Aflatoxins

ROC STATUS: Known human carcinogen since 1980

ALSO KNOWN AS: Aflatoxin B¹, aflatoxin B², aflatoxin G¹, aflatoxin G², aflatoxin M¹

RELATED CANCERS: Liver cancer, primary liver cell cancer, hepatocellular carcinoma, lung cancer

DEFINITION: Aflatoxins are naturally occurring toxic metabolites produced by certain fungi that grow on some agricultural products. At least fourteen different aflatoxins are produced in nature, with the four major aflatoxins called aflatoxin B¹, B², G¹, and G². Aflatoxin B¹ is typically the most predominant as well as the most toxic. Aflatoxin M¹ is found primarily in milk.

Exposure routes: Ingestion and inhalation

Where found: Numerous agricultural commodities, including corn and other grains, peanuts, tree nuts, and cottonseed meal. Milk, eggs, and meat products can be contaminated if animals consume aflatoxin-contaminated feed.

At risk: Those living in countries where agricultural products that readily support the growth of aflatoxin-producing fungi are a dietary staple. Farmers and other agricultural workers are at risk for occupational exposure through inhalation of dust generated during the handling of contaminated crops and feeds.

Etiology and symptoms of associated cancers: Aflatoxin-producing fungi can grow on a wide range of agricultural products. Corn and groundnuts are major sources of human exposure because of greater susceptibility to contamination and widespread consumption. Worldwide, corn is probably of greatest concern because it is grown in climates that readily support the growth of fungi and is a dietary staple in many countries. Aflatoxin-producing fungi often grow on crops in the field before harvest, particularly if the crops have experienced drought stress. After harvest, contamination can occur during storage. The growth of aflatoxin-producing fungi and subsequent production of aflatoxins are influenced by weather conditions, such as high temperature and humidity. As a result, aflatoxin contamination varies with geographic location, agricultural and agronomic practices, and the susceptibility of crops to fungal growth. In the twenty-first century, global climate change could have a worrying impact on the prevalence of aflatoxins, as temperature and precipitation could promote increased growth. Aflatoxins are also likely to adapt to changing conditions, which increases crop susceptibility. 

Exposure to aflatoxins occurs primarily by consuming contaminated food. Aflatoxin consumption is commonplace in developing countries where food supplies are limited, and regulations of aflatoxin levels are not enforced or nonexistent. In developed countries, food supplies are generally more abundant and diverse, and aflatoxin levels are monitored to limit toxin ingestion. Although the sale of heavily contaminated food supplies is not permitted in developed countries, chronic exposure to low levels of aflatoxins may still be a concern.

The most common aflatoxin-producing fungi are Aspergillus flavus and Aspergillus parasiticus. Although many aflatoxins are produced by these fungi, aflatoxin B¹ is the most prevalent and the most toxic. Aflatoxin B¹ is also the most potent naturally occurring carcinogen. Aflatoxins are both toxic and carcinogenic, with exposure to high levels resulting in toxic effects referred to as aflatoxicosis and chronic exposure to low levels potentially resulting in cancer. Susceptibility to aflatoxin-related diseases is influenced by many factors, including age, exposure level, duration of exposure, health, nutritional status, and exposure to other agents, such as the hepatitis B virus (HBV).

The liver is the primary target organ of aflatoxin exposure, although other organs can also be affected. Metabolic activation by liver enzymes is required for the carcinogenic effects of aflatoxin B¹. In the liver, aflatoxin B¹ is metabolized to a highly reactive form that readily binds deoxyribonucleic acid (DNA) and proteins and can lead to liver damage and subsequent formation of tumors in the liver. Exposure to aflatoxins in the diet has been shown to be one of the major etiological factors in the development of primary hepatocellular carcinoma in some countries, such as China and many African countries. Concurrent infection with HBV and exposure to aflatoxins result in significantly greater liver damage than either infection or exposure alone, a synergy that is likely produced because HBV interferes with the liver’s ability to detoxify aflatoxins. Although aflatoxin is best known as an agent that promotes liver cancer, inhalation of contaminated grain dust has been associated with an increased incidence of lung cancer.

Liver cancer is not associated with any symptoms in the early stages. As the cancer progresses, symptoms may include pain in the upper abdomen on the right side, which may also extend to the back and shoulder. Other symptoms include a swollen or bloated abdomen, weight loss, loss of appetite, feeling of fullness, weakness, fatigue, nausea and vomiting, yellowish skin and eyes (jaundice), dark urine, and fever.

History: Aflatoxins have been recognized as a significant contaminant since the 1960s, when more than one hundred thousand young turkeys on poultry farms in England died from what was termed turkey X disease. The mortalities were traced to consumption of mold-contaminated peanut meal. In 1961, the toxin-producing fungus, A. flavus, was identified, and the toxin given the name aflatoxin. The International Agency for Research on Cancer (IARC) first recognized aflatoxins as carcinogenic in 1976. In 1987, naturally occurring mixtures of aflatoxins and AFB¹ were classified as Group I carcinogens.

Aflatoxins are considered unavoidable contaminants of food and feed, even when good manufacturing practices have been followed. For example, in 2024, a massive recall of multiple peanut butter brands in South Africa occurred due to high levels of aflatoxins. This incident highlighted the often-overlooked impact of food safety, even in developed countries. Although absolute safety can never be achieved, many countries have attempted to limit exposure to aflatoxins by imposing regulatory limits on commodities intended for consumption. The US Food and Drug Administration has established specific guidelines that regulate this toxin to very low concentrations in human food and animal feed.

Bibliography

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Eaton, D. L., and J. D. Groopman. The Toxicology of Aflatoxins. New York: Academic, 1994.

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Le Roux, Cornelia. “Aflatoxin Alert: Clover GoNuts Peanut Butter Latest Recall - What to Know and Do.” The Citizen, 11 Mar. 2024, www.citizen.co.za/lifestyle/food-and-drink/peanut-butter-brands-recall-aflatoxin-clover-latest-march-2024. Accessed 14 June 2024.

Shan, Xueyan, and W. Paul Williams. "Toward Elucidation of Genetic and Functional Genetic Mechanisms in Corn Host Resistant to Aspergillus flavus Infection and Aflatoxin Contamination." Frontiers in Microbiology, vol. 5, 2014, pp. 1–7.

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