SWRHL-13r POTENTIAL HAZARDS AS A RESULT OF INHALATION OF RADIOIODINES: A LITERATURE SURVEY by Ronald E. Engel, DVM, PhD Bioenvironmental Research Program Southwestern Radiological Health Laboratory U. S. Public Health Service Department of Health, Education, and Welfare Las Vegas, Nevada January 5, 1966 This study performed under a Memorandum of Understanding (No. SF 54 373) for the U. S. ATOMIC ENERGY COMMISSION ------- LEGAL NOTICE This report was prepared as an account of Government sponsored work. Neither the United States, nor the Atomic Energy Commission, nor any person acting on behalf of the Commission: A. Makes any warranty or representation, expressed or implied, with respect to the accuracy, completeness, or usefulness of the information contained in this report, or that the use of any infor- mation, apparatus, method, or process disclosed in this report may not infringe privately owned rights; or B. Assumes any liabilities with respect to the use of, or for dam- ages resulting from the use of any information, apparatus, method, or process disclosed in this report. As used in the above, "person acting on behalf of the Commission" in- cludes any employee or contractor of the Commission, or employee of such contractor, to the extent that such employee or contractor of the Commission, or employee of such contractor prepares, disseminates, or provides access to, any information pursuant to his employment or contract with the Commission, or his employment with such contractor. 01 ------- SWRHL-13r POTENTIAL HAZARDS AS A RESULT OF INHALATION OF RADIOIODINES: A LITERATURE SURVEY by Ronald E. Engel, DVM, PhD Bioenvironmental Research Program Southwestern Radiological Health Laboratory U. S. Public Health Service Department of Health, Education, and Welfare Las Vegas, Nevada Copy No. 1 to: Oliver R. Placak Officer in Charge SWRHL January 5, 1966 This study performed under a Memorandum of Understanding (No. SF 54 373) for the U. S. ATOMIC ENERGY COMMISSION ------- TABLE OF CONTENTS I. INTRODUCTION 1 II. POTENTIAL SOURCES OF RADIOIODINE 3 A. Introduction 3 B. Nuclear Reactors 4 1. Levels of Radioiodine in the Atmosphere 6 2. Radioactive Decay and Diffusion 7 C. Weapons Development Tests and Plowshare Experiments 8 1. Weapon Development Tests Conducted Above Ground 8 2. Underground Nuclear Explosions 9 III. TRANSPORT OF RADIOIODINES FROM SOURCES TO BIOSPHERE 12 A. Introduction 12 B. Chemical States of Radioiodines Usually Observed 13 C. Physical States of Radioiodines Usually Observed 13 IV. INFLUENCE OF CERTAIN RESPIRATORY MECHAN- ISMS ON DEPOSITION, RETENTION, CLEARANCE AND TRANSLOCATION OF INHALED RADIOIODINES 17 A. Introduction 17 B. Deposition: Influence of Physiological Factors 18 1. Upper Respiratory Tract 18 2. Lower Respiratory Tract 20 3. Lung Volumes and Capacities 20 4. Mechanics of Breathing 24 5. Lung Model 30 C. Retention and Clearance 31 1. Physiological Mechanisms of Pulmonary Clearance 32 a. Ciliary Clearance 32 b. Alveolar Phagocytosis 33 c. Alveolar Membrane Transfer 35 d. Non-Phagocytic Penetration of Alveolar Wall 37 ------- D. Translocation 39 1. Fate of Radioiodines in Body 40 2. Excretion of Radioiodines into the Mammary Glands 44 3. Excretion of Radioiodines into the Feces and Urine 46 V. SUMMARY 51 VI. CONCLUSIONS 54 VH. SUGGESTED EXPERIMENTS FOR THE STUDY OF POTENTIAL HAZARDS FROM INHALATION OF RADIOIODINES 55 A. Field Type Experiments 55 B. Laboratory Type Experiments 56 REFERENCES 58 APPENDIX List of Tables 68 DISTRIBUTION 11 ------- LIST OF FIGURES Figure 1. Percentage deposition in various regions of the respiratory tract as a function of aerosol particle size; unit density spheres assumed. 21 Figure 2. Lung volumes. 23 LIST OF TABLES See APPENDIX 111 ------- I. INTRODUCTION This report gives a brief survey of some of the existing literature relative to the subject of potential hazards to man which might result from releases of radioiodines into the biosphere. The related topic of potential hazards from ingestion of radioiodine is also touched upon since the determination of total hazard to man must be the ultimate goal of any research program which has been designed to assess the overall public health significance of any radioiodine releases. There has been a general assumption on the basis of limited data that the ingestion hazard is such that any concurrent inhalation hazard would be of negli- gible significance. No issue will be taken with this assumption. Rather this report will attempt to survey the present state of knowledge on the subject of potential radioiodine inhalation hazards in an effort to iden- tify specific areas in which additional research is required, either to fortify the usual assumptions or to determine under what conditions they might be invalid. For the sake of brevity, an exhaustive discussion of each subject considered is not attempted. For amplification of any spe- cific topic the reader is encouraged to consult pertinent references given at the end of the report. It is impossible to investigate every facet of radioiodine fallout in detail,3 nevertheless, a systematic and well organized approach to test a hypothesis that there is an inhalation hazard of radioiodines to man is feasible because radioiodine has a relatively high percentage of release among fission products, an appreciably high fission yield, and is biologically available to man and animal. Accurate exposure and dosage determinations are required for establishment of radiation pro- tection procedures and maximum doses. To make these determinations, ------- with regard to inhalation of radioiodines, answers to the following questions should be useful: 1. What are the potential sources of atmospheric radioiodine contamination ? 2. What are the chemical and physical properties of the radio- iodines and the conditions of their release, e.g. , gaseous, particulate, fractionation? 3. What is the particle size distribution inhaled by the animal and biological fate of each size ? 4. What fraction of the intake of radioiodines is retained in the body following inhalation? 5. What is the deposition, retention, translocation, and elim- ination of inhaled radioiodines in normal physiological states ? 6. What is the distribution of radioiodines in specific tissues and organs of various species of animals? The scope of this report, .other than for limited information of potential sources and physico-chemical aspects of the radioiodines, is primarily confined to question's 5 and 6. The discussion will attempt to expose areas of paucity in research on radioiodine inhalation and thereby hope- fully serve as a reference in any contemplated inhalation studies in the field or in the laboratory. Folio-wing the discussion of the literature, research problems will be suggested, keeping in mind that a research program on inhaled ra- dioiodine is universally concerned with the fate and effects of the in- haled radioiodine directly and indirectly upon nearly all mammals, especially man. ------- II. POTENTIAL SOURCES OF RADIOIODINE A. INTRODUCTION Radioiodines released into the atmosphere and available to the pul- monary system may be a hazard only under specific pertinent conditions existing at the time of release. Biological availability will depend on such physical factors as the source of the radioiodines, the proximity of the source to the population, and meteorological conditions existing before and after release. Most nuclear reactors maintain high inventories of radioiodines. The quantity, for the most part, is dependent on the thermal power and the length of operation of the reactor. Under normal operating proce- dures the radioiodines reach equilibrium and are contained for a pre- determined time to allow for radioactive decay to take place. However, if an accidental release of fission products should occur, the Health Physicist would have to determine the amount of radiation to which the surrounding population would be exposed. Accidental releases can occur from direct exhaust from faulty reactor assemblies, off gases, and un- contained accidental criticality. These nuclear reactor accidental re- leases can normally be quantitated more accurately than releases from nuclear devices following detonation. Nuclear weapons detonated in the atmosphere may release large quantities of radioiodines; however, the levels or concentrations of radioiodines observed under different conditions will be extremely variable. The measured radioactivity is often orders of magnitude different from predicted values. Inhalation of radioiodines by livestock following nuclear weapon detonation has been considered to be of no major importance. 31 ------- Underground nuclear explosions are normally contained under- ground unless cratering is planned. Following underground detona- tion, the volatile elements of which radioiodines are representative, may be inadvertently released into the atmosphere. The release of the volatile elements could become a very acute inhalation problem especially with the release of large quantities of short-lived radio- iodines. One major area of importance lies in the chemistry and physics of radioiodines in the gas and aerosol formation preceding and follow- ing release to the atmosphere from nuclear fission reactions. Little is known about the transport of these elements in the biosphere, and less is known quantitatively about inhalation of radioiodines from field sources than any other aspect of radioactivity resulting from nuclear fission reactions. A brief discussion of potential sources of radio- iodines will be presented with reference to specific conditions which allow radioiodines to become biologically available. A comprehen- sive coverage of each subject is considered to be beyond the scope of this report. B. NUCLEAR REACTORS A major contributing source of radioiodines to the atmosphere is the nuclear reactor. In general, all nuclear reactors, regardless of size or shape, are composed of the fuel moderator, reflector, blanket, controls, cooling system, cladding, reactor vessel, radia- tion shielding, radiation monitoring system, and containment mechan- ism. Further details on reactor construction and fission reactions can be found in any nuclear science textbook. ->5 Low power auxiliary units, as opposed to primary propulsion reactors such as the Kiwi, possess similar characteristics that may be considered uniformly for all hazard estimates. These may differ ------- in parameters such as type of fuel, cladding, and operating time or temperature; however, the actual levels or quantity of radioiodines produced within the reactor will be dependent mainly on the power level and the operating time. Once a release occurs, the ensuing trans- port and diffusion of fission products are usually considered to be uni- form for all proposed units since the physico-chemical nature of the products depends more on release conditions than on reactor type.°^ The increasing use of low power auxiliary units increases the probability that more fission products will be released into the atmosphere due to inherent problems of containment. In contrast, power producing reactors such as the Calder-Hall type may have leaks in the containment mechanism or have fission product leaks into the cooling gas from faulty fuel elements. In such cases, fission products are usually discharged into the environment in signi- ficant quantities only during the release of the CO2 coolant following reactor shut-down. '° Irrespective of reactor type, fission products will normally be re- leased in large quantities from the destruction of fuel material. In fuel element melting experiments, which were designed to simulate core meltdown during an uncontrolled nuclear excursion or other similar accident conditions, iodine and rare gas isotopes were released from the core in higher percentages than other fission products. This is to be expected since Roberts'^ found that fission products are retained almost entirely within the high temperature zone -with the exception of noble gases, iodine, cesium, and tellurium, and, if oxygen is present, ruthenium. Another possible source of radioactivity that might become biolog- ically available is the activation of particulates present in the operating region of a reactor. These particulates could be from construction ------- materials such as cement, sand, and dust within the reactor area. If these are allowed to escape to the outside atmosphere, it would probably be found that the particles would have the normal size dis- tribution associated with corrosion products of construction material dust.42 1. Levels of Radioiodine in the Atmosphere During the design of a nuclear reactor, guides to maximum permissible concentrations of 131I must be considered. Barry listed permissible concentrations of 1 31I that were meant to serve as guides to reactor designers and were not intended for normal health physics control levels. Griffiths and Erickson^" reported that prior to the assembly and operation of a reactor at the Nuclear Rocket Development Station (NRDS), an analysis is prepared to determine safety characteristics of the reactor including evaluation of reactor effluent release for planned oper- ations and for creditable accidents. For a normal test the gross fission product release is assumed near 5% with radio- active iodine release values of 1 - 6%. Calculations for deter- mining the thyroid dose contributed by inhalation of radioiodine released during reactor operations are usually based on the Sutton model for atmospheric diffusion. 10 In predicting the thyroid dose, it is most difficult to relate the degree of absorption or adsorption of the radioiodines to various sized particles. However, those particles whose diam- eter is above the respirable range may be considered relatively unimportant in contributing to the thyroid dose resulting from inhalation only. Since it is possible that inhalation of radioiodines could be a hazard, the primary objective of an environmental monitoring ------- program should be to establish, within reasonable confidence, that the radiation exposure received by individual members of the gen- eral public will not exceed specified safety levels. Measurements intended to serve this purpose should, therefore, be capable of being related to these levels. Levels of radioiodines released into the atmosphere will usually depend on the type of reactor release that occurs. Whether the release is from one time releases, from nuclear reactor accidents or emergencies, or from continuous routine reactor operation, the quantity of the radioiodines is re- duced by two processes--radioactive decay and diffusion. 2. Radioactive Decay and Diffusion Radioactive decay for radioiodines can be predicted -with con- siderable accuracy (See Table 1). Knowledge of the decay scheme is extremely important in dose determinations following release, especially if short-lived radioiodines are being considered. When computing dose determinations for radioiodines released as fis- sion products within close proximity of the release, rate of radio- active decay plays a major role. Dolphin and Beach-" used one hour post release time conditions in calculating the relative haz - ard of the significant iodine isotopes (l 311, l 3 2 I, 133I, 134I, 135I) following accidental release of fission products from criticality incidents or from irradiated reactor fuel elements. One hour was chosen because it was thought that no appreciable amount of fission product activity could be released, become airborne, subsequently inhaled, and concentrated in the thyroid in a shorter time. It is apparent that the greater the elapsed time following release,, the greater is the l 31I contribution to a possible hazard (See Table 2). » Diffusion, however, is not as simple to calculate as decay rate because of the vast number of parameters, such as particle ------- size, particle density and composition, velocity of wind, wind shear, temperature gradients and topographical features. These are seldom known with sufficient accuracy at the precise time of radioiodine release. Predictions are usually poor estimates at best. For example, prediction of the air concentrations follow- ing the SL-1 accident (80 curies of l 31I released) were in reason- able agreement with measured air concentrations of 1 31I up to several miles around the reactor, but predicted values were a factor of ten or more lower than the measured values at distances beyond fifteen miles. °° C. WEAPONS DEVELOPMENT TESTS AND PLOWSHARE EXPERI- MENTS The biological availability of the radioiodines (1 31I to l 3 5 I) de- pends on many physico-chemical interactions as well as meteorolog- ical conditions, type of detonation and fission yield. The interactions of the latter three conditions have been -well documented in "The Effects of Nuclear Weapons' ^ and are beyond the scope of this paper. 1. Weapon Development Tests Conducted Above Ground Rates and mechanisms of distribution and transfer of radio - iodines in the atmosphere from low yield detonations are of more concern to the problem of inhalation as a possible hazard than are high yield detonations. This is understandable since it is generally true that tropospheric contamination is greater, local fallout is less, and external exposure is reduced to within a nar- row band in high yield detonations. The very close-in local fall- out is of no concern here because large particles measuring more than 30 microns, even though they contain roughly 80% of the ra- dioactivity, are not within the respirable range. However, the ------- ten microns in diameter particle, settling velocity of 0. 845 cm/sec, contains the highest percentage of biologically available elements and will be deposited or suspended within a narrow band outside of the heavy local fallout area. ^3 Outside of the heavy local fallout implies that the external dose is negligibly small and arrival times are measured in hours. This period of time is sufficiently soon after detonation for short-lived nuclides, i.e., half-lives less than one day, to be present. The quantities of biologically available fission products may vary in the air and on surfaces due to fractionation. The phenom- enon of radionuclide fractionation following nuclear explosions com- plicates the attempt to define contamination surface density in pre- cise terms because the composition of each particle may vary, i.e. , a profile of different biologically available fission products may be developed. " This profile of available fission products, of which the radioiodines are representative, may present a high percentage of biologically available radioiodines to the pulmonary system during intervals following detonation of a low yield nuclear explosion. Clark, attempting to simulate a realistic fallout en- vironment for a land surface nuclear detonation, utilized a simpli- fied mathematical fallout model to estimate: a. Fallout particle sizes. b. Deposited mass per unit area. c. Standard radiation intensities as functions of downwind distance of weapon yields from 1 KT to 100 MT. 2. Underground Nuclear Explosions Underground nuclear explosions of Plowshare experiments and weapon development tests are usually designed to be contained, although they are capable of causing cratering with substantial re- lease of radioactivity, especially radioiodines, into the atmosphere. ------- Containment of the radioiodines will depend in part on the nature of the soil structure of the medium -where the detonation takes place. Presence of seams, faults or fractures of the medium and estimation of the nuclear yield must be considered. If an in- advertent release occurs, the most gaseous and volatile elements appear to be restricted to the lower layers of the troposphere. Following an underground cratering explosion of 0.42 kiloton, Nordyke and Wray^ reported a base surge cloud which rose to an altitude of about 8000 feet and was 15 to 20 miles in width at a distance of 75 miles downwind. Seventy miles to the north of the detonation site, an atmospheric concentration of 576 picocuries per cubic meter of radioiodine was observed. ^ Data obtained following a large nuclear excavation (Sedan) showed that the fall- out pattern was clearly asymmetrical. " There was a steep gra- dient, a "hot line" and a feathering out of fallout. All were con- sistent with shearing of the upper portion of the cloud. The moving debris and the widespread nature of a fallout pattern usually com- plicate the evaluation and interpretation of data leading to uncer- tainties as to the mechanism of transport of radioiodines through the biosphere. Dunning reported that relatively high concen- trations of fallout material are found in the air for only a few hours and essentially all of the calculated intake by inhalation is com- pleted within 24 hours following low-yield detonations. This band of high atmospheric specific activity, apparently within the re^ spirable range, is of importance in evaluation of inhalation hazards of radioiodine. O 1 Martell stated that the only practical procedure for assess- ing the extent of an inadvertently released radioiodine and other radioactivity products appears to be the direct measurement of the 10 ------- escaping clouds and vapors for each individual event. Likewise, it appears that a practical approach for assessing the extent of the hazard from inhalation of radioiodines is having knowledge of deposition, retention, translocation, and secretion of radioiodines in individual animals, man included, at the time of cloud passage for each individual event. 11 ------- HI. TRANSPORT OF RADIOIODINES FROM SOURCES TO BIOSPHERE A. INTRODUCTION Iodine has an atomic number of 53 and 24 isotopes which range from 117 to 140 atomic mass units. Iodine-127 is the only stable iso- tope of the iodine family. Since l 2 7I is not radioactive it will not be discussed in the mechanics of transport, but will be included in the discussion of translocation of inhaled radioiodines. The physical half- lives of the remaining isotopes vary from approximately 1. 5 seconds for 140I to 1.6xl07 years for l 29I. Relative yields of these isotopes from fission of 2 35U or 239Pu are shown in Table 3. The quantities, in curie amounts, following 1020 instantaneous fissions of 235U, as well as the quantities remaining after a period of time, are given in Table 4. Decay sequences for l 29I, l 311 to l 35I are listed in detail in Table 1. Because of the relatively short half-lives of * 32I, l 33I, l 34I and 1 35I, these isotopes appear to have received inadequate consideration for being possible contributors to the total radiation dose. Although inhalation of these isotopes has not generally been regarded as ex- tremely hazardous, the possibility always exists that a release could cause some segment of the population to be exposed to large respirable quantities of these radioiodines. The circumstances of release and, therefore, exposure of the population to radioiodines has normally been such that l 31I, for the most part, overshadowed the importance of the other iodine isotopes as the radiation hazard most commonly encountered. This section of the report •will deal only briefly with the physico- chemical properties of the radioiodines. In particular, physical and 12 ------- chemical forms, particle size distribution and transport will be dis- cussed with reference to biological availability to the respiratory tract. B. CHEMICAL STATES OF RADIOIODINES USUALLY OBSERVED Iodine can undergo rapid chemical transformations as well as Q Q physical changes. Megaw and May showed that approximately one hour following release of elemental I2 in the Pluto reactor shell, 40 to 80% of the airborne iodine -was associated with particulate material. Much of the iodine vapor changed from the elemental form to unidenti- fied gaseous species during their experiments of 3 to 5 hours duration. In vapors, such as above and others released in reactor shells of var- ious types and from nuclear explosions, the volatile forms are found as elemental I2, as inorganic vapors, as organic vapors (methyl iodide)^ and as many oxidized states°^(See Table 5). Perkins reported"^ that experiments on gaseous effluents from the Hanford chemical separation plant indicated that less than 0. 3% was in the particulate form. Iodines leached from the particulate material were shown to be about. 66% in the reduced state (I2 or I ), about 33% in the iodate form, and less than 5% in the periodate form. The data, according to Perkins, suggested that 1 31I released into the atmosphere does not immediately adsorb on par- ticulate material in the air and even several miles away may still be in a gaseous state (See Table 6). The gaseous form varied from 10 to 90% of fallout from plant emission. C. PHYSICAL STATES OF RADIOIODINES USUALLY OBSERVED Particle sizes, upon which radioiodines are adsorbed or absorbed, depend on the origin of the particulate matter. In the heating of irra- diated uranium, Gallimore and Mercer found some form of 1 31I was carried on particles of peak diameters of 15 A and 60 A. Approximately 10% seemed to be a gas or vapor. Karioris et al found that particle size distribution is multimodal when two or more chemical species are 13 ------- present in aerosols when studied in an exploding conductor aerosol generator. Particle sizes resulting from the heating of UO2 to 400°C, 600°C and 800°C and subjected to a 8. 3 centimeter per second air- stream" were found to be within the 2 to 5 microns diameter range 20 inches downstream from the UO2 source. Under similar condi- tions, but with the UO2 heated to 1200°C, the particles measured 0.015 to 0.5 microns in diameter. It is probable that particulate size depends on the temperature of the fuel and the amount of air flow over the heated fuel. The form and amount of iodine found on particulates appears to be influenced accordingly. Distribution of particulate size following nuclear explosions will, among other factors, depend on the type of detonation and total fission yield. Following a land surface shot, roughly 80% of the radioactivity will be in particles greater than 30 microns in diameter. On the other hand, these particles are not primarily within the respirable range of interest and are not included in this discussion. The particles less than 20 microns are carried into the atmosphere and their motions are normally determined, because of their MMD (mean mass diameter) and -weight, by atmospheric motions rather than by gravitational fall. If the shot does not intersect the surface of the earth, as in an air burst, the spectrum size of particulates averages approximately 3 microns in diameter. With increased yield and height of burst, the particle size 7 ^ may shift to much smaller diameters. '-> Irrespective of type of deto- nation, the chemical states of the radioiodines and, therefore, absorp- tion or adsorption on the particulate matter, may be independent of the origin or environmental history. ' Because of the variances that normally exist, Holland"° feels that it is very difficult to conduct realistic experimental research on radio- iodine behavior in fallout. Nevertheless, it is necessary to develop 14 ------- realistic experimental procedures regardless of difficulties encoun- tered because not only is there the requirement that the distribution and chemical state of the radioiodines in or on these particle sizes be known, but also there is a requirement to know the particle size dis- tribution. The extent to which the radioiodine is physically incorpor- ated within the particulate matter, •whether it be dust, fuel material, etc. , may affect the participation in chemical or biochemical reactions and possibly have an importance equal to or greater than the specific chemical form in which it exists in the particle. It is a well known fact that a dust suspension, such as that caused by a nuclear excavation or emitted from nuclear reactor stacks, contin- ually undergoes a change with respect to the particle size distribution and percentage of particulate matter containing 131I. Agglutination, sedimentation and impaction can be considered to cause this instability •JO of a suspension. J These phenomena complicate the problem of calcu- lating and predicting the quantity of radioiodine that is carried on the surface of a carrier dust from the point of release. The radioactive particulates after being collected by conventional means show a total radioactivity deposition that bears no simple predictable relationship to the mass deposition. Since an aerosol cloud will act as a carrier for the transport of radioactive material into the respiratory tract, the radioactivity per mass of particle or the ratio of the quantity of adsorbed activity per respirable particle of the aerosol must be con- sidered in computing the radiation dose. The particle size will deter- mine the behavior of the aerosol and the quantity of radioactivity will determine the contribution of the inhaled dose. The chemical forms and solubilities of the radioiodines greatly influence their deposition on particulate matter and hence their absorp- tion in the biological systems. Keisch and Koch' stated that, after 15 ------- studying 1 31I leached from fallout, their results implied that the rate at which the leachable l 31I was removed was not dependent on the chemical state in which it existed in the particulate phase. They further stated that the dissolution of a sparingly soluble material in which the radioiodine was adsorbed was more likely to be the rate and equilibrium determining factor for the leaching mechanism. This is not surprising since it is known that iodine reacts with many materials and as a halogen is usually found with valences ranging from -1 to +7 (See Table 5). Therefore, it would be expected to dissolve in water droplets to form iodide (I ), iodate (IO3 ), and periodate (IO4 ) ions. Leach yields have shown 65. 5%, 29. 5% and less than 5% for the iodide, iodate and periodate states respectively. »'' The chemical form of approximately 60% of the 1 311 remaining in the particles after leaching -was not determined. ^ The author is of the opinion that the present state of knowl- edge of the transport of radioiodines through the biosphere can be summed up rather quickly by quoting the summary from a paper presented by Holland in 1963. ^5 He stated: "The only conclusion which can be drawn at this time regarding the partitioning of I1 31 between vapor and particulates, between soluble and in- soluble forms and among elemental, reduced, and oxidized states is that none is clearly dominant over any great range of conditions." 16 ------- IV. INFLUENCE OF CERTAIN RESPIRATORY MECHANISMS ON DEPOSITION, RETENTION, CLEARANCE AND TRANSLOCATION OF INHALED RADIOIODINES A. INTRODUCTION A major and, under special conditions, possibly the most impor- tant route for entry of radioiodine into the body is by inhalation. Lang- *7 o ham'0 listed seventeen different variables that affect the deposition, retention and translocation of particulate matter in the respiratory tract. Some of these parameters are particle size and shape, solu- bility, hygroscopicity, wetting, concentration, respiration rate, par- ticle density, flocculation, chemical nature or form, and inspired and expired air flow rate. Of the above, particle size has received the most attention and has been investigated both experimentally and theoretically. Langham'''0' reported that Stannard attached special significance to the possibility that a large fraction of the total radioactivity introduced into the atmos- pheric environment may be associated with a number of particles and not with mass concentration. However, the minimum in the mass re- tention curve may be severely misleading with regard to lung retention of radioactivity unless specific activity is considered. He further stated that this aspect of the potential inhalation hazard is -worthy of continued investigation. Emphasis on respiratory gas exchanges diffusion, dis- tribution of ventilation, perfusion and mechanics of respiration is re- quired for a more rational approach to an ideal lung model. It is im- portant to be able to predict the time-rate of respiratory uptake and internal transport and body storage of absorbed gases if there is ever to be a basis on which to relate the effective toxic dose at critical sites within the body to the atmospheric concentration and time pattern of exposure. ""* 17 ------- This section will cover deposition, retention, translocation5 and excretion of radioactive materials, particularly the radioiodines. Depo- sition will be discussed with reference to vapor or particulate matter deposited in various regions of the respiratory tract. Retention will be concerned with the percentage of the radioiodines remaining and the mechanisms of removal from the lung. Translocation will deal with the mobilization of the iodines into the critical organ, assumed to be the thyroid. Discussion of the thyroid will be in detail since the end result of inhalation of radioiodine is normally assumed to be thyroid damage. A brief statement of the up-to-date pathological findings will be included. B. DEPOSITION: INFLUENCE OF PHYSIOLOGICAL, FACTORS 1. Upper Respiratory Tract Flow of air into the lungs must enter through the oral or nasal cavities and proceed down the trachea into the bronchi to reach the pulmonary lobules. When nasal breathing is predominant, deposi- tion of particulate matter of 1 - 3 microns is noted in the alveoli. Beyond this range, deposition diminishes with decreasing particle size to 0. 1 micron, then Brownian motion tends again to increase deposition. Practically all particles of over 10 microns are fil- tered out at this level. Nasal absorption of vapors such as Sarin was shown to be 98% in the rabbit, 93% in the monkey and 96% in man. ^ In oral breathing, deposition in the alveoli is minimal at 0. 5 micron and increases for both smaller and larger particle sizes. Oral inhalation of Sarin vapor showed that a significant portion of the gas reached the bronchial tree, particularly at rapid flow rates. Flow rate is the velocity with which the air enters or leaves the lungs and airways during the act of breathing. The inspiratory and expiratory flow rates and resistances can be represented by 18 ------- flow curves developed by measuring instantaneous flow as a func- tion of time. Silverman reported development of a linear- response flow meter that records instantaneous changes in air flow during inspiration and expiration. He reported a new con- cept of respiratory work rate and the information obtained can be used for study of deposition of aerosols in various collecting devices under pulsating flow. As the air enters the bronchi, par- tial mixing of the gaseous stream occurs. Flow may be laminar or turbulent, depending on velocity. In the segmental bronchi, there are many large pulses of flow that are synchronous with 117 37 the heart beat. Drasche demonstrated that the inspiratory velocity pattern was predominantly dependent on constitutional factors such as tension, anxiety, fear, etc. Conduction of streams of gases and vapors is through the so-called anatomical dead space. This space is defined as the internal volume of the conducting airway from the nose and mouth down to but not including the alveoli. By definition, the anatom- ical dead space is a conducting system to the alveoli; therefore, no gas exchange is accomplished in this space. In this discussion the expression respiratory dead space will include "anatomical" and "physiological" dead space. Both components normally vary with tidal volume. ' Variations that are observed in tidal volumes during measurements of the dead space might represent 122 unperfused alveoli that are ventilated, or too much air reach- ing the alveoli in proportion to their capillary blood flow. During movement of streams of gases, the removal of par- ticulate matter down to and including the terminal bronchioles is observed to be 100% of particles over 10 microns in diameter and 19 ------- 80% of particles over 5 microns in diameter."^ However, there are significant differences in the uptake of dust particles smaller than 5 microns in healthy subjects (man) with equal lung vol- umes and equal ventilation capacities. The total transit time for air, and probably particulates, from the mouth to the alveolus is directly proportional to the length of the bronchial airway sup- plying the alveolus. -^1 This transit time, determined by breath- ing frequency, greatly influences the deposition rate. As the breathing frequency decreases, deposition of particles with diam- eters of 1 to Z microns increases. 2. Lower Respiratory Tract Below the terminal bronchioles are the respiratory bronchi- oles, atria, alveolar ducts and alveoli; together they make up the pulmonary lobule. This area of the lung, the distinct anatomy depending on the species, '-*» °^ is where rapid gas exchange occurs. Hatch"^» °3 reported that the highest probability for particle deposition in the pulmonary lobule occurs in the range of 1 to 2 microns where precipitation by diffusion takes place. Within 0. 25 to 0. 5 micron particle diameter, the combined forces of precipitation by gravitation and diffusion are minimal and, therefore, have the lowest probability for deposition in the lobules. Particles below 0. 25 micron average diameter are deposited mainly by diffusion. (See Figure 1 and Table 7). For the most part, deposition of particles less than 0. 1 micron is limited only by the fraction of inspired air that goes to the lungs. "^ 3. Lung Volumes and Capacities Lung burden estimates from particle deposition cannot or should not be made without knowledge of the lung volumes (essen- tially anatomical measurements) and pulmonary ventilation 20 ------- CO O Q. UJ O UJ O cc UJ a. DIFFUSION <— IMPACTION 100 r- 0.01 SE DIM ENTATION NASO- PHARYNGEAL TRACHEO- BRONCHIAL Q.I 1.0 AERODYNAMIC SIZE IOJO IOQJD DIAMETER) Figure 1. Percentage deposition in various regions of the respiratory tract as a function of aerosol particle size; unit density spheres assumed. ------- (a function measurement). Lung volumes and capacities are de- fined in Table 8 and Figure 2. Residual volume, inspiratory re- serve volume and expiratory reserve volume are only static vol- umes, whereas tidal volume is dependent on mechanics of inspir- ation and expiration. Because pulmonary ventilation is a dynamic process, quantitation of air movements through the conducting airway to the alveoli is necessary to be able to calculate the al- veolar ventilation rate, i.e. , the volume of air reaching the al- veoli per minute. The volume of pulmonary lobule ventilation is, therefore, primarily dependent on frequency of breathing, tidal volume, and amount of respiratory dead space. The degree of alveolar ventilation -will normally be reproducible in the same animal as long as pulmonary pathology does not exist. The amount of ventilation per alveolus will differ in the various species and with the frequency of breathing of a particular subject. The rate of breathing will influence differences in relative distribu- tion of the dead space gas. " (See Tables 9 and 10). Although the overall pressure gradient to all alveoli is usually regarded to be about the same, differences in transit time are observed. This leads to differences in effective ventilation, of alveoli even though total ventilation of all alveoli is the same. It is therefore logical to assume that all alveoli do not necessarily contribute to the expired air simultaneously. Total and effective ventilation of the lungs depends on numer- ous physiological and anatomical features of the species under study. Two animals of equal body size may have lungs of the same vital capacity, but if one of these animals has a higher rate of metabolism, the alveoli of the lung will usually be smaller, as the size of the alveoli appears not to be always related to the 22 ------- STATIC LUNG VOLUMES EXPIRATORY RESERVE VOLUME INSPIRATORY RESERVE VOLUME Inspirotory Capacity rf'LCjii i;vc; iiR'vi; F'RCli TV •RV- Functional Residual Capacity MAXIMAL INSPIRATORY LEVEL MAXIMAL EXPIRATORY LEVEL Figure 2. Lung volumes. (Courtesy of Year Book Medical Publishers, Inc. and Dr. Julius H. Comroe, Jr. ) 23 ------- body size, ^ but appears to be related to rate of metabolism. For example, (See Table 11) the mouse has the smallest alveoli mean diameter, the guinea pig and rat almost two times that of the mouse and the cat and man approximately three times the mouse. From such data, Tenny^^ attempted to relate pulmon- ary ventilation to easily measured physiological and physical measurements. He determined that total alveolar ventilation is proportional to metabolic rate of the species; respiratory fre- quency correlates inversely with body mass to the 0. 28 power; metabolic rate correlates with body -weight to the 0. 74 power; total lung volume is a constant fraction of body mass and tidal volume is directly proportional to body weight. 4. Mechanics of Breathing Air flows from a region of higher pressure to one of lower pressure. Respiratory movements, reflex or not, determine the degree and extent of pulmonary pressures through voluntary and involuntary muscular control. Active contraction of the in- spiratory muscles causes enlargement of the thorax and lowers the intrathoracic pressure, thereby enlarging the alveoli, ex- panding the alveolar gas, and lowering the overall alveolar gas pressure to less than atmospheric so that air flows into the al- veoli. Active muscular contraction during inspiration provides: a. The force necessary to overcome elastic recoil of the lungs and thorax. b. The force required to overcome frictional resistance during movement of the lung and thoracic tissues. c. The force necessary to overcome frictional resistance to air flow through the tracheobronchial tree. At end-inspiration, the muscles of inspiration relax and no longer exert a force -which distends the lungs and thorax, the 24 ------- elastic tissues of the lung and thorax now recoil. In normal sub- jects the elastic recoil results in the lungs and thorax returning very rapidly to the resting expiratory level even though expira- tion is completely passive. There are species differences in the breathing mechanisms as one would expect. The eupneic horse moves approximately 6000 ml of air over a span of five seconds. °^ The respiratory cycle is polyphasic with dual expiratory and inspiratory phases. The thoracic movement is usually less than the abdominal. The dual cycle normally becomes obscure in abdominal movements during hyperpnea, but persists in increased respiratory (nasal and trachea) and intrapleural inspiratory pressures. In the dog, the intercostal muscles and the diaphragm do not act together in inspiration with respect to time. The early air flow peak that is observed in inspiration is due to the action of the intercostals, and the late peak flow is due to the action of the diaphragm. 1" In the eupneic rat, the respiratory cycle moves 1.5 ml of air per second. The cycle is diphasic with single expiratory and inspiratory phases." The elastic properties of the lung and thoracic tissues are combined into a parameter called pulmonary compliance which is defined as the volume change per unit pressure change and is expressed in units of liters/cm H2O. Pulmonary compliance is measured under static conditibns. When elastic properties are measured under dynamic pressure-flow relationships, they are referred to as pulmonary resistance and are defined as pres- sure differential required for unit flow change and are expressed in units of cm Hz O/liter/sec. 25 ------- Lungs of small and large animals tend to have approximately equal pulmonary compliance thereby requiring approximately equal thoracic pressures for intake of one tidal volume. ^° Pul- monary compliance differences nevertheless exist and are tabu- lated for the various species in Table 12. It is apparent by exam- ination of Table 12 that species differences are observed in other respiratory parameters such as tidal volume and frequency of breathing. Agostoni and co-workers reported that the expiratory re- serve per unit vital capacity and the functional residual capacity per unit total lung capacity are larger in the animals breathing at a lower frequency. The relationship between rate of work.of breathing and breathing frequency was such that the frequency typical of each animal at rest corresponded to the minimum rate of work. This increased frequency and its effect on alveolar pO2 is possibly the primary factor concerned in species differ- ences. ' The panting mechanism supports this view, as respir- atory impedance is least : at the resonant frequency of the thoracic system, and volume flow is obtained with least effort 27 8 ^ at this frequency. McCutcheon described a complementary cycle in the horse and rat. He defined the cycle as a predictable recurrence in regular sequence. This cycle is a very deep, rapid inspiratory movement (initial rapid respiratory movement) followed by a very slow expiratory movement. The complement- ary cycle frequency was found to vary with body size but the dur- ation of the cycle varied more with the alveolar size than with body size. (See Tables 10 and 11). He suggested that diffusion regulation in respiration is a principle of the comparative phy- siology of atmospheric respiration of various species and that 26 ------- periodic breathing is the primitive pattern of atmospheric ven- tilation. Other factors influencing the pulmonary ventilation and, therefore, deposition are: * a. Protective reflexes: (1) Cough reflex - produced by forceful expiratory ef- fort generated as a response to foreign materials or secretions introduced into the respiratory tract. (Z) Upper respiratory reflex - causes apnea, closure of the glottis and bronchial constriction when irri- tating materials enter the upper airway. (3) Swallowing reflex - food passes from the mouth to the esophagus by closure of the glottis and inhibi- tion of inspiration. (4) Submersion reflex - causes apnea and bradycardia when water enters the upper respiratory tract. b. Pulmonary stretch reflexes: (1) Hering-Breuer inflation reflex - inhibition of in- spiration in response to lung inflation. It has been seen in such animals as man, dog, cat, monkey, rabbit, guinea pig, rat and mouse. ° The inhib- ition period in man is 2 to 20 times shorter than the rabbit. (2) Hering-Breuer deflation reflex - deflation or col- lapse of portions of the lungs causes earlier and more rapid inspiration and acceleration of respir- atory frequency. The reflex is weak, in humans, but strong in many other animals. *1° (3) Head's paradoxical reflex - this has been observed in cats, dogs, monkeys and rats, but never in man.11? c. Thoracic chemoreflexes: (Bezold-Jarisch reflexes) Stimulation of coronary and pulmonary chemoreflexes results in reflex apnea, bradycardia and hypotension via vagal stimulation. Effects may be dramatic and sometimes catastrophic in experimental animals, ^^ but effects vary in different species and the physiologic or pathologic significance of these reflex effects in man is still obscure. 27 ------- d. Circulatory factors: (1) Increase in arterial blood pressure in the carotid sinus and aortic arch reflexly diminishes pulmon- ary ventilation, and a decrease in arterial blood pressure augments the pulmonary ventilation. (2) Severe hypotension may cause ischemia in the ca- rotid and aortic bodies resulting in an intense re- spiratory stimulation. (3) An increase or a decrease in cerebral blood flow may decrease or increase pulmonary ventilation respectively by permitting a change in CO2 content of neurons in the respiratory center. e. Reflexes from joints: Back and forth motion of a limb will reflexly increase the rate and occasionally the depth of breathing. f. Pain receptors: Respiratory stimulation or inhibition may be caused by pain depending on the character, origin and intensity. g. Temperature: An increase in body temperature -will cause an increase in pulmonary ventilation. This results, in part, from "warming" of the medullary centers and chemoreceptors. h. Supramedullary regulation: Supramedullary areas exert important effects on areas such as pontine, pneumotaxic center and cortical areas. Pathological or physiological alterations in the respiratory tract will considerably modify the air flow and, therefore, the amount of alveolar ventilation; the latter indirectly affects the deposition and the distribution of material in the bronchials and pulmonary lobules. For example, the different air velocities and alveolar ventilation rates in a fast shallow breather versus a slow deep breather in the human may be compared to a panting 28 ------- dog with dyspnea or to a horse with emphysema. The variation in ventilation rates will cause differences in the total amount of material deposited and probably differences in the distribution to the specific areas of the respiratory tract. The distribu- tion of air to the normal lung lobes is not necessarily in propor- tion to their volumes nor does each lung lobe become ventilated equally. Rahn et al, by perfusion of canine lung with radio- active materials following autopsy, observed unequal ventilation of the lung in the supine and erect positions. The typical radioactive field aerosol is heterogenous in that it contains a large fraction of small particles of relatively high radioactivity, such that the contribution of these particles to the radiation dose, despite relatively low deposition, may pro- duce a major fraction of the total dose. A point to remember is that physiological parameters, such as breathing frequency, can exert about as much influence as particle size. It has been shown numerous times that the fast shallow breather -will have relatively less material deposited in the lungs than the slow deeper breather when all other factors are equal. This same effect has been seen by investigators for the sub-micronic range t *• i 42 of particle sizes. It is quite evident that there are many physiological and physical factors involved in the study of total lung volumes. Neither metabolic rate nor surface area directly affects this volume; however, total lung volume appears to be a constant fraction of body mass in that tidal volume is directly proportional to body weight and a constant fraction of the lung volume. ^ 29 ------- Some of the physiological factors which may determine the gas flow into the tracheo -bronchial tree have been discussed with emphasis on participate deposition and interspecies differ- ences. Before discussing work done in radioiodine inhalation a brief discussion of a lung model is in order. 5. Lung Model The lung model to be discussed here assumes some form of an airflow (velocity versus time) pattern in the airways and still air in the alveoli. Silverman10-' stated: "In many instances these model assumptions can be improved by adaptations of actual air flow data. The important consideration is that air flow varies throughout the whole respiratory cycle, except for a short pause following expiration under sedentary conditions only. This would indicate that inertial mechanisms of removal in the nasal passages and in the upper respiratory tract and at bifurcations, etc. , must be essentially a function of a variable velocity, a consideration that requires an exten- sion of the existing theories for inertial deposition. " The model does not consider pulsations of gas flow within the lung which are caused by movement of the heart or great vessels, West^^ stated: "The observations of pulsatile flow will affect any theory of dust deposition which is based on the as- sumption of still air in the smaller airways. " However, the proposed lung model is used for calculation of deposition and clearance information and for determining max- imal permissible air levels of gases, vapors or particulate matter. Hursh^8 stated: "The lack of element specific information and the excuse of long practice have justified the use of this convenient device." 30 ------- This model predicts that 75% of the total radioactive partic- ulates inspired will be deposited, 25% will be expired. Of the 75% deposited, 50% -will be deposited in the upper respiratory tract and the remaining 25% in the pulmonary lobules. It distin- guishes between the behavior of soluble and insoluble classes of inhaled materials in the pulmonary lobules. In the case of sol- uble materials, the 25% passes rapidly into the blood; in the case of insoluble materials 12. 5% is removed by the pulmonary system and ends up in the gut; the other 12. 5% is slowly removed from the lung by absorption in blood and lymph with a half-life period of 120 days (See Table 13). Gibb reported approxi- mately 12% alveolar deposition in the dog of an insoluble 59Fe oxide aerosol -with a biological half-life for alveolar clearance of 62 + 8. 8 days. These amounts of deposition were highly re- producible; however, this is not always true for man because total lung deposition of dusts has been observed to vary from 20 to 90%. 91 It should be noted that there is marked evidence that any pulmonary study will show conspicuous species differences not usually considered in the lung model. These differences become more acute as the methods of study begin to obtain refinement and calculations of radiation dose become more critical. C. RETENTION AND CLEARANCE Retention is defined as the amount or fraction of deposited ma- terial that remains in the respiratory tract at any given time. Reten- tion is expressed as the percent of the total radioactive aerosol in- haled which remains deposited in the lungs. The transport of the deposited material out of the respiratory tract is referred to as 31 ------- clearance. As the material is being deposited, pulmonary clearance mechanisms are normally functioning to remove the material; there- fore, deposition, retention and clearance, when measured as such, vary as a function of time. The end result is removal of material from the respiratory tract. The four physiological mechanisms involved in the transport of the particulate material from the lungs are 1) action of the ciliated bronchial epithelium, 2) alveolar phagocytosis, 3) transfer of relatively soluble material across the alveolar mem- brane, and 4) penetration of the alveolar wall without mediation of phagocytic cells. 1. Physiological Mechanisms of Pulmonary Clearance a. Ciliary Clearance The ciliated epithelial lining of the bronchial tree plays a major role in the clearance mechanism of the lung. Mu- cosa which comes into contact with the majority of inhaled impurities is located in the nostrils, trachea and larger bronchi. The degree of contact with the finer bronchi and bronchioles is, for the most part, dependent on deposition mechanics and absorption higher up in the bronchial tree. Regardless of how particles are brought in contact with the ciliated epithelium, the particles normally never contact the cilia directly, but lie on and/or in a blanket of very thick and viscous mucus which overlays the cilia of the bronchial epithelial cells. ^ The mucus and the embedded particles are driven upwards "in bloc" by the rhythmic beat- ing of the cilia. The cilia have been reported to average on 1099 beats per minute in the rabbit. The cilia force the mucus upward along the bronchial tree in a spiral path to the pharynx where it is eliminated either by coughing or by 32 ------- swallowing. ' In rats, radioactive particles have been shown to be cleared from the ciliary lined air passages 1 f\ o within one day. The linear velocity of particles moving up the bronchi varies from 0. 25 to 1 centimeter per minute and increases to as high as 3 centimeters per minute in the trachea. Ai> » The process by which particles are car- ried up the surface of the bronchus toward the pharynx is referred to as a "mucus-cilia escalator". b. Alveolar Phagocytosis Clearance of the pulmonary tract of matter, foreign or secretive, involves a second mechanism referred to as al- veolar phagocytosis. Inhalation of particulate matter causes the appearance of a large number of amoeboid cells that ap- parently have a dual capacity to act as macrophages or to remain free in the alveolar lumen. These cells, referred to by many as pneumocytes, may phagocytize inert dusts in large quantities and undergo mitosis or may engulf toxic dusts and then undergo degenerative changes. ^ Schiller distinguishes between two types of pulmonary phagocytes. The first type is the cell derived from the alveolar epithe- lial cells. These cells are on the alveolar surface and do not enter the interstitial tissue, but are removed with the pulmonary fluids. The second type is a cell derived from the inter stitium and is considered to be sub-epithelial in origin. These are found most generally in the interstitial connective tissue of the lung. He concluded that there are two phases of phagocytosis, the epithelial phase of phago- cytosis by pneumocytes and the interstitial phase of phago- cytosis by macrocytes. Casarett's ' theory differs 33 ------- somewhat in that the origin of the phagocyte is apparently the alveolar epithelial cell. The phagocytic ability of the cell is considered to be the manner in which the cell mem- brane is arranged with regard to the adjacent cell; i. e. , one cellular membrane may be on the lumen side of the al- veolar segment whereas the cellular membrane below it is on the interstitial side of the segment. He, therefore, is of the opinion that the particle-laden phagocytes that appear in the alveolar lumen are those cells that have full cellular exposure to the lumen; those particle-laden phagocytes found in the interstitium are those cells that have cellular exposure to the interstitium. He also feels that particles can penetrate the alveolar wall directly without benefit of phagocytic transportation. The rate of phagocytosis has been found to be a function of the particle size, particle concentration, '' physico- chemical properties of the particulate matter, and sur- face tension of pulmonary fluids. It appears that the process would continually progress, regardless of rate, as long as there were potential histiocytic cells to respond to the irritation of foreign matter. If the alveolar cells were destroyed or the cells became amitotic for one reason or another, phagocytic activity would cease and alveolar fibrosis would normally occur. La Belle, '^ by estimating the number of free phagocytic cells in the lungs of rats, concluded that transport of depos- ited particles by phagocytes was the primary mechanism by •which inhaled insoluble dust particles were eliminated from the lung following inhalation. He showed that the amount of 34 ------- dust eliminated from the lung during the early post-exposure period was proportional to the number of free phagocytic cells present and that the kinetics of elimination of the par- ticles was identical with the kinetics of the disappearance of phagocytic cells following exposure to dust, whether the dust was given by inhalation or by injection. c. Alveolar Membrane Transfer Transfer of relatively soluble material across the al- veolar membrane into the blood stream is the third mechan- ism of respiratory tract clearance. The terms "soluble" and "insoluble" are placed in quotes since solubility is de- pendent principally on chemical composition; however, phy- sical properties such as size, shape and surface area are also involved. Simple solubility in pure solutes need not be a measure of solubility in the lung. For example, Ag I3ll, a most water-insoluble iodine compound, once in- haled does not act as a purely insoluble compound. 120, 121 The assumption that material leaving the lung passed into the systemic circulation via the blood vascular system if the particle were soluble, and via the lymphatics if it were insoluble,was made before actual experimentation •was at- tempted. Balance sheets for pulmonary deposition, reten- tion, and transport have been proposed in an attempt to ex- plain the clearance of the lung. Numerous calculations and observations indicate that a satisfactory explanation of the observed dynamics of the lung itself has not yet been ob- tained. Harper and Morton" demonstrated that inhaled 32P tagged aggregates of bacterial spores were eliminated via 35 ------- the gastrointestinal tract. This apparently was the earliest experimental demonstration of clearance of inhaled, insol- uble particles from the lung via the "mucus-cilia escalator" into the gastroenteric tract. This clearance was chiefly from the upper respiratory tract where total percentage retention of spores is known to decrease. •* The remain- ing particles may or may not have contained radioactive material that could cross the alveolar membrane. If gas- eous and particulate matter are inhaled, such as often hap- pens with radioiodines or ^compounds that sublime easily, the transport of these compounds through the lining com- plex of the alveoli is dependent, for the most part, on physico- chemical interactions of the inhaled matter with body compo- nents. Pattle described the lining of the alveoli as an insol- bule layer formed from a thicker layer of a substance which he called the "lining .complex". This layer was found cap- able of reducing the surface tension of the alveolar surface to nearly zero while being fully permeable to air (and pre- sumably to any vapors). He was of the opinion that it is possible that the lining complex responds to inhaled irritants by an increase in secretion, thereby lowering the surface tension and providing a protective mechanism for the alveoli. It is apparent that more than solubility is involved in clearance of material from the lung, since it has been dem- onstrated that translocation is not necessarily predictable " fi 7 7 from the solubility of compounds in pure substances. °» ' ' Vapor pressure is possibly a more important limiting factor than water solubility during short term experiments. 36 ------- d. Non-Phagocytic Penetration of Alveolar Wall The fourth mechanism involved in lung clearance is the penetration of the alveolar wall without mediation of phago- cytic cells.6' 19,33,42, 102 Thig mechanism affects par- ticulate matter which has been deposited in the deeper por- tions of the respiratory tract where, for the most part, clearance by the "mucus-cilia escalator" has been ineffective, non-functional or non-existent; however, the existence of this mechanism has not been fully proven. The penetra- tion of the lining complex of the alveolus is thought to take place at multiple, small, scattered foci near the juxtaposi- tion of alveoli and large vessels and bronchi. 42 Others have suggested that the penetration of the alveolar lining membrane occurs through defects in the membrane. ^3 Schiller maintains that only free particles can penetrate the walls of the alveoli and that a pneumocyte or phagocyte laden with dust either stays in the lumen of the alveolus or is transferred to the bronchioles and expectorated. If de- struction of a phagocyte occurs, the process of clearance is repeated. Barclay^ discussed the mechanism by which phagocytes cross the continuous cytoplasmic structures and vital membranes. The mechanism is unknown and probably related to diapedesis. Discussion of the mechanisms of lung clearance have purposely omitted the nose, sinuses and extreme upper re- spiratory tract. Clearance mechanisms of this portion of the respiratory tract are similar; however, removal rates are more rapid, probably because the majority of this por- tion of the respiratory tract is lined with ciliated epithelium. 37 ------- Over 90% of a very soluble gas such as Sarin was found to be absorbed in the nasal cavity; however, the nose would not protect the lungs during a prolonged exposure to the gas. ^ Pattle' also found that after prolonged exposure to a noxious soluble gas, the nasal mucosa would reach a balance between the absorption of the gas and its diffusion into the blood stream. Retention in the nose was nearly 100% for particles above 9 microns in diameter and vari- able between 1 and 9 microns. Penetrations posterior to the trachea and below were 90% at particle sizes of 1 micron in diameter. The variation in retention suggests that impac- tion is the main mechanism by -which these particles are re- tained. Particles measuring 0. 054 to 0.4 micron in diam- eter showed penetrations averaging 80%; no regular varia- tion with flow rate or particle size could be detected. 118 West found that the upper respiratory tract removed water vapor with a high degree of efficiency. He scanned the respiratory tract of three human subjects immediately after they had inhaled 1 5O labeled water vapor. It was found that the mouth, pharynx and upper trachea retained a large percentage of the l 5O water vapor (See Table 14). Barrall compared the radioactivity on nose swabs to re- sulting thyroid burden in a patient accidently exposed during a contamination incident. He found the ratio of micro- curies on the nose swabs to microcuries in the thyroid was 2. 6xl02 -with all values -within a factor of six. 38 ------- D. TRANSLOCATION Translocation is defined as the movement of material from one tissue to any other tissue or tissues. Translocation takes place to a certain extent irrespective of the physico-chemical nature of the in- haled radioactive material. This leads not only to a direct radiation hazard to the lung, in the case of inhaled material, but also to a sys- temic radiation hazard by virtue of absorption and deposition in other tissues. During clearance of radioiodines from the lungs, the radioiodine may enter the systemic circulation via such routes as the pulmonary or the gastroenteric complex. The distribution of radioiodine in tissues following lung clearance, is qualitatively similar to the distribution in tissues following intravenous administration. Certain radio- iodine compounds may be exceptions to this under special conditions. Pulmonary clearance was apparently very rapid in mice following in- halation of l 31I vapor. '"' ' The maximum concentration of 1 311 was shown to appear in the thyroid at about 30 hours. There •was a simultaneous decrease of * 31I in the lung and other tissues. This was probably a reflection of the 1 31I uptake of the circulating blood. Under similar experimental conditions, but substituting a relatively insoluble Ag l 311 compound for the carrier free l 31I, mice were found to retain 12% of the Ag 1 31I; however, the time of maximum thyroid uptake was 10 hours. A finding such as this could be regarded as an exception to the statement made previously. Nevertheless, it still may be true that the blood and lungs, with re- spect to inhaled iodine, will rapidly enter into iodine equilibrium. Sheep and rats were found to be qualitatively similar in deposition, retention and thyroid translocation, although quantitative results did not completely agree. » Fountain ° showed the thyroid uptake 39 ------- following cloud passage from Project Sedan was 92% of the total 1 33I available to the respiratory tract of Beagles. It is highly probable that the dogs licked themselves following exposure to the cloud and therefore one cannot assume that the entire intake of radioiodine was by inhalation. The concentration of radioiodines in the systemic circulation may be due to a large percentage of the deposited particulate matter containing the radioiodines being eliminated from the lung via the "mucus-cilia escalator" and then being coughed up, swallowed and absorbed via the gastroenteric route. It has been suggested that the gastrointestinal tract can be an important route of entry of inhaled material into the systemic circulation. If this is true, evaluation of the internal hazard associated with radioiodines, either in soluble or insoluble forms, requires further investigation and consideration of parameters that influence transport of radioiodines across the gas- trointestinal membrane. Regardless of how radioiodine enters the systemic circulation, a large percentage of the iodine is usually translocated to the thyroid under normal physiological conditions. The thyroid, therefore, is assumed to be the critical organ with regard to internal radiation hazards from radioiodine. 1. Fate of Radioiodines in Body The thyroid consists of two lobes, one on each side of the trachea, and, in the horse, cow, sheep or dog, a very narrow connecting isthmus near to or in contact with the larynx. In the dog the isthmus usually disappears in embryonic life. ' In the pig, the glands are usually found a distance from the larynx and are united to a considerable extent ventrally by an isthmus which 40 ------- cannot be distinguished. The gland is composed of numerous follicles that are lined by a single layer of low cuboidal epithelial cells which contain colloid. There are species differences in size and weight of the gland as well as differences in volume of air breathed per gram of thyroid and weight of thyroid per kilo- gram of body weight. Dairy cattle breathe approximately two liters of air per gram of thyroid per minute, but in contrast, man breathes only 0. 2 liters of air per gram of thyroid per min- ute115 (See Tables 12 and 15). Grazing type animals breathe a large quantity of air and also ingest large amounts of food per gram of thyroid. Van Middles- worth115 was of the opinion that these characteristics explain the reason why thyroids are early indicators of radioiodine in the biosphere. He suggested that the lowest retentions of radio- iodine fallout may represent only the respiratory intake. Another factor that should be considered is the physiology of the mechan- ism of eructation in the ruminant. Dougherty et al reported that the pulmonary system provides a route of absorption of eructated gas. They found that various gases such as CO2 , CO, H2S, and O2 (and no doubt radioactive iodine vapor if it -were present) after being placed in the rumen -were more capable of causing changes either in the blood gas levels or in physiologi- cal activities of the animal when the trachea was patent and cap- able of receiving these gases during eructation. Dennis and Harbaugh found that average blood CO2 for the Jersey was 53. 6 volumes percent and for the Holstein (a big breed of cow) was 56.5 volumes percent. These percentages varied inversely with the ambient temperature of their environment. 41 ------- Following absorption into the blood vascular system the ma- jority of iodine appears as an organic iodide which diffuses ra- pidly into the extracellular space ^ or is oxidized and incorpor- ated into organic compounds, usually proteins. •*• ^ The first mechanism is referred to as the extrathyroidal iodine pump. This mechanism transfers iodide ions from the plasma into other pools where the I concentration is maintained 10 to 40 times greater than in plasma. Apparently, the salivary duct and gland, gastric mucosa, and skin concentrate iodide ions in much the same manner as the thyroid gland. Salivary glands and gastric juice have been found to contain iodine 30 and 40 times greater than plasma, respectively. ^ Iodides are normal- ly freely exchangeable with plasma in the skin, cerebrospinal fluid and placenta. ' Concentrations of l 31I in the fetal thyroid during advanced gestation maybe 1 to 2 times the adult thyroid in sows, 2 to 3 times the thyroid in ewes, and up to 6 times the thyroid in cows. ^ Blood iodine will directly influence the thyroid function if it is readily available as an iodide ion. However, variations are also associated with age, breed and season in some animals. 123 In sheep the maximum thyroid uptake was found to be during the period from August to January and the minimum uptake from April to July. ' A suggestion of increased thyroid uptake has 1 Q occurred following parturition in the dairy cow. Swanson et al reported the maximum accumulation of 1 31I in the thy- roid of the dairy cow was about two times as great in November as May, about the same in September as in May and lowest in July. The extrathyroidal iodide pools may function as buffers and act as a control system to aid in the maintenance of a constant 42 ------- mass of iodine transferred into the thyroid per day. The quan- tity of iodine, whether radioactive or stable (l 2 7 I), accumulated each day by the thyroid gland is characteristic of the species and is the fraction of the daily iodine intake and extrathyroidal iodine pool which is trapped by the thyroid gland. Rapid accumulation of iodine by the thyroid may indicate inefficient utilization of iodine and pathological alterations. The thyroid gland removes iodide from the plasma through the thyroidal trap, -which depends on intact follicular cells and possibly a binding on a special protein. " The trapping does not apparently depend on specific metabolic pathways for iodide because these can be blocked by antithyroid drugs without abol- ishing the concentrating activity. Recycling was found to be pre- vented in dairy heifers by giving thiouracil at the rate of 0. 2 grams per kilogram of body -weight, but not by giving subcutane- ous KI. Bair and co-workers" found that to reduce the 1 31I uptake 50 - 100 fold in rats and 3 fold in dogs, it required a con- centration of iodine (* 2 7 I) aerosol that acted as an irritant to the respiratory tract. Thus it appeared that a near toxic level of l 2 7 I in air was required to significantly depress the thyroidal uptake of J 31I under the condition of the experiments. The me- chanisms that are involved deal with metabolic pathways which are not easily traced and are concerned with many interactions of various hormones. Recent advances in iodine metabolism and the biochemistry of hormones are well documented in pub- 00 07 QQ 1 1 A lished references. »'77> These references should be consulted for greater detail. Comparisons between various methods of administration of the radioiodines contributing to the iodine pool show variations 43 ------- in percentage of uptake by the thyroid. A single dose of Na l 31I injected subcutaneously in 63 dairy heifers of four different breeds resulted in a maximum thyroid uptake in 48 hours^O (See Table 16). The thyroid was found to contain 41. 6% of the in- 123 jected dose. Wood and co-workers reported that rates, total uptake and effective half-life were similar in young sheep follow- ing oral, intravenous and subcutaneous administrations of l z 5 I and 1 31I. A lower uptake and a longer effective half-life were seen following topical administration of both isotopes. There are found in the literature conspicuous differences in absorption rates of various radioiodine compounds given by various methods (See Table 17). The absorption from the different sites empha- sizes the unusual properties of body fluids and shows that one cannot always predict the absorption of 1 311 from the body tis- sues on the basis of solubility of the compound. 2. Excretion of Radioiodines into the Mammary Glands Iodide loss by excretion is predominantly through the mam- mary gland, hair and perspiration. Iodine is concentrated in the hair, but the biological importance of this fact is a relatively unexplored field. The sweating mechanism is markedly dif- ferent between species. Man has the most refined mechanism whereas the dog has relatively few sweat glands. In domestic animals, especially dairy cows, a major portion of the iodide loss is through the mammary gland. Available iodide passes to and from the mammary gland and blood with ease,- entering the milk independent of milk secretion. °' The iodide or iodine enters the udder of the cow passively, but once in the milk col- lecting spaces, a portion of the iodine is bound and is rendered non-available for resorption. The greater iodine excretion of 44 ------- higher yielding cows is no doubt related primarily to increased mammary circulation and therefore to their greater volume of milk. The milk seldom contains more than two times the plasma concentration of iodide. The protein-bound iodine is between 30 to 50% of the total iodine. However, this does not appear to be true in the goat and sheep. The milk from either of these species has been found to contain 10 times the iodine concentra- 51 tion normally appearing in cow's milk. Garner et al demon- strated the presence of a concentrating mechanism in the udder of the dairy cow. The comparison of the total * 31Iin milk to plasma dialyzable l 31I at different times of the year indicated that the concentrating ability may be lower in the summer than in the autumn and spring months. Excretion, if the reader will accept this term, of 1 31I into the mammary gland per liter of milk has been determined to be approximately 0.4 to 1% of the daily l 31I intake after reaching 1R equilibrium; however, a marked variation is encountered among individual cows and among herds. Garner et al-' showed a total recovery of l 3 JI in milk during a 6-day collection period as 1. 3 to 19.4% of the initial dose. Other authors have shown recovery of 6. 2 + 2. 0% of the dose during a period of seven days. " Bustad et al, after spiking forage with 5 microcuries of 3 I and feeding this twice daily found that on the fourth day, 0. 4% of the first day's dose of 10 microcuries was observed per liter of milk. Peak concentration of the thyroid was seven days and •was about 70% of the first day's dose. Swanson et al demon- strated that 7. 2% of the initial intravenous dose of Na 13ll was recovered from the milk by the third day post-injection. Squire 108 et al reported that there appeared to be no evidence of any 45 ------- difference between the total excretion from cows fed fission pro- ducts serially or on a single occasion. The fission products, which were collected on gauze-backed, oil impregnated filters following round 1 and round 3 of Operation Buffalo, contained 131 I, 132I, 132Te, * 33I and other radionuclides. The material on the filters was considered comparable to long range fallout. They found that 1.48% and 3.48% of the administered dose was recovered during a nine day and six day period, respectively. The concentration in milk of 1 3 2I was at least twice as high as 131 I in the early stages. Iodine-132 declined to 50% at the end of six days. Iodine-133 decayed to an insignificant amount after eight days. 3. Excretion of Radioiodines into the Feces and Urine Fortunately, the largest quantity of iodine is lost through excretion into the feces and urine (See Table 18). Fecal loss of iodine is apparently a major route of depletion in rats, cattle and sheep because these animals not only have large daily re- quirements of thyroid hormone, but also excrete large quantities of organic iodine in the feces. Swine and man are more con- servative with their iodine reserves for only a small fraction of thyroxin that enters the gastrointestinal tract is excreted in the 17 24 feces. ' The major difference appears to be the fecalturine ratio in the various species. The factors involved in the excretion of thyroxin into the feces are unknown. Renal clearance of iodine in euthyroid humans is a linear function of the glomerular filtration rate and appears to be pri- marily an overflow mechanism for iodide. ' Rats will excrete more iodide if given Na Cl whereas the human is not 46 ------- affected by electrolytic changes as such. Taplin and co-workers suggested that l 33I could have been inhaled by rabbits following a tower detonation. Urine was found to be suspicious at 55 and 117 hours post-exposure, but they could not establish this with any certainty. Barry reported that a 24-hour urine sample collected from rats that had inhaled l 31I contained over 50% of the estimated inhaled dose. Bair et al" reported that 96% of the excreted J 31I was in the urine of rats exposed to l 31I-1 2 7I aerosol. Monogastric animals have been found to excrete more 1 31I in the urine than in the feces. Barrall demonstrated that in man the ratio of microcuries in a 24-hour urine sample to the microcuries of I in the thyroid was'5..7 with all values within a factor of two. Radioactive iodines that are not translocated to the thyroid, secreted or excreted are found in various organs. Less than 1% of an oral dose of 1 31I was found in body organs other than the thyroid of patients either at autopsy or surgery. '" Organs of uptake in descending order were lung, kidney, pituitary, liver, gonad (testes -were always measurable), spleen, adrenal and pancreas. In rats, » following inhalation of 1 311 or Ag 131I, the gastrointestinal tract, liver, lung, kidney, spleen and thyroid were found to contain measurable amounts of radio- activity (See Table 19). This was considered as a reflection of iodine equilibrium beginning to establish itself in the plasma. By 50 hours the thyroid had received 60% of the total body bur- den. Bustad et al listed the tissues containing l 31I following establishment of l 31I equilibrium in the blood of the sheep; the thyroid, feces, mandibular salivary gland, milk, abomasal wall and urine contained concentrations of 1 31I higher than those 47 ------- found in the blood. Other tissues, listed in descending order, that contained concentrations of 1 311 less than the blood were the parotid gland, liver, ovary, kidney, adrenal, pituitary, lung, lacrimal gland, heart, pancreas, spleen, thymus, brain and lens. Although the thyroid apparently receives the greatest per- centage of body burden following exposure to radioiodine, other organs and tissues are also exposed at some time during the circulatory and/or storage phase. The rates of exposure depend on many factors such as solubility, route of administration, spe- cies, etc. ; however, the rate of translocation, for the most part, depends on the concentration of J 311 in blood and the integrity of the blood-vascular system to the various organs and tissues. When the blood concentration of * 311 is 1 picocurie per gram of blood, the following relations exist in the tissues of the O 1 sheep and supposedly other ruminants. Blood Concentration of Tissue * 311 in Pi'coeuries-per . ' . • Gram Muscle, spleen, thymus, pancreas 1 Kidney, liver, ovary 2-3 Salivary glands, urine 3-5 Feces, milk. 5-15 Thyroid 10,000 The obvious factor is that the thyroid receives by far the greatest fraction of the total body burden. The radiation dose to the thyroid gland from a chronic exposure to radioiodines would be a function of the total deposited radioisotope in the gland. In a single exposure the radiation dose would be determined by the rate of thyroid uptake and be related to the biological half- life. Species characteristics will, however, determine the 48 ------- radiation dose to that particular species since there is a varia- tion in biological half-life of iodine in each (See Table 15). Not taken into consideration are the seasonal fluctuations that occur as well as pregnancy, lactation, temperature and possibly photo- periodicity. 17,115 Irrespective of how the individual (man or beast) is exposed to radioiodines, the end result has been assumed to be thyroid damage. The degree of damage apparently depends on species, although rate of uptake and iodine in the diet have to be considered as well. In the cow the minimum radiation dose to the thyroid required to produce a deleterious effect on the animal was esti- mated to be of the order of 70, OOO31 to 100, 000 rad. 53 Wood et al ^3 estimated the total radiation dose to the sheep thyroid from oral administration •was 6 to 8 rad per microcurie and from topical administration was 2 to 3 rad per microcurie.. Review of the comparative pathology following exposure to radioiodines suggests that there is morphological evidence of inflammation and necrosis in the thyroid. ~* An apparent se- quence of morphological alterations appears to occur more ra- pidly in rats and mice than in dogs, and even more slowly in human beings. ' Definitive pathological findings in the human are still in question in the greater percentage of cases. These findings on pathological effects from thyroid irradiation were 94 summarized and reported by a panel of experts in 1962. Their findings were: a. Differences in size and proportion of proliferating cells of the thyroid in infants, children, and adults do exist. b. There may be significant alterations in absorption, me- tabolic turnover and cell sensitivity with advancing age. 49 ------- c. Any of the above factors might affect the amount of bio- logical damage resulting from a given radiation dose. d. At high dose levels, the thyroids of infants and children may be somewhat more susceptible to radiation carcino- genesis than those of adults. e. Evidence of carcinogenesis at very low doses is lacking because no case of thyroid cancer at these levels is known. f. Radioactive iodine has been shown to be carcinogenic in some animals, but no case of thyroid cancer ascrib- able to it has been found in man. 50 ------- V. SUMMARY Quantities of radioiodines released into the biosphere are dependent on the characteristics of the source of fission products. However, after being released, atmospheric, terrestrial and aquatic influences will nor- mally determine the transport and the ultimate deposition. Following release into the biosphere, the transport and diffusion of radioiodines are usually considered to be uniform for the same release and meteor- ological conditions since the physico-chemical nature of the contaminant depends on the nature of the total release conditions. The biological availability will, therefore, depend a great deal on such physical factors as the source of radioiodines, proximity of the source to biological sys- tems of interest and meteorological conditions existing pre- and post- release. The problem, however, is the prediction of the many different chemical forms as well as physical forms the radioiodines may assume. They may be adsorbed in or on particulate matter, may exist as gases or vapors, or may be present in combinations of all three. The iodines may be found as elemental iodine, iodide (I ), iodate (IO3 ) and perio- date (IO4 ) or as organic compounds. The chemical states, solubility and physical states of the radioiodines greatly influence their behavior and in turn their possible absorption in a biological system and their availability to the respiratory system. The size of the particle upon which the radioiodines are absorbed or adsorbed depends in part on the origin of the particulate matter. The availability of the particulate mat- ter to the respiratory tract will depend on whether the MMD of the par- ticles is within the respirable range, i.e. , a significant number of par- ticles below approximately 10 microns in diameter. The region of deposition will depend upon such parameters as the particulate size, 51 ------- oral or nasal inhalation, flow rates through the respiratory dead space, and the alveolar ventilation. Rate of deposition of particles within the respirable range in the lung is dependent, for the most part, on the physiological characteris- tics of the pulmonary system of the species. There is a conspicuous difference in oral or nasal breathing among the various species. .. Man as a rule is a nasal breather; horses usually breathe through the nose as do cows and sheep; dogs use oral and nasal breathing inter- changeably depending on body temperature regulation, and cats are similar to dogs except they normally pant less. Flow rates through the airways depend, in part, on the diameter of these passages, their length and the degree of "straightness". The volume of alveolar ven- tilation is dependent on frequency of breathing, tidal volume and amount of respiratory dead space. These three factors will determine the total and effective ventilation of the lungs and indirectly determine the amount of deposition of "respirable" particles. Quantity of total ventilation, however, is characteristic of the physiological and anatomical features of the species. Each species differs in metabolic rates, respiratory frequencies, body mass, and total lung volume. Each of these has an effect on the total alveolar ventilation. In addition, there are species differences in the mechanics of breathing. The horse has a diphasic breathing pattern with no complementary cycles and the rat has mono- phasic pattern with many complementary cycles. Man and domestic animals exhibit patterns between these two extremes. Retention and clearance are usually considered under the same dis- cussion since they are inversely proportional to each other and are treated as rate functions. The removal of foreign matter from the lungs is by four physiological mechanisms peculiar to the lung. These mechanisms are found to be functional in all species of mammals, but 52 ------- differ in the degree to which they participate to clear the lung of foreign matter. As retention and clearance are taking place, translocation (the movement of material from one tissue to any other tissue or tissues), is usually being accomplished. This takes place, to a certain extent, regardless of the physico-chemical nature of the inhaled radioactive material. Translocation of the radioiodines is predominantly to the thyroid irrespective of the route of entry into the body. Since the most common route of entry of the radioiodines has been assumed to be by ingestion, past interest has been in ingestion with very little, if any, regard for inhalation. This is not surprising since investigative programs to study inhalation of radioiodines are not easily done, especially in large animals such as the milk cow. The contribu- tion of the radioiodines to total body burden following inhalation by dairy cows in the field and excreted into the milk has not been investi- gated in detail. The excretion of the iodines into milk and uptakes by thyroids of sheep and cows from other routes of entry are well docu- mented; however, individual variances appear to be the rule. Time of year, pregnancy, age, breed, production, and diet, to mention a few, are important factors in the uptake of iodines by the thyroid and the excretion into the milk. The excretion rates in the urine and feces will normally differ according to the species also. 53 ------- VI. CONCLUSION Numerous scientific investigations have been carried out iri an attempt to develop a system for the prediction of fallout levels or the amount of contamination of the biosphere. The data have not always been satisfactory nor have the results been conclusive enough to pre- dict, with any degree of accuracy, future fallout levels resulting from nuclear explosions under similar conditions. This limited ability to be able to predict levels of fallout is due to the many inherent unknowns that enter into the calculation of amounts of fallout as well as the inher- ent difficulties of measurement of the total fission release conditions. It appears that if a study of any quality is to be attempted in the in- halation of radioiodines, it is unwise to assume that deposition of in- haled radioiodine is the same in the sheep as in the cow; that the per- centage of uptake by the thyroid is the same in each cow of the herd; or that percentage of excretion in the milk is identical from one cow to the next under different conditions of season, diet and production. It is ap- parent from the survey of the literature that none of the results, under similar conditions of investigation, agreed well with each other. These results were for the most part from 1 31I ingestion. Therefore, in proposing areas of needed research in determining the potential hazard of radioiodines from inhalation, consideration will be given to species, season, diet, climate, topography, etc. It is under> stood that every animal to be used must be shown to be free of signs and symptoms of any infectious disease, free of physical defects, and having all physiological parameters being measured -within normally acceptable limits. 54 ------- VII. SUGGESTED EXPERIMENTS FOR THE STUDY OF POTENTIAL HAZARDS FROM INHALATION OF RADIOIODINES In general, recommended experiments will make comparisons of different routes of administration of 1 31I in various mammalian species particularly dairy cows and dogs. Following the interpretation of the experimental results of the kinetics of 1 31I uptake and excretion, and normal physiological limits of variance under the existing laboratory and field conditions, more sophisticated approaches to the inhalation of fresh fission products will be suggested. The species of choice will depend on what physiological parameter of interest is to be measured. The one chosen will, if possible, fall within the normal limits of man. Other related parameters will also be measured under similar experi- mental conditions for possible use in evaluation of potential hazards from inhalation of radioiodines. The following recommendations will attempt to follow a pattern of investigation that will give each succeeding experiment a sound physiological foundation. Recommendations for de- termination of certain physiological limits of deposition, retention, translocation and excretion of inhaled radioiodines are given below: A. FIELD TYPE EXPERIMENTS 1. Determine the minimum quantity of fresh fission products, especially radioiodines, in a field aerosol that could be sub- sequently detected in measurable amounts in the thyroid and/or milk of the dairy and beef cow and of the rat. 2. Using dairy cattle, determine the biological half life, excre- tion and ratio in thyroid to milk, total dose to thyroid, and total dose to milk of radioiodines following ingestion of feed exposed to fresh fission products in the field. 55 ------- 3. Following exposures of dairy cattle and/or feed to field aero- sols, determine quantitatively the differences in radiation dose from inhalation only, ingestion only, and a combination of in- halation and ingestion. 4. Determine food consumption per gram of thyroid in cattle which have been raised on typical dairy and beef farms and ranches in and near the Great Basin region. 5. Determine lung, body, and thyroid weight for different breeds and ages of dairy cattle, beef cattle and sheep that have been raised in the Great Basin region. 6. Determine relationship of levels of radioiodine in milk versus levels in sheep thyroids at the same geographical location. 7. Determine the relationship of gamma and gamma plus beta levels of forage (contaminated with fresh fission products and fed to dairy cows) to the thyroid uptake and milk excretion. 8. Determine the respiration rate, temperature and pulse of indi- vidual dairy cows and dogs by implantation of telemetri'c-appa- ratus so that field data can be correlated -with laboratory findings, B. LABORATORY TYPE EXPERIMENTS 1. Determine deposition of fresh fission products and carrier free 1 311 in the lungs of an intact animal (dog and cat) by lung scan- ning, folio-wed by lung scanning of the sacrificed animal and followed in turn by lung scanning of the removed lungs. 2. Using dairy cows and dogs, determine the biological half life, excretion, ratio in thyroid and milk to.total dose of carrier free 1 31I and fresh fission products following intravenous, oral, intratracheal or inhaled routes of entry. 56 ------- 3. Determine the minimum air concentration of * 31I or fresh fis- sion products necessary for its subsequent appearance in mea- surable amounts in the thyroid of rats. 4. Determine limits of normal dietary stable iodine in cattle feed which will not abnormally influence the uptake or excretion of fresh fission products and carrier free 1 31I. 5. Determine respiratory minute volume per gram of thyroid in dairy and beef cattle and dogs. 6. By dosimeter implantation, determine tissue dosage to the thyroid and parathyroid glands of dairy or beef cows follow- ing ingestion and/or inhalation of fresh fission products. 7. Determine absolute and functional respiratory dead space at various respiratory velocities in dogs. 8. 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Physiol. 153:87 (1948) 110. Swanson, E. W. , R.A. Monroes and C. L. Comar, Using Identi- cal Twin Dairy Cows to Determine the Effect of lodinated Casein (Protamone) on Milk Production, Thyroid Activity and Body Weight Changes. J. Dairy Sci. 37:659(1954) 111. Swanson, E. W. , F. W. Lengemann, and R.A. Monroe, Factors Affecting the Thyroid Uptake of 1-131 in Dairy Cows. A. Animal Sci. 16:318 (1957) 112. Taplin, G. V. , O. M0 Meredith, Jr., and H. Kade, Evaluation of the Acute Inhalation Hazard from Radioactive Fallout Materials by Analysis of Results from Field Operations and Controlled In- halation Studies in the Laboratory. USAEC Health and Safety UCLA Calif. WT-1172 (1958) 113. Tenny, S. M. and J. E. Remmers, Comparative Quantitative Mor- phology of the Mammalian Lung and Diffusing Area. Nature 197:54 (1963) 66 ------- 114. U.S. Department of Health, Education and Welfare, Radiological Health Data. Vol III: Nos. 5 and 10, May and Oct (1962) 115. Van Middlesworth, L. , Factors Influencing the Thyroid Uptake of Iodine Isotopes from Nuclear Fission - A Review. Health Physics 9:1197 (1963) 116. Werner, S.C., (Ed) The Thyroid. 2nd Ed. Harper and Row Publishers (1962) 117. West, J. B. , Observations on Gas Flow in the Human Bronchial Tree. Inhaled Particles and Vapours.. Ed. C.N. Davies, Per- gamon Press, London (1961) 118. West, J. B. andC.T. Dollery. Absorption of Inhaled Radioactive Water Vapour. Nature 189:588 (1961) 119- Widdicombe, J.G., Respiratory Reflexes in Man and Other Mam- malian Species. Clin.Sci. 21:163 (1961) 120. Willard, D.H. and W. J. Bair. Behavior of 1-131 Following Its Inhalation as a Vapor and as a Particle. Hanford, Wash. USAEC HW-58221 (1958) 121. Willard, D.H. and W. J. Bair. Behavior of 1-131 Following Its Inhalation as a Vapor and as a Particle. Acta.Radiol. 55:486 (1961) 122. Williams, M. Henry, Jr., and Claudia M. Rayford, Effect of Variation of Tidal Volume on Size of Physiological Dead Space in Dogs. J. of Appl.Physiol. 9:30(1956) 123. Wood, D.H., E.E. Elefson, V.G. Horstman, and L. K. Bustad, Thyroid Uptake of Radioiodine Following Various Routes of Ad- ministration. Health Physics 9:1217 (1963) 124. Woods, Alan C. , Jr., Donald F. Proctor, James P. Isaacs, and B. Noland Carter II, Studies in Respiratory Air Flow III. The Mechanics of Respiration in the Dog as Reflected by Changes in Intrapeiritioneal Pressure. Bulletin, Johns Hopkins Hosp. 88:291 (1951) 67 ------- APPENDIX Table 1. Fission product radioiodine chains.' 68 Table 2. Activities of the radioiodines and tellurium-132 expressed as a fraction of the activity of iodine-131 for various decay times. 69 Table 3. Iodine isotopes formed in fission. 70 Table 4. Iodine activity and dose to the thyroid versus time after 10EO instantaneous fissions of 235U. 71 Table 5. Iodine chemical forms. 73 Table 6. Physical form of 1-131 in air at various distances from stocks of a chemical separation processing plant. 74 Table 7. Deposition processes and the size ranges of importance in each. 75 Table 8. The lung volumes and capacities. 76 Table 9. Composition of alveolar air of several species. 77 Table 10. Ventilation and complementary cycles of various species. 78 Table 11. Diameter of alveoli of various species. 79 Table 12. Tidal volume frequency and compliance of various species. 80 Table 13. Distribution of inhaled particles. 84 Table 14. Retention of 1 5O water vapor in three human subjects. 85 Table 15. Average values for thyroid size, iodine content and biological half-life of thyroid iodine in different species. 86 Table 16. Forty-eight hour uptake of 1 31I by thyroid gland of dairy calves. 87 Table 17. Comparison of rate and percentage uptake of radioiodines. 88 Table 18. Fate of 131I in the dairy cow. 89 Table 19. Translocation of iodine-131 following inhalation. 90 ------- Table 1. Fission product radioiodine chains.* Mass Number 49(In) Atomic Number 50(Sn) 51(Sb) 52(Te) 53(1) 54(Xe) 55(Cs) 56(Ba) oo 129 1.5 sec—^-.6.2 min-^-4. 2 hr 5^70 min —>-l. 6x10?yr>-Stable A 2 day 131 1 sec 132 133 134 135 sec 23 min - 5»-25 min— >- 8. 05 day— ^--Stable 2.5 sec—>- 2 min >-78 hr >~2. 3 hr >- Stable 4.5 min 5»-2 min^-20. 8 hr ^—>- 5. 3 day- —r _ _ _r 2 sec- mn 10 sec >-44 min^-52. 5 min—^-Stable 6 sec sec 9 hr A 30% mn •Stable 97% , -A -io 5x10 sec -Stable ^Reference: 65 ------- Table 2. Activities of the radioiodines and tellurium-132 expressed as a fraction of the activity of iodine-131 for various decay times.* FISSION "PR ODTTfT Jr ±\ \J±J U ^- L 132 Te 131 I 132 I 133 I 134 I 135 I 1 HOUR Reactor Criticality 1.01 5.50 1.00 1.00 1.06 8.50 1.46 22.0 1.38 378 1.34 84.5 10 HOURS Reactor Criticality 0.98 3.30 1.00 1.00 1.00 3.57 1.15 15.4 0.43 0.54 19.7 1 DAY Reactor Criticality 0.90 2.95 1.00 1.00 0.93 3.05 0.75 10.3 - 0.13 5.41 1 WEEK Reactor Criticality 0.43 1.25 1.00 1.00 0.43 1.30 0.01 0.17 - — — vO *Reference: 35 ------- Table 3. Iodine isotopes formed in fission.* Iodine Mass 124 125 126 127 129 ji- *.i> 131 132 133 134 135 136 137 138 139 Half Life 4 56 13. 0 days days days Stable 1. 72 x 8.04 2.4 22 51 6.7 86 22 5.9 2. 7 10 years days hr hr min hr sec sec sec sec Parent Nuclide Primary products of high energy fission bismuth and lead not found in fis- sion at moderate energies. 90 days Te-127m 9. 3 hr Te-127 32 days Te-129m 72 min Te-129 30 hr Te-131m 25 min Te-131 77 hr Te-132 60 min Te-133 43 min Te-134 Either primary fission products or formed from very short-lived tellurium parents. Cumulative yields from smoothed urine 235U 239Pu 0. 0. 2. 3. 4. 5. 6. 6. 6. 6. 6. 15 90 80 4 7 9 0 1 2 2 1 0. 1. 3. 4. 5. 5. 5. 5. 5. 5. 5. 38 6 7 8 0 3 6 8 9 9 9 -J o ^Reference: 82 ##1-128 and 1-130 (-which have not been reported in fission) are shielded by Stable Te-128 and Te-130 respectively. ------- 20 235 Table 4. Iodine activity and dose to the thyroid versus time after 10 instantaneous fissions of U. Iodine Mass eff eff Number (days) (Mev) 131 7.6 0.23 132 0.097 0.65 133 0.87 0.54 134 0.036 0.82 135 0.28 0.52 Total 131 132 133 134 135 Total I (Curies) .45 380 1100 16000 3700 21225 71 265 1250 500 2200 4286 1 H I o 1 5 75 17 6 H 1 6 29 11 51 O U /I Qt . 211 . 79 . 19 .4 .4 0 U .66 . 19 . 2 .6 .4 R 3 H O U R S D /D °(%)t0t 4. 1. 31. 28. 33. 100. R S 11. 1. 55. 1. 30. 100. 8 5 8 9 1 1 7 6 4 4 1 2 I (Curies) 64 275 1250 7000 3000 11589 1 71 250 1050 I c 2 10 60 25 2 H O 2 9 40 11 Qt . 553 . 39 .8 .4 .9 U R S .76 . 73 .8 D /D °(%)t0t 8 1 43 15 32 100 15 2 61 . 3 . 3 .4 . 2 . 2 .4 .4 .0 . 1 Negligible 1200 2571 46 .6 21 100 .6 . 1 continued ------- 20 235 Table 4. Iodine activity and dose to the thyroid versus time after 10 instantaneous fissions of U.*(cont') Iodine Mass Number 131 132 133 134 135 Total 131 132 133 134 135 Total 131 132 133 134 135 Total 24 H O U R S 1 Z l\ * (Cu°rieS) °(%{0t 71 5.25 220 16.2 720 53.3 Negligible I 340 25. 1 1351 4 D AY S 63 21.5 130 44.4 100 34.1 Negligible 0.45 0. 15 293.4 10 D A Y S 39 54.6 32 45.8 0.35 0.49 Negligible Negligible 71. 35 D /D °(%)t0t 23. 6 2.5 64. 3 9.4 99.8 66.6 4. 97 28.4 0. 04 100. 01 96.8 2.9 0. 2 99.9 2 D A Y S I I /I D (Caries) ?(%!?* 71 170 350 29 620 58 100 30 0. 188. 11.4 27.4 56.4 Negligible 4. 68 5 D A Y S 30.8 53. 1 15.9 Negligible 23 0. 12 2 /D °(%)t0t 40.8 3.6 54. 3 1.4 100. 1 83. 1 5. 2 11. 6 0. 02 99.92 3 D A Y S I I II «. (Cur°ies) °(%50t 68 14. 6 155 34.4 190 42. 1 Negligible 40 8.87 451 7 D A Y S 50 43.5 60 52.2 5 4. 35 Negligible Negliginle 115 D /D °(%f0t 52.4 4.4 40.6 2.6 100. 0 93.4 4. 0 2. 5 99. 9 ts) ^Reference: 107 ------- Table 5. Iodine chemical forms* Valence -1 0 + 1 + 5 + 7 Organic Common Chemical Species I", HI, Nal, HI n HO I 2 ICI, IB2, HOI 10, IO ~ HIO0, NaIO0 253 3 3 IO ~ HIO., NalO. 444 ^•TT T f~*TJ T /^TJT /"* TUT T C* \J T a ' 9 ;?' ^"tllQ» 7 c ' 749 -vl OJ 'Reference: 65 ------- Table 6. Physical form of 1-131 in air at various distances from stocks of a chemical separation processing plant.*, **. Distance from Source, Miles Percent Particulate *** 1 3 5 10 20 25 12 8 20 34 38 34 --Reference: 97 **Hanford Laboratory, G. E. Company, Hanford, Washington. *-.<#Sampled by aircraft 600' above ground. ------- Table 7.* Deposition processes and the size ranges of importance in each.** In Environment Process Sedimentation [mpaction Brownian motion Thermal precipitation Electrostatic precipitation Condensation Aggregation Lower Limit 0. SJJL 0. 2|i 50 51 50 A 50 51 0. l(Ji All sizes Upper Limit None None 0. IM- 0. 1|JL 0. In In Respiratory Tract Lower Limit Upper Limit 0. 5(j. 30 O.ZJJL 30 50 & 0. 1 Not important Not important 0. In All respirable sizes M- M- V *Reference: 42 **Values for upper and lower limits are approximate. ------- Table 8. The lung volumes and capacities.* VOLUMES. - There are four primary volumes which do not overlap (Figure 2): 1. Tidal Volume, or the depth of breathing, is the volume of gas inspired or expired during each respiratory cycle. 2. Inspiratory Reserve Volume (formerly complemental or complementary air minus tidal volume) is the maximal amount of gas that can be inspired from the end-inspiratory position. 3. Expiratory Reserve Volume (formerly reserve or supplemental air) is the maximal volume of gas that can be expired from the end-expiratory level. 4. - Residual Volume (formerly residual capacity or residual air) is the volume of gas remaining in the lungs at the end of a maximal expiration. CAPACITIES. - There are four capacities, each of which includes two or more of the primary volumes (Figure 2): 1. Total Lung Capacity (formerly total lung volume) is the amount of gas contained in the lung at the end of a maximal inspiration. 2. Vital Capacity is the maximal volume of gas that can be expelled from the lungs by forceful effort following a maximal inspiration. 3. Inspiratory Capacity (formerly complemental or complementary air) is the maximal volume of gas that can be inspired from the resting expiratory level. 4. Functional Residual Capacity (formerly functional residual air, equilibrium capacity or mid-capacity), is the volume of gas remaining in the lungs at the resting expiratory level. The resting end-expiratory position is used here as a base line because it varies less than the end-inspiratory position. *Reference: 22 ------- Table 9. Composition of alveolar air of several species. Species Horse Cattle Sheep Goat Dog Man Number 1* - 3* 3* 3* - 3* - co2% 4. 93 4. 74 4. 75 4. 59 5. 18 2.95 5. 32 4. 21 o2% 15. 09 15. 97 15.40 15. 65 15. 04 17.80 14.99 16.29 pCO mm Hg** 35.4 - 34. 2 33.65 38. 0 - 39. 0 40 pO mm Hg*** 107.4 - 107.4 114.4 110.4 - 108. 6 106 Reference 41 39 41 41 41 39 41 39 *Five different measurements on each animal. **Vapor pressure of CO in mm Hg in the alveolus. ***Vapor pressure of O in mm Hg in the alveolus. L* ------- Table 10. Ventilation and complementary cycles of various species. Species Mouse Rat Guinea Pig Rabbit Cat Dog Man Horse (Standardbred) Body Weight Kg 0. 015 0. 273 0.495 3. 0 2.6 19.2 70 550 £** 125 60 84 66 26 14 16 12 Ventilation Cycle Tidal Volume Duration in ml in sees 0.1 0.5 1.4 1.0 1.9 0.7 18.3 0.9 12.4 2.3 110.0 4.3 500.0 3.5 6000 5.0 Complementary Cycle f/hour Volume Duration in ml in sees 45 4.7 4 26 - 5 17 7 10 - 6 6 - 9 5 - 7 3 8 0 - 0 oo -'Reference: 83 --'^Respiratory frequency ------- Table 11. Diameter of alveoli of various species. Species Number Feline 21 Canine 8 Guinea Pig 14 Mouse 6 Rat 17 Monkey Man 1-1.5 years 18-20 years 50-60 years Mean Diameter in (j. 116.9+14.4 133.2 93.9 + 14. 1 74. 1 65.4+8.5 • 83.4 46.6+2.4 38.7"" 70. 2+6.6 59.1 89. 1 166.1 100 200 300 150 Reference 113 29 113 29 113 29 113 29 113 29 29 29 60 60 60 33 -J vO ------- Table 12. Tidal volume frequency and compliance of various species. Species Number Body Weight Measured in kg Mouse 14 0. 024 7 0. 024 5* 0. 023 0.032 (0. 037-0. 038) 0.0198 56 0. 198 (0. 012-0. 026) 0. 88+0. 12 0.69 .(0.43-1. 05) 0.47 61 0.466 (0. 274-0.941) V ml 0. 15 0. 13+_0. 06 0. 09±0. 06 0. 18 (0. 09-0. 38) 0. 15 (0. 09-0.23) 0. 15 (0. 09-0.23) - 3. 7 (2. 3-5. 3) 1.8 1. 75 (1.0-3.9) f2 154 210+_50 120+60 109 (97-123) 163 (84-230) 163 (84-230) 75 42 (16-67) 90 (69-104) 90 (69-90) V Compliance m ml ml/cm HO 23.1 0.029 27.3+3 10.8+3.6 21 0.049 '(9-46) (0.025-0.068) 23 (11-36) 24. 5 (11-35. 8) 1. 5+0. 14/kg 130 1.26 (80-190) (0.76-2.33) 160 (90-380) 155 (100-382) .Reference 38 47 47 29 60 58 1 29 60 58 oo o ------- Table 12. Tidal volume frequency and compliance of various species. (Cont!) Species Number Body Weight Measured in kg Monkey 6 2. 68 (2. 0-3. 08) 2.45 (1.8-3.05) 2.68 Rat 9 0.203 0. 25 (0. 19-0. 32) 0.112 35 0.112 (0. 063-0. 52) 0. 207+0. 007 Man ? 70 70 70 * 60 70 10 68.5 (55. 7-82. 1) V ml 21. 2 (9.8-29. 1) 20 (9-29) 21 (9.8-29) 1. 3 1. 55 (1. 03-2. 13) 0.86 (0.60-1. 25) 0.86 (0. 60-1. 25) - 500 400 - - - 616 (315-745) 2 f 40 (31-52) 33 (27-47) 40 (31-52) 80 97 (84-126) 85 (66-114) 85 (66-114) 110 15 16 - - 15 14 (10. 5-19.3) 3 V Compliance Reference m ml ml/cm HO 863 (311-1410) 700 12.3 (260-1340) (7.1-20.2) 860 (310-1410) 97 0. 148 160 0.39 (90-270) (0.22-0.52) 74 (50-102) 72.9 (49.8-101. 2) 1.94+0. 04/kg 7500 85 6400 120 62 2/kg 8732 (4900-12200) 58 29 60 38 29 60 58 1 38 29 60 60 1 58 oo ------- Table 12. Tidal volume frequency and compliance of various species. (Cont1) Species Number Body Weight Measured in kg Dog 15 16.3+4.3 3 17 12* 18.3+5.6 39* 13.4+_5 12.6 (10. 0-15. 5) * 20 * 11.8 4 23.6 10.4+0.48 Rabbit 3 2.6 2.4 (2. 05-3. 0) * 2 2.98+0.31 2.07 vtl ml 16+5. 8ml/kg 107 228 12. 5+2. 5 ml/kg 247+_17 144 (122-176) ' - 320 - 16 15.8 (11.5-24.4) - - _ 20 f2 26+_13 22 46+_15 28+_3 21 (6-31) - - 17 (H-21) 18 38 39 (32-53) - 50 _ 61 v 3 m ml 6656 2354 10488 4199^51 2300 (800-3500) - - 5200 (3300-74000) - 608 620 (370-890) - -• 800 (270-1200) 12300 Compliance ml/cm HO 4. 6+1. 54/kg 30 63+20 50.8+3 40 (27-61) 48 26.5 _ 2. 56+_0. 3/kg 2.4 6. 0 (3. 5-10. 8) 2.3 1.41 + 0. 19/kg _ Reference 23 38 86 4 29 60 60 60 1 38 29 60 1 60 60 oo ------- Table 12. Tidal volume frequency and compliance of various species. (Cont!) Species Number Body Weight Measured in kg Rabbit(cont') 31 2.069 (0. 79-3.09) Horse - 430 1 696 19* 28+_3 225 Cat - 3.54+0.32 3. 7 (2.3-5. 7) * 3. 2 * 2. 6 2.45 Cow 4 (lying) 439 4(standing)439 Sheep 50* 42. 6+_4. 7 63 Goat 1 37 V ml - - 9060 (8520-9680) 286+25 - - 34 (20-42) - - 12.4 3200 3800 249+51**- 310 - - f2 - - 11.9 24. 5+_2 - 30 30 (24-42) - - 26 30 28 - 19 28 - v 3 m ml 800 (270-1208) - 107 L - 37 L - 960 (860-1090) - - 322 96 L 106 L, - 5700 - - Compliance ml/cm HO £i - 800 - 57+6 - 2. 86+0. 28/kg 13.4 (9.9-17.4) 6.8 5. 7 - - - 106+J31 - - 50 Reference 58 60 60 4 60 1 29 60 60 60 60 60 59 60 70 5 00 u> * Anesthetized **Tidal volume in ml/M^ 1 - Tidal volume in ml 2 - Respiratory frequency 3 - Minute volume ------- Table 13. Distribution of inhaled particles.* oo Distribution Exhaled Deposited in upper respiratory passages and subsequently swallowed. Deposited in the lungs (lower respiratory passages) . Readily "Soluble" Compounds 25 50 25** Other Compounds 25 50 25*** *Reference: Recommendations of International Commission on Radiological Protection. Brit. J. Radiol. Supp. 6, 1955 (from 42) **This is taken up into the body almost immediately. ***Of this, half is eliminated from the lungs and swallowed in the first 25 hours making a total of 62. 5% swallowed. The remaining 12. 5% is retained in the lungs with a half-life of 120 days, it being assumed that this portion is taken up into the body fluids. ------- 1 5 00 Table 14. Retention of O -water vapor in three human subjects. Region of Respiratory Tract Mouth Phar ynx Upper trachea Mid trachea Corina Right lung base Activity Counts/sec. 170 120 160 100 33 3 Percent of Total Activity 28.9 20.4 27.4 17.0 5.8 0.5 ''-Reference: 118 ------- oo Table 15. Average values for thyroid size, iodine content and biological half-life of thyroid iodine in different species. * Species Cattle Swine Lamb Rat Man Thyroid Gram 18 15 2 0.02 25 Size mg/kg Body Weight 45 80 50 80 360 Thyroid Iodine mg 8-16 6-20 1-3 0.02 8 Biological Half Life in Days 16 30 14 4 94 ''-Reference: 115 ------- oo -j Table 16. Forty-eight hour uptake of 3 I* by thyroid gland of dairy calves. ** Breed Ayrshire Brown Swiss Guernsey Holstein Jersey Number 2 19 7 19 16 Average Age Months 6. 4. 6. 3. 5. 2 2 7 5 8 Uptake % 42. 33. 47. 44. 45. 5 2 9 1 8 Standard Deviation - 18. 21. 15. 19. 3 6 8 9 ^Injected subcutaneously -"-Reference: 80 ------- Table 17. Comparison of rate and percentage uptake of radioiodines. Animal Isotope Sheep i 3 i j 131I 131I 131I 131I Ag131I Mice 1 31 1 vapor Ag131I Dog 133Iand fiss. prod. Cattle Na l 31I 131I Swine * 3 1 1 Rat 131I Man(neonatal) 1 3 x I 2 mos-18 yrs 1 31I Adults J 3 1 1 Method of Adminis - t rat ion Oral Intravenous Subcutaneous Topical Inhaled Inhaled Inhaled Inhaled Inhaled Subcutaneous Oral Oral Inhaled Oral Oral Oral Effective Half Life in Days 6. 5-8 6. 5-8 6. 5-8 7 - - - - Short - 4. 5 6.5 - _ Time of Maximum Uptake in Hours 48-96 48-96 48-96 48-96 20-35 20-24 30 10 48-72 48 30 24 44 48 24-48 24 Percentage Uptake 17-19 17-19 17-19 2-14 3-8 3-8 2.5 1.6 92 41.6 35 30 26.9 62 31+7.63 36+9.9 Reference 123 123 123 123 121 121 121 121 48 80 18 17 13 45 45 45 oo oo ------- Table 18. Fate of * 31I in the dairy cow. oo Route of Elimination Thyroid Milk Urine Feces Method of Administration Oral Intravenous Oral Intravenous Oral Oral Intravenous Oral Oral Intravenous Percent of Dose 15+6.0 18 6.2+2.0 7.2 3. 28 55+14 43.7 27.8 17+7 17.6 Recovery Period (Days) 7 3-5 1 3 6 7 3 6 7 3 Reference 24 111 24 111 108 24 111 108 24 111 ------- Table 19. * Translocation of iodine-131 following inhalation. ** xO o Tissue Lung Bone Thyroid Liver Lymph Spleen Adrenal Kidney Ovary Ag13 Immediately 45 - 750 17 36 36 43 18 108 10 Hour*** 9 - 6800 5 48 5 13 11 38 Immediately 15 - 130 20 67 17 20 25 150 30 Hour*** 0.7 - 1700 0.7 2.2 0. 17 0.6 1.0 3.5 *Reference: 7 **Percentage of total deposited per gram tissue at various times after inhalation. ***Time of maximum concentration in thyroid. ------- DISTRIBUTION 1-15 SWRHL, Las Vegas, Nevada 16 James E. Reeves, Manager, NVOO, AEC, Las Vegas, Nevada 17 Col. E. G. Halligan, DASA, NVOO, AEC, Las Vegas, Nevada 18 Otto H. Roehlk, OSD, NVOO, AEC, Las Vegas, Nevada 19 Henry G. Vermillion, NVOO, AEC, Las Vegas, Nevada 20 Gordon M. Dunning, DOS, USAEC, Washington, D. C. 21 Richard Hamburger, DPNE, USAEC, Washington, D. C. 22 JohnS. Kelly, DPNE, USAEC, Washington, D. C. 23 Robert E. Baker, USAEC, Washington, D. C. 24 Philip W. Allen, USWB, NVOO, AEC, Las Vegas, Nevada 25 Frank D. Cluff, USWB, NVOO, AEC, Las Vegas, Nevada 26 G. D. Ferber, USWB, MRPB (R-3. 3)> Washington, D. C. 27 Ernest C. Anderson, DRH, PHS, Washington, D. C. 28 Donald J. Nelson, TOB, DRH, PHS, Washington, D. C. 29 James G. Terrill, Jr. , DRH, PHS, Washington, D. C. 30 Donald L. Snow, DRH, PHS, Washington, D. C. 31 Raymond Moore, DRH, PHS, Region VII, Dallas, Texas 32 Bernd Kahn, DRH, RATSEC, Cincinnati, Ohio 33 Arve H. Dahl, DRH, PHS, Rockville, Maryland 34 Samuel Wieder, DRH, PHS, Rockville, Maryland 35 Northeastern Radiological Health Laboratory, Winchester, Mass. 36 Southeastern Radiological Health Laboratory, Montgomery, Ala. 37 Rockville Radiological Health Laboratory, Rockville, Maryland 38 Edmund L. Fountain, USA, MEDS, VS, Chicago, Illinois 39 Capt. Stanley Wampler, WRAIR-WRAMC, Washington, D. C. ------- 40 Clifford M. Bacigalupi, LRL, Mercury, Nevada 41 Bryce L. Rich, LRL, Mercury, Nevada 42 Robert H. Goeckermann, LRL, Livermore, California 43 Duane E. Sewell, LRL, Livermore, California 44 Edward H. Fleming, LRL, Livermore, California 45 Gary H. .Higgins, LRL, Livermore, California 46 John W. Gofman, LRL, Livermore, California 47 William E. Ogle, LASL, Los Alamos, N. Mex. 48 Fred Sanders, LASL, Mercury, Nevada 49 Harry S. Jordan, LASL, Los Alamos, N. Mex. 50 Orin Stopinski, LASL, Los Alamos, N. Mex. 51 Charles I. Browne, LASL, Los Alamos, N. Mex. 52 Victor M. Milligan, REECo, Mercury, Nevada 53 L. G. von Lossberg, Sheppard T. Powell & Assoc. , Baltimore, Md. 54 Paul Kruger, Hazelton-Nuclear Science Corp. , Palo Alto, Calif. 55 G. B. Maxey, Desert Research Institute, U. of Nev. , Reno, Nev. 56 Ray Gibb, University of Rochester AEP, Rochester, N. Y. 57 Robert H. Wilson, University of Rochester AEP, Rochester, N. Y. 58 Mail and Records, NVOO, AEC, Las Vegas, Nevada ------- |