A handbook of environmental toxicology: human disorders and ecotoxicology.

Chapter 2 (Page no: 19)

Mycotoxins.

Mycotoxins induce adverse effects in humans and other vertebrate animals. Their production is determined by ecological and environmental factors (temperature, humidity and substrate water activity). The preponderance of specialized fungi in particular niches determines the type and range of mycotoxins that may contaminate food or indoor environment. Claviceps, Fusarium and Alternaria species are classical exponents of plant pathogens with toxigenic potential. C. purpurea produces the ergot alkaloids, while the principal Fusarium mycotoxins include the trichothecenes, zearalenone and fumonisins. A. alternata synthesizes tenuazonic acid, alternariol and altenuene. Aspergillus and Penicillium species exemplify food spoilage fungi, associated with particular conditions in post-harvest ecology. Aspergillus flavus and A. parasiticus produce the aflatoxins B1, B2, G1 and G2, but A. ochraceus together with Penicillium viridicatum and P. cyclopium synthesize ochratoxin A (OTA). P. citrinum and P. expansum are principal sources of citrinin, with the latter also producing patulin. In temperate countries, mycotoxin residues in cereal grains are largely the result of fungal disease of standing crops in the field. Consequently, host-pathogen interactions are important components in mycotoxin production. In warm humid tropical regions, fungal proliferation generally arises during post-harvest storage, particularly if the products have been inadequately dried, but the inoculum for these microorganisms may originate from field sources such as plant debris and soil. Current surveillance indicates widespread mycotoxin contamination of primary and processed plant products with global implications for human health. Concentrations of aflatoxins in maize and groundnuts regularly exceed safety threshold limits. OTA, certain trichothecenes and zearalenone occurr primarily in cereal grains and derived products. In addition, OTA may occur in dried vine fruits and green coffee beans. Of considerable concern is the widespread contamination of maize and associated products with fumonisins. The use of contaminated feedstocks in livestock nutrition may result in the transfer of mycotoxins to animal products, particularly milk and offal. Consequently, humans may be exposed to combinations of different foodborne mycotoxins. Although mycotoxins may be graded according to acute lethality tests, the major concerns in human health relate to epidemiological evidence. A broad spectrum of adverse outcomes has been associated with chronic exposure, including carcinogenesis, hepatitis, nephrotoxicity and endocrine disruption. Mycotoxins may compromise health by modulating other disorders. For example, foodborne aflatoxins may enhance the carcinogenic potential of hepatitis B virus. In addition, it has been proposed that kwashiorkor in African children may be a manifestation of aflatoxicosis. Nevertheless, in toxicological classification, aflatoxin B1 has been designated as a group 1 carcinogen, specifically implicated in liver, lung and gallbladder malignancy. Epidemiological evidence also links human oesophageal cancer in South Africa with dietary exposure to fumonisins. This group has been cited as a possible contributory risk factor in primary hepatocellular cancer in China. OTA has been linked with the incidence of Balkan (and possible Tunisian) endemic nephropathy, but the co-occurrence of OTA with citrinin suggests an interaction between the 2 mycotoxins. Current studies focus on molecular and biochemical dimensions, particularly in the context of mycotoxin-induced carcinogenesis. In the case of aflatoxin B1, this work includes nucleotide excision repair, DNA adduct reduction, cellular gene expression modulation, signalling pathways activation, mutational spectra, microRNA expression, interferon anti-cancer pathway and factors in cancer cell migration. It is envisaged that molecular and biochemical investigations should resolve cause-and-effect issues raised by epidemiological evidence and assist in evaluating alternative mechanisms in the aetiology of hepatocellular carcinoma. There may be scope for the characterization of improved biomarkers for the assessment of mycotoxin-induced human malignancy. Despite enhanced awareness of health risks and the adoption of legal or advisory guidelines, human exposure to foodborne mycotoxins continues unabated and on a global scale. The evidence for residues of aflatoxins and OTA is particularly striking as demonstrated by analysis of body fluids, mother's milk and tissue specimens. Further studies are being undertaken to establish or confirm the link between mutational fingerprints and mycotoxin exposure. Of considerable concern in environmental toxicology is the inefficacy of fungicides to control fungal diseases of plants and, therefore, mycotoxin contamination of harvested grain. The development of fungicide resistance in these fungal phytopathogens is an added risk. It is concluded that factors such as ecology, environmental temperature and humidity or substrate water activity predispose to production of mycotoxins by plant pathogenic and saprophytic fungi, resulting in worldwide contamination of staple foods. These compounds constitute a continuing hazard to human health following acute and/or chronic exposure. Measures to mitigate risk, such as the use of fungicides and preservatives, are of limited efficacy. The use of sub-lethal doses or the development of fungicide resistance may exacerbate potential hazards.

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