© 1998 Oxford University Press
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Bioavailability and Pharmacokinetics of Microencapsulated 1,3-Dichloropropene in Rats
The Toxicology Research Laboratory Building 1803, The Dow Chemical Company, Midland, Michigan 48674 *Environmental Chemistry Laboratories Building 306, DowElanco, 9330 Zionsville Road, Indianapolis, Indiana 46268
Received November 27, 1996; accepted June 17, 1997
The potential oral toxicity of 1,3-dichloropropene (1,3-D) has been evaluated in a number of dietary toxicity studies. The relatively high vapor pressure of 1,3-D, its short half-life in drinking water, and its reactivity with constituents of feed necessitated the use of a microencapsulated formulation (starch-sucrose shell) of 1,3-D in these studies. The bioavailability of ingested microencapsulated 1,3-D was determined by characterizing and comparing the kinetics of 1,3-D in the blood of female F344 rats coadminis-tered microencapsulated 1,3-D and neat 13C-1,3-D (25 mg/kg each) via gavage. Blood concentrations of total or cis- and trans-is-isomers of 1,3-D in treated rats were determined using gas chromatography-mass spectroscopy (GC-MS) or in situ membrane extraction MS. Urine was also collected and analyzed by GC-MS for the presence of the mercapturate excretion product of 1,3-D [N-acetyl-S-(3-chloropropenyl-2)L-cysteine; 1,3-DMA]. Blood levels of 1,3-D and 13C-1,3-D displayed similar kinetics, peaking within 10 min of dosing followed by a rapid biphasic elimination. Higher peak blood levels and greater blood curve areas (AUC) were attained for trans- than cis-l,3-D and 13C-1,3-D and greater amounts of cis- than trans-l,3-DMA and 13C-1,3-DMA were excreted in the urine consistent with the known rapid and disproportionate glutathione conjugation of the cis-isomer in the gastric mucosa. Slightly higher cis-l,3-D than cis-13C-l,3-D blood levels and AUCs were also consistently noted while the reverse was true for urinary excretion of cis-13C-13-DMA and cis-l,3-DMA suggesting that 1,3-D derived from microencapsulated test material may be absorbed and/or metabolized in the stomach mucosa at a slightly slower rate than that from neat material. The latter, however, would be of no consequence during the administration of 1,3-D to animals via their diets as competing test materials would not be present and 1,3-D blood kinetics were unaffected. Overall, the results of this study demonstrate the ready bioavailability of microencapsulated 1,3-D and rapid elimination of 1,3-D from the blood of rats.