ATTACHMENT 20 (Title and Credit Page) This is a Joint Publication of Work Performed under Contract No._____ Los Alamos Scientific Laboratory and Contract No. W-74C1-eng-49, The University of Rochester. K. K. Bradberry, Director of Los Alamos Scientific Laboratory Andrew E. Dowdy, Director of Manhattan Department, The University of Rochester [ILLEGIBLE] OF PLUTONIUM ADMINISTERED INTRAVENEOUSLY TO MAN. RATE OF EXCRETION IN URINE AND RECES WITH TWO OBSERVATIONS OF DISTRIBUTION IN TISSUES. Work done by: Samuel E. Bassett Jeanne Carritt Robert Fink Wright Langham Elizabeth Maxwell Arthur Murray III Anne Farley Hannah Silberstein Helen E. Van Alstine Report written by: Samuel E. Bassett Wright Langham With acknowledgment to: William F. Bale, L. H. Hempelmann, William S. Mc Cann, and Stafford L. Warren [ILLEGIBLE] OF PLUTONIUM ADMINISTERED INTRAVENEOUSLY TO MAN. RATE OF EXCRETION IN URINE AND RECES WITH TWO OBSERVATIONS OF DISTRIBUTION IN TISSUES. I. Introduction II. Methods A. Clinical 1. Selection of patients 2. Management of patients a. Control period b. Observation period c. Routine tests (1) Blood tests (2) Urine and kidney function tests, etc. d. Collection and preservation of samples (blood feces and urine) 3. Method of Administration of Plutonium a. Preparation and nature of solutions b. Choice of size of dose c. Technique of Injection (1) Discussion of actual injection procedure (2) "Dummy" injection for evaluating amount of plutonium given B. Chemical Methods 1. Blood analysis 2. Feces analysis 3. Urine analysis 4. Tissue analysis III. Description of Subjects (case reports). Short paragraph about of 12 giving A. History B. Physical C. Laboratory D. Diagnosis (if known) 1 IV. Results A. Concentration of Plutonium in blood following intravenous administration as Pu+4 Citrate. B. Excretion of Plutonium in the urine following intravenous administration as Pu+4 Citrate. C. Excretion of Plutonium in feces following intravenous administration as Pu+4 Citrate. D. Deposition of Plutonium in tissues following intravenous administration as Pu+4 Citrate. E. Clinical Results V. Discussion and Conclusions A. Correlation between blood concentration and urinary and fecal excretion of Plutonium. 1. Possible significance of one abnormal case. B. Half-time of Plutonium in the body. C. Choice of urinary excretion value for diagnosing Plutonium exposure by urine assay. D. Discussion of results in relation to tolerance amount of Plutonium in the body. E. Discussion of results in relation to Chicago and California experiments of man. F. Discussion of results in relation to experiments on mice, rats and dogs. VI. Summary or Abstract 1. Clinical 1. Selection of subjects The individuals chosen as subjects for the experiment were a miscellaneous group of male and female hospital patients for the most part with well established diagnoses. Preference was given to those who might reasonably gain from continued residence in the hospital for a month or more. Special treatments and other therapy thought to be of benefit to the patients were carried out in the usual manner. The necessity of studying urinary and fecal rates of excretion of Pu automatically included cases of advanced renal disease or disturbance in the function of the gastrointestinal tract. Patients with malignant disease were also omitted from the group on the grounds that their metabolism might be affected in an unknown manner. The life expectancy of the individual was carefully considered. As a rule, the subject chosen was past 45 years of age and suffering from a chronic disorder such that chance of survival for ten years or more was improbable and adhering to these criteria it was hoped: (a) That the possibility of late radiation effects developing in the course of ten or fifteen years would be avoided. (b) That an opportunity would present itself to obtain post mortem material within a period of months or at most a few years. Of eleven patients in the Rochester group, ten were past the age of 45. One was only 15 years old but has since died of Cushing's Syndrome: a woman aged 49 years may have a greater life expectancy than originally anticipated due to an error in the provisional diagnosis. Up to the time of compilation of this report and approximately two years since the initiation of the study, five subjects have died of their disease. 1 Complete autopsies with tissue analyses for Pu were obtained in three instances: one death occurred in another institution with a [ILLEGIBLE] post mortem but no analyses of tissues: one subject died in another hospital and permission for autopsy could not be obtained. 2. Management of patients Ten of the twelve subjects were cared for in the special ward of the hospital where they were continuously under observations of in charge of the experimental work and of a specially trained staff of . One patient HP-11, remained on the general ward. No collections could be because he was in the terminal phase of his illness when the Pu was injected. Material from the subject HP-12 was obtained at Oak Ridge. The general plan of procedure with patients resident in the [ILLEGIBLE] ward was as follows: During a control period the subject was carefully instructed in quantitative collection of urine and fecal specimens. He became adjusted to ward routine and any necessary modifications in diet, medication, etc., The period of indoctrination usually required about ten days. After the [ILLEGIBLE] had proven himself capable of cooperation, control specimens of were collected. The period of observation following the injection was originally set at 22 days, however, as the work progressed, it became evident that more prolonged studies were desirable. Whenever possible these have been carried and include a longer initial period of observation as well as follow-up study made a year or more after the injection. Details are given in the case history (Section III) and in Section IV. Preceding the injection of Pu, the physical examination were evaluated, blood counts, area clearances, and blood chemistry were obtained. (Details are given in Section III). 2 Routine for collection of blood, urine, and feces Blood Blood was drawn into dry sodium citrate as an . Exactly 15 ml of well mixed whole blood was into a glass capsule and sealed. At first formalin was added as a preservative but later this was omitted because of the precipitation of protein with the attendant difficulty in removing the material from the capsule. Specimens were drawn before the injection of Pu and at stated intervals thereafter. The schedule evolved was one control specimen and post injection specimens at 4 hours, 24 hours, 3 days, 6 days, 10 days, 15 days, and at the termination of the period of hospitalization. The number of samples contributed by each subject and the relation to injection of Pu appear in the protocol of Section IV. Urine Urine was collected by having the subject void directly into a new half gallon fruit jar. The usual collection period for urine was 24 hours except for the day on which the Pu was given, when it was collected in two 12 hour periods. At the completion of each collection a label was affixed giving the subject's number and the dates and hours of collections. Fifteen of 40% was added as a preservation and the specimen heated or the steam bath for about two hours. This sufficed to expel much of the air from the jar which was then sealed and cooled to room temperature. Enough radiation in pressure was obtained in the jar to hold the lid firmly in place and prevent loss in transit. As a further precaution, an adhesive [ILLEGIBLE] was placed at the top level of the liquid in the jar in order that any leakage which might have occurred would be revealed to the person receiving the urine for analysis. The system worked very satisfactorily and losses were negligible.