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HO—CH2—CH2—O—CH2—CH2—OH

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HISTORY AND EPIDEMIOLOGY

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Diethylene glycol (DEG) is a solvent with physical and chemical properties similar to propylene glycol used throughout the chemical industry. Pharmaceutical-grade propylene glycol is a safe and commonly used solvent for water-insoluble pharmaceuticals (Chap. 55). However, unlike propylene glycol, DEG is a potent nephrotoxic and neurotoxic chemical. Substitution of DEG for propylene glycol and other diluents such as glycerin in oral pharmaceutical elixirs has repeatedly caused epidemics of mass poisoning (Chap. 2). This substitution has occurred early in the pharmaceutical manufacturing process due to the intentional mislabeling of DEG as a replacement for the intended pharmaceutical-grade glycerin,42 for financial gain49 and other reasons, without regard to safety.15 As medication-associated DEG mass poisonings have recurred, numerous quality assurance and control guidelines have been developed to identify DEG-contaminated materials.Failure to adhere to these guidelines throughout the pharmaceutical manufacturing and distribution process contributes to this public health ­problem.49 In DEG poisoning, patients develop acute kidney injury (AKI) that can rapidly progress to renal failure and death. Those patients who do not die quickly after exposure, but who develop AKI, often become ­dialysis dependent and may go on to develop neurological signs and symptoms. These patients may deteriorate further after onset of neurotoxic signs and symptoms and subsequently die.

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The metabolism of DEG and the pathophysiology of DEG-associated disease are incompletely understood and most of what is known comes from animal studies. Indeed, very little data are available in humans. Previously, DEG was thought to be metabolized to two ethylene glycol molecules which, when metabolized to glycolic acid and oxalic acid, caused AKI; this theory has been disproven.57 Current evidence supports that the terminal DEG metabolite diglycolic acid (DGA) is nephrotoxic. Diglycolic acid appears to be neurotoxic as well based on a single, published case report of poisoning.44 This chapter will provide a brief history and epidemiology of DEG poisoning, describe existing pharmacokinetic and toxicokinetic data collected primarily from animal studies, and then discuss available information on the toxic dose, pathophysiology, clinical manifestations, testing and treatment for DEG poisoning. When specific doses of DEG in the literature were reported in mL/kg, they were converted to g/kg by taking into account the density of DEG (1.118 g/mL) and the concentration. If information on concentration was not provided, then a 100% concentration was assumed. For the reader’s convenience, the original dose (if it was in mL/kg) and commensurate DEG concentration are provided following the converted dose in g/kg or mg/kg.

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DEG is produced by the condensation of two ethylene glycol molecules forming an ether bond,1 which yields a compound with a molecular weight of 106 g/mol.1,46 It was first identified in 1869 and has been used in industry and manufacturing since 1928.1 It has found use as an antifreeze, as a finishing agent ...

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