A medicinal diluent prompted the passage of the Food, Drug, and Cosmetic Act of 1938 after it resulted in an outbreak of mass nephrotoxicity and deaths. What is the toxic metabolite of this diluent that is believed to be responsible for nephrotoxicity?
Diglycolic acid (DGA) is believed to be the nephrotoxic metabolite of diethylene glycol.
Diethylene glycol has been used as a medicinal diluent in substitution for propylene glycol and glycerin. It has resulted in multiple mass poisonings and fatalities. Animal testing was mandated by the Food, Drug, and Cosmetic Act of 1938 after an elixir of sulfanilamide (containing 72% diethylene glycol) resulted in 105 deaths in the United States.
1.) Robinson CN, Latimer B, Abreo F, Broussard K, McMartin KE. In-vivo evidence of nephrotoxicity and altered hepatic function in rats following administration of diglycolic acid, a metabolite of diethylene glycol. Clin Toxicol (Phila). 2017 Mar;55(3):196-205. doi: 10.1080/15563650.2016.1271128. Epub 2017 Jan 11. PMID: 28074668.
2.)Geiling EMK, Cannon PR. Pathologic effects of elixir of sulfanilamide (diethylene glycol) poisoning: a clinical and experimental correlation: final report. Journal of the American Medical Association. 1938;111(10):919-926. doi:10.1001/jama.1938.72790360005007
Contributed by: Emily Kershner, DO of The Medical Toxicology Fellowship Virginia Commonwealth University