estimates of the toxicity of hydrocyanic acid vapors in man

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ents.library.ucsf.edu/tobacco/docs/zrcm0068

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i .,DEPARTNENT OF iHE AR1iY

EIX:EW0oD ARSENALTechnical 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: B.. P . McNamara, Ph .D . .

DATE : February 1976

CLASSIFICATI~ON

: UNCLASSIFIED Please change date on Cover and DDForm 1473 from .February 1976 to August 1'876 .

HElIRY 7 . BIELECKIChief, Technical Relesaea DivisionTechnical Support Directorate


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he•n the data pn which 1he Iateamtlonally accepted F,C130 of Inhaled hydrocyanle acld (AC . HCN) vapnn inman .etc revierad and thee llgum ptA -kbsd wWely In sdantlfk journals twxe .¢mined, it .nc dedded that morcv.lW ntlm+rel of the toc/cltyo( 1lCH In man should ee LCt'L fac 1% . 1(,%. 7096 . SO% . 81% . ud 99% of .fan cxposed popu W Im tor eapwure timr of frorn 03 to 30 mtnuta w~erb dxiwd . Because of the p[ucity of data onio,mrDued experirnwns aMh man, h wwaa nace.nry lo D, anhnfl dats . Among the nwmptlom made were that man

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PREFACE

The work desentxd in this report was authorrzed under Protect/TaskN'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 thet:wdc h:r the ('are and Use of Laboratory Animah" as promulgatcd by the Committce onRevr.ion ul the Guidc for Laboratory Animals Facilities and f' .ire of the Institute of LaboratoryAnun .d Renourccs, .National Research Council .

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

Rrpmduction of this document in whole or in part is prohiMtedexcept withtx•rrrucsron nf the Commander, Edgewood Arsenal, Attn : SAREA-TS-R. Aberdeen Proving Ground,Maryland _1010 : however ; DDC and the National Technical Information Service are authorized toreprcalu,c the document for USGovernment purposes .

Acknowledgments

The author acknowledges the cooperation of Mn. Martha Langan . Mrs. MarionRrqston . and Miss Fonda Jackson inn preparing this manuscript .

2


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CONTENTS

I INTRODVCTION~. .

11 BACKOROUND . . . . . . . . . . . . 5

A . Previously Accepted Estimates of the Toxicity of HCN in Man . . . . . 5

I . Military Estimates . . . . . . . . . . . . . . . . . . . . . 52. Origin of Widely Published Open Literature Estima :cs .- . . . . . N

B. Toxicity Data on Deliberately Expns :d Men . . . . . . . . . . . . .I I

C. Toxicity Data on hmmals . . . . . . . . . . . . . . . . . . . . 13

111 . l'URRtNT RECOMMENDED AND APPROVED ESTIMATES OF THETOXICITY OF HCN VAPORS IN MAN . . . . . . . . . . . . . . . . 13

A . Derivation of the Estimates . . . . . . . . . . . . . . . . . . . . . . .

B. Ltmitations of the Estimate . . . . . . . . . . . . . . . . . . .

LITERATURE CITED . . . . . . . . . . . . . . . . . . . . . . .

DISTRIBUT7ON LIST . . . . . . . . . . . . . . . . . . . . . . .

3

13

19

21

23


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 fiEUrr-puhh .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 andChemical 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 atI 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 . ChemicalWarfare. 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 forIv minutes) and 4500 mg min/cu.m (150 mg/cu m for 30 minutes) appear to be based.on mousedata without consideration that the mouse is known to be more sensitive than man to HCN' . (Scctable I .)

Moore and Gatestestimated the LCtSO for HCN in man in the following manner :

different species are stimulated to different degrees by HCN : 7-fold in the dog . 2- to 3-fold in the

The intravenout LD50's for HCN in mg/kg are 1 .34, 0 .81, 1 .30, 0 .66, 1 .43, 0 .81 . and0.99 for dog, .cat, monkey, rabbit, guinea pig, nt; and mouse, respectively . Assuming man to bc likeother mammak . an intravenous LDSC of 1 .1 mg/kg was estimated for man . The minute volumes of

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Tlxintravenous rnlection of cyanide snmulatn rerppr.non in man to vanou, depecNdeprndmp upon.dose and apectf of adrnrnrstntson . IHowever_ Barcmfts could detect no cffc .r . .+rresprranon when a con:ntratron of about 550 mg/cu m was tnsprred .I

The detoxruuon rate for HCM infectedmtnvenously in mar, n .dvmttl (I .I 7 mg.!kglmm . Thn.value is not markedly different for animah

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/miht° 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/kgC- 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 timesar.d breathing rates calculated by this method are shown in table 2 . An earlier calculation of thistype by British investigators led to the internationally agreed estimate of 5000 mg min/cu m for . theLCt50 for HCN in man .

Table 2. LQ50 Estimates for NCN in Man Calculatedby the Moore-Gates Formula

LCtSrJ'sExpowre

time 251iten/min• 15 Gters/min•

Concentration Ct Concentn6on Ct

min mg/cu m mg min/cu m mg/cu m mg min/cu m

I 0.5 8,800 4,400 14.400 7,200

I 4,400 4,400 7,590 7,590

3 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


The LC I50's calculated lor man aree much higher than those for even the most resictantarumal 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 reportedto have originated with . K . B.Lehmann prior to 1912 . A report by Kobert9 is the firstt journalpublication reference to the work of Lehmann . Kobert's paper and the numerous subsequentcttanons of the worY: consistently presented toxicity values for man without developing theexperimental basis for the values . As shown below, .prior to 1919„Lehmann studied, lh~ toxicity offiCti in rabbits onlyanddeciined from making quantitative statements concerning the toxicity ofHCN for manJa .

The following abstracts are given for historical purposes and to show the commonongin ol' toxicity values which are accepted for HCN in man .

a.Kobert, Rudnlph (Kompendium der Praktischen Toxikoingie zumGebrauche 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 noindication 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 thePrindpks of Respintion Influencing Their Action . The Chemical CatalogCo., lnc., 1927 N . Y., N. Y., pp 110-112) .l s

In 11027 . Henderson and Haggard reported the work cf KobertO as follows :

8


"Physiologieal Response to Various Concentrations of Hydrocyanic Acid Gas•

t

t

Parts of Hydrogen Cyanide Per MillionParts of Air

Several symptoms after several hours expcsure 20 to 40

Maximum.amount that can be inhaled for 1 hourwithout 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 Idoes uot agree with that given by Y.obert9

c. - Flury, F ., and F. Zemik (Sch'rd6che Gase, Springer, 1°L1) .t 2

Flury and Zemik stated that the degree of toxicity of inhaled HCN for man is probablythe 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 .nutimmediate or :ate ;ffects

0.05-0.06 45-54

Slight s, mptoms after severalhours (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 :'

9


d. Dudley, H. C., T. R . Sweeney' and 1 . W. Mrllcr (ToxicoioFy ulAaylonilrile (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'racid as published by Lehmanmand Hess and quoted from Flury.and 7.emik are summarized . ._-

"Toxicity of HCN'I forHumar.s (Flury and Zcrnik, 1931)

ConcentrationS t

mg/Gter . --- ._p .p.m .ymp oms

0 .3 270 Immediately fatal

0 .12-0 .15 110-135 F3tal after 112 .1 hour or lnter ordangerous to life

0.05-0 .06 45-54 Tolerated for t, 2-I Eour withoutimmediate or late efdects

0.02-0 .04 18-36 Some efkctsaftcr exposure forseveral hours ."

e . Fassett, D . W. Cyanides and. Nitriles . Chapter XLIV in industrial Hygieneand Toxicorogy . Patty, F. A .,eid) . 2d Edition. Volume 11 . intersciencePublishers, New York tSty . 1963.14

A table similar to that appeating in Dudley et al .t 3 was presented in Patty's bookt 4 asshown belOw :

"Physiological Response to Various Concentrations ofHydrogen Cyanidain Air -Man'

ConcentrationResponse

mg/liter p .p .m .

Immediately fatal 0.3 270

Fatai after 10 min 0.2 181

Fatal after 30 min 0.15 135

Fatal after 1/2 to I hr or tater, 0.12-0.15 110-135or dangerous to life.

Tolerated for 1/2 to I hr without 0.05-0.06 45-54immediate or late effects

Slight symptnnts after severaiAoun 0.02-0.04 18-36

'H. C . Daidley . T . P. Sw«ney and J . W . MiL'cr,1 . ind . Hyg. Tuxicol :. 24 . 255 5 (1942)

F. Fluryand P . Zernik, SeMldhdie Gase, Springer. Bcrlln. 193 t"

10

r

1


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 originatedw nh t: . B . Lehmann prior to 191 2 when lirst quoted by Koberi .9 None of these references give thevrperirnentalbasis for the human values . The publication .is not cited by any of those who quoteLehmann . Our attemuts tolorrte such an article have been fruitless ..However, the above referencedtcxlhnoR 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 rahhitwith some increased respiration even for 2 hrs ; others died even at 0 .13 mg in I hr, .and at (Y15 mFirt 1 :.l'_ hr . At. 0.2 mg even rfter 4 min . sudden collapse occurs : we saw an actual pulmonaryhemorrhage in a rabbit : poisoned with HCN vapor (until now published only in the dissertations utmy students)

. As yet we have not conducted experiments on cats and dogs . I can make noquantitative 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)dwhich 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- and374.ounce sodium cyanide per 1000 eu ft for 2 minutes and for 1-1 /2 minutes, respectively, withoutfeeling any e[fect, but that this has at other times caused dizziness. One-half ounce of sodiumcyanide in 1000 cu fl yields a concentration of about 501 mg/cu m of sodium cyanide . theequivalent of about 276 mg/cu m of cyanide ion . Three-quarters ounce of sodium cyanide in1000 cu ft yields a conctntration of 750 mg/cu m of sodium cyanide, equivalent to 401 mg/cu m ofcyanide ion . The respectiveCt's would be about 522 (2 minutes) and 602 (1-1/2 minutes) forcyaniBcion ;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, theystated 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 ExperimentalPharmacologytl) exposed tuberculous patients to concentrations up to 20 mg/cu m for120 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 citedfrom his paper .

"The question of where man stands in relation to the animal is most important . Clearlyit is very difficult to obtain exact information on this subjest, for when fatalities are octncerned theconcentrations which produce them are not known .

"The experiment about: to be desaibed shows, however, that man is not verysusceptible . It took place in the airti:ht chamber aheady described, the human suSject was about45 years of age and weighed about 70 kg .

I I'


"One human being .and one dog.(9bou( 12 kg)t were exposed simultaneously, withoutprotection, to an atmosphere containing a nominal concentration of I/I600hydrocyanicacidl'Ic theactuai 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 oneanother. The utmost care was taken lest if the dog succumbed first it should not be because itsrespiration was stimu,ted by' a greater degree of muscular activity, .therefore each movement madeby the dog was followed by an imitative movement on the part~ of the man, so that the degree ofactivityy of two might be as nearly as possible the same . This procedure was followed up to the pointat which the dog became unconscious . After that no effort was made by the man to imitate themuscular spasms which form so conspicuous a feature of the later stages of cyanide poisoning . Theexpenment ran the coursee as shown in the following notes which werc taken by the man as the .expcriment proceeded .

"rime front Zero

50 sec . . Became unsteady

I min. 15 sec. On floor unconscious

Utrtlt}IN

I min. 30 sec. Crying sounds and tetanicconvulsions sufficiently established

_ to render it probabkthat animalwas in extremis

Man

I min. 31 sec. - Came out of chamber and puton respirator having felt nosymptoms. No apparentdyspnea .

I min. 33 sec. Respiration apparently ceased, Re-entered chamber in respiratoranimal 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 of nausea .

10 min . Attention difficult to concen-trate in close conversation .

'Although the corpe was set adde for burial about .6 :30 pm, the dog dW In point of fact recover, and wasfound 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

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1

I Cyanide is rapidly detosi0ed.1 •t s However, there are somc accounts that Barcroftsuil'rred certain persistent eff,cts of this exposure for about a year .t9•2o It was stated thatProfessor Barcroft suffered nausea and deflatte mental symptoms a few minutes after hiswithdrawal from the gas atmosphere but that at Ieast some of these symptoms persisted for about aycar19 2° 1 Continuing with the quote from Barcrofta - "A report by S . H. Katz andP. . S. Longfellow from the American Bureau of Mines i .sued in July 1923 states : 'Men employed infumigation with HCN have been tcsted while at rest in 250 parts per million of air for 2 minutesf'Iand ?500 parts per million for 1-1 /2 minutesl"I but felt no dizziness, although possibly on exertionthey m4.ht have done so .' In experiments during the war men have been exposed to 500 parts permillion foi about a minute without injury . Hydrocyanic acid gas was formerly considered ; ne of thedeadliest gase~ in minute concentrations, but later experience, especially in the war, has shown thatman is more resistant than some other forms of life . -(Lshmann, Tabelle der Kleinsten Mengen .w-ekhe allenfalls ertragen werdcn, in book by Kobert . Kompendium der Praktischen Toxikologiczum Gebrauche ftIr Arzte

. Studierende und Medizinalbeamte . Stuttgart, p. 45) whereas recentlyKohn-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 datafrom some of the reports were analyzed by the Bliss statistical method to obtain dose-responseregression lines and frequency distributions for mortality fractions of 1%, 16%, 30% . 50%, 94%, and49 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 .sAlthough the data are somewhat inconsistent, they indinte that the I-Ct50's increase with exposuretimc to a greater degree than that indicated by calculations for man (table 2) which were based onintravenous 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 theMooreGates method .

~Ill. CURRENT RECOMMENDED AND APPROVED ESTIMATES OF THE TOXICITY OF HCNVAPORS IN MAN III.

A. Derivation of the Estimates.

The animal data contained in this report indicate that goats, sheep, pigs, monkeys, anuguinea pigs are relatively insenstive to the lethal effects of HCN, whereas dogs, mice, rats, andrabbits are relatively sensitive . Barcrotts reported that when two dogs and two monkeys wereexposed to3ether, the monkeys were only beginning to show signs of unsteadiness when the dogsdied . He also reported that vthen a tnarr and a dog were exposed together, the dog almost died, butthe 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/arr•h 1971 Raar .reh Labor.taka 9umm F.+timates Commlttee, ~wb)ect: Rurtarch Laboratories Hurrm Brttsoats forHl?I,dWd 311farch 1971 . ~

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

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Asi:ns!.penn

CfslsntntlonF~t?owredFM

CtMortaOty .fractloal

my/w m min m8 mfnlcu m

Gou 120 60 7,200 0/4

150 60 9,000 014

180 60 13J00 0/4

240 1S 3 .600 0/4240 30 7,200 3/4240 60 14,400 4/8

300 30 9,000 4/4

~ 360 ls 5,400 114I360 20 7,20 314360 24 8,6/0 414

{80 5 2,400 0/4480 10 4,800 314480 20 9,600 314

- 600 6 3,600 114- 630 10 6,300 414

860 3 2,580 113920 3 ~. 2,760 111

I~00 i 3,600 5/5

Mankey 120 60 7,200 0/8

I80 30 5,400 113200 60 12j000 313 .240 30 7,100 113360 20 7,200 0/2 .

- 480 3 1,440 013

600 2 1,200 1/2600 6 3,600 012600 10 6.000 1(2600 30 18,000 I11720 5 I 3h(10 212B6o 3 2,580 1/2

1 .200 3 t 3,:00 114

pop 70 6a 4200 014

:CO 30 3P00 144

120 ls 1,800 Sl2

120 10 .1,200 0/2

240 ls 3,600 212

240 10 2,400 2/3

w 5 1,200 013400 3 1 j00 2/2600 1 600 2/2

Bpp I !00 1/1

I 1,2pQ I 1,200 2J4

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16


Table 5 . (Contd)

Animalspecies

ConcentrulonExposure

timeCt Morullty

fractfon

mgJcu m m1n mg min/cu m

Rabbit 120 60 7;200 0/2

I80 60 10.800 2/4240 30 7.200 0/4

I 240 IS 3.600 2/6

300 10 3.000 1/2

300 7 2,100 0/1300 5 1 .500 013

350 10 ~, 3,500 2/6

350 7 2,450 0/1350 4 1,400 - 0/1

350 2 700 olt380 3 1,140 1/2

480 8 3 .940 112- 480 5 2 .400 5/8

- 480 2 960 2/3

I 480 lo 4,1100 4/4

600 3 1,800 3/4.

600 l0 6,000 4/4

660 2 1,320 212860 1 860 1/1 .

1,200 3 3.600 4/41,200 1 1 .7m 2/2

Cats 120 60 7,200 0/3120 1 30 3,600 0/3180 60 10~00 2/5

180 3 540 al200 15 3,000 2/2200 10 2;000 112

240 30 7.200 3/3240 13 3,600 3/3240 10 2,400 313350 lo 3,500 4/4380 3 1,140 0/2420 3 1,260 0/2600 10 6,000 3/3600 3 1.800 4/S690 1 690 1/2730 3 2.190 212840 1 840 2/2

1.200 3 3A00 313

1 .200 1 1,200 3/4


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II 180 60 10.800 I/6 ~Ii i 240 30 7,200 4/4

~~ 240 13 3b00 1/4ii 400 3 1.200 116

II600 10 6.000 6/6600 3 1A00 316

~ '. 600 1 600 1/6~' 1100 3 3jA0 6/6~~ 1,200 2 2A00 216II Mroe 60 60 3A00 3!6II 1I0 60 6.600 2/6ii 1S0 60 9A00 4/6iI 170 60 10,200 4/6ii ISO 24 4,320 I/l~~ 200 16 3.200 l/l

- 220 30 6A00 1(1- 240 13 3,120

270 20 S,400 1/i290 11 3.190 I/l460 5 2.300 1/1 .570 3 1,710 1/1

Fo.4 1l0 803 11•S50 1/3~ 170 49 9.330 1/1

250 9 2,250 1(1300 14 4,NJ0 1/1340 6 2A/0 1/1420 5 . 2,100 1/1540 3 1,620 I/1

Guloss pi8' 390 60 23A00 -420 31 ll A20 -480 12 5,760 -600 4s 2,700 -720 u l .eo0 -960 2 1920 _

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

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Although there have been few controlled expenments with man, those reportedindicate that man bclongs among the resistant species. However . itt is doubtful that man is so muchmore resistantt than the monkey as could be assumed if the LCt50's obtained by the MooreGatescalculation were compared with those for the monkey .

There is another doubt concerning the rAlidity of the NooreGatcs formula . TheLCt50's for HCN in animals increase with exposure time, or perhaps with decrease in concentrationof agem . The same phenomenon occurs with other inhaled substances . In the case of sarin, theincrcasc in LCt50 i&iarealer than that attributable to the systemic detoxication of the agent . Perhapsthiss represents a detoxication on the surfaces of the lungs at low concentrations . The experimentalLCt50'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 humanestimates have been derived based on the following assumption'

Man has a susceptibility to HCNN similar to that of the resistant goat or monkey .

tY

2 . Only in the mouse arn LCt50 values available at various exposure times from 0 .5to 30 minutes. These values allow estimation of the LCt50 as related to exposure time . The valuesfor mice were multiplied by 4 to obtain LCt50 estimates for man at each time interval . Thesederived LCt50's are comparable to available corresponding values for the goat . thus placing mannear the goat in sensitivity to HCN .

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

4. The dorresponse distribution found at a given exposure would apply over thecxp.nure range of 0.5 to 30 minutes.

5 . Sinaall experimental values are for inactive animal .s, resting breathing ratesmust 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 similarto that for the resistant goat .

The La50 values for man, shown in tabb 6, were derived by using the frequency ofdeaths in a population of goats a a model to derive oonesponding percantages of deaths in apopulation 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 exceeded550 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 animalexperimental data .

19


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

~t Avenge moueeExpoiure time

1% 16% 3076 5o76 84% i 99% LCt50

min nq minlcu m li mg min/tu m

Goat

1,369 !

1

1,867 I ' 2,083 I 2 .354 I 2,967, 4,046

~Man (eatimates)

I 0.5 1 . .177 1,606 1,791 2,032' 2.552 ),4d0 508

I 1 1930 2.632 .,937 3,4040 ~ 4,183 5.705 851

~i 3 2.546 3.473 3 .874 4,400• 5.519

I

7.526 I~ 1,100

I 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

' 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 theseare 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 detamfoedc;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 amanner similar to that noted in the mous .

4. There is no available information on tnan on which to develop dose-responseregression lines for kthality . The tne of the information on pats to develop a frerluencydistribution (s baoed only an the postulation that man and 4oat aro among the relatively resistantspecies .

20


LITERATURE CITED

I . Moore, S.,, and Gates, M . Hydrogen Cyanide and Chloride . . Chaptcr 2 inSummary Technical Report of Division 9, National Defense Research Committce, Chemical WarfareAgents 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. TheToxicity of Hydrocyanic Acid Gas on Dogs, Monkeys, Mice, Guinea Pigs, and Rabbits . 31 December1923 .

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 . HydrocyanicAcid 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(kAnte. Studierende und Medizinalbeamte . Ferdinand Enke (Publisher), Stuttgart, Germany. 1912 .

10. Lehmann, K. B. Kurzes Lehrbuch der Arbcits und Gerwerbehydiene . Verlagvon S . Hirzel, Leipzig,Gernuny• 1919 .

11 . Henderson, Y., and Haggard, H . W. Noxious Cases and the Principles ofRespiration 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, NewYork. 1963 .

21


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) .

w!.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 Summaryof Its Properties . 20 May 1937 .

21 . Artostrong, G.C. EATR 136. Toxicity of Hydrocyanic Acid Gas to Mice byInhalation for a 10-Min . Exposure. 10 May 1933 .


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estimates of the toxicity of hydrocyanic acid vapors in man

Documents

d date

d renourccs

toxicity data

blt projecf

ttus report

lrsa c

c mducting

nucroue cwrurmc roa