Abstract

The toxicity and metabolism of methyl salicylate were investigated in the belief that it functions primarily as its hydrolytic product, free salicylate. Methyl salicylate possesses essentially the same LD5O in mice as sodium salicylate. Plasma analyses for methyl salicylate and free salicylate after oral administration of the ester to rats and dogs demonstrate complete hydrolysis shortly after administration, while somewhat less is hydrolyzed in human subjects. No elevation of salicylate brain concentrations is detected after the administration of the ester to rats as compared to acetylsalicylic acid and sodium salicylate. The major site of hydrolysis of methyl salicylate in the rat, rabbit, dog and monkey is the liver, although intestine, kidney, pancreas, and spleen may play a minor role in such breakdown. It appears that in lower animals the toxicity of methyl salicylate is essentially identical with that of salicylic acid, although it is conceivable that in man the small proportion of unhydrolyzed ester might have a more toxic action.