Toxicokinetics of 1,2-dibromo-3-chloropropane (DBCP) in the rat.
The objective of this study was to determine the kinetics of absorption, distribution, and elimination of DBCP after intravenous (iv) administration in plasma, and after oral administration in water or corn oil, to conscious, fed, male Fischer 344 rats. Rats were prepared with an external jugular vein cannula and were dosed with 0.1, 1, or 10 mg/kg DBCP into the penile sinus or orally as a solution in water or in corn oil (1 mg/kg only). Blood was sampled at various times up to 12 hr, concentrations of DBCP were determined by gas chromatography, and data were evaluated by classical pharmacokinetic techniques. After oral administration in water, absorption of DBCP was rapid, and the distribution and elimination phase was biexponential. There did not appear to be any saturation of DBCP absorption, distribution, or elimination at the high oral or iv dose. After oral administration of DBCP in a corn oil vehicle, absorption was prolonged, suggesting retention of DBCP in the stomach; this could contribute to the toxic effects of DBCP on the forestomach when chronically administered in corn oil. The areas under the blood concentration/time curve were similar regardless of vehicle, suggesting that systemic toxicity might be independent of the vehicle.
Gingell
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R
Toxicology Department, Shell Oil Company, Houston, Texas 77210.
Beatty
P W
PW
Mitschke
H R
HR
Page
A C
AC
Sawin
V L
VL
Putcha
L
L
Kramer
W G
WG
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D003314:Corn Oil / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D014677:Pharmaceutical Vehicles; D011407:Propane / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility; D014867:Water / Q000008:administration & dosage
D014677:Pharmaceutical Vehicles; D014867:Water; D003314:Corn Oil; C007318:1,2-dibromo-3-chloropropane; D011407:Propane