An analysis and evaluation of 241Am in the whole body of a donor to the U.S. Transuranium Registry (USTR) is presented in five parts. The USTR donor's pertinent medical history, autopsy findings and antemortem evaluations of intake and systemic burden are described in Parts I and II. The donor was a 49-yr-old male Caucasian radiochcmist who died of metastic melanoma in 1979. His work with actinide elcments began in 1952, and the greatest potential for intake of 241Am was when he used an unsealed 241Am source in his doctoral research (1952-54). The first indication that an intake had occurred was the detection of 241Am in a urine sample collected in 1958 as part of an internal dosimetry surveillance program. In-vivo estimates of the initial 241Am intake, based on sporadic urine samples and three sets of external photon measurcments, ranged from 0.23-1.1 uCi depending on the calculational models and calibration factors used. No chelation therapy was applied. The time of intake was estimated to be approximately 25 yr before death. External photon measurements made on the donor's body and dissected bones, presented in Part III, have yielded new and more accurate calibration factors for external in-vivo measurcment of the 60-keV gamma rays of 241Am and the 13.2- and 14-keV x rays of 239Pu and 238Pu. The symmetrical distribution of 241Am in the bones of the right and left sides of the body and the reliability of total skeletal 241Am estimated from external measurcments of 241Am in the head were confirmed. The soft tissues and about one-half of the skeleton were weighed wet, ashed, reweighed and analyzed radiochemically for 241Am, as described in Part IV. The measured total 241Am in the body was 147.4 nCi, distributed as follows: soft tissues of left hand, 1.9%; liver, 6.3%; respiratory tract tissues, 1.5%; other organs, 0.9%; combined structural soft tissues (muscle, skin, connective tissue), 8.6%; mineralized tissues (bones, teeth}, 80%. The expectations of similar 241Am concentrations in bones of grossly similar structure and also in parts of bones of similar microscopic structure were confirmed. The range of 241Am concentrations in the bones and parts of bones at about 25 yr after the most probable time of intake (79 +- 18 dis/min/g ash in 21 specimens of compact bone to 130 +- 9 dis/min/g ash in 14 specimens of cancellous bone in red marrow) is substantially narrower than is found in the bones of animals shortly after 241Am is administered, suggesting that skeletal concentration approaches uniform concentration at long burden times. About 80% of the skeletal 241Am was in compact bone and cancellous bone in fatty marrow and 20% was in cancellous bone in red marrow. The weights of the bones and the radiochcmical data from the tissues and bones of the USTR donor were used in Part V to develop and evaluate a five-compartment metabolic model for 241Am and to assess the model recommended currently by the International Commission on Radiological Protection (ICRP) (1979). The model includes an implicit, rather than explicit, transfer compartment (plasma) that communicates with urinary excretion and four tissue compartments: liver, which also communicates with fecal excretion through bile; two bone compartments (Bs. which remodels slowly, and BF, which remodels more rapidly); two soft tissue compartments (ST2, which is depleted rapidly, and ST2, a non-returning sink which communicates only with ST2). The bone compartments were defined anatomically: BF consists of skeletal parts that are mainly cancellous bone in red marrow, and Bs, the rest of the skeleton, consists mainly of compact bone and cancellous bone in fatty marrow. The initial distribution of 241Am in the adult male human skeleton was estimated by combining the initial concentrations (activity/g ash) of 241Am in monkey bones and bone parts and the ash weights of the same skeletal parts of the USTR donor. The five distribution fractions, the initial 241Am contents of the five tissue compartments and three of the seven turnover rates needed to solve the model were assigned numerical values based on animal experiments and available human experience. The four unknown rate constants were evaluated with a Numerical Algorithms Group library computer program by requiring the results of the model predictions to match within one percent the observed excretion rates and the tissue distribution of 241Am in the USTR donor at about 25 yr after intake. Numerical solution of the modei equations yielded values for the unknown rate constants with the original intake calculated to be 0.214 [mu]Ci of 241Am. The small fraction of the 241Am body content in the testes of the USTR donor (15 dis/ min) suggests that the current ICRP model of Am metabolism overestimates the genetic risk. The model also predicts a decline in the daily rate of urinary excretion from 8 X 10-5 of the contemporary body content at about six months after intake to 1.5 X 10-5 at about 25 yr and numbers of transformations in 50 yr in the skeleton and liver, respectively, of 1.5 and 0.25 times the values obtained from the current ICRP model. About 75% of the transformations in the skeleton occur in bone compartment Bs, which is mainly compact bone. Most of the Am initially deposited in the skeleton will be recirculated at least once; at about 40 yr after intake, the Am concentration in the skeleton will approach uniformity. Applications of this general model to patterns of intake other than brief exposures, to women and to men of different ages and races, to the modelling of other bone-seeking elements and as a tool in planning and assessment of chelation therapy are discussed. Detailed summaries appear at the end of each section.
(C)1985Health Physics Society