Aflatoxins are naturally occurring mycotoxins that are produced by Aspergillus flavus and Aspergillus parasiticus, species of fungi. The name, aflatoxin, was created around 1960 after the discovery that the source of "Turkey 'X' disease" was Aspergillus flavus toxins. Aflatoxins are toxic and among the most carcinogenic substances known. 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 1
- Contamination conditions 2
- Pregnancy 3.1
- Microbiology 4
- Detection in humans 5
- Animals 6
- List of outbreaks 7
- See also 8
- Notes 9
- External links 10
Major types of aflatoxins and their metabolites
At least 14 different types of aflatoxin are produced in nature. 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 that harmful levels of aflatoxin also are present, it does imply a significant risk in consumption. Aflatoxins M1, M2 originally were 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 may come from a mother's milk)
- Aflatoxin M2, metabolite of aflatoxin B2 in milk of cattle fed on contaminated foods
- Aflatoxin Q1 (AFQ1), major metabolite of AFB1 in in vitro liver preparations of other higher vertebrates
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. In 2003, 120 people died in Kenya after eating maize with very high aflatoxin levels.
The native habitat of Aspergillus is in soil, decaying vegetation, 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 minimizing exposure to aflatoxins.
Organic crops which are not treated with fungicides may be more susceptible to contamination with aflatoxins.
International sources of commercial peanut butter, cooking oils (e.g. olive, peanut and sesame oil), and cosmetics have been identified as contaminated with aflatoxin. In some instances, 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.
High-level aflatoxin exposure produces an acute hepatic necrosis, resulting later in cirrhosis, or carcinoma of the liver. Acute liver failure is made manifest by bleeding, edema, alteration in digestion, changes to the absorption and/or metabolism of nutrients, and mental changes and/or coma.
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.
Chronic, subclinical exposure does not lead to symptoms so dramatic as acute aflatoxicosis. Children, however, are particularly affected by aflatoxin exposure, which leads to stunted growth and delayed development. Chronic exposure also leads to a high risk of developing liver cancer, as aflatoxin metabolites may intercalate into DNA and alkylate the bases through 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.
Moreover, aflatoxin B1 can permeate through the skin. Dermal exposure to this aflatoxin in particular environmental conditions may lead to serious health risks.
Some studies showed significant relationship between exposure of aflatoxin B1 (4 mg/kg, single dose) and teratogenesis (the appearance of developmental anomalies) in hamsters.
Aflatoxins are recognized as the most important mycotoxins. They are synthesized by only a few
List of outbreaks
In 2005, Diamond Pet Foods discovered aflatoxin in a product manufactured at their facility in Gaston, South Carolina. 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 with the "Best By" dates of April 3, April 4, April 5, and April 11 had the potential to be toxic.
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 sampled subsequently and tested for aflatoxin.
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.
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.
Low levels of aflatoxin exposure require continuous consumption for several weeks to months in order for signs of liver dysfunction to appear. Some articles have suggested the toxic level in dog food is 100–300 ppb and requires continuous exposure or consumption for a few weeks to months to develop aflatoxicosis. No information is available to suggest that recovered dogs will later succumb to an aflatoxin-induced disease.
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 who develop liver disease will recover. Those exposed to large doses for extended periods may not.
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 or months.
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 during the past 24 hours. This technique measures only recent exposure, however. Due to the half-life of this metabolite, the level of AFB1-guanine measured may vary from day to day, based on diet, it is not ideal for assessing long-term exposure.
There are two principal techniques that have been used most often to detect levels of aflatoxin in humans.
Detection in humans
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.