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 Ám. 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 ▀-(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

 

 

 


Page 2

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


Page 3

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.