Mycotoxins Indoors and Health Effects: Empirical Results
Moldy Claims
Mycotoxins Indoors and Health Effects: Empirical Results
Stachybotrys is only one of a number of molds that can grow indoors and that are capable of producing mycotoxins, but as previously described neither Stachybotrys nor any other toxigenic species always produces mycotoxins. Mycotoxins clearly can be produced by molds growing indoors on building materials, but little has been published regarding the amount of mycotoxins produced or the environmental factors that regulate their production under those conditions.
Most of the published information on mycotoxin production by molds was developed under the artificial conditions of mold growing on defined or semi-defined media in the laboratory, and the mold strains used often were standard laboratory strains known to be good producers of mycotoxins. Only rarely were strains brought to the laboratory from an indoor environment. When toxigenic molds have been grown on building materials (for example, wood, gypsum board, insulation, etc.) the amount of mycotoxin produced has been undetectable or low relative to amounts produced on defined or semi-defined media. These facts reinforce the notion that the mere presence of a toxigenic mold species is not evidence that mycotoxins are present. See Jarvis, supra note 27; Nikulin et al., supra note 20; Ren, P. et al., Comparative study of Aspergillusmycotoxin produced on enriched media and construction material, J. Industrial Microbiol. Biotechnol. :210-213 (1999); Tobin et al.
The Basic Requirements for Toxicity in Fungal Exposure
An Assessment of the Scientific Literature with an Emphasis on Dose
The Basic Requirements for Toxicity in Fungal Exposure
If mycotoxins are to have human health effects in the indoor environment, three conditions must all be met. First, there must be an actual presence of mycotoxins. As we have just seen, that cannot be assumed on the basis of a toxigenic species being present. Second, there must be a pathway of exposure from the source to the susceptible person. As we have also seen, mycotoxins do not evaporate into the air. Exposure requires generation of airborne particles to carry the mycotoxin from the source into the breathing air of people in the area. Third, the amount of mycotoxin inhaled must be sufficient to cause toxicity. In other words, a toxic dose must be delivered.
An Assessment of the Scientific Literature with an Emphasis on Dose
“Dose” is a fundamental concept in the science of toxicology, but we all have a basic understanding of the concept from our daily lives. We all understand that too much of anything can be harmful. A medication taken as prescribed, e.g., one pill three times daily, is beneficial, whereas all of the pills consumed at once could be fatal. We also understand from our daily lives that it generally takes more to affect a large person than a small person. A single alcoholic beverage might make a small person lightheaded, whereas it might require two or three drinks to have the same effect on a larger person. Toxicologists acknowledge that familiar concept by expressing dose as the amount taken in divided by body weight (mg/kg). The question is, if mold growing indoors produces mycotoxins and if spores or other particles containing mycotoxins are present in the breathing air, can a toxic dose of mycotoxins be inhaled?
That question has not been addressed directly in scientific publications, but it is possible to make calculations that suggest the minimal numbers of particles in the air that would be required. Single doses of Stachybotrys spores, known to contain mycotoxins, have been directly introduced into the noses of mice See Nikulin, M. et al. Experimental lung mycotoxicosis in mice induced by Stachybotrys atra, Int. J. Exp. Pathol. 77(5):213-218 (1996). and lungs of rats. See Rao, C. Y. et al. Reduction of pulmonary toxicity of Stachybotrys chartarumspores by methanol extraction of mycotoxins, Appl. Environ. Microbiol. 66(7):2817-2821 (2000); Rao, C. Y. et al. The time course of responses to intratracheally instilled toxic Stachybotrys chartarumspores in rats, Mycopathologia 149(1):27-34 (2000). A variety of doses were used with the rats and their condition was monitored using sensitive laboratory methods.
Severe effects were produced when the higher doses were placed directly into rat lungs, but there were no effects at the lowest dose used, which was 3 million spores per kilogram of body weight (3,000,000 spores/kg). Those spores were placed all at once directly into the lungs, but we can calculate how many spores would have to be in the air in order to inhale the same dose of spores over a 24-hour period. Since it has been hypothesized that small infants are especially vulnerable we can use standard reference values for the body weight and breathing rate of infants: according to the EPA, 95% of all one-month-old infants weigh more than 3.16 kg (7 pounds) and infants under one year of age breathe approximately 4.5 cubic meters (m³) of air per day. See EPA, Exposure Factors Handbook, Update of May 1989 Office of Research and Development, US Environmental Protection Agency (EPA), Washington, DC 20460, EPA/600/P-95/002Fa, Washington, DC (1997). In order to inhale 3,000,000 spores/kg over a 24-hour period of continuous exposure, such an infant would have to be exposed to over 2 million spores per cubic meter of air (2,000,000 spores/m3). Still higher spore concentrations would be required for the average school-aged boy (over 6 ½ million spores per cubic meter) and for the average adult man (over 15 million spores per cubic meter). Thus, absorbing even the dose that caused no ill effects in rats would require numbers of airborne spores that vastly exceed the numbers actually seen even in heavily mold-contaminated homes, offices, or schools.
The comparison is even more dramatic if we remember that the spores were introduced instantaneously and directly into the lungs of the rats. A sudden, direct application of that kind overwhelms the normal processes that protect the lungs by removing foreign materials, either by physically carrying them away or by changing them chemically. We can think of the rat experiments as representing a dose rate of 3 million spores per kilogram of body weight per minute (even though the spores were administered in much less than one minute). To make a more direct comparison not just with the total dose but with the dose rate that had no ill effects on rats, we can calculate how many spores would have to be in the breathing air to deliver 3 million spores per kilogram body weight in a one-minute exposure. For the small, one-month-old infant, that concentration would have to be 3 billion spores per cubic meter of air. The average school-aged child would have to be exposed for one minute to over 9 billion spores per cubic meter of air and the average adult to 22 billion spores per cubic meter of air.
Other studies have been done in which mycotoxin-containing Stachybotrys spores were introduced directly into the nasal passages of mice two times a week for three weeks. See Nikulin, M. et al., Effects of intranasal exposure to spores of Stachybotrys atra in mice, Fundam. Appl. Toxicol. 35(2):182-188 (1997). Only two doses were used, and effects were seen with both. The higher dose caused severe inflammation and bleeding in the lungs visible at the end of three weeks. In contrast, the lower dose, which was 46,000 spores per kilogram body weight at each treatment, produced mild inflammation and no bleeding in the lungs of the treated mice. Combining all six treatments, the lower dose totaled 280,000 spores per kilogram body weight. We can calculate how many spores would have to be in the breathing air to deliver that dose over a three-week period of continuous, 24-hour per day exposure. For the 3.16-kilogram one-month-old infant, that concentration would be 9,400 spores per cubic meter of air. The average school-aged child would have to be exposed continuously for three weeks to over 29,000 spores per cubic meter of air, and the average adult to 68,000 spores per cubic meter of air.
Even though this calculation ignores the more severe impact expected from repeated instantaneous dosing (as compared to slow, continuous intake by natural breathing), it still produces a concentration of Stachybotrys spores in air that would not be seen in real home, school, or office settings. For example, in data from 9,619 indoor air samples from 1,717 buildings, Stachybotrys was detected in the indoor air of 6% of the buildings. In those 103 buildings, the median (“middle,” meaning half of values were lower and half were higher) airborne concentration was 12 colony-forming units (viable spores) per cubic meter of air. See Shelton, B.G. et al., Profiles of airborne fungi in buildings and outdoor environments in the United States, Appl. Environ. Microbiol. 68(4):1743-1753 (2002).
The calculations above suggest minimum airborne concentrations of Stachybotrys spores (with all of them actually containing mycotoxins) that are required to achieve doses in humans that would be equal to doses that had essentially no effect in artificially exposed animals. These calculations do not tell us where to draw a line between "safe" and "unsafe" conditions, but they do make it clear that it would be difficult to deliver a toxic dose of mold toxins by inhaling spores in the indoor air. We can be confident that it is nearly impossible for anyone to inhale a harmful dose of mold toxins in homes, offices, or schools because even the most heavily contaminated of them have total spore concentrations that are far lower than the values calculated.
back
