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Plutonium injection studies - a report- the excretion of hexavalent uranium following intravenous administration by samuel h. Bassett, albert frenkel, nathan cedars, helen vanalstine, christine waterhouse, and katherine cusson. Studies employing uranium enriched in the isotopes uranium 234, uranium 235 have been carried out in six human subjects; four males and two females. The uranium was given intravenously in the hexavalent state as urenyl nitrate in amounts ranging from 6 micrograms to 70 micrograms per kilogram of body weight. Each individual in the series received a single injection of the metal except for subject 6 who was given 2 widely spaced doses. The first of these was when his condition was normal and the second after an acidosis had been produced by ingestion of ammonium chloride. Renal function tests including urinary catalaso, protein, amino n to creatinine n ratio, and clearances of mannitol and p - aminohippurate were done before and after administration of uranium. Only at the 70 microgram per kilogram level in subject 6 was there a slight rise in urinary catalaso and protein suggesting that tolerance had been reached. All other tests were negative. The excretion of uranium was mainly in the urine, where from 70 to 85 percent of the administered dose appeared in the first 24 hours. Urine of the second 24 hours contained about 4 percent and the third 24 hour urine, 1.5 percent of the administered dose. Detectable amounts were excreted for at least tw0 weeks. It is surmised that this late excretion represented uranium originally stored in the bones. Negligible amounts of uranium were found in the feces.
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Argonne Natjonal La bra tory Armed Forces Special ;Yeapolus Project Atomic Eiergy Cord ssion, iTashinlP;eon Battelle IJmorial Imt it ute Brookhaven National Laboratory Carbide & Carbon Chemicals Corporation (K-25 A w a ) Carbido & Carbon Chendcals CorporaLion (Y-12 Area) Gamral Electric Campang Hanford Directed Operations Ioa State Colle p Uas9acfiuwtt.s Institute of Technology &!omanto Charnical Conipqy, Daytun National Buxau of Stzndarcb Naval Kadjiition Laboratory Patent Advisor, Washxhgbon Technical In form ti or ! Division, OHDO UCLA Medical Reaearch Laboratory University of California Radiation Laboratory Univex-aiky of R o c ha ster Western Reserve University (fi ic doll)
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Nature o f Material Injocted and Te~micptreo f ...........Mechanism o f Excretion of Hoxavkdent Um n tun
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dosec from 10 to 20 per c a t , 'baeooios f i x 0 3 to tOso phosphate groups of of it elimination, the chief toxicity o f uranium is for the kidnoy, where it produces a amere tubular n epb it is (3). It has been found recently thnt x b b i t o &nd doge pftexi shdv r6@.6.,-16 in increased urinary catalase and prote"a to injections of uranyl acetate 'given intravenously a t a level of O o O l mg. per Rgo of body weight (Oo006mga o f uranium metal) (41, This dose is well below thu level that w l l l produce
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decreased the rata af excretion. At tm pts at mobilization of tha fraction retained by InJection of citrate and by the use of a low ealchm diet plus dibydrotochysterol were ia$'fective.
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go~cllddney. function with urine freo from protsfn and with a normal sediment oonthued ba~.'~:aslimfGionand medical care vas a l n o a factor in the cbolceo Criteria of importance In ddng the soleetion were reasona'bly The probabtlitgr. that the patient would benefit fr m
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radiation effects might occur, and the enriched isotopic mixture was 'rtiluted with ordinary uranium, The initial dose was set at npproximtely 6 rnicr&ymns of ths mtR1 per kilo of body vrei;:ht and was chosen because this i s tho amouni; which will ocaaslorally produce just detectsable temporary rbml damage in the rabbit, a susceptible animl (4), dosage provided that no signa of injury. to t ! i e kidney Gore do'ieotcd,. The plan called for a siowly incraaqhg Until it was established that t how te of, alzd total excretion were of the same order as that for expr ims nts l &ni&ls,, no cUbjGc'w received n!om than t h e enriched mixture of isotopes of U234,, U235 ww dilu'cod 1-4 using uranyl acetate of the ordinary isotopic con position, It was estirrsted that %hiswould decrease tho radioao-iAvity to a point idioro "ny late radiatjon effectti would be highly f q rob rr lla Subject 6 recoived t h e 1nrg;est anlourit of .ji.dniua, ubout '?I micrclgram p r kilo and was given a second injwAion sftw & cidil ' io atl on with ammiurn chloride, No renal toxic ao tion 1-s noted. -A, .
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tho Jisedh mmved, A second 20 map needle fill lsd nl th water was attached
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Alk. Phosphatase 2.3 Bodansky Units These t e s t s likevriso indicate a necatlve effect at the present level of dosage,
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Ratio of Urinary &no Acid NitroKen t o Urinary Creatinine ' Point of Uranium Raminis tra tion
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Total Serrvn Protein Max hum tabular (para amino hippuric acid) Excretory Capacity -- 81 fi id mi rie
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2b Standard Clcarmce 75% of norinial, - Urine Ihmination: Specific Grnvity - lo0Pj1 no albumin casts or sugar, Red blood calls 3*7 x 106 per cu, rim,
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Bogative q u a h c roadtion. for Blood on admisefon to metabollrsu Rasalving pneumonic procoss in right -upper lobe with
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Decrease I n size o f the ulcer on the lesser ourkture. Baal Function: 1/9/47 (Condition normal) intravenouely at lO:25 A, 14. on January 10, 1947, Subjeote 4 and 5, the enriched mixture ob the isotopes U2340 U235 wae B e in the camof ratio h a h o lV/CreatInbe PI In the, urine (table 201,
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Ratio of urinary amino acid nitrogen to urinary creatinine, (Analyzed by He Berke and El, Crossmon)
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0 0 m wore abms GO .sal& per cent, a considerable acidaeie was achieved
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Possible tstent%onin body 1167 nicrograms The flnal toots of kt bey hc t la a were done on Jwwry 33.. 1947 tho period of acidoeia. to test the effect of meamre8 slued at mobilization of the ursalum preatam- ... 1
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Dounce (13) haa sham that uranyl ious conplez readily with Carbonate 'or blcarbcnata, or@.s.iic acids a8 citrate, nnlate and acetate, o f bicarbonate, abut 60 per cent of 'Js -1s ~IX-W+-.+t 0.0 i'or~? a f i & a complex carry out, man bebavst; as does the mbbit and other aaimda with regard Evidently f~*arothe studies i f 8 1 ~ v - ebeen able ta through the ah in intra bioi- of amr;or!5.~xnchloride i s rcs:mmZ.ble for slowing
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OFFIGIRL USE ONLY --- I inti6 the urine or at loast become mare poiulecabLe and leak cataltlse in& It?0 The early proteinuria of uranium poisoning no dou3t ha8 a similar The small and i n o w experiments incoxiiPsquenti+l mounts of upwiurd (V,)found in the feces.ars also 431 apzmaent k t h t h e aninal work Possibly a very rnlnute fraction a f the Injected & omio excreted in thg,-. bile and tracas,probably apparr i n other Jintaqtird s2cretionso presence o f dietary phaephoms m d the reaction of tho fntestlml coneants would favor flxatlon of any uraniun entering tho g c L t LLDa phosphate
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