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On 10 Decemtxr 1948 the Zxecutive Coxxittee of the 8iPA Lk dic A kivisory Soamittee on the ih.iiation Tolerance or' Idi lita ry Personnel ;ieC i n San Francisco, a t diich tine the group deliberated upon the l'Availatlt-s The Executive Somxittee also reviewed and recornxended changesi in the outline entitled '?Xstiaated !iesults t o Ihmms 5xpose:i t o Filtered, vised and recirciilated on two different occasions. elicited approvals of approxinately sixto one for the presents toten ents preparation of these statements relative to the exact nording and the dctermination 2f the dosage levels, and it isle lt that the cie ci sims are The last circulation A great deJ of the and effort have Gem expended inthe 2s nearly un an hous as can be expected, 2 trust that these materials :nay be co[!yletely dcclassir'ied, but in any event they wU l be sent t-,each nenber of the Cornittee within the next three weeks. It is hoped that you will carefully consider the material &or t o our nee ting in Kzshington on Sunday, 3April 1949, 2nd that the CJenerral atsd Results t o Humans" a t that meting, It is further hoped that we sha3.1 be able t o dispose of &he mtters a ent i one d above during the l'orsnoon.oP April 3rd, The afternoon can then be devoted t o the I'omulation d recomaendations t o %PA relative t o future prop in s in research,In this connection, 1 shall appreciate your sending t o %e within the next three weeks, itnci i;o the address i;iven belor;, your suggestions Cor research problems not ROW in progress but nnich you feel :rill be of assistance in the so lu tio - of NEY'A% problems, fine such suggestions to a brief statenient of each problex 3nJ its relation - shiptoN SPA, ornitting de tai is of procedure, etc,I shall attempt to edit and correlate these i'or the forth co airy rneetlng, 1: xri grateful for ;our cooperation so far in this undertaking. And my I offer apologies lor the great mount of tine whi:h has elapsed has been considerable, and It rust that our results justify both the the I an sure you are :*~c3^1a wre tha3 the rmrk involved Very sincerely yours,
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Report on Survey o f Opinion i n Regard t o Desperation Doses of Irradiation Twenty-four consultants returned answers t o questionnaire (one returned two, which agreed well, only the first beinz tabulated with the others). The averages are given in the table. The estimates scatter widely, maximum reaching a factor of 40 i n one instance (almost the entire length of the scale provided). (Last Question: Cooney 800 r, also Xempelmann; Portmann 25 r) The scatter is greater in roentsens for the lar2er doses, but much greater i n percentage for the lower doses. We are probably dealing with a psychological effect here, the questions being posed i n such a way that 25 r seen3 no further away from 50 r than 1000 r is from 900 r. Also the top fi zur e eligible was 1030 r p which probab1:ir acted to dissuade many from guessing hie her. Where a larger figure was writ - tenin,I have recorded it a s 1000 r. It is also not impossible that the consultants do have more experience of larger doses (in practical therany) and that the better agreement inthe upper levels is due in part to this larger body of If one can speak ofa consensus of such widely scattered opinion, one may say with some dependability that these consultants think, on the whole, that : The dose which rapidly renders troops ineffective is not much smaller than the lethal dose. Given more slowly the same total dose re3ders about the same 7ercentane ineffective by the end o f two days and kills about the same percenta3e. When the exposure i s spread over a month, the tolerance is less than doubled, except for the single class of no radiation deaths, where it i s estimated to require slightkg more than twice the exposure i f received slowly. The average probable error over allis 35$, varying from 25% inthe upper brackets t o 50;: for those est in at es For military purposes and i n desperate circumstances gene rally, one is likely to have t o depend on pretty roueh observations. Maybe the present estimates, for all their lar ze probable errors, may prove yetto be good compared to the poor reliability of a field commander's in for a ation. However, they are pretty unsatisfactory for,pid aq ce in regard to voluntary over-exposure ina measured radiation field.. They ought tobe improved by the acquisition of dependable experi-
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Opinion as to Effect of Total Body Exposure 90% ineffective in a few hours 9O$ die within two months 160 r ( 70 r ) no deaths within two months 2. CONTI NUI I JG or REPEATED EXPOSURE: 120 r ( I' 96 r > no immediate symptoms 3 . LOVGER CONTINUING or R3:PERTED EXPOSURE over a period ofa month: 600 r ( It 210 r ) 9O$ ineffective by end o f month I 1 11 If If It
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1. Znflluenco of whole body exposure on life span loty dosam levels b) Continued intermittent SXPOSWO Plan experiments so that if there is an average shortening of life, ons may decide whether it is due t o a large effect i n a few individuals ortoa smaller effect on all members of the group. available nay supply information on this point,) Plan expriments so that extrapolation to man is reesonnbly Look up vital statistics on sge at death of radiologists and Also cause of death. DeterniinatJ.on of individual susceptibility to radiation b fore This is a difficult but, important problem. Every effort should be matie t o get atleast som leads, Nausea would seein t o bo oneo This could be studied in large hospitels whore many patients ere treated with x-rays - eepecially treatments i n the region of the abdomen. Since the problem is a l s o of interest t o rsdiologists, it should be possible to s e t up a few projects on it; under favorable There may be ao or relation between oar sickness snd radiation The susceptibility t o nausea might be es that ad by determining the . amount of a suitable drug necessary t o produce musea or vomiting. Then this might be correlated with susceptibility to radiation musea. Skin exythenra induced by radiation is of no great h port an co to Nopa, since exposure t o penatrating rodistion thst produces an erythema will.mast
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likely prove fatal, However, it is a relatively simple metter t o determine susceptibility to erythema i n humans, and conceivably soot0 correlation Hith other effects may be found, between radiation erythema and skin reaction to certain drugs, including A t the same time one may look for a correlation The effect of radiation on the blood forming organs is of fmportancre patients treated wi"& x-rays - perhaps on some patients treated with internally administered isotopes, radiation damago before exposure occursc damage after exposlare has occurred, but (1) before it manifests itself, and (2) after it bscomss apparent, 5 0 Uetermine effect oIE radiation on fi bil it y to pssform certain tes ks, involving: (1) physical strength, (2) nental aI-er.tness * This part of the problem could be investigated t o some extent on Undertako studios intended t o provide means of increasing resistance to Undertake studies intended t o provide meana of counteracting radiation Study effect of rediatior. on susceptibility to infectious disease so Determine influence of a first exposure on reactions to 8 s e c o ~ d
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I n regard to the effects of total body irradiation, Please check your best estimate. I.. ACUTE EXPOSURE, i.e.within a few hours (1-6) excluding inA., To render 90% o f exposed persons ineffective within a few hours B. To render 50% o f exposed persons ineffective within a few hours C.. To render 10% of exposed persons ineffective within a few hours D e The upper Unit o f exposure which 2roduces no immediate sgmTo cause death by radiation effect in 90% of those exposed, To cause death by radiation effect in 50% o f those exposed, To cause death by radiation effect in 10% of those exposed, H. The upper l i m i t of exFosure which will lead t o no deaths from 11. CONTI NUI RG OR REPEATED EXPOS'VRES over a period of 48 hours., hours, and continuing ineffective for atleast 24 hours longer will hours and continuing ineffective for at Least 24 hours longer will hours, and continuing ineffective for atleast 24 hours longer will To render 90% o f exposed persons ineffective by the end o f 48 To render 50% of exposed persons ineffective by the end o f 48 To render 10% of exposed persons ineffective by the end o f 48
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L. The upper limit of exposure accumulated i n 48 hours that will produce no immediate symptoms (v;ithin that time orthe subse uent IdD To cause death by radiation effect in 90% of the persons exposed, the total accumulsltion (in 48 hour period) riiust be: N. To cause death by radiation effect in 50% o f the persons exposed, the total accumulation (in 48 hour period) must be: 0. To cause death by radiation effect in 10% of the persons exposed, the total accumulation (ina 48 hour period) must be: 25 r, that will lead to no deaths by radiation effect is: 25 r, 50 r, The upper limit of exposure accumulated within a 48 hour period II L LONGER CONTINUING OR REPEATED EXPOSURES, over a period of 1 month, Q. Bit h out regard t o how long the incapacitation persists, and with - out regard to any later effects like leukemia, skin cance??, etc., 90% of the persons exposed mill become ineffective by the end of1 month from exposures accumulating to a total of 25 r, 50 r, 100 r, R. Githout regard t o how long the in capac ik tion persists, and mithout regard to any later effects like leukemia, akin cancer, etc., 50% of the persons exposed will become ineffective by the end of 1 month from exposures accumulating to a total of 25 r, 50 r, 100 r, So5it h out regard to how long the incapacl.cu C & 3 i ? +. persists, and without regard to any later effects like leukemia, skin cancer, etc., 10% of the persons exposed will become ineffective by the end of1 month from exposures accmiulating to a total of 25 r, 50 r, 100 r r T. Li th out regard to late effects like leukemia, skin cancer, etc., the up2er limit of exposure accumulated in a period of1 month which produces practically no symptoms nor inmediate signs of radiation U. To cause death by redi ation effect ill 90% of the persons exposed, the sum of exposures ina period of 1 month must reach a total o f :
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posed, the SUM of exposures in a period of1 month must reach a total posed, the sum o f exposures in a period of 1 month must reach a total To cause death by radiation effect? in 50$ of the persons exTo cause death by radiation effect in 10% of the persons exX. The upper limit of.to tale qo sure accumulated in a period of 1 month.that will lead to qo deaths from radiation effect is: 25 r, Return completed questionnaire to Dr, Eugene Pendergrass, University of Pennsylvania Hospital, Philadelphia, Pa.
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rupt;- a reaction chain mechanism, "hie antioxygenic action m y man occur by preferential r action with certain rscsptm calla, Ethylene diprulfonatre does not diffor too radically in tslructura fmm many of the moat potent antiaxidants known $0 d a t e 9 ( ~ 2 " 1 3 3 ~ t ~ lthe nso=vllad.n E(26jp all developed at the University of Iowao Thoss nntioxidantcr have proved to bo extremely effectima in low concentrations in 211 P a t s and oils t.e&xi Lo data ae WSU.as being effective in both natural arid synthetic rubber products, to ethylene dfsulfonato, all theso potent antioxidants have 8 carboxyl, a m1fonic or a phosphonic wid grouping with a proximal activating groq eruch a@ an unsil turn ted m upr keto, amino, hafogen or another carboxyl, aulfonfc a r From experimental data a general theory of the in vitro mechanism af antioxygenic action was developed in a recent pspar(l3)and thle thsory has much in common with one postulated for tha in vivo mechanism of a&ihi6tvninPc action, Both theories arO concerned with preferential coap~sxin;:to pwont rwdction with undesirable eornpotmds. Baaed on tho foretgohg data it appears t h a t it weald be abvan%qp&uefor Nspa to institute a ljniited program to attempt Lo increase the crcmts to16Pranc@ leva1d radiation by studying tha effects of antioxidants aid obhar eompo~da au fortifying agents for protection against t h e radiotoxic nyndrome. than intending to make a thorough study of all p&ential prophylactic substances f o r the prevention of radiation dPsc4asciB it irt proposed t o make shart-tmm studieb of potential compounds which from th mre tic dl considerations end existing data soem most likaly to rmceesd, It l a also expected $hat then mbar af anbalec util f zed WUbe only enough to indica h trends that pint the way for further
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work a.t Nopa or elsewhere., fruitful remits but will &so mrve to itiitiato m d $ h e impntua to the planned Such a yrqresn might, not o n l y be productiva of 80Napa biological proginsac It is proposed to administor ti66 caxprunda to m t a and dags both orany and of 3503750 r eingle dose whole body X-irradiation by mrrurror of a 250 kvp X-ray machine. PPemortem arid piist-mrtam axmination of tbafr tiasuss w i l l then be mad@w ith particular smpherzfa boPing placed upn the dogma of say hemorrhagic Comparison w i l l be mdtp of the d*prasaiarn of the hamatological elements in t h e that, en undesirable synerejstfc effect. might rerrult from the use of various combinations of coapunds, it a p p a r s t,hi?t due t.o the hstoro~emecusfactors involved that the use d such mmbfnatiom a m not; only Jr;s&siablebut mybe ing Prom irrzidiation a m listed togtptkar with the cumpornids and combhatione of eompmnds to b e used to combat these a ff wto,, LF+yaiol.ogic&l Ef f acts of Irradiation
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Tha following manple is j u s t one illustration of how the abcve carpounds One animal would receive all the following compounds prio ra odd be utilized - Co irra&iet.ion; 1) For tAe henorrhitgic syndrom, an anti he par in compound such as Coluidine blue t o maintain blood coa gul ability ada flavanone such as rutin to control vascular integrity, 2) For the non-descript toxic phenomenon, …
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