Metabolic fate of benzo(a)pyrene in vivo

Thesis/Dissertation · Wed Jan 01 04:00:00 EST 1986

OSTI ID:6991342

Weyand, E H

(/sup 3/H)-B(a)P absorption, distribution, metabolism, excretion and macromolecular binding in male Sprague-Dawley rats were investigated following administration by intratracheal instillation. (/sup 3/H)-radioactivity in various organs was determined at timed intervals between 5 and 360 min. Elimination of radioactivity from lungs was biphasic with half-lives of 5 and 116 min. Radioactivity in liver increased rapidly, reaching a maximum of 21% of the dose within 10 min after instillation and decreasing thereafter, until less than 5% of the dose was detected at 360 min. Radioactivity in intestinal contents accounted for 45% of the dose 360 min after instillation. Carcass accounted for 15-30% of the dose within the time intervals investigated.Toxicokinetic parameters following intratracheal administration were similar to those following intravenous injection of B(a)P. HPLC was used to identify various types of metabolites in lungs, liver, and intestinal contents. Notably, quinones were a highest concentration in both lung and liver 5 min after instillation, accounting for 12 and 7% of organic extractable material, respectively. Covalent binding of B(a)P metabolites to DNA, RNA, and protein was also quantified for lung and liver. There was extensive binding of metabolites to RNA while much lesser amounts of metabolites were associated with protein and DNA in both organs. Six B(a)P:DNA adducts were detected in lung, while only three such adducts were detected in liver. Biliary excretion of B(a)P was investigated in Sprague-Dawley rats, Gunn rats, hamsters, and guinea pigs following instillation of (/sup 3/H)-B(a)P at concentrations ranging from 6 ng to 380 ..mu..g. In addition, tissue distribution of radioactivity was determined. Rats and guinea pigs, but not hamsters, exhibited differences in biliary excretion of low and high doses of B(a)P. Phase II metabolites of B(a)P in bile were quantified for all species.

• Research Organization: Virginia Polytechnic Inst. and State Univ., Blacksburg (USA)
• OSTI ID: 6991342
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ABSORPTION
ANIMALS
AROMATICS
BENZOPYRENE
BILE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CHALCOGENIDES
CLEARANCE
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DISTRIBUTION
DNA
EXCRETION
GLANDS
GLUCURONIDE CONJUGATES
GUINEA PIGS
HAMSTERS
HYDROCARBONS
INTRATRACHEAL ADMINISTRATION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIVER
LUNG CLEARANCE
LUNGS
MAMMALS
MATERIALS
METABOLISM
METABOLITES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PROTEINS
QUINONES
RATS
REACTION KINETICS
RESPIRATORY SYSTEM
RNA
RODENTS
SKELETON
SULFIDES
SULFUR COMPOUNDS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES