Correlation of blood cholinesterase levels with toxicity of sarin in rats.
The dose-mortality response curve for sarin when administered to pregnant rats is extremely steep. The pregnant animal either died during the treatment or survived with no observable fetal toxicity. Animals that died displayed many symptoms characteristic of anticholinesterase toxicity. The present study was conducted to determine whether the maternal deaths, clinical observations, and/or weight loss could be correlated with baseline blood cholinesterase levels in individual animals. Cholinesterase levels (plasma and erythrocyte) were obtained prior to, during, and following treatment of nonpregnant rats by gavage with 380 microg/kg/d sarin for 10 d. After the first dose, there was a drop in the plasma cholinesterase levels, which then remained low throughout the dosing period. There was a statistically significant correlation between body weight loss and plasma cholinesterase levels of the sarin dosed animals. The surviving animals also had lower plasma cholinesterase levels and lower body weights, both of which recovered on the cessation of dosing. The erythrocyte cholinesterase levels were not different between treated and nontreated rats. Neither plasma or erythrocyte baseline cholinesterase levels nor relative or absolute cholinesterase decline values could be used as predictors of mortality from sarin administration in rats.
Young
J F
JF
National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079-9502, USA. jyoung@nctr.fda.gov
Gough
B J
BJ
Suber
R L
RL
Gaylor
D W
DW
D000818:Animals; D001800:Blood Specimen Collection / Q000379:methods; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood*; D003392:Cranial Sinuses; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D051381:Rats; D012524:Sarin / Q000633:toxicity*; D013623:Tail / Q000098:blood supply; D015431:Weight Loss / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D012524:Sarin; D002802:Cholinesterases