Determination of miosis threshold from whole-body vapor exposure to sarin in African green monkeys.
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.
Genovese
Raymond F
RF
Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. Raymond.Genovese@US.ARMY.MIL
Benton
Bernard J
BJ
Oubre
John L
JL
Fleming
Patrick J
PJ
Jakubowski
E Michael
EM
Mioduszewski
Robert J
RJ
D000280:Administration, Inhalation; D000818:Animals; D001822:Body Burden; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002522:Chlorocebus aethiops; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D003627:Data Interpretation, Statistical; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005740:Gases; D008568:Memory / Q000187:drug effects; D015877:Miosis; D011680:Pupil / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects; D012524:Sarin / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D012867:Skin / Q000166:cytology* / Q000187:drug effects*
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D005740:Gases; D012524:Sarin