Health Considerations for Workers Exposed to Plutonium

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HEALTH CONSIDERATIONS FOR WORKERS EXPOSED TO PLUTONIUM From the Los Alamos National Los Alamos, New Mexico Reprint requests to: Occupational Medicine Group Los Alamos National Laboratory The story about radiobiological studies in search of the information needed to protect people working with plutonium (Pu) during and after World War II is an exciting bit of occupational health history. Discovered in trace quantities by G.T. Seaborg and colleagues in February 1941, this man-made transuranium metal was being handled in kilogram quantities in 1945 by wartime workers who were developing the atomic bomb Only a year earlier, Seaborg himself suggested, in January 1944, that due to its alpha radiation and long life, “The physiological hazards of working with plutonium and its compounds may be very great.”l6 Until then, not enough Pu had been made to see or to worry about. Seaborg suggested that a highest priority program be initiated to study this problem as soon as possible. Consequently, a portion of the first small batch of Pu produced was immediately made available for radiobiological studies in early February 1944. T h e results of the first experiments of Pu in rodents by J.G. Hamilton (University of California, Berkeley) were mentioned in the monthly report of the Metallurgical Laboratory (University of Chicago) for February 1944.2 A special symposium on the Pu bioIogical research project was held at the annual meeting of the Radiological Society of North America in 1946.10 I t is interesting to observe that today the discussions, public concerns, and legal battles over health risks presented by Pu are not only vigorous but also accelerating. Most of the time it seems difficult, if not impossible, to bring the technical results from extensive research efforts to bear on these questions. OCCUPATIONAL MEDICINE: State of the Art ReviewsVol. 6,No. 4, October-December 1991 Philadelphia. Hanky & Belfus. Inc. 681

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Our knowledge o i thc biochcrnistr). pd:i-,ophysiology, dosimetry, and radiobiology of Pu has increased enormously during the intervening 45+ years since the first experiments. For the first time in the history of science and industry, extensive epidemiologic studies are being conducted on the majority of all people in this country who have worked with a material since its introduction and before anyone has had any known acute or chronic illness from exposure to it. PLUTONIUM STUDIES IN ANIMALS Experimental studies in rodents and dogs during 1944-1945 searched for the levels of Pu that could cause acute, lethal, and subacute ~ffects.2~These studies also looked at the uptake pathways and distribution in the body, effects in organs, and excretion mechanisms. Contrary to some common perceptions, Pu was found to be less "toxic" on an acute LDw, basis than the "supertoxic" chemicals (e.& literature uses "acute toxicity" as a term to compare LDMvalues of radionuclides or chemicals. Use of this terminology is unfortunate, because it confuses chemical toxicity with acute radiation effects for radionuclides like Pu. The radiological hazard of Pu far exceeds any known chemical hazard of heavy metals.) The main routes to internal deposition in animals were found to be absorption from contaminated wounds or by inhalation of respirable particles. Absorption through the gastrointestinal tract was noted to be v e q low (for humans it is now considered to be lO-J-IO-' depending on the chemical formi4).Essentially no absorption was. observed after contamination on intact skin. Major research efforts were also expended, especially in the post-World War I 1 years, on the comparative hazards of various radionuclides. It was soon apparent from experiments in rodents that Pu was about 15 times more acuteIy injected per unit body weight. Such studies played an important role in settiirz the first protective guidelines for worker protection. Research interest turned immediately to a concern for late healtl: effects, especially cancer, that may result from Pu deposition in the body. For example, a 1946 report by Brues et a1.6 reported on cancers, including osteogenic sarcoma, that were found in rodents exposed to Pu. The results of that study were also pubtished in the proceedings of the 1946 Pu Sympo ~ iurn. ~ ~ Animal studies on the late effects of Pu have gone on at U.S. universities, national laboratories, and other research laboratories around the world for nearly five decades. No summary does justice to the details of this mass of technical work, but fortunately there are several superb books that put much of the information in easy reach for the reader. Hodge et a1.I' produced a reference that is still valuabk even though i t was published almost 20 years ago. Stannard, in his nearly 2,000-page history of radiobiology.**has brought together in one book the major results of research on all the internal emitters. This monumental work covers the period of World War 11 through the end of the 1970s. Th0mpson2~ summarizes four decades of investigation ol the effects of ionizing radiation in dogs, including the effects of internal deposition of Pu and other radionuclides. The bibliography lists over 1,100 citations. Pu was identified as a bone seeker in initial radiobiological studies.27 Hamilton10 was the first to recognize that Pu deposits on bone surfaces. In this respect, i t differs from radium, which deposits more uniformly throughout bone. Liver is the other organ in which higher concentrations of injected Pu are

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consistently found. Exposure by inhalation of relatively insoluble particles of Pu, e.g., 23qPu02,results in retention of a significant proportion (5040%) of the particles in the lung and associated lymph nodes for years. The portion of paniculate Pu that becomes soluble in body fluids is distributed by the systemic circulatory system primarily to bone (50%) and liver (30%)." It is thus not surprising that animal experiments showed excess cancers primarily in bone, lung (after inhalation exposures only), and liver.u.w Bone tumors in dogs were most frequently osteogenic sarcomas arising in trabecular bone. Types of liver tumors, in descending frequency, were bile duct adenomas, bile duct carcinomas, various sarcomas, and, infrequently, hepatic cell tumors. Liver tumors usually occurred late in the dog's life and were a less common cause of death than were bone tumors. Lung tumors occurred principally after inhalation of insoluble Pu particles, e.g., high-fired 21QPu02.The more soluble Pu than in lung tumors. About 3-7% of Pu deposited in human bone is located in the bone marrow,21 which raises a question about the risk of inducing leukemias or myeloprofiferative disorders. These diseases are not a significant finding in the dog studies? however, high doses of Pu result in considerable damage to hematopoiesis and bone marrow function in mouse experirnents.3' Some radiobiologists consider the leukemogenic risk from plutonium to be significant? however, animal data do not support this . HISTORY OF PROTECTIVE GUIDELINES Use of health protective standards in Pu work evolved rapidly during World War I1 as a result of both early recognition of the hazard and the immediate radiobioiogical studies. Initially, provisional and tentative standards were uscd at 'the several facilities using Po in the Manhattan Project.'6 By March 1945, officials responsible for the health and safety of workers in the project judged that a maximum allowable Pu body burden would be I pg (0.06 pCi or 2,200 Bq). Air and water tolerance concentrations were ais0 derived for workers and the general Standard Based on Radium Data The allowable Pu body burden was based on a comparison of energy deposition from Pu and 0.1 pCi of radium with a safety factor of 5 or IO as a precaution against the difference in distribution between radium and Pu in bone.15 The value of 0.1 gCi of radium was recommended by the National Bureau of Standards (Handbook 27) in 1941 as the maximum permissible internal deposit. The clinical study of 3 persons exposed to 226Ra and 22*Ra on which this recommendation was based, plus 27 other cases, was fully described by Aub et a!.' In 1949, a meeting of knowledgeable scientists from the United States, the United Kingdom, and Canada took place at Chalk River, Ontario, Canada, L O review the Pu biological data. Judgments on the risk of Pu were still based primarily on the toxicity ratio of plutonium to radium. These deliberations led to the establishment of 0.04 pCi ( I ,480 Bq) as the maximum permissible amount of L 3 9 P ~fixed in the body.16This guideline was used for protection of workers until the early 1980s. when gradual implementation of new radiation protection concepts using calculated organ doses began.

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Standard Based 011 Dosimetry In 1977, the International Cornmission on Radiological Protection (1CR P) produced Publication 26," in which it described a new radiation protection concept. In it. the maxiniurn occupational dose guideline is based on a calculated effective dose equivalent by the use of organ doses and weighting factors. The overall guideline for occupational exposure is not to exceed an effective wholebody dose equivalent of 50 mSv ( 5 rem) annually from all types of occupational radiation exposure. internal and external. Between 1979 and 1988, a series of reports known collectively as ICRP Publication 30 contained the derived annual limits of intakes (ALI) of radionuciides for the protection of workers. The current revision of ALls for plutonium was published in 1988 (ICRP 30)1-\and is based on current understanding of the behavior of Pu in the body as given in ICRP Publication 48 (ICRP 481.'' Although the conceptual basis for linliting exposure to Pu has changed drastically, from a practical standpoint, the limit on internal deposition is not SO greatly changed. n e ICRP protection concept requires calculations of organ doses. For Pu. these doses are uncertain, because the internal distribution of Pu varies greatly from one case to the next and the microdistribution of dose within organs is poorly understood. Therefore, the effective dose equivalent for Pu is normally calculated using standard models as recommended in ICR P Publication 30. One of the advantages of the ICRP dose concept is the ability to add internal and external radiation doses for radiation protection purposes. Over the past decade, the 1CRP concept has gradually found its way into national regulatory standards. This revised worker protection guidance was placed into effect for U.S. Dcpartment of Energy facilities at the beginning of 1989. The Nuclear Regulatory Commission has developed similar regulatory guidance, which is planned for implementation in the near future. New lCRP recommendations were published in the spring of 1991.1SThe occupational radiation exposure guideline limit will be reduced to 20 mSv (2 rem) per year (external plus internal radiation doses). This limit may be:averaged over 5 years, but there is a funher provision that the dose should not exceed 50 rnSv ( 5 rem) in any single year. PLUTONIUM STUDIES IN MAN The above synopsis of radiobiological studies on the biological hazards of Pu and the brief history of protective guidelines point up that the s t m of such efforts occurred almost simultaneously with the earllest handling of this material. It was not the witness of ill health or disease among Pu workers that triggered the studies, as is common in the history of occupational medicine. There is no series of case studies to demonstrate the risk of Pu exposure. Protection from Pu exposure was a major concern of those responsible for protecting the health of workers at Pu facilities. The protective guidelines that regulated Pu exposures in this industry were based on a limit judged to be as safe as the limits !or other types of ionizing radiation. Admittedly, protection methods and equipment have improved greatIy through the years. & u t the concern and the effort to control and eliminate exposure were present from the beginning. The above activities. if based on good risk estimates and effective irnpletnenlation, should iiifluence thc expectation of findings in epidemiologic studies of PUexposed workers. Under controlled working conditions. nsh from small exposures within the guidelines will be difficult, if not impossible. to detect by epidemiologic

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methods. Accidental exposures to air releases of Pu particles or to contaminated wounds did occur, but the numbers of workers exposed in excess of the guideline limits are surprisingly small. Interestingly, the first long-term medical surveillance of Pu workers was started only a few years after the first exposures. T h e study consisted of the workers who had helped to build the first atomic bomb at Los Alamos, New Mexico, during World War 11. Wright Langham and Louis Hcmpcimann had responsibility for the health and safety ai those who did this work at Los Alamos in 1944-f945. In 1951, Langham and Hernpelmann traced and located 26 workers who were judged to have had the highest Pu exposures. Most of them had left Los Alamii immediately after the war. The objective of the study was simple. Were the workers stili healthy or not? Medical examinations were obtained on all. No health problems attributable to Pu exposure were found. It was the stm of a small but important study that is continuing 40 years later. Perhaps the most important outcome of this study was the recognition in the mid-1970s that epidemiologic studies needed to be extended to a large segment of Pu workers in the U.S.nuclear industry. Epidemiologists at Los Alamos National Laboratory have been collecting and analyzing data on the long-term health experience of Pu workers. Table 1 lists the number of workers employed from the onset of operations until 1978-1979 for the facilities under study: Los Alamos National Laboratory and Zia Co., Los Alamos, New Mexico; the Rocky Flats plant near Denver, Colorado; and Mound facility near Dayton, Ohio. Data have been collected on all workers at tht3e locations, whether or not involved in Pu operations, and include more than 54.000 workers. These workers include a majority (over 80%) of all persons i n v a t u :n Pu work in the United States. Vital status of the persons in these cohorts is currently known with about 95% completeness to the end of 1983. In the futurc, dat- ~ i )a smaller number of Pu workers at the Hanford Site, Oak Ridge National Laborator, and Savannah River facilities will also be obtained from uti.<< ongoing epkmiology studies to be used in pooled data analyses. ;ab& L lists the number of white males in these cohorts who have been exposed to radiation from external radiation doses and internal Pu depositions. Arbitrary levcls of > 1 rem externai and > 74 Bq (2 nCi) Pu deposition are used to define an exposed worker. By this definition, about 20% of the cohort hgve h t ~ n exposed to external radiation and about 5.6% to internal Pu depositiori. White males are listed, because they compose the largest number of workers involved in exposure at these plants. A much smaller proportion of females in the work force were exposed during the period of these studies. To monitor workers for potential Pu intake, scheduled periodic urine samples are measured for Pu excretion. This general method has k e n used since 1944 and has proved 10 be the most sensitive biological indicator available. Persons with TABLE 1. Cohorts Included in the Study of Health Effects from Plritnnium' Fiicilitv …