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

• Published in: Toxicological sciences 1998-01, Vol.41 (1), p.21-28
• Main Authors: Stott, W. T., Gilbert, J. R., McGuirk, R. J., Brzak, K. A., Alexander, L. M., Dryzga, M. D., Mendrala, A. L., Bartles, M. J.
• Format: Article
• Language: English
• Subjects: Allyl Compounds - pharmacokinetics; Animals; Area Under Curve; Biological Availability; Drug Compounding; Drug Stability; Female; Hydrocarbons, Chlorinated; Insecticides - pharmacokinetics; Rats; Rats, Inbred F344; Tissue Distribution
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/41.1.21

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.