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MYCOTOXINS:
Molds can produce other secondary metabolites such as antibiotics and mycotoxins. Antibiotics are isolated from mold (and some bacterial) cultures and some of their bacteriotoxic or bacteriostatic properties are exploited medicinally to combat infections. Mycotoxins are also products of secondary metabolism of molds. They are not essential to maintaining the life of the mold cell in a primary way (at least in a friendly world), such as obtaining energy or synthesizing structural components, informational molecules or enzymes. They are products whose function seems to be to give molds a competitive advantage over other mold species and bacteria. Mycotoxins are nearly all cytotoxic, disrupting various cellular structures such as membranes, and interfering with vital cellular processes such as protein, RNA and DNA synthesis. Of course they are also toxic to the cells of higher plants and animals, including humans. Mycotoxins vary in specificity and potency for their target cells, cell structures or cell processes by species and strain of the mold that produces them. Higher organisms are not specifically targeted by mycotoxins, but seem to be caught in the crossfire of the biochemical warfare among mold species and molds and bacteria vying for the same ecological niche. Not all molds produce mycotoxins, but numerous species do (including some found indoors in contaminated buildings). Toxigenic molds vary in their mycotoxin production depending on the substrate on which they grow (Jarvis, 1990). The spores, with which the toxins are primarily associated, are cast off in blooms that vary with the mold’s diurnal, seasonal and life cycle stage (Burge, 1990; Yang, 1995). The presence of competitive organisms may play a role, as some molds grown in monoculture in the laboratory lose their toxic potency (Jarvis, 1995). Until relatively recently, mold poisons were regarded with concern primarily as contaminants in foods. More recently concern has arisen over exposure to multiple mycotoxins from a mixture of mold spores growing in wet indoor environments. Health effects from exposures to such mixtures can differ from those related to single mycotoxins in controlled laboratory exposures. Indoor exposures to toxigenic molds resemble field exposures of animals more closely than they do controlled experimental laboratory exposures. Animals in controlled laboratory exposures are healthy, of the same age, raised under optimum conditions, and have only the challenge of known doses of a single toxic agent via a single exposure route. In contrast, animals in field exposures are of mixed ages, and states of health, may be living in less than optimum environmental and nutritional conditions, and are exposed to a mixture of toxic agents by multiple exposure routes. Exposures to individual toxins may be much lower than those required to elicit an adverse reaction in a small controlled exposure group of ten animals per dose group. The effects from exposure may therefore not fit neatly into the description given for any single toxin, or the effects from a particular species, of mold. Field exposures of animals to molds (in contrast to controlled laboratory exposures) show effects on the immune system as the lowest observed adverse effect. Such immune effects are manifested in animals as increased susceptibility to infectious diseases (Jakab et al., 1994). It is important to note that almost all mycotoxins have an immunosuppressive effect, although the exact target within the immune system may differ. Many are also cytotoxic, so that they have route of entry effects that may be damaging to the gut, the skin or the lung. Such cytotoxicity may affect the physical defense mechanisms of the respiratory tract, decreasing the ability of the airways to clear particulate contaminants (including bacteria or viruses), or damage alveolar macrophages, thus preventing clearance of contaminants from the deeper lung. The combined result of these activities is to increase the susceptibility of the exposed person to infectious disease, and to reduce his defense against other contaminants. They may also increase susceptibility to cancer. Because indoor samples are usually comprised of a mixture of molds and their spores, it has been suggested that a general test for cytotoxicity be applied to a total indoor sample to assess the potential for hazard as a rough assessment (Gareis, 1995). The following summary of toxins and their targets is adapted from Smith and Moss (1985), with a few additions from the more recent literature. While this compilation of effects does not describe the effects from multiple exposures, which could include synergistic effects, it does give a better idea of possible results of mycotoxin exposure to multiple molds indoors.
It should be noted that not all mold genera have been tested for toxins, nor have all species within a genus necessarily been tested. Conditions for toxin production varies with cell and diurnal and seasonal cycles and substrate on which the mold grows, and those conditions created for laboratory culture may differ from those the mold encounters in its environment. Toxicity can arise from exposure to mycotoxins via inhalation of mycotoxin-containing mold spores or through skin contact with the toxigenic molds (Forgacs, 1972; Croft et al., 1986; Kemppainen et al., 1988 -1989). A number of toxigenic molds have been found during indoor air quality investigations in different parts of the world. Among the genera most frequently found in numbers exceeding levels that they reach outdoors are Aspergillus, Penicillium, Stachybotrys, and Cladosporium (Burge, 1986; Smith et al., 1992; Hirsh and Sosman, 1976; Verhoeff et al., 1992; Miller et al., 1988; Gravesen et al., 1999). Fungi are ubiquitous to the environment and primarily saprophytic, using nonliving organic material as a nutrient source for growth and reproduction. Many of these saprophytes can colonize organic water-damaged building materials. During the digestion process fungi secrete enzymes into the nutrient source to break down complex compounds into simpler compounds, which are taken up by the fungi and digested. The digested nutrients are classified into two categories, primary and secondary metabolites. The primary metabolites consist of cellulose and other compounds that are used for energy to grow and reproduce. The secondary metabolites, called mycotoxins, are produced to give fungi a competitive edge against other microorganisms, including other fungi. There are over 200 recognized mycotoxins, however, the study of mycotoxins and their health effects on humans is in its infancy and many more are waiting to be discovered. Many mycotoxins are harmful to humans and animals when inhaled, ingested or brought into contact with human skin. Mycotoxins can cause a variety of short term as well as long-term health effects, ranging from immediate toxic response to potential long-term carcinogenic and teratogenic effects. Symptoms due to exposure to mycotoxins include dermatitis, cold and flu symptoms, sore throat, headache, fatigue, diarrhea, and impaired or altered immune function, which may lead to opportunistic infection. Historically, mycotoxins have been a persistent problem to farmers and the animal husbandry industry in Eastern Europe and developing countries. Mycotoxins are a known agent in biological warfare as a moderate illness compared to the other biologicals. Recently, however, research has implicated many toxin-producing fungi, such as Stachybotrys, Penicillium, Aspergillus and Fusarium species, to indoor air quality problems and building related illnesses. Inhalation of mycotoxin producing fungi in contaminated buildings is the most significant exposure, however, dermal contact from handling contaminated materials and the chance of ingesting toxin containing spores through eating, drinking and smoking is likely to increase exposure in a contaminated environment. Recent advances in technology have given laboratories the ability to test for specific mycotoxins without employing cost-prohibitive gas chromatography or high performance liquid chromatography techniques. Currently, surface, bulk, food and feeds, and air samples can be analyzed relatively inexpensively for the following mycotoxins: | |