Evaluation of the biodisposition of diisopropylfluorophosphate (DFP) in mice and guinea pigs after inhalation

Thesis/Dissertation · Wed Dec 31 23:00:00 EST 1986

OSTI ID:7138251

Scimeca, J A

The disposition of /sup 3/H-DFP and its metabolites was determined in the major tissues of the mouse and guinea pig from 5 min to 24 hr after treatment. /sup 3/H-DFP rapidly penetrated all tissues in both species and was quickly hydrolyzed to /sup 3/H-diisopropylphosphoric acid (free /sup 3/H-DIP), or was covalently bound to tissue (bound /sup 3/H-DIP). By 1 hr, the greater portion of the radioactivity in the tissues of the mouse was in the form of bound /sup 3/H-DIP, with similar results found in the guinea pig at 4 hr. Studies were also performed to determine the effect of acute DFP exposure on /sup 3/H-(+/-)-nicotine binding to mouse brain homogenate. The nicotinic binding sites in brain homogenate from DFP-treated mice that were sacrificed 20 min or 10 hr after exposure did not exhibit significant alterations from control. However, brain homogenate from treated mice that were sacrificed 24 hr after exposure resulted in statistically significant differences in the low-affinity KD and Bmax values from controls. Since no alterations were found in the high-affinity binding parameters and DFP had only a minimal effect on the low-affinity site at 24 hr, it was concluded that nicotinic receptor down regulation does not appear to be a compensating mechanism for DFP-induced cholinesterase inhibition.

• Research Organization: Virginia Commonwealth Univ., Richmond (USA)
• OSTI ID: 7138251
• 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.
ALKALOIDS
AMINES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARBOXYLESTERASES
CHOLINESTERASE
DISTRIBUTION
DRUGS
ENZYMES
ESTERASES
ESTERS
GUINEA PIGS
HETEROCYCLIC COMPOUNDS
HOMOGENATES
HYDROLASES
INHALATION
INTAKE
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
METABOLISM
METABOLITES
MICE
NICOTINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PHOSPHORIC ACID ESTERS
PROTEINS
PYRIDINES
PYRROLES
PYRROLIDINES
REACTION KINETICS
RECEPTORS
RODENTS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES