1. [1,2]-14C-Ethylene glycol (EG) was given to female CD (Sprague-Dawley) rats and CD-1 mice in order to determine tissue distribution and metabolic fate after intravenous (iv), peroral (po), and percutaneous (pc) doses. Rats were given doses of 10 or 1000 mg/kg by each route, and additional pc doses of 400, 600 or 800 mg/kg. Mice were also given iv and po doses of 10 or 1000 mg/kg, and intermediate po doses of 100, 200 or 400 mg/kg. Mice were given po doses of 100 or 1000 mg/kg, and both species were given a 50% (w/w) aqueous po dose to simulate antifreeze exposure. 2. For both species, EG is very rapidly and almost completely adsorbed after po doses. Perorally administered EG doses produced similar dose-dependent relationships described in prior studies for the disposition and excretion of iv doses. 3. The tissue distribution of EG following either iv or po routes was essentially the same, with similar percentages recovered for each dose by both routes and for either species. 4. Cutaneously-applied EG was slowly and rather poorly adsorbed in both species, in comparison with po-dose administration, and urinalysis after undiluted po doses indicated that EG probably penetrates rat skin in the parent form. There was an absence in both species of dose-dependent changes in disposition and elimination following the pc application of EG. 5. 14C-labelled EG, glycolic acid and/or oxalic acid accounted for the majority of the detectable radioactivity in the urine samples from all dose routes in the rat, while glycoaldehyde and glyoxylic acid were not detected in any of the urine fractions evaluated. Similar increases in glycolate production with increasing dose were also observed in mouse urine samples from iv and po dosing. Also, glyoxylate and oxalate were absent from mouse urine. 6. Oxidative metabolic pathways appeared to be saturated at high po doses in both species, resulting in a shift from principally 14CO2 exhalation to urinary 14C excretion, while the onset of capacity-limited metabolic changes appears to occur at lower doses for mice than for rats. 7. In summary, rats and mice displayed several similarities in the manner in which low doses of EG by several routes are distributed, metabolized, and excreted, but the onset of capacity-limited changes in metabolism occurs at lower doses for mice than for rats. Such differences in the disposition of EG may provide important interpretive information to help explain differences observed in developmental toxicity and nephrotoxic responses between these two rodent species.

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Acrylic acid (AA) is used in large amounts to produce acrylic esters and polymers. Here we report on the disposition and metabolism of [1-14C]AA in male C3H mice and Fischer 344 (F344) rats after oral (40 and 150) mg/kg) or cutaneous (10 and 40 mg/kg) administration. Although these and other strains of rodents have been used frequently in toxicity studies of AA, results of pharmacokinetic studies are available for only the Sprague-Dawley rat. In the current study, C3H mice rapidly absorbed and metabolized orally administered AA, with about 80% of the dose exhaled as 14CO2 within 24 h. Excretion in urine and feces accounted for approximately 3% and 1% of the dose, respectively. Elimination of 14C from plasma, liver, and kidney was rapid but was slower from fat. The disposition of orally administered AA in F344 rats was similar to the results obtained from mice. After cutaneous administration to C3H mice, about 12% of the dose was absorbed, while the remainder apparently evaporated. Approximately 80% of the absorbed fraction of the dose was metabolized to 14CO2 within 24 h. Excretion in urine and feces each accounted for less than 0.5% of the dose. Elimination of radioactivity from plasma, liver, and kidney was rapid; however, levels in fat were higher at 72 h than at 1 or 8 h. After cutaneous administration to F344 rats, 19-26% of the dose was absorbed, and the rest apparently evaporated. Disposition of the absorbed fraction of the dose was similar to results found in mice. Results from an in vitro experiment with rat skin showed that at least 60% of the applied dose evaporated and about 25% was absorbed, confirming the in vivo results. High-performance liquid chromatography (HPLC) analysis of rat urine and rat and mouse tissues indicated that absorbed AA was rapidly metabolized by the beta-oxidation pathway of propionate catabolism. In summary, rapid detoxification of systemically absorbed AA, as observed here in C3H mice and F344 rats, can explain findings that AA causes minimal systemic toxicity despite its causing irritation at portal-of-entry tissues.

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