Aflatoxin

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Not to be confused with Alpha toxin.
Chemical structure of aflatoxin B1

Aflatoxins are naturally occurring mycotoxins that are produced by Aspergillus flavus and Aspergillus parasiticus, species of fungi. The name was created around 1960 after the discovery that the source of turkey X disease was Aspergillus flavus toxins.[1] Aflatoxins are toxic and among the most carcinogenic substances known.[2] After entering the body, aflatoxins may be metabolized by the liver to a reactive epoxide intermediate or hydroxylated to become the less harmful aflatoxin M1.

Major types of aflatoxins and their metabolites[edit]

At least 14 different types of aflatoxin are produced in nature.[3] Aflatoxin B1 is considered the most toxic and is produced by both Aspergillus flavus and Aspergillus parasiticus. Aflatoxin G1 and G2 are produced exclusively by A. parasiticus. While the presence of Aspergillus in food products does not always indicate harmful levels of aflatoxin are also present, it does imply a significant risk in consumption. Aflatoxins M1, M2 were originally discovered in the milk of cows that fed on moldy grain. These compounds are products of a conversion process in the animal's liver. However, aflatoxin M1 is present in the fermentation broth of Aspergillus parasiticus.

  • Aflatoxin B1 & B2, produced by Aspergillus flavus and A. parasiticus
  • Aflatoxin G1 & G2, produced by Aspergillus parasiticus
  • Aflatoxin M1, metabolite of aflatoxin B1 in humans and animals (exposure in ng levels can come from a mother's milk)
  • Aflatoxin M2, metabolite of aflatoxin B2 in milk of cattle fed on contaminated foods[4]
  • Aflatoxicol
  • Aflatoxin Q1 (AFQ1), major metabolite of AFB1 in in vitro liver preparations of other higher vertebrates[5]

Contamination conditions[edit]

Aflatoxin-producing members of Aspergillus are common and widespread in nature. They can colonize and contaminate grain before harvest or during storage. Host crops, which include maize, sorghum and groundnuts, are particularly susceptible to infection by Aspergillus following prolonged exposure to a high-humidity environment, or damage from stressful conditions such as drought, a condition that lowers the barrier to entry. In 2003, 120 people died in Kenya after eating maize with very high aflatoxin levels.[6]

The native habitat of Aspergillus is in soil, decaying vegetation, hay, and grains undergoing microbiological deterioration, and it invades all types of organic substrates whenever conditions are favorable for its growth. Favorable conditions include high moisture content (at least 7%) and high temperature. The Aflacontrol project, conducted by IFPRI with scientists from CIMMYT, the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) and other organisations, sought to provide evidence of the cost-effectiveness of aflatoxin risk-reduction strategies along maize and groundnut value chains in Africa, and to understand what prevented adoption of these control strategies. The project found that, in both Kenya and Mali, maize drying and storage practices were inadequate in minimising exposure to aflatoxins.[7]

The toxin can also be found in the milk of animals that are fed contaminated feed.

International sources of commercial peanut butter, cooking oils (e.g. olive, peanut and sesame oil), and cosmetics have been identified as contaminated with aflatoxin.[8][9][10] In some instances, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and other analytical methods, revealed anywhere from 48–80% of selected product samples as containing detectable quantities of aflatoxin. In many of these contaminated food products, the aflatoxin exceeded U.S. Food and Drug Administration (FDA), or other regulatory agency, safe limits.[9][10][11][12]

The United States Food and Drug Administration (FDA) has established action levels for aflatoxin present in food or feed to protect human and animal health which range between 20 and 300 ppb.[13]

Pathology[edit]

High-level aflatoxin exposure produces an acute hepatic necrosis, resulting later in cirrhosis, or carcinoma of the liver. Acute hepatic failure is made manifest by hemorrhage, edema, alteration in digestion, changes to the absorption and/or metabolism of nutrients, and mental changes and/or coma.[citation needed]

No animal species is immune to the acute toxic effects of aflatoxins; however, adult humans have a high tolerance for aflatoxin exposure and rarely succumb to acute aflatoxicosis.[14]

Chronic, subclinical exposure does not lead to symptoms as dramatic as acute aflatoxicosis. Children, however, are particularly affected by aflatoxin exposure, which leads to stunted growth and delayed development.[15] Chronic exposure also leads to a high risk of developing liver cancer, as aflatoxin metabolites can intercalate into DNA and alkylate the bases through its epoxide 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.[16]

Medical research indicates that a regular diet including apiaceous vegetables, such as carrots, parsnips, celery and parsley, may reduce the carcinogenic effects of aflatoxin.[17]

Moreover, aflatoxin B1 can permeate through the skin. Dermal exposure to this aflatoxin in particular environmental conditions can lead to serious health risks.[18]

Because aflatoxin B1 can cause immune suppression, exposure is associated with an increased viral load in HIV positive individuals.[19][20]

Pregnancy[edit]

Some studies showed significant relationship between exposure of Aflatoxin B1 (4 mg/kg, single dose) and teratogenesis (the appearance of developmental anomalies) in hamsters.[21]

Microbiology[edit]

Aflatoxins are recognized as the most important mycotoxins. They are synthesized by only a few Aspergillus species of which A. flavus and A. parasiticus are the most problematic. 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 is primarily 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.[22]

A. flavus and A. parasiticus are weedy molds that grow on a large number of substrates, in particular under high moisture conditions. 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, chillies, corn, cotton seed, millet, peanuts, rice, sorghum, sunflower seeds, tree nuts, wheat, and a variety of spices intended for human or animal consumption. When processed, aflatoxins get into the general food supply where they have been found in both pet and human foods, as well as in feedstocks for agricultural animals. Aflatoxin transformation products are sometimes found in eggs, milk products and meat when animals are fed contaminated grains.[23]

Detection in humans[edit]

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

The first method is measuring the AFB1-guanine adduct in the urine of subjects. The presence of this breakdown product indicates exposure to aflatoxin B1 in the past 24 hours. However, this technique measures only recent exposure, and, due to the half-life of this metabolite, the level of AFB1-guanine measured can vary from day to day, based on diet, and thus is not ideal for assessing long-term exposure.

Another technique that has been used is a measurement of the AFB1-albumin adduct level in the blood serum. This approach provides a more integrated measure of exposure over several weeks/months.

Animals[edit]

Aflatoxin has potential to lead to liver disease in dogs; however, not all dogs exposed to aflatoxin will develop liver disease. As with any toxic exposure, development of aflatoxicosis is a dose-related occurrence. Some dogs that develop liver disease will recover; those exposed to large doses for extended periods may not.

Low levels of aflatoxin exposure require continuous consumption for several weeks to months in order for signs of liver dysfunction to appear.[24] Some articles have suggested the toxic level in dog food is 100–300 ppb and requires continuous exposure/consumption for a few weeks to months to develop aflatoxicosis.[25] 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 B1 in the liver of turkeys and deficient glutathione-S-transferase mediated detoxification. The mechanistic understanding of the susceptibility of turkeys to aflatoxin B1 is very relevant since turkeys are important from an agricultural standpoint.[26][27]

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.

As a precautionary measure, both human and pet food recalls have occurred, casting a wide safety net to prevent exposure to potentially unsafe food. Recalled food products are subsequently sampled and tested for aflatoxin.

In 2005, Diamond Pet Foods discovered aflatoxin in a product manufactured at their facility in Gaston, South Carolina.[28][29] Diamond voluntarily recalled in 23 states 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 with the "Best By" dates of April 3, April 4, April 5, and April 11 were potentially toxic.[30]

See also[edit]

Notes[edit]

  1. ^ Wannop, C. C. (March 1961). "The Histopathology of Turkey “X” Disease in Great Britain". Avian Diseases 5 (4): 371–381. doi:10.2307/1587768. JSTOR 1587768. 
  2. ^ Hudler, George W. (1998). Magical Mushrooms, Mischievous Molds: The Remarkable Story of the Fungus Kingdom and Its Impact on Human Affairs. Princeton University Press. ISBN 978-0-691-07016-2. 
  3. ^ Boutrif, E. (1998). "Prevention of aflatoxin in pistachios". Food, nutrition and agriculture 21. 
  4. ^ Aflatoxin M2 product page from Fermentek
  5. ^ Smith, John E.; Sivewright-Henderson, Rachel (1991). Mycotoxins and animal foods. CRC Press. p. 614. ISBN 978-0-8493-4904-1. 
  6. ^ Eastern and Southern Africa highlights 2011, ICRISAT, 2012.
  7. ^ No chance for aflatoxins Rural 21, the International Journal for Rural Development, 3 April 2013.
  8. ^ Bao L, Trucksess MW, White KD. (2010). "Determination of aflatoxins B1, B2, G1, and G2 in olive oil, peanut oil, and sesame oil". Journal of AOAC International 93 (3): 936–42. PMID 20629398. 
  9. ^ a b Li, Feng-Qin; Li, Yu-Wei; Wang, Ye-Ru; Luo, Xue-Yun (13 May 2009). "Natural Occurrence of Aflatoxins in Chinese Peanut Butter and Sesame Paste". Journal of Agricultural and Food Chemistry 57 (9): 3519–24. doi:10.1021/jf804055n. PMID 19338351. 
  10. ^ a b Mahoney, Noreen; Russell J. Molyneux (14 April 2010). "A Rapid Analytical Method for Determination of Aflatoxins in Plant-Derived Dietary Supplement and Cosmetic Oils". J Agric Food Chem. 58 (7): 4065–70. doi:10.1021/jf9039028. PMC 2858461. PMID 20235534. 
  11. ^ Leong, Y. -H.; Ismail, N.; Latiff, A. A.; Manaf, N. A.; Rosma, A. (1 January 2011). "Determination of aflatoxins in commercial nuts and nut products using liquid chromatography tandem mass spectrometry". World Mycotoxin Journal 4 (2): 119–127. doi:10.3920/WMJ2010.1229. 
  12. ^ McDaniel, A. (1 January 2011). "Effect of Matrix Clean-Up for Aflatoxin Analysis in Corn and Dried Distillers Grains". Natural Resources 02 (4): 250–257. doi:10.4236/nr.2011.24032. 
  13. ^ Guidance for Industry: Action Levels for Poisonous or Deleterious Substances in Human Food and Animal Feed. Food and Drug Administration. August 2000. Retrieved March 10, 2013 
  14. ^ Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, Aggarwal D (November 2004). "Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions". Am. J. Clin. Nutr. 80 (5): 1106–22. PMID 15531656. 
  15. ^ Abbas, Hamed K. (2005). Aflatoxin and Food Safety. CRC Press. ISBN 0-8247-2303-1. 
  16. ^ Aguilar F, Hussain SP, Cerutti P (September 1993). "Aflatoxin B1 induces the transversion of G→T in codon 249 of the p53 tumor suppressor gene in human hepatocytes". Proceedings of the National Academy of Sciences of the United States of America 90 (18): 8586–90. doi:10.1073/pnas.90.18.8586. PMC 47402. PMID 8397412. 
  17. ^ Peterson S, Lampe JW, Bammler TK, Gross-Steinmeyer K, Eaton DL (September 2006). "Apiaceous vegetable constituents inhibit human cytochrome P-450 1A2 (hCYP1A2) activity and hCYP1A2-mediated mutagenicity of aflatoxin B1". Food Chem. Toxicol. 44 (9): 1474–84. doi:10.1016/j.fct.2006.04.010. PMID 16762476. 
  18. ^ Boonen, Jente; Malysheva, Svetlana V.; Taevernier, Lien; Diana Di Mavungu, José; De Saeger, Sarah; De Spiegeleer, Bart (2012). "Human skin penetration of selected model mycotoxins". Toxicology 301 (1–3): 21–32. doi:10.1016/j.tox.2012.06.012. PMID 22749975. 
  19. ^ Jolly, P.E.; Inusah, S.; Lu, B.; Ellis, W.O.; Nyarko, A.; Phillips, T.D.; Williams, J.H. (2013). "Association between high aflatoxin B1 levels and high viral load in HIV-positive people". World Mycotoxin Journal 6 (3): 255. doi:10.3920/WMJ2013.1585. 
  20. ^ "Common food fungus can accelerate onset of AIDS". digitaljournal.com. Sep 1, 2013. 
  21. ^ Goldblatt, Leo (2012-12-02). Aflatoxin: Scientific Background, Control, and Implications. ISBN 9780323148498. 
  22. ^ Machida, M; Gomi, K (editors) (2010). Aspergillus: Molecular Biology and Genomics. Caister Academic Press. ISBN 978-1-904455-53-0. 
  23. ^ Fratamico, PM et al. (editors) (2008). Foodborne Pathogens: Microbiology and Molecular Biology. Horizon Scientific Press. ISBN 978-1-898486-52-7. 
  24. ^ Bingham AK, Phillips TD, Bauer JE (March 2003). "Potential for dietary protection against the effects of aflatoxins in animals". J. Am. Vet. Med. Assoc. 222 (5): 591–6. doi:10.2460/javma.2003.222.591. PMID 12619837. 
  25. ^ Bastianello SS, Nesbit JW, Williams MC, Lange AL (December 1987). "Pathological findings in a natural outbreak of aflatoxicosis in dogs". Onderstepoort J. Vet. Res. 54 (4): 635–40. PMID 3444619. 
  26. ^ Rawal S, Yip SS, Coulombe RA Jr (August 2010). "Cloning, expression and functional characterization of cytochrome P450 3A37 from turkey liver with high aflatoxin B1 epoxidation activity". Chem. Res. Toxicol. 23 (8): 1322–9. doi:10.1021/tx1000267. PMID 20707407. 
  27. ^ Rawal S, Coulombe RA Jr (August 2011). "Metabolism of aflatoxin B1 in turkey liver microsomes: the relative roles of cytochromes P450 1A5 and 3A37". Toxicol. Appl. Pharmacol. 254 (3): 349–54. doi:10.1016/j.taap.2011.05.010. PMID 21616088. 
  28. ^ FDA Inspection Report-Diamond Gaston SC Plant 12/21/2005-1/19/2006.
  29. ^ 2005 Recall, FDA
  30. ^ AKC Standard Article Contaminated Diamond Pet Food Products and 'Best By' Dates Narrowed Akcstandard.com[dead link]

External links[edit]