Comparison of low-level sarin and cyclosarin vapor exposure on pupil size of the Gottingen minipig: effects of exposure concentration and duration.
The current studies estimated effective (miosis) concentrations of the nerve agents' sarin (GB) and cyclosarin (GF) as a function of exposure duration in the Gottingen minipig and determined dependency of the median effective dosage (ECT50) over time. Male and female Gottingen minipigs were exposed to various concentrations of vapor GB or GF for 10, 60, or 180 min. Infrared images of the pig's pupil before, during, and after nerve agent exposure were captured digitally and pupil area was quantified. An animal was classified "positive" for miosis if there was a 50% reduction in pupil area (as compared to baseline) at any time during or after the GB or GF exposure. Maximum likelihood estimation was used on the resulting quantal data to calculate ECT50 (miosis) values, with approximate 95% confidence intervals, for each of the six gender-exposure duration groups. As a group, male minipigs were significantly more sensitive to the pupil constricting effects of GF than were female minipigs. In male minipigs, GF is approximately equipotent to GB for 60-min exposures and more potent for 10- and 180-min exposures. In the female minipig GF is slightly more potent than GB for 10-min exposures but then progressively becomes less potent over the 60- and 180-min durations of exposure. The values of the toxic load exponents were essentially independent of the model fits used: 1.32 +/- 0.18 for GB exposures and 1.60 +/- 0.22 for GF exposures. Since neither of these intervals overlaps 1, Haber's rule is not an appropriate time-dependence model for these data sets.
Hulet
Stanley W
SW
Research and Technology Directorate, U.S. Army Edgewood Chemical and Biological Center (ECBC), Aberdeen Proving Ground, Maryland 21010, USA. hulet@us.army.mil <hulet@us.army.mil>
Sommerville
Douglas R
DR
Crosier
Ronald B
RB
Dabisch
Paul A
PA
Miller
Dennis B
DB
Benton
Bernard J
BJ
Forster
Jeffry S
JS
Scotto
Jacqueline A
JA
Jarvis
Jill R
JR
Krauthauser
Candice
C
Muse
William T
WT
Reutter
Sharon A
SA
Mioduszewski
Robert J
RJ
Thomson
Sandra A
SA
D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019570:Inhalation Exposure; D016015:Logistic Models; D008297:Male; D015877:Miosis / Q000139:chemically induced; D009943:Organophosphorus Compounds / Q000633:toxicity*; D011680:Pupil / Q000187:drug effects*; D012524:Sarin / Q000633:toxicity*; D012727:Sex Characteristics; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014835:Volatilization
D002619:Chemical Warfare Agents; D009943:Organophosphorus Compounds; D012524:Sarin; C053914:cyclohexyl methylphosphonofluoridate