Nasal symptoms can be associated with indoor mold overgrowth, even absent allergic sensitization. An alternative pathogenic mechanism—mucous membrane irritation by microbial volatile organic compounds (MVOCs)—has been proposed. We conducted a pilot human study of nasal irritation by two MVOCs, 1-octen-3-ol and 3-octanol, hypothesizing that the former would show greater irritant potency based upon the compounds’ relative irritant potencies in rodents.
Serial dilutions of the test compounds were prepared in odorless mineral oil vehicle, with headspace vapor concentrations documented by gas chromatography. Eight-step dilution series (with ascending concentration ratios ~ 1.34) were prepared. A nasal lateralization protocol was utilized. Ten subjects (seven females), aged 23–69, were each tested on four separate days, with each test compound being presented twice in alternating/counterbalanced order over the four testing days. Individual lateralization thresholds for a given compound, taken as dilution step, were averaged across subjects.
Eight subjects were reliably able to lateralize stimuli for one or both test compounds. Among the 32 testing sessions completed by these eight subjects, 1-octen-3-ol was successfully lateralized in 15/16 and 3-octanol in 11/16. The mean dilution step at threshold was 3.125 for 1-octen-3-ol and 2.58 for 3-octanol.
When presented as brief (~ 4 s.) stimuli, high concentrations of identified MVOCs can act as nasal mucosal irritants. Both detectability and repeatability, but not absolute (ppm) thresholds, exhibited compound-specific trends consistent with animal experimental data. Studies involving more protracted exposures with larger sample sizes may yield more realistic irritant threshold estimates.
At sufficiently high concentrations, MVOCs can produce nasal irritation in humans.
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We wish to acknowledge the assistance of Drs. Wenhao Chen, Janet Macher, and Mark Mendell (of the Indoor Air Quality Section of the California Department of Public Health), who provided advice on study design—as well as hands-on technical assistance—at various stages of the project. We also wish to acknowledge the assistance of Dr. Enrique Cometto-Muniz of the University of California, San Diego in the selection of appropriate study materials, and Drs. Scott Meschke and Russell Dills of the University of Washington for providing input on an earlier version of this proposal.
Funds for this study were provided by the Department of Medicine, Division of Occupational and Environmental Medicine, University of California, San Francisco. In-kind support for analytical procedures was provided by the California Department of Public Health, Indoor Air Quality Section.
Conflict of Interest
The authors declare that they have no conflict of interest.
- Inter-test interval
The minimum time allowed between successive threshold tests (at least 1 day)
- Inter-trial interval
The time allowed between successive trials (nominally, 60 s)
- Lateralization threshold
For a given test compound, the average (ascending concentration) step at which an individual successfully lateralizes stimuli on five successive trials
Stimulus dilution step (0 = most concentrated; 7 = most dilute)
- Stimulus order:
i.e., “1212” vs. “2121”
Half of subjects with each of two alternating stimulus orders
- Threshold test
The entire testing procedure for a given day, incorporating five trials at each (ascending concentration) step until five of five are correctly lateralized
The simultaneous presentation of a stimulus and blank stimulus to opposite nostrils, with randomized lateralization
Visual analog scale [rating of subjective nasal irritation]
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Shusterman, D., Wang, P. & Kumagai, K. Nasal Trigeminal Perception of Two Representative Microbial Volatile Organic Compounds (MVOCs): 1-Octen-3-ol and 3-Octanol—a Pilot Study. Chem. Percept. 11, 27–34 (2018). https://doi.org/10.1007/s12078-017-9235-5
- Microbial volatile organic compounds (MVOCs)
- Nasal irritation
- Sensory irritation
- Trigeminal irritation