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Appendix C
Example Use of Probits for Developing
Chemical Casualty Estimating Guidelines
INTRODUCTION
Chemical casualty estimating guidelines (CCEGs) were introduced by
the subcommittee for the purpose of better informing commanders of poten-
tial decrements in troop strength that might jeopardize the ability of troops
to successfully complete missions. The CCEGs will provide data sets that
can be used quantitatively to estimate the nature and extent of impacts on
mission performance. Specifically, CCEGs are tools by which the severity
of adverse outcomes to mission accomplishment can be estimated from
chemical concentrations. Generally they will be set for atmospheric com-
pounds whose toxic potency is quite high. The application of these tools
will generate specific response rates (e.g., 25%, 50%) for defined concentra-
tions of chemicals in the breathing zone of military personnel.
The health impacts of chemical agents generally form a continuum from
mild physical or sensory alterations—such as mild skin irritation—that pose
distractions but are easily accommodated, to impairment of vision and
balance that might limit effective use of battlefield equipment, to central
nervous system (CNS) depression that would limit necessary cognitive
functions, to asphyxiation or serious organ damage and failure leading to
death. The medical outcome depends directly on the delivered dose and the
inherent toxicity of the chemical. For airborne substances, exposures are
characterized by the concentration(s) in air at the breathing zone and the
duration of contact.
145
OCR for page 146
146 APPENDIX C
For field commanders to make informed choices between one course of
action and another, arguably less dangerous one (within the context of an
assortment of many types of risks), appropriate comparisons must be made.
Two types of information in particular are needed to make such compari-
sons of estimated impacts on troop viability and vulnerability: (1) the sever-
ity of the immediate medical consequences during the course of the mission,
and (2) the likely number of troops affected in the exposure scenario envi-
sioned during the course of the specific mission.
OBJECTIVE
The purpose of the exercise reported herein is to explore the feasibility
of using an approach that relies in part on probit analysis to describe, for
three levels of severity (mild, moderate, and severe), the expected exposure-
incidence response for the reasonably healthy young adults that comprise
the deployed population. As discussed in Chapter 4, this is not a definitive
protocol for how to develop CCEGs. Rather, it is an example of one possi-
ble approach. The subcommittee recommends that the U.S. Department of
Defense (DOD) develop guidance for establishing CCEGs and have that
methodology peer-reviewed before application (see Chapter 4).
This analysis focuses on inhalation as the dominant pathway of expo-
sure for military personnel. Unlike military exposure guidelines (MEGs)
and other methods to identify levels of exposure that are unlikely to cause
injury, the CCEGs (as envisioned here) are media-specific chemical concen-
trations expected to cause health impairments sufficient to reduce unit
strength and therefore pose what the Army calls a medical threat. They are
designed to evaluate course-of-action options that are expected to involve
chemical exposures. Combat situations can result in human casualties that,
although undesired, must nevertheless be tolerated to achieve military ob-
jectives. With that in mind, CCEGs allow commanders to weigh chemical
risks against other operational risks and decide which chemical risks should
be avoided and which must be borne for the sake of the mission.
Note that the approach described herein is intended to produce informa-
tion about potential health impacts in a form that would allow field com-
manders to compare the impacts on the achievability of mission objectives
from an assortment of chemical and nonchemical hazards that could de-
grade mission effectiveness. That is accomplished by using an approach
that estimates the percentage of troops likely to be incapacitated (and the
nature and duration of that incapacitation) by exposures to toxic agents.
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APPENDIX C 147
Such output is comparable to outputs from other processes that estimate, for
example, casualties from enemy fire or from weather conditions that might
disable mechanized equipment.
APPROACH AND ORGANIZATION
The probit analysis the subcommittee envisions is predicated on having
available incidence data for acute toxicity (i.e., for effects that materialize
within minutes to several days following initial exposure). Those data must
be reliable to provide useful guidance; peer-review is one major means of
achieving the desired level of reliability and predictability.
To be most useful, the toxicity data should span three levels of severity:
• Mild pathological responses. Most commonly sensory discomfort
and irritation and some mild non-sensory effects observed in groups con-
taining a range of normally distributed susceptibilities that would also be
found in populations of healthy, young adults.
• Moderate pathological responses. Temporarily debilitating sys-
temic dysfunctions in groups containing a range of normally distributed
susceptibilities that would be found in healthy, young adults.
• Severe pathological responses. Reversible or irreversible damage
to organ functions that is incapacitating, life-threatening, or actually lethal
observed in groups comparable to healthy, young adults.
This scheme resembles the graded acute exposure guideline levels (AEGLs)
of the U.S. Environmental Protection Agency (NRC 2001) in several re-
spects, and similar classifications might be adopted for CCEGs.
The data should be subjected to some form of weight-of-evidence anal-
ysis in which the quality of the data are examined critically and the degree
of consistency and concordance is evaluated closely. That process should
include some decision rules for determining the relative value of and reli-
ance on primarily human and secondarily animal data, and vice versa.
Several compounds were identified as prospective candidates for this
feasibility exercise. The compounds are divided into two groups: (1) those
for which AEGLs have been published (NRC 2000, 2002, 2003), and (2) a
sampling of compounds identified in U.S. Army Center for Health Promo-
tion and Preventive Medicine’s Technical Guide 230 (TG-230), but not
included among the AEGLs, that would likely have some applicable inci-
dence data. The compounds in each group are listed in Table C-1.
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148 APPENDIX C
TABLE C-1 Candidate Compounds
Compounds in TG-230 with AEGLs Compounds in TG-230 with No AEGLs
Aniline Acrolein
Arsine Ammonia
Diborane Benzene
Dimethylhydrazine Carbon tetrachloride
Hydrogen cyanide Carbon monoxide
Hydrogen sulfidea Ethylene oxide
Methyl isocyanate Formaldehyde
Monomethylhydrazine Hydrazine
Nerve agents: GA, GB, GD, GF, VX Methyl bromide
Phosgene Toluene diisocyanate
Propylene glycol dinitrate
Sulfur mustard
1,1,1,2-tetrafluoroethane (HFC-134a)
1,1-dichloro-1-fluoroethane (HCFC-
141b)
a
A draft AEGLs document is available, but has not yet been finalized.
From among the candidate compounds, seven substances were selected,
and their acute toxicity data was analyzed to obtain data relevant to the
plotting of incidence on the basis of the three categories: mild, moderate,
and severe. The dose unit selected for this exercise, a reflection of exposure
via the inhalation pathway, is parts per million-hour (ppm-hour) (and ppm-
minute [min] for acrolein), which is the product of concentration and time
(C × t). To the extent possible, the same unit was used for all plots to sim-
plify comparisons. Probits were plotted for the log-dose versus the log-
percent response between 2% and 98% (see data sheets and graphs at the
end of this appendix; note that the probit scale is on the left side of the plot).
Each curve was derived by plotting the values for the data. Alternatively,
however, probit values could also be calculated against log-dose. Indeed,
calculating at least two probit values for each curve offers the advantage of
being able to estimate any point on the curve in order to estimate the ex-
pected consequences for specific log-doses. In either case, the plots can be
computerized to facilitate field comparisons of medical consequences from
exposures to toxic agents.
Doses were obtained from data derived from observations of either
humans or laboratory animals. For simplicity, uncertainty factors were not
used in the analysis. However, when the selected doses were obtained from
data from laboratory animals, consideration was given to adjusting the
inhalation doses for differences in inhalation rates and metabolic rates be-
tween humans and the test species. When adjusting the doses, consideration
OCR for page 149
APPENDIX C 149
was given to the application of a methodology that was proposed by EPA
(1994) in its guidelines for the derivation of reference concentrations (RfC)
for substances present in ambient air. The subcommittee authoring this
report chose its own set of relatively simple decision rules for these exam-
ples. Those rules were applied to achieve dose-equivalency for inhaled
substances when using probit analysis to estimate the number of potential
casualties from short-term exposures to toxic agents. Ultimately, DOD
would need to develop its own approach and have it peer-reviewed. The
decision rules used here apply solely to situations in which human doses are
estimated from laboratory animals. They include the following:
• If a substance causes local toxicity (e.g., skin or lung irritation), the
inhaled concentration for humans is set equivalent to that obtained from the
data in laboratory animals. This was applied to acrolein and sarin (“mild”).
• If the substance causes systemic toxicity (e.g., CNS depression) and
the effect is caused by the parent substance or stable metabolites (i.e., half-
life measured in hours or more), the inhaled concentration for humans is set
equivalent to that obtained from the data in laboratory animals. This was
applied to aniline, hydrogen cyanide, and sarin (“severe”).
• If the substance causes systemic toxicity (e.g., liver injury) and the
effect is caused by the reactive parent substance or highly reactive metabo-
lite(s) (i.e., half-life measured in minutes), the inhaled concentration for
humans is estimated by adjusting the concentration obtained from the data
in laboratory animals in accordance with the body weight of the species to
the -0.75 power, because there exists considerable evidence for the validity
of such a procedure (Clewell et al. 2002; NRC 2001). This was applied to
dimethylhydrazine and propylene glycol dinitrate.
The results of this process were estimated doses for humans that were con-
sidered equipotent in their toxic severity.
FINDINGS
The compounds evaluated in detail are aniline, 1,1- and 1,2-dimethyl-
hydrazine, hydrogen cyanide, propylene glycol dinitrate, acrolein, the
chemical warfare agent sarin, and hydrogen sulfide. AEGLs values were
available for all of these compounds except acrolein. The relevant informa-
tion for each compound is described at the end of this appendix on two
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150 APPENDIX C
pages: (1) a fact sheet with a summary of the relevant data for the subject
compound and (2) the actual plot of the data.
These compounds span a range of chemical classes and acute toxicolog-
ical manifestations. However, this is merely a small sample that was useful
for an initial feasibility study; the exercise would need to be expanded to
draw any firm, generalized conclusions about the validity of this means of
data analysis and visualization.
With the exception of acrolein, the interpretations of the raw toxicity
data on which the chemical plots were based were adopted directly from the
AEGL documents (NRC 2000, 2002, 2003; EPA 2002). Reliance on those
documents provides a strong element of peer-review that should minimize
controversy about data selection and application. Note also that, in many
cases, the dose-response relationships are bounded by only a few points and
that some points require inference from the range of toxicological informa-
tion available for a substance. Ultimately, however, the plots enable identi-
fication of all values along each curve.
The results indicate that, for the compounds examined, it is generally
possible to obtain estimates of toxicological impacts within each of the
three categorical groups of severity in terms of the fraction of a group im-
pacted. The exception was dimethylhydrazine. There were no data on that
chemical suitable to estimate the frequency of dose-dependent, mild adverse
consequences. Also, the information on acrolein is somewhat different
from that on the other compounds. For both mild and moderate impacts, the
irritation effects are more time-dependent than they are for the other com-
pounds; but for severe outcomes, the impact can be scaled by concentration,
keeping time fixed.
Aniline and hydrogen cyanide had the most directly applicable data
sets; the data sets for the other compounds were less robust for the purpose
of this report. This leads to perhaps the most vital observation: this ap-
proach, regardless of its desirability, might be impractical for several rea-
sons. First, the number of compounds having toxicity data in the form
required for the approach to be functional appears to be very limited. Al-
though many studies describe changes in pathological severity with increas-
ing doses, they report far less often on the incidence rates in members of the
groups observed. That is particularly true for human studies. Indeed, many
human studies are merely case reports, and they have the added limitation
of having either no exposure data or data that are highly imprecise.
Available animal studies of acute toxicity also have major limitations.
Although most compounds have been tested for lethality (lethal dose in
50% of subjects [LD50] and lethal concentration in 50% of subjects [LC50]),
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APPENDIX C 151
few have been tested for less severe effects. Only longer-duration studies
report on sublethal effects and the frequency of responders. Another major
limitation is the lack of statistical power. Studies deemed most toxicologi-
cally significant often have been performed in dogs or monkeys. Such
studies frequently use only three to five experimental subjects per group.
Thus, the points on the subcommittee’s probit plots appear to be more pre-
cise than they actually are. This limitation precluded the calculation of
standard deviations around data points or confidence intervals around
curves.
Table C-2 provides an example of how CCEGs could be used to esti-
mate impacts on troop strength. For the seven example chemicals, the
concentrations estimated to severely affect 15%, 30%, 40%, and 50% of the
unit are tabulated to correspond to the affiliated operational risk-manage-
ment (ORM) risk level and unit status, assuming that the fraction F of the
unit exposed is F = 1.0 (i.e., that 100% of the unit is exposed). A measured
or modeled concentration for a given chemical could be compared with the
values in the table to estimate the potential impact on missions. (See Chap-
ter 4 and Appendix E for how to estimate mission impacts for cases in
which only a percentage of the unit is exposed. See Appendix E for how
to estimate impacts from exposures to multiple chemicals.)
CONCLUSIONS
Military field commanders need reliable estimates of the nature and
magnitude of health impairment resulting from toxic exposures to agents
that could be encountered during missions that have military objectives.
This process seems comparable to the estimation of battle casualties when
planning missions with combat roles.
Estimating toxic effects that might impair the performance of deployed
units during missions is theoretically possible by evaluating the limited
number of acutely toxic agents that could be encountered in some battlefield
conditions. However, the data needed to perform those evaluations and to
obtain reliable estimates easy to use in the field (e.g., graphic representa-
tions) appear to be available for only some of the substances of interest to
the military. Furthermore, for those compounds for which estimates are
feasible and graphic displays are possible, the information should be applied
with some understanding of the strengths and limitations of the data, and
caution should be exercised to avoid placing too much confidence in the
seeming precision of numerical values.
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152 APPENDIX C
TABLE C-2 Sample CCEGs for Seven Chemicals for “Severe”
Responsea
Approximate Concentration in Breathing Zone
(ppm-hour)
Chemical C15 C30 C40 C50
Aniline 1,400 1,600 1,800 1,850
1,1-Dimethylhydrazine 250 540 800 1,400
Hydrogen sulfide 640 680 700 710
Hydrogen cyanide 95 115 130 140
Propylene glycol dinitrate 40 70 90 120
Acrolein 34 40 45 48
Sarin 10 30 52 90
Evaluation Degree of Medical Threat
% of unit severely affected, P* 15% 30% 40% 50%
Unit troop strengtha 85% 70% 60% 50%
a
ORM risk level Low Moderate High Extremely
High
Unit statusa Green Amber Red Black
a
Assumes 100% of the unit is exposed.
Abbreviations: C15, concentration estimated to effect 15% of the unit; C30, concentration
estimated to effect 30% of the unit; C40, concentration estimated to effect 40% of the unit;
C50, concentration estimated to effect 50% of the unit.
Unit Status
Black: Unit requires reconstitution. Unit below 50% strength.
Red: Combat ineffective. Unit at 50-69% strength.
Amber: Mission capable, with minor deficiencies. Unit at 70-84% strength.
Green: Mission capable. Unit at 85% strength or better.
OCR for page 153
APPENDIX C 153
FACT SHEETS AND PROBIT PLOTS1
Acrolein
Mild Effects—irritation of eyes, nose, and throat
NOAEL (human) = 0.1 ppm for 8 hour
Data (human) from Stevens et al. 1961:
0.5 ppm-5 min 25% response
? ppm-min 50% response (estimated)
0.5 ppm-12 min 90% response
Mode of toxic action: local tissue damage on immediate contact, with increasing time
of contact
Allometric scaling: not applicable
Uncertainty factors: none
Data plotted for humans:
2.5 ppm-min 25% response
3.8 ppm-min 50% response (estimated)
6.0 ppm-min 75% response
Moderate Effects—severe irritation of eyes, nose, and throat; respiratory distress
Data (human) from Sims and Pattle 1957:
1.2 ppm-5 min 25% response
2.5 ppm-5 min 50% response (estimated)
8 ppm-10 min 75% response
Mode of toxic action: local tissue damage on immediate contact, with increasing time
of contact
Allometric scaling: not applicable
Uncertainty factors: none
Data plotted for humans:
6.0 ppm-min 25% response
3.8 ppm-min 50% response
? ppm-min 75% response
Severe Effects—respiratory failure to mortality
Data (rat) from Smyth 1956
8 ppm-4 hour 8% response
10 ppm-4 hour 25% response (estimated)
12 ppm-4 hour 50% response (estimated)
14 ppm-4 hour 75% response (estimated)
(Continued)
1
The data used and values reported herein are provided for illustrative purposes only.
OCR for page 154
154 APPENDIX C
Acrolein (continued)
Mode of toxic action: local tissue damage on immediate contact, with increasing time
of contact
Allometric scaling: 1:1 for rat:human
Uncertainty factors: none
Data plotted for humans:
32 ppm-hour 8% response
40 ppm-hour 25% response
48 ppm-hour 50% response
56 ppm-hour 75% response
Mode of Action: tissue damage on immediate contact, cumulative with time of
contact
Dose-duration relationship: linear, C1 × t = k (?)
Delayed sequellae: decrements in respiratory function
For comparison: OSHA PEL = 0.1 ppm-8 hour
OSHA STEL = 0.3 ppm-15 min
OCR for page 155
ACROLEIN
98
98
7.0
7.0
Mild Response
95
95
Moderate Response
6.5
6.5 Severe Response
90
90
85
85
6.0
6.0
80
80
75
75
70
70
5.5
5.5
60
60
50
5.0 50
5.0
40
Probits
40
4.5 30
Percentile Response
4.5 30
25
25
20
20
4.0
15
15
4.0
10
10
3.5
3.5
5
5
3.0 2
3.0 2
1 4 7 3 4 5 2
1 22 33 45 56 7 8 9 10
6 9 10 22 3 5
4 6 7 8 89 91000
67 1 2 33 4 4 5 5 6 6 8 98 9
77
Log Dose (ppm-min) Log Dose (ppm-hour)
155
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164
HYDROGEN CYANIDE
98
98
7.0
7.0
Mild Response
95
95
Moderate Response
6.5
6.5 Severe Response
90
90
85
6.0 85
6.0
80
80
75
75
70
70
5.5
5.5
60
60
Probits
50
5.0 50
5.0
40
40
4.5 30
Percentile Response
30
4.5
25
25
20
20
4.0
15
15
4.0
10
10
3.5
3.5
5
5
3.0
3.0 22
1 2 3 5 2 3 5 6 2 3 5 7
1 2 34 4 6 77 8 69 10
5 8 9 10 2 34 5 6 77 8 89 1001 0 0
4 9 2 34 4 6 5 86 9 7 8 9
Log Dose (ppm-min)
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APPENDIX C 165
Hydrogen Sulfide
Mild Effects—eye pain, photophobia, headache, irritation
Data (human) from WHO 1981 and Vanhoorne et al. 1995:
6 ppm-hour 0% response
? ppm-hour 50% response
? ppm-hour 75% response
Mode of toxic action: direct effect on contact; edema systemically
Allometric scaling: not applicable
Uncertainty factors: none
Dose-duration relationship: log, C4.4 × t = k (Note - may not apply to all asthmatic
individuals)
Data plotted for humans:
6 ppm-hour 0% response
Source: EPA 2002
Moderate Effects: lacrymation, photophobia, corneal opacity, tracheobronchitis,
central nervous system depression, nasal passage necrosis
Data: insufficient
Dose-duration relationship: Cn × t = k (Note – might not apply to all asthmatic indi-
viduals)
Source: EPA 2002
Severe Effects—cerebral and pulmonary edema to respiratory arrest to
unconsciousness to death
Data (rat) from MacEwen and Vernot 1972:
635 ppm- hour 10% response
712 ppm- hour 50% response
800 ppm- hour 90% response
Mode of toxic action: pulmonary and cerebral edema
Allometric scaling: 1:1 for rat:human
Uncertainty factors: none
Data plotted for humans:
635 ppm-hour 10% response
712 ppm-hour 50% response
800 ppm-hour 90% response
Source: EPA 2002
Mode of Action: inhibition of electron transport in tissues with high oxygen demand
Dose-duration relationship: varies with types of responses
Delayed sequellae: none known or anticipated
For comparison: AEGL-1 = 0.51 ppm-hour; 0.33 ppm-8 hour
AEGL-2 = 27 ppm-hour; 17 ppm-8 hour
AEGL-3 = 50 ppm-hour; 31 ppm-8 hour
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166
HYDROGEN SULFIDE
98
7.0
Mild Response
95
Moderate Response
6.5
Severe Response
90
85
6.0
80
75
5.5 70
60
Probits
5.0 50
40
4.5
30
Percentile Response
25
20
4.0
15
10
3.5
5
3.0
2
10 2 3 4 5 6 7 8 9 100 2 3 4 5 6 7 8 9 1000 2 3 4 5 6 789
Dose (ppm-hour)
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APPENDIX C 167
Propylene Glycol Dinitrate
Mild Effects—headache
NOAEL (human) = 0.03 ppm for 8 hour
Data (human) from Stewart et al. 1974:
0.1 ppm-hour 25% response
0.2 ppm-hour 50% response
0.4 ppm-hour 75% response
Mode of toxic action: reactive metabolite produces vasodilation of cerebral vessels;
decreased blood pressure
Allometric scaling: not applicable
Uncertainty factors: none
Data plotted for humans:
0.1 ppm-hour 25% response
0.2 ppm-hour 50% response
0.4 ppm-hour 75% response
Source: NRC 2002
Moderate Effects—severe headache, slight loss of equilibrium
Data (human) from Stewart et al. 1974
0.5 ppm-hour 25% response (estimated)
1.0 ppm-hour 50% response
2.0 ppm-hour 75% response (estimated)
Mode of toxic action: reactive metabolite producing vasodilation of cerebral vessels;
decrease in blood pressure
Allometric scaling: not applicable
Uncertainty factors: none
Data plotted for humans:
0.5 ppm-hour 25% response
1.0 ppm-hour 50% response
2.0 ppm-hour 75% response
Source: NRC 2002
Severe Effects—vomiting, central nervous system depression, semi-consciousness,
clonic convulsions, mortality
Data (monkey) from Jones et al. 1972:
33 ppm-hour 25% response (estimated)
70 ppm-hour 50% response (estimated)
140 ppm-hour 75% response
280 ppm-hour 100% response (estimated)
(Continued)
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168 APPENDIX C
Propylene Glycol Dinitrate (continued)
Mode of toxic action: reactive metabolite producing decreased systolic pressure; in-
creased diastolic pressure; myocardial eschimia; increased MetHb
Allometric scaling: (body weight)-0.75
Uncertainty factors: none
Data plotted for humans:
60 ppm-hour 25% response
119 ppm-hour 50% response
238 ppm-hour 75% response
Source: NRC 2002
Mode of Action: cardiovascular toxicity and central nervous system depression
Dose-duration relationship: linear, C1 × t = k; for severe, long-duration extrapola-
tion C3 × t = k
Delayed sequellae: none identified
For comparison: AEGL-1 = 0.17 ppm-hour; 0.03 ppm-8 hour
AEGL-2 = 1.0 ppm-hour; 0.13 ppm-8 hour
AEGL-3 = 13 ppm-hour; 5.3 ppm-8 hour
OCR for page 169
PROPYLENE GLYCOL DINITRATE
(PART 1)
98
7.0
Mild Response 95
6.5
Moderate Response
90
85
6.0
80
75
70
5.5
60
5.0 50
Probits
40
4.5
30
Percentile Response
25
20
4.0
15
10
3.5
5
3.0
2
0.01 2 3 4 5 6 7 8 9 0.1 2 3 4 5 6 7 8 9 1.0 2 3 4 5 6 789
Log Dose (ppm-hour)
169
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PROPYLENE GLYCOL DINITRATE
170
(PART 2)
98
7.0
95
Severe Response
6.5
90
85
6.0
80
75
70
5.5
60
50
5.0
Probits
40
4.5
30
Percentile Response
Percentile Response
Percentile Response
Percentile Response
25
20
4.0
15
10
3.5
5
3.0
2
10 2 3 4 5 6 7 8 9 100 2 3 4 5 6 7 8 9 1000 2 3 4 5 6 789
Log Dose (ppm-hour)
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APPENDIX C 171
Sarin (GB)
Mild Effects—miosis, rhinorrhea
NOAEL (human) . 0.016 mg/m3 for 20 min
Data (human) from NRC 2003:
0.32 mg-min/m3 0% response
? mg-min/m3 25% response
4 mg-min/m3 50% response (ECT50)
? mg-min/m3 75% response
Mode of toxic action: local
Allometric scaling: not applicable
Uncertainty factors: none
Data plotted for humans:
0.32 mg-min/m3 0% response
4 mg-min/m3 50% response
Moderate Effects—insufficient data
Severe Effects—acetylcholinesterase inhibition to convulsions to mortality
Data (monkey) from NRC 2003:
1 mg-hour/m3 1% response (estimated from rat data)
? mg-hour/m3 25% response
27-150 mg-hour/m3 50% response
? mg-min/m3 75% response
Mode of toxic action: stable metabolite leading to acetylcholinesterase inhibition
Allometric scaling: 1:1 for monkey:human
Uncertainty factors: none
Data plotted for humans:
1 mg-hour/m3 1% response
90 mg-hour/m3 50% response
Mode of Action: inhibition of acetylcholinesterase leading to convulsions and then
to death
Dose-duration relationship: linear, C2 × t = k (?)
Delayed sequellae: delayed neuropathy
For comparison: AEGL-1 = 0.0028 mg-hour/m3
AEGL-2 = 0.035 mg-hour/m3
AEGL-3 = 0.13 mg-hour/m3
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172
SARIN (GB)
98
7.0
Mild Response 95
6.5 Severe Response
90
85
6.0
80
75
70
5.5
60
50
5.0
Probits
40
4.5
Percentile Response
30
25
20
4.0
15
10
3.5
5
3.0
2
0.1 2 3 4 5 6 7 8 9 1.0 2 3 4 5 6 7 8 9 10 2 3 4 5 6 7 89
Log Dose (ppm-min) Log Dose (ppm-hour)
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APPENDIX C 173
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Representative terms from entire chapter:
laboratory animals