Toxicological
Profile
for
PLUTONIUM
U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Agency for Toxic Substances and Disease Registry
TP-90-21
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TOXICOLOG1CAL PROFILE FOR
PLUTONIUM
Prepared by:
Clement International Corporation
Under Contract No. 205-88-0608
Prepared for:
Agency for Toxic Substances and Disease Registry
U.S. Public Health Service
In collaboration with:
U.S. Environmental Protection A.gency
December 1990
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ii
DISCLAIMER
The use of company name or product name(s) is for identification
only and does not imply endorsement by the Agency for Toxic Substances
and Disease Registry.
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FOREWORD
The Superfund Amendments and Reauthorization Act (SARA) of 1986
(Public Law 99-499) extended and amended the Comprehensive Environmental
Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund).
This public law directed the Agency for Toxic Substances and Disease
Registry (ATSDR) to prepare toxicological profiles for hazardous
substances which are most commonly found at facilities on the CERCLA
National Priorities List and which pose the most significant potential
threat to human health, as determined by ATSDR and the Environmental
Protection Agency (EPA). The lists of the 250 most significant hazardous
substances were published in the Federal Register on April 17, 1987, on
October 20, 1988, on October 26, 1989, and on October 17, 1990.
Section 104(i)(3) of CERCLA, as amended, directs the Administrator of
ATSDR to prepare a toxicological profile for each substance on the list.
Each profile must include the following content:
(A) An examination, summary, and interpretation of available
toxicological information and epidemiological evaluations on the
hazardous substance in order to ascertain the levels of significant
human exposure for the substance and the associated acute, subacute,
and chronic health effects,
(B) A determination of whether adequate information on the health
effects of each substance is available or in the process of
development to determine levels of exposure which present a
significant risk to human health of acute, subacute, and chronic
health effects, and
(C) Where appropriate, an identification of toxicological testing
needed to identify the types or levels of exposure that may present
significant risk of adverse health effects in humans.
This toxicological profile is prepared in accordance with guidelines
developed by ATSDR and EPA. The original guidelines were published in the
Federal Register on April 17, 1987. Each profile will be revised and
republished as necessary, but no less often than every three years, as
required by CERCLA, as amended.
The ATSDR toxicological profile is intended to characterize succinctly
the toxicological and adverse health effects information for the hazardous
substance being described. Each profile identifies and reviews the key
literature (that has been peer-reviewed) that describes a hazardous
substance's toxicological properties. Other pertinent literature is also
presented but described in less detail than the key studies. The profile
is not intended to be an exhaustive document; however, more comprehensive
sources of specialty information are referenced.
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iv
Foreword
Each toxicological profile begins with a public health statement,
which describes in nontechnical language a substance's relevant
toxicological properties. Following the public health statement is
information concerning significant health effects associated with exposure
to the substance. The adequacy of information to determine a substance's
health effects is described. Data needs that are of significance to
protection of public health will be identified by ATSDR, the National
Toxicology Program (NTP) of the Public Health Service, and EPA. The focus
of the profiles is on health and toxicological information; therefore, we
have included this information in the beginning of the document.
The principal audiences for the toxicological profiles are health
professionals at the federal, state, and local levels, interested private
sector organizations and groups, and members of the public.
This profile reflects our assessment of all relevant toxicological
testing and information that has been peer reviewed. It has been reviewed
by scientists from ATSDR, the Centers for Disease Control, the NTP, and
other federal agencies. It has also been reviewed by a panel of
nongovernment peer reviewers and is being made available for public
review. Final responsibility for the contents and views expressed in this
toxicological profile resides with ATSDR.
Wi ., M.P.H.
Administrator
Agency for Toxic Substances and
Disease Registry
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V
CONTENTS
FOREWORD iii
LIST OF FIGURES ix
LIST OF TABLES xi
1. PUBLIC HEALTH STATEMENT 1
1.1 WHAT IS PLUTONIUM? 1
1.2 HOW MIGHT I BE EXPOSED TO PLUTONIUM? 2
1. 3 HOW CAN PLUTONIUM ENTER AND LEAVE MY BODY? 2
1.4 HOW CAN PLUTONIUM AFFECT MY HEALTH? 3
1.5 WHAT LEVELS OF EXPOSURE HAVE RESULTED IN
HARMFUL HEALTH EFFECTS? 3
1.6 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE
BEEN EXPOSED TO PLUTONIUM? 8
1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL
GOVERNMENT MADE TO PROTECT HUMAN HEALTH? 8
1.8 WHERE CAN I GET MORE INFORMATION? 8
2. HEALTH EFFECTS 11
2.1 INTRODUCTION 11
2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 12
2.2.1 Inhalation Exposure 13
2.2.1.1 Death 14
2.2.1.2 Systemic Effects 21
2.2.1.3 Immunological Effects 24
2.2.1.4 Neurological Effects 25
2.2.1.5 Developmental Effects 25
2.2.1.6 Reproductive Effects 25
2.2.1.7 Genotoxic Effects 25
2.2.1.8 Cancer 26
2.2.2 Oral Exposure 31
2.2.2.1 Death 31
2.2.2.2 Systemic Effects 31
2.2.2.3 Immunological Effects 34
2.2.2.4 Neurological Effects 34
2.2.2.5 Developmental Effects 34
2.2.2.6 Reproductive Effects 34
2.2.2.7 Genotoxic Effects 34
2.2.2.8 Cancer 34
2.2.3 Dermal Exposure 34
2.2.3.1 Death 34
2.2.3.2 Systemic Effects 34
2.2.3.3 Immunological Effects 35
2.2.3.4 Neurological Effects 35
2.2.3.5 Developmental Effects 35
2.2.3.6 Reproductive Effects 35
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2.2.3.7 Genotoxic Effects
2.2.3.8 Cancer
2.2.4 Other Routes of Exposure
2.2.4.1 Death
2.2.4.2 Systemic Effects
2.2.4.3 Immunological Effects . . .
2.2.4.4 Neurological Effects . . .
2.2.4.5 Developmental Effects . . .
2.2.4.6 Reproductive Effects . . .
2.2.4.7 Genotoxic Effects
2.2.4.8 Cancer
2.3 TOXICOKINETICS
2.3.1 Absorption
2.3.1.1 Inhalation Exposure ....
2.3.1.2 Oral Exposure
2.3.1.3 Dermal Exposure
2.3.1.4 Other Routes of Exposure
2.3.2 Distribution
2.3.2.1 Inhalation Exposure ....
2.3.2.2 Oral Exposure
2.3.2.3 Dermal Exposure
2.3.2.4 Other Routes of Exposure
2.3.3 Metabolism
2.3.4 Excretion
2.3.4.1 Inhalation Exposure ....
2.3.4.2 Oral Exposure
2.3.4.3 Dermal Exposure
2.3.4.4 Other Routes of Exposure
2.4 RELEVANCE TO PUBLIC HEALTH
2.5 BIOMARKERS OF EXPOSURE AND EFFECT
2.5.1 Biomarkers Used to Identify or
Quantify Exposure to Plutonium . . .
2.5.2 Biomarkers Used to Characterize
Effects Caused by Plutonium ....
2.6 INTERACTIONS WITH OTHER CHEMICALS
2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE
2.8 ADEQUACY OF THE DATABASE
2.8.1 Existing Information on Health Effects
of Plutonium
2.8.2 Identification of Data Needs ....
2.8.3 On-going Studies
3. CHEMICAL AND PHYSICAL INFORMATION
3.1 CHEMICAL IDENTITY
3.2 PHYSICAL AND CHEMICAL PROPERTIES
4. PRODUCTION, IMPORT, USE, AND DISPOSAL
4.1 PRODUCTION
4.2 IMPORT
4.3 USE
4.4 DISPOSAL
35
35
35
35
41
44
45
45
45
46
47
48
49
49
50
50
51
51
51
52
52
53
55
55
55
56
56
56
58
64
65
66
66
69
69
69
71
76
79
79
79
85
85
85
85
86
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5. POTENTIAL FOR HUMAN EXPOSURE 87
5.1 OVERVIEW 87
5.2 RELEASES TO THE ENVIRONMENT 89
5.2.1 Air 89
5.2.2 Water 89
5.3.3 Soil 90
5.3 ENVIRONMENTAL FATE 92
5.3.1 Transport and Partitioning 92
5.3.2 Transformation and Degradation 95
5.3.2.1 Air 95
5.3.2.2 Water 96
5.3.2.3 Soil 96
5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 96
5.4.1 Air 96
5.4.2 Water 98
5.4.3 Soil 100
5.4.4 Other Media 100
5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 101
5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 102
5.7 ADEQUACY OF THE DATABASE 103
5.7.1 Identification of Data Needs 103
5.7.2 On-going Studies 105
6. ANALYTICAL METHODS 107
6.1 BIOLOGICAL MATERIALS 107
6.2 ENVIRONMENTAL SAMPLES 113
6.3 ADEQUACY OF THE DATABASE 114
6.3.1 Identification of Data Needs 115
6.3.2 On-going Studies 115
7. REGULATIONS AND ADVISORIES 117
8. REFERENCES 125
9. GLOSSARY 163
APPENDIX A -- PEER REVIEW 183
APPENDIX B -- OVERVIEW OF BASIC RADIATION
PHYSICS, CHEMISTRY AND BIOLOGY 185
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LIST OF FIGURES
2-1 Health Effects Associates with Plutonium
Deposition - Inhalation 19
2-2 Health Effects Associated with Plutonium
Deposition - Oral 33
2-3 Health Effects Associates with Plutonium Deposition -
Other Routes of Exposure 39
2-4 Existing Information on Health Effects of Plutonium 70
3-1 Plutonium-239 Decay Series 83
3-2 Plutonium-241 Decay Series 84
5-1 Frequency of Sites with Plutonium Contamination 88
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LIST OF TABLES
1-1 Human Health Effects from Breathing Plutonium 4
1-2 Animal Health Effects from Breathing Plutonium 5
1-3 Human Health Effects from Eating or Drinking Plutonium ... 6
1-4 Animal Health Effects from Eating or Drinking Plutonium ... 7
2-1 Health Effects Associates with Plutonium Deposition -
Inhalation 15
2-2 Levels of Significant Exposure to Plutonium - Oral 32
2-3 Health Effects Associated with Plutonium Administration -
Other Routes of Exposure 36
2-4 Genotoxicity of Plutonium In Vitro 62
2-5 Genotoxicity of Plutonium In Vivo 63
3-1 Chemical Identity of Plutonium and Selected
Plutonium Compounds 80
3-2 Physical and Chemical Properties of Plutonium
and Selected Plutonium Compounds 81
3-3 Radiological Properties of Plutonium Isotopes 82
5-1 Plutonium Levels Detected in Air 97
5-2 Plutonium Levels Detected in Water . 99
6-1 Analytical Methods for Determining Plutonium
in Biological Materials 108
6-2 Analytical Methods for Determining Plutonium
in Environmental Samples 109
7-1 Regulations and Guidelines Applicable to Plutonium
and Plutonium Compounds 118
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1. PUBLIC HEALTH STATEMENT
This Statement was prepared to give you information about plutonium
and to emphasize the human health effects that may result from exposure
to it. The Environmental Protection Agency (EPA) has identified 1,177
sites on its National Priorities List (NPL). Plutonium has been found
above background levels at five of these sites. However, we do not know
how many of the 1,177 NPL sites have been evaluated for plutonium. As
EPA evaluates more sites, the number of sites at which plutonium is
found may change. The information is important for you because
plutonium may cause harmful health effects and because these sites are
potential or actual sources of human exposure to plutonium.
When a radioactive chemical is released from a large area such as
an industrial plant, or from a container such as a drum or bottle, it
enters the environment as a radioactive chemical. This emission, which
is also called a release, does not always lead to exposure. You can be
exposed to a chemical only when you come into contact with the chemical.
You may be exposed to it in the environment by breathing, eating, or
drinking substances containing the chemical or from skin contact with
it.
If you are exposed to a hazardous substance such as plutonium,
several factors will determine whether harmful health effects will occur
and what the type and severity of those health effects will be. These
factors include the dose (how much), the duration (how long), the route
or pathway by which you are exposed (breathing, eating, drinking, or
skin contact), the other chemicals to which you are exposed, and your
individual characteristics such as age, sex, nutritional status, family
traits, life style, and state of health.
1.1 WHAT IS PLUTONIUM?
Plutonium is a silvery-white radioactive metal that exists as a
solid under normal conditions. It is produced when uranium absorbs an
atomic particle. Small amounts of plutonium occur naturally, but large
amounts have been produced by man in nuclear reactors. Plutonium can be
found in the environment in several forms called isotopes. The most
common plutonium isotopes are plutonium-238 and plutonium-239. Because
plutonium is a radioactive element, it constantly changes or "decays."
In this decay process, energy is released and a new product is formed.
The energy released is called radiation. When plutonium decays, it
divides into two parts -- a small part that we call "alpha" radiation
and the remainder, different from original plutonium, called the
daughter. The daughter is also radioactive, and it, too, continues to
decay until a nonradioactive daughter is formed. During these decay
processes, alpha, beta, and gamma radiation are released. Alpha
particles can travel only very short distances and cannot go through the
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1. PUBLIC HEALTH STATEMENT
thickness of your skin. Beta particles can travel farther and can
penetrate a few millimeters into your tissues. Gamma radiation travels
the farthest and can go all the way through your body. It takes about
90 years for one-half of a quantity of piutonlum-238 to break down to
its daughter and about 24,000 years for this to happen to plutonium-239.
Plutonium-238 is used to provide on board power for electronic
systems in satellites. Plutonium-239 is used primarily in nuclear
weapons. Most plutonium is found combined with other substances, for
example, plutonium dioxide (plutonium with oxygen) or plutonium nitrate
(plutonium with nitrogen and oxygen). More information about the
properties and uses of plutonium can be found in Chapters 3, 4, and 5.
1.2 HOW MIGHT I BE EXPOSED TO PLUTONIUM?
Plutonium has been released to the environment primarily by
atmospheric testing of nuclear weapons and by accidents at weapons
production and utilization facilities. In addition, accidents involving
weapons transport, satellite reentry, and nuclear reactors have also
released smaller amounts of plutonium into the atmosphere. When
plutonium was released to the atmosphere, It returned to the earth's
surface as fallout. Average fallout levels in soils in the United
States are about 2 millicuries (mCi)/square kilometer (about 0.4 square
miles) for plutonium-239 and 0.05 mCi/square kilometer for plutonium-
238. A millicurie is a unit used to measure the amount of
radioactivity; 1 mCi of plutonium-2 39 weighs 0.016 gm, while 1 mCi of
plutonium-238 weighs 0.00006 gm. Measurements in air have been made at
a few locations. For example, air levels of plutonium-239 in New York
City in the 1970s were reported to be 0.00003 plcoc.uries (pCi) per cubic
meter of air. One pCi is one billionth of a mCi. Persons who work at
nuclear plants using plutonium have a greater chance of being exposed
than individuals in the general population. However, you could be
exposed to plutonium if there was an accidental release of plutonium
during use, transport, or disposal. Because plutonium does not release
very much gamma radiation, harmful health effects are not likely to
occur from being near plutonium unless you breathe or swallow it. You
may find more information about exposure to plutonium in Chapter 5.
1.3 HOW CAN PLUTONIUM ENTER AND LEAVE MY BODY?
You are most likely to be exposed to plutonium by breathing it in.
Once breathed in, the amount that stays in the lungs depends upon
several things, particularly the particle size and form of the plutonium
compound breathed in. The forms that dissolve easily may be absorbed
(pass through the lungs into other parts of the body) or some may remain
in the lung. The forms that dissolve less easily are often coughed up
and then swallowed. However, some of these may also remain in the lung.
Plutonium taken in with food or water is poorly absorbed from the
stomach, so most of it leaves the body in feces, Absorption of
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1. PUBLIC HEALTH STATEMENT
plutoniura through undamaged skin is very limited, but it may enter the
body through wounds.
Some of the plutoniura absorbed into the body leaves the body in
urine. The rate of plutonium removal from the tissues of the body is
very slow, however, occurring over years. Most of the plutonium that
stays in the body is found in the lungs, liver, and skeleton. You may
find more information about this subject in Chapter 2.
1.4 HOW CAN PLUTONIUM AFFECT MY HEALTH?
Plutonium may remain in the lungs or move to the bones, liver, or
other body organs. It generally stays in the body for decades and
continues to expose the surrounding tissues to radiation. This may
eventually increase your chance of developing cancer, but it would be
several years before such cancer effects became apparent. The
experimental evidence is inconclusive, and studies of some human
populations who have been exposed to low levels of plutonium have not
definitely shown an increase in cancer. However, plutonium has been
shown to cause both cancers and other damage in laboratory animals, and
might affect the ability to resist disease (immune system). We do not
know if plutonium causes birth defects or affects the ability to have
children. However, radioactivity from other radioactive compounds can
produce these effects. If plutonium can reach these sensitive target
tissues, radioactivity from plutonium may produce these effects. More
information on the health effects of plutonium is presented in
Chapter 2.
1.5 WHAT LEVELS OF EXPOSURE HAVE RESULTED IN HARMFUL HEALTH EFFECTS?
Plutonium is odorless and tasteless so you cannot tell if you are
being exposed to plutonium. If you breathe in plutonium, some of it
will be retained in your body. When discussing harmful health effects,
the amount of plutonium that caused these effects is usually given as
the amount of plutonium retained or deposited in the body rather than as
the amount that was in the air. As indicated in Tables 1-1 through 1-4,
there is no information from studies in humans or animals to identify
the specific levels of exposures to plutonium in air, food, or water
that have resulted in harmful effects. However, it is generally assumed
that any amount of absorbed radiation, no matter how small, may cause
some damage. When expressed as the amount of radioactivity deposited in
the body per kilogram of body weight (kg bw) as a result of breathing in
plutonium, studies in dogs report that 100,000 pCi plutonium/kg bw
caused serious lung damage within a few months, 1,700 pCi/kg bw caused
harm to the immune system, and 1,400 pCi/kg bw caused bone cancer after
4 years, In each of these cases the dogs were exposed to the plutonium
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1. PUBLIC HEALTH STATEMENT
TABLE 1-1. Human Health Effects from Breathing Plutonium*
Short-term Exposure
(less than or equal to 14 days)
Levels in Air
Length of Exposure
Description of Effects
The health effects
resulting from short-
term exposure of humans
breathing specific
levels of plutonium
are not known.
Long-term Exposure
(greater than 14 days)
Levels in Air
Length of Exposu££
Description of Effects
The health effects j
resulting from long- j
term exposure of humans !
breathing specific !
levels of plutonium j
are not known. !
*See Section 1.2 for a discussion of exposures encountered in daily life.
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1. PUBLIC HEALTH STATEMENT
TABLE 1-2. Animal Health Effects from Breathing Plutonium
Short-term Exposure
(less than or equal to 14 days)
Levels in Air
Lenpth of ExDOSure Descrintion of Effects
The health effects
resulting from short-
term exposure of animals
breathing specific
levels of plutonium
are not known.
Long-term Exposure
(greater than 14 days)
Levels in Air
Lenpth of Exnosure Description of Effects
The health effects
resulting from long-
term exposure of animals
breathing specific
levels of plutonium
are not known.
L.
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1. PUBLIC HEALTH STATEMENT
TABLE 1-3. Human Health Effects from Eating or Drinking Plutonium*
Short-term Exposure
(less than or equal to \U days)
Levels in Food Lenpth of Exposure Description of Effects
The hen 1th effects result-
ing from short-term
exposure of humans to
food containing specific
levels of plutonium are
not known.
T.PVP.1S in Water
The health effects result-
ing from short-term
exposure of humans to
water containing specific
levels of plutonium are
not known.
Long-term Exposure
(greater than 14 days)
I ewis in pood Lenpth of Exposure Descriut ton of Effects
The health effects result-
ing from long-term
exposure of humans to
food containing specific
levels of plutonium are
not known.
TpvpIs in Water
The health effects result-
ing from long-term
exposure of humans to
water containing specific
levels of plutonium are
not known.
*See Section 1.2 for a discussion of exposures encountered in daily life
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1. PUBLIC HEALTH STATEMENT
TABLE 1-4. Animal Health Effects from Eating or Drinking Plutonium
Short-term Exposure
(less than or equal to 14 days)
Levels
in
Food
Length of Exposure
Description of Effects
The health effects result-
ing from short-term
exposure of animals to
food containing specific
levels of plutonium are
not known.
Levels
in
Water
The health effects result-
ing from short-term
exposure of animals to
water containing specific
levels of plutonium are
not known.
Long-term Exposure
(greater than 14 days)
Levels
in
Food
Length of Exposure
Description of Effects
The health effects result-
ing from long-term
exposure of animals to
food containing specific
levels of plutonium are
not known.
Levels
in
Water
The health effects result-
ing from long-term
exposure of animals to
water containing specific
levels of plutonium are
not known.
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1. PUBLIC HEALTH STATEMENT
in air for one day. You can find more information on the health effects
of plutonium in Chapter 2.
1.6 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO
PLUTONIUM?
There are tests available that can reliably measure the amount of
plutonium in a urine sample even at very low levels. These measurements
can be used to estimate the total amount of plutonium that is carried by
the body. However, these measurements cannot be used to directly
determine the levels to which the person was exposed or to predict the
potential for health effects. In addition, there are tests to measure
plutonium in soft tissues (such as body organs), feces, bones, and milk.
These tests are not routinely available in your doctor's office because
special laboratory equipment is required. You can find more information
on methods used to measure levels of plutonium in Chapters 2 and 6.
1. 7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT
HUMAN HEALTH?
Guidelines for radiation protection have been established for the
general public and for occupational settings. These guidelines are
expressed in units called rems. A rem is a unit that measures the
amount of radiation absorbed by the body. For people in the general
population, national guidelines recommend dose limits of 0.5 rems/year,
while international guidelines set dose limits of 0.5 rems/year for
short-term exposure and 0.1 rems/year for long-term exposure. For
workers in industries where exposure to radiation may occur, the EPA has
recommended a dose limit of 5 rems/year. This is the same dose limit
set for workers by the International Commission on Radiological
Protection (ICRP). The ICRP has developed limits for the amount of
radioactivity we take into the body, called Annual Limits on Intake
(ALIs), and for the amount of radioactivity in the air we breathe,
called Derived Air Concentrations (DACs). For workers exposed to
plutonium-239 in air, the ALI is 20,000 pCi/year and the DAC is 7 pCi/m3
of air. The ALIs and DACs vary with each plutonium isotope. You may
find more information on regulations and guidelines in Chapter 7.
1.8 WHERE CAN I GET MORE INFORMATION?
If you have any more questions or concerns not covered here, please
contact your State Health or Environmental Department or:
Agency for Toxic Substances and Disease Registry
Division of Toxicology
1600 Clifton Road, E-29
Atlanta, Georgia 30333
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1. PUBLIC HEALTH STATEMENT
This agency can also give you information on the location of the
nearest occupational and environmental health clinics. Such clinics
specialize in recognizing, evaluating, and treating illnesses that
result from exposure to hazardous substances.
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2. HEALTH EFFECTS
2.1 INTRODUCTION
This chapter contains descriptions and evaluations of studies and
interpretation of data on the health effects associated with exposure to
plutonium. Its purpose is to present levels of significant exposure to
plutonium based on toxicological studies, epidemiological
investigations, and environmental exposure data. This information is
presented to provide public health officials, physicians, toxicologists,
and other interested individuals and groups with (1) an overall
perspective of the toxicology of plutonium and (2) a depiction of
significant exposure levels associated with various adverse health
effects.
Plutonium is a radioactive element. Radioactive elements are those
that undergo spontaneous transformation (decay) in which energy is
released (emitted) either in the form of particles, such as alpha or
beta particles, or waves, such as gamma or X-ray. This transformation
or decay results in the formation of new elements, some of which may
themselves be radioactive, in which case they will also decay. The
process continues until a stable (nonradioactive) state is reached (see
Appendix B for more information).
Radionuclides can produce adverse health effects as a result of
their radioactive properties. With toxicity induced by the chemical
properties of an element or its compounds, the adverse effects are
characteristic of that specific substance. With toxicity induced by
radioactive properties, the adverse effects are independent of the
chemical toxicity and are related to the amount and type of radiation
absorbed by the target tissues or organs. While the chemical properties
affect the distribution and biological half-life of a radionuclide and
influence the retention of the radionuclide within a target organ, the
damage from a type of radiation is independent of the source of that
radiation. The adverse health effects reported in Chapter 2 are related
to the radioactive properties of plutonium rather than its chemical
properties. In this profile, there is little or no specific information
regarding the influence of plutonium on specific target organs in
humans, leading to reproductive, developmental, or carcinogenic effects.
There is evidence, however, from the large body of literature concerning
radioactive substances that alpha radiation can affect these processes
in humans (BEIR IV 1988; UNSCEAR 1982) (see Appendix B for additional
information on the biological effects of radiation).
Plutonium exists in several isomeric forms, the most important of
which are plutonium-238 and plutonium-239. When plutonium decays, it
emits primarily alpha particles (ionized helium atoms), except for
plutonium-241 which decays by beta emission. Alpha particles are highly
ionizing and, therefore, damaging, but their penetration into tissue is
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2. HEALTH EFFECTS
slight. Biological damage is limited to cells in the immediate vicinity
of the alpha-emitting radioactive material.
The potential for adverse health effects caused by the plutonium
isotopes is dependent on several factors including solubility,
distribution in the various body organs, the biological retention time
in tissue, the energy of the radioactive emission, and the half-life of
the isotope (EPA 1977). A potential health hazard results when
plutonium is inhaled and deposited in lung tissue or is ingested or
enters the body through wounds. Subsequent translocation of some of the
plutonium from the lungs to tissues and organs distant from the site of
entry results in radiation damage to these tissues as well as to the
lung. For the two most studied isotopes, plutonium-238 and plutonium-
239, radioactive half-life (86 and 24,000 years, respectively) and
biological retention time are very long, resulting in prolonged exposure
of body organs to alpha radiation (EPA 1977). Plutonium isotopes
generally exist as complexes with other elements or compounds (see
Chapter 3 for information on chemical and physical properties of
plutonium and plutonium compounds). Plutonium-238 compounds and certain
plutonium-239 compounds, such as the nitrate forms, are more soluble in
lung tissue than plutonium-239 dioxide. Thus, plutonium-2 39 dioxide
will be retained longer in lung tissue following inhalation than the
more soluble forms, plutonium-238 compounds or plutonium-239 nitrate.
Insoluble plutonium is inhaled as particles. Particle size determines
deposition patterns and consequently, clearance patterns from the lung;
therefore, particle size is directly related to retention and the
resulting radiological dose. These characteristics also affect the
toxicity and target organs of the various isotopes.
Numerous studies have been conducted in laboratory animals to
develop a better understanding of the physiological effects of exposure
to plutonium. These studies have increased our understanding of the
deposition of plutonium in various body organs and of the time of
retention, as well as providing an extensive database on the adverse
health effects of plutonium. The relevant toxicological properties of
plutonium and significant health effects related to exposure to
plutonium are described in this chapter.
2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE
To help public health professionals address the needs of persons
living or working near hazardous waste sites, the data in this section
are organized first by route of exposure -- inhalation, oral, and dermal
-- and then by health effect -- death, systemic, immunological,
neurological, developmental, reproductive, genotoxic, and carcinogenic
effects. These data are discussed in terms of three exposure periods --
acute, intermediate, and chronic.
-------
13
2. HEALTH EFFECTS
Levels of significant exposure for each exposure route and duration
(for which data exist) are presented in tables and illustrated in
figures. The points in the figures showing no-observed-adverse-effect
levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs)
reflect the actual levels of exposure used in the studies. LOAELs have
been classified into "less serious" or "serious" effects. These
distinctions are intended to help the users of the document identify the
levels of exposure at which adverse health effects start to appear,
determine whether or not the intensity of the effects varies with dose
and/or duration, and place into perspective the possible significance of
these effects to human health.
The significance of the exposure levels shown in the tables and
figures may differ depending on the user's perspective. For example,
physicians concerned with the interpretation of clinical findings in
exposed persons or with the identification of persons with the potential
to develop such disease may be interested in levels of exposure
associated with "serious" effects. Public health officials and project
managers concerned with response actions at Superfund sites may want
information on levels of exposure associated with more subtle effects in
humans or animals (LOAEL) or exposure levels below which no adverse
effects (NOAEL) have been observed. Estimates of levels posing minimal
risk to humans (Minimal Risk Levels, MRLs) are of interest to health
professionals and citizens alike.
The activity of radioactive elements has traditionally been
specified in curies (Ci). The curie is approximately 37 billion
disintegrations (decay events) per second (3.7xl010 dps). In discussing
plutonium, a smaller unit, the picocurie (pCi) is used, where 1 pCi is
equal to lxlO'12 Ci. In international usage, the S.I. unit (the
International System of Units) for activity is the Becquerel (Bq), which
is equal to one disintegration per second or about 27 pCi. (Information
for conversion between units is given in Chapter 9 and Appendix B.) In
the text of this profile units expressed in pCi are followed by units in
Bq contained in parentheses. The activity concentration is a
description of the amount of plutonium deposited In lungs after
inhalation exposure or administered to animals by the oral route or by
other routes of exposure rather than an expression of dose. In
radiation biology, the terra dose refers specifically to the amount of
energy imparted by the emitted radiation that is absorbed by a
particular tissue or organ. This dose is expressed in rads (Grays).
2.2.1 Inhalation Exposure
Numerous inhalation studies in rats, mice, hamsters, dogs, and
nonhuman primates have been conducted or are still on-going. In the
majority of these studies, the test animals received a single inhalation
exposure to either plutonium-238 or plutonium-239, administered as the
dioxide, the citrate, or the nitrate. Observation continued, or is
-------
14
2. HEALTH EFFECTS
continuing, for the lifespan of the animals. Among the issues studied
were the comparative toxicity of plutonium-238 and plutonium-239, the
effect of particle size on deposition and expressed toxicity, the effect
of age at first exposure, the target organs and time-course of the
disease process, and the differences in species sensitivity. In each
case, animals were exposed by inhalation to an aerosol of plutonium
particles of different aerodynamic sizes and to different amounts of
radioactivity in the aerosol. Environmental levels (i.e., the amount of
plutonium radioactivity present in the aerosol) were usually not given.
Rather, the amount of plutonium was expressed as a "lung burden" or
"initial alveolar deposition" or "initial lung deposition," i.e., the
total amount of radioactivity retained in the lung after the exposure.
Working from experiment-specific body weights, plutonium deposition
levels in this profile have been expressed as pCi plutonium/kg body
weight. When literature values were expressed as "radioactivity per
gram of lung tissue," these values were also converted to pCi
plutonium/kg body weight if lung weight or ratio of lung weight to body
weight was given. Health effects associated with plutonium deposition,
in units of pCi plutonium/kg body weight, for acute, intermediate, and
chronic exposure duration (for which data exist) are presented in Table
2-1 and illustrated in Figure 2-1.
2.2.1.1 Death
Analyses of mortality among persons chronically exposed to
plutonium in the workplace have been conducted. In the three
occupational cohorts studied (Los Alamos Laboratory, Rocky Flats
facility, and Hanford Plant), there were consistently fewer deaths than
pxnected based on data for United States white males (Gilbert and Marks
1979- Voelz et al. 1983a, 1983b; Wilkinson et al. 1987). This
phenomenon is generally attributed to the "healthy worker effect," which
holds that individuals in the worK lorce are healthier than those in the
general population. However, in f refined cohort from the Rocky Flats
facility, the mortality of plutonium-exposed workers was compared to
that of unexposed workers from the same plant. It was reported that
dPflt-h from all causes was elevated in exposed individuals but the
increase was not statistically significant (Wilkinson et al. 1987).
Statistically signif i-cant 8 in mean survival time in
1-rPAted animals compared to coritro s have been reported in rats, mice,
hamsters, dogs, and baboons £o. .;ngU. acute lnhalatltm
exposure to plutonium-239 or pi it.^Um;238- A single exposure to
plutonium-239 resulting m depon levels ranging from 2.3x10 to
7 2xl06 oCi (8.5xl02 to 2.7xiu m /Kg body weight produced a decrease
in survival time in rats (Metiv « et al. 1986; Sanders et al. 1976,
1988) in mice (Lundgren et ir> hamsters (in the high-dose
group,' males only) (Sanders 197/J. In do^ (Dagle et al. 1988;
Muggenburg et al. 1987a; Park 1 1988) , and in baboons (Metivier et
-------
TABLE 2-1. Health Effects Associated with Plutoniw Deposition - Inhalation
Figure
Key
Species
Exposure
Frequency/ NOAEL
Duration Effect (pCi/kg)
LOAEL (Effect)
Less Serious
(pCi/kg)
Serious
(pCi/kg)
Reference
Chemical
Species
ACUTE EXPOSURE
Death
Rat
Rat
Mouse
Hamster
Dog
Dog
Systemic
7 Rat
8
10
11
12
Rat
Rat
Rat
Mouse
Hamster
Id
Id
30 min
Id
Id
30 min
Id
Id
Id
30 min
Id
Id
30 min
Id
Resp
Resp
Resp
Other
Resp
Id (days) Resp
Other
ldose
30 min
Resp
Other
1.7xl04
2.5x10s
4.9x10 (dec lifespan)
2.5x10® (dec lifespan)
2.1x10® (dec lifespan)
6.2xl03 (dec lifespan)
2.8xl04 (dec lifespan)
1.6x10® (pneumonitis)
1.6x10® (fibrosis)
6.3x10® (pneumonitis)
4.3x10® (inc collagen ct)
3.6xl03 8.4x10® (biochem effects)
8.4x10® (inc lung wt)
Metivier et al.
1986
Sanders et al.
1977
Lundgren et al.
1987
2.1xl04 (dec lifespan) Sanders 1977
1.4x10®
1.4x10® (metaplasia) Sanders 1977
239PuO,
HPuO,
239
Park et al. 1988
Park et al. 1988
Sanders and
Mahaffey 1979
Sanders et al.
1988
Sanders et al.
1977
Metivier et al.
1978a
Talbot and
Moores 1985
PuO,
239PuO,
239PuO,
°PuO,
239PuO,
239PuO,
238PuO„
PuO,
239PuO,
236
5
EC
m
pi
o
H
on
PuO,
-------
Figure
Key Species
Exposure
Frequency/ NOAEL
Duration Effect (pCi/kg)
13 Hamster Id
30 min
14 Dog Id
15 Dog Id
16 Dog Id
17 Dog Id
IS Dog Id
19 Dog Id
Imnunological
20 Mouse Id
21 Hamster Id
22 Dog Id
23 Dog Id
Resp
Other 1.4xl06
Resp
Resp
Hemato
Hepatic
Hemato
Hepatic
Resp
Beaato
Hepatic 4.6x10s
Resp
TABLE 2 1 (continued)
Less Serious
(pCi/kg)
LOAEL (Effect)
Serious
(pCi/kg)
Reference
Chemical
Species
1.4x10 (pneumonitis) Sanders 1977
PuO~
1.0x10s (pneumonitis)
1.3x10 (pneumonitis)
1.3x10s (lymphopenia)
4.4x10s (altered em)
i.lxlO3 (lymphopeni a)
6.1xl03 (inc enzymes)
4.6x10s (pneumonitis)
6.1xlD3 (dec lymphocytes)
1.1x10s (dec resp funct)
Muggenburg et
al. 1987a
Dagle et al.
1988
«9PuO,
239?u(H03)4
Park et al. 1988 238PuO.
Park et el. 1988 239PuO,
Muggenburg et 239PuOz
al. 1988
S3
f
H
a;
m
in
o
H
CO
1.0x10s (fibrosis)
Mewhinney et al. 23®Pu02
1987a
4.5xl04 (dec macrophage)
7.1xl04 (dec Ab form cell)
Hoores et al.
1906
239
PuO,
Bice et al. 1979 Z39PuO,
1.7xl03 (lymphodenopathy) Park et al. 1988 239Pu02
6 1*103 (lymphadenopathy) Park et al. 1988 238PuOz
-------
Figure
Key Species
Exposure
Frequency/ NOAEL
Duration Effect. (pCi/kg)
Cancer
2h Rat Id
30 min
25 Rat Id
26 Rat Id
'27 Dog Id
28 Dog Id
29 Dog Id
30 Dog Id
31 Dog Id
INTERMEDIATE EXPOSURE
Death
32 Mouse 1 yr
bimonthly
33 Hamster lyr 7.1x10*
bimonthly
TABLE 2-1 (continued)
LOAEL (Effect)
Less Serious
(pCi/kg)
Serious
(pCi/kg)
Reference
Chemical
Species
3.1x10* (CEL-lung)
4.3x10* (CEL-lung)
1.7x10* (CEL-lung)
2.3x10* (CEL-skeletal)
l.AxlO3 (CEL-skeletal)
2.1x10* (CEL-lung)
1.9x10* (CEL-liver)
8.7x10* (CEL-lung)
Sanders et al.
1977
Sanders et al.
1988
1986
z38PuO,
239PuO,
Metivier et al. 239PuO,
Dagle et al. Z39Pu(N03>4
1988
Park et al. 1988 z38PuO,
Muggenburg et
239PuO,
al. 1987a
Gillett et al. 238Pu02
1988
Park et al. 1988 239Pu02
s?
5
X
m
m
o
H
CO
4.1x10s (dec lifespan)
Lundgren et al. z39PuOz
1987
Lundgren et al. 239Pu02
1983
-------
TABLE 2-1 (continued)
Figure
Key Species
Exposure
Frequency/ NOAEL
Duration Effect (pCi/kg)
Less Serious
(pCi/kg)
LOAEL (Effects
Serious
(pCi/kg)
Reference
Chemical
Species
Systemic
34 Hamster
1 yr Resp
bimonthly
1.4jc104 (pneumonitis)
Lundgren et al.
1983
z39PuO-
Cancer
35
36
Rat
Mouse
Multiple
1 yr
bimonthly
8.6xl04 (CEL-lung)
1.8x10* (CEL-lung)
Sanders and
Mahaffey 1981
Lundgren et al.
1987
239PuO,
yPuO~
ro
Ab form cell ¦ antibody forming cells; biochem = biochemical; CEL
funct - function; Hemato » hematological; inc - increased; LOAEL "
adverse effect level; Resp ™ respiratory; wt - weight; yr—year
¦ cancer effect level; ct » count; d ~ day;
lowest observed adverse effect level; min ¦
dec ¦ decreased; enz " enzymes;
' minute; NOAEL - no observed
5
X
CI
"1
PI
o
H
00
-------
ACUTE
(< 14 Days)
(pCi/kg)
1.000,000,000
100.000.000
10.000.000
1,000,000
100,000
10,000
1,000
/
/ /
9im
#1Bd
• 1r #17d
• ISd
1«d
>12» •13»
0'2« 0,3»
><*
HOr
3l5d O'W
3l1m
^ 3isd
OZH
~31d
>6d.
~ Sd
Oi'
01,m
Olfid (Jl7d 3lEd
#22ri
(Jzorn
~27d ~aod^!
+28d
2Sr
24f
26r
r Rat
m
d Dog
Key
• LOAELta serious effects (animals)
9 LOAELior less serious sltow (animals)
O NOAEL (animals)
~ CELCancer Effect Level
Ths number next to each point coneepondstoenMee In Table 2-1.
FIGURE 2-1. Health Effects Associated with Plutonium Deposition - Inhalation
-------
INTERMEDIATE
(15-364 Days)
(pCi/kg)
1,000,000.000
100,000,000
10,000,000
1,000,000
100,000
10,000
1,000
/ /
132m
134*
Key
r Rat
m Maun
* Hamtar
# LOAEL lor aarioua eflscti (animals)
O NOAH, (animate)
~ CEL-Canoar Effect Laval
TT» numbar naxt to aacti poM oonaapondi K> antrtaa In TaUa 2-1.
FIGURE 2-1 (Continued)
N>
5
DC
M
•n
m
o
H
in
rntiu
-------
21
2. HEALTH EFFECTS
al. 1974). In all species tested, death occurred within 1 to 3 years
after exposure and was usually caused by radiation pneumonitis
accompanied by edema, fibrosis, and other signs of respiratory damage.
Survival time decreased in a dose-related manner at deposited levels in
excess of approximately 1x10* pCi (3.7xl02 Bq) plutonium-239 dioxide/kg
body weight.
Similar results were observed in animals given a single, acute
inhalation exposure to plutonium-238, as the more soluble dioxide or
nitrate (Mewhinney et al. 1987a; Park et al. 1988; Sanders 1977; Sanders
et al. 1977). Studies in dogs (Park et al. 1988) and hamsters (Sanders
1977) have demonstrated that plutonium-239 was more toxic than
plutonium-238. The primary cause of death in animals treated with
plutonium-238 was also radiation pneumonitis.
Exposure of hamsters for an intermediate duration (once every other
month for a total of seven doses over 12 months) to plutonium-239
dioxide resulted in a statistically significant decrease in median
survival time only in the highest exposure group [at deposition levels
of 3.5xl05 pCi (1.3x10* Bq) plutonium-239/kg body weight] (Lundgren et
al. 1983). Hamsters receiving lower exposures [at deposition levels of
1.4x10'' or 7. 1x10* pCi (5.2xl02 or 2.6xl03 Bq) plutonium-239/kg body
weight] had survival times comparable to controls. Similar exposure of
mice (once every other month for a total of six doses over 10 months) to
plutonium-239 [at deposited levels of 1,8x10*, 8.1x10*, or 4.1xl05 pCi
(6.7xl02, 3.0xl03, or 1.5x10* Bq) plutonium-239/kg body weight] resulted
in statistically significant decreases in survival in all three exposure
groups (Lundgren et al. 1987).
2.2.1.2 Systemic Effects
No studies were Located regarding gastrointestinal, cardiovascular,
renal, or dermal/ocular effects in humans or animals after inhalation
exposure to plutonium.
Respiratory Effects. No studies were located concerning
respiratory effects in humans after inhalation exposure to plutonium.
Radiation pneumonitis, characterized by alveolar edema, fibrosis,
and, in some cases, pulmonary hyperplasia and metaplasia, has been
observed in dogs, mice, rats, hamsters, and baboons following exposure
to high levels of plutonium-239 or plutonium-238 dioxide. In dogs,
radiation pneumonitis and pulmonary fibrosis were two of the primary
causes of death among high-dose groups receiving a lung deposition of
approximately l.OxlO6 pCi (3.7x10* Bq) plutonium-238/kg body weight
(Mewhinney et al. 1987a) or 1.0x10s to 4.6xl05 pCi (3.7xl03 to 1.7x10*
Bq) plutonium-239/kg body weight (Muggenburg et al. 1987a; Park et al.
1988). The time to death was inversely related to the initial lung
-------
22
2. HEALTH EFFECTS
burden; dogs that received approximately 1.0x10s pCi (3.7x10
plutonium-238/kg body weight were dead by 600 days post-exposure, while
those receiving 2.1x10s pCi (7.8xl03 Bq) plutonium-238/kg body weight
survived 1,000 to 2,000 days (Mewhinney et al. 1987a). In dogs _ neither
the size of the particles (Muggenburg et al. 1987a) nor the age Df the
animal at initiation of treatment (Guilmette et al. 1987, uggenburg et
al 1987b) altered the course of the respiratory effects. The pattern
of disease in dogs 8 to 10 years old (Muggenburg et al. 1987b) and
immature dogs (Guilmette et al. 1987) was similar to that seen in young
adult dogs, that is, radiation pneumonitis occurred in the high-exposure
groups resulting in shortened survival times. Lung carcinomas were
observed in lower exposure groups in which dogs survived for a longer
period of time (see Section 2.2.1.8 Cancer and Table 2-1)-
Rats also developed radiation pneumonitis within 12 months after a
single exposure that resulted in a deposited level of approximately
1 6xl06 pCi (5.9x10* Bq) plutonium-239/kg body weight (Sanders and
Mahaffey 1979). However, in another study, temporarily increased
collagen deposition, but not pneumonitis, occurred in rats following
deposition of 2.8xl03 to 2.7xl06 pCi (1.0xl0z to 1.0x10s Bq) plutonium-
239/kg body weight (Metivier et al. 1978a). Radiation pneumonitis and
fibrosis were the major pathological findings and causes of death in
male hamsters at deposited levels of 1.4x10 pCi (5.2x10 Bq) plutonium-
239/kg body weight (Sanders 1977) or 1.7x10 pCi (6.3x10* Bq) plutonium-
238/kg body weight (Mewhinney et al. 1986).
Baboons and monkeys displayed a respiratory disease pattern similar
to that seen in dogs and rodents. Some baboons died of radiation
pneumonitis accompanied by pulmonary edema within 50 days after a single
exposure to plutonium-239 dioxide at deposited levels of 2.88xl05 to
7.2x10* pCi (1.1x10* to 2.7x10s Bq)/kg body weight (Metivier at al.
1974; 1978b). Radiation pneumonitis and pulmonary fibrosis were also
seen in Rhesus monkeys exposed to plutonium dioxide at deposited levels
of 3.4x10* to 2.3xl05 pCi <1.3xl03 to 8.5x10 Bq)/kg body weight (Hahn et
al. 1984; LaBauve et al. 1980). Death from pulmonary fibrosis occurred
in Rhesus monkeys following lung deposition of 3.4x10* pCi (1.3xl03 Bq)
plutonium-239 dioxide/kg body weight (Ha n et al. 1984).
At levels below those that caused acute radiation pneumonitis,
chronic alpha irradiation of lung tissue rom the deposited plutonium
produced interstitial fibrosis. The terminal stage of
pneumonitis/fibrosis was characterized by an increased respiratory rate
and decreased pulmonary compliance. Th® Cardiopuln>onary function of
some of the dogs in the study by Mugg«n urg et al. (1986) was studied
further (Muggenburg et al. 1988). Pulm°^ dysfu»ction was observed in
these animals and appeared to be a chr° *orm radiation pneumonitis
or pulmonary fibrosis. The authors not chat this chronic lung injury
occurred at lower doses or after a ency period and, unlike the
radiation pneumonitis that was fatal to gs usually within 1-2 years,
-------
23
2. HEALTH EFFECTS
occurred over the same time period and same doses as the pulmonary
carcinoma.
Exposure of hamsters to plutonium-239 dioxide [at tissue deposition
levels of 1.4x10*. 7.1x10*, or 3.5xl05 pCi (5.2xl02, 2.6xl0\ or 1.3x10*
Bq) plutonium-239/kg body weight, once every other month for a total of
seven doses over 12 months] resulted in several respiratory effects over
lifetime observation (Lundgren et al. 1983). Radiation pneumonitis was
observed at all dose levels. Bronchiolar hyperplasia was seen in all
groups, including controls, but incidences were statistically
significantly increased over controls only in the highest dose group.
The highest dose group also showed a statistically significant increase
in alveolar squamous metaplasia (Lundgren et al. 1983).
In a similar experiment, mice were exposed (once every other month
for a total of six doses over 10 months) to plutonium-239 dioxide
resulting in deposition levels ranging from 1.8x10* to 4.1xl05 pCi
(6.7xl02 to 1.5x10* Bq) plutonium-239/kg body weight, and were observed
for life (Lundgren et al. 1987). Radiation pneumonitis and fibrosis
were seen only in the highest dose group. However, the incidence of
bronchial hyperplasia was statistically significant in the mid- and
high-dose groups [at deposition levels of 8.1x10* or 4.1xl05 pCi
(3.0xl03 or 1.5x10* Bq) plutonium-239/kg body weight]. The highest
NOAEL values and all reliable LOAEL values for respiratory effects in
each species and duration category are recorded in Table 2-1 and plotted
in Figure 2-1.
Hematological Effects. No studies were located regarding
hematological effects in humans after inhalation exposure to plutonium.
In on-going studies in dogs (Dagle et al. 1988; Park et al. 1988;
Ragan et al. 1986) the earliest observed biological effect was in the
hematopoietic system. Aerosols of plutonium-239 or plutonium-238, as
the dioxide (Park et al. 1988), or plutonium-239 nitrate (Dagle et al.
1988) were each administered at six treatment levels. With plutonium-
239 or plutonium-238, as the dioxide, lymphopenia occurred in the four
highest exposure groups [at deposited levels of approximately 6.1xl03 to
4.6xl05 pCi (2.3xl02 to 1,7x10* Bq) plutonium/kg body weight] (Park et
al. 1988), but only in the two highest dose groups with plutonium-239
nitrate [1.3xl05 to 4.3xl05 pCi (4.8xl03 to 1.6x10* Bq) plutonium-239
nitrate/kg body weight] (Ragan et al. 1986). The lymphopenia was dose-
related and correlated both in magnitude and time of appearance post-
exposure with the initial lung burden for each plutonium isotope, The
highest NOAEL values and all reliable LOAEL values for hematological
effects in each species and duration category are recorded in Table 2-1
and plotted in Figure 2-1. .
-------
24
2. HEALTH EFFECTS
Hepatic Effects. No studies were located regarding hepatic effects
in humans after inhalation exposure to plutonium.
In a study by Dagle et al. (1988), increases in liver enzymes
occurred in dogs after a single exposure that resulted in deposition
levels above 4.4xl05 pCi (1.6xl02 Bq) plutonium-239 nitrate/kg body
weight, compared to untreated controls. In dogs, 4 to 13 years
following a single inhalation exposure to plutonium-239 dioxide [at
deposited lung tissue levels of 2.4x10* to 8.7x10'' pCi (8.9xl02 to
3.2xl03 Bq) plutonium-239/kg body weight] the livers were congested,
granular, and pigmented (Park et al. 1988).
Exposure of Syrian hamsters to plutonium-239 dioxide (once every
other month for a total of seven doses over 12 months) resulted in a
statistically significant Increase in degenerative liver lesions in the
highest exposure group [at deposition levels of 3.5x10s pCi (l^xlO11 Bq)
plutonium-239/kg body weight] (Lundgren et al. 1983). These lesions
included degeneration, necrosis, fibrosis, and amyloidosis. However,
Lundgren stated that the lesions observed in these hamsters were typical
of those usually seen in aged Syrian hamsters. Hamsters receiving lower
levels of deposited radioactivity [1.4x10* or 7.1x10'' pCi (5.2xl02 or
2.6xl03 Bq) plutonium-239/kg body weight] exhibited nonsignificant
increases in liver lesions.
Musculoskeletal Effects. No studies were located regarding
musculoskeletal effects in humans after inhalation exposure to
plutonium.
Investigations of the radiation effects of plutonium in laboratory
animals indicated that translocation of plutonium from the lungs to
other tissues was dependent on several factors including the solubility
of the plutonium isotope or compound. Translocation to the bone
occurred with plutonium citrate and with plutonium nitrate (Bair et al.
1973). By 4,000 days post-exposure, osseous atrophy and radiation
osteodystrophy occurred in dogs given a single inhalation exposure to
plutonium-238 dioxide (Gillett et al. 1988). The dose which resulted in
these specific effects was not reported. For further discussion of this
study see Section 2.2.1.8.
2.2.1.3 Immunological Effects
No studies were located regarding the immunological effects in
humans after inhalation exposure to plutonium.
Plutonium-239 was transported to the tracheobronchial and
mediastinal lymph nodes where it concentrated with time, often reaching
higher levels in the lymph nodes than in the lungs (Bair et al. 1973).
Lymphadenopathy was associated with a high concentration of plutonium in
-------
25
2. HEALTH EFFECTS
the thoracic and hepatic lymph nodes of dogs at lung tissue deposition
levels as low as 1.7xl03 pCi (6.3X101 Bq) plutonium-239 dioxide/kg body
weight or 6.lxlO3 pCi (2.3xl02 Bq) plutonium-238 dioxide/kg body weight
(Park et al. 1988). Radiation-related effects in dogs included atrophy
and fibrosis of the tracheobronchial lymph nodes (Gillett et al. 1988).
Decreases in pulmonary alveolar macrophages in mice (Moores et al. 1986)
and depressed-antibody-forming cells in hamsters (Bice et al. 1979) were
reported. In addition, decreases in primary antibody responses in dogs
(Morris and Winn 1978) were also reported. The highest NOAEL values and
all reliable LOAEL values for immunological effects in each species and
duration category are recorded in Table 2-1 and plotted in Figure 2-1.
No studies were located regarding the following effects in humans or
animals after inhalation exposure to plutonium.
2.2.1.4 Neurological Effects
2.2.1.5 Developmental Effects
2.2.1.6 Reproductive Effects
2.2.1.7 Genotoxic Effects
Epidemiological studies have thus far been limited and have not
established conclusively a direct association between plutonium exposure
by the inhalation route and increases in genetic effects. A dose-
related increase in chromosomal aberrations was observed among 343
plutonium-exposed workers at the Rocky Flats facility. In this group,
systemic and lung plutonium burdens of 18.6 to 571.4 pCi (0.69 to 21.2
Bq) plutonium/kg body weight were estimated based on urine analyses and
lung deposition estimates (Brandom et al. 1979). Because the
frequencies of aberrations were relatively low and the dose estimates
imprecise, the authors advised caution regarding use of the data. A
study of blood lymphocyte chromosomes of 54 plutonium workers in the
United Kingdom was conducted by Tawn et al. (1985). (This study is a
continuation of that reported in Schofield (1980).) Systemic body
burdens of 114 to >570.8 pCi (4.3 to >21.1 Bq) plutonium/kg body weight
were estimated based on urine analyses. While some differences in the
distribution of aberrations were seen in the radiation exposed groups,
the authors concluded that significant deposits of plutonium did not
cause an increase in aberrations. In other studies, Manhattan Project
plutonium workers (26 individuals) were followed for 27 to 32 years; no
apparent correlation was observed between the frequency of chromosomal
aberrations and plutonium body burdens [71.4 to 3.1xl03 pCi (2.6 to
114.8 Bq) plutonium/kg body weight based on urine analyses] (Hempelmann
et al. 1973; Voelz et al. 1979).
Chromosomal aberrations were observed in Rhesus monkeys and Chinese
hamsters following inhalation exposure to plutonium. Increases in
-------
26
2. HEALTH EFFECTS
chromosomal aberrations in blood lymphocytes were seen in immature
Rhesus monkeys in the high-exposure groups exposed for a single day to
plutonium-239 dioxide [deposited levels of 5x10* to 5x10s pCi (1.9X103
to 1.9xl04 Bq) plutonium-239 dioxide/kg body weight] at 1 and 3 months
post-exposure, but not at lower levels (LaBauve et al. 1980). Dose-
related increases in the frequency of chromosomal aberrations were
observed in Chinese hamster blood cells 30 days after exposure of the
animals to plutonium at deposited levels of lxlO7 to 2.6xl08 pCi
(3.7xl05 to 9.6x10s Bq) plutonium-239 dioxide/g of lung tissue (Brooks
et al. 1976a).
2.2.1.8 Cancer
Epidemiological studies of occupational cohorts exposed to plutonium
have been conducted at two plutonium processing plants, the Los Alamos
National Laboratory and the Rocky Flats Nuclear Weapons Plant. a causal
link between plutonium exposure and cancer has not been demonstrated in
these studies, although there are some suggestions of effects. a
prospective mortality study was begun in 1952 on a group of 26 subjects
who worked with plutonium at Los Alamos Laboratory during World War II
in the Manhattan Project. They have now been studied for 37 years
(Voelz et al. 1985). Follow-up has included extensive medical
examinations and urine analyses to estimate plutonium body burdens
which showed systemic plutonium deposition ranging from 2,000 to 95 000
pCi (74 to 3,500 Bq) plutonium with a mean of 26,000 pCi (9.6xl02 Bq)
plutonium. Mortality in this group as compared to that of United States
white males in the general population was significantly less than
expected (2.0 vs. 6.6). In addition, no malignant neoplasms have
occurred during this extensive period of follow-up. Despite the fact
that this study involves only a small number of individuals, it provides
information about those who have encountered relatively high plutonium
exposures (resulting in deposition of up to 95,000 pCi) and have been
followed over a considerable length of time, a study of an additional
cohort of 224 Los Alamos male workers was begun in 1974 (Voelz et al.
1983a). Average whole body deposition was estimated at 19,000 pCi (700
Bq) plutonium. Mortality, adjusted for age and year of death, was
compared to that of United States males in the general population.
Among the cohort, 43 deaths were observed as compared to 77 expected.
The number of deaths due to malignant neoplasms among the cohort was
also considerably lower than expected (8 vs. 15) including only one lung
cancer death vs. five expected.
The studies at the Rocky Flats facility consisted of mortality
studies of workers at the plant (Voelz et al 1983b; Wilkinson et al.
1987) and a study of residents living downwind from the facility
(Johnson 1981, 1988). Voelz et al. (1983b) reported the results of a
study of 7,112 workers employed at the Rocky Flats facility during 1952-
1979. Observed deaths were significantly lower than expected (452 vs.
831). Malignant neoplasms were also lower than expected (107 vs. 167).
-------
27
2. HEALTH EFFECTS
In a re-analysis of the same Rocky Flats cohort, Wilkinson et al.
(1987) investigated mortality patterns among those employed at the
facility for at least 2 years. This reduced the cohort size to 5,413
white males. Comparisons of mortality through 1979 were made with
expected mortality for United States males in the general population.
In addition, employees were ranked according to plutonium body burden,
estimated by urinalyses, as either less than 2,000 pCi (74 Bq) or
greater than 2,000 pCi (74 Bq) plutonium body burden. Comparisons were
made between these two exposure groups. When the cohort with at least 2
years of employment was compared to United States white males, the
observed mortality was less than expected. However, the incidences of
benign and unspecified neoplasms were greater than expected. These
conclusions regarding mortality are in complete agreement with Voelz et
al. (1983b). However, when the cohort reported by Wilkinson et al.
(1987) was categorized by exposure [less than or greater than 2,000 pCi
(74 Bq)] and the two groups compared, it was reported that the group
with greater exposure had slightly elevated risk for mortality from all
causes of death and from all lymphopoietic neoplasms (Wilkinson et al.
1987). However, the mortality ratios for lung, bone, and liver cancer
were not elevated. The authors cautioned that comparisons between the
two exposure groups were often based on small numbers of cases, so the
precision of these observations is low. There were only four cases of
cancers classified as lymphopoietic neoplasms. In addition, they
suggested that the results could have been confounded by external
radiation exposure (from working in the plutonium facility) or by
potential interaction between plutonium radiation and external
radiation.
A study of cancer mortality for 1969-1971 in residents near the
Rocky Flats facility indicated a somewhat higher incidence than normal
for all cancers in individuals living in the areas contaminated with
plutonium (Johnson 1981). Tumors of the gonads (testes and ovaries),
liver, pancreas, and brain contributed to the higher incidence, whereas
the incidences of lung and bone tumors, frequently observed in
laboratory animal studies, were not elevated. In a re-analysis of the
1969-1971 data, as well as cancer mortality in 1979-1981 (a more
appropriate cancer latency period for the Rocky Flats area
contamination), Crump et al. (1987) did not find an increase in the
likelihood of developing cancer for those living near the Rocky Flats
facility. Crump et al. (1987) attributed the findings of Johnson (1981)
to the lack of consideration of confounding urban factors in the design
of the study.
Case control studies have been conducted to evaluate the incidence
of brain tumors and melanomas, in order to examine the potential
associations with plutonium exposure. The study of brain tumors at the
Rocky Flats facility and melanomas at Los Alamos did not reveal an
association of either disorder with plutonium exposure (Reyes et al.
1983; Acquavella et al. 1983a).
-------
28
2. HEALTH EFFECTS
Two epidemiology studies have been conducted on a cohort of workers
at the Hanford Plant, which produced plutonium in nuclear reactors.
Because plutonium exposure was minimal, the studies primarily related to
external radiation. Radiation work at Hanford includes reactor
operation, chemical separation, fuel fabrication, and research. The
radiation is primarily gamma, but also includes neutron, X-radiation,
and tritium exposure (Gilbert and Marks 1979) . Exposure levels of
plutonium were not reported and individuals with plutonium body burdens
comprised less than 3% of the cohort. In one study, a cohort of 12,500
white male workers employed at the Hanford Plant for at least 2 years
was analyzed for mortality as well as cause of death (Gilbert and Marks
1979). The mean dose was reported to be 4.75 rem. Mortality from all
causes was significantly less than that of United States white males.
Death from malignant neoplasms of the pancreas and multiple myeloma
occurred at rates higher than expected; deaths from these causes
occurred in the group with a dose greater than 15 rem. This correlation
was based on a small number of deaths (three each for cancer of the
pancreas and multiple myeloma vs. 1 and 0.5 expected, respectively);
however, only the increase in the incidence of multiple myeloma was
statistically significant.
In a re-evaluation of the Hanford cohort, which included
approximately 28,000 male and female workers, Kneale et al. (1981)
detected a significant increase in the cancers in radiosensitive tissues
in workers exposed to external radiation. Radiosensitive tissues
grouped together in their analyses included cancers of the stomach,
large intestine, pancreas, pharynx, lung, breast, reticuloendothelial
system (lymphoma, myeloma, myeloid leukemia and others), and thyroid.
Approximately 50% of these cancers were in the lung; however, smoking
histories were not considered in the analysis. Of the male population,
only 3% or 225 men had definite evidence of internal radiation. Due to
this fact the authors stated that they could safely assume that the
incidence of cancer from internal radiation was small compared with that
associated with external radi-ation.
Studies have indicated that plutonium is a lung, skeletal, and liver
carcinogen in animals depending on its chemical form, route of exposure
and species. Inhaled plutonium- 39 dioxide is insoluble and is retained
primarily in the lungs and assoc ated lymph nodes (Muggenburg et al
1987a; Park et al. 1988). Inhaled plutonium-238 is solubilized and is
subsequently translocated from e lung to the bone and liver (Gillett
et al. 1988). While the pattern of nonmalignant toxicity among the
laboratory species tested was sJ^Ur (i.e., radiation pneumonitis and
pulmonary fibrosis occurred n e higher radiation dose groups in all
species tested), species di erences in the induction of cancer were
apparent. With the exception o Syrian hamsters, cancer developed in
animals in the lower exposure groups or anjma^s that survived initial
radiation damage to the lungs.
-------
29
2. HEALTH EFFECTS
Experiments in dogs have provided the most extensive database on
radiation-induced cancer following inhalation exposure to plutonium.
The most frequently observed cancer in dogs treated with plutonium-239
dioxide was lung cancer. The majority of lung tumors in dogs were
bronchiolar-alveolar carcinomas. In dogs treated with plutonium-238 or
the more soluble forms of plutonium-239, such as the nitrate, plutonium
translocates from the lungs to other sites, where liver and bone tumors,
in addition to lung tumors, have been reported.
Lung tumors were the primary cause of death in dogs exposed to
plutonium-239 dioxide at an initial lung deposition as low as 2.1xl04
pCi (7.8xl02 Bq) plutonium-239/kg body weight (Muggenburg et al. 1987a;
Park et al. 1988). In the study by Park et al. (1988), early deaths
among dogs in the highest dose group receiving plutonium-239 resulted
from radiation pneumonitis accompanied by respiratory dysfunction,
fibrosis, focal hyperplasia, and metaplasia. Increases in the incidence
of lung cancer were statistically significant at three lower doses of
6.2xl03 pCi/kg (2.3xl02 Bq/kg), 2.4x10* pCi/kg (8.9 Bq/kg), and at
8.7xlOA pCi/kg (3.2xl03 Bq/kg)/kg body weight. The first lung tumor was
found in a dog that died 37 months following exposure; ultimately, after
16 years post-exposure, 55 of the 136 dogs had lung tumors.
With exposure to plutonium-238 dioxide, the primary cause of cancer
deaths was osteosarcomas rather than lung tumors. However, lung tumors
frequently developed in dogs given a single inhalation exposure to
plutonium-238 dioxide resulting in lung deposition levels as low as
1.4xl03 pCi (5.2X101 Bq) plutonium-238/kg body weight (Gillett et al.
1988; Park et al. 1988). In the on-going study by Gillett et al.
(1988), of 144 dogs at the beginning of the experiment, 112 died by day
4,000 post-exposure; of these, 100 had osteosarcomas and 28 had lung
cancer. With increasing time after exposure, liver lesions increased in
severity, with the first liver tumor observed after 3,000 days; the
occurrence of primary liver tumors after Inhalation exposure to
plutonium-238 had not been reported previously.
Osteosarcomas were the principal cause of death among dogs given a
single inhalation exposure resulting in deposited levels of 2.3xl04 to
1.3xl05 pCi (8.5xl02 to 4.8xl03 Bq) plutonium-239 nitrate/kg body
weight, although some lung tumors were observed (Dagle et al. 1988).
All dogs in the highest exposure group [4.2xl05 pCi (1.6x10* Bq)
plutonium-239 nitrate/kg body weight] died of radiation pneumonitis.
Cancer mortality in the three lowest exposure groups were comparable to
controls.
Statistically significant increases in lung cancer have been
reported in rats with lung deposition levels of 3.1x10'' pCi (l.lxlO3 Bq)
plutonium-238/kg body weight (Sanders et al. 1977) or greater than 3x10*
pCi (l.lxlO3 Bq) plutonium-239/kg body weight (Sanders and Mahaffey
1979; Sanders et al. 1988). While pulmonary tumors in mice exposed to
-------
30
2. HEALTH EFFECTS
plutonium-239 dioxide increased with increasing initial lung deposition,
the incidence of lung tumors in any treated group was not statistically
significantly different from the untreated controls (Lundgren et al.
1987) .
The pulmonary toxicity of plutonium-239 dioxide in Rhesus monkeys
and baboons was similar to that of other species; however, they appear
to be less sensitive to radiation-induced lung tumors than dogs and
rats. A primary lung tumor occurred in one of nine Rhesus monkeys that
survived for 9 years post-treatment (Hahn et al. 1984). Two of 32
baboons developed lung tumors (Metivier et al. 1974) at deposition
levels of 2. 88xl05 to 7 . 2xl06 pCi (1.06x10'' to 2.67xl05 Bq) plutonium-239
dioxide/kg body weight; these deposition levels are comparable to those
that resulted in lung tumors in dogs.
Syrian hamsters appear to be resistant to lung tumor induction
following inhalation of plutonium-239 or plutonium-238 particles.
Hamsters were also resistent to radiation-induced lung cancer following
exposure to other alpha-emitting radionuclides, such as radon and radon
daughters (ATSDR 1990). No statistically significant increases in tumor
incidence occurred in lifetime studies in hamsters that had received a
single inhalation exposure to plutonium-238 dioxide or plutonium-239
dioxide at lung deposition levels of approximately 1.4xl06 to 1.7xl06
pCi (5.2x10* to 6.3x10* Bq) plutonium-238/kg body weight (Mewhinney et
al. 1987a; Sanders 1977) or 1.4xl06 pCi (5.2x10'' Bq) plutonium-239/kg
body weight (Sanders 1977).
Exposure of Syrian hamsters for an intermediate duration (once
every other month for a total of seven doses over 12 months) to
plutonium-239 dioxide, at deposited levels of 1.4x10'', 7.1x10'', or
3.5xl05 pCi (5.2xl0z, 2.6xl03, or l-SxlO* Bq) plutonium/kg body weight,
resulted in several respiratory effects (see Section 2.2.1.2), but no
lung tumors were observed in this study (Lundgren et al. 1983). The
authors stated that the Syrian hamster may be an inappropriate animal
model for lung cancer induction with alpha emitters.
Exposure of mice to plutonium-239 dioxide for an intermediate
duration (once every other month for a total of six doses over 10
months) at deposited levels of 1. 8xl0\ 8.1xl04, or 4.1xl05 pCi (6.7xl02,
3.0xl03, or 1.5xl04 Bq) plutonium-239/kg body weight resulted in
significant lung tumor development in the two lower dose groups
(Lundgren et al. 1987). Early mortality precluded tumor development in
the highest dose group. Pulmonary tumors (adenomas and adenocarcinomas)
were seen in less than 2% of controls but in 13% of low-dose animals and
18% of mid-dose animals.
In a study designed to investigate the effect of temporal dose-
distribution, rats were exposed to Plutonium-239 dioxide once a month
for 3 months with lung depositi°n levels totaling 8.6x10'' pCi (3.2xl03
-------
31
2. HEALTH EFFECTS
Bq) plutonium-239/kg body weight, or once a week (for up to 22 weeks)
with lung deposition totaling 1.3xl05 to 4.0xl05 pCi (4.8xl03 to 1.5xlOA
Bq) plutonium-239/kg body weight (Sanders and Mahaffey 1981) . Lung
tumor occurrence ranged from 19 to 60% in treated animals with tumors
primarily categorized as adenocarcinomas and squamous carcinomas. No
significant difference in lung tumor incidence was observed in mice
exposed once a week versus mice exposed once a month for 3 months.
Based on total alveolar deposition, a dose-dependent increase in the
incidence of all lung tumors was observed. Untreated controls were
included in the study, but tumor incidence for these animals was not
reported.
2.2.2 Oral Exposure
Exposure by the oral route may occur; however, absorption of
plutonium from the gastrointestinal tract appears to be limited (see
Section 2.3). Health effects associated with oral exposure to plutonium
are presented in Table 2-2 and Figure 2-2.
2.2.2.1 Death
No studies were located regarding death or lifespan shortening in
humans after oral exposure to plutonium.
Neonatal rats were given 3.3xl08 pCi (1.2xl07 Bq) plutonium-238
citrate/kg body weight by gavage (Fritsch et al. 1987). This single
exposure to plutonium resulted in the death of 45% of the treated
animals by 2 weeks post-exposure. No deaths were reported in groups
given lxlO5 pCi (3.7xl03 Bq) plutonium-238/kg (Fritsch et al. 1987).
2.2.2.2 Systemic Effects
No studies were located regarding respiratory, cardiovascular,
hematological, musculoskeletal, hepatic, renal, or dermal/ocular effects
in humans or animals after oral exposure to plutonium.
Gastrointestinal Effects. No studies were located regarding
gastrointestinal effects in humans after oral exposure to plutonium.
Gastrointestinal effects were observed in neonatal rats following
administration by gavage of lxlO5 or 3.3x10® pCi (3.7xl03 or 1.2xl07 Bq)
plutonium-238 citrate/kg body weight (Fritsch et al. 1987). In the
lower treatment group, mild hypertrophy of the crypts of the small
intestine, which form the secretions of the small intestine, was
observed 11 days post-exposure. Total disappearance of epithelial cells
and crypts, combined with intestinal hemorrhaging, was observed in the
higher treatment group, also sacrificed at 11 days. However, neonatal
rodents have immature and poorly enclosed crypts in the small intestine,
-------
TABLE 2-2. Levels of Significant Exposure to Plutonian - Oral
Exposure
Figure Frequency/
Key Species Duration
NOAEL
Effect (pCi/kg)
LOAEL (Effect)
Less Serious
(pCi/kg)
Serious
(pCi/kg)
Reference
Chemical
Species
ACUTE EXPOSURE
Death
Rat
(G) Id
l.OxlO5
3.0xl08
Fritsch et al.
1967
238Pu citrate
Systemic
fo
2 Rat (G) Id Gastro 1.6xlOn (path change) Sullivan et al. z39Pu02
1960 x
PI
3 Rat (G) Id Gastro 1.0x10s (hypertrophy) 3.3xl08 (intestinal Fritsch et al. 238Pu citrate [S
heroor) 1987 H w
Other 1.0x10s 3.3x10s (growth
inhibit) 2
^
Pi
n
d ~ day; (G) * gavage; Gastro 88 gastrointestinal; hemor * hemorrhaging; inhibit = inhibition; LOAEL * lowest observed adverse effect level; ^
NOAEL * no observed adverse effect level; path = pathological w
-------
(pCi/kg)
1,000,000,000.000
100,000,000,000
10,000,000,000
1,000,000,000
100,000,000
10,000,000
1,000,000
100,000
ACUTE
(<14 Days)
32r
•3r
r
(-3
SC
PI
~rl
TI
PI
n
H
cn
UJ
LO
Olr ®3' C)3r
Key
^al 0 LOAEL for serious effects (animals)
9 U3AEL tor less serious effects (animals)
O NOAEL (animals)
The number next to each point corresponds to entries in Table 2-2.
FIGURE 2-2. Health Effects Associated with Plutonium Deposition - Oral
00114-3
-------
34
2. HEALTH EFFECTS
which is the main site of plutonium retention following c>ral exposure
(see Section 2.3.2.4), as compared to other neonatal mammals.
Therefore, neonatal rats could be expected to be more sensitive to the
radiologic effects of plutonium than other neonates or adult mammals
(Fritsch et al. 1987). Gastrointestinal effects have also been observed
in adult rats given 1.6xlOi: pCi (5.7xl09 Bq) plutonium-239 dioxide/kg
body weight. At 3 days post-exposure, there was an increase in
neutrophils on the surface epithelium and superficial cellular layers of
the large intestine (Sullivan et al. 1960). At 6 days post - exposure
this increase was no longer observed.
Other Systemic Effects. No studies were located regarding other
effects in humans or animals after oral exposure to plutonium.
No studies were located regarding the following health effects in
humans or animals after oral exposure to plutonium.
2.2.2.3 Immunological Effects
2.2.2.4 Neurological Effects
2.2.2.5 Developmental Effects
2.2.2.6 Reproductive Effects
2.2.2.7 Genotoxic Effects
2.2.2.8 Cancer
2.2.3 Dermal Exposure
2.2.3.1 Death
No studies were located regarding death or the shortening of
lifespan in humans or animals after dermal exposure to plutonium.
2.2.3.2 Systemic Effects
No studies were located regarding respiratory, cardiovascular,
gastrointestinal, hematological, musculoskeletal, hepatic, renal, or
dermal/ocular effects in humans or animals after dermal exposure to
plutonium.
No studies were located regarding the following health effects in
humans or animals foll°wln£ dermal exposure to plutonium.
-------
35
2. HEALTH EFFECTS
2.2.3.3 Immunological Effects
2.2.3.4 Neurological Effects
2.2.3.5 Developmental Effects
2.2.3.6 Reproductive Effects
2.2.3.7 Genotoxic Effects
2.2.3.8 Cancer
2.2.4 Other Routes of Exposure
Health effects associated with plutonium administered by injection
are presented in Table 2-3 and Figure 2-3.
2.2.4.1 Death
No studies were located regarding death or lifespan shortening in
humans after exposure to plutonium by other routes.
A significant decrease in lifespan was observed in rats, mice, and
hamsters following a single injection of plutonium-239 at concentrations
ranging from 2xl05 to 7.5xl07 pCi (7.4xl03 to 2.8xl06 Bq) plutonium-
239/kg body weight given as the citrate (intravenous) or dioxide
(intraperitoneal) (Ballou et al. 1967; Brooks et al. 1983; Sanders
1973a; Svoboda et al. 1980a, 1980b). Survival times decreased with
increasing doses in rats and hamsters (Brooks et al. 1983; Sanders
1973a). Death resulted from bone marrow hypoplasia in hamsters
approximately 400 days following an intravenous exposure [2xl07 pCi
(7.4xl05 Bq) plutonium-239 citrate/kg body weight] (Brooks et al. 1982).
In rats injected intraperitoneally at concentrations up to 8.3x10s pCi
(3.1xlQ5 Bq) plutonium-239 dioxide/kg body weight, death resulted mainly
from large malignant abdominal tumors accompanied by hemorrhage - induced
anemia approximately 350 to 580 days post-exposure (Sanders 1973a).
An age-dependent effect on lethality was observed in rats injected
intravenously with 6xl06 to 9xl07 pCi (2.2xl05 to 3,3xl06 Bq) plutonium-
239/kg body weight as the monoraeric (citrate) or polymeric (nitrate)
forms (Mahlum and Sikov 1974). Neonates were more susceptible to the
lethal effects of the monomeric form of plutonium-239, while adults and
weanlings were more susceptible to the polymeric form.
Animal studies indicate that the polymeric (nitrate) forms of
plutonium-239 and plutonium-238 are more acutely toxic than the
corresponding monomeric (citrate) forms (see Section 2.3.2.4). In rats,
30-day LD50s for the monomeric [9.7xl07 pCi (3.6xl06 Bq)/kg] and
-------
TABLE 2-3. Health Effects Associated with Plutoniu Aifainistration - Other Routes of Exposure
Figure
Key
Species
Exposure
Frequency/
Duration
NOAEL Less Serious
Effect (pCi/kg) (pCi/kg)
LOAEL (Effect)
Serious
(pCi/kg)
Reference
Chemical
Species
ACUTE EXPOSURE
Death
1 Rat
Rat
(IV) Id
(IV) Id
B
Rat (IV) Id
Rat (IV) Id
Rat (IV) Id
Rat (IV) Id
Mouse (IV) Id
Hamster (IV) Id
Systemic
9 Human (IV) Id
10 Rat (IP) Id
11 Rat (IV) Id
12
Rat (IV) Id
1.3x10®
Hemato 7.3xl03
Resp 8,3xl06
Musc/skel
Hemato
Hepatic
Ballou et al.
1967
9.7xl07 (30 day LD50) Mahlum and Sikov
1974
9.8xl07 (30 day LD50) Mahlum and Sikov
1969a
1.6*10® (30 day LD5Q) Mahlum and Sikov
1969a
4.7xl07 (30 day LD50) Mahlum and Sikov
1974
7.9xl07 (dec lifespan) Ballou et al.
1967
4.9*10® (dec lifespan) Svoboda et al.
1980a
2.0xl06 (dec lifespan) Brooks et al.
1983
Langham et al.
1980
Sanders 1975a
230Pu citrate
239Pu citrate
238Pu nitrate
238Pu citrate
239Pu nitrate
239Pu citrate
239Pu citrate
239Pu citrate
«8Pu or 239Pu
citrate
239PuO„
1.8xl07 (dec break
strength)
3.6*107 (dec WBC 4
RBC count)
7.5*107 (liver damage)
Sikov and Mahlum 239Pu citrate
1976
Ballou et al.
1967
23®Pu citrate
3=
W
>
5
K
m
ra
n
H
C/i
-------
TAHt.B 2~3 (continued)
Exposure
Figure Frequency/
Key Species Duration
NOAEL Less Serious
Effect (pCi/kg) (pCi/kg)
LOAEL (Effect)
Serious
(pCi/kg)
Reference
Chemical
Species
13
14
15
16
17
IS
19
20
21
Rat (IP) Id
Mouse (IV) Id
Hamster (IV) Id
Dog (IV) Id
Dog (SB) Id
Dog
Dog
Dog
Dog
(IV) Id
(IV) Id
(IV) Id
(IV) Id
(SB) Id
Resp
Hemato
Hemato
Hepatic
Musc/skel 3.0x10s
Derm/oc
Hemato 9.0x10s
Musc/skel 1.0x10s
Hepatic
Hepatic 6.3xl0z 1.9xl03 (nodules)
Immunological
22 Dog
Developmental
23 Rabbit (IV) 9,15,27,9
15-28 Gd
2.0x10s (pneumonitis) Sanders 1973a
8.2x10® (lymphopenia)
3.6x10s (dec stem cells) Svoboda et al.
1987
2.0x10® (hep degener) Benjamin et al.
1976
1.0x10s (fractures)
9.8xl04 (scarring)
2.9x10® (dec
Taylor et al.
1962
Dagle et al.
1984
PuOz
239Pu citrate
"9Pu citrate
239Pu citrate
239Pu nitrate
Dougherty and 239Pu citrate
lymphocytes) Rosenblatt 1971
Bruenger et al. 239Pu citrate
1978
3.0x10® (func impair) Cochran et al,
1962
Taylor et al.
1986
7.5x10s (scarred Dagle et al.
lymph nodes) 1984
l.OxlO7 (fetal lethal) Keljnan et al.
1982a
239Pu citrate
239Pu citrate
239pu oxide
239Pu citrate
re
m
>
t-
i-3
EC
W
PJ
O
H
c/i
u>
-------
tact F 2-3 (continued)
Exposure
Figure Frequency/
Key Species Duration
NOAEL Less Serious
Effect (pCi/kg) (pCi/kg)
LOAEL (Effect)
Serious
(pCi/Tcg)
Reference
Chemical
Species
Cancer
24 Rat (IT) Id
8.2xl04 (CEL-lung) Sanders 1975b 239Pu02
25 Rat (IV) Id
26 Rat (IP) Id
27 Rat (IP) Id
28 Mouse (IP) Id
29 Mouse (IV) Id
30 Hamster (IV) Id
31 Dog (IV) Id
32 Dor (IV) Id
INTERMEDIATE EXPOSURE
Cancer
33 Mouse (IP) 8 wk
2 d/wk
16 d
3.0x10s (CEL-skeletal) Sikov et al.
1978a
z39Pu citrate
2.0xl05 (CEL-
abdominal)
Sanders 1973
3.6x10® (CEL -manmary) Sanders 197A
3.2x10® (CEL-skeletal) Taylor et al.
1983
239
PuO,
238PuO,
z39Pu citrate
A.9x10® (CEL-leukemia) Svoboda et al. 239Pu citrate
1981
2.0x10® (CEL-skeletal, Brooks et al. 239Pu citrate
liver) 1983
l.OxlO4 (CEL-skeletal) Mays et al. 1987 z39Pu citrate
1.9xl03 (CEL-liver) Taylor et al. z39Pu citrate
1986
5,0xl04 (CEL-leukemia) Humphreys et al. z39Pu nitrate
1987
tfi
m
>
t-
H
EC
w
n
H
w
CO
break - breaking; CEL - cancer effect level; d - day; dec » decreased; Derm/oc ~ dermal/ocular; func impair » functional; Hemato "
hematological; hep degener ~ hepatic degeneration; (IP) - intraperitoneal; (IT) * intratracheal; (IV) - intravenous; LD50 - dose which
produces lethal effects in 50X of the animals; LQAEL » lowest observed adverse effect level; Musc/skel » musculoskeletal; NOAEL " no observed
adverse effect level; RBC ~ red blood cell; Resp - respiratory; (SB) - subcutaneous; WBC = white blood cell; wk ¦ week
-------
ACUTE
(<14 Days)
(pCi/kQ)
1,000,000,000 r
J
/ f
/ /
«/
/
$
100.000.000
10,000.000
1,000,000
100,000
10,000
1,000
Jlr
4r
2r ¦*
5f
17m
OlOr
M3r
#18d
OlBd
V16d
>,4m Ol6d
O'Sd
A»
#20d
921d
021d
123d
+30»
~28m
~27r
~25r
~26r
~24r
+31d
~32d
G
sc
PI
~n
~n
m
o
H
w
W
vO
100
r Rat
m Mouse
h Rabbit
s Hamster
d Dog
Key
¦ LD50
# LOAEL tor serious effects (animals)
9 LOAEL for less serious effects (animals)
O NOAEL (animals)
A NOAEL (humans)
~ CEL-Cancer Effect Level
Ttw number next to each point corresponds to entries in Table 2-3.
FIGURE 2-3. Health Effects Associated with Plutonium Deposition - Other Routes
of Exposure
noun
-------
(pCi/kfl)
1,000,000,000
100,000,000
10,000,000
1.000,000
100,000
10,000
1,000
100
INTERMEDIATE
(15-364 Days)
/
~33m
Key
m Mouse + CEL-Canow Effect Level
TJw number next la each point corresponds to afflrias in TaMs 2-3
FIGURE 2-3 (Continued)
-------
41
2. HEALTH EFFECTS
polymeric [4.7xl07 pCi (1.7xl06 Bq)/kg] forms of plutonium-239 were
lower than 30-day LD50s for the corresponding forms of plutonium-238
[monomeric, 1.6x10® pCi (5.9xl05 Bq)/kg; polymeric, 9.8xl07 pCi (3.6xl06
Bq)/kg] (Mahlum and Sikov 1969a; 1974).
Plutonium-239 is more acutely toxic than an equivalent picocurie
amount of plutonium-238 (Ballou et al. 1967). Survival times in rats
given a single intravenous injection of 7.9xl07 to 1.3x10® pCi
(2.9xl06to 4.8xl06 Bq) plutonium-239 citrate/kg body weight were
decreased, while survival times of rats administered equivalent amounts,
on a radioactivity basis, of plutonium-238 citrate were not reduced
(Ballou et al. 1967),
2.2.4.2 Systemic Effects
No studies were located regarding cardiovascular or
gastrointestinal effects in humans or animals after exposure to
plutonium by other routes.
Respiratory Effects. No studies were located regarding respiratory
effects in humans after exposure to plutonium by other routes.
Increases in the incidence of pneumonitis, inflammation, and edema
were observed in the lungs of rats following administration of 2xl05 pCi
(7.4xl03 Bq) plutonium-239 dioxide/kg body weight as a single
intraperitoneal injection (Sanders 1973a). However, the statistical
significance of these increases in respiratory effects could not be
determined based on the reported data.
Hematological Effects. No acute effects, as measured by evaluation
of hematological end points, occurred in a case study of 18 humans
following a single intravenous injection at levels ranging from 4xl03 to
7.3xl03 pCi (1.5xl02 to 2.7xl02 Bq) plutonium-238 or -239 citrate/kg
body weight (Langham et al. 1980). (While reported in a memorial
publication that republished Dr. Langham's work, this particular study
was conducted in the early 1950s.) Thirty years following exposure to
plutonium, 4 of the 18 individuals were still alive. One case could not
be located for follow-up. The authors reported that plutonium could not
be considered a contributing factor to the cause of death in the 13
cases (Rowland and Durbin 1976).
Anemia was observed in laboratory animals following a single
injection of plutonium-238 or -239. Rats given a single intraperitoneal
injection of plutonium-239 dioxide [8xl06 pCi (3.0xl05 Bq)/kg] or a
single intravenous injection of plutonium-238 citrate [3.6xl07 pCi
(1.3xl06 Bq)/kg] developed anemia (Ballou et al. 1967; Sanders 1973a;
Sanders and Jackson 1972). In rats exposed intravenously, a decrease in
viable bone marrow with replacement of marrow by a calcified plug
-------
U2
2. HEALTH EFFECTS
accompanied the anemia (Ballou et al. 1967). Anemia, characterized by
decreases in red blood cell volume, accompanied by increases in the
number of new red blood cells (reticulocytes), was observed in dogs
exposed to a single intravenous injection of 2.9xl06 pCi (1.1x10s Bq)
plutonium-239 citrate/kg (Dougherty and Rosenblatt 1971).
A decrease in the number of white blood cells, which continued to
decrease with time post-exposure, was observed in rats given a single
intravenous injection of 3.6xl07 pCi (1.3xl06 Bq) plutonium-238
citrate/kg (Ballou et al. 1967). Lymphopenia was observed in rats given
a single intraperitoneal injection of 8.2xl06 pCi (3.0xl05 Bq)
plutonium-239 dioxide/kg (Sanders 1973a; Sanders and Jackson 1972).
Decreased white blood cell counts were also observed in dogs given a
single intravenous injection of 2.9xl06 pCi (3.7xl03 Bq) plutonium-239
citrate/kg (Dougherty and Rosenblatt 1971) .
Svoboda and co-workers (1979, 1980a, 1980b, 1982a, 1983, 1985,
1987) have conducted extensive research on mice concerning the effects
of plutonium-239 on stem cells, the blood producing cells of the bone
marrow. These effects on bone marrow are considered to be "preleukemic"
by these authors (Svoboda and Kotaskova 1982). Administration of
monomeric plutonium-239 citrate [3.6xl05 pCi (1.3x10* Bq)/kg] as a
single intravenous injection resulted in a decrease in the number of
hematopoietic stem cells of the bone marrow in mice as soon as 4 weeks
after exposure (Svoboda et al. 1987). This initial damage in one
portion of the bone marrow appeared to be partially compensated, as
exhibited by a slight increase in the number of stem cells (due to
increased proliferative activity) in another part of the tissue by
approximately 30 weeks post-exposure; however, the number of stem cells
was still less than the number observed in untreated controls (Svoboda
and Kotaskova 1982; Svoboda et al. 1979). The authors hypothesize that
persistent radiological damage to the stem cells from plutonium-239 may
lead to an early stage of leukemia (Svoboda and Kotaskova 1982). A
similar decrease in stem cells was reported in mice given a single
intravenous injection of polymeric plutonium-239 nitrate [5xl06 to
1.5xl07 pCi (1.9xl05 to 5.6x10s Bq)/kg] (Joshima et al. 1981).
Musculoskeletal Effects. No studies were located regarding
musculoskeletal effects in humans after exposure to plutonium by other
routes.
Increased numbers of spontaneous fractures occurred in dogs given a
single intravenous injection of 1x10s to 3xl06 pCi (3.7xl03 to 1.1x10s
Bq) plutonium-239 citrate/kg body weight (Taylor et al. 1962). Total
incidence of fractures decreased with decreasing dose with only one
fracture observed in the two lowest treatment groups [lxl05 and 3xl05
pCi (3.7xl03 and 1.1x10* Bq) plutonium-239/kg] combined. The anatomical
range of the fractures increased with increasing dose. Plutonium
-------
43
2. HEALTH EFFECTS
exposure did not result in growth retardation in neonatal dogs as
measured by the growth of long bones (Bruenger et al. 1978).
Age-dependent differences in the musculoskeletal effects induced by
plutonium have been observed in adult, weanling, and neonatal rats given
single intravenous injections of plutonium at concentrations ranging
from 6xl06 to 9xl07 pCi (2.2xl05 to 3.3xl06 Bq) plutonium-239/kg body
weight, administered in the monomeric or the polymeric forms (Mahlum and
Sikov 1969b; Sikov and Mahlum 1976). Weanlings were more susceptible to
the musculoskeletal effects of plutonium (Mahlum and Sikov 1969b) ,
possibly due to the rapid growth of the bone cells, and greater
radiosensitivity of these cells to plutonium. An increase in the
incidence of spontaneous fractures was observed in weanlings, but not in
adults or neonates, given the monomeric form of plutonium-239 (Sikov and
Mahlum 1976). A decrease in the breaking strength of the femur was
observed in weanling and adult rats, but was more pronounced in
weanlings (Sikov and Mahlum 1976). In neonatal rats, the only
musculoskeletal effects, which were mild and sporadic, were observed in
the higher treatment groups administered greater than 6xl07 pCi (2.2xl06
Bq)/kg (Sikov and Mahlum 1976; Mahlum and Sikov 1969b).
Hepatic Effects. No studies were located regarding hepatic effects
in humans after exposure to plutonium by other routes.
Hepatic damage was observed in rodents after a single intravenous
injection of high levels of plutonium. Severe hepatic degeneration
occurred in hamsters observed for life following administered levels as
low as 2xl06 pCi (7.4x10'' Bq) plutonium-239 citrate/kg body weight
(Benjamin et al. 1976). A single intravenous injection of 7.5xl07 pCi
(2.8xl06 Bq) plutonium-239 citrate/kg resulted in damage to the liver
parenchyma of rats as early as 15 days post-exposure (Ballou et al.
1967).
In studies in which dogs were given a single intravenous injection
of plutonium-239 citrate, hepatic effects were observed to be dose-
related. No hepatic effects were reported in dogs given 630 pCi (23 Bq)
plutonium/kg body weight (Taylor et al. 1986), while gross and
microscopic liver nodules and/or hyperplasia were observed by year 8
following injection of 1.9xl03 to 3xl05 pCi (7.0X101 to 1.1x10* Bq)
plutonium-239/kg (Cochran et al. 1962; Taylor et al. 1986). At higher
levels [lxlO6 and 3xl06 pCi (3.7xl04 and 1.1x10s Bq) plutonium-239/kg],
functional impairment of the liver was observed 4 years post-exposure
(Cochran et al. 1962). Some of the animals at the highest treatment
level [3xl06 pCi (1.1x10s Bq)/kg] had functional impairment, as well as
shrunken livers and ascites, which the authors described as indicative
of decompensated cirrhosis (Cochran et al. 1962).
-------
44
2. HEALTH EFFECTS
Renal Effects. No studies were located regarding renal effects in
humans after exposure to plutonium by other routes.
Mild to severe chronic nephritis was observed in Sprague-Dawley
rats following a single intraperitoneal injection of 2xl05 pCi (7.4xl03
Bq) plutonium-239 dioxide (Sanders 1973a). However, the statistical
significance of these renal effects could not be determined based on the
reported data. In addition, renal nephritis may be a common occurrence
in the strain of rats used in this study.
Dermal/Ocular Effects. No studies were located regarding
dermal/ocular effects in humans after exposure to plutonium by other
routes.
Loss of hair, thickening of the dermis, and focal scarring were
observed around subcutaneous implants of plutonium-239 in dogs
administered plutonium dioxide [ 7. 5x10s pCi (2.8x10'' Bq)/kg] or
plutonium nitrate [ 9.8x10'' pCi (3.6xl03 Bq)/kg] (Dagle et al. 1984).
These effects may have resulted from exposure to plutonium; however, the
statistical significance of these dermal effects could not be determined
based on the reported data.
Other Systemic Effects. Other systemic effects have been observed
in rats following a single injection of plutonium. Mesothelial
hyperplasia was observed in rats injected intraperitoneally with 8xl06
pCi (3.0xl05 Bq) plutonium-239 dioxide/kg (Sanders and Jackson 1972).
A single intravenous injection of 6xl06 to 9xl07 pCi (2.2xl05 to
3.3xl06 Bq) plutonium-239 citrate/kg, administered as either the
monomeric or polymeric form, resulted in a sex-related decrease in
weight gain in weanling rats; the decrease in weight gain in males
occurred at a lower level [6xl05 pCi (2.2x10'* Bq)/kg] than in females
[1.8xl07 pCi (6.7xl05 Bq)/kg] (Mahlum and Sikov 1974), As seen with
musculoskeletal effects (see previous section), weanlings were more
susceptible to a decrease in weight gain following exposure to plutonium
than adults or neonates. A decrease in weight gain was observed in
adult rats following a single intravenous injection of 1.8xl07 pCi
(6.7xl05 Bq) plutonium-239/kg or greater, administered in the monomeric
form, but was not observed following administration of the polymeric
form. Decreased weight gain in neonatal rats was observed only
following lethal doses of plutonium-239 (Mahlum and Sikov 1974).
2.2.4.3 Immunological Effects
No studies were located regarding immunologic effects in humans
after exposure to plutonium by other routes,
-------
45
2. HEALTH EFFECTS
Effects on some tissues of the immune system have been observed in
dogs following a single subcutaneous injection of 7.4x10s pCi (2.7x10''
Bq) plutonium-239 dioxide/kg (Dagle et al. 1984). The regional lymph
nodes, which drained the injection sites of plutonium, were reduced in
size in six of eight dogs exposed and in five of the dogs the lymph
nodes consisted of only scar tissue (Dagle et al. 1984).
2.2.4.4 Neurological Effects
No studies were located regarding neurological effects in humans or
animals after exposure to plutonium by other routes.
2.2.4.5 Developmental Effects
No studies were located regarding developmental effects in humans
after exposure to plutonium by other routes.
Rabbits were given a single intravenous injection of lxlO7 or 4xl07
pCi (3.7xl05 or 1.5xl06 Bq) plutonium-239/kg, administered in the
monomeric form, on various days of gestation (Kelman et al. 1982a).
Fetal weights of the offspring of does given 4xl07 pCi (1.5xl06 Bq)
plutonium-239/kg were significantly decreased compared to the fetal
weights of the offspring of does given lxlO7 pCi (3.7xl05 Bq) plutonium-
239/kg or the offspring of untreated controls. In contrast, fetal
weights of does given lxlO7 pCi (3.7xl05 Bq) plutonium-239/kg were
significantly increased above controls. The number of litters
containing dead fetuses was significantly increased in the group of dams
given lxlO7 pCi (3.7xl05 Bq) plutonium-239/kg on gestation days 15 to
28. Rabbits given either lxlO7 or 4xl07 pCi (3.7xl05 or 1.5xl06 Bq)/kg
on gestation days 9 to 28 had significantly fewer fetuses. No
teratogenic effects of plutonium-239 were observed (Kelman et al.
1982a).
2.2.4.6 Reproductive Effects
No studies were located regarding reproductive effects in humans
after exposure to plutonium by other routes.
In mice, dominant lethality has been shown to result from plutonium
exposure. Fetal intrauterine deaths occurred in female mice mated with
male mice treated 4 weeks prior to mating. Male mice were given
(intravenously) plutonium-239 at levels ranging from 1.6xl06 to 1.6xl07
pCi (5.9x10'' to 5.9x10s Bq) plutonium-239/kg body weight (Liining et al.
1976a, 1976b). The effects of the dominant lethal mutations were also
observed when untreated females were mated with male mice from the F1
generation. Exposure of male mice to higher doses of plutonium-239
resulted in sterility 12 weeks post-exposure (Liining et al. 1976a,
1976b). Exposure of female mice to plutonium also resulted in dominant
lethal mutations (Searle et al. 1982). Female mice intravenously
-------
46
2. HEALTH EFFECTS
injected with 2xl07 pCi (7.4xl05 Bq) plutonium-239 citrate/kg body
weight exhibited a marked oocyte killing which resulted in a reduction
in the number of mice which became pregnant, compared with the controls.
Both pre- and post-implantation dominant lethals were induced at long
periods (12 weeks) after intravenous exposure to plutonium.
2.2.4.7 Genotoxic Effects
Open wounds represent a significant route through which plutonium
workers might be exposed to plutonium alpha-particles. Chromosomal
aberrations were observed in lymphocytes among 8 plutonium workers in
the United Kingdom occupationally exposed to plutonium with the primary
routes of exposure through wounds, punctures, or abrasions [estimated
body burdens from 2.1xlOA to 4xl04 pCi (7.8xl02 to 1.5xl03 Bq) plutonium,
based on urine analyses]. In exposed individuals the number of
dicentric aberrations averaged 5 per 500 cells, while the natural
population background frequency of this aberration is 1 per 4,000 cells
(Schofield 1980; Schofield et al. 1974).
Increased chromosomal aberrations were observed in liver tissue of
Chinese hamsters intravenously given plutonium-239 or plutonium-238, as
the citrate or the dioxide, to achieve levels ranging from 7xl02 to
2x10* pCi (2.6X101 to 7.4xlOz Bq) plutonium-239 or plutonium-238/g of
liver tissue (Brooks et al. 1976a) or 2xl06 pCi (7.4xl0A Bq) plutonium-
239 citrate/kg of body weight (Benjamin et al. 1976). The frequency of
aberrations was much higher in hamsters exposed by intravenous injection
to plutonium-239 or plutonium-238 citrate, than in hamsters exposed to
plutonium-239 or plutonium-238 dioxide (Brooks et al. 1976b). No
statistically significant increases in the incidence of chromosomal
aberrations per spermatogonia cell were observed in mice or hamsters
following intravenous administration of plutonium-239 citrate [2xl03 pCi
(7.4X101 Bq) plutonium-239/kg body weight], compared to untreated
controls (Brooks et al. 1979).
Other genetic effects attributed to plutonium are dominant
lethality and chromosome translocations in spermatocytes. Fetal
intrauterine death occurred in female mice mated with male mice treated
4 weeks prior to mating. Male mice were given (intravenously)
plutonium-239 at levels ranging from 1.6xl06 to 1.6xl07 pCi (5.9xl04 to
5.9x10s Bq) plutonium-2 39/kg body weight (Liining et al. 1976a, 1976b).
The effects of the dominant lethal mutations were also observed when
untreated females were mated with male mice from the F1 generation.
Exposure of male mice to higher doses of plutonium-239 resulted in
sterility 12 weeks post-exposure (Liining et al. 1976a, 1976b).
Increased frequency of reciprocal translocations in spermatogonia
was observed in male mice 6 to 18 weeks after intravenous Injection of
lxlO7 pCi (3.7xl05 Bq) plutonium-239 citrate/kg body weight (Beechey et
al. 1975). An increase in the frequency of heritable translocations was
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47
2. HEALTH EFFECTS
also observed in male mice intravenously injected with lxlO7 pCi
(3.7xl05 Bq) plutonium-239 citrate/kg body weight (Generoso et al.
1985). The frequency of translocations increased as a function of time
and dose. However, induction of reciprocal translocations was not
significant in male mice intravenously injected with 4xl06 pCi (1.5x10s
Bq) plutonium-239/kg body weight (Searle et al. 1976).
Exposure of mice to 3.6xl05 pCi (1.3x10* Bq) plutonium-239
citrate/kg body weight resulted in increased chromosomal aberrations in
bone marrow cells (Svoboda et al. 1987). The highest incidence of these
mutations was observed in the early days following exposure to
plutonium.
2.2.4.8 Cancer
No studies were located regarding cancer effects in humans after
exposure to plutonium by other routes.
Following a single intravenous injection of plutonium-239 citrate,
osteosarcomas were found in mice [3.2x10s pCi (1.2x10* Bq)/kg] (Taylor
et al. 1983), rats [ 3xl05 pCi (1.1x10* Bq)/kg) (Sikov et al. 1978a),
hamsters [2xl06 pCi (7.4x10* Bq)/kg] (Brooks et al. 1983), and dogs
[1x10* pCi (3.7xl02 Bq)/kg] (Mays et al. 1987). Latency periods for the
induction of these bone tumors were not reported. However, lifespan was
significantly shortened only in hamsters. Lifespan studies in beagle
dogs provided evidence that certain skeletal sites were more prone to
develop plutonium-induced osteosarcomas than others (Miller et al.
1986). In these dogs, most osteosarcomas originated in trabecular
(spongy) bone areas, such as the ends of long bones, the pelvis,
vertebrae, and the area surrounding the marrow of the bone (endosteal
surfaces) (Miller et al. 1986). Because these areas may have a greater
blood flow, a greater amount of plutonium may deposit in these areas of
the bone (see Section 2.3.2.4).
Induction of osteosarcomas following a single injection of
plutonium-239 appeared to be age-dependent as well as sex-dependent. A
statistically significant increase in the incidence of bone tumors was
observed in adult and weanling rats given a single intravenous injection
of 3xl05 pCi (1.1x10* Bq) plutonium-239 citrate/kg (Sikov et al. 1978a).
At higher levels [3xl06 to 3xl07 pCi (l.lxlO5 to 1.lxlO6 Bq) plutonium-
239/kg via intracardiac injection], a nonsignificant increase in the
incidence of bone tumors was observed in neonatal rats. The anatomical
distribution of these bone tumors was markedly influenced by age at time
of injection. In neonates one-third of all tumors were in the head
while older groups had bone tumors primarily in the extremities or
vertebrae (Sikov et al. 1978a). A statistically significant increase in
the incidence of bone tumors was observed in female mice, but not in
male mice given a single intraperitoneal injection of plutonium-239
citrate [9xl05 pCi (3.3x10* Bq)/kg] (Taylor et al. 1981a). Females may
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48
2. HEALTH EFFECTS
be more sensitive to the toxic bone effects following a single exposure
to plutonium-239 because the induction of osteosarcomas could be
estrogen related (Taylor et al. 1981a).
Liver tumors have been observed in dogs following a single
intravenous injection of plutonium-239. A statistical y sign fleant
increase in the incidence of hepatic tumors, mostly bile duct tumors,
has been observed in dogs given 1.9xl03 pCi <7.0x10* Bq) plutonium-239
citrate/kK body weight (Taylor et al. 1986). These tumors were observed
orimarily in the lower dose groups following long latency periods. Most
of the liver tumors observed were in dogs sacrificed due to bone cancer;
however, liver tumors were primary liver tumors and not metastases.
Liver and bone tumors were observed in hamsters administered a
single intravenous injection of 2x10* pCi (7.4x10* Bq) plutonium-239/kg
body weight, administered as plutonium citrate (monomeric) (Brooks et
ll 1983) However, in hamsters given a single intravenous injection of
9v106 oCi (7 4x10* Bq) plutonium-239 dioxide/kg (polymeric), a
significant increase in the incidence of liver tumors was observed with
no accompanying bone tumors (Brooks et al. 1983).
No conclusive evidence exists that plutonium induces leukemia in
laboratory animals. However, in mice with a high spontaneous incidence
of leukemia (ICR mice), administration of plutonium as a single
intravenous injection (A.9xi06 pCi (1.8x10* Bq) plutonium-239
citrate/kg] decreased the latency period for the appearance of leukemia
(Svoboda et al. 1981).
Various types of tumors have been observed in rats following a
sinele intraperitoneal injection of plutonium dioxide. A dose-dependent
increase in the incidence of mesotheliomas and soft-tissue sarcomas was
observed in rats given 2xl05 to 8xl06 pCi (7.4xl03 to 3.0x10 Bq)
clutonium-239 dioxide/kg (Sanders 1973). Death in many of the treated
rats resulted from large malignant abdominal tumors. It appears that
Plutonium-239 particles, administered as plutonium dioxide, can produce
mesotheliomas in the abdominal cavity, but a greater radiation dose is
needed to induce mesotheliomas than is needed to induce sarcomas
,Canr1prs 1973) An increase in the incidence of mammary tumors was
observed in rats given 3.6x10* pCi (1.3xl05 Bq) plutonium-238 dioxide/kg
(Sanders 1974).
2.3 TOXICOKINETICS
In radiation biology the term dose has a specific meaning. Dose
refers to the amount of radiation absorbed by the organ or tissue of
interest and is expressed in rads (grays). For example estimation of
this radiation dose to lung tissue or specific cells in the lung from a
eiven exposure to plutonium is accomplished by modeling the sequence of
events involved in the inhalation, deposition, clearance, and decay of
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49
2. HEALTH EFFECTS
plutonium within the lung. While based on the current understanding of
lung morphometry and experimental data on plutonium toxicokinetics,
different models make different assumptions about these processes,
thereby resulting in different estimates of dose and risk. Other models
estimate dose from ingestion of plutonium. These models are described
in numerous reports including Bair (1985), EPA (1988), ICRP (1978),
James (1988), and NEA/OECD (1983) . In this section the toxicokinetics
of plutonium is described based on the available experimental data
rather than on descriptions derived from models.
2.3.1 Absorption
2.3.1.1 Inhalation Exposure
The most common route of exposure to plutonium is inhalation. The
absorption of plutonium following inhalation was dependent on its
physicochemical properties including isotope number, the mass deposited,
valence, chemical compound, and particle size (Bair et al. 1962b;
Guilmette et al. 1984). Depending on the plutonium compound, it may be
either soluble or insoluble. Plutonium as the citrate or nitrate was
more soluble than the dioxide compound. Plutonium dioxides prepared at
temperatures of 700°C or higher had a slower absorption rate compared to
air-oxidized forms (Sanders and Mahaffey 1979). The absorption of
plutonium was also dependent upon its respirable fraction, or that
fraction of the total concentration of plutonium which may deposit in
the nonciliated part of the lung. The respirable fraction of plutonium
is composed of particles less than 10 |im Activity Median Aerodynamic-
Diameter (AMAD) , which indicates that only particles less than 10 jim
AMAD would be retained in the nonciliated part of the lung and would be
available for absorption (NEA/OECD 1981; Volchok et al. 1974).
The more soluble the form of plutonium, the more rapidly and
extensively it was absorbed by the lungs (Ballou et al. 1972; Dagle et
al. 1985). The insoluble forms of plutonium were absorbed from the
lungs very slowly (Bair et al. 1962b; Bair and Willard 1962; Guilmette
et al. 1984; Park et al. 1985) with the majority being deposited in the
tracheobronchial region and then removed by the mucociliary apparatus.
Insoluble particles may be engulfed by macrophages and alveolar cells
(Metivier et al. 1980a; Sanders and Adee 1970) and taken up into the
reticuloendothelial system (Leggett 1985).
Plutonium-238 administered as the soluble nitrate or as the less
soluble dioxide form to dogs was absorbed from the lungs more rapidly
than the corresponding forms of plutonium-239, possibly due to the lower
mass of plutonium-238 (Dagle et al. 1983; Park et al. 1972) or more
likely, due to the higher specific activity of plutonium-238. However,
when plutonium-239 nitrate was administered to rats, it was absorbed
more readily than the plutonium-238 nitrate (Morin et al. 1972).
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50
2. HEALTH EFFECTS
2.3.1.2 Oral Exposure
Absorption of plutonium from the gastrointestinal tract was minimal
and was dependent on age, chemical properties, stomach content, dietary
iron intake and nutritional factors (Bomford and Harrison 1986;
Harrison et al 1986; Stather et al. 1980; Sullivan and Ruemmler 1988;
Sullivan et al. 1983; Weeks et al. 1956). Oxidation state,
administration media, extent of polymer formation, rate of hydrolysis,
and mass administered did not appear to effect the absorption of
Plutonium (Carritt et al. 1947; Harrison and David 1987; Larsen et al.
1981; Stather et al. 1980, 1981).
Absorption of plutonium was slightly increased when administered in
a citrate or nitrate solution and when administered as a very acidic
solution (Weeks et al. 1956). Absorption of 0.003 to 0.01% of the
administered plutonium citrate or nitrate has been reported in rats and
hamsters (Carritt et al. 1947; David and Harrison 1984; Katz et al.
1955; Stather et al. 1981).
The absorption of plutonium after oral administration was age-
related in laboratory animals. From 3 to 6% of administered plutonium
may be absorbed by neonatal rats, hamsters, guinea pigs, and dogs
(Cristy and Leggett 1986). A rapid decrease in absorption has been seen
with increasing age. It, halters between 1 day and 30 days of age
absorption of plutonium decreased from 3.5 to 0.0032 of the administered
dose (David and Harrison 1984).
Gastrointestinal absorption increased when plutonium was
administered on an empty stomach. In hamsters that had been fasted for
8 to 24 hours, absorption increased to 0.1 to 0.15% of the administered
plutonium citrate or ascorbate compared to 0.01% in animals which had
not been fasted (Harrison et al. 1986).
Absorption of plutonium from the gastrointestinal tract was
dependent on iron status. A four-fold increase in plutonium absorption
occurred in rats that were iron deficient compared to those with normal
iron status (Ragan 1977; Sullivan et al. 1986). Absorption of plutonium
in nursing neonates of iron deficient dams was twice as much as neonates
of iron-replete dams (Sullivan et al. 1986).
2.3.1.3 Dermal Exposure
The absorption of plutonium following dermal exposure was very
limited The amount absorbed depended on the thickness of the skin, the
area of the skin exposed, the mass applied, the integrity of the skin,
and the solution in which the plutonium is dissolved. Plutonium
absorption through the intact palmar skin of a human was found to be
less than 0 0002%/hr when administered as the nitrate in a 0.4N nitric
acid solution (Langham 1959) . Plutonium has been found to migrate down
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51
2. HEALTH EFFECTS
hair follicles (Weeks and Oakley 1955) and into sweat and sebaceous
glands (Buldakov et al. 1970).
2.3.1.4 Other Routes of Exposure
The absorption of plutonium after exposure was dependent on the
route of administration. Intravenous injection delivered plutonium
directly into the blood stream where it may then distribute in the body.
Injection of plutonium into the peritoneal cavity (Sanders 1975a;
Sanders and Jackson 1972) or into the muscle (Nenot et al. 1972)
resulted in phagocytosis of particles which then enter the blood stream
through the lymphatics. Intramuscular injection of plutonium-238
citrate to monkeys resulted in absorption of 95% of the administered
dose from the site of injection in 10 days (Durbin et al. 1985).
Absorption of plutonium after intraperitoneal injection was
dependent on iron status. A two-fold increase in plutonium absorption
occurred in rats which were iron-deficient compared to those with normal
iron status (Ragan 1977).
Absorption of plutonium through wounds has occurred in humans
occupationally exposed (Hammond and Putzier 1964). Experiments in
animals where plutonium-239 as the nitrate or dioxide was injected under
the skin have been conducted to simulate this exposure. From these
studies it has been found that about 80% of the administered plutonium
nitrate or dioxide was absorbed (Dagle et al. 1984).
2.3.2 Distribution
2.3.2.1 Inhalation Exposure
The distribution of plutonium following absorption from the lungs
was dependent on the physicochemical form deposited. In general,
plutonium was distributed to the skeleton, liver, and lymph nodes;
however, some plutonium has been found in all tissues. Information from
humans who have been occupationally exposed to plutonium indicated that
the highest concentrations of the absorbed plutonium were found in the
tracheal-bronchial lymph nodes, followed by the liver, skeleton, and
kidneys (Lagerquist et al. 1973). However, a more recent study by
Mclnroy et al. (1989) reports that plutonium deposition in a small
number of former nuclear industry workers was greatest, exclusive of the
respiratory tract, in the skeleton followed by the liver, striated
muscle, and other organs and tissues. These authors suggested that
muscle and other soft tissues may act as a long-term storage depot for
plutonium. Results from studies in laboratory animals indicated that
absorption of the more soluble forms of plutonium led to greater
distribution in the skeleton and liver (Dagle et al. 1985; Morin et al.
1972), while the less soluble dioxide form was distributed to a greater
extent to the trachea-bronchial lymph nodes and the liver (Bair et al.
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52
2. HEALTH EFFECTS
1966- Park et al. 1972). Distribution to the bone was greater with
Plutonium-238 nitrate than with plutonium-239 (Morin et al. 1972) and
with the air-oxidized form of both plutonium-238 and plutonium-239
compared to the high-fired form (Sanders and Mahaffey 1979).
Particle size did not appear to affect distribution to the liver
and skeleton in dogs (Guilmette et al. 1984). An age-related effect on
distribution to the bone was reported by Guilmette et al. (1986). In
immature dogs, a five-fold increase in distribution to the bone was seen
compared to that in young adult dogs. Most information available on the
distribution of plutonium following inhalation exposure is from studies
where plutonium-239 dioxide was administered in a single dose to dogs.
Additional information is also available on other chemical compounds,
and isotopes in rodent species (Buldakov et al. 1972; Nenot et al. 1972;
Sanders 1973b; Sanders et al. 1977).
The distribution of plutonium within the lungs after inhalation
exposure was also dependent on several variables. In rats a more
uniform exposure of lung cells occurred from administration of the air-
oxidized form compared to the high-fired form (Sanders and Mahaffey
1979) Initially after exposure to the dioxide form, distribution in
the lungs of hamsters was random with particles becoming more clumped
with time (Diel et al. 1981).
The distribution of plutonium in the liver differed between the
nitrate and dioxide forms. Administration of the nitrate form to dogs
resulted in diffusely distributed activity found as single tracks, while
administration of the dioxide form resulted in localized activity found
as "alpha stars" with radioautography (Dagle et al. 1985).
2.3.2.2 Oral Exposure
In rats and dogs following absorption of plutonium from the
gastrointestinal tract, up to 95% of the absorbed dose has been found to
be distributed to the skeleton (Carritt et al. 1947; Larsen et al. 1981;
Toohey et al. 1984). Plutonium was also distributed to a less extent to
the liver, carcass, and soft tissues (Carritt et al. 1947; Katz et al.
1955' Larsen et al. 1981; Sullivan et al. 1984). The distribution of
plutonium-237 in a bicarbonate solution administered via a gelatin
capsule was greatest to the axial skeleton (Toohey et al. 1984).
2.3.2.3 Dermal Exposure
At early times after dermal exposure of rabbits to plutonium-239
nitrate, activity in blood was uniformly distributed, but later changed
to a nonuniform distribution (Khodyreva 1966). Distribution of
plutonium was greatest to the skeleton followed by muscle tissue, liver,
kidney, spleen, heart, and lungs (Khodyreva 1966). In an earlier study
in rats, the absorption of plutonium through Intact skin did not appear
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53
2. HEALTH EFFECTS
to result in distribution to the liver as compared to absorption through
skin damaged by punctures or wounds where deposition in the liver was
seen (Oakley and Thompson 1956).
2.3.2.4 Other Routes of Exposure
The distribution of plutonium was studied in terminally ill
patients who had been given an intravenous injection of plutonium
(Langham et al. 1980). Blood concentrations decreased rapidly (0.3%
remained in the blood after 30 days). At death, which occurred from 16
to 450 days after injection, an average of 56% of the administered
plutonium was in the bone marrow and on bone surfaces, while 23% was in
the liver (Langham et al. 1980).
Although exposure by injection routes in humans is not likely, data
from distribution studies in laboratory animals provides insight into
the toxicokinetics of plutonium in the body. In dogs, once plutonium
entered the blood stream, it was bound to transferrin, a serum transport
protein (Stevens et al. 1968). Plutonium competed with iron for the
transferrin in the blood. If transferrin was saturated with iron, then
more plutonium would deposit in the liver and not in the bone (Ragan
1977) . Similar binding of plutonium to transferrin was observed in
human blood serum (Stover et al. 1968a).
In laboratory animals that received plutonium by intravenous
injection, most plutonium was deposited in the liver and skeleton. No
differences in distribution between plutonium-238 and plutonium-239 were
reported in mice (Andreozzi et al. 1983); however, Ballou et al. (1967)
reported that in rats deposition in the liver and other soft tissues was
twice as great after intravenous administration of plutonium-239 than
after administration of plutonium-238. In dogs, the concentration of
plutonium polymer decreased in the lungs, spleen, and liver with time
and increased in the skeleton and kidney (Stevens et al. 1976).
The distribution of plutonium after intravenous injection was age-
dependent. The distribution of different chemical forms of administered
plutonium did not differ in neonates, and activity was more uniformly
distributed than in weanlings and adults (Mahlum and Sikov 1974; Sikov
and Mahlum 1976). In immature dogs, increased deposition of plutonium
was associated with bones that were undergoing active growth (Bruenger
et al. 1978). The concentration of plutonium in the skull of neonates
was twice as great as that in young adults, but distribution to the
liver was not as great in neonates as in other age groups (Bruenger et
al. 1978). Age at time of injection influenced distribution between the
skeleton and the liver (Bruenger et al. 1980; Lloyd et al. 1978a,
1978b). In rats plutonium distribution within bone was different in
weanlings compared to adults. In weanlings, there was a tendency for
localization on periosteal surfaces and plutonium was seen in compact
bone at earlier times (Sikov and Mahlum 1976).
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2. HEALTH EFFECTS
In dogs and mice administered plutonium-239 as the citrate or as
the polymer by intravenous injection, 15 to 31% or 59 to 70%,
respectively, of the injected dose was distributed to the liver after 6
days (Baxter et al. 1973; Stover et al. 1959). In rats at 30 days post-
exposure to plutonium as the citrate or as the polymer, 9.6 or 40%,
respectively, was distributed to the liver (Carritt et al. 1947). The
distribution of activity in the liver was uniform following
administration of the citrate and nonuniform after administration of the
polymer (Baxter et al. 1973; Brooks et al. 1983; Cochran et al. 1962).
The percent of plutonium-239„ administered by intravenous injection
as the citrate or as the polymer, that distributed to the skeleton of
dogs and mice was 2.8 to 3.1% or 0.1 to 0.2%, respectively, after 6 days
(Baxter et al. 1973). In rats 30 days after exposure to plutonium-239
as the citrate or as the polymer, 56.9 or 29.4%, respectively,
distributed to the bone (Carritt et al. 1947). In dogs plutonium
distribution in the skeleton was greatest to the trabecular or "spongy"
bone and more was found in the red bone marrow, which is perfused with
blood, compared with yellow or fatty bone marrow (Smith et al. 1984;
Wronski et al. 1980). The rate of deposition in bone may be related to
the rate of blood flow to bone, and in mice there appears to be a
threshold rate for blood flow below which plutonium will not deposit to
bone (Humphreys et al. 1982).
A small fraction of the plutonium taken in has been found to
distribute to the gonads of mice following intravenous exposure. In
mice exposed to plutonium-239 citrate, about 0.02 to 0.06% of the
administered dose was distributed to the testes (Andreozzi et al. 1983;
Ash and Parker 1978; Green et al. 1976). In the testes, plutonium was
associated with the interstitial tissue (Ash and Parker 1978; Brooks et
al 1979; Green et al. 1976). Plutonium has also been measured in the
ovarian tissue of mice exposed to plutonium-239 citrate (Green et al.
1 rt \
Plutonium-239 citrate has been shown to cross the placental
membrane and has been found in the fetus in both mice and baboons
following intravenous injection (Green et al. 1979; Sikov et al. 1978b;
Weiss and Walburg 1978). The fractional placental transfer of plutonium
citrate was found to be inversely proportional to the administered dose
(Weiss and Walburg 1978). The greatest amounts of plutonium were found
in the fetal membranes followed by the placenta and then the fetus
(Sikov et al. 1978b). Plutonium was distributed to the gastrointestinal
tract, liver, and mineralized areas of the bone in the fetus (Green et
al. 1979).
After the absorption of plutonium from a wound site, it may be
absorbed in the blood stream and distributed to the regional lymph
nodes, liver, spleen, skeleton, and other tissues. In dogs exposure to
plutonium dioxide through a wound resulted in greater distribution to
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55
2. HEALTH EFFECTS
the lymph nodes and less to the skeleton as compared with exposure to
plutonium nitrate (Dagle et al. 1984). Distribution to the spleen of
dogs exposed to the dioxide form vas greater than to the skeleton, while
distribution to the spleen of dogs exposed to the nitrate form was less
than to the skeleton. Comparable amounts of both forms were distributed
to the liver and the skeleton (Dagle et al. 1984).
2.3.3 Metabolism
Plutonium occurs naturally in several valence states, but in the
body the most common state is (IV) due to stabilization by ligands and
complexing agents (ICRP 1972). Plutonium does not exist as a simple ion
at physiological pH and, therefore, tends to hydrolyze and form
polymers. The tendency for plutonium to hydrolyze should increase with
increasing atomic number because the hydrolytic behavior is determined
by ionic charge and size (ICRP 1972). When plutonium is complexed with
citrate, it is less likely to form polymers and remains more soluble in
the body.
2.3.4 Excretion
2.3.4.1 Inhalation Exposure
Elimination of plutonium following exposure by inhalation appears
to be dependent upon the form of plutonium and may vary among species.
After inhalation exposure to plutonium, the clearance pattern from the
lungs appeared to be biphasic. In rats, the half-time for clearance of
plutonium-238 or -239 dioxide from the lungs for the first phase was
from 20 to 30 days and for the second phase was from 180 to 250 days
(Sanders et al. 1976, 1977, 1986). In the first phase, 70 to 76% of the
plutonium was removed with the remainder of that excreted removed in the
second phase. Retention of plutonium in the body after it translocates
to other tissues may be very long. In dogs exposed to plutonium-239
dioxide, 85% of the administered amount was retained in the body 9 to 10
years after exposure (Park et al. 1972). Retention of plutonium dioxide
In the lungs of dogs was not constant over time, which may be related to
an increased rate of solubilization of the particles with time,
resulting in greater translocation to other organs (Hahn et al. 1981).
The retention half-time increased with increasing particle size (Bair et
al. 1962b; Guilmette et al. 1984). The retention half-time for the
plutonium-239 isotope was greater than for the plutonium-238 isotope
(Park et al. 1972). With repeated exposure to plutonium-239 dioxide, it
appeared that each administered amount was retained independently with
its own retention characteristics (Diel and Lundgren 1982).
The excretion of plutonium by humans approximately 30 years after
occupational exposure to plutonium particles, primarily by inhalation,
appeared to indicate that more plutonium was cleared in the urine than
in the feces (Voelz et al. 1979). However, Leggett (1985) stated that,
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56
2. HEALTH EFFECTS
at equilibrium, 4 times more plutonium was eliminated in the feces than
in the urine. In laboratory animals, the primary route of excretion of
plutonium was reportedly through the feces. From 10 to 35 times more
plutonium was excreted in the feces than in the urine in dogs and rats
(Bair and McClanahan 1961; Diel and Lundgren 1982; Sanders et al. 1976,
1977). In rats exposed by inhalation or intramuscular injection,
greater amounts of plutonium have been found in the feces as soon as 8
days following inhalation exposure. This may be due to the removal of
particles from the respiratory tract by the mucociliary elevator and the
consequent swallowing of these particles or due to biliary clearance
(Morin et al. 1972).
2.3.4.2 Oral Exposure
Most of plutonium administered to dogs in a bicarbonate solution by
the oral route was eliminated in the feces, with an average excretion of
98% of the administered dose after 5 or 6 weeks (Toohey et al. 1984).
In mice and rats total retention of plutonium varied from 0.17 to 0.24%
of the administered activity and was not dependent on oxidation state or
on the medium in which it was administered (Larsen et al. 1981).
Retention in the liver of mice and rats was 0.036 and 0.054%,
respectively, of the initial dose (Larsen et al. 1981) and in the
skeleton plus liver of fasted dogs was 0.063% of the administered dose
(Toohey et al. 1984).
Retention of plutonium in rat neonates was 100 times greater than
in adults (Sullivan et al. 1984). More plutonium was found in the wall
of the small intestine than in the walls of the stomach and large
intestine of rats (Fritsch et al. 1988).
2.3.4.3 Dermal Exposure
No studies were located regarding excretion in humans or laboratory
animals after dermal exposure to plutonium.
2.3.4.4 Other Routes of Exposure
Little information is known about the excretion of plutonium in
humans after exposure through other routes. From terminally ill humans
who were administered an intravenous injection of plutonium it appeared
that the major route of elimination was in the urine (Langham et al.
1980). The biological half-time in these individuals was estimated to
be 118 years and the retention half-time in the liver was estimated to
be greater than 1 year. Data from humans occupationally exposed through
wounds indicated that excretion patterns could not be predicted
following this type of exposure (Hammond and Putzier 1964).
From injection studies in laboratory animals it was found that
retention was dependent on the isotope, chemical form, and sex. In dogs
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2. HEALTH EFFECTS
plutonium-239 was retained longer than plutoniura-237 (Bair et al. 1974).
The retention of plutonium-242 and plutonium-244 was similar, and was
longer than the retention time for plutonium-236 and plutonium-239
(Guilmette et al. 1978). In mice no difference was seen in fractional
retention at low and high doses (Andreozzi et al, 1983). In hamsters
more plutonium administered intravenously in an insoluble form
(plutonium dioxide) was retained than plutonium administered in a
soluble form (plutonium citrate) (Brooks et al. 1976b). Retention after
intraperitoneal injection of mice and hamsters may be sex-dependent;
females retained more in the liver than males (Smith et al. 1976, 1978).
However, retention after intravenous injection was not sex-dependent
(Smith et al. 1978). Total retention and liver retention increased with
age (Bruenger et al. 1980; David and Harrison 1984).
The whole body retention of intravenously administered plutonium-
237 and/or -239 citrate in dogs varied from approximately 85% to almost
100% (Bair et al. 1974; Lloyd et al. 1976, 1984) with liver retention of
about 25% (Bair et al. 1974; Lloyd et al. 1976, 1984; Stover et al.
1962) and skeletal retention of about 50% (Bruenger et al. 1980; Lloyd
et al. 1978a, 1978b, 1984). Liver retention was found to be dose-
dependent (Stover et al. 1962). In hamsters, the whole body retention
of plutonium-239 dioxide was approximately 100% (Brooks et al. 1983).
Plutonium was found to be retained for an indefinite time in the testes
and ovaries of mice and rats (Green et al. 1977; Miller et al. 1989;
Taylor 1977). Retention at the site of administration after exposure
which simulated wounds was from 16 to 21% of the administered dose
(Dagle et al. 1984).
The half-life for removal of plutonium was very long. In mice the
biological half-life of plutonium-238 or 239 citrate in the skeleton was
one to two times the animal's lifespan and in the liver the half-life
was 350 days (Andreozzi et al. 1983). In dogs the half-life of
plutonium-239 citrate in the liver was 3,081 days, in the spleen was 995
days, and in the kidney was 1,520 days (Stover et al. 1968b). A long
effective half-life has been reported in hamsters with 85% of injected
plutonium-239 citrate still in the bone and liver 700 days after
administration (Benjamin et al. 1976).
In mice plutonium-239 administered as a polymer in a non-citrate
solution was cleared from the blood rapidly, 99% in 15 minutes, while
only 20% of plutonium administered as a monomer in a citrate solution
was cleared in the same time (Baxter et al. 1973). Most plutonium was
retained in the body, and the remainder was excreted. In mice,
hamsters, and dogs from 10 to 30% of plutonium was excreted primarily in
feces (Baxter et al. 1973; Brooks et al. 1983; Lloyd et al. 1976, 1978b,
1984). Plutonium was also shown to be removed from the body through
lactation; however, the amount of plutonium in milk was not reported
(Taylor 1980). In nursing rats administered plutonium-239 citrate, the
total body burden was decreased 10% by lactation (Taylor 1980).
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2. HEALTH EFFECTS
2.4 RELEVANCE TO PUBLIC HEALTH
Plutonium isotopes are products of neutron absorption processes in
nuclear reactors generated by nuclear Processes. Exposure to plutonium
in environmental media poses the potential for causfng adverse health
effects. Plutonium and other alpha-emitting radionuclides (ATSDR 1990)
exert their biological effects after entering the body and depositing in
radiosensitive tissues. Inhalation is the primary route of plutonium
exposure for humans in either occupational or environmental settings
Translocation from the lungs to other organs in the body depends on a
variety of factors including the solubility Qf the plutonium compound
and the particular plutonium complex. Plutonium is not readily absorbed
from the gastrointestinal tract or through intact skin.
Plutonium emits ionizing radiation primarily in the form of alpha
particles. The type and severity of the biological response to this
radiation will depend not only on the amount of radiation emitted but
also on the radiosensitivity of the tissue and contact (retention) time
In general, tissues undergoing rapid cell regeneration are more
radiosensitive than slower or nonregenerating cell systems (see
Appendix B).
Animal studies have demonstrated that exposure to high radiation
doses of plutonium isotopes have resulted in decreases in lifespan
diseases of the respiratory tract, and cancer. The target tissues'
appear to be the lungs and associated lymph nodes, the liver, and bones
However, these observations in animals have not been corroborated by
epidemiological investigations in humans exposed to smaller amounts of
plutonium.
Death. No deaths in humans specifically associated with plutonium
have been reportedfollowing acute plutonium exposure. Epidemiological
studies of occupational cohorts did not report any increases in deaths
due to nonmalignant leases. However, the highest radiation levels
reported in workers were 100- to 1,000-fold lower than the radiation
levels that resulted in death (due to respiratory failure) in some
laboratory animals. Acute exposures to high levels of plutonium
isotopes, administere as dioxides, citrates, or nitrates, were fatal to
several laboratory species when exposure occurred by the inhalation
oral, or injection routes. Survival time was radiation dose-related for
all of these routes of exposure. By the inhalation route in animals
nonmalignant respira ory disease was characterized by radiation
pneumonitis, pulmonary fibrosis, alveolar edema, and occasionally
hyperplasia and metap asia with death occurring within weeks or months
of the initial expos e to high concentrations. It is likely that
mortality due to ra lation-induced sickness, such as radiation
pneumonitis, c°ul ^humans at sufficiently high radiation doses
Such amounts of radi ion, however, would be expected to occur only with
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59
2. HEALTH EFFECTS
an extremely large accidental release but not at the radiation levels
attributable to plutonium currently identified in the ambient
environment.
Respiratory Effects. Neither deaths due to respiratory disease nor
reduced respiratory function have been reported among the occupationally
exposed cohorts. Respiratory diseases characterized by pneumonitis,
fibrosis, edema, and respiratory dysfunction have been reported in all
laboratory species tested following acute exposure to high
concentrations of plutonium by the inhalation or injection routes. The
severity of the respiratory disease and the time to death from
respiratory disease correlated with the activity concentration.
Induction of this type of respiratory disease in humans could occur at
high exposure levels, which greatly exceed those commonly found in the
environmental setting. However, the radiation dose that might result in
either pulmonary dysfunction or pulmonary disease in humans has not been
specifically identified. A no observed adverse effect level (NOAEL) was
not established with certainty based on the data from animal studies.
The types of adverse respiratory effects observed appear to be
consistent with the pattern of alpha radiation damage that may occur in
slower regenerating tissues such as the lungs (see Appendix B). That
being the case, production of respiratory tissue damage in the lungs may
occur but may not be immediately apparent, especially at low
environmental exposures.
Hematological Effects. No acute hematological effects were
observed among human volunteers given a single injection of plutonium,
but no follow-up study was conducted to assess the possibility of
delayed effects. No adverse hematological effects were reported among
the various occupational cohorts who underwent medical examinations.
There is considerable evidence from animal experiments that plutonium
produces adverse effects in the hematopoietic system. Lymphopenia was
the most common finding following inhalation exposure in animals, while
anemia, bone marrow depression, and decreases in white blood cells and
hematopoietic stem cells occurred following injection of plutonium in
animals. The lymphopenia was dose-related and correlated both in
magnitude and time of appearance post-exposure with the initial lung
burden of inhaled plutonium. Hematological abnormalities have occurred
in human populations following exposure to external radiation (i.e.,
gamma and high-energy beta), and blood-forming cells could be a target
for internally deposited alpha radiation (see Appendix B); however, the
relevance of the hematological effects seen in animals at high doses to
potential health effects in humans environmentally exposed to plutonium
is unclear.
Hepatic Effects. Adverse hepatic effects associated with plutonium
exposure have not been reported in humans. There is evidence in animals
that inhalation or injection of plutonium results in degenerative liver
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60
2. HEALTH EFFECTS
injury and functional impairment of the liver. It is ,
effects are directly related to the radiation toxicity Qf6 T t^lese
(since liver tumors have been observed), rather than a seco jt0niUm
response to other adverse biological events in the body alth
liver is expected to be less radiosensitive than more r' °U^
regenerating cells. Subtle changes in liver function as ^
doses of plutonium have not been evaluated. It is uncle & f8SU °^ ^"OW
reported literature whether complete liver function tes^at r°m t^le
in the occupational cohorts under investigation. As with th" P®rf°rnied
nonstochastic biological effects discussed, the level below
hepatic effects are unlikely to occur has not been clear lv^^I°
therefore, the effects of plutonium on hepatic function and hi '
levels encountered in the environment have not been identifiedSt° a**
Musculoskeletal Effects. Adverse musculoskeletal effects
associated with plutonium exposure have not been reported ' h
There is limited evidence of noncancerous bone damage and ^ U"!l^nS'
muscle damage in laboratory animals exposed to plutonium "m 6V* ?e of
is considered to be relatively resistant to the effects of 6 t*SSue
radiation (see Appendix B); therefore, damage to muscle tis ? ?
expected in animals and should not be of concern to individSU^ S
to plutonium in the environment. Bone damage occurred i u?ls exPosed
plutonium by the inhalation route and the injection route S SiV6n
soluble forms of plutonium resulted in bone damage when inhal d
Spontaneous fractures, which were age - dependent, alone wither
osteodystrophy, were seen at high radiation doses. These sk 1r0fTy and
effects may be due to radiation damage to rapidly dividing
especially in the ends of long bones; therefore/chil^gc^^«s
sensitive subpopulation and could be more sensitive to radiati -i a
bone damage. on-induced
Gastrointestinal Effects. Adverse gastrointestinal effects
associated with plutonium exposure have not been renori-»H i u
Gastrointestinal effects in animals have been reported onlv ln"!^' ,
study in neonatal rats. Because the epithelial cells of neonat ? °
rodents are immature and poorly enclosed, these cells may be more
sensitive to radiation damage in the neonate than in the adult
possible that infants would represent a sensitive suboomilation -
people exposed to plutonium by the oral route. Gastrolnt.st^, "S
absorption is limited, and translocation to othov
limited. The probability of exposure of humans to^lutoni^bv the*1*0
route is expected to be small; however if it Piuton 11111 °y the oral
radiation damage to the epithelial cells of the t t0 °ccur' ocalized
& "-ens or the stomach may occur.
Immunological Effects. Adverse immunological effects assort ^
with plutonium exposure have not been reported in humans
Inununotoxicity has been observed in several species administered
plutonium by inhalation and in dogs glven plutonium by injection
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61
2. HEALTH EFFECTS
Plutonium is translocated from the lungs to the tracheobronchial and
mediastinal lymph nodes, and has also been found in the hepatic lymph
nodes. Immunotoxicity ranged from alterations in antibody-forming cells
to atrophy and fibrosis of lymph glands. The animal data present a
consistent view that plutonium affects immune function either by
destruction of lymph nodes or circulating lymphocytes or other
alterations in immune system competence. The implications of this for
human health are unknown; however, it is possible that if alterations in
immune system competence were to occur, then the ability to respond to
other disease situations unrelated to plutonium could be affected. The
immunotoxicity which occurred in laboratory animals was observed at
concentrations lower than those that resulted in overt clinical
(respiratory) effects. These findings suggest that individuals exposed
to plutonium could develop subtle changes in the immune system that may
reduce immune competence at doses that may not induce overt signs of
toxicity.
Genotoxic Effects. Tables 2-4 and 2-5 present the results of in
vitro and in vivo genotoxicity studies, respectively.
Epidemiological studies do not provide evidence that plutonium
produces genetic damage in humans. In particular, the data from persons
involved in the Manhattan project after a 30-year follow-up have been
negative. In vitro tests using human lymphocytes irradiated with
plutonium-238 or plutonium-239 demonstrated increases in sister
chromatid exchange (Aghamohammadi et al. 1988) and chromosomal
aberrations (Purrott et al. 1980), respectively. In vitro studies have
also shown a dose-related linear increase in mutation frequencies at the
hypoxanthine-guanine phosphoribosyl transferase locus in cultured human
fibroblasts (Chen et al. 1984).
The animal in vivo and in vitro studies are in agreement.
Plutonium induced chromosomal aberrations in several species in vivo and
in the corresponding cell lines when cultured in vitro. Chromosomal
aberrations (Welleweerd et al. 1984) and gene mutations (Thacker et al.
1982) were seen in Chinese hamster cells cultured in vitro. Plutonium
was not genotoxic using the Ames test for mutagenicity in several
strains of Salmonella tvphimurlum (Fritsch et al. 1980).
Cancer. Epidemiological studies of occupational cohorts with long-
term exposure to plutonium include those of workers at Los Alamos
National Laboratory, Rocky Flats Nuclear Weapons Plant, or Hanford
Weapons Plant and the cohort involved in the original Manhattan project
at Los Alamos. None of these studies has demonstrated an unequivocal
association between exposure to plutonium and mortality from cancer at
any anatomical location in workers after 30 or more years. These
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62
2. HEALTH effects
TABLE 2-4. Genotoxicity of Plutonium In Vitro
End Point
Species/Test System
Prokaryotic organisms:
Gene mutation Salmonella typhimuyjum/
TA-100, TA-98, TA-1535
TA-1537, TA-1538,
TA-2420, TA-2421
Mammalian cells:
Gene mutation
Chromosomal
aberrations
Gene mutation
DNA damage
Reduction in
radio-
resistance
Sister
chromatid
exchanges
Chinese hamster/ovary
cell line
Human/lymphob1a s t i c
cell line
Human/lymphocytes
Chinese hamster/M3-l
cells
Human/embryonic skin
fibroblasts
Chinese hamster/ovary
cell line
Chinese hamster/V79-4
cells
Chinese hamster/V79-
379A cells
Mouse-rat/hybrid cell
line
Human/lymphocytes
+
+
+
+
+
+
+
+
+
Result
Reference
Fritsch et al. 1980
Fritsch et al. 1980
Fritsch et al. 1980
Purrott et al. 1980
Welleweerd et al. 1984
Chen et al. 1984
Barnhart and Cox 1979
Thacker et al. 1982
Prise et al. 1987
Robertson and Raju 1980
+ Aghamohammadi et al
1988
- - negative result
+ - positive result
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2. HEALTH EFFECTS
TABLE 2-5. Genotoxicity of Plutonium In Vivo
End Point
Species/Test System
Result
Reference
Mammalian systems:
Chromosomal
aberrations
Dominant lethal
Reciprocal/
chromosome
translocation
Chinese hamster/
testes
Mouse/testes +
Chinese hamster/liver +
cells
Mouse/bone-marrow +
cells
Syrian hamster/lung +
cells
Chinese hamster/blood +
cells
Human/peripheral (+)
lymphocytes
Human/whole blood
Human/blood lymphcytes +
Monkey/blood lyphocytes +
Mouse/germ cells
Mouse/germ cells +
Mouse/ovaries (+)
Mouse/spermatogonia +
Brooks et al. 1979
Brooks et al. 1979;
Beechey et al. 1975
Benjamin et al. 1976;
Brooks et al. 1976b
Svoboda et al. 1987
Stroud 1977
Brooks et al. 1976a
Brandon et al. 1979;
Tawn et al. 1985
Hempelmann et al. 1973;
Voelz et al. 1979
Schofield et al. 1980
LaBauve et al. 1980
Searle et al. 1976
Ltining et al. 1976a,
1976b
Searle et al. 1982
Beechey et al. 1975;
Generoso et al. 1985
Searle et al. 1976
+ - positive result
- - negative result
(+) - positive or marginal result
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2. HEALTH EFFECTS
studies have one or more of the same limitations inherent in other
epidemiological studies. These include small cohort size, poorly
defined exposure information, or insufficient follow-up periods.
However, the Rocky Flats study was extensive and exposures were
documented from health physics records. One limitation of the Rocky
Flats study is that the worker cohort was divided into only two exposure
categories based on body burden, less than or greater than 2,000 pCi
(74 Bq) plutonium. The authors concluded that the study suggested an
increased risk of lymphopoietic cancers based on a total of four such
lymphopoietic neoplasms, one each of lymphosarcoma/reticulosarcoma, non-
Hodgkin's lymphoma, multiple myeloma and myeloid leukemia. However, no
elevated cancer incidences were noted in tissues with the highest
concentrations of plutonium (tracheobronchial lymph nodes, lungs, liver,
and bone) as demonstrated in autopsy samples.
In contrast, the results from numerous animal studies are
conclusive. Plutonium at the concentrations administered produced lung,
liver, and bone cancers primarily when administered by the inhalation or
injection routes in dogs, mice, rats, and nonhuman primates. Only
Syrian hamsters appeared to be resistant to plutonium-induced tumors,
even though hamsters developed the same nonmalignant respiratory
effects. The current understanding of radiation-induced carcinogenesis
is that it is a stochastic process, that is, one without a threshold for
developing cancer. Mechanistically, plutonium should be considered to
have the potential to cause cancer due to the emission of alpha
particles (ATSDR 1990). While it is true that cancer in animals
resulted from extremely large concentrations that are orders of
magnitude higher than any occupational or environmental exposure (except
under an accident scenario), it is appropriate and health protective to
assume that some level of risk of cancer exists from exposure of humans
to plutonium.
2.5 BIOHARKERS OF EXPOSURE AND EFFECT
Biomarkers are broadly defined as indicators signaling events in
biologic systems or samples. They have been classified as markers of
exposure, markers of effect, and markers of susceptibility (NAS/NRC
1989) .
A biomarker of exposure is a xenobiotic substance or its
metabolite(s) or the product of an interaction between a xenobiotic
agent and some target molecule or cell that is measured within a
compartment of an organism (NAS/NRC 1989). The preferred biomarkers of
exposure are generally the substance itself or substance-specific
metabolites in readily obtainable body fluid or excreta. However,
several factors can confound the use and interpretation of biomarkers of
exposure. The body burden of a substance may be the result of exposures
from more than one source. The substance being measured may be a
metabolite of another xenobiotic (e.g., high urinary levels of phenol
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2. HEALTH EFFECTS
can result from exposure to several different aromatic compounds).
Depending on the properties of the substance (e.g., biologic half-life)
and environmental conditions (e.g., duration and route of exposure), the
substance and all of its metabolites may have left the body by the time
biologic samples can be taken. It may be difficult to identify
individuals exposed to hazardous substances that are commonly found in
body tissues and fluids (e.g., essential mineral nutrients such as
copper, zinc and selenium). Biomarkers of exposure to plutonium are
discussed in Section 2.5.1.
Biomarkers of effect are defined as any measurable biochemical,
physiologic, or other alteration within an organism that, depending on
magnitude, can be recognized as an established or potential health
impairment or disease (NAS/NRC 1989). This definition encompasses
biochemical or cellular signals of tissue dysfunction (e.g., increased
liver enzyme activity or pathologic changes in female genital epithelium
cells), as well as physiologic signs of dysfunction such as increased
blood pressure or decreased Lung capacity. Note that these markers are
often not substance specific. They also may not be directly adverse,
but can indicate potential health impairment (e.g., DNA adducts).
Biomarkers of effects caused by plutonium are discussed in
Section 2.5.2.
A biomarker of susceptibility is an indicator of an inherent or
acquired limitation of an organism's ability to respond to the challenge
of exposure to a specific xenobiotic. It can be an intrinsic genetic or
other characteristic or a preexisting disease that results in an
increase in absorbed dose, biologically effective dose, or target tissue
response. If biomarkers of susceptibility exist, they are discussed in
Section 2.7, "POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE."
2.5.1 Biomarkers Used to Identify or Quantify Exposure to Plutonium
Biomarkers of exposure to plutonium include the presence of
plutonium in urine, which is identified by measuring alpha activity.
From the levels of radioactivity in the urine, body burdens of plutonium
may be estimated by the use of models. Body burdens of plutonium in
several populations, including workers at Los Alamos National
Laboratory, the Rocky Flats facility, and the Hanford facility, have
been estimated from urinalysis data. However, whole body burdens
determined from selected tissues obtained at autopsy have generally been
lower than those estimated from urinalysis data (Voelz et al. 1979).
The presence of radioactivity from plutonium in urine is specific to
plutonium exposure. Plutonium may be found in the urine after any
exposure duration (e.g., acute, intermediate, chronic). Although it can
be assumed that exposure to greater levels of plutonium would result in
the presence of greater levels of radioactivity in the urine, no
information was located to directly quantify this relationship.
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2. HEALTH EFFECTS
2.5.2 Biomarkers Used to Characterize Effects Caused by Plutonium
Limited information is available regarding biomarkers of effect of
plutonium exposure. The presence of chromosome aberrations has been
reported in laboratory animals following exposure to plutonium.
Chromosome aberrations have also been reported in humans following
exposure through open wounds, but evidence from epidemiologic studies
where exposure occurred via inhalation have been equivocal (Brandora et
al. 1979; Hempelmann et al. 1975; Tawn et al. 1985; Voelz et al. 1979).
Although the presence of chromosome aberrations could be considered a
biomarker of effect, the number of chemicals that could cause this
effect is so great that the effect would not be considered plutonium-
specific. In dogs, the earliest observed biological effect of exposure
to plutonium is a dose-related lymphopenia that correlated in magnitude
and time of appearance post-exposure with initial lung burden (Park et
al. 1988; Ragan et al. 1986). Although there is currently no
information in humans regarding the occurrence of this effect, the
presence of lymphopenia in humans following plutonium exposure might be
a potential biomarker of effect.
Biomarkers of effect for plutonium exposure may exist but were not
located in the reviewed literature. For more information on biomarkers
of effects for the immune, renal, and hepatic systems see ATSDR/CDC
Subcommittee Report on Biological Indicators of Organ Damage (1990) and
for biomarkers of effect for the neurological system see OTA (1990).
For more information on health effects following exposure to plutonium
see Section 2.2.
2.6 INTERACTIONS WITH OTHER CHEMICALS
The toxicokinetics of plutonium appear to be influenced by exposure
to cigarette smoke. Cigarette smoke, when administered to mice
following inhalation exposure to plutonium-239 dioxide, appeared to
inhibit the clearance of plutonium. (Talbot et al. 1987). At 49 days
post - exposure, animals exposed to plutonium and cigarette smoke retained
approximately 20% more plutonium than those animals exposed to plutonium
alone.
Exposure to inhaled plutonium-239 dioxide followed by intratracheal
instillation of benzo(a)pyrene resulted in a higher incidence of lung
tumors and a decrease in median survival time compared to animals
exposed to plutonium-239 dioxide alone (Metivier et al. 1984). As the
dose of benzo(a)pyrene increased, survival time decreased. Exposure of
rats to a single intra-abdominal injection of a mixture of plutonium-239
dioxide and benzo(a)pyrene resulted In an additive effect in the
induction of abdominal sarcomas, compared to animals given
benzo(a)pyrene or plutonium only (Sanders 1973a).
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2. HEALTH EFFECTS
A decrease in median survival time was observed in rats injected
intravenously with plutonium-239, immediately followed by exposure to X-
rays (Ballou et al. 1962), as compared to those animals exposed to
plutonium alone. As exposure to X-rays increased, survival time
decreased. However, when exposure to X-ray was delayed (as much as 14
days) following exposure of the rats to plutonium-239, the number of
deaths occurring before 40 days was reduced.
Exposure of rats to plutonium-239 dioxide and asbestos by
intraperitoneal injection resulted in a higher incidence of abdominal
tumors compared to animals exposed to plutonium-239 dioxide alone
(Sanders 1973a). However, this additive effect of asbestos and
plutonium was not observed in the induction of pulmonary sarcomas when
asbestos was administered to rats in combination with plutonium-239
oxide via intratracheal instillation (Sanders 1975b). In the same
study, asbestos did not influence the translocation of plutonium in
rats. However, asbestos increased the pulmonary retention of plutonium
compared to those exposed to plutonium only (Sanders 1975b).
An increased incidence of metaplasia was observed in rats exposed
via inhalation to a single exposure of plutonium-239 dioxide followed by
administration of 1 or 10 mg vitamin C/ml of drinking water for 1 year
post-exposure, compared to those animals exposed to plutonium only
(Sanders and Mahaffey 1983). However, the incidence of squamous cell
carcinomas in animals exposed to plutonium and vitamin C decreased with
increasing dose of vitamin C. The authors state that vitamin C may
interfere with the progression of squamous cell metaplasia to squamous
cell carcinoma.
Studies in laboratory animals have also shown the influence of
metals on the toxicokinetics of plutonium. Pretreatment of rats with a
subcutaneous injection of cadmium or copper followed by an intravenous
injection of plutonium-239 or plutonium-238 resulted in changes in the
distribution patterns of plutonium, but not in total retention of either
isotope. Plutonium retention of both isotopes, following pretreatment
with either metal, was increased in the spleen and the kidneys, as
compared to animals treated with plutonium only (Volf 1980) . Copper
pretreatment appeared to increase the retention of plutonium in the
liver, while cadmium pretreatment appeared to decrease plutonium
retention in the liver. These differences in retention of plutonium in
the liver may reflect different properties of the respective metal-
binding proteins or different mechanisms of action (Volf 1980).
Exposure of rats via inhalation to beryllium oxide followed by
exposure to plutonium-239 oxide resulted in increased retention of
plutonium in the lungs of rats and subsequently, increased translocation
of plutonium to thoracic lymph nodes as compared to plutonium-treated
controls (Sanders et al. 1978). Although lung retention of plutonium
was increased and beryllium and plutonium are both considered to be lung
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68
2. HEALTH EFFECTS
carcinogens, combined exposures of beryllium and plutonium-239 did not
significantly increase the incidence of lung tumors in rats, compared to
rats treated with plutonium only (Sanders et al. 1978).
Administration of alcohol prior to exposure to plutonium appears to
have an effect on the toxicokinetics of plutonium. Rats were treated
orally with 12.5 or 25% ethanol (in 25% sucrose) for 1 or 6 weeks
followed by an intravenous injection of polymeric plutonium-239 and were
sacrificed 1 or 41 days post-exposure (Kahlum and Hess 1978). In
animals given ethanol for 6 weeks, retention of plutonium in the liver
was increased at 1 day post-exposure, but returned to normal Al days
post-exposure, compared to animals exposed to plutonium only. At 1 day
post-exposure, lung retention of plutonium was increased in animals
given ethanol for 1 week, while lung retention of plutonium was
decreased in animals given ethanol for 6 weeks. These differences were
still apparent at 41 days post-injection (Mahlum and Hess 1978).
Animal studies have been conducted to study the relative hazards of
"diffuse" vs. "localized" irradiation of the lung (Anderson et al. 1979)
to determine if there is a "hot particle" or "hot spot" effect. In
these studies, hamsters were exposed by instillation or intravenous
injection to plutonium-238 or -239 oxide contained in zirconium dioxide
spheres. Following "localized" exposure, the incidence of lung tumors
was significantly increased (3/102) only at the highest exposure
[3.5xl06 pCi (1.3xl05 Bq) plutonium-238/kg body weight]. However,
following "diffuse" exposure, a significant increase in the incidence of
lung tumors was observed at exposures of 8.4xl05 pCi (3.1x10* Bq)
plutonium-238/kg body weight and 9.4xl05 pCi (3.5x10* Bq) plutonium-
239/kg body weight. The authors concluded that for a given lung burden
of plutonium, the most hazardous distribution was "diffuse."
Animal studies have shown the effects of chelation therapy on the
removal of previously incorporated actinide elements, such as plutonium.
Exposure of young adult beagle dogs to a single intravenous injection of
polymeric plutonium-239 plus plutonium-237 as a tracer, followed by
weekly exposure to diethylenetriamine-pentaacetate (DTPA) as calcium
salt (Ca-DTPA) or daily exposure of DTPA as zinc salt (Zn-DTPA) ,
resulted in 14.6% or 10.4% plutonium-237 excretion, respectively, vs.
7.1% plutonium excretion at 24 hours post-exposure in those animals
exposed to plutonium alone (Lloyd et al. 1978c). After 28 days,
cumulative excretion (corrected for radioactive decay) reached 38.2% for
Ca-DTPA, 49.4% for Zn-DTPA, and 12.1% for those animals treated with
plutonium alone. The study indicated that daily exposure of beagle dogs
to Zn-DTPA is more effective in increasing the excretion of incorporated
plutonium than weekly exposure to Ca-DTPA. As speculated by the
authors, the enhanced plutonium excretion may have occurred as a result
of calcium replacement in Ca-DTPA or zinc replacement in Zn-DTPA by
plutonium at the cellular level.
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2. HEALTH EFFECTS
2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE
Children may be particularly susceptible to the adverse effects of
plutonium. Cells are replicating much faster in growing children than
in adults. Rapidly regenerating cells are more radiosensitive than
slowly regenerating cells (see Appendix B). Therefore, children may be
more susceptible to the radiation effects of plutonium than adults.
Persons with chronic obstructive lung diseases may be more
susceptible to the toxic effects of inhaled plutonium. Based on results
from studies in rats with pulmonary emphysema, plutonium deposition
would be decreased in a person with pulmonary emphysema, but retention
would be increased (Lundgren et al. 1981). Therefore, a greater
radiation dose would be delivered to the lungs of a person with
emphysema or other chronic obstructive lung diseases.
Persons who are anemic due to an iron deficiency may be more
susceptible to the toxic effects of plutonium. Studies by Ragan (1977)
have demonstrated that iron-deficient mice absorbed four times as much
plutonium from the gastrointestinal tract as mice with normal iron
levels. Therefore, persons who are iron deficient may absorb more
plutonium (Sullivan and Ruemmler 1988).
2.8 ADEQUACY OF THE DATABASE
Section 104(i)(5) of CERCLA, directs the Administrator of ATSDR (in
consultation with the Administrator of EPA and agencies and programs of
the Public Health Service) to assess whether adequate information on the
health effects of plutonium is available. Where adequate information is
not available, ATSDR, in conjunction with the National Toxicology
Program (NTP), is required to assure the initiation of a program of
research designed to determine the health effects (and techniques for
developing methods to determine such health effects) of plutonium.
The following categories of possible data needs have been
identified by a joint team of scientists from ATSDR, NTP, and EPA. They
are defined as substance-specific informational needs that, if met would
reduce or eliminate the uncertainties of human health assessment. In
the future, the identified data needs will be evaluated and prioritized,
and a substance-specific research agenda will be proposed.
2,8.1 Existing Information on Health Effects of Plutonium
The existing data on health effects of inhalation, oral, and dermal
exposure of humans and animals to plutonium are summarized in
Figure 2-4. The purpose of this figure is to illustrate the existing
information concerning the health effects of plutonium. Each dot in the
figure indicates that one or more studies provide information associated
with that particular effect. The dot does not imply anything about the
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70
2. HEALTH EFFECTS
SYSTEMIC
Inhalation
Oral
Dermal
HUMAN
SYSTEMIC
£
Inhalation
Oral
Dermal
ANIMAL
Existing Studies
FIGURE 2-4. Existing Information on Health Effects of Plutonium
100031-B
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71
2. HEALTH EFFECTS
quality of the study or studies. Gaps in this figure should not be
interpreted as "data needs" information.
Figure 2-4 graphically describes whether a particular health effect
end point has been studied for a specific route and duration of
exposure. Information on health effects in humans is very limited
largely because exposed populations are small. Epidemiological studies
of people who have been occupationally exposed by inhalation to
plutonium have evaluated end points such as mortality, cancer, and
systemic effects following chronic exposure. No information on health
effects in humans after acute or intermediate exposure to plutonium was
located. Information on health effects from animal studies is more
extensive than that which has been reported in epidemiological studies.
These studies in animals provide information on health effects following
both acute and intermediate inhalation exposure and limited information
on acute oral exposure.
2.8.2 Identification of Data Needs
Acute-Duration Exposure. The possibility of brief exposure of
humans to plutonium exists at hazardous waste sites or at accidental
spill sites. However, no data are available for humans exposed acutely
via inhalation or oral routes. Information on the toxicity of plutonium
in laboratory animals following single high-dose inhalation exposure is
extensive and indicates that the lung is the main target organ for
inhaled plutonium. Laboratory animals exposed by this route have
developed pneumonitis, fibrosis, metaplasia, and cancer. Acute exposure
of laboratory animals to lower doses of plutonium would be useful to
identify possible inhalation toxicity in humans. Limited information on
adverse effects in laboratory animals following acute oral exposure
indicates that the gastrointestinal tract is the main target organ.
However, kinetic studies indicate that plutonium absorbed from the
gastrointestinal tract is distributed to the skeleton and other tissues;
therefore, other organs may also be affected. Because there are no data
on humans and animal data are insufficient, additional information is
needed on adverse effects following acute exposure by the oral route.
No data are available on adverse effects following acute dermal exposure
in humans or animals. Limited information from kinetics studies in
humans and animals indicates that there is little absorption of
plutonium through intact skin. However, plutonium deposited in wounds
is absorbed and distributes to numerous organs, including regional lymph
nodes and the liver. Since industrial accidents resulting in plutonium-
contaminated wounds are known to occur, additional information on
adverse effects following this type of exposure would be helpful. One
outstanding problem with all of the existing acute exposure tests in
laboratory animals is that the doses tested are extremely high. Further
single-dose studies for all exposure routes using a number of lower
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72
2. HEALTH EFFECTS
exposure concentrations would be useful in determining anv dr.**
relationship for adverse health effects. g Y dose'resP0nse
Intermediate-Duration Exposure. Limited data from intermediate
duration exposure studies in laboratory animals indicate that the lu
is the target organ for inhaled plutonium. In one study, hamsters ^
developed pneumonitis following intermittent exposure to'plutonium
However, no data are available on effects of inhalation exposure for
this duration in humans. Kinetics studies in animals exposed by
inhalation are extensive but all are single-exposure studies No
information is available in animals or humans following intermediate
duration exposure by the oral or dermal routes. A single kinetics st
in rats exposed to plutonium by the oral route for an intermediate
period indicated that significant deposition was found in the
gastrointestinal tract, the skeleton, and soft tissues. Because limited
or no data are available on systemic effects or kinetics following
intermediate-duration exposure by all three routes, studies to provide
such data would be useful. These data could be used to predict human
health effects from exposure for this duration in populations livine
near hazardous waste sites and in the workplace, and to determine th
relative contribution of each of the three routes of exposure to theL
adverse health effects.
Chronic Duration Exposure and Cancer. No information on noncancer
health effects following chronic exposure of animals or humans to
plutonium by any route exists. Epidemiological studies generally renort-
only mortality from cancer and do not report deaths from noncancer
causes or other noncancer adverse effects that may have been identified
Limited kinetics studies of occupationally exposed individuals indicate'
that plutonium concentrations were higher in the lungs and tracheal
bronchial lymph nodes than in any other single organ, indicating that
the lung would be the target organ for inhaled plutonium. However no
noncancer effects were reported in these individuals Studies of '
kinetics following exposure by any route in laboratory animals are onlv
for single exposures._ Due to the general lack of data on noncancer 7
health eff cts following chronic exposure, results of tests in animals
exposed chronically to plutonium would be informative. Although such
tests may be difficult to design and carry out due to the radioactive
nature of plutonium, it would be useful to compare such data to
noncancer adverse effects which are commonly reported in single-dose
studies^ These studies would also be useful in evaluating toxicitv
other than cancer to the general public, as well as occupationally'
exposed individuals. In addition, it would be worthwhile to report
information on noncancer effects seen in follow-up of existing
occupational cohorts or new cohorts.
Scud.ie.s. ln r,ats and d°g* exposed to plutonium for 1 day have
indicated at plutonium via inhalation causes cancer. At various times
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73
2. HEALTH EFFECTS
following high doses of plutonium, tumors were found primarily in the
lung, but also in the skeleton and liver. Chronic studies of animals
exposed to plutonium via inhalation would be useful in order to compare
the type of cancers that may occur and the onset of these effects to
those reported in single-dose studies. Epidemiological studies have
been equivocal. Most epidemiological studies of occupationally exposed
individuals have consistently reported fewer cancer deaths in exposed
cohorts than in an unexposed cohort or in the normal population.
However, these epidemiological studies have many confounding factors
including small cohort size, poorly defined exposure information,
insufficient follow-up period, or possible concurrent exposure to
external radiation. In one epidemiological study, the authors report a
suggested increased risk of lymphopoietic cancers. However, the
incidence of this type of cancer was based on limited data, and no
increase in cancer incidence was noted in tissues with the highest
concentration of plutonium as demonstrated in autopsy samples. Chronic
animal studies at low radiation doses would be useful to provide
information to assist in the interpretation of inconclusive
carcinogenicity information from existing epidemiologic studies. No
information is available on kinetics or development of cancer in animals
or humans following oral or dermal exposure. Although acute studies
report that absorption via these routes is much less than absorption via
inhalation, chronic animal studies would provide information on kinetics
and possible carcinogenicity of plutonium by these routes.
Genotoxicity. Epidemiological studies of occupationally exposed
cohorts have reported equivocal results concerning exposure to plutonium
and increased incidence of chromosomal aberrations. However, in vitro
tests using human lymphocytes irradiated with plutonium demonstrated
increases in sister chromatid exchange. Laboratory animals have
exhibited increased chromosomal aberrations in blood lymphocytes
following exposure to plutonium by inhalation. Other effects seen in
vivo in animals include dominant lethality and reciprocal chromosomal
translocation. In vitro tests using mammalian cells confirm the in vivo
results. The evidence is clear that plutonium is genotoxic. However,
more extensive study of individuals occupationally exposed would be
useful, and would hopefully clarify the equivocal reports of previous
studies.
Reproductive Toxicity. There are no data available regarding the
reproductive toxicity of plutonium after inhalation, oral, or dermal
exposure in either humans or animals. In laboratory animals given a
single injection of a high dose of plutonium, significant fetal deaths
were reported and were attributed to dominant lethality. Kinetics
studies following single injection of plutonium indicate that plutonium
is distributed to the testes or ovaries of laboratory animals (Green et
al. 1976, 1977) and is retained there for an indefinite period of time
(more than 575 days) (Green et al 1977; Taylor 1977). Although this
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Ik
2. HEALTH EFFECTS
route of exposure is not relevant to humans, results of these studies
would indicate that studies to evaluate reproductive effects in
laboratory animals following single, repeated, or multi-generation
exposure to plutonium via inhalation or ingestion would be worthwhile.
Developmental Toxicity. There are no data available regarding the
developmental toxicity of plutonium after inhalation, oral, or dermal
exposure in either humans or animals. However, results of kinetics
studies in which animals were given a single injection of plutonium
showed that plutonium crosses the placenta and is retained in the fetus
(Green et al 1977; Sikov et al 1978b). These studies would indicate
that additional data are needed to evaluate developmental effects in
laboratory animals following single or repeated exposure to plutonium
via inhalation or ingestion.
Immunotoxicity. There are no data available regarding
immunotoxicity of plutonium after inhalation, oral, or dermal exposure
in humans. In dogs exposed to plutonium via inhalation for a single
day, damage to lymph nodes was observed in conjunction with pneumonitis
(Gillett et al. 1988). Once plutonium particles have been deposited in
the lung, macrophages play a role in the clearing process. in this
clearing'process, macrophages phagocytize plutonium particles and
ultimately deposit them in the lymph nodes. This mechanism may lead to
secondary damage to the lymph nodes and thus to the immune system. In
dogs given a single subcutaneous injection of plutonium, damage to lymph
nodes draining the injection site, as well as lymphopenia, were observed
(Dagle et al. 1984). The studies in dogs, together with knowledge of
the clearing process in the lung, indicate that studies designed to
evaluate the direct toxic effects of plutonium on the function of the
immune system would be useful.
Neurotoxicity. No studies have been done to determine the
neurotoxicity of plutonium. However, cells and tissues of the nervous
system may be less radiosensitive than faster regenerating cells of the
gastrointestinal tract or pulmonary epithelium. Consequently, neuronal
impairment would not be expected. For this reason, tests of the
neurotoxicity of plutonium may not be necessary at this time.
Epidemiological and Human Dosimetry Studies, Epidemiological
studies of occupational cohorts with long-term exposure to plutonium
include those established from employees at Los Alamos National
Laboratory, the Rocky Flats Facility, and the Hanford Facility, as well
as the cohort involved in the original Manhattan project at Los Alamos.
These studies have failed to demonstrate an unequivocal association
between exposure to plutonium and mortality from cancer following
occupational exposure. However, these studies contain many limitations
including small cohort size, poorly defined exposure information, or
insufficient follow-up periods. Because these occupational cohorts have
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2. HEALTH EFFECTS
been exposed to plutonium levels many times higher than environmentally
exposed populations, continuation of the follow-up of these cohorts
would generate useful information. Examination of these cohorts for end
points other than cancer, such as genetic effects and effects on the
immune system, would be useful.
Epidemiological studies in which humans were occupationally exposed
to plutonium attempted to correlate adverse health effects with body
burdens of plutonium. However, definite correlations between plutonium
exposure and body burdens have not been reported. Further information
in this area is needed. Epidemiological studies in which activity
concentrations in the workplace are reported also are needed. If an
epidemiological study were conducted in which activity concentrations in
the workplace were known, attempts could be made to correlate exposure
levels with body burdens, as well as with health effects. Isolated
measurement of plutonium levels resulting from fallout have been made in
air, water, food, and soil. Overall, information regarding levels of
plutonium in the environment is limited. If epidemiologic data could
provide dose-response information, additional studies on environmental
levels could provide information to evaluate the extent of the hazard
associated with environmental plutonium exposure or exposure to
individuals living near hazardous waste sites.
Biomarkers of Exposure and Effect. Currently, the only biomarker
of exposure that has been identified is the presence of radioactivity,
released by plutonium, in the urine. The presence of this activity in
the urine is specific to plutonium exposure and can be used to monitor
short-term, intermediate, or long-term exposure. Although the detection
of plutonium radioactivity in the urine is not a direct measurement of
exposure, estimates may be derived using mathematical models. Other
biomarkers of exposure may exist, such as the presence of plutonium in
blood, bone, teeth, or hair.
Biomarkers of health effects resulting from plutonium-released
radiation are not known. It is possible that early damage to bone
marrow resulting from radiation exposure may be indicated by a decrease
in stem cells or by a decrease in the number of red blood cells (Joshima
et al. 1981). It is also possible that abnormal sputum cytology may be
used as an early indicator of radiation damage to lung tissue (ATSDR
1990). Although a decrease in stem cells and abnormal sputum cytology
may indicate exposure to radiation, additional research to determine if
these methods are reliable and to correlate these effects with plutonium
exposure levels would be worthwhile.
Absorption, Distribution, Metabolism, and Excretion. For
laboratory animals, detailed quantitative information is available
regarding the absorption, distribution, and excretion of plutonium
compounds following acute exposure by inhalation or injection. There is
-------
76
2. HEALTH EFFECTS
no information on the toxicokinetics of plutonium following chronic
exposure to low levels, and studies in this area would be more
applicable to human exposure situations than single exposure studies.
Information concerning the toxicokinetics of plutonium in adult animals
following oral exposure is available. However, previous animal studies
have indicated that very little plutonium is absorbed following oral
exposure. Therefore, studies of kinetics following oral exposure are
not needed at this time. Studies of age-related changes in the
toxicokinetics of plutonium would be very valuable, especially those
age-related differences that may indicate enhanced exposure or
susceptibility. Very little is known regarding the absorption,
distribution, and excretion of plutonium compounds following dermal
exposure. However, it appears that the skin is an effective barrier
against most plutonium compounds.
Comparative Toxicokinetics. There is limited information regarding
comparative toxicokinetics among laboratory animal species and humans.
However, similar target organs have been identified among laboratory
animals exposed to plutonium. Toxic effects that have been observed in
animals have not been observed in humans. In addition, hamsters develop
many of the toxic effects in the lung following exposure to inhaled
plutonium, but have not been found to develop lung tumors. This may be
indicative of differences in anatomy and physiology or species
sensitivity. Information to help identify the appropriate animal model
to provide insight into the toxicokinetics of plutonium compounds in
humans would be useful.
2.8.3 On-going Studies
G.L. Voelz (Los Alamos National Laboratory) is investigating the
correlation between low-level plutonium and/or external radiation
exposure and lung cancer incidence or other diseases among current and
former workers at Rocky Flats, Los Alamos, Mound, Savannah River, Oak
Ridge, and Hanford.
Mechanisms of alpha-emitting and bone-seeking radionuclide-induced
skeletal cancers are being investigated by W.S. Jee (University of Utah)
in humans and dogs.
The long-term toxicity of inhaled plutonium-239 dioxide (B.A.
Muggenburg and his colleagues, Inhalation Toxicology Research Institute
and F.W. Bruenger, University of Utah) in juvenile and mature beagle
dogs is being studied. Influence of age at the time of exposure is the
focus of the studies. Studies by Muggenburg include single and multiple
exposure of rats, Syrian hamsters, and mice to plutonium-239 dioxide
aerosols similar to human exposure.
-------
77
2. HEALTH EFFECTS
J.H. Diel (Inhalation Toxicology Research Institute) has been
studying health effects in laboratory animals following repeated
exposure to insoluble plutonium over a long fraction of their lifetime.
Single exposures at comparable radiation dose levels are included for
comparison. Experiments using rats and dogs are still in progress,
whereas experiments using mice and hamsters have been completed.
The effects of inhaled plutonium-239 nitrate (G.E. Dagle, Pacific
Northwest Laboratories), or plutonium-239 dioxide or plutonium-238
dioxide (J.F. Park, Pacific Northwest Laboratory), on lifespan have been
under investigation in beagle dogs. The current investigation by Dagle
involves determining the interrelationship of lung cancer, bone cancer,
and noncancerous lesions in dogs exposed to low levels of plutonium.
Park is continuing to investigate the mechanisms of lymph node damage
and lymphopenia in these animals. The role of oncogenes in plutonium-
induced cancers will be examined in both studies by Dagle and Park.
Furthermore, M.E. Frazier (Pacific Northwest Laboratory) is studying
whether oncogenes are activated in plutonium-induced lung cancer or
whether oncogene activation is a cause or an effect of cancer
development.
An extensive investigation of the effects of lifetime inhalation of
low-levels of plutonium-239 dioxide [5xlO+z to 1.9xl0"5 pCi (1.9X101 to
7.0xl03 Bq) initial alveolar depositions] in rats is in progress by C.L.
Sanders (Pacific Northwest Laboratory).
Among the few studies in progress pertaining to plutonium
genotoxicity is the investigation of heritable plutonium-induced gene
mutations, chromosome aberrations, and dominant lethal mutations in mice
(P.B. Selby, Oak Ridge National Laboratory). P.G. Kale at Hampton
University is studying the genetic effects of plutonium in Drosophila.
Special emphasis will be placed on the dose-response relationship in
predicting consequences of low-level plutonium exposures.
Current studies by S.E. Dietert at Hanford Environmental Health
Foundation focus on elucidating the biokinetics and dosimetry of
plutonium and related elements in humans. The study includes
determining the distribution and concentration of transuranic elements
in man by radiochemical analysis of donated autopsy tissues from
occupationally exposed individuals. The uptake and distribution
patterns of plutonium and other actinides in humans are being studied by
J.F. Mclnory (Los Alamos National Laboratory). N.P. Singh at the
University of Utah is studying the biological half-lives of plutonium in
liver and bone of the general population of northern Utah.
M.F. Sullivan at Pacific Northwest Laboratory is investigating the
transfer factors involved in the absorption of plutonium in animals and
other actinides across the gastrointestinal tract under conditions that
may be experienced by humans (such as the oxidation state of plutonium,
-------
78
2. HEALTH EFFECTS
fasting, high acidity, iron and calcium deficiency). Plutonium
gastrointestinal tract absorption is being studied in three baboons in
order to obtain information on possible human gastrointestinal tract
absorption of plutonium (M.H. Battacharyya, Argonne National
Laboratory).
R.G. Cuddihy at Inhalation Toxicology Research Institute is
studying the mechanisms involved in the deposition and clearance of
inhaled plutonium in the respiratory tract of rats and other animals.
E. Shek (Pbarmatec) is investigating methods for improving
gastrointestinal tract absorption of orally administered chelating
agents, which bind metals such as plutonium and facilitate excretion
from the body. New actinide-chelating agents produced by microorganisms
are being tested by P.W. Durbin at Lawrence Berkeley Laboratory. It is
assumed that these agents bind plutonium(IV) and enhance its excretion.
Another study by Durbin includes the development of metabolic models for
plutonium and other radionuclides in order to verify and/or modify
metabolic models currently recommended by the International Commission
on Radiation Protection (ICRP) for these radioelements.
S C. Miller (University of Utah) is determining the localization
and distribution of plutonium-239 and other actinides in tissue,
cellular and subcellular compartments of the gonads (testes and
ovaries) in different species and in human tissue.
R E. Filipy (Pacific Northwest Laboratory) is continuing the
investigation of the effects of cigarette smoke on rats and dogs exposed
to plutonium as compared to sham-exposed animals or those exposed to
plutonium alone. The findings of the study will contribute to the
understanding of the potential health effects of inhaled plutonium among
the cigarette-smoking population.
-------
79
3. CHEMICAL AND PHYSICAL INFORMATION
3.1 CHEMICAL IDENTITY
The chemical formula and identification numbers for plutonium are
listed in Table 3-1.
3.2 PHYSICAL AND CHEMICAL PROPERTIES
Important physical and chemical properties of plutonium and its
compounds are listed in Table 3-2. There are 15 known isotopes of
plutonium which have atomic weights ranging from 232 to 246. Of these,
only plutonium isotopes 236 to 243 are of particular biological interest
either as a result of their production in nuclear processes or because
of other uses (Nenot and Stather 1979). Therefore, only these isotopes
are listed in the tables. The radiological properties for plutonium
isotopes are presented in Table 3-3. Decay schemes for plutonium-239
and plutonium-241 are given in Figure 3-1 and Figure 3-2.
Plutonium is a very reactive metal and oxidizes readily in moist
air. In finely divided form, plutonium metal is pyrophoric (Taylor
1973) . Plutonium exhibits five oxidation states from plutonium(III) to
plutonium(VII). The four lower oxidation states are stable in solution
and may co-exist in the same solution. Complex (coordination) compounds
are formed with many of the common inorganic anions, such as plutonium
nitrate (Pu(N03)<1) .
A large number of plutonium compounds have been prepared in the
solid state. Plutonium metal is attacked by all common gases at
elevated temperatures; thus ammonia and nitrogen form nitrides, hydrogen
forms hydrides, the halogens and gaseous halogen acids produce halides,
carbon monoxide forms carbides, and carbon dioxide produces carbides and
dioxides (Cleveland 1970). An in-depth review of the chemistry of
plutonium and its compounds is given in Cleveland (1970).
-------
TABLE 3~1. Chemical. Identity of Flutonita and Selected Plutoniw Compounds*
Property
Plutonium
Plutonium
Dioxide
Value
Plutonium
Nitride
Plutonium Plutonium Plutonium
Hexafluoride Oxalate Tetrafluoride
Chemical name
Isotopes
Plutonium
Plutonium-236
Plutonium-237
Plutonium-238
Plutonium-239
Plutonium-240
Plutonium-241
Plutonium-242
Plutonium-243
Plutonium metal
Trade naroesb
Chemical formula Pu
Chemical structure No data
Identification numbers:
CAS Registry0 7440-07-5
NIOSH RTECS No data
EPA Hazardous
Waste No data
OHM/TADS No data
DOT/UN/NA/IMCOd
Shipping UN 2918
HSDB No data
NCI No data
Plutonium
dioxide
No data
Oxide
Pu02
No data
No data
No data
No data
No data
No data
No data
No data
Plutonium
nitride
No data
Plutonium Plutonium
hexafluoride oxalate
Nitride
PuN
No data
No data
No data
No data
No data
No data
No data
No data
No data
No data
Halide
PuF6
Ho data
No data
No data
No data
No data
No data
No data
No data
Oxalate
complex
Pu(C204)a'
6H20
No data
No data
No data
No data
No data
No data
No data
No data
Plutonium
tetrafluoride
No data
Halide
PuF4
No data
No data
No data
No data
No data
No data
No data
No data
O
EC
n
>
t-1
00
o
CAS — Chemical Abstract Service
DOT/UN/NA/IMCO * Department of Transportation/United Nations/North America/International Maritime Dangerous Goods Code
EPA = Environmental Protection Agency
HSDB - Hazardous Substance Data Base
NCI = National Cancer Institute
NIOSH - National Institute for Occupational Safety and Health
OHM/TADS ¦ Oil and Hazardous Materials/Technical Assistance Data System
RTECS - Registry of Toxic Effects of Chemical Substances
'Source: Weast 1980, unless otherwise stated.
"Trade names were obtained from Taylor 1973.
cCAS Registry number obtained from Windholz 1983.
dDOT identification number obtained from 49 CFR 172.101 1988.
-------
TABIJR 3-2. Physical and dnlctl Properties of Plutooitv and Selected Plutcoiw Ca^oimds*
Value
Property
Molecular weight
Color
Physical $tateb
Meltins point, °C
Boiling point, °C
Density at 20°C
Odor
Odor threshold:
Hater
Air
Solubility:b
Water at 20°C
Plutonium
242.00
Silver-white
Metal
639.5
3232
19.84
Odorless
No data
No data
No data
Plutonium
Plutonium
Plutonium
Plutonium
Plutonium
Dioxide
Nitride
Hexafluoride
Oxalate
Tetrafluoride
274.00
256.01
355.99
526.13
317.99
Yellowish-
Black
Reddish-
Yellowish-
Pale brown
green
brown
green
Solid
Hard solid
Solid
Solid
Solid
2200-2400
No data
50.75
No data
No data
No data
No data
62.3
No data
No data
11.46
14.25
No data
No data
7.0
No data
No data
No data
No data
No data
No data
No data
No data
No data
No data
Hydrolized
in cold
No data
No data
Decomposes
in cold
No data
No data
Insoluble
in water
No data
No data
Insoluble
in water
water
water
Organic solvents
No
data
No
data
No
data
No
data
No
data
No
data
Partition coefficients
Log octanol/water
No
data
No
data
No
data
No
data
No
data
No
data
Log Koc
No
data
No
data
No
data
No
data
No
data
Ho
data
Vapor pressure
No
data
No
data
No
data
No
data
No
data
No
data
Henry's law constant
No
data
No
data
No
data
No
data
No
data
No
data
Autoignition
temperature
No
data
No
data
No
data
No
data
No
data
No
data
Flashpoint
No
data
No
data
No
data
No
data
No
data
No
data
Flamnability limits
No
data
No
data
No
data
No
data
No
data
No
data
Valence state
+3,
,+4,+5,+6,+7
No
data
No
data
No
data
No
data
No
data
O
SC
O
>
t-
o
*3
n
>
r
55
O
'Source: Weast I960, unless otherwise noted.
'The physical state for all compounds and the solubility for PuF4 were obtained from Taylor (1973).
O
Z
-------
TABLE 3-3 Radiological Properties of Plutonium Isotopes"
Specific
Half-life
Decay Modes
Decay
Activity
Isotope
(vearsl
and Enerevb (Mev)
Productc
(uCi)/em)
236Pu
2.85
«, 5.75
Uranium-232
5.32x10®
SF, 5.722
237pu
0.125
EC, 0.22
Uranium-233
1.21xl010
23Bpu
87.8
a, 5.46
Uranium-234
1.71xl07
SF, 5.456
239pu
24,390.0
a, 5.243
Uranium-235
e.nxlO''
240pu
6,537.0
a, 5.255
Uranium-236
2.28xl05
SF, 5.123
24ipu
15.02
fi, 0.0208
Americium-241
9.90xl07
2«pu
387,000.0
«, 4.89
Uranium-238
3.82xl03
2*3pu
56,600.0
£, 0.59
Americium-243
2.60xl012
SF - Spontaneous Fission
EC - Electron Capture
"Source: Nenot and Stather (1979), unless otherwise stated.
Spontaneous fission and electron capture energies obtained from Weast (1980).
cDecay product information derived from Walker et al. (1977).
-------
83
3. CHEMICAL AND PHYSICAL INFORMATION
Am
Pu
239
Pu
24.065
yn
Np
i
U
23S
U
7.038E8
yis
Pi
i
231
P«
3.276E4
, yri
Th
231 '
Th
25.52 Irj
1
227
Th
10.718
Li diyi
Ac
227 '
AC
21.773
ys
I
Ri
223
Ri
11.43
diyi
Fr
1
Rn
219
Rn
3.96 i
At
I
Po
215
Po
0.0017B0
I
Bi
1
211
Bi
2.14 mill
Pb
211 '
Pb
36.1 min
I
207
Pb
itible
•n
207
Ti
4.77 min
i iJphi decay
/* beudecty
Figure 3-1. Plutonium-239 Decay Series
-------
84
3. CHEMICAL AND PHYSICAL INFORMATION
Am
2
A
41
Am
32.2 yis
—
Pu
?*•
2-11
Pu
14.4 yis
I
Np
Z57
Np
2.14E6
U
I
i
233
U
1.SB5ES
_JHi
Pa
233
P>
27 days
I
Th
229
Th
7.340yn
Ac
i
225
Ac
10.0 d»yi
r - -
1 ^
225 '
fca
14.8 dayi
i
Fi
221
Fi
4.8 mm
Rji
I
At
217
At
0.0323 s
Po
1
213
Po
4.2pi
Bi
213
Bi
45.65
mm
i
209
Bi
stable
..f -
Pb
209
Pb
3.253
hrs
/
Ti
X alpha decay
f beta decay
Figure 3-2. Plutonium-241 Decay Series
-------
85
4. PRODUCTION, IMPORT, USE, AND DISPOSAL
4.1 PRODUCTION
Plutonium exists in trace quantities in naturally occurring uranium
ores (Weast 1980). Plutonium is produced by the bombardment of uranium
with neutrons. The most important isotope, plutonium-239, is produced
in large quantities from natural uranium in nuclear reactors (Weast
1980). Plutonium-240, -241, and -242 are produced from successive
absorption of neutrons by the plutonium-239 atoms. The successive
absorption of two neutrons rather than one by uranium leads to the
production of plutonium-238. Plutonium-237 is usually produced by the
helium ion bombardment of uranium-235.
During neutron bombardment of plutonium-239 and -241, fission
occurs in addition to neutron capture. With plutonium-239 about 70%
undergoes fission, while the remainder is transmuted to plutonium-240.
With plutonium-241, 20% undergoes fission and the remainder is
transmuted to plutonium-242 (Choppin and Rydberg 1980).
The plutonium in spent uranium fuel from light water reactors (LWR)
is 56% plutonium-239, 26% plutonium-240, 12% plutonium-241, 5%
plutonium-242, and 1% plutonium-238 (Choppin and Rydberg 1980). This
composition will vary with other types of reactor fuel, but this type is
the most common in reactors operating in the United States.
As of 1980, the world's nuclear power reactors were producing more
than 20,000 kg of plutonium per year (Weast 1980). In addition to
these, the United States Department of Energy (DOE) has operated nuclear
reactors to produce nuclear materials for the nation's defense program.
These include plants at Savannah River, South Carolina, and the Hanford
Works in Richland, Washington.
4.2 IMPORT
There is no information on the importation of plutonium. However,
small quantities of nonweapon plutonium have been produced at the Atomic
Energy Commission's (now Department of Energy) production reactors for
foreign sales (Liverman et al. 1974).
4.3 USE
The majority of the plutonium, in the form of plutonium-239, is
used as an ingredient in nuclear weapons. As a result of the
atmospheric testing of these weapons during the 1950s, plutonium has
been dispersed throughout the atmosphere. An estimated 400 kCi
(1.5xl016 Bq) plutonium-239 and -240 were produced during weapons
testing, of which approximately 325 kCi (1.2xl016 Bq) was globally
dispersed (Bennett 1976a). Four hundred kCi of plutonium-239 weighs
approximately 4,600 kg. Approximately 100,000 kCi (3.7xl012 Bq)
-------
86
4. PRODUCTION, IMPORT, USE, AND DISPOSAL
plutonium have been dispersed within our environment from about 400
nuclear explosive tests, including those by the United States, Great
Britain, and the Soviet Union between 1945 and 1963 (Facer 1980).
The nuclear reactors at the Richland and Savannah River plants were
built to produce nuclear materials for the nation's defense program.
The amounts of plutonium involved in the weapons program are necessarily
classified.
Plutonium-238 is used as a heat source in thermo-electric power
devices, such as have been employed on various satellites and had been
proposed for powering artificial hearts (Bair and Thompson 1974) . The
estimated total quantity of plutonium-238 required for these
applications through the year 2000 ranges from 25 to 75 kg (430 to 1,300
kCi; 1.6xl016 to 4.8xl016 Bq) (Liverman et al. 1974).
4.4 DISPOSAL
Plutonium is considered a transuranium (having an atomic number
greater than that of uranium) element. It has a very long radiological
half-life (86 and 24,000 years for plutonium-238 and -239,
respectively), and, therefore, the radioactivity diminishes very slowly.
Spent nuclear fuel is not reprocessed in the United States at the
present time, and the fuel must be disposed of intact (Lamarsh 1983).
The usual method of disposal has been to place the fuel in suitable
containers and bury them in a waste repository. Prior to 1970 solid
wastes containing radioactive wastes generated by nuclear power plants
were buried at commercial waste sites located at Sheffield, Illinois;
Beatty, Nevada; Morehead, Kentucky; Richland, Washington; and West
Valley, New York. As of 1974, approximately 80 kg of plutonium was
contained in this waste (Daly and Kluk 1975).
At present, radioactive wastes are being held at the DOE facilities
including those in Richland, Washington, Savannah River, South Carolina,
and at other reactor sites. These transuranic wastes are stored either
above ground or in shallow burial pits. Neither of these methods are
intended as long-term storage solutions.
-------
87
5. POTENTIAL FOR HUMAN EXPOSURE
5.1 OVERVIEW
Plutonium is a radioactive element produced by neutron capture and
beta decay of uranium-238 (or other elements), both naturally (in
minuscule amounts) and as a result of human activities. Plutonium is
found in the environment in the form of several isotopes. The source of
plutonium can be traced based on the isotope or isotopes detected in a
sample. Plutonium is found naturally in uranium-rich ores in
concentrations of one part per 1011 parts uranium (i.e., lxlO"11 kg
plutonium/kg uranium) (Leonard 1980).
The principal plutonium isotopes used in commerce and by the
military are plutonium-238 and plutonium-239. These two isotopes are
used because of their ease of production and their relatively long half-
lives. Plutonium-238 is used in thermoelectric generation systems in
spacecraft, cardiac pacemakers, and other power sources (Harley 1980;
NEA/OECD 1981). Plutonium-239 and -240 are produced in nuclear power
plants as a product of nuclear fission as well as in production
facilities for use in nuclear weapons.
Possible sources of plutonium to the environment include: weapons
testing, accidents involving weapons transport, nuclear reactors and
radioisotope generators, fuel processing and reprocessing, and fuel
transport (NEA/OECD 1981). Plutonium-239 is generated in irradiated
uranium fuel when neutrons are captured by uranium-238 nuclei. Some of
the plutonium-239 is consumed during the operation of the reactor.
Production of plutonium by nuclear reactors generating electricity and
by weapons production was estimated at 3.8xl06 kg in 1978 (NEA/OECD
1981) .
Atmospheric testing of nuclear weapons has been the main source of
plutonium dispersed in the environment. Accidents and routine releases
from weapons production facilities are the primary sources of localized
contamination. Consumer and medical devices containing plutonium are
sealed and are not likely to be environmental sources of plutonium (WHO
1983) . Plutonium released to the atmosphere reaches the earth's surface
through wet and dry deposition to the soil and surface water. Once in
these media, plutonium can sorb to soil and sediment particles or
bioaccumulate in terrestrial and aquatic food chains.
According to the NPL database (VIEW 1989), plutonium has been
identified above background levels at five NPL sites. Plutonium-238 has
been identified at three of these sites, plutonium-239 at five sites,
and plutonium-240 at one site. The frequency of these sites within the
United States can be seen in Figure 5-1.
-------
FIGURE 5-1. FREQUENCY OF SITES WITH PLUTONIUM CONTAMINATION
-------
89
5. POTENTIAL FOR HUMAN EXPOSURE
5.2 RELEASES TO THE ENVIRONMENT
5.2.1 Air
Anthropogenic (man-made) releases of plutonium are the primary
sources of plutonium to the atmosphere. Atmospheric testing, fires
involving plutonium-containing materials, and routine releases due to
normal activities at processing and generating plants are all potential
sources of airborne plutonium. Resuspension of plutonium sorbed to
contaminated surface soils via fugitive dust emissions is an indirect
pathway by which plutonium may be re-released Into the atmosphere
(Harley 1980).
Plutonium released during nuclear weapons testing is the largest
source of plutonium-239 and -240 in the environment (Harley 1980).
Approximately 320 kCi (1.2x1016 Bq) of plutonium-239, -240 and 9 kCi
(3.3xl01^ Bq) of plutonium-23B have been released to the atmosphere by
nuclear tests and distributed worldwide (Eisenbud 1987) . Concentrations
of transuranics introduced into the environment through underground test
venting, accidents involving United States nuclear weapons, and releases
during weapon production operations have been negligible in comparison
with those released during atmospheric testing of nuclear explosives in
the 1960s (Facer 1980).
In April, 1964, a Transit Navigational Satellite was launched in
California with a payload that included a Satellite for a Nuclear
Auxiliary Power Generator (SNAP-9A) containing 17 kCi (6.3X1D1* Bq) of
plutonium-238. The rocket system failed and the satellite reentered the
atmosphere in the Southern Hemisphere and burned over the Indian Ocean
at an altitude of about 50 km {Harley 1980). The destruction of the
SUAF-9A resulted in the largest single release of plutonium-238 to the
atmosphere, primarily in the form of very small oxide particles (Harley
1980).
Research facilities and plants have also released plutonium to the
atmosphere. For example, the Mound Plant in Hiamisburg, Ohio, released
about 0.03 kCi (lxlO10 Bq) to the atmosphere from the beginning of its
operation through 1976 (NEA/OECD 1981). A commercially operated
reprocessing plant in West Valley, New York, has reportedly released
0,000005 kCI (1.7x10s Bq) to the atmosphere over the course of 6 years
(NEA/OECD 1981).
5.2.2 Water
Fallout from atmospheric weapons testing, accidents involving
nuclear weapons, planned as well as accidental reactor effluent
releases, and disposal of radioactive wastes are all means by which
plutonium can be introduced into water systems (Harley 1980; NEA/OECD
1981). In a typical 1,000 megawatt electric (MWe) light water reactor
-------
90
5. POTENTIAL FOR HUMAN EXPOSURE
in a nuclear power plant about 200 kg of plutonium [equivalent to 13 kCi
(4.8xl01'i Bq) ; one curie of plutonium-239 - 16g] are generated per year
of operation in the spent fuel (NEA/OECD 1981; Facer 1980).
Contaminated cooling water containing plutonium from nuclear production
facilities may have been discharged into oceans or rivers. If release
occurs from waste containers, buried radioactive wastes may migrate or
seep into groundwater (NEA/OECD 1981). As an example of plant
emissions, the Mound Plant in Miamisburg, Ohio, discharged a total of
about 0.0005 kCi (1.9xl010 Bq) plutonium-238 into a river near the site
from the beginning of its operation through 1976 {NEA/OECD 1981) .
In January, 1968, while attempting to make an emergency landing, a
United States military aircraft with four nuclear weapons on board
crashed in Thule, Greenland. The impact resulted in detonation of the
high explosives in all four nuclear weapons aboard. The oxidized
plutonium was dispersed by both the explosion and the fire involving the
fuel in the jet (Harley 1980). Amounts of plutonium released to the air
in this accident have been estimated at 0.024 kCi (9X1011 Bq) of
insoluble plutonium (NEA/OECD 1981). The maximum concentration of
plutonium in ocean sediments was found 1 km from the point of impact.
The sediment-bound plutonium was found to migrate both downward in the
sediment column and horizontally from the point of impact. The
concentrations decreased with distance from the point of impact.
Sediments can act as both a repository for and a source of
waterborne plutonium. Atmospheric fallout reaching surface water can
settle in the sediments. The plutonium in the ocean sediments at Bikini
Atoll, for example, was found to be resuspended and released to the
bottom waters (Schell et al. 1980). In a freshwater waste pond at the
Hanford reactor, plutonium was found to be bound to the sediments and
was not available for uptake by plants or animals in the pond (Emery et
al 1980). The difference between the observations in the two
ecosystems may be due to the dynamic nature of the ocean water near
Bikini Atoll versus the relatively static nature of a waste water pond.
5.2.3 Soil
Plutonium has been detected in extremely small amounts as a
naturally occurring constituent of some minerals and ores. Uranium and
thorium ores in Canadian pitchblende, Belgium Congo pitchblende,
Colorado pitchblende, Brazilian monazite, and North Carolina monazite
have been found to contain plutonium-244 at a weight ratio of up to
9.1xl0"12 kg plutonium/kg ore (Leonard 1980).
Soils may become contaminated from fallout associated with nuclear
weapons tests, such as those conducted at the Trinity Site in southern
New Mexico, the Pacific Proving Ground at the Enewetak Atoll, and the
Nevada Test Site or with accidental, non-nuclear detonation of nuclear
weapons, such as occurred at Palomares, Spain. Research facilities,
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5. POTENTIAL FOR HUMAN EXPOSURE
such as the Los Alamos National Laboratory, Los Alamos, New Mexico, may
release treated radioactive wastes under controlled conditions.
Production facilities, such as the Hanford and Savannah River Plants and
experimental reactor stations, for example, the Idaho National
Engineering Laboratory, Idaho Falls, Idaho, also released treated
plutonium-bearing radioactive wastes under controlled conditions to
soils (Hanson 1975).
Atmospheric weapons testing fallout has been a global source of
transuranics, Including plutonium, in soils (Harley 1980; NEA/OECD
1981). It has been estimated that approximately 100 kCi (3.7xl015 Bq)
of plutonium from weapons have been distributed globally from all
testing sources and could be environmentally available. Of that amount,
approximately 1.0 to 10 kCi (3.7xl013 to 3.7xl014 Bq) were deposited on
test site surface soils in the United States (Facer 1980).
Several of the major nuclear facilities in the United States use
plutonium and some of these have released plutonium to the environment.
These releases have taken place at remote sites and generally have not
been measurable outside the plant property. Approximately 0.002 kCi
(7.4xl010 Bq) of plutonium have been disposed in the Los Alamos National
Laboratory canyon waste disposal sites (Harley 1980). The Savannah
River Plant, Aiken, South Carolina, has released a total of 0.005 kCi
(1.6xl0u Bq) of plutonium to local soil (Harley 1980). Leakage of
stored waste released between 0.01 and 0.1 kCi (3.7xlOn and 3.7xl0lz Bq)
of plutonium to the soil over a period of several years at the Rocky
Flats facility, Golden, Colorado (Facer 1980). A break in a waste
transfer line caused the release of about 0.3 kCi (l.lxlO13 Bq) of
plutonium-238 at the Mound Plant, Miamisburg, Ohio, in 1969 (Facer
1980).
A fire on May 11, 1969, occurred at the plutonium processing
facility at Rocky Flats, Golden, Colorado. Subsequently, a study of the
plutonium content in off-site soils was performed. The results of the
study indicated that the plutonium found off-site was due, primarily, to
small emissions from the facility rather than to the fire, and that a
total of 0.003 kCi (9.6xl010 Bq) of plutonium was deposited in soils
within a 7 mile radius from the facility (Eisenbud 1987).
Another source of soil contamination at Rocky Flats was the leakage
of plutonium-contaminated oil. Plutonium was present as the dioxide
when it was released. The dioxide was then adsorbed to the soil.
Fugitive dust emissions caused plutonium-contaminated soil to be
distributed away from the spill. Most of the plutonium remained on the
surface, although some was released and migrated downward through the
soil column (Little and Whicker 1978).
A United States military aircraft carrying four nuclear bombs
collided with a tanker aircraft during refueling in Palomares, Spain, in
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5. POTENTIAL FOR HUMAN EXPOSURE
January, 1966. The bombs broke free of the airplane and the high
explosive in two of the weapons detonated when the bombs hit the ground
Initial surveys showed that 0.00003 Ci plutonium/m2 (1.2xl06 Bq/m2) in
the form of a finely powdered dioxide, were spread over 2 hectares
(20,000 m2) (Harley 1980).
5.3 ENVIRONMENTAL FATE
5.3.1 Transport and Partitioning
Plutonium enters the environment primarily through releases to the
atmosphere or direct discharge to ponds, streams, or oceans. Emissions
to the atmosphere will result in plutonium fallout. In the case of
weapons testing, approximately one-fifth of the plutonium released falls
on the test site (Harley 1980). The rest is carried in the atmosphere
adsorbed to particulate matter and is transported back to earth via dry
or wet deposition. Once plutonium is deposited either on the land or
surface water, sorption to soils or sediments is the primary
environmental fate of plutonium. A small fraction of plutonium reaching
the soil will become solubilized either through chemical or biological
processes, depending upon its chemical form. In soluble form, plutonium
can either migrate in groundwater or surface water or be available for
uptake into plants.
Atmospheric releases of plutonium occur as a result of nuclear
weapons testing or routine or nonroutine nuclear reactor operations and
fuel reprocessing. The rate at which plutonium is removed from the
atmosphere will depend on the chemical and physical properties of
particles to which it is adsorbed, as well as the meteorological
conditions. The larger the particles, the faster fallout will occur.
The particle size expected to be released from either of the above
mentioned sources ranges from 0.3 (im to 1.1 pm. Based on computer
modeling, these particles are expected to reach the earth's surface
within 60 days of their release (NEA/OECD 1981). The global fallout
rate of plutonium-238, predominantly from the SNAP-9 accident, as
determined by Harley (1980), is 0.002 pCi/m2/day (7.4xl0~5 Bq/m2/day)
based on plutonium levels measured in surface soils. The global
deposition rate of plutonium-239 and plutonium-240 combined is equal to
0.03 pCi/m2/day (l.lxlO-3 Bq/m2/day) (Corey et al. 1982).
Plutonium deposited on soil surfaces may be resuspended in the
atmosphere especially in areas that have low soil moisture levels, such
as the Nevada Test Site. In drier areas, the levels of ambient airborne
dust are expected to be higher than In areas with normal rainfall
(Harley 1980). The highest concentrations of plutonium are likely to be
found in the fine silt-clay particle size range. Particles of this size
tend to be transported the farthest distance by wind and water (WHO
1983).
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5. POTENTIAL FOR HUMAN EXPOSURE
The transport and partitioning of plutonium in soils depends on the
form of the compound. The solubility of plutonium depends on the
properties of the soil, the presence of organic and inorganic complexing
agents, the form of plutonium that enters the soil environment, and the
presence of soil microorganisms (Bell and Bates 1988; Kabata-Pendias and
Pendias 1984; WHO 1983; Wildung and Garland 1980). Plutonium fallout
from the atmosphere, for example, tends to be deposited primarily as the
insoluble dioxide (Harley 1980; Wildung et al. 1987). The majority of
plutonium remains within the top few centimeters of the soil surface as
the dioxide form (WHO 1983). Microorganisms can change the oxidation
state of plutonium, thereby either increasing or decreasing its
solubility.
Plutonium will migrate in soils as the hydrolyzed ion or as a
complex, formed with organic or inorganic acids. Mewhinney et al.
(1987b) found that particles subjected to wetting and drying, such as
those found on the soil surface, released more plutonium than soils
continually immersed in a solvent, such as that found in lakes. This
phenomenon is attributed to the formation of a soluble dioxide layer on
the particle's surface during the drying phase. Soil organisms have
also been found to enhance the solubility of plutonium (Wildung et al.
1987). Once plutonium enters the soluble phase, it then becomes
available for uptake by plants. The plutonium(IV) oxidation state is
found in plants due to its ability to hydrolyze in the environment
(Garland et al. 1981, 1987). Cataldo et al. (1987) postulate that
reduction of the higher oxidation states, such as plutonium(VI), occurs
prior to absorption/transport across the root membrane.
The behavior of plutonium in surface waters is dependent upon the
oxidation state and the nature of the suspended solids and sediments.
Plutonium(III) and plutonium(IV) are considered to be the reduced forms
of plutonium while plutonium(V) and plutonium(VI) are the oxidized
forms. The oxidized forms of plutonium are found in natural waters when
the concentrations of dissolved organic matter or dissolved solids are
low (Nelson et al. 1987). Humic materials (naturally occurring organic
acids) were found to reduce plutonium(V) to plutonium(IV) in sea water.
This was followed by adsorption of plutonium(IV) onto iron dioxides and
deposition into the sediments (Choppin and Morse 1987) .
The partitioning of plutonium from surface water to sediments in
freshwater and marine environments depends on the equilibrium between
plutonium(IV) and plutonium(V), and the interaction between
plutonium(IV) in solution and plutonium sorbed onto sediment particle
surfaces (NCRP 1984). Sorption onto marine clays was found to be
largely irreversible (Higgo and Rees 1986). Higgo and Rees (1986) also
found that the initial sorption of plutonium onto clays was effective in
removing most of the plutonium species that would be able to sorb onto
the clay. When sorption to carbonate marine sediments was investigated,
it was found that some desorption from the surface would also occur.
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5. POTENTIAL FOR HUMAN EXPOSURE
This behavior was due to the presence of plutonium carbonate complexes
on the sediment surfaces which were sorbed less strongly than plutonium
dioxide complexes (Higgo and Rees 1986). In fact, the formation of
plutonium complexes with organic carbon causes plutonium to remain in
solution as a complex (NCRP 1984) .
Plutonium can be taken up from various environmental media into
plants and animals. The highest concentrations of plutonium in plants
are found in the roots where plutonium is present as a surface-absorbed
plutonium complex, a stabilized complex, or as a soluble plutonium
complex (Garland et al. 1981). The concentration of plutonium in soil
can be compared with the concentration in plants to determine what
fraction present in soil reaches the plant. Soil to plant concentration
ratios of lxlO'6 to 2.5xlO~4 plutonium In wet vegetation/plutonium In dry
soil have been calculated based on radioisotope experiments in plants
grown in controlled environments. The stems and leaves have lower
overall concentrations of plutonium than the roots, but higher
concentrations of soluble plutonium. The seeds were found to have low
concentrations of plutonium, which indicated that plutonium was not very-
mobile in plants (Cataldo et al. 1987). In studies on orange trees,
Pinder et al. (1987) found that plutonium-238 was deposited on the leaf
or soil surface, remained there, and that no measurable quantities were
transferred to the fruits. Grain crops grown near the Savannah River
Plant, Aiken, South Carolina, were found to contain higher
concentrations of plutonium the closer to the facility they were grown.
During harvesting, plutonium from soils or straw was resuspended and
mixed with the crop. Plutonium in vegetable crops grown at Oak Ridge
National Laboratory, Oak Ridge, Tennessee, contained higher plutonium
concentrations in the foliage biomass than in the fruit. Peeling of
potatoes and beets removed 99% of the residual plutonium (Adriano et al.
1980)-
Plutonium transferred from soil or plants to grazing herbivores was
redominantly associated with the animal's pelt and gastrointestinal
tract (Hakonson and Nyhan 1980). Rodents studied near the Los Alamos
and Trinity sites in New Mexico support this claim. Hakonson and Nyhan
(1980) found no evidence of bioconcentration through the food chain from
soil to plants to rodents. They concluded that soil was the source of
plutonium in rodents. In contrast, a study by Sullivan et al. showed
that rodents absorbed more plutonium-238 when it was incorporated into
aifalf3 (by growing it in soil containing plutonium) than when it was
adiii:lrlistered inorganic form (Sullivan et al. 1980). This study
sug6ests that Plutonium bound to organic compounds may have increased
availability¦ However, the authors indicate that further study is
needed.
plutonium was found to bioaccumulate in aquatic organisms,
a** l°wer end of the food chain. The bioconcentration
factors amount of the chemical found In the organism divided
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5. POTENTIAL FOR HUMAN EXPOSURE
by the concentration in the surrounding water over the same time period)
were 1,000 for raollusks and algae, 100 for crustacea, and 10 for fish
(WHO 1983). Plutonium is concentrated in the bones of fish rather than
in muscle tissues, as seen by whole fish to muscle tissue ratios of
2xl06 to 5x10* or 40:1 (NCRP 1984).
5,3.2 Transformation and Degradation
Plutonium is formed and transmuted through radioactive decay.
Three common types of radioactive processes involve the release of alpha
or beta particles or gamma rays. Alpha decay results in the release of
an alpha particle, which is a charged particle emitted from the nucleus
of an atom having a mass and charge equal in magnitude to a helium
nucleus (i.e., two protons and two neutrons). In alpha decay, the
atomic mass of the nuclide is reduced by four and the atomic number by
two. For example, plutonium-239 undergoes alpha decay to form uranium-
235.
Beta particles are charged particles emitted from the nucleus of an
atom with a mass and charge equal in magnitude to that of an electron.
In beta decay reactions, as the electron is ejected, the number of
protons in the resulting atom increases, changing the atomic number of
the atom but not the mass. For example, plutonium-241 undergoes beta
decay to form americium-241.
A gamma ray is short wavelength electromagnetic radiation emitted
from the nucleus. Nuclei which have undergone transmutation by alpha or
beta decay or by capture of a neutron often return to the ground state
by emission of gamma radiation. Addition of a neutron changes the
atomic mass or isotope number of the element but not the atomic number,
as seen by the formation of plutonium-242 from plutonium-241.
The chemical transformation reactions plutonium undergoes in the
environment are primarily oxidation and reduction reactions. There are
five oxidation states found in the environment. These are
plutonium(III), plutonium(IV), plutonium(V), plutonium(VI), and
plutonium(VIl). The last, plutonium(VII), is not commonly found and it
is only found under very alkaline conditions. The dominant oxidation
state of plutonium in the environment is plutonium(IV) (Wildung et al.
1987) .
5.3.2.1 Air
Plutonium does not undergo transformation processes in the air
beyond those related to radioactive decay. Radioactive decay will be
important for the short-lived Isotopes with half-lives less than the
average residence time in the troposphere of approximately 60 days. For
example, plutonium-237 has a half-life of 46 days and undergoes electron
capture to form neptunium-237 which has a half-life of 2.lxlO6 years
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5. POTENTIAL FOR HUMAN EXPOSURE
(Nero 1979). Therefore, neptunium-237 may form in the stratosphere
prior to deposition of plutonium-237 on the earth's surface as fallout.
5.3.2.2 Water
The important chemical transformation process in surface water is
the oxidation or reduction of plutonium. In waters with low suspended
solids, plutonium is generally found in oxidized forms, dissolved in the
water.' In waters with high suspended solids, plutonium is generally
reduced and sorbed onto either suspended solids or sediments (Choppin
and Morse 1987; Higgo and Rees 1986; Nelson et al. 1987).
Plutonium behaves differently than many other inorganic elements in
that it can exist simultaneously in four oxidation states over a range
of pH values. Under acidic conditions, the nature of the complexing
ligands present in solution will influence the oxidation state of
plutonium. The presence of fulvic acid (a naturally occurring organic
acid) facilitates the reduction of plutonium(IV) to plutonium(III),
especially below pH 3.1. The reduction of the higher oxidation states
appears to be even less dependent on pH, especially below pH 6
(Bondietti et al. 1976).
5.3.2.3 Soil
Plutonium found in soils may undergo the same oxidation/reduction
reactions described for surface waters in places where soil contacts
water. In addition to oxidation/reduction reactions, plutonium can
react with other ions in soil to form complexes. These complexes may
then be absorbed by roots and move within plants; however, the relative
uptake by plants is low. In plants, the complex can be degraded but the
elemental plutonium will remain.
5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT
5.4.1 Air
Table 5-1 summarizes plutonium levels measured in air at nine
different locations. Since 1945, when the first nuclear weapon test at
Alamogordo, New Mexico, was conducted, approximately 360 kCi (1.3xl016
Bq) of plutonium-239, -240 have been released into the atmosphere from
various sources. The accidental burn up of the SNAP-9 satellite added
17 kCi (6.3x10" Bq) to the higher altitudes of the atmosphere (Perkins
and Thomas 1980).
A 15-year study (1966 to 1980) in Palornares, Spain, reported levels
of plutonium in air near the site of a crash between a United States
military aircraft carrying four nuclear bombs, and a tanker aircraft
following the cleanup of the contaminated area (Iranzo et al. 1987).
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5. POTENTIAL FOR HUMAN EXPOSURE
TABLE 5~1. Plutcnim Level* Detected in Air
Location
Quantity
[pCi/m3 (Bq/m3)]
Study
Comments
Spain, weapon accident:
Urban area
Near farm land
1.5xl0"4 (5,5xl0~6) 239.2*°Pu
1.4xl0"3 (5.2xl0"s) 239.z«pu
Iranzo et al. 1987 Average over 15
years
Savannah River Plant:
First year:
Second year:
Rocky Flats facility:
1 m
1 km
2. 5 km
New York City
Hew York City
3.1x10"® (1.2x10-®) 238Pu
1. 5xl0"s (4 . 3xl0"7) 239.2*0^
1.15xl0"3 (5.6xl0"5) 238Pu
3.2xl0"5 (1.2xl0"6) 239.2«0pu
2.2xl0"3 (8.1x10-5) 239.240pu
U.6xl0"4 (1.7xl0"5) 239.240pu
7.OxlO"5 (2.6xl0*6) Z39,240pu
3.4xl0"5 (1.3xl0"6) 239.2*Opu
3.OxlO"5 (l.lxlO"6) 239Pu
1.OxlO"5 (3.7xl0"7) z38Pu
Corey et al. 1982
Cumulative concen-
trations over one-
year time period
(not an average)
Volchok et al. 1977 Average concentra-
trations over 7
years
Volchok et al. 1977 Average concentra-
trations over 7
years
Hardy 1973
Typical radioactivi-
ty concentrations
in ground-level air
(no further specifi-
cation)
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5. POTENTIAL FOR HUMAN EXPOSURE
Air sampling conducted continuously for 2 years (1975 to 1977) near
the Savannah River Plant measured the average yearly concentrations of
plutonium-238 and of plutonium-239, -240. The data for the first and
second years of the study are presented in Table 5-1 (Corey et al.
1982). The data in Table 5-1 indicate that releases from the Savannah
River Plant and levels detected in New York City (Hardy 1973) are on the
same order of magnitude and are much lower than those observed in
Palomares, Spain, following the cleanup of the weapon accident.
Continuous air sampling in the vicinity of the Rocky Flats facility
near Denver was initiated in 1970. The data in Table 5-1 are from
locations 50 meters, 1 kilometer, and 2.5 km from the facility and are
arithmetic means of data from sampling years 1970 to 1976. For purposes
of comparison, sampling data for New York City for the same time
interval are included. Data from all four locations indicated declining
levels following 1971 (Volchok et al. 1977).
5.4.2 Water
Table 5-2 presents plutonium levels detected in several surface
waters and groundwaters. The Pacific Ocean was sampled for plutonium
and Northern Pacific concentrations were, on the average, greater than
those detected in the Southern Pacific for both plutonium-239, -240 and
plutonium-238 (Miyake and Sugimura 1976). The plutonium content of the
particulate matter in three South Carolina estuarine systems was
investigated by Hayes et al. (1976). The Neuse and Newport River
estuaries received plutonium only through atmospheric fallout; the
Savannah River estuary received effluent from the Savannah River Plant.
Concentrations detected in the three estuaries are comparable. Raw
water samples taken from three locations on the Savannah River were also
found to contain levels comparable to the Savannah River estuary samples
(Corey and Boni 1976). The estuarine and river concentrations were
greater than the Pacific surface water samples, but were on the same
order of magnitude as seawater samples taken from Trombay (Bombay,
India) (Pillai and Mathew 1976). These results indicate that plutonium
is found throughout the globe but that the highest concentrations of
plutonium in water are found near source areas.
The groundwater at Enewetak Atoll and near the Idaho National
Engineering Laboratory disposal well were found to contain plutonium-
239, plutonium-240 and plutonium-238, respectively (Cleveland and Rees
1982; Noshkin et al. 1976). The isotope composition differs in the two
areas (Table 5-2), and the levels detected in Idaho were, on average,
lower than those detected at Enewetak Atoll. The range of groundwater
concentrations at the Nevada Test Site was greater than the range
detected in either of the other two groundwaters (Gonzalez 1988) .
Rainwater samples taken from Trombay (Bombay, India) in 1971 were
reported to contain plutonium-239 concentrations greater than those
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5. POTENTIAL FOR HUMAN EXPOSURE
TABLE 5~2. PLutoniiaa Levels Detected in Hater
Location Quantity Reference
pCi/L (Bq/L)
North Pacific surface water Z.ZxlO"4 to 9.4xl0"4 238Pu & 239,240^ Miyake and Sugimura 1976
(8.2*10-® to 3.5xl0"5)
South Pacific surface water 1.3xl0"4 to 3.4*10"* 238Pu & 239,240pu
(4.8xl0"6 to l.Srlfl-6)
Enewetak, South Pacific: 2.0xl0"4 to 2.8x10"' 239,240^ Noshkin et al. 1976
Groundwater (7,4xlQ"€ to l.OxlO"2)
Idaho National Engineering l.lxlO"2 to 7.8xlQ"2 Z3BPu Cleveland and Rees 1982
Laboratory: (A.1x10"* to 2.9xl0"3)
Groundwater
South Carolina:
Estuarian waters 1.7x10-' to 2.5xl0"3 239,Z40pu Hayes et al. 1976
<6.3xl0"6 to 9.4xl0"5)
River waters 4.3x10"* to 2.3xl0"3 239.240^ Corey and Boni 1976
<1.6xl0"5 to 8.3X10"5)
Trombay, India:
Rainwater B.2xl0"2 O.OxlO"3) 239Pu Pillai and Mathew 1976
4xl0-3 to 2xl0-2 239Pu
(1.5xl0"4 to 7.4xl0"4)
New York City:
Drinking water 8xl0'5 to 6.1xl0"4 239,z«0pu Bogen et al. 1988
O.OxlO"6 to 2.3xl0'5)
Nevada Test Site:
Groundwater
4.2xl0-2 to 2.6 239Pu
<1.6xl0"3 to 9.6xl0"2)
Gonzalez 1988
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5. POTENTIAL FOR HUMAN EXPOSURE
detected in seawater from the same area, as seen in Table 5-2 (Pillai
and Mathew 1976).
Plutonium concentrations in the New York water supply measured
between 1974 and 1979 showed a peak concentration of plutonium-239, -240
in the summer of 1974 which fell within the range of other surface
waters analyzed (Table 5-2). The low concentration detected during the
following autumn was below the concentrations detected in other waters
(Bogen et al. 1988).
5.4.3 Soil
Average fallout levels in soils in the temperate United States are
about 2,100,000 pCi/km2 (7.8x10* Bq/km2) plutonium-239, -240 and 50,000
pCi/km2 (1.9xl03 Bq/km2) plutonium-238 (Hanson 1975). Mean deposition
rates of stack-released plutonium-238 to soils around the Savannah River
Plant range from 0.008 to 0.64 pCi/m2/day (3.0x10"* to 2.4xl0"z
Bq/m2/day). The range for plutonium-239, -240 was found to be 0.027 to
0.36 pCi/m2/day (l.OxlO"3 to 1.33xlO"2 Bq/m2/day) . The lower
concentrations were measured 9 km from the plant and the higher
concentrations were measured 0.23 km from the plant (Corey et al. 1982).
Plutonium levels in soils at Rocky Flats, Colorado, were analyzed
by Little and Whicker (1978). Plutonium concentrations in soil samples
collected to a depth of 21 cm had plutonium concentrations ranging from
1,400 to 59,000 pCi/kg (52 to 2,200 Bq/kg). A recent study on particle
size and radionuclide levels in Great Britain soils reported plutonium-
238 levels detected at a range of 200 to 18,000 pCi/kg (7.4 to 676
Bq/kg) and plutonium-239, -240 levels detected at a range of 800 to
83,000 pCi/kg (29.6 to 3,070 Bq/kg) (Livens and Baxter 1988). Core
samples of surface soil at the Maxey Flats facility, where radioactive
wastes were buried, were reported to contain a mean concentration of
1.9xl05 pCi/kg (67 Bq/kg) of plutonium-238 and 22,000 pCi/kg (8 Bq/kg)
of plutonium-239 and plutonium-240 (NEA/OECD 1981).
Plutonium concentrations found in Lake Michigan sediments were
reported to range from 35 to 250 pCi/kg dry sediment (9.5xl0"22 to
6.8xl0~21 Bq/kg) (Edgington et al. 1976). It was estimated in this
report that radioactivity in the sediments was confined to the upper 6
cm of the sediments, and in many of the core samples, no radioactivity
was detected below a depth of 3 cm.
5,4.4 Other Media
A 1972 study on plutonium levels in the diet reported
concentrations of plutonium-239, -240 ranging from <2xlO"7 pCi/g
(<7.4x10"' Bq/g) for canned fruit to 1.1x10"* pCi/g (4.1xl0~6 Bq/g) in
shellfish (Bennett 1976b). Of the shellfish sampled in this report
(clams and shrimp), clams showed eight times the levels of plutonium
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5. POTENTIAL FOR HUMAN EXPOSURE
found in shrimp. Fish and shellfish sampled in the Windscale and
Northeast areas of the Irish Sea were reported to contain between
2.0xl0~4 pCi/g (7.4xl0~6 Bq/g) (herring muscle) and 2 pCi/g (0.074 Bq/g)
(soft parts of mussel) (Hetherington et al. 1976).
5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE
Daily ingestion of plutonium-239, -240 in food in Japan between
1978 and 1980 due to atmospheric fallout was estimated to be 0.0045
pCi/day (1.7x10"'' Bq/day) (Hisamatsu et al. 1987). In 1974, the mean
intake of plutonium in New York City from all sources including tap
water was reported to be 0.0044 pCi/day (1.6xl0~* Bq/day) (Bogen et al.
1988). This same value was reported for daily intakes of plutonium in
Italy from 1975 to 1978 (Bennett 1976b). Ingested plutonium is poorly
absorbed from the gastrointestinal tract, although the form of plutonium
will influence absorption (ICRP 1982).
The isotope of plutonium inhaled will affect its behavior in the
body. The bones and the liver are the primary organs for plutonium
deposition following translocation in the body (ICRP 1982). However,
Mclnroy et al. (1989) indicate that muscle tissue may also be a site of
deposition. Plutonium-238 dioxide is more rapidly translocated from the
lungs than plutonium-239 dioxide thereby causing more plutonium-238 to
be concentrated in other body tissues (ICRP 1982).
Mean concentrations of plutonium-239, -240 in human tissues from
autopsy specimens in Japan ranged from 0.00025 pCi/g (9.3xl0~5 Bq/g)
(cerebrum) to 0.0015 pCi/g (5.4xl0~5 Bq/g) (gonads) fresh weight
(Takizawa 1982).
Wrenn and Cohen (1977) reported plutonium-239 levels in tissues
derived from 12 autopsy cases in New York City from 1973 to 1976.
Average levels for lung, liver, vertebrae, and gonads were 0.00024 pCi/g
of tissue (8.9xl0"6 Bq/g), 0.0007 pCi/g (2.6xl0"5 Bq/g), 0.00017 pCi/g
(6.3x10"6 Bq/g), and 0.0004 pCi/g (1.5xl0~5 Bq/g), respectively.
Tissue samples from autopsy cases of nonoccupationally exposed
individuals from Great Britain showed median plutonium-239, -240 levels
for ribs, vertebrae, femur, liver and lungs of 0.00016 pCi/g (5.9xl0~6
Bq/g), 0.00012 pCi/g (4.4xl0"6 Bq/g), 0.000095 pCi/g (3.5xl0"6 Bq/g),
0.0007 pCi/g (2.6xl0~5 Bq/g) and 0,000049 pCi/g (1.8xl0~6 Bq/g),
respectively. Comparable samples taken from autopsy cases from a region
in Great Britain located near a plutonium processing plant had median
concentrations of 0.00022 pCi/g (8.1xl0"6 Bq/g), 0.00019 pCi/g (7.0xl0"6
Bq/g), 0.00015 pCi/g (5.6xl0"6 Bq/g), 0.00014 pCi/g (5.2xl0"s Bq/g) and
0.00018 pCi/g (6.7xl0"fc Bq/g) for those tissues mentioned above
(Popplewell et al. 1988).
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102
5. POTENTIAL FOR HUMAN EXPOSURE
The estimated 50-year dose commitment from plutonium for people in
the north temperate zone due to atmospheric tests conducted before 1973
is 0.2 mrad (0.002 mGy) to the bone lining cells (Eisenbud 1987). [The
gray is an SI unit of absorbed dose and is equal to 0.01 rad.] The
average annual dose equivalent from all background radiation to an
individual residing in the United States is estimated to be 360 mrem
(3.6 mSv) (NCRP 1987). (The sievert is an SI unit of dose equivalent
and is equal to 0.01 rem.]
5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES
Individuals employed at facilities using plutonium or uranium have
high exposure potentials. Voelz et al. (1985) studied workers who
participated in the Manhattan Project to determine if they had been
exposed to levels of plutonium which would result in adverse health
effects. Examination of the study group showed that their health was as
good, if not better, than the general population. Similar results were
reported by Wilkinson et al. (1987) for individuals employed at a
plutonium weapons facility. These authors found, however, that
individuals with body burdens >.2,000 pCi (>74 Bq) had a slightly higher
mortality from all causes of death and from lymphopoietic neoplasms than
that found in employees with body burdens <2,000 pCi (<74 Bq). (See
Section 2.2.1.8 for a more complete discussion of this study.)
Cobb et al. (1982) obtained autopsy tissues from individuals who
had lived in one of three areas around the Rocky Flats facility (449
decedents) and from individuals who had lived outside of these areas for
use as control data. Total plutonium burden, as well as the ratio of
plutonium-239, -240, were measured in lung and liver tissues from these
individuals. Next of kin were interviewed to assure that none of the
study population had been exposed to plutonium from sources other than
fallout and/or environmental contamination from the Rocky Flats
facility, and to obtain information on smoking history. Multiple
regression analyses suggested that plutonium burden is related to age,
sex, and smoking history, but showed no definitive relationship to
residence near the Rocky Flats facility. The correlation of plutonium
burden with smoking (measured in pack-years) indicated that smokers
could be a population at risk for increased body burden. The authors of
the study hypothesize that this may result from damage to the clearing
mechanisms of the lungs, resulting in a decrease in the rate of natural
elimination of particles.
Individuals living near facilities which utilize plutonium in their
operations may have higher exposure potential due to regular releases
through stack-emissions or waste water. In addition, atmospheric
fallout to the soil can result in secondary releases due to dust
generation while farming or due to uptake by crops and subsequent
ingestion of contaminated crops (Corey et al. 1982).
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103
5. POTENTIAL FOR HUMAN EXPOSURE
Individuals living in Palomares, Spain, were exposed to plutonium
after the dispersal of the plutonium in two bombs released during the
midair collision of two airplanes (Iranzo et al. 1987). Exposure via
inhalation due to the resuspension of contaminated soil was studied for
15 years following the release. Those individuals living near
cultivated lands with the highest contamination received a cumulative
total of 52.3 mrem (5.2X10"1 mSv) from 1966 to 1980 while those in the
urban area of Palomares, farther away from the source, received 5.4 mrem
(5.4xl0~2 mSv) (Iranzo et al. 1987).
Kathren et al. (1987) determined levels of plutonium-239 at autopsy
in bones of an individual known to have had occupational exposure to
plutonium. Values ranged from l^xlO'4 to 1.14xl0~2 pCi/g ash (7.0xl0~6
to 5.0xl0~5 Bq/g ash), with the highest value detected in the scapula.
Kathren et al. (1988) found a greater percentage of plutonium-238 in the
skeleton than plutonium-239.
Kawamura (1987) estimated the plutonium-239, -240 inhalation intake
of visitors to Kiev after the Chernobyl accident to be 0.8 pCi/day
(0.03 Bq/day) during peak fallout exposure.
5.7 ADEQUACY OF THE DATABASE
Section 104(i)(5) of CERCLA, directs the Administrator of ATSDR (in
consultation with the Administrator of EPA and agencies and programs of
the Public Health Service) to assess whether adequate information on the
health effects of plutonium is available. Where adequate information is
not available, ATSDR, in conjunction with the NTP, is required to assure
the initiation of a program of research designed to determine the health
effects (and techniques for developing methods to determine such health
effects) of plutonium.
The following categories of possible data needs have been
identified by a joint team of scientists from ATSDR, NTP, and EPA. They
are defined as substance-specific informational needs that, if met would
reduce or eliminate the uncertainties of human health assessment. In
the future, the identified data needs will be evaluated and prioritized,
and a substance-specific research agenda will be proposed.
5.7.1 Identification of Data Needs
Physical and Chemical Properties. The physical and chemical
properties of plutonium have been studied. The information is adequate
to permit estimation of plutonium*s environmental fate.
Production, Use, Release, and Disposal. The potential for human
exposure to plutonium is great due to its ubiquitous presence in the
environment, resulting from releases from production facilities and from
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104
5. POTENTIAL FOR HUMAN EXPOSURE
„h radiological half-life. However, the level of
weapons testing, and 1 cma11. The production and use of Plutonium
exposure to plutonium may e -^ere little information regarding the
238-243 are well documented. amounts Gf these plutonium isotopes
production of plutonium- . have been documented; however the
produced for various app c 1974. More recent data is needed in
most current intonation is production and to project future
order to compare past and p formatlon on the production and use of
production. The majori ^ ° nation's defense program. Information on
plutonium is classified in from weapons testing and from the
past major releases of piuton ite ±s availabie. However, current
explosion of a navigational duction facilities is unavailable and is
information on release® tr°™ ^ulations that might be exposed. The
needed in order to mon or 1970 is documented, but again, more
disposal of plutonium Pr^or ounts being held for mandated disposal in
recent information regarding facllicy is needed. Rules and
the proposed high-leve isp plutonium have been established and
regulations for the disposal o£ P
these are reported m Chapte
, t. The major transport processes involved in the
Environmental Fate. mej ^ ^ relates t0 potential human
environmental fate o p u ° ^ defined. These processes include
exposure, have been fair y Wwhgn adsorbed to particulate matter and dry
transport in the atmosplhere water Inf0rmation on environmental
or wet deposition on land a gs _ and the mechanisms and rates of
compartments, such as t ux ^ biogeochemical cycling of plutonium
several processes invo e available regarding uptake of plutonium
are still undefine • Xhere is s0®e information regarding the
by plants are limited^ formS of plutonium to reduced forms followed
conversion of the oxi ize formation regarding the influence of inorganic
by uptake into plants. n r(Jing the media-specific effects of pH on
complexes on transport ana x
cnium would be useful in order to more fully
the oxidation states ot p The persistence Gf plutonium isotopes
understand transport rination of plutonium is through radioactive
is well documente ox^^t^OTlyreduction reactions. These processes have
£e%n°chat"c«U.S.
xn uum PlutonlMitt is known to be absorbed following
Bioavailabiii y. oavailability following oral and dermal exposure
inhalation exposure. Conium can be absorbed from contaminated
Is very low; however, p " ° vailable on absorption from contaminated air
wounds. Bioassay a a rniation on the impact of the valence state of
and water. However, n o oral exposure is ambivalent. Such
plutonium on absorpt on r co address the impact of chlorination of
information is nee e in a change in the valence of plut0nium
drinking water, whi lutonluff
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105
5. POTENTIAL FOR HUMAN EXPOSURE
material. Such information is needed in order to quantify the potential
exposure by this route, particularly when children may ingest soil when
playing near NPL sites.
Food Chain Bioaccumulation. Plutonium has been shown to
bioconcentrate in aquatic organisms at the lower end of the food chain.
However, data do not indicate that plutonium is bioconcentrated in
plants, higher aquatic organisms, or animals. In addition, there is no
indication that plutonium is biomagnified in terrestrial or aquatic food
chains. No additional information on bioaccumulation appears to be
necessary at this time.
Exposure Levels in Environmental Media. A number of studies have
been performed throughout the years on the fallout associated with the
testing of nuclear weapons. Information is available on levels in air,
water, soil, plant materials, and foodstuffs. However, no recent data
are available on levels in these media. In particular, information is
very limited on levels in media associated with areas surrounding waste
sites. Such information is needed in order to quantify the potential
exposure via these sources. Data are not available on estimates of
human intake via specific media. This information would be important in
determining the impact of exposure through each of these media.
Exposure Levels in Humans. Plutonium is measurable in urine and in
lung, liver, and bone tissues obtained from autopsy. It is plausible to
expect that occupationally exposed populations are routinely
biomonitored through urinalysis. However, such data are not made
available and are needed to quantify exposure to these individuals. In
addition, no information is available on biomonitoring of individuals
around NPL sites where plutonium has been found or of the general
public. This information is needed so that exposure to these
populations may be quantified.
Exposure Registries. No exposure registries for persons
environmentally exposed to plutonium were located. Plutonium is not
currently one of the substances for which a subregistry has been
established in the National Exposure Registry. The substance will be
considered in the future when chemical selection is made for
subregistries to be established. The information that is amassed in the
National Exposure Registry facilitates the epidemiological research
needed to assess adverse health outcomes that may be related to the
exposure to this substance.
5.7.2 On-going Studies
Long-term research studies on the environmental fate of plutonium
have not been identified. However, with the Chernobyl accident, it is
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106
5. POTENTIAL FOR HUMAN EXPOSURE
anticipated that new information regarding the transport and fate of
materials released during the accident will become available.
N.P. Singh (University of Utah) is determining the concentration
and accumulation of plutonium in different organs of the younger
population of the United States, who were born after 1963. Another
study includes determining the concentrations of plutonium-238,
plutonium-239, and plutonium-240 in the liver, kidney, and bone of 30
people who lived in northern Utah.
C.R. Olsen (Oak Ridge National Laboratory), along with other
researchers, is investigating whether radionuclides released from the
Department of Energy Savannah River facilities might be useful
environmental tracers. The study includes transport pathways, transfer
rates, and geochemical fate of plutonium in the Savannah River estuary.
RE Wildung at Pacific Northwest Laboratory is studying the influence
of soil, soil microbial, and plant processes on behavior and cycling of
cationic elements (including plutonium) in terrestrial environments.
The behavior of long-lived radionuclides in natural water (W.R.
Penrose Argonne National Laboratory) and the behavior of fallout-
derived' plutonium in estuarine sediments as a function of various
environmental parameters (H.J. Simpson, Columbia University) have been
under investigation. The study by Simpson includes determining factors
which control the distribution of plutonium in the sediments of the
Hudson River. Studies by Noshkin and Penrose include characterizing
rates and mechanisms of various physical and chemical processes that
control the behavior of such pollutants, and characterizing the
importance of oxidation states and natural complexing agents on the
sorption behavior of plutonium and other radionuclides.
Geochemistry of plutonium in the Gulf of Mexico is being studied by
M.R. Scott (Texas A&M University). Plutonium isotopes will be measured
in both oxic and anoxic sediments in the Gulf of Mexico and in suspended
sediments from major rivers emptying into the Gulf.
G.R. Choppin (Florida State University) is investigating the
synergistic reaction of actinide-TTA complexes with brown ether adducts
in benzene solutions and interaction of plutonium and other transuranic
elements with the components of marine sediments under different
conditions. The interaction of plutonium-238 dioxide heat source with
the marine environment is also under investigation by H.V. Weiss (Naval
Coastal Systems Center).
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107
6. ANALYTICAL METHODS
The purpose of this chapter is to describe the analytical methods
that are available for detecting and/or measuring and monitoring
plutonium in environmental media and in biological samples. The intent
is not to provide an exhaustive list of analytical methods that could be
used to detect and quantify plutonium. Rather, the intention is to
identify well-established methods that are used as the standard methods
of analysis. Many of the analytical methods used to detect plutonium in
environmental samples are the methods approved by federal agencies such
as EPA. Other methods presented in this chapter are those that are
approved trade associations, such as the Association of Official
Analytical Chemists (AOAC) and the American Public Health Association
(APHA). Additionally, analytical methods are included that refine
previously used methods to obtain lower detection limits and/or to
improve accuracy and precision.
The accurate and reliable determination of plutonium in biological
and environmental samples is important because of the potential impact
of this element on public health. Analytical methods used to measure
plutonium in biological and environmental media are highly refined
compared to other transuranics.
Analytical methods used to quantify plutonium in biological and
environmental samples are listed in Tables 6-1 and 6-2. Emphasis has
been placed on well-established methods approved by EPA, the American
Public Health Association, and in accordance with accepted standards of
the American Society for Testing and Materials (ASTM). Reviews of
analytical methods for measuring plutonium concentrations are provided
by Brouns (1980), Bernhardt (1976), Metz and Waterbury (1962), and Singh
and Wrenn (1988).
General environmental survey instruments (e.g., alpha particle
meters) are available, but they are not specific for plutonium. The
predominant analytical method for measuring plutonium present at or near
background concentrations in both biological and environmental media
requires radiochemical separation and purification in conjunction with a
quantitative measurement technique (e.g., alpha spectrometry, liquid
scintillation, or mass spectrometry).
6.1 BIOLOGICAL MATERIALS
The procedures that have been developed for the determination of
small quantities of plutonium in biological as well as in environmental
samples include the following steps:
¦ Release of plutonium from the sample's matrix into solution
and the addition of plutonium tracers;
-------
TABU. 6-1. Analytical Methods for Determining Plntapiia in Biological Material*
Sample Matrix
Sample Preparation
Analytical Method
Sample
Detection
Limit
Accuracy
Reference
Biological soft
tissues
Wet ash; filter; extract; electrodeposit on
platinum disk
« spectrometry 238Pu,
239/240pu
no data
no data
Singh and Wrenn 1988
Urine
Evaporate; wet ask; filter; extract, electro-
deposit on platinum disk
¦ spectrometry 238Pu,
239/240^
no data
no data
Singh and Wrenn 1988 cr>
Fecal matter
Bones
Milk
Plant
Wet ash; filter; extract; electrodeposit on
platinum disk
Dry ash; reduce valence state; extract;
electrodeposit on platinum disk
Dry ash; extract; reduce valence state;
coprecipitate with lanthanum fluoride
Dissolve starch; filter; wet ash; extract;
electrodeposit on platinum disk
« spectrometry Z38Pu,
239/240pu
a spectrometry 238Pu,
239/2'Opu
< spectrometry
¦ spectrometry
238pu 239/240py
no data
no data
no data
no data
no data
no data
Singh and Wrenn 1988
0.0027 pCi no data
(D.lxlO"4 Bq)
EPA 1984
Bunzl and Kracke
1987
>
H
Singh and Wrenn 1988 — C
>' a
>
r
s
m
H
5C
O
D
l/l
-------
TABLE 6-2, Analytical Methods for Determining Plutoniw in Environmental Samples
Sample
Detection
Sample Matrix Sample Preparation Analytical Method Limit Accuracy Reference
Air
Extract; filter; coprecipitate with cerium
fluorides; electrodeposit on platinum disk
ft spectrometry (solid
state detector)
(tentative Method
605)
0.08x10"®
pCi/m3 (2x
10"s Bq/m3)
±101
APHA 1977
Air
Soil
Soil, Water
Water
Dry ash; filter; extract; reduce valence;
coprecipitate with lanthanum fluoride
Digest; filter; extract; electrodeposit on
platinum disk
Ash soil or evaporate water samples; reduce
valance; extract; wet ash; coprecipitate with
lanthanum fluoride
Filter; extract; coprecipitate with lanthanum
fluoride
« spectrometry no data
« spectrometry 238Pu, no data
239/340^
« spectrometry z38Pu, no data
238/240^
(t particle counter no data
(either proportional
or scintillation
detectors) (EPA
Method 907.0)
no data
no data
no data
EPA 1984
15X
>
t"<
Singh and Wrenn 1988
EPA 1984
EPA 1980
n
>
a
M
H
sc
o
o
&o
o
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110
6. ANALYTICAL METHODS
¦ Concentration by precipitation with a nonisotopic carrier
by solvent extraction; or
¦ Purification by precipitation, liquid extraction, or ion
exchange chromatography; and
¦ Determination of the plutonium content of the sample by
alpha-particle counting or other techniques (Brouns 1980)
Two common methods for releasing plutonium from the sample's mat *
into solution are acid extraction and acid dissolution. Samples are ri*
wet, or dry, ashed prior to solubilization. Leaching the sample with
mixture of acids (e.g., nitric acid and hydrochloric acid) has the &
advantage of easily handling large sample volumes, but with the
potential disadvantage of leaving plutonium compounds in the residue
The acid dissolution procedure includes the addition of excess
hydrofluoric acid (HF) to the above mixture of acids and results in
dissolution of much, if not all, of the sample matrix. Refractory
plutonium compounds (e.g., Pu02) are more likely to be dissolved upon
addition of HF. However, dissolution of interfering elements such "
iron, phosphorous, and other rare earths (e.g., alpha-particle S
emitters), is also increased in acid dissolution. A third example of
dissolution method is fusion. It is less routinely used, however ° &
because it is relatively labor intensive. Fusions with pyrosulfate
a combination potassium fluoride and pyrosulfate fusion, can insure' ^
complete dissolution of the sample matrix. The potassiilm fluoride
fusion dissolves the siliceous material in the sample, whereas the
pyrosulfate fusion dissolves the nonsiliceous matrix materials
especially the refractory plutonium dioxides (Bernhardt 1976)
Plutonium solutions that contain: (1) other alpha-particle
emitters (e.g, americium and neptunium), (2) large amounts of fissio
products (e.g., cesium), or interfering amounts of other substances s
as iron, calcium, uranium, and phosphorous need to undergo addition 1
chemical separation procedures. Nonisotopic carriers, such as lant-h
fluoride (LaF3) and zirconium phenylphosphate (ZrC6H6PO<) are used
selectively precipitate the rare earths. Solvent extraction and ion°
exchange separation methods are preferred methods because of better
separations. In addition, they do not involve the addition of
nonvolatile substances resulting in an easier preparation of the
co-precipitation source used for alpha-particle counting.
These extraction techniques can be made very efficient and
selective by adjusting the oxidation state of the plutonium and other
sample constituents. Common extraction methods specifir for nW •
uSe 2-chenoyltrifluoroacecone (IIA), eetrapropylaL.nl™ ["J
isopropylacetone or triisooctylamine, cupferron in chloroform
tributylphoshphate, and tri-octylphosphine dioxide. Anion exchange
-------
Ill
6. ANALYTICAL METHODS
methods with either nitric or hydrochloric acid solutions are commonly
used. Cation exchange column methods are less frequently used (Brouns
1980).
Alpha-particle counting is the most commonly used method for
determining plutonium concentrations at low levels in biological
samples, as well as in process waste streams, and in soil, water, and
air filter samples (Brouns 1980). This method does not distinguish
between the different alpha-particle emitters of plutonium (plutonium-
236, plutonium-238, plutonium-239, plutonium-240, plutonium-242) , nor
does it detect plutonium-241, a beta-particle emitter.
Prior to measurement, the separated and purified plutonium must be
incorporated into a source to produce a low mass, uniformly distributed
deposit on a highly polished metal surface. Two techniques that are
commonly used are: (1) electrodeposition, and (2) co-precipitation with
a carrier. Electrodeposition is currently used in a minority of
laboratories to prepare a thin, uniform, and reproducible source. The
alpha-particle emitting isotopes of plutonium are electrodeposited on a
polished stainless steel, or platinum disk. In the co-precipitation
technique, a small amount of a carrier (e.g., LaF3) is used to co-
precipitate the separated and purified plutonium from solution. The
precipitate is then prepared for counting by either filtration or by-
evaporation of a slurry of the precipitate onto a stainless steel disk
or planchet (ASTM 1982; 1987). Recent methods use a glass fiber filter
which can be used as the source for alpha counting techniques. It has
been suggested that low yields result from electrodeposition due to the
presence of traces of interfering elements (e.g., iron) (Bernhardt
1976) .
Alpha spectrometry is the single most widely used method for
measuring concentrations of plutonium-238, or a mixture of plutonium-239
and plutonium-240. However, the energy of the alpha particles emitted
from plutonium-239 and plutonium-240 are too close to be resolved by
alpha spectrometry. The two remaining alpha-particle emitters among the
plutonium isotopes, plutonium-236 and plutonium-242, are normally not
found in environmentally significant quantities, and are not common
constituents of nuclear fuels or waste waters. Therefore, they can be
used as tracers to aid in the analysis of other isotopes. In this
calibration procedure, a known quantity of a tracer is added to the
sample being analyzed in order to determine the yield. This is the
percentage of the total amount of plutonium in the sample that is
actually measured in the electrodeposited amount after the separation,
purification, and preparation of the source (ASTM 1987; Brouns 1980).
The most critical step in the analysis of biological samples is
complete dissolution of the sample to assure solubilization of all
plutonium compounds. Biological samples are generally dissolved by wet
ashing or a combination of wet and dry ashing. High temperatures (700°C
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112
6. ANALYTICAL METHODS
to 1,000°C) during ashing should be avoided in order to prevent the
formation of an insoluble form of plutonium dioxide (Nielsen and Beasley
1980; Sill 1975). Plutonium that has been distributed to urine, blood,
or soft tissue as a result of metabolic processes is usually in a
readily soluble form. Lung tissue, feces, and excised tissue from wound
sites will likely contain insoluble forms of plutonium and will require
treatment with HF and repeated ashings to effect solubilization.
Tissues, feces, and vegetation require repeated treatment with a mixture
of concentrated nitric acid (HN03), perchloric acid (HCIO^), and
sulphuric acid (H2S0<) in order to oxidize the large amount of organic
materials in these samples. If an insoluble residue remains after
repeated ashings, then fusion of the residue with gram quantities of an
inorganic flux (e.g., sodium carbonate, sodium pyrosulfate) can be used
to effect solution. Known amounts of a plutonium isotope are commonly
added subsequent to the dissolution step so that the percentage of
plutonium recovered after separation and purification (i.e., the yield)
may be determined. This added plutonium must be in the same chemical
form as the plutonium in the sample or the yield estimates will not
reflect the percentage of plutonium recovered from the dissolved sample
(Bernhardt 1976; Nielsen and Beasley 1980).
Methods used for concentrating plutonium in a sample by a carrier
are often specific to one oxidation state of the plutonium. For
example, the classical bismuth phosphate-lanthanum fluoride method of
concentrating plutonium from urine samples is specific to plutonium in
the tri- and tetravalent states and will leave plutonium(VI) in
solution. The fate of the various oxidation states of plutonium in man
is not well understood and analysis procedures must insure reduction or
oxidation of plutonium into appropriate oxidation states. Liver and
kidney samples may contain metals (e.g., iron) which may greatly reduce
chemical yields during the final electrodeposition step (Bernhardt
1976) .
Sensitive methods for analysis of plutonium in urine are
particularly important for estimating occupational plutonium body
burdens. Routinely available instrumentation, such as the alpha
spectrometer, can readily detect these low concentrations. More
sensitive methods are commonly required for urine samples in order to
assess chronic exposures to plutonium. These low detection limits were
first achieved in the past by nuclear emulsion track counting (see Table
6-1). In this method, the electrodeposited sample is exposed to nuclear
track film, subsequent to the isolation of plutonium. The alpha-
particle emitting isotopes of plutonium will leave tracks on the film
which are counted to quantify the amount of plutonium. Nuclear emulsion
track counting has been used in the past to measure plutonium
concentrations in the urine of workers at a nuclear reactor plant
(Nielsen and Beasley 1980). A type of scintillation counting has been
used to measure plutonium-239 and americium-241 in animal tissues (NCRP
-» r\ Q RN
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113
6. ANALYTICAL METHODS
6.2 ENVIRONMENTAL SAMPLES
Common analytical methods used to measure plutonium in
environmental samples are listed in Table 6-2. The separation and
extraction methods used to prepare biological samples for plutonium
analysis are commonly used for environmental samples.
Large volumes of air particulate samples (e.g., 10,000 m3) should
be collected in order to obtain detectable amounts of plutonium.
Fiberglass filters may have trace amounts of metals which decrease the
yield when electroplating is used to prepare the sample source for alpha
spectrometry (Bernhardt 1976).
Field survey instruments for measuring photons of americium-241 in
surface soils and on airborne particulates are available (e.g., Field
Instrument for Detecting Low Energy Radiation: FIDLER) with a minimum
detection limit of approximately twice the magnitude of a background
level of plutonium-239 (l-2xl03 pCi/ra2; 37-74 Bq/m2) . The FIDLER uses a
sodium iodide or calcium fluoride crystal and photon-height
discrimination in order to detect the 17 KeV X-rays emitted from the
progeny of plutonium, or the 60 KeV gamma photons of americium-241.
These instruments are useful for identifying areas of contamination, but
cannot be used to accurately predict the concentration of plutonium in
surface soils (Bernhardt 1976). This instrument has been used in aerial
surveys of large area sources, such as the Nevada Test Site.
Since soil-adsorbed plutonium contamination exists as discrete
particles of various sizes, analysis of larger soil volumes (25 to 100
grams) is recommended (Bernhardt 1976). Commonly, soil samples with
high amounts of carbonate are difficult to analyze. More rapid,
efficient, and economical procedures are being developed to sequentially
analyze a number of radioactive actinides (Hindman 1986).
An EPA-approved procedure for the analysis of plutonium in water is
listed in Table 6-2. In addition, the following ASTM standard methods
relate to the measurement of plutonium in water: D 3648, D 3084, D 3972,
and D 1943 (ASTM 1981, 1982a, 1982b, 1987). Recent work has focused on
more rapid analytical methods in order to routinely monitor plutonium
levels in waste process streams at nuclear facilities. For example,
Edelson et al. (1986) have investigated the applications of inductively-
coupled plasma-atomic emission spectrometry (ICP-EAS) to routinely
analyze water samples.
Alpha counting and alpha spectrometry are the two most common
analytical methods for measuring plutonium concentrations in
environmental samples. Other measurement techniques available are
liquid scintillation, mass spectrometry, and gamma spectrometry.
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114
6. ANALYTICAL METHODS
Liquid-scintillation counting is a less common method used to
measure plutonium concentrations from the various alpha-particle
emitters among the isotopes of plutonium. Although liquid scintillation
counting avoids the interferences from iron and other metals seen with
electrodeposition, this method generally has higher detection limits
than obtained with alpha spectrometry. In addition, the composition of
the scintillation solution must be carefully controlled to prevent
polymerization, deposition, or precipitation of the plutonium (NCRP
1985).
Mass spectrometry is used by some research laboratories to
determine the concentration of each plutonium isotope, including the
naturally-occurring plutonium-244. Mass spectrometry determines the
number of atoms of a given mass number and, therefore, can measure the
concentration of all of the plutonium isotopes, not only the alpha-
particle emitters as in alpha spectrometry. Mass spectrometry is
several orders of magnitude more sensitive than alpha spectrometry in
determining the quantities of plutonium isotopes with long half-lives
which also tend to be the heavier isotopes. However, plutonium-238 is
most accurately determined by alpha spectrometry (Bernhardt 1976)
because of its relatively short half-life and the potential
interferences from traces of uranium-238.
Quantities of plutonium-241, a beta-particle emitter, can be
quantified from: (1) assumed isotopic abundance ratios, (2) estimated
in-growth of its progeny americium-241 by gamma spectrometry, or by (3)
mass spectrometry (Bernhardt 1976). Americium-241 is produced from the
beta decay of plutonium-241 and> therefore, can be used to indirectly
measure the concentration of plutonium-241 (Metz and Waterbury 1962)
Direct determination of plutonium-241 by measurement of its low energy
beta-particle decay has been reported using liquid scintillation
analysis (Martin 1986) .
6.3 ADEQUACY OF THE DATABASE
Section 104(i)(5) of CERCLA, directs the Administrator of ATSDR M
consultation with the Administrator of EPA and agencies and proeramc
the Public Health Service) to assess whether adequate information on rh
health effects of plutonium is available. Where adequate Information i
not available, ATSDR, in conjunction with the NTP, is required to assu^!
the initiation of a program of research designed to determine the health
effects (and techniques for developing methods to determine such healH-T
effects) of plutonium. m
The following categories of possible data needs have been
identified by a joint teani of scientists from ATSDR, NTP, and EPA. They
are defined as substance-specific informational needs that, if met would
reduce or eliminate the uncertainties of human health assessment. In
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115
6. ANALYTICAL METHODS
the future, the identified data needs will be evaluated and prioritized,
and a substance - specific research agenda will be proposed.
6.3.1 Identification of Data Needs
Methods for Determining Biomarkers of Exposure and Effect. There
are methods available for measuring the isotopes of plutonium in
biological samples. The measurement of plutonium in the urine is
considered a biomarker of exposure to plutonium. Methods are available
to detect plutonium in the urine. However, no information was available
concerning the reliability of these methods for determining plutonium
levels in the urine. In the studies that reported these methods of
analyses, neither the sample detection limit nor the accuracy of the
method was reported. Therefore, more information is needed to define a
detection limit and to determine the accuracy of the method used to
analyze plutonium in the urine. On-going studies continue to refine
these procedures. Additional studies would be helpful to determine the
migration of plutonium in the body over time.
No biomarkers have been linked to plutonium health effects in
humans. Further testing to identify any potential biomarkers of effect
should be conducted; if biomarkers are identified, testing will then be
needed to determine what analytical methods will detect these biomarkers
with the greatest degree of accuracy.
Methods for Determining Parent Compounds and Degradation Products
in Environmental Media. Environmental media are analyzed to identify
contaminated areas and to determine if contaminant levels constitute a
concern for human health. The detection of plutonium in air, water, and
soil is of concern due to the potential for human exposure. There are
many steps involved in the analysis of plutonium in environmental media.
Reliable and accurate methods are available to detect plutonium in air.
However, no detection limit or degree of accuracy was reported for the
methods used to determine plutonium in soil and water. Attempts to
improve these methods should be focused on separation techniques,
increasing yields, and increasing the measurement efficiency.
6.3.2 On-going Studies
The Environmental Research Laboratory of the U.S. Department of
Energy located in New York is conducting studies to refine analytical
methods for the measurement of plutonium in biological and environmental
media. Lawrence Livermore National Laboratory in California is
currently refining techniques for the measurement of plutonium in
biological samples. On-going studies of the solution chemistry of
plutonium are currently being undertaken at Brookhaven Laboratory in New
York and by researchers in Japan (Aoyagi et al. 1987).
-------
116
6. ANALYTICAL METHODS
Individuals occupationally exposed to plutonium in the past are
continually monitored in programs across the country. For example,
whole body counting studies are currently conducted at Los Alamos
National Laboratory in New Mexico. Animal studies conducted at the
Lawrence Berkeley Laboratory, University of California, Berkeley, by
P. Durbin are evaluating the behavior and movement of plutonium inhaled
into the lungs. Models used to estimate body burden based on urinary
excretion data and other biological measurements of plutonium (Leggett
and Eckerman 1987) are under continual revision.
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117
7. REGULATIONS AND ADVISORIES
International and national regulations and guidelines pertinent to
human exposure to plutonium and to other radioactive substances are
summarized in Table 7-1. Recommendations for radiation protection for
people in the general population as a result of exposure to radiation in
the environment are found in the Federal Radiation Guidance (FRC 1960)
and ICRP No. 26 (ICRP 1977). National guidelines for occupational
radiation protection are found in the "Federal Radiation Protection
Guidance for Occupational Exposure" (EPA 1987). This guidance for
occupational exposure supersedes recommendations of the Federal
Radiation Council for occupational exposure (FRC 1960). The new
guidance presents general principles for the radiation protection of
workers and specifies the numerical primary guides for limiting
occupational exposure. These recommendations are consistent with the
ICRP (ICRP 1977).
The basic philosophy of radiation protection is the concept of
ALARA (As Low As Reasonably Achievable). As a rule, all exposure should
be kept as low as reasonably achievable and the regulations and
guidelines are meant to give an upper limit to exposure. Based on the
primary guides (EPA 1987), guides for Annual Limits on Intake (ALIs) and
Derived Air Concentrations (DACs) have been calculated (ICRP 1977,
1979). The ALI is defined as "that activity of a radionuclide which, if
inhaled or ingested by Reference Man (ICRP 1975), will result in a dose
equal to the most limiting primary guide for committed dose" (EPA 1988a)
(see Appendix B). The DAC is defined as "the concentration of
radionuclide in air which, if breathed by Reference Man (ICRP 1975) for
a work-year, would result in the intake of one ALI" (EPA 1988a). The
ALIs and DACs refer to occupational situations but may be converted to
apply to exposure of persons in the general population by application of
conversion factors (Table 7-1).
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118
7. REGULATIONS AND ADVISORIES
Agency
TABLE 7-1. Regulations and Guidelines Applicable to
Plutonium and Plutonium Compounds
Description
Value*
References
Guidelines:
ICRP
ICRP
ICRP
Regulations:
a: Air:
NRC
NRC
International
Occupational - whole body 5 rem/yr
exposure (50 mSv)
Individual - short-term, 0.5 rem/yr
to critical populations (5 mSv)
Individual - chronic exposure 0.1 rem/yr
(1 mSv)
National
Cumulative annual dose
limit for general popu-
lation from nuclear
power plant operations
Maximum concentration above
background released at the
0.5 rem/yr
boundary of power
plant:
DCi/ml
(Bq/ml1)
Plutonium-238
S
7xl0"8
3xl0~9)
I
lxlO"6
4xl0"8)
Plutonium-239
S
6xl0~8
2xl0~9)
I
lxlO"6
4xl0"8)
Plutonium-240
S
6xl0~8
2xl0"9)
I
lxlO"6
4xl0"8)
Plutonium-241
s
3xl0~6
lxlO"7)
I
lxlO"3
4xl0"5)
Plutonium-242
s
6xl0"8
2xl0"9)
I
lxlO"6
4xl0"8)
Plutonium-243
s
6xl0"z
2xl0"3)
I
8xl0"2
3xl0"3)
Plutonium-244
s
6xl0"8
2xl0"9)
I
lxlO"6
4xl0"8)
ICRP 1977
ICRP 1977
ICRP 1977
NRC 1988"
10 CFR 20.105(a)
NRC 1988"
10 CFR 20.106(a)
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119
7. REGULATIONS AND ADVISORIES
TABLE 7-1 (Continued)
Agency
Description
Value
References
NRC
b.
Water:
EPA
ODW
NRC
Maximum concentration above
background in restricted areas
of:
Plutonium-238
Plutonium-239
Plutonium-240
Plutonium-241
Plutonium-242
Plutonium-243
Plutonium-244
MCL
Gross alpha particle
activity (excluding
radon and uranium)
Maximum concentration above
background released at the
pCi/ml
2xl0"6
3xl0"5
2xl0~6
4xl0"5
2xlCT6
4xl0"5
9xl0"5
4xl02
2xl0"6
4xl0"5
2
2
2xl0"6
3xl0"5
(Ba/ml)
(7xl0"8)
(lxlO"6)
(7xl0-8)
(lxlO'6)
(7xl0-8)
(lxlO"6)
(3xlO"6)
(lxlO1)
(7xl0"B)
(lxl0~6)
(7xl0-2)
(7xl0-2)
(7xl0"8)
(lxlO"6)
NRC 1988a
10 CFR 20.103(a)
pCi/L (Bq/L)
15 (6xl0_1)
boundary of power plant:
DCi/ml
(Ba/ml)
Plutonium-238
S
5
(0.2)
I
30
(1.1)
Plutonium-239
S
5
(0.2)
I
30
(1.1)
Plutonium-240
s
5
(0.2)
I
30
(1.1)
Plutonium-241
s
2x102
(7.4)
I
lxlO3
(37.0)
Plutonium-242
s
5
(0.2)
I
30
(1.1)
Plutonium-243
s
3xl02
(11.1)
I
3xl02
(11.1)
Plutonium-244
s
4
(0.1)
I
10
(0.4)
EPA 1988a
40 CFR 141.15
NRC 1988a
10 CFR 20.106(a)
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120
7. REGULATIONS AND ADVISORIES
TABLE 7-1 (Continued)
Agency
Description
Value
c. Nonspecific media:
EPA
Reportable quantity
Ci (BcO
Plutonium-234
1000
(3. 7xl013)
Plutonium-235
1000
(3. 7xl013)
Plutonium-236
0.1
(3.7xl09)
Plutonium-237
1000
(3 . 7xl013)
Plutonium-238
0.01
(3.7xl0B)
Plutonium-239
0.01
(3.7xl0B)
Plutonium-240
0.01
(3.7xl0B)
Plutonium-241
1
(3.7xl06)
Plutonium-242
0.01
(3.7xl08)
Plutonium-243
1000
(3. 7xl013)
Plutonium-244
0.01
(3.7xl08)
Plutonium-245
100
(3. 7xl012)
References
EPA 1989
Guidelines:
EPA
FRC
FRC
EPA
Occupational - the
committed effective dose
equivalent (internal) and
annual effective dose
equivalent (external)
combined
Individual - whole body-
exposure
Individual - operational
guide for "suitable sample
of population" when
individual whole body doses
are not known
5 rera/yr
(50 mSv)
0.5 rera/yr
(5 mSv)
0.17 rem/yr
(1.7 mSv)
EPA 1987
FRC 1960b
FRC 1960b
Occupational ALI for
of class W forms ofc:
Plutonium-234
Plutonium-235
Plutonium-236
Plutonium-237
Plutonium-238
Plutonium-239
Plutonium-240
Plutonium-241
inhalation EPA 1988b
PCI (Ba)
2x10® (8xl06)
3xl012 (lxlO11)
2x10* (7xl02)
3xl09 (1x10s)
7xl03 (3xl02)
6xl03 (2xl02)
6xl03 (2xl02)
3xl05 (1x10'')
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121
7. REGULATIONS AND ADVISORIES
TABLE 7-1 (Continued)
Agency Description Value References
Plutonium-242
7xl03
2xl02)
Plutonium-243
4xl010
1x10®)
Plutonium-244
7xl03
3xl02)
Plutonium-245
5x10s
2xl08)
Plutonium-246
3x10®
9xl06)
Occupational ALI
for
inhalation
EPA 1988b
of class Y forms
ofc:
pCi
Bq)
Plutonium-234
2x10®
7xl06)
Plutonium-235
3xl012
9xl01Q)
Plutonium-236
4x10*
2xl03)
Plutonium-237
3x10®
1x10®)
Plutonium-238
2xl04
7xl02)
Plutonium-239
2x10*
6xl02)
Plutonium-240
2x10*
6xl02)
Plutonium-241
8xl05
3x10*)
Plutonium-242
2x10*
6xl02)
Plutonium-243
4xl010
1x10®)
Plutonium-244
2xl04
7xl02)
Plutonium-245
4x10®
2x10®)
Plutonium-246
3x10®
lxlO7)
Occupational ALI
for
EPA 1988b
ingestion ofd:
oCi
Bq)
Plutonium-234
8x10®
3x10®)
Plutonium-235
9xlOu
3xl010)
Plutonium-236
2xl06
9x10*)
Plutonium-237
lxlO10
5x10®)
Plutonium-238
9xl05
3x10*)
Plutonium-239
8xl05
3x10*)
Plutonium-240
8x10s
3x10*)
Plutonium-241
4xl07
lxlO6)
Plutonium-242
8xl05
3x10*)
Plutonium-243
2xl010
6x10®)
Plutonium-244
8xl05
3x10*)
Plutonium-245
2x10®
8x107)
Plutonium-246
4x10®
lxlO7)
Occupational DAC
for
inhalation
EPA 1988b
of class W forms
of6:
nCi/cm3
(Ba /m3)
Plutonium-234
9xl0~2
(3xl03)
Plutonium-235
lxlO3
(5xl07)
Plutonium-236
8xl0"6
(3xl0_1)
Plutonium-237
1
(5x10*)
Plutonium-238
3xl0"6
(lxlO-1)
Plutonium-239
3xl0~6
(lxlO"1)
-------
122
7. REGULATIONS AND ADVISORIES
TABLE 7-1 (Continued)
Agency Description Value References
Plutonium-240
3xlCT6
(lxlO"1)
Plutonium-241
1x10"*
(5)
Plutonium-242
3xl0"6
(lxicr1)
Plutonium-243
2X101
(6xl05)
Plutonium-244
3xl0~6
(lxKT1)
Plutonium-245
2
(7xl0A)
Plutonium-246
lxlO"1
(4xl03)
EPA Occupational DAC for inhalation EPA 1988b
if class Y forms of8:
oCi/cm3
(Bq/m3)
Plutonium-
234
8xl0~2
(3xl03)
Plutonium-
235
lxlO3
(4xl07)
Plutonium-
236
2xl0"5
(7xl0_1)
Plutonium-
237
1
(5x10*)
Plutonium-
238
8xl0"6
(3X10-1)
Plutonium-
239
7xl0"6
(3xl0_1)
Plutonium-
240
7xl0"6
(3X10"1)
Plutonium-
241
3xl0"4
(lxlO1)
Plutonium-
242
7xl0"6
(3X10"1)
Plutonium-
243
2X101
(6xl05)
Plutonium-
244
7xl0"6
(3xl0"x)
Plutonium-
245
2
<6xl04)
Plutonium-
246
lxlO"1
(4xl03)
*See Glossary and Appendix B for definitions of units.
ALI - Annual Limit of Intake
DAC - Derived Air Concentration
EPA - Environmental Protection Agency
FRC - Federal Radiation Council
I - Insoluble
ICRP - International Commission for Radiation Protection
MCL - Maximum Contaminant Level
mSv - millisievert
NRC - Nuclear Regulatory Commission
OCW — Office of Drinking Water
S - Soluble
-------
123
7. REGULATIONS AND ADVISORIES
TABLE 7-1 (Continued)
Agency Description Value References
"The Nuclear Regulatory Commission limits in 10 CFR 20 are in the process of
revision.
bFRC guidance for occupational exposure is superseded by EPA (1987) Federal
Radiation Protection Guidance.
Conversion of the ALI for occupational settings to apply to exposure of
persons in the general population is:
ALIi - ALI * 0.1
where ALIj is the intake for the general population, ALI is the intake for
occupational exposures and 0.01 is the ratio of the dose limit to the
individual (0.5 rem/yr) and the dose limit for occupational workers (5
rem/yr).
dBased on a fractional uptake from the small intestine to blood (fa) of 0.001.
Conversion of the DAC for occupational exposure to apply to the general
public is:
DACa - DAC * 0.03
where DACi refers to the "Derived Air Concentration" for exposure to the
general population and 0.03 represents the adjustment for hours of exposure
(168 hrs per month occupational vs. 720 hr per month of continuous exposure),
breathing rate (29 m3/day for occupational vs. 22 m3/day for the general
population) and dose limits (0.5 rem/yr for individuals vs. 5 rem/yr for
occupational settings).
-------
125
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163
9. GLOSSARY
Absorbed Dose -- The mean energy imparted to the irradiated medium, per
unit mass, by ionizing radiation. Units: gray (Gy), rad.
Absorbed Fraction -- A term used in internal dosimetry. It is that
fraction of the photon energy (emitted within a specified volume of
material) which is absorbed by the volume. The absorbed fraction
depends on the source distribution, the photon energy, and the size,
shape and composition of the volume.
Absorption -- The process by which radiation imparts some or all of its
energy to any material through which it passes.
Self-Absorption -- Absorption of radiation (emitted by radioactive
atoms) by the material in which the atoms are located; in
particular, the absorption of radiation within a sample being
assayed.
Absorption Coefficient -- Fractional decrease in the intensity of an
unscattered beam of x or gamma radiation per unit thickness (linear
absorption coefficient), per unit mass (mass absorption coefficient), or
per atom (atomic absorption coefficient) of absorber, due to deposition
of energy in the absorber. The total absorption coefficient is the sum
of individual energy absorption processes. (See Compton Effect,
Photoelectric Effect, and Pair Production.)
Linear Absorption Coefficient -- A factor expressing the fraction
of a beam of x or gamma radiation absorbed in a unit thickness of
material. In the expression I-I0e",,JC, I0 is the initial intensity,
I the intensity of the beam after passage through a thickness of
the material x, and |i is the linear absorption coefficient.
Mass Absorption Coefficient -- The linear absorption coefficient
per cm divided by the density of the absorber in grams per cubic
centimeter. It is frequently expressed as |i/p, where (i is the
linear absorption coefficient and p the absorber density.
Absorption Ratio, Differential -- Ratio of concentration of a nuclide in
a given organ or tissue to the concentration that would be obtained if
the same administered quantity of this nuclide were uniformly
distributed throughout the body.
Activation -- The process of inducing radioactivity by irradiation.
Activity -- The number of nuclear transformations occurring in a given
quantity of material per unit time. (See Curie.)
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9. GLOSSARY
Activity Median Aerodynamic Diameter (AMAD) -- The diameter of a unit-
density sphere with the same terminal settling velocity in air as that
of the aerosol particulate whose activity is the median for the entire
aerosol.
Acute Exposure -- Exposure to a chemical for a duration of 14 days or
less, as specified in the toxicological profiles.
Acute Radiation Syndrome -- The symptoms which taken together
characterize a person suffering from the effects of intense radiation.
The effects occur within hours or weeks.
Adsorption Coefficient (Koc) -- The ratio of the amount of a chemical
adsorbed per unit weight of organic carbon in the soil or sediment to
the concentration of the chemical in solution at equilibrium.
Adsorption Ratio (Kd) -- The amount of a chemical adsorbed by a sediment
or soil (i.e., the solid phase) divided by the amount of chemical in the
solution phase, which is in equilibrium with the solid phase, at a fixed
solid/solution ratio. It is generally expressed in micrograms of
chemical sorbed per gram of soil or sediment.
Alpha Particle -- A charged particle emitted from the nucleus of an
atom. An alpha particle has a mass charge equal in magnitude to that of
a helium nucleus; i.e., two protons and two neutrons and has a charge of
+2.
Annihilation (Electron) --An interaction between a positive and a
negative electron in which they both disappear; their energy, including
rest energy, being converted into electromagnetic radiation (called
annihilation radiation) with two 0.51 Mev gamma photons emitted at an
angle of 180° to each other.
Atomic Mass -- The mass of a neutral atom of a nuclide, usually
expressed in terms of "atomic mass units." The "atomic mass unit" is
one-twelfth the mass of one neutral atom of carbon-12; equivalent to
1.6604xl0"2'1 gm. (Symbol: u)
Atomic Number -- The number of protons in the nucleus of a neutral atom
of a nuclide. The "effective atomic number" is calculated from the
composition and atomic numbers of a compound or mixture. An element of
this atomic number would interact with photons in the same way as the
compound or mixture. (Symbol: Z)
Atomic Weight -- The weighted mean of the masses of the neutral at
an element expressed in atomic mass units. °ms °^
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9. GLOSSARY
Auger Effect -- The emission of an electron from the extranuclear
portion of an excited atom when the atom undergoes a transition to a
less excited state.
Background Radiation -- Radiation arising from radioactive material
other than that under consideration. Background radiation due to cosmic
rays and natural radioactivity is always present. There may also be
background radiation due to the presence of radioactive substances in
building materials.
Becquerel (Bq) -- International System of Units unit of activity and
equals one transformation (disintegration) per second. (See Units.)
Beta Particle -- Charged particle emitted from the nucleus of an atom.
A beta particle has a mass and charge equal in magnitude to that of the
electron. The charge may be either +1 or -1.
Biologic Effectiveness of Radiation -- (See Relative Biological
Effectiveness.)
Bone Seeker -- Any compound or ion which migrates in the body
preferentially into bone.
Branching -- The occurrence of two or more modes by which a radionuclide
can undergo radioactive decay. For example, radium C can undergo a or
6" decay, 6'*Cu can undergo 6", or electron capture decay. An
individual atom of a nuclide exhibiting branching disintegrates by one
mode only. The fraction disintegrating by a particular mode is the
"branching fraction" for that mode. The "branching ratio" is the ratio
of two specified branching fractions (also called multiple
disintegration).
Bremsstrahlung -- The production of electromagnetic radiation (photons)
by the negative acceleration that a fast, charged particle (usually an
electron) undergoes from the effect of an electric or magnetic field,
for instance, from the field of another charged particle (usually a
nucleus).
Cancer Effect Level (CEL) -- The lowest dose of chemical in a study, or
group of studies, that produces significant increases in the incidence
of cancer (or tumors) between the exposed population and its appropriate
control.
Capture, Electron -- A mode of radioactive decay involving the capture
of an orbital electron by its nucleus. Capture from a particular
electron shell is designated as "K-electron capture," "L-electron
capture," etc.
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9. GLOSSARY
Capture K-Electron -- Electron capture from the K shell by the nucleus
of the atom. Also loosely used to designate any orbital electron
capture process.
Carcinogen -- A chemical capable of inducing cancer.
Carcinoma -- Malignant neoplasm composed of epithelial cells, regardless
of their derivation.
Cataract -- A clouding of the crystalline lens of the eye which
obstructs the passage of light.
Ceiling Value (DL) -- A concentration of a substance that should not be
exceeded, even instantaneously.
Chronic Exposure -- Exposure to a chemical for 365 days or more, as
specified in the Toxicological Profiles.
Compton Effect --An attenuation process observed for x or gamma
radiation in which an incident photon interacts with an orbital electron
of an atom to produce a recoil electron and a scattered photon of energy
less than the incident photon.
Containment -- The confinement of radioactive material in such a way
that it is prevented from being dispersed into the environment or is
released only at a specified rate.
Contamination, Radioactive -- Deposition of radioactive material in any
place where it is not desired, particularly where its presence may be
harmful.
Cosmic Rays -- High-energy particulate and electromagnetic radiations
which originate outside the earth's atmosphere.
Count (Radiation Measurements) -- The external indication of a
radiation-measuring device designed to enumerate ionizing events. it
may refer to a single detected event to the total number registered in €
given period of time. The term often is erroneously used to designate {
disintegration, ionizing event, or voltage pulse.
Counter, Geiger-Mueller -- Highly sensitive, gas-filled
radiation-measuring device.
high to produce avalanche ion^a^un,
Counter, Scintillation -- The combination of phosphor,
photmultiplier tube, and associated circuits for counting light
emissions produced in the phosphors by ionizing radiation.
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167
9. GLOSSARY
Curie -- A unit of activity. One curie equals 3.7xl010 nuclear
transformations per second. (Abbreviated Ci.) Several fractions of the
curie are in common usage.
Megacurie -- One million curies. Abbreviated MCi.
Microcurie -- One-millionth of a curie (3.7x10* disintegrations
per sec). Abbreviated fiCi.
Millicurie -- One - thousandth of a curie (3.7xl07 disintegrations
per sec). Abbreviated mCi.
Nanocurie -- One-billionth of a curie. Abbreviated nCi.
Picocurie -- One-millionth of a microcurie (3.7xlO~z
disintegrations per second or 2.22 disintegrations per minute).
Abbreviated pCi; replaces the term utic.
Decay, Radioactive -- Transformation of the nucleus of an unstable
nuclide by spontaneous emission of charged particles and/or photons.
Decay Chain or Decay Series -- A sequence of radioactive decays
(transformations) beginning with one nucleus. The initial nucleus, the
parent, decays into a daughter nucleus that differs from the first by
whatever particles were emitted during the decay. If further decays
take place, the subsequent nuclei are also usually called daughters.
Sometimes, to distinguish the sequence, the daughter of the first
daughter is called the granddaughter, etc.
Decay Constant -- The fraction of the number of atoms of a radioactive
nuclide which decay in unit time. (Symbol JL). (See Disintegration
Constant).
Decay Product, Daughter Product -- A new isotope formed as a result of
radioactive decay. A nuclide resulting from the radioactive
transformation of a radionuclide, formed either directly or as the
result of successive transformations in a radioactive series. A decay
product (daughter product) may be either radioactive or stable.
Delta Ray -- Energetic or swiftly moving electrons ejected from an atom
during the process of ionization. Delta rays cause a track of secondary
ionizations along their path.
Developmental Toxicity -- The occurrence of adverse effects on the
developing organism, that may result from exposure to a chemical prior to
conception (either parent), during prenatal development, or postnatally
to the time of sexual maturation. Adverse developmental effects may be
detected at any point in the lifespan of the organism.
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168
9. GLOSSARY
«finn Constant -- The fraction of the number of atoms of a
Disintegration C®n*Mn' ^ ^ ^ 1 u ^ syBbol £or the
radioactive nuc ^ . N„N e-xt where N„ is the initial number
o£CaM«s"J"senin and S is the number of atoms present after some time,
t. (See Decay Constant.)
xiiir>i oar* -- A spontaneous nuclear transformation
Disintegration, haracterized by the emission of energy and/or mass from
(radioactivity^en g numbers of nuclei are involved, the process is
characterized by a definite half-life. (See Transformation, Nuclear.)
Dose -- A general term denoting the quantity of radiation or energy
absorbed For special purposes it must be appropriately qualified. If
unqualified, it refers to absorbed dose.
Absorbed Dose -- The energy imparted to matter by ionizing
radiation per unit mass of irradiated material at the place of
interest The unit of absorbed dose is the rad. One rad equals
100 ergs per gram. In SI units, the absorbed dose is the gray
which is 1 J/kg. (See Rad.)
Cumulative Dose (Radiation) -- The total dose resulting from
repeated or continuous exposures to radiation.
Dose Assessment -- An estimate of the radiation dose to an
dividual or a population group usually by means of predictive
modeling techniques, sometimes supplemented by the results of
measurement.
Dose Equivalent (DE) -- A quantity used in radiation protection
Lnrpsses all radiations on a common scale for calculating the
effective absorbed dose. It is defined as the product of the
absorbed dose in rad and certain modifying factors. (The unit of
dose equivalent is the rem. In SI units, the dose equivalent is
the sievert, which equals 100 rem.)
Dose Radiation -- The amount of energy imparted to matter by
f ,!,n. radiation per unit mass of the matter, usually expressed
ITS? « i»51 unlts' 100 rad"16ray
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169
9. GLOSSARY
Threshold Dose -- The minimum absorbed dose that will produce a
detectable degree of any given effect.
Tissue Dose -- Absorbed dose received by tissue in the region of
interest, expressed in rad. (See Dose and Rad.)
Dose, Fractionation -- A method of administering radiation, in which
relatively small doses are given daily or at longer intervals.
Dose, Protraction -- A method of administering radiation by delivering
it continuously over a relatively long period at a low dose rate.
Dose-distribution Factor -- A factor which accounts for modification of
the dose effectiveness in cases in which the radionuclide distribution
is nonuniform.
Dose Rate -- Absorbed dose delivered per unit time.
Dosimetry -- Quantification of radiation doses to individuals or
populations resulting from specified exposures.
Early Effects (of radiation exposure) -- Effects which appear within 60
days of an acute exposure.
Electron - - A stable elementary particle having an electric charge equal
to ±1.60210xl0~19 C (Coulombs) and a rest mass equal to 9.1091xlCT31 kg.
A positron is a positively charged "electron." (See Positron.)
Electron Volt -- A unit of energy equivalent to the energy gained by an
electron in passing through a potential difference of one volt. Larger
multiple units of the electron volt are frequently used: keV for
thousand or kilo electron volts; MeV for million or mega electron volts.
(Abbreviated: eV, 1 eV-1.6xl0~12 erg.)
Embryotoxicity and Fetotoxicity -- Any toxic effect on the conceptus as
a result of prenatal exposure to a chemical; the distinguishing feature
between the two terms is the stage of development during which the
insult occurred. The terms, as used here, include malformations and
variations, altered growth, and in utero death.
Energy -- Capacity for doing work. "Potential energy" is the energy
inherent in a mass because of its spatial relation to other masses.
"Kinetic energy" is the energy possessed by a mass because of its
motion; MKSA unit: kg-m2/sec2 or joules.
Binding Energy -- The energy represented by the difference in mass
between the sum of the component parts and the actual mass of the
nucleus.
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170
9. GLOSSARY
Excitation Energy -- The energy required to change a system from
its ground state to an exited state. Each different excited state
has a different excitation energy.
IotiUlTig Energy - The average energy lost by Ionizing "Ration
In producing an ion pair In a gas. Tor air, it is about 33.73 eV.
Radiant Energy -- The energy of electromagnetic radiation, such as
radio waves, visible light, x and gamma rays.
Enriched Material -- (1) Material in which the relative amount of one or
ZA isotopes of a constituent has been increased. (2) Uranium m which
the abundance of the 235U isotope is increased above normal.
opjl Health Advisory -- ^ estimate of acceptable drinking water levels
Sr a chemical substance based on health effects information. A health
advisory is not a legally enforceable federal standard, but serves as
technical guidance to assist federal, state, and local officials.
Femilibrium Radioactive -- In a radioactive series, the state which
nrevails wh^n the ratios between the activities of two or more
successive members of the series remains constant.
Secular Equilibrium -- If a parent element has a very much longer
half life than the daughters (so there is not appreciable change
in its amount in the time interval required for later products to
attain equilibrium) then, after equilibrium is reached, equal
numbers of atoms of all members of the series disintegrate in unit
time This condition is never exactly attained, but is
essentially established in such a case as radium and its series to
a riium D The half-life of radium is about 1,600 years; of radon,
aDcroximately 3.82 days, and of each of the subsequent members, a
few minutes After about a month, essentially the equilibrium
amount of radon is present; then (and for a long time) all members
of the series disintegrate the same number of atoms per unit time.
Transient Equilibrium -- If the half-life of the parent is short
enough so the quantity present decreases appreciably during the
period under consideration, but is still longer than that of
successive members of the series, a stage of equilibrium will be
reached after which all members of the series decrease in activity
exponentially with the period of the parent. An example of this
is radon (half-life of approximately 3.82 days) and successive
members of the series to Radium D.
Eauilibrium, Radiation -- The condition in a radiation field where the
energy of the radiations entering a volume equals the energy of the
radiations leaving that volume.
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171
9. GLOSSARY
Equilibrium Fraction (F) -- In radon-radon daughter equilibrium, the
parents and daughters have equal radioactivity, that is, as many decay
into a specific nuclide as decay out. However, if fresh radon is
continually entering a volume of air or if daughters are lost by
processes other than radioactive decay, e.g., plate out or migration out
of the volume, a disequilibrium develops. The equilibrium fraction is a
measure of the degree of equilibrium/disequilibrium. The working-level
definition of radon does not take into account the amount of
equilibrium. The equilibrium fraction is used to estimate working
levels based on measurement of radon only.
Excitation -- The addition of energy to a system, thereby transferring
it from its ground state to an excited state. Excitation of a nucleus,
an atom, or a molecule can result from absorption of photons or from
inelastic collisions with other particles. The excited state of an atom
is a metastable state and will return to ground state by radiation of
the excess energy.
Exposure - - A measure of the ionization produced in air by x or gamma
radiation. It is the sum of the electrical charges on all ions of one
sign produced in air when all electrons liberated by photons in a volume
element of air are completely stopped in air, divided by the mass of the
air in the volume element. The special unit of exposure is the
roentgen.
Fission, Nuclear -- A nuclear transformation characterized by the
splitting of a nucleus into at least two other nuclei and the release of
a relatively large amount of energy.
Gamma Ray -- Short wavelength electromagnetic radiation of nuclear
origin (range of energy from 10 keV to 9 MeV).
Genetic Effect of Radiation -- Inheritable change, chiefly mutations
produced by the absorption of ionizing radiation by germ cells. On the
basis of present knowledge these effects are purely additive; there is
no recovery.
Gray (Gy) -- SI unit of absorbed dose. One gray equals 100 rad. (See
Units.)
Half-Life, Biological -- The time required for the body to eliminate
one-half of any absorbed substance by regular processes of elimination.
Approximately the same for both stable and radioactive isotopes of a
particular element. This is sometimes referred to as half-time.
Half-Life, Effective -- Time required for a radioactive element in an
animal body to be diminished 50X as a result of the combined action of
radioactive decay and biological elimination.
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9. GLOSSARY
Effective half-life: - Biological half-life x Radioactive half-life
Biological half-life + Radioactive half-life
Half-life, Radioactive -- Time required for a radioactive substance to
lose 50Z of its activity by decay. Each radionuclide has a unique half-
life.
Immediately Dangerous to Life or Health (IDLH) -- The maximum
environmental concentration of a contaminant from which one could escape
¦within 30 minutes without any escape-impairing symptoms or irreversible
health effects.
Immunologic Toxicity -- The occurrence of adverse effects on the immune
system that may result from exposure to environmental agents such as
chemicals.
In Vitro -- Isolated from the living organism and artificially
maintained, as in a test tube.
In Vivo -- Occurring within the living organism.
Intensity -- Amount of energy per unit time passing through a unit area
perpendicular to the line of propagation at the point in question.
Intermediate Exposure -- Exposure to a chemical for a duration of 15 to
364 days as specified in the Toxicological Profiles.
Internal Conversion -- One of the possible mechanisms of decay from the
metastable state (isomeric transition) in which the transition energy is
transferred to an orbital electron, causing its ejection from the atom.
The ratio of the number of internal conversion electrons to the number
of gamma quanta emitted in the de-excitation of the nucleus is called
the "conversion ratio.*'
Ion -- Atomic particle, atom, or chemical radical bearing a net
electrical charge, either negative or positive.
Ion Pair -- Two particles of opposite charge, usually referring to the
electron and positive atomic or molecular residue resulting after the
interaction of ionizing radiation with the orbital electrons'of atoms.
Ionization -- The process by which a neutral atom or molecule acquires a
positive or negative charge.
Primary Ionization -- (1) In collision theory: the ionization
produced by the primary particles as contrasted to the "total
ionization" which includes the "secondary ionization" produced by
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173
9. GLOSSARY
delta rays. (2) In counter tubes: the total ionization produced
by incident radiation without gas amplification.
Specific Ionization -- Number of ion pairs per unit length of path
of ionizing radiation in a medium; e.g., per centimeter of air or
per micrometer of tissue.
Total Ionization -- The total electric charge of one sign on the
ions produced by radiation in the process of losing its kinetic
energy. For a given gas, the total ionization is closely
proportional to the initial ionization and is nearly independent
of the nature of the ionizing radiation. It is frequently used as
a measure of radiation energy.
Ionization Density -- Number of ion pairs per unit volume.
Ionization Path (Track) -- The trail of ion pairs produced by ionizing
radiation in its passage through matter.
Isobars -- Nuclides having the same mass number but different atomic
numbers.
Isomers -- Nuclides having the same number of neutrons and protons but
capable of existing, for a measurable time, in different quantum states
with different energies and radioactive properties. Commonly the isomer
of higher energy decays to one with lower energy by the process of
isomeric transition.
Isotones -- Nuclides having the same number of neutrons in their nuclei.
Isotopes -- Nuclides having the same number of protons in their nuclei,
and hence the same atomic number, but differing in the number of
neutrons, and therefore in the mass number. Almost identical chemical
properties exist between isotopes of a particular element. The term
should not be used as a synonym for nuclide.
Stable Isotope -- A nonradioactive isotope of an element.
Joule -- The unit for work and energy, equal to one newton expended
along a distance of one meter (lJ-lNxlm).
Labeled Compound -- A compound consisting, in part, of labeled
molecules. That is molecules including radionuclides in their
structure. By observations of radioactivity or isotopic composition,
this compound or its fragments may be followed through physical,
chemical, or biological processes.
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174
9. GLOSSARY
t ^ Fffects (of radiation exposure) -- Effects which appear 60 days or
following an .cut, exposure.
Lethal Concentration(ui) (LC^) -- The lowest concentration of a chemical
in air which has been reported Co have caused death in humans or
animals.
_ tic \ -- The calculated concentration of a
S2S.frSrU*^?ih^.ur.Tf.r a specific !e„Sth of time la
expected to cause death in SOS of a defined laboratory annul
population.
/¦m \ rhf> lowest dose of a chemical introduced by a
route other'"thar^lnhaiation that is expected to have caused death in
humans or animals.
(Va •) -- The dose of a chemical which has been
calculated to'cause" death in 50% of a defined laboratory animal
population.
•l i rnima fLTcr,~) -- A calculated period of time within which a
^ecific concentration of a che.ical is expected to cause death in 50*
of a defined laboratory animal population.
tinear Energy Transfer (LET) -- The average amount of energy transferred
locally to the medium per unit of particle track length.
Low-LET -- Radiation characteristic of electrons, x-rays, and
gamma rays.
High-LET -- Radiation characteristic of protons or fast neutrons.
LET - is specified to even out the effect of a particle
rhTtis slowing down near the end of its path and to allow fox the
fact that secondary particles from photon or fast-neutron beams
are not all of the same energy.
v observed-Adverse-Effect Level (LOAEL) -- The lowest dose of
Lovest-0 ^ ^ of studles> tlriat produces statistically or
bioloeically significant increases in frequency or severity of adverse
effects between the exposed population and its appropriate control.
Linear Hypothesis - The assumption that a dose-effect curve derived
* Lt-ain the high dose and high dose-rate ranges may be extrapolated
rhroueh the low dosf and low dose range to zero, implying that,
rteoStically: any amount of radiation will cause some damage.
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175
9. GLOSSARY
Malformations -- Permanent structural changes in an organism that may
adversely affect survival, development, or function.
Mass Numbers -- The number of nucleons (protons and neutrons) in the
nucleus of an atom. (Symbol: A)
Minimal Risk Level --An estimate of daily human exposure to a chemical
that is likely to be without an appreciable risk of deleterious effects
(noncancerous) over a specified duration of exposure.
Mutagen -- A substance that causes mutations. A mutation is a change in
the genetic material in a body cell. Mutation can lead to birth
defects, miscarriages, or cancer.
Neurotoxicity -- The occurrence of adverse effects on the nervous system
following exposure to chemical.
Neutrino -- A neutral particle of very small rest mass originally
postulated to account for the continuous distribution of energy among
particles in the beta-decay process.
No-Observed-Adverse-Effect Level (NOAEL) -- The dose of chemical at
which there were no statistically or biologically significant increases
in frequency or severity of adverse effects seen between the exposed
population and its appropriate control. Effects may be produced at this
dose, but they are not considered to be adverse.
Nucleon -- Common name for a constituent particle of the nucleus.
Applied to a proton or neutron.
Nuclide -- A species of atom characterized by the constitution of its
nucleus. The nuclear constitution is specified by the number of protons
(Z), number of neutrons (N), and energy content; or, alternatively, by
the atomic number (Z), mass number A-(N+Z), and atomic mass. To be
regarded as a distinct nuclide, the atom must be capable of existing for
a measurable time. Thus, nuclear isomers are separate nuclides, whereas
promptly decaying excited nuclear states and unstable intermediates in
nuclear reactions are not so considered.
Octanol-Water Partition Coefficient (Kow) -- The equilibrium ratio of
the concentrations of a chemical In n-octanol and water, in dilute
solution.
Pair Production -- An absorption process for x and gamma radiation in
which the incident photon is annihilated in the vicinity of the nucleus
of the absorbing atom, with subsequent production of an electron and
positron pair. This reaction only occurs for incident photon energies
exceeding 1.02 MeV.
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176
9. GLOSSARY
Parent -- A radionuclide which, upon disintegration, yields a specified
nucUde--either directly or as a later .ember o£ a radxoaccive series.
nuantitv of electromagnetic energy (E) whose value in joules
is°the product of It. frequency (v) In hertz and Planck constant .
The equation is: E-hv.
- ,a^rir Effect -- An attenuation process observed for x- and
Photoelectric incident photon interacts with an orbital
electron^f an atom delivering all of its energy to produce a recoil
electron, but with no scattered photon.
BarH(1u eaual in mass to the electron (9.1091xl0"31 kg) and
having°an~equal but positive charge (+l.«02l0xl0-» Coulombs,.
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177
9. GLOSSARY
Radiation -- (1) The emission and propagation of energy through space or
through a material medium in the form of waves; for instance, the
emission and propagation of electromagnetic waves, or of sound and
elastic waves. (2) The energy propagated through space or through a
material medium as waves; for example, energy in the form of
electromagnetic waves or of elastic waves. The term radiation or
radiant energy, when unqualified, usually refers to electro-magnetic
radiation. Such radiation commonly is classified, according to
frequency, as Hertzian, infra-red, visible (light), ultra-violet, X-ray
and gamma ray. (See Photon.) (3) By extension, corpuscular emission,
such as alpha and beta radiation, or rays of mixed or unknown type, as
cosmic radiation.
Annihilation Radiation -- Photons produced when an electron and a
positron unite and cease to exist. The annihilation of a
positron-electron pair results in the production of two photons,
each of 0.51 MeV energy.
Background Radiation -- Radiation arising from radioactive
material other than the one directly under consideration.
Background radiation due to cosmic rays and natural radioactivity
is always present. There may also be background radiation due to
the presence of radioactive substances in other parts of the
building, in the building material itself, etc.
Characteristic (Discrete) Radiation -- Radiation originating from
an atom after removal of an electron of excitation of the nucleus.
The wavelength of the emitted radiation is specific, depending
only on the nuclide and particular energy levels involved.
External Radiation -- Radiation from a source outside the body --
the radiation must penetrate the skin.
Internal Radiation -- Radiation from a source within the body (as
a result of deposition of radionuclides in body tissues).
Ionizing Radiation -- Any electromagnetic or particulate radiation
capable of producing ions, directly or indirectly, in its passage
through matter.
Monoenergetic Radiation -- Radiation of a given type (alpha, beta,
neutron, gamma, etc.) in which all particles or photons originate
with and have the same energy.
Scattered Radiation -- Radiation which during its passage through
a substance, has been deviated in direction. It may also have
been modified by a decrease in energy.
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178
9. GLOSSARY
Secondary Radiation -- Radiation that results from absorption of
other radiation in matter. It may be either electromagnetic or
particulate.
Radioactivity -- The property of certain nuclides to spontaneously emit
particles or gamma radiation or x radiation following orbital electron
capture or after undergoing spontaneous fission.
Artificial Radioactivity -- Man-made radioactivity produced by
particle bombardment or electromagnetic irradiation, as opposed to
natural radioactivity.
Induced Radioactivity -- Radioactivity produced in a substance
after bombardment with neutrons or other particles. The resulting
activity is "natural radioactivity" if formed by nuclear reactions
occurring in nature, and "artificial radioactivity" if the
reactions are caused by man.
Natural Radioactivity -- The property of radioactivity exhibited
by more than 50 naturally occurring radionuclides.
Radioisotopes -- A radioactive atomic species of an element with the
same atomic number and usually identical chemical properties.
Radionuclide - - A radioactive species of an atom characterized by the
constitution of its nucleus.
Radiosensitivlty -- Relative susceptibility of cells, tissues, organs,
organisms, or any living substance to the injurious action of radiation.
Radiosensitivity and its antonym, radioresistance, are currently used in
a comparative sense, rather than in an absolute one.
Reaction (Nuclear) -- An induced nuclear disintegration, i.e., a process
occurring when a nucleus conies in contact "with a photon, an elementary
particle, or another nucleus. In many cases the reaction can be
represented by the symbolic equation: X+a-Y+b or, in abbreviated form,
X(a,b) Y. X is the target nucleus, a is the incident particle or
photon, b is an emitted particle or photon, and Y is the product
nucleus.
Reference Dose (R£D) -- An estimate (with uncertainty spanning perhaps
an order of magnitude) of the daily exposure of the human population to
a potential hazard tftat is likely to be without risk of deleterious
effects during a lifetime. The RfD is operationally derived from the
NOAEL (from animal and human studies) by a consistent application of
uncertainty factors that reflect various types of data used to estimate
RfDs and an additional modifying factor, which is based on a
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179
9. GLOSSARY
professional judgment of the entire database on the chemical. The RfDs
are not applicable to nonthreshold effects such as cancer.
Relative Biological Effectiveness (RBE) -- The RBE is a factor used to
compare the biological effectiveness of absorbed radiation doses (i.e.,
rad) due to different types of ionizing radiation. More specifically,
it is the experimentally determined ratio of an absorbed dose of a
radiation in question to the absorbed dose of a reference radiation
required to produce an identical biological effect in a particular
experimental organism or tissue. NOTE: This term should not be used in
radiation protection. (See Quality Factor.)
Rem -- A unit of dose equivalent. The dose equivalent in rem is
numerically equal to the absorbed dose in rad multiplied by the quality
factor, the distribution factor, and any other necessary modifying
factors.
Reportable Quantity (RQ) -- The quantity of a hazardous substance that
is considered reportable under CERCLA. Reportable quantities are (1) 1
lb or greater or (2) for selected substances, an amount established by
regulation either under CERCLA or under Section 311 of the Clean Water
Act. Quantities are measured over a 24-hour period.
Reproductive Toxicity -- The occurrence of adverse effects on the
reproductive system that may result from exposure to a chemical. The
toxicity may be directed to the reproductive organs and/or the related
endocrine system. The manifestation of such toxicity may be noted as
alterations in sexual behavior, fertility, pregnancy outcomes, or
modifications in other functions that are dependent on the integrity of
this system.
Roentgen (R) -- A unit of exposure for photon radiation. One roentgen
equals 2.58x10"'' Coulomb per kilogram of air.
Short-Term Exposure Limit (STEL) -- The maximum concentration to which
workers can be exposed continually for up to 15 minutes. No more than
four excursions are allowed per day, and there must be at least 60
minutes between exposure periods. The daily TLV-TWA may not be
exceeded.
SI Units -- The International System of Units as defined by the General
Conference of Weights and Measures in 1960. These units are generally
based on the meter/kilogram/second units, with special quantities for
radiation including the becquerel, gray, and sievert.
Sickness, Radiation -- (Radiation Therapy): A self-limited syndrome
characterized by nausea, vomiting, diarrhea, and psychic depression
following exposure to appreciable doses of ionizing radiation,
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180
9. GLOSSARY
particularly to the abdominal region. Its mechanism is unknown and
there is no satisfactory remedy. It usually appears a few hours after
irradiation and may subside within a day. It may be sufficiently severe
to necessitate interrupting the treatment series or to incapacitate the
patient. (General): The syndrome associated with intense acute
exposure to ionizing radiations. The rapidity with which symptoms
develop is a rough measure of the level of exposure.
Sievert -- The SI unit of radiation dose equivalent. It is equal to
dose in grays times a quality factor times other modifying factors, for
example, a distribution factor; 1 sievert equals 100 rem.
Specific Activity -- Total activity of a given nuclide per gram of an
element.
Specific Energy -- The actual energy per unit mass deposited per unit
volume in a given event. This is a stochastic quantity as opposed to
the average value over a large number of instance (i.e., the absorbed
dose) .
Standard Mortality Ratio (SMR) -- Standard mortality ratio is the ratio
of the disease or accident mortality rate in a certain specific
population compared with that in a standard population. The ratio is
based on 200 for the standard so that an SMR of 100 means that the test
population has twice the mortality from that particular cause of death.
Stopping Power -- The average rate of energy loss of a charged particle
per unit thickness of a material or per unit mass of material traversed.
Surface-seeking Radionuclide -- A bone-seeking internal emitter that is
deposited and remains on the surface for a long period of time. This
contrasts with a volume seeker, which deposits more uniformly throughout
the bone volume.
Target Organ Toxicity -- This term covers a broad range of adverse
effects on target organs or physiological systems (e.g., renal,
cardiovascular) extending from those arising through a single limited
exposure to those assumed over a lifetime of exposure to a chemical.
Target Theory (Hit Theory) - - A theory explaining some biological
effects of radiation on the basis that ionization, occurring in a
discrete volume (the target) within the cell, directly causes a lesion
which subsequently results in a physiological response to the damage at
that location. One, two, or more "hits" (ionizing events within the
target) may be necessary to elicit the response.
Teratogen -- A chemical that causes structural defects that affect the
development of a fetus.
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9. GLOSSARY
Threshold Limit Value (TLV) --An allowable exposure concentration
averaged over a normal 8-hour workday or 40-hour workweek.
Toxic Dose (TD50) -- A calculated dose of a chemical, introduced by a
route other than inhalation, which is expected to cause a specific toxic
effect in 50% of a defined laboratory animal population.
Transformation, Nuclear -- The process by which a nuclide is transformed
into a different nuclide by absorbing or emitting a particle.
Transition, Isomeric -- The process by which a nuclide decays to an
isomeric nuclide (i.e., one of the same mass number and atomic number)
of lower quantum energy. Isomeric transitions, often abbreviated I.T.,
proceed by gamma ray and/or internal conversion electron emission.
Tritium -- The hydrogen isotopes with one proton and two neutrons in the
nucleus (Symbol: 3H or T).
Unattached Fraction -- That fraction of the radon daughters, usually
218Po (Radium A), which has not yet attached to a particle. As a free
atom, it has a high probability of being retained within the lung and
depositing alpha energy when it decays.
Uncertainty Factor (UF) -- A factor used in operationally deriving the
RfD from experimental data. UFs are intended to account for (1) the
variation in sensitivity among the members of the human population, (2)
the uncertainty in extrapolating animal data to the case of human, (3)
the uncertainty in extrapolating from data obtained in a study that is
of less than lifetime exposure, and (4) the uncertainty in using LOAEL
data rather than NOAEL data. Usually each of these factors is set equal
to 10.
Units, Radiological --
Units
Equivalents
Becquerel*
1
Bq -
1 disintegration per second - 2.7xl0~u Ci
Curie
1
Ci -
3.7xl010 disintegrations per second - 3.7xl010
Bq
Gray*
1
Gy -
1 J/kg - 100 rad
Rad
1
Rad -
100 erg/g - 0.01 Gy
Rem
1
Rem -
0.01 Sievert
Sievert*
1
Sv -
100 rem
~International Units are designated (SI).
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182
9. GLOSSARY
Working Level (WL) -- Any combination of short-lived radon daughters in
1 liter of air that will result in the ultimate emission of 1.3xl05 MeV
of potential alpha energy.
Working Level Month (WLM) -- Inhalation of air with a concentration of 1
WL of radon daughters for 170 working hours results in an exposure of 1
WLM.
X-rays -- Penetrating electromagnetic radiations whose wave lengths are
shorter than those of visible light. They are usually produced by
bombarding a metallic target with fast electrons in a high vacuum. In
nuclear reaction, it is customary to refer to photons originating in the
extranuclear part of the atom as X-rays. These rays are sometimes
called roentgen rays after their discoverer, W.C. Roentgen.
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183
APPENDIX A
PEER REVIEW
A peer review panel was assembled for plutoniura. The panel
consisted of the following members: Dr. Dominic Cataldo, Staff
Scientist, Environmental Science Department, Battelle Northwest,
Richland, Washington; Dr. Ingeborg Harding-Barlow, Consultant,
Environmental and Occupational Toxicology, Palo Alto, California; Dr.
John Harley, private consultant; and Dr. Laurence Holland, Program
Manager, Industrial Hygiene Group, Los Alamos National Laboratory, Los
Alamos, New Mexico. These experts collectively have knowledge of
radon's physical and chemical properties, toxicokinetics, key health end
points, mechanisms of action, human and animal exposure, and
quantification of risk to humans. All reviewers were selected in
conformity with the conditions for peer review specified in Section
104(i)(13) of the Comprehensive Environmental Response, Compensation,
and Liability Act of 1986, as amended.
A joint panel of scientists from ATSDR and EPA has reviewed the
peer reviewers' comments and determined which comments will be included
in the profile. A listing of the peer reviewers' comments not
incorporated in the profile, with a brief explanation of the rationale
for their exclusion, exists as part of the administrative record for
this compound. A list of databases reviewed and a list of unpublished
documents cited are also included in the administrative record.
The citation of the peer review panel should not be understood to
imply its approval of the profile's final content. The responsibility
for the content of this profile lies with the Agency for Toxic
Substances and Disease Registry.
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185
APPENDIX B
OVERVIEW OF BASIC RADIATION PHYSICS, CHEMISTRY AND BIOLOGY
Understanding the basic concepts in radiation physics, chemistry,
and biology is important to the evaluation and interpretation of
radiation-induced adverse health effects and to the derivation of
radiation protection principles. This appendix presents a brief
overview of the areas of radiation physics, chemistry, and biology and
is based to a large extent on the reviews of Mettler and Moseley (1985),
Hobbs and McClellan (1986), Eichholz (1982), Hendee (1973), and Early et
al. (1979).
B.l RADIONUCLIDES AND RADIOACTIVITY
The substances we call elements are composed of atoms. Atoms in
turn are made up of neutrons, protons, and electrons; neutrons and
protons in the nucleus and electrons in a cloud of orbits around the
nucleus. Nuclide is the general term referring to any nucleus along
with its orbital electrons. The nuclide is characterized by the
composition of its nucleus and hence by the number of protons and
neutrons in the nucleus. All atoms of an element have the same number
of protons (this is given by the atomic number) but may have different
numbers of neutrons (this is reflected by the atomic mass or atomic
weight of the element). Atoms with different atomic mass but the same
atomic numbers are referred to as isotopes of an element.
The numerical combination of protons and neutrons in most nuclides
is such that the atom is said to be stable; however, if there are too
few or too many neutrons, the nucleus of the atom is unstable. Unstable
nuclides undergo a process referred to as radioactive transformation in
which energy is emitted. These unstable atoms are called radionuclides;
their emissions are called ionizing radiation; and the whole property is
called radioactivity. Transformation or decay results in the formation
of new nuclides some of which may themselves be radionuclides, while
others are stable nuclides. This series of transformations is called
the decay chain of the radionuclide. The first radionuclide in the
chain is called the parent; the subsequent products of the
transformation are called progeny, daughters, or decay products.
In general there are two classifications of radioactivity and
radionuclides: natural and man-made. Naturally-occurring radionuclides
exist in nature and no additional energy is necessary to place them in
an unstable state. Natural radioactivity is the property of some
naturally occurring, usually heavy elements, that are heavier than lead.
Radionuclides, such as radium and uranium, primarily emit alpha
particles. Some lighter elements such as carbon-14 and tritium
(hydrogen-3) primarily emit beta particles as they transform to a more
stable atom. Natural radioactive atoms heavier than lead cannot attain
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186
APPENDIX B
a stable nucleus heavier than lead. Everyone is exposed to background
radiation from naturally-occurring radionuclides throughout life This
background radiation is the major source of radiation exposure to man
and arises from several sources. The natural background exposures are
frequently used as a standard of comparison for exposures to various
man-made sources of ionizing radiation.
Man-made radioactive atoms are produced either as a by-product of
fission of uranium atoms in a nuclear reactor or by bombarding stable
atoms with particles, such as neutrons, directed at the stable atoms
with high velocity. These artificially produced radioactive elements
usually decay by emission of particles, such as positive or negative
beta particles and one or more high energy photons (gamma rays)
Unstable (radioactive) atoms of any element can be produced.
Both naturally occurring and man-made radioisotopes find
application in medicine, industrial products, and consumer products
Some specific radioisotopes, called fall-out, are still found in the
environment as a result of nuclear weapons use or testing.
B.2 RADIOACTIVE DECAY
B.2.1 Principles of Radioactive Decay
The stability of an atom is the result of the balance of the force
of the various components of the nucleus. An atom that is unstable
(radionuclide) will release energy (decay) in various ways and transform
to stable atoms or to other radioactive species called daughters often
with the release of ionizing radiation. If there are either too'many^r
too few neutrons for a given number of protons, the resulting nucleus *
may undergo transformation. For some elements, a chain of daughter
decay products may be produced until stable atoms are formed.
Radionuclides can be characterized by the type and energy of the
radiation emitted, the rate of decay, and the mode of decay. The mode
of decay indicates how a parent compound undergoes transformation
Radiations considered here are primarily of nuclear origin, i.e th
arise from nuclear excitation, usually caused by the capture of cha
or uncharged nucleons by a nucleus, or by the radioactive decay or ^
transformation of an unstable nuclide, The type of radiation may be
categorized as charged or uncharged particles (electrons, neutrons
neutrinos, alpha particles, beta particles, protons, and fission '
products) or electromagnetic radiation (gamma rays and X-rays) Tabl
B-l summarizes the basic characteristics of the more common types of &
radiation encountered.
B.2.2 Half-Life and Activity
For any given radionuclide, the rate of decay is a first-order
process that depends on the number of radioactive atoms present and is
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187
APPENDIX B
TABLE B-l. Characteristics of Huclaar Radiations
Bndiation
Rest Mass
Charge
Typical
Energy Range
Path Length
(Order of Magnitude)
Air Solid
General Comments
(negatron)
4.00 amu
5.48x10"* amu
0.51 MeV
2+
Positron 5.48x10"^ amu
(B positive) 0.51 MeV
Proton
Neutron
938.26 MeV
1.0073 amu
1.0086 amu
939.55 MeV
(e.m. photon)
(e.m. photon)
*-10 MeV
0-4 MeV
0-15 MeV
eV-100 keV
5-10 cm 25-40 |im
0-1 a
0-1 em
0-1 m 0-1 cm
Identical to ionized He
nucleus
Identical to electron
Identical to electron
except for charge
0-100 ra 0-100 era Free half life: 16 min
0.1-10 m« 0-1 m*
10 KeV-3 MeV 0.1-10 m* 1 nm-1 m
Photons from electron
transitions
Photons from nuclear
transitions
'Exponential attenuation in the case of electromagnetic radiation.
a » alpha
B - beta
X - X-ray
ganma
amu " atomic mass unit
MeV - Mega electron volts
KeV » Kiloelectron volts
cm " centimeter
m * meter
Jim " micrometer
¦ millimeter
e.m. " electromagnetic
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188
APPENDIX B
characteristic for each radionuclide. The process of decay is a series of
random events; temperature, pressure, or chemical combinations do not effect
the rate of decay. While it may not be possible to predict exactly which atom
is going to undergo transformation at any given time, it is possible to
predict, on the average, how many atoms will transform during any interval of
time .
The source strength is a measure of the rate of emission of radiation.
For these radioactive materials it is customary to describe the source
strength in terms of the source activity, which is defined as the number of
disintegrations (transformations) per unit time occurring in a given quantity
of this material. The unit of activity is the curie (Ci) which was originally
related to the activity of one gram of radium, but is now defined as:
1 curie (Ci) = 3.7xl010 disintegrations (transformations)/second (dps) or
2 22xl012 disintBgrations (transformations)/minute (dpm) .
The SI unit of activity is the becquerel (Bq); 1 Bq - 1 transformation/second.
Since activity is proportional to the number of atoms of the radioactive
material the quantity of any radioactive material is usually expressed in
curies regardless of its purity or concentration. The transformation of
radioactive nuclei is a random process, and the rate of transformation is
directly proportional to the number of radioactive atoms Resent For any
pure radioactive substance, the rate of decay is usually described by its
radiological half-life, TR, i.e., the time it takes for a specified source
material to decay to half its initial activity.
The activity of a radionuclide at time t may be calculated by:
A - Aoe"0-693t/Trad
where A is the activity in dps, A0 is the activity at time zero, t is the time
at which measured, and Trad is the radiological half-life of the radionuclide.
ti- iq amarent that activity exponentially decays with time. The time when
the activity of a sample of radioactivity becomes one-half its original value
is the radioactive half-life and is expressed in any suitable unit of time.
The specific activity is the radioactivity per unit weight of material.
This activity is usually expressed in curies per gram and may be calculated by
curies/gram - 1.3xl08/(Trad)(atomic weight)
where Trad is the radiological half-life in days.
Tn the case of radioactive materials contained in living organisms, an
additional consideration is made for the reduction in observed activity due to
regular processes of elimination of the respective chemical or biochemical
substance from the organism. This introduces a rate constant called the
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APPENDIX B
biological half-life (Tbiol) which is the time required for biological
processes to eliminate one-half of the activity. This time is virtually the
same for both stable and radioactive isotopes of any given element.
Under such conditions the time required for a radioactive element to be
halved as a result of the combined action of radioactive decay and biological
elimination is the effective half-life:
TefE ~ (Tbiol x Trad)/(Tbiol + Trad) •
Table B-2 presents representative effective half-lives of particular interest.
B.2.3 Interaction of Radiation with Matter
Both ionizing and nonionizing radiation will interact with materials,
that is, it will lose kinetic energy to any solid, liquid or gas through which
it passes by a variety of mechanisms. The transfer of energy to a medium by
either electromagnetic or particulate radiation may be sufficient to cause
formation of ions. This process is called ionization. Compared to other
types of radiation that may be absorbed, such as ultraviolet radiation,
ionizing radiation deposits a relatively large amount of energy into a small
volume.
The method by which incident radiation interacts with the medium to cause
ionization may be direct or indirect. Electromagnetic radiations (X-rays and
gamma photons) are indirectly ionizing; that is, they give up their energy in
various interactions with cellular molecules, and the energy is then utilized
to produce a fast-moving charged particle such as an electron. It is the
electron that then secondarily may react with a target molecule. Charged
particles, in contrast, strike the tissue or medium and directly react with
target molecules, such as oxygen or water. These particulate radiations are
directly ionizing radiations. Examples of directly ionizing particles include
alpha and beta particles. Indirectly ionizing radiations are always more
penetrating than directly ionizing particulate radiations.
Mass, charge, and velocity of a particle all affect the rate at which
ionization occurs. The higher the charge of the particle and the lower the
velocity, the greater the propensity to cause ionization. Heavy, highly
charged particles, such as alpha particles, lose energy rapidly with distance
and, therefore, do not penetrate deeply. The result of these interaction
processes is a gradual slowing down of any incident particle until it is
brought to rest or "stopped" at the end of its range.
B.2.4 Characteristics of Emitted Radiation
B.2.4.1 Alpha Emission. In alpha emission, an alpha particle consisting
of two protons and two neutrons is emitted with a resulting decrease in the
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APPENDIX B
TABLE B-2. Half-Lives of Some Radionuclides in Adult Body Organs
Half-Life8
Radionuclide
Hydrogen-3b
(Tritium)
Whole body
12.3 y
12 d
11.97d
Iodine-131
Thyroid
8 d
138 d
7.6 d
Strontium-90
Bone
28 y
50 y
18 y
Plutonium-239
Bone
24,400 y
200 y
198 y
Lung
24,400 y
500 d
500 d
Cobalt-60
Whole body
5.3 y
99.5 d
9.5 d
Iron-55
Spleen
2.7 y
600 d
388 d
Iron-59
Spleen
45.1 d
600 d
41.9 d
Manganese-54
Liver
303 d
25 d
23 d
Cesium-137
Whole body
30 y
70 d
70 d
ad - days, y - years.
bMixed in body water as tritiated water.
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APPENDIX B
atomic mass number by four and reduction of the atomic number by two, thereby
changing the parent to a different element. The alpha particle is identical
to a helium nucleus consisting of two neutrons and two protons. It results
from the radioactive decay of some heavy elements such as uranium, plutonium,
radium, thorium, and radon. Alpha particles have a large mass as compared to
electrons. Decay of alpha-emitting radionuclides may result in the emission
of several different alpha particles. A radionuclide has an alpha emission
with a discrete alpha energy and characteristic pattern of alpha energy
emitted.
The alpha particle has an electrical charge of +2. Because of this
double positive charge, alpha particles have great ionizing power, but their
large size results in very little penetrating power. In fact, an alpha
particle cannot penetrate a sheet of paper. The range of an alpha particle,
that is, the distance the charged particle travels from the point of origin to
its resting point, is about 4 cm in air, which decreases considerably to a few
micrometers in tissue. These properties cause alpha emitters to be hazardous
only if there is internal contamination (i.e., if the radionuclide is
ingested, inhaled, or otherwise absorbed).
B.2.4.2. Beta Emission. Nuclei which are excessively neutron rich decay
by E-decay. A beta particle (£) is a high-velocity electron ejected from a
disintegrating nucleus. The particle may be either a negatively charged
electron, termed a negatron (£-) or a positively charged electron, termed a
positron (£+). Although the precise definition of "beta emission" refers to
both 6- and £+, common usage of the term generally applies only to the
negative particle, as distinguished from the positron emission, which refers
to the 6+ particle.
B.2.4.2.1 Beta Negative Emission. Beta particle (S-) emission is
another process by which a radionuclide, usually those with a neutron excess,
achieves stability. Beta particle emission decreases the number of neutrons
by one and increases the number of protons by one, while the atomic mass
remains unchanged. This transformation results in the formation of a
different element. The energy spectrum of beta particle emission ranges from
a certain maximum down to zero with the mean energy of the spectrum being
about one-third of the maximum. The range in tissue is much less. Beta
negative emitting radionuclides can cause injury to the skin and superficial
body tissues but mostly present an internal contamination hazard.
B.2.4.2.2 Positron Emission. In cases in which there are too many
protons in the nucleus, positron emission may occur. In this case a proton
may be thought of as being converted into a neutron, and a positron (£+) is
emitted, accompanied by a neutrino (see glossary). This increases the number
of neutrons by one, decreases the number of protons by one, and again leaves
the atomic mass unchanged. The gamma radiation resulting from the
annihilation (see glossary) of the positron makes all positron emitting
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APPENDIX B
isotopes more of an external radiation hazard than pure £ emitters of equal
energy.
B.2.4.2.3 Gamma Emission. Radioactive decay by alpha, beta, positron
emission or electron capture often leaves some of the energy resulting from
these changes in the nucleus. As a result, the nucleus is raised to an
excited level. None of these excited nuclei can remain in this high-energy
state. Nuclei release this energy returning to ground state or to the lowest
possible stable energy level. The energy released is in the form of gamma
radiation (high energy photons) and has an energy equal to the change in the
energy state of the nucleus. Gamma and X-rays behave similarly but differ in
their origin; gamma emissions originate in the nucleus while X-rays originate
in the orbital electron structure.
B.3 ESTIMATION OF ENERGY DEPOSITION IN HUMAN TISSUES
Two forms of potential radiation exposures can result -- internal and
external. The term exposure denotes physical interaction of the radiation
emitted from the radioactive material with cells and tissues of the human
body. An exposure can be "acute" or "chronic" depending on how long an
individual or organ is exposed to the radiation. Internal exposures occur
when radionuclides, which have entered the body (e.g., through the inhalation
ingestion, or dermal pathways), undergo radioactive decay resulting in the
deposition of energy to internal organs. External exposures occur when
radiation enters the body directly from sources located outside the body, such
as radiation emitters from radionuclides on ground surfaces, dissolved in
water, or dispersed in the air. In general, external exposures are from
material emitting gamma radiation, which readily penetrate the skin and
internal organs. Beta and alpha radiation from external sources are far less
penetrating and deposit their energy primarily on the skin's outer layer.
Consequently, their contribution to the absorbed dose of the total body dose
compared to that deposited by gamma rays, may be negligible.
Characterizing the radiation dose to persons as a result of exposure to
radiation is a complex issue. It is difficult to: (1) measure internally the
amount of energy actually transferred to an organic material and to correlate
any observed effects with this energy deposition; and (2) account for and
predict secondary processes, such as collision effects or biologically
triggered effects, that are an indirect consequence of the primary interaction
event.
B.3.1 Dose Units
B.3.1.1 Roentgen. The roentgen (R) is a unit of exposure related to the
amount of ionization caused in air by gamma or x-radiation. One roentgen
equals 2.58xlO~A Coulomb per kilogram of air. In the case of gamma radiation,
over the commonly encountered range of photon energy, the energy deposition in
tissue for a dose of 1 R is about 0.0096 joules(J)/kg of tissue.
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APPENDIX B
B.3.1.2 Absorbed Dose and Absorbed Dose Rate. Since different types of
radiation interact differently with any material through which they pass, any
attempt to assess their effect on humans or animals should take into account
these differences. The absorbed dose is defined as the energy imparted by the
incident radiation to a unit mass of the tissue or organ. The unit of
absorbed dose is the rad; 1 rad - 100 erg/gram - 0.01 J/kg in any medium. The
SI unit is the gray which is equivalent to 100 rad or 1 J/kg. Internal and
external exposures from radiation sources are not usually instantaneous but
are distributed over extended periods of time. The resulting rate of change
of the absorbed dose to a small volume of mass is referred to as the absorbed
dose rate in units of rad/unit time.
B.3.1.3 Working Levels and Working Level Months. Working levels are
units that have been used to describe the radon decay-product activities in
air in terms of potential alpha energy. It is defined as any combination of
short-lived radon daughters (through polonium-214) per liter of air that will
result in the emission of 1.3xl05 MeV of alpha energy. An activity
concentration of 100 pCi radon-222/L of air, in equilibrium with its
daughters, corresponds approximately to a potential alpha-energy concentration
of 1 WL. The WL unit can also be used for thoron daughters. In this case,
1.3xl05 MeV of alpha energy (1 WL) is released by the thoron daughters in
equilibrium with 7.5 pCi thoron/L. The potential alpha energy exposure of
miners is commonly expressed in the unit Working Level Month (WLM). One WLM
corresponds to exposure to a concentration of 1 WL for the reference period of
170 hours.
B.3.2 Dosimetry Models
Dosimetry models are used to estimate the internally deposited dose from
exposure to radioactive substances. The models for internal dosimetry
consider the quantity of radionuclides entering the body, the factors
affecting their movement or transport through the body, distribution and
retention of radionuclides in the body, and the energy deposited in organs and
tissues from the radiation that is emitted during spontaneous decay processes.
The models for external dosimetry consider only the photon doses to organs of
individuals who are immersed in air or are exposed to a contaminated ground
surface. The dose pattern for radioactive materials in the body may be
strongly influenced by the route of entry of the material. For industrial
workers, inhalation of radioactive particles with pulmonary deposition and
puncture wounds with subcutaneous deposition have been the most frequent. The
general population has been exposed via ingestion and inhalation of low levels
of naturally occurring radionuclides as well as man-produced radionuclides
from nuclear weapons testing.
B.3.2.1 Ingestion. Ingestion of radioactive materials is most likely to
occur from contaminated foodstuffs or water or eventual ingestion of inhaled
compounds initially deposited in the lung. Ingestion of radioactive material
may result in toxic effects as a result of either absorption of the
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APPENDIX B
radionuclide or irradiation of the gastrointestinal tract during passage
through the tract, or a combination of both. The fraction of a radioactive
material absorbed from the gastrointestinal tract is variable, depending on
the specific element, the physical and chemical form of the material ingested
and the diet, as well as some other metabolic and physiological factors. The
absorption of some elements is influenced by age usually with higher
absorption in the very young.
B.3.2.2 Inhalation. The inhalation route of exposure has long been
recognized as being of major importance for both nonradioactive and
radioactive materials. The deposition of particles within the lung is largely
dependent upon the size of the particles being inhaled. After the particle is
deposited, the retention will depend upon the physical and chemical properties
of the dust and the physiological status of the lung. The retention of the
particle in the lung depends on the location of deposition, in addition to the
physical and chemical properties of the particles. The converse of pulmonary
retention is pulmonary clearance. There are three distinct mechanisms of
clearance which operate simultaneously. Ciliary clearance acts only in the
upper respiratory tract. The second and third mechanisms act mainly in the
deep respiratory tract. These are phagocytosis and absorption. Phagocytosis
is the engulfing of foreign bodies by alveolar macrophages and their
subsequent removal either up the ciliary "escalator" or by entrance into the
lymphatic system. Some inhaled soluble particulates are absorbed into the
blood and translocated to other organs and tissues. Dosimetric lung models
are reviewed by James (1987) and James and Roy (1987).
B.3.3 Internal Emitters
The absorbed dose from internally deposited radioisotopes is the energy
absorbed by the surrounding tissue. For a radioisotope distributed uniformly
throughout an infinitely large medium, the concentration of absorbed energy
must be equal to the concentration of energy emitted by the isotope. An
infinitely large medium may be approximated by a tissue mass whose dimensions
exceed the range of the particle. All alpha and most beta radiation will be
absorbed in the organ (or tissue) of reference. Gamma - emitting isotope
emissions are penetrating radiation and a substantial fraction may travel
great distances within tissue, leaving the tissue without interacting. The
dose to an organ or tissue is a function of the effective retention half-time
the energy released in the tissue, the amount of radioactivity initially
introduced, and the mass of the organ or tissue.
B.4 BIOLOGICAL EFFECTS OF RADIATION
When biological material is exposed to ionizing radiation, a chain of
cellular events occurs as the ionizing particle passes through the biological
material. A number of theories have been proposed to describe the interaction
of radiation with biologically important molecules in cells and to explain the
resulting damage to biological systems from those interactions. Many factors
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APPENDIX B
may modify the response of a living organism to a given dose of radiation.
Factors related to the exposure include the dose rate, the energy of the
radiation, and the temporal pattern of the exposure. Biological
considerations include factors such as species, age, sex, and the portion of
the body exposed. Several excellent reviews of the biological effects of
radiation have been published, and the reader is referred to these for a more
in-depth discussion (Hobbs and McClellan 1986; ICRP 1984; Mettler and Moseley
1985; Rubin and Casarett 1968).
B.4.1 Radiation Effects at the Cellular Level
According to Mettler and Moseley (1985), at acute doses up to 10 rad (100
mGy), single strand breaks in DNA may be produced. These single strand breaks
may be repaired rapidly. With doses in the range of 50 to 500 rad (0.5 to 5
Gy), irreparable double - stranded DNA breaks are likely, resulting in cellular
reproductive death after one or more divisions of the irradiated parent cell.
At large doses of radiation, usually greater than 500 rad (5 Gy), direct cell
death before division (interphase death) may occur from the direct interaction
of free-radicals with essentially cellular macromolecules. Morphological
changes at the cellular level, the severity of which are dose - dependent, may
also be observed.
The sensitivity of various cell types varies. According to the Bergoni6-
Tribondeau law, the sensitivity of cell lines is directly proportional to
their mitotic rate and inversely proportional to the degree of differentiation
(Mettler and Moseley 1985). Rubin and Casarett (1968) devised a
classification system that categorized cells according to type, function, and
mitotic activity. The categories range from the most sensitive type,
"vegetative intermitotic cells," found in the stem cells of the bone marrow
and the gastrointestinal tract, to the least sensitive cell type, "fixed
postmitotic cells," found in striated muscles or long-lived neural tissues.
Cellular changes may result in cell death, which if extensive, may
produce irreversible damage to an organ or tissue or may result in the death
of the individual. If the cell recovers, altered metabolism and function may
still occur, which may be repaired or may result in the manifestation of
clinical symptoms. These changes may also be expressed at a later time as
tumors or mutations.
B.4.2 Radiation Effects at the Organ Level
In most organs and tissues the injury and the underlying mechanism for
that injury are complex and may involve a combination of events. The extent
and severity of this tissue injury are dependent upon the radiosensitivity of
the various cell types in that organ system. Rubin and Casarett (1968)
describe and schematically display the events following radiation in several
organ system types. These include: a rapid renewal system, such as the
gastrointestinal mucosa; a slow renewal system, such as the pulmonary
epithelium; and a nonrenewal system, such as neural or muscle tissue. In the
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APPENDIX B
rapid renewal system, organ injury results from the direct destruction of
highly radiosensitive cells, such as the stem cells in the bone marrow.
Injury may also result from constriction of the microcirculation and from
edema and inflammation of the basement membrane (designated as the
histohematic barrier - HHB), which may progress to fibrosis. In slow renewal
and nonrenewal systems, the radiation may have little effect on the
parenchymal cells, but ultimate parenchymal atrophy and death over several
months result from HHB fibrosis and occlusion of the microcirculation.
B.4.3 Acute and Chronic Somatic Effects
B.4.3.1 Acute Effects, The result of acute exposure to radiation is
commonly referred to as acute radiation syndrome. This effect is seen only
after exposures to relatively high doses (>50 rad), which would only be
expected to occur in the event of a serious nuclear accident. The four stages
of acute radiation syndrome are prodrome, latent stage, manifest illness
stage, recovery or death. The initial phase is characterized by nausea,
vomiting, malaise and fatigue, increased temperature, and blood changes. The
latent stage is similar to an incubation period. Subjective symptoms may
subside, but changes may be taking place within the blood-forming organs and
elsewhere which will subsequently give rise to the next stage. The manifest
illness stage gives rise to symptoms specifically associated with the
radiation injury. Among these symptoms are hair loss, fever, infection,
hemorrhage, severe diarrhea, prostration, disorientation, and cardiovascular
collapse. The symptoms and their severity depend upon the radiation dose
received.
B.4.3.2 Delayed Effects. The level of exposure to radioactive
pollutants that may be encountered in the environment is expected to be too
low to result in the acute effects described above. When one is exposed to
radiation in the environment, the amount of radiation absorbed is more likely
to produce long-term effects, which manifest themselves years after the
original exposure, and may be due to a single large over-exposure or
continuing low-level exposure.
Sufficient evidence exists in both human populations and laboratory
animals to establish that radiation can cause cancer and that the incidence of
cancer increases with increasing radiation dose. Human data are extensive and
include epidemiological studies of atomic bomb survivors, many types of
radiation-treated patients, underground miners, and radium dial painters.
Reports on the survivors of the atomic bomb explosions at Hiroshima and
Nagasaki, Japan (with whole-body external radiation doses of 0 to more than
200 rad) indicate that cancer mortality has increased (Kato and Schull 1982).
Use of X-rays (at doses of approximately 100 rad) in medical treatment for
ankylosing spondylitis or other benign conditions or diagnostic purposes, such
as breast conditions, has resulted in excess cancers in irradiated organs
(BEIR 1980, 1990; UNSCEAR 1977, 1988). Cancers, such as leukemia, have been
observed in children exposed in utero to doses of 0.2 to 20 rad (BEIR, 1980,
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APPENDIX B
1990; UNSCEAR 1977, 1988). Medical use of Thorotrast (colloidal thorium
dioxide) resulted in increases in the incidence of cancers of the liver, bone,
and lung (ATSDR 1990a; BEIR 1980, 1990; UNSCEAR 1977, 1988). Occupational
exposure to radiation provides further evidence of the ability of radiation to
cause cancer. Numerous studies of underground miners exposed to radon and
radon daughters, which are alpha emitters, in uranium and other hard rock
mines have demonstrated increases in lung cancer in exposed workers (ATSDR
1990b). Workers who ingested radium-226 while painting watch dials had an
increased incidence of leukemia and bone cancer (ATSDR 1990c). These studies
indicate that depending on radiation dose and the exposure schedule, ionizing
radiation can induce cancer in nearly any tissue or organ in the body.
Radiation-induced cancers in humans are found to occur in the hemopoietic
system, the lung, the thyroid, the liver, the bone, the skin, and other
tissues.
Laboratory animal data indicate that ionizing radiation is carcinogenic
and mutagenic at relatively high doses usually delivered at high dose rates.
However, due to the uncertainty regarding the shape of the dose-response
curve, especially at low doses, the commonly held conservative position is
that the cancer may occur at dose rates that extend down to doses that could
be received from environmental exposures. Estimates of cancer risk are based
on the absorbed dose of radiation in an organ or tissue. The cancer risk at a
particular dose is the same regardless of the source of the radiation. A
comprehensive discussion of radiation-induced cancer is found in BEIR IV
(1988), BEIR V (1990), and UNSCEAR (1982, 1988).
B.4.4 Genetic Effects
Radiation can induce genetic damage, such as gene mutations or
chromosomal aberrations, by causing changes in the structure, number, or
genetic content of chromosomes in the nucleus. The evidence for the
mutagenicity of radiation is derived from studies in laboratory animals,
mostly mice (BEIR 1980, 1988, 1990; UNSCEAR 1982, 1986, 1988). Evidence for
genetic effects in humans is derived from tissue cultures of human lymphocytes
from persons exposed to ingested or inhaled radionuclides (ATSDR 1990c,
1990d). Evidence for mutagenesis in human germ cells (cells of the ovaries or
testis) is not conclusive (BEIR 1980, 1988, 1990; UNSCEAR 1977, 1986, 1988).
Chromosome aberrations following radiation exposure have been demonstrated In
man andn in experimental animals (BEIR 1980, 1988, 1990; UNSCEAR 1982, 1986,
1988).
B.4.5 Teratogenic Effects
There is evidence that radiation produces teratogenicity in animals. It
appears that the developing fetus is more sensitive to radiation than the
mother and is most sensitive to radiation-induced damage during the early
stages of organ development. The type of malformation depends on the stage of
development and the cells that are undergoing the most rapid differentiation
at the time. Studies of mental retardation in children exposed in utero to
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198
APPENDIX B
radiation from the atomic bomb provide evidence that radiation may produce
teratogenic effects in human fetuses (Otake and Schull 1984). The damage to
the child was found to be related to the dose that the fetus received.
B.5 UNITS IN RADIATION PROTECTION AND REGULATION
B.5.1 Dose Equivalent and Dose Equivalent Rate. Dose equivalent or rem
is a special radiation protection quantity that is used to express the
absorbed dose in a manner which considers the difference in biological
effectiveness of various kinds of ionizing radiation. The ICRU has defined
the dose equivalent, H, as the product of the absorbed dose, D, the quality
factor, Q, and all other modifying factors, N, at the point of interest in
biological tissue. This relationship is expressed as follows:
H = D X Q x N.
The quality factor is a dimensionless quantity that depends in part on the
stopping power for charged particles, and it accounts for the differences in
biological effectiveness found among the types of radiation. By definition it
is independent of tissue and biological end point and, therefore, of little
use in risk assessment now. Originally Relative Biolotical Effectiveness
(RBE) was used rather than Q to define the quantity, rem, which was of use in
risk assessment. The generally accepted values for quality factors for
various radiation types are provided in Table B-3. The dose equivalent rate
is the time rate of change of the dose equivalent to organs and tissues and is
expressed as rem/unit time or sievert/unit time.
B.5.2 Relative Biological Effectiveness. The term relative biologic
effectiveness (RBE) is used to denote the experimentally determined ratio of
the absorbed dose from one radiation type to the absorbed dose of a reference
radiation required to produce an identical biologic effect under the same
conditions. Gamma rays from cobalt-60 and 200 to 250 KeV X-rays have been
used as reference standards. The term RBE has been widely used in
experimental radiobiology, and the term quality factor used in calculations of
dose equivalents for radiation protection purposes (ICRP 1977; NCRP 1971;
UNSCEAR 1982). The generally accepted values for RBE are provided in Table
B-4.
B.5.3 Effective Dose Equivalent and Effective Dose Equivalent Rate. The
absorbed dose is usually defined as the mean absorbed dose within an organ or
tissue. This represents a simplification of the actual problem. Normally
when an individual ingests or inhales a radionuclide or is exposed to external
radiation that enters the body (gamma), the dose is not uniform throughout the
whole body. The simplifying assumption is that the detriment will be the same
whether the body is uniformly or nonuniformly irradiated. In an attempt to
compare detriment from absorbed dose of a limited portion of the body with the
detriment from total body dose, the ICRP (1977) has derived a concept of
effective dose equivalent.
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199
APPENDIX B
TABLE B-3. Quality Factors (QF)
1. X-rays, electrons, and positrons of any specific ionization
QF - 1.
2. Heavy ionizing particles
Average LET in Water
(MeV/cnO OF
35 or less 1
35 to 70 1 to 2
70 to 230 2 to 5
230 to 530 5 to 10
530 to 1750 10 to 20
For practical purposes, a QF of 10 is often used for alpha particles" and
fast neutrons and protons up to 10 MeV. A QF of 20 is used for heavy
recoil nuclei.
aThe ICRP (1977) recommended a quality factor of 20 for alpha particles.
LET = Linear energy transfer
MeV/cm - Megaelectron volts per centimeter
MeV - Megaelectron volts
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200
APPENDIX B
TABLE B-4. Representative LET and RBE Values*
Radiation
Energy
(•MeV)
Av. LET
(keV/u)
RBF.
Quality
Factor
X-rays, 200 kVp
0.01-0.2
3.0
1.00
1
Gamma rays
1.25
0.3
0.7
1
4
0.3
0.6
1
Electrons (6)
0.1
0.42
1.0
1
0.6
0.3
1.3
1
1.0
0.25
1.4
Protons
0.1
90.0
6
2.0
16.0
2
10
5.0
8.0
2
10
Alpha particle
0.1
260.0
_ _
5.0
95.0
10-20
10
Heavy ions
10-30
-150.0
-25
20
Neutrons
thermal
4-5
3
1.0
20.0
2-10
10
*These values are general and approximate. RBE and QF values vary widely with
different measures of biological injury.
MeV — Megaelectron volts
KeV/p - Kiloelectron volts per micron
RBE - Relative biological effectiveness
kVp - Kilovolt potential
LET - Linear energy transfer
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APPENDIX B
The effective dose equivalent, HE, is
He = {the sum of) Wt Ht
where Ht is the dose equivalent in the tissue, Wt is the weighting factor,
which represents the estimated proportion of the stochastic risk resulting
from tissue, T, to the stochastic risk when the whole body is uniformly
irradiated for occupational exposures under certain conditions (IGRP 1977).
Weighting factors for selected tissues are listed In Table B-5.
The ICRU (L9S0), ICRP (1984), and NCRP (1985) now recommend that the rad,
roentgen, curie and rem be replaced by the SI units: gray (Gy) , Coulomb per
kilogram (C/kg), becquerel (Bq), and sievert (Sv), respectively. The
relationship between the customary units and the international system of units
(SI) for radiological quantities is shown in Table B-6.
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202
APPENDIX B
TABLE B-5. Weighting Factors for Calculating
Effective Dose Equivalent for Selected Tissues
Tissue Weighting Factor
Gonads 0.2 5
Breast 0.15
Red bone marrow 0.12
Lung 0.12.
Thyroid 0.03
Bone surface 0.03
Remainder 0.30
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203
APPENDIX B
TABLE B-6. Comparison of Common and SI Units
for Radiation Quantities
Quantity
Customary
Units
Definition
SI Units Definition
Activity (A)
Curie (Ci)
3. 7xl010
transforma-
tions s'1
becquerel
(Bq)
Absorbed Dose (D)
Absorbed Dose
Rate (D)
Dose Equivalent
(H)
Dose Equivalent
Rate (H)
Linear Energy
Transfer (L.)
rad (rad) 10 2Jkg_1
gray (Gy)Jkg"1
rad per
second
(rad s"1)
rem (rem)
rem per
second
(rem s"1)
kiloelectron
volts per
micrometer
(keVuM"1)
10"2Jkg"1s"1
10~2Jkg_1
10"2Jkg"1s"1
gray per
second
(Gy s"1)
Jkg 1s
-lo-l
sievert (Sv) Jkg*1
sievert per Jkg 1s"1
second
(Sv s"1)
1. 602xlO"10Jm"1 kiloelectron 1. 602xlO"10Jm'1
volts per
micrometer
(keV^m"1)
S"1 = per second
Jkg"1 = Joules per kilogram
Jkg^s"1 = Joules per kilogram per second
Jnf1 = Joules per meter
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204
APPENDIX B
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APPENDIX B
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