Het. Spruit et al., Intravenous and inhalation toxicokinetics of sarin stereoisomers in atropinized guinea pigs, TOX APPL PH, 169(3), 2000, pp. 249-254
We report the first toxicokinetic studies of (+/-)-sarin. The toxicokinetic
s of the stereoisomers of this nerve agent were studied in anesthetized, at
ropinized, and restrained guinea pigs after intravenous bolus administratio
n of a dose corresponding to 0.8 LD50 and after nose-only exposure to vapor
concentrations yielding 0.4 and 0.8 LCt50 in an 8-min exposure time. Durin
g exposure the respiratory minute volume and frequency were monitored. Bloo
d samples were taken for gas chromatographic analysis of the nerve agent st
ereoisomers and for measurement of the activity of blood acetylcholinestera
se (AChE).
In all experiments, the concentration of (+)-sarin was below the detection
limit (<5 pg/ml). The concentration-time profile of the toxic isomer, i.e.,
(-)-sarin, after an intravenous bolus was adequately described with a two-
exponential equation. (-)-Sarin is distributed ca, 10-fold faster than C(-)
P(-)-soman, whereas its elimination proceeds almost 10-fold slower,
During nose-only exposure to 0.4 and 0.8 LCt50 of (+)-sarin in 8 min, (-)-s
arin appeared to be rapidly absorbed. The blood AChE activity decreased dur
ing the exposure period to ca. 15 and 70% of control activity, respectively
. There were no effects on the respiratory parameters. A significant nonlin
earity of the toxicokinetics with dose was observed for the respiratory exp
eriments. (C) 2000 Academic Press.