AFRRI

March 1993

93-2

TECHNICAL REPORT

Protocol for

Monitoring Gulf War

Veterans with

Imbedded Fragments

of Depleted Uranium

Project Leader

LTC Eric G . Daxon, MS, USA

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AFRRI Technical Report 93-2

PROTOCOL FOR MONITORING

GULF WAR VETERANS

WITH IMBEDDED DEPLETED URANIUM FRAGMENTS

Project Leader

Eric G. Daxon, LTC, MS, USA

March 1993

Radiation Biophysics Department

Armed Forces Radiobiology Research Institute

8901 Wisconsin Avenue

Bethesda, Maryland 20889-5603
The research requirements of this protocol will be approved by the appropriate DoD or VA

Institutional Review Board for the Protection of Human Subjects .
Preface

The Army's Office of The Surgeon General (OTSG) initiated this effort to care for Desert

Storm veterans with imbedded depleted uranium (DU) shrapnel . In February 1992, OTSG

requested that the Armed Forces Radiobiology Research Institute (AFRRI) conduct a

review of the potential health hazards (radiological and toxicological) of allowing DU

shrapnel to remain imbedded throughout the lifetime of the soldier . Specifically, OTSG

wanted to know if there was any reason to change the current surgical practice for

fragment removal . No compelling evidence was found in the literature review' to change

current surgical criteria for fragment removal . There were, however, significant

uncertainties about the impact of DU fragments on the health of these patients that

warranted long-term follow-up .

OTSG concurred with this finding and initiated action to implement this follow-up in the

Army . The Department of Veterans Affairs (DVA) agreed to perform the follow-up for

personnel discharged from the service . Both the DVA and OTSG requested AFRRI's

assistance in drafting the protocol to be used in the follow-up effort .

A group of DoD physicians and scientists met at AFRRI to draft the protocol . At a

subsequent meeting on 10 September 1992, a panel of experts reviewed and revised the

draft protocol ; representatives of the DVA and OTSG also attended this meeting . The

protocol was once again reviewed and approved by the panel of experts .
Members of the Initial Draft Committee

Project Leader

Eric G . Daxon, Ph.D.

LTC, MS, USA

Armed Forces Radiobiology

Research Institute (AFRRI)

Bethesda, MD

Doris Browne, M .D.

LTC, MC, USA

Chairman, Military Requirements

and Applications Department

Armed Forces Radiobiology

Research Institute

Bethesda, MD

Clifford Ferguson, M .D .

LTC, MC, USA

Uniformed Services University

of the Health Sciences

Bethesda, MD

William E . Shiels, M .D.

MAJ, MC, USA

Radiology Consultant, Office Of

The Army Surgeon General

Falls Church, VA

Maurice Weeks

US Army Environmental

Hygiene Agency

Aberdeen Proving Ground, MD

Kenneth Philips, M .D.

MAJ, MC, USA

Walter Reed Army

Medical Center

Washington, DC

Mark Melanson

CPT, MS, USA

Walter Reed Army

Medical Center

Washington, DC
Members of the Review Panel

Patricia Durbin, Ph .D.

Fun Fong, M .D .

Lawrence Berkeley Laboratory

Oak Ridge Institute for

Berkeley, CA Science and Education

Oak Ridge, TN

Raymond Guilmette, Ph .D .

Inhalation Toxicology

Research Institute

Albuquerque, NM

George Voelz, M .D.

Los Alamos National Laboratory

Los Alamos, NV

11

M . E . Wrenn, Ph .D.

Environmental Radiation and

Toxicology Laboratory

University of Utah

Salt Lake City, UT
Belton Burrows, M .D .

Department of Veterans Affairs,

Boston DVA Medical Center

Boston, MA

Layne Drash

Department of Veterans Affairs,

Acting Director

Environmental Agents Service

Washington, DC

Han Kang, Ph .D .

Department of Veterans Affairs

Environmental Epidemiological

Services

Washington, DC

Susan Mather, M .D .

Department of Veterans Affairs

Assistant Chief Medical Director

Environmental Medicine and

Public Health

Washington, DC

Agency Representatives to the Review Panel

iv

Eric Daxon, Ph .D.

LTC, MS, USA

Project Leader

Armed Forces Radiobiology

Research Institute

Bethesda, MD

Frederick Erdtmann, M .D .

COL, MC, USA

Chief, Preventive Medicine

Office of The Army Surgeon General

Falls Church, VA

Eric Kearsley, Ph .D .

CDR, MSC, USN

Chairman, Radiation Biophysics Department

Armed Forces Radiobiology

Research Institute

Bethesda, MD

Peter Myers

COL, MS, USA

Radiological Hygiene Consultant

Office of The Army Surgeon General

Falls Church, VA
Protocol for Monitoring Gulf War Veterans

With Imbedded Depleted Uranium Fragments

1 . Objectives

This protocol will implement two separate but complementary efforts . The first is the

clinical follow-up of Desert Storm patients with known or suspected imbedded depleted

uranium (DU) fragments, DU contaminated wounds or significant amounts of inhaled

DU . The second is the conduct of research into the toxicological and radiological

effects of this unique exposure modality . Specifically, this protocol will provide the

following :

a . Early detection of abnormalities related to the presence of DU so that

prompt, efficacious treatment is effected if required . The study will also provide the

scientific data required to fairly settle claims for compensation .

b . Treatment recommendations that will provide a firm clinical basis for

fragment removal decisions and for decisions concerning the need for efforts to

reduce the uranium in the body.

c. Quantification and documentation of the toxicological (heavy metal toxicity)

and radiological (cancer and tissue necrosis) risks of imbedded uranium fragments by

(1) measuring and documenting uranium levels in each soldier using in vivo

and in vitro measurement techniques,

(2) determining the parameters and models needed to translate uranium

levels in the body into estimates of the increased cancer risk from this exposure,

(3) comparing the clinical course of the body's response to the DU fragments

with that for other non-DU fragments to determine whether clinically significant

differences exist due to either the chemical or radiological properties of depleted

uranium, and

(4) determining the risk of chronic kidney toxicity due to the long-term

chronic exposure to elevated levels of uranium .
2. Approach

The comparison of the clinical course of DU fragments with non-DU fragments will be

made using a prospective study approach . The data from patients with internalized

DU (the exposed population) will be compared to that from two unexposed

populations: patients with fragments that are not DU and soldiers who were not

wounded and not exposed to DU .

a . Exposed Population

Each crew member of the attacked vehicles is a candidate for inclusion in the

exposed group. An initial check has revealed that there are approximately 22 soldiers

whose records indicate that they have imbedded fragments that might be DU . There

are an additional 13 soldiers who were wounded and hospitalized but were not

specifically identified as having shrapnel . The remaining crew members (besides the

35 already discussed) were either not wounded during the incident or had minor

wounds that were treated in the field . The latter two sets of soldiers might have

inhaled uranium or experienced DU contamination of wounds or minor fragmentation

wounds that were either not noticed or did not require extensive treatment .

The small size of the exposed population limits the study's ability to detect differences

to only those effects where the differences between DU and non-DU imbedded

fragments are large . For example, it is highly unlikely that definitive conclusions

concerning cancer induction will be obtainable from the study . However, this approach

will allow a direct comparison of differences that may exist in deterministic effects .

Examples of such effects include differences in the body's propensity to encapsulate a

DU fragment, the onset of local or whole-organ tissue necrosis, thorotrastoma-like

growth induction, or the onset of chronic kidney toxicity . In addition, following a

nonexposed group will provide information concerning nominal values for each

metabolic value studied in protocol (e .g ., normal concentrations of uranium in the body

and body fluids as well as kidney function variations with age) .

There are two criteria for including a soldier in the exposed group . First, the soldier

must have been in or on the vehicle when the vehicle was struck by DU munitions .

Second, the soldier must have internalized DU at levels that are high enough to cause

the uranium in the urine either to exceed background levels of uranium excretion by a

factor of four or to be detected by whole-body or partial-body counting . Uranium in

urine measurements from the control group will establish the background levels for

these two measurements . The exposed group has two subgroups .

2
(1) The first consists of those soldiers with internalized DU not from imbedded

fragments. This group will consist of personnel who have DU from inhalation or

through wound contamination . The data from this group will be used in both the

metabolic modelling and chronic kidney toxicity studies .

(2) The second consists of soldiers with imbedded DU fragments . The data

from this group will be used to compare the clinical course of DU fragments with

non-DU shrapnel as well as to provide information for the metabolic modelling and

kidney toxicity studies .

Determining the presence of DU shrapnel is not as straightforward as verification of

the presence of internalized DU . The analysis is complicated because the penetration

of an armored vehicle by a DU penetrator generates DU fragments, non-DU

fragments, and fragments that are a mixture of DU and the other components of the

vehicle . In addition, the size of these fragments will vary dramatically . In the two

cases that have been studied so far, the fragment sizes ranged from just at the

resolution limit of film radiography (approximately 0 .5 mm) to 15 mm in diameter . Until

more experience is gained, a patient is assumed to have DU shrapnel if shrapnel is

detected radiographically and internalized DU is detected .

b . Special Study Group

A subset of the exposed group will be selected for inclusion in the special study

group . This group will receive the more intensive testing required to determine

uranium metabolism accurately, identify early signs of toxicity, monitor fragment

dissolution rates, and determine how the uranium is partitioned in the body as a

function of time . Evaluation of these variables will provide the information required to

construct the metabolic models needed to assess the risks associated with

internalized DU .

Criteria for selection include the presence of DU fragments in the body, uranium in

urine levels that exceed 14 μg/d (10 μg/l a) and the soldier's availability for the

intensive monitoring envisioned . Recognizing that participation in the special study

group will require a significant commitment, soldiers will be selected who are highly

motivated to participate and are located near testing facilities .

'All conversions were calculated based on an assumed urinary excretion rate of 1 .4 l/d.

3
c. Nonexposed Groups

The data from the exposed population will be compared with that from two

unexposed populations, which will serve as control groups for the study . The first

control group, patients with non-DU fragments, is needed to determine whether the

body's response to DU fragments differs from the body's foreign body normal

response to shrapnel . The second group, unwounded and nonexposed, is needed to

compare normal changes in kidney function with changes that might be due to the

presence of uranium . The need for the second control group is based upon the

assumption that non-DU fragments might cause changes in the parameters being

measured .

Members of the non-DU fragment control population (the first control population) will

be selected from veterans wounded in incidents not involving DU munitions . This will

eliminate the possibility of a control group member having a small undetected DU

fragment. Members of the unwounded and nonexposed control group will be

selected from any unwounded population that does not meet the criteria for inclusion

in the exposed population . In each case, groups will be appropriately matched (age,

sex, smoking habits, similar Desert Storm experiences, etc .) with the exposed

population .

d. Study Duration

At this point, it is difficult to determine the study duration, but the long latent

periods for some effects' require that the study last at least 5 years . The study could

extend for the lifetime of the members of the study groups .

3 . Program Management

The program management group will supervise the initiation and conduct of the

measurements, analysis, and documentation required by this project . The group will

exercise oversight of each phase of the study and will control its overall direction . The

group will consist of four representatives, at most, from the Department of Veterans

Affairs, the Department of the Army and/or the Armed Forces Radiobiology Research

Institute (AFRRI) . The group has the following responsibilities :

a. Fiscal Management

The group will establish yearly budgetary requirements and maintain the

records required to track the expenditure of funds during the fiscal year .

4
b. Patient Management

The group will identify the patients in each study group and establish

mechanisms for patient tracking .

c . Data Gathering

The group will serve as the central repository for the data gathered in all

phases of this study, including selecting the laboratories that will perform the required

tests and developing and supervising the quality assurance program for these

laboratories .

d. Data Analysis

The results of each required test will be submitted to this group for analysis and

study . This group will be responsible for calculating and documenting dose estimates

for each patient as well as determining if clinically significant changes had occurred .

e . Protocol Changes

The group will direct any changes required to meet the objectives of this study .

f . Treatment Recommendations

The group will be responsible for evaluating the data received to determine if an

alteration in treatment is required and will make its recommendations to the" attending

physician,

g . Research Recommendations

The group will make recommendations for further research based upon their

findings as appropriate .

h . Subject Matter Experts

To ensure the availability of the expertise required for this effort, the program

management group will be augmented by a panel of subject matter experts . This

panel will consist of physicians and scientists with expertise in radiation injury,

epidemiology, health physics, uranium toxicology, and the laboratory procedures

required by this protocol .

5
4. Patient Briefing

This briefing will be in sufficient detail to meet the requirements for informed-consent

for participation in a human research project . Since long-term patient participation is

key to the success of this study, it is recommended that this briefing be given by

someone who will be with the project for an extended period of time and who has

experience with this type of long-term study. This briefing will include a discussion of

a. the scope of the program and how the data will be used ;

b'. the tests and the frequency of testing, along with the risks entailed with

participation and non participation in the program ;

c . the benefits and requirements of participation in the U .S . Uranium Registry ;

d . procedures to follow for fragment removal . Standard medical guidelines

should be used for decisions concerning fragment removal .' Once the removal

decision is made, surgeons should use the procedures listed in paragraph 6 .d . below

for the removal of DU and non-DU fragments .

5. Protocol Test Requirements

a. Tests Required

(1) Table 1 outlines the required tests and test frequencies for each of the

study populations . The specifics for each of the tests are explained in paragraph 6 .

(2) The increased frequency of testing for soldiers with uranium

concentrations in their urine at levels greater than 14 μg/d (10 μg/I) of urine (see

Table 2) is based on the clinical need to monitor for signs of long-term kidney toxicity .

b. Modifications of the Test Protocol

(1) The program management group (see paragraph 3) will make

modifications to the protocol as a whole or for an individual patient based upon its

analysis of the results received . This re-evaluation should take place at least annually .

(2) The presence of symptoms in a patient (e .g ., indications of toxicity,

unusual growths, or other abnormalities) will trigger an immediate re-evaluation of the

required tests and their frequency, and the need for medical/surgical intervention .

s
Table 1 . Recommended Tests and Test Frequencies.

'Fecal samples will be performed whenever inhalation exposure is suspected . Control group fecal analysis will be

used to provide estimates of normal uranium levels in feces .

2 Tissue analysis will be performed on tissue samples taken as a result of a fragment removal procedure for both DU

and non-DU fragments.

"Repeat after fragment removal or as required by the program management group.

4 Radiographs are only required for personnel with imbedded fragments . This is not required for exposed or control

group patients who do not have fragments . 6. Test Specifications

This section describes the purpose and specifications for each of the tests required in

the protocol . The specifications are designed to provide minimum test standards

required to meet the objectives of the protocol . Selection of the laboratories where

these tests are done will be made by the program management group based upon the

guidance in this section and an assessment of the site's capabilities . The laboratories

must meet the quality assurance requirements in paragraph 7 below . It is highly

recommended that the same laboratory be used for each test whenever possible .

References 2 and 3 contain a partial listing of commercial and government

_laboratories with the capability for whole-body counting and for radiobioassay . While

DoD laboratories are not specifically listed, the Army (U .S . Army Environmental

Hygiene Agency) and the Air Force (Armstrong Laboratory) have the technology

required to perform some of the radiobioassay procedures listed .

7

TEST

Exposed Population

Urinary Excretion Special Study

Group

Control

<14 μg/d Groupsa14 μg/d

Uranium in Urine Annually Table 2 Twice Weekly Annually

Urine Chemistry Annually Table 2 Table 2 Annually

Uranium in Feces' As Needed As Needed

Tissue Analysis 2 As Needed As Needed As Needed As Needed

Whole Body and

Regional Counting-' Initially Initially Biennially Initially

Uranium in the Skeleton

Annually Annually

Uranium in Blood Quarterly Annually

Blood Chemistry Annually Table 2 Table 2 Annually

Clinical Evaluation Annually Annually Quarterly Annually

Diagnostic Imaging' Annually Annually Annually Annually
Table 2. Test Frequency for Selected Tests as a Function of Initial Urine Uranium Concentration .

Tests include uranium in urine, urine chemistry, and blood chemistry.

a . Uranium Concentration in Urine

(1) Purpose . This test will provide a direct determination of the uranium

excretion rate which will be used for metabolic model construction and risk

assessment.

(2) Specifications

(a) While a 24-hour urine sample is desirable, timed urine samples are

acceptable . For 24-hour urine samples, it is important that all voids be collected . For

timed urine samples, accurate accounting of the time period is a requirement and time

periods of not less than 12 hours are recommended .

(b) Urine samples must be processed in a laboratory where the uranium

measurement methods have a minimum detection limit of 0 .4 μg of uranium per liter of

urine or better . The laboratory must meet the quality assurance requirements listed in

paragraph 7.

(c) Detailed sample collection and preservation procedures will be

established by the laboratory performing the analysis .

(d) The nonexposed group will provide urine samples that will be used

to establish background urinary excretion levels for uranium .

8

Uranium Excretion Rate in

Urine (μg/d) Test Frequency Remarks

14-50 Quarterly

50-250 Monthly Potential for the onset of

kidney toxicity .

> 250 At Least Weekly Potential for kidney

toxicity
b. Urine Chemistry

(1) Purpose . The primary purpose of this test is to monitor the urine for

signs of kidney toxicity or other abnormal changes in kidney function .

(2) Specifications . Urine chemistry to include a quantitative analysis of

gamma-glutamyltransferase, beta-2-microglobulinuria, protein, amino acids, creatinine,

phosphorus, and urinalysis (specific gravity, albumin, glucose, and microscopic

sediment analysis) is required . Serum creatinine and creatinine clearance studies are

needed to assess glomerular function and tubular integrity . It should be noted that

these tests might underestimate filtration rate if tubular injury is present.

c. Uranium in Feces

(1) Purpose . This test is designed to give an indirect assessment of the

uranium content in the lung and to assist in establishing lung clearance rates for

metabolic modeling . This test should be administered only if significant lung

contamination is suspected .

(2) Specifications . The specifications for fecal samples will be determined

based upon the requirements for each test . As a general rule, the minimum detection

limits for laboratories should be less than 3 μg of uranium per sample (less than 1 pCi

per sample) . Preservation and shipment requirements will be determined by the

laboratory doing the analysis .

d . Tissue Analysis

(1) Purpose . This series of tests will be performed on tissues removed from

a patient as a result of the patient's decision to have a fragment removed . The

purpose of these examinations will be to determine

(a) the uranium content of the tissue (information will be useful in both

metabolic modelling and risk assessment) and

(b) whether significant changes have occurred in the tissues surrounding

the fragment. Thorotrast data indicate that long-term exposure to low-dose-rate alpha

emitters can cause tissue fibrosis and necrosis with latent periods in excess of 5

years.'

(2) Specifications

(a) Surgical Removal of the Fragment . In addition to standard

procedures, the following steps should be accomplished .

9
- Photograph the procedure . Of particular interest is evidence of

total or partial fibrotic encapsulation ; local tissue necrosis ; growing granuloma ; or if

there is evidence of a breakdown, a formed fibrotic capsule .

- If the fragment is encapsulated, remove and save the intact

capsule (with the fragment still inside) if possible . If the fragment must be removed

from the capsule or if the capsule breaks during removal, document the capsular fluid

appearance and volume . The capsule, capsular fluid, and any other tissue removed

should be saved for histopathology and radioassay. Take careful note of the physical

characteristics of the fragment upon removal . Specifics include color, shape, and any

evidence that the fragment is breaking up . Color photographs of the fragment with a

means of measuring its size are desirable . Seal the fragment in a plastic bag .

Contact the program management group for instructions concerning the disposition of

the fragment .

(b) Histopathology . The objective of this series of experiments is to

determine if there are any unusual changes in cell structure of the surrounding tissue .

(c) Uranium in Tissue and Fluids . The uranium in retained tissue or

fluids should be determined using techniques with the capability of detecting uranium

levels on the order of 0 .2 μg (0 .06) pCi per tissue sample submitted . It should be

noted that there are ultrasensitive fission-track counting techniques that can be used

to detect 10-14 grams of uranium . At this level, the same tissue samples could be

used for both histopathology and uranium concentration determinations .

(d) Sample Preservation Techniques . The sample preservation

techniques used will depend upon which of the two procedures will be performed . At

this point, it is uncertain if the same tissue sample can be used for both uranium

concentration and histopathologic procedures . Once notified that a fragment will be

removed, the program management group will decide which of the two procedures will

be performed .

e. Whole-Body Counting, Regional-Area Counting, and Skeletal Uranium

Determination

(1) Purpose . The combination of whole-body and regional-area counting

allows for the quantification of the total amount of uranium in the body and the

amounts of uranium in key locations in the body, using external measurement

techniques . This information will be used in conjunction with urine and feces uranium

contents to determine the metabolic models for uranium retention . The in vivo skeletal

counting is an attempt to track uranium deposition in the skeletal system .

1 0
(2) Specifications

(a) The systems used must be capable of performing both whole-body

and regional-area counting of uranium . Current systems can provide minimum

detectable activitiesb (MDA) for regional-area counting of the lung on the order of at

least 2 nCi (6 mg of DU) of DU in the lung by measuring the

234

Th progeny of

238 U . 3

(b) Regional-area counting is required for the lungs, kidneys, liver, all

wound or burn sites (regardless of how minor the wound), and of all areas with

suspected DU fragments .

(c) Radiographs will be used to determine fragment location(s) so that

estimates of tissue absorption and self absorption corrections for each of the areas

counted .

(d) The in vivo skeletal-counting systems used should have an MDA of

10 nCi (30 mg) with adequate procedures for discriminating sources originating in the

bone from those originating in the remainder of the body . The skeletal counting

system developed at New York University is a good example of an acceptable

skeletal-counting system . 3

f . Uranium Concentration in the Blood

(1) Purpose . The test will measure the concentration of uranium in the

blood by measuring the uranium concentration in the serum and cellular components

of the blood .

(2) Specifications . Typical minimum detection limits for systems designed to

measure the uranium content of the blood are on the order of 1 nano-gram of uranium

per ml of blood . The laboratory selected to perform this test should have comparable

efficiencies .

g . Blood Chemistry Evaluation

(1) Purpose . These tests are aimed at determining whether or not heavy

metal toxicity and/or bone-marrow suppression has occurred .

(2) Specifications . SMA -12/20 or equivalent with complete blood count with

differentials and platelet count .

"The referenced work defined MDA as 4 .65a where a is the standard deviation of the background

count .

1 1
h . Clinical Evaluation

(1) Purpose . Clinical evaluation will determine the presence of any

abnormalities such as nodules or unknown growths in the vicinity of fragmentation

wounds or a degradation in the viability of the tissues . Reference 1 contains a

discussion of potential abnormalities and estimates of the latent periods associated

with each.

(2) Specifications . Emphasis will be placed on organ/structure dysfunction

related to the location of the fragment(s) and to the consequences of the potential

radiological and chemical effects . Specific tests are determined by the location of the

fragment(s) . Particular attention will be given to detecting thorotrastoma-like growths

at the site of fragment implantation . A thorotrastoma is a growth that appears at the

sites of extravascular Thorotrast with a latent period of 5-35 years post injection

.

4-" In

some instances, these granulomas grew to enveloped clinically significant blood

vessels and nerves and, in some cases, proved fatal .

i . Diagnostic Imaging

(1) Purpose

(a) Determine the composition of the fragments in an attempt to

differentiate between solid DU and aluminum DU mixtures .

(b) Determine the approximate size and anatomic location of the

fragment(s) in the body with sufficient detail to make absorption and self absorption

corrections for whole-body counting data .

(c) Detect or confirm the presence of the formation of the fibrous

encapsulation or of a thorotrastoma-like growth .

(d) Determine if there have been any gross changes in the location or

size of the fragment .

(2) Specifications

(a) Both magnetic resonance imaging (MRI) and radiographic imaging

are required for patients with imbedded fragments . MRI will be used to detect soft

tissue abnormalities (granulomas, thorotrastomas) in the tissues surrounding

imbedded fragments . MRI will only be performed after determining that there are no

ferromagnetic fragments or objects in the patient .

1 2
(b) Radiographic imaging will be used to determine the size and position

of imbedded fragments with sufficient accuracy to detect changes in the location of the

fragment and to make the tissue absorption and self-shielding corrections required for

whole-body counting . It is anticipated that at least two projections will be required .

7. Quality Assurance

The long-term nature of this protocol mandates the implementation of a stringent

quality assurance program to ensure the accuracy and precision of the data collected .

The program management group will develop the details of the quality assurance

program . The program must incorporate the following provisions :

a. The use of accredited laboratories when possible . The laboratory

performing each of these tests must be accredited by an appropriate accrediting

agency to perform the required test . The laboratory must have a viable quality

assurance program that is in accordance with the guidance provided in References 9

and 10 . The program management group will establish standards based upon the

guidance in this protocol when such accreditation is not available .

b . The use of the same laboratory to perform each type of test when possible .

Adoption of this strategy will ensure the consistency of the data and enhance the

program management group's ability to monitor the quality of the data collected .

When the same laboratory cannot be used, the program management group must

develop procedures to ensure the comparability of the data generated .

c. The use of intercomparisons by the specific laboratories chosen . The

quality assurance program must include either a program of intercomparisons with

other laboratories or, ideally, comparisons with a national standard .

Standard records management quality control procedures will be implemented to

ensure the accuracy of the records maintained by the program management group .

1 3
Glossary of Terms

Exposed population. There are two criteria for including a soldier in the exposed

group . First, the soldier must have been in or on the vehicle when the vehicle

was struck by DU munitions . Second, the soldier must have internalized DU at

levels that are high enough to cause the uranium in the urine either to exceed

background levels of uranium excretion by a factor of four or to be detected by

whole-body or partial-body counting . Uranium in urine measurements from the

control group will establish the background levels for these two measurements .

Nonexposed population .

The nonexposed population is composed of two

subgroups : The first subgroup includes those soldiers with fragment wounds that

are known not to be DU . The second consists of those soldiers who were

not wounded and do not have internalized DU . DU is considered not to be present

in significant amounts if the uranium concentrations in the urine are less than four

times the background level and the results of whole-body or partial-body counting

are negative .

Minimum detectable amount (MDA) . The smallest amount of a substance that can be

detected with a probability p of nondetection (Type II error) while accepting a

probability a of erroneously deciding that a positive (non-zero) quantity is

present in an appropriate blank sample (Type I error) . 9 For this protocol both a

and R are set at 0 .05.

Program management group . A multi-disciplinary team that will oversee the

implementation of the protocol and evaluate the results and direct changes in the

protocol as required .

Radiobioassay procedure . For the purposes of this protocol, a radiobioassay

procedure is any procedure used to measure the uranium in the body (wholebody counting) or in biologic material excreted or removed from the body for the

purposes of estimating the uranium content in the body . 9

Special study group . A subset of the exposed group that will receive the more

intensive testing required to accurately determine uranium metabolism, to

identify early signs of toxicity, to monitor fragment dissolution rates, and to

determine how the uranium is partitioned in the body as a function of time .

1 4
Thorotrastoma. A large growth that appeared at the sites of extravascular thorotrast in

patients injected with thorotrast, a thorium containing radiographic contrast agent .

The growth appeared with a latent period of 5-35 years postinjection . These

granulomas grew to large sizes and some enveloped clinically significant blood

vessels and nerves and, in some cases, proved fatal . Thorotrastomas are

discussed in the references .

1 5
References

1 .

Daxon, E . and J . Musk, Assessment of the risks from imbedded

depleted uranium fragments . Armed Forces Radiobiology Research

Institute Technical Report, AFRRI TR 93-1, March 1993 .

2 .Boecker, B ., R . Hall, K. Inn, et . al ., Current status of

bioassay procedures to detect and quantify previous exposures to

radioactive materials . Health Phys . 60 :45-109 ; 1991 .

3 .

Toohey, R ., E . Palmer, L. Anderson, et . al ., Current status

of whole-body counting as a means to detect and quantify previous

exposures to radioactive materials . Health Phys . 60 :7-42 ; 1991 .

4 . Dahlgren, S ., Effects of locally deposited colloidal thorium dioxide . 786-790, in

Distribution, Retention, and Late Effects of Thorium Dioxide, R. Swarm, Ed .,

Ann . N .Y . Acad . Sci ., 145 (December 1967) .

5 .da Silva Horta, J ., Effects of colloidal thorium dioxide extravasates in the

subcutaneous tissues of the cervical region in man . 776-785, in Distribution,

Retention, and Late Effects of Thorium Dioxide, R . Swarm, Ed ., Ann . N .Y .

Acad . Sci ., 145 (December 1967) .

6. van Kaick, G ., D. Lorenz, H . Muth, and A . Kaul, Malignancies in German

Thorotrast patients and estimated tissue dose . Health Phys . 35 :127-136 ;

July 1978 .

7. Stover, B, Effects of Thorotrast in humans. Health Phys . 44 (SUP 1) :253-257 ;

1983.

8. Graham, S., R . Heaton, D . Garvin, and J . Cotelingham, Whole-body analysis

of a patient with Thorotrast-induced myelodysplasia . Health Phys. 63:20-26;

1992.

9.Draft American National Standard for Performance Criteria for

Radiobioassay, Report ANSI-N13 .30 . January 1993 .

10 .

Draft American National Standard for Measurement Quality Assurance for

Radioassay Laboratories, Report ANSI-N42 .2, August 1992 .

1 6
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