Comparative distribution, excretion and metabolism of di-(2-ethylhexyl) phthalate in rats, dogs and miniature pigs.

Abstract Di-(2-ethylhexyl phthalate (DEHP) was administered in the diet to male Sprague-Dawley rats, beagle dogs and miniature swine of the Hormel strain in doses of 50 mg/kg/day for 21–28 days before administration of a single dose of [ 14 C]DEHP at 50 mg/kg. The animals were then killed at various times, and tissues, organs, urine and faeces were analysed for distribution of radioactivity. Approximately 84% of the [ 14 C]DEHP radioactivity was excreted in the urine and faeces of rats during the first 24 hr; in dogs and pigs, excretion during this time was 67 and 37%, respectively. Elimination of 14 C was rapid in rats, slightly prolonged in dogs and least rapid in pigs; excretion in all three species was virtually complete in 4 days. Faecal excretion (75%) predominated in dogs, and urinary excretion (79%) predominated in pigs. Thin-layer chromatography showed the presence of at least four radioactive substances in rat urine, three in dog urine and five in pig urine. No more than a trace of unmetabolized DEHP was found in the urine of rats, dogs or pigs. In all three species, bile contained some metabolites that differed from those in urine, although some metabolites appeared to be common to both. Bile from rats and dogs contained a substance that, when hydrolysed under slightly acidic conditions, yielded a substance that migrated like mono-(2-ethylhexyl) phthalate in the chromatographic system used.