Structure-activity relationships of airway irritating aliphatic amines. Receptor activation mechanisms and predicted industrial exposure limits.

Sensory irritation due to inhalation of diethyl-, triethyl-, dibutyl-, tributyl- and cyclohexylamine was estimated from the decrease in respiratory rate in normal mice (American Standard Method E981-84). The concentration-effect relations followed Michaelis-Menten equations, except for diethylamine, for which a threshold was found. The concentrations depressing the respiratory rate by 50% (RD50) for diethyl-, triethyl-, dibutyl- and cyclohexylamine were 184, 186, 81 and 27 ppm, respectively. For tributylamine the maximum response was too low to achieve a RD50 value. Pulmonary irritation was estimated from the decrease in respiratory rate in tracheal-cannulated mice. The respective concentrations depressing the respiratory rate by 50% (tRD50) were 549, 691, 101, 96 and 78 ppm for diethyl-, triethyl-, dibutyl-, tributyl- and cyclohexylamine. Only minor or no effects on the tidal volumes were found at the lower exposure concentrations. The trigeminal and pulmonary receptors are believed to be activated directly by the amines, and the receptor environments are believed to be lipophilic. Structure-activity analysis was made by comparing the effects of the amines with the effects of previously investigated primary n-alkylamines. Occupational exposure limits (TLV) were estimated for both effects. Finally, the sensory irritation effect was found to be an important part of the odour sensation, also below the TLVs.