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APPENDIX E CASE-FILE DATA ON E=EWOOD SUBJECTS. SUMMARY OF VOLUMES TESTING ~TH GB (M ) A total of 246 subjects was tested with GB under gracious conditions. Twenty-five subjects were selected for review, representing approximately lOX of the test ~group. Selections were based upon she f allowing cri teria: No Treatment ~ 9 subjects) _ Route: Intravenous (3~0 ~ 4.0 p8/kg) 9 subjects No symptoms Treatment ( PAMCL) ( 9 sub jec ts ) Dizziness, frontal headache, blurred vision lethargy, nausea, stomach pain, voiding. Route: 1~ ~g/kg) (P2S) 2 sub jects Intravenous (3.0 - 4.0 ~g/kg) (TMB4) 3 subjects Whole-body exposure to vapor (Atropine) 1 subject Whole-body exposure to vapor (Pyrbenzamine) 1 subject Rhinorrhea ~ chest tightness, wheezing. SUMMARY OF YOLU~EER TEST ING ~TH VX ( A2 ) A total of 740 subjects was tested under various conditions with VX. Seventy-five sub jec ts were selected for review, representing lOX of the test group. Selections were based upon the following cri teria: Hen ~ Route: Oral (single dose~kg) 1 subjec t Percutaneous (single dose; 5 - 45 ~g/kg) 22 subjects Oral (multiple dose) 29 subjects Treatment ~ 23 sub jects 2-P - , Atropine, Regitine Route: Intravenous (1. 2 - 2.0 ,ug/kg) 7 subjects Intramuscular 3 sub jects Oral (4.25 - 4.5,ug/kg) 3 sub feces Percutaneous (5.0 - 45 ug/kg) lO subjects The vast mad ority of these sub jects reportedly experienced little or no effect from the drug. ~ s (RBC) level was less that 20Z of normal in subjects multiple doses, but in each case the toeing was stopped and the cholinestera~e levels returned to normal limits within 6-7 days post exposure. No visible effects of the Snug were observed in any of these subjects. One subject (A2(BN)) received 30 ug/kg, pare utaneou~ly, ~ normal, nervous) and was treated with multiple doses of atropine ant 2-PAM. Sub ject recovered and RBC~E was 97Z of di scharget ~ Another subject (A2(BA) ) received 1~5 ~ug/kg in~cra~renously, developed twitching (fasciculation?) of leg muscles, perspiration of palms ant soles of feet IS min after injection when RBC ChE was 87% *This represents selection of high-lose subjects. A second set of records of equal number was also procured, on the basis of random selection. E 1

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of coronal (bopping tO 17% at lie). By 30 min. handa and feet were cold and the eyes felt "heavy." A third subject (42(BS)), who received 3.2 ,ug/ltg intra'~uacularly, wee dizzy, nauseated, and very drowsy after 2h. During the next 10 hour e, the subject lacked conceneration and stared vacantly into space. Slight dizziness and blurred vision persisted at 26h when he wee treated with 2-PAM and rec-o~rered. Some others reportedly experienced dlzzinesa, light-headednesa, nausea, voollting, "stiff Jaw," headache, and ptocia lasting for at least 24h af ter exposure . SUMMARY OF VOLUNTEER TESTING WITH GA (43 ) A total of 26 aubJeces vea tested under various conditions with GA. Thirteen (13) subjects were selected for review, representing 50Z of the teat group. Selections were based upon the following cri tart a: Treatment ( 10 subjec ts) Route: Intravenous (2.0 - 3.o~ugJkg)+(PAMcl. Pretreat Bent) 3 subjects Intravenous (~.0 0 2.0 ug~kg)+(PAMCI, Post Treatment) 2 subjects Intravenous (3 . O ~g/kg)+ OCR for page 103
experienced. They also developed persistent vomiting and nausea to a point. of dehydration. One subject was referred to Walter Reed Hospital for psychiatric observation ant diagnosed for anxiety reaction, acute agitation ant hysterical reaction; he was later released for duty. SUMMARY OF VOLUNTEER TESTING WITH DFP A total of I] subjects was tested with DFP under various test conditions. Fire (5) subjects were selected for review, representing approximately 45% of the test group. Selections were based upon the following cri teria: No Treatment ~ ~ sub jec t ~ Route: Intramuscular (16.0 ~g/kg) ~ subject 'treatment ( 4 subject s ) Route: Intramuscular (40 - 55,ug/kg) (PAMC1) 3 subjects Intramuscular (65 ~g/kg) (PAMCl + Atropine) 1 sub ject (Weak, shaky knees, dizziness, nausea, blurred vision, per sp iration) . SUMMARY OF VOLUNTEER TESTING WITH EA 3148 (Al ) A total of 32 subjects was tested under various conditions with EA 3148. Sixteen (16) subjects were selected for review, representing 50: of the test group. Selections were based upon the following cri teria: No Treatment ( 13 subjects) . Route: Intravenous (O. 7 - 1.15 ~g/kg) 13 subjects lE~ Route: Intr~) Intravenous ( 1.15 ug/kg ~ PAMCl ~ ~ sub jec t _ ~ ~ Scopolamine) 2 sub jects Sub jects wi th large doses experienced a rapid, severe depre ssion of RBC ChE following agent administration. For example, volunteer #3799 (case fI385), who received 1.15 ug/kg EA 314B, showed 22: of normal R8C ChE values at 15 min after tio8ing and 0% af ter 4Sh; this recovered to t3 63: of normal at 72d post-exposure. Of the subjects that ~ `" pua~-~:^pu~u~e _ received no additional treatment, two sub jec ~ s who had received the highest dose ~ ~ .15 ,ug/kg) showed toxic signs with 5 to ~ minutes post-exposure. These sub jects fell dizzy, weak, tired, sweating, with hands and feet very moist. Within 2 hours po~-exposure, these sub jects reportedly were resting, eating well ant feeling fine. Anorexia, poor sleep, fatigue, unusual dreams, dizziness, euphoria, blurred vision, increased calibration, restlessness are rec orded in an Army report summarizing the expert ence with EA 3148 (CRDL. Tech. Memo 2-3-~) . The report also notes one individual whose schizoid personality seemed to be exaggerated by the drug. Four individuals had decrements on the tes ~ of numerical facility . Subjects treated with PAMC] or Scopolamine did not have any severe drop in ChE, and there were no long lasting effects of the rug o bserved . E 3

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SUMMARY OF VOLUNTEER TESTING WITH T" (A9), Tacrine total of 15 subjects was tested under various conditions with ~A. Five (5) subjects were selected for review, representing approximately 33X of the test group. Selections were based upon the following criteria: Route: Intravenous (2~EU) 1 sub ject Oral (250 ma, total) 1 sub jece Treatment ( 3 sub ject e ) Route: Oral (192-200 ma, total) (Atropine) 2 subjects Oral ( 250 ma, total ) ( PAMCl+Atroplne ) 1 sub jec ~ The subjects' blood cholinesterase levels were monitored continuously, along with BEG, EKG, respiratory rate and volume with pneumotact, and blood pressure. There were no significant changes in the parameters measured. Untreated subjects were aeg~pto~atic at the tose levels given, ant even though there wee some drop in ChE (28% of nomal) in pla - ~, the RBC ChE was unaffected. Subjects treated with atropine alone, or with PAMC1, responded well to relief of severe parasympa thomimetic ~actions. No residual effects of the drug reportedly were obeer~red in any of the subjects tested. SUMMARY OF VOLUNTEER TESTING W~ PHY~STIG=" (MO) A total of 138 sub Jects was tested Erich phy~ostigeine and 22 were selected for review, representing approximately 16: of the tese group. The criteria for selection was based upon the following: Dose, Route, Frequency ant Treatment. No Treatment ( 6 subjects) Route: Intramuscular he (TWO ,ug/kg) 2 sub jects Intramuscular, multiple dose (15-30 ~g/kg) 4 subjects ~ Route: PhysoatlgoIine in Single (45 ~g/kg) and mulelple doses over 1 to 2 days was administered intramuscularly in subjects that had beers previously dosed with a variety of drugs such as: BZ (7.4 - 14.5 ug/kg) aerosol inhalation, 2 subjects 3834 (2.0 me) percutaneous, 1 sub ject Atropine ( 125 ,ug/l~g ) intramuscular ~ 3 sub jects Prolixin (15.0 - 23.0 ~g/kg) intramuscular, 6 subjects 302668 (lO.O,ug/kg) intravenous, 1 subject 302196 (75. 6 .ug/kg) oral, ~ sub ject TAB (90 mg total) intramuscular, 1 subject Pretreatmen~c with methyl scopola - ice (~.C On 19. 2 sub jects (~03) and (AlOK) who received ma) 1 sub ject doses of BZ and were subsequently treated with physostigo~ne, showed any prolonged central effects (hallucinations, disorientation, confusion) lasting 4 to 6 days post~exposure. Both sub jects were as~pto~atic and appeared normal when discharged from test. One subject (~0-0) was exposed to Prolixin (23.0 ~g/kg) and then treated with multiple doses (~.0 mg x 7 doses) over a 2-day period, intramuscularly: At 27 hours post-exposure, the sub ject complained of blurred Piston, and facial expression was mask-~ike, tongue "thick" and jaws open. By 28 hours post-exposure, subject was having an oculo~gyric crisis, mouth to one side, and left f Got tremulous and turned inward . E 4 -

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SubJect was further treated with Cogentin, Intravenously (l.O fig ant 1.3 fig), in two doses. Within 30 minutes poet-treatment, Subject was relaxed and dozing ant , by 31 hours post-exposure, the sub jec appeared normal. At SO hours post-exposure, the sub ject was asymptomatic and was discharged at 73 hours post-exposure with no complaint s . SUMMARY OF VOLONTEER TESTING WITH PROSTIGlIINE (All) A total of 27 subjects was rested with proatig~ine as a part of the esophageal motility studies. Seven ~7) subjects were selected for review, representing approximately 26Z of the test group. Selections were based upon the following criteria: No Treatment ~ ~ sub iect ~ . Route: Intramuscular (0.5 ma) 1 subject Treatment (6 subiecto) Route: Intramuscular (1.5 mg3 (A~cropine/PAMCI) 6 subjects The esophageal motility studies (EPP) were performed by the subjects before ant after administration of the bug. ChE levels were also determined in many of the subjects. One subject developed severe cramps in the abdomen, necessitating termination of the study (ARAB) . Al1 o ther subjects reportedly tolerated all procedures very well. SUMMARY OF VOLUNTEER TESTING WITH HEXAFl UORENTUM (!lylaxinR) (Ai2) . A total of 11 subjects was testes with Mylaxin an a part of an esophageal test. 11 Subjects were selected for review, representing 100% of the test group. Selections were based upon the following cri teria. No Treatment (11 subjects) Route: Intravenous (0.4 ~7~ subjects The ma jort ty of subjects tested expert enced a sensation of "warmness" in the stomach and nausea very shortly (2-10 minutes) after receiving the drug, foil-owed by vomiting within 5-15 minutes. The plasma ChE levels in all subjects were depresses while RBC ChE Petrels were not significantly affected. Esophageal motility studies disclosed marked spasm of the lower 2/3 during deglutltion. This coincided with depression of the plasma ChE. There were no prolonged or long-lasting effects reported in any of these subjects as a result of this drug. All sub jects reportedly had recovered within 24 hours post-exposure. SUMMARY OF VOLUNTEER TESTING WITH MALATHION (A14) A total of lO sub Jects was tested witch l.~% malathion powder dusted over the entire body for up to lO days. Fire (5) subjects were selected for review, representing 50: of the test group. All of these sub Sects report edly were asymptomatic and developed no signs of intoxication. One subject (Al44), showed low R8CChE which could not be ascribed to laboratory error; however, there were no o ther significant drops in this subject 's ChE levels. All other subjects showed no significant decreases in choline~terase. E 5

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Sl~iMARY OF VOLUNTEER TESTING WITH CHOLINE A total of 9 subjects was tested with otecholyl alone or with EA 1729. Several of these subjects also received other drugs such as neostigmine, urecholine, PANC1, epinephrine by various routes. Three (3) subjects were selected for review, representing 33X of the test group. Although these subjects were tested or treated with several of these drugs, as well as mecholyl, their vital signs reportedly returned to normal and they were all in good condition by the end of the testing period. There were no prolonged or delayed effects from thi s drug re port ed in these subjects . SIXTY OF VOLUNTEER TESTING WITH U~CHOLI~_ (A21) _ A total of 15 subjects was tested with urecholine under various conditions, under the (E~P) . Five (5) subjects were selected for review, representing 33% of the test group. Selections were based upon the following criteria: No Treatment (2 subjects) Route: Subcutaneous (5.0 Ogle dose) ~ subject Subcutaneous ~ 5.0 ma) (multiple dose) ~ subject Treatment of Multiple Compounds (3 subjects) Route: Subcutaneous (5.0 ma) (PAMCl+Prostigmine) 1 subject Subcutaneous (5~0 ma) (Prostigmine+Curare+PAMCl) 1 subject Su he utaneous ( 5 . O rag ~ ~ Tu bocura re+Pr 0 st igmi ne+At rapine 1 subject EPP were performed before and after administration of the drug. ChE was also monitored in sore cases. All subjects tolerated these procedures very well, and there were reportedly no untoward effects of the drugs ire "ny of the subjects tested. E 6