Mycotoxins in Indoor Environments Harriet M. Ammann

[Guest guest]

Mycotoxins in Indoor Environments

Harriet M. Ammann1

1Senior Toxicologist, Air Quality Program

Washington State Department of Ecology

http://www.doh.wa.gov/SBOH/Meetings/Meetings_2006/2006-

03_08/documents/Tab09c-MycotoxinsIndoors.pdf

Abstract

Exposure to mycotoxins produced by toxigenic molds growing in damp

indoor spaces has been difficult to assess. Monitoring methods limit

the characterization of inhalation exposure of any bioaerosol,

especially that of mycotoxins. Biomarkers promise better ability to

determine mycotoxin exposures 1.) through direct measures of toxins

and their products in human tissues, 2.) through immunochemical

methods, and 3.) measures of effect through novel approaches, e.g.,

proteomics or genomics. This paper summarizes both the problems

inherent in measuring exposures and some of the promising methods

that could help to resolve the current impasse.

Introduction

Reports of illness among occupants of damp buildings have become a

concern, especially with respect to both fungi and bacteria that

colonize damp spaces. While much illness can be explained as

allergic sensitization, a number of complaints involving the immune,

respiratory and nervous system have implicated mycotoxins.

Epidemiological studies have been able to relate building " dampness "

as the lowest common denominator among studies that differ in

exposure parameters to asthma and other allergic respiratory

disease. Such relationships have not been clearly established for

immune and nervous system effects due to a small number of studies,

small statistical power of existing studies, and difficulty in

assessing agents such as mycotoxins.

Buildings become moist because of leaks in plumbing, roofs, walls,

windows, or foundations, through flooding, or due to condensation in

areas that lack sufficient ventilation. Certain toxigenic fungi,

such as species of Aspergillus, Penicillium, Stachybotrys,

Memnoniella, and Chaetomium grow frequently in damp indoor

environments under conditions in which they can produce mycotoxins

(1, 2). The various fungi and other microorganisms such as bacteria,

yeasts, and protozoa form an ecosystem that changes over time as

moisture and nutrient levels and activity of the microorganisms

change. Competition for available ecological niches also can

increase production of mycotoxins.

Mycotoxins are well-known agents of disease in animals and humans

who consume them in foods in sufficient amounts. Inhalation of

toxins associated with grain dusts and other organic dusts are known

to be a problem for workers who have developed pulmonary

mycotoxicoses (including, but not limited to organic dust toxic

syndrome or ODTS). Establishing that illnesses seen in workers and

other occupants of damp indoor environments are caused by inhalation

of mycotoxins has been more difficult. This paper examines reasons

1

why this has occurred and explores means of determining better

estimates of exposure to indoor (mold and) mycotoxins.

Methods

Information regarding health effects from exposure to mycotoxins

produced by toxigenic molds commonly found in damp indoor spaces is

reviewed. Evidence for considering other exposure agents besides

spores of toxigenic fungi is examined, and the lack of correlation

of toxins with disease in epidemiological studies is explored.

Methods for identification of mycotoxins in environmental media and

within human tissues are discussed. Biomarkers and broadening the

concept to markers of toxic effect are considered.

Discussion

Symptoms Reported from Occupants of Moldy Buildings

The most frequent complaints of occupants of moldy buildings are of

cough, rhinosinusitis and worsening of asthma, and increased

susceptibility to respiratory and other infections. Such infections

last longer than " normal, " recur and are often recalcitrant to

treatment as occurs in immune-compromised patients. Complaints of

extreme fatigue, headache, memory problems, difficulty in

concentrating or thinking clearly, numbness and other nervous system

effects are also not rare. Complaints overlap toxic, allergenic and

irritative symptoms, and are difficult to assign to specific agents

found in buildings (3).

Molds that grow in damp buildings, and a number of bacteria,

especially Streptomyces species, have been implicated in studies

addressing signs of allergy, such as increase in inflammatory

markers, or increased immunoglobin titers (3). Allergic reaction to

molds can explain such signs and symptoms in atopic people, while

those who are not atopic often have illnesses (3, 4), that are

likely due to other causes such as toxicity. Allergy also does not

explain increased susceptibility to infection and nervous system

effects. These are in keeping with mycotoxicoses in herd animals

consuming moldy feed.

Problems with Measuring Mycotoxin Exposure Indoors

Inhalation has generally been considered the route of exposure from

indoor mold contamination. Because molds such as Aspergillus and

Penicillium colonize new habitats by casting their spores into the

air, inhalation of airborne spores has been thought to be the

primary means of mycotoxin exposure in damp buildings. However,

mycotoxins are not found only in and on spores (1, 5). They are also

found in hyphae and hyphal and spore fragments, which are

considerably smaller than whole spores or conidia. Mycotoxins are

secreted into the substrate on and in which molds grow, and are

found on dust from substrate (1, 5, 6, 7, 8) as well as in small

airborne particles generated directly by the organisms (6, 10).

Settled

2

carpet dusts from damp buildings contain mycotoxins (7) as do dusts

from ventilation systems (8, 9).

A recent study of aerosolization of fungal propagules using a newly

designed aerosolization chamber, determined that fragments of molds

are released from infested ceiling tiles in much greater numbers

than spores. Depending on fungal species, velocity of air past

contaminated surfaces, texture of the surface, and amount of

vibration, concentration of small particles released may be 320

times greater than spore concentration (6). These particles are of

considerably smaller size than spores (1.6 & #956; average for fragments,

compared to 2-3.5 & #956; for Aspergillus versicolor spores, and 4-7 & #956; for

Cladosporium cladosporoides spores) (6). Air velocities as low as

0.3 meters/second caused spores and small particles to be released

(11).

Inhalation of a mixture of spores, fragments, fungal propagules and

dust represents a much greater potential for exposing occupants to

mycotoxins than inhalation of spores alone. Smaller particles, with

their large aggregate surface area, can adsorb more mycotoxins than

the same mass of larger spores. Small particles are more easily

inhaled and deposited in airways and the lung, where toxins can

cause damage locally, or be absorbed into the bloodstream and

lymphatic circulation and distributed to target organs. Measuring

toxin concentration of settled or airborne dust could more

realistically estimate mycotoxin exposure. However, airborne and

settled dust samples will reflect different spectra of fungi because

of settling characteristics and other factors, so that using both is

probably necessary (12). Accurate assessment of exposure is

essential for establishing links with mycotoxicoses.

Studies that tried to relate symptoms with spore levels from air

samples have found little correlation with incidence or severity.

Researchers often conclude that no exposure occurred. Allergic

symptoms suffered by atopic persons were attributed to mold

exposure, while similar symptoms suffered by non-atopic individuals

could not be explained (3), and were dismissed.

Problems with Determining Mold Exposure

Problems inherent to characterization of spore concentrations make

correlation with symptoms of occupants difficult (13). Health

complaints often predate building investigations, so researchers

have to attempt to re-construct episodic past exposures. Non-viable

or viable sampling procedures, usually in only a few locations in a

building, are performed for short periods of time. Samples are dawn

by pumps at a few liters per minute for a 5- or 10- minute period.

Spores captured for non-viable sampling are analyzed via light

microscopy, and only generic identification can be performed.

Closely related species such as Aspergillus and Penicillium spores

cannot be distinguished. Identification to the species level of any

spore from these genera requires viable sampling. To capture spores

alive, volumes of air are drawn onto liquid or semi-solid growth 3

media that contain selective nutrients. Sampling times are limited

on agar by a need to have spores dilute enough to be separated on

the surface so that they can be subcultured and identified. In

either case the process of sampling captures only a few moments in

the life of airborne spores.

Spore production is episodic and unpredictable, and periodic taking

of air samples may miss concentrations of spores that occur with

blooms, and overcount more buoyant spores that are likely to remain

airborne longer. Such periodic sampling may also miss occupant

activities that re-mobilize spores into the air. Whether or not

spores that are captured are actually enumerated depends on the

skill of the mycologist/microscopist in identifying visible spores

in non-viable samples, and on a number of limitations imposed by

sampling technology, and the biology of the organisms. The choice of

growth medium may not support the growth of all species of spores

captured, since different species have different growth

requirements. Spores impacting the sides of the sampler may be

damaged and not grow. Spores may be driven below the surface of the

growth medium, and may not grow. Molds that can produce mycotoxins

can inhibit growth of competitors which would not be counted even

though they may be impacting occupants. Representative sampling of

what occupants breathe during the day is severely compromised by

these inherent difficulties.

Air sampling for spores, regardless of the analytical technique used

for counting and identification, underestimates exposure to

microbes. Since toxins are isolated from captured samples, exposure

to toxins is also underestimated. Dust sampling for spores gives a

different spectrum of microbes, and has some usefulness for

assessing contamination that has occurred over time, but it still

underestimates genera that are buoyant, and even if all components

are assayed, will still miss toxic content.

Extraction of mycotoxins from captured mold spores has been assumed

to be a way of measuring mycotoxin exposure in most studies. Usually

the amount of toxins measured is so small as to be below threshold

for toxic effect. Because of the problems inherent in capturing

representative samples of spores from which exposure can be

determined, and because toxins in smaller particles that are more

likely carriers of mycotoxins are not characterized, attempts to

determine toxic cause of human disease indoors have been largely

unsuccessful.

Biomarkers of exposure

The whole problem of exposure assessment of mycotoxins may be more

usefully addressed through biomarkers. However, since people are

exposed to certain mycotoxins in food as well through inhalation,

estimates of exposure indoors must take ingestion exposure into

account. A number of biomarker techniques have been developed.

4

A few mycotoxins can be detected directly in tissues. Ochratoxin can

be measured directly in blood and urine and has been used to

determine exposure from both ingestion and inhalation. Gliotoxin,

produced by Aspergillus fumigatus, a mold that is responsible for

most cases of invasive aspergillosis, is a strong immune suppressor,

and is thought to facilitate the invasion of lung tissue by this

mold. A liquid chromatography-tandem mass spectroscopy (LS-MS-MS)

assay measured gliotoxin in the lungs and sera of mice infected

experimentally with A. fumigatus, and in patients with this disease

(14). Danish researchers have developed a standardized LC-UV-MS

micro-scale method for screening fungal metabolites and mycotoxins

from culture extracts, and report that they have been able to detect

more than 400 fungal metabolites, including penitrems and macro-

cyclic trichothecenes (15). However, it is not yet known whether

these can be detected in human sera or other tissues. Recent work on

macro-cyclic trichothecene–producing Stachybotrys chartarum isolated

a protein (stachylysin) that could be a marker for exposure, as well

as account for an effect (bleeding from respiratory membranes) (16).

Aflatoxin adducts, formed when these mycotoxins interact with DNA,

RNA or protein, can be detected in sera and urine of those exposed

through a variety of methods. However, DNA-adducts result from DNA-

repair, and individual variation in ability to repair affected DNA

may not reflect true exposure or true effect.

Detection of toxins using immuno-chemical methods has been well-

addressed for many environmental sampling media, especially for food

products and livestock. For instance specific monoclonal antibodies

against aflatoxins, ochratoxin A, zearalenone, diacetoxyscirpenol

and T-2 toxin, have been prepared by various researchers through the

application of hybridoma technology to mycotoxins (17). Nanogram-

range concentrations in milk, butter, maize, peanuts, peanut butter

and porcine kidneys have been detected through the use of enzyme-

linked or radio-immunoassay or immunoaffinity chromatography. Assays

for other toxins, including aflatoxin M1, 3-acetyl deoxynivalenol

fusarenon X and roridin A have been developed by another laboratory

(18, 19. 20). Monoclonal antibodies have been developed that are

capable of detecting fumitremorgin B, produced by Aspergillus

fumigatus, in rice, buckwheat and corn in the 10 to 60 ng/g range

(21). Satratoxin G and related satratoxins can be detected in

environmental samples through an enzyme-linked immunosorbent assay

in 100 pg/ml concentrations (22). Detection of mycotoxins in an

exposure medium such as food, or in an air sample can be used to

estimate nominal exposure and are useful for risk assessment.

Further development of methods that can measure mycotoxins in human

sera and tissues would enhance the ability to use such techniques in

exposed humans and would eliminate some of the uncertainty from

extrapolation of exposure from media concentrations, and could be of

clinical relevance.

Monoclonal antibodies against aflatoxin-B1-lysine adducts have been

used to measure aflatoxin-albumin adducts in human serum collected

from residents in areas at high risk for liver cancer (23). A recent

study of Gambian children

5

discovered that IgA antibodies in saliva were reduced in areas of

West Africa with high infection-related mortality. Reduction of

antibodies (and immune defense) may occur through aflatoxin exposure

(24).

Investigators of an outbreak of lung problems in workers repeatedly

exposed to fungi in a water damaged building (25), used an antibody

assay for the macrocyclic mycotoxin Roridin A (19, 20). One subject

among eight developed elevated Immunoglobin G (IgG) antibodies

against Roridin-hemisuccinate Human Serum Albumin (R-H BSA),

indicating exposure. However, others thought to have been exposed

did not develop this immune response (25). The environmental portion

of this investigation focused on spores captured in the building,

and did not consider other airborne sources of mycotoxin exposure.

Satratoxin-hemisuccinate Bovine Serum Albumin (S-H BSA) has also

been prepared against the potent toxic macrocyclic trichothecene

produced by Stachybotrys chartarum (26). Immunoglobin G (IgG)

antibodies against satratoxin H were measured among patients exposed

to a mixture of molds who tested positive for antibodies against

Stachybotrys chartarum exposure. Both exposure to the mold and

exposure to the toxin were quantified through serum antibody tests

(27). A follow-up study examined these patients for damage that

could account for neuropsychological symptoms and peripheral

neuropathies such as numbness, tingling and muscle weakness in the

extremities (28). Patients with documented, measured exposure to

molds had elevated titers of antibodies (immunoglobulin A,

immunoglobin A and immunoglobin M, and IgG) to neural-specific

antigens, such as myelin basic protein, myelin-associated

glycoprotein, ganglioside GM1, sulfatide, myelin oligodendrocyte

glycoprotein, alpha-B-crystallin, chondroitin sulfate, tubulin, and

neurofilament, which are markers of neural damage. They also

suffered neuropsychological disorders and peripheral neuropathies,

as determined by tests.

This series of studies indicates that immunochemical methods may be

useful in finding the nexus between exposure to mycotoxins and

related disease. These studies (26, 27, 28) also point in the

direction of a broader concept of biomarker, which is to include

markers of effect. The development of techniques such as genomics

and proteomics has made it possible to develop profiles of gene

expression that could be related to toxic exposures. A number of the

more potent mycotoxins produced by molds commonly found in moisture-

damaged buildings are potent inhibitors of protein synthesis.

Measurement of changes in protein profile can indicate exposure to

specific individual or multiple toxins. Proteomics has been used to

study the complex nephrotoxicity of OTA. Microarrays were used to

assess OTA-specific profiles of expression involved in DNA damage

and apoptosis, response to oxidative stress and inflammatory

reactions (29).

Aflatoxins produced most often by Aspergillus flavus and Aspergillus

parasiticus, and sterigmatocystin, produced by Aspergillus

versicolor, are also potent

6

inhibitors of protein synthesis. The trichothecenes are among the

most potent inhibitors of protein synthesis known. Macrocyclic

trichothecenes, such as the satratoxins, verrucarins B and J,

Roridin A produced by Stachybotrys chartarum and Ochratoxin A,

produced by both Aspergillus and Penicillium species, are all potent

inhibitors of protein synthesis (30).

A number of effects that result from inhibition of protein synthesis

can be related to symptoms of occupants of damp buildings (Table 1).

Key among symptoms that are reported frequently are those that

affect the immune system (induction of autoimmunity, greater

susceptibility to infectious disease), neuropsychological deficits,

headache, nausea, and deficits in memory and concentration. Protein

synthesis is important for antibody and cytokine production and

other markers of immunologic effect. Learning and memory depend on

protein synthesis, and depression of protein synthesis in the brain

could account for frequent reports of memory and learning deficits

in mold-exposed patients. The use of proteomics to detect changes in

protein patterns as the result of exposure to protein synthesis–

inhibiting mycotoxins is another tool that could bring more linkage

between exposure to mycotoxins indoors and effects suffered by

occupants of moldy buildings.

Use of measures that assess total toxicity can be used in

conjunction with mycotoxin assays and environmental contamination

measures to establish relationships between toxic exposure and

disease. For instance, total toxicity of captured microbial material

(spores, fragments and toxin containing particles) can be determined

through toxicity assays such as the methylthiazoltetrazolium (MTT)-

cleavage test for cellular toxicity. Determination of cytotoxicity

of the entirety of environmental samples is a first key step in

determining toxic influence on disease from exposure to damp

environments (31). Such assays have already been used in clinical

investigations, although mycotoxin assessment was limited to

toxicity of captured spores (32).

Conclusion

Epidemiological studies, with few exceptions, have been unsuccessful

in associating mycotoxin exposure from molds growing indoors. The

reason for this has been the lack of means to determine toxic

concentrations in inhaled materials. Attention has focused on

extracting toxins from spore samples. Yet there is no means of

measuring actual exposure to spores through the airborne route.

Inhaled particles of fungal or substrate origin that contain

mycotoxins are more likely to be agents of exposure, since they have

a larger aggregate surface area to which mycotoxins can adsorb, and

they are more likely to be inhaled and deposited into the lung.

Such particles, like spores, are likely to have more than toxic

effects. For instance, they may also be allergenic or irritating to

mucous membranes. Symptoms of allergy and irritation can complicate

the presentation of disease

7

since they overlap those caused by toxicity. However, biomarkers

such as those described in this paper may make toxic exposure

determination more comprehensive. However, representative assessment

of mold species growing in damp indoor environments remains

tentative, and standardized methods for characterizing air

concentrations are essential, and underlie determination of toxic

exposure as well.

Table 1. Mycotoxins that inhibit protein synthesis and effects.

MYCOTOXINS AND MECHANISMS

HEALTH EFFECTS

Trichothecenes:

• Inhibit translation of mRNA into protein; highly potent inhibitors

of protein synthesis

• Lipophylic; easily traverse membranes including lung, capillary

and blood brain barrier

Inhibition of Protein Synthesis leads to deficits in

• Learning and memory

• Autonomic function and other neural function

• Change Immune response (antibodies, TNFa, macrophage activity,

etc.) resulting in increase in susceptibility to infectious disease

and cancer and trigger of autoimmune disorders

Aflatoxins, sterigmatocystin, Ochratoxin A inhibit protein synthesis

• At transcription level

• At translation level

DNA damage results in

• Decrease in antibody production, inhibition of immune defenses,

results increased infectious disease, cancer promotion

Tremorgens; paralytic mycotoxins

• Inhibit CNS transmitters, e.g., GABA, Glu, Asp

Decrease in inhibitory transmitters results in

• Tremors, hyperexcitability, inco-ordination

• Paralysis

Gliotoxin

• Affects astrocytes

• Immune modulator

• Apoptosis inducer: increases

Decrease in immune defenses and neural changes

• Facilitates infection by A. fumigatus

• Affects CNS function

8

caspase-3 activity

References

1. JD, Rand TG, Jarvis BB (2003) Stachybotrys chartarum:

cause of human disease or media darling? Med Mycol 41: 271-291.

2. Dillon HK, JD, Sorenson WG, Douwes J, s RR (1999)

Review of methods applicable to the assessment of mold exposure to

children. Environ Health Perspect 107 (Sup 3): 473-480

3. Institute of Medicine of the National Academies of Science,

Committee on Damp Indoor Spaces and Health (2004) Damp Indoor Spaces

and Health. The National Academies Press. Washington D.C.

4. Dales R, D (1999) Residential fungal contamination and

health: microbial cohabitants as covariates. Environ Health Perspect

107 (sup 3): 481-483.

5. Sorenson WG, Frazer DG, Jarvis BB, Simpson J, VA (1987)

Trichothecene mycotoxins in aerosolized conidia of Stachybotrys

atra. Appl Environ Microbiol 53(6): 1370-1375

6. Górny, RL, Reponen T, Willeke K, Schmechel D, Robine E, Boissier

M, Grinshpun SA (2002) Fungal fragments as indoor air

biocontaminants. Appl Environ Microbiol 68(7): 3522-3531

7. Englehart S, Loock A, Skutlarek D, Sagunski H, Lommel A, Färber

H, Exner M (2002) Occurrence of toxigenic Aspergillus versicolor

isolates and sterigmatocystin in carper dust from damp indoor

environments. Appl Environ Microbiol 68(8): 3886-3890

8. Smoragiewicz W, Cossette B, Boutard A, Krzystyniak K (1993)

Trichothecene mycotoxins in the dust of ventilation systems in

office buildings. Int Arch Occ Environ Health (Historical Archive) 65

(2): 1432-1436

9. JL, Plattner RD, May J, Liska SL (1999) The occurrence of

ochratoxin A in dust collected from a problem household.

Mycopathologia 146: 99-103.

10. Brasel TL, DR, SC, Straus DC (2005) Detection of

airborne Stachybotrys chartarum macrocyclic trichothecene mycotoxins

on particulates smaller than conidia. Appl. Envir. Microbiol. 2005

71: 114-122.

11. Kildesø J, Würtz H, Nielsen KF, Kruse P, Wilkins K, Thrane U,

Gravesen S, Nielsen PA, Schneider T. (2003) Determination of fungal

spore release from wet building material. Indoor Air 13 (2): 148-155

12. Chew Gl, C, Burge HA, Muilenberg ML, Gold DR. (2003)

Dustborne and airborne fungal propagules represent a different

spectrum of fungi with differing relations to home characteristics.

Allergy 58: 13-20

13. Stetzenbach LD, Buttner MP, Cruz P. (2004) Detection and

enumeration of airborne biocontaminants. Current Opinion in

Biotechnology 15:170-174.

9

14. RE, Wiederhold NP, Chi J, Han XY, Komanduri KV,

Konttoyiannis DP, Prince RA (2005) Detection of gliotoxin in

experimental and human aspergillosis. Infection and Immunity 73(1):

635-637

15. Nielsen KF, Smedsgaard J. (2003) Fungal metabolite screening:

database of 474 mycotoxins and fungal metabolites for dereplication

by standardized liquid chromatography-UV-mass spectroscopy

methodology. J Chromatography A 1002(1-2): 11-136.

16. Van Emon JM, AW, Yike I, Vesper SJ (2003) ELISA measurement

of stachylysin in serum to quantify human exposure to the indoor

mold Stachybotrys chartarum. J Occup Med 45(6): 582-591.

17. Candlish AA, JE, Stimson WH (1989) Monoclonal antibody

technology for mycotoxins. Biotechnology Adv 7(3): 401-418.

18. Dietrich R, Schneider E, Usleber E, Märtlbauer E. (1995) Use of

monoclonal antibodies for the analysis of mycotoxins. Nat Toxins 3

(4): 288-293.

19. Märtlbauer E, Gareis M, Terplan G. (1988) Enzyme Immunoassay for

the macrocyclic trichothecene Roridin A: production, properties, and

use of rabbit antibodies. Applied Environ Microbiol 54(1): 225-230

20. Hack R, Märtlbauer E, Terplan G. (1988) Production and

characterization of monoclonal antibodies to the macrocyclic

trichothecene Roridin A. Applied Environ Microbiol 54(9): 2328-2330.

21. Liu J, Meng ZH (1998) Production and characterization of

monoclonal antibodies against fumitremorgin B. Biomed Environ Sci 11

(4): 336-344

22. Chung Y-J, Jarvis BB, Tak H, Pestka JJ (2003) Immunochemical

assay for satratoxin G and other macrocyclic trichothecenes

associated with indoor air contamination by Stachybotrys chartarum.

Toxicology Mechanisms and Methods 13(4): 247-252

23. Wang J-S, Abubaker S, He X, Sun G, Strickland PT, Groopman JD.

(2001) Development of aflatoxin B1-lysine adduct monoclonal antibody

for human exposure studies. Applied Environ Microbiol 67(6): 2712-

2717.

24. , PC, SE, Hall AJ, Prentice Am, Wild CP. (2003)

Modification of immune function through exposure to dietary

aflatoxin in Gambian children. Environ Health Perspect 111(2): 217-

220.

25. Trout D, Bernstein J, ez K, Biagini R, Wallingford K

(2001) Bioaerosol lung damage in a worker with repeated exposure to

fungi in a water-damaged building. Environ Health Perspect 109(6):

641-644.

26. Vojdani A, AW, Kashanian A, Vojdani E (2003) Antibodies

against molds and mycotoxins following exposure to toxigenic fungi

in a water-damaged building. Arch Environ Health 58(6): 1-9

27. Vojdani A, Thrasher JD, Madison RA, Gray MR, Heuser G,

AW (2003). Antibodies to molds and satratoxin in individuals exposed

in water-damaged buildings. Arch Environ Health 58(7): 464-474

28. AW, Thrasher JD, Madison JD, Vojdani A, MR,

A (2003) Neural autoantibodies and neurophysiological

abnormalities in patients exposed to molds in water-damaged

buildings. Arch Environ Health. 2003 Aug: 58(8):464-74.

10

29. Lühe A, Hildebrand H, Bach U, Dingerman T, Ahr H-J. 2003. A new

approach to studying ochratoxin A (OTA)-induced nephrotoxicity:

expression profiling in vivo and in vitro employing cDNA

microarrays. Toxicological Sciences 73: 315-328.

30. Sorenson WG (1993) Mycotoxins: toxic metabolites of fungi. In:

Fungal Infections and Immune Response. JW et al., eds. New

York, Plenum Press, pp. 469-491

31. Hanelt M, Gareis M, Kollarczik B (1994) Cytotoxicity of

mycotoxins evaluated by the MTT-cell culture assay. Mycopathologia

(Historical Archive) 128 (3): 167-174.

32. Johanning E, Landsbergis P, Gareis M, Yang CS, Olmsted E (1999)

Clinical experience and results of a sentinel health investigation

related to indoor fungal exposure. Environ Health Perspect 107(sup

3): 489-494.

11