Toxicokinetics of diethylene glycol (DEG) in the rat

Abstract

Oral doses of 1 and 5 ml/kg 14C-diethylene glycol (DEG) given to rats were rapidly and almost completely absorbed, the invasion constants being 2.95 h-1 and 4.24 h-1. The kinetics of invasion were determined with the method of residuals (Rowland and Tozer 1989) and by reconstruction of the invasion curves according to Kübler (1970). 14C-DEG was rapidly distributed from the blood into the organs and tissues in the order kidneys > brain > spleen > liver > muscle > fat, i.e. the same order as the blood flow. The relative volume of distribution, app. VD, was determined at 298 ml, indicating distribution over the whole body. After oral doses of 1, 5, and 10 ml 14C-DEG/kg 64, 87, and 91% of 14C activity in rat blood disappeared in 12-16 h with a half-life of 3.4 h and the remaining 9, 5, and 4% with half-lives of 39 h, 45 h, and 49 h. A total of 73-96% of 14C activity in blood was excreted with the urine and 0.7-2.2% with the faeces. From the cumulative urinary excretion kinetics half-lives of 6 h were determined for doses of 1 and 5 ml/kg and 10 h for the dose of 10 ml/kg. After doses of 5 ml/kg and 10 ml/kg 14C-DEG semi-logarithmic plots of elimination rate versus time were constant for 5 and 9 h, respectively, indicating that DEG accelerated its renal elimination by inducing osmotic diuresis. Thereafter urinary excretion followed first order kinetics with elimination half-lives of 3.6 h. After oral doses of 5 ml/kg 14C-DEG given to rats of 336 g body weight with an app. VD of 297 ml, the total clearance of 14C activity was determined at 63 ml/h, and the renal clearance of unmetabolized DEG was 66 ml/h. The ratio of ClDEG to Cl(inulin) = 0.64 indicated that DEG and its metabolite 2-hydroxyethoxyacetate (2-HEAA) were reabsorbed from the tubuli into the blood capillaries. DEG produced metabolic acidosis, which was completely balanced after doses of 1 and 5 ml/kg, but doses greater than 10 ml/kg produced non-compensated metabolic acidosis, hydropic degeneration of the tubuli, oliguria, anuria, accumulation of urea-N, and death in uraemic coma.

Diethylene Glycol

“…8,16 Animals have signs of CNS depression soon after exposure. 15,27 Dogs sometimes vomit. 16 Initial clinical effects are usually minor unless a large amount has been ingested.…”

“…It has occasionally been used as a less expensive substitute for propylene glycol or glycerin in pharmaceutical preparations, resulting in hundreds of human deaths. 1,6,[7][8][9][10][11][12][13][14][15][16][17] …”

Medical toxicology and public health—Update on research and activities at the centers for disease control and prevention and the agency for toxic substances and disease registry

“…Since then it has been used as an antifreeze solution; as a finishing agent for wool, cotton, silk, and other fabrics; and in dye manufacturing. DEG is chemically inert, does not ignite at normal temperatures, and has a higher boiling point than EG [6,7]. However, it has physical properties that are generally quite similar to EG, including a sweet taste [6,7].…”

“…DEG is chemically inert, does not ignite at normal temperatures, and has a higher boiling point than EG [6,7]. However, it has physical properties that are generally quite similar to EG, including a sweet taste [6,7]. DEG has been used as a hygroscopic agent for paper, glue, tobacco, gelatin, cheese, and gum drops; it has even been used as a solvent for food flavoring in products such as ice cream [7].…”

“…However, it has physical properties that are generally quite similar to EG, including a sweet taste [6,7]. DEG has been used as a hygroscopic agent for paper, glue, tobacco, gelatin, cheese, and gum drops; it has even been used as a solvent for food flavoring in products such as ice cream [7]. It is used as an intermediate in the production of polymers, higher glycols, morpholine, and dioxane [8].…”