Children are particularly affected by aflatoxin exposure, which is associated with stunted growth, delayed development, liver damage, and liver cancer. An association between childhood stunting and aflatoxin exposure has been reported in some studies but could not be detected in all. Furthermore, a causal relationship between childhood stunting and aflatoxin exposure has yet to be conclusively shown by epidemiological studies, though such investigations are under way. Adults have a higher tolerance to exposure, but are also at risk. No animal species is immune. Aflatoxins are 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.
Aflatoxins are most commonly ingested. However the most toxic type of aflatoxin, B1, can permeate through the skin.
The term "aflatoxin" is derived from the name of one of the molds that produce it, Aspergillus flavus. It was coined around 1960 after its discovery as the source of "Turkey X disease". Aflatoxins form one of the major groupings of mycotoxins.
Aflatoxin B1 and B2 (AFB), produced by Aspergillus flavus and A. parasiticus
Aflatoxin G1 and G2 (AFG), produced by some Group II A. flavus and Aspergillus parasiticus
Aflatoxin M1 (AFM1), 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
Aflatoxicol (AFL): metabolite produced by breaking down the lactone ring
Aflatoxin Q1 (AFQ1), major metabolite of AFB1 in in vitro liver preparations of other higher vertebrates
AFM, AFQ, and AFL retain the possibly to become an epoxide. Nevertheless, they appear much less capable of causing mutagenesis than the unmetabolized toxin.
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.
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 include high moisture content (at least 7%) and high temperature. 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.
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.
Organic crops, which are not treated with fungicides, may be more susceptible to contamination with aflatoxins.
There is very limited evidence to show that agricultural and nutritional education can reduce exposure to aflatoxin in low to middle income countries.
No animal species is immune to the acute toxic effects of aflatoxins. Adult humans have a high tolerance for aflatoxin exposure and rarely succumb to acute aflatoxicosis, but children are particularly affected, and their exposure can lead to stunted growth and delayed development, in addition to all the symptoms mentioned below.
Chronic, subclinical exposure does not lead to symptoms so dramatic as acute aflatoxicosis. Chronic exposure increases the risk of developing liver and gallbladder 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. As with other DNA-alkylating agents, Aflatoxin B1 can cause immune suppression, and exposure to it is associated with an increased viral load in HIV positive individuals.
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.
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. 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.
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.
Some studies on pregnant hamsters showed a significant relationship between exposure of aflatoxin B1 (4 mg/kg, single dose) and the appearance of developmental anomalies in their offspring.
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 had the potential to be toxic.
In December 2020 and January 2021, Midwestern Pet Foods recalled dog food that contained fatal levels of aflatoxin. As many as 70 dogs had died from aflatoxin poisoning by January 12, 2021.
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 AFB1-guanineadduct 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.
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.
List of outbreaks
This section needs expansion. You can help by adding to it. (December 2014)
^Voth-Gaeddert LE, Stoker M, Torres O, Oerther DB (April 2018). "Association of aflatoxin exposure and height-for-age among young children in Guatemala". International Journal of Environmental Health Research. 28 (3): 280-292. doi:10.1080/09603123.2018.1468424. PMID29706087. S2CID23510545.
^Neal GE, Eaton DL, Judah DJ, Verma A (July 1998). "Metabolism and toxicity of aflatoxins M1 and B1 in human-derived in vitro systems". Toxicology and Applied Pharmacology. 151 (1): 152-8. doi:10.1006/taap.1998.8440. PMID9705898.
^Machida M, Gomi K, eds. (2010). Aspergillus: Molecular Biology and Genomics. Caister Academic Press. ISBN978-1-904455-53-0.
^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 and Chemical Toxicology. 44 (9): 1474-84. doi:10.1016/j.fct.2006.04.010. PMID16762476.
^Bingham AK, Phillips TD, Bauer JE (March 2003). "Potential for dietary protection against the effects of aflatoxins in animals". Journal of the American Veterinary Medical Association. 222 (5): 591-6. doi:10.2460/javma.2003.222.591. PMID12619837.
^Bastianello SS, Nesbit JW, Williams MC, Lange AL (December 1987). "Pathological findings in a natural outbreak of aflatoxicosis in dogs". The Onderstepoort Journal of Veterinary Research. 54 (4): 635-40. PMID3444619.
^Rawal S, Yip SS, Coulombe RA (August 2010). "Cloning, expression and functional characterization of cytochrome P450 3A37 from turkey liver with high aflatoxin B1 epoxidation activity". Chemical Research in Toxicology. 23 (8): 1322-9. doi:10.1021/tx1000267. PMID20707407.
^Rawal S, Coulombe RA (August 2011). "Metabolism of aflatoxin B1 in turkey liver microsomes: the relative roles of cytochromes P450 1A5 and 3A37". Toxicology and Applied Pharmacology. 254 (3): 349-54. doi:10.1016/j.taap.2011.05.010. PMID21616088.
^ abLi FQ, Li YW, Wang YR, Luo XY (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. PMID19338351.
^Leong YH, Ismail N, Latiff AA, Manaf NA, 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.