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Review Article

Fungal spores: A critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting

Pages 799-864 | Received 11 Sep 2008, Accepted 03 Sep 2009, Published online: 28 Oct 2009
 

Abstract

Fungal spores are ubiquitous in the environment. However, exposure levels in workplaces where mouldy materials are handled are much higher than in common indoor and outdoor environments. Spores of all tested species induced inflammation in experimental studies. The response to mycotoxin-producing and pathogenic species was much stronger. In animal studies, nonallergic responses dominated after a single dose. Allergic responses also occurred, especially to mycotoxin-producing and pathogenic species, and after repeated exposures. Inhalation of a single spore dose by subjects with sick building syndrome indicated no observed effect levels of 4 × 103 Trichoderma harzianum spores/m3 and 8 × 103 Penicillium chrysogenum spores/m3 for lung function, respiratory symptoms, and inflammatory cells in the blood. In asthmatic patients allergic to Penicillium sp. or Alternaria alternata, lowest observed effect levels (LOELs) for reduced airway conductance were 1 × 104 and 2 × 104 spores/m3, respectively. In epidemiological studies of highly exposed working populations lung function decline, respiratory symptoms and airway inflammation began to appear at exposure levels of 105 spores/m3. Thus, human challenge and epidemiological studies support fairly consistent LOELs of approximately 105 spores/m3 for diverse fungal species in nonsensitised populations. Mycotoxin-producing and pathogenic species have to be detected specifically, however, because of their higher toxicity.

Acknowledgements

This criteria document was prepared in cooperation with the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals (NEG). NEG’s main task is to produce criteria documents to be used by the regulatory authorities as the scientific basis for setting occupational exposure limits for chemical substances. Whereas NEG adopts the document by consensus procedures, thereby granting the quality and conclusions, the author is responsible for the factual content of the document. The final version was accepted by NEG October 10, 2006. The following individuals participated in the elaboration of the document: Gunnar Johanson (Sweden, chairman), Maria Albin (Sweden), Karin Sørig Hougaard (Denmark), Kristina Kjærheim (Norway), Vidir Kristjansson (Iceland), Kai Savolainen (Finland), Vidar Skaug (Norway), Jill Järnberg (Sweden, secretary), Anna-Karin Alexandrie (Sweden, secretary). We gratefully acknowledge Aino Nevalainen for valuable comments on the draft document. Editorial work and technical editing were performed by the NEG secretariat. This work was financially supported by the Swedish National Institute for Working Life, the Norwegian Ministry of Labour and Social Inclusion, and the Nordic Council of Ministers.

All criteria document produced by the Nordic Expert Group can be down-loaded from www.nordicexpertgroup.org.

Declaration of interest: This paper was prepared during the normal course of the author’s employment as identified on the first page. The author has no other interests to declare.

Abbreviations and acronyms
ACGIH=

American Conference of Governmental Industrial Hygienists

AED=

aerodynamic diameter

bw=

body weight

CAMNEA=

collection of airborne microorganisms on nucleopore filters, estimation and analysis

cfu=

colony-forming units

CI=

confidence interval

ECP=

eosinophilic cationic protein

EU=

endotoxin units

FEV1=

forced expiratory volume in 1 second

FVC=

forced vital capacity

IFNγ=

interferon gamma

IgE=

immunoglobulin E

IgG=

immunoglobulin G

IL=

interleukin

LD50=

lethal dose for 50% of the animals at single exposure

LOEL=

lowest observed effect level

MCP=

monocyte chemoattractant protein

MEF25=

maximum expiratory flow at 25% of FVC

MIP=

macrophage inflammatory protein

MVOC=

microbial volatile organic compound

NEG=

The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals

NO=

nitric oxide

NOEL=

no observed effect level

ODTS=

organic dust toxic syndrome

OEL=

occupational exposure limit

OR=

odds ratio

PaO2=

arterial oxygen tension

PMN=

polymorphonuclear leukocytes (mainly neutrophils)

PPR=

prevalence proportion ratio

RAST=

radio-allergosorbent test

ROS=

reactive oxygen species

SEM=

scanning electron microscope

sp/spp=

species (singular/plural)

TGFβ=

transforming growth factor beta

Th cells=

T helper cells

TLco=

lung transfer factor for carbon monoxide

TLR=

Toll-like receptor

TLV=

threshold limit value

TNFα=

tumour necrosis factor alpha

Data bases used in the search for literature

A literature search was conducted in the Medline, Toxline, Arbline, OSH-ROM, and ISI bases as well as the author’s own database. Further references were obtained from reviewed papers. The last search was performed in November 2006. The following terms were used in the literature search:

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