Variability in soman toxicity in the rat: correlation with biochemical and behavioral measures.
The inhibition of cholinesterase (ChE) activity in the central nervous system of the rat by the potent organophosphorus compound soman was examined. At soman doses greater than 55 micrograms/kg s.c. (0.5 LD50), there were: (1) dose-related inhibition of ChE activity in brain regions; (2) variability in the degree of ChE inhibition at each soman dose in each brain region; and (3) variability in the severity of signs of intoxication at each dose. These data suggest that measurements of ChE should be made directly or predicted individually in each animal for which the effects of soman are assessed. At the estimated ED50 soman dose for signs of intoxication (66 micrograms/kg s.c.), the remaining ChE activity in brain correlated poorly with ChE activity in plasma and red blood cells (R = 0.14-0.20), moderately with behavioral scores based on overt signs of intoxication (R = 0.63-0.94), and well with spinal cord ChE activity (R = 0.93-0.98). Finally, ChE activity in the thoracic and lumbosacral regions of spinal cord were not affected by headfocused microwave inactivation of brain enzymes, demonstrating that ChE activity in these regions of the cord can be used to predict the level of ChE inhibition in brain when direct measurement in brain is unfeasible.
Jimmerson
V R
VR
Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Shih
T M
TM
Mailman
R B
RB
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000032:analysis / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D008872:Microwaves; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology
D002800:Cholinesterase Inhibitors; D012999:Soman; D002802:Cholinesterases