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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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