Mycotoxins in water damaged buildings

? Stachybotrys chartarum, with about 1/3 of the isolates producing macrocyclic trichothecenes, including satratoxins G, H and roridins E and L-2 (20-200 ng/cm2) and the remaining 2/3 of the isolates producing atranones and trichodermin/trichodermol.

All Stachybotrys spp. produces a series of spiriocyclic compounds (usually > 50) which is usually the major portion of the secondary metabolites, several magnitudes bigger than the atranones and trichothecenes. The spiriocycles have had the attention of the pharmaceutical industry, especially in Japan, and various effects have been reported, especially complement inhibitors, and fibrinolytically activity seems to be interesting.

It seems unlikely that it satratoxins are the compounds responsible for the Pulmonary Heammorrhage cases in Cleveland, as several homes have only contained atranone producing isolates (Croft et al., 1986; Nikulin et al., 1994; Johanning et al., 1996, Nielsen et al., 1998a; 1998b; Vesper et al. 2000)

? Aspergillus versicolor, sterigmatocystin and 5- methoxy-sterigmatocystin (up to 20 and 7 ¦Ěg/cm2). The production is highly dependent on the water activity and only occurs at water activities > 0.9 (Nielsen et al., 1998b; 1999; 2000)

? Penicillium chrysogenum, meleagrin, chrysogin (Nielsen et al., 1999)

? Penicillium polonicum, 3-methoxy-viridicatin, verrucosidin, verrucofortine (Nielsen et al., 1999)

? Chaetomium globosum, chaetoglobosin A and C ( up to 50 and 7 ¦Ěg/cm2), > 10 unknown (Nielsen et al., 1999)

? Penicillium brevicompactum, mycophenolic acid, asperphenamate (Nielsen et al., 1999)

? Aspergillus ustus, kotanins, > 40 unknown. No austamide, austdiol, or austocystins were detected (Nielsen et al., 1999)

? Trichoderma longibrachiatum, T. harzianum, T. citrinoviride, T. atroviride, T. viride, no trichothecenes detected, we have tested > 40 isolates from buildings (L¨ąbeck et al. 2000; Nielsen et al., 1998b)

? Alternaria alternata, which is very rarely growing on the materials in real buildings (it's almost always Ulocladium sp.), but when grown on building materials, is produces alternariol and alternariol monomethyl ether (Ren et al., 1998; Nielsen et al., 1999)

? Although Aspergillus flavus is not very common in buildings, it can grown on building materials, but is incapable of producing aflatoxins on this substrate (Rao et al., 1997; Ren et al., 1999; Nielsen et al., 2000).

? Aspergillus ochraceus is very rare in buildings, but Richard et al., 1999, have shown that ochratoxin A was produced in a home with severe problems.

? Aspergillus niger, orlandin, nigragillin, >20 unknown metabolites including naphtho-g -pyrones and tetracyclic compounds (Nielsen et al., 1999)

Fig. 1. Mycotoxins detected on mouldy building materials.

Other observations done during mycotoxin analyses.

? Materials infested recently usually contains much higher concentration of secondary metabolites

? "Spiking" experiments showed that reextraction of several sterigmatocystins and trichothecenes was impossible using methanol or dichloromethan (Nielsen et al., 1998b).

Biological effects

Biological effects of mycotoxins with agricultural importance, as the aflatoxins , ochratoxins and the trichothecenes DAS and T-2 toxin, are well described especially in vitro studies and also in vivo studies, but epidemiological data only exists for the aflatoxins and perhaps for the ochratoxin. Most publications concerns cargicogenicty or lethal doses ¨C which is not the issue in mouldy buildings. But the biggest problem is the route of exposure - usually intravenous injection (IV) or orally administrated (OA) - but inhalation is the way of exposure in mouldy buildings!

Generally the mycotoxins found in buildings are considered to have the following effects:

? Spiriocyclic compounds, including the stachybotrylactones, stachybotrylactams and K-76, immunosuppressants

? Alterariaols are cytotoxic, and perhaps mutagenic (IV but not OA)

? Sterigmatocystins, acute toxic, stops cilia moments, and carcinogenic. Cargicogenicty by binding to DNA, after oxidation to epoxide. (10% of Aflatoxin B1).

? Ochratoxin A, kidneycarciogen

? Verrucosidin, neurotoxic

? Chaetoglobosins (cytochalasins), acute toxic (IV but not OA), by blocking cytoplasmatic division.

? Trichothecenes, immunosuppressants, highly cototoxic, acute toxic (100-1000 cm2 S. chartarum infested material may contain a lethal dose)

References

? Croft, W.A., Jarvis, B.B., Yatawara, C.S. (1986). Airborne outbreak of trichothecene toxicosis. Atmospheric Environment 20: 549-552.

? Etzel, RA, Montana, E, Sorenson, WG, Kullman, GJ, Allan, TM, Dearborn, DG (1998): Acute Pulmonary hemorrhage in infants associated with exposure to Satchybotrys atra and other Fungi. Archives of Pediatr. Adolesc Med. 152:757-762

? Gravesen, S., Nielsen, P.A., Iversen, R. and Nielsen, K.F. (1999) Microfungal contamination of damp buildings - examples of risk constructions and risk materials. Environmental Health Perspectives, 107, 505-508.

? L¨ąbeck, M., Poulsen, S.K., L¨ąbeck, P.S., Jensen, D.F., and Thrane, U. (2000): Identification of Trichoderma strains from building materias by ITS1 ribotypning, UP-PCR fingerpintning and UP-PCR cross hybridization. FEMS micro.biol.lett., 185:129-134.

? Johanning, E., Biagini, R., Hull, D., Mory, P., Jarvis, B.B., Landsbergis, P. (1996). Health and immunology study following exposure to toxigenic fungi (Stachybotrys chartarum) in a water-damaged office environment. International Archives of Occupational and Environmental Health 68: 207-218.

? Nielsen, K.F., Gravesen, S., Nielsen, P.A., Andersen, B., Thrane, U., Frisvad, J.C.(1999) Production of Mycotoxins on artificially and naturally infested building materials. Mycopathologia 145(1): 43-56.

? Nielsen, K.F., ?stergaard, M., Larsen, T.O., Thrane, U. (1998a) Production of mycotoxins on water damaged gypsum boards. International Biodeterioration & Biodegradation 42: 1-7.

? Nielsen, K.F., Thrane, U., Larsen, T.O., Nielsen, P.A., Gravesen, S. (1998b). Production of mycotoxins on artificially inoculated building materials. International Biodeterioration & Biodegradation 42: 8-15.

? Nikulin, M., Pasanen, A.-L., Berg, S., Hinitikka, E.-L. (1994). Stachybotrys atra growth and toxin production in some building materials and fodder under different relative humidities. Applied and Environmental Microbiology 60: 3421-3424

? Nikulin, M., Reijula, K., Jarvis, B.B. and Hintikka, E.-L. (1997) Experimental lung mycotoxicosis induced by Stachybotrys atra. International Journal of Experimental Pathology, 77, 213-218.

? Nikulin, M., Reijula, K., Jarvis, B.B., Veijalaninen, P. and Hintikka, E.-L. (1997) Effects of intranasal exposure to spores of Stachybotrys atra in mice. Fundamental and Applied Toxicology, 35, 182-188.

? Ren, P., Ahearn, D.G. and Crow, S.A. (1998) Mycotoxins of Alternaria alternata produced on ceiling tiles. Journal of Industrial Microbiology, 20, 53-54.

? Vesper, S.J., Dearborn, D.G., Yike, I., Sorenson, W.G., and Haugland, R.A. (1999): Hemolysis, toxicity, and randomly amplified polymorphic DNA analysis of Stachybotrys chartarum strains. Appl Environ Microbiol, 3175-3181.

? Richard, J.L., Plattner, R.D., Mary, J., and Liska, S.L. (1999): The occurence of Ochartoxin A in dust collected from a problem household. Mycopathologia, 146:99-103.

? Vesper, S., Dearborn, D.G., Yike, I., Allen, T., Sobolewski, J., Hinkley, S., Jarvis, B.B., and Haugland, R.A. (2000): Evaluation of Stachybotrys chartarum in the House of an Infant with Pulmonary Hemmorrhage: Quantitative Assessment before, during, and after Remediation. Journal of Urban Health, 77:68-85.

? Nielsen, K. F., Nielsen, P. A., and Holm, G. (2000) Growth of moulds on building materials under different humidities. Proceedings of Healty Buildings 2000, Espoo 3: 283-288.

? Ren, P., Ahearn, D.G., and Crow, S.A. (1999): Comparative study of Aspergillus mycotoxin production on enriched media and construction material. J ind.microbiol.biotechnol., 23:209-213.

? Rao, C.Y., Fink, R.C., Wolfe, L.B., Liberman, D.F., and Burge, H.A. (1997): A study of aflatoxin production by Aspergillus flavus growing on wallboard. Journal of the American Biological Safety Association, 2:36-42.

? Jarvis, B.B., Sorenson, W.G., Hintikka, E.-L., Nikulin, M., Zhou, Y., Jiang, J., Wang, S., Hinkley, S., Etzel, R.A., and Dearborn, D.G. (1998): Study of Toxin Production by Isolates of Stachybotrys chartarum and Memnoniella echinata isolated during a study of pulmonary hemosiderosis in infants. Appl Environ Microbiol, 64:3620-3625.

? Anderson, M.A., Nikulin, M., K?ljalg, U., Anderson, M.C., Rainey, F., Reijula, K., Hintikka, E.-L., and Salkinoja-Salonen, M. (1997): Bacteria, Moulds, and Toxins in Water-Damaged Building Materials. Appl Environ Microbiol, 63:387-393.

? Gravesen, S. (2000): Microbiology on Indoor Air '99- what is new and interesting? An overview of selected papers presented in Edingburgh August, 1999. Indoor Air, 10:74-80.

Scientifuc staff on this project Kristian F. Nielsen (ph.d. stud), and Thomas O. Larsen (isolation and structural elucidation of unknown metabolites ).

Building Physics and Materials - Technical University of Denmark

"to improve the basic understanding of materialsˇ® properties with the aim of establishing better modelling tools and of providing a basis for the development of better materials, better production techniques and better methods for maintenance and repair."




Mycology at Technical University of Denmark, DTU

"a multi-disciplinary approach our fundamental research today covers all aspects of fungal evolution, secondary metabolism, mycotoxin production, physiology and ecology."




Mycotoxins in water damaged buildings

for many fungal species and chemical composition "Determination of the mycotoxins actually produced in water-damaged buildings can most adequately be done by analyzing contaminated building materials."