Mycotoxins are highly toxic metabolic products of higher filamentous fungi, which arise naturally in the secondary metabolism of the micromycetes and are released into the medium. Poisonings by mycotoxins are referred to as mycotoxicoses, with the chronic toxicity of these toxins in particular needing to be borne in mind.
Several routes of uptake are possible, with uptake through food as a rule being the main source. Fungal growth during storage at the retailer’s or consumer’s is usually recognisable macroscopically, so that such foods can be discarded. On the other hand, however, mycotoxins can form even before and during the production of a food, in some cases even before the plants are harvested in the field. Since these toxins are frequently not destroyed during food production and processing, even foods that are visually completely unremarkable can contain mycotoxins. This is discussed further below. When contaminated feed is given to farm animals, residues can moreover occur in the edible tissues. In addition, direct uptake of mycotoxins through contact via mucous membranes and through inhalation of spores must also be taken into account. Finally, it must also be assumed that mycotoxin formation can occur in systemic fungal infections, as has been demonstrated in various animal species. The formation of mycotoxins during the multiplication of higher fungi in tissue presumably serves the active confrontation with the host organism.
Mycotoxins are in general low-molecular-weight substances that are largely heat-stable and are not destroyed in foods by thermal processes such as boiling, roasting, etc. After uptake into the organism, because of the low-molecular-weight structures no antibody formation takes place either, so that humans cannot build up corresponding protective mechanisms. In acute toxicity the mycotoxins mostly rank behind the bacterial toxins. With regard to their chemical structure, numerous mycotoxins behave like alkylating agents, which can actively intervene in the DNA or RNA synthesis of cells. Because of their intervention in the natural processes of cell division, such substances must be regarded as potential carcinogens. This applies, for example, to the aflatoxins.
Aflatoxins
The most important producers of the aflatoxins are the moulds Aspergillus (A). flavus and A. parasiticus.
Metabolism and toxicity
The target organ of the aflatoxin effect is the liver, with aflatoxin B1 having by far the greatest hepatotoxic and carcinogenic potential. Aflatoxin B1 is partly metabolised in the liver, and only a relatively small percentage is excreted in urine, faeces and milk. One metabolic product is aflatoxin epoxide, to which the actual mutagenic effect is attributed. Other metabolites, such as aflatoxin M1, can be detected, for example, in cow’s milk. The toxic activation to aflatoxin-7,8-epoxide is catalysed by the microsomal cytochrome P450 system of the liver (see also information sheet “Liver and detoxification”).
Numerous epidemiological studies from Third World countries such as China, Kenya, Uganda, etc. have suggested a causal connection with the increased incidence of primary hepatocellular carcinomas observed there. In these tropical regions the growth of moulds and thus aflatoxin formation is favoured. In Europe the aflatoxins are said to be of lesser importance, but it must be borne in mind that numerous foods, and above all also feedstuffs in animal husbandry, are imported from Third World countries. Corresponding regulations on maximum levels are therefore intended to limit the intake of aflatoxins.
Occurrence
Positive aflatoxin findings can frequently be detected in peanuts and peanut products, other nuts and dried figs. For Germany a maximum limit of 4ug/kg applies with regard to total aflatoxins for cereals, nuts, fruit, vegetables, dairy products, meat and offal, and of 0.05ug/Kg for dietetic foods for infants and young children. The occurrence of aflatoxin M1 in milk and dairy products can be something of a problem. Here Germany has a maximum limit of 0.05 ug/kg aflatoxin M1 for milk and of 0.01 ug/kg for dietetic foods for infants and young children.
Ochratoxin A1
Ochratoxin A is a coumarin derivative. In addition, ochratoxin B and ochratoxin C occur as esters of ochratoxin A. The highest toxicity, however, is found with ochratoxin A. The toxins were named after Aspergillus (A.) ochraceus, as this species was the first to be identified as a producer of these coumarin derivatives. In addition, other aspergilli such as A. glaucus, A. sulfureus and others, as well as Penicillium species, are also capable of forming ochratoxin A.
Sources
Ochratoxin A is widespread in numerous foods of plant origin. All native cereal species are affected. Ochratoxin A levels show a strong dependence on the condition of storage. In various European states corresponding limit values for cereals have been issued. Recently it has been established that coffee, too, is frequently contaminated with ochratoxin A. The feeding of ochratoxin-containing feed can lead to corresponding residues in the blood and tissues of slaughter animals, particularly in offal. High levels are detected above all in pigs. For the pig a biological half-life of 88.8 days was determined, and there are indications that considerably longer half-lives are likely to apply in humans. Very high ochratoxin A concentrations were found in the blood plasma of pigs. If this is used for sausage production, corresponding residues are also to be expected in sausage products. Humans, as the final link in the food chain, cannot escape this constant intake of ochratoxin A, and ochratoxin A is detectable in practically all serum samples in the German population.
Toxic effects
Ochratoxin A exhibits high nephrotoxicity, and animal experiments show a mycotoxic nephropathy characterised by tubular atrophy. In various animal species corresponding kidney damage can be produced experimentally with ochratoxin A. In addition, a further kidney-damaging fungal metabolite, citrinin, is also likely to play a role. The so-called Balkan nephropathy, which occurs endemically in humans in countries of the Balkans, shows a clinical picture similar to ochratoxin A intoxication in animals and has therefore also been linked to increased ochratoxin A exposure. This may possibly be attributable to the one-sided consumption of contaminated home-grown produce. The disease usually becomes manifest only at the age of around 25 to 30 years and is not infrequently fatal. Besides tubular damage, the function of the glomeruli also becomes impaired in the further course. While ochratoxin A in low doses initially has a nephrotoxic effect, hepatotoxic effects have also been shown at higher concentrations. At the same time there are also indications of a tumorigenic effect.
Zearalenone
Zearalenone is a metabolite of the secondary metabolism of field fungi, above all of Fusarium species. The toxic effect of zearalenone is based essentially on its oestrogenic properties.
Sources
Fusarium species can infest practically all cereal species in the growing areas of the cool temperate zones of Europe, Asia, North America and Australia. Toxin formation often begins on the cereal plant even before harvest and can then continue if the storage conditions after harvest permit this. Particularly large amounts of zearalenone are formed by the pathogen causing Fusarium ear rot of maize, Fusarium roseum. The feeding of zearalenone-contaminated feed can also lead to zearalenone exposure in farm animals.
Toxic effects
From animal studies, particularly in pigs, fertility disorders, pathological enlargement of the vulva and uterus, death of the foetuses and, in male pigs, testicular atrophy were observed under increased zearalenone exposure.
In humans, too, there may be a health risk if they take in zearalenone or the primary metabolites alpha- and beta-zearalenol with food, the toxic effects here also being determined by the oestrogenic properties. Studies from Costa Rica made a possible connection between early sexual development in male adolescents and zearalenone exposure appear probable. On the basis of the animal studies, an influence on conception, teratogenic effects on embryos and a possible promotion of liver tumours cannot in principle be ruled out in humans either.