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.,

DEPARTNENT OF iHE AR1iY


EIX:EW0oD ARSENAL
Technical Support Dlrectorete
Aberdeen Proving .Ground, Naryland21010

ERRATUN SHEET

REPORT NO . . :

EB-TR-760Z3

TIPLE : Estimatea of the Toxlclty of Hydrocyanlc Acid Vapors !n


!7a n
AUTHOR :
DATE :

B . . P . McNamara, Ph .D . .

February

1976

CLASSIFICATI~ON
: UNCLASSIFIED Please change date on Cover and DDForm 1473 from .

February 1976 to August 1'876 .

HElIRY 7 . BIELECKI
Chief, Technical Relesaea Division
Technical Support Directorate

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Human estimates Toxiaty
Hydrocyanic add
N.

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hen the data pn which 1he Iateamtlonally accepted F,C130 of Inhaled hydrocyanle acld (AC . HCN) vapnn in

man .etc revierad and thee llgum ptA -kbsd wWely In sdantlfk journals twxe .mined, it .nc dedded that morc

v.lW ntlm+rel of the toc/cltyo( 1lCH In man should ee LCt'L fac 1% . 1(,%. 7096 . SO% . 81% . ud 99% of .f
i an cxposed popu W Im tor eapwure timr of frorn 03 to 30 mtnuta w~erb dxiwd . Because of the p[ucity of data on
o,mrDued experirnwns aMh man, h wwaa nace.nry lo D, anhnfl dats . Among the nwmptlom made were that man
, rew into die apadu that an nLtMly r..latast to HCN : that mm r er leat u realuant r the goat : and that man Is
at least foutt tima as redalant a the muuae . The valur deriwd an gtvM
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n .

PREFACE
The work desentxd in this report was authorrzed under Protect/Task

N'r . `-I NA1)'101 , Toxi .otogy of !'hemical Agents . This report is a review of existing data . .

In c mducting the resaarch descrilxd in this report . the investigator adhered to the
t :wdc h:r the ('are and Use of Laboratory Animah" as promulgatcd by the Committce on
Revr.ion ul the Guidc for Laboratory Animals Facilities and f' .ire of the Institute of Laboratory
Anun .d Renourccs, .National Research Council .

The use of trade names i:r this report does not ,o n stitute an ofGcial endorsement or
.~ppn+ . :d o1 the use of such commercial hardware or softwarc . Ttus report may not be cited for
t\IlrtMly'

PI

advertisement .

Rrpmduction of this document in whole or in part is prohiMtedexcept with


txrrrucsron nf the Commander, Edgewood Arsenal, Attn : SAREA-TS-R. Aberdeen Proving Ground,
Maryland _1010 : however ; DDC and the National Technical Information Service are authorized to
reprcalu,c the document for USGovernment purposes .
Acknowledgments
The author acknowledges the cooperation of Mn. Martha Langan . Mrs . Marion
Rrqston . and Miss Fonda Jackson inn preparing this manuscript .

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CONTENTS

I INTRODVCTION~.

11 BACKOROUND .

A . Previously Accepted Estimates of the Toxicity of HCN in Man


I . Military Estimates . . . . . . . . . . . . . . . . .
2 . Origin of Widely Published Open Literature Estima :cs .B . Toxicity Data on Deliberately Expns :d Men .

niaiPc

.
.

.
5
. . N

.I

13

111 . l'URRtNT RECOMMENDED AND APPROVED ESTIMATES OF THE


TOXICITY OF HCN VAPORS IN MAN
. . . . . . . . . . . . .

13

13

C . Toxicity Data on hmmals .

A . Derivation of the Estimates . . . . .

B . Ltmitations of the Estimate

. .

LITERATURE CITED

. .

DISTRIBUT7ON LIST

. .

. .

. .

.. .

. .

. .

. .

. .

.. .

. .

19

21

23

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I SfIMA?FS r"` T' :f T(lYl('ITYGr nr uROCYANI(' ACU) VAIirHS IiN MAN


I INTRODU(TION
A reexamination nl Ihr e .timated LCI's for tnhaledhydrncyanic acidlAC . f1(-\,
. .q+or. revealed that the mternatmnally accepted Ggure of 50(H/ rng min/cu mt and thc fiEUrrpuhh .h :d in scientific journals were invalid for reasons explained in this rcprut . A new c .hmarcc h . .
hren prnppsed . .

11 BACKGROUND .
A . Previously Accepted Estimates of the Toxii :ity of HCN in Man .
I . Military Estimates .
a . Departmenl of the Army Technical Manual 3-215 . Military Chemistny and
Chemical Agents . December 1963 . p 19?
The following is cited from this reference : "Median lethaldosage varies widely with
:oncentration- because of the rather high rate at which AC is detoxified by the body . For example .
at 200 mg/m3 concentration, the lethal dosage is approximately 2000 mg min/m3, whereas at
I SO mg/m3 thee lethal dosage is approximately 4,500 mg min/m3 ."
These estimates appear to be based on mouse data without consideration of specic,
difference in toxicity (see table I) .
b . Summary Technical Report of Division 9 . NDRC, Vol 1 . Chemical
Warfare. Agents and Related Chemical Problems, Washington . 1946. p 12 .1
As mentioned above, the estimates of 2000 mg min/cu m(200 mg/cu m for
Iv minutes) and 4500 mg min/cu.m (150 mg/cu m for 30 minutes) appear to be based .on mouse
data without consideration that the mouse is known to be more sensitive than man to HCN' . (Scc
table I .)
Moore and Gatestestimated the LCtSO for HCN in man in the following manner :
The intravenout LD50's for HCN
0 .99 for dog, .cat, monkey, rabbit, guinea pig,
other mammak . an intravenous LDSC of 1 .1
different species are stimulated to different
rabbit, and 1 .5-fold in the guinea pig .

in mg/kg are 1 .34, 0 .81, 1 .30, 0 .66, 1 .43, 0 .81 . and


nt ; and mouse, respectively . Assuming man to bc like
mg/kg was estimated for man . The minute volumes of
degrees by HCN : 7-fold in the dog . 2- to 3-fold in the

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Tlxintravenous rnlection of cyanide snmulatn rerppr.non in man to vanou, depecN

deprndmp upon.dose and apectf of adrnrnrstntson . IHowever_ Barcmfts could detect no cffc .r . .+r
resprranon when a con:ntratron of about 550 mg/cu m was tnsprred .I

The detoxruuon rate for HCM infectedmtnvenously in mar, n


tl (I .I 7 mg .!kglmm . Thn .value is not markedly different for animah

.dvmt

The LCt50 was calculated from the following formula


VaC - Dt = K
where
V= total volume of air breathed in liters/kp
. a .- fraction of inhaled gas absorbed (70'F measurad in doga r.
C = concentration in mg/liter

D= nte of detoxication in mg/kg/mih


t exposure time in minutes
K= lethal dose in mg/kg
For a 70-kg man breathing 25 liters for I minute . the calculation would be :
0 .361iten/kg X 0 .7 X C-0 .017 mg/kg/min .x I min = 1 .1 mg/kg
C- 4 .4 mg/h ter, or 4400 mg/cu m

The LCt5O for I minute would be 4400 mg min/cu m . Values for other exposure times
ar.d breathing rates calculated by this method are shown in table 2 . An earlier calculation of this
type by British investigators led to the internationally agreed estimate of 5000 mg min/cu m for . the
LCt50 for HCN in man .
Table 2 . LQ50 Estimates for NCN in Man Calculated
by the Moore-Gates Formula
Expowre
time

LCtSrJ's

251iten/min

15 Gters/min

Concentration

Ct

Concentn6on

Ct

min

mg/cu m

mg min/cu m

mg/cu m

mg min/cu m

0.5

8,800

4,400

14 .400

7,200

4,400

4,400

7,590

7,590

1,500

4,500

2,610

7 .830

10

504

5,040

860

8,600

30

210

6,300

360

10,800

60

140

8 .400

240

14,400

' Breathing nte .


7

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The LC I50's calculated lor man aree much higher than those for even the most resictant

arumal cpeaes . . The calculations include two mator assumptions : the intravenous LD50 of
: I1 mN .'kR and the pulmonary.ahsorpuun of 70% .
I

(kigin of Widely Published Open Literature Estimates .

The most widelvpublished values for the toxicity of HCN vapors in man are reported
to have originated with . K . B .Lehmann prior to 1912 . A report by Kobert9 is the firstt journal
publication reference to the work of Lehmann . Kobert's paper and the numerous subsequent
cttanons of the worY: consistently presented toxicity values for man without developing the
experimental basis for the values . As shown below, .prior to 1919Lehmann studied, lh~ toxicity of
fiCti in rabbits onlyanddeciined from making quantitative statements concerning the toxicity of
HCN for manJa
.
The following abstracts are given for historical purposes and to show the common
ongin ol' toxicity values which are accepted for HCN in man .
a .Kobert, Rudnlph (Kompendium der Praktischen Toxikoingie zum
Gebrauche 1Lr Arzto, Studierende und Medizihalbeamte . Ferdinand Enke,
Publisher, Stuttgart, 1912) .9
This compendium presents a table which was credited to K . B . Lehmann . There was no
indication of whether the toxicity estimates for man were based on human or animal experiments,
or whether there was any basis for the values .

The following citztions were made by Kobert :


"Concentrations (parts per thousand by volume) . . . of HCN which:

Producarapid death for man and animals

0 .3

Are dangerous to life after 1/2-1 hr

0 .12-0 .15

May be tolerated for 1/2-I hr without severailiness

0 .05-0 .06

Cause only minimal symptoms after several hours exposure

0 .02-0 .04

Multiply by 1000 to convert to parts per million ."

b . Henderson, Yandell, and Howard W . Haggard (Noxious Cases and the


Prindpks of Respintion Influencing Their Action . The Chemical Catalog
Co ., lnc ., 1927 N . Y ., N . Y ., pp 110-112) .l s
In 11027 . Henderson and Haggard reported the work cf KobertO as follows :

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"Physiologieal Response to Various Concentrations of Hydrocyanic Acid Gas


Parts of Hydrogen Cyanide Per Million
Parts of Air
Several symptoms after several hours expcsure

20 to 40

Maximum .amount that can be inhaled for 1 hour


without serious disturbance

50 to 60

Dangerous in 30 minutes to I hour

120 to 150

Rapidly fatal

3,000

. Kobert . R ., Kompend- der Prak .


.'ozikol
Stuttgart,
.
1912."

- Note thatt the rapidly fatal value of 3000 ppm, as given by Hendersonand Haggard,t I
does uot agree with that given by Y.obert9
c. - Flury, F ., and F . Zemik (Sch'rd6che Gase, Springer, 1L1) .t 2
Flury and Zemik stated that the degree of toxicity of inhaled HCN for man is probably
the same as f .,r the monkey, the dog, or the cat . The following table was prexnted .
"Toxicity of Inhaled HCN According to Lehmann-Hess

mg/I

!`irts e : Vapor in
I :
. ullion (cm3/m3 )
about :

Immediatelv fatal

0 .3

270

Fatal after 1/2-I hr, or later

0.12-0 .15

I 10-135

Dangerous to life after 1/2-1 hr


(Hess)

0 .12-0 .15

l 10-135

Tolerated for i/2-I hrwiG .nut


immediate or :ate ;ffects

0 .05-0 .06

45-54

Slight s, mptoms after several


hours (Hera)

0 .02-0 .04

18-36

Toleruted 6 hrs without symptoms

0.02 (-0 .04)

l8 (-36)

' I mg/kg Inhaled HCN it absolutely fatal to man according to Lihmann :'

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d . Dudley, H . C ., T . R . Sweeney' and 1 . W . Mrllcr (ToxicoioFy ul


Aaylonilrile (Vinyl Cyanide) . 11 Ind . tlvg . TioxicA ?4 =55-'5x
(1942)1 .t3
~
Dudley et al .t 3 stated the following : " . . . Data nm the acutc ioxicity of hydrocyani'r
acid as published by Lehmanmand Hess and quoted from Flury.and 7.emik are summarized . ._"Toxicity of HCN'I forHumar.s (Flury and Zcrnik, 1931)
Concentration

mg/Gter

S ymp t oms

--- ._p .p .m .

Immediately fatal

0 .3

270

0 .12-0 .15

110-135

F3tal after 112 .1 hour or lnter or


dangerous to life

0 .05-0 .06

45-54

Tolerated for t, 2-I Eour without


immediate or late efdects

0 .02-0 .04

18-36

Some efkctsaftcr exposure for


several hours ."

e . Fassett, D . W . Cyanides and. Nitriles . Chapter XLIV in industrial Hygiene


and Toxicorogy . Patty, F . A .,eid) . 2d Edition . Volume 11 . interscience
Publishers, New York tSty . 1963 .14
A table similar to that appeating in Dudley et al .t 3 was presented in Patty's bookt 4 as
shown belOw :
"Physiological Response to Various Concentrations of
Hydrogen Cyanidain Air -Man'
Concentration

Response

mg/liter

p .p .m .

Immediately fatal

0 .3

270

Fatai after 10 min

0 .2

181

Fatal after 30 min

0 .15

135

0.12-0 .15

110-135

Tolerated for 1/2 to I hr without

0 .05-0 .06

45-54

Slight symptnnts after severaiAoun

0 .02-0 .04

18-36

Fatal after 1/2 to I hr or tater,


or dangerous to life .

immediate or late effects

'H . C . Daidley . T . P. Swney and J . W . MiL'cr,1 . ind . Hyg. Tuxicol :. 24 . 255 5 (1942)
F . Fluryand P . Zernik, SeMldhdie Gase, Springer . Bcrlln. 193 t"

10

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Lehmann, K . . B . . . Short Textbook on Mechanical an& Induslrial


Hygiene - S . Hirzel, .LeipziR, 1919 .1 0

All of the above references on the toxicity of HCN' in humans apparently originated
w nh t: . B . Lehmann prior to 191 2 when lirst quoted by Koberi .9 None of these references give the
vrperirnentalbasis for the human values . The publication .is not cited by any of those who quote
Lehmann . Our attemuts tolorrte such an article have been fruitless . .However, the above referenced
tcxlhnoR indicated t,tat the original research was performed only on mbbits . This publication statc,
ihe following : .
"I have studied the effect of HCN vapors quantitativtllywith my students Hagschal and
.4hlmano. Doses of 0-06 mg are tolerated well even after 5 hrs :0 .14 mg was tolerated by a rahhit
with some increased respiration even for 2 hrs ; others died even at 0 .13 mg in I hr, .and at (Y15 mF
irt 1 :.l'_ hr . At . 0 .2 mg even rfter 4 min . sudden collapse occurs : we saw an actual pulmonary
hemorrhage in a rabbit :poisnedwthHCNvapor(unilwbshedonlyit seraonutmysde)
. As yet we have not conducted experiments on cats and dogs . I can make no
quantitative statem-nts .about men . .- See Sehankies Dissertation, Konigsberg, 1918 ."
The doses, given by Lehmann as mg, appear to correspond with the parts per thousandnmg/liter)d
which were Tedited to Lehmann by Kobert .9
B . Toxicity Data on Deliberately Exposed Men .
In 1927, ( ;rubbsts reported that several volunteers breathed gas from 1/2- and
374 .ounce sodium cyanide per 1000 eu ft for 2 minutes and for 1-1 /2 minutes, respectively, without
feeling any e[fect, but that this has at other times caused dizziness. One-half ounce of sodium
cyanide in 1000 cu fl yields a concentration of about 501 mg/cu m of sodium cyanide . the
equivalent of about 276 mg/cu m of cyanide ion . Three-quarters ounce of sodium cyanide in
1000 cu ft yields a conctntration of 750 mg/cu m of sodium cyanide, equivalent to 401 mg/cu m of
cyanide ion . The respectiveCt's would be about 522 (2 minutes) and 602 (1-1/2 minutes) for
cyaniBcion ;and 1002 (2 minutes) and 1125 mg min/cu m(1-t/2 minutes) for sodium cyanide .
Katz and Longfellowt' cited the human exposures of Grubbs .1 S!n addition, they
stated thatirr experiments during the war, men had been exposed to concentrations of 500 ppm
(550 mg/cu m) for abou t I minute without injury .
Koritschoner (cited by Reid Hunt in Heffter's Handbook of Experimental
Pharmacologytl) exposed tuberculous patients to concentrations up to 20 mg/cu m for
120 minutes twice daily . These patients rapidly developed a tolerance to HCN .
In 1931, Barcrofta studied the toxicity of inhaled HCNN in man . The following is cited
from his paper .
"The question of where man stands in relation to the animal is most important . Clearly
it is very difficult to obtain exact information on this subjest, for when fatalities are octncerned the
concentrations which produce them are not known .
"The experiment about : to be desaibed shows, however, that man is not very
susceptible . It took place in the airti :ht chamber aheady described, the human suSject was about
45 years of age and weighed about 70 kg .

I I'

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"One human being .and one dog .(9bou( 12 kg)t were exposed simultaneously, without
protection, to an atmosphere containing a nominal concentration of I/I600hydrocyanicacidl'Ic the
actuai ooncentration being probablyIxtween th :t and 1/2000 .f'I
. The dog was placed in onecorner of the chamber, the man in the corner diagonally opposite to him, so that they faced one
another . The utmost care was taken lest if the dog succumbed first it should not be because its
respiration was stimu,ted by' a greater degree of muscular activity, .therefore each movement made
by the dog was followed by an imitative movement on the part~ of the man, so that the degree of
activityy of two might be as nearly as possible the same . This procedure was followed up to the point
at which the dog became unconscious . After that no effort was made by the man to imitate the
muscular spasms which form so conspicuous a feature of the later stages of cyanide poisoning . The
expenment ran the coursee as shown in the following notes which werc taken by the man as the .
expcriment proceeded .

"rime front Zero

Man

50 sec . . Became unsteady


I min . 15 sec . On floor unconscious
I min . 30 sec . Crying sounds and tetanic
convulsions sufficiently established
_ to render it probabkthat animal
was in extremis
I min . 31 sec .

Came

out

of

Utrtlt}IN

chamber and put


on respirator having felt no
symptoms. No apparent
dyspnea .

I min . 33 sec . Respiration apparently ceased, Re-entered chamber in respirator


animal believed to be dead, was for purpose of pulling out dog .
pulled out by lead . Having done this he remained
outside .
5 min .

?domentary

feeling

10 min .

of

nausea .

Attention difficult to concentrate in close conversation .

'Although the corpe was set adde for burial about .6 :30 pm, the dog dW In point of fact recover, and was
found walking about neat morning. It dtowed no further symptoms.

I lhe weight of this dng Is not rcoonted and the abore tlyura b guaatd from memory of Ita genersl appearanee .
It is lntended only to givean idea of the sort of dmd dog used ."

;// 1/ 1600 - 625 ppm, 689 ng/w m, . Ct, 1032 mg mio/cv m .


. . 1/2000 - 500 ppm, 550 mgku m, Ct, 825 mg ndn/eu m .

12
I

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I Cyanide is rapidly detosi0ed .1 t s However, there are somc accounts that Barcroft
suil'rred certain persistent eff,cts of this exposure for about a year .t92o It was stated that
Professor Barcroft suffered nausea and deflatte mental symptoms a few minutes after his
withdrawal from the gas atmosphere but that at Ieast some of these symptoms persisted for about a
ycar19 2 1 Continuing with the quote from Barcrofta - "A report by S . H . Katz and
P. . S . Longfellow from the American Bureau of Mines i .sued in July 1923 states : 'Men employed in
fumigation with HCN have been tcsted while at rest in 250 parts per million of air for 2 minutesf'I
and ?500 parts per million for 1-1 /2 minutesl"I but felt no dizziness, although possibly on exertion
they m4.ht have done so .' In experiments during the war men have been exposed to 500 parts per
million foi about a minute without injury . Hydrocyanic acid gas was formerly considered ; ne of the
deadliest gase~ in minute concentrations, but later experience, especially in the war, has shown that
man is more resistant than some other forms of life . -(Lshmann, Tabelle der Kleinsten Mengen .
w-ekhe allenfalls ertragen werdcn, in book by Kobert .KompendiurPaktschenToxilgzumGebrachftIAze
. Studierende und Medizinalbeamte . Stuttgart, p. 45) whereas recently
Kohn-Abrcst (Notice toxicologique surks gas . Annales des Falsifications,8 :215-39, 1915)
determined that 1000 parts per million are impossible to breathe for many minutes ."
C . Toxicity Data on Animals .
A summary of toxicity values for HCN in anintals is shown in tab :c .1 . The original data
from some of the reports were analyzed by the Bliss statistical method to obtain dose-response
regression lines and frequency distributions for mortality fractions of 1%, 16%, 30% . 50%, 94%, and
49 h . These values are shown in tables 3 and 4 .

tNHNf-0t

Thee toxicity data shownn in table .5 were read from figures published by Barcroft .s
Although the data are somewhat inconsistent, they indinte that the I-Ct50's increase with exposure
timc to a greater degree than that indicated by calculations for man (table 2) which were based on
intravenous LD50 and inlemal detoxication rate .
These data (tables I through 4) also indicate that LCt50's in animals for 0 .5- . 1-, 2- .
and 3-minute exposure times are consistently lower than those calculated for man by the
MooreGates method .
~
Ill . CURRENT RECOMMENDED AND APPROVED ESTIMATES OF THE TOXICITY OF HCN
.
VAPORS
IN
MAN
III
A . Derivation of the Estimates.
The animal data contained in this report indicate that goats, sheep, pigs, monkeys, anu
guinea pigs are relatively insenstive to the lethal effects of HCN, whereas dogs, mice, rats, and
rabbits are relatively sensitive . Barcrotts reported that when two dogs and two monkeys were
exposed to3ether, the monkeys were only beginning to show signs of unsteadiness when the dogs
died . He also reported that vthen a tnarr and a dog were exposed together, the dog almost died, but
the man had minimal effects .
I'1275 mg/cu m . Ct, 550 rnj mtnhu m .

(`1385 mg/cv rt, . Ct, 582 rtr aJn/cu in .


t Recommended and approved In rrdnutea of 31 l/arrh 1971 Raar .reh Labor .taka 9umm F.+timates Commlttee,
wb)ect : Rurtarch Laboratories Hurrm Brttsoats forHl?I,dWd 311farch 1971 .

13

Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

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Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

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Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

.,
T .bk 5 . Tock4tyof ffC:! :i VutuugAnlmal Specks (Oua from Bucrofl)d

Asi:ns!
.penn

Cfslsntntlon

my/w m
Gou

13J00

0/4

240

60

14,400

4/8

360

ls

5,400

120
I80
200
240
360

60
30
60
30
20

360
360
{80
480
480
- 600
- 630
860
920
I~00

480

600
600
600
600
720
B6o
1 .200

1S
30

3 .600
7,200

0/4
3/4

4/4

7,20
8,6/0
2,400
4,800
9,600
3,600
6,300
2,580
~ . 2,760
3,600

314
414
0/4
314
314
114
414
113
111
5/5

7,200
5,400
12j000

0/8
113
313 .
113
0/2

7,100

7,200
1,440

2
6
10
30
5
3
3

014

9,000

30

20
24
5
10
20
6
10
3
3
i

9,000

I
t

1,200
3,600
6 .000
18,000
3h(10
2,580
3,:00

013

1/2

114

4200

014

120

ls

1,800

Sl2

:CO

3P00

144

120

10

.1,200

0/2

5
3

Bpp
1,2pQ

1
I

3,600
2,400
1,200
1 j00
600
!00
1,200

1/2
012
1(2
I11
212

30

ls
10

114

6a

400
600
I

60

70

240
240

m8 mfnlcu m

180

300

pop

fractloal

0/4

240
240

min

MortaOty .

7,200

150

Mankey

Ct

dFM

60
60

120

I~

F~t?owre

212
2/3
013
2/2
2/2
1/1

2J4

16

Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

Table 5 . (Contd)
Animal
species

Concentrulon

120

mg min/cu m
7;200

60
30

10 .800
7 .200

300

10

3 .000

350

10

350

IS

300
300

7
5

350

350

380

Morullty
fractfon

0/2
2/4
0/4

3 .600

2/6

2,100
1 .500

0/1

2,450

0/1

~, 3,500

1/2

013
2/6

1,400 -

0/1

1,140

1/2

700

olt

3 .940

- 480

2 .400

5/8

480

lo

4,1100

4/4

600

l0

6,000

4/4

480

- 480

600

660
860
1,200
1,200
Cats

m1n
60

I80
240
240

Ct

time

mgJcu m
Rabbit

Exposure

120
120

2
1
3
1

60
30

960

2/3

1,800

3/4.

1,320

1 .7m

212
1/1 .
4/4
2/2

7,200
3,600

0/3
0/3

540
3,000

al
2/2

7 .200
3,600
2,400
3,500
1,140
1,260
6,000
1 .800
690

3/3
3/3
313
4/4
0/2
0/2
3/3
4/S
1/2
212

860
3 .600

60

10~00

200

15
10

2 ;000

840

2 .190
840

1,200

180

180
200

240
240
240
350
380
420
600
600
690
730
1 .200

1 .200

30
13
10
lo
3
3
10
3
1
3
3

112

3A00

2/5

112

2/2

313

3/4

Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

T .bk S . (Cnntd)
M''TnJ
tpcdev

Concmtntion .

ma/c u m

I IR
I
.n

II
ii
ii

~ '.

~'
~~

60
30

10 .800
7,200

3
10
3
1

1 .200
6 .000

60
1I0
1S0
170

ISO

200
- 220
- 240
270
290
460
570

Fo.4

60
45
30

13

Mortality
(nctlan

2 .400
7,200
5 .400
3A(l0

116
3/6
5/6
2/6

I/6
4/4

1/4

3b00
1A00

600

3
2

3jA0
2A00

60
60
60
60
24
16
30
13
20
11

3A00
6 .600
9A00
10,200
4,320
3.200
6A00
3,120
S,400

6/6
216

3!6
2/6
4/6
4/6
I/l
l/l
1(1

1,710

1/i
I/l
1/1 .
1/1

1l0

803

11S50

1/3

250
300
340

9
14
6

2,250
4,NJ0
2A/0

1(1
1/1
1/1

1,620

420

540

3
49

5.

390
420
480
600

60
31
12
4s

960

720

~
I

116
6/6
316
1/6

3.190
2.300

170

Guloss pi8'

m4 m4t/cu m

180
240

1100
1,200

II Mroe
II
ii
iI
ii
~~

min

60

400
600
600
600

II

Ct

40

120
120
120

240

~~

'W4NIIf1

ExpOaK
tLne

9.330

1/1

2,100

1/1

I/1

23A00
ll A20
5,760
2,700

1920

l .eo0

' qssd fmm p.pb -w ydnt U..bh to diwmNm maa .Yry fr.edos.

C8

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Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

.r

Although there have been few controlled expenments with man, those reported
indicate that man bclongs among the resistant species . However . itt is doubtful that man is so much
more resistantt than the monkey as could be assumed if the LCt50's obtained by the MooreGates
calculation were compared with those for the monkey .
There is another doubt concerning the rAlidity of the NooreGatcs formula . The
LCt50's for HCN in animals increase with exposure time, or perhaps with decrease in concentration
of agem . The same phenomenon occurs with other inhaled substances . In the case of sarin, the
incrcasc in LCt50 i&iarealer than that attributable to the systemic detoxication of the agent . Perhaps
thiss represents a detoxication on the surfaces of the lungs at low concentrations . The experimental
LCt50's for HCN in animals increase with exposure time at a greater rate than the LCtSO's-calculated for man by the MoortGales formula
.
Since the=e is reason to question the previous LCt50 values for HCN, r.ew human
estimates have been derived based on the following assumption'
Man has a susceptibility to HCNN similar to that of the resistant goat or monkey .
2 . Only in the mouse arn LCt50 values available at various exposure times from 0 .5
to 30 minutes . These values allow estimation of the LCt50 as related to exposure time . The values
for mice were multiplied by 4 to obtain LCt50 estimates for man at each time interval . These
derived LCt50's are comparable to available corresponding values for the goat . thus placing man
near the goat in sensitivity to HCN .

3 . The LCt50 for HCN in man inaeases with exposure time in a manner similar to
that determined experimentaUy in animals .
tY

4 . The dorresponse distribution found at a given exposure would apply over the
cxp.nure range of 0 .5 to 30 minutes.
5 . Sinaall experimental values are for inactive animal .s, resting breathing rates
must be used . The resting rate for man is assumed to be I0liters per minute .
6 . The frequascy of death for man ( I% . 16% . 30% . 5776, 84%, and 99%) is similar
to that for the resistant goat .

The La50 values for man, shown in tabb 6, were derived by using the frequency of
deaths in a population of goats a a model to derive oonesponding percantages of deaths in a
population of men whose LCtSO's were thas eatablished as expEained in assumption 2, above .
B . Limitations of the Estimate .
1 . The concentrations of HCN in controlled human exposures have not exceeded
550 to 625 mgJcu m . or Ct's of 925 to 1032 mg min/cu m .
2 . The estimated 1.050s s for hurmro have been derived primarily from animal
experimental data .

19

Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

Table 6 . Estlmetes of the Toxklty of Hydrocyank Acid Vapan in Man

Expoiure time

~t
1%

16%

min

3076 5o76

Avenge mouee
84%

LCt50

i 99%

nq minlcu m

li mg min/tu m

Goat
1,369 !

1,867 I ' 2,083 I 2 .354 I

2,967,

4,046

Man (eatimates)

0 .5

1 . .177

1,606

1,791 2,032'

2 .552

),4d0

508

1930

2 .632

.,937 3,4040 ~

4,183

5 .705

851

2 .546

3 .473

3 .874 4,400

5 .519

7 .526

I~ 1,100

10

3 .888

5302

5 .916 6,V72'

8.426

11,491

1,518

30

11 .992

, 16355

18,247 20,632

25.991

35 .443

5 .158

~i
I

' Mm LCtSO - mousc LCtSO X 4 at nriom expoeum tima . .


This places ean in the sendti .ity range of the goat (and monkey) . 7be mouae valua .ert used slnee these
are aveilable at all expoaue timn (OS to 30 mMnes) .
,
The fwquenty dirtributfma for peromta'e of deaths (other than 50%) an based an tho .e detamfoed
c ;perimentally ib gaata and dwlated by the uatlstinl method of tillr,.

3 . It is assumed that the LCt5O for man will inaease with exposure time in a
manner similar to that noted in the mous .

4 . There is no available information on tnan on which to develop dose-response


regression lines for kthality . The tne of the information on pats to develop a frerluency
distribution (s baoed only an the postulation that man and 4oat aro among the relatively resistant
species .

20

Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

LITERATURE CITED
I . Moore, S .,, and Gates, M . Hydrogen Cyanide and Chloride . . Chaptcr 2 in
Summary Technical Report of Division 9, National Defense Research Committce, Chemical Warfare
Agents and Related Chemical Problems . Washington, D .C : 1946 .
2 . Department of the Army Technical Manual 3-215 . Military Chemistry and
Chemical Agents . December 1963 .
3 . Coon, . J . M ., Glass, H . . Sonkin, L . S ., and Lushbaugh, C . C . OSP.D 1432 .
Hydrocyanic Acid Toxicity Studies . May .18, 1943 .
4 . Armstrong, G . C . . Koontz, A . R ., and Witherspoon, M . G . EAMRD 20 . The
Toxicity of Hydrocyanic Acid Gas on Dogs, Monkeys, Mice, Guinea Pigs, and Rabbits . 31 December
1923 .

5 . Silver. S . D ., Ferguson,''R . L ., McGrath, F . P ., and Hunt, C . M. EATR 360 .

Hydrocyanic Acid . Median Lethal Concentrations for Mice : 2- and 30-Min Exposures .
26 November 1941 .
6 . Silver . S . D ., McGrath, F . P., and Krackow . E. H . TRLR 22 . Hydrocyanic
Acid LCSO for Rats Exposed for 2 Min . 21 January 1944 .
7 . Silver, S . D., McGrath, F . P., and Krackow . E . H . TRLR 23 . Hydrocyanic
Acid . LC50 for Goatr 2-Min Exposure ;Time for Incapacitation . 7 January 1944.

8 . Barcruft, 1 . The Toxicity of Atmospheres Containing Hydrocyanic Acid Gas .


J . Hyg . 31, 1-34 (1931) .
9 . Kobert, R . Kompendium der Praktischen Toxikologie zum Gebrauche f(k
Ante . Studierende und Medizinalbeamte . Ferdinand Enke (Publisher), Stuttgart, Germany . 1912 .
10 . Lehmann, K . B . Kurzes Lehrbuch der Arbcits und Gerwerbehydiene . Verlag
von S . Hirzel, Leipzig,Gernuny 1919 .
11 . Henderson, Y ., and Haggard, H . W . Noxious Cases and the Principles of
Respiration Influencing Their Action . pp 110-112 . The Chemical Catalog Co . . Inc ., New York,
New York . 1927 .

12 . Flury, F ., and Zernik, F . Scliidliche Gase . Springer, Germany . 1931 .


13 . Dudley, H . C., Sweeney, T. R . . and Miller, J . W . Toxicology of Acrylonitrile
( Vinyl Cyanide). J . Ind . Hyg. Toxicol.l4, 255-25R (1942) .
14 . Fasett ., D . W . Cyanides and Nitrilea . Chapter XUV in Industrial Hygiene and
Toxtcu6.:;. P-CY. %s, cd . 7d Edition . Volume 11 . Interscience Publishera, New York, New
York . 1963 .

21

Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

15 . . Gtubbs, S . B . . Detection of Hydrocyanic Acid Gas, Use of Small Animals for


this Purpose . U .S. Public Health Report 32(16), 565-569 (1917)' .
!.6 . Katz, S. H ., and l .ongfellow, E . S . Tcst Papers for Estimating HydrocyanirAcid
Gas in Air . U .S. Bureau of Mines Report, Invest . 2504 . July 1923 .
17 . Heffter, A ., ed . Handbuch der Experimentellen Pharmakologie . Volume I .
p 775, Verlag von Julius Springer, Berlin, .Germany 1923 . .
18 . Hayes, Wayland J ., Jr . Essays in Toxicology . Volume 3 . p 69 . Academic Press,
New York, New York, and London, England . 1972 .

1935 .

19 . White . S. A . EATR 198 . A Brief for Hydrocyanic Acid as a War Gas . 16 April

20 . Macy, R . EATR 219 . Hydrocyanic Acid : Its Military History and a Summary
of Its Properties . 20 May 1937 .
21 . Artostrong, G .C . EATR 136 . Toxicity of Hydrocyanic Acid Gas to Mice by
Inhalation for a 10-Min . Exposure . 10 May 1933 .

Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

D ISTR IBUTIONiIST NO . 3
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Coprr

Wme.

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Coper

(-rmm.nAcrdn[Tiel
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US ARMY HEALTII SFRVICE COMMAND

Fredenck . MD 21701 .

DIRECTOR OF PRODUC7 ASSURANCE


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Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

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Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068

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OUTSIDE AGENCIES

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Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/zrcm0068