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

The disposition of 3H-DFP and its metabolites was determined in the major tissues of the mouse and guinea pig from 5 min to 24 hr after treatment. 3H-DFP rapidly penetrated all tissues in both species and was quickly hydrolyzed to 3H-diisopropylphosphoric acid (free 3H-DIP), or was covalently bound to tissue (bound 3H-DIP). By 1 hr, the greater portion of the radioactivity in the tissues of the mouse was in the form of bound 3H-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 3H-(+/-)-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