Studies in detoxication. 86. The metabolism of 14C-labelled ethylene glycol

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Abstract
[C142]Ethane-1,2-diol has been prepared from [C142]ethylene and its fate in the animal body investigated. In the rabbit, at dose levels of 0.1-2.0 g/kg about 20% of the dose of radio-activity is excreted in the urine in 2 days, mainly as unchanged ethanediol, with smaller amounts as urea and oxalic acid; at higher doses (2.5 and 5.0 gAg), the radioactivity in the urine increases to about 50%. At a dose level of 0.1 g/kg about 40% of the glycol is eliminated as C14O2 in the expired air in 1 day, and 60% in 3 days. The remainder of the activity is mostly located in the tissues. In the rat, the radioactivity excreted in the urine in 24 hr. increases from 21% at a dose level of 0.1 gAg to 58% at 1.0 gAg and the C14O2 in the expired air decreases from 23% in 24 hr. at 0.1 g/kg to 2.4% in 12 hr. at 10 g/kg. Rabbit and guinea pig excrete only traces (about 0.05% of dose) of oxalate in the urine at dose levels of ethanediol of less than 1 gAg, which increases (about 0.5% of dose) at doses of 1-5 g/kg. Larger amounts of oxalate are excreted by rats (0.5-1.1% of dose) and by cats (0.7-3.7% of dose). At dose levels of 0.1-1 g of [C142]ethanediol/kg, the total radioactivity excreted in the urine by cats (43-78%) is greater than that excreted by rats (21-49%), rabbits (21-26%) or guinea pigs (26-37%), but both rats and rabbits show considerable increases at higher doses. The concentration of radioactivity in the tissue of rats was greatest in liver, kidney and bone. It has been shown in rat-liver slices that glycolaldehyde and glyoxylic acid are intermediates in the oxidation of [C142]ethanediol to C14O2. Further evidence that glyoxylic acid is a metabolite of ethanediol is shown by the excretion of [Cl4]hippuric acid by rats injected with [C142]-ethanediol and benzoic acid simultaneously. The relative toxicity of ethanediol in different species, probable metabolic pathways and the toxicities of the metabolic intermediates are discussed.