Archives of Toxicology

, Volume 67, Issue 10, pp 655–666

Toxicokinetics of diethylene glycol (DEG) in the rat

  • R. Heilmair
  • W. Lenk
  • D. Löhr
Original Investigations

DOI: 10.1007/BF01973688

Cite this article as:
Heilmair, R., Lenk, W. & Löhr, D. Arch Toxicol (1993) 67: 655. doi:10.1007/BF01973688

Abstract

Oral doses of 1 and 5 ml/kg14C-diethylene glycol (DEG) given to rats were rapidly and almost completely absorbed, the invasion constants being 2.95 h 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 Kübier (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 ml14C-DEG/kg 64, 87, and 91% of14C 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% of14C 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/kg14C-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/kg14C-DEG given to rats of 336 g body weight with an app. VD of 297 ml, the total clearance of14C activity was determined at 63 ml/h, and the renal clearance of unmetabolized DEG was 66 ml/h. The ratio of ClDEG to Clinulin = 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.

Key words

Toxicokinetics Dose-dependent toxicity Diethylene glycol 

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • R. Heilmair
    • 1
  • W. Lenk
    • 1
  • D. Löhr
    • 1
  1. 1.Walther Straub-Institut für Pharmakologie und Toxikologie der LM-Universität MünchenMunichGermany

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