Sensory irritation, pulmonary irritation and structure-activity relationships of alcohols

• Published in: Toxicology (Amsterdam) Vol. 88; no. 1-3; p. 81
• Main Authors: Hansen, L F, Nielsen, G D
• Format: Journal Article
• Language: English
• Published: Ireland 11-03-1994
• Subjects: Administration, Inhalation; Alcohols - administration & dosage; Alcohols - toxicity; Animals; Butanols - toxicity; Dose-Response Relationship, Drug; Heptanol; Male; Mice; Mice, Inbred Strains; Neurons, Afferent - drug effects; Pentanols - toxicity; Respiratory System - drug effects; Structure-Activity Relationship; Time Factors
• ISSN: 0300-483X
• DOI: 10.1016/0300-483X(94)90112-0

Sensory irritation due to inhalation of n-pentanol, n-heptanol, sec-butanol and tert-pentanol was determined from the reflexively induced decrease in respiratory rate in CF-1 mice. The concentration-effect relations followed Michaelis-Menten equations, complying with receptor mediated processes. The relations were transformed into nearly rectilinear relationships in log concentration-effect plots, and the extrapolated threshold concentrations (RD-0) from the lines were 120, 28, 640 and 1210 ppm, respectively, obtained from the first 2 min of the exposure period. These values were comparable to those found in Swiss-Webster mice and to those obtained by electrophysiological experiments in Sprague-Dawley rats. The hydrophobic properties of the receptor biophase were found to approach that of the internal part of the bilayer membrane. Estimates on threshold limit values (TLV) were obtained and were found in reasonable agreement with the established values. The nose has a scrubbing effect, which reduces the concentration in the lungs in normal mice. n-Pentanol, sec-butanol and tert-pentanol decreased tidal volume in normal mice, explained either by an activation of receptors in the upper airways or by a sensitization of the stretch receptors. Two types of pulmonary responses were seen in tracheal-cannulated mice, which could be explained by an effect on stretch receptors and another type of lung receptors.