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Mycotoxins and public health: a review.

This article provides an overview of the public health implications of mycotoxins--including a review of mycotoxin-related diseases documented in humans and animals, recent associations between mycotoxin exposure and carcinogenicity, a catalogue of foodstuffs documented to have been contaminated by mycotoxins, and a description of the distribution of mycotoxins in both the United States and worldwide. The article also advocates that public health professionals utilize recent developments in the field of mycotoxicology to explore associations between these fungal metabolites and acute and chronic disease in humans.

Aflatoxins↗

Mycotoxins in crude building materials from water-damaged buildings.

We analyzed 79 bulk samples of moldy interior finishes from Finnish buildings with moisture problems for 17 mycotoxins, as well as for fungi that could be isolated using one medium and one set of growth conditions. We found the aflatoxin precursor, sterigmatocystin, in 24% of the samples and trichothecenes in 19% of the samples. Trichothecenes found included satratoxin G or H in five samples; diacetoxyscirpenol in five samples; and 3-acetyl-deoxynivalenol, deoxynivalenol, verrucarol, or T-2-tetraol in an additional five samples. Citrinine was found in three samples. Aspergillus versicolor was present in most sterigmatocystin-containing samples, and Stachybotrys spp. were present in the samples where satratoxins were found. In many cases, however, the presence of fungi thought to produce the mycotoxins was not correlated with the presence of the expected compounds. However, when mycotoxins were found, some toxigenic fungi usually were present, even if the species originally responsible for producing the mycotoxin was not isolated. We conclude that the identification and enumeration of fungal species present in bulk materials are important to verify the severity of mold damage but that chemical analyses are necessary if the goal is to establish the presence of mycotoxins in moldy materials.

Aspergillus↗

Cultural and genetic approaches to managing mycotoxins in maize.

Infection of maize kernels by toxigenic fungi remains a challenging problem despite decades of research progress. Cultural practices, including crop rotation, tillage, planting date, and management of irrigation and fertilization, have limited effects on infection and subsequent mycotoxin accumulation. Current infrastructure and grain storage practices in developed countries can prevent postharvest development of mycotoxins, but this aspect remains a threat in developing countries, especially in tropical areas. Because most mycotoxin problems develop in the field, strategies are needed to prevent infection of growing plants by toxigenic fungi. Developing genetic resistance to Aspergillus flavus, Gibberella zeae, and Fusarium spp. (particularly F. verticillioides) in maize is a high priority. Sources of resistance to each of these pathogens have been identified and have been incorporated into public and private breeding programs. However, few, if any, commercial cultivars have adequate levels of resistance. Efforts to control infection or mycotoxin development through conventional breeding and genetic engineering are reviewed. The role of transgenic insect control in the prevention of mycotoxins in maize is discussed.

Mycotoxins↗

Mycotoxins in laboratory rodent feed.

Twenty-one batches of fixed-formula rodent diets from three feed manufacturers were tested for the presence of five mycotoxins: deoxynivalenol (DON), nivalenol (NIV), HT-2 toxin, T-2 toxin and ochratoxin A (OTA). Five batches were also tested for the presence of zearalenone (ZEN) and six batches for aflatoxins. Detectable levels of DON (up to 298 microg/kg), NIV (up to 118 microg/kg), OTA (up to 3.1 microg/kg) or ZEN (up to 26.7 microg/kg) were found in samples from all manufacturers. Three batches contained two (DON or NIV and OTA or ZEN) and one batch contained three (DON, OTA and ZEN) different mycotoxins. Aflatoxins, T-2 and HT-2 were not detected in any of the batches. The concentrations of mycotoxins detected in the feed were low, but indicated that feed ingredients, probably the cereal ingredients, were contaminated by mycotoxins. Since mycotoxins are known to have toxic and/or immunosuppressive effects, non-contaminated ingredients should be used for production of laboratory animal feed. The results imply that an improved quality control of ingredients used for laboratory rodent feed should be implemented.

Animal Feed↗

Fusarium mycotoxins (fumonisins, nivalenol, and zearalenone) and aflatoxins in corn from Southeast Asia.

Corn samples collected from the Philippines, Thailand, and Indonesia were surveyed for the natural occurrence of Fusarium mycotoxins (fumonisins, trichothecenes, and zearalenone) and aflatoxins. Fumonisins B1 and B2 were found in over 50% of corn samples in individual countries, and their co-occurrences with aflatoxins at the incidence of 48% were noted. In addition to these mycotoxins, a trichothecene, nivalenol, and an estrogen, zearalenone, both mycotoxins of Fusarium species, were detected in these Southeast Asian samples. This is the first report on the simultaneous occurrence of two carcinogenic mycotoxins, fumonisins and aflatoxins, together with Fusarium mycotoxins (nivalenol and zearlenone) in corn from Asian tropics.

Aflatoxins↗

Food mycotoxins survey and monitoring programs.

Traditionally, mycotoxin problems have come to our attention mainly because of outbreaks of animal diseases and in several instances human diseases and there are then related to a mycotoxin as the causative agent. Undoubtedly this will continue to be a very important means for uncovering mycotoxin problems. However, in recent years, now that practical, sensitive analytical methods have become available, we have been able to seek out mycotoxin contamination, monitor problem foods and survey problem foods for a number of mycotoxins. Examples of effective programs, and effective peanut control program; import, export and manufacturing quality control programs are presented. Points of testing, sampling, sample preparation; types of tests such as screening, multidetection chemical and confirmation tests are discussed.

Food Analysis↗

Application, effectiveness, and limitations of the electrophysiological diagnosis of neurotoxic effects of chronic environmental mycotoxins in humans.

An extensive body of data demonstrates that diverse groups of mycotoxins can alter the structure and function of the nervous system in a variety of ways with notable human health consequences. Myconeurotoxicity refers to any adverse effects of exposure to mycotoxins or byproducts of primary and secondary mold metabolism, including volatile organic compounds (VOCs) on the structural or functional integrity of the developing or adult nervous system. Neuromycotoxic effects may involve a spectrum of biochemical, morphological, behavioral, and physiological abnormalities whose onset can vary from immediate to delayed action, following exposure to a mycotoxin, and whose duration may be transient or persistent and result in disability, while some may have life-threatening consequences. Myconeurotoxicity may result from effects of the mycotoxins acting directly on the elements of the nervous system or acting on other biological systems, which then adversely affect the nervous system. This paper reviews the application, effectiveness, and limitations of the electrophysiological diagnosis of myconeurotoxic effects of chronic environmental exposure to mycotoxins. The systemic targets of mycotoxic effects were reviewed for greater understanding as to why different neurophysiological test techniques have different levels of outcomes. Thus, nerve conduction velocity, sensory, motor, and evoked potentials, electroencephalographic techniques were evaluated using previously published papers and our clinical experience. Although, neuromycotoxic disorders can be established using clinical electrophysiological diagnosis, there is always the possibility of false positive and false negative results in some patients, which may be due to a multi-factorial etiopathogenesis of neuromycotoxicity. Detection of nervous system toxicity and other measures of toxicity could be achieved using a combination of these neurodiagnostic techniques.

Air Pollution, Indoor↗

Tremorgenic mycotoxin intoxication with penitrem A and roquefortine in two dogs.

In this report, we describe the natural intoxication of 2 dogs that consumed moldy dairy products found in the household garbage and the procedures used to identify and quantify the tremorgenic mycotoxins, roquefortine and penitrem A, in the remaining portions of ingested materials. Following the ingestion of mycotoxins, the dogs of our report developed muscle tremors or seizures that resembled clinical signs of strychnine poisoning. Roquefortine was the predominant mycotoxin in a moldy cream cheese wrapper that was found among scattered garbage consumed by the first dog. Penitrem A was the only mycotoxin detected in discarded moldy macaroni and cheese that was consumed by the second dog. Treatment of dogs with tremorgenic mycotoxin intoxication involves supportive care. Close monitoring is important because the development of aspiration pneumonia is common and has been reported as the cause of death. Clinical signs of intoxication gradually resolve within 24 to 48 hours.

Animals↗

Incidence of molds and mycotoxins in commercial animal feed mills in seven midwestern states, 1988-1989.

A total of 82 feed manufacturers located within seven midwestern states (Iowa, Nebraska, Minnesota, Illinois, Indiana, Ohio, Michigan) participated in a survey of mold and mycotoxin contamination of corn. Samples were submitted from a composite of the grading samples taken from each incoming load of corn. The survey was initiated in July 1988. During the 12-mo period, moisture content of the corn samples upon receipt at the laboratory ranged from 10.5 to 13.3%. The greatest variation occurred in the springtime. Iowa's corn samples were driest (11.2%), and samples submitted from Ohio were wettest (12.8%). Mold counts averaged 2.63 x 10(4) per gram during the year. The predominant mold found was Fusarium sp. Samples were checked by black light and averaged 25.4% positive during the period. When assayed for mycotoxins, 19.5% of the samples were positive for at least one of the following: aflatoxin, zearalenone, T2 toxin and deoxynivalenol (vomitoxin). Aflatoxin and T2 toxin made up the majority of these samples containing toxin. The highest incidence of mycotoxin-contaminated corn (48%) occurred in samples submitted in July of 1988. Over the 12-mo period, the highest mycotoxin contamination occurred in Iowa, Illinois and Michigan. When samples were subjected to 90% relative humidity and 32 degrees C, an average of 3.9 d was required for mold growth to appear. After incubation, 24.7% of the samples contained one of the four toxins. The data indicate that mold and mycotoxin contamination of mixed samples of corn is widespread, even in the midwestern corn belt of the U.S.

Aflatoxins↗

Recent progress on analytical techniques for mycotoxins in feedstuffs.

Analysis of mycotoxins in feedstuffs is a difficult task because only trace amounts of the toxins are present in the sample. However, rapid progress in the area of mycotoxin analysis has been made during the last few years. Simplified sample cleanup protocols and new chromatographic methods, especially HPLC, have been developed. New, more sensitive and versatile instruments such as high-resolution mass spectrometry (MS) and gas chromatography/tandem MS/MS are coming to the market. After 15 yr of laboratory research, immunoassay techniques have gained more acceptance as analytical tools for mycotoxins. Several immunoassay kits for mycotoxins are currently available. The development of these new techniques and their application for monitoring various mycotoxins in foods and feeds are described in this review.

Animal Feed↗

Mycotoxins and reproduction in domestic livestock.

Molds are parasitic plants that are ubiquitous in livestock feedstuffs. Even though molds themselves reduce the quality of grains, their synthesis of chemical substances termed mycotoxins causes the greatest monetary loss to the animal industry. Five major mycotoxins that impair growth and reproductive efficiency in North America are aflatoxins, zearalenone, deoxynivalenol, ochratoxin, and ergot. Aflatoxins are produced by Aspergillus flavus and Aspergillus parasiticus. Consumption of grains containing aflatoxins by swine affects reproduction indirectly by reducing feed intake and growth. In swine, aflatoxins impair liver and kidney function, delay blood clotting, increase susceptibility to bruising, and interfere with cellular humoral immune systems. Ruminants are comparatively resistant to aflatoxicosis, but presence of aflatoxins in milk of dairy cows is closely monitored for human safety. Depending on environmental conditions, Fusarium roseum can produce either zearalenone or deoxynivalenol. Days 7 to 10 postmating seem to be a critical period of gestation for zearalenone to exert its detrimental actions on early embryonic development. Presence of deoxynivalenol in swine feedstuffs decreases feed intake, causes feed refusal, and induces occasional vomiting. Several species of Penicillium and Aspergillus produce ochratoxin, a mycotoxin that causes necrosis of kidney tissue. Ergot alkaloids produced by Claviceps purpurea on wheat can cause reproductive problems and are associated with lactational failure in swine. Various methods have been developed to remove mycotoxins from infected feedstuffs. Chemical analyses in laboratories as well as diagnostic kits suitable for use at the elevator or farm can be used successfully to identify which mycotoxins are present in suspect feedstuffs.

Animals↗

The toxicology of mycotoxins.

Mycotoxin problems are one of great concern to health scientists. Toxic fungal metabolites such as aflatoxins, trichothecenes, zearalenone and others are contaminated in our environments and induce various diseases. In this manuscript, the author will summarize the recent advances on toxicology of mycotoxins in special references to toxicological characters, cytotoxicity, genotoxicity (mutagenicity and carcinogenicity), metabolism, and biochemical mode of action. Interaction of mycotoxins with cellular components will be reviewed in order to clarify the toxicological characteristics of mycotoxins such as aflatoxins, trichothecenes, zearalenone, toxic peptides, and anthraquinoid mycotoxins.

Adenosine Triphosphatases↗

Analysis for mycotoxins: the chemist's perspective.

Mycotoxins are fungal metabolites that pose a health risk to exposed animals and humans. In recent years, concern has mounted regarding human exposure to mycotoxins via inhalation of mold spores produced in damp buildings and homes. Although mycotoxins can be detected in such buildings, reliable means for measuring an occupant's level of exposure to most mycotoxins are lacking. The author briefly reviews the chemical methods currently available for mycotoxin analysis, outlining accepted practices and discussing the limitations of these measurements.

Air Pollution, Indoor↗

Threat assessment of mycotoxins as weapons: molecular mechanisms of acute toxicity.

Mycotoxins are impractical as tactical weapons, butthey can be used by small poor terrorist organizations to poison food and water sources or can be released in crowded, confined areas. Crude concentrated or dried extracts of readily grown fungal cultures can be used as weapons. The production of fungal weapons does not require elaborate facilities for the growth of fungi, sophisticated equipment for the purification of the toxins, or highly trained personnel. Aflatoxin B1, fumonisin B1, ochratoxin A, and the trichothecenes T-2 toxin and deoxynivalenol could be weaponized for bioterrorism. Knowledge of the symptoms of intoxication and the biochemical mechanisms of action of mycotoxins is necessary for the rapid identification of the toxins, the development of prophylactic antidotes, and the design of effective treatments of affected persons. All of these mycotoxins except deoxynivalenol are carcinogens (Stark, A. A., Annu. Rev. Microbiol. 34:235-262, 1980; Stark, A. A., p. 435-445, in P. S. Steyn and R. Vleggaar, ed., Mycotoxins and phycotoxins, 1986; Stark, A. A., p. 47-60, in C. L. Wilson and S. Droby, ed., Microbial food contamination, 2000; Stark, A. A., and N. Paster, p. 60-64, in M. L. Wahlqvist, A. S. Truswell, R. Smith, and P. L. Nestel, ed., Nutrition in a sustainable environment, 1994). Because immediate and widespread death, illness, or panic is the goal of bioterrorists, the mechanisms by which mycotoxins exert acute toxicity are the focus of this article.

Aflatoxins↗

Contamination of food with mycotoxins and human health.

Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They are produced by various strains of moulds, particularly in tropical countries. Due to significant trade of cereals, humans in temperate countries can also be exposed to mycotoxins. The most common route of exposure to mycotoxins is ingestion, but it may also involve dermal, respiratory, and parenteral routes, the last being associated with drug abuse. Apart from acute and chronic toxic effects on human health called mycotoxicosis, some mycotoxins are proved or suspected human carcinogens. This paper describes various human diseases caused by ergot, afflatoxin, ochratoxin A, 3-nitropropionic acid, trichothecene, zearalenone, and fumonisin. It also gives a quick review of human carcinogenicity evaluations of the international Agency for Research on Cancer and of regulatory limits of mycotoxin concentrations in various commodities.

Animals↗

[Filamentous fungi and mycotoxins as potential occupational risk factors among farmers harvesting various crops].

The studies to determine the level of filamentous fungi and mycotoxins were carried out in samples of grain and grain dust during threshing of cereals by a combine harvester. High concentration of fungi was noted in grain and grain dust samples, it ranged from 5.0 to 520.0 cfu/g.10(3) and from 275.0 to 2825.0 cfu/g.10(3), respectively Allergizing and toxigenic fungi of Alternaria, Geotrichum, Cladosporium, Penicillium, Aspergillus and Fusarium species were observed in the study samples of grain and grain dust. In the samples of wheat grain, mycotoxins were also noted: moniliformin (MON), deoxynivalenol (DON) and ochratoxin A (OTA); their concentrations ranged from 0.025 to 0.088 microgram/g; 0.015-0.068 microgram/g; and from 0.0004 to 0.0008 microgram/g, respectively. The level of mycotoxins in the grain dust samples was within the range of 0.025-0.149 microgram/g-MON; 0.015-0.215 microgram/g-DON; 0.015-0.360 microgram/g-NIV; and 0.0004-0.0012 microgram/g-OTA. A significant correlation was observed between the occurrence of fungi of Fusarium species and the concentration of pathologic mycotoxins. The results confirm a considerable occupational risk among farmers engaged in grain threshing due to inhalation of pathogenic species of filamentous fungi and mycotoxins.

Agricultural Workers' Diseases↗

Trichothecene mycotoxins and their determinants in settled dust related to grain production.

We hypothesise that inhalant exposure to mycotoxins causes developmental outcomes and certain hormone-related cancers that are associated with grain farming in an epidemiological study. The aim of the present study was to identify and validate determinants of measured trichothecene mycotoxins in grain dust as work environmental trichothecene exposure indicators. Settled grain dust was collected in 92 Norwegian farms during seasons of 1999 and 2000. Production characteristics and climatic data were studied as determinants of trichothecenes in settled dust samples obtained during the production of barley (N = 59), oats (N = 32), and spring wheat (N = 13). Median concentrations of trichothecenes in grain dust were <20, 54, and < 50 mg/kg (ranges < 20-340, < 30-2400, and < 50-1200) for deoxynivalenol (DON), HT-2 toxin (HT-2) and T-2 toxin (T-2) respectively. Late blight potato rot (fungal) forecasts have been broadcast in Norway to help prevent this potato disease. Fungal forecasts representing wet, temperate, and humid meteorological conditions were identified as strong determinants of trichothecene mycotoxins in settled grain dust in this study. Differences in cereal species, production properties and districts contributed less to explain mycotoxin concentrations. Fungal forecasts are validated as indicators of mycotoxin exposure of grain farmers and their use in epidemiological studies may be warranted.

Agricultural Workers' Diseases↗

[Are mycotoxins in food a health hazard?].

The effects of mycotoxins are well known since antiquity. Modern trace analysis show the wide prevalence of mycotoxins in the food chain. Aflatoxins (AFB1, AFB2, AFG1, AFG2), trichothecenes (deoxynivalenol, T-2 Toxin, HT-2 Toxin), zearalenone, fumonisins (FB1, FB2) and ochratoxin A are the most important mycotoxins world wide. Foods of plant origin are normally contaminated more frequently and in higher concentrations than food of animal origin. The mean concentrations of mycotoxins analysed in European foods can be assed as low. This may be one reason why acute poisonings are rare incidences and why the limits of the tolerable daily intake (TDI) levels are exceeded only very seldom; however the population group "infant" exceed the preliminary TDI-level for trichothecenes. The consequences of a chronic intake of low amounts of mykotoxins is hardly to assess. A participation of the aflatoxins in the pathogenesis of primary liver cancer is considered as certain. Other coherence between the dietary intake of mycotoxins and specific clinical symptoms of man are not convincingly shown till now.

Aflatoxins↗