PT - JOURNAL ARTICLE AU - Lorrene A. Buckley AU - Donna P. Coleman AU - Jason P. Burgess AU - Brian F. Thomas AU - Leo T. Burka AU - A. Robert Jeffcoat TI - Identification of Urinary Metabolites of Isoprene in Rats and Comparison with Mouse Urinary Metabolites DP - 1999 Jul 01 TA - Drug Metabolism and Disposition PG - 848--854 VI - 27 IP - 7 4099 - http://dmd.aspetjournals.org/content/27/7/848.short 4100 - http://dmd.aspetjournals.org/content/27/7/848.full SO - Drug Metab Dispos1999 Jul 01; 27 AB - Isoprene, a major commodity chemical used in production of polyisoprene elastomers, has been shown to be carcinogenic in rodents. Similar to findings for the structurally related compound butadiene, mice are more susceptible than rats to isoprene-induced toxicity and carcinogenicity. Although differences in uptake, and disposition of isoprene in rats and mice have been described, its in vivo biotransformation products have not been characterized in either species. The purpose of these studies was to identify the urinary metabolites of isoprene in Fischer 344 rats and compare these metabolites with those formed in male B6C3F1mice. After i.p. administration of 64 mg [14C]isoprene/kg to rats and mice, isoprene was excreted unchanged in breath (∼50%) or as urinary metabolites (∼32%). In rats isoprene was primarily excreted in urine as 2-hydroxy-2-methyl-3-butenoic acid (53%), 2-methyl-3-buten-1,2-diol (23%), and the C-1 glucuronide conjugate of 2-methyl-3-buten-1,2-diol (13%). These metabolites are consistent with preferential oxidation of isoprene’s methyl-substituted vinyl group. No oxidation of the unsubstituted vinyl group was observed. In addition to the isoprene metabolites found in rat urine, mouse urine contained numerous other isoprene metabolites with a larger percentage (25%) of total urinary radioactivity associated with an unidentified, polar fraction than in the rat (7%). Unlike butadiene, there was no evidence that glutathione conjugation played a significant role in the metabolism of isoprene in rats. Because of the unidentified metabolites in mouse urine, involvement of glutathione in the metabolism of isoprene in mice cannot be delineated. The American Society for Pharmacology and Experimental Therapeutics