Disposition of 1,2,3-trichloropropane in the Fischer 344 rat: conventional and physiological pharmacokinetics
To investigate the disposition of 1,2,3-trichloropropane (TCP), (14C)-TCP was administered iv to male Fischer 344 rats. Unchanged TCP and total radiolabel were determined in tissues and excreta at varying intervals after administration. The compound was distributed and eliminated rapidly. Initial and terminal half-lives of unchanged TCP in the blood were 0.29 and 23 hr. Adipose tissue accumulated 37% of the dose within 15 min and retained more of the dose than any other tissue until 4 hr; most (69%) of the radiolabel in adipose tissue through 4 hr was unchanged TCP. After 4 hr, the liver contained the largest fraction of the dose, primarily as metabolites. Thus TCP disappeared from adipose tissue while metabolites appeared in liver and other tissues. Excretion was nearly complete (90% of the dose) in 24 hr and was predominantly via the urine (47% of the dose). Expiration was the only route by which unchanged TCP (5% of the dose) was excreted. In addition, 25% of the dose was expired as carbon dioxide. There were numerous other metabolites, none accounting for more than 10% of the dose. Nonvolatile metabolites were longer lived than the parent compound. On the basis of high water solubility, reaction with 2,4-dinitrofluorobenzene, and diminished radiolabel in bile of glycidol-treated rats, glutathione conjugation is suggested as an important metabolic route for TCP. A physiological pharmacokinetic model was developed to describe the time course of trichloropropane concentration in tissues. The model demonstrates the possibility of using physiological and pharmacokinetic data to predict concentration-time relations for toxic compounds.
- Research Organization:
- Department of Pharmacology/Toxicology, College of Pharmacy, University of Arizona, Tucson
- OSTI ID:
- 6546388
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Vol. 75:1
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
CHLORINATED ALIPHATIC HYDROCARBONS
EXCRETION
TISSUE DISTRIBUTION
ADIPOSE TISSUE
CARBON 14 COMPOUNDS
LIVER
METABOLISM
RATS
TRACER TECHNIQUES
URINE
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CLEARANCE
CONNECTIVE TISSUE
DIGESTIVE SYSTEM
DISTRIBUTION
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
RODENTS
TISSUES
VERTEBRATES
WASTES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550501 - Metabolism- Tracer Techniques