The effect of 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide on tissue cholinesterase and carboxylesterase activities of the rat.
The dose-response (0.1 to 1000 mg/kg sc) effects of 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP; a metabolite of the organophosphorus compound tri-o-cresylphosphate) 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 (greater than 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 ED50 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 much greater than plasma ChE much greater than red blood cell (RBC) ChE. The biphasic dose-response curve and preferential inhibition of the blood esterases may reflect the inhibition of butyrylcholinesterase 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.
Jimmerson
V R
VR
U.S. Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, Maryland 21010-5425.
Shih
T M
TM
Maxwell
D M
DM
Kaminskis
A
A
Mailman
R B
RB
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000097:blood*; D002802:Cholinesterases / Q000097:blood*; D008297:Male; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D009943:Organophosphorus Compounds; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D002265:Carboxylic Ester Hydrolases; D002091:Butyrylcholinesterase; D002802:Cholinesterases