Bioavailability and Pharmacokinetics of Microencapsulated 1,3-Dichloropropene in Rats

The potential oral toxicity of 1,3-dichloropropene (1,3-D) hasbeen evaluated in a number of dietary toxicity studies. Therelatively high vapor pressure of 1,3-D, its short half-lifein drinking water, and its reactivity with constituents of feednecessitated the use of a microencapsulated formulation (starch-sucroseshell) of 1,3-D in these studies. The bioavailability of ingestedmicroencapsulated 1,3-D was determined by characterizing andcomparing the kinetics of 1,3-D in the blood of female F344rats coadminis-tered microencapsulated 1,3-D and neat ¹³C-1,3-D(25 mg/kg each) via gavage. Blood concentrations of total orcis- and trans-is-isomers of 1,3-D in treated rats were determinedusing gas chromatography-mass spectroscopy (GC-MS) or in situmembrane extraction MS. Urine was also collected and analyzedby GC-MS for the presence of the mercapturate excretion productof 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 biphasicelimination. Higher peak blood levels and greater blood curveareas (AUC) were attained for trans- than cis-l,3-D and ¹³C-1,3-Dand greater amounts of cis- than trans-l,3-DMA and ¹³C-1,3-DMAwere excreted in the urine consistent with the known rapid anddisproportionate glutathione conjugation of the cis-isomer inthe gastric mucosa. Slightly higher ^cis-l,3-D than cis-¹³C-l,3-Dblood levels and AUCs were also consistently noted while thereverse was true for urinary excretion of cis-¹³C-13-DMA andcis-l,3-DMA suggesting that 1,3-D derived from microencapsulatedtest material may be absorbed and/or metabolized in the stomachmucosa at a slightly slower rate than that from neat material.The latter, however, would be of no consequence during the administrationof 1,3-D to animals via their diets as competing test materialswould not be present and 1,3-D blood kinetics were unaffected.Overall, the results of this study demonstrate the ready bioavailabilityof microencapsulated 1,3-D and rapid elimination of 1,3-D fromthe blood of rats.