Effects of mycotoxins in humans

HumansHumans are exposed to mycotoxins due to various reasons. They can consume plant derived foods, like cereals, oilseeds, spices and tree nuts or they are exposed to mycotoxins due to carry over to animal products, from animals fed with mycotoxin containing feed, such as milk, meat and eggs. Furthermore they can be exposed to air or dust containing the toxins.1,2 Mycotoxins of greatest public health significance range from aflatoxins, ochratoxins, trichothecenes, fumonisins, zearalenone and ergot alkaloids.3 In regions where food security standards are higher, mycotoxin exposure does not represent a significant risk for humans, compared to other regions, where food scarcity problems exist, and the climate offers better conditions for growth of molds and regulations are not enforced, e.g. Africa and other unregulated markets. The symptoms of mycotoxicoses (diseases associated with mycotoxins) depend on the type of the mycotoxin, the amount and the duration of mycotoxin exposure, and the age, sex and health of the exposed individual. Furthermore there are many poorly understood synergistic effects that might play an important role in the development of mycotoxicoses.4

Aflatoxins

Aflatoxins (Afla) can contaminate numerous food products, like cereals (maize, sorghum, rice, wheat), oilseeds (groundnut, soybean, sunflower), spices (chillies, black pepper, coriander), tree nuts (almonds, pistachios, walnuts, coconuts) and milk and milk products.5 Around 4.5 billion individuals of the world’s population are exposed to aflatoxins.6 Aflatoxins represent a group of naturally occurring carcinogens. The diseases resulting from aflatoxin intoxication are called aflatoxicoses and can be divided into acute and chronic diseases. Acute aflatoxicoses result from the consumption of moderate to high levels of aflatoxin and lead to hemorrhage, acute liver damage, malnutrition and possibly death (e.g. aflatoxin outbreak in 2003 in Kenya, where 120 people died), mainly in children. In children aflatoxins have been associated with kwashiorkor and marasmus, diseases leading to death due to protein malnutrition. Chronic aflatoxicoses result from the ingestion of low to moderate levels of aflatoxins. Aflatoxins are highly liver carcinogenic with toxicity and carcinogenic potential decreasing from B1>M1>G1>B2>G2. Aflatoxin B1 is classified as group 1 carcinogen (human carcinogen) by the IARC and is strongly associated with primary hepatocellular carcinoma, especially in individuals already exposed to hepatitis B, representing a heavy cancer burden in developing countries.4,6,7 Aflatoxins have also been reported to have effects on the digestive system, like vomiting, diarrhea and intestinal hemorrhage. Furthermore it is associated with neoplasms in extrahepatic tissues, particularly in the lungs, reported for example in Dutch peanut processing workers.6 In recent years immunosuppressive effects, nutritional and toxic encephalopathy, leading to loss of balance, recent memory decline, headaches, insomnia and loss of coordination have been reported.6,8 Strong evidence exists that aflatoxin exposure can increase susceptibility to infectious diseases and only recently it has been published that co-occurrence of aflatoxin and human immunodeficiency virus (HIV) might lead to faster progression to acquired immune deficiency syndrome (AIDS) in infected individuals.9 Aflatoxin M1, the metabolite of Aflatoxin B1 present in milk and milk products (e.g. 2013 European aflatoxin contamination), is classified as group 2B carcinogen and affects mostly the young individuals but also adults, leading to vomiting, abdominal pain, pulmonary edema and also necrosis of the liver.6,10 This provides evidence that Aflatoxin M1 is of great concern also for the Serbian adult population.11,12

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Trichothecenes

Trichothecenes

The most important representative of trichothecenes affecting human health is Deoxynivalenol (DON). T-2 toxin and its metabolite HT-2 and Nivalenol can also occur in food. Trichothecenes occur mainly in grains and cereals, for example breakfast cereals, but they occur also in beer. DON is also called vomitoxin as it causes acute temporary nausea, vomiting, diarrhea, abdominal pain, headaches, dizziness and fever.14 Historical evidence suggests that DON causes acute human illness, as outbreaks of human gastroenteritis after consumption of Fusarium-infested foods were reported in Korea and China.15 It also might act as an immunosuppressant and cause kidney problems.10 T-2 toxin and its metabolite HT-2 cause mainly diseases of the immune system and is associated with reduced food intake and vomiting.10 Historically, T-2 toxin in grain infected with different species of Fusarium led to a disease called “Alimentary Toxic Aleukia” during the second world war in Russia, an incredibly vicious disease including vomiting, diarrhea, profuse sweating, swelling, necrosis of the oral cavity and others.16 Furthermore direct skin contact with trichothecenes might lead to dermatosis.4

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Ergot Alkaloids

Ergot alkaloids can contaminate a variety of grass species, including small grains. Ergotism is one of the oldest known mycotoxicoses. Already in the Middle Ages a disease called “St. Anthony’s Fire” was described from affected individuals as sensation of fire shooting from the tips of their appendages.10 Two types exist: gangrenous, like dermal lesions, and convulsive with effects on the central nervous system and also gastrointestinal effects, like nausea and vomiting.10

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Ochratoxin

The main toxin in this group, Ochratoxin A (OTA), is found in wheat, corn, oats, cheese and meat products, but also may be found in soybeans, beans, nuts, dried fruit, coffee, grapes and grape products. In Chile studies have shown the presence of Ochratoxin A in human breast milk. The OTA intake of breastfed infants exceeded the tolerable daily intake giving rise to the suggestion to give dietary recommendations for pregnant women and nursing mothers to reduce OTA exposure of newborn.13 Ochratoxin A was classified as a group 2B carcinogen (possibly carcinogenic in human) by the International Agency for Research of Cancer (IARC).7 Ochratoxin is a potent nephrotoxin with the kidney as its primary target organ, but might also affect the liver.4 Furthermore Ochratoxin is suspected to cause a human disease called Balkan Endemic Nephropathy, affecting the kidneys and often resulting in tumors.10

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Fumonisins

Fumonisins (FUM) are mainly found in maize-containing food. Amongst the existing fumonisin compounds, the fumonisin B group is the most important regarding food contamination. Fumonisin B1, the most abundant one, was classified by the IRAC as group 2B carcinogen.4,7 It is suspected as tumor promoter and a probable link exists between it and esophageal cancer, as potential coincidence of esophageal cancer and high occurrence of Fumonisin B1 contamination was reported for example in the Transkei in South Africa.4,17 Fumonisins are also reported to lead to transient abdominal pain and diarrhea. Furthermore they are associated with neural tube defects like spina bifida or anencephaly, as they inhibit the uptake of folic acid.4,7

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Zearalenone

Zearalenone (ZEN) is almost entirely found in grains. ZEN has no acute toxicity, but due to its oestrogen-like activity it can disrupt steroid hormone functions when being consumed in sufficient levels. This might lead to hyper-oestrogenism in humans.7 Precocious pubertal changes in young children have been reported in Puerto Rico18 and gynecomastia with testicular atrophy in rural males in southern Africa19. Cases of premature breast development in girls under 8 years of age related to ZEN-contaminated food intake were reported in Hungary and Italy.20

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Effects of Mycotoxins in Humans

AFB1 – Aflatoxin B1 | AFM1 – Aflatoxin M1 | DON – Deoxynivalenol | FUM – Fumonisins | OTA – Ochratoxin A | T-2 – T-2 Toxin | HT-2 – HT-2 Toxin | ZEN - Zearalenone | Ergots – Ergot, Alkaloids

References
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  2. Jarvis BB. Chemistry and toxicology of molds isolated from water-damaged buildings. Mycotoxins and Food Safety; Adv. Expt. Med. Biol., 2002; 504:43-52
  3. Zain ME. Impact of mycotoxins on humans and animals. Journal of Saudi Chemical Society, 2011; 15:129-144
  4. Bennett JW, Klich M. Mycotoxins. Clin. Microbiol. Rev., 2003; 16(3):497-516
  5. Lopez C, et al. Aflatoxin B1 in human serum: Aflatoxin B1 content in patients with hepatic diseases. Medicina (Buenos Aires), 2002; 313-316
  6. Williams JH, et al. Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am. J. Clin. Nutr., 2004; 80:1106-1122
  7. Shephard GS. Impact of mycotoxins on human health in developing countries. Food Additives and Contaminants, 2008; 25(2):146-151
  8. Bbosa GS, et al. Review of the Biological and Health Effects of Aflatoxins on Body Organs and Body Systems. Intech Open Science, 2013; Chapter 12:239-265
  9. Jolly PE, et al. Association between high Aflatoxin B1 levels and high viral load in HIV-positive people. World Mycotoxin Journal, 2013; 6(3):255-261
  10. Krska R, et al. Romer Labs Guide to Mycotoxins [4th Edition]
  11. Skrbic B, et al. Levels of Aflatoxin M1 in different types of milk collected in Serbia: Assessment of human and animal exposure. Food Control, 2014; Vol.40:113-119
  12. Kos J, et al. Occurrence and estimation of Aflatoxin M1 exposure in milk in Serbia. Food Control, 2014; Vol.38:41-46
  13. Munoz K, et al. Exposure of neonates to Ochratoxin A: first biomonitoring results in human milk (colostrum) from Chile. Mycotox. Res., 2010; 26:59-67
  14. Sobrova P, et al. Deoxynivalenol and its toxicity. Interdis. Toxicol., 2010; Vol.3(3):94-99
  15. Pestka JJ. Deoxynivalenol: mechanisms of action, human exposure, and tocxicological relevance. Arch. Toxicol., 2010; 84:663-679
  16. Mayer CF. Endemic panmyelotoxicosis in the Russian grain belt. I. The clinical aspects of alimentary toxic aleukia (ATA); a comprehensive review. Military Surgeon, 1953; 113(3):173-189
  17. Myburg RB, et al. Cytotoxicity of Fumonisin B1, Diethylnitrosamine, and Catechol on the SNO Esophageal Cancer Cell Line. Environmental Health Perspectives, 2002; Vol.10(8):813-815
  18. Saenz de Rodrigues CA, et al. An epidemic of precocious development in Puerto Rican children. Journal of Pediatrics, 1985; 107:393-396
  19. Campbell GD. Trichothecene mycotoxicosis B a new entity? South African Medical Journal, 1991; 80:361-362
  20. European Food Safety Authority. Scientific Opinion on the risks for pubic health related to the presence of zearalenone in food. EFSA Journal, 2011; 9(6):2197