Produced by : Aspergillus flavus, A. parasiticus

Introduction and structure :

Aflatoxins are toxic metabolites produced by Aspergillus flavus or A. parasiticus in/on foods and feeds. They are probably the best known and most intensively researched mycotoxins in the world. Aflatoxins have been associated with various diseases, such as aflatoxicosis, in livestock, domestic animals and humans throughout the world. The occurrence of aflatoxins is influenced by certain environmental factors; hence the extent of contamination will vary with geographic location, agricultural and agronomic practices, and the susceptibility of commodities to fungal invasion during preharvest, storage, and/or processing periods. Aflatoxins have received greater attention than any other mycotoxins because of their demonstrated potent carcinogenic effect in susceptible laboratory animals and their acute toxicological effects in humans. As it is realized that absolute safety is never achieved, many countries have attempted to limit exposure to aflatoxins by imposing regulatory limits on commodities intended for use as food and feed.

In the 1960 more than 100,000 young turkeys on poultry farms in England died in the course of a few months from an apparently new disease that was termed "Turkey X disease" . It was soon found that the difficulty was not limited to turkeys. Ducklings and young pheasants were also affected and heavy mortality was experienced.

A careful survey of the early outbreaks showed that they were all associated with feeds, namely Brazilian peanut meal. An intensive investigation of the suspect peanut meal was undertaken and it was quickly found that this peanut meal was highly toxic to poultry and ducklings with symptoms typical of Turkey X disease.

Speculations made during 1960 regarding the nature of the toxin suggested that it might be of fungal origin. In fact, the toxin-producing fungus was identified as Aspergillus flavus (1961) and the toxin was given the name Aflatoxin by virtue of its origin (A. flavus --> Afla).

This discovery has led to a growing awareness of the potential hazards of these substances as contaminants of food and feed causing illness and even death in humans and other mammals. Studies revealed that aflatoxins are produced primarily by some strains of A. flavus and by most, if not all, strains of A. parasiticus .

There are four major aflatoxins : B1, B2, G1, G2. Whereas the B designation of aflatoxins B1 and B2 resulted from the exhibition of blue fluorescence under UV-light, while the G designation refers to the yellow-green fluorescence of the relevant structures under UV-light. In addition, two metabolic products, aflatoxin M1 and M2, that are of significance as direct contaminants of foods and feeds. These were first isolated from milk of lactating animals fed aflatoxin preparations; hence, the M designation.

These toxins have closely similar structures and form a unique group of highly oxygenated, naturally occurring heterocyclic compounds :

Structure of aflatoxins

Occurrence

Aflatoxins often occur in crops in the field prior to harvest. Postharvest contamination can occur if crop drying is delayed and during storage of the crop if water is allowed to exceed critical values for the mould growth. Insect or rodent infestations facilitate mould invasion of some stored commodities.

Aflatoxins are detected occasionally in milk, cheese, corn, peanuts, cottonseed, nuts, almonds, figs, spices, and a variety of other foods and feeds. Milk, eggs, and meat products are sometimes contaminated because of the animal consumption of aflatoxin-contaminated feed. However, the commodities with the highest risk of aflatoxin contamination are corn, peanuts, and cottonseed.

Fungal growth and aflatoxin contamination are the consequence of interactions among the fungus, the host and the environment. The appropriate combination of these factors determines the infestation and colonization of the substrate, and the type and amount of aflatoxin produced. However, a suitable substrate is required for fungal growth and subsequent toxin production, although the precise factor(s) that initiates toxin formation is not well understood. Water stress, high-temperature stress, and insect damage of the host plant are major determining factors in mould infestation and toxin production. Similarly, specific crop growth stages, poor fertility, high crop densities, and weed competition have been associated with increased mould growth and toxin production.

Aflatoxin formation is also affected by associated growth of other moulds or microbes. For example, preharvest aflatoxin contamination of peanuts and corn is favoured by high temperatures, prolonged drought conditions, and high insect activity; while postharvest production of aflatoxins on corn and peanuts is favoured by warm temperatures and high humidity.

Effects on human health

Outbreaks of aflatoxicosis in farm animals have been reported from many areas of the world. The liver is mainly affected in such outbreaks and also in experimental studies on animals, including nonhuman primates. The acute liver lesions are characterized by necrosis of the hepatocytes and biliary proliferation, and chronic manifestations may include fibrosis. A feed level of aflatoxin as low as 300 µg/kg can induce chronic aflatoxicosis in pigs within 3-4 months.

Aflatoxin B 1 is a liver carcinogen in at least 8 species including nonhuman primates. Dose-response relationships have been established in studies on rats and rainbow trout, with a 10% tumour incidence estimated to occur at feed levels of aflatoxin B 1 of 1 µg/kg, and 0.1 µg/kg, respectively. In some studies, carcinomas of the colon and kidney have been observed in rats treated with aflatoxins.

The acute toxicity and carcinogenicity of aflatoxins are greater in male than in female rats; hormonal involvement may be responsible for this sex-linked difference. Nutritional status in animals can modify the expression of acute toxicity or carcinogenicity or both.

There is little information on the association of acute hepatoxicity in man with exposure to aflatoxins but cases of acute liver damage have been encountered that could possibly be attributed to acute aflatoxicosis. An outbreak of acute hepatitis in adjacent districts of two neighbouring states in north-west India, which affected several hundred people, was apparently associated with the ingestion of heavily contaminated maize, some samples of which contained aflatoxin levels in the mg/kg range, the highest reported level being 15 mg/kg.

Liver cancer is more common in some regions of Africa and south-eastern Asia than in other parts of the: world and, when local epidemiological information is considered together with experimental animal data, it appears that increased exposure to aflatoxins may increase the risk of primary liver cancer. Pooled data from Kenya, Mozambique, Swaziland, and Thailand, show a positive correlation between daily dietary aflatoxin intake (in the range of 3.5 to 222.4 ng/kg body weight per day) and the crude incidence rate of primary liver cancer (ranging from 1.2 to 13.0 cases per 100 000 people per year). There is also some evidence of a vital involvement in the aetiology of the disease.

In view of the evidence concerning the effects, particularly the carcinogenic effects, of aflatoxins in several animal species, and in view of the association between aflatoxin exposure levels and human liver cancer incidence observed in some parts of the world, exposure to aflatoxins should be kept as low as practically achievable. The tolerance levels for food products established in several countries should be understood as management tools intended to facilitate the implementation of aflatoxin control programmes, and not as exposure limits that necessarily ensure health protection.