Is indoor mold contamination a threat to health? Part two.
Many species of mold (including some found indoors in contaminated buildings) produce mycotoxins. Mycotoxins are secondary metabolites. Nearly all are cytotoxic, disrupting cellular structures and interfering with vital cellular processes such as protein, RNA, and DNA synthesis. Their function seems to he to give molds a competitive advantage over molds of other species and bacteria.
The potency of mycotoxins varies by species and strain of mold, as does specificity to targeted cells, cell structures, or cell processes. Higher organisms are not specifically targeted by mycotoxins, but seem to get caught in the crossfire of the biochemical warfare among mold species and molds and bacteria.
The production of mycotoxins depends on the substrate and environment in which molds grow. The toxins are associated with mold spores, which are cast off in blooms that vary with the mold's life cycle stage. The presence of competitive organisms may play a role; some molds grown in monoculture in the laboratory lose their toxic potency.
Recently, concern has arisen over exposure to multiple mycotoxins from mixtures of mold spores growing in wet indoor environments. Health effects from exposures to such mixtures can differ from those associated with single mycotoxins in controlled laboratory exposures.
In animals in the field, immune system effects are associated with the lowest levels of exposure at which adverse effects have been observed. The immune system effects are manifested as increased susceptibility to infectious diseases. Almost all mycotoxins have an immunosuppressive effect, although the exact target within the immune system may differ. Many are also cytotoxic, causing route-of-entry effects that may be damaging to the gut, the skin, or the lung. 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 it may damage alveolar macrophages, preventing clearance of contaminants from the deeper lung. The combined result is to increase susceptibility to infectious disease, and to reduce defenses against other contaminants. Mycotoxins may also increase susceptibility to cancer.
The following summary of body systems and the mycotoxins that affect them does not describe the effects of multiple exposures. Nevertheless, it does give some idea of possible results from exposure to multiple molds indoors:
* Vascular-system effects (including vascular fragility and hemorrhaging in tissues or from the lungs) are associated with aflatoxin, satratoxin, and roridins.
* Digestive-system effects (including diarrhea, vomiting, intestinal hemorrhage, and liver effects such as necrosis and fibrosis) are associated with aflatoxin; caustic effects on mucous membranes are associated with T-2 toxin; and anorexia is associated with vomitoxin.
* Respiratory-system effects (including respiratory distress and bleeding from the lungs) are associated with trichothecenes.
* Nervous-system effects (including tremors, incoordination, depression, and headache) are associated with tremorgens and trichothecenes.
* Cutaneous-system effects (including rash, burning sensation, sloughing of skin, and photosensitization) are associated with trichothecenes.
* Urinary-system effects and nephrotoxicity are associated with ochratoxin and citrinin.
* Reproductive-system effects (including infertility and changes in reproductive cycles) are associated with T-2 toxin and zearalenone.
* Immune system effects (including changes or suppression) are associated with many mycotoxins.
It should be noted that not all mold genera have been tested for toxins, nor have all species within a genus necessarily been tested.
Exposure to mycotoxins can occur via inhalation of mold spores or through skin contact with molds. 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 outdoor levels are Aspergillus, Penicillium, Stachybotrys, and Cladosporium. Penicillium, Aspergillus, and Stachybotrys toxicity; especially as it relates to indoor exposures, will be discussed briefly in the paragraphs that follow.
Penicillium species have been shown to be fairly common indoors, even in clean environments, hut especially in problem buildings. Spores have the highest concentrations of mycotoxins, although the vegetative portion of the mold, the mycelium, can also contain the poisons. Viability of spores is not essential to toxicity
Important toxins produced by penicillia include nephrotoxic citrinin, from P citrinum, P. expansum, and P. viridicatum; nephrotoxic ochratoxin, from P. cyclopium and P. viridicatum; and patulin (which is cytotoxic and carcinogenic in rats), from P. expansum.
Aspergillus species also are fairly prevalent in problem buildings. The genus contains several toxigenic species, among which the most important are A. parasiticus, A. flavus, and A. fumigatus.
Aflatoxins produced by A. parasitus and A. flavus are among the most extensively studied mycotoxins. They are some of the most toxic substances known, being acutely toxic to the liver, brain, kidneys, and heart. With chronic exposure, they are potent carcinogens of the liver. They are also teratogenic. Symptoms of acute aflatoxicosis are fever, vomiting, coma, and convulsions.
A. fumigatus, which has been found in many indoor samples, is more often associated with the infectious disease aspergillosis, but this species does produce poisons, for which only crude toxicity tests have been done. Recent work has found a number of tremorgenic toxins in the conidia of this species.
A. ochraceus produces ochratoxins (also produced by some penicillia, as mentioned above). Ochratoxins damage the kidney and are carcinogenic.
A. flavus is found indoors in tropical and subtropical regions, and occasionally in specific environments such as flowerpots. A. fumigatus has been found in many indoor samples. A more common Aspergillus species in wet buildings is A. versicolor, which has been found growing on wallpaper, wooden floors, fiberboard, and other building materials. A. versicolor does not produce aflatoxins, but it does produce a less potent toxin, sterigmatocystin, which is an aflatoxin precursor. While symptoms of aflatoxin exposure through ingestion are well described, symptoms of exposures that might occur in most moderately contaminated buildings are not known. Undoubtedly they are less severe because of reduced exposure. Because of the potent toxicity of these agents, however, prudent measures to prevent exposures are warranted when levels of aspergilli indoors exceed outdoor levels by any significant amount.
Stachybotrys chartarum (atra)
Stachybotrys chartarum (atra) has been much discussed in the popular press and has been the subject of a number of building-related illness investigations. This mold is not readily measured from air samples because when its spores are wet, they are sticky and not easily aerosolized. Also, it is often not identified in culturing of samples because it does not compete well with other molds or bacteria and does not grow well on standard media. Even if it is overgrown by other molds in a sample, however, it may be present in the environment, and those who breathe it can have toxic exposures. S. chartarum has a high moisture requirement, growing vigorously where moisture has accumulated from roof or wall leaks or in areas chronically wet from plumbing leaks. It is often hidden in the building envelope. This mold has a very low nitrogen requirement, and it can grow on wet hay and straw, paper, wallpaper, ceiling tries, carpets, and insulation material (especially cellulose-based insulation). It also grows well when wet filter paper is used as a capturing medium. When S. chartarum is found in an air sample, it should be searched for in walls or other hidden spaces, where it is likely to be growing in abundance.
S. chartarum has a well-known history in Russia and the Ukraine, where it has killed thousands of horses, which seem to be especially susceptible to the macrocyclic trichothecenes. They cause lesions of the skin and gastrointestinal tract, and interfere with blood cell formation. People handling material heavily contaminated with S. chartarum have described the following symptoms: cough, rhinitis, burning sensations of the mouth and nasal passages, and cutaneous irritation at the point of contact, especially in areas of heavy perspiration, such as the armpits or the scrotum.
Among members of a family exposed to S. chartarum in a home with water damage from a leaky roof, complaints included (variably, among family members and a maid) headaches, sore throats, hair loss, flu symptoms, diarrhea, fatigue, dermatitis, general malaise, and psychological depression. In a case of office workers exposed to aerosols containing S. chartarum, intensity and duration of exposure were found to be related to illness. Statistically significant differences for more exposed groups were increased lower-respiratory symptoms; dermatological, eye, and constitutional symptoms; chronic fatigue; and allergy history. Duration of employment was associated with upper-respiratory, skin, and central nervous system disorders. A trend of frequent upper-respiratory infections, fungal or yeast infections, and urinary-tract infections also was observed. Abnormal findings for components of the immune system were quantified, and it was concluded that higher and longer indoor exposure to S. chartarum results in immune modulation and even slight immune suppression.
S. chartarum also has been investigated in connection with acute pulmonary hemorrhage in infants, including the death of several infants. Infants in a Cleveland outbreak were reported to have pulmonary hemosiderosis, a sign of an uncommon lung disease that involves pulmonary hemorrhage. Stachybotrys chartarum was shown to have an association with acute pulmonary bleeding, but additional studies are needed to confirm association and establish causality.
While the studies of mycotoxin effects indoors have not been sufficient to establish cause-and-effect relationships, the toxic endpoints and potency of this mold have been well described. What is less clear is whether exposures indoors are of sufficient magnitude to elicit illness.
Sampling, Toxicology, and Epidemiology Issues Some of the difficulties in establishing a link between mold-contaminated buildings and illnesses derive from the nature of the organisms and their toxic products, as well as from variations in the susceptibilities of those exposed. Other difficulties are common to retrospective case control studies. Some of the problems are discussed below:
* Few toxicological experiments involving mycotoxins have been conducted for inhalation, the most probable route for indoor exposures. Experimental evidence suggests that the respiratory route may produce more severe responses than the digestive route.
* Effects from low-level exposure to, chronic low-level exposure to, or ingestion of mycotoxin mixtures generally have not been studied.
* Effects of multiple exposures to mixtures of mycotoxins in air, as well as the combination of mycotoxins with toxic air pollutants present in all indoor air, are not known.
* It is not known what impact mycotoxins may have in combination with other biologically active molecules with allergic or irritant effects.
* Measurement of mold spores and fragments varies, depending on instrumentation and methodology used.
* While many mycotoxins can be measured in environmental samples, it is not yet possible to measure mycotoxins in human or animal tissues.
* Response of individuals exposed indoors to complex aerosols varies by age, gender, state of health, and genetic make-up, as well as degree of exposure.
* Microbial contamination in buildings can vary greatly, depending on location and exposure pathways. Presence in a building alone does not constitute exposure.
* Investigations of patients' environments generally occur after patients have become ill, and do not necessarily reflect the exposure conditions that occurred during development of the illness. Indoor environments are dynamic ecosystems that change over time with changes in moisture, temperature, food sources, and the presence of other growing microorganisms.
Conclusions and Recommendations
Prudent public health practice indicates removal of exposure through cleanup or remediation, and public education about the potential for harm. Not all species of the mold genera discussed here are toxigenic, but it is prudent to assume that when these molds are found in excess indoors, they should be treated as though they are toxin producing. It is not always cost-effective to measure toxicity. Also, other health effects can be associated with excessive exposure to molds and their products. It is unwise, therefore, to wait to take action until toxicity is determined by laboratory culture, especially since molds that are toxic in their normal environment may lose their toxicity in laboratory monoculture over time.