Sensory irritation and pulmonary irritation of C3-C7 n-alkylamines: mechanisms of receptor activation.
Sensory irritation due to inhalation of a series of alkylamines was estimated from the decrease in respiratory rate in normal (non-cannulated) mice (American standard method E 981-84, 1984). The irritation effects rapidly reached stable levels. The concentration-response relationships followed Michaëlis-Menten equations. The maximum response decreased with increasing chain length. The concentrations depressing the respiratory rate by 50% (RD-50) were 184, 121, 97, 51, and 27 p.p.m. for n-propylamine, n-butylamine, n-pentylamine, n-hexylamine, and n-heptylamine, respectively. It is suggested that the receptor is activated partly by the amines and partly by hydroxide ions. The nose has a scrubbing effect, which partly protects the lungs against water soluble irritants. Pulmonary irritation was estimated from the decrease in respiratory rate in tracheally cannulated mice. The plateau-level of the response was reached slowly. The respective concentrations depressing the respiratory rate by 50% (tRD-50) were 416, 300, 128, 66, and 36 p.p.m. for the C3-C7 n-amines. It is suggested that the pulmonary receptor environment is lipophilic and the receptor, probably the J-receptor, is activated chemically by the amines. The sensory and pulmonary irritation data were used to estimate workplace exposure limits (TLV's) which protect against these effects.
Nielsen
G D
GD
Danish National Institute of Occupational Health, Hellerup.
Vinggaard
A M
AM
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007509:Irritants / Q000633:toxicity*; D008168:Lung / Q000187:drug effects*; D008297:Male; D008452:Maximum Allowable Concentration; D051379:Mice; D011984:Sensory Receptor Cells / Q000032:analysis / Q000187:drug effects*; D012995:Solubility; D013329:Structure-Activity Relationship
D000588:Amines; D007509:Irritants