Memo to J S Robertson, Subject: Congressional Inquiry Into Follow-Up Studies on Human Radiation Experiments (Att: Journal Article Health Physics 1963 Vol 9 PP 1307-1323 re Same)

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CONGRESSIONAL INQUIRY INTO FOLLOW-UP STUDIES ON HLJMAN RADIATION EXPERIMENl J. S . Robertson, Director, Human Health and Assessments Division, Office of Heal t h and Environmental Research ER-73, Headquarters, Germantown, In addttion t o the informatton provided t o you i n my memorandum o f November 5, 1986, subject as above, another humar! radioisotope experiment has been brought t o our attention by a researcher involved i n the containing todine-131. Two subjects ingested a single dose (92nCi) each i n one experiment; and in another experiment, a l l subjects ingested daily doses of 150 o r 1840 uuCi f o r perlods ranging fran 1 t o 63 days. The highest calculated total dose t o the thyroid was 0.176 rem. In that experiment, five human volunteers drank milk The experiment was reported in Health Physics i n 1963. A copy of the report i s attached for your convenience. - .li .2& William R. Bibb, Director Research and Waste Management Divisior

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3. S. Robertson, Dlrector, Hman HealU1:and' Asseshenu Division, Offfcr o f Health and Envl rotmental Research, the p last lc disks contalnlng phosphorus42 has not been located so far4 We have checked local sources with no success. ORAU o f course has extenslve listings of people recelvlng alpha, neutron, and X-rQ radiation, but none for beta irradlatlon. I f the Info mt lon exists, Three t tans i n the l i stlng o f Congressman Harkey' s subcannl tte esta fC report are relevant for Oak RIdge Operatlons Offlce. Status o f those 1. Pluto n lw Injections - As dlscussed wlth you by a member o f ny staff, we understand that the subject o f plutonlun ln j ect lons w l ll be addressed by persons responsible for the Plutoniun Reglstry. A 1976 by many people. fact sheet on plutoniun lnjectlons i s attached whlch has been 2. Lanthanun-140 - We are informed by Dr. C. C. Lushbaugh t h a t you have discussed t h l s matter wlth hlm. Dr. Lushbaugh has provided Informatlo about the lanthanun-140 Ingesttons dlr ect ly to you. It appears that admlnlstratlon of th ls radtonuclide was In fact part o f diagnostic studles wfth anemia patients and thus was not an "experiment."

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'by page search likely would be necessary. Conslderlng the concerns abou privacy, even I n 1945, itis pmbably unlikely that the people were identified by name I n such recolds. Original Signed by William R. Bibb, Director Research and Waste Management Dlvislon

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Hcnlfh Physics Pergamon Press 19G3. Val. 9, pp. 1307-1323. Printed in Northern Ireland HUMAN THYROID UPTAKE AND BODILY ELIMINATION INGESTION OF BOUND IODINE I N OF 1131 FOR THE CASE OF SINGLE AND CONTINUAL Health Physics Division, Oak Ridge National Laboratory,. Oak Ridge, Tennessee for periods of time ranging from 1 to 63 days and in amounts ranging from 0.15 to 92 nc. In the first experiment all subjects ingested daily dosages of 1131 for periods ranging from 4 to 63 days. Thyroid uptake was measured by pray scintillation countings of all subjects. Urinary excretion was measured on two subjects, one of which was followed for 67 days. In a second experiment, two subjects ingested a single dose each. Thyroid uptake and urinary excretion were measured as in the fintexperiment. Extrapolations are made from the single-intake data to the case of continuous intake and are compared with the daily intake data. From these data, estimates are made offW,/,,f2 and Tbfor thyroid gland and are compared with ICRP and NCRP recommendations. mend a value of 2 x 10-5pc~cm3for the (MPC), (168-hr week) of based on the thyroid as the critical organ and a maximum permissible dose rate of 0.6 rems/week to this organ. This (MPC), value is estimated in the usual way, i.e. the dose to the organ is taken to be approxima rely proportional to the assumed uniform cr ::centration in the organ, and the relationship between the concentration in the organ to the concentration in drinking water is assumed to obey first-order kinetics. ICRP states that Tb, the biological half-life for iodine in the thyroid gland, is 138 days and that f,, the fraction absorbed from the gut and going to the thyroid, 1s 0.3. T h e value of Tbis stated to be estimated from their equation (48) which is "here: m (= 20g) is the mass of the thyroid gland, t (= 4 x 104g/g organ) is the conCCWation of stable iodine in the organ, I Operated by Union Carbide Corporation for the '3. Atomic Energy Commission. (= 2 x lo-' glday) is the daily intake of stable iodine in the body, and f, is as defined above.? ICRP has carefully pointed out that, in this method of estimating T,,,the assumption is made that the radionuclide has the same biological elimination time as the stable element. Although there is an abundance of data on iodine metabolism by both humans and small animals provided by the research of medical scientists and radiobiologists, this assumption does not appear to have been tested. This is t There is evidently an inconsistency in the ICRPcalculated value of Tb,because when one inserts the above values into their equation it t u r n out that Tb = 92 days and not 138 days as stated. Even though this differs from the stated value by a ractor of -1.5, the effect on the (MPC), value is negligible, because in calculating it, the effective half-life is used, and due to the shortness of the radiological half-life (8 days), there is only a slight change in the (MPC),. However, it does make a difference in the (MPC), for a long-lived isotope of iodine such as whose radiological half-life is 6.3 x IOD days. In this case the effective half-life is approximately equal to the biological half-life and the (MPC), for this isotope will almost be doubled when the corrected, 92-day value is employed.

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1308 HUMAN THYROID UPTAKE AND BODILY ELIlllINATION OF 113* undcrstandable in view of the fact that radiobiologists focus on the important problem of effects of on the gland, while medical scientists are interested in physiological tests of the gland. For the most part, neither group appears to have tested the assumptions in models for estimating biological parameter values applicable to internal dose estimation work. The ICRP report uses a single-intake model and integrates the retention predicted by this model to obtain the retention from chronic exposure. It mentions that exploratory studies have indicated a fairly satisfactory extrapolation can be made. This has been found to be true in the case of CosOingestion by miceI3) and, also in the case of Cs13' ingestion by mice.'4) There does not seem to be any human data for the case of chronic ingestion of 1131 with which to test gland, Jl3l-uptake data on sheep fed chronically for periods as long as 4 years. However, in sheep there is a seasonal variation in uptake. In man it is not obvious that the uptake is affected by seasonal factors."'] Some exploratory experiments were carried out in this laboratory (ORNL) on the problem extrapolating to the case of continuous ingestion and comparing the extrapolated data with the measured amounts in the thyroid gland. In this experiment, five male volunteers ingested, daily, for periods ranging from 4 to 63 consecutive days, constant doses of ranging from 150 to 1840 p p c in resin-treated milk, and their thyroid glands were monitored utilizing a y-ray scintillation counter to determine the uptake. One subject, ingesting 63 daily doses of 1840 ppc/day, collected 24-hr samples of urine for 63 days, a n d these were measured for their 1131 content. After the intake stopped on the sixty-third day, the subject continued to collect 24-hour urine samples for a period of 4 days. Also, his thyroid gland was counted six times, using the y-ray counter, in a period of 4 weeks. Thus, the decrease in activity could be followed. Three of the above subjects also ingested daily doses of 150 p p c for 11 consecutive days, and their thyroid uptake was measured. Two of these subjects also took a single dose of 92 nc and (at various times) their thyroid glands were samples for a period of 5 days after the lnbkc, One subject ingested 1840 ppclday for 11 mined both during intake and after the From the data obtained on these five sub jects, a partial test of the ICRP assumptionr was made. It was found that the predicted up containing protein-bound iodine) obtained from extrapolation of single-intake data gave slight overestimate of the burden in a perid of 11 days of intake. Extrapolating from decay. ' curve data of the subject who ingested sixty. three daily intakes also yielded a slight overestimate of the thyroid-gland burden, but the over-all agreement between the predicted and the observed burden was fairly satisfactory. The Tbfor in the thyroid glands of four subjects (the data on the fifth subject were inadequate to estimate his T,)ranged from 37 to 153 days. T h e mean value of 74 (k70) days does not significantly differ from the 92-day value of ICRP. T h e average value of f, was 0.16 (f0.08) (the range was 0.08-0.29). This mean value does not differ significantly from the 0.3 value a t the 95 per cent confidence level. It u the purpose of this report to present these Preparation of ingestion dose Cows' milk containing 1131 and obtained from the UT-AEC Agricultural Research Laboratory was passed over a n anionic exchange resin (Dowex 1 x 8-50-100 mesh in 3-cm id. column), recycled twice to remove the ionic iodine from the milk, and then pasteurized. Two cylindrical columns were connected in series. T h e milk flowed through the colUmns at the rate of 20 ml/min. T h e column-effluent milk contained -3.8 per cent of the original concentration in the raw milk. The alkaline precipitation, ZnS04-NaOH method of iodine from serum was applied to the columneffluent milk. Greater than 97 per cent of the total 1131activity was precipitated as compared with only -4.7 per cent precipitated from raw untreated milk. No tests were made of the iy. It was ting in the c ler to acco:

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e luinn-treated milk to establish definitively $lid, proteins were binding the I131. However, is believed that the resin-treated milk conThe bound to the protein constituents of L e milk is apparently very firmly attached as for a period of -30 days and re-treating the milk. When the milk was recycled over the column again, only about 4 per cent of the could be removed onto the exchange resin. There is a n advantage in using resin-treated milk in a continual-intake study and this is connectcd with the stable-iodine intake into the bod!.. It was desirable to maintain a constant pating in the chronic-ingestion experiment. In order to accomplish this, the volume of milk must be increased each day to compensate for the loss of by radiological decay. When a significant concentration of stable iodine is present in the milk, the increased volume of milk ingested will result in an increased intake of stable iodine which will affect the uptake of P. In this study the raw milk contained an at.<rage of 0.03 p g stable iodinelml. In the resin-treated milk this was reduced to -0.001 pg/ml. Some of the subjects ingested as much as 500 ml of milk, and thus only 0.5 pg of stable iodine was taken into the stomach, which is negligible in comparison with the daily average intake of 200 p g of stable iodine. Ingaslion doses, ages, wci,qhls, and radialiori d1JStS t of hyoid glands of subjects Table 1 presents the age, weight, pp'c of Ii3' ingested singly or daily, the estimated peak-dose rate to the thyroid gland, and the estimated total dose received by the gland. All subjects were found to bc euthyroid as indicated by tests of protein-bound iodine in blood. All suljjects ate regular meals consisting of their usual diets. T h e average age of the five subjects was 41 ycars (range, 36-53 years) and the average wcight gested 92,000 ppc in a single intake, expcricilced the highest estimated total dose (0.176 rcms) to his thyroid, and the peak-dose rate was 110 burden of 0.14 pc delivers 0.6 rernslweek to this organ). T h e total dose to the gland \.vas obtained by integrating the rems/week dclivcred to this organ from 0 to 00. I n the chronic ingestion studies, subjects A, B and E drank the resin-treated milk betwccn 0900 a.m. and 1500 hours and after being couiitcd on the thyroid counter (except on weekends). Subjects C and D drank their milk at -1600 liours a n d were counted before the ingestion. Excreta sample collection and analysis Each individual void of urine was cdlccted by subjects A and B for a period of about 5 days after the single ingestion of 92 nc of I131. Four Table 1. Data an human subjecb participating b I'31 expm'mml LLDaily of ingestion Single to thyroid dow Lo Wt. intake 1131 intake gland thyroid * All subjects were euthyroid as indicated by tests of protein-bound iodine in blood perfomrtl 10' the ORNL Health Division.

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1310 HUMAN THYROID UPTAKE AND BODILY ELIhlINATION OF IL3' fecal samples were submitted by subject A. Subject C collected 24-hr urine specimens for a period of 67 days and submitted two fecal samples on days 55 and 56 after his first intake of 1840 ppc of The daily collection period for urine was from 1600 hours to 1559 hours, that is, from the time after ingesting a dose at 1600 hours to the time just before ingestion of the next daily dose. by taking an aliquot of the specimen (100 or 200 ml depending on the volume of the specimen) and counting in a pickle-barrel counter containing a 4 x 2 in. NaI(T1) crystal connected to a 200-channel analyzer. Figure 1 shows the counter and the analyzer. Fecal samples contained in plastic bags were also monitored in the pickle barrel counter. Urine and fecal samples were corrected for radiological decay. For a single-ingestion dose, the countslmin in the urine (or fecal) sample voided at t units of time after intake and analyzed on day tn (ta 2 t ) were corrected for radiological decay by multiplying by co.ogs(l.). For consecutive ingestions, the urine samples were Urine samples were analysed for collected in the interval-1559 hours on day t to 1600 hours on day t + 1. T h e sample was analyzed on day t, and the measured counts were multiplied by eo.oeeft*-t); that is, the measurements were corrected for decay from the time of ingestion on day t to the time of analysis, t,. T o illustrate, a sample voided on day 20 (= t + 1) and analyzed on day 23 Counting methods and techniques A 3 x 3 in. NaI(T1) crystal having a 9 in.- thick lead side shield and …