Irritative effects: Modulation and course of chemosensory effects – Module "Sensitization" (Modulation of local effects by allergic rhinitis and chemical sensitivity)

Status:

completed 07/2021

Aims:

The research project "Irritative Effekte IV" (FP-0399) funded by German DGUV investigates the impact moderating factors on different levels (perception, physiology, and behavior). The project is subdivided into three modules – "körperliche Arbeit" (physical workload), "akute Effektverläufe" (courses of acute effects) und "Sensibilisierung" (sensitization). It investigates moderating factors that should be considered when experimental exposure studies have to be transferred to work environments.

Activities/Methods:

In four comprehensive, experimental human exposure studies, the influence of sensitivity of subjects, moderate physical workload, and exposure peaks and exposure time. As recommended by the "Forschungsbegleitkreis" (research advisory board), formic acid was used as a local irritant in all experiments. The results of the investigation of the modulating factors were – to the full extent – presented in the interim reports enclosed in the appendix. Therefore, this final report is used to compare and to classify the extent of effects of the modulating factors. This comparative summary of four experimental human exposure studies using formic acid comprises a total number of 148 subjects. Similarities between the experiments allow for a reliable and valid analysis of the influences of exposure level and exposure duration. The influences of corollary and pre-existing diseases (allergy), physical work, and the influence of exposure characteristics (exposure peaks, total exposure duration) can, thus, be partly analyzed and classified across experiments.

Results:

While formic acid exposure (at the level of the MAK-value) shows clear effects on almost all subjective assessments, formic acid exposure only has isolated, smaller effects on physiological measurements: Rhinometry measures (larger volumina after exposure) and an effect on eyelid closure frequencies at the end of the last measurement. Exposure duration systematically affects subjective assessments: olfactory sensations decrease over time, nonspecific trigeminal sensations of nasal irritation, such as nasal irritation, sneezing irritation, and tickling, increase over time, other trigeminal assessments (e.g., burning and stinging) and annoyance remain the same. An increase in an inflammation marker (High-Mobility-Group-Protein 1/HMGB1) in nasal lavage fluid is most apparent immediately following peak exposure to formic acid. While the allergy as a pre-existing condition has almost no influence on the measured subjective assessments, exposure-dependent, effect-enhancing influences of the allergy on the eyelid closure frequency are evident.

Physical work shows slight effects on subjective assessments of nonspecific nasal irritation especially with formic acid exposure. Effects of physical work on middle and lower airways (Fractional exhaled Nitric Oxide/FeNO) are visible but very small. Physical work has effects on respiratory rate and depth, but these are independent of formic acid exposure. Physical work in combination with formic acid exposure leads to increased HMGB1 levels in nasal lavage fluid.

Prolongation of the exposure time has effects on subjective assessments even in the control condition without exposure (only time in the laboratory is extended) and on single sensations in the MAK exposure: mainly on nonspecific sensations of nasal irritation, so the increasing trend found in the first hours of exposure continues.

The sequence of different exposure levels, especially peaks, in one single work shift has a great impact on subjective assessments, if a constant exposure at the level of the MAK value follows a peak exposure with the same mean shift value: The estimates are then significantly higher compared to the same exposure at the beginning of the shift.

The magnitude of the effects is compared purely descriptively in the subjective assessments, a joint statistical analysis is not possible due to differences in the experiments. The largest effect is observed by formic acid exposure compared to control exposure, followed by the sequence effect (both leading to significant increases in all assessments). Exposure duration also has considerable effects in both directions: Decrease over time in olfactory assessments, increase over time in some trigeminal assessments. Physical work has smaller effects on some trigeminal assessments (e.g. nasal irritation and sneezing) with exposure to formic acid at the MAK level.

Perceived eye irritation/ocular symptoms were related to eyelid closure frequency. Especially at the beginning, high correlations between subjective assessments and eyelid closure frequency were found. Comparing the control and exposure conditions, formic acid exposure has an additional effect on the subjective assessments of eye irritation, which is not seen to the same extent in the eyelid closures.

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