Comparative study of the pharmacokinetics of carbon tetrachloride in the rat following repeated inhalation exposures of 8 and 11. 5 hr/day
To evaluate whether exposure to inhaled vapors for periods longer than 8 hr/day could affect the rates and routes of elimination, male Sprague-Dawley rats were repeatedly exposed to 100 ppm of radiolabeled carbon tetrachloride (/sup 14/CCl/sub 4/) in a closed-loop chamber. One group was exposed for 8 hr/day for 5 days and another group for 11.5 hr/day for 4 days. Two other groups were exposed for either 8 hr/day for 10 of 12 consecutive days or 11.5 hr/day for 7 of 10 days. The elimination of /sup 14/C activity was measured in the expired air, urine, and feces for up to 100 hr following exposure and the pharmacokinetic parameters were determined. Following 2 weeks of exposure to the 8-hr/day schedule, /sup 14/CCl/sub 4/ in the breath and /sup 14/C activity in the feces comprised 45 and 48% of the total /sup 14/C excreted, respectively. Following 2 weeks of exposure to the 11.5-hr/day schedule, the values were 32 and 62%, respectively, indicating that repeated exposure to the longer schedule altered the route of elimination of CCl/sub 4/. Regardless of the period of exposure, less than 8% of the inhaled /sup 14/CCl/sub 4/ was excreted in the urine and less than 2% was exhaled in the breath as the /sup 14/CO/sub 2/ metabolite. Approximately 97-98% of the /sup 14/C activity in the expired air was /sup 14/CCl/sub 4/. The quantities of /sup 14/C noted in the feces and urine suggest that more than 60% of the inhaled CCl/sub 4/ was metabolized. Elimination of /sup 14/CCl/sub 4/ and /sup 14/CO/sub 2/ in the breath followed a two-compartment, first-order pharmacokinetic model (r2 = 0.98). For rats exposed 8 hr/day and 11.5 hr/day for 2 weeks, the average half-lives for elimination of /sup 14/CCl/sub 4/ in the breath for the fast (alpha) and slow (beta) phases averaged 96 and 455 min, and 89 and 568 min, respectively. The average alpha and beta half-lives for elimination of /sup 14/CO/sub 2/ in the breath
- Research Organization:
- Purdue Univ., West Lafayette, IN
- OSTI ID:
- 5558466
- Journal Information:
- Fundam. Appl. Toxicol.; (United States), Vol. 3
- Country of Publication:
- United States
- Language:
- English
Similar Records
Effect of vapor concentration on the disposition of inhaled 2,3-dichloropropene in Fischer-344 rats
Effect of an 11. 5-hr/day exposure schedule on the distribution and toxicity of inhaled carbon tetrachloride in the rat
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
CARBON TETRACHLORIDE
BIOCHEMICAL REACTION KINETICS
EXCRETION
CARBON 14 COMPOUNDS
CARBON DIOXIDE
COMPARATIVE EVALUATIONS
FECES
INHALATION
METABOLISM
METABOLITES
RATS
SOLUBILITY
TRACER TECHNIQUES
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON COMPOUNDS
CARBON OXIDES
CHALCOGENIDES
CHLORINATED ALIPHATIC HYDROCARBONS
CLEARANCE
HALOGENATED ALIPHATIC HYDROCARBONS
INTAKE
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
REACTION KINETICS
RODENTS
VERTEBRATES
WASTES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550501 - Metabolism- Tracer Techniques