Prediction of human sensory irritation due to ethyl acrylate: the appropriateness of time-weighted average concentration × time models for varying concentrations

• Published in: Archives of toxicology Vol. 91; no. 9; pp. 3051 - 3064
• Main Authors: Kleinbeck, Stefan, Schäper, Michael, Zimmermann, Anna, Blaszkewicz, Meinolf, Brüning, Thomas, van Thriel, Christoph
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2017; Springer Nature B.V
• Subjects: Acrylates - administration & dosage; Acrylates - toxicity; Adult; Biomedical and Life Sciences; Biomedicine; Blinking; Chemical compounds; Chemoreception; Chemosensory perception; Environmental Exposure - adverse effects; Environmental Health; Exposure; Eye; Eye - drug effects; Female; Goodness of fit; Humans; Irritants - administration & dosage; Irritants - toxicity; Irritation; Male; Mathematical analysis; Mathematical models; Models, Theoretical; Nasal Lavage Fluid; Occupational Medicine/Industrial Medicine; Odorants - analysis; Pharmacology/Toxicology; Predictions; Ratings; Regulatory Toxicology; Rhinomanometry; Risk Assessment; Side effects; Time Factors; Toxicity; Habituation/Sensitization; Risk assessment; Local irritants; Sensory irritation; Haber’s rule
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-017-1934-9

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.