Sensory and pulmonary irritation of aliphatic amines in mice: A structure–activity relationship study

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Abstract
The expiratory bradypnea indicative of upper airway irritation in mice was evaluated during a 15‐min oronasal exposure to increasing concentrations of sixteen aliphatic amines. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each test compound. Moreover, the sixteen amines were tested for pulmonary irritation by measuring the decrease in respiratory rate of (non‐anaesthetized) tracheally cannulated mice (RD50 TC). The RD50 and RD50 TC values and their ratios were related to n‐octanol/water partition coefficients (log P). The RD50 values associated with exposure to saturated amines ranged from 17 to 300 ppm. The RD50TC values for these saturated amines ranged from 35 to 489 ppm. The RD50 and RD50TC values of saturated amines were closely related to the n‐octanol/water partition coefficient, indicating that the more lipophilic amines are more irritant for the upper and lower respiratory tracts. The RD50TC/RD50 values were much less closely related to the n‐octanol/water partition coefficient. Based on the results, tentative standards are suggested for the studied amines.