The metabolic pathway for ethylene glycol is shown in Figure 3-3. Asterisks indicate rate-limiting steps
in the pathway. The metabolism of ethylene glycol was reviewed by NTP-CERHR (2004) and Slikker et
al. (2004). Ethylene glycol is converted to glycolaldehyde by nicotinamide adenine dinucleotide (NAD)
dependent alcohol dehydrogenase. Subsequent reduction of NAD results in the formation of lactic acid
from pyruvate. Glycolaldehyde has a brief half-life and is rapidly converted to glycolic acid (and to a
lesser extent glyoxal) by aldehyde dehydrogenase and aldehyde oxidase, respectively. Glycolic acid is
oxidized to glyoxylic acid by glycolic acid oxidase or lactic dehydrogenase. Glyoxylic acid can be
metabolized to formate, glycine, or malate, all of which may be further broken down to generate
respiratory CO2, or to oxalic acid, which is excreted in the urine. In excess, oxalic acid can form calcium
oxalate crystals. Rate-limiting steps in the metabolism of ethylene glycol include the initial formation of
glycolaldehyde and the conversion of glycolic acid to glyoxylic acid, both of which are saturable
processes. The conversion of glycolic acid to glyoxylic acid is the most rate-limiting step in ethylene
glycol metabolism (Slikker et al. 2004).
Both glycolic acid and oxalic acid are found in the blood and urine of unexposed individuals as a result of
normal metabolism of proteins and carbohydrates (NTP-CERHR 2004). The ranges of background levels
of glycolic acid are 0.0044–0.0329 mM (plasma) and 0.075–0.790 mM (urine) (NTP-CERHR 2004). For
oxalic acid, the background ranges are 0.002–0.0233 mM (plasma) and 0.086–0.444 mM (urine) (NTPCERHR
2004).
In volunteers who inhaled 13C-ethylene glycol for 4 hours, glycolic acid concentrations in the plasma
peaked at about 4–5 hours after the commencement of exposure (Carstens et al. 2003). About 1% of the
estimated dose of 0.96–1.51 mg/kg was excreted in the urine as glycolic acid, and 0.08–0.28% was
excreted as oxalic acid over 30 hours. Expired CO2 was not measured in this study. Similar results were
obtained for two other similarly exposed volunteers (Upadhyay et al. 2008).
Plasma glycolate levels of 12.2 and 15.4 mmol/L were reported upon hospital admission of an infant
female and an adult male, respectively, with ethylene glycol intoxication after oral exposure (Hewlett et
al. 1986). The infant survived, while the adult male died, probably due to delayed treatment. In a case