title: Prediction of human sensory irritation due to ethyl acrylate: the appropriateness of time-weighted average concentration × time models for varying concentrations.
abstract: Human data about the potency of ethyl acrylate to evoke sensory irritation is currently not available. Therefore, we conducted an experimental exposure study and the magnitude of chemosensory effects in healthy human volunteers was mathematically modeled by combining the factors current concentration (c) and duration/time (t). In a repeated-measures design, 19 subjects were exposed for 4 h to constant and varying concentrations (including peaks of 5 and 10 ppm) of ethyl acrylate with either a 2.5 or 5 ppm time-weighted average (TWA) concentration. Clean air served as control condition. Nasal lavage fluid, eye blinking frequencies, and rhinomanometry were used as physiological measures of sensory irritation. Several subjective ratings assessed olfactory and trigeminal perceptions. The blinking frequency was significantly increased during the varying 5 ppm condition. Regardless of the TWA concentration, varying exposures caused stronger effects than constant exposures. Our mathematical modeling showed that olfactory perceptions generally decreased over time while ratings of eye irritation increased over time even under the constant 5 ppm condition. Including the current concentration in the mathematical modeling always increased the goodness of fit substantially. The results showed that the intensity of sensory irritation could be predicted best with a complex c × t model. During the 2.5 ppm conditions, only the current concentration predicted the ratings and time-dependent processes could not be observed. However, in both 5 ppm TWA conditions strong eye irritations and increased blinking frequency, only at the end of the 4-h exposures a dose-dependency of these adverse effects was clearly shown.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund University, Ardeystr. 67, 44139, Dortmund, Germany. kleinbeck@ifado.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kleinbeck
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund University, Ardeystr. 67, 44139, Dortmund, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäper
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund University, Ardeystr. 67, 44139, Dortmund, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund University, Ardeystr. 67, 44139, Dortmund, Germany.
authors.forename: Meinolf
authors.initials: M
authors.lastname: Blaszkewicz
authors.affiliation: Research Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University Bochum, Bürkle de la Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund University, Ardeystr. 67, 44139, Dortmund, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: van Thriel
mesh_terms: D000179:Acrylates / Q000008:administration & dosage / Q000633:toxicity*; D000328:Adult; D004781:Environmental Exposure / Q000009:adverse effects; D005123:Eye / Q000187:drug effects*; D005260:Female; D006801:Humans; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008962:Models, Theoretical; D017817:Nasal Lavage Fluid; D009812:Odorants / Q000032:analysis; D025363:Rhinomanometry; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D000179:Acrylates; D007509:Irritants; C040833:ethyl acrylate
keywords: Haber’s rule; Habituation/Sensitization; Local irritants; Risk assessment; Sensory irritation