TETRAETHYLAMMONIUM CHLORIDE [(C₂H₅)₄NCl]. ACUTE AND CHRONIC TOXICITY IN EXPERIMENTAL ANIMALS

¹ Research Laboratories, Parke, Davis and Company, Detroit, Michigan

Tetraethylammonium chloride [(C₂H₅)₄NCl], an autonomic ganglionic blocking agent, was non-toxic perorally (LD₅₀ = 900 to 2636 mg./kg.) and relatively toxic parenterally (36.4 to 110 mg./kg.) in animals.

It was well tolerated by intramuscular or subcutaneous administration of 15 to 25 mg./kg. twice daily in rats and dogs. Intravenously, dogs were free of reactions on 2.5 to 5.0 mg./kg. twice daily, while a dosage of 7.5 to 10.0 mg./kg. caused mild ocular symptoms of mydriasis, ptosis of eyelids and hyperemia of ocular, nasal and buccal membranes. Administration of progressively greater amounts resulted in incoordination, hyperpyrexia (intravenously), spasticity, respiratory and circulatory depression. Death occurred from respiratory failure and circulatory collapse.

The underlying histopathologic changes were those of severe congestion, stasis and anoxia. Lethal and sublethal single or multiple doses caused edema and degenerative changes in the liver and to a lesser degree in the kidneys. In tolerated doses the tissues were free of degenerative changes.

A 10 per cent aqueous solution of (C₂H₅)₄NCl parenterally produced little or no local tissue injury. A 20 per cent concentration had a tendency to cause tissue necrosis.

No manifest changes occurred in hematology, total blood non-protein nitrogen, bromsulphalein liver function test, total plasma protein, albumen and globulin ratios, and urinalysis of dogs on daily or twice daily administration of tolerated doses.