© 1989 Oxford University Press
research-article |
The Effect of 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide on Tissue Cholinesterase and Carboxylesterase Activities of the Rat1
*U.S. Army Medicol Research Institute of Chemical Defense Aberdeen Proving Ground Maryland 21010-5425
Curriculum in Toxicology, Biological Sciences Research Ceiner, University of North Carolina Chapel Hill, North Carolina 27514-7220
Received December 13, 1988; accepted April 7, 1989
The dose-response (0.1 to 1000 mg/kg sc) effects of 2-(o-cresyl)-4H-l:3:2-benzodioxaphosphorin-2-oxide (CBDP; a melabolite of the organophosphorus compound tri-o-cresylphosphare on total cholinesterase (ChE) and carboxylesterase (CaE) activities in tissues from the rat were examined. Doses of CBDP greater than 1.0 mg/kg inhibited CaE activity maximally (>99%) in plasma and lung, two important sites for detoxification of organophosphorus toxicants. A biphasic dose-dependent inhibition of ChE activity was seen in all tissues; the ED5O values showed a difference of two orders of magnitude between the first and the second phases of the dose-response curves. CBDP inhibited the blood esterases in the order plasma CaE 
plasma ChE red blood cell (RBC) ChE. The biphasic dose-response curve and preferential inhibition of the blood esterases may reflect the inhibition of butyryicholinesterase in preference to acetylcholinesterase in these tissues. At doses of CBDP below 1.0 mg/kg, plasma, RBC, and brain regional ChE activities were inhibited by less than 10%, whereas at doses above 2.0 mg/kg, ChE activities were inhibited substantially (up to 80% in plasma, up to 60% in RBC, and greater than 90% in brain regions). On the basis of these results, a dose of CBDP between 1.0 and 2.0 mg/kg should prove useful as a pretreatment for studies of OP toxicity in the rat.