May 20, 1946 TO: Dr. J. J. Nickson FROM: E. R. Russell Subject: Monthly Summary for Biochemical Survey Section The analysis of the urine will give a fair indication of the plutonium incorporated in the body. However, material taken into the lungs is not readily absorbed and a portion of it is eliminated by way of the intestines. From animal experiments it is shown that from 10 to 20% of that reaching the lungs is retained after 90 days. This, then, imposes an additional hazard if individuals constantly work in areas in which the air is even slightly contaminated with plutonium. In order to place an additional safeguard on the individual worker, frequent stool and sputum analyses should be made along with the urines. Two cases are reported in Tables I and II in which these individuals had worked in areas with above tolerance air counts of plutonium. In case 2 the individual remained at home for nearly two weeks and collected urine, sputum, and stool specimens. As is shown, there is a decrease in the amount of plutonium eliminated with the stools. However, since no experiments have been performed to show the rate of elimination of humans, it is not possible to calculate accurately the amount of material retained. These two cases, the only ones studied, are apparently fair indications of what might be a serious problem. Table 1 (Case 1) Date of Urine Stool Sputum Specimen (Body Cont.) (counts) (counts) 2-13-46 <0.1 ug ---- ---- 3-4-46 <0.1 ug ---- ---- 3-8-46 <0.1 ug ---- ---- 4-6-46 <0.1 ug ---- ---- 4-17-46 ---- ---- 2.1 c/m 4-20-46 <0.1 ug ---- 1.6 c/m 4-30-46 <0.1 ug 250 c/m 2.8 c/m 5-4-46 ---- 244 c/m ---- 5-5-46 ---- 42 c/m ---- 5-6-46 ---- ---- 2.68 c/m 3 Table II (Case ) Date of Urine Stool Sputum Specimen (body cont.) (Counts) (Counts) 3-18-46 <0.1 ug ---- ---- 3-29-46 ---- ---- 1.3 c/m 4-4-46 <0.1 ug ---- 2.0 c/m 4-6-46 <0.1 ug ---- ---- 4-9-46 <0.1 ug ---- ---- 4-12-46 <0.1 ug 26.1 c/m 4.0 c/m 4-17-46 ---- ---- 0.27 c/m 4-20-46 <0.1 ug 36.0 c/m 0.10 c/m 4-26-46 <0.1 ug 6.5 c/m 0.90 c/m 4-29-46 0 20.3 c/m 0.23 c/m 4-30-46 0 5.0 c/m 0.05 c/m 5-1-46 0 9.7 c/m 0.22 c/m 5-2-46 ---- 3.3 c/m ----- 5-3-46 ---- 6.12 c/m 0.28 c/m 5-4-46 <0.1 ug 2.2 c/m 0.07 c/m Other Activities I. Routine Urine Survey 249-MLH-3501 (Jackson-Sellers- Monroe-Schuman) A. Urine Specimens Received Chicago .................. 71 Other ................... 10 Backlog .................. 20 Total ...........................101 B. Specimens Analyzed Chicago .................. 71 Other .................... 10 Total ........................... 81 C. Backlog Chicago ................... 20 Other ..................... 0 Total ............................ 20 4 Special Urines (R. Lesko) A. Received ...........................34 B. Analyzed ..........................32 The daily urinary plutonium excretion of the subject MX-200 is being, followed. The Table below is a continuation of the one from MUC-HG-1203 Table III Daily Plutonium Urinary Excretion Days after 24-hour % of injected Injection Volume dose excreted 98 310 ml* .006 99 900 .0096 101 1150 .009 102 280 .006 103 1600 .019 104 730 .0086 105 1180 .0075 106 800 .0098 109 370* .0085 110 300* .015 111 630 .0095 112 560 .011 113 780 .0145 114 410* .0069 116 840 .0066 119 1600 .0115 121 1110 .0106 123 1100 .008 127 650* .0075 129 480* .0088 __________________________ * Incomplete collection II. Stool Analysis 249-MLH-3510 A. Specimens Received ...................... 24 B. Specimens Analyzed ...................... 22 5 III. Sputum Analysis 249-MLH-3520 A. Specimens Received ........................ 24 B. Specimens Analyzed ........................ 24 IV. Experimental Tissue Analysis 365-MLH-3530 (Reed-Brown) A. Specimens Received ........................122 B. Specimens Analyzed ......................... 79 Effect of Citrate on the Concentration of Plutonium in the Urine: Nearly a year ago an experiment was tried in which a dog, having been injected several months previous with a known quantity of plutonium, was injected daily with 5 cc of a 3% sodium citrate solution for 10 days. The plutonium excretion during this period was increased 2-3 fold. It was suggested by Drs. Nickson and Brues that since citrate is rapidly destroyed the immediate excretion following the injection may have been several times higher. In order to test this hypothesis, two dogs containing plutonium were injected with 5 cc of a 3.5% sucrose solution containing 3.5% sodium citrate and 3% citric acid. The bladder of each animal was emptied immediately before the injection. Following the injection, the urine from each was collected (catheter) for 10 minutes in 5- minute intervals. In one case the concentration of plutonium in the urine increased 5 fold in the first period and 8.5 fold in the second. The second animal showed a 6.5 fold increase in the first period and 9.7 fold increase in the second. It is obvious that the collections should have been for a longer period, however the test does indicate that citrate solutions injected IV may be useful in removing plutonium from the body. Plutonium Therapy Studies: Metal Displacement. (J. Schubert- D.Revinson-J.Tolmach) On October 25, 1946, a 7 KGM dog, PX-121, was given an IV injection of 0.423 mgms of plutonium. By January 3, 1946 the urinary plutonium excretion rate had become relatively constant with an average daily excretion of 0.0077% of the injected dose. The excretion varied from 0.011% as a maximum to 0.0045% as a minimum. Beginning January 3 various treatments were tried in an attempt to increase the plutonium excretion. Briefly, the treatments up to date have consisted of: (a) lead administration followed by an acidosis producing diet, (b) subcutaneous injection of 10 mgms of BAL per kgm, and (c) the I. V. injections of increasing amounts of zirconium. Treatments (a) and (b) did not result in any significant rise in plutonium excretion while a definite rise was observed following each zirconium injection. 6 The first zirconium injection was given March 29, the second April 10, and the third April 23. In the first injection 2 cc of a 15% ammonium citrate solution containing 44 mgms of zirconium was given. The second injection was twice that of the first and the third was four times the first. Following the first injection, the average plutonium excretion up to April 10 was 1.5-2 times normal. Following the second injection the average excretion was 3 times normal and after the third injection the plutonium excretion was 2.5 times normal. During the three-day period immediately following the third injection, the daily plutonium excretion rose as high as 5 times normal. Inasmuch as the dog can safely tolerate at least ten times as much zirconium as was given, increased amounts may be used in future experiments. Comparative studies of the effect of the solution, 15% ammonium citrate, will be made. In preparation for further plutonium therapy investigations, the chemical toxicity of zirconium on 200 gram female albino rats is being ascertained. As much as 50 mgms of zirconium (250 mgms/Kgm) was administered to one group of rats in a single dose by I.P. injection. Some of the animals have received as much as 200 mgms (1 gram/kgm) and after several weeks have shown no ill effects. It appears that zirconium given I.P. is rapidly absorbed. The zirconium solution was prepared by adding an excess of sodium citrate solution to an aqueous solution of zirconyl chloride. The resulting solution contained 9.6% sodium citrate and 26 mgms zirconium per ml at a pH = 6.0. The solution is stable toward dilution, pH changes and addition of phosphate ion, that is, non of these factors resulted in a precipitation of zirconium salts. A method for the quantitative determination of zirconium in rat excreta and tissues is being developed.