399 |doi=10.3390/toxins13060399 |doi-access=free |pmc=8227755 }}</ref>
* 1961: Identified ''Aspergillus flavus'' associated with toxicity of groundnuts 
* 1962: Studies conducted on physicochemical properties of aflatoxins, aflatoxin B and G identified in TLC analysis, and isolation and synthesis of crystalline aflatoxins.
* 1963: Aflatoxin B2, G1, and G2 were identified and chemically characterized as difurocoumarin derivatives
* 1965: FDA approved the first regulation on aflatoxins 30 μg/kg
* 1966: Milk toxins were designated as AFM1 and AFM2 and AFM1 was detected in milk, urine, kidney, and liver
* 1973 Poland: 10 died following the opening of the [[tomb of Casimir IV Jagiellon]], which contained aflatoxin-producing molds.<ref>{{cite news |last1=Staff |title=Gdy otwarto grób królewski, zaczęła działać klątwa Jagiellończyka|trans-title= When the royal tomb was opened, the Jagiellon curse began its work |url=https://gazetakrakowska.pl/gdy-otwarto-grob-krolewski-zaczela-dzialac-klatwa-jagiellonczyka/ar/3441137 |access-date=18 January 2023 |work=Gazeta Krakowska |date=19 May 2014}}</ref> 
* 2004 Kenya: acute outbreak of aflatoxicosis resulting from ingestion of contaminated maize, 125 confirmed deaths.<ref name="Acute Aflatoxicosis"/>
* February–March 2013: Romania, Serbia, Croatia imported into western Europe – [[2013 aflatoxin contamination]].
* February 2013: Iowa contamination.<ref>{{cite news | url = https://www.reuters.com/article/usa-corn-aflatoxin-idUSL1N0BP9SP20130225 | title = Dog food recall underscores toxic danger in drought-hit U.S. corn | date =February 25, 2013 | work = Reuters}}</ref>
* 2014 (ongoing): [[Nepal]] and [[Bangladesh]], neonatal exposures, found in [[umbilical cord]] blood.<ref name="scidev">{{Cite news|url=http://www.scidev.net/south-asia/health/news/aflatoxin-threat-in-nepal-bangladesh.html|title=Aflatoxin threat in Nepal, Bangladesh|date=2014-12-17|newspaper=SciDev.Net South Asia|access-date=2016-10-17|archive-date=2016-03-03|archive-url=https://web.archive.org/web/20160303225435/http://www.scidev.net/south-asia/health/news/aflatoxin-threat-in-nepal-bangladesh.html|url-status=dead}}</ref>
*2019 Kenya: five brands of maize flour recalled due to contamination.<ref>{{Cite news|url=https://www.bbc.com/news/world-africa-50407159|title=How safe is Kenya's staple food?|last=Mutahi|first=Basillioh | name-list-style = vanc |date=2019-11-15|access-date=2019-11-15|language=en-GB}}</ref>
*2021 US: Contamination of pet food manufactured by Midwestern Pet Food, causing the deaths of at least 70 dogs.<ref>{{Cite news|date=2021-01-14|title=US pet food recalled after 70 dogs die and others fall sick|language=en-GB|work=BBC News|url=https://www.bbc.com/news/world-us-canada-55659116|access-date=2021-01-14}}</ref>
*2021 Sri Lanka: contaminated coconut oil released for public consumption by local government.<ref>{{Cite news|date=2021-03-26|title=Coconut oil stocks containing aflatoxins in market|language=en-GB|work=themorning.lk|url=https://www.themorning.lk/customs-to-probe-coconut-oil-allegation|access-date=2021-03-26}}</ref>
*2023 Kenya: lactating women exposure of dietary aflatoxin among mothers of children with children 0-6 months. 
*2024 South Africa: The National Consumer Commission recalled various peanut butter brands due to contamination<ref>{{Cite web |date=2024-02-11 |title=Various peanut butter brands recalled {{!}} SAnews |url=https://www.sanews.gov.za/south-africa/various-peanut-butter-brands-recalled |access-date=2025-01-01 |website=www.sanews.gov.za |language=en}}</ref>

== See also ==
* [[Aflatoxin total synthesis]]
* [[2013 aflatoxin contamination]]
* [[Mycotoxins in animal feed]]
* [[Nixtamalization]]
* [[Sterigmatocystin]], a related toxin
* Other ways in which aspergillus can cause disease in mammals: 
** [[Aspergillosis]]
** [[Primary cutaneous aspergillosis]]

==References==
{{reflist|32em|refs=

<ref name= Fratamicopm>{{cite book
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| title = Foodborne Pathogens: Microbiology and Molecular Biology
| date = 2008 | publisher = Horizon Scientific Press | location = Norofolk, UK | isbn = 978-1-898486-52-7 }}
</ref>

<ref name=Iqbal>{{cite journal
 | last=Iqbal|first=Shahzad Zafar | name-list-style = vanc|title=Natural incidence of aflatoxins, ochratoxin A and zearalenone in chicken meat and eggs |journal=Food Control| date=2014 |volume=43 |pages=98–103 |doi=10.1016/j.foodcont.2014.02.046|display-authors=etal}}</ref>

<ref name=hamed2005>{{cite book
 | title=Aflatoxin and Food Safety |last=Abbas |first=Hamed K. | name-list-style = vanc |year=2005 |publisher=CRC Press |isbn=978-0-8247-2303-3 }}</ref>

<ref name=hudler>{{cite book
 | first=George W. |last=Hudler | name-list-style = vanc |title=Magical Mushrooms, Mischievous Molds: The Remarkable Story of the Fungus Kingdom and Its Impact on Human Affairs
 | url=https://books.google.com/books?id=Bob1Uo_hNTgC |year=1998 |publisher=[[Princeton University Press]] |isbn=978-0-691-07016-2}}</ref>

<ref name=fda2000>{{Cite web
 | date=August 2000
 | title=Guidance for Industry: Action Levels for Poisonous or Deleterious Substances in Human Food and Animal Feed |publisher=[[Food and Drug Administration]]
 | url=https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-action-levels-poisonous-or-deleterious-substances-human-food-and-animal-feed | access-date=November 14, 2020}}</ref>

<ref name=wannop>{{cite journal
 | last=Wannop|first=C. C. | name-list-style = vanc |title=The Histopathology of Turkey "X" Disease in Great Britain|journal=Avian Diseases
 | date=March 1961|volume=5|issue=4|pages=371–381|jstor=1587768|doi=10.2307/1587768}}</ref>

<ref name="Acute Aflatoxicosis">{{cite journal | last1=Probst | first1=Claudia | last2=Njapau | first2=Henry | last3=Cotty | first3=Peter J. | title=Outbreak of an Acute Aflatoxicosis in Kenya in 2004: Identification of the Causal Agent | journal=Applied and Environmental Microbiology | volume=73 | issue=8 | date=2007-04-15 | issn=0099-2240 | pmid=17308181 | pmc=1855601 | doi=10.1128/AEM.02370-06 | pages=2762–2764| bibcode=2007ApEnM..73.2762P }}</ref>

<ref name=smith>{{cite book
 | last1 = Smith | first1 = John E. | last2 = Sivewright-Henderson | first2 = Rachel | name-list-style = vanc |title=Mycotoxins and animal foods |publisher=[[CRC Press]] |year=1991
 | isbn=978-0-8493-4904-1 |page=614 |url=https://books.google.com/books?id=pNZHeXG8DJQC&pg=PA614}}</ref>

<ref name=bao>{{cite journal | vauthors = Bao L, Trucksess MW, White KD | title = Determination of aflatoxins B1, B2, G1, and G2 in olive oil, peanut oil, and sesame oil | journal = Journal of AOAC International | volume = 93 | issue = 3 | pages = 936–42 | year = 2010 | doi = 10.1093/jaoac/93.3.936 | pmid = 20629398 | doi-access = free }}</ref>

<ref name=peanut>{{cite journal | vauthors = Li FQ, Li YW, Wang YR, Luo XY | title = Natural occurrence of aflatoxins in Chinese peanut butter and sesame paste | journal = Journal of Agricultural and Food Chemistry | volume = 57 | issue = 9 | pages = 3519–24 | date = May 2009 | pmid = 19338351 | doi = 10.1021/jf804055n }}</ref>

<ref name=analytical>{{cite journal | vauthors = Mahoney N, Molyneux RJ | title = Rapid analytical method for the determination of aflatoxins in plant-derived dietary supplement and cosmetic oils | journal = Journal of Agricultural and Food Chemistry | volume = 58 | issue = 7 | pages = 4065–70 | date = April 2010 | pmid = 20235534 | pmc = 2858461 | doi = 10.1021/jf9039028 }}</ref>

<ref name=leong>{{cite journal
 | vauthors = Leong YH, Ismail N, Latiff AA, Manaf NA, Rosma A
 | title=Determination of aflatoxins in commercial nuts and nut products using liquid chromatography tandem mass spectrometry
 | journal=[[World Mycotoxin Journal]]|date=1 January 2011|volume=4|issue=2|pages=119–127|doi=10.3920/WMJ2010.1229}}</ref>

<ref name=fermetek>[http://www.fermentek.com/Aflatoxin_M2 Aflatoxin M2] product page from [[Fermentek]]</ref>

<ref name=bingham>{{cite journal | vauthors = Bingham AK, Phillips TD, Bauer JE | title = Potential for dietary protection against the effects of aflatoxins in animals | journal = Journal of the American Veterinary Medical Association | volume = 222 | issue = 5 | pages = 591–6 | date = March 2003 | pmid = 12619837 | doi = 10.2460/javma.2003.222.591 | doi-access = free }}</ref>

<ref name=bastianello>{{cite journal | vauthors = Bastianello SS, Nesbit JW, Williams MC, Lange AL | title = Pathological findings in a natural outbreak of aflatoxicosis in dogs | journal = The Onderstepoort Journal of Veterinary Research | volume = 54 | issue = 4 | pages = 635–40 | date = December 1987 | pmid = 3444619 }}</ref>

<ref name=rawal1>{{cite journal | vauthors = Rawal S, Yip SS, Coulombe RA | title = Cloning, expression and functional characterization of cytochrome P450 3A37 from turkey liver with high aflatoxin B1 epoxidation activity | journal = Chemical Research in Toxicology | volume = 23 | issue = 8 | pages = 1322–9 | date = August 2010 | pmid = 20707407 | doi = 10.1021/tx1000267 }}</ref>

<ref name=rawal2>{{cite journal | vauthors = Rawal S, Coulombe RA | title = Metabolism of aflatoxin B1 in turkey liver microsomes: the relative roles of cytochromes P450 1A5 and 3A37 | journal = Toxicology and Applied Pharmacology | volume = 254 | issue = 3 | pages = 349–54 | date = August 2011 | pmid = 21616088 | doi = 10.1016/j.taap.2011.05.010 }}</ref>

<ref name=aflacontrol>[http://resourcespace.icrisat.ac.in/filestore/1/1/3/8_16726338976b6c5/1138_d1bbb815d3a3d2d.pdf ''No chance for aflatoxins''] {{webarchive |url=https://web.archive.org/web/20151017005918/http://resourcespace.icrisat.ac.in/filestore/1/1/3/8_16726338976b6c5/1138_d1bbb815d3a3d2d.pdf |date=October 17, 2015 }} Rural 21, the International Journal for Rural Development, 3 April 2013. – The Aflacontrol project was conducted by [[International Food Policy Research Institute|IFPRI]] with scientists from [[CIMMYT]], the [[International Crops Research Institute for the Semi-Arid Tropics]] (ICRISAT), [[Directorate of Groundnut Research]] and other organizations. It sought to provide evidence of the cost-effectiveness of aflatoxin risk-reduction strategies along [[maize]] and [[Faboideae|groundnut]] [[value chain]]s in Africa, and to understand what prevented adoption of these control strategies.</ref>

<ref name=boonen>{{cite journal | vauthors = Boonen J, Malysheva SV, Taevernier L, Diana Di Mavungu J, De Saeger S, De Spiegeleer B | title = Human skin penetration of selected model mycotoxins | journal = Toxicology | volume = 301 | issue = 1–3 | pages = 21–32 | date = November 2012 | pmid = 22749975 | doi = 10.1016/j.tox.2012.06.012 }}</ref>

<ref name=williams>{{cite journal | vauthors = Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, Aggarwal D | title = Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions | journal = The American Journal of Clinical Nutrition | volume = 80 | issue = 5 | pages = 1106–22 | date = November 2004 | pmid = 15531656 | doi = 10.1093/ajcn/80.5.1106 | url = http://www.ajcn.org/content/80/5/1106.full | doi-access = free }}</ref>

<ref name=jolly>{{cite journal | doi=10.3920/WMJ2013.1585 | title=Association between high aflatoxin B<sub>1</sub> levels and high viral load in HIV-positive people | year=2013 | vauthors = Jolly PE, Inusah S, Lu B, Ellis WO, Nyarko A, Phillips TD, Williams JH | journal=World Mycotoxin Journal | volume = 6 | issue = 3 | pages = 255–261 | pmid=31534557 | pmc=6750767 }}</ref>

<ref name=jolly2>{{cite web
 | url = http://www.digitaljournal.com/article/357485
 | title = Common food fungus can accelerate onset of AIDS | publisher = digitaljournal.com | date = September 1, 2013}}</ref>

<ref name=petersen>{{cite journal | vauthors = Peterson S, Lampe JW, Bammler TK, Gross-Steinmeyer K, Eaton DL | title = Apiaceous vegetable constituents inhibit human cytochrome P-450 1A2 (hCYP1A2) activity and hCYP1A2-mediated mutagenicity of aflatoxin B1 | journal = Food and Chemical Toxicology | volume = 44 | issue = 9 | pages = 1474–84 | date = September 2006 | pmid = 16762476 | doi = 10.1016/j.fct.2006.04.010 }}</ref>

<ref name= MachidaMGomiK>{{cite book
 | veditors= Machida M, Gomi K
 | year=2010
 | title=''Aspergillus'': Molecular Biology and Genomics | publisher=Caister Academic Press | isbn= 978-1-904455-53-0}}</ref>

<ref name=goldblatt>{{Cite book
 | url = https://books.google.com/books?id=0rhSiCG3Ii4C&q=aflatoxin+pregnancy&pg=PA136
 | last = Goldblatt | first = Leo | name-list-style = vanc | date = 2012-12-02
 | title = Aflatoxin: Scientific Background, Control, and Implications | publisher = Elsevier | isbn = 9780323148498}}</ref>

}}

== External links ==
{{Wiktionary|aflatoxin}}
* {{usurped|1=[https://web.archive.org/web/20081204112027/http://www.aspergillus.org.uk/secure/metabolites/list_by_secmet.php?toxin=y Detailed listing and information on all ''Aspergillus'' mycotoxins]}}
* [http://www.icrisat.org/aflatoxin/ Aflatoxin] {{Webarchive|url=https://web.archive.org/web/20140228185900/http://www.icrisat.org/aflatoxin/ |date=2014-02-28 }}, ICRISAT
* {{usurped|1=[https://web.archive.org/web/20070307151941/http://www.aspergillusflavus.org/ Aspergillusflavus.org]}}
* [https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/aflatoxins Aflatoxins – Cancer-Causing Substance]
* [https://www.acs.org/content/acs/en/molecule-of-the-week/archive/a/aflatoxin-b1.html Aflatoxin B<sub>1</sub>]

{{Toxins}}
{{Consumer Food Safety}}
{{Authority control}}

[[Category:Aflatoxins| ]]