Human health effects of indoor mycotoxin exposure in fungi - contaminated indoor environments
In
recent years, a great deal of interest has been generated regarding
the study
of
toxigenic fungi and mycotoxins. Historically, mycotoxins have been a
problem related to agricultural, food, poultry and cattle industries.
However, many
toxigenic fungi have been found to infest buildings with indoor
environmental problems.
Several recent cases have related toxigenic fungi and mycotoxins to building
occupant
health problems caused by contaminated indoor environments. For example:
*Courthouses in Florida were closed
for extensive decontamination of toxigenic fungi at a cost that equaled the
buildings' original construction cost (Yang 1).
*An old
school building in Canada
was so infested with toxigenic fungi that
it
had to be burned (Yang 1).*Cases of pulmonary hemorrhage
were reported in infants who were living
in homes
in the Cleveland area that were
contaminated with toxigenic fungi (ACGIH Bioaerosols 24-26).
This article examines how mycotoxins are produced in the indoor environment
and describes their potential health effects to humans with respect to expo-
sure to indoor environmental sources.
TOXIGENIC FUNGI & MYCOTOXINS
To
understand the health effects of mycotoxins, one needs a basic understanding
of the
biology of fungi and how mycotoxins are produced. Typically,
fungi found in indoor
environments consist of microscopic molds and yeasts. (Since yeasts do not
produce mycotoxins,
they are not discussed in this article.) Fungi are eukaryotic organisms com-
posed of rigid-walled cells that contain a nucleus, other membrane
organelles and
mitochondria (Johanning). They are often categorized by their need for
moisture.
For example, hydrophylic fungi require extremely damp (close to saturation)
con-
ditions to proliferate, while Xerophilic fungi can grow in drier conditions.
Fungi colonize substrates in the form of long chains of cells called hyphae
that
range in size from 2 to 10 µm. These networks of hyphae are termed a
mycelium.
Most mycelial fungi produce airborne spores from the hyphae for
reproduction.
Most fungi found in indoor environments are saprotropic-they obtain the
nutrients they need for metabolism from dead, moist organic materials or
sub-
strates such as wood, paper, paint, soft furnishings, potting soil, dust,
skin scales
and food (Johanning). Fungi known to produce toxins (mycotoxins) are
described as toxigenic fungi.
These fungi are ubiquitous in the air and soil throughout the world;
however, the
most-common and well-documented species found in indoor environments
include many species in the genera of Aspergillus, Penicillium and Clado-
sporium (Yang 2). Other toxigenic fungi often found in indoor environments
include Alternaria, Trichoderma, Fusarium, Paecilomices, Stachybotrys, Chae-
tomium, Acremonium and Myrothecium (ACGIH Guidelines 3).
Fungi are known to produce several agents that can be toxic if
exposure is suf-
ficient. These toxic agents consist of 1) secondary products of
fungal metabo-
lism and 2) fungal structural components. The
first category includes
mycotoxins, antibiotics and volatile organic compounds; the second includes
cellular membrane components such as ß-(13)-D-glucans (ACGIH Bioaerosols
24). A 1990 World Health Organization publication establishes that more than
200 mycotoxins are produced by various toxigenic fungi.
Mycotoxins consist of relatively low molecular weight, nonvolatile com-
pounds with diverse chemical structures ranging from the simple
monolliformin
to
complex polypeptides with molecular 26
PROFESSIONAL SAFETY AMERICAN SOCIETY OF SAFETY ENGINEERS
INDOOR AIR QUALITY II Human Health
NOVEMBER 2001 27 weights over 2000 (ACGIH Guidelines 1)
Human Health Effects of Airborne Mycotoxin
Exposure
in Fungi-Contaminated Indoor
Environments and include polyketides, terpenes and indoles (ACGIH
Bioaerosols 24). With
respect to indoor environmental exposures, the mycotoxins of primary concern
are cytotoxins (i.e., aflatoxin) produced by Aspergillus flavus and
Aspergillus
parasiticus, and the trichothecene toxins produced by Stachybotrys
chartarum,
Mycrothecium verrucaria and others (Burge and Hoyer 402).
Mycotoxin production (types and amounts) depends on the
fungal species,
metabolism substrate, temperature, pH, presence of other organisms and
related
environmental factors. More than one fungal species or genus can produce the
same
mycotoxin compound. Additionally, a single fungal
species can produce more than
one mycotoxin. This is evidenced by the production of the mycotoxin
sterigmato-
cystin by Aspergillus versicolor, Emericella nidulans and Cochliobolus; and
produc-
tion of the mycotoxins satratoxin F, G and H, roridin E and verrucarin J by
Stachy-
botrys chartarum (ACGIH Bioaerosols 24). When mycotoxins are produced, they
are
typically identified in the fungal spores
(mycelia) and in the growth substrates
(wood, paper, etc.) in quantities dependent on the specific
fungal species and strain.
MYCOTOXIN GENERAL HEALTH EFFECTS
Several toxicological studies published within the last 30 years have
examined the human health effects of
mycotoxins. However, most of these studies have focused on contamination of
animal feed and occupational
exposures of agricultural grain handlers, not on indoor environmental
substrates. These
historical studies have established that cytotoxins cause cell disruption
and interfere with cellular
processes while trichothecenes impact the immune system and specific organs
(ACGIH
Guidelines 2). Mycotoxin exposures have been linked to a variety of acute
and chronic adverse
health affects. Generally, these effects include acute symptoms such as
pulmonary hemorrhage,
dermatitis, recurring cold and flulike symptoms, burning/sore throat,
headaches, excessive fatigue and
diarrhea. Chronic effects include carcinogenicity, mutagenicity,
teratogenicity, cen-
tral nervous system effects, immune system damage, and specific effects of
the
heart, liver, kidneys and other organs
(ACGIH
Guidelines
2). Table 1 lists some common indoor toxigenic fungi, their associated
mycotoxins
and possible health effects.
TOXICOLOGICAL INFORMATION
As
Table 1 indicates, mycotoxins are produced by various toxigenic fungi and
are
able to produce deleterious health effects. Doses of mycotoxins that
cause toxic effects
vary with each specific toxin, the animal species exposed, and the route and
duration
of
exposure. Toxicological data for some
trichothecene toxins indicate rat ingestion LD50
values below 1.0 mg/kg
(ACGIH
Guidelines
2). However, the chronic effects from aflatoxin
exposure
may occur at
dose concentrations as
low as the microgram per kilogram range
(ACGIH
Guidelines
2). Inhalation exposures using mice, rats, swine and guinea pigs to T-2
toxin indicate a
degree of toxicity 2 to >20 times more than intravenous dosages, which
indicates that
inhalation exposure may increase the potential
for chronic health effects
(ACGIH
Guidelines
2).
INHALATION HEALTH EFFECTS
Since mycotoxins are relatively non-volatile, inhalation
exposure is mostly limited to the inhalation
of
airborne fungal particulates (usually spores) or fungi-contaminated
substrates that contain
concentrations of mycotoxins. Inhalation of these particulates can result in
the transportation of
mycotoxins to the alveoli. Once in the alveoli, trichothecenes could
interfere with immune
responses while other mycotoxins have been shown to interfere with foreign
particle clearance
by
the macrophage response
(ACGIH
Guidelines
2). These effects have the potential to initiate bacterial infections
(ACGIH
Guidelines
2)
and invasiveAspergillosis
(ACGIH
Bioaerosols 24-25).
Human inhalation exposure to mycotoxins, as
indicated by agricultural and manufacturing exposures,
have also been linked to various health conditions.
*
Organic toxic dust syndrome (OTDS). This manifests in the form of
flulike symptoms and is similar to
hypersensitivity pneumoconiosis. The condition results from the inhalation
of organic dusts that
contain a mixture of endotoxins, glucans, antigens and mycotoxins. OTDS has
been termed a pulmonary
mycotoxicosis; however the actual role of mycotoxins has not been proven
(ACGIH
Bioaerosols 24-26).
*Aflatoxin.
Aflatoxin has been linked to various cancers in agricultural and food
processing applications and
interstitial pneumonitis in textile workers
(ACGIH
Bioaerosols 24-26).
*
Miscellaneous.
Fungal
spore exposure
associated with Stachybotrys chartarum, Trichoderma spp. and Acremonium spp.
has been documented to cause skin inflammation and scaling on women working
in a large-scale horticultural
setting. Also, a case of dementia and tremors
has been linked to exposure.
FUNGUS MYCOTOXIN POSSIBLE HEALTH EFFECT
Acremonium spp.
Cephalosporin
antibiotic
Alternaria alternata
Tenuazoic acid
nephrotoxic,
hepatotoxic,
hemorrhagic
Aspergillus clavatus
Cytochalasin E,
Patulin
cell division, protein
synthesis inhibitor,
nephrotoxic,
carcinogenic
Aspergillus flavus,
Aspergillus parasiticus,
Aspergillus fumigatis
Aflatoxins
Fumitremorgens
Gliotoxin
mutagenic, carcinogenic,
hepatotoxic,
tremorgenic, cytotoxic
Aspergillus nidulans,
Aspergillus versicolor
Sterigmatocystin
hepatotoxic,
carcinogenic
Aspergillus ochraceus,
Penicillium verrucosum,
Penicillium viridicatum
Ochratoxin A
nephrotoxic,
hepatotoxic,
carcinogenic
Cladosporium spp.
Epicladosporic acid
immunosuppresive
Chladosporium
cladosporiodes
Cladosporin, Emodin
antibiotic
Fusarium graminearum
Deoxynivalenol
Zearalenone
emetic
estrogenic
Fusarium monoliforme
Fumonisins
neurotoxic, hepatotoxic,
nephrotoxic,
carcinogenic
Fusarium poae,
Fusarium sporotrichoides
T-2 toxin
hemmorrhagic,
hepatotoxic,
nephrotoxic,
carcinogenic
Penicillium
chrysogenum
Penicillin
antibiotic
Penicillium crustosum
Penitrem A,
Roquefortine C
tremorgenic, neurotoxic
Penicillium expansum
Citrinin, Patulin,
Roquefortine C
nephrotoxic,
carcinogenic, protein
synthesis inhibitor,
neurotoxic
Penicillium
griseofulvum,
Penicillium viridicatum
Griseofulvin
tumorigenic, teratogenic,
hepatotoxic
Stachybotrys chartarum
Satratoxins,
Verrucarins, Roridins,
Stachybocins
inflammatory agents,
immunosuppressive,
dermatitis, hemotoxic,
hemorrhagic
Source: ACGIH.
Bioaerosols: Assessment and Control.
1999.
TABLE 1
Mycotoxins & Potential Health Effects
toxin associated with Aspergillus fumigatus during silo unloading. Finally,
reports of farm worker toxicosis
have been associated with exposure to aerosols
from straw containing Stachybotrys chartarum
(ACGIH
Bioaerosols 24-26).
Specific health effects associated with indoor environment (e.g., offices,
schools,hospitals and homes)
inhalation exposures have not been well-documented. As noted, most
epidemiological and toxicology data
available are derived from animal ingestion studies and case studies of
occupational inhalation exposures
among agricultural workers. However, following is one of the few
well-documented cases of human
mycotoxicosis resulting from indoor air exposure
in a home heavily infested with Stachybotrys atra (chartarum).
Water damage had occurred in a house over a period of several years.
Extensive growth of the black sooty-appearing
S.
atra was evident on the ceiling of an upstairs bedroom and in the air ducts.
Numerous S. atra spores were
collected from room air samples, and a series of highly toxic trichothecene
mycotoxins were isolated from both
the ceiling material and the debris found in the air ducts (Croft, et al).
The complaints reported by occupants (ranging
from headaches, sore throats, flu symptoms, diarrhea and hair loss to
fatigue, dermatitis and general malaise)
are consistent with chronic trichothecene intoxication. The symptoms
disappeared after the home was thoroughly
cleaned.
(ACGIH
Guidelines2).
As
noted, one recent study examined infants who had suffered pulmonary
hemorrhage while living in homes
contaminated with Stachybotrys chartarum and other fungi. However, the
actual role of fungi and any mycotoxin
produced has not been positively identified. Other case studies of
fungal infestation and links to mycotoxin
exposure have been documented; however, no
definitive relationship between fungal spore
mycotoxins and
health symptoms has been established. In addition, to date, no significant
evidence links indoor environmental
inhalation
exposure
to mycotoxins with cancer.
CONCLUSION
It
is apparent that there is a significant lack of meaningful data relative to
the human health effects of airborne
exposure to mycotoxins. While a great deal of data are available from animal
ingestion studies and epidemiological
studies of agricultural and industrial workers, even these data do not
appear to demonstrate a definitive link between
inhalation exposure of mycotoxins and disease. Extrapolation of the animal
toxicology data proves difficult due
to
several factors:
*Dose variations and ingestion route of exposure
of the mycotoxin to animal species create a great deal
of
uncertainty when attempting to transfer to human indoor environmental
exposures. *Experimental animals
used and their various sensitivities to particular toxins introduce problems
when attempting to extrapolate to
human health effects. *Use of animal data to predict human risk involves the
drawing of many assumptions such
as
1) humans will react to a toxin in a similar manner as the test animal and
2) the natural human exposure scenario
is
identical to the test animals' laboratory exposure.
Use of epidemiological study data of human occupational
exposures to predict health risks associated with indoor environmental
exposures also proves problematic
for many of the same reasons, specifically in terms of dose, route of
exposure
and environmental variables.
Based on these uncertainties, there does not appear to be sufficient,
definitive information to predict human health
exposure
effects when dealing with
inhalation of mycotoxins in a typical, nonindustrial indoor environment.
Thus,
further study is needed. This lack of definitive information creates the
need to eliminate or reduce the potential for
exposure. This can only be achieved via the
proactive control of mold growth. As noted, mold growth requires
an
adequate substrate (food source), suitable temperature conditions and
moisture. Controlling one-or all-of these
parameters will help prevent mold growth. To do so, a facility should
establish an effective preventive maintenance
program that includes:
*systematic facility inspections that focus on typical moisture sources such
as roofs, piping systems, HVAC systems,
condensation sources and humidification systems; *timely repair or
elimination of identified water leaks or other
unwanted sources of water; *routine HVAC maintenance that includes filter
change-outs, humidity control adjustments,
airflow adjustments and cleaning; *routine inspections to look for visible
evidence of mold growth/water damage;
*adequate cleaning of mold growth/water-damaged nonporous materials with
suitable cleaning agents such as a
10-percent bleach solution and/or the removal of potentially contaminated
porous materials such as carpeting, dry-
wall, furniture and ceiling tiles. These simple tips can also help a
facility control mold growth: *Repair plumbing
and other building leaks as soon as possible. *Watch for condensation
sources and fix them. To achieve this,
1)
increase the surface temperature by insulating or increasing air flow or 2)
reduce indoor humidity levels by
repairing leaks, increasing ventilation or dehumidification. *Maintain HVAC
drip pans, piping systems and other
components in a clean, unobstructed condition. *Vent moisture-generating
appliances and processes directly
to
the outside. *Maintain indoor relative humidity levels in the range of 30 to
50 percent. *Clean and dry wet/damp
spots as soon as possible. *Keep foundations as dry as possible through
proper drainage and sloping.
REFERENCES
American Conference of Governmental
Industrial Hygienists (ACGIH).
Bioaerosols
Assessment and Control.
Cincinnati: ACGIH,
1999.
ACGIH.
Guidelines for the Assessment of
Bioaerosols in the Indoor Environment.
Cincin-
nati: ACGIH, 1989.
American Industrial Hygiene Assn.
(AIHA).
Biosafety Reference Manual.
2nd ed.
Fairfax,
VA: AIHA Publications, 1995.
Burge, H. and M.E. Hoyer, ed.
The Occu-
pational Environment: Its Evaluation and
Control.
Chapter 19, "Indoor Air Quality."
1997.
Croft, W.A., et al. "Airborne Outbreak of
Trichothecene Toxicosis."
Atmospheric Envi-
ronment.
20(1986): 549-552.
EPA. "Mold Remediation in Schools and
Commercial Buildings." Washington, DC:
EPA, 2001.
Johanning, E. "Hazardous Molds in
Homes and Offices: Stachybotrys atra and
Others." The EnvirosVillage Library web-
site, November 1999.
Wald, P.H. and G.M. Stave.
Physical and
Biological Hazards of the Workplace.
New
York: Van Nostrand Reinhold, 1994.
Williams, P. and J.L. Burson, eds.
Industrial Toxicology Safety and Health
Applications in the Workplace.
New
York: Van
Nostrand Reinhold, 1985.
Yang, C.S. "Toxic Effects of Some Common Indoor Fungi."
Enviros: The Healthy Building Newsletter.
Sept. 1994.
David M. Albright,
CSP, CIH, is a senior industrial hygienist/safety specialist with Gannett
Fleming
Inc. in
Harrisburg, PA. He holds a B.S. in Safety Sciences from Indiana University
of Pennsylvania
and an M.S. in Environmental Science and Management
from Duquesne University. A member of
ASSE's
Central Pennsylvania Chapter and a Diplomate
in AIHA, Albright has 10 years' experience in
environmental safety and health.
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