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
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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.
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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
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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
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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
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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."
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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. ""*
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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
-------
CO
O
Q.
UJ
O
UJ
O
cc
UJ
a.
DIFFUSION
<—
IMPACTION
100 r-
0.01
SE DIM ENTATION
NASO-
PHARYNGEAL
TRACHEO-
BRONCHIAL
Q.I 1.0
AERODYNAMIC SIZE
IOJO
IOQJD
DIAMETER)
Figure 1. Percentage deposition in various regions of the respiratory tract as a function of
aerosol particle size; unit density spheres assumed.
-------
(a function measurement). Lung volumes and capacities are de-
fined in Table 8 and Figure 2. Residual volume, inspiratory re-
serve volume and expiratory reserve volume are only static vol-
umes, whereas tidal volume is dependent on mechanics of inspir-
ation and expiration. Because pulmonary ventilation is a dynamic
process, quantitation of air movements through the conducting
airway to the alveoli is necessary to be able to calculate the al-
veolar ventilation rate, i.e. , the volume of air reaching the al-
veoli per minute. The volume of pulmonary lobule ventilation is,
therefore, primarily dependent on frequency of breathing, tidal
volume, and amount of respiratory dead space. The degree of
alveolar ventilation -will normally be reproducible in the same
animal as long as pulmonary pathology does not exist. The
amount of ventilation per alveolus will differ in the various species
and with the frequency of breathing of a particular subject. The
rate of breathing will influence differences in relative distribu-
tion of the dead space gas. " (See Tables 9 and 10). Although
the overall pressure gradient to all alveoli is usually regarded
to be about the same, differences in transit time are observed.
This leads to differences in effective ventilation, of alveoli even
though total ventilation of all alveoli is the same. It is therefore
logical to assume that all alveoli do not necessarily contribute
to the expired air simultaneously.
Total and effective ventilation of the lungs depends on numer-
ous physiological and anatomical features of the species under
study. Two animals of equal body size may have lungs of the
same vital capacity, but if one of these animals has a higher rate
of metabolism, the alveoli of the lung will usually be smaller,
as the size of the alveoli appears not to be always related to the
22
-------
STATIC LUNG VOLUMES
EXPIRATORY RESERVE VOLUME
INSPIRATORY RESERVE VOLUME
Inspirotory Capacity
rf'LCjii
i;vc;
iiR'vi;
F'RCli
TV
•RV-
Functional Residual Capacity
MAXIMAL INSPIRATORY LEVEL
MAXIMAL EXPIRATORY LEVEL
Figure 2. Lung volumes.
(Courtesy of Year Book Medical Publishers, Inc.
and Dr. Julius H. Comroe, Jr. )
23
-------
body size, ^ but appears to be related to rate of metabolism.
For example, (See Table 11) the mouse has the smallest alveoli
mean diameter, the guinea pig and rat almost two times that of
the mouse and the cat and man approximately three times the
mouse. From such data, Tenny^^ attempted to relate pulmon-
ary ventilation to easily measured physiological and physical
measurements. He determined that total alveolar ventilation is
proportional to metabolic rate of the species; respiratory fre-
quency correlates inversely with body mass to the 0. 28 power;
metabolic rate correlates with body -weight to the 0. 74 power;
total lung volume is a constant fraction of body mass and tidal
volume is directly proportional to body weight.
4. Mechanics of Breathing
Air flows from a region of higher pressure to one of lower
pressure. Respiratory movements, reflex or not, determine
the degree and extent of pulmonary pressures through voluntary
and involuntary muscular control. Active contraction of the in-
spiratory muscles causes enlargement of the thorax and lowers
the intrathoracic pressure, thereby enlarging the alveoli, ex-
panding the alveolar gas, and lowering the overall alveolar gas
pressure to less than atmospheric so that air flows into the al-
veoli. Active muscular contraction during inspiration provides:
a. The force necessary to overcome elastic recoil of the
lungs and thorax.
b. The force required to overcome frictional resistance
during movement of the lung and thoracic tissues.
c. The force necessary to overcome frictional resistance
to air flow through the tracheobronchial tree.
At end-inspiration, the muscles of inspiration relax and no
longer exert a force -which distends the lungs and thorax, the
24
-------
elastic tissues of the lung and thorax now recoil. In normal sub-
jects the elastic recoil results in the lungs and thorax returning
very rapidly to the resting expiratory level even though expira-
tion is completely passive.
There are species differences in the breathing mechanisms
as one would expect. The eupneic horse moves approximately
6000 ml of air over a span of five seconds. °^ The respiratory
cycle is polyphasic with dual expiratory and inspiratory phases.
The thoracic movement is usually less than the abdominal. The
dual cycle normally becomes obscure in abdominal movements
during hyperpnea, but persists in increased respiratory (nasal
and trachea) and intrapleural inspiratory pressures. In the dog,
the intercostal muscles and the diaphragm do not act together in
inspiration with respect to time. The early air flow peak that is
observed in inspiration is due to the action of the intercostals,
and the late peak flow is due to the action of the diaphragm. 1"
In the eupneic rat, the respiratory cycle moves 1.5 ml of air
per second. The cycle is diphasic with single expiratory and
inspiratory phases."
The elastic properties of the lung and thoracic tissues are
combined into a parameter called pulmonary compliance which
is defined as the volume change per unit pressure change and
is expressed in units of liters/cm H2O. Pulmonary compliance
is measured under static conditibns. When elastic properties
are measured under dynamic pressure-flow relationships, they
are referred to as pulmonary resistance and are defined as pres-
sure differential required for unit flow change and are expressed
in units of cm Hz O/liter/sec.
25
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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
-------
d. Circulatory factors:
(1) Increase in arterial blood pressure in the carotid
sinus and aortic arch reflexly diminishes pulmon-
ary ventilation, and a decrease in arterial blood
pressure augments the pulmonary ventilation.
(2) Severe hypotension may cause ischemia in the ca-
rotid and aortic bodies resulting in an intense re-
spiratory stimulation.
(3) An increase or a decrease in cerebral blood flow
may decrease or increase pulmonary ventilation
respectively by permitting a change in CO2 content
of neurons in the respiratory center.
e. Reflexes from joints:
Back and forth motion of a limb will reflexly increase
the rate and occasionally the depth of breathing.
f. Pain receptors:
Respiratory stimulation or inhibition may be caused by
pain depending on the character, origin and intensity.
g. Temperature:
An increase in body temperature -will cause an increase
in pulmonary ventilation. This results, in part, from
"warming" of the medullary centers and chemoreceptors.
h. Supramedullary regulation:
Supramedullary areas exert important effects on areas
such as pontine, pneumotaxic center and cortical areas.
Pathological or physiological alterations in the respiratory
tract will considerably modify the air flow and, therefore, the
amount of alveolar ventilation; the latter indirectly affects the
deposition and the distribution of material in the bronchials and
pulmonary lobules. For example, the different air velocities
and alveolar ventilation rates in a fast shallow breather versus
a slow deep breather in the human may be compared to a panting
28
-------
dog with dyspnea or to a horse with emphysema. The variation
in ventilation rates will cause differences in the total amount of
material deposited and probably differences in the distribution
to the specific areas of the respiratory tract. The distribu-
tion of air to the normal lung lobes is not necessarily in propor-
tion to their volumes nor does each lung lobe become ventilated
equally. Rahn et al, by perfusion of canine lung with radio-
active materials following autopsy, observed unequal ventilation
of the lung in the supine and erect positions.
The typical radioactive field aerosol is heterogenous in
that it contains a large fraction of small particles of relatively
high radioactivity, such that the contribution of these particles to
the radiation dose, despite relatively low deposition, may pro-
duce a major fraction of the total dose. A point to remember is
that physiological parameters, such as breathing frequency,
can exert about as much influence as particle size. It has been
shown numerous times that the fast shallow breather -will have
relatively less material deposited in the lungs than the slow
deeper breather when all other factors are equal. This same
effect has been seen by investigators for the sub-micronic range
t *• i 42
of particle sizes.
It is quite evident that there are many physiological and
physical factors involved in the study of total lung volumes.
Neither metabolic rate nor surface area directly affects this
volume; however, total lung volume appears to be a constant
fraction of body mass in that tidal volume is directly proportional
to body weight and a constant fraction of the lung volume. ^
29
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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
-------
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
-------
swallowing. ' In rats, radioactive particles have been
shown to be cleared from the ciliary lined air passages
1 f\ o
within one day. The linear velocity of particles moving
up the bronchi varies from 0. 25 to 1 centimeter per minute
and increases to as high as 3 centimeters per minute in the
trachea. Ai> » The process by which particles are car-
ried up the surface of the bronchus toward the pharynx is
referred to as a "mucus-cilia escalator".
b. Alveolar Phagocytosis
Clearance of the pulmonary tract of matter, foreign or
secretive, involves a second mechanism referred to as al-
veolar phagocytosis. Inhalation of particulate matter causes
the appearance of a large number of amoeboid cells that ap-
parently have a dual capacity to act as macrophages or to
remain free in the alveolar lumen. These cells, referred
to by many as pneumocytes, may phagocytize inert dusts
in large quantities and undergo mitosis or may engulf toxic
dusts and then undergo degenerative changes. ^ Schiller
distinguishes between two types of pulmonary phagocytes.
The first type is the cell derived from the alveolar epithe-
lial cells. These cells are on the alveolar surface and do
not enter the interstitial tissue, but are removed with the
pulmonary fluids. The second type is a cell derived from
the inter stitium and is considered to be sub-epithelial in
origin. These are found most generally in the interstitial
connective tissue of the lung. He concluded that there are
two phases of phagocytosis, the epithelial phase of phago-
cytosis by pneumocytes and the interstitial phase of phago-
cytosis by macrocytes. Casarett's ' theory differs
33
-------
somewhat in that the origin of the phagocyte is apparently
the alveolar epithelial cell. The phagocytic ability of the
cell is considered to be the manner in which the cell mem-
brane is arranged with regard to the adjacent cell; i. e. ,
one cellular membrane may be on the lumen side of the al-
veolar segment whereas the cellular membrane below it is
on the interstitial side of the segment. He, therefore, is
of the opinion that the particle-laden phagocytes that appear
in the alveolar lumen are those cells that have full cellular
exposure to the lumen; those particle-laden phagocytes
found in the interstitium are those cells that have cellular
exposure to the interstitium. He also feels that particles
can penetrate the alveolar wall directly without benefit of
phagocytic transportation.
The rate of phagocytosis has been found to be a function
of the particle size, particle concentration, '' physico-
chemical properties of the particulate matter, and sur-
face tension of pulmonary fluids. It appears that the
process would continually progress, regardless of rate,
as long as there were potential histiocytic cells to respond
to the irritation of foreign matter. If the alveolar cells
were destroyed or the cells became amitotic for one reason
or another, phagocytic activity would cease and alveolar
fibrosis would normally occur.
La Belle, '^ by estimating the number of free phagocytic
cells in the lungs of rats, concluded that transport of depos-
ited particles by phagocytes was the primary mechanism by
•which inhaled insoluble dust particles were eliminated from
the lung following inhalation. He showed that the amount of
34
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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
-------
the gastrointestinal tract. This apparently was the earliest
experimental demonstration of clearance of inhaled, insol-
uble particles from the lung via the "mucus-cilia escalator"
into the gastroenteric tract. This clearance was chiefly
from the upper respiratory tract where total percentage
retention of spores is known to decrease. •* The remain-
ing particles may or may not have contained radioactive
material that could cross the alveolar membrane. If gas-
eous and particulate matter are inhaled, such as often hap-
pens with radioiodines or ^compounds that sublime easily,
the transport of these compounds through the lining com-
plex of the alveoli is dependent, for the most part, on physico-
chemical interactions of the inhaled matter with body compo-
nents.
Pattle described the lining of the alveoli as an insol-
bule layer formed from a thicker layer of a substance which
he called the "lining .complex". This layer was found cap-
able of reducing the surface tension of the alveolar surface
to nearly zero while being fully permeable to air (and pre-
sumably to any vapors). He was of the opinion that it is
possible that the lining complex responds to inhaled irritants
by an increase in secretion, thereby lowering the surface
tension and providing a protective mechanism for the alveoli.
It is apparent that more than solubility is involved in
clearance of material from the lung, since it has been dem-
onstrated that translocation is not necessarily predictable
" fi 7 7
from the solubility of compounds in pure substances. °» ' '
Vapor pressure is possibly a more important limiting factor
than water solubility during short term experiments.
36
-------
d. Non-Phagocytic Penetration of Alveolar Wall
The fourth mechanism involved in lung clearance is the
penetration of the alveolar wall without mediation of phago-
cytic cells.6' 19,33,42, 102 Thig mechanism affects par-
ticulate matter which has been deposited in the deeper por-
tions of the respiratory tract where, for the most part,
clearance by the "mucus-cilia escalator" has been ineffective,
non-functional or non-existent; however, the existence of
this mechanism has not been fully proven. The penetra-
tion of the lining complex of the alveolus is thought to take
place at multiple, small, scattered foci near the juxtaposi-
tion of alveoli and large vessels and bronchi. 42 Others
have suggested that the penetration of the alveolar lining
membrane occurs through defects in the membrane. ^3
Schiller maintains that only free particles can penetrate
the walls of the alveoli and that a pneumocyte or phagocyte
laden with dust either stays in the lumen of the alveolus or
is transferred to the bronchioles and expectorated. If de-
struction of a phagocyte occurs, the process of clearance
is repeated. Barclay^ discussed the mechanism by which
phagocytes cross the continuous cytoplasmic structures and
vital membranes. The mechanism is unknown and probably
related to diapedesis.
Discussion of the mechanisms of lung clearance have
purposely omitted the nose, sinuses and extreme upper re-
spiratory tract. Clearance mechanisms of this portion of
the respiratory tract are similar; however, removal rates
are more rapid, probably because the majority of this por-
tion of the respiratory tract is lined with ciliated epithelium.
37
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
-------
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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1. Agostoni, Emilio, Frederick Thimm, andW.O. Fenn, Compar-
ative Features of the Mechanics of Breathing. J. Appl. Physiol.
14(5):679 (1959)
2. Ainsworth, M. and R. J. Shephard, The Intrabronchial Distribu-
tion of Soluble Vapours at Selected Rates of Gas Flow. Inhaled
Particles and Vapours. Ed. C.N. Davies, Pergamon Press,
London (1961)
3. Atmospheric Radioactivity and Fallout Research. Biology and
Medicine, USAEC TID-12616, Dec (1962)
4. Attinger, Ernst O. and John M. Cahill, Cardiopulmonary Me-
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5. Avery, Mary Ellen and Charles D. Cook, Volume-Pressure Re-
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Goats. J. Appl. Physiol. 16:1034 Nov (1961)
6. Bair, W. J. , Radioisotope Toxicity: From Pulmonary Absorp-
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Caldecott and L.A. Snyder. U. of Minnesota, Minneapolis,
Minn. (I960)
7. Bair, W. J. , Deposition. Retention. Translocation. and Excre-
tion of Radioactive Particles. Inhaled Particles and Vapours.
Ed. C.N. Davies, Pergamon Press, London (1961)
8. Bair, W. J. , B.O. Stuart, J.F. Park and W. J. Clarke. Factors
Affecting Retention. Translocation. and Excretion of Radioactive
Particles. Hanford Lab, Wash. HW-SA-3161 (1963)
9. Bair, W. J. , M.D. Snyder, R.A. Walters andR.F. Keough,
Effect of 1-127 on Thyroid Uptake of Inhaled 1-131. Health Phy-
sics 9:1399 (1963)
10. Baker, R.E., Calculation of Critical Organ Dose from Inhala-
tion of Fission Products. Undated.
11. Barclay, E.E. and J. Franklin, The Rate and Excretion of India
Ink Injected into the Lungs. J. Physiol. 90:482(1937)
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12. Barrall, R. C. . Nose Swabs and Urinalysis as Indicators of Expo-
sure to 1-131. Health Physics Society 8th Annual Meeting June 10
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67
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APPENDIX
Table 1. Fission product radioiodine chains.' 68
Table 2. Activities of the radioiodines and tellurium-132
expressed as a fraction of the activity of iodine-131
for various decay times. 69
Table 3. Iodine isotopes formed in fission. 70
Table 4. Iodine activity and dose to the thyroid versus time
after 10EO instantaneous fissions of 235U. 71
Table 5. Iodine chemical forms. 73
Table 6. Physical form of 1-131 in air at various distances
from stocks of a chemical separation processing
plant. 74
Table 7. Deposition processes and the size ranges of
importance in each. 75
Table 8. The lung volumes and capacities. 76
Table 9. Composition of alveolar air of several species. 77
Table 10. Ventilation and complementary cycles of various
species. 78
Table 11. Diameter of alveoli of various species. 79
Table 12. Tidal volume frequency and compliance of
various species. 80
Table 13. Distribution of inhaled particles. 84
Table 14. Retention of 1 5O water vapor in three human subjects. 85
Table 15. Average values for thyroid size, iodine content and
biological half-life of thyroid iodine in different
species. 86
Table 16. Forty-eight hour uptake of 1 31I by thyroid gland
of dairy calves. 87
Table 17. Comparison of rate and percentage uptake of
radioiodines. 88
Table 18. Fate of 131I in the dairy cow. 89
Table 19. Translocation of iodine-131 following inhalation. 90
-------
Table 1. Fission product radioiodine chains.*
Mass
Number 49(In)
Atomic Number
50(Sn) 51(Sb) 52(Te) 53(1) 54(Xe) 55(Cs) 56(Ba)
oo
129 1.5 sec—^-.6.2 min-^-4. 2 hr 5^70 min —>-l. 6x10?yr>-Stable
A
2 day
131 1 sec
132
133
134
135
sec
23 min - 5»-25 min— >- 8. 05 day— ^--Stable
2.5 sec—>- 2 min >-78 hr >~2. 3 hr >- Stable
4.5 min 5»-2 min^-20. 8 hr ^—>- 5. 3 day-
—r _ _ _r
2 sec-
mn
10 sec >-44 min^-52. 5 min—^-Stable
6 sec
sec
9 hr
A
30%
mn
•Stable
97%
, -A -io
5x10 sec
-Stable
^Reference: 65
-------
Table 2. Activities of the radioiodines and tellurium-132 expressed as a fraction of the activity of
iodine-131 for various decay times.*
FISSION
"PR ODTTfT
Jr ±\ \J±J U ^- L
132
Te
131
I
132
I
133
I
134
I
135
I
1 HOUR
Reactor Criticality
1.01 5.50
1.00 1.00
1.06 8.50
1.46 22.0
1.38 378
1.34 84.5
10 HOURS
Reactor Criticality
0.98 3.30
1.00 1.00
1.00 3.57
1.15 15.4
0.43
0.54 19.7
1 DAY
Reactor Criticality
0.90 2.95
1.00 1.00
0.93 3.05
0.75 10.3
-
0.13 5.41
1 WEEK
Reactor Criticality
0.43 1.25
1.00 1.00
0.43 1.30
0.01 0.17
-
— —
vO
*Reference: 35
-------
Table 3. Iodine isotopes formed in fission.*
Iodine Mass
124
125
126
127
129
ji- *.i>
131
132
133
134
135
136
137
138
139
Half Life
4
56
13. 0
days
days
days
Stable
1. 72 x
8.04
2.4
22
51
6.7
86
22
5.9
2. 7
10 years
days
hr
hr
min
hr
sec
sec
sec
sec
Parent Nuclide
Primary products of high
energy fission bismuth
and lead not found in fis-
sion at moderate energies.
90 days Te-127m
9. 3 hr Te-127
32 days Te-129m
72 min Te-129
30 hr Te-131m
25 min Te-131
77 hr Te-132
60 min Te-133
43 min Te-134
Either primary
fission products
or formed from
very short-lived
tellurium parents.
Cumulative yields
from smoothed urine
235U 239Pu
0.
0.
2.
3.
4.
5.
6.
6.
6.
6.
6.
15
90
80
4
7
9
0
1
2
2
1
0.
1.
3.
4.
5.
5.
5.
5.
5.
5.
5.
38
6
7
8
0
3
6
8
9
9
9
-J
o
^Reference: 82
##1-128 and 1-130 (-which have not been reported in fission) are shielded by Stable Te-128 and
Te-130 respectively.
-------
20 235
Table 4. Iodine activity and dose to the thyroid versus time after 10 instantaneous fissions of U.
Iodine
Mass eff eff
Number (days) (Mev)
131 7.6 0.23
132 0.097 0.65
133 0.87 0.54
134 0.036 0.82
135 0.28 0.52
Total
131
132
133
134
135
Total
I
(Curies)
.45
380
1100
16000
3700
21225
71
265
1250
500
2200
4286
1 H
I
o
1
5
75
17
6 H
1
6
29
11
51
O U
/I Qt
. 211
. 79
. 19
.4
.4
0 U
.66
. 19
. 2
.6
.4
R
3 H O U R S
D /D
°(%)t0t
4.
1.
31.
28.
33.
100.
R S
11.
1.
55.
1.
30.
100.
8
5
8
9
1
1
7
6
4
4
1
2
I
(Curies)
64
275
1250
7000
3000
11589
1
71
250
1050
I
c
2
10
60
25
2 H O
2
9
40
11 Qt
. 553
. 39
.8
.4
.9
U R S
.76
. 73
.8
D /D
°(%)t0t
8
1
43
15
32
100
15
2
61
. 3
. 3
.4
. 2
. 2
.4
.4
.0
. 1
Negligible
1200
2571
46
.6
21
100
.6
. 1
continued
-------
20 235
Table 4. Iodine activity and dose to the thyroid versus time after 10 instantaneous fissions of U.*(cont')
Iodine
Mass
Number
131
132
133
134
135
Total
131
132
133
134
135
Total
131
132
133
134
135
Total
24 H O U R S
1 Z l\ *
(Cu°rieS) °(%{0t
71 5.25
220 16.2
720 53.3
Negligible
I 340 25. 1
1351
4 D AY S
63 21.5
130 44.4
100 34.1
Negligible
0.45 0. 15
293.4
10 D A Y S
39 54.6
32 45.8
0.35 0.49
Negligible
Negligible
71. 35
D /D
°(%)t0t
23. 6
2.5
64. 3
9.4
99.8
66.6
4. 97
28.4
0. 04
100. 01
96.8
2.9
0. 2
99.9
2 D A Y S
I I /I D
(Caries) ?(%!?*
71
170
350
29
620
58
100
30
0.
188.
11.4
27.4
56.4
Negligible
4. 68
5 D A Y S
30.8
53. 1
15.9
Negligible
23 0. 12
2
/D
°(%)t0t
40.8
3.6
54. 3
1.4
100. 1
83. 1
5. 2
11. 6
0. 02
99.92
3 D A Y S
I I II «.
(Cur°ies) °(%50t
68 14. 6
155 34.4
190 42. 1
Negligible
40 8.87
451
7 D A Y S
50 43.5
60 52.2
5 4. 35
Negligible
Negliginle
115
D /D
°(%f0t
52.4
4.4
40.6
2.6
100. 0
93.4
4. 0
2. 5
99. 9
ts)
^Reference: 107
-------
Table 5. Iodine chemical forms*
Valence
-1
0
+ 1
+ 5
+ 7
Organic
Common Chemical Species
I", HI, Nal, HI n HO
I
2
ICI, IB2, HOI
10, IO ~ HIO0, NaIO0
253 3 3
IO ~ HIO., NalO.
444
^•TT T f~*TJ T /^TJT /"* TUT T C* \J T
a ' 9 ;?' ^"tllQ» 7 c ' 749
-vl
OJ
'Reference: 65
-------
Table 6. Physical form of 1-131 in air at various distances from stocks of a
chemical separation processing plant.*, **.
Distance from Source,
Miles
Percent Particulate ***
1
3
5
10
20
25
12
8
20
34
38
34
--Reference: 97
**Hanford Laboratory, G. E. Company, Hanford, Washington.
*-.<#Sampled by aircraft 600' above ground.
-------
Table 7.* Deposition processes and the size ranges of importance in each.**
In Environment
Process
Sedimentation
[mpaction
Brownian motion
Thermal precipitation
Electrostatic precipitation
Condensation
Aggregation
Lower Limit
0. SJJL
0. 2|i
50 51
50 A
50 51
0. l(Ji
All sizes
Upper Limit
None
None
0. IM-
0. 1|JL
0. In
In Respiratory Tract
Lower Limit Upper Limit
0. 5(j. 30
O.ZJJL 30
50 & 0. 1
Not important
Not important
0. In
All respirable sizes
M-
M-
V
*Reference: 42
**Values for upper and lower limits are approximate.
-------
Table 8. The lung volumes and capacities.*
VOLUMES. - There are four primary volumes which do not overlap (Figure 2):
1. Tidal Volume, or the depth of breathing, is the volume of gas inspired or expired during each
respiratory cycle.
2. Inspiratory Reserve Volume (formerly complemental or complementary air minus tidal volume)
is the maximal amount of gas that can be inspired from the end-inspiratory position.
3. Expiratory Reserve Volume (formerly reserve or supplemental air) is the maximal volume
of gas that can be expired from the end-expiratory level.
4. - Residual Volume (formerly residual capacity or residual air) is the volume of gas remaining
in the lungs at the end of a maximal expiration.
CAPACITIES. - There are four capacities, each of which includes two or more of the primary
volumes (Figure 2):
1. Total Lung Capacity (formerly total lung volume) is the amount of gas contained in the lung at the
end of a maximal inspiration.
2. Vital Capacity is the maximal volume of gas that can be expelled from the lungs by forceful
effort following a maximal inspiration.
3. Inspiratory Capacity (formerly complemental or complementary air) is the maximal volume
of gas that can be inspired from the resting expiratory level.
4. Functional Residual Capacity (formerly functional residual air, equilibrium capacity or
mid-capacity), is the volume of gas remaining in the lungs at the resting expiratory level.
The resting end-expiratory position is used here as a base line because it varies less than
the end-inspiratory position.
*Reference: 22
-------
Table 9. Composition of alveolar air of several species.
Species
Horse
Cattle
Sheep
Goat
Dog
Man
Number
1*
-
3*
3*
3*
-
3*
-
co2%
4. 93
4. 74
4. 75
4. 59
5. 18
2.95
5. 32
4. 21
o2%
15. 09
15. 97
15.40
15. 65
15. 04
17.80
14.99
16.29
pCO mm Hg**
35.4
-
34. 2
33.65
38. 0
-
39. 0
40
pO mm Hg***
107.4
-
107.4
114.4
110.4
-
108. 6
106
Reference
41
39
41
41
41
39
41
39
*Five different measurements on each animal.
**Vapor pressure of CO in mm Hg in the alveolus.
***Vapor pressure of O in mm Hg in the alveolus.
L*
-------
Table 10. Ventilation and complementary cycles of various species.
Species
Mouse
Rat
Guinea Pig
Rabbit
Cat
Dog
Man
Horse
(Standardbred)
Body Weight
Kg
0. 015
0. 273
0.495
3. 0
2.6
19.2
70
550
£**
125
60
84
66
26
14
16
12
Ventilation Cycle
Tidal Volume Duration
in ml in sees
0.1 0.5
1.4 1.0
1.9 0.7
18.3 0.9
12.4 2.3
110.0 4.3
500.0 3.5
6000 5.0
Complementary Cycle
f/hour Volume Duration
in ml in sees
45 4.7 4
26 - 5
17 7
10 - 6
6 - 9
5 - 7
3 8
0 - 0
oo
-'Reference: 83
--'^Respiratory frequency
-------
Table 11. Diameter of alveoli of various species.
Species Number
Feline 21
Canine 8
Guinea Pig 14
Mouse 6
Rat 17
Monkey
Man
1-1.5 years
18-20 years
50-60 years
Mean Diameter
in (j.
116.9+14.4
133.2
93.9 + 14. 1
74. 1
65.4+8.5 •
83.4
46.6+2.4
38.7""
70. 2+6.6
59.1
89. 1
166.1
100
200
300
150
Reference
113
29
113
29
113
29
113
29
113
29
29
29
60
60
60
33
-J
vO
-------
Table 12. Tidal volume frequency and compliance of various species.
Species Number Body Weight
Measured in kg
Mouse 14 0. 024
7 0. 024
5* 0. 023
0.032
(0. 037-0. 038)
0.0198
56 0. 198
(0. 012-0. 026)
0. 88+0. 12
0.69
.(0.43-1. 05)
0.47
61 0.466
(0. 274-0.941)
V
ml
0. 15
0. 13+_0. 06
0. 09±0. 06
0. 18
(0. 09-0. 38)
0. 15
(0. 09-0.23)
0. 15
(0. 09-0.23)
-
3. 7
(2. 3-5. 3)
1.8
1. 75
(1.0-3.9)
f2
154
210+_50
120+60
109
(97-123)
163
(84-230)
163
(84-230)
75
42
(16-67)
90
(69-104)
90
(69-90)
V Compliance
m
ml ml/cm HO
23.1 0.029
27.3+3
10.8+3.6
21 0.049
'(9-46) (0.025-0.068)
23
(11-36)
24. 5
(11-35. 8)
1. 5+0. 14/kg
130 1.26
(80-190) (0.76-2.33)
160
(90-380)
155
(100-382)
.Reference
38
47
47
29
60
58
1
29
60
58
oo
o
-------
Table 12. Tidal volume frequency and compliance of various species. (Cont!)
Species Number Body Weight
Measured in kg
Monkey 6 2. 68
(2. 0-3. 08)
2.45
(1.8-3.05)
2.68
Rat 9 0.203
0. 25
(0. 19-0. 32)
0.112
35 0.112
(0. 063-0. 52)
0. 207+0. 007
Man ? 70
70
70
* 60
70
10 68.5
(55. 7-82. 1)
V
ml
21. 2
(9.8-29. 1)
20
(9-29)
21
(9.8-29)
1. 3
1. 55
(1. 03-2. 13)
0.86
(0.60-1. 25)
0.86
(0. 60-1. 25)
-
500
400
-
-
-
616
(315-745)
2
f
40
(31-52)
33
(27-47)
40
(31-52)
80
97
(84-126)
85
(66-114)
85
(66-114)
110
15
16
-
-
15
14
(10. 5-19.3)
3
V Compliance Reference
m
ml ml/cm HO
863
(311-1410)
700 12.3
(260-1340) (7.1-20.2)
860
(310-1410)
97 0. 148
160 0.39
(90-270) (0.22-0.52)
74
(50-102)
72.9
(49.8-101. 2)
1.94+0. 04/kg
7500 85
6400
120
62
2/kg
8732
(4900-12200)
58
29
60
38
29
60
58
1
38
29
60
60
1
58
oo
-------
Table 12. Tidal volume frequency and compliance of various species. (Cont1)
Species Number Body Weight
Measured in kg
Dog 15 16.3+4.3
3 17
12* 18.3+5.6
39* 13.4+_5
12.6
(10. 0-15. 5)
* 20
* 11.8
4 23.6
10.4+0.48
Rabbit 3 2.6
2.4
(2. 05-3. 0)
* 2
2.98+0.31
2.07
vtl
ml
16+5. 8ml/kg
107
228
12. 5+2. 5 ml/kg
247+_17
144
(122-176)
'
-
320
-
16
15.8
(11.5-24.4)
-
-
_
20
f2
26+_13
22
46+_15
28+_3
21
(6-31)
-
-
17
(H-21)
18
38
39
(32-53)
-
50
_
61
v 3
m
ml
6656
2354
10488
4199^51
2300
(800-3500)
-
-
5200
(3300-74000)
-
608
620
(370-890)
-
-•
800
(270-1200)
12300
Compliance
ml/cm HO
4. 6+1. 54/kg
30
63+20
50.8+3
40
(27-61)
48
26.5
_
2. 56+_0. 3/kg
2.4
6. 0
(3. 5-10. 8)
2.3
1.41 + 0. 19/kg
_
Reference
23
38
86
4
29
60
60
60
1
38
29
60
1
60
60
oo
-------
Table 12. Tidal volume frequency and compliance of various species. (Cont!)
Species Number Body Weight
Measured in kg
Rabbit(cont') 31 2.069
(0. 79-3.09)
Horse - 430
1 696
19* 28+_3
225
Cat - 3.54+0.32
3. 7
(2.3-5. 7)
* 3. 2
* 2. 6
2.45
Cow 4 (lying) 439
4(standing)439
Sheep 50* 42. 6+_4. 7
63
Goat
1 37
V
ml
-
-
9060
(8520-9680)
286+25
-
-
34
(20-42)
-
-
12.4
3200
3800
249+51**-
310
-
-
f2
-
-
11.9
24. 5+_2
-
30
30
(24-42)
-
-
26
30
28
-
19
28
-
v 3
m
ml
800
(270-1208)
-
107 L
-
37 L
-
960
(860-1090)
-
-
322
96 L
106 L,
-
5700
-
-
Compliance
ml/cm HO
£i
-
800
-
57+6
-
2. 86+0. 28/kg
13.4
(9.9-17.4)
6.8
5. 7
-
-
-
106+J31
-
-
50
Reference
58
60
60
4
60
1
29
60
60
60
60
60
59
60
70
5
00
u>
* Anesthetized
**Tidal volume in ml/M^
1 - Tidal volume in ml
2 - Respiratory frequency
3 - Minute volume
-------
Table 13. Distribution of inhaled particles.*
oo
Distribution
Exhaled
Deposited in upper respiratory passages
and subsequently swallowed.
Deposited in the lungs (lower respiratory
passages) .
Readily "Soluble"
Compounds
25
50
25**
Other Compounds
25
50
25***
*Reference: Recommendations of International Commission on Radiological
Protection. Brit. J. Radiol. Supp. 6, 1955 (from 42)
**This is taken up into the body almost immediately.
***Of this, half is eliminated from the lungs and swallowed in the first 25 hours
making a total of 62. 5% swallowed. The remaining 12. 5% is retained in the
lungs with a half-life of 120 days, it being assumed that this portion is taken
up into the body fluids.
-------
1 5
00
Table 14. Retention of O -water vapor in three human subjects.
Region of
Respiratory Tract
Mouth
Phar ynx
Upper trachea
Mid trachea
Corina
Right lung base
Activity
Counts/sec.
170
120
160
100
33
3
Percent of
Total Activity
28.9
20.4
27.4
17.0
5.8
0.5
''-Reference: 118
-------
oo
Table 15. Average values for thyroid size, iodine content and biological half-life of
thyroid iodine in different species. *
Species
Cattle
Swine
Lamb
Rat
Man
Thyroid
Gram
18
15
2
0.02
25
Size
mg/kg Body
Weight
45
80
50
80
360
Thyroid Iodine
mg
8-16
6-20
1-3
0.02
8
Biological Half
Life in Days
16
30
14
4
94
''-Reference: 115
-------
oo
-j
Table 16. Forty-eight hour uptake of 3 I* by thyroid gland of dairy calves. **
Breed
Ayrshire
Brown Swiss
Guernsey
Holstein
Jersey
Number
2
19
7
19
16
Average Age
Months
6.
4.
6.
3.
5.
2
2
7
5
8
Uptake
%
42.
33.
47.
44.
45.
5
2
9
1
8
Standard
Deviation
-
18.
21.
15.
19.
3
6
8
9
^Injected subcutaneously
-"-Reference: 80
-------
Table 17. Comparison of rate and percentage uptake of radioiodines.
Animal Isotope
Sheep i 3 i j
131I
131I
131I
131I
Ag131I
Mice 1 31 1 vapor
Ag131I
Dog 133Iand
fiss. prod.
Cattle Na l 31I
131I
Swine * 3 1 1
Rat 131I
Man(neonatal) 1 3 x I
2 mos-18 yrs 1 31I
Adults J 3 1 1
Method of
Adminis -
t rat ion
Oral
Intravenous
Subcutaneous
Topical
Inhaled
Inhaled
Inhaled
Inhaled
Inhaled
Subcutaneous
Oral
Oral
Inhaled
Oral
Oral
Oral
Effective
Half Life
in Days
6. 5-8
6. 5-8
6. 5-8
7
-
-
-
-
Short
-
4. 5
6.5
-
_
Time of
Maximum
Uptake in
Hours
48-96
48-96
48-96
48-96
20-35
20-24
30
10
48-72
48
30
24
44
48
24-48
24
Percentage
Uptake
17-19
17-19
17-19
2-14
3-8
3-8
2.5
1.6
92
41.6
35
30
26.9
62
31+7.63
36+9.9
Reference
123
123
123
123
121
121
121
121
48
80
18
17
13
45
45
45
oo
oo
-------
Table 18. Fate of * 31I in the dairy cow.
oo
Route of
Elimination
Thyroid
Milk
Urine
Feces
Method of
Administration
Oral
Intravenous
Oral
Intravenous
Oral
Oral
Intravenous
Oral
Oral
Intravenous
Percent
of Dose
15+6.0
18
6.2+2.0
7.2
3. 28
55+14
43.7
27.8
17+7
17.6
Recovery
Period
(Days)
7
3-5
1
3
6
7
3
6
7
3
Reference
24
111
24
111
108
24
111
108
24
111
-------
Table 19. * Translocation of iodine-131 following inhalation. **
xO
o
Tissue
Lung
Bone
Thyroid
Liver
Lymph
Spleen
Adrenal
Kidney
Ovary
Ag13
Immediately
45
-
750
17
36
36
43
18
108
10 Hour***
9
-
6800
5
48
5
13
11
38
Immediately
15
-
130
20
67
17
20
25
150
30 Hour***
0.7
-
1700
0.7
2.2
0. 17
0.6
1.0
3.5
*Reference: 7
**Percentage of total deposited per gram tissue at various times after inhalation.
***Time of maximum concentration in thyroid.
-------
DISTRIBUTION
1-15 SWRHL, Las Vegas, Nevada
16 James E. Reeves, Manager, NVOO, AEC, Las Vegas, Nevada
17 Col. E. G. Halligan, DASA, NVOO, AEC, Las Vegas, Nevada
18 Otto H. Roehlk, OSD, NVOO, AEC, Las Vegas, Nevada
19 Henry G. Vermillion, NVOO, AEC, Las Vegas, Nevada
20 Gordon M. Dunning, DOS, USAEC, Washington, D. C.
21 Richard Hamburger, DPNE, USAEC, Washington, D. C.
22 JohnS. Kelly, DPNE, USAEC, Washington, D. C.
23 Robert E. Baker, USAEC, Washington, D. C.
24 Philip W. Allen, USWB, NVOO, AEC, Las Vegas, Nevada
25 Frank D. Cluff, USWB, NVOO, AEC, Las Vegas, Nevada
26 G. D. Ferber, USWB, MRPB (R-3. 3)> Washington, D. C.
27 Ernest C. Anderson, DRH, PHS, Washington, D. C.
28 Donald J. Nelson, TOB, DRH, PHS, Washington, D. C.
29 James G. Terrill, Jr. , DRH, PHS, Washington, D. C.
30 Donald L. Snow, DRH, PHS, Washington, D. C.
31 Raymond Moore, DRH, PHS, Region VII, Dallas, Texas
32 Bernd Kahn, DRH, RATSEC, Cincinnati, Ohio
33 Arve H. Dahl, DRH, PHS, Rockville, Maryland
34 Samuel Wieder, DRH, PHS, Rockville, Maryland
35 Northeastern Radiological Health Laboratory, Winchester, Mass.
36 Southeastern Radiological Health Laboratory, Montgomery, Ala.
37 Rockville Radiological Health Laboratory, Rockville, Maryland
38 Edmund L. Fountain, USA, MEDS, VS, Chicago, Illinois
39 Capt. Stanley Wampler, WRAIR-WRAMC, Washington, D. C.
-------
40 Clifford M. Bacigalupi, LRL, Mercury, Nevada
41 Bryce L. Rich, LRL, Mercury, Nevada
42 Robert H. Goeckermann, LRL, Livermore, California
43 Duane E. Sewell, LRL, Livermore, California
44 Edward H. Fleming, LRL, Livermore, California
45 Gary H. .Higgins, LRL, Livermore, California
46 John W. Gofman, LRL, Livermore, California
47 William E. Ogle, LASL, Los Alamos, N. Mex.
48 Fred Sanders, LASL, Mercury, Nevada
49 Harry S. Jordan, LASL, Los Alamos, N. Mex.
50 Orin Stopinski, LASL, Los Alamos, N. Mex.
51 Charles I. Browne, LASL, Los Alamos, N. Mex.
52 Victor M. Milligan, REECo, Mercury, Nevada
53 L. G. von Lossberg, Sheppard T. Powell & Assoc. , Baltimore, Md.
54 Paul Kruger, Hazelton-Nuclear Science Corp. , Palo Alto, Calif.
55 G. B. Maxey, Desert Research Institute, U. of Nev. , Reno, Nev.
56 Ray Gibb, University of Rochester AEP, Rochester, N. Y.
57 Robert H. Wilson, University of Rochester AEP, Rochester, N. Y.
58 Mail and Records, NVOO, AEC, Las Vegas, Nevada
------- |