Mycotoxins are produced by some fungi (Campbell et al, 2004; Jarvis, 2002; Li and Yang, 2004; Nielsen, 2003). Mycotoxin production is influenced by substrate composition, water activity and temperature.
It is crucial to inventory indoor molds to species in order to assess if toxigenic molds are present. Exposure of occupants mainly results from inhalation and, to a lesser extent, skin absorption and ingestion.
Molds produce mycotoxins during rapid growth (Straus, personal communication). At low concentrations, they cause mycotoxicosis in humans and animals. The mycotoxins causing disease include aflatoxins, ochratoxin A, trichothecenes, citreviridins, fumonisins and gliotoxins (Bennett and Klich, 2003; Peraica et al, 1999; Richard 2007).
Mycotoxins can regulate the immune system up or down as well as inhibit synthesis of protein, RNA and DNA (Bok et al, 2006; Stanzani et al, 2005). Moreover, they can form DNA adducts (Peng et al, 2007; Pfohl-Leszkowicz et al., 2007), protein adducts (Campbell et al, 2004; Vojdani et al., 2003a,b; Yike et al, 2006) and cause oxidative stress (Gardiner et al, 2005; Peng et al, 2007) as well as mitochondrial directed apoptosis (Chan, 2007; Stanzani et al, 2005).
Some of the animal and human health concerns from mycotoxin-producing fungi are listed in Table 2.
Conjugation of mycotoxins to human serum albumin and detection of the conjugates have been reported.
Aflatoxin B1-albumin adducts occur with up to 350 pg of AFB1-lysine equivalent/mg albumin (Wild et al, 1990). The conjugation is reported to be permanent and irreversible (Nassar et al, 1982).
Humans form aflatoxin–albumin conjugates equivalent to similar conjugates formed in animals sensitive to the mycotoxin (Wild et al, 1996). Aflatoxin–albumin adducts are present in children with impaired growth (Gong et al, 2004) and in cases of acute aflatoxicosis (Azziz-Baumgartner et al, 2004).
Genetic polymorphism in glutathione S-transferases affects adducts level. Individuals with glutathione S-transferase M1 (GSTM1) null had increased levels of adducts versus individuals with normal GSTM1 enzymatic activity. This enzyme conjugates aflatoxin B1 8, 9-epoxide to albumin (Chen et al, 2000; Sun et al, 2001; Wojnoski et al, 2004).
In addition, polymorphism in CYP3A5 and CYP3A affects aflatoxin–albumin adduct levels. CYP3A5 haplotypes with high enzyme activity had increased levels compared to individuals with low activity. The effect was more evident in individuals with low CYP3A4 enzyme activity (Wojnoski et al, 2004).
More recently, attention has been directed towards the study of S. chartarum and trichothecenes.
Albumin conjugates with satratoxin G have been demonstrated. As many as 10 satratoxin molecules adduct with albumin at lysyl, cysteinyl and histidyl amino acid residues of the protein. Satratoxin G-albumin adducts were identified in the sera of exposed humans and rat pups (Yike et al, 2006).
In addition, antibodies to satratoxin H were present in the systemic circulation of humans exposed to S. chartarum (Vojdani et al, 2003a,b).
The neurotoxic mycotoxins include ergot alkaloids, trichothecenes, citreviridin, patulin, fumonisins and tremorgens. The neurotoxic effects of the tremorgens in laboratory animals are on the brainstem, stellate ganglion and Purkinje cells of the cerebellum.
The tremorgens can affect neuroreceptor sites (e.g., gamma aminobutyric acids [GABA] and inositol 1, 4, 5-trisphosphate receptor), inhibit acetylcholinesterase, and release excitatory neurotransmitters (e.g., glutamate aspartate, GABA, serotonin) (Campbell et al, 2004; Chen et al, 1999; Land et al, 1987; Selala et al, 1989; Valdes et al, 1985).
In humans, the tremorgens verrucologen and fumitremogen C produced by A. fumigatus have been implicated in wood trimmer’s disease, characterized by alveolitis and tremors (Land et al, 1987). Verruculogen decreases GABA levels in the mouse brain (Hotujac et al, 1976).
Fumonisin-contaminated corn tortillas have been linked to an increased risk of neural tube defects and fetal death in residents along the Texas–Mexico border (Missmer et al, 2006). These mycotoxins inhibit ceramide synthase causing an accumulation of bioactive intermediates of sphingolipid metabolism
(sphinganine and sphingoid bases). They also interfere with folate transport and cause craniofacial defects in mouse cultures and in utero. The administration of folic acid or a complex sphingolipid was preventative with respect to the in utero defects (Marasas et al, 2004).
Intrathecal instillation of extracts of P. brevicompactum and chrysogenum that contained mycophenolic acid and roquefortine C in mice at concentrations of the mycotoxins ranging from 0.5 to 12.5 nM/g body weight caused inflammation within 6 hours at concentrations of mycotoxins.
Cellular and chemical markers of inflammation were elevated, including macrophages and neutrophils, MIP-2, TNF and IL-6 concentrations in bronchoalveolar lavage fluid (BALF). A dose response was seen for mycophenolic acid (macrophages) and MIP-2. In addition, brevianamide A induced cytotoxicity with increased LDH concentrations.
Albumin, a marker of pulmonary capillary vascular leakage, was also elevated in the BALF (Rand et al, 2005).
Finally, zearalenone and zearalenol are estrogenic compounds already associated or correlated with increased incidence of infertility, abortion and uterine prolapse in livestock (Zinedine et al, 2007). They probably have estrogenic action in humans exhibited by precocious puberty (Leffers et al, 2001; Massart et al, 2008).
Mycotoxins have been detected in the air and building materials following water intrusion. Sterigmatocystin produced by A. versicolor was detected in 2 of 11 carpet dust samples from water-damaged homes (Englehart et al, 2002).
Bulk samples from a Finnish building with moisture problems were analyzed for 17 different mycotoxins. Sterigmatocystin was present in 24% of the samples. Trichothecenes were detected in 19% of the materials as follows:
Satratoxin G or H (five samples); diacetoxyscirpenol (five samples); 3-acetydeoxynivalenol (three samples) and deoxynivalenol, verrucarol or T-2 tetraol in an additional five samples. Citrinine was found in three samples. A. versicolor was present in most sterigmatocystin-containing samples. Stachybotrys spp. were present where satratoxins were detected (Tuomi et al, 2000).
Screening of dust samples from the ventilation system of office buildings revealed the presence of the trichothecenes, T-2 toxin, diacetoxyscirpenol, roiridine A and T-2 tetraol (Smoragiewicz et al, 1993).
Satratoxin G and H were identified in buildings with dampness in Denmark (Gravesen et al, 1999) and Germany (Gottschalk et al, 2008) and the United States (Hodgson et al, 1998).
Finally, Johanning et al (1996, 1999, 2002a,b) demonstrated that indoor air of S. chartarum contaminated structures is cytotoxic in an in vitroMTT (-4, 5-dimethylthiazolyl)-2, 5-diphenlytetrazolium bromide) assay. MTT is a colorimetric assay that involves the reduction by mitochondria of living cells of the yellow MTT to purple formazan.
Trapped particulates from the indoor air of moldy buildings contain macrocyclic trichothecenes (satratoxins) and spirocyclic lactones. However, mycotoxins produced by other genera of molds in the indoor air cannot be ruled out. Thus, the MTT cytotoxicity assay responds to mycotoxins, e.g., gliotoxin,
fumonisins, aflatoxins, patulin, etc., as well as Type A and B trichothecenes (Hanelt et al, 1994; Schultz et al, 2004; Smith et al, 1992; Visconti et al, 1991; Yike et al, 1999).