PHARMACOKINETICS OF ETHYLENE-GLYCOL .2. TISSUE DISTRIBUTION, DOSE-DEPENDENT ELIMINATION, AND IDENTIFICATION OF URINARY METABOLITES FOLLOWING SINGLE INTRAVENOUS, PERORAL OR PERCUTANEOUS DOSES IN FEMALE SPRAGUE-DAWLEY RATS AND CD-1(R) MICE

1. [1,2]-C-14-Ethylene glycol (EG) was given to female CD (Sprague-Daw ley) rats and CD-1(R) mice in order to determine tissue distribution a nd metabolic fate after intravenous (iv), peroral (po), and percutaneo us (pc) doses. Rats were given doses of 10 or 1000 mg/kg by each route , and additional po doses of 400, 600 or 800 mg/kg. Mice were also giv en iv and po doses of 10 or 1000 mg/kg, and intermediate po doses of 1 00, 200 or 100 mg/kg. Mice were given pc doses of 100 or 1000 mg/kg, a nd both species were given a 50 % (w/w) aqueous pc dose to simulate an tifreeze exposure. 2. For both species, EG is very rapidly and almost completely adsorbed after po doses. Perorally administered EG doses pr oduced similar dose-dependent relationships described in prior studies for the disposition and excretion of iv doses. 3. The tissue distribu tion of EG following either iv or po routes was essentially the same, with similar percentages recovered for each dose by both routes and fo r either species. 4. Cutaneously-applied EG was slowly and rather poor ly adsorbed in both species, in comparison with po dose administration , and urinalysis after undiluted pc doses indicated that EG probably p enetrates rat shin in the parent form. There was an absence in both sp ecies of dose-dependent changes in disposition and elimination followi ng the pc application of EG. 5. C-14-labelled EG, glycolic acid and/or oxalic acid accounted for the majority of the detectable radioactivit y in the urine samples from all dose routes in the rat, while glycoald ehyde and glyoxylic acid were not detected in any of the urine fractio ns evaluated. Similar increases in glycolate production with increasin g dose were also observed in mouse urine samples from iv and po dosing . Also, glyoxylate and oxalate were absent from mouse urine. 6. Oxidat ive metabolic pathways appeared to be saturated at high po doses in bo th species, resulting in a shift from principally (CO2)-C-14 exhalatio n to urinary C-14 excretion, while the onset of capacity-limited metab olic changes appears to occur at lower doses for mice than for rats.