The Los Alamos Scientific Laboratory's Experience with Plutonium in Man (Health Physics Pergamon Press 1962, Vol. 8, PP. 753-760)

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Heaith Phytcs Pergzmon Press 1962. Yo1 8, pp. ij3-i60. Printed in Sorrhcrn Ireland THE LOS ALAMOS SCIENTIFIC LABORATORY'S EXPERIEXCE WITH PLUTOSIUM IN MAS* Los .-\lamas Scientific Laboratory University of California Los Aamos, Sew Sfexico Abstract-The present paper presents an historical account of the Lor.hot Scientific Laboraton's industrial medical experience with exposure of personnel to Pu*~*.Observations cover the period from the beginning of the Manhattan Project through 1960. I n the early days, exposures were of an acute or semiacute nature. Improved industrial hygiene and engineering methods have changed the problem to one of chronic low-level exposure, lugely via inhalation. Consideration of the Laboratory's experience during the past 17 years suggests that the present problem a r e a are: ., I ! the diagnosis of body burden under chronic exposure conditions and with little or no specific index of exposure other than a persistent low-level urinaw excretion rate. and :2 the choice of the critical organ when exposure is largely via chronic low-level inhalation. A COHPREHEXSIL-E discussion of the Los Alamos perience with Puss would be a history of the nuclear weapons program. During the latter part of 1943 and the first part of 1944, the Laborasearch activities involving milligram amounts of material. During the latter part of 1944, gram amounts were processed in research activities directed principally toward production of pure plutonium metal and studies of iu physical and nuclear properties. By mid-1945, kilogram amounts of plutonium were procased from which nuclear components of the Alamagordo and Nagasaki weapons were fabricated. Plutonium processing ha- remained at the kilogram level, although major operatiom no longer consist of production and fabrication of weapon components. The specific purpose of this report, however, is not historical documentation of the Laboratory's activities in the nudear weapons field, but rather emphasis, in a chronologic manner, of some a peri enc a and observations Thii report i based on work performed under the + Present addreu: Strong Memod Hoapital, auspices of the U.S. Atomic Energy Comrm9ion. t'nivenitv of Rochester, Rochater, New York. that may be helpful in present and future industrial medical control of this important &- PERMISSIBLE BODY BURDEN Although no satisfactory method of diagnosing personnel exposure to plutonium was in operation during 1943 and the first nine months of 1944, a maximum body burden of 3 - 5 pg was assumed to be acceptable as an operational guide. This value was derived on the basis of bone as the critical organ and direct comparison of energy deposition from the 0.1 pg maximum permissible body burden of fixed radium, aEsuming a 50 per cent exhalation of radon: In the spring of 1945, a representative Director's Office of the Manhattan District convened a meeting at Los Alamos to discuss the Laboratory's maximum permissible body burden

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7.54 SCIEhTIFIC ESPERIESCE IVITH PLUTOSICSI IS LLLY of plutonium. By this time, a merhod of estimating body burden from urinary analyses had been worked out and nine Laboratory personnel were believed to have burdens approaching 1 pccg. Because of apparent differences in the bone deposition patterns of radium and plutonium in ram, the decision was made to introduce a safety factor of approximatell; 5 and lower the maximum permissible body burden to 1 pg. This value remained in effect until the Tripartite Permissible Dose Conference at Chalk River, Canada, on September 29-30, 1949. At this meeting, Dr. Austin Brua presented results of comparative chronic toxicity experiments in rats and mice which indicated PuSD was 15 times as damaging as RaZa when the two were injected in equivalent microcurie amounts. The Conference recommended, therefore, that the maximum permissible body burden be IoFvered to 0.1 The stringent maximum permissible air concentrations imposed by such a conservative body burden would produce serious delays in the Chalk River Conference recommendations ology and Medicine prior to official adoption. Re-examination consisted of a wave of intense minated in a meeting in the office of the Division of Biology and .Medicine on January 24, 1950. At that time, Dr. BRL'ESpointed out that two factors mitigated the assumption that 0.1 p c of k e d Pups was equivalent to 0.1 p c of fixed Ram for the derivation of a human tolerance lrvcl. First, the Pu :Ra toxicity ratio of 15 : 1 was based on injected amounts in s d animals and, since plutonium was -75 per cent retained in rodents and radium about 25 per cent, the ratio on the basis of retained dose could be lowered by a factor of 3. Second, since radon was approximately 50 per cent retained in man and only 15-20 per cent retained in rodents, the toxicity ratio on the basis of relative energy deposited could be lowered by at least another factor of 2. Strictly on biological grounds, therefore, a fixed plutonium body burden for man could be derived from the animal experiments, as follows: -4s a result of this meeting, Dr. SHIELDS WARRENof the Division of Biology and Medicine authorized 0.5 pg (0.033 pc) of Puag as the AEC's official operating maximum permissible body burden. In 1951, the International Committee on Radiological Protection at a meeting in London recommended 0.04pc. This value was endorsed at the Tripartite Conference on Permissible Dose at Harriman, Xew York, in March of 1953, and in the fall of 1953 both the National Committee on Radiation Protection and Measurementsi1' and the International commended in their official publications a Pu"9 maximum permissible body burden of 0.04 pc. Both organizations have held to the 0.04 pc value in their most recent recommendation^.'^^^' Although derivation of the presently accepted value differs somewhat from that proposed by BRL'ESin 1953, it is still based on a comparison with 0.1 pc of Rana, assuming the skeleton as the critical organ. Two difficult questions still prevent unanimous acceptance of the recommended value. The first question involves adequacy of the maximum permissible body the choice of the skeleton as the critical organ for PuSg under conditions of chronic inhalation exposure."-g' In the latter case, plutonium concentrations in the pulmonary lymph nodes, lung tissue, and liver appear to be considerably higher than in bone.i10' The question, therefore, becoma one of relative sensitivity of these tissua to damage under conditions of chronic rr-radiaExpcrimmtation in support of thc estimation of During the early days of the Manhattan Project, the excretion and retention data on which to base a method of diagnosing Pups body burden were largely from experiments on rats. It seemed imperative, therefore, to determine

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retention and excretion of plutonium in a limited number of terminal human patients. Sixteen cases were studied, the first beginnin: in .April of 1945.(11) Life expectancy of the individual and relative freedom from kidney disease \\.ere the principal criteria for case selection. .& a rule, individuals were chosen t i 110 r\.ere past 45 yr of age and tvho \\ere sufferinq from tcell-estahlished disorders that made sur\-iva1for 10 more yr highly improbable. .Xdhercnce to this rule avoided the possibility of development of late radiation effects from plutonium. Dose ranged from 4.6 to 6.5 ug. =Uthough no acute toxic effects \\ere expected from such small doses, clinical laboratory observations rvere carried out. especially tvith regard LO hematological changes and liver and kidney functions. S o acute subjective or objective clinical effects were observed. Urine and fecal samples u.ere collected daily for plutonium analyses. T h e results of these studies have been reported previously.(11-*4' The data shourd that piutonium excretion in man was expressed most conveniently by power functions. Over a period of 138 days after injection, urinary excretion .:Y,: \vas represented by the expression, in which Yuwas the per cenr of the injected dose excreted per day. and t '> 1:. was the number of days benb-een injection and sample collection. The empirical fit to the fecal excretion data < Y,) and to urinary plus fecal excretion i(Yu+,) was: It is not possible to state specifically the limits of accuracy of these expressions for the representation of plutonium excretion by normal healthy men. First, the cases were not normal; second, many of them died within 30 days (only three lived the full 138-day observation period), which seriously limited the period ofobservation ; and third, methods of plutonium analysis in 194-1946 were crude and inaccurate compared to present methods. The primary virtue of the expressions is that they are based on the only human data available. tribution studies \cas obtained from seven of the 16 cases. =Uthough tissue sampling was extremely poor, it \\'as possible to make a crude estimate of plutonium in the major organs and Tissues. Table I shotvs a comparison ofthese data with more extensive and accurate observations nium distribhon in the beagle and in man \\.as quite good and perhaps fortuitous. considering the inadequacy of human samples. The primary value of the human data lies in the fact that it adds confidence to the use of animal data as a basis for deriving a maximum permissible plutonium body burden for man. Table 1. Distribution of intraienou(v adminisrerrd piutonium in major tissues of the beagle and man Tissue Beagle hlan PLCTONIVM EXPOSURES DURING .Vuher and nature of curb exposures Before the .AEC assumed responsibility from the Manhattan District (January 1, 1947), 27 Los =Uamos Scientific Laboratory personnel had accumulated plutonium body burdens of from 0.1 to 1.3 pg !0.0074.09 p). Twelve of the 27 cases had body burdens of 0.5 p g or greater. Nine of the 12 cases occurred in the same operation-recovery of plutonium from wmte mater&. This operation consisted of dissolving the waste materials and plutonium in strong acids, pH adjustment of the solution, precipitation of the plutonium as the peroxide, resolution of the peroxide, and final precipitation of the plutonium as the oxalate. T h e entire operation was conducive to the formation of a fine aerosol of plutonium salts, perhaps largely Pu(N03j,.

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FIG.1 , Crinarv excretion curves indicating relarivelv acute exposure of four plutomum rccoverr- process operaton. Although respiratory protection was provided, the route of exposure undoubtedly was via inhalation, as indicated by a strong correlation beween high urine counis and frequency of contamination of the nasal vestibule.(16) Figure 1 shows urine assay curves for four of the plutonium recovery process operators and the monthly amount of material put through the recovery process The shape of the assay curves and their apparent relation to the amounts of plutonium processed show the exposures were of a relatively acute nature. .Although it was not possible to estimate the amount of plutonium in the respiratory lymph node and lungs of thae cases. the insoluble nature of PuiIV) at tissue p H would lead to the supposition that the concentrations in these tissues might have been considerably greater than in the skeleton, Foilouwp examinations of .\fanhattan Project Twenty-four of the 27 Laboratory employees who had accumulated measurable body burdens of plutonium prior to January of 1947 were carefully examined in 1952, 1955 and again in 1960. Examinations consisted ofmedical history, complete physical check-up, laboratory studieq and roentgenograms. Laboratory studia included white blood cell, red blood cell, and differential blood counts, and urinalyses. .4t the recommendation of Dr. William Christensen (who made radiographic studies of the beagles at the University of Utah plutonium toxicity project), the roentgenograms taken were of the chest, pelvis, single projection film of right femur, right distal femur showing metaphyseal detail, and detailed dental film showing interOne member of the group died in 1959 from coronary thrombosis. His body burden of plujects were in good health and actively employed in 1960. At no time have any of the subjects showed s>mptoms or signs of radiation injury. Laboratory examinations and roentgenograms in 1960 were within the normal limics, and their medical histories revealed no uiiusual incidence of medical complaints. After 15 yr there were no subjective or objective indications that they had small body burdens of plutonium. In 1958 (12-13 years after their original exposures), 24-hr urine samples were collected from all follow-up cases and analyzed for plutonium by the current nuclear track-counting technique. Re-estimation of their body burdens showed that three of the group originally thought to have burdens of 0.1-0.3pg were negative. The majority of the o t h m showed burdens of from 1 to 3 times their original estimates. This is not surprising, considering the possible error in extrapolation of the urinary excretion c w e to 12-13 years. A 10 per cent error in the exponent o f t would produce an error of at least a tation of the roentgenogram.

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factor of nvo in the body burden, when the ex- burden under conditions of chronic exposure, cretion curve is extrapolated to 10 years. Recal- LAWRESCE"" applied his computer method to culation of the urinary excretion function, using the plutonium urinary excretion data collected a weighted least squares analysis programmed for the IBM 7090 computer, suggests the possibility of at least a 10 per cent error in the Diagnosis of body burden Because of vastly improved industrial hygiene and engineering measures, relatively acute exposures like those experienced during the Manhattan Project have not been encountered. A very important current problem, therefore, is diagnosis of body burden under conditions of very low-level chronic exposure. In many instances, there may be little or no specific indication i high air counts, contamination accidents, etc.) of any positive exposure, but rather a gradual increase in urine assavs with increasing lengrh of employment. In this case, there is no kn0tk.n time of exposure on which to base an estimation of body burden from the urinary exgrams, based on the orisjnal urinary excretion equation, that attempt to estimate chronically accumulated body burden from a series of urine assay values. Applicability of these methods to the estimation of body burden under presently prcvaiiing conditions of exposure has not been LAWRENCEhas applied his computer method to all urinary data accumuiated at the Los Alamos Scientific Laboratory, including the data collected from the original 27 exposure cases that occurred during the Manhattan Project. His estimates117)of the body burdens of the latter group average approximately 50 per cent higher on ail Los Alamos employees from 1945 to 1960. Data were available on 4215 employees. Many had terminated; others had transferred to jobs not involving further potential exposure; and 1639 were on the active employment list as of December 3 I , 1960. S o attempt is made here to look for correlations of body burden with length of emplo);ment, specific job assignment, air counts, operational procedures, frequency of contamination accidents, etc. A search for such correlations could be thesubject ofa future paper. Table 2 merely shows a breakdown of the number of employees as a function of the fraction of the maximum permissible body burden derived from the urine assay data by the computer Tablc 2 . Summarv of Los dlamos plutonium cxposurcs maximum p mirs i bk body burdrn Fraction of maximum permissible bodv burden S o . of employees This ageement is surprisingly good. However, the accuracy of either of the atimata k not known, and both are subject to the inherent uncertainties in the basic …