TABs

B-I. Chemical Properties of Sarin and Cyclosarin

B-II Summary of Acute Lethality Data for GB and GF; Toxicity Data for GB

 

TAB I to APPENDIX B — Chemical Properties of Sarin and Cyclosarin

Table B-I-1. General Chemical Properties of Sarin and Cyclosarin

PROPERTY

SARIN

CYCLOSARIN

Abbreviation GB GF
Chemical Name Isopropyl Methylphosphonofluoridate Cyclohexyl Methylphosphonofluoridate
Chemical Formula CH3PO(F)OCH(CH3)2 CH3PO(F)OC6H11
Molecular Weight1 140.1 180.2
State At 20 C1 Colorless liquid Liquid
Odor1 Almost none when pure Sweet, musk, peaches, shellac
Vapor Density (Air = 1 )1 4.86 6.2
Liquid Density (g/cc) 1.0887 @ 25 C1 1.1278 @ 25 C2
Freezing/Melting Point ( C)1 -56 -30
Boiling Point ( C)1 158 239
Vapor Pressure (mm Hg)1 2.9 @ 25 C; 2.1 @ 20 C 0.044 @ 20 C
Volatility (mg/m3)1 22,000 @ 25 C; 16,090 @ 20 581 @ 25 C; 438 @ 20 C
Flash Point1 C Nonflammable 94 C
Decomposition Temp. ( C)1 150 not available
Heat of Vaporization (cal/g)1 80 90.5
Eye and Skin Toxicity1 Very high Very high
Rate of Action1 Very rapid Very rapid
Physiological Action1 Cessation of breathing; death Cessation of breathing; death
Stability1 Stable when pure Relatively stable in steel
Log Kow 0.723 1.4934
Kh (atm-m3/mol) 5.4 x 10-73 2.8 x 10-7 @ 20 C5
Aqueous Solubility Miscible Almost insoluble in water
Log Koc 0.593 1.823

Sources

1. OATSDNCB, 1997

2. Samuel et al., 1983

3. MacNaughton and Brewer, 1994

4. King and Brown, 1993

5. Rosenblatt, 1996

 

TAB II to APPENDIX B — Summary of Acute Lethality Data for Sarin and Cyclosarin;
Toxicity Data for Sarin

Table B-II-1. Summary of Acute Lethality Data for Sarin (GB)

Species

Dose
(g/kg)

LCt

mg-min/m3

Endpoint

Reference

Comments

Inhalation Exposure

human

-

50-100

LCt50

Somani et al., 1992  

human

-

35-100

LCt50

DHS, 1997a; Johns, 1952

Resting

mouse

-

240-380

LCt50

McNamara and Leitmaker, 1971  

rat

-

80-300

LCt50

McNamara and Leitnaker, 1971  

guinea pig

-

100-200

LCt50

McNamara and Leitnaker, 1971  

rabbit

-

75-144

LCt50

McNamara and Leitnaker, 1971  

cat

-

42-100

LCt50

McNamara and Leitnaker, 1971  

monkey

-

25-300

LCt50

McNamara and Leitnaker, 1971  

dog

-

81-120

LCt50

McNamara and Leitnaker, 1971  

pig

-

34

LCt50

McNamara and Leitnaker, 1971  

goat

-

134

LCt50

McNamara and Leitnaker, 1971  

Dermal Exposure

human

28,000

-

LD50

DHHS, 1995; in ORNL, 1996  

human

24,000

-

LD50

US Army ERDEC, 1994; Oak Ridge National Laboratory (ORNL); 1996  

human

1,700

-

LD50

Zajtchuk, et al., 1997

Based on 70 kg man

human

1,429-7,143

-

LD50

Somani, et al., 1992

Based on 70 kg man

pig

115,900

-

LD50

US Army ERDEC, 1994; ORNL, 1996  

rat

2,500

-

LD50

US Army ERDEC, 1994; ORNL, 1996  

mouse

1,080

-

LD50

DHHS, 1995; ORNL, 1996  

Intravenous Exposure

human

14

-

LD50

US Army ERDEC, 1994; ORNL, 1996  

monkey

20

-

LD50

US Army ERDEC, 1994; ORNL, 1997  

pig

15

-

LD50

US Army ERDEC, 1994; ORNL, 1998  

rat

39

-

LD50

DHHS, 1995; ORNL, 1996  

rat

45

-

LD50

US Army ERDEC, 1994; ORNL, 1996  

Intramuscular Exposure

human

30

-

Lethal Level

Grob and Harvey, 1957; ORNL, 1996  

monkey

22

-

LD50

DHHS, 1995; ORNL, 1996  

rat

170

-

LD50

Grob and Harvey, 1957; ORNL, 1996  

rat

108

-

LD50

DHHS, 1995; in ORNL, 1996  

rat

112

-

LD50

US Army ERDEC, 1994; ORNL, 1996  

Subcutaneous Exposure

rat

103-108

-

LD50

DHHS, 1995; ORNL, 1996  

mouse

200

-

LD50

DA, 1990  

mouse

170

-

LD50

Clement, 1991; Clement, 1994  

Intraperitoneal Exposure

rat

218

-

LD50

US Army ERDEC, 1994; ORNL, 1996  

rat

250

-

LD50

DHHS, 1995; ORNL 1996  

Oral Exposure

human

71-285

-

LD50

Somani, et al., 1992; ORNL, 1996

Assumes 70 kg man

human

140

-

Lethal Level

Grob and Harvey, 1957; ORNL, 1996  

rat

550

-

LD50

DHHS, 1995; ORNL, 1996  

rat

600

-

LD50

Grob and Harvey, 1957; ORNL, 1996  

rat

870-1060

-

LD50

US Army ERDEC, 1994; ORNL, 1996  

 

Table B-II-2. Summary of Acute Lethality Data for Cyclosarin (GF)

Species

Dose
(g/kg)

LCt

mg-min/m3

Endpoint

Reference

Comments

Inhalation Exposure

human

35

 

LCt50

Table B-II-3.

Data questionable

Dermal Exposure

human

350

-

LD50

Table B-II-3.  

Subcutaneous Exposure

mouse

16-400

-

LD50

DA, 1990  

mouse

243

-

LD50

Clement, 1991; Clement, 1994  

mouse

184

-

LD50

Clement, 1994

GF/GB combined

Table B-II-3. Summary of Toxicity Data for Sarin (GB)

Species
Study Type
or Limit
Dosing
Paradigm
Dose1
g/kg
Concentration mg min/m3
Endpoint
AChE Levela
Reference
Comments
Inhalation Exposure
human
limit
 
~0.0028 (72 hr)
0.01296
(72 hrs)
General population limit averaged
 
DA, 1990; Fed. Reg., 1989; McNamara and Lietnaker, 1971 As developed by McNamara and Leitnaker, 1971, based on plasma AchE inhibition and miosis
human
limit
 
~0.0013
(1 hr)
~0.006
(1 hr)
General population ceiling limit for 1 hour
 
DA, 1990; McNamara and Leitnaker, 1971  
human
limit
 
~0.01
(8 hr)
0.048
(8 hr)
Occupational limit averaged over an 8 hour workday
 
DA, 1990, Fed. Reg, 1989; McNamara
and Leitnaker, 1971
As developed by McNamara and Lietnaker, 1971, based on plasma A ChE inhibition and miosis. Originally posed 10 consecutive period limit.
human
MSCb
 
~0.03
(8 hr)
~0.144
(8 hr)
Maximum safe concentration for single 8 hr occupational exposure
 
McNamara and Lietnaker, 1971  
human
MSCb
 
~0.013
(1 hr)
0.06
(1 hr)
Maximum safe concentration for single 1 hr occupational exposure
 
McNamara and Lietnaker, 1971  
human
 
 
~0.12
0.5
<1% of working population would show miosis, ChE depression, or other mildest symptoms. Approximately 10% RBC-AChE depression occurs per 1 ug/kg dose (no ref).
<1% would show any depression
McNamara and Lietnaker, 1971 Based on kinetic data, does may accumulate with daily exposure of 0.05 mg min/m3
human
limit
 
~0.21
1 mg min/m3
First level effects
 
CIA and DoD, 1997  
human
 
 
~0.43 – 0.64
2-3 mg min/m3
Miosis and rhinorrhea
 
Johns, 1952 % responding not identified in Z, 1997
human
 
 
~0.86
4
ECt50 for miosis (20 minute or less exposure)
 
McNamara and Leitnaker, 1971 15 1/min. 8 hr [C] = 0.0083 mg/m3; 24 hr [C] = 0.0028 mg/m3
human
 
 
0.88
4.1
No systemic effects
 
McNamara and Leitnaker, 1971 15 1/min. 8 hr [C] = 0.0085 mg/m3; 24 hr [C] = 0.0028 mg/m3
human
 
 
2.1
10
No deaths
 
McNamara and Leitnaker, 1971 15 1/min. 8 hr [C] = 0.2 mg/m3; 24 hr [C] = 0.007 mg/m3
human
 
 
4.3
20
ECt50 for ChE depression
 
   
human
 
 
7.5
35
1Ct50
 
U.S. Army ERDEC, 1994 Resting
human
 
 
~15
70
LCt50
 
U.S. Army ERDEC, 1994; McNamara and Leitnaker, 1971 15 1/min. 8 hr [C] = 0.14 mg/m3; 24 hr [C] = 0.047 mg/m3
rat
multiple
0.001 mg/m3
6 hr/day, 5 days/week for up to 24 weeks
 
0.151
No signs of toxicity
 
Weimer et al., 1979;
ORNL, 1996
Also no effects at 0.0001 mg/m3
rat mouse dog
multiple
0.001 mg/m3
6 hr/day, 5 days/week for up to 52 weeks
c
0.15
No signs of toxicity and no statistically significant dose-related changes in RBC-AChE.
No statistically significant changes
Weimer et al., 1979;
ORNL, 1996
5 of 20 dogs had abnormal EKGs at time of sacrifice; colony and Fischer rats had higher incidence of trachetis than controls; atrophy of eminiferous tubules occurred in one group of Fischer rats.
mouse
multiple
5 mg/m3 for 20 mins/day for 10 days
d
 
Significant inhibition of brain, spinal cord and platelet NTE. Focal axonal degeneration in 6 animals.
Blood AChE decreased by 27.3% and brain AChE decreased by 19.2%
Husain et al., 1992;
ORNL, 1996
 
Oral Exposure
human
RfD
 
 
0.02
RfD-no inhibition of RBC-AChE
 
ORNL, 1996  
human
acute
single dose
2
 
Excessive dreaming and talking in sleep
RBC and plasma A ChE reduced ~ 15%
Thienes and Haley, 1972;
ORNL, 1996
 
human
multiple
Average daily dose of 2.3 /kg for 3 days, given in 0.008 to 0.016 increments at average interval of 7.4 hrs
2.3
2.3
RBC-AChE reduced 27 and 33% but no toxic effects.
(n = 2)
RBC-AChE decreased by 27 and 33%.
P-AChE reduced 14 and 29%.
Grob and Harvey, 1957 Small number of subjects. Authors saw no change in EEGs in asymptomatic subjects, slight changes with mild symptoms, and more irregularities with moderate symptoms
(p. 356).
human
acute
single dose
10
 
Oral EgD50 for inhibition of RBC-AChE
RBC-AChE reduced 50%
Grob and Harvey, 1957  
human
acute
single dose
20
 
Insomnia, excessive dreaming, withdrawal, depression
 
Thienes and Haley, 1972; ORNL, 1996  
human
acute
single dose
22
 
Mild toxic effects, anorexia, nausea, heartburn, tightness in stomach and chest, increased fatigue, nervous tension, anxiety, and other CNS responses including insomnia and excessive dreaming
RBC and plasma AChE reduced ~75%
Grob and Harvey, 1957  
human
acute
Single dose
28
 
Moderate toxic effects
 
Grob and Harvey, 1957  
human
multiple
Average daily dose of 29 g/kg for 3 days, given in 0.008 to 0.016 increments at average interval of 7.4 hrs
29
29
Mild toxic effects
RBC-AChE decreased 97-99%.
P-AChE reduced 81-88%
Grob and Harvey, 1957  
human
multiple
Average daily dose of 34 g/kg for 3 days, given in 0.008 to 0.016 increments at average interval of 7.4 hrs
34
34
Moderate toxic effects; >90% reduction in
RBC-AChE activity
RBC-AChE decreased 99%.
P-AChE reduced 84-88%
Grob and Harvey, 1957  
human
acute
Single dose
140
 
Estimated lethal dose
 
Grob and Harvey, 1957  
human
multiple
0.075 mg/kg
5 days per week for 13 weeks
75
542
(7 days)
LOAEL based on statistically significant reduction in RBC-AChE in male rats
RBC-AChE reduced to 77 and 63% of baseline
Bucci and Parker, 1992; ORNL, 1996 GB Type II
rat
acute
Single dose
600
 
LD50
 
Grob and Harvey, 1957  
Dermal Exposure
human
 
 
 
 
LD50
 
Zajchuk, et al., 1997 1,700 mg/70-kg man
Intra-arterial Exposure
human
acute
Single dose
3
 
ED50 inhibition of
RBC-AChE
RBC-AChE decreased by 48%.
P-AChE reduced by 30%
Grob and Harvey, 1957 Symptoms occur after RBC-AChE is depressed 88% (12% of baseline) after a single oral dose or 50% after a single intra-arterial dose.
human
acute
single dose
5
 
Moderate symptoms
RBC-AChE decreased by 72%.
P-AChE reduced by 58%
Grob and Harvey, 1957  
Intravenous Exposure
monkey
acute
 
5
 
Alterations in EEG at
24 hr and 1 yr post exposure
 
Burchfiel and Duffy, 1982 All animals convulsed
Intramuscular Exposure
human
acute
Single dose
30
 
Estimated lethal dose (LD50)
 
Grob and Harvey, 1957;
ORNL, 1996
 
monkey
multiple
Ten 1 g/kg doses at 1 week intervals
3
 
Alterations in EEG at 24 hr and 1 yr post exposure
 
Burchfiel and Duffy, 1983 "A series of subclinical but near-threshold exposures showing few, if any, signs of overt poisoning. Stats on this study have been questioned."
rat
acute
Single dose
170
 
LD50
 
Grob and Harvey, 1957  
Subcutaneous Exposure
rat
acute
 
157-177
 
Brain lesions; myocardial degeneration and necrosis
 
Singer et al., 1987 These were convulsant doses. Cardiomyopathy appeared reversible at these dose levels.
Interperitoneal Exposure
rat
acute
 
125
 
Behavior, motor performance, learning frequency, nociception
 
Sirkka et al., 1990 No significant effects
rat
acute
 
50
 
Behavior, motor performance, learning frequency, nociception
 
Sirkka et al., 1991 Affected behavior and motor performance
Oral OPIDN Studies
hen
acute
 
70.2-280.7
 
No evidence of OPIDN at 8-48 days
 
Bucci et al., 1992;
ORNL, 1996
GB Type II
hen
multiple
70.2-280.7 divided into three increments given one week apart
23.4-93.57
 
No evidence of OPIDN at 43 days
 
Bucci et al., 1992;
ORNL, 1996
GB Type II
hen
acute
 
70.2-750
 
No dose-related changes in NTE
 
Bucci et al., 1992;
ORNL, 1996
GB Type II
Other OPIDN Studies
hen
 
 
20-30 x LD50
 
OPIDN induced
 
Davies et al., 1960,
Davies and Holland, 1972,
Gordon et al., 1983
Animals protected with atropine and oximes.
LD50 = 25 g/kg, i.m.

1 Approximations assume a human weighing 70 kg, breathing 15 L/min, and complete absorption

2 75 x (5/7)

3 Assuming monkey weighing 0.35 kg, breathing 0.29 m3/day, and complete absorption

a AchE: Acetylcholinesterase

b MSC: Maximum Safe Concentration

c Concentration (mg/m3) = 0.001

d Concentration (mg/m3) = 5


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