Editing Aflatoxin (section)

==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]]