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Archives of Toxicology

, Volume 78, Issue 12, pp 671–680 | Cite as

Ethylene glycol: an estimate of tolerable levels of exposure based on a review of animal and human data

  • Robert HessEmail author
  • Michael J. Bartels
  • Lynn H. Pottenger
Review Article

Abstract

Upon ingestion ethylene glycol (EG, monoethylene glycol) is rapidly absorbed from the gastrointestinal tract, and depending on the severity of exposure signs of toxicity may progress through three stages. Neurological effects characterize the first step consisting of central nervous depression (intoxication, lethargy, seizures, and coma). The second stage, usually 12–24 h after ingestion, is characterized by metabolic acidosis due to the accumulation of acidic metabolites of EG, primarily glycolic acid (GA), contributing to the ensuing osmolal and anion gaps. Stage 3, generally 24–72 h after ingestion, is determined mainly by oxalic acid excretion, nephropathy, and eventual renal failure. Because the toxicity of EG is mediated principally through its metabolites, adequate analytical methods are essential to provide the information necessary for diagnosis and therapeutic management. The severe metabolic acidosis and multiple organ failure caused by ingestion of high doses of EG is a medical emergency that usually requires immediate measures to support respiration, correct the electrolyte imbalance, and initiate hemodialysis. Since metabolic acidosis is not specific to EG, whenever EG intoxication is suspected, every effort should be made to determine EG as well as its major metabolite GA in plasma to confirm the diagnosis and to institute special treatment without delay. A number of specific and sensitive analytical methods (GC, GC-MS, or HPLC) are available for this purpose. Due to the rapid metabolism of EG, the plasma concentration of GA may be higher than that of EG already upon admission. As toxicity is largely a consequence of metabolism of EG to GA and oxalic acid, the simultaneous quantification of EG and GA is important. Formation of calcium oxalate monohydrate in the urine may be a useful indicator of developing oxalate nephrosis although urine crystals can result without renal injury. The pathways involved in the metabolism of EG are qualitatively similar in humans and laboratory animals, although quantitative differences have been reported. Comparison between species is difficult, however, because the information on humans is derived mainly from acute poisoning cases whereas the effects of repeated exposures have been investigated in animal experiments. Based on published data the minimum human lethal dose of EG has been estimated at approx. 100 ml for a 70-kg adult or 1.6 g/kg body weight (calculation of dose in ml/kg to mg/kg based in EG density=1.11 g/l). However, human data from case reports are generally insufficient for the determination of a clear dose-response relationship and quantification of threshold doses for systemic toxicity, in particular renal effects, is limited. As toxicity is largely a consequence of metabolism of EG to GA, it is important to note that no signs of renal injury have developed at initial plasma glycolate concentrations of up to 10.1 mM (76.7 mg/dl). Plasma EG levels of 3.2 mM (20 mg/dl) are considered the threshold of toxicity for systemic exposure, if therapeutic strategy is based on the EG concentration alone.

Keywords

Ethylene glycol Glycolic acid Analysis Toxicokinetics Nephrotoxicity 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Robert Hess
    • 1
    Email author
  • Michael J. Bartels
    • 2
  • Lynn H. Pottenger
    • 2
  1. 1.Institut für PathologieUniversity of BaselBaselSwitzerland
  2. 2.Toxicology & Environmental Research and ConsultingThe Dow Chemical CompanyMidlandUSA

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