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

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                         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

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                                           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

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                     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

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       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

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                        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

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                        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,

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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.

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           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

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     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

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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

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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

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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

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     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

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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.

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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

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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

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            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

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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

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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

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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

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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

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   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

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    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

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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

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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

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  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

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                              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

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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

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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

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    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

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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

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    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

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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

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    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

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         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

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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

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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

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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

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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

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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

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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

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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

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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

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                        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

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      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

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    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

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 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.   Determine tissue distribution of fresh fission products as a



     function of time following various routes of administration in



     the cow and dog.





 9-   Determine extent of participation eructation plays in the ab-



     sorption of 1 311 from the rumen.





10.   Determine dose-response curves relating changes in pulmon-



     ary flow resistance  produced by exposure to different levels



     of l 31Iin aerosols.
                            57

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101. Ross,  B.B., Influence of Bronchial Tree Structure on Ventila-
     tion in the  Dog's  Lung as Inferred from Measurements of a Plas-
     tic Cast. J. Appl. Physiol.  10(1):1 (1957)
                                 65

-------
102. Schiller, Erich, Inhalation, Retention,  and Elimination of Dusts
     from Dogs and Rats Lungs with Special Reference to the Alveolar
     Phagocytes and Bronchial Epithelium.  Inhaled Particles and
     Vapours.  Ed. C.N.  Davies, Pergamon Press,  London (1961)

103. Scott, K. G. ,  D. Axelrod,  J. Crowley and J. G.  Hamilton, Arch.
     Path.  48:31 (1949) Quoted by Heppleston, A. G. ,  Observations
     on the Disposal of Inhaled Dust by Means of the Double Exposure
     Technique.  Inhaled Particles and Vapours.  Ed. C.N. Davies,
     Pergamon Press,  New York (1961)

104. Severinghaus, J. W. ,  and M. Stupfel, Alveolar Dead Space.
     Am. J. Physiol.   183:660(1955)

105. Silverman,  Leslie and Charles E. Billings,  Pattern of Airflow
     in the Respiratory Tract.  Inhaled Particles and  Vapours.  Ed.
     C.N. Davies, Pergamon Press,  London (1961)

106. Sisson,  S. and J.D. Grossman,  The Anatomy of  the Domestic
     Animals.  4th Ed. W.B.Saunders Company,  Philadelphia (1953)

107. Smith,  Geneva, Unpublished data.
108. Squire,  H. M. ,  L. J.  Middleton,  B. F.  Sansom, and R. C. Coid,
     The Metabolism in Dairy Cows of Fission Products. Biological
     Sciences Vol. 3.   The  Entry of Fission Products into Food Chains.
     Ed.  J. F. Lautit and R.Scott Russell,  Pergamon Press,  New
     York (1961)

109. Stacy, Ralph  W. ,  W. V. Whitehorn and  Fred A.  Hitchcock,  Sus-
     ceptibility of  Cats and Dogs to Progressive Anoxia.  Am. J.
     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

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       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

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          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.

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                                        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

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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

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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

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          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

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             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

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             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.

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                             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



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    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.

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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

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