Bioavailability and pharmacokinetics of microencapsulated 1,3-dichloropropene in rats.
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 coadministered microencapsulated 1,3-D and neat 13C-1,3-D (25 mg/kg each) via gavage. Blood concentrations of total or cis- and trans-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-1,3-D and 13C-1,3-D and greater amounts of cis- than trans-1,3-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-1,3-D than cis-13C-1,3-D blood levels and AUCs were also consistently noted while the reverse was true for urinary excretion of cis-13C-1,3-DMA and cis-1,3-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.
Stott
W T
WT
Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674, USA.
Gilbert
J R
JR
McGuirk
R J
RJ
Brzak
K A
KA
Alexander
L M
LM
Dryzga
M D
MD
Mendrala
A L
AL
Bartels
M J
MJ
D000498:Allyl Compounds / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000498:Allyl Compounds; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; C023891:1,3-dichloro-1-propene