Pharmacokinetics and metabolism of super(14)C-1,3-dichloropropene in the Fischer 344 rat and the B sub(6)C sub(3)F sub(1) mouse

• Published in: Xenobiotica 2004-02, Vol.34 (2), p.193-213
• Main Authors: Bartels, MJ, Hansen, S C, Thornton, C M, Brzak, KA, Mendrala, AL, Dietz, F K, Kastl, P J
• Format: Article
• Language: English
• ISSN: 0049-8254

super(14)C-1,3-dichloropropene ( super(14)C-DCP) is rapidly absorbed and eliminated in both the male F344 rat and B sub(6)C sub(3)F sub(1) mouse following oral administration of 1 or 50 mg kg super(m1) (rat) or 1 or 100 mg kg super(m1) (mouse). It is extensively metabolized in both species. Urinary excretion was the major route of elimination, accounting for 50.9-61.3 and 62.5-78.6% of the administered dose in rat and mouse, respectively. Urinary elimination half-lives ranged from 5 to 6 h (rat) and from 7 to 10 h (mouse). Elimination via faeces or as super(14)CO sub(2) accounted for 14.5-20.5 and 13.7-17.6% of the administered dose, respectively. Metabolites arising from glutathione conjugation account for 36-55 and 48-50% of the administered dose in excreted from rats and mice, respectively. Hydrolysis of the 3-chloro moiety of DCP accounted for 24-37 and 29% of the dose administered to rats and mice, respectively. Two novel dimercapturic acid conjugates were also identified at low levels that might arise via initial hydrolysis of DCP or of epoxidation of DCP-glutathione conjugate or of DCP itself. Structural confirmation of these dimercapturates was obtained via analysis of deuterium retention from D sub(4)-DCP in the male F344 rat. Only quantitative differences are seen between the overall metabolic profile of DCP in these two species.