We determined the threshold concentration of
sarin vapor exposure producing
miosis in African green monkeys (Chlorocebus aethiops). Monkeys (n=8) were exposed to a single concentration of
sarin (0.069-0.701mg/m3) for 10min. Changes in pupil size were measured from photographs taken before and after the exposure.
Sarin EC50 values for
miosis were determined to be 0.166mg/m3 when
miosis was defined as a 50% reduction in pupil area and 0.469mg/m3 when
miosis was defined as a 50% reduction in pupil diameter. Monkeys were also evaluated for behavioral changes from
sarin exposure using a serial probe recognition test and performance remained essentially unchanged for all monkeys. None of the concentrations of
sarin produced specific clinical signs of toxicity other than
miosis.
Sarin was regenerated from blood sampled following exposure in a concentration-dependent fashion. Consistent with a predominant inhibition of
acetylcholinesterase (AChE), more
sarin was consistently found in RBC fractions than in plasma fractions. Further, elimination of regenerated
sarin from RBC fractions was slower than from plasma fractions. Blood samples following exposure also showed concentration-dependent inhibition of AChE activity and, to a lesser extent,
butyrylcholinesterase activity. At the largest exposure concentration, AChE inhibition was substantial, reducing activity to approximately 40% of baseline. The results characterize
sarin exposure concentrations that produce
miosis in a large primate species in the absence of other overt signs of toxicity. Further, these results extend previous studies indicating that
miosis is a valid early
indicator for the detection of
sarin vapor exposure.