Inhaltsverzeichnis
Disclaimer: Dieser Artikel ist ein Beitrag im Rahmen der Konferenz "Innenraumluft 2024" und spiegelt nicht die Meinung des Umweltbundesamtes wider. Für die Inhalte sind die genannten Autoren und Autorinnen verantwortlich.
Autorin
Joan W. Bennett
Distinguished Professor of Plant Biology and Pathology at Rutgers University, NJ, USAEmpfohlene Zitierweise: Bennett, J. W. (2024). Embracing volatility: The emerging public health relevance of gaseous emissions from indoor mold. Beitrag A27 zur Fachtagung „Innenraumluft 2024 - Messen, Bewerten und Gesundes Wohnen“, 6.-8. Mai 2024, Dessau-Roßlau.
Embracing volatility: The emerging public health relevance of gaseous emissions from indoor mold
Backround
Microscopic fungi (“molds”) cause negative impacts on human health through infections, allergies, and asthma. In addition, ingestion, inhalation, and dermal contact with mold toxins (mycotoxins) are known health hazards. In contrast, the possible health implications of the volatile products of mold metabolism have received far less research attention, in part because of demanding methodologies and absent animal models or other toxicity assays. It is known that many volatile organic compounds (VOCs) associated with industry cause adverse health effects, but the toxigenic effects of biologically produced volatiles have been rarely studied. In nature, fungal VOCs are found as combinations of alcohols, aldehydes, acids, ethers, esters. In particular, the 8-carbon volatile 1-octen-3-ol is commonly emitted by molds in water-damaged moldy buildings/residences and is responsible for much of the distinctive moldy odor associated with molds. Limited studies in Scandinavia with 1-octen-3-ol have indicated mild toxicity in human volunteers.
Our laboratory has developed several genetic models for use as bioassays to measure the toxigenicity of selected mold VOCs. We have exposed these genetic models to the volatile emissions from growing molds and demonstrated toxicity. Subsequently, the chemical profiles of the mixtures of mold volatiles emitted from growing molds have been determined using gas chromatography and mass spectrometry (GC-MS), and then controlled concentrations of chemical standards of individual VOCs have been re-tested in the same genetic models.
Hypotheses
Many volatile products are, like their non-volatile counterparts, physiologically active and may cause adverse health outcomes in exposed human populations.
Methods
We developed several genetic model systems for use in toxicity testing including the fly Drosophila melanogaster; the yeast Saccharomyces cerevisiae; and human embryonic stem cells. The genetic models were grown in a shared atmosphere with fungal cultures isolated in the aftermath of hurricane events, or with different concentrations of chemical standards of selected VOCs. A yeast knock-out library was used to determine which genes were associated with 1-octen-3-ol toxicity
Results
We used adult wild type Drosophila flies (i.e. those with an intact immune system) and found that exposure to low concentrations of volatile phase 1-octen-3-ol, 2-octanone, trans-2-octenal, 2,5 dimethylfuran, and 3-octanol produced truncated life span, locomotory abnormalities and selective loss of dopaminergic neurons in adult Drosophila. The antioxidant vitamin E increased survival and delayed VOC-mediated alterations in dopaminergic neurons, demonstrating that VOC-mediated toxicity was partially caused by the formation of reactive oxygen species. Mechanistically, 1-octen-3-ol caused an increase in the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and its ability to inhibit uptake of dopamine in vitro, thereby disrupting dopamine homeostasis and enhanced dopaminergic neurodegeneration. We hypothesized that this common fungal metabolite might contribute to Parkinson’s disease. In addition to adult flies, wild type Drosophila larvae was used in an eclosion test to assay the toxicological effects of the same fungal VOCs. At low concentrations, many biogenic fungal volatiles were more toxic to Drosophila than identical concentrations of vapors of common industrial VOCs such as benzene, formaldehyde, toluene or xylene. When larvae were exposed to low concentrations of chemical standards of 1-octen-3-ol, 80% of larvae pupated but only a small number of exposed pupae emerged into adults. Most of our studies on the impact of fungal volatiles on flies utilized wild type flies, however we have also done tests on mutant flies carrying three different immune deficiencies (NOS, Imd and Toll). A double mutant carrying blocked immune system mutations in both the Imd and Toll pathways was resistant to the toxigenic effects suggesting that components of the wild-type innate immune system of Drosophila are responsible for causing death in adult flies exposed to eight carbon volatiles. In human embryonic stem cells, vapors of 1-octen-3-ol were more toxic than toluene. When tested in a yeast knock out library, the genes involved in resistance to toxic concentrations of 1-octen-3-ol all mapped to a gene for the microscopic cell component called the retromer. The retromer is a highly conserved complex that mediates recycling of protein cargo within cells and recycling of transmembrane receptors.
Conclusions
Mold volatiles such as1-octen-3-ol class have disruptive effects across several species including dopaminergic neurons of Drosophila melanogaster and the yeast Saccharomyces cerevisiae. In Drosophila flies with defective immune systems, the toxicity of VOCs is greatly diminished, suggesting that in this animal model, VOC toxicity is mediated through the reactions of the innate immune system. Future research on possible negative health impact of fungal VOCs necessarily will be a multidisciplinary challenge that will require basic scientists, public health officials and building inspectors to pay more attention to the gaseous constituents associated with indoor mold contamination. We suggest that the precautionary principle advocates that the potential toxicity of mold volatiles should be included in decisions concerning the safety of indoor air for human occupants.
