Leaching of Zinc Compound from Rubber Stoppers into the Contents of Automatic Atropine Injectors

摘要

Atropine sulfate has been used over a number of years for treating nerve agent intoxication. An automatic injector was developed to permit a rapid and convenient means for the self-administration of the antidote. A metal cartridge in the automatic injector contained 0.7 mL of a formulation consisting of atropine, glycerin, phenol, and citrate buffer. This report describes how a material within the cartridge of an automatic injector contaminated its contents. On prolonged storage, a formulation that contained atropine produced lethality in mice. The toxic material originated from zinc compounds that were present in the rubber stopper and plunger of the container and that subsequently leached into the formulation. The contents of cartridges that contained > or - 0.75 mg/mL of solubilized zinc were lethal to at least 20% of the mice tested; those that contained 0.42 mg/mL showed no lethality. The problem resulted from the physicochemical properties of the rubber, not the concentration of zinc used in the vulcanization process.