Human Thyroid Uptake and Bodily Elimination of Iodine-131 for the Case of Single and Continual Ingestion of Bound Iodine in Resin-Treated Milk (Health Physics Dec 1963 No. 12, Vol 9 PP 1307-1323)

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Hrolfh Physics Pergamon Press 1963. Vol. 9,pp. 1307-1323. Printed in Northern Ireland HUMAN THYROID UPTAKE AND BODILY ELIMINATION OF IIa1 FOR THE CASE OF SINGLE AND CONTINUAL INGESTION OF BOUND IODINE I N Health Physics Division, Oak Ridge National Laboratory,+ Oak Ridge, Tenncssee for periods of time ranging from 1 to 63 days and in amounts ranging from 0.15 to 92 nc. for periods ranging from 4 to 63 days. Thyroid uptake was measured by y-ray 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 wen measured as in the first experiment. Extrapolations are made from the single-intake data to the case of continuousintake and are compared with the daily intake data. From thee data, estimate are made of/,,f,,f, and T,for thyroid gland and are compared with ICRP and NCRP recommendations. In the first experiment all subjects ingested daily dosages of INTRODUCTION (= 2 x 1 0 4 g/day) is the daily intake of stable 68-hr week) of1181 based on the thyroid as the tical 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 approxiWtely proportional to the assumed uniform bncentration in the organ, and the relationship between the concentration in the organ to the $Concentration in drinking water is assumed to 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' &om their equation (48) which is iodine in the body, and f, is as defined ab0ve.t ICRP has carefully pointed out that, in t h i s method of estimating Tb, 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 dots not appear to have been tested. This is t There is evidently an inconsistencyin the ICRPcalculated value of Tb,because when one inserts the above values into their equation it turns out that T,= 92 days and not 138 days as stated. Even though this differs from the stated value by a factor 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 1'" whose radiological half-life is 6.3 x lo' 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, 92day value is employed. Of 'b is stated to be -'twhere: m (= 20 g) is the mass of the thyroid ,T centration of stable iodine in the organ, Operated by Union Carbide Corporation for the

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1308 HUMAN THYROID UPTAKE AND BODILY ELIMIS.\TIOS OF 1la1 understandable in view of the fact that radiobiologists focus on the important problem of effects of 1181 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 a p plicablc 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 w e of Corningestion by mice@'and, also in the case of (2.9"' ingestion by mice.1') There does not seem to be any human data for the case of chronic ingestion of 1'31 with which to test gland, 11"-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.16) Some exploratory experiments were carried out in this laboratory (ORNL) on the problem extrapolating to the case of continuous ingestion and comparing the extrapdated 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 1ls1 mnging from 150 to 1840 ppc 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 ppclday, collected 24-hr samples of urine for 63 days, and t h e e were measured for their 1181 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 ppc 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 counted. Also, they collected 24hr urine samples for a period of 5 days after the intake. One subject ingested 1840 ppclday for 11 da!x. mined both during intake and after the intake From the data obtained on t h e five subjects, a partial test of the ICRP assumptiom was made. It was found that the predicted up take for chronic ingestion (of resin-treated milk containing protein-bound iodine) obtained from extrapolation of single-intake data gave a slight overestimate of the burden in a period oi 11 days of intake. Extrapolating from decaycurve data of the subject who ingested si.t)- three daily intakes also yielded a slight overestimate of the thyroid-gland burden, but the over-a11 agreement between the predicted and the observed burden was fairly satisfactory. The Tb for in the thyroid glands of four subjects (the data on the fifth subject were inadequate to estimate his Tb) ranged from 37 to 153 dap. The mean value of 74 (f70) days does not significantly differ from the 92-day value d ICRP. The average value off, was 0.16 (*0.08) (the range was 0.08-0.29). This mean value does not differ significantly from the 0.3 value at the 95 per cent confidence level. It the purpose of this report to present thm Preparation of 1"' ingestion dose Cows' milk containing 11*1and obtained f r m was passed over an anionic exchange (Dowex 1 x 8-50-100 mesh in 3-cm id. column), recycled twice to remove the ionic iodine from the milk, and then pasteur a series. The milk flowed through the c o l u ~ at the rate of 20 ml/min. The column-emumt milk contained 4 3 . 8 p e r cent of the 0riff-l 1'" concentration in the raw milk. The a b line precipitation, ZnS0,-NaOH method iodine from serum was applied to the co1effluent milk. Greater than 97 per cent Of *total 11aactivity was precipitated as ~ m p r r a d with only - 4 . 7 per cent precipitated from nr untreated milk. No tests were made of *

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column-treated milk to establish definitively which proteins were binding the I1sl. However, The 11" bound to the protein constituents of h e milk is apparently very firmly attached as evidenced by letting the resin-treated milk Bund 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 11= could be removed onto the exchange ruin. There is an advantage in using resin-treated milk in a continual-intake study and this is connected with the stable-iodine intake into the body. It was desirable to maintain a constant intake of 1181 by the human subjects participating 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 11*l 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 'ofstable iodine which will affect the uptake of Im. I n this study the raw milk contained an average of 0.03 pg stable iodine/ml. In the =in-treated milk this was reduced to 4 . 0 0 1 pg/ml. Some of the subjects ingested as much L) 500 ml of milk, and thus only 0.5 pg of stable ,iodine was taken into the stomach, which is A negligible in comparison with the daily average htake of 200 pg of stable iodine. Ingesfion doses, ages, weights, and radiation doses to thyroid glands of subjects Table 1 presents the age, weight, ppc of ingested singly or daily, the estimated peak-dosc rate to the thyroid gland, and the estimated total dose received by the gland. All subjects were found to be euthyroid as indicated by tests of protein-bound iodine in blood. All subjects ate regular meals consisting of their usual diets. The average age of the five subjects was 41 yean (range, 3&53 years) and the average weight gested 92,000 ppc in a single intake, experienced the highest estimated total dose (0.176 rems) to his thyroid, and the peak-dose rate was 110 burden of 0.14 pc delivers 0.6 remslweek to this organ). T h e total dose to the gland was obtained by integrating the remslweek delivered to this organ from 0 to CO. In the chronic ingestion studies, subjects A, B a.m. and 1500 hours and after being counted on the thyroid counter (except on weekends). Subjects C and D drank their milk at -1600 houn and were counted before the ingation. Excreta samFle collection and analyrir Each individual void of urine was collected by subjects A and B for a period of about 5 days after the single ingestion of 92 nc of Four Duration dose rate Daily of ingestion Single to thyroid dose to aiAll subjects were euthyroid as indicated by t a t s of protein-bound iodine in blood perlomed by the

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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. Urine samples were analyscd for I131 content 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 t. (1. 2 t ) were corrected for radiological decay by multiplying by P.@@W). For consecutiveingestions, the urine sampleswere collected in the interval -1 559 hours on (lay f to 1600 hours on day r $. 1. The sample \\u were multiplied by 8-OBB('*-');that is, the measurements were corrected for decay from the time of ingestion on day t to the time of analysis, t,. To illustrate, a sample voided on day 20 (= t + 1) and analyzed on day 23 (= t,,) was corrected by multiplying the coiinu Counting metho& and techniques A 3 x 3 in. SaI(T1) crystal having a 4 in.- thick lead side shield and connected to a 200channel analyzer was used to measure the counts due to 1'31 in the thyroid gland. The suhjcct lay on a cot, and the crystal was located immediately over his thyroid gland with the outer edge of the side shield indexed over the sternal notch (Fig. 2). Counting periods varied dcpending on the amount ingested by the subjca, ranging from 5 min to as long as 40 min. for the 3 x 3 in. crystal placed over the thyroid gland of a subject is shown in Fig. 3. The area A typical spectrum of the prays from FIG.3. Typical gross spectrum or pray activity in thyroid gland for a few days after ingestion of 92 nc of P I .

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FIG. 2. Position For counting XIs1 in thyroid gland with XaI(T1) cvstal.)

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beneath the curve in the energy band 312408 keV was used to estimate the burden of in the gland. The efficiency of the counter was determined by counting the thyroid gland of a plastic phantom which contained a known amount of a solution of KP31 in the thyroid gland. This factor was used to convert the counts determined on the gland of all the subjects to pc. There is probably some systematic error in the estimated burden because the depth and position of thyroid glands are known to differ for different subjects. Thus, the geometry and absorption layers will be different. Also, there was an opportunity for some additional random error in the estimated burdens due to kck of reproducibility of the placement of the crystal over the gland. Attempts were made to keep this at a minimum by locating the subject's neck as close to the counter as possible and by reference to the midline position of the body. A few whole-body counts were also taken with an 8 x 4in. NaI(T1) crystal located over the subject when he reclined on a curved bed having , a radius of 1 M-the 1-M arc position. In this measurement a 512-channel analyzer was used to record the y-ray spectrum. The efficiency for this count was estimated from measurements made on a plastic phantom whose organs jcontained a known amount of 1131 approximating that found in standard man. Only a few counts were made on two of the subjects in the 1-M arc position. Some error of relatively ~ n a l l ,but unknown, magnitude is to be ex- % pccted in this measurement because of variations h distribution of 1ls1 in the organs. Further -dies need to be camed out to determine the5 s magnitude of this error. Inkrprrtation and least-squares treatment of tk data In interpreting the data, the approach and terminology employed by ICRP is used. Let q denote the total pc in the body,f 2the ratio ofthe pc in the critical organ to that in the body, P the rate of intake into …