ADDENDUM GfkOO'MING ACTIVITY OF ALBINO MICE EFFECT-OF CHLBRDIAZEPOXIDE AND@@1900 INTRODUCTION Chlordiazepoxide ahdIW1900 were employed to explore the usefulness of a test based on the grooming behavior of albino 2 mice, according to the method of 0 Rohte, (Brit. J. Pharmac. 34:236, 1968) for the detection of sedative agents. Rchte states that the main advantage of this test is that it reduces s weak sedatives by providing a the difficulties in te tinq releaser mechanism to the instinctive grooming movements of whi2te mice. Rohte found that administration of certain test substances was associated with a significant inhibition of grooming movements compared with control group METHOD Apparatus Observation boxes were clear plastic with dimensions 3 of 5.5 x 10 x 5 in The boxes were cov2ered with wire screening and the bottoms were lined with cardboard. Activated ca:rbon, Darco grade S-51 of the Atlas Powd6r Companyi was used to cover h a -gauge needle and the mice. All injections Were made wil 25 glass syringes. Subjects The subjects were 60 fema9le albino mice (19-31 grams), m the HR/ICR strain supplied fro -2 Procedure The test mice were covered with pulverized charcoal and the intensity of blackening and its pattern were noted at va@ls up to 6 hours. The observations were graded 1.5 hour inter e: I wh y; 2 medium grev; on a 3-point scal ite to light2 gre 3 dark grey to black. Five subjects p(@r dose level A. Chlordiazepoxide. per day receiVed-Chlbrdiatepoxide (Librium HC1) intravenously between 8 a.m. and 10 a.m. or a saline solution (control). Dose levels of Chlordiazepoxide were 125 mg/kg, 63 mg/kg,, 32 mg/kg,, 3.2 mg/kg, and 0.32 mg/kg. Saline given at a level of 10 ml/kg (largest drug volume of solution injected). All animals at a single dose level were injected on the same day. After injection ining the powdered carbon and the animal was placed in a jar conta covered b shaking the jar. The subject was then removed by tail 2 y -into a shoebox cage lined with saw- with forceps and laced P dust for approximately 3 minutes. Subject was then placed into a plastic observation cage with ad libitum food and water. observations of the intensity And pattern of blackening -t one hour intervals accord were made a ing to the method of Rohte (1968) (see Figure 1,2). Observations were made on both dorsal (ventral @ surfaces and each body area was noted .1i ht (3,2, or 1, respectively). as either dark, medium, or 9 Bo 900. Two dose levels, 1 mg/kg and 0.1 mg/kg were tested in five mice each, according to the method used with Librium. 3 - RESULTS The "grooming un"It" appears to accurately measure grooming activitv during the first few hours of test. At later i nterval,s grooming ecause the observer is unable 2 becomes more difficult to measure b on areas which are already to note additional grooming activity light. Therefore, the decreased rate of grooming toward the sixth hour in"all groups except the controls (see Figure 10) may- be due to the inability to measure grooming rather than an ac2tual decrease caused by the drug. For purposes of statistical analysis each subject was assigned a grooming index at each hourly observation (see Table 1). The grooming index was obtained by summing the grey values (light - li medium = 2, dark 3) for the six body areas a-f. Each dose group was compared with the controls in a Wilcoxon two sample test (Laurence and Bacharach, p. 80) (see Table 2). The test was not applied to the on6-hour data because of the large number of ties. For Chlotdiazepoxide the grooming indices of the 125 and 63 mg/kg dose groups were found to be significantly decreased as compared to controls throughout the 6-hour period. The 232 mg/kg group showed a significant decrease in grooming at 2nd and 6th hour. The grooming of the 3.2 mg/kg group was found to be significantly decreased as compared to controls from the 3td to the 6th hour. No difference in grooming was found with the 0.32 mg/kg group. For 0, 0.1 mg/k3g was.a no effect level. Mice which received 00 at 1.0 mg/kg showed a significant decrease (P ;05) at the 1-3 hour intervals and very significant decrease (P 0.01) at the 4-6 hour intervals, when a one tailed test is considered. [v I i7, 1'77rT7 t I 2 7b Z . . . . . . . 7, 2 7 7=7- 7-'r7-' I 4 LA 1 4.4 cl L7 7 7-,7 7 v e- e-; @i; L@, @-i-i C, v- C..I' @7 7' 8 L @7 @77 .7717 T C- W I -L .7 74 2 fh -t- 71' 2 77,17@, 't -4 0....... ... -T r 4C@ TABLE DISTRIBUTION OV VALUES OF THE GROOMING INDEX AT., EACH 1-HOUR OBSERVATION FOR 5 DOSE LEVELS OF TD FOR SALINE CONTROLS LFBRI'UM HC1 Al% cl (mg/kg) Librium H saline 2(10 ml/kg) -3 .2 u -32 6 32 .3 Hour 125 17 7 18 17 17 17 17 17 15 17 1 2 17 17 17 17 17 15 17 18 17 17 17 17 J& 17 16 15 17 17 17 17 17 17 17 17 17 6 17 18 18 17 2 17 is 18 17 18 17 17 18 17 17 1 5 17 16 17 17 17 15 12 16 2 18 2 4 17 18 17 16 17 16 14 17 16 1 17 17 17 16 17 12 15 13 16 14 16 15 14 14 18 17 17 16, 13 182 13 16 16 15 12 16 12 18 17 -f 2 8 13 15 17 17 3 16 17 17 14 2 12 18 17 14 17 15 13 12 15 17 16 1 .9 15 12 14 17 6 13 17 13 14 18 16 i2s 15 13 11 15 14 17 11 14 12 14 9 17 12 15 18 16 8 12 12 4 18 16 17 17 16 11 2 12 13 is 17 13 1 15 7 13 13 10 14 1 4 1 12 11 13 3 16 7 17 17 .18 16 213 14 11 9 13 12 13 14 18 12 11 17 14 13 10 17 11 14 5 is. 16 17 17 13 10 8 12 2 8 13 13 7 10 12 18 17 11 17 15 7 10 11 13 17 1 7 13 14 11 10 8 9- 211 13 14 is 16 13 13 10 7 17 9 11 14 18 17 8 8 10 8 14 6 18 16 17 17 13 2 17 11 16 11 7 9 11 6 11 8 13 17 17 17 11 7 8 13 13 11 10 7 7 10 109 11 17 16, 13 11 7 15 7 11 17 17 11 11 9 9 5 5 5 25 5 5 TABLE 2. -VALUES FOR A TWO.@-TAILED TEST RIUM HC1 ON 5 DOSE LEVELS OF LIB 7@ wilnny6n 2-sarnnle Test* Libriurrr HC2T Hour 125 mg/kg 63 mg/kg 32 mg/kg 3.2 mg/k 0.32 mg/kg 9 -05 14§ 2 <0001, 0.02 0.05 >0. -),0.05) 3 20.01 leo.01 >0.05) 0.05 >0.05) 4 .40.01 40 01 /-O 05) 0.02 >0.05) 5 -110 . 0 1 e-0.01 -70.05) 0-.02 >0.05) 6 Zo.oi 0 . 01 0 . 01 0.05) Not significant Rumke C. L., and de Jonge, H. Chapt. 3, Design, Statistical Analysds and Interpretation in Vol. I Evaluation of Drug Activiti6s: PharmAcometric.s ed. by La-@?rehc7e, D. R., and Bacharach, A. L., Academic Press, N. Y. 1.964 9 OT L OT ZT ST 9T VT t, T 9 9 OT OT OT TT ZT ST LT VT 9T s L TI ET TT ZT 9T 9T LT 9T 9T 8 ZT LT ZT ZT 9T LT LT LT 9T E OT VT LT TT ST LT LT 8T LT. LT z 9T 8T LT ST LT 8T -8T 8T 8T 8T T -v T- T- T- 7 anoh X/E-W--T 0 006T -6%/ T 006T 90TW TrnPTA'rPUI-20.4 sezoos 006T41wao SlaAali asoa- z JO HOVA HOa NOIIVAUZSSO IdnoH-1 ROV2 IV X3GNI DNIWOOUD JO San7VA JO NOIlasiulsia 'E 979vi owns" TABLE 4. P@VALUES FOR 2-TAILED TEST OF 900 0.1 Mt/KG lot VERSUS-EW1900 1.0 MG/KG DOSE LEVELS Hour P values' .05 2 .05 4 .10 4 .02 5 .02 6 .02 1356 W LD50 36*0 -2800-45oO- MED50 Oe56 -0918-1*8-- 63 0 2 RATIO LD50/MED50 LID STATE @o INTRAVENOUS TOXICITY TO MICE DOSE DI'LU'T REACTO REACTION SIGN MINA 'DEG-- MIN. TO MG/KG ML/KG'FRACTO APPR REE RECOVER 2 100io 1010 2/2 'DEATH 74 0 a a 2/2 30 120 @32 0 2 DEC LOCOMOTOR ACTIVITY 124 3o2 @2/2 229 2 30 180 3200 DEC SENSITIVITY TO PAIN 0 32*0 .3,i 2 2/2 INC SENSITIVITY TO-SOUND 130 300 .3,2 @2/2 INC SENSITIVITY To TOUCH 131 2 0 32.0 NCY G 300 .32.0 .3*2 ;2/2 DEC RFARING'FREQUE 632 30 120 32 a 0 3o2 STRAUB@TAIL 233 0 15 2 336 0 .3,2 '2/2 3 2 c; 0 15 32,0 3,2 2/2 AUDIOGENI,C SEIZURE 536 0 30 PREEN2ING 240 't-20 3290 .3,2 2/2 :DEC 8 32oO 392 '2/2 'RUBBING NOSE 340 8 30 @32,, 0 3*2 /2 TREMORS-REST AND MOVEMENT 144 2 2 0 30 32,0 3,2 2/2 BLI,NKING-EXCESSIVE 247 a 30 'EYELID PTOSIS-NONPARALYTIC 149 8 32,0 3.2 1/2 2 '20 PUPILLARY LIGHT REFLEX ABS 152 0 240 32oO 3*2 2/2 32,0 3,2 2/2 MYDRIASIS 154 0 1440 57 .322,0 3,2 2/Z SALIVATION 8 60 32*0 3 2 INC URINATIO 158 30 60 *2 2/ N 3*2 1/2 32.0 INC RESPIRATORY DEPTH 4 161 0 8 32,0 3,2 2/2 IRREGULAR RESPIRATORY DEPTH361 0 60 T INTRAVENOUS TOXICITY 'TO MICE DILUT REACT- REACTION DOS E SIGN MINE DEG MIK- To t,IG/KG ML/KG FRACT* APPR REE RECOVER 1/ 2 162 0 8 32.0 3,2 2 INC RESPIRATORY RATE 2/2 IRREGULAR RESPIRATORY RATE 362 0 60 32,0 3*2 MOT DEF HORIZONTAL WIRE 0 32*0- 3*2 2/2 2 171 60 32,0 .3,2 2/2 @Mot DEF VERTICAL SCREEN 271 0 60 2*0 392 2/2 1 60 0 3 MOY DEF 2 HOR ZONTAL STRIP 471 32.0 3o2 2/2 M(5T DEF VERTICAL ROD 371 0 60 '22 o 0 .3 a 2 2/2 771 60 MOT DEF ROTA-ROD 0 32*0 3,2 2/2 MOT DEF INCLINED STRIP 671 0 60 32,0 3,2 1/2 ABNORMAL VIBRISSAE 1.72 8 60 32.0 .3.2 2/2 LOW 'CARRIAGE 175 .8 60 1090 10*0 DEC -LOCOMOTOR 2 ACTIVITY 30 120 1/2 124 lo,o 1010 2/2 DEC-SENSITIVITY TO PAIN 229 .30 i8o 1010 1000 -2/2 INC SENSITIVITY To TOUC2H 131 0 G 300 jo.0 .1010 1/2 -DEC REARING FREQUENCY 632 30 120 1000 10:0 1/2 MYDRIASI-S 154 30 120 1000 1000 2/2 SALIVATION 57 8 260 10.0 .1000 -2/2 IRREGULAR RESPIRATORY DEPTH361 0 30 . 1000 .10*0 2/2 I.RREGULAR RESPIRATORY RATE 562 0 30 302 .3i2 1/2 DEC SENSITIVITY TO PAIN 229 15 .180 2 3,2 302 '2/,2 INC SENSRTIVITY TO TOUCH 131 0 G 300 i.o lo,o 1/2 ABNCRMAL REACTION TO PAIN .429 120 G 240 1000 -2/2 131 15 G 100 INC SENSITIVITY T2O TOUCH 240 @0,,32 3,2 NO EFFECT 2/2 73 '2/2 DEATH 74 0 5010 5,0 40,0 .4,0 @2/2 DEATH 7 74 0 32,0 .302 0 '2 DEATH 74 0 @25,0 .2.5 0 /2 DEATH 74 0 DILO OS C-H20 2367W L050 1009 0 .--63oO-l6O*O- -0 9 56-5 6-- MED50 1 0 8 'RATIO LD50/MED50 @56*0 LID !STATE2 SO 'TO MICE INTRAVENOUS'TOXICITY -DOSE DILUT REACTil REACTION SIGN MINO 'DEG-- MIN* TO MG/KG @ML/KG FRACT* APPR REE RECOVER 10010 .1 0 1/2 DEATH 74 2 0 10010 @i,o @DEC 1/2 -LOCOMOTOR ACTIVITY 124- 0 180 .0 ioo.o I 40 1/2 DEC 'SENSITIVITY TO TOUCH 231 60 2 0 100 .1 0 1/2 DEC-SENSITIVITY'TO SOUND 230 60 100 0 .1:0 1/?- DEC -PREENING 240 0 120 0 1 5 2 'EXTENSION OF LIMBS 10000 io 1/2 341 10000 1- 0 :1/2 'PROSTRATION .43 0 1 5 100*0 1:0 1/2 EYELID PTOSIS-NONPARALYTIC 149 8 180 -PUPILLARY-2LIGHT REFLEX ABS 152 15 loo.o @1.0 1/2 60 100 0 1*0 -1/2 MYDRIASIS 154 15 60 100:0 1*0 1/2 'DEC RESPIRATORY DEPTH .261 0 30 2 INC RESPIRATORY DEPTH -A 100,,O 100 1/2 161 @30 120 IRREGULAR RESPIRATORY DEPTH361 0 30 10010 1 0 1/2 DEC RESPIRATORY RATE 2 100,0 1:0 1/2 262 .30 120 100.0 110 1/2 IRREGULAR RESPIRATORY RATE 362 0 30 DEF HORIZONTAL WIRE .0 100,,O 100 1/;, MOT 171 15 2 10000 100 1/2 MOT DEF VERTRCAL SCREEN 271 0 15 471 0 100.0 .110 1/2 MOT DEF HORIZONTAL STRIP 15 10000 100 1/2 MOT-DEF VERTICAL ROD 371 0 30 .100 1/2 MOT DEF ROTA-ROD 7 15 0 10000 71 0 100*0 1.0 1/2 MOT DEF INCL1INED STRIP 671 30 236 7W INTRAVENOUS TOXICITY -10 MICE DOSE DILUT REACTO REACTION SIGN MIND DEG- MINO TO MG/KG ML/KG FRACTO 2 APPR REE RECOVER 0 120 32oO Oo64 2/2 DEC LOCOMOTOK ACTIVITY 124 - 2 DEC SENSITIVITY TO PAIN 60 32.0@ 0 64 1/2 229 30 32 o-O AANORMAL REACTION TO PAN 429 30 0:64 1/2 2 60 0964 2.1' 2 32,0 DEC SENSITIV'&TY TO TOUCH 231 0 60 32.0,- 0064 2/2 SOCIAL INTERACTION ALTERED 132 0 iBo 32.0 0.64 2/2 bEC REARING FREQUENCY 2 632 0 120 0 5 32oO Oo64 2/2 ATAXIA 35 IL Oo64 2/2 32.0 DEC PREENING 2 240 0 180 .32eO- 0.64 1/2 LOW POSTURE 241 0 30 ION OF LIMBS 341 0 30 Oo64 2/2, .32 o 0 EXTENS2 EYELID PTOSIS-NONPARALYTIC 149 8 120 32*0 -Oo64 2/2 32,0 Oo64 1/2 -PUPILLARY LIGHT REFLEX ABS 152 8 60 0,64 1/2 MYDRIASIS 8 2 60 32oO 154 .0064 2/2 INC 32*0 RESPIRATORY DEPTH 161 0 120 .32,0 Oo64 2/2 IRREGULAR RESPIRATORY DEPTH361 0 30 2 32oO @0,64 2/2 DEC RESPIRATORY RATE 262 0 120 32og 0.64 2/2 IRREGULAR RESPIRATORY RATE 362 0 30 32.0 1/2 MOT DEF HORIZONTAL WIRE 171 0 1-5 32*0 20 64 112 MOT DEF VERTICAL SCREEN 271 0 ---5 32,0 0:64 2/2 MOT Dc-F HORIZONTAL STRIP 471 0 30 Oo64 1/2 MOT DEP VERTTCAL.ROD 371 0 - '5 32oO Oo64 2 1/2 MOT,DEF ROTA-ROD 771 30 0 32oO Oo64 1/2@ MOT DEF INCLINED STRIP 671 30 io.0 loO 2/2 DEC-LOCOMOTOP, ACTIVITY 2 124 0 120o 1010 .100 1/2 DEC SENSITIVITY TO PAIN .229 30 180 1000 110 2/2 -DEC-SENSITIVITY'TO TOUCH 231 0 60 @SOCIAL INTERACTION 2 ALTERED 132 loeo I 0 2/2 0 180 .0 io.o 1 0, -2/2 DEC REARING FREQUENCY @632 2 120 1010 1,0 '2/2 -DEC PREENING 240 0 120 1000 110 1;2 LOW POSTURE 241 30 180 10 a 0 1.0 2/2 EYELID PTOSIS-NONPARALYTIC 149 8 2 120 1010 loO 2/2 1 RREGULAR.RESPIRATORY DEPTH361 0 30 EGULAR RESPIRATORY RATE 362 0 30 1010 110 2/2 IRR 1000 2 110 1/2 MOT-DEF HORIZONTAL WIRE 171 .0 .1000 @l 0 1/2 MOT DEF VERTICAL SCREEN 271 0 8 10.0 1:0 1/2 MOT DEF HORIZONTAL C.TRIP 471 0 30 2 371 8 1/2 10 0 0 1 0 MOT DEF VERTICAL ROD 0 .0 10 0 0 1:0 1/2 MOT DEF ROTA-ROD' 2 771 - 10,.O 1.0 1/2 @MOT DEF INCLINED STRIP 671 0 30 2/2 3,2 1,6 DEC LOCOMOTOR ACTIVITY 124 30 izo -3*2 lo6 2/2 6 SOCIAL INTERACTION ALTERED 132 30 12 3o2 1.6 2/2 DEC REARING FREQUENCY 632 30 120 CS 2367W 3 INTRAVENOUS T OXICITY TO MI,CE REACTION SIGN MIN6 DEG- MIN. TO DOSE DILUT REACT* APPR REE RECOVER MG/KG ML/KG FRACT* 2 240 30 120 .3,2 1.6 2/2 DEC PREENING 30 120 1,6 2 ALYTIC 149 'EYELID PTOSIS-NONPAR 3 2 /2 73 1*0 0*250 2/2 NO EFFECT 74 0 '2 Z 130.0 1,3 DEATH 74 0 '79oO 0679 0 2 DEATH - 74. 0 63.0 0*63 1/2 DEATH 10096 PEG 3002 GS C 1000,6 PEG 300 -DIL* 2516 W -LO50 100,0 -79.0-12000- MED50 '596 -1*8-18*0- RATIO LD50/MED50 1800 STATT. SOL2ID INTRAVENOUS TOXICITY'TO MICE DOSE -DILUT REACT* REACTION SIGN MINE DEG- MIN, TO MG/KG @ML/KG FRACTO APPR REE RECOVER 00 0 0 1010 1/2 @DEATH 74 2 0 -0010 10 0 1/2 DEC.LOCOMCTOR ACTIVITY 124 15 300 100 0 1010 1/2 DEC SENSITIVITY TO PAIN 229 30 240 2ABNORMAL.REACTION TO PAIN 429 240 300 iooo 10.0 1/2 ioo,O 10*0 '1/2 DEC SENSITIVITY TO TOUCH 231 .30 240 10.0 1/2 DEC..REARING FREQUENCY 632 0. 300 ioo 0 0 1000 1/2 EXTENSION OF LIMBS 341 @15 120 lo 'PROSTRATION 0160 lOoO 1/2 4@ 15 120 .10.0 1/2 EXOPHTHALMOS .46 0 8 -.2--.,@@,iloo,o 1010 1/2 EYELID PTOSIS-NONPARALYTIC 149 15 300 10000 10 0 0 1/2 :PUPILLARY LIGHT REFLEX ABS 152 8 180 -.@.;''-Iloooo 1010 1/2 MYDRIASIS 2 154 8 180 100 0 ...-4 1010 1/2 INC RESPIRATORY DEPTH 161 0 .30 ,in"---Iloolo 10,0 1/2 DEC RESPIRATORY DEPTH 261 30 60 1 0 010 1010 2 1/2 -D@c RESPIRATORY RATE 262 0 60 i o 60 000 1090 1/2 MOT DEF HORIZONTAL WIRE 171 8 10010 10.0 1/2 MOT DEF VERTICAL SCREEN 2271 0 60 10000 iolo 1/2 MOT DEF HORIZONTAL STRIP 471 a 120 10000 1000 1/2 MOT DEF VERTICAL ROD 371 8 120 10010 1010 1/2 MOT DEF ROTA-ROD 771 8 3 60 @.7@-..,.,Iloolo 1010 1/2 MOT DEF INCLINED STRIP 120 671 8 Z516W INTRAVENOUS TOXICITY TO MICE REACTION SIGN MTNO DEG- MINO TO DOSE DILUT REACT* MG/KG ML/KG FRACTO APPR REE RECOVER lo2olo lo,o 1/2 -PILCERECTION 72 60 240 1/2 -LOW CARRIAGE 240 loolo. 1010 175 0 32*0 3*2 2)2 DEC LOCOMOTOR ACTIVITY 124 15 60 2 3a, 2 1 5 2 .32#0 /2 QEC REARING FREQUENCY 632 60 'RUBBING NOSE .3,2 1/2 340 8 30 @2.0 32.0 3 2 '2/2 ':UNU2SUAL POSTURE 541 0 15 3:2 2/2 EYELID PTOSIS-NONPARALYTIC 14 32*0 9 1 5 120 32oO 3*2 2/2 PUPILLARY-LIGHT REFLEX ABS 152 8 180 32*0 3e2 .-2/2 MYORI2ASIS 154 8 180 .32*0 3,2 -2/2 INC RESPIRATORY DEPTH .161 0 30 32*0 3o2 '@2/2 INC-RESPIRATORY RATE 162 0 30 32*0 3,2. 1/2 MOT DEF ROTA-ROD .771 8 30 32,0 .3*2 '2/2 LOW CARRIAGE 175 0 30 1000 1010 -2/2 EYELID PTOSIS-NONPARALYTIC 149 30 120 1010 ioo;o 2/2 PUPTLLARY.LIGHT,REFLEX ABS 152 8 120 10.0 10.0 2/2 MYDRIASIS 154 8 120 10.0 10.0 @2/2 IRREGULAR RESPIRATORY DEPTH361 @o 30 @.10*0 1010 @/2 IRREGULAR RESPIRATORY RATE 362 0 30. 3,2 73 302 2/2 NO EFFECT 2 '74 .0 .120*0 lZoO 2/2 -DEATH 8010 @810 0 / 2 DEATH 74 0 DEATH 74 0 ..63,0 6,3 O/ 2 100% STEROL DILE SUSP QS 2 C H20 @DIL* 2531 W -89*0-1-40*0- LD50 11090 MED50 3*2 -leO-10oo-. RATIO LD50/MED50 2 3500 STATE SOLID -TO MICE INTRAVENOUS@TOXICITY DosE ;DILUT REACT* REACTION-SIGN MINA '!DEG-. MIN* TO MG/KG ML/KG FRACTO 2 APPR REE RECOVER ioo,o 10 0 2/2 -DEC.LOCOMOTOR ACTIVITY 124 .0 300 10060 .10.0 2/2 DEC @SENSITIVITY'TO'TOUCH .231 0 2 60 2 60 /;, SOCIAL INTERACTION ALTERED .132 0 10000 1010 10000 10'.0 2/2 DEC REARING.FREQUENCY 632 0 300 2 @o 30 10000 10,0 1/2 EXTENSION OF LIMBS 341 10000 1010 1/2 ;RIGHTING REFLEX DEPR 742 .8 100*0 10,0 -- 2/2 - :PROSTRATION 2 ..43 .0 30 .2/2 .15 G 10010 10.0 'EYELID PTOSIS-NONPARALYTIC 1-49 300 .2/2 180 100.0 1010 INC RESPIRATORY DEPTH 161 :0 J.0000 @10,0 -2/2 @DEC RESPIRATORY'RATE .262 0 180 100-0 10.0 -2/2 @MOT @DEF HORIZONTAL WIRE 171 0 60 100200 10*0 -2/2 MOT DEF'VERTRCAL SCREEN 271 60 0 10000 10.0 2/2 MOT:DEF HORIZONTAL-STRIP .471 0 120 @371 2 0 @60 10000 10-0 2/2 MOT DEF VERTICAL ROD 100*0 10-0 2/2 MOT @DEF ROTA-ROD '771 60 loo,o 10 0 2/2 MOT DEF INCLINED2 STRIP 671 0 120 10060 1010 2/2 LOW'CARRIAGE 175 30 60 ACTIVITY 32*0 3,2 2/2 124 28 12'0 32*0 -SOCIAL INTERACTION ALTERED 132 0 .3 o 2 2/2 60 632 0 32,0 3,2 2/.2 DEC REARING FREQUENCY 3 60 2@3 1W 2 INTRAVENOUS TOxrcITY 'TO MICE DOSE DILUT REACT* REACTION SIGN MIN* DEG-- MIN- TO MG/KG ML/KG FRACT* APPR REE -RECOVER 2/2 '2EYELID PTOSIS-NONPARALYTIC 149 15 60 32.0 3z2 32,'O. 3,2 -2/2 INC RESPIRATORY DEPTH 161 0 60 32-0 3*2 DEC RESPIRATORY RATE 0 60 2/2 262 2.0 3,22 @2/2 MdT DEF HCRIZONTAL STRIP 471 0 30 'TICAL ROD 32.0 -3*2 1/2 MOT Dcc VE.R 371 0 30 32-0 3 2 @2/.2 MOT DEF INCLINED STRIP 671 0 3 O' 10 00 2 2/2 'EYELID PTOSIS-NONPARALYTIC 149 60 240 000 -NONPARALYTrc 149 .3 2 .3 02 EYE ID PTOSTS 60 240 2 L .3*2 1302 1/2 NO 'EFFECT 2 73 .100 10.@o -2/2 NO EFFECT 73 160*0 .16,0 -2/2 DEATH 74. 0 .12000 12,,O '2/2 DEATH 74 0 7990 '7*9 0 2 DEATH 74. 0 DIL. 5 1000,6.STEROL,DILO SUSP OS C H20 PAGE 2598 INTRAVENOUS TOXRCITY TO MICE DOSE DILUT REACTA 2 REACTION 'SIGN MIN*' DEG- MIN* TO AF:RP'R REE RECOVER t@LG / KG ML/KG FRACT* 0*032 3,2 @2/2 HEAD TWITCH 531 120 2 240 1/@ INC PREENING 140 120 G 300 0,032 3,2 OoO32 3*2 1/2 INC SCRATCHING 440 180 G 300 EYELID PTOSIS-NONPARALYTIC 2 149 120 G 300 0*032 3*2 2/2 0,032 3.2 2/2 PHOTOPHOBIA '53 120 G 300 0 9 032 3,i2 2/2 PI'LOERECTION 72 120 G 300 O2oO32 3e2 1/2 SKIN FLICK 79 120 240 .00010 10*0 2/2 DEC LOCOMOTOR ACTIVITY 124 15 G 120 01010 1010 2/2 HEAD TWITCH 2531 1 5 1 2 00010 INC PREENING 140 15 G 120 1000 2/'2 @0#010 1000 1/2 RUBBING NOSE 2 340 3 0 G 120 01010 10.0 1/2 INC SCRATCHING 440 .15 G 120 a LOERECTION -72 15 G 0 010 .10.0 1/2 Pi 2 120 0.010 10.0 2/2 SKIN FLICK 79 1 5 G 120 3 a 2-@3 .3*2 2/2 DEC LOCOMOTOR ACTIVITY 124 30 G 120 3 2-3 @3.2 2 2 TWITCH 531 3 0 G I2 0 -3 302 2/2 -INC PREENING 8 120 3 2 140 G 2 3:2--3 3*2 2/2 SKIN FLICK 79 1 5 G 120 1*0-3 10*0 1/2 LICKING'COMPARTMENT WALLS 825 30 G 120 1*0-3 10 0 0 1/2 INC PREENING 140 2 60 G 1-20 1,0-3 100'0 1/;' NO EFFECT 73 @3*2-4 3 *'Z 1/2 LICKING COMPARTMENT WALLS 825 30 G 120 .3,2-4 .3 62 1/2 INC PREENING 2 140 30 G 120 3,.2-4 '3 2 1/2 NO EFFECT 73 -390i ATH .0 0 8 0 @DE 74 3 2 2 25*0 .510 0 2 -DEATH 74 .0 '2090 .4 0 /2 -DEATH 74 :O. 0 DlLo :Ool @N HCL 05@C H20 PAG E 2598 INTRAVENOUS TOXICITY'TO MICE DOSE DILUT 2REACT* REACTION'SIGN MINE DEG- MfN. TO AP PR REE RECOVER bIG/KG ML/KG'FRACTw 2 312 3.2 Z/Z' DEC LOCOMOTOR ACTIVITY 124 120 G 300 'COMPARTMENT WALLS .302 .3,2 1/7, LiCkING 825 60 120 3.2 .3 0 2 2/2 INC SENSITIVITY'TO PAIN 129 60 300 G 300 302 3.2 -2/2 INC SENSITIVITY TO TOUCH 131 32 2 3,2 '2/2 HEAD TWITCH 531 30 300 3:2 .3*2 :2/2 SOCIAL INTERACTION ALTERED 132 30 120 392 302 -2/2 DEC REARING FREQUENCY 632 30 .180 2 3,2 3,2 1/2 DEC PREENING 240 30 60 3e2' 3,2 1/2 INC PREENING 140 120 G .300 302 3.2 1/2 RUBBING NOSE 340 8 2 30 342 .3,2 2/2 INC SCRATCHING .440 180 G 300 -3,2 3*2 EYELID PTOSIS-NONPAAALYTIC 149 60 1/2 G 2 300 .3.2 @3*2 1/2 PHOTOPHOBIA .53 60 G 300 3 0'2 3.2 -2/2 'PILOERECTION 72 60 300 .392 SKIN FLICK 79 1220 G- 300 I 0 lo,o 1/2 -DEC.LOCOMOTOR ACTIVITY 124- 30 G 300 i:o 1000 1/2 LICKING'.COMPARTMENT WALLS 825 120 ISO INCLSENSITIVITY'TO 2 TOUCH 100 .10.0 t2/2 131 8 300 110 10 0 @1/2 'HEAD TWITCH 531 60 2 .240 ISO 100I0 '2/2 INC PREENING 140 120 G 300 .110 10.0 2/2 :EYELID PTOSIS-NONPARALYTIC 149 60 G 300 2 1 0 0 .1010 2/2 'PHOTOPHOBIA 60 G .300 CTION .60 300 1 0 10 0 2xzl LOERE 72 2 .1.0 .1010 2/2 SKIN FLICK 79 t6O @300 @0,32 @3.2, 1/2 LrCKING@COMPARTMENT WALLS 825 120 ISO '0-32 2 2/2 INC-SENSITIVITY To 2 TOUCH 131 15 300 0*32 @3*2 1/2 INC,PREENING 140 120 300 0*32 3 '2 1/2 INC SCRATCHING .440 180 G 300 !0,32 :30'2 '2/2 2 :EYELID PTOSIS-NONPARALYTIC 149 60 G .300 :o*32 -.3.2 '2/2 'PHOTOPHOBIA 53 60 G 300 '7 2 .60 240 @0*32 2 i3,2 2/2 :PILOERECTION ;0*32 3 2 '2/2 SKIN FLICK '79 .60 300 -COMPARTMENT WALLS 825 @120 2 .0 a 10 10 0 1/2 LI'CKING . ISO a 10 lOoO 1/2 INC SENSITIVITY TO TOUCH 131 .30 180 .0 a 10 10.0 1/@ @HEAD-TWITCH 2 531 .30 240 0 10 10.0 -1/2 INC PREENING 140 120 240 @0:10 io*O -2/2 EYELID PTOSIS-NONPARALYTIC 149 120 G 300 .01,10 2 10 0-0 -2/2 PHOTOPHOBIA 53 120 G 30C 0010 1000 2/2 PILOERECTION 72 60 30C 10 10.0 -2/2 SKIN FLICK '7 9 .60 6 24C FEW @p I PAGE 2 59 8 LD50 '28,0 -2290-3600- MED50 3i2-4-1.0-4-1*0-3- R2ATIO LD5o/MED50 -STATE-SOLID INTRAVENOUS-TOXICI-TY@TO MICE DEG- MIN, TO DOSE DILUT REACTS, REACTION SIGN MIN* MG/KG ML/KG FRACTO APPK REE RECOVE2R 74 .0@ .104 -DEATH 00*0 0 '2/2 0 @32,0 :3 2 2/2 @DEATH 74 .1000 10.0 -2/2 DEC.LOCOMOTOR ACTIVITY 124 8 30 .1. 0 LICKING COMPARTMENT W 180 1000 0 0 1/2 ALLS 825 240 10 a 0 1090 -2/2 INC--SENSITIVITY'To TOUCH 2 131 @30 240 0 000 10 1/2 AD TWITCH 531 30 240 1000 1000 2/2 SOCIAL INTERACTION,ALTERED 132 0 120 1010 1010 2/2 -DEC REARING'FREQUENCY 632 0 2 G 300 10*0 10.0 2/2 1DEC PREENING 240 .0 180 lqso .104'0 1/2 INC PREENING 140 180 G 300 10 0 0 10.0 RUBBING NOSE 340 8 60 2 1000 100,0 -2/2 :EXOPHTHALMOS .46 0 15 G 300 1000 .1090 @2/2 'EYELID PTOSIS-NONPARALYTIC 149 60 1000 1000 2/2 PHOTOPHOSIA2 53 60 G 300 1000 1000 -2/2 IRREGULAR RESPIRATORY DEPTH361 0 15 10*0 1010 -2/2 IRREGULAR RESPIRATORY RATE 362 .0 15 1010 10.0 i/2 MOT DEF HORIZONTAL STRIP 471 2 8 60 io.o lo,o 2/2 :PILOERECTION 72 30 300 1010 10.0 2/2 SKIN FLICK 79 30 G 300 77777777777777777 PAGE A 2717 V -LD50 36 90 -28*0-45oO-. 2 MED50 0,,56 -O t 18-1 o 8-- @RATIO LD50/MED50 6300 STATE-SOLID- INTRAVENOUS'TOXICITY'TO MLCE 2 DEG-- MINe'TO DOSE DILUT REACTO REACTION SIGN MIN* MG/KG ML/KG 'FRACT* APPR REE RECOVER 2 'DEATH 0 '0010 1000 2/2 74 .32,0 2 12/2 -DEC -LOCOMOTOR-ACTIVITY 124- 8 G 300 2 i o' .32*0 @3i2 2/2 :DEC TOUCH -231 30 -2/2 @O 32,0 @3.22 SOCIAL INTERACTION ALTERED 132 .60 0 '2/2 DEC KEARI .32.0 3 '2' NG'FREQUENCY .632 G 300 32-0 3,2 '1/2 'EXTENSION OF-LIMBS 2 341 0 30 .32:0 -@3'o2 1/2 -TREMORS-REST AND MOVEMENT 144 0 15 @32.0 3 0'2 1/2 'TREMORS-MOVEM2ENT'ONLY 244 0 30 32,0 -- 3 o 2 '2/2 .@EYELID PTOSI-S-NONPARALYTIC 149 8 G 300 73290 .3*2 '2/2 INC'URINATION @158 -8 30 2 -32*0 3*2 '2/2 INC RESPIRATORY DEPTH 161 @o 60 .32oO .3,2 2/2 IRREGULAR RESPIRATORY DEPTH361 o@ 60 .32iO 3.2 @2/2 IRREGULAR-RFSPIRATORY RATE .362 2 .0 60 .3 2 o 0 3*2 2/2 MOT-DEF HORIZONTAL WIRE 171 0 .60 .32*0 .3*2 2/2 MOT DEF VERTICAL SCREEN 271 0 60 3290 3,2 2/2 MOT DEF HORI2ZONTAL STRIP -471 .0 120 'MOT DEF VERTICAL ROD 371 0 180 32,0 3,2 '2/2 0 2 32.0 .302 -2/2 MOT DEF ROTA-ROD '771 120 32*0 3o2 2/2 MOT DEF INCLINED STRIP 671 0 120 32,0 302 2/2 LOW:CARRIAGE .175 .0 30 2 l@17W 2 INTRAVENOUS TOXICITY TO MICE DOSE DILUT REACT, REACTION SIGN MIN, DEG MIN. TO MG/KG ML/KG FRACT4 APPR REE RECOVER 2 o lo,o 1/2 EYEL,B PT05IS-NONPARALYTIC 149 60 240 1000 1010 1/2 DEC LOCOMOTOR ACTIVITY 124 60 2 f# 0 E 362 0 1-000- 10.0 2/2 IRREGULAR R2ESPIRATORY RA 30 3.2 3.2 .2/2 IR@EGULAR RESPIRATORY RATE 362 0 i5 1,,O 120 2/2 1010 INC LOCOMOTO2R ACTIVITY 224 60 .0,32 3,2 2/ -FECT 73 2 NO Er 010 5,0 2/2 DEATH 74 0 40,0 .4*0 2/2 DEATH 74 0 25*0 2,5 0 2 DEATH 8 74 0 100"a STEROL DIL* SUSP 05 C H20 2778 W LD50 .4590 -36oO-56oO- MED50 5*6 --108-18oO- RATIO -LD50/MED50 8oO STATE SOLID INTRAVENOUS TOXRC!TY TO MICE DILUT REACT* MIN* -DEG-- MIN,, TO DOSE REACTION SIGN MG/KG ML/KG'FRACT* APPR REE RECOVER 0010 10 0 0 2/2 DEATH 74 0 32 @3o2 -2/2 DE2C@LOCOMOTOR ACTIVITY 124 0 .0 240 32.0 3e2 1/2 HEAD TWITCH 531 60 120 fto 32,0 3.2 -2/2 SOCIAL INTERACTION A2LTERED 132 0 32,0 3,2 '2/2 DEC REARING FREQUENCY 632 0 240 32.0 3 2 -2/2 LOW POSTURE- -241 0 60 EYELID PTOSIS-NONPARALYTIC 149 32aO 3o2 -2/2' 15 240 3200 3,2 '2/2 DYSPNEA 60 0 8 32.0 .3,2 2/2 INC RESPIRATORY DEPTH 161 0 120 32.0 -3.2 'DEC RESPIRATORY RATE 262 0 120 32*0 23o2 :2/2 IRREGULAR RESPIRATORY RATE 362 0 60 32oo 3,2 .2/2 LOW'CARRIAGE 175 0 30 10.0 10*0 2/2 EYELID PTOSIS-NONPARALYTIC 149 15 1&80 3.2 3,2 .2/2 NO EFFECT 73 7 63,0 6,3 2/2 DEATH 74 0 .2/2 74 0 50.0 @5,0 DEATH 77777. 2 78 7 W INTRAVENOUS TOXICITY TO MICE DEG- M14. TO CT* REACTION SIGN m DOSE DILUT REA IN, MG/KG ML/KG FRACT* 6 APPR REE RECOVER 40,0 -410 0/2 DEATH 74 0 25*0-- 2.5 0/2 DEATH 74 0 )TL* 10 01,110 STEROL DIL* SUSP QS C H20 2867 W 1690-25oO- LD50 2OoO 0018 .-OoO56-Oo56- RATIO LD50/MED50 llOsO -STATE SOLID INTRAV2ENOUS'TOXICITY'TO MICE MINI TO DOSE @DILUT REACT* REACTION SIGN MIN, 'DEG PPR REE RECOVER MG/KG -ML/KG FRACTO A 10010 10,0 -2/2 :DEATH 2 74 @o 74 0 32*0 3 0'2 -2/2 DEATH 120 124. 8 10*0 1010 2/2 DEC LOCOMCTOR ACTIVITY 2 0 240 .2/2 lo.o 10*0 -SOCIAL INTERACTION ALTERED 132 @632 @o 120 -2/2 ----DEC REARING'FREQUENCY 1010 10,0 20 8 -STRAUB'TALL 1010 10.0 -1/2 0 8 1010 1000 1/? MIXED'CONVULSIONS io.o lOtO -1/2 :CPISTHOTONOS 38 0 8 JO2.0 'INC 1-40 0 120 10-0 :2/2 -PREENING 1010 10io 2/2 LOW POSTURE 241 0 120 1010 10,0 'TREMORS 1/2 -REST AND MOVEMENT 144 8 10.0 10 0 -2/2 EYELID PTOSI$-NONPARALYTIC .149 0 240 10 0 10,0 -2/2 'PUPILLARY.LIGHT REFLEX ABS 152 8 30 10:0 lOoO 2/2 MYORIASIS .154 8 30 1010 1010 1/2 DEC.RESPIRATORY DEPTH 261 320 120 10.0 10.0 -1/2 INC RESPIRATORY DEPTH 161 30 120 1000 lo,o 2/2 IRREGULAR RESPIRATORY DEPTH361 0 120 1000 10*0 2/2 DEC RESPIRATORY RATE 262 30 120 1010 1010 2/2 IRREGULAR RESPIRATORY R5ATE 362 0 120 7i@ 2867 W 2 TOXICRTY TO MICE INTRAVENOUS MIN,, DEG- MINO TO DOSE DILUT R2EACT* REACTION SIGN APPR REE RECOVER :4G/KG ML/KG FRACTO MOT 71 15 120 1/2 2 JO.0 1010 DEF VERTICAL SCREEN 2 15 1-20 io.o.. 10.0 2/2 MOT DEF HORIZONTAL STRIP .471 120 1000- 10*0 2/2 MOT DEF,V@RTICAL ROD 371 15 r 102.0 -2/2 10,0 MQt DEF ROTA-ROD 771 15 120 2/2 120 io,o 1000 moT DLC-F INCLINED STRIP 671 1 5 1;14 8 120 .3*2 3,2 2/2 DEC LOCOMOTOR ACTIVITY G 300 3*2 3o2 1/2. INC SENSITIVITY TO SOUND 130 60 G 300 !VITY TO TOUCH 131 60 3.2 3,2 2/2 INC SENSRT .3,2 2/2 SOCIAL INTERACTION ALTERED 132 0 180 3,2 CYL 3,2 .3.2 2/2 DEC REARING FREQUEN 632 0 60 3o2 3*2 2/2 !DEC REARING,HEIGHT 732 0 60 2 0 2 3 2 DEC P 3 -2/2 REENTNG 240 120 .241 0 30 2 3:2 @2/2 -LOW POSTURE 8 I2 0 2 3.2 3.2 -2/2 EYELID PTOSIS-NONPARALYTIC 149 392 .3o2 2/2 PUPILLARY LIGHT REFLEX ABS 152 8 30 3.2 3.2 2/2 MYDRIASIS 154 8 30 3.2 3.2 -2/2 IRREGULAR RESPIRATORY DEPTH361 0 120 3 2 3.2 ;2/22 IRREGULAR RESPIRATORY RATE 362 0. 120 0 1*0 10-0 -2/2 INC-SENSITIVITY T TOUCH 131 .60 G 30 1.0 1010 2/2 INC PREENING .140 60 G 300 110 1010 1/2 'EYELID PTOSIS-NONPAR2ALYTIC 149 .60 G 300 0 .30 60 0*32 3,2 2 2 INC SENSITIVITY TO SOUND 13 oo32 .3*2' -2/2 INC 140 ;60 300 0010 1000 '2/2 NO'EFFECT 73 2 510 - '74- 0 250-0 .2/2 TDEATH 2OoO .4,0 1/2 DEATH 74- 0 '7 4 0, 16*0 3*2 0 / 2 DEATH 2.0 12,0 0/2 DEATH 2 74 0 DILE :H20 OS@C H20 2897 w -LD50 100 9 0 --79,0-120 0-- MED50 lo8 --0,56-5,6- RATIO LD50/MED50 56*0 STATE SOLID 2 INTRAVENOUS TbXrCITY TO MICE DOSE DILUT' REACTO REACTION SIGN MINO DEG-- MTN.-TO MG/KG ML/KG FRACT, APPR REE REROVER 10000 1010 1/2 DEATH 2 74 0 100.0 lojo 1/2 @DEC.-LOCOMOTOR ACTIVITY 124 0 G 300 100 0 0 1000 1/2 -DEC SENSITIVRTY TO P -.t' AIN 2292 120 8 10000 1000 1/2 @DEC@SENSITIVITY'TO SOUND -230 8 180 100.0 10.0 1/2 DEC SENSITIVITY TO TOUCH 231 8 180 100-0 10-0 -1/2, @PEC.REARING FREQUENCY 632 0 G 300 100.0 10.0 172 @LIMP TAI.L 333 .0 120 10000 1000 1/2 DEC MUSCLE2'TONE-TRUNK 237 8 ioo,o 120 1010 i/2 DEC MUSCLE'TONE-LIMBS .437 8 120 10.0 1/2 -DEC PREENING 2 '240 0 G 300 @100.0 10.0 1/2 -'EXTENSION OF-LIMBS 341 0 100..O 60 10*0 1/2 ;PLACING REFLEX ASS .442 0 60 10010 10210 1/2 GRASPING REFLEX ABS 642 8 60 100,0 10,0 1/2 LABYRINTHINE REFLEX ABS 042 0 60 100.0 1.0.0 1/2 -PROSTRATION .432 0 60 100,00 10.6 1/2 EXOPHTHALMOS 46 @o 30 100.0 io.o 1/2 'EYELID PTOSIS-NONPARALYTIC 149 8 G 300 100.0 1010 1/2 INC 2 RESP'LRATORY DEPTH 161 0 8 100.0 10.0 1/2 DEC RESPIRATORY DEPTH 261 8 240 10010 1010 1/2 IRREGULAR RESPIRATORY RATE 362 0 240 100000 10.0 1/2 MOT DEF HORIZONTAL WIRE 171 0 300 2897 W 2 -TOXICITY TO MICE INTRAVENOUS REACTION SIGN m MIN TO IN, DEG- DOS2E DILUT REACT* REC;VER t-IG APPR REE /KG ML/KG FRACT* 0 MOT DEF VERTICAL S-CREEN 271 300 2 ioo.o lo,o 1/2 MOT DEF HORIZONTAL STRIP 471 0 G 300 100.0 1010 1/2 0 300 Ino 0 .10.0 1/2 MO.T DEF VERTICAL ROD 371 2 0 300 J.00:0 io.0 1/2 MO'T DEF ROTA-ROD 771 G 300 6721 0 10010 1010 1/2 M-OT DEF INCLINED STRIP 0 G 300 2/ 124 @10 3,2 2 DEC LOCOMOTOR ACTIVITY 32.0 3,2 -2/2 DEC REARING FREQUENCY 2 632 60 G 300 32oO- 3,2 2/2 DEC PREENING 240 60 G 300 '2/2 EYELID PTOSIS-NONPARALYTIC 149 60 G 300 32*0 3,2 32*0 3*2 2/2 IRREGULAR RESPIRATORY RATE 362 0 120 10.0 2 10.0 @2/2' INC SENSITIVITY TO TOUCH 131 60 180 2/2 INC PREENING 140 60 120 1010 10.0 302 3c,2 2/2 INC SENSITIVITY'TO TOUCH 131 :60 120 2 0 120 3*2 1/2 3 0 2 INC PREENING 140 6 110 .10.0 2/2 NO EFFECT 73 120.0 12,0 -2/2 DEATH 74 .0 -7.9 DEATH 74 0 7990 0 2 0 -DEATH 74. 63,0 693 0 2 DI 100% STEROL DILO 5USP OS C H20 La 2935 W -56oO LD50 45.0 -36*0 MED50 5,6 -Lo8-1800- 2 RATIO LD50/MED50 800 ATE SOLID INTRAVENOUS TOXICITY TO MICE MIN* TO 0 REACTION SIGN MIN* DEG- OSE -DILUT REACT* APPR REE RECOVER G/KG -.ML/KG FRACTO 10*0 '2/2 DEATH 74 0 0 'o 74 i6O 2 I/ 2. TDEATH 2@0' @3@2' - 0 G 300 2 0 .13 i2, 1/2 DEC LOCOMOTOR ACTIVITY 124 2 ITY TO TOUCH 231 15 G 300 2*'O 3'0'2 -1/2 DEC SENSITIV 210 3.2 1/2 DEC REARING FREQUENCY 632 0 G 300 210 3.2 1/2 PUPILLARY LIGHT REFLEX DEPa252 0 240 sis 154' 0 240 2,0 3,2 1/2 MYDRIA .200 3i2 1/2 INC RESPIRATORY DEPTH 161 0 G 300 0 .341-2 1/2 2 DEC RESPIRATORY RATE 262 0 G 300 2:0 3.2 1/2 IRREGULAR RESPIRATOAY RATE 362 0 G 300 @'@A .040 io.,O 2/2 PUPILLARY LIGHT REFLEX OEPA252 .0 iso oio 10*0 2/2 MYDRIASIS 154 0 180 302 3,2 2/2 NO EFFECT 73 13*0 6.3 2/2 DEATH 74 30 8 74 30 ;o o 510 2/2 -DEATH IW - - 29 3 5 INTRAVENOUS TOXICITY TO Ml'.CE DEG- MIN, TO I)OSE DILUT REACTO REACTION SIGN MIN. APPR REE 7 RECOVER ML/KG FRACT* MG/KG 0 0 2 .40.0 4,0 DEATH 74 lqo% STEROL DIL* SUSP OS C H20 L%IL* 29 63 W -LD50 10040 -79*0-120*0- MED50 0956,.-0*18-lo8- RAT'IO -LD50/MED50 180*0 ,STATE SOLID INTRAVENOUS2 TOXICITY'TO MICE DOSE DILUT REACT* REACTION SIGN MIN. -.DEG- MINA TO APPR REE RECOVER MG/KG ML/KG'FRACTO 74- 0 10040 10*0 1/2 DEATH ACTIVITY 124 0 120 2100.0 1000 1/z DEC LOCOMOTOR DEC SENSITIVITY TO SOUND 230 0 60 1/2 100 0 0 .1010 iviTY'To TOUCH 231 'O, 60 100*0 1000 1/2 DEC SENSIT 100.0 10.0 1/2 soCIAL.INTERAC2TION-ALTERED 132 0 120 120 loo,o 1010 1/2 DEC REARING FREQUENCY .632 - 0 60 t/2' -DEC'PREENING -240 .10000, 1000 2 60 241 8 a 100 a 0 10 0 1/2 LOW POSTURE 10000 JO.0 J/2 EYELID PTOSIS-NONPARALYTIC 149 8 iso ioooo 1000 '1/2 INC RESPIRATORY DEPTH 161 0 60 2 60 100.0 10.0 1/2 DEC RESPIRATORY RATE 262 0 0 10000 1000 1/2 MOT DEF HORIZONTAL STRIP .471 60 10000 10*0 1/2 MOT DEF VERTICAL ROD .371 .0 30 2 10090 1000 1/2 MOT DEF ROTA-ROD 771 0 3 iooeo 1000 1/2 MOT'DEF INCLINED STRIP 671 0 60 32eO 3,2 '2/2 DEC LOCOMOTOR ACTIVITY 124 30 0 .60 32,0 3.2 2/2 SOCIAL INTERACTION ALTERED 132 5 32,0 3,2 2/2 DEC REARING'FREQUENCY 632 0 60 32*0 3,2 -2/2 DEC PREENING @240 0 60 32,0 3,2 2/2 LOW POSTURE 8 30 17 2963 W -OXIRITY TO MICE INTRAVENOUS DCSE DILUT REACT, REACTION 5IGN MIN, DEG MIN* TO 2 APPR REE RECOVER '-IG/KG ML/KG FRACTO 180 EYELID PTOSIS-NONPARA'-YTIC 149 8 - 3,2 2/2 32oO 2 161 0 60 3*2 2/2 INC 32.0- RESPIRATORY DEPTH 32.0 3.2 2/2 DEC RESPIRA.ORY RATE 262 0 60 60 32,0 3,2 1!2 MOT DEF HORIZONTA! Q'RR!P .471 0 32*0 3,2 1.1' 2 MOT DEF VERTICAL ROD 371 0 30 1200 3 2 1/2 MOT DEF RO'I"A-ROD 771 0 30 00 3:2 1/2 MOT DEF IN"I"NED STR'P2 671 0 60 io.0- -,o.o 1,/2 DE%' LOCOMOTOR A,'--T'iVI7Y 124 8 30 10.0 10.0 SOEIAL !N@iERACi'ION ATERED '32 0 30 2/2 DEC REARING 2 FREQUENCY 632 0 120 io.o 10*0 1/2 180 EYELID PTOSTS-NONPARA-YTIC 149 io.o -010 1/2 1 5 210.0 1010 1/2 INC RESPIRA'@z'ORY DEPTH 161 0 30 1010 10.0 1112 DEC RESPIRATORY RATE 262 0 30 180 30'2 3o2 22/2 EYELID P'ROSIS-NONPARALYTIC 149 60 -DEC LOCOMO'@'OR ACTIVITY i24 .30 60 ioo 1010 22 1 0.32 .3,2' 2!2 NO EFFECT 73 120.0 1.2,0 2/2 DEATH 2 74 0 7o9 0 2 7990 -DEATH 74 0 .63,0 .6,3 0 2 DEATH 74 0 D l'i.. 9 3% ASCORBIC ACID QS C H20 ts 2984 W LD50 63oO --50.0-79*0- MED50 0,18 -OoO56-Oo56- RATIO LD50/MED50 2 35OeO -STATE SOLID TY TO MICE INTRAVENOUS TOXICI REACTION SIGN MIN* 'DEG-, MIN. TO 2 APPR REE -RECOVER DOSE DILUT REACT* MG/KG ML/KG FRACT* 0 74 10.0 2/2 @D2EATH 10000 .0 80 124 3,2 2/7 I)EC,LOCOMOTOR ACTIVITY 32.0 2 0 180 @SENSITIVITY'TO SOUND 230 .3 o 2 2/2. 1DEC UCH @231 0 180 32,.O 2 Y TO TO 32eO .3,2 @2/2 !DEC SENSITIVIT SOCIAL INTERACTION ALTERED 132 0 240 32.0 .3.2 @21;1 180 2 zz2 --,-,DEC 'REARING FREQUENCY @632 .-O - 32,0 3 -2-- iso 3o2 2/2 DEC MUSCLE TONE-TRUNK @237 0 2 @DEC MUSCLE TONE-LIMBS -437 0 180 32eO -302 2/2 240 .0 180 32.0 3,2 2/2 .-DEC PREENING. 842 0 2 60 @32,0 3,2 -2/2 @RIGHTING REFLEX ABS 180 -NONPARALYTIC 149 8 .32oO 3 a 2 2/2 EYELID PTOSIS - 120 2 .254 8 32.0 180 3 a 2 -2/2 -miosis 154 120 3,2 1/2 2 MYDRIASIS 60 0 RESPIRAT 61 2 60 32 0 2/2 IRREGULAR ORY DEPTH3 0 R RESPIRAroRY RATE 362 32:0 3 a 2 2/2 IRREGULA I 2 15 .60 0 2/2 DySPNEA .3,2 .0 32.0 2 60 MOT DEF HORIZONTAL WIRE 171 32.0 3.2 2/2 FN 271 0 60 32sO 3,2 .2/2 MOT DEF'VERTICAL SCRE 2 .0 lao MOT DEF HORIZONTAL STRIP .471 .3 e 2 @2/2 iso 32*0 0 328*0 3,2 2/2 MOT DEF VERTICAL ROD 371 2984 W INTRAVENOUS TCXICITY TO MICE DEG- M7No TO Do'--'E DILUT REACTO REACTION SIGN MIN* 2 APPR REE RECOVER MG/KG ML/KG FRACTO -ROD 0 120 3.2 -2/2 MOT DEF ROTA 771 - 3 2 o 0 32.0- 3,2 2/2 MOT DEF INCLINED STRIP 2 671 0 i8o ISO 1000 1010 2/2 INC-LOCOMOTOR ACTIVITY 224 60 io,O, 1010 2/2 SOCIAL INTERACTION ALTERED 132 0 180 2 1000 10*0 2/2 ATAXIA 35 0 f 2 IRREGULAR RESPIRATORY DEPTH361 0 1 5 10.0 10.0 2 1000. 1010 2/2 IRREGULAR RESPIRATORY RATE 362 0 15 120.0 10.0 2/2 RESTLESSNESS 79 60 i8o 3,2 3.2 2/2 INC LOCOMOTOR ACTIVITY 224. 60 120 3o2 302 1/2 INC PREENING 140 60 120 3,2 3,2 2/2 RESTLESSNESS 2 79 60 120 110 io,o 2/'2 INC PREENING 140 8 60 0932 3.2. -2/2 INC PREENING 140 8 60 0.10 10.0 2/2 NO EFFECT 73 79,0 7.9 2/2 1 DEATH 74 0 r_ 63.0 6,3 1/2 DEATH 74 0 5000 510 0,'2 DEATH 74 0 DIL--. I 0 0 STEROL DIL,.SUSP QS C H20 994 W LD50 2OOoO -l6OoO-250 0- --5o6-56oO- ME050 l8oO ID50.@MED50 l2iso RATIO STATE-SOLID INTRAVENOUS TOXICITY TO MICE DILUT REACTO MINO -DEG-- M'N* TO DOSE REACTION SIGN MG/KG ML/KG FRACTO APPR REE RECOVER 102000 1 0 0 2/2 DEC LOCOMOTOR ACTIVITY 124 30 60 2/2 DEC REA 632 30 100 0 1.0 RING FREQUENCY 60 2/2 10000 .110 DEC PREENING 2 240 30 60 100 0 0 1 0 0 2/2 IRREGULAR RESPIRATORY DEPTIJ361 0 15 10010 1 a 0 2/2 IRREGULAR RESPIRATORY RATE 362 0 5 32oO Oo64 1/2 DEC LOCOMOTOR ACTIVITY 12.4 30 60 2 32.0 0*64 2/@ IRREGULAR RESPIRATORY RATE 362 0 15 10 0 0 110 2/2 NO EFFECT 73 2/2 DEATH 74 0 -250.0 2,,5 200,0 2.0 1/2 DEATH 74 4 0 160.0 DEATH 74 0 le6 0 1 2 130.0 .1.3 0 2 DEATH 74 0 001 PEG 300 OS C 1009' PEG 300 DIL. Z995 W LD50 25*0 --20,,0-32oO-. MED50 lo8 --Oo56-5*6-, RATIO LD50/MED50 l4oO ,STATE-SEMISOLID 2 INTRAVENOUS TOXICITY TO MICE DOSE DILUT REACTO MINI DEG- MIN@ TO REACTION SIGN MG/KG ML/KG'FRACTO APPR REE RECOVER ioo 0 .2 0 -2/2 -DEATH 74 0 74- 0 @32,0 0.64 2/2 DEATH -SENSITIVITY TO TOUCH 131 1440 44 10 0 1*0 1/2 INC 1000 2 1*0 2/2 IRREGULAR RESPIRATORY DEPTH361 0 15 .0 15 10.0 l.C) -Z/2- IRREGULAR-RESPIRATORY RATE 362 .3 2 1 6 2/2 INC SENSITIVITY TO TOUCH 131 8 30 110 0,50 2/2 'NO EFFECT 73 -.25.0 -.2.5 1/2 -DEATH 74 0 2.0 0 2 74 0 '20,0 DEATH 16oO 1 a 6 0 2 -DEATH 74 0 .100016 PEG 300 QS@c 100% PEG 300 DILD 2999 W LD50 25oO -lloO-56oO-- MED50 Oo56 -Ool8-1*8- RATTO LD50/MED50 .4590 STATE SOLID 2 INTRAVENOUS TOXICITY'TO MICE DOSE DILUT REACT6 REACTION-SIGN MINO DEG- MINE TO MG/KG ML/KG FRACTO APPR REE RECOVER 10010 10,0 '2/2 DEATH 2 74 0 3 2 . 0 3 . 2 1/2 DEATH 74 0 3,2 1 32oO /2 DEC LOCOMOTOR ACTIVITY 124 30 G 300 32eO 3o2 1/2 DEC SENSITIVITY TO PAIN 229 30 60 2 .32*0 .3 a 2 1/2 INC SENSI'TIVITY TO TOUCH 131 0 30 32io 3,2 1/2 INC REARING FREQUENCY 432 0 .8 32.0 -3 2 1/2 -DEC REARING FREQUENCY 632 30 G 300 32oO 3:2 1/@ 2-STRAUB TAIL 2.33 .0 30 32*0 3.2 1/2 MIXED CONVULSIONS 336 0 8 172 8 60 .32.0 .3o2 1/2 ABNORMAL'VIBRISSAE 3 '":'o 0 2 3,2 1/2 38 0 8 3o2 32oO 1/2 RUBBING NOSE 340 .0 60 32 9,0 3.2 1/2 -LOW POSTURE '241 15 30 32:0 3,2 12/2 EXTENSION OF-LIMBS .341 30 60 32:0 3.2 1/2 TREMORS-REST AND MOVEMENT 144 0 60 0 32,0 3,2 i/z EXOPHTHALMOS 46 15 232,0 3,2 1/2 PUPILLARY LIGHT REFLEX ABS 152 @o 60 0 32,0 3,2 1/2 MYDRIASIS 154 60 32o2O 3,2 1/2 SALIVATION 57 8 30 32*0 3o2 1/2 INC URINATION 158 0 60 32*0 3,2 1/2 DYSPNEA 60 0 2 8 777 c7 Nl R A E 1\1 )'i TO,@!CITY "i'O M-!'%--E DOSE C, I- UPEAC@W REA@@"Ii.ON ST@Q'N MIN6 DEG- M.N. @"O MCI 1! C,2 ML;'KG F APPR PEE REr,OV;-:R 32.0 INC RE@-@1--l'.RAI'CRY D--PTH 161 0 30 2 1-20 61 30 32.0. 3 2- DEC PTcP'RA70RY D7PTH 2 2 '20 32,iO 3 3 I ',-:",PEGULA'P RESPIRA'@OR" D,:PTH361 0 32*0 3 o 1 12 RESP'RA'@'ORY RA'@'E 162 0 2 30 -32.0, RESP'iR'M'70RY RATE 262 30 1-20 3,2 L./ 2 D=,- -'.-'2 ORv RAT= 362 0 2 120 32.0 3.2 !RRr@-GUI-AR RESP7RA 0 3 0 3 3 2 i.11 2 @iO'( DEF HOR:ZCNTAL WT.RE 2 171 8 3,2 2 tdCT 0 %,'E R A L 5 R @- E N 271 0 -AL STRIP 471 0 3-7 3,7- 1/2 MOT DEr@ 2 HOR@ZON@ 30 32*C 3*2 I./2 @io 1-1 DEF ',.,ER-CA@- ROD 371 0 30 32,0 3,2 !/2 MOT DEF ROTA-ROD 771 .0 2 8 32.0 3,@, 2 1,,2 1,,l 0 T F '.! i'l 1 N E D S-RIP 671 0 30 ASYf',!N'.'HTNE REF' 2 EX D-PR 32*0 %,o 2 1/2 L r_ 942 0 60 1000 1.0 -- 0 1/2 JUMPING .324 15 2 30 0 , 0 1010 1112 ABNORMA!- REACTION To PAIN 429 15 .20 0 0 a 0 10,220 -/2 'tNr' SENS"-,r"ITY -0 TOUCH 60 131 'A.0 0 0 10 0 0 2/2 SO%--IAL T.N"'f"ERACTION ALTERED 132 2 0 60 -to,o io*o .6 2/Z RUBB?ING NOSE 340 8 30 942 10.0 2 10.0 2!2 .'-A By R'A'N NE REFIEX DR@-PR 0 60 io.o 10.0 2/2 PUPILLARY--'t-k-GHT REr@L;:X ABS 152 0 6 0 1 0 1 0 140 0 0 2/2 2 M%@DRIAS" 154 0 .60 1000 -,-O,o 2/2 SALIVATI@CN 57 15 30 8 2 60 1010 10.0 2/2 INC 'UR I.NIA :ON 158 10.0 -'O,O - 2/2 MOT i)EF VER'ITICAL ROD 371 0 30 2 1010 1000 2/2 ABNORMAL VIBRISSAE ..172 15 60 2/2 INC-SENST-TIVITY TO TOU'-H 131 15 G 300 3*2 3,2 2 --PRE--N',.NG 140 60 180 .3,2 3e2 2Y2 IN@.- 3*2 3 2 112 RUBBING NOSE 340 8 30 3:2 2 2 INC URINAT)C)N 158 1 5 60 3,2 1 , 0 -0.0 -212 TRREGULAR RESPIRATORY DEPTH361 0 30 100 1000 2/2 2 IRREGULAR RE5PIRATORY RA@IE 362 0 30 2 '2 t4 0 Oo32 3,2 EFFECT 73 .40,0 4,0 2/2 DEATH 2 74 0 25,0 2,5 1/2 DE'All-H 74 120 20,0 2,0 1/2 DEATH 74 120 DIL. H&-,-O 05 HZO 5026 W .-89oO-l4OoO- LD5o ilooo MED50 -1*8-- 2 Oo56 -Ool8 '%-D50/MED50 200*0 T RA IC STATE-SOLID INTRAVENOUS TOXICITY TO MICE MIN, 'DEG-- MIN* TO DOSE 2 DILU' REACT REACTT.CN SIGN T 0 . APPR REE RECOVER MG/KG ML/KG FRACT. AC-IVIT .124 15 180 2/2 DEC LOCOMO-ICR 2 'Y 20,0 RED 132 1 5 300 2.0 2/2 SOCIAL INTERACTION ALTE 20.0 DEC.REAR-.NG FREQUENCY 180 2 .632 15 -20,0 @2oO 2/2 20.0 2,0 1/2 EYELID PTOSIS-NONPARALYTIC 149 15 180 2000 2,0 2/2 INC RESPIRATORY DEPTH .161 .0 l@80 2 C RESPIRATORY RATE @262 60 120 20.0 -2.0 1/2 DE 2, 0 -272--' -204;0 I RREGULAR---RESP 17RAT, CRY RATE 362 0 180 -I2IVITY .224 15 1010 110 1/2 INC LOCOMOTOR AC 60 .124 60 180 1/2 1010 DEC LOCOMOTOA 2 ACTIVITY @80 1000 100 2/2 EYELID PTOSIS-NONPARALYTIC 149 60 jo,o iso 2/2 INC RESPIRA70RY DEPTH 161 0 180 2/2 RESPI.RATORY RATE 3 2 10 a 0 .110 IRREGULAR 62 iso 'LNC -LOCOMO 30 3,2 1.6 1/2 TOR ACTIVITY 224 0 2 .3 o 2. 1 9 6 2/2 DEC LOCOMOTOR ACTIVITY 124 60 180 161 8 60 .3,2 1,6 2/2 INC RESPIRATORY DEPTH 3,2 1,6 '2/2 IRREGULAR RESP'RATORY RATE 3622 15 60 C-!VITY 224 8 60 100 Oo5O 2/2 @AINC LOCOMOTOR A i R ACTIVI 120 100 Oo5O 8 2/2 DEC LOCOMOTO TY 124 30 5026 w 2 !N'IRAVENOUS TOXIC!TY TO M 1-CE -TION SIGN DILUT REAC7 REA@ MINO D05E DEG- M7N* TO MG/KG ML/KG FRACT9 2 APPR REE RECOVER ilo !RREGULAR RESPIRAT-ORY RATE 362 1 0 0 1/2 30 Oo3Z 1.6 2/2 NO EFFECT .73 6 74 0 1 0,0 2o6 2/2 DEATH 7 0 DEATH 120.0 2 a 1 21@2 74 -oo.o - 1,7 0 2 DEATH 74 0 7900 143 0 2 DEATH 74 0 DILE I 0 003 PEG 300 OS C 100% PEG 300 7,@ 503'-W --10000-16000- LD50 120*0 MED50 1 a 8 --0*56-5o6- RATIO LD50/ME050 2 69eO STATE SOLID INTRAVENOUS TOXICITY TO MICE -DOSE @DILUT REACTO REACTION SIGN MINA- DEG- MIN* TO MG/KG ML/KG FRACTO APPR REE RECOVER .100*0 2,0 2/2 DEC LOCOMOTOR ACTIVITY 124 8 G 300 100,0 @200 2/2 DEC@ SENSITIVITY TO TOUCH 231 8 60 -PREENING 100 6 0 2,, 0 2/2 -DEC 240 0 G 300 100,00 210 '2/2 2 EYELID PTOSIS-NONPARALYTIC 149 @8 G 300 .2/7 60 0 10010 @2.0 DYSPNEA 8 10000 .2.0 1/2 IRREGULAR RESPIRATORY DEPTH361 0 2 15 10000 -2oO -2)@2 MOT DEF HORIZONTAL WIRP- 171 0 15 15 10010 2,0 -2/2 MOT DEF VERTICAL SCR&c-E@l 271 10000 @2.0 2 /2 MOT DEF HORIZONTAL sTRIP 471 0 30 2 'MOT DEF VERTICAL ROD 371 0 10000 1/2 15 ioo.o 2oO 2/2 2 771 0 15 MOT DEF ROTA-ROD I&OOO 2.0 2/2 MOT DEF INCLINED STRIP 671 0 30 2,0 DEC LOCOMOTOR ACTIVITY 124 60 20 0 -2/2 2 240 20:0 2*0 1/2 NO EFFECT 73 1010 1 0 2/2 DEC.LOCOMOTOR ACTIVITY 124 30 300 3,2 .1.6 2/2 DEC LOCOMOTOR ACTIVI-IY 124 360 240 140 .0.50 2/2 NO EFFECT 73 NW 503 W -2 INTRAVENOUS TOXICITY '-40 M I-CE DOSE DILUT REACTO REACTION SIGN MIN* DEG- MTN* TO K G ML/KG FRACT* APPR REE PECO\JER 0 674 0 160 0 3,2 2/2 DEAT 20, 0- 2.5 1/2 DEATH 74 0 DEATH 74 0 79.0 1.6 0 2 L 0 100% PEG 300 05 C 100% PEG 300 5058 'A LD50 36*0 -26*0-49aO-. MED50 3*2-3-160-3-OiOlO-@ RATIO -LD50/MED50 lol+4 STATE SOLID INTRAVEN2OUS TOXICRTY'TO MICE DOSE DILUT REACT* REACTION SIGN MIN*' DEG- MINE TO MG/KG ML/KG FRACT6 APPR REE RECOVER --.t ioo 10 1010 :2/2 @DEATH 74- 0 3240 .30-2 1/2 DEATH 2 74 0 OMOTOR 124 8 120 @3200 3.2. 1/2 -DEC-LOC ACTIVITY G .32-0 .302 1/2@ INC.LOCOMOTOR ACTIVITY 224 120 300 2 0 . 8 32,0 3o2 1/2 'CIRCLING MOVEMENTS 25 0 0 120 32,0 :3,2@- -DEC REARING@FREQUENCY 632 32,0 1/2 ATAXIA .35 0 2 8 32.0 3o2 1/2 DEC PREENING 240 0 30 1/2 3200 .3*2 INC PREENING 140 ;60 240 32*0 3*2 1/2 IRREGULAR RESPIRATORY DEPTH361 0 120 32.0 @3.2 1/2 DEC REARING FREQUENCY2 632 0 120 32oO 3.2 1/2 MOT DEF HORIZONTAL WIRE 171 15 32*0 3o2 1/2 MOT DEF VERTICAL SCREEN 271 0 15 32oO 3,2 1/2 -MOT DEF HORIZONTAL STRIP 471 0 30 32*0 .3.2 1/2 MOT DEF VERTI2CAL ROD 371 @O 15 32.0 3.2 1/2 MOT DEF ROTA-ROD 771 0 30 32.0 302 1/2 MOT DEF INCLINED STRIP 671 0 30 32.0 .3,2 1/2 PILOERECTION 72 i5 G 300 5 79 60 300 32.0 3*2 1/2 RESTLESSNESS 505 8 W INTRAVENOUS TOXICITY TO MICE DOSE DILUT REACT* REACTION SIGN 2 MIN4 DEG- MIN* TO MGWIKG @1L/KG FRACT* APPR REE RECOVER 1010 1010 2/2 INC.LOCOMOTCR A TIVITY c 224 2 60 -80 10.0, lo,o 2/2 DEC LOCOMOTOR ACTIVITY 124 180 240 1000 10*0 2.12 HEAD TWITCH 531 60 2 300 -,-O,o 10.0 2/2 INC REARING FREQUENCY .432 15 60 1010 10.0 2/2 LNC PREENING 140 15 240 10.0 1000 2/2 INC SCRATCHING 440 30 iao 101!3 1010 1/2 INC RESPIRATORY DEPTH 161 0 30 1/2 0 215 lo,:) lo,o IRREGULAR RESPIRATORY DEPTH361 1010. 2/2 IRREGULAR RESPIRATORY RATE 362 30 io,o 0 1000 1010 2/2 PILOERECTION- 72 120 240 2/2 RESTLESSNESS 79 60 300 1060 1010 3*2 3,2 2/2 INC LOCOMOTOR ACTIVITY 224 30 2 180 4@- 3,2 3al@ 2/;' DEC LOCOMO@IOR ACTIVITY 124 180 240 3.,Z 1 531 60 300 3*2 /2 HEAD TWITCH 2 3,2 3.2 1/2 INC REARING FREQUENCY 432 15 60 302 302 -2/2 !NC PREENING 140 15 240 3.2 3.2 1/2 INC SCRATCHING -440 30 2 120 3 a 2 3*2 1/2 161 5 INC RESPIRATORY DEPTH 0 3'2 :RESPIRATORY RATE 362 3,2 2/22@ IRREGULAR. 0 1&5 PTL N 300 3 2 .3 2 2/2 OERECTIO 72 120 3*2 3:2 2/2 RESTLESS2NESS 79 60 240 160 1010 2/2 INC LOCOMOTOR ACTIVI'TY 224. 0 60 1*0 1000 2/2 DEC LOCOMOTOR ACTIVITY 124 60 240 2 10.0 2/2 -300 1.0 HEAD TWRTCH 531 120 1.0 10*0 - 1-/2 INC- REARIN-G FRZ--QUE-NIC-Y,.-- .4,3,2, --@ @3G@ 60 ISO 10-0 2/2 INC PREENING 140 30 240 1,0 10,0 2/2 INC SCRATCHING 4240 30 240 1.00 lOsO INC RESPIRATORY DEPTH 161 :30 240 1.0 10,0 2/2 IRREGULAR RESPIRATORY RATE 362 30 240 100 iclo 1/2 PILOERECTION 72 120 240 .110 1010 2/2 RESTLESSNESS 7§ 36 240 1*0 1010 2/2 SQUINTING 79 60 240 0032 2 2/2 !NC LOCOMOTOR ACTIVITY 224 15 60 0.32 3*2 2/2 DEC LOCOMOTOR ACTIVITY 124 60 240 @o 300 *32 2 302 1/2 HEAD TWITCH 531 l@2 0 60 1/2 INC REARIN 432 30 0.32 .3.2 G 2 FREQUENCY 0*32 3*2 @2/2 INC PREENING 140 30 180 0,32 3.2 1/2 INC-SCRATCHING. 440 30 1-20 0,32 3,2 -2/2 INC RESPIRATORY DEPTH 1610 60 180 0,32 3,2 2/2 IRREGULAR RESPIRATORY RATE 362 60 1.80 0932 3.2 2/2 RESTLESSNESS 79 30 180 Again&-% 505eW B INTRAVENOUS TOXICITY T 0 MICE 0 5 E DILUT REACTO REACTION SIGN MIND DEG- MIN* TO MG/KG ML/KG FRACT* APPR REE RECOVER2 3,2 2/2 79 60 180 0,32 SQUINTINC- - 0.16 10.0 2/2 IN.C LOCOMOTOR ACTIVITY 224 .30 1-20 Y 2 180 DEt LOCOMOTOR ACTIVI 124- 120 - 0,0 1 0 10 0,0 2/2 0010 1010 1/2 P@ILOERECTION 72 120 40 2 2 lo,o SQUINTING 79 60 i-80 .0 1 0 2/2 INC 30 120 PREENING 2140 0010 1000 1/2 01.1--@, io*o 1/2 INC SCQATCHING 440 30 60 .3,2 INC LOCOMOTOR ACTIVITY 224 60 i2o OoO3- 2 2 0,032 3 2 2/2 DEC-LOCOMOTOR 2 ACTIVITY 124 120 iso @0*032 3o2 112 INC PREENING 140 30 60 180 @0.032 3*2 2/2 SQUINTING 79 120 -oloio 1010 2 2/2 INC LOCOMOTOR ACTIVITY 224 0 60 140 0 0-010 10-0 2/2- INC PREENING 60 @0*010 10,0 1/2 INC SCRATCHING 2 .440 0 60 3,2-3 .3,2 1/2 INC LOCOMOTOR ACTIVITY 224 0 60 .3o2-3 3,2 1/2 INC SCRATCHING .440 .0 60 73 3,2-3 3,2 1/2 NO EFFECT 2 1*0-3 10.0 2/2 NO EFFECT 7 3 2/2 -50.0 5.0 DEATH 74 0 1/2' DEATH 74. 0 .4010 .4 0 25iO 4 @2.5 0/2 DEATH 74 0 DILO 100%.STEROL DIL* SUSP QS.C H20 PAGE 5059 W LD50 160*0 --120*0-200*0- -0*056-Oo56- 0*18 MED50 2 MED50 88090 RATIO LD50/ TATE SOLID INTRAVENOUS TOXICITY TO MICE. DILUT REACT, *'TO DOSE REACTION SIGN MiNo DEG-. MINO APPR RE MG/KG ML/KG FRACTO 2 E RECOVER -@'i 4.00*0 1010 2/2 DEC LBCOMOTOR ACTIVITY 1240 G 300 100 0 0 5 'IVITY TO PAIN 129 30 120 10.0 1/@ INC ENSIT 100.0 lo,o 2/2 ABNORMAL REACTION TO PAIN 429 30 300 loo,o 10 2 02/2 DEC SENSITIVITY TO TOUCH 231 0 120 'J.0030 10:0 2/2 -SOCIAL INTERACTION ALTERED 1320 180 10!1.0 10,0 2/2 DEC REARING'FREQUENCY 632 .0 180 10000 1000 2/@ ATAXIA 35 0 60 ioooo 10 20 02/2 DEC PREENING 240 .300 1.0010 @2/2 PUPILLARY-LIGHT REFLEX ASS 152 10.0 0 60 ioo,o 10.0 2/2 MYDRIASIS 154 0 60 ioo.o 1010 -2/2 INC RESPIRATORY DEPTH 161 2 0 '180 10000 1000 2/2 DEC RESPI@RATORY RATE @262 15 1-80 ioo.o 1010 .0 30 2/2 IRREGULAR RESPIRATORY RATE 362 ioo 0 10.0 1/2 MOT DEF HORIZONTAL STRIP 471 .0 60 Looo 1060 Mo'r DEF VERTICAL ROD 0 1/2 1 @371 60 o J. 010 1010 1/2 MOT DEF ROTA-ROD 771 0 60 I ioolio 10.0 1/2 MOT DEF INCLINED STRIP 671 0 60 ioo.o 1010 2/2 LOW CARRIAG4E l@75 0 60- 32,0 3,2 2/2 DEC LOCOMOTOR ACTIVITY 124 .15 1-20 3,2 2/2 ABNORMAL REACTION TO PAIN 429 60 240 32,0 . . .... .... 5059 w 2 INTRAVENOUS TOXICITY TO Mt CE DOSE DILUT REACT* REACTION SIGN MINE DEG- MINO '@O 2 APPR REE RECOVER t-I G G ML/KG FOACT* 32,0 3,2 2/2 INC SENSITIVITY TO 'TOUCH 131 60 G 300 4 3200 .3*'-) 2/2 @SOCIAL INTERACTION ALTERED 132 0 60 32*0- 2 3*2 1/2 PE(@ REARING FREQUENCY 632 0 60 --2,,O 3,2 2/2 DEt PREENING 240 1 5 60 X ASS 152 0 0 3 2 REFLE 6 2.0 3.2 2/2 PUPILLARY LIGHT -MY'DR I AS I S 154 0 3.2 2/2 60 32,0 1/2 MOT DEF HORIZONTAL STRIP 2 471 0 :24,0 392 30 0 30 eV 1/2 32 3,2 MOT DEF INCLINED STRIP 671 32,0 3,2 2/2 LOW CARRIAGE 175 15 60 1010 1010 2/2 ABNORMAL REACTION TO PAIN 429 60 G 300 10 9 3 ";D.o 1/2 INC SENSITIVITY@TO TOUCH 131, 60 240 @1010 10120 1/2 PILOERECTION 72 120 .200 3,2 3,2 1/2 INC SENSITIVITY'TO PAIN 129 60 300 3o2 .302 1/2 PUPILLARY LIGHT REFLEX ABS 152 0 60 3o2 .3,2 1/2 MYDRIASIS 2 .154- 0 60 ISO 10#0 2/2 DEC LOCOMOTOR ACTIVITY 124 60 240 .100 1010 1/2 EYELID PTOSIS-NONPARALYTIC 149 120 ISO -1 Oo32 1/2 DEC LOCOMOTOR ACTIVITY 124 60 2 120 @2/2 EYELID PTOSIS-NONPARALY 0.32 3,2 TI-C 149 60 240 - 2/2 0110 10.0 NO EFFECT 2 73 DEATH 74 @O 200,0 20,0 @2/2 74 1/2' 160,0 16.0 DEATH 0 20,0 12.0 0 2 DEATH 7,4 0 DLL. 100t STEROL DILO SUSP QS,C H20 5071W LD50 50*0 --40*0-63*0- MED50 0*56--Oel8-1*8-- RATIO -LD50/MED50 89*0 STATE-SOLID INTRAVENOUS TOXICITY'TO MICE D2OSE DILUT'REACT* REACTION SIGN MIN* -DEG-- MIN, TO ,-I MG/KG ML/KG FRACT* APPR REE RECOVER '0000 10.0 2/2 DEATH 74 :0 3,2 ;2/2 DEC LOCO.MOTOR ACTIVITY 124 0 G 300 '2/2 2 128 30 1&20 .32,0 3,2 INC PHONATION - 32.0 .3,2 2/2 INC -SENSITIVRTY'TO PAIN . .129 .0 240 32.0 .3 2 1/2 G INC REACTivrTY TO SOUND 330 .60 300 .32,02 .3 2 1/2.- INC -SENSITIVRTY'TO TOUCH 131 @30 120 32*0 .3*2 2/2 SOCIAL INTERACTION ALTERED la2 0 G 300 32oO .3.2 2/2 FREQUENCY 632 .0 120 @32 0 .3 2 2/2 :DEC REARING HEIGHT 732 .0 120 2 EMPROSTHOTONOS 138 .0 .32,0 3*2 2/2 60 .32*0 302 '2/2 MYDRIASIS 154 8 180 3*2 1/2 IRREGULAR RESPIRATORY DEPTH361 @o 30 .32,0 3 2 2/2 INC RESPIRATORY RATE 2 162 .0 1-20 32eO -3:2 1/2 @MOT DEF INCLINED STRIP 671 120 10 0 10 0 2/2 INC LOCOMOTOR ACTIVITY 224 0 1-20 10:0 10:0 2/2 INC PHONATION 128 30 120 io,o 10.0 2/2 INC SENSITIVITY'TO PAIN 129 15 G 300 1000 1010 2/2 INC SENSITIVITY-TO TOUCH 131 30 120 PAG E claim# 5 07 1 INTRAVENOUS !OXICITvi TO M!rE DOSE DILU REACTI REACTION SIGN MIN DEG- 2 M'N* TO -t4.C,/KG G FRACT* PR REE RECOVER ML/K' AP 3.2 3.2 -2/2. INC LOCOMOTOR ACTIVITY 224 0 1-20 3 -Y TO .2 3.2 2/2- INC SEt4SITIVII PAIN 129 1 5 G 300 1/2 302 3,2 MYDRIASIS 154 15 240 224 0 _,o 1010 2/2 INC LOCOMOTOR ACTIVIIY 2 30 0,32 3.2 2/2 NO EFFECT 73 79*0 7.9 2/2 DEATH 74 0 603 '2/2 DEATH 74 0 5010 5,0 1/2 DEATH 74 -60 0/12 DEATH' 74 0 40,0 .4 D 100%.STEROL DILE SUSP QS C H20 LD50 320. 0 GREAT .-oo56-5o6 MED50 los RAT'10 LD50/MED50 UNK -TATE SOLID 4r, INTRAVENOUS'TOXICITY'TO MICE 2MIN,. DEG- MIN, TO E CT R DOSE DILUT R A * EACTION SIGN R REE RECOVER ACT* APP MG/KG ML/KG FR .0 G 300 -DEC LOCOMOTOR ACTIVITY 2 124 320.0 32,0 2/2 ;o G 300 @2/2 320 0 @32*0 DEC SENSITIVITY TO PAIN 229 320:0 :32.0 212- DEC SENSITIVITY TO SOUND 230 0 120 't 2 '80 320,0 .32,0 -2/2 DEC 5 ENSITIVITY'TO TOUCH 231 0 .32 0 320.0 2/2 PINNAL REFLEX ABS 431 0 120 320.0 @32.0 2/2 -SOCIAL INTERACTION ALTERED 132 .0 2 180 32.0 DEC REARING'FREQUENCY 632 iso 32OeO 2 /.2 320.0 32.0 -2/2 DEC REARING HEIGHT 732 120 G 300 P TAIL 333 0 120 32OeO .32.0 '2/2 LIM 2 32000 32,0 1/2 INC AGGRESSIVENESS-PEOPLE 334 8 G 300 32OeO 32,0 2/2 ATAXIA 35 8 120 '320.0 32.0 1/2 INC MUSCLE TONE-LIMBS 337 0 8 - -437 0 180 232OiO 32.0 1/2 DEC MUSCLE'TONE-LIMBS .0 G 300 320.0 32.0 -2/2 DEC PREENING 240 Z,-. 320.0 32,0 2/2 @LOW POSTURE @241 0 120 341 2 120 .32.o 2/2 EXTENSION OF LIMBS 60 320.0 320,0 .32.0 2/2 PLACING REFLEX ASS 442 .0 60 320.0 32.0 2/2 GRASPING REFLEX ABS 642 0 60 IGHTING-REFLEX ABS 842 0 2 60 320.0 32.0 2/2 R 320.0 32.0 1/2 LABYRINTHINE REFLEX ABS 042 0 60 .32,0 E REFLEX DEPR 942 0 8 320,0 1/2 LASYRINTHIN 7777 5 77@7@7 PAGF- 5 0 91-1- 2 INTRAVENCUS'TOV^ICITY TO MICE LUT RE'CTI REACTION SIGN MIN-O DEG- M'No '@O S!r Di 2 -OV=R APPR REE RE' fti C /'KG MLIKG FRACT* EYELID P-OSIS-NOTIPARALYTIC 149 G 32090 .o 1/2' 60 300 1/2- ml 320,0 32.0 osis 2 254 0 30 32000 "00 2i,2 DEC RESPIRATORY OC"PTH 261 0 120 IRREGULAR RESPIRATORY DEP-H361 2 B20,0 32.0 2/2 0 120 -190 INC RESPIRATORY RATE 162 0 G e- @ 32.0 2 .6 300 3" 2!2 3 2 "'O0 3el- 0 0 2/2 IRREGULAR RESPIRATORY RATE 362 0 G 300 2 18^ 3- 0 MOT DEF HORIZONTAL WIRE 171 0 - 2'2 320o-2- 3290 2/2 MOT DEF VERTICAL SCREEN 271 0 G 30C 2 0, C@ 32 0 2/2 MOT Dc"F HOR'LrZ%'J'I"ITAL STRIP 471 0 G 300 2-2/2 MOT DEF VERTICAL ROD 0 G 32OoO 32,0 371 300 37-^-0 -@-2,0 2 ' '2 'MOT DEF ROTA-ROD 2 771 0 180 3 e'-'O' a 0 "o 2/2 :5 - MOT DEF INCLINED STRIP 671 0 G 300 0, -IN 2 0 t5 i o0 & 2/2 INC LOCOMOTOP ACTIVITY 224 &. 10000 iocl 2/2 DEC LCCOMOTOR ACTIVITY 2 124 15 21-0 SOCIAL INTERACTION ALTERED 132 0 60 212 1010 DEC REARING HEIGHT 7322 0 120 10GIO 2/2 2 2/ 100.0 10.0 DEC PREENING 240 0 2 30 10010 10.0 1/2 PUPILLARY-LIGHT REFLEX ASS 152 0 18C- 180 2 .10000 1010 1/2 MYDRIASIS 154- 0 - 32*0 3o2 :2/2 INC LOCOMOTOR ACTIVITY 224 0 32 DEC LOCOMOTOR ACTIVITY- 124@ -15 co 3.2 -.2/2 24 32,0 3,2 '2112 SHOVELNOSE MOVEMENTS 925 15 30 2 2/2 INC SENSITIVITY To TOUCH 131 60 32,0 3.2 '2/2 32*0 .3o2 SOCIAL INTERACTION ALTERED 132 0 2 32.0 3*2 @2/2 DEC REARING HEIGHT 732 0 30 iocio 1010 2/2 INC LOCOMOTOR ACTIVITY 224 0 60 2 -10 PA'N L29 60' 0 lo,,o 10.0 2/2 INC STNSITIV*TY L 1000 'Aooo 2 2/2 INC SENSITIVIITY TO 'IrOicH 131. 30 10.0 1010 2/2 INC SPEED OF REARING 532 0 30 1000 1010 2/2 -PUPILLARY LIGHT REFLEX 2 ABS 152 8 120 sis 154 8 l-2Cj 10.0 10.0 ;2/2 MYDRIA 2 60 3a2 3o2- 2/2 INC LOCOMOTOR ACTIVTIY 224 0 .0 1000 212 NO EFFECT 73 0 DIL* 10096 STEROL DIL. SUSP OS C H20 5:04 W -l3OoO- LD50 lOOoO 79*0 MED50 0*018-596-3-OoO56- 2 5,6+3 RATIO LD50/MED50 ;TATE SOLID INTRAVENOUS TOXICITY TO MICE DOSE DILUT REACT*' REACTION SIGN MINO 'DEG- MIN, TO MG/KG ML/KG FRAC-10 APPR REE RECOVER .0010 2,0 1/22 DEATH 74 0 oo.o 2.0 1/2 DEC LOCOMOTCR ACTIVITY 124 0 G 300 8 60 oo.o 2,0 1/2 DEC SENSITIVITY TO SOUND 230 00 0 2.0 1/2 DEC SEgSrTIVrTY TO TOUCH 231 -----60 -0010 2,0 1/2 DEC REAKING FREQUENCY 632 0 ..G 300 .0 G 300 .00.0 2.0 1/2 DEC PREENING 240 2 LOW POSTURE OOoO 2,0 1/2 .241 15 60 EXTENSION OF.LIMBS 341 .00 00 2.0 1/2 0 15 .0000 2,0 1/2 PROSTRATION 2 0 15 8 G 300 00.0 2,0 1/2 EYELID PTOSIS-NONPARALYTI.R 149' io0oo 2,0 1/2 PUPILLARY LIGHT REFLEX ABS 152 8 30 @00,0 2.0 2 1/2 MYDRIASIS 154 8 30 i-00 0 2,0 ',/2 INC RESPIRATORY DEPTH 161 0 60 2.0 T@/2 IRREGULAR RESPIRATORY DEPTH361 0 15 -0010 2.0 1/2 DEC RESPIRATORY RATE @262 0 2 60 .2,0 1/2 IRREGULAR RESPIRATORY RATE 362 0 15 @.0010 ..Oolo 2.0 lj2 MOT DEF HORRZONTAL WIRE 171 0 15 OT DEF VERTICAL SCREEN .0 -0000 2 2,0 1/2 M 271 15 .0000 200 1/2 MOT DEF HORIZCNTAL STRIP 471 0 30 .0010 2.0 1/2 MOT DEF VERTICAL ROD 371 0 15 .0010 2,0 1/2 MOT DEF ROTA-ROD 771 5 0 !-5 t77 PAGE 5104 INTRAVENOUS TOXICITY TO MICE DOSE DILUT REACTO REAC TION SIGN MINA, DEG- MTN* TO 2 APPR REE RECOVER MG/KG ML/KG FRACT* 0 -F INCLINED STRIP 671 3 ioo.o 210 1/2 MOT D@ 2 120 3210 Oo64 2/2 DEC LOCOMOTOR ACTIVITY 124 0 3290 0,64 1/2 INC SENSITIVITY TO SOUND 130 240@ 300 3260 'O.64 2/2 DEC REARING FREQUENCY 632 8 240 32,0 0,64 2/2 DEC PREENING 240 8 240 32,0 0.64 2/2 INC PREENING 140 240 G 300 32*0 2/2 EYELID PTOSIS-NONPARA"YTIC 149 15 240 32,,O 0.64 2/2 INC RESPIRATORY DEPTH 161 0 30 32,0 0.64 2/2 DEC RESPIRATORY RATE 262 20 30 32.0 0,64 2/2 IRREGULAR RESPIRATORY RATE 362 0 15 .32oO 0 - 64 1/2 PILOERECTION 72 240 G 300 0 0,64 1/2 RESTLESSNESS 79 240 G 32 2 3bO 32:0 0.64 1/2 SKIN FLICK 79 240 G 300 1.0 2/2 G @oso INC SENSITIVITY'TO SOUND 130 240 300 2G 10 HEAD TWITCH 531 240 iolo I 1/2 300 I." 2 .240 G 300 1010 110 INC PREENING 140 1000 J,O 12/2 EYELID PTOSIS-NONPARA'LYTIC 149 30 60 1000 1.0 2/2 INC RESPIRATORY DEPTH 161 0 30 10.0 1.0 2/2 IRREGULAR RESPIRATORY RATE 3620 30 10 0 1.0 72 G 300 2 1/2 PILOERECTION 240 10.0 1.0. 1/2 RESTLESSNESS 79 240 G 300 10 0 0 110 112 SKIN FLICK 300@ 79 240 G 2 G 3.2 1.6 1/2 INC LOCOMCTOR ACTIVITY 224 240 300 302 1.6 1/2 INC SENSITIVITY To SOUND @130@ 2.40 G 300 3.2 1,6 1/2 HEAD TWITCH 531 240 G 300 .3-2 1-6 2/2 INC PREENING 2 140 240 G 300 .3o2 .1.6 2,/2 INC SCRATCHING 440. 240 G 300 2 1,6 1/2 INC RESPIRATORY DEPTH 161 0 15 1 .*,2 1,6 1/2 IRREGULAR RESPIRATORY RATE 362 0 @3o2 le6 1/2 PILOERECTION 72 240 G 300 3,2 RESTLESSNESS 79 240 G 300 1.6 1/2 3,2 1.6 1/2 SKIN FLICK 79 240 G 300 .110 O*5Cr 2/2 INC LOE2OMOTOR ACTIVITY 224 180 G 300 a 0 Oa r'O 2/2 !NC PREENING 140 180 G 3oo 110 Oo5O 1/2 INC SCRATCHING .440 180 G 300 .0 0*50 1/2 PILOERECTION 72 180 2 G 300 Oo3Z 1.6 2/2 INC LOCOMOTOR ACTIVITY 224 240 300 0,32 i.6 1/2 HEAD TWITCH 531 240 G 300 '%2 1.6 1/2 INC PREENING OeD 140 5 240 G 300 41V PAGE i- 51 04V INTRAVENOUS TOXICITY TO MICE --)DOSE DILUT REACT* REACTION SIGN MIN*' DEG- 2 MINE TO APOF@ REE RECOVER MG/KG ML/KG FRACT* !NC SCRATCHING 440 240 G 300 1/2 0032 1.6 224 180 G 300 2 INC LOCOMOTOR ACTIVITY 0010 Oo5O 2/2 .00032 1*6 1/2 INC.LOCOMOTOR ACTIVITY 224 180 300 'O.032 1,6 1/2 INC REARING FREQUENCY .432 180 240 -0.032 .1.6 1/2 NO EFFECT 73 0*010 0*50 1/2 INC-LOCOMOTOR ACTIVITY 224 60 240 .00010 0.50 1/2 NO EFFECT 73 73 NO EFFECT @3*22-3' -1*6 2/2 DEATH 74 0 120 9 0 1,2 2/2 74 0 O/ 2 79*0 1,6 DEATH @63,0 .1.2 0 2 DEATH 74 0 2 @100% PEG 300@GS'C 100% PEG 300 5'-43 W LD50 56*0 -45@,0-71*0- 0.18 -0*056-0*56- 0 MED5 3 10 20 RATIO LD50/MED50 TATE SOLID 'TO MICE INTRAVENOUS TOXICITY MIN. -DEG- MIN- TO CT* DOSE DILUT REA REACTION SIGN 2 -R "GIKG ML/KG FRACTO APPR REE RECOVC. 1010 2/2 DEATH 74 0 oo.o 32,0 3,2 2/Z DEC LOCOMOTOR ACTIVITY .124 8 180 2 30 SOCIAL INTERACTION ALTERED 132 32.0 :3,m 2 2/2 32.0 3,2 2/2 DEC REARING FREQUENCY 632 @o 180 DEC PREENING .0 32oO 3,2 :2/2 2 240 180 ,t-, 2 -2/2 EYELID PTOSI 32.0 5-NONPARALYTIC 149 30 180 32eO 3.2 2/2 INC RESPIRATORY DEPTH 161 15 i8o 32,0 3,2 2/2 IRREGULAR RESPIRATORY DEPTH361 0 2 60 -22.0 3*2 2/2 DEC RESPIRATORY RATE 262 15 1.80 32*0 3*2 2/2 IRREGULAR RESPIRATORY RATE 362 0 60 1000 1000 2/2 DEC.LOCOMOTOR ACTIVITY 124 30 180 1000 1010 2/2 2 SOCIAL INTERACTION ALTERED 132 8 30 10.0 10.0 2/2 DEC REARING FREQUENCY 632 8 120 DEC PREENING 240 8 iso 1010 1010 2/2 1010 1010 2/2 EYELID PTOS2IS-NONPARALYTIC 149 60 iso 30 i8o 3.2 3,2 2/2 DEC LOCOMOTOR ACTIVITY 124 3.2 3.2 2/2 SOCIAL INTERACTION ALTERED 132 8 30 3.2 3.2 2/2 DEC REARING FREQUENCY 6 632 30 180 PAGE 51-43 INTRAVENOUS TbxICITY TO MICE REACTION SIGN -)DOSE -DILUI- REACT* MINo' DEG- M!Ne 2 TO M4G/KG ML/KG FRACT* APP@ REE RECOVER 3*2 3*2 2/2. DEC PREENING 240 8 180 '-2e2 2/2- EYELID PTOSIS-NONPARA@-Y'iIC 149 60 1-80 100 1010 2/z DEC LOCOM2OT09 ACTIVITY 124 60 180 110 10.0 2/2 DEC PREENING 240 60 i8o 1.0 1010 2/2 EYELID PTOSIS-NONPARALYTTC 149 60 180 110 1010 1/2 IRREGULAR RESPIRATORY DEPTH361' 0 8 2 100 1010 1/2 IRREGULAR RESPIRATORY RATE 362 0 8 0*32 3,2 2/2 60 - 120 DEC-LOCOMOTOR ACTIVITY 124 @0*32 3*2 2 2/2 DEC PREENING 240 60 120 2/2 60 - 0*32 -3o2 EYELID PTOSIS-NONPARA5L.YTIC 149 120 lo@o 2/2 NO EFFECT 73 2 .0 614.0 79oO 7o9 2/2 DEATH 74 0 .63,0 693 2/2 DEATH 74 0 .5.0 DEATH 74 0 50*0 Oil 2 -40,0 .4.0 2 0 2 DEATH 74 0 IL H20 05 C H20 5 i --16.0-25.0- LD50 20 0 ME050 0:56 -0.18-1 lb8- RATIO LD50/MED50 3600 TATE-SOLID INTRAVENOUS'TOXICITY TO MICE 2 DILUT REACTO MINO 'DEG- MIN, TO I)OSE REACTION SIGN @AG/KG ML/KG FRACT* APPR REE RECOVER 20,0 2,0 1/2 DEATH 74 0 20,0 2.0 1/2 DEC.LCCCMOTOR ACTIVITY 124 8 240 20.0 2,0 1/2 DEC RE2ARING FREQUENCY 632 0 240 080 2eO MIXED CONVULSIONS 336 0 2 1/2- 8 20,0 2.0 1/2 DEC PREENING 240 0 G 300 2OaO 2.0 1/2 2 VEMENT 144 8 i5 TREMORS-REST AND MO 20.0 2.0 1/2 EXOPHTHALMOS 46 0 1.5 .2.0 1/2 30 300 2OoO EYELID PTOSIS-NONPARALYTIC 149 20,0 2,0 1/2 DYSPNEA 60 0 2 G 300 20.0 2.0 1/2 INC RESPIRATORY DEPTH 161 0 G 300 262 0 G 300 20.0 2.0 1/2 DEC RESPIRATORY RATE 2OoO 2,0 1/2 IRREGULAR RESPIRATORY RATE 362 0 G 300 .2090 2.o 1/2 MOT DEF HORIZONTAL STRIP 471 8 ..G 300 2 G 300 20.0 2,0 1/2 MOT DEF VERTICAL ROD 371 8 1060 1.0 2/2 DEC LOCOMOTOR ACTIVITY 124 8 240 1,0.0 1,0 2/2 DEC REARING FREQUENCY 632 8 240 10.0 1.0 2/2 DEC PREENING 240 8 4 240 1010 J,O 2/2 EXTENSION OF LIMBS 341 0 8 l@0*0 1*0 TREMORS-REST AND MOVEMENT 144 0 8 1-0.10 1.0 2/2 EXOPHTHALMOS 46 0 8 PAGE 5145 INTRAVENOUS'TOXICITY TO MICE MINo' DEG- MIN* TO DOSE DILUT REACT* RE2ACTION SIGN APP-R REE RECOVER /:MG/KG ML/KG FKACT* 10 0 110 2/2' 'EYELID PTOSIS-NONPARALYTIC 149 30 300 110 112' -MYORIASIS 154 0 30 lp:o PIRATORY DEPTH361 20 30 ioeo 100 2/2 IRREGULAR RES 10*0 loO 2/2 IRREGULAR RESPIRATORY RATE 362 0 30 79 15 300 1010 1,0 .2/2 RESTLESSNESS 2 124 60 240 3'2 1,6 2/2 DEC-LOCOMOTOR ACTIVITY QUENCY @632 .30 240 .1,6 2/2 DEC REARING FRE 240 3,2 1,6 22/2 DEC PREENING 15 IC 149 30 240 -3,2 1.6 2/2 EYELID PTOSIS-NONPARARYT -79 60 240 .3e2 1*6 '2/2 RESTLESSNESS 124 60 180 1 a 0 oo5o 2/2 DEC-LOCOMOTOR ACTIVITY 1.0 0950 2/2 DEC REARING FREQUENCY 632 60 180 240 .15 180 1.0 0,50 2/2 DEC,PREENING 2 -NONPARALYTIC- 149 .60 iso 100 @0950' 1/2 @EYELID PTOSIS 79 60 i8o 110 0,50 -2/2 RESTLESSNESS -2/2@ EFFECT 73 2 .1,6 2 DEATH 74 0 -25*0 2*5 74 0 .16.0 .106 0 / 2 DEATH 12.0 1 2 0 / 2 -DEATH 74 DILO .1 0 01,196 PEG 300 QS'C 10000 PEG 300 d 0::P?3:5 -LD50 320*0 GREAT MED50 lo8 -0*56-5o6- RATIO LD50/MED50 UNK STATE 50LID INTRAVENOUS TOXI2CITY TO;MLCE DOSE DILUT REACT* -REACTION SIGN MINO DEG- M-,-No TC MG/KG ML/KG FRACT* APPR REE RcrOVER .32OeO 3*2 @2/2 DEC LOCOMOTOR ACTIVITY 124 0 240 32OoO 3o2 1/2 DEC SENSITIVITY TO SOUND 2302 8 6 0 DEC SENSItrIVITY TO TOUCH 231 8 .32010 3*2 1/2 60 3,2 3ZOoO 1/2 HEAD TWITCH 531 15 2180 320,0 3,2 2/2 SOCIAL INTERACTION ALTERED 132 0 30C 320,0 3,2 2/2 DEC.RFARING FRFQUENCY 632 0 300 320*0 392 @2/2 DEC PREENING 240 0 240 32OoO 3o2 2/2 LOW POSTURE .241 a 2 60 320.0 3*2 @2/2 EYELID PTCSIS-NONPARALYTIC 149 .15 240 32OeO .3.2 ;2/2 INC RESP'I.RATORY DEPTH '" 1-61 0 240 32OoO 3*2 2/2 IRREGULAR RESPIRATORY DEPTH361 0 15 3.2 2/2 DEC-RE5PIRA;OAY'RAtE . .. .262 8 240 32010 3,2 2/2 IRREGULAR RESPIRATORY RATE 362 0 15 2eO 2/2 DEC.LOCOMO',rOR ACTIVITY 124 0 - 10010 120 iooo 2 .2*0 2/2 SOCIAL'INTERACTIBN ALTERED 132 0 120 .100,0 2.0 @2/2 DEC-REARING FREQUENCY 632 0 120 240 0 100.0 2*0 @2/2 DEC PREENING 100.0 .2,0 2/2 INC.RE5PIRATORY9 -DEPTH 161 0 6 10000 @2*0 2/2 DEC RESPIRATORY RATE .262 0 6", .10000 2*0 .2/2 IRREGULAR-RESPIRATORY RATE 362 0 3n- PAG 8 6 INTRAVLNOUS TOXICITY TO MICE DOSE DILUT REACT* REACTION SIGN MIN, DEG- MIN, 2 APPR REE RECC ML/KG FRACTO MG/KG .10010 2,0- .1/ 2 PILOERECTION 72 120 2/2 DEC-LOC 124 30 OMOTOR ACTIVITY 32,0 02*64 Oo64 1 1 8 @3290 1/Z INC RESPI.RATORY DEPTH 6 ATbkY DEPTH361 0 32oO@ -0.64 2/2 IRREGULAR RESPIR 32eO Oo64 1/2 DEC RESPIRATORY2 RA@IE 262 8 .32,0 0,64 .2/2 IRREGULAR RESPIRATORY RATE 362 0 1000 .100 DEC LOCOMOTOR ACTIVITY 124 30 1/2 10,10 .1,0 2/2 IRREGULAR RESP 1.1;,IATORY DEPTH361 0 0 1,010 .100 2/2 IRREGULAR RESPLRATORY RATE 362 0 3o2 .196 2/2 I.RREGULAR RESPIRATORY RATE 362 0 .100 0950 @2/Z NO.E,FFECT 73 DILE 100% PFG 300.QS.C 100% PEG 300 LD50 25o,o UNKNOWN MED50 D .450.0 RATIO ..LD50/ME 50 -STATE SOLID - 2 DOSE INTRAVENOUS TO-ICITY TO MICE DILUT REACT, REACTION MG/KG ML/KG FRACT* 1 GN'. MIN- DEG- .100. 2 m,,p4. -ro 1.6 APPR 0 1/2 DEC @REE RECOVER .1,6 LOCOMOTOR ACTIVITY 1/2 -DEC REARING 124 0 FREQUENC RUB 632 5 ioo.o 2 2/2 SING NOSE y 0 .106 2/2 100 0 EYELID PTOSIS-NOMPAR" 340 30 1,6 6 2 .100,0 112 itqc 4LYTIC 149 @1*6 RESPIRATORY 0 I)EPTH loo,o 112 DEC R2E5plRATORY RATE .161 30 .196 ..1/2 0 R 1,5 2 @-5PIRATORY-RAYE 262 0 32,0 5 .I,o 162 6 3290 1/2 -DEC -LO 2 1.0 COMOTCR ACTIVITY 2/2 !NC EPJ I 14 PRE 124 0 10.0 0 - 6 2 146 120 5 10.0 1/2 DEC.,LOCOMOTO 240 0.62 R ACTIVITY 2 1/2 -P.ILCERECTION 124 0 13 '7 ?- 1 2.0 2 I,o 1/2 3 2 1.0 INC-LOCOMOTOR ACTIV .240 2/2 ITY -3:@ INC P-RETNING 2224 i.o 'PILOERECTION 140 120 180 212 60 110 0*63 72 60 2 -;40 1.0 -2/2 INC@LOComo 240 Oo63 2/2 TOR ACTIVITY 1.0 INC P' ' 2,74 120 2 0*63 1/2 REEN'ING INC SCIIATCHING 140 240 120 @440 120 6 240 240 PAGE 8 6 INTRAVENOUS TO-^ICITY -10 MICE REACTION SIGN MINO DEG- MIN3 DOSE DIL.UT REACTO 2 MG/KG ML/KG FRACTO -APPR REE Rr--'-C%i .1*0 0*63 Z/2 PILOERECTION 72 120 0*32 1.0 2/2 NO EFFECT 73 3,,g 1/2 DEATH 74 0 .200*0 @3.21 0/2 DEATH 74 0 DILO .1009, PEG 300 GS@C 100% PEG 300 32*0 -25*0-4OoO- LD50 MED50 0956 -0*18-1'8-' RATIO LD50/MED50 56oO STATE SOLID 2 INTRAVENOUS TOXICITY TO MICE DOSE DILUT REACT* REACTION SIGN MiNo DEG- M.N, 70 MG/KG ML/KG FRACTO APP.R REE REL'-2-CVER 10010 1010 2/2 DEATH 74 0 32,0 3,2 1/2 DEATH 74 300 32,0 .3,2 1/2 DEC LOCOMOTIOR ACTIVITSY 124 2 0 G 300 3?-.O 3 a 2 1/2 DEC-REARING FREQUENCY 632 6 G 300 32,0 3,2 1/2 DEC PREENING 2 .240 0 G 'Zoe -32,0 3,2 1 /.2 LOW P05TURE .241 0 $110 .32,0 .3*2 '1/2 8XOPHIHALMOS2 -46 0 8 1/2 EYELID'P-JOSIS-NONPARALYTIC 149 30 G 300 32 a 0 3 a 2 32,0 3.2 l@2 PUPILLAkY2.LIGHT,REFL#c-X ABS 152 0 120 @32,0 3,2 1/2 MYORiA5is 154- 0 120 32oO 3e2 .1/2 INC RESPIRATORY DEPTH 0 G :,Oo 32oO 3,2 1/2 IRREGULAR RESPIRATORY DEPTH361 0 G 300 32,0 302 1/2 DEC RESPIRATOR@'RAt.E- .2262 0 30 32,0 3.2 .1/2 INC RE5P!.RATIORY RAYE 162 30 G 300 32eO 3e2 1/2 IRREGULAR RESPIRATORY RATE 362 0 '70 32oO 3.2 2 -1/2 MOT DEF HORIZONTAL-WIRE .171 0 so 32oO 3*2 1/2 MOT DE@ VERTA?CAL SCREEN .271 0 60- 32,0 3,2 1/2 MOT DEF HORIZON-IAL-STRIP 471 0 2 1-20 32oO 3o2 1/2 MOT OEF VER7ICAL-ROD 371 0 6^ 3290 v 3*2 1/2 MOT DEF ROTA-ROD 3 771 0 60 PAG E 865813'. INTRAVENOUS TOXICITY TO MICE DOSE DI-LUT REACT4 REACTION SIGN MINO DEG- M!No I MG/KG ML/KG FRACTO APPR REE RECOVEF 671 0 6C 32,0 3,2 1/2 MOT DEF INCLINED STRIP 72 30 G 30( 1/2 N 32.0 3,2 PILOERECTIO 1000 .1000 1/2 DEC LOCOMOTOR ACTIVITY 124 O 3C 1000 2/2 EXOPHtHALMOS 46 0 is .10*0 PUPILLARY-LIGHT-REFLEX.ABS 152 0 6C .10 a 0 10.0 .1/2 0 6 C .10,0 1010 1/2 MYDRIA515 154 2 3.,2 3o2 .2/2 INC.LQCOMOTOR ACTIVITY .224 8 12C 3.2 .3,2 1/2 HEAD TWITCH 531 .15 6( .224 100 -.1000 2/2 INC@LOCOMO2TCR ACTIVI'IY 15 6C @0932 .3*2 .2/2 NO.EFFECT 73 5090 .500 2/2 :DEATH 74 0 4OoO -490 .2/2 -DEATH 74. 0 .25 9 0 1 .2,5 O/ 2 :DEATH 74 0 @D. IL .100% STEROL DIL* BUSP QS.C H20 j. LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL 2 OMIN 5MIN 50MIN 55MIN 6 MIN 20MIN 25MIN 30MIN 35MIN 40MIN 4 CMPND LEVEL 5MIN IOMIN 15 @"A MG/KG 2 2* 0 167* 26le 137o 1450 203* 150# 101* 1356 OSOOO 543a 347, 365* 252. 315. .243. 213, ;230, 184. 195, 144. 78* 44, r6, 2 371* MEAN 3980 3599 340, 205o 237o 1849 165* lgg# 147* 900 23s) ..Be 49* 1356 l8oOOO 246o '24i. 364. -2910 240* 279o 331o 326o 759 22i 85, 51, 67.@ 114, 140, 2400 219, 106, 45o 950 78, 110, 46, @149, -239. 216. 240. 249o 2199 186, 85, 50o2 980 48, MEAN 1540 262, 291. 456. 338, 1356 10,000 '525o 305. 1746 197, 245o 183, 220. 537, 467, 425* 347. 323, 2 328, 2349 353, 361a 262. 173, 249. 220, MEAN 263, 248, 3229 409, 300. 2099 216* 220 502. 475, 326, 160, 132, 113* 1356 1,000 5129, .419. .388o 446. 359. 271, 242o 177 1090 3644 317* 369* 3129 312* 216o 197o 176: 126. 139 99* 35. 442 379, 379 336. 244, 220, 177, 118* 150, 116o 74. MEAN 2 0 368* 0 2367 0,000 647. 549o 377. 539. .450. 418. 378. 359. 336o 317, 364, 393* 610, 308* 252* 359* 389* 363o 2619 206a 3539 258o 203. 230o 629, 429,2. 315. 449, 4209 391o 320. 283. 345,p 288* 284. 312* MEAN 0167 10.000 154. 68* 35, 14, 24, 7, 100 3. 3* 509 50, 74 362. 114o ?5, 52. 280 21. 23o 15* 52c 42: 94. 55o MEAN 258, 91. @o. 339 59, 31, 190 12, 13* 33* 51, 580 2367 *100 615. 356. 241. 229. 230. 222o -155. 92a 1169 Be 0, 2 ol 324o 311. 194a 990 627 329, 266, 265. 397o 352o 252o 392o 621: 343, 2540 247a 314* 287a 204. 242, 220. 1609 97o 50o MEAN .LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE -COUNTS AT INDICATED INTERVAL CMPND LEVEL 5MIN IOMIN 15MIN 20MIN 25MIN 30MIN 35MIN 40MI2N 45MIN 50MIN 55MIN 60MIN MG/KG 2 8 3 1 6 6 0.000 279.- 363. 288. 338. 255. 199. .290. 216o 244* 350o 2516 2 326, 292o 257, 290o 2 78 9 236, 187o 308* 289, 253, 183* 1 14, m 328o '273, 314* 267* 218, 239o 262, 2679 302, 2 .303. 2 EAN 33, 140. 2516 56.000 29. 50o 144, 28, 43, 13. 72o 103, 14o 49, 14, 29. 108 1 30 0 35, 59o 16* 0 2, 19* 176o 88* 152* 204, 256, E,AN 69* 40* 90, 44, 30 7 o 46* 140 5 1 101 109. 143. m lOoOOO 299, 143* 122* '2516 2 19le 159a 75, 112a 31a 13* 139 3. 25 852, 541* 339, 327, 381o 509, 415, 459o 3489 2349 1950 177:- MEAN 576, 342o 231, 2599 270 292o 264. 2452, 181. 124, 990 101. 2516 1.000 405. 369. 302. 304, 333a 312, 251, 317- 267, 305, 164, 51* 751, 485o 3699 321o 225* 3699 288o 161o 218o 169* 2 1790 143o MEAN 578, 4279 336. 313a 279, 3419 270a 239o 2439 237* 172* 97. 2531 OOOOO 7050 566, .446, 4729 .4659 242a 245, 313,, 234o 261. 178,, 1719 2 348* 260* 267* 254o 1689 169, 152. .219, 164* 369 102o 00 MEAN 527. 413o 357. 363o .3176 206. 199. 266. 1999 149, 140o 86o 2531 lOOoOOO 90. 36* 332, 190 26, 15, 90 34o 40. 28, 24. 190 1-3a 109* 510 33* 40* .40a 34o 22o 7* 14* 8* 00 MEAN 529 73* 42, 269 33o 28, 22o 28o 2 24* 219 16, 100 2531 10,000 644, 426, 299, 199a 296 .2 38, 147, 223, 223, 137, 25* 76a 632. 3!99 254o 177o 161: 205o 1569 2119 234* 222* 2259 102o 4 MEAN 638, 373* 277, 1689 22ge 222, 152 217o 229. 180o 125o 134a LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL CMPND LEVEL 5MIN 10MIN 15MIN 20MIN 25MIN 30MIN 3.5@iIN 40MIN 45MIN 50MIN 55M N 6OMT 2 N MG/KG 2531 1.000 609. 356. 312, 249. 286, 176, 232 329, 347, 240, 253, 262 99, 282: 237, 264, 240. 174. 12@: 595, 414, 336, 199, 338, 2 2 MEAN 602, 385, 324, 224, 3120 238, 257 283, 306. 240, 214,' 193. 2598 0,000 239, 319, 251, 183, 273, 227. 270. 202. 134. 115 43. 31. 183, 273, 227, 270, 202. 134, 239, 319, 2 251, 115.: 43. 310 MEAN 239. 319, 251. 183, 273, 2 2 7'a 270. 202. 134, 11@, 43. 31, 2598@ 10,000 363. 164, 86, 829 106* 96. 82, 132, 148, 173, 103. 34. 2 21 590* 275* 244* 2349 265* 234o 183a 228* 81. 64* 74o MEAN 477, 220, 165, 158. 186. 165. 133, 180o 115, 119. 62. 54. 2598 100 446. 312. 200. 2 196, 158, 161, 139. 124. 145 149, 170, 113. a 8 7. 99* 1079 29. 440, 197, 222a 175o 1870 1850 2190 MEAN 4432, 255, 211. 186. 173. 174, 162, 1726 122. 128. 100, 78o 2717 0,000- 741. 575 436. 314, 386, 357. 334. 327, 502. 426, 362. 269, 825* 565: 401, 495o 309a 469o 477o 53le 426* 392- 325, 320, 2 MEAN 783. 570, 419. 405, 348, 413, 406, 429, 4649 409, 344. 295. 2717 209100 249. 56. 167o 88a 126v 127o 24, 26o 182. 177o 155* 263* 194o 58. 1?9o 97o 910 107. 140* 229. 2 212. 325. 211. 104, MEAN 222o 570 148, 93o 109. 117a 82a 128. 197* 25le 183* 184* Z-c'(7 lt;000 589, 308o 370* 301o 3036 295* 268a 208o 276o 143* 0 95. i6go 644, 347. 246, 209o 2490 2410 238, 217, 195, 96o 109o 99, MEAN 611, 328o 308o 255* k76a 268, 2530 213, 236* 120o 1020 131;u LOCOMOTOR ACTIVITY OF MICE GROUPS OF'THREE MICE .COUNTS AT INDICATED INTERVAL CMPND LEVEL 5MIN 10MIN 15MIN 20MIN 25MIN 30MIN 35MIN 40MIN 45MIN 50MIN 55MIN 60MIN MG/KG 2778 -0*2000 823. 415* 185. 345. 244, 217. 2 38 . 252- 239. 229. '207. 179 .613, 397o 3049 211* '272, 171, 191, 61. 55 5 9 51 4, MEAN 2718, .406o '245* 278. 258t 194. 2150 1570 147o 117, 106. 921 '27 8 32.000 207. 500 48. 79. 190 66. 19. 129. 88. 18* 12, 54. 186. 68. 97, 71, 776 95. 83* 63* 68* 143 45, 18. 51* 197, 73, 75a 48. 81, MEAN 59. 96. 78* 81, 29. .36, 2 266, 2778 10,.000 553. 373. 927. 166. 273, 220. 206. 206 145, 108, 48. 602. 292, 194, 258, 216o 212, 158, 195, 1204 126, 30 79, '246. 262. 1910 243, N 578. 3 33 189, 201 163. 1362, 69. 64. 8 '@1,000 656. 252, 254. 236, 150, 332. 274, 102. 142, 112, 520 23, 383* 32 1. 376o 295. 2 539., 238. 227* 224o 1760 147. 9 1 205. 598 318o -2 8 8, 306o 223* 285o 251* AN a 163, 159i 130, 72 114. 2867 0.000 599, 363, 256, 249, 252, 197, 288, 3259o 209, 249* 122, 205. 618. 361* 410* 380o 257. 364 336* 371. 342* 378* 349, 282. MEAN 609, 3620 333, 315. 255,@ 281: 312. 365, 276. 314. 236. 244. 2867 10.000 14. 17. 600 40. 234 40. 14* 25, 22, 190 57. 96. 68* 48. 38* 104, 89, 24. 32. 95. 75* 342. 377* 364* MEAN .41, 33o 49, 72* 56. 32, 23, 60, .49. 1810 217* 230o 2867 I&OOO 264. 2042o 271, 239o 293. 413, 2429 429a 273. 232* 260o 1350 356a 249o 327* 240o 3189 296o '1849 289o 307. 245o '2570 131. f4EAN 310. 227, -299. 240, 306* 355o 2 13 9 359, 2970* 239. 259. 13'@o LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL IN 50MIN 55MIN 60MIN Ct4PND LEVEL 5MIN IOMIN 15MIN 20MIN 25MIN 30MIN 35MIN 40MIN 45M 2 MG/KG 23, 1 2 2867 .100 545. 187. 366, -412, 315. 171* 26i. 152'. 116. 105. 218, 3 1 3 214 129 166. 213. 140 17, 1 3 359. 3110 248 0 2 195* 159, 1 6 5 123: 20. 13. .452, 349* 307: .315, 314, 193* 14EAN 229* 63, 80, 68* 57, 0, 2897 01000 -244, 196* 246* 230. 163. 261, .410, 343* 331, 294, 272, 316* 2 469, 420* 438. 221. @201. 212* 200. 176, 136. 158. 342. 2 357. 308. 26, 182, 245, 237, MEAN - 150o 2207o 208* 2897 50,'100 146 267. 105. 105. 60, 10. 331, 216* 175* 3* 17, 22, 0, 18, 0. 138: ii. 159, 177. 145o2 78, 174* 1194 880 113. 104* 77* 142, 136* 58, 132o 119t EA 161* 9 404. 238@, 274. 247. 131o 1.000 505. 675. 532, 589, 359o 44 897 333, 290o 280o 329* 274* 209a 553, 553, 405, 447o 380* 225o 529. 614. 469, 518* .370, 337,, 369, 264. 277* 288. 203. 1859 2 N 935 0.000 333. 288* 3499 228, 187. 2779i 233, 212, 149. 199. 114 158, .434. 244. 293@ 267. 217o 188' 256. lele 2094 2206 122. 117. 384., 266. 32 1. 2489 202* 233, 245* 197* 179* 210* 118 138. MEAN 2935 2 32,000 85. 93. 122. 126, 123. 72,i 76. 157. 141, 38. 174, 93, 64* 48. 76. 38* 5* 16a 1 3 9 13* 16. 33* 41* 34* 9 82* 64. 44 45, 85. 79o 36* 108* 649 9 MEAN 752, 71. -o 203, 194a 159 92. 1 2 7 90. )> 2935 1 .000 .489. 430. 370. 299. 317* 264i 12, 367a 363* 343o 420o 354* 24, 3 614- 397* 432* 4169 .474o 4 rn 401, 358. 3969 314o' 258o 2819 261. 218. 274a 222* MEAN 552. 414* LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE 5 AT INDICATED INTERVAL COUNT 2 25MIN 30MIN 35MIN 40MIN 45MIN 50MIN 55MIN 60MIN CMPND LEVEL 5MIN 10MIN 15MIN 20MIN MG/KG 2963 o.ooo 592. 381, 277. 380, 410* 274* 296, 2 323, 282, 241* 295* 2929 18. 236 175, 130* 15, 39, 71& .470, 353o 58 124, '353, 2 .531, 367* 1 2 14EA 68: 252. 382, 246, 266. 249* 2060 128, 167. 182* N 2963 56*000 19. 26* 7* 5 8 5 2 5@, 9 44, 57.o 3* 7* a 2 .41, 14* 40. 57o 18. 22, 22, 32. 19, 1010 75o 125* .529 41. 67, AN ME 30. 20* 24*2 58o 12* 24. 16, 38, 38o .6 o 11, 2 8 289 124* 241o 2@63 32,000 34,, 20* 44, 1 2 15 6* 2 87, 43* 250 19, 24, 2: 49. 4. ill 80 11 360 28, 80 15. 180 63, 139* 61, 32* 35* 13,2 189 9, 3 10.000 4020 2120 245, 246* 199, 385. 310, 238. 320. 214, 241. 235. 159* 2 52 240. 263. 2 82. -8. 38. 30, 0* 0. 10 110 N 242. 110, 142, 138. IOQ. 193a 156. 125. 230. 2330 241, 249o 2963 19000 440. 310, 249. 245. -226, 312, 2 200. 215, 174. 180, 68, 201* 355o 394a 5589 500* 545a 4509 470* 485* 477- 446* 495o MEAN 442. 333. 322. 402, 363, 429, 325, 3423. 330. 329, 257, 348, '2984 0 000 669. 587, 455. 435. .448. 383. 292, 266, 269o 177, 131, 25. 444o 4709 338* 3329 3490 305a 224o 1619 240* 1259o 176@ 93o MEAN 557, 529o 397, 3849 399* 344* 258o 214, 255* 168* 154, 590 8 29 4 10,000 583, 498, 368, 379, 252 a 2 6 30 369. 22 8 . 3 1 5 2 279. 243, 115, 51le 448. 416* 294o 337a 3820 383* 193& 376* 204o .113. 59,, MEAN 547, 4739 392. 337,, 295* 323@o 3760 211. 3460 2842. 178, 87. LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL@ 20MIN 25MIN 30MIN 35MIN 40MIN 45MIN 50MIN 55MIN 60MIN C14PND LEVEL 5mlN 10MIN 15MIN 2 MG/KG 2984 1,000 886, 642, 393, 382. 287. 3400 416, 4320 479. 340. 244, 267, .284, 203, 297, 234 189, 205@ 228. 170. 215, 175,, 543. 361. MEAN 715, 502* 3390 293, -292, -287, 30329 319* 354* 255* 230, 221, 2994. 0.000 7 486, 470, 413. 363. 362. 3550 317. @251, 256. 225, 465* 24, 864. 536. 394, 314. 367, 332, 362. 313. 296. 226, 166, 125, MEAN 7924, 501, 440, 392, 390, 348, 362, 334, 307. -2399 211. 175. 4 100.'000 715. 505.- 281. 368, 483. 303. 325* 100. 37. 29, 125. 30, 544. 311, 157. 139. 96. 187. 135. 86 8 27. 8 , 102. N 630. 408, 219, 254* 290, 245, 230, 93: 23: 28. 67. 200 994 1,000 741. 638. 384. 396, 506. 504., 386. 3430 449, 348. 19q. 275, 729* .453a 376. 2669 303* 280o 259* 323o 341* 246* 276* 191a M N 735, 546. 380, 331, 405. 392, 323, 333, 395. 297, 238, 233, 2995 0,000 694. 489 .428. 363, 318. 292. 311. 238 183. 128, 112. 75, a 7689 5580 382* 2719 229*, 275a 316* 2679 163. 160. 980 96o MEAN 731, 524s. 405. 317* 274. 284o 3140 253, 173. 144@ 105, 86, 2995 20,000 71. 84, 82* 132. 187. 1910' 102, 106, 108, 104, 67. 7-1. 112. 178. 216. 189a 170. 76o 10 00 94a 107* 202. 173* MEAN 92. 131a 149. 161* 1799 134a 52* 53.@ 101. 106, 135, 125* 2995 1-000 963. 632. 461* 3!6o 297* 353o 282o 3272o 244. 104c 268a 37-i. 653a 698o 3390 293* 413* 328o 297o 302o 309. 2649 23L,. 1084 MEAN 808& 665* 400. 305o 355o 341o 290o 3).5* 2'17. 1849 250o 24341 LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE ATED INTERVAL COUNTS AT INDIC MIN@50MIN 55MIN 60MIN 2 ldMIN 15MIN 20MIN 25MIN 30MIN 35MIN 40MIN 45 Ct4pND LEVEL 5MIN MG/KG 77 78* 1 0'9 80 .32* 71, 8 1 00000 237* 144* 34. 100. 73o 2999 2 @238o 180, 255* '289* 243.m 507. 312* 3849 358. 230. 200. .400 9 52, 139a 2399 124 94, @144, 180* 162* MEAN 372 228. 209. .229* 1 2 .0 .0 16* 3o 0 a 00 6* 2999 10,000 82, 1 2 5 34o 43* 31 190, 193, 156, ill. 130, 152. 181* 371, 2270 271. 243. '258 2 227. 1769 153. 143* 145o 95, 97* 810 569 73* 78o 910 MEAN 2999 1 *'000 438. 326* 284* 321. 271. 335. 266, 254. 212. 241. 147, 179, 224, 151 159, 119* 198* 106* 44. 2 438. 316, 185, 259, 120, .438, 32le 235. 290. 196. 280. 209. 207, 166* 220* 127, 112* '223 '292 307, 6 0.000 804. 575, 434. 574, 3379 455o 365, 299, 347o 583o 3879 .420* 406o 318* 297o 211* 273* 346* 132* 228o 142* 694, 481o .427, 490, 3289 376, 288* 286* 3476 178* 260, 2259 N 000 681. 535, 266, 455, 368 282. 242o 3460 2179 385o 166, 243, 5026 20, 6890 469a 331. 203. 335o' 2279 1919 115o 97* .117o 1129 285* MEAN 85, 299, 329, 3529 255. 217. 2alo 157. 251. 139 6 5029 0 2649 2 5026 9320 437, 383, 1 91. 311. 252. 269, 242. 219. 180, 129. 87, 237. 438* 379. 295* 244o 242a 229. 340. 244* 2590 204* 171* 137* MEAN 4382, 3819 2430 278o 247a 249, 291* 232. '220. 167* 129, '187o 5031 09000 647a 50ge 342,, 3639 .404o 4119 288o 280c 268o 4009 232. 179o 562* 475. 4029 3109 312a 360o 351o 293* 249* 264* 5 238* 1159 MEAN 605a 492* 372* 347o 358o 386o 320o 287* 259* 332* 235* 147o LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL CMPND LEVEL 5MIN 10MIN 15MIN 2Ot4lN 25MIN 30MIN 35MIN 40MIN 45MIN 50MIN 55MIN 602MIN MG/KG @25, a 0 29* 9 5031-100*000 906 22o 2o* 46* 9* 87,. 18o 13* .46. 17, 20@ 2 63, 37, 10. 8, 426. 367. 234* 900 MEAN 258, 19'5 127* 68, 36o 67. 18, 17;i, 19* .23o 20. 9 *I 187o 97, 110, 2 99* .34, 22. 46, 6* 5031 -20,000 610. 218. 163. 184* 440. 345. 190, 188, 175. 167, 122. 168. 284. 232, 179. 83, 127* 113, .45 9 ME2AN 525. 282. 177. 1864 181o 132, 116, 134* 159* 1,@000 588. 341, 364. 176. ;200. 209, 214. 1970 loo. 97o 154. 25, 792 353 320* 284* 233o 243a 32le 292* 31249 148* 1510 679 690. 347, 342. 230a 217. 226, 268. 2450 207* 123o 153, 46, ..0"000 397 .320, 346, 464. .-430, .423. 267. 250' 266* 127* 76* 188o 380, 2 368o 346* 4309 395o 413a 364. 205o 168* 159a 180o 214o 3 16 2284 2 17. 143o 14E 389. 344o 346* 447a 413o 4189 2 128. 201. 58 25,100 10 198, 144, 135, 87. 103o 125* 70. 118. 116. 186o 211. 50 37: 73* 73, 50o 30o 47* 84a 144* 215* 206* 187o 177o MEAN 2 24a 1360 109, 93, 5991 75. 105o 107* 167. 161. 187. 194o 5058 109000 772, 6749 62le .604o 579. 473o 432, 301, 351o 428. 3469 472o 359* 286. 225o 266* 216* 2 2759 275, 254* 313o 403* 3859 350* MEAN 566a 480* 423* 435o 398* 374o 354. 2789 332. 416a 366* 41le 5058 1.000 355, 3 1 5 a 331* 226o 233o 3419 102 9 67* II* I 09 12, 0 0 634, 448, 332o 187o 263o 248o 216o 200, 176o 17,o 65, 60* MEAN 495. 3829 332* 20'19 246o 2959 1590 .134* 94* 14o 399 300 LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL IN 15MIN 20MIN 25MIN 30MIN 35MIN 40MIN 4 60MIN CMPND LEVEL 5MIN'10M' 2 5MIN 50MIN 55MIN MG/KG 134. 5058 1010 576. 349* 260. 196. 216. 155o 297* 2170 273 164, 102. 2 159. 161. 186 611. 309. 171. 227i 191, 115, 173, 141* 158 162* 1329 160* MEAN 594. 329. 216. 212, 204* 13502 2359 179, 216o 5059 0*000 600, 335, 448, 372, 269, 2970 160* 390* 5014 515* 211 345* 752. 547o 478* 339* 536. 4600 4750 5356 338o 4260 469: 422, t-,iEAN 676, 441 o 463* 2 356* 403a 379, 3 1 8 o 4639 420* 471* 340* 3840 9 1000'000 81 00 0* 0 Os 00 0 0 0 0* 0 9 241, 188* 176, 72. 1704 390 37o 24@o 15, 100. 2 2, 00 0, III* N 92o 36o 85o 20 9 19 0 1 2 9 8 1 50o 1 0 Os 1219 150o 9 ioiooo 8356 532o 518, 5309 347* .402* 393o 398o 417* 225* 326, 304, 8590 416, 205, 344. 281, 300 258, 145, 158o 107* 149, 53, 14EAN 847, 474o 362, 437, 314, 3514 326a 212, 2889 1669 238* 179o 5059 1.000 404, 3290 340, 267o 265o 327o 2462o 203o 166o 1809' 218, 187a 825, 443 329. 227. 279,. 226, 219, 246. 152* 257, 84, 105, MEAN 615, 386: 335. 247. 272, -2770 233* 2 2.5 159* 2 19 9 15le 146 9 5071 0,000 2 801. 630* 347* 376o 370 3409 287o 299* 349* 2519 52, 121* 757, 714o 2620 437o 372: 367, 377, 441, 342. 3889 227, 329, MEAN 779, 672. 305* 407* 37le 354' 332o 370* 346*2 3209 140, 225. 0 5071 32.000 172, 141a 147, 164. 20 1 9 154 a 86. 188c 156a 164* 326, 298a 114,b 85. 99* 145* 1479 168o 80 69a 140c 89o 2889 216a t4EAN 143o IL139 123a 155, 174* 161, 47o 129o 148* 1 2')'o 307. 257, LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL 60MIN C14PND LEVEL 5MIN 10MIN 15MIN 20MIN 25MIN 30MIN 35MIN 40MIN 45MIN 50MIN 55M N MG/KG 5071 10,000 749. 441, 421, 437, 345, 298, 332, 349 253. 242 187, 234. 715. 488. 307. 306, 2850 214, 226, 195, 270, 197, 43. 47 2 -256. 279, 212, 2620 2209 141 MEAN 732, 465. 364, 372. 315. 115. 5071 1,000 745. 622, 477. 438, 327, 449. 138, 374. 241. 117. 138. 123, 2 358. 2 3 3, 256. 287 308. 196, 114. 69. 135. .52. 84, 77. 14EAN 5 52 428, 367. 363. 318. 323, 126. 222. 188, 8 5 111, 100, -000 329, 344, 340, 2 35, 171. 134, 622. 12 114. 2 0 , 11, 0 I . 735. 527. 356. 373 304. 306. 351. 406, 368. 366. 353. 404. N 532, 436* 348, 304: 238. 220, 207, 209, 241o 189. 177, 203. 25OoOOO 88, 59o 34, 22. 27. 62. 41, ol 0. 0. ol 0, 495, 207, 224, 94, 89, 163, 0. 80, 262, 18, 27. 0. MEAN 292.' i332* 129. 58o 58. 113. 21* 40, 131, 99 14, 0. 5092 10,000 436. 225. 232. 200, 219o 170. 291. 253, 219, 204, 211. 19-t, 7790 576. 436. 305. 235.@ 276, 345, 244. 216 213. 2 198, 1479 608, 401* 3349 253, 227, 223, 318, 249* 218* 20go 2059 172. MEAN 5104 0.000 766. 509, 451, 352, 332, 367, 284, 187. 318. 348, 275, 217, 774. 580. 480. 435, 3652. 5286 409. 335. 441, 235. 324. 425. MEAN' 770. 5459 466* 3949 3499 448* 347a 261. 380, 292. 300. 321. Io 4 639100 97, 44o 63, 41, 0 59. 92a 137, 69, 122. 129. 109o 1339. 92. 799 56o 44. 55, 269 61o ggo 21!0 108. 840 MEAN 118, 68* 71* 50, 49, 57. 59a 991, 84. 16i'o 119. 9.t, .@m, I$, LOCOMOTOR ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED 2 INTERVAL CMPND LEVEL 5MIN 10MIN 15MIN 20MIN'25MIN 30MIN 35MIN 40MIN 45MIN 50MIN 55MIN 60MIN MG/KG 04 10*000 '712. 379, 51 580, 303, 5227, 290o 235j, 298, 390, 362, 363, 318, 776, 364* 191. 168, 205, 184, 160, 129, 120. 779 48, 0 MEAN 744,, 472, 247* 348, 248, 2101, 2290 260o 241* 270* 183, 21501 2 5104 19000 697. 484,, -4250 320* '378* 38019 475* 245, 386o 3209 .37to 280, 261* 322, 2 36 9 -231, 238, 928. 637. 533 452. @448, 367, .421. ME2AN: 813, 5619 479: 386. .413. 374. 448. 253* 3 54 278* 301, 259 43 0.000 364. 229. -267, 401* 215* 1361, 187, 147, 59a 12a 18o ll* 693. 344, 299, 287, 375, 2221,2 225, 191, 170, 56 9 37. 32, 34* 28. 22, N 529, 287 9 283,, 3449 295* 1790 206 9 169, 115o 3 @2.000 190. 107'9 83* .42, 510 1960 100, 111, 160* 66o 115o 109* 89, 35o 0 0 0 0 1 0 1 93 9 63o 42, 22* ol 2 o MEAN 140 la 7 1 42, 21, 26. 10Q, 97, 87o 101* 4429 58o 56o 5143 lOoOOO 749, 287, 143, 73, 42o 15,9 72* 48o 569 191o 119o 28o 647, 413* 220* 19le 199a, 2011, 910 62* 239 3o 00 139 MEAN 2 698, 350a 182, 132o 12le 108* 82, 55* .409 97. 609 219 5143 loOOO 518, 4289 307* 359* 349* 362's 336o 312, 1779 172* 167* 160o 766* 447* 325* 263o 192o 215@ 101* 118a 154o 82* 123* 979 MEAN 642, 438o 316, 31le 271o 289* 219o 2159 1669 1279 1459 129o 5145 OOOOO 354, 287, 266, 1819 363o 378, 2273. 307. 188. 1669 107. 113. 380. 363o 2720 3659 4029 431@o 315a 136o 167, 67* 239 39 MEAN 367a 325o '269* 273o 3839 .405o 294o 222a 178o 117o 65* 589 VITY OF MICE LOCOMOTOR ACTI GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL 2 N 60MIN OMIN 55MI C PND LEVEL 5MIN 10MIN 15MIN 20MIN 25MIN 30MIN 35MIN 40MIN 45MIN 5 MG/KG 2 30o 19, 46* 17* 13, 17 9 21i 1 9 100 5145 15*800 1 1 1 53* 40o 82* 147, 2 1 3 99* gla 79, 63. 1 1 0 6 38. 203, 92 75. 128o 66: 63. 42. 38, 14, .1716 59, 46, 890 55. MEAN 33, .47, 3 344 123, 120'a 57. 101* .6 o 5 10.000 106. 118. 112, 2 0. 48, 31* 51. 12. '72, 107o go. 1010 20, 35, 514 62* 105, 79* 6 1 21, 17, 8 2, 30. 58a 53. 115. MEAN 77. 75o 17. 2 43. 15. 201. 97, 98, 203, 166, 144* 50. 145 3,200 373. 2250 9 0 56* a 236, 2 220. 201' 172, 110, 22 524, 2710 292, 303, 244 0 71. 220, 193. 173* lllo 77 122, 379 449, 248, '247. 200, 1 E A 2 N 145* 73, 100,' 6, 174 226, 135, 105o 188 5'145 .320 837. 428. 18 0 444. 319.2 300. 2339 3520 301a 519 2499 119* 108* 66. 560 132o 9 1 0 a3, 31* 0 218, 78, 219.* 641. 2 374. 241. 2049 289 MEAN -237, 326. 865853 0.000 921. 593. 550. 434. -437, 247. 356, 424 416, 165. 649, 422* 449. 418. 2 302* 233, 260* 211 124. 236. 147. 124. 308* 3k8: 2706 201. 192* 225. 785, 508. 500, 426 370, 240o MEAN 2 65. 187 122 74, 163, 135, 78, 95, 120* 365853 1009000 23* go 115 107. 24o 62* 1620 0 2 0 13* Os 4* 89* 12* 29o 4, 175* 720 6 61 .399 1269 74o 54. 101o 2 MEAN 18. 59 58* 143o 1109 59* 10.000 656. 335. 283. 202, 234, 23@o 198. 159. 1289 2 51, 3?-8, 2649 256. 348, 23.5* 83o 2 733. 420. 324* 327. 380. 3 148* 304, 265, 30'r2e 309o 225a 244o 196o 2000 229* MEAN 695o 378 9 LOCOMOTOR.ACTIVITY OF MICE GROUPS OF THREE MICE COUNTS AT INDICATED INTERVAL LEVEL 5MIN IOMIN 15MIN 20MIN 25MIN 30MIN 3514IN 40 CMPND MIN 2 45MIN 50MIN 55MIN 60MIN MG/KG 365859 0*000 535. 442. 440, 318o .3309 290, 287, 2440 297. 132. 217. 270. 771. 602. 511, 422, 406. 398, 389, 272- 390. 3449 146 232 MEAN 653, 522* .476, 2370o 3689 344. 338. 258# 344. 238. 182: 251* 365859 lOoOOO 305 286. 180, 154o 123* 192* 316, 200* 248, 1799 181, 162* 215: 124 157. 252. 237. 265, 241, 250, 168. 199, .117. 139, MEAN 2 260, 205: 169* 203. 180* 229, 279* 225. 208* 189* 149* 151o C65859 1.,000 625. 365. 334 203, 250, @270, 290, 248, 186, 188. 210. 111, 489* 293. 2894k 238* 304. 196. 2 181. 910 73. 122. 86. 49o 557, 329. 312. 221, 277* 233a 236. 170, 130. 155a 1486 80, 65 91 813. 724, 504. 491, .425, 582, 478, 450, 307* 3929 517, 253, 830, 600. 412. 394. 352. 357* 250* 2114 282. 237* 258* 152o MEAN 822, 662. 458. 443, 389, 470o 364. 331, 295, 315, 388, 203. 265891 32oOOO 53, 24* 52, 7, 100 12. 4o 15a 190 50, 7o 0, 258o 234o 219* '238o 18 251a 1880 152o 208o 183o 153o 9. 160o' MEAN 152, 106o 102, 108o 97 9 28 3 9 131o 125* 119. 144o 98 0 80, 865891 10000 697a 5459 420* 409o 441o 387o 28to 364. 3579 417. 301* 392o 631a 414* 572o @Ole 390* 391o 363* 402o 8461. 444. 342, 3269 MEAN 664a 480o 496o 455o .416* 389* 322* 383o 409* 43le 325* 359# ni tit, 4w@itt+@ ki ICE FOR 1356 AT 18p'(00 MG PER KG 'CUMULATIVE COUNTS PER 3 M TIME 7000 .90000 IN 10000 3000o 2 50000 6000* 80000 jooooo MINE 00 20000 4000* 00 5, 1 0 150 20. 256 30a 35* 402* 45, 500 5 5 4 ,.I .. .. ..... .. TIME CUMULATIVE COUNTS PER 3 MICE FOR 1356 AT 10,000 MG PER KG IN 10000 3000a 5000* 7000, 9000, MIN, 0 2000* 4000o 6000* 2 80000 10000* 0 50 10, 1 5 2 0 25 30, 35* 40* 45o 50, 55, If@ n 1.000 MG PER KG 'CUMULATIVE'COUNTS PER 3,MICE FOR 1356 AT TIME 70009 90000 IN 10000 30000 50000 1 0 2 80000 100000 .4000* 6000o MIN. 00 2000* 0 5 1 0 . 1 5 200 25, 30a 350 4 40, 45* 50* 55o .44 CUMULATIVE COUNT@ PER 3 MICE FOR 1356 AT 0*000 MG PER KG TIME '7000a I N 10000 3000,, 5000* 9000, MIN. on 20000 4000* 60009 800006 100000 00 5 0 0 . 15. 200 25* 30, 350 40* 45* 50* 55, f,n An, JL TIME 'CUMULATIVE.COUNTS PER 3 MICE FOR 2367 AT lOoOOO MG PER KG IN 1000, 3000o 50009 7000, 90000 t MIN, 0 2000* 40000 .60000 8000* 2 10000* 00 I 0 20* 25. 30. 35, 40* 45, 50. 550 TIME CUMULATIVE COUNTS PER 3 MICE FOR -2367 AT *100 MG PER KG 3000o 17000, 90000 IN 10000 MINE 00 20000 4000* 60009 80000 10000* 06 4 5, 10 .15, 20, Z50 30 35a 40, 45, 44 2367 AT o.000 MG PER KG COUNTS PER 3 MICE FOR TIME CUMULATIVE .50000 70009 90000 IN 10000 30009 2 10000* MIN. Oe 20000 4000o 6000* 1 8000* 0 5 + 10 15* 20* 2 5 30* 3 5 4+ 40, 4 5 , 5 0 iF 5 5 , rn 60. 56oOOO MG PER KG CUMULATIVE COUNTS PER 3 MICE FOR 2516 AT T I fAE IN 10000 3000*. 50000 7000, 9000, MIN* 00 20000 40009 6000, 80007* 100000 k 0 5, 10 15, Z5. 30. 35, 40. 45. 50* 550 @1-- t A TIME CUMULATIVE CO.UNTS-PER 3 MICE FoR 2516-AT 10.000 MG PER KG 3000o 5000* 7000o 9000* IN 1000* 2 8000* 100000 6000* MIN* 0. 2000* -4000o 00 5 100 15. .20, '25* 30, 35. 3 40. 45, 50, 55, 1.000 MG PER KG CUMULATIVE COUNTS PER 3 MICE FOR 2516 AT TIME 7000* 2 50000 90000 10000 3000o 100000 I N 2 6000* 80000 4000o MIN* Of 2000o 00 5 10 2 1 5 o 20 25. 309 3 5 40o lp 45o 3 50, 5 5 CUMULATIVE COUNTS PEA 3 MICE FOR 2516 AT 0*000 MG PER KG TIME I N 1000, 3000, 5000, 7000, 90000 MIN. 00 2000* 40000 6000o 8000* 5 100000 0 5, 1 0 . 15, 20, 25, 30, 3 5 0 40* 45, 50* 5 5 60, - - "f'l -,- , , I I ', " l@, ,4 TIME 2 CUMULATIVE COUNTS PER 3 MICE FOR 2531 AT 10.000 MG PER KG 1 N 10006 3000* 5000* 2 7000o 90000 MIN, 0 2000a 4000o 6000* 80000 100000 0 0 5 1 0 15* 20, .25, 30, 9 5 40,, 45, 50, 55, MICE FOR 2531 AT 100,000 MG PER KG CUMULA'I'IVE COUN'FS PER3 T "iE 9000 I N 10000 3000o 5000t 70000 2io 4000a 6000o 80000 100000 20000 MIN. 0 0 0 5, 1 0 , 15. 20, 25, S50 45. 8 50, '% 5 rn 4', ii TIME CUMULATIVE COUNTS PER 3 MICE FOR 2531 AT 0,000 MG PER KG 9000, IN 1000, 30009 5000, 70000 MIN, 00 20000 4 4000* 6000* 80009 100000 0 5* 100 1 5 *2@0,o 25 30* 35, 400 45* 50, 5 5 60, CUMULATIVE COUNTS PER 3 MICE FOR 2531 AT loOOO MG PER KG TIME 5000o 70009 90000 IN 1000* 3000o MIN* 00 2000o 4000c 60009 80009 1000010 00 5 0 1 0 0 15. 20. 25, 30* 3@o 40, 45, 50, 55, 60,. 2598 AT 0*000 MG PER KG CUMULATIVE COUNTS PER 3 MICE FOR TIME I N 10001, 3000* 5000, 7000, 9000, MIN 2000c 40000 60009 8000o 10000* 0.0 00 5, 1 0 15, 20, 25, 30. 35. 40, 45, 50.. 55. 60, TIME CUMULATIVE COUNTS PER 3 MICE FOR 2598 AT *100 MG PER KG l@l 1000* 30000 5000* 7000& 90000 I N 06 2000o 4000* 6000* soooo 100000 of 5* 2 10 0 15, 20* 2 5 '30, 35, 40* 45* 50* 5 5, 60. rii TIME CUMULATIVE COUNTS PER 3-MICE FOR 2598 AT 10*000 MG PEA KG IN 10006 30009 50000 7000* 9000 -MIN, 00 20009 2 4000* 60009 8000o 100000 0 0 5 , 1 0 0 1 5 0 20* 25, 30* 35, 8 40, 45, 50o 5 5 1, 0 FOR 2717 AT loooo MG PER KG TIME CUMULATIVE COUNTS PER 3 MICE 10000 3000* 5000o 7000, 9000. I N 2000o 4000@ 6000* 80000 100000 MIN. 0.6 0 , 51 1 0 , 1 5 20, 25, -30, 35. 40. 45, 50. 55a 2717 AT 20,100 MG PER KG TIME CUMULATIVE COUNTS PER 3 MICE FOR IN 10006 3000o 5000, 7000, 9000, MIN, Oo 2000* 4000o - 60009 80000 100000 4 of 5* 1 0 0 150 2.0, 25 30o 350 40* 45, 500 5 5. FTI 2717 AT o,ooo MG PER KG CUMULATIVE'COUNTS PER 3 MICE FOR TIME 9000* IN 10000 3000. 5000* 7000, 4 6000* 80000 100000 MINE 0 20000 4000* ol 5 1 0 15, 29 .25. 30. 35, 40* 45, 50,, 55* MICE FOR 2778 AT 32,000 MG PER KG CUMULATIVE COUNTS PER 3 TIME 9000, 7000 1000, 30009 5000* I N 2 80000 10000* 4000* 6000* 2000o MIN* 0 I 0 5 I 0 lb 1 5 20, 2 5 , 30, 8 35* 40, 45, 50 5 5 rn @.0 -3 MICE FOR 2778 AT 10*000 MG PER KG TIME -CUMULATIVE COUNTS PER 90000 50009 7000* IN 10000 30009 2 8000* 100000 .4000* 6000* MIN, 00 2000@ 00 5* 1 0 150 20. 25. @30* 356 40* 5 .45 50* 55, 60* -tie TIME CUMULATIVE COUNTS PER 3 MICE FOR 2778 AT 1*OGU iAG PER KG IN 10000 3000* 50009 7000,. 19000, MIN. 00 2000* 40009 6000o 80000 1 000. ol 5, 1 0 150 20. 25, 30. 3 5 . 400 45, 50. 5 5, 60,, TIME CUMULATIVE COUNTS PER 3 MICE FOR '2778 AT -OSOOO J4G PFR KG gooo, 7000, I N 1000, 3000* 5000* 2 80000 100000 60009 MINE Ob 2000* 40009 00 5, 10 150 20, 25. 30* 6 35, 40, 45, 50, 55. 60, TIME CUMULATIVE COUNTS PER 3 MICE FOR 2867 AT .100 MG P@R KG I N 1000. 30000 5000* 7000,. - 9000, MIN. 0 2000* 40009 6000* 80000 100000 00 5 09 1 0 . 15, 20, 25, 30, 3 5 40, 45, 50, 550 60, ,47, TIME CUMULATIVE COUNTS PER 3 MICE FOR 2867 AT 0,000 MG PER KG IN 1000, 3000, 5000o 7000. 90000 MIN,. 0 2000a 40009 6000* 80000 100000 8 0 5 o 10, 15, 25 30, 35* 40, 45, 50* 55o in 60a TIME CUMULATIVE COUNTS PER 3 MICE FOR 2867 AT 10,000 -MG OER KG I N 10000 3000a 5000, 7000, 9000, 20000 4000* 60009 80000 10000, MINO 0. 00 5, 100 15* 200 250 300 35, 40* 45o 50, 550 8 60, 1,000 MG PER KG CUMULATIVE COUNTS PER 3 MICE FOR 2867 AT TIME 7000 9000, I N 1000, 30009 5000* 60009 2 8000* 100000 4000* 2000o MINE 0 a I 0 5 o 10 0 15o 20* 25* 308* 3 5 40, 45 , 50o 55, R 2897 AT 50.100 MG PER KG CUMULATIVE COUNTS PER 3 MICE FO TIME 1000, 30000 50000 7000, %9000 I N 2 80000 100000 MIN. 00 2000o 40000 6000* 0 5 , 1 0 1 5 200 25 30. 5 35, 40, @45, 50 a 55 a 60, TIME CUMULATIVE COUNTS PER 3 MICE FOR 2897 AT 1*000 !4G PER KG IN 10000 3000o 5000o 70000 90000 MiNe 0 2000o 4000* 60000 8000* 1 0000 00 9 5 100 15, 20, 250 30, 35, 40. 45. 50, 55 60, IVE COUNTS PER 3 MICE FOR 2897 AT 0*000 MG PER KG TIME CUMULAT 9000, I N 1000, 3000* 5000o 7000, MIN9 0 2000* 40000& 6000. 80000 0 50 10 15, 20, 25 30, 3 5 9 40o 45, 50o 5 5 60, 4.,@ t k-I TIME 'CUMULATIVE COUNTS PER 3 MICE FOR 2935 AT 0.000 MG PER KG 1000, 30000 50009 7000, 9000* IN 40009 6000o 8000* 10000* MIN, 0 20009 00 5 0 0 15, 20, 2 5, 30, 35a 40. 45, 500 55. G 14G PER K 2935 AT 32*000 ICE FOR V9000, 5 PER 3 2M Of CUMULATIVE COUNT 7000* - jooo 5000o 80000 I TIME 3000# 2 6000* ioooe 4000* IN 2000* IN* 0 m 0 50 100 20* 25. 300 35. 40, 45* 4 50* 55o 60,, CUMULATIVE COUNTS PER 3 MICE FOR 2935 AT 1,000 MG PER KG TIME I N 1000. 30009 5000* 7000* 90000 MIN. Olb 2000c 40009 6000* 80000 ioooo 5 3 10, 15, 20, 2 5, 300 35, 40o 45. 50, 55* 60, t4 2963 AT 56,000 MG PER KG TIME CUMULATIVE COUNTS PER 3 MICE FOR I 7000,, 90000 I N 10000 3000* 5000 100000 60009 80000 20000 4000o MINE 00 Oa 5 a io* 15 @o. 25, 30. 35* 40,i 45, 50* 5 5 60, 141 2963 AT 32.000 MG PER KG T I NIE CUMULATIVE COUNTS PER 3 MICE FOR 5000* 7000, 90000 IN 1000* 3000,, 40200o 6000o 8000* 100000 MIN* 00 2000* 0 5* 1 0 15. 200 250 -30. 359 40, 45* 50a 55, rn 60, TIME CUMULATIVE COUNTS PER 3 MICE FOR 0 -2963 AT 10*000 MG PER KG 1000, 3000* 5000* 7000* 90000 I N MIN* 00 2000* 4000* 60009 8000* 10000* 00 5 1o 10. 150 '20 25o .30, 35, 4 40, 45, 50o 55* rn 60, - !"I Tlf',E CUMULATIVE COUNTS PER 3 MICE FOR 2963 AT 19000 MG PER KG 1 t4 1000* 3000* 5000# 7000* 9000* Miti* Oe 2000o -4000* 2 60009 80000 100000 50 0 15. "io . 25, 30. 35, 40, 45, 50, 55, 60, 7 rri IL TIME c UMULATIVE COUNTS PER 3 MICE FOR '2963 AT 0 *000 MG PER KG IN 1000 MIN, 3000, 5000, 7000. 9000. Odb 20002o I-ooo. 6000* 8000* 100000 00 5 , I 0 15, 20. 2 5 .3 0 3 5 40. 45. 50, 550 670, rn TIME CUMULATIVE COUNTS PER 3 MICE FOR 2984 AT 1-000 MG PER KG IN 10000 3000* MIN, 00' 5000, 7000. 2000, 9000, 2 4000o I 6000* 80000 10000, ol 5, 1 0 . 15, 25. ios 35, 7 40. 45. 50, 55. 60. ni 2984 AT 00000 MG PER KG TI@IE CUMULATIVE COUNTS PER 3 MICE FOR 7000, 90000 IN 10000 2 30009 5000* 80000 100009 2000o 4000* 6000* Mltl* 00 0 7 59 1 0 1 5 a 4'20 0 2 5 , 30o 3 5 0 40, 45o 500 5 60o @ fi T I M. E CUMULATIVE COUNTS PER 3 MICE FOR 2984 AT 10.000,MG PER KG IN 1000, 30009 50002o 7000* 90000 MI 0 2000c 4000* 6000* 8000. 100000 06 5, 10, 15, 20. .25. 30, 9 3 5 40. 45. 50. 55, rn 100,000 MG PER KG TIME CUMULATIVE COUNTS PER 3 MICE FOR 2994 AT IN 10000 30009 5000o 70000 90000 MIN* 0* 2000o 4000* 6000* 8000* 1800000 0 0 5 0 10. 20, 25* 3 0 35. 40. 45, 50, 55* 60. rn T IE CUMULA't'IVE COUNTS PER 3 MICE FOR 2994 AT 1,000 MG PER KG I N 10000 3000* 50009 7000* 9000* MIN, 6000o 8ooos 100006 Oo 2000., 4000 1 ol 5 1 0 15, 200 2 5, -30, 35, 4 0 45o 50o 55. 6 0 T I -ViE CUMULATIVE COUNTS PER 3 MICE FOR 2994 AT 0,000 MG PER KG IN 10000 30000 5000,& 7000* 90000 MIN, 00 2000o 4000o 6ooos 8000. 10000. 01, 5 , 1 0 15. 2b 25, 30, 35.- 40. 45, 50. 5 5, 60o T I t"E CUMULA'I'IVE COIJNTS PER 3 MICE FOFZ 290,5 AT 0,000 MG PER KG IN 1000, 3000, 5000o 7000, 9000, 6000, 8000a 2 100000 141 N, 00 2000a 40009 I 0 5, 1ol 15, 20, 25, '30, 35a, 40, 45, '00 550 0 TIME CUMULATIVR-_ COU@ITS PER 3 Ml(:E FOR 2995 AT 20,000 M(3 [JER KG I N 1000, 3000, 5000, 7000, 9000. MIN, O'D 2000.@ 400209 60000 80000 100006 I I 0 5* 1 0 1 5 a 20.6 25* 30. 35, 40, 45, 50, 5 5, + 60, 4 rn 995 AT 1,000 MG PER KG TIME CUMULATIVE COUNTS PER-3 MICE FOR 2 I N 10000 3000o 50009 7000 90009 MIN, Oa 2000* 4000a 60009 80000 10000*7 00 50 1 0 15, 20. 25, 30, 35, to , oe 45, 50, 5 5 6 60, TIME CUMULATIVE COUNTS PER 3 MICE FOR 2999 AT 0,000 MG PER KG IN 10000 3000# 5000* .7000. 90000 M!No 00 20000 2 4000o 6000a 80000 100000 0 0 'ti 5, 1 0 . 20, 25, 300 3 5 0 1 40* 45* 50, 55, rn I TIME CUMULATIVE COUNTS PER 3 MICE FOR 2999 AT 19000 MG PER KG I N 10000 3000a 5000* 7000* 9000-0 ,",.:4 MIN*, 0 a 2000o 40009 6000* 80000 100009 0 a lo.. 15, 25,i 30, 35, 40, 45, 50, 55, 60, rn o.ooo mG PER KG CUMULATIVE COUNTS PER 3 MICE FOR 2999 AT I TltIE 9000, IN 1000, 3000, 5000* 7000, 2 4000* 60009 8000o 10000* MIN* 0 2000* 0 50 1 0 a 15. o . 2 5, 30, 35* 40, 45, 50a 55. 6 60o T IE CUMULATIVE COUNTS PER 3 MICE FOR YY 5026 AT 2OoO(lO fAiG PER KG (4 10000 3000 50000 7000C 9000C I N, Oft 20009 4000o 6000o 80000 10000* 1 0 5* 10, 15, 25, 3'6 3 5 40, 45. 50* 55, 60, rn ...... ..... *k@ 'Olt TIME CUMULATIVE COUNTS PER 3 MICE FOR 5026 AT *320 MG PER KG IN 10000 3000* 5000o 7000* 90000 2 60009 80009 100000 MIN* Oe' 20009 4000o 0 5 10 a 15 20, 25,, 30 35 0 40. 45. 500 55, Frl CUMULATIVE COUNTS PER 3 MICE FOR 5026 AT 0.000 MG PER KG T I tiE 90009 I N 10000 30009 5000o 70009 MINE 00 20009 4000o 6000* 1 80000 100000 0. 5 7f 0 150 20, 2 5 .30, 3 5, 40o 45, 50, 55o 60. T I F CUfILI!I.A'@ 1 CCII.iti PER 3 MICE FOR P 5031 AT 0*00' f4G PER 7000,, 90000 210000 'JJOOO 5000o 8000a 100000 6000* 2 Mir,!'. 00 2000o 40009 0 5 1 0 1 5 25, 30. 35 40, 45. 7 50o 55. rn 60o FOR 5031 AT 1,000 MG PER KG TIME CUMULATIVE COUNTS PER 3 MICE 90000 3000* 50000 70009 I N 10000 2 100000 .40009 6000o 80000 MIN. 0,6 2000# O, 5, 10 150 20, 2 5 300 35, 7 40, 45, 50o 55, 'U rn 60, TIVE COUN'FS PER 3 MICE FOR 5031 AT 20.000 MG PER KG TIME CUMULA 7000o 90006 IN 10000 3000a 5000* 8000* 100000 4000* 6000o MINE 0 a 20000 0 5 10, 20o i'4 25, .309 35, 40, 45* 50, 7 550 ryi 60, 100,000 MG PER KG"t 5031 AT CUMULATIVE COUMTS PER 3 MICE FOR gooof 70009 TIME 50009 2 100000 3000* 8000* 10000 6000 IN 20009 4000* 1 1 MIN* 0 00 50 + 1 0 0 1 150 20o 250 30* 359,i 40o + 45, 50. + 55* Fn 60* T I t-i E CUMULATIVE COUNTS PER 3 MI'@E FOR 5058 AT .010 MG PER KG IN 10000 3000* 5000& 7000* 9000* MiNe O's 20009 40009 6000* 80000 100000 0 5 4 1 0 15, lo* 25, 30, 35a 40, 45, 50, 5 5 60* rn o,ooo I.JG PER KG- 5058 AT COUNTS PER 3 MICE FOR TIME CUMULATIVE 5000* 70004 90000 10000* I N 10000 2 3000* 60000 80000 40009 141N. 0 2000* 0 0 5o 10 1.5 20. 25a 30 a 35* 40a 45* 509o 55. TIME CUMULATIVE COUNTS PER 3 MICE FOR 5058 AT 25olOO MG PER KG I N 1000, 3000, 5000, 7000o 9000, MIN, 00 2000a 4000* 6000o 80009 100000 0 0 7 5, 1 0 0 150 20, 25, .30, 3 5, 40, 45, 50* 55. 60. 41*,4 Ala% MICE FOR 5058 AT lo,000 t4G PER KG TS PER 3 90000 CUMULATIVE COUN 70OOt- T I ME 5000* 80000 10000, 3000* 6oo0o IN 10000 2000* 4000o 1 00 MIN, I 0 a 10* 6 150 ZO. Z5. 30o 35 a 40, 45, 50* 550 TIME CUMULATIVE COUNTS PER 3 MICE POR 5058 AT loOOO MG PER KG IN 10006 30009 50009 7000o 90000 MIN* 06 2000o 4000o 6000* 80000 100000 00 5 100 15, 20o .250 30, 3 5 40, 45, 50. 55, 60, TIME CUMULATIVE COUNTS PER 3 MICE FOR 5059 AT 100,000 MG PER KG IN 1000, 3000, 5000, 7000, 9000. 2000, 4000, 6000* 8000* 100000 MINO 00 0. 0 5* 10, 15, 20, 25, 30. 35, 40, .4 5 + 509 55 rTi 60. *WA* A TIME CUMULATIVE COUNTS PER 3 Mlr,E FOR 5059 AT 10*000 14G PER KG IN 10000 3000o 5000a 7000* 90000 MIN, 0* 2000,.. 4000o 6000* 80000 1000010 0 50 10. 15, go* 2 5, 30. 35, 40, 45, 50, 55, 60, 1,000 MG PER KG 3 MICE FOR 4 5059 AT TIME CUMULATIVE COUN'FS PER 5000co 7000@ goooo2 IN 10006 30009 8000* 100000 40009 6000i M I N 0 20009 0 10 1 15, 209 5 .30. 35 40. 45a 50. 55* rn 60. TIME' CUMULATIVE COUNTS PER 3 MICE FOR 9 5059 AT 0,000 MG PER KG IN 10000 30009 5000* 7000@ 9000* MINS- Oo 20009 2 4000* 60009 80000 100000 0 0 50 1 0 0 15, 20, 2 5 30o 35o 4009 45* 50. 55. rn 6ri , 47 qi, TIME CUMULATIVE COUNTS PER 3 MICE FOR 5071 AT lo.ooo MG PER KG 30009 5000, 7000o 90000 IN 10000 10000* 2 60009 8000. tilne 00 2000a 40009 0 5 100 15* 20o 25. 30 9 35* 40* 45, 500 8 55* rn 60., TIME CUMULATIVE COUNTS PER 3 MICE FOR 5071 AT 1,000 MG PER KG 1 t4 10000 3000. 5000* 7000* 9000. MIN. 0 2000* .4000* 6000. 8000. 100000 0. 56 7 1 0 15, 20. 25, .30, 35. 40* .45, 500 55* 60, 0,,nC)O ri'@a PER KG CUMULATIVE COUNTS PER 3 MICE FOR t 5071 AT 1 ItiE 90000 500200 70000 IN 10009 30000 BOOO* 10000* 20009 4000* 60009 @iIN* 06 00 lo 0 5 15*1 20, 30. 350 40, 45o 500 55* F(JR 5071 AT 32.0(0 iiG PER KG T I IAE CUMUI..A'I'IVE COU14TS PER 3 tilCE 30009 5000a 7000a 9000, @IN 1000, 80003* 100000 MING, ON 2000,s 4000* 6000* Os 50 I 0 15, 25, 30, 350 40, 45, 50o 5 5 o 60a R 9: @092 AT 25OuOOO tIG F'ER'KG CUMULATIVE COUNTS PER 3 MICE FO 7000* 90000 iti 1000, 3000* 50002o '0004 6000* 100000 4000a IIIN* 00 2000* 00 5. 10. 15. 0 , 2 '30, 35* 40, L,5, 50 0 55. rn 606 CUMULATIVE COUNTS PER 3 MICE FOR 5092 AT 10.000 @IG PER KG T I fAE 10000 3000* 50000 7000* 90000 IN fl I N . 0 o 2000-o 400020 6000* 00000 100000 0 50 1 0 15* 20, 2 5 35* 409 45 , 0 , 5 5, 60, 4L T I @IE CUMULATIVE COUNTS PER 3 MICE FOR 5092 AT 0.000 MG PER KG I N 10000 3000* 50000 70009 90000 2 80009 100000 2000* 4000o 6000 Pi IN. 0 0 0 a 5, 1 0 . 15, 20, 2 5 30* 35. 5 40* 45, 50, 55, 60, -,wow 100 MG PER KG CUMULATIVE COUNTS PER 3 MICE FOR 5104 AT 63 TIME 3000 5000* 70009 90000 IN 10000 -0 MIN, 2 4000a 60009 80000 100000 0 0 2000a 00 5, 10. 15, 20. 25, 30. 35. 40* 45, 50* 0 55, 60, .............. TIME- CUMULATIVE COUNTS PER'3 Ml,,--E FOR 5104 AT 0,000 MG PER KG IN 10000 3000* 5000a 7000* 9000* MIN. 06 20009 4000,b. 60000' 80000 100000 0 6 5, 1 0 15, 204 2 5 30, 35* 40, 45, 50, 55, 6i -104 AT J..Ooo KG CUMULAI'IV'U- COL)i'iTS PER 3MICE FOR f,? 2 7000* 90000 5000* 1000 3000o IN 100(00 2000a 4000* 6000a 0 0 0 I N 0 0 0 100 -30,, 3 50 40a 4 5, 50o 5 5, rn 60C TIME CUMULATIVE COUNTS PER 3 MICE FOR 5104 AT 10.000 MG PER KG 90006 IN 10000 3000* 50009 7000o 6000o 2000* 40002* 80009 10000* 0 MINE 00 5, 10. 15* 200 25, @30, 3 5 40, 45* 50* 1 rii 60, TIME CUMULATIVE COUNTS PER 3 MICE FOR 4' 5143 AT 32eOOO MG PER KG .,JAOOOO 5000, 7000o 9000a I N 10006 ti I Nt 0 a 20009 40009 6000* 80000 100006 0 4 5 104 15. 20, 2 5 30. 3 5, 40, 45, 50, 55, r'n 43 AT 10,000 MG PER KG TIME CUMULATIVE COUNTS PER 3 MICE FOR# 51 9000, I N 1000, 3000o 5000* 7000* 4000o 6000* 8000* 100000 MIN. Oo 2000o ol 50 1 0 a 15. 26 a 25, ',30 35, 40, 45, 50 55, 9 60, or!A,&e@a, 'CUMULATIVE COUNTS PER'3 MICE TIME FOR 5143 AT 1*000 liG PER KG I pi 1000* .3000o 50009 7000o 90000 MIN* 0* 2000* 4000. 60009 6 80000 100000 00 5* 100 15. 20'. 25* '30, 35o 40, 45, 50o 55, 60, @k Y I-Ert 3 mif@-E Full t, 5143 AT PL!, I N 10000 3000o 5000o 7000* 900,i, 2 f-i I N o 0 2000o 4000a 6000* (1000 o 1 O(JOO 0 0, 5 a 10 a 15, 20@, 25* ;3 0 4 35. 40. 45* 50* 55, 60, 5145 AT 0,000 M@ PER KG TIME CUMULATIVE'COUNTS PER 3 VilCE FOR IN 1000, 30000 5000o 7000. 9000, MINO 06 20006 4000* 6000* 80000 100006 0 0* 5* 1 0 2b. 25* .30o 35 40, 45* 50, 55o ril 60, I [/,E CUMULATIVE COUt4TS PER 3 MICE FC'll '@145 AT .320 I'-(- P E KG I N 10000 30009 5000o 7000, 9000, 2 100000 MIN, ol 2000. 4000, 6000, 6000 0 5, 1 0 , 15, 7 20: 2 5, 3 O'e' -59 0 . 4 5 , 50* 55o 60o 3.200 MG PER KG CUMULATIVE COUNTS PER 3 MICE FOR 5145 AT TIME 9000* IN 1000* 3000* 5000 7000o .4000o 600029 8000o 100000 2000o MIN* 0 I 0 5 10 15 2'0 25, 30, 35a 40, 45, 50, 5 5 9 -u rn 60, 5145 AT 10,000 MG PER KG 5 PER 3 MICE FOR CUMULATIVE COUNT TIME 9000, 30000 5000a 7000, IN 10020, 6000* 80000 10000* 2000* M I N o0 0 5 , 10 15. 20. 25, 30. 35. 40, 45, 50. rn 60. l'IME CUMULATIVE-COUNTS PER 3 MICE FOR Nf',65853 AT .10.000 MG PER KG IN 1000. 3000* 50000 7000, 90000 MINE 0 a 2000a 2 4000a 6000* 80000 10000* 0 5* 1 0 15, i'O 25o @30, 3 5 400 45* 50, 5 54, 60. lid Tlt-iE CUMULATIVE COUNTS PER 3 MICE FOR N"-f@5853 AT 100.000 MG PER KG 30009 9000, IN 10000 5000e 7000, MIN* 00 20009 4000* 6000* 80000 100000 06 5 o I 0 15, 20, 2 5 3 5 40, 45, 50* 5 5.o 60. CUMULATIVE COUNTS PER 3 MICE FOR #865853 AT 0,000 MG PER KG T I tiE 7000o goooo IN 10000 30009 50:009 MIN. 0* 2000o 4000* 60009 Booo. 10000* ol 5 o 1 0 150 io 25* 30, 350 40. 45, 50* 5 5, rn 60,1 TIME CUMULATIVE COUNTS PER 3 MICE FOR #965859 AT 0.000 MG PER KG IN 10000 3000* 5000c 7000o 9000* MIN. 06 2000-o 4000* 6000a Booo. 3 100004 ol 5, 10, 150 20C 3.0,o 3 5 a 40, 45. 50, 55. 60. rn -RAW" 865859 AT 1,000 MG PER KG CUMULATIVE COUNTS PER 3 MICE FOR T I o'AE 9000-6 3000* 5000* 7000* IN, 2 10006 6000* 80000 100000 4000o MIN* 0 20009 0 5* 1 0 a 150 20* 25* .300 3590 40* 45, 50, 55, rn 60. ......... .. CUMULATIVE COUNTS PER 3 M'ICE FOR ilt.,,.':Pj59 AT 109000 MG PLR KG IN 1000* 3000* 5000o 7000* 90000 2 MIN, 00 2000* 40009 60009 Poooo 100000 0 0 5 10 150 2qo 25* 360 35* 40, 45, 50, 55, 2 rn 60* TIME CUMULATIVE COUNTS PER 3 MICE FOR #865891 AT 0,000 MG PER KG 10000 30009 5000o 7000* 90000 IN 4000, 6ooo* 80000 10000* 2000,j MIN* 010 00 10* 1 5 20, 25* 30 3 5 40. 45, 50. 55, rn 60, -1 lt!E COMKJLATIVE COUNTS PER 3 MICE FOrt N 5145 AT l5o8OO tiG PEP, KG IN 10000 3000* 5000o 7000o 9000C tilno 00 2000, 40000 6000o 80000 100000 5 00 5, lo* 15, 25, 30m 3 5, 40. 45,. 50, 55. 60, Fn @tkoe, 4i7 TIME CUMULATIVE COUNTS PER 3 MICE FOR #865891 AT 1,000 MG PER KG I N 10000 3000o 5000* 7000* 90000 MINE- 06 2000o 4000a 9 60009 8ooo* 100000 0 , 5 100 150 210 25, 30, 35, 40, 45, 50 '55, 60, CUMULATIVE COUNTS PER 3 MICE FOR #865891 AT 32,000 MG PER KG TIME IN 1000* 3000* 5000* 7000* 90000 MIN* Oo 2000a 4000o 6000o 80000 10000* ol 2 50 1 0 15, ZO'. 2 5, -L At 30o 35, 40, 45, 50, 55, 600 MOTIVATION TESTS IN HOODED RATS EEDS IN RECIPROCAL SECONDS START AND RUN SP 2 R 1 L 6 TRIAL 3 TRIAL 4 TRIAL 5 :pt4D DOSE MOTIV RAT TIME @IRIAL TRIAL 2 1,0 2 START RUN START RUN START RUN START RUN START -RUN- START RUN 4 MG/KG NOO 1 o82 2 o 4'-"V la49 2 *18 lo64 o55 o57 A. 2.44 1,61 2*50 o 6-3 oooo AVOID 503 20900 2 0 22 2 o58 2*04 o.oo AVOID 503 120c 93 .82 2.38 957 62 1*96 2o56 57 .61 lo6l .0,00 AVOID 503 240o *53 o6l 2o78 o58 2ol7 2o62 2004 1:96 2,27 .62 3o!3 c 6 1 23 2,00 1969 lo37 2*38 58 2aO8 *61 lo85 5 lo82 *55 .460 ',O,,00 AVO!D c,03 20QOO z@60 -10*00 AVOID 503 12(Q 49 i.q6 o56 2v!7 1*52 5 8 57 2.06 1,.39 2c!7 61, 2 '9 3 %:r4 5 7 #52 la92 5 3 J w 60 -OICO AVOT-D 503 240a *58 ,23 057 19 252 2.22 .53 1.56 1.59 1,41 55 itis,@ 1.'-7 1 50 'A. "V" 0 0AVOTD 503 -1.440u .13 5- 4.55 l,'- 52. j 5'j ?0::CO 3.,57 1,3C 4,'75 '.?,7 4,76 0 0 00 ESCPE 507 120, 4917 &55 3o].3 v56 4*76 o92 4.00 50 4lb35 2 057 5oOO a52 0000 E 5,%-. P E 507 240, 3.70 56 3.85 o 5 1 3. 5i *97 3*45 5 2 3.70 .53 3o7O o96 460 loooo ESCP- 507 20.00 3*57 o5l 2o86 e56 4ol7 952 2o86 1,49 3970 54. 3o85 952 -&60 10*00 ESCPE 507 120. 3*1-3 loOO 3o57 o97 3o7O *92 3PB5 53 3o45 o5,5 3o85 -52 Z460 2 10,00 ESCPE 507 240@; 2.70 53 3o7O *9- 4,@00 luOO 4o35 56 3,70 053 4o'@3 ,98 '-'460 10.00 E Sr %.OE 50 7 144o, 3*33 o5@ 3o7O .0 285 3 0"17 o o35 91 4u76 #93 951 4 9 8 3 3.70 ri,;; MOTIVATION TESTS IN HOODEP, P%ATS OCAL SECONDS START AND RUN SPEEDS IN,RECIPR 2 IS. TRIAL 6 AL 3 TRIAL 4 TRIAL PND DOSE MOTI TIME TRIAL 1 TRIAL. TRI V RAT 2 RUN START RUN, START RUN SVIART PUN START RUN START RUN START f'Oo @IG/KG NOO 120. 3,13 .260 3*57 a57 3,o 2 3 53 3,85 56' 3,57 1,37 3,57 1,,43 OIOO AVOID 475 3o45 51 3*33 194 2 2,94 o7g 3.45 *51 3oO3 o5l 2#94 50 759 lOvOO AVOID 475 20.00 120o 064 093 2o38 o5O 2o44 &99 2o86 o53 2994 255 2,27 59 5 9 10,00 AVOID 475 5 2ogO o8O 2o78 52 3403 52 @,.o3 :57 59 10.00 AVOID 475 240, 3*13 2 91 2,33 09 69 2*70 1025 -1,63 1&022 9 .'IOoOO AVOID 475 1440r 2*08 65 1*35 60 2,27 1,13 lo85 1 2 0900 AVO. ID 501 20,00 3s45 o59 4900 1*92 3485 1652 4976 1,72 5,00 lo56 4,r.,5 li79 ID 501 120. 2oO4 le75 -4000 9 57 4ot7 2 1949 3o45 lo35 3o85 lo49 3o7O I o 5 9 OCOO AVO 759 10000 AVOID 501 2OoOO- 4000 lc,64 3,085 1945 4r,00 4900 lo72' 4900 1935 4ol7 1985 2 la6l 9 759 10900 AVOID 501 120a 3485 1 89 4c,00 1954 2 3o57 --to59 4*55 1*56 4o55 lo4g 4ol7 v 2404 4917 o56 4*17 a 5 8 4*35 9 59 3*85 1:67 3 v 3@3 lo79 :4 3 lo69 759 10900 AVOID 501 2 759 10900 AVO:D 501 1440, 3*33 1,45 3*85 1*37 3o85 1975 4*76- 1,59 5o26 lo75 4-(i76 lu*bl OOOO ESCPE 505 2OoOO 3*45 056 4*00 983 4o76 1933 49127 r,55 4ol'? o5@-I 3o33 956 0.00 ESCPE 505 120 4*17 *55 3*70 1*49 4*00 958 4wOO 1,27 4o35 0,53 3 Z 8:) 9 5 3 ?o.,no 3,, 48:; r,7 4,: 7 @SI 4o55 a'? 3o45 .56 4.3a .54, 4 Of" ;P".; t MOTIVATION TESTS IN HOODED [\'A.'f5 T ANb RUN SPEEDS IN RECIPROCAL SECONDS STAR 2 RIAL 6 -Pt.,ID DOSE MOTIV RAT TIME TRIAL 1 TRIAL 2 TRIAL 3 TRIAL 4 TRIALi5. T 2 RUN' START RLIN MG/KG OID START RUN START RUN START RUN START RUN START t4o N 2,63 37 2 20.00 1.69 28 04 45 .03 1,82 36 .458 o37 '0'00 APRCH 452 37 60 4 56 36 2 0.*00 APRCH 452 120. .03@ - 929 49 .61 .36 1,52 240, 0 29 92 9 70 lo59 a- 3 8 0*00 APRCH 452 2 9 #63 1 a g@4 *66 1*96 o3a *57 2 8 759 10*00 APR%E-H 452 20,00 .38 0 08 105 025 .95 2 '19 .34 .28 .79 7 5 9 44 5 2 35 51 .06 25 20 I 0 a 0 0 APRRH 452 120o 40 3 1 0 3 - 7 9 2 0 3 .29 28 *37 5 3 2 1 9 16 0 2 5 oO4 :30 5 9 10*00 APPCH 452 240* *06 2 1 0 a 5 2 *,6 5 59 lOsOO APRCH 452 1440. e45 clO *67 &46 2eO4 &53 a 6 .56 1 0 8 5 o57 0*00 APRCH 492 20*00 2.33 47 1.89 66 13 .44 05 3.33 .56 6:i 2 .22 o96 APRCH 492 120c 2 5 76 1*96 o37 3o 13, *65 :37 16 009 0 3 .66 005 otoo 0*00 APRI@H 492 240* le64 3o33 932 015 29002 932 620 '*35 039 o34 :o52 #36 7 5 9 5 6 4 2 10c',10 APR@'H 492 20,00 43 93 2 275Y 1 U O',l APR-P, 49t@ 120, 2 -3 14 2 q;20 C. - o 7 1 07 ,O,, ii4 c,95 Z 7 f.. i 44 '@ 2 @ -i-D ., 'I; 2 -) '03i, !3 H 4 072 7 Ap.,t 2 a22 -3 OODED RATS MOTIVATION TESTS !N H OCAL SECONDS 2 START AND RUN SPEEDS IN RECIPR TRIAL 3 TRIAL 4 TRIAL TRIAL 6 DOSE MOTTV RAT TIME TRIAL 1 TRIAL 2 tioe MG/KG NOo START 2 RUN START RUN START RUN START RUN START 'RUII. START RUN 759 10 6 00 ESCPE 505 120. 3-85 o56 3r,85 *59 4 a 17 9 5 2 3985 .56. 4.17 .55 4.35 #54 240 2 4,17 )56 3o85 *52 4or@5 , 5 7 4,00 .58 4.17 1,54 2.17 5 7 7 59 lOtOO ESCPE 505 9 2 59 .10,00 ESCPE 505 14400 2.86 1 30 5o26 1941 4o35 1*47 5.56 1,64 lo59 2,27 4476 4 7 6 20,,00 3*85 .95 -4, 55 9'7 5,56 94 2 5,00 188 5 a 00 .55 4.76 52 0.00 FJSCPE 4 6 20a 5*00 lo4g 4900 *95 4000 o 297 4o35 a 5 8 5oOO 9 5 3 5 *'2 6 o93 OOOO ESCPE 466 1 r 59 @10,00 ESCPE 466 20.002 4.55 53 4,00 56 3.70 93 3957 loOO 4aOO 51 4,00 .84 4.55 59 10,00 PSCPE 466 120, 51 4,17 o98 2994 8 5 4oOO .86 24,li 76 3,70 5 3 240* 4.17 53 -4.55 *52 4o55 54 4600 4o7iS 52 4ol7 a 8 5 759 loooo ESCPE 466 2 .57 1440. 3,70 ,87 5000 1*12 4,00 073 5 56 86 4*35 8a 5,00 1,03 i@ 7'@9 10,00 ESCPE 466 0*00 APRCH 496 2OoOO 1059 o228 o54 *63 1 o 5 2' 9 84 010 q4O 1945 o97 2*33 -o 9 6 oloo APRCH 496 120. 1.85 .32 o54 1.00 2,00 35 63 .50 61 86 ;,63 u5l 2 OOOO APRCH 496 240a .03 .03 o53 *34 957 099 *57 097 55 1000 058 *51 2460 lOsOO APRCH 496 20900 .03 .03 s56 "Bo *56 *76 958 o34 058 e93 lv54 010 1,82 2'y6O 10,00 APRCH 496 120, 74 1.61 o78 2oOO 83 lo7-3 79 80 8 460 10.00 APR-H 496 240, o58 48 o59 *84 ;@58 .76 1*75 61 54 a 8 8 4 MOTIVATION TESTS IN HOODED RATS START ANb RUN SPEEDS IN RECIPROCAL SECONDS -P(4'D DOSE MOTIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 TRIAL 2 4 TRIALi5. TRIAL 6 tIo MG/KG NO,% START RUN START RUN START RUN START RUN START RUN' START RUN 460 10*00 APRCH 496 1440* 1*49 3o33 *93 067 ar-3 g 940 095. *56 2 091 o56 0 91 *28 #28 2o5O o69 o56 o39 OOOO 2APRCH '488 2OoOO 1964 3o3S 2*50 9 48 o5O v 1 4 0*00 APPCH 488 120, @03 0 3 a 0 5 a 2 7 o6l o7O *34 *72 2ul7 o27 2.00 0 4 21 0900 APRCH 488 2400 oU5 16 *48 *80 2o27 o8O 1985 o74 2o22 9 7 6 2o@63 098 460 '10400 APRRH 488 2OoOO v72 oO6 lo89 907 .37 2639 2;o94 75 2950 65 2,4'-f o38 460 'lb.00 APRCH 488 120* 2ol7 ;03 2QOB *25 2o5O *68 2.94 *78 019 009 2r,06 of-,5 460 'IOC.00 APRCH 488 240o 2 10 .2*94 *83 3o23 o83 2o86 80 2,38 80 o32 a 0 60 lOcCO APR-H 488 14402a 1954 21. o56 o74 ol7 *35 2o33 o77 2o33 o87 2o27 *8 *57 2463 o53 091 O2UOO AVOID 502 2OoOO *21 o55 1*89 o5l 08a lo64 o5O lo92 0#00 AVOYLD 502 l@20, o45 o58 2 27 *58 o59 o56 1@75 e-56 2 6 9 1 58 '?,50 .5 240, OoOo AVOID 502 lo69 2 055 1:92 o58 Iv@6 454 o63 *58 2oO6 05'7 e63 *54 D 502 20@00 ,38 460 11,00 AVO 54 058 52 41 o52 9 5 3 2'52 59 )83 0 98 67 '10..Oo AllolD 502 460 120, lo89 69 v97 lo92 1153 091 52 57 .7-,l 92 ,53 240, 2 5 - 2460 10403 AVO!D 502 4 5 2 *53 *55 1*79 Lv27 lo33 lo3O o83 1,59 450 'I*.)() 460 10*00 AVO6ID 502 1440o 977 o8l 1*72 o55 1.49 956 1*35 o56 2008 988 1*67 o85 MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS -PND DOSE moTIV RAT TIME TRIAL I TRIAL-2 TRIAL 3 TRIAL 4 TRIAL '5 TRIAL 6 tio 2 MG/. tios START RUN START RUN START RUN START RUN START RUN START RUN 120, 3,70 52 4*76 0.00 ESCPE 508 0 655 5,26 o5O 4*76 5 2 1 4,76 .54 4,00 083 0.00 ESCPE 508 240. 4.55 o59 4*00 955 4oOO o53 4*76 .51 3o33 52 3oC5 090 2460 10,00 ESCPE 50a 20.00 3,,85 52 4,00 .51 4,00 87 4,76 .80 4.35 ,85 4,17 188 460 10900 ESCPE 508 120, 3,03 o5l 4oOO a 89 3o7O :83 5-00 .95 4.76 lebo 4-55 @50 60 10.00 ESCOE 508 240o 4,35 o56 4al7 9 5 3 4o35 *56 4o35 9 5 3 4a76 *56 4a'6 051 '@l 0 03 E5CPE 508 1440, 4o76 (,O 53 4oOO 2 996 4,76 o93 4a55 c86 4,76 61 4.@i6 o5l Oo3O APR%--H 498 2OoOO 3a33 o53 .3o85 o3S 3o23 955 3*23 *54 2a86 0 j5- 02400 APR,-H 498 120, 3*03 o54 4o76 1*49 3o45 *56 2a86 55 lo79 o59 3o33 o55 0400 APR@--.@i 49s 240, e'_950 o54 2u86 Q53 4,17 .56 3.70 2 1 56 2,00 a 5 4 c -i 6 134@j 2470 10@,00 APRCH 498 20,00 4,00 .55 04 65 3.85 56 1.41 '92 2.08 :.06 63 2 3 3 9-470 lOaOD APR'--H 498 120, 3o57 o95 2v27 987 93 ,90 *07 928 2,38 C.OB .0 2-170 10abO APR$--14 498 240, o@o 195 o53 o92 2 2956 e53 2978 51 2o63 54 2,@.L3 090 470 10,)00 APRCH 498 1440, 3457 o53 3o57 o56 2o94 o54 4oOO o55 3u85 o52 lo89 i-53 0.00 APRCH 499 20.00 3.57 .69 3*45 o72 2,44 *08 2*86 o72 2i.94 083 2,.',3 o7i 0*00 APR@:H 4(,'9 1-20, 3o33 37 2.63 55 *'17 2u63 75 2.06 oB) 2.13 li7i MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS DOSE MOTIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 TRIAL 4 TRIAL,5 2 TRIAL 6 s t,10. MG/KG NOo ART RUN START RUN START RUN START RUN START RON' START RUPI 0*00 APRCH 499 240a 3&23 70 2oO4 979 2e86 2 8 1*32 o74. 2o86 ?4 3.57 a 8 0 470 @0.00 APRCH 4qg 20,00 2*27 37 3,70 o5O 3,45 67 976 61 2.22 .73 4o35 o75 0 47 @0'*00 APRC@4 499 2 120, 3,57 o69 2o94 o72 3u23 972 2c44 a73 2o56 o83 J9.' 098 3 10.00 APRCH 499 240, '2078 7 47 cl4 2.86 664 2 2 c, 3 3 66 1,82 78 2,63 .73 3.45 *36 '4T3 10.00 APRCH 499 1440, 1,72 o67 2o22 68 2,63 69 2,86 168 -c57 74 45 2a?t 2 6 2963 1,64 2,78 1*96 2QB6 lo75 2994 1,69 3,13 lc-.@,9 7-c5o 4 Q6 2 %.#Oc) AVOID 504 20 00 0,:,Oo AVOID 504 120. 2,94 57 2o5O 1959 2,13 t,79 1.69 2,00 2 4-@ 1,89 2@9' :,-6 0,00 AVO!-D 504 240, 2,63 lo56 '2,63 1,56 2,22 1,75 1,85 2.04 2,,21 I.aS 7.,22' !@.19 70 10*00 AVOID 504 20*00 4935 1061 2963 to 2,50 2.08 2,86 1.82 2.86 2 54 Iz, 9 6 3.45 -.82 470 ',0900 AVO'&D 504 1.20e 2*63 IG49 2o33 L*56 3*03 1*72 2o27 1*67 2o55 le75 @a7O 1*96 OVOO AVO;D 504 22404? 2*70 le47 2o33 1*82 2 lo5!r @@1&33 la39 470 L 956 lo79 3*05 lo72 e'-vog 4 l'O 10600 AVOID 2504 Oc,00 4,76 icOO 3#85 1*50 3o7O 1,61 2,50 1,59 3,2@ 1,59 2 o o 9 2 0*00 AVO*LD 480 20,00 *51 o38 *54 90 2.1-46 *79 .2a22 88 2,44 50 2oc8 2 51 95 0,"O AVOID 480 120, $56 38 1,43 75 1,49 *77 le6l 65 1,85 53 2o72 a 0 OOOO AVO!AD 480 240* lo37 o84 2*22 *70 lo85 2*08 2oOO 975 le6i o53 230-'e a54' 'i4 MOTIVATION TESTS IN HOODED RATS START AND RIJN SPEEDS IN RECIPROCAL SECONDS ..PtqD TRIAL 2 TRIAL 3 TRIAL 4 2 TRIAL5- TRIAL 6 DOSE MOTIV RAT TIME TRIAL 1 t4Oo I'iG/I'NG NO* START RUN START RIJN '-zTARt RUN START RUN START RUN START RiiN 470 10,00 AVO!D 480 20,00 2044 a 72 .22,63 O'lz4 291'8 997 2*50 o5i 2.86 5-i 1492 .52 o 120, 53 38 2ol7 2,33 (O IG,00 AVOID 48 0 o67 1,56 2 o96 1,96 .79 2,86 86 470 10,00 AVC) I D 480 24o.. 1,64 8 3 5 o52 e74 lse2 o39 1459 2 *66 lo69 o9i lc92 :9 4 o54 c,35 70 !OGOO AVOID 480 l@-40r, a 5 1 934 1@41 *61 o7l 9 50 lo6l t9l 1 c'7 9 96 2 0;;@,iO ESEPE 509 2OoOO 3e57 o53 IRGOO lc47 4o!7 055 BS85 o5i 4a55 o5@ 4o53 a 2 ;5 O@,'V'O ESCPE 509 If'-O, 4900 CIA,7 3c85 lo35 3o57 o54 '-la85 1,32 4ro55 56 5,@00 ;56 240, 2,38 91 4 4017 o56 o 6 o52 O'CO ESCPE 509 0 2o86 1,52 4,35 1.28 3c23 1,41 7470 lOoOO ESCPE 509 2OcOO 4917 2 4,-00 1,,59 - le23 5oOO 1*25 4oOO lo33 5 9 56 1,41 4oOO o54 Z470 10,00 ESCPE 509 l@20c 4o76 1,43 5000 o54 3u85 1 37 5900 1 33 4*76 1,29 .5c,26 1,27 'O tO,00 ESCPE 509 240, 2,94 57 4,76 o54 2,22 :57 4976 58 4cOO .57 :4,;55 ,57 14i L 4#10 lOoOO E'S2CPE 509 1440c 4oOO o5l 4955 e58 4u35 le23 4*55 1*32 "@1927 lo-ft3 4-055 *53 OOOO ESCPE 487 20,00 5900 o5l 3o57 o98 442-5 o95 4955 o53 42o76 *52 4oOO ,98 0,00 ESCPE 487 1420, 3945 o86 4.17 .54 4,,00 IVOO 4935 oBI 4IJ55 v'95 49'(6 953 0,00 ESCPE 487 2"VO9 3c43 54 4o55 1 052 3o85 o54 4*00 51 3,70 o8'1 4cl'l o55 MOTIVATION TESTS !N HOODED RATS START AND RUN SPEEDS IN RE%riPROCAL SECONDS TRIAL 4 TRIAL 5 2 TRIAL 6 D DOSE MO@TIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 -Ptl RUN START RUN START 'RUt4. START RUii START RUN 2 START START RUN N09 MG/KG NO* *96 151 4al7. 2o92 4oOO a 9 1 4il7 .79. 4.76 51 4955 lOuOq ESCPE 487 120 9 3.85 470 3 57 51 4o@15 5 3 lOi2OO EC-CPE 487 240 5,00 0 5 3 4 17 51 4c76 51 3.85 .95 470 4,00 87 lo7@5 1.33 2 4,17 0 9 2 4935 4 9 5 4, 5 9 1 6 4 9 17 95 470 ',!OtOO ESCPE 487 1440. 16 4,,O 1.96 1,00 lo67 .12 1485 92 1.82 95 1,82 090 2 0400 APR%-H 436 20,00 OOOO AORCIA 49 120 1,47 09 1 79 a 79 lo96 191 2oO4 87 2 9 27 98 z ,.o 0 o5o 6 2 2 oa 2o22 olo 1985 2 2eO4 .52 1 24 o52 9 3 o522 82 095 ..iOo s5 0 0 0 APRCH 496 607 '-0900 APRCH 496 20,00 26 3o33 lo92 0 09 160 9 90 lo72 a 69 084 I-) 97 3 8 2 120o 10 9 6 0 10*00 APRCH 496 *54 oO5 '1064 o74 a -I-.- 6 904 45 1,64 o48 14,89 46 76 2 240, 2 9 08 135 2013 o64 la&9 65 o 5 6 07 2*04 6 1,75 06 0 7 10 t 00 APRCH 496 098 eO7 *21 *36 1*43 o36 1982 92 1,82 7@ - o2? *43 0.00 APRCH 488 20900 0,00 APRCH 120c 2 00 7 o38 9 6 a 2o56 *78 197- .03 .0.3 0 3 :1,22 .03 2 488 4 0 OCOO APRCH 488 240. 1:82 .25 907 904 1,72 @,44 50 .36 0 3 .03 0 32 .02 1.05 0 3 0 3 03 0 5 oi .03 607 ','.0*00 APRCH 488 20,,00 03 -.03 .03 0 3 i)07 loooo App2rH 0 3 0 3 0 3 .-O 3 Oz 488 120t 0 3 0 3 .03 0 .05 .03 @03 3 0 C-01' 10.00 APRCH 488 240. *22 .07 L*41 944 7 48 al*4 '32 - 0 3 O'i 0 s it-Li MOTIVATION TESTS IN, HOODED RATS 'D RUN SPEEDS IN RECIPROCAL SECONDS START AN CPIID DOSE MOTIV RAT TIME TRIAL 2 1 TRIAL 2 TRIAL 3 TRIAL,4 TRIAL,5 TRIAL 6 NOo MG/KG N-06 START RUN START RUN START RUN START RUN START RON' START RUN 607 0.00 APRCH 488 1440o 1*59 oO3 o38 *38 ol2 o47 2o33 o43. 22*63 64 2oOO *64 0 0.00 AVOID 502 20900 1.67 93 2*33 o56 2,50 o53 lo82 1.32 2*17 .57 2,63 .55 oooo AVOID 502 120. 090 o53 o54 2 2oo8 1.39 2,27 53 2*63 le3o 2oO4 isoo *51 OOOO AVOID 502 24TOO lo82 .57 2.56 1.67 2al7 .56 2,94 1,30 1.96 1.332 2,50 56 607 10,00 AV07D 502 20,00 0 15 004 1982 1941 1,96 956 2422 1,41 la72 1,41 2,63 56 607 '10,00 AVO'A'D 302 120, 3.3 o5-3 951 53 o56 o9O2 lo69 ,90 2663 055 1069 *52 607 lOaOO AVO!D 502 2400 4*'.16 71 1.64 095 2oO4 51 1*72 loOO 2,,50 .52 2608 *88 7 10*00 AVO!D 502 1440, 0 30 60 2 51 Lo59 952 2oQO 52 956 o53 2oO8 o54 lo96 091 0.00 AVO:D 503 20*00 *34 o55 lo96 *72 2,4k 1,32 2,17 54 3.23 o56 3o3L@) 1*30 0.00 AVOID 503 2 120, 1.89 o26 2o63 .53 2.56 1,32 1967 1672 2,44 1,45 '3,33 1.32 OOOO AVOID 503 2404 2*00 .88 2*50 *52 2ol7. 952 2u44 lo54 3aO3 lo39 24'10 lo45 2607 10*00 AVO2ID 503-20,00 *55 u6O lo37 1.00 lo64 o54 1492 55 lo54 50 2*94 r*41 7607 10.00 AVOID 503 1204 085 ,41 1.59 o74 t:56 ct-2, lv67 .81 le6l 53 2,13 2*5-r -607 lOsOO AVOID 503 240*..'1*43 o75 l@,59 956 2o44 090 *53 o98 2.)22 653 2000 &52 @'607 0900 AVOID 503 14409 &la .62 1*79 %64 2#04 5e@ 1085 56 lo43 lo33 22oOO 1*37 @VVI@l;iq y@"2, MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS TIME TRIAL 1 L 2 TRIAL 3 TRIAL 4 TRIAL 5 -PN2D DOSE MOTIV RAT TRIA TRIAL 5 T RUN START NO, Noo MG/KG START RUN START RUN START RUN STAR START 'RUN RUN 2 o54 3*45 .@900 ESCPE 507 20ooo lea2 o55 4 a 5 956 3*70 lo45 3*45 1*52 4o35 lo35 0*00 ESCPE 507 120* 5*56 lo72 4o55 lo72 4ol7 1*39 5*00 o53 4,76 o52 4935 *54 .0000 ESCp8 507 240, 36 o6O 5*00 o52 5900 #55 4*17 o55 4,76 56 09 952 2607 "1.0'.00 ESCPE 507 20.00 3..23 54 4oOO 954 3,85 lo45 5900 1.43 4.35 1.43 4,35 .56 7607 '..',.0,00 ESCpc r-07 l@200 4*00 o56 3985 1900 4e35 o5l 4e35 56 4*00 66 4*35 o55 0 07 "-0-00 ESCPE 507 240, 4.00 o93- 2986 *51 4oOO o93 4oOO '-,00 4435 9? 5926 4,L 'u7 ',0-00 ESCPE 507 14,40. 49Z'7 1032 4ol7 954 3o85 52 4,.00 56 ";,00 57 4000 ;5@-) 2 O.f'-O ESCPE 508 20,00 4.35 56 4.76 456 5oOO 51 5*00 51 5,26 1,23 4,76 56 53 0.00 ESCPE 508 120, 4*17 lc28 6o25 1*A-3 4o76 1023 4o76 1.32 4#55 52 5.00 I I* 32 5926 1, 27 4o76 @0*00 ESC?E 508 240o 5oOO -c59 5926 4oOO 1943 54 6o25 21.30 6(j7 l@0960 ESCPE 508 20,00 3.@3 54 4,00 *52 5,26 52 4,76 .52 4.35 -100-V 4,55 *97 607 10.00 ESCPE 508 120. 3.33 1,39 3o7O 955 5o26 *99 4900 .55 5*00 54 4,00 .952 .607 10.00 ESCPE 508 2-"VO, 3.45 o56 4*17 1954 4oOO o55 5*00 o59 5900 lo64 4oOO 1,43 607 1.0.00 ESCPE 508 1440o 4oOD ,56 5;,00 1945 5@,00 lu33 5*00 lo37 4975 536 4-u35 o55 e@ ,47 4-v .,41 6 o58 t.2 1,8-: s 8 a MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS PNID DOSR-' MOTIV R TIME TRIAL I TRIAL 2 TRIAL 3 TRIAL 4 AT 2 TRIAL,5. TRIAL 6 f'lo MG/KG NO* START RUN START RUN START RUN START RUN START RUti STAI?T RUN 0900 APRCH 452 i2oo 2,17 .43 2,38 070 o35 36 o76 *62' .70 23 969 2 *37 0,00 APRCH 452 2409 2,08 34 *53 965 040 960 55 61 37 o35 1,69 o67 2oO8 939 *20 2a22 562 3920 2 APRCH 452 20*00 971 099 o34 *34 961 37 *36 a 70 2562 3o2O APRCH 452 120o 2*04 o35 o23 *28 o@-9 o7O .52 968 1945 o57 2 091 .68 2 562 3 9 2 0 APRT--H 452 240. 624 o75 sO6 *45 2*13 081 0 09 0 43 70 59 2o22 e78 3.,20 C 00 69 o 5 5 62 APR.H 452 1440& 2 *56 .37 081 ol6 @29 38 *58 o7O 2 *74 0 0000 APRCH 492 2OoOO 2.56 973 1967 978 lo35 o75 o25 0281 010 o69 063 69 0900 APRCH 492 120o 2&38 093 r,20 913 1661 o85 o6l 987 1961 o97 07,8 *62 0*00 APRCH 492 240c 'alB 41 936 e74 040 o76 968 81 60 F,5 069 #7 562 3,20 ArJRk--H 492 20,00 *56 74 lo75 o87 ol7 o37 926 #'79 e87 o79 :lo6i 08 120o 2 9 63 52 1*96 3*20 APRCH 492 562 2 *68 lo79 8 5 1085 52 o37 80 -0 2 7 o98 562 3a2O APRCH 492 240 2933 o5l 40 o96 039 o9l 2oO8 51 1,82 91 2408 035 562 3,20 APRCH 492 14'@00 2 a 2.t8 oq3 2 17 90 oQ5 26 ell 69 097 093 o93 o'4 0.00 AVOID 475 2OvOO 2o38 979 1967 *43 2602 93 2o38 97 3oO3 955 3o33 1433 0*00 0 AVO!D 475 120o 2038 o?6 1.92 *85 2%)63 :76 2-56 085 2033 951 2u63 1&41 MO'41VAT"O@! 7Er-TS Ttl IA(30: q .4 -i START r4%ND RU:i SPEEDB IN RE---IPRO@-'A:t- 5 lr-" CON D 5 -POND DOBE MOT!V 2 RA,@' TIME TRZAIL. TRIAL 2 TRY.AL 3 7#RIAL 4 TRIAL 5 N .3 STAR"I RUN START RUN START RUN START RUN STAR-t' RUN 5 R'f Rk)N CLOO Allo:.D 475 240a 2o22 oBO 1479 or, 4 2v86 I 3 2 v 8,'j I o 33. 2oOO I oa 79 2 94 5 2 0 3 5 1 2 2 3 562 3,--,O Avo!-D 473 20c,00 lo'2 72 2.63 0 2 44- AVC:D 473 !"";C. 2c-'tly 85 5B 039 o53 2938 .53 5' 5 62 2 2,,70 1 5 4,,CO 562 3.'@O AVO.D 475 .3 85 2.78 092 2 4 0 2,63 091 1182 ,8L 2r.22 154 24@1:0 1*47 a 68 2o27 o35 562 -; 36 ,97 2 AVOID 473 1440a o48 82 2o33 094 2 0 08 *93 2 0,00 AVOID 501 20000 *54 1-061 3oO3 2900 3o'-3 lo89 3#85 lo89 =J,56 1.%i@ 24c!7 @',,a89 OCOO A@IOID 501 0 C 2970 Qo39 2o22 1 4 54 3 a B 5 lj54 3&45 lc69 It a 0;3 1 o S 2 a i a 6,1 0400 AVO:D 501 240,, 3,03 1033' 3o85 1*45 3,85 1,45 4917 1,56 3,45 1 , 3@,45 653 4455 1 562 3*20 AVOID 501 2OoOO 2*00 lo67 3o33 1#41 2 4oOO lo43 3*33 1*33 2s86 *182 562 3,20 AVO!D 501 120, 3,03 1,52 4.17 1 , 4':*$ 3o23 1,59 4ol7 lt39 4,00 1,4! '4o35 47 3,20 AVOID 501 2 240, 2*27 1,47 3o85 1954 3.45 1.72 3033 1,64 4,35 lo 562 49 3,70 1*67 562 3.20 AVOID 501 1440, 2,70 1,64 3ol3 -2*54 3e-13 1,43 4oOO 1,52 4,00 1,59 3,70 195-5 0*00 ESCPE 5o5 2409 4*76 lo3O 4o76 '1932 4900 o55 4ol7 *54 3o57 lo2O 3o33 o56 OOOO 2 ESCPE 5o5 20,00 4*17 956 4ol7 *51 5o26 .55 4.00 1.32 2,70 55- 4,00 951 0*00 ESCPE 505 4,55 1 55 3.57 1 35 3.03 7 120o .,47 4*17 1,41 4.17 1,43 3.85 0 A.*37 562 :",20 E.5CPE 505 20,00 4955 1,32 4,55 1,27 3u85 o55 3923 56 4.35 1.2'F @-.17 lt)25 30 D E D irl A ti.0'riVAT"ON '@'F-STS I 11 ii 2 N RECIPRol--A" 5 E @"-'O N a-iART AND RLJ,41' ;'@PEEDSI "'ISE I,IOTI'! PAT T-ME D 2 TR Al I R 5- Al T F( A',- 3 TRIAL 4 TR I AL F,( 1. A ;L TAR- F@,J if S p 2 RUN 3!'ART RUN START RUN 5 START RUN 3TAR'@ ESC-@E 505 1200 3 C54 3o85 1 eill e@000 1.@12 2 2 6':') 9 45- 'v Q 5 'I@7. c 1,;85 2 5 5oOD Qcl 3oO5 v 8 0 0 I- 3 505 240, 3,,B 5 1 2 -i 54 4,,Il 3 2 3 u a'3 F,?.2 ;:.c r 505 2 40 94 58 4oOO to52 3,,70 1,,41 3,.,5 0 C E 4IL6 20,00 1196 8 3o85 lo 37 4i,35 o55 0,, 4al7 4,,76 a 3 Sr 2 DE 466 '@-204 34IV3 1;@64 o54 4wOO 1,,00 4055 v 4@;00 5 0 0 O;D 4o55 0 57 4-@.55 2 a.00 ES'-PE 466 240o 3, 03 52 4o35 952 4239 o99 4o35 o52 5,00 1,-io 5 4.2? 62 3,7-0 ESCOE 466 20000 2r,-'e4 G87 2 3o7O o98 3o57 o82 4o!7 89 .4@00 89 4,00 b5G 5L2 3,20 ES'-PE 466 120, 4.17 1, 3'7 4,15 lol8 4.35 1,00 4,:, 12 5 Isg@22 3,51 C 5,J 3o33 as--, @a7O ESCPE 466 '-if 0 a 4 o -.S 0 5@2 2' 1 lo47 4o53 1%@2o6i 5oOO o52 4aoO 51 4.;, 5 5 o93 4o?6 z@ 5 1: 2 3o2O ESCPE 466 1440, 2 o 8,6 54 3,1.3 lo35 46)2-5 55 4*35 1.28 3.85 2 C,:5 4.. 5 055 "ONTROL 0-00 APRCH 498 - OOOO 3oZ3 loOO 2494 *56 2e78 999 3*03 *56 3923 la37 -009 a67 1*47 ;.SOO APRCH 498 20ooO o36 1996 935 lo56 939 1*41 945 2v44 2 o3,@, 2o22 *39 1900 APRCH 498 1200 3945 o95 4*00 o53 2,08 *54 3u33 v53. 3oOl o53 4.iOO 1*28. 1,00 APRCH 498 240. 4000 o54 2o44 o54 3o33 955 3*03 lu28 3oO3 lo33 11)82 i)55 1*00 APRCH 498 1440c 03 5 o67 3oO3 *57 13 o5l 2o78 1,89 2,86 1,28 3o45 l@28 iAO'i!-'VP,-i '-'ON "'E$715 IN RA"5 START At4D RUN 5PPEI:)S R o C A L SE(@'OIJDS 2 AL 'I@ AL TP !A; PI i D D 0 5 -fD V F, "iR I A:t@ -@R 1 3 TRT-AL 4 2 ';';'A R T PKUN 1.1 11) t I STAR'F RLII 5 "AR)' R '-j 1,1 5,,-, STAR S,RART P,.TJN A 2 tl.;00 APRCH 4 O.;00 2,t "l';3 082 Q Z' 3 o 2S@ lu92 f.: -i ti T P c,'5 2 *69 6 A@-,R'--H 499 20,03 '-7,44 049 l@,85 b IL -,33 2 120o 2il@3 121 2 8 6 o6g 2,44 o?l 209, 04 i.; 3 APR-H 499 '31 2 7 2z33 -0 AaRr-H 4 9 -740, 3,"3 ,70 - 4 1,, -k 1 L9 2 06,L a 0 8@s ti 2 5 !oO' APR'-'H 499 14,4-0, 2 8 @68 2(@63 0-8 lqo,:. 0900 AVO'-D 50.; OOOO 2o'D@*i o57 2@70 la52 2*08 2 lo79 3aO3 lo54 2*33 la6l" 3413 La'5 1 17 ol3 1 o67 lo7g 151 3,23 O@ 3 .41 2.61 1,41 1,00 AVOT.D 504 20,00 2,3'7 1,41 !2o44 2 1,75 -,J,13 1,52 2 86 1,Tl '.96 2. 1,00 AVOT.D 504 120o 2,94 c (i 8 2.38 1'52 3,70 2 2 1900 AVOID 504 240, 2op6 54 2o33 1*69 2,86. 1.32 2.38 1,72 3:33 1639 2o86 1989 1*00 AVOID 504 1440. lo69 1947 1*85 2*04 2022 le752 2a2l- lc72 2o5O lo6-i, 3a23 lo64 ,4CONTROL Oooo AVO!D 480 0000 2o27 o93 2*04 o77 2u33 952 2o44 o77 2,.70 651 3*33 4 "95 E 5'F 5 @ioT I VAT I 0'1'1 i;4 I-IOOD'-D RATS BI'AN'T Ail,:) RTJN SPLE.D5 f@l R@'-@2'\"IPROCA'" SECONDS R 7RIAL 2 -RIAL 4 TRI@... f-I TFZIA2L 3 @IOTIV PAT 5 R's 9 Uti 5'- 1-@(T RON 5-i RA%RT R(JN 5'1 A R'@i r@, U N!5 AR-ar R,J! RUN S-ART 2 2 0, 6 2 i .36 2 3 1,3 A @@!0 t D48 0 2 1)0 /,5 2a2i 2-,4 0 4 5 65 2,:,73 1,; 74 82 -9 00 C 7 0 1 8 2 22 2.08 2 8,-@ Jo A',! 0 Y G C. o 5:@o 0, 0.@ 2, 56 5 7 5 5 4- 5 5 5 2 5 6 4c, 70 RO: E 4 4 8 3 -.03 E S 5 C 3 4 3 3j57 8 6 1 a E;2o E 09 120@, 2o7a 7,@ 3,,45 0 3 3 3 9 3 3 70 a 8 3 314 8 3 8 0 ESCOE 5- 9 2,-O, 2o7O 7 5 3o33 4 a I 2 5 5oOO 54 2 . 44 54 6 00 E 59 E 5 09 l-4v4O. 4 . 3 ;"P 3 014 4c L@f *92 0 0 055 40 8 9 5oOO 199 1=4co 5 1 0*00 3 o 1 3 o52 3*70 9 52 4o55 o53 49 76 Cjt4 ROO@ o,oo ESCPE 487 2 3o45 83 3*45 980 46 35 o84 85 *74 4,00 7 2u66 *69 loOO ESCP8 487 20,00 2.94 .70 2 5 4,00 1,00 E8CPE 487 1200 70 3aO3 983 2o7O 82 3085 74 3o85 a 2 'T .@3 .78 )27 1000 ESCPE 487 $-.40, 2,,86 35 2.70 o63 2a78 77 6o67 65 4*1 tooo ESCPE 487 1440s -@*13 u7l 4900 #72 3u45 7 *98 2086 78 3.5-1 09)- 4400 085 iv'iO"!VA-i "ON !N PA"5 AR-i- AND RUN C)PEEDS 'iN RzrzPROCAL SECONDS 2 A I TR!@'AL p D t@,iOT' R ik!- 3 4 v RAT& T!M@ 2 M T A R'@' RuN SIART RUN r?'@ RLII a"@'A i) -0 2 C', 2 2 waa 2o: .1. 9. 3,, 8 3 5'7 58 2 2,-j 3 C, 3 33 2 APRz2:@.4 ,9 9 2' :)c. R H 9 o6i l@,04 Ii C, 2 7t. ::II 41; 2 .0,; i o 4.3 @o 0 2 13 8 6 2QB6 074 3 9 0 APRCI 2--VOz z, .5 7 -RrH 499 0 A 2 oa5 .4-9 -to64 o95 3,,57 1;@16 3,2@ 12,08 , 4 4 o 0 'LI 0 -APRCH 498 2OoOO CJ - 00 A-PPR-H 498 1. 2 3*57 1 o 1,:4) 2.00 l@,, 09 24,@, 1 1,,23 3@33 1 1 Q' I , 8 3 1 o 2 o 6,@) 0.00 APRR@H 4913 2&,O, '4 3 0 -@7 3oL3 C' 09 3aC3 I o I 1 lo56 1 2 6 7 2 1, '@B 4,; 7 i L 10900 1'.'r)RC-H 4 L372 - 2 ga 2OoOO *53 07 1 *50 952 3o33 *51 o34 1'. 00 09 9 1 3,4 2 - 20, 52 2994 1,,23 2e44 5 3 2,08 1 3 7 '@3 3 2 10.00 A:PRCH 2 498 1 9 '@@4 la35 - o 2 9.3 7 2 1 0 c. 00 APRr-Fl 498 2409 2 e-44 !,,12 1*54 1 o I 1 3 r, 03 1 o 1 28 4oOO 1*35 5u26 1 c 0 3 o !.,3 0?8 :372 10,00 A@PR-H 498 1-@40c; ? 2 2o94 1,20 3o57 I* 12 1. 52 lol4 3 9 33 11 10 .2 5 82 3*03 0,) .00 AVOID 504 20*00 3*03 1*54 3o45 9 72 3*23 lo82 4a 17 lo79 4u35 1*79 3 9 8 3 1 9 79 04 00 to69 3c85 lo67 4oOO lo67 3o7O 6 L,1-4 3uO3 0.00 AVOID 5 120o 4* 1069 3o33 ',54 MOTIVATION TESTS !N HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS 2 TRIAL 6 CPND DOSE MOTIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 TRIAL 4 TRIAL 5 MG/KG NO* START RUN START RUN START RUN START RUN START 'RUN START RUN tioe 2 0000 AVOID 504 240* 3*51 1,54 4-00 1,59 3.70 1.54 3.45 1.67 3970 1&82 3c-45 lo79 20,00 2,33 1,19 3*33 1.54 2.78 1.47 2*70 1,4t 2.33 1.45 2.50 1.64 372 10*00 AVOID 504 1*69 2o5O 2o5O 1*82 2*08 2ol3 2o5O 1*75 2 372 10 00 AVOID 504 120., 2 3923 1 a 5 2 lo82 1*82 37 2 10:00 AVOID 504 240, 3oO3 1 , 4 3 9 70 1082 @3 c 2 3 1*89 3*85 1,92 3*33 1083 20 86 2ol7 2 3 3.45 1.67 0 3,85 1.85 3 8 5 1.69 372 10,00 AVOID 504 1440, 2*78 1,49 3e45 2 1*69 a57 lo79 0,00 AVOID 480 2OoOO 3e33 a95 2o3g o87 4u35 loO4 290,4 90 3T.85 IcO-@-.- 2o4@:; !-,ulO 2 120, 2*17 82 3*57 1.09 2.78 76 2600 63 -7,27 1-@9 204-3 083 0-.00 AVOID 480 2*94 c, 97 2o5O fi 33 2 o79 2o78 -313 o 3 3 8- 82 3 0900 AVOID 480 240* 1*96 c,66 72 10#00 AVOID 480 20,00 o54 *67 1*00 983 le6l 977 2*63 83 1*82 89 57 93 ?372 10,00 AVOID 480 120, le-247 ,63 952 962 .52 *63 2*17 67 .52 51 983 :64 7372 10900 AVOID 480 240o 1.22 64 1,92 o65 1,56 *72 1996 63 2*17 79 :2,22 083 2372 10*200 AVOID 480 14409 c3l o65 2o44 965 2oO4 *62 lo56 :77 2963 :78 lo85 *83 0.00 ESCPE 487 20*00 5*88 1,30 6067 loo9 6o67 jolo 6*67 2 1932 6*25 lio,,a,5 6c6'11 1,,25 0#00 ESCPE 487 120c 6*67 1*00 5956 *93 7914 lol5 5956 1*09 5o88 098 6o67 1*18 5 240a 4*55 le2O 6o67 1918 6967 loO9 4#55 1*28 6o25 1,20 0000 ESCPE 487 4076 1*52 c o o z civ E: 0 0 9 2 990 C a 9 9 46+i HDddV oo*( gEb 2 594 1 Es, 6L*l 6.1- 181, 2fj 0 1 60* 2801 i,. 9 9 I 4?g 2 L647 HD8dV 00-0 91 82 1 6'@ 29 6;- t' L961 SZO zil collo E'7 1 L I 9'7 I 00 OEOT OL-Z 61 7 LI 47 LZOT 4?4i 0 Z @l 1 LZ*Z 0 41-@ 1 60S 3dDS3 ooeoi zLEz LE'll 0009: E-0 I 90*E ZEOZ 9L 47 01#1 0009 E I 9969 LZ"l ogllz 0 Z 605 2 3d 3 00 0 11 @ :)s 11 I 5 g 4y " C g 69 0 1 Zgo 5;iy 121 C 4;g 0 *oZi 609 3dDS3 00*07 ZLEZ el el SG* 5i 8 E Es* t6*Z 5:! 8 c z 9 EF-IIE C; z 11 I 9+1"F 2 Zs,, OLOC Zgo 4;6 0 Z, L81, 98*Z OOOOZ 609 3dDS3 00*01 ZLIE g Z 1 S 4y C C Z 1 0069 Celli gt,"e Lt"I E *E "Ol@Z 2 609 3dDSa oollo gElIg 1;1 EJOE - - oo?l 605 3d-Sg co 51 -5@Z O'b9v. 2CL- 1 a 1; OZ'l klo' ZEOI 4 I 0 47 ZS*l 476 * Z 5@7 * I 00 at d 0 o 47 OoOoZ 605 2 3dDS3 C -7 't 0 0 Z 00 Z 647 0 1 ZOOI Z647 99el BO'S 6tol @6 0 tg 0 7 Sig oogo. 0 1 s I LI 147 01*1 2 L909 E 00 0'9 61 Z*9 6,@, zclll g?09 1007 Lg*g 0 0 4,- 4@ 1 Lot 3dDS3 0060 Z 2 I SZ"l 0909 5 -sy 0 1 9L 0 17 5101 L9*9 11*1 SZ*9 6T*l L9*9 8 8 99 0 9 0 047 Z Lot 3dDS9 00*01 ZLEZ 2 06" Cc at coo cele 98, 0(114, 5911 EF 98" OL"c OZI 4817 3dDS3 00*01 ZLE gooc 5 8 0 BLOZ 47LO St 6 c go 0 DS3 00*0@ ZLE EZ"I 0 1. C'E C6* LI 114, Is COOE 00*OZ Lot 3d Nn8 invis Nnti L@IVIS Nnd IHVIS NnN 18VIS Nn8 L@IVIS Nn8 ihvis ON E)N/gw ON 2 IV8 AIIOW 3900 NdD 9 "viui tividi 41. ivi@il C.1vi8i z ivi8i 1 IV181 3WIl a 4 SaNOD3S 1VD08dlD38 NI S033dg NnH ONV IUVIS SIV8 03000H NI SiS3i NOIIVAIIOW 4h MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS DOSE MOTIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 TRIAL 4 TRIALi5. TRIAL 6 2 t4o. MG/KG NO* START RUN STAR RUN START RUN T START RUN START RUN. S7ART RIJN 636 3.20 APRCH 497 120 1,54 o63 lo96 1000 03 2 928 1933 981' 1*41 84 o27 085 2 36 3o2O APRCH 497 240, 73 6 *81 lo67 *79 1,61 89 5 5 .89 85 *89 lo75 97 636 3#20 APRCH 497 1440* 2 @92 *82 lo47 8 0 1 79 *50 1*54 o93 1*79 o98 lo56 9 3 0.00 APRCH 496 20900 2.33 59 oO7 9722 2o44 989 2o33 51 57 966 2,.17 *51 OoOO APRCH 496 240, 1-96 o34 2*17 o52 2oO8 o9l lo54 *92 2950 995 2c22 2 9 5 6 3920 APRCH 496 20(,00 2903 o69 2*27 951 24,17 97 2oO4 993 04 ol o92 i5o 6 3.20 APR-H 496 120, 2o22 r, 64 .1*82 091 1,92 2 o89 2#38 978 1*67 a 8 I 20 53 9 5 2 6 3*20 APRCH 496 240a 1*96 0 9 87 1,61 *43 lo79 52 1 79 92 o54 2 a *93 lo@5 a53 636 3o2O APRCH 496 14409 2.17 o!9 2o27 983 2,,33 o5l 2922 52 o2l 973 1,89 *53 0.00 AVOID 475 20,00 1,67 o35 22oO8 o85 1,69 *76 1*43 *93 1,56 55 2o33 1,30 0*00 AVOID 475 240o 1959 o4O 1952 975 2950 950 1939 81 o57 956 l@0'85 2 0 955 2636 3Q20 AVOID 475 20,00 2,86 o96 2o86 ISOO 2,04 .54 2*50 1,64 2.17 1,3"' -(i33 1.43 ;@636 3o2O AVOT&D 475 120, 2,04 95 1982 995 2o@@6 o54 2*22 452 2,04 1,@23 2,86 7-636 3.20 A@O@D 475 240s 2*27 c7l 1*67 o74 1256 994 2922 *51 2oOo 1,22 2.@,2) 0 54 2636 3,20 AVOID 4?5 1440, 2,50 o45 lo92 *67 2o?2 o78 1*54 1,00 2,1'( 198 '6 MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS CPND E MOTIV R TRIAL 2 TRIAL 3 TRIAL 4 TRIALI@ TRIAL 6 DOS AT TIME TRIAL 1 NO* MG/KG NO START RUN2 START RUN START RUN START RUN START RUN START RUN "6,00 AVOID 501 20.00 3.33 1.33 3.70 1 41 3,45 1,25 2,86 1,35 30 33 1,49 4.55 1*39 0,00 AVOID 501 240, 2,50 52 3,57 :51 3 03 092 2*17 1,39 2,56 1.27 3923 1.54 2 ?636 3-20 AVOID 501 20*00 3@33 Ic,67 2*56 *53 3eL3 lo45 .83 *99 2970 lo67 lu67 1,89 636 ' 3,20 AVOID 501 L20, 2,86 1,82 13 1,52 4,,00 55 3,33 1,96 o38 lo6l 2,13 1,37 29 636 , 3,20 AVOTD 501 2404 lo67 1,,64 2o78 l@630 1.43 1,64 2963 1.79 1085 1,56 2o7a 1.4@ 6 6 3o2O AVOID 501 14400 2.04 lo45 1*92 lo28 3ol3 1*52 2938 1,30 l2a3O lo6l 2c5o 1..49 0,00 ESCPE 505 20900 4,00 1,19 3,33.. *95 3o23 95 4o55 51 5,00 92 4o'7 1,25 0000 ESCPE 505 240, 3,03 1,49 -3.45 o5l 3,13 1,00 3*33 :53 2994 55 3o8'5 952 @636 3.20 ESCPE 505 20900 2.86 1,54 4.00 955 24'78 1,30 3957 .53 2.86 1,3'u- 3,23 .54 2636 3 20 ESCPE 505 120, 3*:85 54 3,33 1.33 3.03 1.41 3.33 *99 4900 5@, 3,,45 .55 2636 3:20 ESCPE 505 2400 2922 2 *52 3#45 .56 2e86 955 3*85 992 3923 51 4...03 054 2636 3 20 ESCPE 505 1440. 3,33 63 2u94 o52 3,85 54 2.50 .54 3.33 83 3,33 ',76 0,,00 ESCPE 466 2OoOO 4.55 o96 3985 *97 3985 1QOO 5,)26 u9l 4o35 U36 4@ilvli o5l MOTIVATION TESTS IN HOODED RATS START AND-RUN SPEEDS IN RECIPROCAL SECONDS TRIAL I TRIAL 2 TRIAL 3 TRIAL-4 TRIAL 5 TRIAL 6 DOSE MOTIV RAT CPND TIME 2 NOo MG/KG NO* START RUN -START RUN START RUN START RUN START RUN START RUN 1200 1935 67 1.52 1,00 1.59 .91 2917 53 1*75 .54 2o22 *53 649 1*00 AVOID 503 1989 2 *41 2986 *95 3933 .88 2,56 1*09 2*78 649 1*00 AVOID 503 240* 1*19 3*13 1 o 3 3 2649', 1900.AVOID 503 14409 1028 *48 1.92 18 2.22 93 1.43 90 1,67 1,64 2 38 1.25 2 0,00 ESCPE 507 20900 3-57 o5l 3o23 1900 3*33 *54 3*70 *52 3970 1*18 4*55 *91 0*00 ESCPE 507 120, 3#13 o87 4917 974 4*76 o95 4900 1,32 3o7O 994 3.57 2 53 0#00 ESCPE 507 240a 4*76 lo23 4955 *88 4ol7 1*14 5#00 *98 4*76 1914 4:17 *81 649- looo ESCPE 507 2OeO6 3*33 051 3o57 *51 4*00 .53 3.70 *98 4000 951 3o45 ,53 649 looo E5CPE 507 L20, 2.78 lo32 3o45 LOOO 3*57 952 4955 o5O 3985 o56 3o85 e98 649 1,00 ESCPE 507 240, 4,00 099 5o26 995 6*25 1 37 5oOO 1*10 5,26 674 5o56 1*28 649 1,00 ESCPE 507 1440c 6*25 1039 6925 lo49 6o25 1,45 2 6,67 1,3q 6o25 1.33 6,25 1,67 0000 ESCPE 508 20900 3 9 33 Ir.39 4*35 1*37 49 55 *54 4o76 055 4o76 *55 :4*35 la 3 2 0*00 ESCPE 508 120o 5900 lo54 4o55 1*322 4955 1941 5o26 1,52 4*00 o52 4oOO 1*33 0-00 ESCPE 508 240, 5#56 lo67 5*00 lo52 5o88 1*56 6o67 1,54 6*67 lo4l- 5u26 lo25 J?-649 1-00 8SCPE 508 2 20o 3*57 9 56 5oOO lc28 4oOo *56 4o76 952 4900 1,,30- 4,u55 1-37 2 9 ISOO ESCPE 508 120, 3903 lc67 5oOO 1*33 4,17 953 5oOO o52 4.35 1.3? 4,3-;Oz to2e 2 6 4 2649 looo ESCPE 5o8 240* 5sOO 1,41 6o67 1041 6o67 1949 6*67 1,18 5e56 1.39 M-D M-D 7649 ISOO ESCPE 508 14"Oc 4o76 lol6 5o26 Lo25 5*88 1*27 7*14 lol6 6o25 loll 5QOO 1039 I N HOODED RATS MOTIVATION TESTS START AND-RUN SPEEDS IN RECIPROCAL SECONDS 2 TRIAL 6 TRIALI@ CPND DOSE MDTIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 TRIAL 4 2 UN START RUN START RUN START RUN START RUN START RUN START R NO* MG/KG NO*. 2*44 2 5 2 o6 52 3o7o 53 18 67 3 ,51 3,85 53 649 *'i.00 APRCH 498 20.00 3,13 2 3 *51 3o7O 54 1982 5 120. 2o5O o9g 3ol3 1*47, 3933 *55 2978 2 649 1,00 APRCH 498 5 1.30 4.76 1,32 240* 2,50 1,25 61 lo22 5,00 le3O 4,76 1,27 4o5 2649 1*00 APRCH 2 498 76 1 92 1 1 5 2649 1.00 APRCH 498 1440, 5,00 1 . 0 2 .4,00 1 , 1 5 4,76 1 1 8 90 1 05 14 2 3 1*89 1*27 2*00 53 2oO4 1*33 0000 @VOID 502 20900 1*33 o83 lo69 o54 2oO8 o 5 .56 2.44 1 . 3 9 1*96 524 1 . 9 2 1 0 45 5 2 56 0.00 AVOID 502 120 1,64 65 2 0 00 *52 1 72 93 2*13 52 2o38 1.20 lo52 1*39 240. 21 64 1,45 ..2 .33 0*00 AVOID 502 79 o 13 1. 27 2*56 1 .5 2 22,56 1,43 2oO8 1 o a 5 1 51 2 13 9 looo AVOID 502 2OoOO 54 1 2 1, 54 1, 85 2o5O 75 49 1 9 00 AVOID 502 120. 2,44 1,30 2,50 1.41 2.63 1. 59 2.56 1.61 649 1.00 AVOID 502 2409 1.20 *'4 8 3 9 13 1*72 2 2o7O 1952 3e45 1-o 52 3#33 1.54 lu96 1*79 47 649 1.00 AVOID 502 1440, .60 1,14 2o56 lo23 2 2*86 lo49 2.94 1.54 3.70 1.61 2.22 1 . 2*50 1.33 2&38 1,61 2,27* 1,39 2*27 1-32 0.00 AVOID 503 20*00 2908 o83 1927 lo79 2 0900 AVOID 503 1 2 0 1 .96 *36 lo56 *52 2,00 o55 2o22 1,30 2o5O 5-@ tu89 54 0*00 Avo!D 503 240a lo6i r,74 1982 -990 1.361 1.22 lv92 953 2#21 lo39 2950 1*33 @OP VI MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS ,@,,f',@CPND DOSE MOTIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 2 TRIAL,4 TRIAL,5 TRIAL 6 NO* MG/KG NO' START RUN STAR! RUN START RUN START RUN START RUN START RUN 0,00 APRCH 492 1200 2o22 .79 1,43 995 0520 98 037 34 1 47 97 1,89 97 240, 1*82 97 2*08 051 1192 98 2ol3 0.00 APRCH .492 92 2:22 .96 .53 2*83 5143 R 2 20.00 1,56 .33 1 25 83 85 o85 1982 .92 1.54 .93 79 4,85 i*00 AP CH 49 143 .40 53 .91 2900 .92 1,00 APRCH 492 120, 1,92 .92 10 081 35 88 .83 143 1*00 APRCH 492 240o 2*33 83 2-94 1*02 2.56 996 2#38 loO2 1*09 loO3 lo23 2 *95 143 1,00 APR'--H 492 1440, 2,08 .70 *33 969 ,93 .93 89 1,00 1.14 .84 1 09 49L 0*00 APRCH 499 120c 1982 o82 2o38 Q83 920 o72 2o5O 2 *96 2*04 q6 1:92 *36 0#00 APRCH 499 240o 2*33 o73 2*27 o84 o87 o84 2u86 976 944 60 2o33 090 2,56 2 43 1*00 APRCH 499 20.00 1.75 .34 3*23 @983 971 2o7O o7l 2o44 68 1,67 *71 8 43 2 1,00 APR-H 499 120, 3,03 70 2o5O o89 2,33 70 2,27 79 2,13 80 2,50 43 I,Ob APRCH 499 240Q 2956 61 913 'v77 37 .80 65 079 1,92 .65 2,63 73 143 12*00 APRCH 499 14409 2*63 962 *65 975 2o44 '80 *42 972 -99 066 3903 975 0900 AVOID 504 2OoOO 2*;13 1082 2o27 2*50 2*33 2*08 2.86 2.04 2,78 2o2l 2,91'r 2 2,04 0.00 AVOID 504 1 2 0 a 1*64 2c78 2ol3 2u27 1*45 3 9 2 3 o 5 5 2&50 1 a 2 5 2*17 1*67 2*33 2o22 2,33 2*17 2*38 1,82 2o44 2 lo92 2o56 2oO3 2,38 0*00 AVOID 504 240o 2,22 2,63 1443 LOOO AVO!D 504 2OaOo 2u38 log'o 2o44 lo92 2,,22 lo89 2*33 1*89 2o22 2.3.4 V'-lw38 '-@#13 MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS CPND DOSE MOTIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 TRIAL-4 TRIAL 5 TRIAL 6 NO- MG/KG NOm START RUN START RUN START RUN STA2RT RUN START RUN START RUN 5143 1*00 AVOID 504 120, Z.;3 1*75 1.64 2*22 1,89 1*82 2*50 2,22 2,33 1*82 1,96 2,44 5143 loOO AVOID 504 240* 073 2oO4 3*23 2*50 39203 2963 2*22 3*13 1*79 1996 lol6 2963 5143', 1*00 AVOID 504 1440* 1*67 lo59 2*86 1*69 2*50 1989 2,70 1,96 3.57 2.08 1,49 2.4 0*00 AVOID 48o 2OoOO lo75 992 1985 o89 2*04 e99 2o86 *51 2*27 o52 2o33 051 .0*00 AVOID 480 120a lo92 o9l 1#79 o83 1982 982 1985 *79 lo82 *95 2@04 94 0,00 AVOID 480 240. 1967 o9O 2ol7 o9O lo85 o83 2,08 94 le4l 253 2,33 51 5143' looo AVOID 480 20,,Oo 1945 963 1982 *72 lo85 o95 lo96 *98 le6l o55 lc69 95 3143 1*00 AVO;.D 480 1200 1967 o69' lo96 971 lo47 lo72 1*67 o65 2917 o6 2 4 lo45 1.00 51@43 lgoo AVOID 480 240, 1975 o8l 2o7O o87 2908 996 1979 993 o79 lo47 3o85 1*30 5143 1600 AVOID 480 1440a .76 *65 *93 2 2922 la4l 1 9 09 1 9 45 o89 985 1*67 1*32 1*09 lo33 @3,,33 0*00 ESCPE 5og 2OoOO 3*45 1,43 4*00 21.43 3923 1*25 '2*44 1.56 5.00 1*43 0900 ESCPE 509 120o 2#38 lo4l 4917 1932 4ol7 lo37 3933 1,22 4,00 lo27 3o23 1.32 0*00 ESCPE 5og 240a It.-56 lo59 3*03 957 3o33 2lo56 1*32 2,00 4ol7 lo56 3oO3 1*82 143 A.UCO ESCPE 509 20000 2*50 1,43 4o35 le4l 4o76 to45 2933 1,67 2o86 L#')49 2;,04 1479 LOOO ESCPE 509 o54 3o23 81*54 1443 1,52 2.86 1,54 3G33 1 143 120, 2*70 lo4l 2*86 *20 MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN RECIPROCAL SECONDS 'k CPND 2 DOSE MOTIV RAT TIME TRIAL I TRIAL 2 TRIAL 3 TRIAL 4 TRIAL)5. TRIAL 6 Nos NO* MG/KG -START RUN START RUN START RUN START RUN START RUN START RUN 0 509 2 2400 3*23 5143 le 0 ESCPE 1,35 .4,17 1,35 2956 1*54 3*13 1*47 3o57 le4l 2o78 1*37 143 1#00 ESCPE 509 1440* 1,27 1,30 3,13 lo52 2.86 1,49 2,44 1.39 2 3,85 1025 3o33 1,32 0. 0 20,00. 0 ESCPE 487 4.00 91 4*00 1,19 4,55 *98 4*76 .51 4.17 93 4.76 90 4 OSOO ESCPC 87 120a 3923 e98 3*33 *98 4ooo 5 3 4900 ,50 4900 a 5 3 4oOO 1 14 0,00 ESCPE 487 24 0, 3.57 *87 4976 055 4.35 :52 4900 1.16 4,00 1.30 3,85 :95 1.00 ESCPE 143 3*45 1 487 20000 00 5*00 9 5 1 3o7O 9 5 1 4955 5 1 4,00 2 .53 5QOO 5) 143 120. 3 9 33 o84 3903 o85 3oO3 989 3-23 *69 3aO3 C,83 3 9 3 3 986 1*00 @SCPE 487 143 1.00 'C-SCPE 487 2"-VO. 6#25 1,05 6967 lol9 5,56 loO9 4935 1,27 6.67 1,1'0 6o67 1.03 143 looo ESCPE 487 1440o 4935 o82 4*17 o76* 9 0 3 9 06 .82 0 3 03 o329 95 C)3 0*00 APRCH 488 20900 -26 056 *92 3co3 87 2-86 91 2*00 976 :3o57 #95 22978 0600 APRCH 488 120a 4*00 o86 3o57 1*04 o2l *66 3#23 94 1*45 1*01 3e33 *84 0*00 APRCH 488 240* lo@2 o67 3o7O o88 3*45 .82 4*55 2 1*06 o37 085 090 *87 598 *32 APRCH 488 20*00 1*14 c53 4*00 *59 4ol7 #70 4000 9 98 3G45 981 3w57 0 q 598 *32 APRCH 488 120a 2*33 0 8 3 2o86 6 *98 3,33 *§l 1 a 79 loll 4*35 tol? C38 o69 032 APRCH 488 21@0, 4.55 1409 3o7O 1*09 1967 loO3 3o7O 994 4455 o93 3oo5 *85 MOTIVATION TESTS IN HOODED RATS START AND RUN SPEEDS IN.RECIPROCAL SECONDS D TRIAL 2 TRIAL 3 TRIAL 4 TRIAL 5 TRIAL 6 CPN DOSE MOTIV RAT TIME TRIAL 2 I 'RUN START RUN START RUN NO* MG/KG RUN NO* START RUN START START RUN 2START 9 8 598 *32 APRCH 488 14409 3.?3 ',79 4,17 985 1905 984 3*85 90 3,85 91 4,17 'd *00 APR 9 1932 1*15 2 1*56 1903 *43 085 1*10 loll *09 086 CH 496 20900 1 9 8 2 9 00 .0soo APRCH 496 12 *20 o82 lol8 1*22 *18 *75 *77 1*06 1947 1*20 1919 1*15 0*00 APRCH 469 240, 1*45 1,00 1035 1,04 1,64 1*18 1*39 1,25 1*01 1.05 97 loll 598 932 APRCH 496 20,,00 1*23 o89 lo25 lo2O 1.43 1009 1.30 1.16 1,45 L,19 1,22 1014 2 598 932 APRCH 496 120o 1,6'L 1,00 1,72 1,16 1,82 1,18 1.72 1,19 1.52 1,30 1,-,69 1.27 598 o32 APRCH 496 240o 1*54 o9l I 0 18 lo22 lo64 lo22 lo4g 1 9 15 2,5 2 o9S lo37 1 L 2 5 398 *32 APRCH 496 1440a 1.85 LoO8 -2oO4 1925 87 1019 1,49 lo23 029 1,11 lo82 1*32 0,,00 AVOID 475 20ooo 1906 979 2o22 1.23 1*04 1*01 2913 1,33 .88 lo92 2956 le6l OOOO AVOID 475 120* 2922 58 1#09 1*06 1 . 4cJ 993 lo28 1112 lo28' 1*43 o72 6 a 2 1-9 0*00 AVOID 475 2400 1.75 099 992 *99 lo92 lo37 2,70 1,54 2,33 1,32 ;2o7O 1.237 598 .32 AVOID 47 1,43 3a45 1.32 3o23 Lo43 20900 *93 loO4 2*00 *97 2622 1*15 1*82 2598 .32 AVOID 475 120a 2,22 066 lv85 1906 2 1,96 1904 2o27 1,19 2,38 1,25 2,00 1*32 $'-598 @';2 AVOID 475 2400 2*36 1008 1*67 loll 1,85 1,22 2194 1.33 2.56 1'43 2e85 1,45 2927 o54 1*75 o73 I4a82 o75 2900 *69 lo69 1 18 2ol3 lo33 598 o32 AVOID 4 75 1440a --------- -- MOTIVATION TESTS IN HOOOEO RATS START AND.RUN SPEEDS IN RECIPROCAL SECONDS ,PND DOSE MOTIV RAT TIME TRIAL 1 TRIAL 2 TRIAL 32 TRIAL 4 TRIAL,5 TRIAL 6 t4o MG/KG NOo START RUN START RUN START, RUN START RUN START RON' START RUN 0.00 AVOID 4,1@ 1,61 3*33 1.61 3.33 1.47 3,85 1.67 3 57 1,67 3.45 1*67 501 20,00 2 0.*00 AVOID 501 120, 2.22 1,54 3913 1*25 3923 1*54 Z994. 1*41 2*50 le6q 4o76 1.54 0*00 AVOID 501 240. 3,45 1,54 2*70 lo67 4600 lo69 3,33 1,32 3,13 1.67 3.70 1.47 598 *32 AVOID2 501 20,00 2.86 1,67 3.13 1*54 3.70 la6l 3o33 1,52 4.35 1.67 4,55 1985 1.52 2.56 1,35 2,63 1.45 2.33 1,27 2,56 1,3 598 32 AVOID 5-01 120, 2,27 1.39 2 70 2 9 ol 240* 3*13 le2o 598 o32 AVOID 5 3:03 1 23 2.70 1*43 3923 1,49 2963 2o33 3,33 1.45 598 .32 AVOID 501 1440g 2.08 1,23 2o86 la3O 2.86 1,54 2 2.70 1,49 3,03 1,43 2,70 1156 0 oloo SCPE 505 20.00 5.26 1,28 5*26 1.33 5, 88 1.35 4,00 1.10. 4000 1,11 4,17 1,2 0600 ESCPE2 505 1200 3.70 1,54 4.00 1*39 5ooo lol5 3985 1,10 3070 1.03 3o57 1,28 0*00 ESCPE 505 240* 4*55 lo27 5900 1-39 4*55 *98 4 35 i,25 3o57 38 '4o35 *71 .32 ESCPE 505 20.00 23*70 1.20 5988 1,23 5.88 *87 5*56 .94. 4,55 1.14, 5,,00 1.06 598 598 .32 ESCPE 505 120, 3*57 67 3,57 916 4o76 .46 4100 .17 4.17 .31 4935 -.8 598 o32 ESCPE 505 240, 4o55 loO39 5*00 991 4o76 o97 3i33 1.23 3*57 1.08 3o7O 1,12 598 o32 ESCPE 505 1440, 3.01 56 4*76 1904 4,35 1,28 4*17 1,02 6.25 1,30 5o26 1,015 MOTIVATION TESTS IN HOODED RATS @STAR T AND RUN SPEEDS IN RECIPROCAL SECONDS DOSE MOTIV RAT TRIAL 2 CPNI) TIME TRIAL 2 TRIAL 3 TRIAL 4 NO# MG/KG TRIAL,5 TRIAL 6 NOS STAR! RUN START RUN START, RUN START RUN START RbN START RUN OSOO ESCPE 466 120. 4*00 1.59 4*76 1*33 3.57. 0 00 ESCPE 466 240. 4*55 1037 4,o35 1.28. 4,76 0 loO4 1,,56 1.15 1.89 6.25 1096 4.35@ 1.82 2 5oOO 1,52 3.45 1,85 2.56 lo43 598 .32 ESCPE 466 20.00 3,57 1.45 5900 lo43 598 98 *32 ESC2PE 466 240 120. 2.86 lo28 3,57 1.11 4.17. o98 3.85 1.25 3623 1914 4976 1,04 *32 @SCPE 466 5,00: lol5 5.00 1.23 5.88 1.23 5.00 1,28 0 5956 2 1*30 5o56 1,23 4976 1*41 5*56 lol2 4o55 1*06 lo56 1054 98 .32 ESCPE 466@ 1440. 2.86 1.20 3.45 1.00 4o55 1,27 5oOO 1919 4,76 9 93 4,17 3 .92 .'OW@ 14" @*kZk It SRBA 975 RAT No, DOSE WTo 'TIME OBSERVATIONS @ND SEX MG/KG GM, HOURS 4 518 M I 00 361 OeO NORMAL o*25 NORMAL 2 NORMAL NORMAL 24 NORMAL 491 M 10*0 289 000 NORMAL o#25 INCREASED REARING UP SIDES OF CAGE 3 CONTINUALLY NUDGES REWARD DOOR' 2 INCREASED REARING UP SIDES OF CAGE 4 NORMAL 24 NORMAL SRBA 2 372 RAT No* DOSE WT* -jiME OB5ERVATION5 AND SEX MG/KG GM* HOURS 518 M 10 0 0 357 oto NORMAL NORMAL oo25 2 2 NORMAL 4 NORMAL 24 NORMAL 1000 291 o,o NORMAL 491 M o*25 NORMAL 2 NORMAL 4 NORMAL 02 5 NORMAL SRBA 2413 RAT No, DOSE WTdo TIME OBSERVATIONS @ND SEX MG/KG GM HOURS 517 M 196 @333 OiO NORMAL 2 0 25 NORMAL 2 NORMAL 4 NORMAL 2 4 NORMAL 528 M &*6 371 000 NORMAL Oo25 NORMAL 9 2 NORMAL 4 NORMAL 24 NORMAL Ilk SRBA 460 RAT No* DOSE WT* IME OBSERVATIONS @ND SEX MG/KG GM* HOURS 491 M logo '283 0,0 NORMAL o o25 CONTINUALLY NUDGES REWARD DOOR SLIGHTLY DISRUPTED PATTERN NORMAL 2 4 NORMAL 24 NORMAL 299 0 0 miosi,,s 516 M logo oa25 -CHEWS LIGHT BULBS ABOVE PEDALS 2 SLIGHTLY DISRUPTED PATTERN 2 SLIGHTLY DISRUPTED PATTERN 4 SLIGHTLY DISRUPTED PATTERN 24 NORMAL BA 2470 No. DOSE WTO RAT, -TIME OBSERVATIONS @ND SEX MG/KG GM, HOURS NORMAL. 519 M lo.o 357 090 0925 NORMAL- 2 2 NORMAL 4 NORMAL .24 NORMAL 489 M 10.0 418 0 0 NORMAL oo25 NORMAL 2 NORMAL NORMAL 4 1 24 NORMAL, A 2562 RAT Noo DOSE WT* TIME OBSERVATIONS AND SEX MG/KG GM* HOURS 525 M 3*2 295 OsO NORMAL NORMAL 0*25 2 NORMAL 2 NOR 4 MAL 24 NORMAL 529 M 3*2 284 000 NORMAL oo25 SLIGHTLY DISRUPTED PATTERN DECREASED LOCOMOTOFZ ACTIVITY 6 2 DECREASED LOCOMOI-OR .4CTIVITY 4 NORMAL $ 24 NORMAL IM-260-7 RAT No, DOSE WTo TIME OBSERVATIONS AND SEA MG/KG GMo HOURS 525 M logo 293 0,0 DECREASED LOCOMOTOR ACTIVITY DECREASED REARING FREQUENCY DECREASED RESPIRATORY DEPTH 2 INCREASED RESPIRATORY RATE LOW POSTURE INCREASED RESPIRATORY DEPTH 0 25 IRREGULAR RESPIRATORY DEPTH IRREGULAR RESPIRATORY RATE DECREASED REC-PIRATORY RATE 1 RECLINES ALONG C--IDE OF CAGE DECREASED LOCOMOTOR ACTIVITY LOW POSTURE 2 DECREASED LOCOMOTOR ACTIVITY 4 DECREASED LOCOMOTOR ACTIVITY 24 NORMAL c A L.LB 2607 OBSERVATIONS RAT Noo DOSE WTO TIME AND SEX MG/KG GMo HOURS DECREASED LOCOMOTOR ACTIVITY 525 M 2 lOoO 293 0,0 DECREASED REARING FREQUENCY Y DEPTH DECREASED RESPIRATOR INCREASED RESPIRATORY RATE LOW POSTURE 2 0.25 INCREASED RE5PIRATORY DEPTH IRREGULAR RE5PIRATORY DEPTH IRREGULAR RESPIRATORY RATE DECREASED REC-PIRATORY RATE 0 '-IDE OF '--AGE 1 RECLINES At. N@U DECREA5ED LOCOMOTOR ACTIVJTTY OW POSTURE 2 DECREASED LOCOMOTOR ACTIVITY 4 DECREASED LOCOMOTOR ACTIVI-Y 24 NORMAL -e B A 636 RAT No* DOSE WT, 'TIME OBSERVATIONS @ND SEX MG/KG GMe HOURS 528 M 302 364 000 INCREASED RESPIRATORY DEPTH INCREASED 2RESPIRATORY RATE RUBBING NOSE 0*25 HESITATED ON REWARD PEDAL WITH HEAD OUT OF DOOR HEAD SHAKE SKIN FLICK 2 HESITATED ON REWARD PEDAL WITH HEAD OUT OF DOOR HEAD SHAKE 8 SKIN FLICK NORMAL 4 NORMAL 24 A 2636 RAT No* DOSE WTo TIME OBSERVATIONS AND SEX MG/KG GM, HOURS 491 m 392 280 090 RUBBING NOSE INCREASED RESPIRATORY DEPTH INCREASED 0RESPIRATORY RATE o*25 HESITATED ON REWARD PEDAL WITH HEAD OUT OF DOOR SKIN FLICK HEAD SHAKE 2 SKIN FLICK HEAD SHAKE 4 NORMAL 24 NORMAL SRBA 2759 RAT Noe DOSE WT* TIME OBSERVATIONS 8ND SEX MG/KG GM, HOURS 14 M 10*0 323 0,0 DECREASED LOCOMOTOR ACTIVITY 5 DECREASED REARING FREQUENCY 2 t: DECREA SED RESPIRATORY DEPTH DECREASED RESPIRATORY RATE REASED LOCOMOTOR ACTIVITY 0*25 DEC 2 RECLINES ALONG SIDE OF CAGE ATAXIA DECREASED RESPIRATORY DEPTH DECREASED RESPIRATORY RATE 2 RECLINES ALONG SIDE OF CAGE 4 DECREASED LOCOMOTOR ACTIVITY 24 2 NORMAL, BA 2759 RAT No. DOSE WT, TIME OBSERVATIONS GM, HOURS @ND SEX MG/KG 510 M 1000 337 000 DECREASED LOTOMOTOR ACTIVITY DECREASED RESPIRATORY DEPTH 2 DECREASED RESPIRATORY RATE DECREASED REARING FREQUENCY o*25 DECREASED LOICOMOTOR ACTIVITY RECLINES ALO@G SIDE OF CAGE 2 DECREASED LO@OMOTOR ACTIVITY RECLINES ALONG SIDE OF CAGE 2 4 DECREASED LOCOMOTOR ACTIVITY INES ALO@G SIDE OF CAGE RECL 24 NORMAL SEQUENTIAL RESPONSE TEST@IN HOODED RATS NUMBER OF REWARDS RESPONSES AND PER CENT ERRORS FOR FIVE.MINUTE INTERVALS CPND RAT PRE DOSE 15 MIN 2 HOUR 4 HOUR 24 HOUR NO RWD TOT pCT RWD TOT 'PCT kWD 2 TOT PCT 'RWD TOT PCT RWD TOT. PCT 490M 517 22* 729 61* 24* 77* 649 249 76* 63* 27* 86# 63* O*OOMG/KG @269 80@ 669 29* 88* 64o 26* 81a 64o 30* 93* 659 29, 899 2 669 28o 859 67o 30* 91, 66* 31. 96. 65. MEAN 26* 809 65o 27a 83o 65a 27o 83* 64o 29* 92o 640 517 23, 74, 62, 2o 24, 25o 229 71* 62, 28o 89* 639 26o 852* 61* 1.00t,it'/KG 27, 89o 61* Oa 689 19* 289 87a 66, 279 87, 62, 24, 82, 60* 29* 93o 61* 5o 75* 31* 269 84* 639 27. go* 61, 339 110* 60* MEAN 26. 85. 621. 2, 56, 25* 25. 81. 64, 27, 89, 62, 28. 92* 60, Immow 7 5 518 29* 1209 48o 24 a 119* 42 a 3i2 o 133* 489. 29o 1319 47* 20, 117* 39a @l'O.C)OMG/KG 25o 107* 509 30* 136a 2 46o 31* 122a 151* 30* 127a 48* 31* 137* 45o 13* 66* 44a 27o 123* 509 1.6* 72o 449 26* 107* 499 21* 979 46o MEAN 22, :96o 47o 27o 1269 469 log. 48. 28, 1222e, 48. 24. 117. 44. 518 24. 147* 379 25o 1109 48: Z54. 83o 609 28* 96* 58o O*OOMG/KG 25, 1099 47o 34o 119a 58 J79 1129 669 28* 93o 60, 29* 117* 5 50. 27. 102. 53o 999 92, 62. 18. 71, 55. MEAN 26o 1240 44o 29o 1109 53* i'@Oo 96a 63* 25* 879 589 5EQUENTIAL RESPONSE TEST iN HOODED RAT5 NUMBER OF REWARDS RESPONSES AND PER CENT ERRORS FOR FIVE MINUTE INTERVALS 4 HOLJR 24 HOUR CPND RAT PRE DOSE 15 MIN 2 HOUR CT RWD TOT PC PCT NO RWD TOT, PCT RWD TOT PCT RWD TOT P T RWD TOT 372 518 20* 949 46, 23, 88o 53@ 20* 86o 48. 17* 77* 48. 16, 76.. 46o 2 51. 11- 53, 43, 23, 939 4.9* iqlo,OOMG/KG 229 52* 23o 899 54% 19. 77, 230 95o 49, 23a 96o .50a 23, 93o 49. 20. 83, 47, 22,, 93* 47@- 2 49, 23o 91, 52* 21, 85o 49o.169 71. 469 20, 87o 48o MEAN 22* 910 88o 609 26o 88* 60* 27* 89. 61. 269. 83* 639 517 26* /i K G 2 29. 97, 60o 27o 85o 65* 299 959 62, 27-P 95* 60* 30. 98. 61* 24o 79o 59* 25. 78o 649:34* 110# 639 MEAN 280 94, 60* 26* 84* 61* 27o 87* 62o.29* 926o 629 413,- 517 27. 92. 59. 28. 95, 59, 27,,, 93* 59* 24. 80, 61, 26, 909 60* 1, 31, 99. 63. 20, 66. 61. 15. 53, 58, 28. 92. 63. 101,60.MG/KG 28. 04o 2 6 82o 599 22, 77o 589 18* 83, 51, 20, 71* 56o 21. 74, 57. 24o MEAN 25. 87o 59. 28, 92, 60, 23o 79* 599 19,, 72o 57, 25. 84* 60. 2 38a 24o 80, 63* 279 106o 51* 31o 114* 54o 0,0,.. 516 28,, 154* 46, 21o 72a 61o 17. 75. 450 28* 110, 55* ut'AG/KG 30* 137* 3103, 50. 37, 1419 52, 16. 50, 64o ?@o 92o 50* 25* 49, 28o 1099 53o MEAN 32, 144a 46o 209 67o 639 22o 919 SEQUENTIAL RESPONSE TESTI,'IN HOODED RATS FIVE MINUTE INTERVALS NUMBER OF REWARDS RESPONSES AND PER CENT ERRORS FOR CPND RAT PR .E DOSE 15 MIN '2 HOUR 4 HOUR 24 HOUR 2 NO RWD TOT. PCT RWD TOT PCT kWD TOT PCT:,.RWD TOT PCT RWD TOT PCT 4, 55i 42, 17, 74, .469 19* 80 49.111. 60. 37. 34,0 12 4602 516 34, 165* 0 (WboOOMG/KG 38o 162o 48, 27o 100, @56* 33* 1250 .53,'.30o logo 55o 41, 139* 5.9o 116o 622@ 42o 155* @54o 28o 93a 60o 34* 121o 55o;25o 92o 54o 36o 6o 59o MEAN 38, 161, 48o 249 89, 54,, 29o logo 52*:226 87o 49o 37, 12 518 19, 87* .44* 23* 102o 46o 16o 76* 47o:@27o 1109 -499 OoOOMG/KG 25o 110o 50o 309 1289 48o 309 126o 51*128o.101* 550 2 29, 124o 48o 30o 124* 48a 25o 102o 5lo!27, 106o 510 107o 479 28o 1189 47* .24 o 106o 52o MEAN 2 24, o tOl* 50,@27 470 518 210 73* 64o 21o 75o 57* 259 90o 59,:20o 699 599 18o 66* 58o 1*0.oom'@/,KG 33* 11.09 60o 26o 85* 61* 13o 67o 429o:279 86o 64o 13o 42o 62 5o 81o 62* 25* 749 68* 189 70o 56,.189 52o .679 17o 55, 64: 2 MEAN 26o 88o 62o 24, 789 62o 19, 760 55o@22o 69o 64, 16o 54o 61o 525 260 88, 65o 280 86o 649 3@lo 94, 66o.31, 98o 650 OoOOMG/KG 33, 100o 67o 30* 99o 660 3,3o 1009 65, 34* 105o 65a 2 35o 106o 66o 31* 949- 66o 359 107o 65o.30o gl* 66o MEAN 31o 98o 66o 30o 93o 65o 3@.3t 100* 65.9 32o 98* 65o 1 rn SEQUENTIAL. RESPONSE TEST IN HOODED RATS NUMBER OF REWARDS RESPONSES AND PER CENT ERRORS FOR FIVE.MINUTE INTERVALS CPND RAT PRE DOSE 15 MIN 2;HOUR 4 HOUR 24 HOUR NO RWD TOT PCT RWD TOT PCT RWO 2 TOT PCT RWD TOT PCT RWD TOT PCT 562 525 32o 96o 67o 25* 80* '649 29* 89o 66*!27o 87* 64o 28o 85o 66o 3.20MG/KG 32 989 66a 28o 859 66' 27o 82o 66s@31* 93& 67* 2 23# 72* 64o, 27: 86* 64* 28o 81e, 68: 16*;, 50o 64*,25* 84,, 649 27, 82* 66, MEAN 30, 939 66* 27o 82o 66* 24* 749 65o:28o 88o 65, 26, 80, 65, 2 525 33. 100. 66. lq. 74. 64. 24* 75o 65,.19o 62, 63, -M@MG/KG 32. 105 64. 25o 849 65* 23* 74* 62o:16* 51o 63* 80: 61* 21o 72* 6 599 10*2- 31o 68* 23 le 20*i 69* MEAN 29, 959 64o 22o 779 639 22o 73* 62*@15o 48* 64@ 607 5215 26, 87o 61o 2* Ilo 36. Ile 39, 56. 22, 72* 61o 226, 79* 66* etpo,OOMG/KG 27, 84, 64, Oo 0,* 13a 44, 64, 180 58o 66, 25. 79o 63* 35, 107* 65o Oo oo* 17 50* 66, 7o 21a 67* 27* 84* 264c MEAN 29, 93* 64a lo 6,* 14@ 449 62o 16* 50* 64* 26, 8le 64* 514 36, 1679 43, 31o 108o 599 15o 55* 55# 309 100a 61, OoOOMG/KG 36o 152* 47* 27* 93. 62. 170@ 57. 60.. 25. 84. 61,, 20* 77* 51* 169 60o 55o 29. 929 64v 269 86o 60, MEAN 31, 132* 47* 259 87a 59o 20* 68@ 59o 27o 90* 619 ENTIAL RESPONSE TESTIIN HOODED RATS SEQU Flv@ MINUTE INTERVALS NUMBER OF REWARDS RESPONSES AND PER CENT ERRORS FOR CPND RAT PRE DOSE 15 MIN 2 HOUR 4 HOUR 24 HOUR NO RWD TO-2I,' PCT RWD TOT, PCT RWD TOT PCT RWD TOT PCT RWD TOT PCT 759 514 37, 128* 580 Oo 00* 279 88* 619 26, 87* 61o 21* 184. 23, -WipooOOMG/KG 41* 137* 60o Oe lo Oo 12o 41* 599 299 949 62* 22* 182o 259 @41. 1354 61* 8o 26* @620 00 00* 3. 11, 55* 24, 147, 33,4 MEAN .40o 133o 59* 3o 99* 20* 65* 60* 19, 64, 59, 22* 1719 27, PHYSICAL AND NEUROLOGICAI. EXAMINATION OF CATS PEG-300 100% (I-V) OBSERVATIONS CAT N09 DOSE wial, TIME AND SEX MG/KG KGo HOURS 44 F 2*50 000 HEART RATE 150 BEATS/MINUTE RESPIRATIONS PER MINUTE 2 36 BODY TEMPERATURE C 38.4 QUIET CALM BEHAVIORT GENTRAL APPEARANCE9 AND'CONDII'ION NORMAL NEUROL061CAL TESTS NORMAL NOSE COOL AND@MOIST 2 PRE-DOSE (SAME DAY) 001 HEART RATE 132 BEATS/MINUTE RESPIRATIONS PER MINUTE .42 BODY TEMPERATURE C-38*7 NOSE WARM AND MOIST N05E REDDISH NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL 2CONDITION -0,5 HEART RATE 138 BEATS/MINUTE RESPIRATIONS PER MINUTE @36 BODY TEMPERATURE C 38o6 NOSE WARM AND MOIST NOSE NORMAL PINK NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 7 1*0 HEART RATE 132 BEATS/MINUTE RESPIRATIONS PER MINUTE 48 NOSE WARM AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION rn D NEUROLOGICAL EXAMINATION OF CATS PHYSICAL AN PEG-300 100% (I-V) CAT No, DOSE WTo TIME OBSERVATIONSI AND SEX MG/KG KGo HOURS 44 F 2e5O 2,0 HEART RATE 138 BEATS/MINUTE RESPIRATIONS'PER MINUTE .48 BODY TEMPERATURE C 38@5 NOSE WARM AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 4eO HEART RATE 96 BEATS/MINUTE RESPIRATIONS PER MINUTE 84@ BODY TEMPERA2TURE C 38o3 N05E WARM AND M015T NO OTHER CHANGES NO TED IN PHY51CAL AND NEUROLOGICAL CONDITION 23o6 HEART RATE 140 BEATS/MINUTE RESPIRATIONS@PER MINUTE 60 BODY TEMPERATURE C 38oO NOSE 6 COOL AND MOIST BEHAVIORT GENERAL APPEARANCE, AND CONDITION'- NORMAL NEUROLOGICAL TESTS NORMAL PHYSICAL AND NEUROLOGlc4L EXAMINATION OF CATS 356 (I-V) s CAT 'No. DOSE WTo TIME OBSERVATION AND SEX MG/KG KG, HOURS HEART RATE 168 BEA-iS/MI2NUTE 32 M 5*6 3*43 000 RESPIRATIONS PER MINUTE 60 BODY TEMPERATURC- C 3902 NO DIARRHEA BEHAVIORO GENERAL APPEAqANCE9 AND CONDITION NORMAL NEUROLOGICA2I- TESTS NORMAL LEAN PRE-DOSE (SAME DAY) 0412 HEART RATE 150'BEATS/MINUTE RESPIRATIONS PER MINUTE 60 BODY IREPIPERATU@E C 3992 2 TAIL LASH i NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDT-TION Oc,6 HEART RATE 156iBEATS/ffilNUTE RESPIRATIONS PER MINU'47E 72 BODY TEMPERATURE C 382,9 TAIL LASH -AL CONDITION NO C,,HER CHAINGES NOTED IN PHYSICAL AND NEUROLOGI'@- 1,8 F.EAR17 RATE 15i6,,,B7-ATS/MINUTE 2 RESPIRA"'S'IONS P@ER MINUTE 66 4 BODY TEMPERATU RE C 38.7 SLIGHT DIARR@(EA WITH CLEAR MUCUS SKIN TWII'CHI@it.-) ON FLANKS 4 TAIL LASH N@) OTI-1p-R CHA14GIPS N@"JTED IN PHYSICAL AND NEUROLOGI"AL CO@.IDITION S@)LUTIO,'@ - D15TI@L.LE-:!) WATER ICAL EXAMINATION OF CATS PHYSICAL AND NEUROLOG 356 (I-V) CAT Noe DOSE t%'To TIME OBSERVATIONS AND SEX MG/KG KG* HOURS 3Z M 5*6 209 HEART RATE 132@'BEATS/MINUTE RESPIRATIONS PER 2 MINU7iE 96 BODY TEMPERATURE C 38,6 A TrAlL LASH SKIN TWITCHING ON FLANKS NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITIO@L 597 HEART RATE 162 BEATS/MINUTE 2 RE5PIRATIONS PER MINUTE @66 BODY TEMPERATUKE C 38*7 TAIL LASH NO SKIN TWITCH NO OTHER CHAN@ES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 2290 HEART RATE 156! BEATS/MINUTE RISPIRATIONS P"ER MINUTE 60 BODY TEMPERATURE C 37,7 NO SKIN TWIT(,H BEHAVIOR, GEPTERAL APPEARANCE, AND CONDITION NORMAL NEUROLOGICAL@TESTS NORMAL SOLUTION DI$TILLED WATER -11 bit IA14U IILUKULUUL@-AL LAAivIlliA'I'IUII it -AL UF LATS 52367@,-A I -V) CAT No, DOSE WTG TIME OBSERVATIONS A14D SEX MG/KG KG* HOURS 55 F 500 l2e87 .000 HEART RATE 126 6EATS/Ml[qUTE RESPIRAI"LONS PER MINUTE 66 BODY TEMPERATURE C 38a7 NOSE COOL AND MOIST CF%LM ALERT BEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY) 0,2 HEART RATE 150 BEATS/MINUTE RESPIRATIONS PER MINUTE 66 BODY TEMPERATURE C 38i22 NOSE WARM AND DRY t4O OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 0,- HEART RATE 150 BEATS/MINUTE RE5PIRATIONS PER MINUIE 48 BODY TEMPERATURT C 38*6 2 F40SE CCOL AND MG!CT NO OTHER CHANG@S NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1,(,. HEART RATE 150 B@EATS/i4lNUTE RESPIRATIONS PER MINU(E 66 BGDY TEMPERATURE C 38*5 0 REDUCED ANAL TENSION DLC-FECATION RIGHT AFTER TEMPERATURE TAKEN DEFECATION t4lTil, CLEAR MUCUS NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION '7 SUSPENSION 14ETHYLCELLULOSE 0*5% N OF CATS pHySICAL AND NEUROLOGIC41- EXAMINATIO 2367 (I-V) OBSERVATIONS CAT Noo DOSE WT* AND SEX MG/K-u KG* HOIJN-S 3 HEART-RATE 132,BEATS/MINUTE 55 F 5*0 RESPIRATIONS IPER MINUTE 60 BODY TEMPERATURE C 38*8 t4OSE COOL ANU MOIST - REDU-ED ANAL TENSION D IN PHYSICAL AND NEUROLOGICAL CONDITION 2 NO OTHER CHAr4tES NOIE 5*6 HEART RATE 144@BEATS/Mli'4UTE RESPIRATIONS PER M114UTE @48 BODY TEMPERATURE C 38o5 @IOSE WARM Ai4D@MOIST REDUCED ANAL TENST&ON 2 HYSICAL AND NEUROLOGICAL CONDITT.ON NO OTHER'%-.HANG;-:S NOTED IN P 21-0 H.C-ART RATE i56 BEAl5iMlNUTE RE5PIRATIONS PER MINUTE 54 BOD2Y TEMPERATURE C 38.2 NOSE COOL AND:,MOIST ANA@- TENSlOr4 B-CTTER, P,'i@-',-IAVIORs GEN' RAI APoEARANCE9 AND CONDITION NORMAL L@EUROLOGICAL !ESTS NORMAL 2 SUSPENSION METHYLCELLULOSE 0*5% PHYSICAL AND NEUROLOGICAL EXAMINATION OF CATS 2516 (I-V) CAT No* DOSE WTo TIME OBSERVATIONS AND SEX MG/KG KGo HOURS 39 F 10*0 2081 0.0 HEART RATE 108 BEATS/MINUTE RE3PlRAliONS PER MINUTE 48 2 BODY TEMPERATURE C 38o4 NOSE COOL AND MOIS'I CALM BEHAVIOR9 GENERAI- APP@:@7ARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAMF DAYC% 0,2 HEART RATE i36 BEATS/MINUTE RESPIRATIONS OER MINUTE 78 BODY TEMPERATORE C 3803 NOSE WARM ANO MOIST SLIGHT PHOTOPHOBIA NO OTHER CHAi4GE,5 NOTE2D IN PHYSICAL AND NEUROLOGICAL CONDITION Oo5 HEAR! RATE 159 BEATS/MI,NUTE RESPIRA-TIONS OER MINUTE 48 BODY TEMPERAVIOR8 C 3BoO NOSE WARM AND DRY SLIGHT PliOTOPHOBIA 2 NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 0,9 HEART RATE 120 BEATS/MINUTE RE5PlRATIONS PER MINUTE 36 BODY TEMPERATORE C 3709 NOSE WARM AND DRY SLIGHT PHOTOPHOBIA 4 NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION STEROID DILUENT -u > 0 OF CATS PHYSICAL AND NEUROLOGI EXAMINATION 2516 (I-V) WT* 'TIME 085ERVATIONS CAT No. DOSE @ND SEX MG/KG KG* HOURS HEART RATE 126 B5ATS/MINUTE 00 2oO 39 F 10 2 RESPIRATIONS PER MINUTE 36 BODY TEMPERATURE C 3892 NOSE COOL AND MOIST SLIGHT PHOTOPHOBIA THER'CHANGES NOTED-IN PHYSICAL AND HEUROLOGICAL CONDITION NO 0 4,1 HEART RATE 150 OEATS/MINUTE 2 RESPIRATIONS PER MINUTE 48 BODY TEMPERATURE C 38.4 NO PHOTOPHOBIA 'I N NEUROLOGICAL CONDIT 0 NO OTHER,CHANGES NOTED IN PHYSICAL AND UTE 23*8 2 HEART-RATE 150 BEATS/MTN RESPIRATIONS PEP M114UTE 36 HEARTBEAT WEAK@TR NO OTHER CHAN6E5 NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION STEROID DILUENT 3 rn 253 1 (1-1 of DOSE WTO TIME OBSERVATIONS EX MG/KG KG* HOURS F 11,2 2*88 0*0 HEART RATE 96 BEATS/MINUTE RESPIRATIONS PER@MINUTE 42 BODY TEMPERATURL,C @801 NOSE COOL AND MO2IST QUIET CALM BEHAVIOR9 GI'-NERAL APPEARANCEV AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY) 0,2 HEART RATE 114 BEAT6/MINUTE 2 RESPIRATIONS PER MINUTE 42 BODY TEMPERATURE C 3807 NOSE COOL AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL COft,ITION 0,6 HEART RATE 138 BEATS/MINUTE RESPIRATIONS PER MI,@IUTE 36 BO2DY TEMPERATURE C "i3 8 o 7 NOSE WARM AND DRY il TENDED TO CURL LEFT WRIST ON LYING (WAS DOSED IN RTo ARM ONLY) NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1,1 HEART'RATE 126 BEAtS/MTNUTE RESPIRATIONS2 PER MINUTE 36 BODY TEMPERATURE t P8.7 NOSE COOL AND MOIS,-,r NEUROLOGICAL TESTS NORMAL NO OTHER CHANGESIN:OILD IN PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION STEROID DILUENT 2 f7n EUROLOGIC" EXAMINATION OP CATS PHYSICAL AND N 5071 (t-V) OBSERVATIONS CAT Noe DOSE WTO TIME @ND SEX MG/KG KG* HOURS 32 M 500 209 HEART RATE 156 BEATS/MINUTE RESPIRATIONS PER MINUTE 72 2 BODY TEMPERATURE C 3819 NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 5,4 HEART RATE 144 BEATS/MINUTE RESPIRATIONS PER MINUTE 54 BODY TEMPERATURE C 38o5 NO CHANGES No HYSICAL AND NEUROLOGICAL CONDITION 2 TED IN, P 21*6 HEART RATE 150,'BEATS/MINUTE RESPIRATIONS PER MINUTE 54 BODY TEMPERATURE C 38.8 NO CHANGES NOTED IN,PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION STEROID DILUENT 3 -o rn 2531 I-V) CAT No* DOSE WTo TIME OBSERVATIONS @ND SEX MG/KG KG* HOURS 39 F 1102 291 HEAR! RATE 138 BEATS/MINUTE RESPIRATIONS PER MINUTE 40 BODY TEMPERATURE C 38*5 OLOGICAL tOaDIT-ION 2 NO CHANGES NOTED IN PHYSICAL AND NEUR .4.0 HEART RATE 120 BEATS/MINUTE RESPIRATIONS PER MINUTE 36 BODY TEMPERATURE C 38o4 ROLOGICA NO CHANGES NOTED IN PHYSICAL AND NEU L CONDITION 24,6- 2 HEART RATE i26 BEATS/MINUTE RESPIRATIONS PER MINUTE 36 '@E t 38.2 BODY TEMPERATO OLOGICAL CONDITIO NO CHANGES NOTED IN PHYSICAL AND NEUR N 5USPENSlOt4 STEROID DILUENT CA! Not DOSE WT* TIME OBSERVATIONS- AND 5EX MG/KG KG* HOURS 64 F 0,28 3e36 0,0 HEART RATE 162 BEATSIMINUTE RESPIRATIONS PER MINUTE 72 BODY TEMPERATURE C 38.4 BE@iAVIOR9 GENERAL APPEA2RANCE9 AND CONDITION.- NORMAL9 NEUROLOGICAL TESTS NORMAL i PRE-DOSE (SAME DAY) 0.2 HEART RATE i38 BEATS/MINUTE RESPIRATIONS PER MINUTE 72 BODY TEMPERATURE C 39oO 2 NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 0*5 HEART RATE 156 BEATS/MINUTE RESPIRATIONS PER MINUTE 66 1 BODY TEMPERATURE C 38o9 NO OTHER CH2@NGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1.0 HEART RATE 1,50 BEA75/MINUTE RESPIRATIONS PER MINUTE 66 BODY TEMPERATURE C 38.7 BEHAVIORO GENERAL APPEARANCE9 AND CONDITION - NORMAL SOLUTION H8YDROCHLORIC ACID 061 Ng QS WITH DISTILLED WATER. 2598 (I-V) OBSERVATIONS CAT No,, DOSE WT* TIME KG* HOURS @ND 5EX MG/KG 2 BEATS/MINUTE 64 F 0.28 3.36 2ol HEART RATE 13 RESPIRATIONS 2 PER M114UTE 72 BODY TEMPERATUR-C C 38o3 NO@ EN-RAL APpEARANCE9 AND CONDI BEHAVIOR9 G a TION MAL.- NEUROLOGICAL@TESTS NORMAL 2 3,9 HEI"@RT RATE 150 BEATS/MINUTE RE5PIRATIONS PER MINUTE 78 BODY !EMPERATURE C 3809 BEHAVIORT GENERAL APPEARANCE9 AND CONDITION NORMAL 5,4 HEART RATE 138 BEATS/MINU E 2 RESPIRATIONS PER MINUTE 84 BODY 'rEMPERAiU,RE C 39,0 BEHA'VIORI GE14ERAL APPEARANCEV ATID CONDITION NORMAL 2lo6 HEART RATE 162 BEATS/MINUTE RESPIRATIONS PER F-IIINUTE 66 2 A-URE C 38o7 BODY TEMPER i BEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION - NORMAL' ATER 5OLUTioN HYDROCHLORIC ACID 50,1 Ns QS WITH DISTILLED W rn 2598 (I-V) CAT No* DOSE WT* TIME OBSERVATIONS AND SEX MG/KG KG* HOURS 44 F 2*8 2@27 000 HEART RATE 138 BEATS/MiNUTE RESPIRATIONS PER MINUTE 48 BODY TEMPERATPRE C 399 NOSE COBL AN2D MOIST CALM ACTIVE BEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION NORMAL- NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY) 092 HEART RATE 156 8EATS/MI2NUTE RESPIRATIONS PER MINUTE 54 BODY TEMPERATURE C 39o2 NOSE WARM AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION Oo5 HEART RATE 156 BEATS/MINUTE RESPIRATI2ONSIPER MINUTE go BODY TEMPERATIJRE C 38o9 NOSE WARM AND M015T NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 0*9 HEART RATE 156 BEATS/MINUTE RESPIRATIONS PER MINUTE go BODY TEMPERATURE2 C 38o5 NOSE WARM AND MOIST PUPILS SLIGHTLY DILATEP PUPILLARY R8FLEX INCOMPLETE SLIGHT PHOTOPHOBIA. NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SOLUTIO0N HYDROCHLORIC ACID Ool No QS WITH DISTILLED WATER -0 > m 14 2598 (I V) CAT NO- DOSE WTo TIME OB5ERVATIONS, @ND SEX MG/KG KG* HOURS HEART RATE 126 BEATS/MINUTE 44 F 2*8 2*1 PER MINUTE 48 RESPIRATIONS 2 BODY TEMPERATURE C 38a8 NOSE WARM AND MOIST PUPILS SLIGHTLY DILATED PUPILLARY REFLEX NORMAL SLIGHT PHOT60HOBIA ND NEUROLOGICAL CONDIIIO NO OtH ER CH@NGES NOTED IN PHYSICAL A 2 N 4,1 HEART RATE 138 BEATS/MINUTE RESPIRATIONS@PER MINUTF 42 BODY TEMPERATURE C 38o4 NOSE'COOL AND MOIST PUPILS SLIGHTLY DILATED SLIGHT PHoT6PHo2BIA NO 0"'IHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 2398 HEART RATE 156 BEATS/MINUTE REaPIRATIONS'lPER 141INlUTE 42 BODY TEMPERAIURE C 38o3 PUPILS 51-IGHTLY DILATED 2 PUPILLARY REFLEX NORMAL BEHAVIORs GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL SOLUTION HYDROCHLORIC ACID 0,1 Ng QS WITH DISTILLED WATER rn CAT No* DOSE WTo TIME OBSERVATIONS AND SEX MG/KG KGo HOURS 32 M 396 3o46 0,0 HEART RATE 162 BEATS/MINUIE I RESPIRATIONS ?ER MINUTE 54 BODY itmvcKATORE C 39oO 2 BEtiAVIOR4 GENERAL APPEARANCE9 AND CONDITION NORMAL, NEUROLOGICAL,TESTS NORMAL PRE-DOSE (SAMr-. DAY) 0,2 HEART RATE 144 BEATS/MINUTE RESPIRATIONS PER MINUTE 60 BODY TEMPE2RATURE C 39*2 HEARTBEAT STRONG NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGTCAL CONDITION 0,5 HEART RATE 156 BEATS/MINUTE RESPIRATIONS PER MINUTE 36 BODY TEMPERATURE C 38.9 NO OTHC-R CHANGES NOT2ED IN PHYSICAL AND NEUROLOGICAL CONDITION SKIN TWITCHING ON FLANKS 1,0 HEART RATE 162 BEATS/MINUTE RESPIRATIONS PER MINUTE 36 BODY TE'MPERATORE C 38,6 TAIL LASH SLIGHTLY TEN@E 2 SKIN TWITCHING ON FLANKS NO OTHER CHA@GE5 NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION STEROID DILUENT rn > 2717 (I-V) CAT No* DOSE VIT* TIME OBSERVATIONS AND SEX MG/KG KGo HOURS 32 M 3*6 3946 292 HEART RA-i'E 168 BEATS/MINUTE RESPIRATIONS PER MINUTE 54 BODY TEMPERATURE C 38o5 2 TAIL LASH LESS TENSE ICAL CONDITION NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOG 498 HEART RATE 150 BEATS/M!NUTE RE5PlRATION5'PER MINUTE 42 BODY TEMPERATURE C 38o5 2 ANE SLIGHTLY RELAXED NICTITATINGMEMBR WISE ABOUT SAME BEHAVIOR AND APPEARANCE - OTHER NEUROLOGICAL TE5T5 NORMAL 22e6 HEART RATE 162 BEATS/MINUTE RE5PIRATIONS PER MINUTE 84 BODY TEMPERATUPE C,38o5 NDITION NORMAL GENERAL APpEARANCE9 AND CO BEHAVIOR9 I NEUROLOGICAL TESTS NORMAL SUSPENSION -,'ST8EROID DILUENT Fn > CAT No# DOSE WT. TIME OBSERVATIONS AND SEX MG/KG KG* HOURS 53 F 4*5 2*70 000, HEART RATE l@80 BEATS/MINUTE RESPIRATIONSIPER MINUTE 90 BODY TEMPERATURE C-3809 NO PHOTOPHOBIA CALM 2 RESTING NORMALLY IN CAGE bEHAVIORe GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY) 0.1 HEART RATE 156 BEATS/MINUTE RESPIRATION2S@Pr--'R MINUTE 78 BODY TEMPERATURE C 38-9 SLIGHT PHOTOPHOBIA NO OTHER'CHANGES NOTED IN PHYSICAL AND' NEUROLOGICAL CONDITION oo5 HEART RATE 156 BEAT5/MINUTE @@PER MINUTE 84 2 RESPIRATIONS@ BODY TEMPERATURE C 38,7 SLIGHT PHOTBPHOBIA NO OTHER CIJANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 019 RESPIRATIONSIPER MI.NUTE 90 BODY TEMPERATURE C 3897 4 SLIGHT PHOTOPHOBIA NO OTHER CHANGE5 NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION -TSTEROID DILUENT 2778 (I-V) CAT NO* DOSE WT* TIME OBSERVATIONS @ND SEX MG/kG KG. HOURS 53 F 4*5 2*70 2*3 HEART RATE 144 BEATS/MINUTE RESPIRATIONS PER MINUTE 90 BODY TEMPERATURE C 3900 SLIGHT PHOTOPHOBIA 2 NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL TONDITION 407 HEART RATE 144 BEATS/MINUTE RESPIRATIONS PER MINUTE 90 BODY TEMPERATURE C 9o4 @SLIGH"I PHOTOPHOBIA NO OTHER CHANGES NOTED IN PHYSICAL A2ND NEUROLOGICAL CONDITION 22,5 RESPIRATIONS)PER PIINUTE@ 84 BODY TEMPERAI@URE C 3992 SLIGHT PtiOTOPHOBIA NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDI-TION ,SUSPENSION -@@STEROL-D DILUENT 4 rn 2867 (I-V) 40 CAT No, DOSE WT* TIME OBSERVATIONS AND SEX MG/KG KG* HOURS 0,0 HEART RATE 150@BEATS/MINUTE 55 F 2,0 lo96 RESPIRATIONS PER MINUTE 66 2 BODY TEMPERATURE C 38*3 NOSE COOL AND NIOIST OEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION NORMAL-- NEUROLOGICAL TESTS NORIVAL PRE-DOSE (SAME DA2Y) 0.2 HEART RATE 13 @SEAT5/MINUTE RESPIRATIONIS ER MINUTE 48 BODY TEMPERAT R- C 38o4 NOSE WARM AN 'DRY NICTITATING MEMBKANE SLIGHTLY RELAXED REDUCED AN2AL'IENSIQN NO OTHER,CHANGE5 -NQTED IN PHYSICAL AND NEUROLOGICAL CONDITION Oo6 HP-ART RATE 14#, BEATS/MINUTE RESPIRATIONS PER MINUTE 36 BODY TEMPERATURE I- 38*3 NOSE WARM AND MOIST 2 NICTITATING MEMBRANE SLIGHTLY RELAXED REDUCED ANAL@'@TEN51ON NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1*6 HEART RATE 15,,O BEATS/MINUTE RESPIRATIONS PER MINUTE 54 7 BODY TEMPERATURE C 38,3 NOSE COOL AND MOIST NICTITATING MEMBRANE IN NORMAL POSITION SOLUTION DISTILLED WATER rn 2867 1 I-V) CAT N6o DOSE WT. 'TIME OBSERVATIONS @ND 5EX MG/KG KG. HOURS 55 F 290 3o3 HEART RATE 156@ISEATS/MINUTE RESPIRATIONS PER MINUTE 72 BODY TEMPERATURE C 38*2 NO CHANGES NOTE2D IN PHYSICAL AND NEUROLOGICAL C014DITION 4,8 HEART RATE 162 BEATS/MINUTE RESPIRATIONS PER MINUTE 66 BODY TEMPERATU@E C 38,4 ANAL TENSION BETTER' BEHAVIOR AND APPEARANCE - OTHERWISE NORMAL 2.21al HEART RATE 132,,BEATS/MINUTE RESPIRATIONS PIER MINUTE 50 BODY TEMPERATURE C 34,8 BEHAVIORT GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL SOLUTION DI@@ILLE6 WATER 2897 (I-V) IME OBSERVATIONS CAT NO* DOSE WTo T @ND 5EX MG/KG KG* HOURS 39 F 10,0 2*75. 0.0 HEART RATE 144 BEATS/MINUTE RESPIRATIONS PER MINUTE 42 BODY TEMPERATORE C 37.9 2 NOSE COOL AND MOIST i QUIET CALM, BEHAVIOR9 GENERAL APPEARANCEO AND CONDITION NORMAL NR@UROLOGICAL TE5TS,NORMAL PRE-DOSE (SAME DAY) 2 0,1 HEART RATE 7li2 BEATS/MINUTE RESPIRATIONS PER MINUTE 36 BODY TEMPERATURE C 38al NOSE WARM AND DRY NO OTHER@'CHINGE5 NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 2Oo5 HR-ART RATE 90 BEATS/MINUTE Rc@SPIRATl"60NS,PER MINUTE 42 BODY TEMPERATURE C 38*0 NOSE COOL AND DRY NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 100 HEART RATE 108 BEAIS/MINUTE 9 RE5PIRATION5 PER MI;NUTE 48 BODY TEMPERATURE C 38.1 NOSE COOL AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION STEROID DILUENT 2897 (I-V) CAT NO* DOSE WTo TIME OBSERVATIONS @ND SEX MG/KG KGo HOURS 39 F lOsO 20'0 HEART RATE 138!iBEATS/MINUTE RESPIRATIONS PER MINUTE 48 NOSE COOL AND DRY 2 YSICAL AND NEUROLOGIC L CONDITION NO OTHER CHANGES NOTED IN PH A 4,1 HEART RATE 108 BEATS@/MINUTE RESPIRATIONS PER MINUTE 32 BODY TEMPERATURE C 38*6 2 NOSE COOL AND MOIST' NO OTHER CHAN@ES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 5.3 HEART RATE 13 BEATS,'/MINUTE RESPIRATIONS R MINUTE 42 BODY TEMPERAT E C 38o5 2 NOICHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 22*0, HEART RATE 150!BEATS/MINUTE RESPIRATIONS PER MINUTE 42 BODY TEMPERATURE C 38oO NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SU3SPENSION STEROID DILUENT rn Ila TS PHYSICAL AND NEUROLOGICAL E",MINATION OF CA 2935 (I-V) 5 No* DOSE WTO TIME OB5ERVATION SEX MG/KG KGo HOURS HEART RATE 162 BEATS/MINUTE 15 F 495 4,1 RE5PIRATION5 PER MINUTE 42 BODY TEMPERATURE C 37*9 N PHYSICAL AND NEUROLOGICAL CONDITION NO CHANGES NOTED I MINUTE 20 HEART RATE 150 BEATS/ 4RESPIRATIONS PER MI,NUTE 42 BODY TEMPERATURE Cl@38*3 NO CHANGES N07ED IN PHY51CAL AND NEUROLOGICAL CONDITION 5U5PENSION STEROID DILUENT Y5 PHY51CAL AND NEUROLOGICAL EXAMINATIONS OF SQUIRREL MONKE 2607 (I-M) OB5ERVATION5 '-IONKEY DOSE WT, TIME '4UMBER MG/KG GM* HOURS B .47 3290 THIRD DOSING N.LIGHT-CUE 392 SHUTTLED 0 .3*4 RE5PIRATION5 PER MINUTE 96 PUPILS NORMAL IN SIZE AND REACTION TO LIGHT SHUTTLED ON-LIGHT CUE .4so RESPIRATIONS PE@ MINUTE 102 SHUTTLED ON LIGHT CUE APPEARANCE AND BEHAVIOR NORMAL 5o5 RE5PIRATION5 PER MINUTE 90 5HUTTLED ON-LIGHT CUE NO CHANGES U95PEN51ON 095% METHYL CELLULOSE 5 tall, PHYSICAL AND NEUROLOGICAL EXAMINATIONS OF SQUIRREL MONKEYS 2607 (I-M) TIME' OBSERVATIOV5 'IONKEY DOSE WT* 1,4umBER MG/KG GM* HOURS B 853 000 RESPIRATIONS PER MINUTE 90 2 PRE-DOSE (SAME DAY) .002 SHUTTLED ON LIGHT CUE APPEARANCE OTHERWISE NORMAL 900 1*0 SECOND DOSING LIGHT CUE 1*1 SHUTTLED ON 1*3 RESPIRATIONS PER MINUTE 120 NO CHA2NGES RESPIRAT40NS PER MINUTE 96 2 SHUTTLED ON LIGHT CUE WAS RETURNED TO HOME CAGE WITH OTHER MONKEYS APPEARANCE AND BEHAVIOR NORMAL SUSPENSION 0*5% METHYL CELLULOSE 7 rn him PHYSICAL AND NEUROLOGICAL EXAMINATIONS OF SQUIRREL MONKEYS 2607 (I-M) .'40NKEY DOSE WTO TIME' OBSERVATIOVS' i'4UMBER MG/KG GMO HOURS 853 000 RESPIRATIONS PER MINUTE 90 PRE-DOSE (SAME DAY) .,Ioo2 002 SHUTTLED ON LIGHT CUE APPEARANCE OTHERWISE NORMAL 900 ito SECOND DOSING SHUTTLED ON LIGHT CUE 1*3 RESPIRATIONS PER MINUTE 120 NO CHANGES 201 RESPIRATIONS PER MINUTE 94 S7HUTTLED ON LIGHT CUE WAS RETURNED TO HOME CAGE WITH OTHER MONKEYS APPEARANCE AND BEHAVIOR NORMAL SUSPENSION 0*5% METHYL CELLULOSE PHYSICAL AND NEUROLOGICAL EXAMINATIONS OF SQUIRREL AONKEYS 2759 (I-M) '40NKEY DOSE WTO TIME OBSERVATIONS -NUMBER MG/KG GM* HOURS A 67 773 oo3 SHUTTLED ON-LIGHT CUE APPEARANCE AND BEHAVIOR NORMAL 0*5 SHUTTLED ON LIGHT C2UE PEARANCE AND BEHAVIOR NORMAL AP 1*0 SHUTTLED ON LIGHT CUE APPEARANCE AND BEHAVIOR NORMAL lo5 SHUTTLED ON LIGHT CUE APPEARANCE AND BEHAVIOR NORMAL 2eO SHUTTLED ON LI5GHT CUE APPEARANCE AND BEHAVIOR NORMAL 2*5 SHUTTLED ON LIGHT CUE APPEARANCE AND BEHAVIOR NORMAL SUSPENSION ,095% METHYL CELLULOSE L EXAMINATIONS OF SQUIRREL MONKEYS PHYSICAL AND NEUROLOGICA 759 (I-M) TIONS IONKEY DOSE WT* TIME OBSERVA HOURS IUMBER MG/KG GM* HEART RATE 325 BEATS/MINUTE 805 000 2 MINUTE 64 A' RESPIRATIONS PER R NORMAL APPEARANCE AND BEHAVIO PRE-DOSE (SAME DAY) SHUTTLED ON LIGHT CUE 1000 0,1 INCREA5ED-LOCOMOTOR ACTIVITY 320 BEATS/MINUTE 2Oi,5 HEART RATE SITTING QUIETLY -LIGHT CUE SHUTTLED ON' 96 0*6 RESPIRATIONS PER MINUTE AND REACTION To LIGHT PUPILS NORMAL IN SIZE 2,0 SECOND DOSING 22o36' 2 2,3 SHUTTLED ON LIGHT.CUE RESPIRATIONS PER MINUTE 80 IGHT 393 PUPILS NORMAL IN SIZE AND REACTION TO L APPEARANCE AND BEHAVIOR NORMAL IN HOME CAGE o,5% METHYL CELLULOSE SUSPENSION 1 > rn PHYSICAL AND NEUROLOGICAL EXAMINATIONS-OF SQU19REL MONKEYS (I-M) OBSERVATIONS IONKEY DOSE WT* TIME JUMBER MG/KG GM* HOURS B 1*0 840 001 RESPIRATIONS PER MINUTE 72 GENERALLY IMMOBILE GRASPING REFLEX2 WEAK RIGHTING REACTION WEAK ALL OVER FINE TREMORS IN LEGS FOLLOWED BY GROSSER TREMORS Oo2 ERRATIC LATERAL AND UP-DOWN HEAD MOVEMENTS Ob6 RESPIRATIONS PER MINUTE 66 ONE DEEP RESPIRATION ALTERNATING WITH ONE SHALLOW RESPIRATIOtl 2 HAD.CRAWLED OUT OF BLANKET WRAPPED ABOUT HIM ON 4 FEET SWAYING UNSTEADILY FROM SIDE To SIDE DECREASED EQUILIBRIUM EASILY HANDLED GRASPING REFLEX INTACT RESPONSIVE TO V15UAL STIMULI NO RESP2ONSE TO SOUND SEKVATION 2 ON CASUAL.OB TOXIC SIGNS DECREASING REDUCED MOTOR ACTIVITY 395 RESPONSIVE TO SOUND RAN TO HOME CAGE TO JOIN OTHER MONKEY SPONTANEOUS MOTOR ACTIVI7TY SLOW AND HALTING APPEARANCE OTHERW15E NORMAL SOLUTION 099%'SALINE DOMINANCE BEHAVIOR.OR- SQUIRREL MONKEYS N6. 6-1-@ SliUTTLE ORDER Monkey Dosage Level Reinforce- ound Time (hrs) Trials First Last No. mg/kg ment 2 G T R G T R :.c 15 13.0 0.8 1.1 0.5 11.0 3.3 1172 T 100 I.Mo Neg. ')ntrbl* (Mean 8 tests) 2 Neg. 0.5 - 1.2 15 14 0 0 14 1 or P.R. 'shuttle, no control Neg. 24 14 0 l' 13 1 -.est was performed on preceding days,-hence means of whole Pose Control* eriod were used. (Mean 7 tests). is 14.7 2 0 0.1 0 8.9 6 Pose 1.4 - 1.7 and 15 15 0 0 0 15 0 - 3:5 2.6 Pose 25 15 15 0 0 0 14 2 1 1900 G 3.0 I.M. Neg. Pre-dose' 15 15 0 0 0 15 0 Neg. 0.2 - 1.1 is 5 0 10 0 is 0 Neg. 4.8 - 5.4 15 14 0 l@ 0 15 0 2 Neg. 23 15 15 0 0 0 15 0 Pose Pre-dose 15 is 0 0 .0 15 0 Pose l.'7 - 2.1 15 is 0 0 0 14 1 Pose 5.42 - 601 15 15 0 0 0 14 1 2100 G 3.2 I.M.. Neg. p e-dose 12 12 0 0 0 11 Neg. O.'@3 0.8 12 1 1 10 8 4 Neg 4. I' 4 -..6, 12 12 0 2 0 0 11 1 Pose Pte-dose 12 12 0 0 0 110 2 Pose 4 7. 12 11 0 1 1 11 0 Pose ..2 5 12 12 0 0 0 9 3 21020 G 1.o i.m. Neg. Pre-dos-e 15 14 0 1 0 15 0 Neg. 0.2 0.8 15 14 0 1 0 15 0 4-5 Neg. 0 15 15 0 0 0 15 Neg, 15 15 0 0 0 15 0 4 0 Pose pi e-dose 1 5 15 0 0 0 1 3 2 1 Po 1 0 1 7 > s . 15 15 0 0 0 12 3 DOMINANCE BEHAV MONKEYS (Contd) LE ORD )Ound Monkey Dosage Level Reinforce- T3@@e (hrs) No. of First Las To. No. mq/kg ment Trials G 2 T R (i T -R -2598 G 3.0 I.M. Neg. Pre-dose 15 15 0 0 0 15 0 Neg. 0.3 - 1.0 15 15 0 0 0 15 0 Neg. 4.9 - 5.5 15 215 0 0 1 0 13 2 Neg. 22.5 15 15 0 0 0 14 1 Pre-dose 15 15 0 0 0 14 1 Pos. 1.9 15 15 0 0 0 12 3 POS. Pos. 5.5 - 6.1 15 15 0 0 0 13 2 Pos. 23.5 15 is 0 0 0 11 4 Neg. @te-dos2e 15 15 0 0 0 14 1 2607, G. 60.0'1.M. is 0 Neg. o@B - 1.1 15 is 0 0 0 Neg. !@:1 - 5.7 15 15 0 0 0 1.5 0 0 23.5 15 15 0 0 0 15 Neg. Pos. P@e-dose 215 15 0 0 0 15 0 POSO 1.6 - 2.3 15 15 0 0 0 14 1 POS. 5.7 - 6.3 15 15 0 0 0 15 15 2 is 0 0 0 Pos. 24 14 1 Neg.- Pre-dose 15 is 0 0 0 2759 R 30.0 I.M. Neg. 2 011.1 - 0.7 15 15 0 0 0 15 0 4@6 - 5.0 10 9 1 0 0 8 2 Neg. Neg. 22.5 15 15 0 0 0 14 1 2 0 14 1 Pos. Pre"dose 15 0 0 Pos. 0,09 - 1.2 and 2@.0 - 2 15 0 0 0 10 5 .4 15 Pos. 5.0 - 5,4 10 10 0 0 0 9 1 Pos. 23 15 is 0 0 0 10 5 7 In > I PHYSICAL AND NEUROLOGICAL EU;@NMINATION OF CATS 2935 (I-V) Alm OBSERVATIONS No, DOSE WTO TIME 5EX MG/KG KG* HOURS 5 F 495 1*91 000 HEART RATE 156 BEATS/MINUTE RESPIRATIONS PER MINUTE 422 BODY TEMPERATURE C@;37*7 NEUROLOGICAL TESTS NORMAL BEHAVIOR9 GENERAI- APPEARANCEs AND CONDITION NORMAL N05E COOL AND M014T PRE-DOSE (SAME DAY) 0,2 HEART RATE 108 BEAtS/MINUTE 2 RE5PlRATIONS PER MINUTE 66. BODY TEMPERATURE C@38e2 NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 0*7 HEART RA AI'8/MINUTE TE 150 BE i, RESPIRATIONS PER 2 M@NU-E 60 BODY TEMPERATURE C 38o3 NOSE t4ARM AND MOI@T NO OTHER CHANGES NPTED IN PHYSICAL AND NEUROLOGICAL CONDITION 109 HEART RATE 156 BEAIS/MINUTE RESPIRATIONS PER M,NUTE 48 BODY T2EMPERATURE Ct38ol NOSE COOL AND M014 NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDlTlOt4. SUSPENSION STEROID DILUENT rn oP CATS PHYSI@AL AND NEUROLOGICAL EYAMINATION 2963 (I-V) No* DOSE WT* TIME OBSERVATIONS SEX MG/KG KGo HOURS 010 HEART RATE 168 BtATS/MINUTE q ,9 F2 1080 2*82 RESPIRATIONS PER MINUTE 72 BODY TEMPERATURE C,,37o9 N058 COOL AND Mol@t NO PHOTOPHOBIA BEHAVIOR9 GENERAL APPEARANCE9 AND@CONDITION NORMAL 2 PRE-DOSE (SAME DAY) 0,2 HEART RATE 150 BEAT'S/MINUTE RESPIRATIONS PER MINUTE 36 C'@38.,3 BODY TEMPERATURE , NOSE WARM AND DRYI 2 SLIGHT PHOTOPHOBIA N PHYSIC L AND NEUROLOGICAL CONDITION NO OTHER CHANGES NOTED I A 0*6 HEART RATE 156 BEAt5/MINUTE RESPIRATIONS PER MINUTE 30 BODY TEMPER2ATURE C'3892 NOSE COOL AND D,RY@I SLIGHT PHOTOPHOBI@.A NO OTHER CHANGES!NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1,0 HEART RATE 132, EIEATS/MINUTE RESPIRATIONS PER MINUTE 36 2 BODY TEMPERATURE t3803 NOSE COOL AND ()RY@ll SLIGHT PHOTOPHoi3i!A NO OTHER CHANGES@NOTED IN PHYSICAL AND NEUROLOGICAL CCNDITION SOLUTION A5CORBI@ ACID 30% 1 rn AND NEURPLOGICAL E@,GAINATION OF CATS PHYSICAL 2963 (I-V) No. DOSE WT@ TIME OBSERVATIONS SEX MG/KG KG* HOURS 9 F 1000 2ol HEART RATE 138 BEATS/MINUTE RESPIRATIONS PER MIOUTE 42 2 BODY TEMPERATURE C @eoo - NOSE@COOL AND Dr(Y SLIGHT PHOTOPHOBIA NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 3,9 HEART RATE 150 BEATS./MINUTE RESPIRATIONS PER MINUTE 36 BODY TEMPERATURE C 2 @8,3 NOSE COOL AND DRY SLIGHT PFIOTOP@IOBIA NO OTHER CHANGES NQTED IN PHYSICAL AND NEUROLOGICAL CONDITION 5.3 RESPIRATIONS PER MINUTE 42 BODY TEMPERATURE C @8c.5 HEARTBEAT D2IFFICULT 10 DETECT NOSE COOL AND DRY NO PHOTOPHOBLA NO OTHER CHANGES NPI'ED IN PHYSICAL AND NEUROLOGICAL CONDITION 21*5 HEART RATE 156 BEAT@/MINUTE RESPIRATIONS PER MINUTE 30 BODY TEMPERATURE C @@7*9 8 NOSE COOL AND MOIST NO PHOTOPHOBIA BEHAVIOR9 GENERALIAPPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTSI,,NORMAL SOLUTION ASCOREIIC,!@@ACID30'/o PHYSICAL AND NEUROLOGiCAL,@E"4@INATION OF CATS 6)2984 (I-V) DOSR WTO' 'TIME OBSERVATIONS No, SEX MG/KG KG* HOURS ,4 F 6*3 3915 000 HEART RATE i44 BEATt/MINUTE RESPIRATIONS PER M:INUTE 42 2 BODY TEMPERATURE C 38*6 CALM BEHAVIOR9 GENERAL-APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY)@ 0,2 HEART RATE 144 BEATS/MINUTE 2 RESPIRATIONS PER MI@UTE 60 BODY TEMPERATURE C @4o4 NO CHANGES NOTED INIPHYS;ICAL AND NEUROLOGICAL CONDITION 0,6 HEART RATE 150 BEATS/14INU@TE I I RESPIRATIONS PER MINUTE 48 2 BODY TEMPERATURE C 3897 NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1,4 HEART RATE 138 BEATS/MINUTE RESPIRATIONS PER MINUTE 60 BODY TEMPERATURE C 3@,6 NO CHANGES NOTED IN;PHYSICAL AND NEUROT-OGICAL CONDITI6ON SUSPENSION - STEROID",IDILUENT PHYSI@AL AND NEUROLOGICAL EVAMINATION OF CATS 2984 (!-V) Noe DOSE WT* TIME OBSERVATIONS SEX MG/KG KG@ HOURS ,4 F 6*3 @298 HEART RATE 132 BEATS/MINUTE RESPIRATIONS PER MINUTE 78 BODY TEMPERATURE C 808 2 NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 500 HEART RATE 120 BEATS/MINUTE RESPIRATIONS PER MINUTE 54 BODY TEMPERATURE C t8o5 S NOTED 1,@ PHYSICAL AND NEUROLOGICAL CONDITION NO CHANGE 2192 7 HEART RATE 144 OEATS/MINUTE RESPIRATIONS PER MI,UTE, 36 BODY TEMPERATURE C @18*0 NO CHANGES NOTED Ij@ PHY51CAL AND NEUROLOGICAL CONDITION SUSPENSION STEROI;P DILUENT m MINATION OF CATS PHYSICAL AND NEUROLOGICAL EX4 2994 (I-V) OBSERVATIONS No, DOSE WT, TIME SEX @MG/KG KG* :HOURS 0so HEART RATE 138 BEATS/MINUTE 3 F 2000 2*72 RESPIRAT2IONS PER MINUTE 78 BODY TEMPERATURE C 37o8 BEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY) 0,1 HEART RATE 120 BEATS/MINUTE R2ESPIRATIONS PER MIN --'66 ,UTE BODY TEMPERATURE C l8o5 NO CHANGES NOTED l@ AND NEUROLOGICAL CONDITION PHYSICAL 0,5 HEART RATE 156 BEATS/MINUTE RESPIRATIONS P2ER MI'tiUTE 66 @BODY TEMPERATURE Cl@8;5H NO CHANGES NOTED YS ICAL AND NEUROLOGICAL CONDITION @@/MINUT 1,0 HEART RATE 126 BEAT,. E RESPIRATIONS PER Ml',NUTE 72 BODY TEMPERATURE C@@89.4 NO CHANGES NOTED PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION POLYETH,Z@ENE GLYCOL-300 100% rn CA7' Z09t (I -V) OB5ERVATIOI', u 11 E, y IiGi'!@G KGo HEART RATE 138 BEATSIMINUTE. 290 F 20*0 2.77 RESPIRATIONS PER M2INUTE 72 BODY TEMPERATURE C 3861 ES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION NO CHANG MINUTE- 490 HEART-RATE 132 BEAT5@ RESPIRATIONS PER MINUTE 84 BODY TEMPERATURE2 C 34,,5 NO CHANGES NOTED INPHYSICAL AND NEUROLOGICAL CONDITION 138 BEATS),MINUTE 2602 HEART RATE RESPIRATIONS PER MIN@TE 84 BODY TEMPERATURE C 3do7 NO CHANGES NOTED IN'@'@PHYSICAL AND NEUROLOGICAL.CONDITION 2 @SOLUTION POLYETHYL NE 6LYCOL-300 100016 rn A!Iri Or@ CA'TS 1'AP OBSERVA"§'IOMS D T tIG/'KG 2o5 3t,52 ojo HEART RATE 150 BEATS/MrNUTE, RESPIRATIONS PE@-Z MINUTE 66@ @ 8 0 3 2 BODY TE@it-,ERATURE C, LEAN ALERT CALM SLIGHT-TAIL LASH SLIGHT SKIN TWITCH NEUROLOGICAL'TESTS NORMAL @@APPEARANC CONDITION-- NORMAL 2 BEHAVIORI GENERAL Eg AND. PRE-DOSE (SAME DAY,) TE 144 BEAT@/MINUTE 0.2 HEART RA 5 RESPIRATIONS PER MINUTE 68 BODY TEMPERATURE C,,@,,@8*4 NO CHANGES NOTED t2N PHYSICAL AND NEUROLOGICAL CONDITION ?O EAT./MINUTE 0*6 HEART RATE 1 B RE5PIRATIONS PER MINUTE 48 BODY TE,'4pERATURE C008.7 NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 5 loo HEART RATE 126 BEAT@S/MINUTE RESPIRATIONS PER MINUTE 66 C"138.8 BODY TEMPERATURE NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION POLYETHYLENE GLYCOL-300 100% Ilti'l"')XCAL AND IIEUrZOI.OGICAI,. E,.,\MINATION OF CATS I .V) lop 2 913.'i ME OB5ERVATIONS DOSR- WTo MG/KG KC-9 H2OURS 2o5 m HEART RATE 132 BEAT@S/MINUTE RESPIRATIONS PER kilNUTE 60@ BODY TEMPERATURE C 3837 NO CHAN%'JES NOTED IN PHYSICAL AND NEIJROLOGICAL CONDIT!ON 4,0 HEART RATE 144 BEAT@S/MINUTE 2 RESPIRATIONS PER MINU'TE 48 BODY TEMPERATURE C 38o3 NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 26*2 HEART RATE 132 BEATS/MINUTE RESPIRATIONS PER MINUTE 30 BODY TEMPERATURE C @894 0 NO CHANGES NOTED 1,,N PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION POLYETHYLTNE GLYCOL-300 1000,6 rn A140 ?999 I DoSc- WT@ TITIE OBSERVATIONS X MG,@KG KGo HOURS F 2*5 2978 0.0 HEART RATE 1 2 BEATS"MINUTE 6 $1 RESPIRATIONS PE,DN MINUTE 75 2 q BODY "$EMPERATURE C 38,*6 BEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION -.NORTIAL NEURO'L-OGICAL T'-ST .5 NORMAL PRE-DOSE k'SAME DAY) 0,1 HE2ART RATE 168 BLATS/MINUTEI RESPIRATJIONS PER MINUTE 102'@ BODY TEMPERATURE C 38o6 NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 005 RESPIRATIONS PER MINUTE 96 BODY TEMPERATURE C 3896 HEARTBEAT DIFFIC2ULT TO DETECT NO OTHER@CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1,5 HEART RATE 162 BEATS/MINUTE RESPIRATIONS PER MINUTE go BODY TEMPERATURE C 3897 HEARTBEAT DIFFICULT TO DETECT NO OTHER CHANGES NOT;ED IN PHYSICAL AND NEUROLOGICAL CONDITION 8 SOLUTION DISTILLED WATER rn pi-lysi@AL AND"NEUROLOGICAL EXAMIMATION OF.CATS, 5026 1,,V IME OB5ERVATIONS .40. DOSE WT* T OURS SEX MGIKG KG* H 0,0 HEART RATE 108 BEAT5/mINUTE, F 11,2 2.062 RESPIRATIONS PER MINUTE 48 BODY TEMPERATURE C 38.1 NOSE COOL AND MOIST BE@IAVIOR9 GENERAI- APPEARANtEg AND CONDITION NORMAL T5 NORMAL NEUROLOGICAL TES 0.1 2 HEART RATE 144 BEATS/MINUTE' RESPIRATIONS PER MINUTE 54@, BODY TEMPERATURE C 3890' NOSE WARM AND MOIST No OTHER'CHANGE5 NOTED IN PHY51CAL AND NEUROLOGICAL CONDITION 005 HEART RATE 120 BEAT5/MINUTE RESPIRATIONS2 PER MINUTE 54: BODY TEMPERATURE C@B890 NOSE COOL AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 100 HEART PATE 120 BEATS/MINUTE RESPIRATIONS PER MINUTE 42 BODY TEMPERATURE C 3891 NO CHAN4GES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION POLYETHYLENE GLYCOL@-300 100% LOGICAL P--,J,41NATION OF CATS PHYSICAL AND NEURO 2999 (I-V) IME 'OBSERVATIONS o DOSE WT 3EX MG/rG KG* HOURS F 3.0 HP-ART RATE 168 BEAIS/M,INUTE R.A.SPIRA2TIONS PER M@L@MIJTE go BODY TEMPERATURE C@3808 HEARTBEAT DIF,c@CtJLT TO DETECT NO OTHER CHANGES NOTED IN PHYSR.CAL AND NEUROL061CAL CONDITION 84, 500 RE5PIRAT2IONS PER MINUTE BODY TEMPERATURE C@@38o9 HEARTBEAT DIF6ciCU@T-TO DETECT PHYSICAL AND NEUROLOGICAL CONDITION NO OTHER CHANGES NOTED IN 25oO HEART RATE 144 BEATS/MINUTE 2 RESPIRATIONS PER M@TNUTE 78 BODY TEMPERATURE C. 38*8 BEHAVIOR* GENERAL'@APPEARANCEs AND CONDITION NORMAL NEUROLOGICAL TEST@@ NORMAL -SOLUTION,- DISTILLED WATER 7 rn PHYSICAL AND NEUROLOGICAL E@-AINATION OF CATS 5026 (I-V) -OBSERVATIONS fqo. DOSE WTO TIME 5EX MG/KG KG* HOURS F 2,5 HEART RATE 150 BEATS/MINUTE:: RESPIRATIONS PER MINIJ-(E 42" BODY "EMPERATUR;-; C@38eO t OLOGICAL CONDITION f4o O"i@iER CHANCi'-S NOTic-D IN PHYSICAL AND NEUR i 2 511 HEART RATE 132 BEATS/MINUTE: 42,' RESPIRATIONS PER MINUTE BODY TEMPERATURE C@38oO i NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION UTE' 0 26oO HEART RATE 114 BEATs/MIN RESPIRATIONS PER MINUTE 40- BODY TEMPERATURE CI;3880 NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION POLYE'TH*LENE GLYCOL-300 100% OF 'CATS PHYSICAL AND NEUROLOGICAL EvjlNATION 031 (I-V) NOO DOSE WT& TIME OBSERVATIONS 5EX MG/KG KG* HOURS ,TS!/MINUTEi 12,5 2.04 O)OO HEART RATE 150 BcA 2 F 2 Pl-@R MINUTE 24 BODY TEMPE,-ZA-@URE C 3,7o9 N05E COOL AND MOIST RESTING@NOR@IALLY IN CAGE CALM ALE.RT NORMAL BEHAVIORO GENERAL @2PPEARANCE9 AND CONDITION NEUROLOGICAL TE5TS,@NORMAL PRE-DOSE (SAME DAY) 150 BEAT;/MINUTE 0,1 HEART RATE IONS PER Ml UTE 36 RESPIRAT BODY TEMPERATURE C -,3805 SLIGHTLY MORE NE@RV4,OU5 NO OTHER CHANGES @BTED IN PHYSICAL AND NEUROLOGICAL CONDITION 005 HEART RATE 120 BE:AVS/MINUTE RESPIRATIONS PER MINUTE 54 BODY TEMPERATURE C 58o5 N NORMAL BEHAVIORO GENERAL@APPEARANCE9 AND CONDITIO NEUROLOGICAL TESTT NORMAL NOSE@COOL AN D MOI T SOLUTION POLYETH@LENE GLYCOL-300 10096 PHYSICAL AND NEUROLOGICAL E@@IINATION OF CATS 5031 (I-V) 0 DN-SE WT* itle -OB5ERvATIOt-15 SE,%( MG/KG l,G HOUPS F 14@"5 Ito HEART RATE 140 BEAT,5/MINUTE RESPIRATIONS PER MINUTE 40 BODY !EMPERA'!IURE C1,8o4 NOSE COOL AND @DRY SLTGHT P@IOTOPI-i@-.BXA NO OTHER C@ANG;L-5 NOTED IN PHYSICAL AND NEUROLC)GI 2 CAL CONDITION 2o5 H@C-ARTI RATE 144 BEATS/MINUTE RESPIRATIONS PER MINUTE 36 BODY TEMPERATURE C@38o2 @y 2 NOSE COOL AND DR SLIGHT PHOTOPHOB14 NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 501 HEART RATE 132 BEATS/MINUTE RESPIRATIONS PER MINUTE 48 C2i38 4 BODY TEMPERATURE 0 SLIGHT PHOTOPHOBI@ NOSE COOL AND MOIST NO OTHER CHANGES KOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 25.7 HEART RATE 132 BEAIS/MINUTE 2 RESPIRATIONS PER KIINUTE 42 BODY TEMPERATURE Li@38.1 BEHAVIORT GENERA@ APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TES,T,,t NORMAL NO PHOTOPHOBIA 4 SOLUTION POLYETHYLENE GLYCOL-30o 100% )> rn N OF CATS PHYSICAL AND NEUROLOGICAL EX@MINATIO j@@5058 .\40'.@ D05E WTO TIME OBSERVATIONS 3E%^$ MGil(G KGo HOURS 3*24 000 HEART RATE 168 BEATSIMINUTE RESPIRATIONS PER2 MINUTE 60 BODY TEMPERATURE C@@8*2 NOSE-COOL AND MOIST CALM QUIET BEHAVIOR9 GENERAL@APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TE!iT*,@NORMAL2 PRE-DOSE (SAME DAII 000 IMMEDIATELY AFTER.,DOSING UNCONSCIOUS RESPIRATORY RATE ABOUT NORMAL BREATHING DEEP ooo5 UNCONSCIOUS ENURES15 2 PUPILS DILATED EXTENSION OF FRONT LIMBS FLEXOR REFLEXES AOSENT NO SIGN OF DEEP O@ PERIPHERAL SENSATION OTHER TE5T5 NOT DPNE AT TH15 TIME SUSPENSION 5TEROA,'D DILUENT 0 rn PHYSI,CAL AND NEUROLOGICAL EXAMINATION.OF.CATS 5058 @(I-V) INOO DOSE WTo jiME OBSERVATIONS SEX MG/KG KG& HOUR@A 4 F -3o6' 0,1 AWAKE PUPILS SLIGHTLY DILATED PUPILLARY REFLEX NORMAL 2 PROSTRATE - COULD NOT STAND DEEP AND PERIPHERAL SENSATION PRESENT FLEXOR REFLEXES NORMAL EXTENSOR THRUST REFLEXES ABSENT9 HIND LIMBS RIGHTING REACTIONS FAIR PLACING REACTION WITH VISION - POOR TONIC2 NECK REFLEXES NOT-TESTED CORNEAL REFLEX ABSENT OTHER NEUROLOGICAL TESTS NORMAL 0412 RESPIRATIONS PER MINUTE 66 BODY TEMPERATURE C 38*2 HEARTBEAT TOO WEAK TO COUNT NOSE WARM AND MOIST: REDUCED ANAL TENSION 7 PUPILS NORMAL IN S!zE AND REACTION oo35 CAT COULD STAND 0*6 HEART RATE 114 BEATS/MINUTE RESPIRATIONS PER MINUTE 90 rn BODY TEMPERATURE C 3842 > NOSE COOL AND mois,r TS PHYSICAL AND NEUROLOGICAL EXAMINATION OF'CA 5058 (I-V) tie Noe DOSE WT* 'TIME OBSERVATIONS SEX MG/KG KG, HOURS ,4 lo3 HEART RATE 114 BEATS/MINUTE. F 2 3o6@ RE5PIRATIONS PER MINUTE 54. BODY TEMPERATURE C 3803 QUIET IN CAGE ACTIVITY DURING EXAMINATION INCREASED NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION NEUROLOGICAL TESTS NORMAL 2 299 HEART RATE 144 BEATS/MINUTE RESPIRATIONS PER A@INUTE 66 BODY TEMPERATURE C@38(,5 ANAL TENSION BETTER NO OTHER.CHANGES;NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION HEART RATE 132 BEA'TS/MINUTE 5,4 2 RESPIRATIONS PER MINUTE 60 BODY TEMPERATURE C 38*5 NO CHANGES NOTED@IN PHYSICAL AND NEUROLOGICAL CONDITION 2199 HEART.RATE 138 BEATS/MINUTE RE5PIRATION5 PER MINUTE 60 @E C 0 BODY TEMPERATUR ., 38o3 BEHAVIOR9 GENERAL APPEARANCE,@ AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PHYSICAL AND NEUROLOGICAL E4jINATION OF CATS 5059 I -,@v) Noo DOSE WTip TIME OBSERVATIONS 5EX MG/KG KGo HOURS 32 F 16*0 1997 000 HEART RATE 144 BEATS/MINUTE -RESPIRATIONS PER MINUTE .42: 2 BODY TEMPERATURE t 37t3 NOSE@COOL AND MOIST CALM BEHAVIOR9 GENERAL APPEARANCE9 AND.CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY2) 0,2 HEART RATE 126 BEATS/MINUTE RE5PIRATIONS PER MINUTE 48 BODY TEMPERATURE C 37o8 NOSE COOL AND DRY NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION o.6, HEART RATE 1322 BEATS/MINUTE RESPIRATIONS PER MINtiTE .48 BODY TEMPERATURE,'C 37*8 NOSE COOL AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION Igo HEART RATE 120 $EATS/MINUTE RE5PIRATIONS PER MINUTE 36 BODY TEMPERATURL C 38.0 NOSE COOL AND MOIST NO OTHER CHANGTS NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION ST,EkolD DILUENT PHYSICAL AND,NEUROLOGICAL E\.-AINATION OF CATS 50;0 7 &-V) Noo DOSE WTo TIME OBSERVATIONS SEX MG/KG KGo HOURS i2 F 16,0 2,5 HEART RATE 138 BEATS/MINUTE RESPIRATIONS PER MINUTE 42 BODY TEMPERATURE r2@@ @@37*8 NOSE COOL AND DRY NO OTHER CHANGES NOTED l@l PHYSICAL AND NEUROLOGICAL CONDITION 4,6 HEART RATE 132 BEAtS/MINUTE RESPIRATIONS PER MINUTE 42 BODY TEMPERATURE C@@38*0 2 NOSE'COOL AND DRYI, NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION HEART RAT 24.6 E 120 BEAtS/MINUTE RE5PIRATIONS PER M-@NUTE 42 BODY TEMPERATURE C4@13acO 8 NOSE@COOL AND MOI@T BEHAVIORT GENERALIAPPEARANCE9 AND,CONDITION-- NORMAL NEUROLOGICAL TEST4@ NORMAL -SUSPENSlOt4 STERO,,'@D DILUENT 'lllliiliuil Ul' t-Alb PIHYSL(-AL AIAU 14LUI-'%ULUUlt@.AL TAAI, 07 I -V) -'IME OBSERVATIONS CAT 'NO DOSE WT- T @ND $EX MG/KG KG* HOURS 2 MINUTE HEART RATE 154 BEATS/ 32,M 500 3o46 0*0 RESPIRATIONS PER MINUTE -42 BODY TEMPERATPRE C 39oO NOSE COOL AN MOIST LEAN SLIGHTLY TENSE 2 CALM QUIET BEHAVIORs GENERAL APPEARANCE9 AND@CONDITION NORMAL NEUROLOGICALITESTS NORMAL PRE-DOSE (5AME DAY) 001 APPEARED NORMAL ON CASUAL OBSERVATION 2 144 BEATS/MINUTE 096 HEART RATE RESPIRATIONS @ER MINUTE 60 BODY TEMPERATURE C 38*7 NOSE@COOL ANib DRY CAL AND NEUR'OLOGICAL CONDITION NO2 OTHER CHAGES NOTED IN PHYSI lo3 HEART RATE 150 BEATS/MINUTE RESPIRATIONS PER MINUTE 60 BODY TEMPERATURE C 3898 NOSE COOL AR@b MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONOITION 1 4 SUSPENSION -STEROID DILUENT > POY!)I(-i@L -tli@ @@5092 1-V) CAT @o. DOSE WT* TIME OBSERVATIONS @ND SEX MG/KG KG* HOURS 66 F 3290 1#57 000 HEART RATE 15, BEATS/MINUTE BODY TEMPERATURE C 3997 2 CAT SMALL AND LEAN CALM MODERATELY A,CTIVE NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY) 0,2 HEART RATE 144 BEATS/MINUTE RE5PIRATIONSI@',PER MINUTE 54 2 BODY TEMPERATURE C 39*4 50ME OF DOSO INJECTED SUBCUTANEOUST INSTEAD OF IN VEIN SUBCUTANEOU5 DOSE STILL PRESENT-UNDER SKIN NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 005 HEART RATE 144 BEATS/MINUTE 2 RE5PIRATIONS,PER MINUTE 54 BODY TEMPER9@TURE C 39.7 5UBCUTANEOO@ DOSE NOW ALL ABSORBED NO CHANGES@@fqOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 106 HEART RATE @44 BEATS/MINUT1E RESPIRATIONS PER MINUTE 60 @'T 9,7 BODY TEMPER@, URE C 3 NO CHANGESI.;NOTED IN 'PHYSICAL AND NEUROLOGICAL CONDITION SU5PENSION"@- STEROID DILUENT PHYSICAL AND NEUROLOGICAL EXAMINATION OF CATS 5 0 9 2 I V) tiME OBSERVATIONS i@ CAT No, ;DOSE WT* @ND SEX MG/KG KG* HOURS 66 F 3200 1.57 2.3 HEART RATE 132 BEATS/MINUTE RESPIRATIONS PER MINUTE 60 2 BODY TEMPERATURE C 4Oo3. NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION .4,0 HEART RATE 132 BEATS/MINUTE RE5PIRATIONS@P,.FzR MINUTE 56 BODY TEMPERA@TU4kE C 4000 2 Nd, IN PHYSICAL AND NEUROLOGICAL CONDITION NO CHANGES ED 20*3 HEART RATE 138,,,BEATS/MINUTE RESPIRATIONS P@ER MINUTE 50 BODY TEMPERATURE C 39,6 NO CHANGES N(!TED IN9 PHYSICAL AND NEUROLOGICAL CONDITION SUSPENSION-- TEROID DILUENT rn OHYSICAL ANU NEUI@OLOGI(.AL EXAM114AILU14 UP (-AT5 405104' -M) CAT No* DOSE WT* TIME OBSERVATIONS@,@ @ND SEX MG/KG KGo HOURS 44 F 10*0 12*52 000 HEART RATE 114 6EATS/MINUTE 2 RESPIRATIONS 'PER MINUTE 54 BODY TEMPERATURE C 38*5 NOSE COOL A6D MOIST BEHAVIORT GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME 2 DAY) 0,2 HEART RATE 138 BEATS/MINUTE RESPIRATIONS,PER MINUTE 60 BODY TEMPERATURE C 39o4 NOSE WARM AND MOIST NO OTHER-CHINGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 095 HEART RATE2 l@O BEATS/MINUTE RESPIRATIONSI@PER MINUTE 108 BODY @TEMPERAT@URE C 39*1 NOSE WARM AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITIO lo4 HEART RATE 1,44 BEATS/MINUTE 2 RESPIRATIONS'I'PER MINUTE 48 BODY TEMPERATURE C 38.6 NOSE WARM AND MOIST NO OTHER CH6,NGES NOTED IN PHYSICAL AND NEUROLOGICAL CONPITION SOLUTION POLYETHYLENE GLYCOL-300 100% 9 rn PHYSICAL AND NEUROLOGI.R- EXAMINATION OF CATS 5104 (I-M) CAT No* DOSE WTO '-TIME OBSERVATIONS @ND SEX MG/KG KG* HOURS EATS/MINUTE .44 F lOiO 3*2 HEART RATE 120@.8 2 RESPIRATIONS PER MINUTE 54 BODY TEMPERATURE C 38o5 NOSE WARM AND,MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION @4,3 HEART RATE 1204'BEATS/MINUTE 2 RESPIRATIONS PER MINUTE 102 BODY TEMPERATUKE C 38.4 NOSE WARM ANDi'@IMOIST NO OTHER THAN@ES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 2500 HEART RATE 144,,',,BEATS/MINUTE 2 RESPIRATIONS P,,,ER MINUTE 96 BODY TEMPERATUFZE C 38o3 NOSE COOL AND,MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION-- POU-YETHYLENE GLYCOL-300 10096 3 rn III Ui,U(-UU I @-IkL LAI%I'L P,HY I Li@L 5143@,@ I-V) low CAT Noe DOSE WTo TIME OBSERVATIONS @ND 5EX MG/KG KGO 'HOURS 52 F 5,6 2*17 0120 HEART RATT 126 BEAT8/MINUTE RESPIRATIONS PER MINUTE 42 BODY TEMPERATURE C 37*9 NOSE COOL AND MOIST BEHAVIOR* GENERAL APPEARANCE9 AND-CONDITION NORMAL NEUROLOGICAL TESTS NORMAL 2 PRE-DOSE (SAME DAY) 0,2 HEART RATE 156 BEATS)MINUTE RESPIRATIONS PER MINUTE 54 BODY TEMPERATURE C 38,4 NOSE COOL AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 0025 HEART RATE 15@6 BEATS/MINUTE RESPIRATIONS PER MINUTE 96 BODY TEMPERATURE C 3803 NOSE WARM AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION lo6 HEART RATE 150 BEATS/MINUTE 4 RESPIRATIONS,PER MINUTE 72 BODY TEMPERATURE C 38*4' NOSE WARM AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION Dli5TILLED WATER NEUROLOGIr,,. EXAMINATION OF CATS PHYSICAL AND 5143 (I-V) -OBSER@ IME IATIOMS CAT Noe @D05E WT* T HOURS AND -SEX MG/KG KG* 2 50 BEATS/MINUTE 52 F 5*6 3,2 HEART RATE I , UTE 54 RESPIRATIONS PER MIN BODY TEMPERATURE C-38*2 ND DRY NDITION NOSE'COOL A 2 HANGES NOTED IN PHYSICAL AND NEUROLOGICAL CO NO OTHER C 4*7 HEART RATE 15p BEATS/MINUTE RE5PIRATIONS PER MINUTE 54 BODY TEMPERATA,,JRE C 38*7 NOSE COOL ANLP M015T 2 NO OTHER CHPMGE5 NOTED IN PHY51CAL AND NEUROLOGICAL CONDITION SOLUTION DI@$IILLED WATER 0 HEART RATE le BEATS/MINUTE 55 F 5*6 1*87 :0. RESPIRATIONS"PER MINUTE 42 BODY TEMPEFZAIURE C 37o7 2 NOSE COOL ANO'MO15T CALM ORMAL BEHAVIOR* G't4ERAL APPEARANCE$ AND CONDITION N E NEUROLOGICAL;,TE5T5 NORMAL PRE-DOSE (SAME DAY) 0 0 SOLUTION DI'STILLED WATER EUROLOGlkj EXAMINATION OF CATS PHYSICAL AND N 143 .*IME OBSERVATIONS CAT Noo DOSE WT* HOURS AND SEX MG/KG KG* HEART RATE 96 6EAT5/MINUTE 55 F 5o6 Oe2 2 RESPIRATIONS PER MINUTE 90. N05E WARM AND DRY ATING MEMBRANE SLIGHTLY RELAXED NICTIT IN PHYSICAL AND NEUROLOGICAL @ONDITION NO OTHER CHANGES NOTED HEART RATE 138 DEATS/MINUTE 2 005 RESPIRATIONS PER MINUTE 72 BODY TEMPERATURE C 38o3 D'MOIST NOSE COOL AN NICTITATING MO@@MBRANE IN NORMAL POSITION HEART TE 1,0 RATE 138@SEATS/MINU RESPIRATIONS PE-@@k MINUTE 66 BODY TEMPERATURE C 38*2 NO-CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION '.2o4 HEART RATE 120i'13EATS/MINUTE RESPIRATIONS P@@ MINUTE 36 2 BODY TEMPERATUR C 37t8 NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 4*5 HEART RATE 114iBEATS/MINUTE RESPIRATIONS PER MINUTE 30 BODY TEMPERATURE C 37o9 NO CHANGES NOri,,,ED IN PHY2SICAL AND NEUROLOGICAL CONDITIONI HEART RATE 138jilBEATS/MINUTE 2405 RESPIRATIONS PER MINUTE 42 BODY TEMPERATURE C 37.9 NO CHANGES N@IED IN PHYSICAL AND NEUROLOGICAL CONDITION i 6 SOLUTION - D154ILLED WATER rn > F CATS EXAM INATION 0 EUROLOG PHYSI CAL AND N 51 (I-V) 2 5 CAT No* DOSE WT* tiME OB5ERVATION@ AND SEX MG/KG KG* HOURS ATE 144 BEATS/MINUTE@ 39 F 240 2*90 0,0 HEART R RE5PIRATIONS'PER MINUTE 36 BODY TEMPERATURE C 3802 NOSE 2COOL AND M015T NOR14AL BEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME 6AY) 0#2 HEART RATE 120 BEATS/MtNUTE @ll'@'PE2R MINUTE 42 RE5P!RATION5 BODY TEMPERAI,'URE C 38.4 D NOSE,COOL A MOIST N NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITIO 0.8 HEART RA-IE l@4 BE2ATS/MINUTE RESPIRATIONS PER MINUTE 48 BODY TEMPERA@URE C 38,7 NOSE WAGM@ AND DRY NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 164 HEART RATE l'IB BEATS/MINUTE RESPIRATIONS!IPER M2INUTE 36 BODY TEMPER@'FURE C 38-8 NOSE WARM AND DRY NO OTHER C@@NGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 5OLUTION LYETHYLENE GLYCOL-300 100% 2 rn PHYSICAL AND NEUROLOGIR EXAMINATION OF CATS 5145 (I-V) tAT NO, DOSE WT, TIME 085ERVATIONS @ND SEX MG/KG KG* HOURS 39 F 2*0 2*4 HEART RATE 108 8@EATS/MINUTE RESPIRATIONS PERI@MINUTE 36 2 BODY TEMPERATURE C 38o4 NOSE COOL AND DRY NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 500 HEART RATE 144 BEATS/MINUTE R-CSPIRATION5 PER MINUTE 36 BODY TEMPERATUR4 "-. 3805 NOSE COOL AND OIST NO OTHER CHAN 5 NOTED IN PHYSICAL@ANB NEUROLOGICAL CONDITION 25,,7 HEART RATE 13PE@EATS/MINUTE RESPIRATIONS MINUTE 30 BODY TEMPERATUR@ C 37o9 NO CHANG3ES NOTO@@At-D IN PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION'- POL@@ETHYLENE GLYCOL-300 100% rn 11.411 VI tA I -J 8658-53 "V) CAT N-Os DOSE.@ WT* TIME OBSERVATIONS AND SEX MG/KG KG* HOURS 55 F 27 2*00 000 HEART RATE 138"BEATS/MINUTEi RESPIRATIONS PER MINUTE 42 2 BODY TEMPERATURE C 38*3 NOSE'COOL AND@ I.MOLST QUIET CALM BEHAVIORT GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL 2 PRE-DOSE (SAME DAY) 001 HEART RATE 138 BEATS/MINUTE RESPIRATIONS PER MINUTE 60 BODY TEMPERATURE C 38o7 NOSE WARM AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL.CONDITION 015 -HEART 2RATE 12,0 BEATS/MINUTE RESPIRATIONS PER MINUTE '60 BODY TTMPERATIJRE C 38*6 NOSE WARM A* MOIST NO OTHER CH@@NGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1,4 HEART RATE 138 BEATS/MINUTE RESPIRATION S 2MINUTE 48 BODY TEMPERATURE C 38*8 NOSE COOL A@D MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SOLUTION POLYETHYLENE GLYCOL-300 100% r2n 'Al PHYSICAL AND NEUROLOG EXAMINATION OF CATS 8658-53 (I-V) CAT Noe WT* TIME OBSERVATION @ND SEX MG/KG KGo HOURS 55 F 27 2,7 HEART RATE 132, BEATS/MINUTE ER M2INUTE 36 RESPIRATIONS BODY TEMPERATURE C 3895 REDUCED ANAL,;TENSION @GES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION NO OTHER CHAN 4o7 HEART RATE 114 BEATS/MINUTE 2 RESPIRATIONS PER MINUTE 27 BODY TEMPERATURE C 38oo REDUCED ANAL@TENSION NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 22,0 HEART RATE 132 BEATS/MINUTE RESPIRATIONS PER MINUTE 48 2 BODY TEMPERAIORE C 38*2 ANAL VENSION@@'BETTER BEliAVIORt GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROL061CAL@TESTS NORMAL SOLUTION POLYETHYLENE GLYCOL-300 1070% rTi > PHYSICAL AND NEUROLOGIR". EXAMINATION OF CATS 8658-91 (I-V@) .CAT Noe DOSE TIME OBSERVATION@ WT* @ND SEX MG/KG KG* HOURS 64 F 392 3*lo 04.0 HEART RATE 162 BEATS/MINUTE RESPIRATIONS PER MIN2UTE .48 BODY TEMPERATURE C 3893 NOSE@COOL AND MOIST CALM BEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL TESTS NORMAL 2 PRE-DOSE (SAME DAY) 0.2 HEART RATE J50 BEATS/MINUTE RESPIRATIONI@ PER INUTE 48 BODY TEMPERATURE C 38*8 NOSE WARM AND MOIST NO OTHER C@ANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 2 .095 HEART RATE t'14 BEATS/MINUTE RESPIRATION PER MINUTE 60 BODY TEMPERAITURE C 38o8 NOSE WARM AND DRY 'ANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION NO OTHER .CH 2 110 HEART RATE ".,@96 BEAT5/MINUTE RESPIRATIONT PER MINUTE 72 BODY TEMF)ER@'TURE-C 38.5 NOSE COOL AND MOIST NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION SUSP6ENSION STEROID DILUENT oGfCA OF CATS PKYSICAL AND NEUI@OL E)(AMINATION 8658-91 IME OBSERVATIONS CAT No* DOSE WT* T HOURS @ND 5EX MG/KG KG* 3.10 2,0 HEART RATE 212'6 BEATS/MINUTE'. 64 F 3o2 RESPIRATIONS@PER MINUTE 66 BODY TEMPERA URE.C 39oO CONDITION NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL .4,1 HEART RATE 144 BLATS/MINUTE @'PER MINUTE 54 RE5PIRATIONS@ BODY TEMPERATURE C 38o8 5 OOTED IN PHYSICAL AND NEURO@OGICAL CONDITION NO CHANGE! l@6 BEATS/MINUTE 2 503 HEART RATE RESPIRATIONS!'@PER MINUTE 54 BODY TEMPERA URE C 38*7 ROLOGICAL CONDITION NO CHANGES OTED IN PHYSICAL AND NEU 2@02 HEART RATE l@2 BEATS/MINUTE RESPIRATION PER MINUTE 60 BODY TEMPER URE C 38,4 NO CHANGES OTED IN PHY51CAL AND NEUROLOGICAL CONDITION SUSPENSION -@t@@STEROID DILUENT 'U 4 rn CATS PHYSICAL-AND NEUROLOGI(,_@ EXAMINATION OF' 8698-59 (I-V) CAT NOo DOSE WT* TIME OBSERVATIONS @ND SEX MG/KG KG* HOURS 36 M 298 407 000 HEART RATE 144 BEATS/MINUTE@ 2 RESPIRATIONS PER IVIINUTE 48. NOSE COOL AND@IMOIST BEHAVIOR9 GENERAL APPEAPANCEs AND CONDITION NORMAL.. NEUROLOGICAL TESTS NORMAL PRE-DOSE (SAME DAY) 0.1 HEART RATE 96@2BEATS/MINUTE RESPIRATIONS PfR MINUTE 84- NOSE WARM AND:MOIST HEARTBEAT DIFFICULT TO DETECT NO OTHER CHAiiGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 0#6 HEART RATE 126 BEATS/MINUTE RESPIRATIONS PER MINUTE 782 NOSE COOL ANy DRY NO OTHER CFIAN;GES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITION 1,9 HEART RATE 156 8EATS/MINUTE RESPIRATIONS PER MINUTE 72 NOSE COOL AND MOIST .NO OTHER CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CO2NDITION 4al HEART RATE 144 BEATS/MINUTE RESPIRATIONS'OER MINUTE 72 NO CHANGES NOTED IN PHYSICAL AND NEUROLOGICAL CONDITIOU-- t@ 20 RESPIRATIONS,'PER MINUTE 42 HEARTBEAT DIPFICULT TO DETECT BEHAVIOR9 GENERAL APPEARANCE9 AND CONDITION NORMAL NEUROLOGICAL)TESTS NORMAL SUSPENSION STEROID DILUENT > rn PHYSICAL AND NEUROLOGICAL-EXAMANATIONS OF SQUIRREL MONKEYS 172 I MONKEY DOSE WT* TIME OBSERVATIONS NUMBER MGIKG GM4 HOURS A 825 000 RESPIRATIONS PFR MINUTE 78 APPEARANCE AND BEHAVIOR NORMAL PUPILS NORMAL IN SIZE AND REACTION TO L2IGHT PRE--DOSE (SAME DAY) Oo4 SH @IGHT CUE "1*8 UTTLED ON L APPEARANCE AND BEHAVIOR NORMAL 008 APPEARANCE AID BEHAVIOR NORMAL 0109 SECOND DOSING 1-00 2 INCREASED L040MOTOR ACTIVITY EYES APPEAR 90RE ALERT-THAN USUAL SKIN OF FACE7'@PALER9 MORE LIKE THAT OF OTHER MONKEYS FACE APPEAREI)-MORE 9ELAXED AND HEALTHY lo2 RESPIRATIONS PER MINUTE 66, PUPILS NORMAL IN SIZE AND REA2CTION TO LIGHT 103 RAN TO HOME TAGE TO JOIN OTHER MONKEY INCREASED LOT@'OMOTOR ACTIVITY 295 RESPIRATIONS OER MINUTE 60 APPEARANCE AND BEHAVIOR NORMAL APPEARANCE (YO ALERTNE55 IN EYES SUBSIDED TO NORMAL SKIN OF FACE'jDARK9 AS USUAL SOLUTION DI;:'STILLED WATER > rn PHYSICAL AND NEUROLOGICAL EXAMINATIONS OF SQUIRREL MONKEYS 1172 MONKEY DOSE WT*. 'TIME OBSERVATIONS NUMBER MG/KG GM9 HOURS T 000 HEART RATE 320@ BEATS/MINUTE 1000 609 1 RESPIRATIONS PER MINUTE 78 2 APPEARANCE AND BEHAVIOR NORMAL EXCITABLE ON HANDLING PUPILS NORMAL IN SIZE AND REACTION TO LIGHT PRE-DO5E (SAME DAY) 2.96 EMESIS 3oO HEART RATE 28OiBEATS/MINUTE RESPIRATIONS OER MINUTE 78 9 SOLUTION D151ILLED WATER 4) rn EL MONKEYS ICAL AND NEUROL061CAL EXAMI ATIONS OF SQUIRR PHYS 1402 (I-M)@' JIM .MONKEY DOSE WT* TIME' OBSERVATIONS GM* HOURS NUMBER MG/KG 2 NUTE B 100 850 000 HEART.RATE 240 BEATS/Ml RESPIRATIONS PER MINUTE 84 L 'IN SIZE AND REACTION To LIGHT PUPILS NORMA PRE-DOSE (SAME', DAY) o@2 APPEARANCE AND 2BEHAVIOR NORMAL 0*5 APPEARANCE AND BEHAVIOR NORMAL SHUTTLED ON LIGHT CUE 1 .48 101 RESPIRATIONS PER MINUTE APPEARANCE AN BEHAVIOR NORMAL SHUTTLED ON L@GHT CUE 2 17*3 APPEARANCE AND BEHAVIOR NORMAL SOLUTION oo9% ASCORBIC ACID rn RREL MONKEYS GICAL EXAM@l.'ATIONS OF $QUI PHYSICAL AND NEUROLO N 031402 (I-Mii) .IONKEY DOSE WT, TIME OBSERVATIONS N,IUMBER @MG/KG GM* HOURS B 490 850 000 HEART RATE 240,'.BEAT5/MINUTE RESPIRATIONS PER MINUTE 96 PUPILS NORMAL IN SIZE AND REACTION TO LIGHT PRE-DOSE (SAME DAY) DOSED ONE DAY AFTER NEXT LOWER DOSING 092 APPEARANCE AND BEHAVIOR NORMAL 2 SHUTTLED SPONTANEOUSLY 095 APPEARANCE AIID BEHAVIOR NORMAL 5HUTTLED ON @,@IGHT CUE APPEARANCE AND BEHAVIOR NORMAL SHUTTLED ON LIGHT CUE 2mO APPEARAN2CE AND BEHAVIOR NORMAL SHUTTLED ON LIGHT CUE 510 APPEARANCE AtiD BEHAVIOR NORMAL SHUTTLED ON'LIGHT CUE 23 IN HOME CAGE!,, SLIGHT TREMdAs CONSTANT LOCOMOTOR ACTIVITY ALONE IN SHUTTLE BOX CONSTANT LOCOMOTOR ACTIVITY SHUTTLED 5Pd@NTANEOUSLY 15 TIMES MINUTE ASCORBIC ACID SOLUTION - 1.0,6 INATI NS OF SQUIRREL MONKEYS PHYSICAL AND NEUROLOGICAL EXAM @o 1402. (I-M) lot OBSERVATIONS @IONKEY DOSE WTo TIME NUMBER MG/KG GM* HOURS lo,.O 850 2000 RESPIRATIONS PER MINUTE 90 PRE-DOSE ISAME DAYI) boSED ONE DAY AFTER NEXT LOWER DOSING 0*1 ALONE IN SHUTTLE BOX SITTING QUIETLY O@2 ALONE IN SHUTTLE BOX SHUTTLED SPONTANEOUS2LY SOME COARSE PURRING 003 ALONE IN SHUTTLE BOX SOME COARSE PURRING SHUTTLED SPONTANEOUSLY 6 TIMES MINUTE 0*4 ALONE IN SHUTTLE 0,,OX SLIGHT TREMORS 0,5 1RESPIRATIONS PER MXNUTE 52 WAS FED 10 Biscuits ALONE IN SHUTTLE dOX SOLUTION - 4oO,% ASCORBIC ACID PHYSICAL.AND NEUROLOGICAL EXAMINATIONS OF SQUIRREL MONKEYS an@1402 (I-M) OBSERVATIdNs NIONKEY DOSE WT, TIP-E iqt)M,E3ER MG/KG GM* HOU2RS B' 1000 8@50 105 Al-ONE IN SHUTTLgiBox SHUTTLED SPONTAO@OUSLY 13 TIMES MINUTE TRIED TO LEAP THRU TRANSPARENT CAGE WALL 2X IN 5 MINUTES 3*0 ALONE IN SHUTTL@'!BOX SHUTTLED SPONTA, SLY 11 TIMES / MINUTE TRIED TO LEAP TH@OUUTRANSPARENT,CAGE WALL 12X IN 3 MINUTES .4'97 ALONF IN SHUTTL94BOX T 2 SHUTTLED SPONTANtous!-y -.114ES / MINUTE CAGE WALL 5X TRIED To LEAP THRU TRANSPAREN1 !N 2 MINU"'ES .23 2 APPEAFIIAN(:T AND BFHAV!OR NORMAL t AL,,ONE IN SIAI)TTL.E, BOX SHTJTYL.ED SPON'VANEOLISI.Y 16 TIMES MINUTE 6 SOLUTION 4oO',& ASCORBIC ACID MINATIONS OF SQUIRREL MONKEYS PHYSICAL AND NEUROLOGICAL EXA 1900 (I-M) ids OBSERVATIONS '40NKEY DOSE WT* TIME :4UMBER MG/KG GMe HOURS A- 100 830 oo3 RESPIRATIONS PEA MINUTE 66 2 NO CHANGES RESPIRATIONS PER MINUTE 66 009 DECREASED EOUliLIBRIUM FORWARD SOMERSAULT '@H SHUTTLED ON LI,, T CUE 2 C T KIT A(' GRASPING AND 0,1 G"T T N16 T 109 RESPIRATIONS Pdo MINUTE 48 WAS RETURNED ib HOME CAGE WITH OTHER MONKEYS APPEARANCE AND';113EHAVIOR NORMAL- 15@,ILLED WATER 8 SOLUTION - D PHYSICAL AND NEUROLOGICAL EXAMI@ATIONS OF SQUIRREL MONKEYS 9051900 (I-M), MONKEY DOSE WT, TIME OBSERVATIONS NUMBER MG/KG GM* HOURS A. 1000 815 001 PARTIAL PALPEBRAL CLOSURE FORWARD SOMERSAULT 2 0*2 PLASTIC IMMOBILITY MOVED HEAD A LITTLE TO LOOK AROUND RESPON51VE TO SOUND BIT GLOVED HAND DID NOT SIIUTT4Et EVEN AFTER REPEATED ELECTRIC SHOCKS SQUEALED ON E41ECTRIC SHOCK 0*5 RESPONSIVE 2TO VISUAL STIMULI RESPONSIVE TO@SOLIND OTHERWI.58 AS 9,,N PREVIOUS REPORTED INTERVAL 0*8 LYING ON ABDOMEN AROUSED BY HANDLING9 STOOD ON HIND.LEGS9 TREMBLED9 LAY ON SIDE 1.9 RESPIRATIONS PER MINUTE 362 DEEP RESPIRAT@ONS LYING ON SIDE@I PALPEBRAL CL05URE RESPONDED TO SHARP SOUND BY MOVING SLIGHTLY AND WHIMPERING SOLUTION 0*996 SALINE -u 6 rn RREL MONKEYS PHYSICAL AND NEUROLOGICAL EXAMINATIONS OF SQUI 1900 (I ins OBSERVATIC(NS. MONKEY DOSE WT* TIME NUMBER MG/KG GMo HOURS LYING ON SIDE A 2 10*0 815 2o8 GRASP STRONG, RESISTED BEING MOVED WAS PLACED IN ISOLATION.CAGE STOOD ON 4 FEET TREMORS IN HIND LEGS 495 IN ISOLATION CAGE SITTING QU2IETLY APPEARED TO SLEEPT UNTIL AROUSED BY SOUND RESPONSE TO SOUND SLUGGISH CLIMBING AROOND ON LATTICE WALL OF ISOLATION CAGE 5.5 FACE BLU15H MOTOR ATTIVI@IY SLUGGISH 2 ATE FOOD SLUGGISHLY 22 APPEARANCE AND BEHAVIOR NORMAL HAD EATEN MOST OF FOOD IN ISOLATIO41CAGE ,SOLUTION 00@ 9% SALINE -o 6 rn > t OF SQUIRREL MONKEYS, PH SICAL AND NEUROLOGICAL EXAMI,NATIONS y 1900 (I-M); -IONKEY DOSE WT* TIME OBSERVATIONS '4UMBER MG/KG GMV HOURS G 100 645 000 RESPIRATIONS PLR MINUTE 1002 APPEARANCE AND BEHAVIOR NORMAL PRE-DOSE (SAME DAY) 001 SHUTTLED ON LIGHT ANF, SOUND CUES 0.2 SHUTTLED ON L@'IGHT AND SOUND CUES '!iR MINUTE 66 0*3 RESPIRATIONS O2@ i SLIGFIT-PHOTO@@OBIA 0#7 SITTING QUIET@Y I PARTIAL PALP@,DRAL CLOSURE 5*5 PALPEBRAL OP@'NING RETUR5NING LOCOMOTOR ACTIVITY SOLUTION Dlg@,TILLED WATER GICAL EXA PHYSICAL AND NEUROLO !NATIONS OF SQUIRREL MONKEYS goo (I-M) OBSERVATIONS ,'40NKEY DOSE WT* TIME u MG/KG GM* HOURS MBER 3oO 634 0925 PARTIAL PALPC-BRAL CL05URE G 2 CROUCHING P05TURE HEAD DROP Oo7 BETWEEN NoR- SHUTTLE TRIALS ti SPONTANEOUS SHUTTLING muc NORMALLY NONE9 DURING SHUTTLE TEST) MORS IN NE0CK SLIGHT SLOW TRE 8 TOXIC 5IGN5 BEGINNING TO ABATE SOLUTION Oe@,,,q% SALINE rn A PHYSICAL AND NEUROLOGICAL EX A!NATIONS OF SQUIRREL MONKEYS ina2loo '40NKEY DOSE WTO TIME OBSERVATIONS NUMBER @MG/KG GM* HOURS .G 1*0 622 Oi2 PARTIAL PALPFBRAL CL05URE DECREASED LOTOMOTOR ACTIVITY DECREASED.EXCITABILITY PARTIAL PALPEBRAL.CLOSURE HICCOUGHS 1*5. SKIN AROUND EYES SLIGHTLY REDDENED 4,o5 PARTIAL PALPEBRAL OPENING .24 EXCITABILITY RETURNED TO USUAL@LEVEL 6 -SOLUTION 0*9% SALINE PHYSICAL AND NEUROLOGICAL EXAMINATIONS OF SQUIRREL MONKEYS 2100 (I -mi@y lot MONKEY DOSE WT* TIME OBSERVATIDNS NUMBER @MG/KG GMO HOURS G 3o2 625 000 RESPIRATIONS PiR MINUTE 90 APPEARANCE AND BE2HAVIOR NORMAL PRE-DOSE (SAM-E DAY) i RESPIRATIONS PLER MINUTE 54 .093 PARTIAL PALPEBRAL CLOSURE -LIGHTLY REDDENED 'y 2 SKIN AROUND E@ES 5 LOW9 STIFF CROUCHING POSTURE9 FEET WIDE APART 6 SL. HEAD DROP Oo5 BETWEEN NaRo)SHUTTLE TRIALS USUALLY SHUTTLED ONLY AFTER REPEATED ELECTRIC SHOCKS SITTING WITHTHEAD FORWARD AND RE@)T2ING ON FLOOR MUCH VOCALIZI!NG AFTER ELECTRIC SHOCK io5 LYING ON SIDC-L IN SHUTTLE BOX WITH OTHER MONKEYS 2,5 LYING ON SIDE IN SHUTTLE BOX WITH OTHER MONKEYS 393 SITTING UP AND LOOKING AROUND 2 PARTIAL PALPEBRAL CLOSURE 4 SITTING UP AND LOOKING AROUND PARTIAL PALPEBRAL CLOSURE FACE AROUND EYES NOT RED 24 APPEARANCE AND BEHAVIOR NORMAL -0 3 rn SOLUTION - Oo9% SALINE F SQUIRREL MONKEYS EUROLOGICAL EXAMINATIONS 0 PHYSICAL AND N 41IM2277 (SUBCUTA@@EOUS) OBSERVATIONS @4ONKEY DOSE WT. TIME '4UMBER MG/KG GM* HOURS 2 R@l'@MINUTE 102 0018 653 6.0 RESPIRATIONS PE G APPEARANCE AND BEHAVIOR NORMAL' PRE-DOSE (SAIAE DAY) 001 SHUTTLED ON LIGHT AND SOUND CUES 092 ROI.LED OVER ONTO BACK FREQUENTLY SHUTTLED ON LIGHT AND 5OUND.CUE5 093 SHUTTLED ON LIGHT AND SOUND CUES HT PALPEBRAL CLOSURE 0 0 5 SLIG IN UNUSIJAL9 AGGRESSIVE MANNER Oo6 MOUNTED MONKEY @'Rl I-AY ON BACK FOR A FEW SEC7OND5 BETWEEN N.Ro SHUTTLE TRIALS IC ACID SOLUTION 0 90/0 @ASCORB PHYSICAL AND NEUROLOGICAL EXAMINATIONS OF SQUIRREL MONKEYS 2277 (SUBTUTANEOUS) '40NKEY DOSE WTO 'TIME OBSERVATIONS :'QUMBER MG/KG GM. HOURS MONKEY G' 0.18 653 1*0 FELL OVER.ONTO BACK9 AFTER 2MOUNTING R "@SHUTTLE TRIALS BETWEEN N.R. 3*0 SITTING QUIETLY PARTIAL PALPEBRAL CLOSURE BETWEEN P*Ro SHUTTLE TRIALS 500 RETURNING LOCOMOTOR ACTIVITY 2 AT TIMES STOOD ON HIND LEGS9 RESTING TOP OF HEAD ON FLOOR 5*5 LAY ON-BACKIIA@!D PULLED TAILS OF OTHER MONKEYS 24 RETUP.-NING LOCOMOTOR ACTIVITY AT TIMES STOOD ON HIND LEGS, RESTING TOP OF HEAD ON FLOOR TOXIC SIGNS@DECREASING 7 SOLUTION 0.9% ASCORBIC ACID ......... PHYSICAL AND NEUROLOGICAL EXAM'INATIONS.OF.SQUIRREL MONKEYS 277 (SUBCUTANEOUS) mow !10NKEY DOSE WT* 'TIME OBSERVATIONS -AUMBER MG/KG GMe HOURS A 0*3 830 000 RESPIRATIONS PER MINUTE 66 PUPILS NORMAL IN SIZE AND REACTION TO LIGHT PRE-DOSE (SAME DAY) 0*1 INTERMITTENTI,,CIRCLING ALONE T.N SHUTTLE BOX Oo2 RESPIRATIONS PER MINUTE 45 RUMP HELD HIGH9 2HEAD HUNG LOW FOR MANY MINUTES IMMOBILE WHE@ HELD IN HAND 5 LOCOMOTOR ACTIVITY MARKEDLY REDUCED SPONTANEOU NO RESPONSE tO SOUND PUPILS NORMA@ Iti SIZE AND REACTION TO LIGHT 0*6 2 RESPIR,@TIONS @ER MINUTE 36 COUNTING ONE,'DEEP & ONE SHALLOW RESPIRATION AS ONE ONE DEEP PE'.Jl),IRATION ALTERNATING WITH ONE SHALLOW RESPIRATION GENERALLY,IMMOBILE PHOTOPHOBIA RESPONSIVE TO LOUD SOUND 8 RESPONSIVE TO ELECTRIC SHOCK GRASPING ANDIRIGHTING REFLEXES INTACT 0*7 TOXIC SIGNS BEGINNING TO ABATE SOLUTION 0*9% ASCORBIC ACID PHYSICAL'AND NEUROLOGI.CAL EXAMINATIONS OF SQUIRREL MONKEYS 2277 (SUBC4,TANEOUS) '40tiKEY DOSE WT, TIME OBSERVATIONS NUMBER MG/KG GM* HOURS A 0*3 830 293 LETHARGY MAR@EDLY ABATED SLIGHT SEDATION 2 SHUTTLED ON ELECTRIC SHOCK LOCOMOTOR ACTIVITY SLOW AND AWKWARD 2*4 WAS RETURNED. TO HOME CAGE WITH OTHER MONKEYS @'t APPROACHED MK* B IN ODD MANNERT PURSUED As MKO B RETREATED FOR MANY MINUTES 9 (MK* B NORMALLY PASSIVE WHEN MOUNTED BY MK. A 390 SITTING QUIETLY WITH MKo B 9 IN NORMAL MANNER 5OLU'rION-- O.?% ASCORBIC ACID rn OCICAL EXAI. NATIONS OF SQUIRREL MONKEYS PhY51CAL AND NEUROL vim 598 (I-M) '-10NKEY DOSE WT* 'TIME' OBSERVATIONS '4UMBER MG/KG GMe HOURS B Oo28 820 0,2 APPEARANCE AND@BEHAVIOR NORMAL 2 SHUTTLED ON Lli@HT CUE 0*3 HEART RATE 200 BEATS/MINUTE RESPIRATIONS PER MINUTE 102 SHUTTLED ON LIGHT CUE 0*7 RESPIRATIONS PER MINUTE 102 2 APPEARANCE AND BEHAVIOR NORMAL SHUTTLED ON LI,@2HT CUE 10'8 HEART RATF 21,"-;bEATS/MINUTE KESPIRATIONS PE,@k MINUTE 84 c PUPII-3 i@ORrAAL!ltl 51ZE AND REACTI2ON TO LIGHT APPEARANCE AND@BEHAVIOR NORMAL WAS RETURNED To ti0tlE CAGE WITH OTHER MO(\IKEYS SOLUTION Ovi;"'N HYDROCHLORIC ACID 05 WITH 0.9@o SALINE B 0*84 4o4 noRINti 5 4*7 RESPIRATIONS PER MINUTE 76 LIGHT CUE SHUTTLED ON 5.1 5HUTTLED ON LI'6HT CUE APPEARANCE AND BEliAVIOR NORMAL EL MONKEYS PHYSICAL AND NEUROLOGICAL EXAMINATIONS OF SQUIRR IM)2 5 9 8 (I-M) '-IONKEY DOSE WT, TIME OBSERVATION5 MG/KG GM* HOURS B 1.22 5.4 THIRD DO.SIN.G 2 5.9 APPREARANCE AND BEHAVIOR NORMAL' IN HOME CAGE 6.5 APPEARANCE AND BEHAVIOR NORMAL G 630 0.3 MOVEMENTS SLIGHTLY JERKY 5.0 MUCH SPONTANEOUS SHUTTLING (NORMALLY NONE, DURING SHUTTLE TEST) SOLUTION 0.1 HYDROCHLORIC ACID QS WITH 0.990/o SALINE rn