Sensory irritation and pulmonary irritation of n-methyl ketones : receptor activation mechanisms and relationships with threshold limit values

• Published in: Archives of toxicology Vol. 68; no. 3; pp. 193 - 202
• Main Authors: HANSEN, L. F, NIELSEN, G. D
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-03-1994
• Subjects: Administration, Inhalation; Anesthesia; Animals; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Chemical Phenomena; Chemistry, Physical; Eye Diseases - chemically induced; Irritants - administration & dosage; Irritants - toxicity; Ketones - administration & dosage; Ketones - chemistry; Ketones - toxicity; Lung Diseases - chemically induced; Male; Medical sciences; Mice; Nasal Mucosa - drug effects; Nerve Endings - drug effects; Plethysmography, Whole Body; Receptors, Drug - drug effects; Sensory Thresholds - drug effects; Solvents; Toxicology; Lung disease; Toxicity; Rodentia; Cardiovascular disease; Ketone; Respiratory tract; Organic solvent; Vertebrata; Mammalia; Mouse; Animal; Maximum permissible concentration; Nose; Irritation
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s002040050054

Activation of the trigeminal nerve endings in eyes and nose, termed sensory irritation, was determined from the reflexively induced decrease in respiratory rate in mice for methyl propyl ketone, methyl butyl ketone, methyl amyl ketone and methyl hexyl ketone. The relationship between exposure concentration and the decrease in respiratory rate followed Michaelis-Menten equations. Two estimates of each agonist-receptor dissociation constant were obtained, one from the Michaelis-Menten equation and one from the threshold (RD-0) of the log concentration-effect curve. The values were equal and thus one receptor type could account for the activation process. The hydrophobic properties of the receptor biophase were found to approach that of the internal part of the bilayer membrane. It therefore follows that the receptor-air partition coefficients increase with the size of the ketones, thus accounting for the observed increase in potency. Estimates of Threshold Limit Values (TLV) were obtained and compared with established values. Close agreements were found for methyl propyl ketone and methyl amyl ketone, but not for methyl butyl ketone, where the neurotoxic effect constituted a more sensitive endpoint than sensory irritation.