In 1960, more than 100,000 turkeys died in England in a short period of time. The birds failed to thrive and had subcutaneous haemorrhages. Post-mortem examination revealed necrotic liver damage and cell proliferation in the bile ducts. The cause remained unknown and the disorder was called ‘Turkey X disease’. Coincidently, a high mortality rate was reported among partridges, pheasants and ducks at poultry farms. The disorder was subsequently also detected in swine. During this same period, high incidences of hepatoma were found elsewhere in trout bred at fish farms. Epidemiological investigation eventually traced the problem to feed contamination, specifically a batch of Brazilian peanut meal which had been used as poultry feed for all these animals. This meal, which had been imported into the United Kingdom at the end of 1959, was subsequently termed Rosetti meal, after the name of the ship in which it was carried. It turned out to produce a new disease. Tests for known toxins proved negative.

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After painstaking analysis, the Rosetti meal and the fish food were found to be contaminated with the relatively common fungus, Aspergillus flavus. Depending upon the growing conditions, certain strains of this fungus produce a variety of chemical compounds called aflatoxins. The name of the toxins refers to the organism (the ‘a’ from Aspergillus and the ‘fla’ from flavus). The aflatoxins are a group of secondary metabolites which are formed after the logarithmic growth phase of the fungus. Aflatoxins are found as a natural contaminant in several foods, such as peanuts, cotton seed, maize, cassava, rice, cocoa, soya, wheat, sorghum and barley. Aspergillus flavus has a cosmopolitan distribution. However, this mould and the related fungus, A. parasiticus, only produce aflatoxins under certain conditions. Peanuts are a good substrate for aflatoxin production. It was recognized that Aspergillus flavus did not appreciably affect the peanuts prior to harvesting. The main determining factor for the growth and production of aflatoxin is the relative humidity. Few fungi grow on stored food at a humidity of less than 70%. At a relative humidity of 85% and a peanut water content of 30%, the fungus flourishes. Rapid post-harvest drying of the peanuts prevents attack by this fungus. When peanuts are left to dry in rainy or humid weather, this creates favourable conditions for aflatoxin production. Intact seeds are seldom infected. Damaged seeds, on the other hand (termites or mechanical damage) are more likely to be infected and to contain aflatoxin. When cows are fed infected feed, they secrete aflatoxins in their milk. Humans are exposed to aflatoxins through contaminated food. Toxins in particulates may cause aerogenic toxicity, e.g. in farmers working in a dusty environment with contaminated food products.

Several aflatoxins were found to exist. The aflatoxin B group fluoresces blue and the aflatoxin G group green under UV light. Aflatoxins are metabolized in the liver. Aflatoxin M is formed by biotransformation. This metabolite is found in milk from cows given contaminated feed. Various metabolites (epoxides?) may play a role in the toxicity of the compounds. Aflatoxins are very stable and are not destroyed at ordinary cooking temperatures.

The original bioassay consisted of administering infected peanut meal to 1-day-old ducks. After 8 days the animals were sacrificed and the gall bladder epithelium was examined for proliferation. Fish are also extremely sensitive to aflatoxins. While these bioassays have good sensitivity, they lack specificity. Detection via HPLC (High Performance Liquid Chromatography) allows precise measurements. ELISA detection is likewise reliable.

The carcinogenic potency of aflatoxins in rats and some other animals is extremely high. Aflatoxins have the ability to induce hepatocarcinomas in rats, ferrets, ducks and trout. Lesions also develop in guinea pigs, turkeys, dogs, rabbits and monkeys. In trout, aflatoxin B1 at a concentration of 20 ppb (parts per billion) was found to cause liver tumours in more than 50% of the population after nine months. Aflatoxin B1 is a potent mutagen and is teratogenic in some animal species. Aflatoxins also suppress the immune system.

There are also indications that tumours may be induced in other organs and tissues. Growing evidence indicates that humans are susceptible. There are indications of acute toxicity of aflatoxins in humans but the evidence is still inconclusive. The acute syndrome is similar to Reye’s syndrome in children, with acute liver toxicity and encephalopathy. Given the fact that the precise aetiology of Reye’s syndrome is not entirely clear, this raises questions. In 1974, an epidemic in India (Gujarat and Rajastan) was characterized by icterus, rapid development of portal hypertension and ascites. More than a hundred people died. It was attributed to the consumption of maize contaminated with aflatoxins. In 2001, several people in Kenya died after eating maize containing up to 12,000 ppb aflatoxin. After the problem had been identified, large quantities of mouldy maize were confiscated and destroyed. Chronic toxicity is more important than acute toxicity. Toxins probably play a role in the high incidence of liver carcinoma in the tropics. Naturally, other factors also play a role, such as chronic hepatitis B and C. This should not be confused with cholangiocarcinoma in Southeast Asian countries, where chronic infection with the tiny oriental liver fluke (Clonorchis sinensis) plays a role. The possible influence of aflatoxins on kwashiorkor is not yet clear.