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01397
Hobson, Lawrence B.

Corporate Author
Report/Article Title Human Effects of TCDD Exposure

Bulletin of Environmental Contamination and Toxicology

Year

1984

Month/Day
Color

LI

Number of Images

4

Descripton Notes

Thursday, May 03, 2001

Page 1397 of 1403

�Bull. Environ. Contam. Toxicol. (1984) 33:696-701

»Environmental
I Contamination
land Toxicology

Human Effects of TCDD Exposure
Lawrence B. Hobson
Agent Orange Projects Office, Veterans Administration Central Office (10A7),
810 Vermont Ave., N.W., Washington, D.C. 20420
The Vietnam situation and the exposure of servicemen to the herbicide Agent Orange presented the Veterans Administration with a
series of problems and questions that the agency had not encountered
before. Since about 1978, the VA has undertaken a variety of programs prompted by the Vietnam conflict and herbicide exposure.
Beyond the VA's programs, a number of related efforts are going on in
the world about which one will want to know. Most of them have not
been completed. We shall review them very briefly, but first there
are certain differences among these various studies of which one
must be cognizant.
In the first place, it is literally impossible to determine quantitatively the extent of herbicide-realted exposure in any human study
that is being conducted at present.
Tt sometimes is possible to
divide a population Into groups with a high likelihood exposure, a
low likelihood, and occasionally into even slightly finer divisions,
but these divisions are not truly quantitative. The VA, therefore,
Is conducting a number of studies to determine the effects of the
military experience in Vietnam partly on the assumption that military experience in Vietnam entailed exposure to Agent Orange which
contained on the average about 2 parts per million of TCDD.
Other studies being undertaken, particularly by the Centers for Disease Control, will attempt to determine exposure to Agent Orange in
the field. We do not know whether it is possible to do that, but it
will be attempted in most of the studies that deal with the Vietnam
experience.
One must distinguish clearly between any attempt to
study the effects of exposure to Agent Orange, and therefore TCDD,
and an investigation to evaluate the effects of the military experience as a whole. Tn fact, it is possible to define only one population where we are certain of exposure to Agent Orange. That population is the Ranch Hand group being studied by the Air Force.
When we want to examine the results of exposure to TCDD apart from
the other Ingredients In Agent Orange, we have to go to Industrial
situations where TCDD has been generated In an Industrial process

696

�and Is delivered, If not In pure form, at least In a fairly high
concentration to that population. The VA has no such population
available to it, but they are present around the world.
The Congress at the present time Is considering compensation of
veterans for certain conditions. I shall not discuss questions of
compensation that are the responsibility of an entirely different
subdivision of the VA. When such legislation is being considered,
however, we are expected to advise Congress on what compensation
should be established on "presumptive bases" without definite knowledge that exposure occurred or that any particular defect is due to
exposure to Agent Orange.
For a scientist, this Is an unsatisfactory situation. We have tried
to convince Congress and others that it is important to come to some
medical and scientific consensus as to whether exposure results in a
particular effect before Congress considers compensation for it. As
T am sure you know, there is no clear-cut way to arrive at a medical
consensus even though a number of techniques have been tried.
Basically, they all require that sufficient numbers of statistically
significant and relevant data are available, that these data and the
methods of obtaining them withstand peer review, and finally, that
the results are duplicated. We do not want universal agreement. We
are seeking only a consensus In the medical and scientific community
that these effects can be attributed to TCOD, or to Agent Orange, In
our Instance.
The veterans themselves have reported a wide variety of effects.
Many have recounted symptoms that occurred in Vietnam and, therefore, were presumably acute. In general, the acute effects they
report, as well as the acute effects from other toxic agents, are
more or less generalized:
malaise, headache, nausea, sometimes
diarrhea, or respiratory responses if it is an inhaled toxin. All of
these have been reported by veterans. Tt Is impossible for us to
verify them now since they occurred more than 10 years ago. Some
veterans complain of neurological problems. Some suggest that they
have had liver problems as well.
Other reported reactions have not been discussed in this conference,
but ought to be mentioned, namely, the reproductive effects. Some
veterans have complained of sterility and Impotence as well as miscarriages, abortions and birth defects, some of which occurred to
their wives shortly after their husbands came back from Vietnam;
they might be considered acute effects. More commonly, however, the
veterans complain of chronic effects that have persisted from the
time they left Vietnam. These also have varied. Leading the list a
few months ago were probably birth defects and miscarriages. The
complaints are less frequent now, In part because of some research
results that are being reported.
The possibility of the development of cancers, including soft tissue
sarcomas, Is very much on the minds of the veterans. Many are afraid

697

�that their lives are going to be shortened, that they will have a
shorter life expectancy than they would otherwise.
There have been complaints and still are complaints of chloracne, a
skin eruption, none of which has been verified as being present at
the time of examination. Some veterans complain of porphyria cutanea tarda, either at present or during the time since they left
Vietnam. Some have complained simply that they have dtoxin in their
tissues and it presents a threat to their future health. It has been
said by some people, Including at least one from St. Louts, that this
constitutes a time bomb, that if they ever lose weight the dioxln
will be released in the body and intoxicate them.
We are dealing here with questions of toxiclty which have not been
common in the past. Veterans are complaining of delayed toxic
effects, where the individual has had no symptomatology, nothing
wrong, for 10, 15 or even 20 years after exposure and then suddenly
develops difficulties.
Interest in the delayed effects centers primarily on birth defects
and cancer. A number of studies completed and underway at present
are attempting to define any possible risk of birth defects or reproductive failures. Four studies have been completed, including one
reported this year in Australia and one conducted in Arkansas for the
EPA. One was done in Arkansas by EPA. The Australian study Is a
Vietnam experience study of veterans. They did not evaluate the
exposure to Agent Orange or to TCDD. A New Zealand applicator study,
a the National Institute of Occupational Safety and Health study In
New York and the Arkansas study all deal with exposure to herbicides,
primarily 2,4,5-T, which probably contains TCDD. All of the completed studies found no increased risk of reproductive failure.
Prior to the completion of those studies, two others were Initiated.
One is being conducted by the Centers for Disease Control (CDC) with
support from the VA and the Department of Defense. It Is expected to
be completed next year. The .other Is the Air Force's Ranch Hand
study which will also be reported early in the coming year. The
latter is looking for reproductive effects In their population of
Ranch Banders who are known to have been exposed to Agent Orange.
The CDC study is a Vietnam experience study but an attempt will be
made to determine exposure to Agent Orange and, therefore, to TCDD.
One of the major problems is that of soft tissue sarcomas. Every
study that has been done on herbicides and soft tissue sarcomas and
every study that is In progress is open to question on epidemiological grounds. None is methodologically clean and I know of no way to
make them so. We are going to be faced with the results in a number
of studies, all of which leave questions unanswered.
A group of Swedish studies began In 1978 with the chance observation
that soft tissue sarcomas were occurring among forestry workers who

698

�were exposed to herbicides. These studies deal with herbicides as do
the others in New Zealand and Finland.
Some American industrial studies are a separate group. They have
been mentioned already and I shall not review them In great detail.
A total of seven cases of soft tissue sarcomas was reported among
chemical workers In the United States. This caused great concern but
reexamination of the cases has shown that only two workers had softtissue sarcomas and also had documented exposure to TCDD.
T can give what was reported to be the anticipated number of soft
tissue sarcomas among the exposed population. T must qualify this in
that the exact count of the exposed population has not been reported
and so the number of expected cases Is tentative.
Tt is estimated
that only 0.07 cases of sarcoma would have been anticipated and two
were found. One can juggle numbers, and this Is done very often, but
T never have treated seven-hundredths of a case of any disease. T
either had one case or T did not. The evidence is a little stronger
if you have two cases, but clinicians know that two cases of a rare
disease can appear within a short time even in the same location.
So it is unclear what those industrial studies mean, although they do
tend to lend support to the Swedish studies that claim an association
of the sarcomas with herbicide use. There is certainly no consensus
now on the relationship of exposure to herbicides or TCDD and the
appearance of soft-tissue sarcomas. Some other studies have been
reported In industrial settings apart from those in the U.S. They
have not indicated any relationship between the two experiences.
One study that has been completed In Midland, Michigan. There was an
increased incidence of soft tissue sarcomas among women in that
community, but the men showed no Increase. The rate among women was
less than the rate among women In other Michigan counties where there
was no industrial plant. Midland is the home of two chemical companies, both of which made herbicides. No employment history of
either the patients or their spouses and no geogrpahic location
within the city could be correlated with the sarcoma cases. So what
It means Is an open question.
Other studies include a New York State study that has been completed. Like the National Cancer Institute studies, it is concerned
with exposure to herbicides rather than to pure chemicals.
The VA is undertaking a study which has also been mentioned already.
The Armed Forces Institute of Pathology has the largest collection
of soft tissue sarcomas In this country and probably in the world.
All of the tumors will be reexamlned and diagnosed by the same team,
Including Dr. P.M. Enzlnger, generally considered the world's best
qualified pathologist to characterize these sarcomas. The research
will be a case/control study and Is expected to be completed in 1985.

699

�The National Institute of Occupational Safety and Health has created
a registry of Industrial workers exposed to TCDD and will use It for
a case/control study. A similar but International registry Is being
compiled at present, and It also will be examined for possible causal
factors of soft tissue sarcomas.
The CDC study that Is concerned with the effects of exposure to Agent
Orange In Vietnam will Include an evaluation of the effects of the
Vietnam experience. Tt Incorporates as well a study of the soft
tissue sarcomas In the civilian population, which now Includes
Vietnam veterans.
Tn addition to soft tissue sarcomas, several other forms of cancer
have been reported to be associated with herbicides or TCDD.
The
studies, In general, have shown very disparate malignancies with no
increased prevalence of malignancies as a whole In the various
exposed populations. Many studies will extend Into the future as the
population Is followed. Individuals exposed In Vietnam and during
the Vietnam era are now 10 to 15 years past their exposure and are
entering the period when we would expect most of the solid malignancies to appear If they were due to exposure at that time.
Mortality studies are being conducted around this country and the
world to determine whether exposure to herbicides or TCDD shortens
life. A number of them have been completed. They have found no
Increased death rate. There was likewise no increased mortality
among Ranch Banders as a group. As Is usually true in studies of
industrial and military groups, the mortality rates were below those
anticipated because of the so-called "well worker effect." This is
particularly pronounced In the military studies where, at one point
at least, each Individual has had a careful health evaluation and has
been given medical care throughout the military career.
There Is no evidence of an Increased mortality rate among-veterans or
among industrial workers exposed to TCDD. A major New York State
mortality study is soon to be reported and a larger VA mortality
study Is underway. There are already reports of mortality rates
among industrially exposed groups in England and Europe as well as
the United States. The workers have been followed for two decades or
longer in some studies without more deaths than expected. Also In
the aggregate, they have not died from any single characteristic
cause.
As you can see, research up to the present has not established
definitely that phenoxy herbicides or TCDD cause any prolonged or
delayed toxic effects when exposure has been relatively slight. The
search for such effects has continued, however, and the answers to
our questions may emerge more clearly as the work continues.

700

�SUGGESTED READING
Australian Government Publishing Service (1983) Case-control study
of congenital anomalies and Vietnam service (Birth defects study).
Canberra, Australia.
Coggon D, Acheson ID (1982) Do phenoxy herbicides cause cancer in
man? Lancet 1:1057-1059.
Dolderup LM, Zellenrath D (1983) Dioxin exposure: 20 years followup. Lancet 1:1134-1135.
May G (1982) Tetrachlorodibenzo-dioxin: a survey ten years after
exposure. Br J Tndustr Med 39:128-135.
US Government Printing Office. Review of. literature on herbicides,
including phenoxy herbicides and associated dioxins, vols. I &amp;
IT. Washington DC (stock numbers 051-000-00154-1, 051-000-0001559.
)
Young AL, Calcagni JA, Thalken CT, Tremblay JW (1978) The toxicology, environmental fate and human risk of herbicide orange and
its associated dtoxins. OEHL TR=78-92. Naitonal Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161.
Received July 5, 1984; accepted September 2, 1984.

701

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                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
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                <text>Hobson, Lawrence B.</text>
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                <text>Human Effects of TCDD Exposure</text>
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                    <text>Item ID Number

°1566

Author

Hobson, Lawrence B.

Corporate Author

Veterans Administration

RBpOPt/ArtfClB TltlB Memorandum: from Clinical Assistant (102A) to Acting
Dir. Agent Orange Projects Office (10A7), with subject
Ranch Hand, Advisory Committee, September 28,1982.

Journal/Book Title
Year

000

°

MontD/Day

Color

n

Number of Images 2
Descrlpton Notes

Wednesday, May 23, 2001

Page 1567 of 1608

�Veterans
Administration
Date:

October 20, 1982

Memorandum
From:

Clinical Assistant (102A)

Acting Dir. Agent Orange
lo:

Projects Office (10A7)

Subj.

Ranch, Hand, Advisory Committee
September 28, 1982

1. On September 28, 1982, the Advisory Committee on Special Studies
Relating to the Possible Long-term Health Effects of Phenoxy
Herbicides and Contaminants (the Air Force Ranch Hand study) met at
NIEHS, Research Triangle Park, NC. The purpose was to review the
progress of the study.
2. Dr. J.A. Moore chaired the session with Drs. I. Selikoff,
R. Monson, A. Poland, G. Comstock, and N. Nelson, members in
attendance. Aside from Air Force personnel and me, the only
attendees were Maureen Corcoran and Margaret Warner, the latter a
lawyer from Carr, Jordan, Coyne, and Savits.
3. To date more than 1,000 participants have been examined with
only one serious complaint (nature unspecified). An attempt is
underway to obtain military records and private medical records for
all.
4. Serum (20+cc.) and urine (100 cc.) from each participant are
being retained at - 70°C. Selikoff suggested needle fat biopsies to
obtain 500 mg, of material for storage. This suggestion was
rejected, as it had been before, despite Poland's skeptical report
that Rappe claims measurement in tissue with less than 1 ppt. (less
than 0.1 nanagram) of TCDD. Nelson believes that even smaller
amounts (1 femtogram) can be measured by immunological techniques.
He suggested that red blood cells should be stored since hemoglobin
has proved to be an effective long-term adsorbant for a variety of
chemicals.
5. The morality study, as expected, is showing a death rate below
that for the U.S. population control and equal among Ranch Handers
and their Air Force controls. Analysis of causes of death is not
yet complete and, in any event, the numbers are very small, limiting
the significance of differences (all P's equal to or greater than
0.05).
6. Only 3 Ranch Handers have died from malignant neoplasms, less
than half the rate among controls; 5 died of gastrointestinal
diseases, more than twice the rate among controls. Three
participants are 5 year post-operative survivors of testicular
carinoma but the code has not been broken to determine whether they
are in the exposed or the control cohort.

�7. No chloracne has been observed. Selikoff said that 50 percent
(sic) of the the chemical workers at Nitro who had cloracne
initially still had it 30 years later and that this indicates severe
exposure; laborers who cleared a dump site at Jacksonville,
Arkansas, had no chloracne.
8. An attempt is being made to develop an exposure index for Agent
Orange. The Ranch Banders include individuals who were exposed to
320,000 to 1 million gallons of all herbicides a maximum to 100
gallons as a minimum.
9. Of 1,265 Ranch Banders, 22 were killed in action, 38 are dead of
other causes, and 1,205 were alive on December 31, 1981. The search
for these has resulted in 1,160 cooperative participants, 39 who
refused participation, and 6 who are still not located. The
corresponding numbers for controls are 1,149, 81, and 10. Of the
Ranch Banders it is anticipated that 90 percent will complete the
examination at best, 75 percent at worst; for controls the
percentages are 82 and 65. Lack of time and interest is the most
common reason given for refusal.
10. The immunology testing of a subset of 600 participants was
discussed at length. The Air Force has not included skin tests as
unreliable or dangerous; Selikoff believes that the decision should
be reconsidered.
11. Among laboratory tests, BDL is the least reliable, although BUN,
total and conjugated bilirabins are also poor,. Electrophoresis
studies are also variable but this was shown to be within the
accepted limits of general experience.
12. The study remains on schedules Mortality results will be
available in March, 1983; an interim report on morbidity in April to
June 1983* The next Committee meeting will be in March, 1983, to
consider the mortality data and perhaps the exposure index
determinations.

\ ••.&lt;.,*&lt;:&lt; ''O.
&amp;
LAWRENCE B. HOBSON, M.D.,

Ph.D.

�</text>
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                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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                <text>Hobson, Lawrence B.</text>
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          <element elementId="41">
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                <text>Memorandum: from Clinical Assistant (102A) to Acting Dir. Agent Orange Projects Office (10A7), with subject Ranch Hand, Advisory Committee, September 28, 1982.</text>
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              <elementText elementTextId="18373">
                <text>Air Force Health Study</text>
              </elementText>
              <elementText elementTextId="18374">
                <text>Ranch Hand crew</text>
              </elementText>
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                <text>VA</text>
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                <elementTextContainer>
                  <elementText elementTextId="63404">
                    <text>Item ID Number

°1618

Author

Hobson, Lawrence B.

Corporate Author
RODOrt/ArtlClO TltlB Memorandum: Request for Contract Negotiation with
Dr. Michael L. Gross for Dioxin Assays in Human Fat,
from Lawrence B. Hobson to Director, Supply Service,
January 30, 1979

Journal/Book Title
Year

000

°

Month/Day
Color
Number of Imauos

D

12

Doscrlpton Notes

Wednesday, June 06, 2001

Page 1619 of 1688

�January 30, 1979

Director, Supply Service (134C)
Deputy ACMD for Research and Development (ISA)
Request for Contract Negotiation with Dr. Michael L. Gross
for Dioxin Assays in Human Fat
1. Please negotiate a contract with Michael L. Gross, Ph.D.,
Professor of Chemistry, Department of Chemistry, University
of Nebraska, Lincoln, Nebraska, 68583. This is to cover 20
assays for dioxin content of human fat samples to be
submitted to him by the Veterans Administration.
Dr. Gross has agreed to conduct these assays for $525 per
sample for a total of $10,500.
2. The assay in question is a highly sensitive one detecting
parts per trillion of dioxin and as such it requires
specialized techniques and equipment. Dr. Gross is able to
conduct the assays for so low a sum because he is already
engaged in a series of determinations for the EPA. This
means that he does not have to assemble equipment, standardize
the method, and so on.
3. Attached are the answers to the required 20 questions and
the briefing slip. There is also included a Protocol for
submission with answers to the questions.

LAWRENCE B. HOBSON, M.D., Ph.D.

Attachments
CO •

•rla-7

AP*". 0 3 2
0.

�BRIEFING DOCUMENT

Contractor;

Contract:

Michael L. Gross, Ph.D.
Department of Chemistry
University of Nebraska
Lincoln, Nebraska 68588

Dioxin in Human Tissue; new contract.

R&amp;D Contact; Dr. Lawrence B. Hobson
Deputy ACMD for Research &amp; Development (ISA)
Purpose; This is a contract with an analytical chemist to
perform a series of scout assays comparing the dioxin content,
if any is detectible, in the abdominal wall fat of veterans
exposed to Agent Orange in Vietnam with the dioxin content,
if detectible, in the fat of veterans who were not in Vietnam
and had no known military exposure to Agent Orange.
History: Public pressure to detect dioxin and compensate
veterans for damage supposedly produced by defoliant agents
containing small amounts of the chemical has culminated in
claims that the material is retained indefinitely in human
fat. The quantities, if any material is retained, would be
extremely minute and the first question is whether they can
be detected. To answer this, the most sensitive available
assay will be used to examine fat from 20 veteran volunteers.
Ten (10) will have been exposed and usually will claim
continuing or late effects from the agent. Ten (10)
volunteer control patients who were not in Vietnam but are
matched by age, sex, and place of residence will have fat
removed at an operation done for medical reasons, e.g.,
appendectomy. The necessary operations will be performed in
VA medical centers.
Justification;
(1) Public pressure is the primary impetus for the
study. If dioxin can be detected only in veterans exposed
in Vietnam routine assays could be used as proof of exposure.
If somewhat more dioxin is found in exposed veterans a
larger series would be necessary to establish a significant
difference.
(2) Suspicion that the VA is biased against finding
dioxin only in veterans exposed to it in Vietnam led to a

• AP" C013

�decision to use a non-Federal analytical laboratory. Very
few chemists are now conducting dioxin assays by the
specialized chromatography-mass spectrography method arranged
to detect dioxin in parts per trillion.
(3) Dr. Michael L. Gross is currently assaying for
dioxin for the EPA and is recommended by that agency as the
best qualified analist. As a research contract, this one
does not require an'RFP. The figure of $525 per assay is
low since Dr. Gross already is performing the assays for EPA
and does not have to make separate standardizations, etc.
Costs and Schedules:
This is a new contract.

Current
FY
Costs

1979
$10,500

Future

Total

1980

1 year

0

$10,500

Comments; Should the results suggest a significant difference between veterans exposed to defoliants and the controls,
more cases will have to be studied. This would require an
extension of the contract with additional funding.

AP*"6G14

�Problem on Project
1. Dioxin in Human Tissue. The contract is for highly
sensitive assays of the dioxin content in abdominal wall fat
of veterans exposed to Agent Orange, a defoliant, in Vietnam
and, for comparison, in fat from veterans who were not in
Vietnam and had no known military exposure to Agent Orange.
2. It is not known whether dioxin persists in human fat
over a decade or more. Nor is it known whether it causes a
problem if it does.
3. Lack of knowledge as to the persistence of dioxin can
encourage continuing claims of damage from the chemical.
4.

Not relevant.

5. The dioxin assays are to be done on biopsy specimens
from veteran volunteers, 10 with exposure to Agent Orange
and 10 without known exposure. The biopsies will be performed
in VA medical centers to obtain the fat for assay. The assay
results are critical as the only data to be obtained.
6. The VA could probably conduct the assays. Veterans groups
charge, however, that the VA might bias the results and so a
non-Federal assay laboratory was sought. Dr. Michael L.
Gross, chemist at the University of Nebraska, was chosen over
other analists on recommendation of the EPA as having the
most sensitive, precise, and dependable assay.
7. Not relevant.
8. Results of the assays should disclose whether dioxin can
be detected in the fat of men exposed to Agent Orange and
whether it can also be detected in matched veterans who were
not. If the chemical is present only in the exposed veterans,
the test can be used to prove exposure. If there seems to
be more dioxin in exposed veterans but it occurs in both
groups, this scout experiment would have to be extended to
determine whether the difference is continuous and significant. If no dioxin is detected (in parts per trillion) it
would suggest that current claims for its persistence are
unfounded.

�Equipment and Skills
9.

Equipment lack is no problem.

10. Skills required are those of an organic analytic chemist
experienced in the specific assay for dioxin by the specialized gas-liquid-chromatograph-mass-spectrophotometric
technique for halogenated polycyclic compounds.
Personnel
11. For this scout experiment, qualified VA personnel would
not be suitable if available because of the public fear of
bias.
12. The surgeons who will biopsy the abdominal fat of exposed
veteran volunteers and the surgeons who remove a small
amount of fat from selected volunteers undergoing an
abdominal operation for other reasons, e.g., appendicitis,
are the only VA personnel directly involved in conducting the
trial. Minimal clerical time will be required for mailing
the 20 specimens.
13. The chemist is a full-time faculty member at the
University of Nebraska and the small number of assays would
not justify hiring him.
14. See question 6. Dr. Michael L. Gross, according to the
EPA, is best qualified and already is performing assays for
that agency. A considerable number of other organic chemists
could perform the assays but would require time and money to
"tool up" and standardize the procedure.
Firms
15. Not relevant.
Cost of Contract and Funds
16. &amp; 17. Estimated cost is $10,500 to be paid from Medical
Research funds.

�Attachments
18. "Tentative Protocol for Dioxin Content of Fat in Vietnam
and Non-Vietman Veterans."
19. ~

Automated Data Processing
20. Not relevant.

AP'~ CG17

�TENTATIVE PROTOCOL FOR DIOXIN CONTENT OF FAT
IN VIETNAM AND NON-VIETNAM VETERANS

PURPOSE;

To compare the dioxin content in abdominal wall fat of veterans

presumed to be exposed to Agent Orange in Vietnam with the dioxin content
in the fat of veterans who were not in Vietnam and had no known contact
with Agent Orange.
SUBJECTS: Initially, 10 men will be included in each of two groups:
(a) the experimental group composed of fonner servicemen who were in areas
of Vietnam within 6 months of defoliation by spraying with Agent Orange
and (b) the control group of former servicemen who never served in Vietnam
and who never had known contact with Agent Orange during their military
service.

Each subject in the experimental group will be matched with a

control subject who is resident in the same state, and who lives in the.
urban or rural environment, and who is within 5 years of his age. Each
experimental subject will have a biopsy of the abdominal Vail to obtain a
fat sample or the sample will be obtained at laparotomy for another purpose.
Each control subject will have a fat sample taken during laparotomy for a
medical indication.
SAMPLING TECHNIQUES: During the biopsy or at the start of laparotomy, the
surgeon will obtain a specimen of fat, weighing about 10 grams, from the
anterior abdominal wall.

This corresponds to a volume of about one cubic

inch. The specimen-may be obtained using local or general anesthesia and
there is no restriction on premedication or agents for induction.
The one substance that will interfere with the analysis for
dioxin and is likely to be encountered during surgery is hexachlorophene
(contained in Pre-op and Pre-op Plus Scrub Sponge [Davis &amp; Geek],
pHisoHex [Winthrop], Presulin Cleanser [Schieffelin], and Soy-Dome Cleanser
[Dome]).

Hexachlorophene should be avoided in surgical scrubs,

�pre-operative preparation, and Instrument sterilization prior to obtaining
the fat specimen..
The specimen should be placed in a test tube that has been rinsed
twice with reagent grade acetone and allowed to dry. The tube should
be closed with a cork also twice rinsed with acetone. These rinses renove
interfering compounds. Plastics are intrinsically contaminating and should
not be allowed to touch the specimen.
Each tube will be labeled with ( ) the patient's name and SSN,
1
(2) the hospital name, and (3) the date.
The test tube can be stored in a deep freeze until shipment.
It should be sent air freight in a shipping tube filled with dry ice to
Dr. Michael Lawrence Gross
Professor of Chemistry
Department of Chemistry
University of Nebraska
Lincoln, Nebraska 68588
The material should be shipped on a Monday so that delivery will not bo
attempted on the weekend.
INFORMATION SHEET; A separate Information Sheet will be completed on the
day of biopsy for each subject.

One copy should be mailed to

Another copy should be placed in the subject's medical record. The Sheet
will contain data for (1) identification of the subject, (2) location of
subject's residence, age, and occupation, (3) military exposure to Agent
Orange including place, duration, date, and nature of exposure, (A) known
exposure to chemical herbicides apart from military experience, including
name of herbicide, place, duration or frequency, date, and nature of

.'•••••

•

'

AP

-0019

�exposure, (5) symptoms or conditions (past or present) that patient
ascribes to Agent Orange, (6) current diagnosis or diagnoses, (7) operation
performed, (8) pre-operative medication, agents for induction, and
anesthetic used, (9) date, (10) informant.
INFORMED CONSENT; Each experimental subject and each control patient will
have the procedure and its purpose explained to him. He will then be asked
to sign the consent documents which will be placed in his medical record
prior to the biopsy.
DIOXIN • 'ASSAY: Dr. Gross will analyze an aliquot of each specimen for its
- ' " ' " " -••'•' /
dioxin content. Another aliquot will be analyzed if dioxin is found in
the first. Standards will be analyzed as necessary to assure accuracy and
precision.

L.B.Hobson

8/3/78

'

" • " ' • • -'

AP" 0 2
00

�TENTATIVE PROTOCOL FOR DIOXIN CONTENT OF FAT
IN VIETNAM AND NON-VIETNAM VETERANS

PURPOSE; To compare the dioxin content in abdominal wall fat of veterans
presumed to be exposed to Agent Orange in Vietnam with the dioxin content
in the fat of veterans who were not in Vietnam and had no known contact
with Agent Orange.
SUBJECTS; Initially, 10 men will be included in each of two groups:
(a) the experimental group composed of former servicemen who were in areas
of Vietnam within 6 months of defoliation by spraying with Agent Orange
and (b) the control group of former servicemen who never served in Vietnam
and who never had known contact with Agent Orange during their military
service.

Each subject in the experimental group will be matched with a

control subject who is resident in the same state, and who lives in the.
urban or rural environment, and who is within 5 years of his age. Each
experimental subject will have a biopsy of the abdominal vail to obtain a
fat sample or the sample will be obtained at laparotomy for another purpose.
Each control subject will have a fat sample taken during laparotomy for a
medical indication.
SAMPLIKR TECHNIQUES; During the biopsy or at the start of laparotomy, the
surgeon will obtain a specimen of fat, weighing about 10 grams, from the
anterior abdominal wall. This corresponds to a volume of about one cubic
inch.

The specimen1 may be obtained using local or general anesthesia and

there is no restriction on premedication or agents for induction.
The one substance that will interfere with the analysis for
dioxin and is likely to be encountered during surgery is hexachlorophene
(contained in Pre-op and Pre-op Plus Scrub Sponge [Davis &amp; Geek],
pHisoHex [Winthrop], Presulin Cleanser [Schieffelin], and Soy-Dome Cleanser
[Dome]).

Hexachlorophene should be avoided in surgical scrubs,

�pre-operative preparation, and instrument sterilization prior to obtaining
the fat specimen..
The specimen should be placed in a test tube that has been rinsed
twice with reagent grade acetone and allowed to dry. The tube should
be closed with a cork also twice rinsed with acetone. These rinses remove
interfering compounds.

Plastics are intrinsically contaminating and should

not be allowed to touch the specimen.
Each tube will be labeled with (1) the patient's name and SSN,
(2) the hospital name, and (3) the date.
The test tube can be stored in a deep freeze until shipment.
It should be sent air freight in a shipping tube filled with dry ice to
Dr. Michael Lawrence Gross
Professor of Chemistry
Department of Chemistry
University of Nebraska
Lincoln, Nebraska 68588
The material should be shipped on a Monday so that delivery will not be
attempted on the weekend.
INFORMATION SHEET; A separate Information Sheet will be completed on the
day of biopsy for each subject.

One copy should be mailed to

Another copy should be placed in the subject's medical record. The Sheet
will contain data for (1) identification of the subject, (2) location of
subject's residence, age, and occupation, (3) military exposure to Agent
Orange including place, duration, date, and nature of exposure, (A) known
exposure to chemical herbicides apart from military experience, including
name of herbicide, place, duration or frequency, date, and nature of

�exposure, (5) symptoms or conditions (past or present) that patient
ascribes to Agent Orange, (6) current diagnosis or diagnoses, (7) operation
performed, (8) pre-operative medication, agents for induction, and
anesthetic used, (9) date, (10) informant.
INFORMED CONSENTt

Each experimental subject and each control patient will

have the procedure and its purpose explained to him. He will then be asked
to sign the consent documents which will be placed in his medical record
prior to the biopsy.
DIOXIN ASSAY; Dr. Gross will analyze an aliquot of each specimen for its
dioxin content.

Another aliquot will be analyzed if dioxin is found in

the first. Standards will be analyzed as necessary to assure accuracy and
precision.

L.B.Hobson

8/3/78

�</text>
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            <element elementId="41">
              <name>Description</name>
              <description>An account of the resource</description>
              <elementTextContainer>
                <elementText elementTextId="49809">
                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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          <elementTextContainer>
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          <element elementId="39">
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            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="18810">
                <text>Hobson, Lawrence B.</text>
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          <element elementId="50">
            <name>Title</name>
            <description>A name given to the resource</description>
            <elementTextContainer>
              <elementText elementTextId="18813">
                <text>Memorandum: Request for Contract Negotiation with Dr. Michael L. Gross for Dioxin Assays in Human Fat, from Lawrence B. Hobson to Director, Supply Service, January 30, 1979</text>
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            <description>The topic of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="18815">
                <text>VA Dioxin Fat Assay Study</text>
              </elementText>
              <elementText elementTextId="18816">
                <text>study protocol</text>
              </elementText>
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                  <elementText elementTextId="63406">
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0162

Author

Hobson, Lawrence B.

4

Corporate Author
Memorandum: Work to be Performed by Dr. Gross on
Dioxin, from Lawrence B. Hobson to J.R. Ryan, April 6,
1979

Journal/Book Title
Year

000

°

Month/Day
Color

^

Number of Images

1

Descriptor! Notes

Wednesday, June 06, 2001

Page 1625 of 1688

�April 6, 1979
Mr. J. R. Ryan
Supply Service ( 3 C
14)
Deputy ACMD for Research and Development (15A)
Work to be performed by Dr. Gross on Dloxln
1. The contract with Dr. Gross of the University of Nebraska
should indicate that he will complete the quantitative analysis
for diozia on twenty specimens of human fat sent to him by
various representatives of the Veterans Administration and
should forward the results of the assays to Dr. Lyndon Lee,
Veterans Administration Medical Center, Washington, D.C.
2. I do not believe that we should attempt to characterize the
assay methods to be used by Dr. Gross since he is the outstanding
expert in this area and will be using his standard assay techniques.

LAURENCE B. HOBSON, M.D., Ph.D.

LBHobson:LL

ISA ,&gt;

4/6/79

�</text>
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            <element elementId="50">
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              <elementTextContainer>
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            </element>
            <element elementId="41">
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              <description>An account of the resource</description>
              <elementTextContainer>
                <elementText elementTextId="49809">
                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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            <description>The topic of the resource</description>
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              <elementText elementTextId="18850">
                <text>VA Dioxin Fat Assay Study</text>
              </elementText>
              <elementText elementTextId="18851">
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  </item>
  <item itemId="2658" public="1" featured="0">
    <fileContainer>
      <file fileId="1458">
        <src>https://www.nal.usda.gov/exhibits/speccoll/files/original/0998d73416f2ad3cdb61e5bbad12d9d8.pdf</src>
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01 628
Hobson, Lawrence B.

Corporate Author
ROpOrt/ArtlClB TltlO Memorandum: Dioxin Assay Contract with Michael
Gross, from Lawrence B. Hobson to J.R. Ryan, June
15, 1979

Journal/Book Title
Yoar

000

°

Month/Day
Color
Number of Images

D

6

DescNpton Notes

Wednesday, June 06, 2001

Page 1629 of 1688

�June 15, 1979
Mr. J. fc. Ryan (134C)
Deputy ACMD for Research and Development (ISA)
Dloxin Assay Contract with Michael Gross, Ph.D.

1. This contract will be paid by Medical Research Program Funds
1001-821-101-2580
3906.0(06
601101.1)
CP 102
In initiating the research on the level of dioxin in fat tissue
Dr. Michael Gross, University of Nebraska, was selected to do the
assays, using the most sensitive, analytic method available. He
agreed to do so and a contract was requested. In the meantime,
Dr. Lyndon Lee was authorized to solicit volunteers who would be
biopsied to obtain fat samples. These samples were sent to Dr. Gross
for subsequent assay.
2. The sensitive analysis used is best done on a large group of
samples rather than on individual samples as they are received.
Dr. Gross therefore said that when samples arrived he would hold
them all to be assayed at one time. He was not authorised to
proceed with the assay prior to the receipt and conclusion of the
contract.
3. My information is that when the contract documents arrived
Dr. Gross did not complete and return them immediately to us but
rather at some point in time while he had them in his possession
proceeded with some of the assays. This procedures was not specifically
authorized at any time nor were we informed that the contract had not
been completed and that he was proceeding with the assays. Under these
circumstances, it seems essential that we compensate Dr. Gross for the
work that he has done as well as for the work he will do in the future.

LAWRENCE B. HOBSON, M.D., Ph.D.

15A

LBHobsonrLL

6/15/79

�VETERANS ADMINISTRATION

REFERENCE SLIP
TO (Name or title-Hail muting symbol)

INITIALS-DATE

i.

Dr. Hobson

ISA

2.

3.

4.

5.

REASON FOR REFERENCE
£] AS REQUESTED

I_J FOR YOUR FILES

1

[_J INFORMATION

LJ PER CONVERSATION

LJ NECESSARY ACTION

|_J SIGNATURE

1 COMMENTS

|_J CONCURRENCE

1 1 NOTE AND RETURN

REMARKS

Subject: Authorization for Study
(Dioxin Assays in Human Fats - Agent Orange)
Mr. Ryan, Supply Service, 2577,
Rm. 754, informs us that the cost of the
proposal for the subject study to be
done by Michael Gross, Ph.D., Lincoln, Nebr.,
is $10,000.
What appropriation will be used?
Mr. Ryan needs a Form 2237.

TEU. SXT.

VA FORM
AUG 1976

EXISTING STOCKS OF VA FORM 3230,
OCT 19SS, WILL BE USED WU.S. Qo«rnm«n« PrlntllK Of*lM l»7»-2«»-*4f

�:• C£ c '' 1 E: e o- N-"

SOLICITATION, OFFER i *ND AWARD
1 CONTRACT lf*oc I*U lotfi! 1 NO

~',-.. Dt =fc\£F•.».;«- r ? : - R E : - • *

- ?- J-.'i SEC '

i C*OL

1

RATING

I 0-

' 18

! SOLICITATION NO

Q ADVERTISED ilfB

~ ISSUED ev

Veterans Administratel
Procurement Division
810 Vermont Avenue, N.If.
Washington, D.C. 204213

4/25/79

3 NEGOTIATED '**?&lt;

[

coot
(134C)

6 ADDRESS OFFER TO HI otter ihsn 6/oc* 7;

fn tonnnttt procuwwti o"»r *ntf "ottttot vtii ot comtiufo to m9tr&gt; O'd *r&gt;&lt;? (vow
SOLICITATION
9. -Seeled offers in original and

.'

Q

copies for furnishing the supplies or services in the Schedule win be received at the place specified in block 8. or

ifhtndcamed. in th, *,aos,,en, loema ,„ ':"

^

75

^_

2:0

° P'ny,. locH »m.

,.mii

5/16/79

If this Is &lt;n idvertiied toliciution, offers will be publicly opened «t that time.
CAUTION -LATE OFfERS: See pan. 7 and Sol Solicitation instructions *nd Condition!.
All offers ire lubjeci to the folio wing:
1. The Solicitation Inttructiom »nd Conditions, SF 33-A1— JL28__»_

3. The Schedule included herein and/or attached hereto.

edition which is attached or incorporated herein by reference.
2. The General Provisions. SF 39

4-75

4. Such other provisions, representations, certifications, and specifications

.rim™ which is

at are attached or incorporated herein by reference.

attached or incorporated herein by reference.

Mrtae/imencc art listed in tehtdule.l

rofiiNfOf&lt;UATiONCAi.LiNam&amp;Hinaontao.&gt;(NocoHKia/M*

J.R. Ryan

202-389-2577/2966

SCHEDULE
12. QUANTITY

13
UNIT

1

11 SUPPUES/SERVICES

to ITEM NO

Svc

Dioxin A»s«y&gt; in Human Fats

.

U UNIT MICE

IS AMOUNT

5ft co/mrXMlJOn of scfMtfu'* on tHO* *

OFFER (pages 2 ana 3 must il&amp;o be tally completed t&gt;y olttmr)
In compliance with the above, the undertiQned agrees, if this offer is accepted within ^
calendar days fo*0 C9ltndtr dmys vff/ecr « dUftrtnt pttiod is
inamd by the offtmtl from the date for receipt of offers specified above, to furnish any or all items upon which prices are offered at the price set opposite each
item, delivered at the designated point(s), within the time specified in the schedule.
l*i DISCOUNT FOfl MIOMPT PAYMENtTSM 0«r' 9. Sf &amp;•*!
«, 10 CALENDAR OAVS.
CODE [

17. OFFEROR
NAME AND

p

IM2IPCUHI [_
AREA CODE AND TE1

'

«• W CALENDAR DAYS.
1

% X CALENDAR OAVS.

CALENDAR DAYS

18 NAME AND TITLE OF PERSON AUTHORIZED TO SIGN OFFER
(Typf Of print 1

FACILITY CODE 1

Michael L. Gross, Ph.D.
Department of Chemistry
University of Nebraska
Lincoln, Nebraska 68588

1« SIGNATURE

20 OFt-ER DATE

n GftfC* it iwnmtna Mdrtu if tfi/ft r*nr from «60w — tmtr tuCH •dorvxi (ft Scrwuto
1

AWARD I To be completed by Qovernment)
21 ACCEPTED AS TO ITEMS NUMBERED

22 AMOUNT

25 NEGOTIATED
CUniUAMT TO

24 SUBMIT INVOICES 14 coptl unMIl orMnnw tptalKKtl
TO ADDRESS SHOWN IN ""-"-K

x

23 ACCOUNTING AND APPROPRIATION DATA

... . ...,.--

» AOMINlSTi RED BY

CODE

//r ori&gt;f r rfti

10 U.S.C 23WHI I
—

41USC2H.cn

1
1
0

27 PAYMENT WILL SC MADE BY

i.3
CODE

F

iscal Offic er
Veterans Ada Lnistratioa
810 Vermont &lt;ive., NH

» NAME OF CONTRACTING OFFICER 1 TIM or onnll

&gt;C 90i7n
29. UNITED STATES OF AMERICA

30 AWACIO DATE

BY
J&amp;
. .

RYAN

(Signature of contnclifig officer)
Awiro witt ot fn«o*e on f)ix torn Qr on Sttngtra form K. or OY ottttt oiticiti M" iff n rtocc*

33-131

Standard Form 33 Page 1 (REV 3-77)
PrMCrtbed by QSA, FPft (41 CFR) 1-16.101

AP "0027

�REPRESENTATIONS. CERTIFICATION'S AND ACKNOWLEDGMENTS
REPRESENTATIONS (Check or complete all applicable boxes or blocks.!
The offerer represents as part of his offer that:
1.
SMALL BUSINESS /See par. 14 on SF 33-A.I
He D is, D is not, a small business concern. If offerer is a small business concern »nd is not the manufacturer of the supplies offered.
h« also represents that all supplies to be furnished hereunder G will, O will not, be manufacturer^ or produced by * small business concern
in the United States, its possessions, or Puerto Rico.

2.

MINORITY BUSINESS. ENTERPRISE
He Q is. D is not, a minority business enterprise. A minority business enterprise is defined as a "business, at least'50 percent of which
is owned by minority group members or,in case of publicly owned businesses, at least 51 percent of the stock of which is owned by minority
group members." For the purpose of this definition, minority group members are Negroes, Spanish-speaking American persons,
American-Orientals, American-Indians, American Eskimos, and American-Aleuts.
3.

REGULAR DEALER - MANUFACTURER (Applicable only to supply contracts exceeding $10.000.)
He is a Q regular dealer in O manufacturer of, the supplies offered.

4.

CONTINGENT FEE (See par. IS on SF 33-A.I
..
.
(a) He O has, D has not, employed or retained any company or persons (other than a full-time bona fide employee working solely for
the offerer! to solicit or secure this contract, and (b) he Q has, O has not, paid or agreed to pay any company or person (other than a fulltime bona fide employee working solely for the offerorl any fee, commission, percentage, or brokerage fee contingent upon or resulting from
the award of this contract; and agrees to furnish information relating to (ai and (bl above, as requested by the Contracting Officer. (Interpretation of the representation, including the term "bont fide employee." see Code of Federal Regulations. Title 41, Subpart 1-1.5.1

6.

TYPE OF BUSINESS ORGANIZATION
He operates as Q an individual, Q a partnership, G a nonprofit organization, D a corporation, incorporated under the laws of the State

of.

6.

AFFILIATION AND IDENTIFYING DATA (Applicable only to advertised solicitations.I
Each offeror shall complete (a) and (b) if applicable, and (c) below:

(a) He Q is, D it not, owned or controlled by a parent company. /See par. 16 on SF 33-A.I
(b) If the offeror is owned or controlled by a parent company, he shall enter in the blocks below the name and main office address of
the parent company:

NAME Of PARENT COMPANY
AND MAIN OFFICE ADDRESS

(Cl EMPLOYERS IDENTIFICATION NUMBEHlSff MB itoaSfn-ti

OFfEflOflSt.l NO.

wr. COMPANY £./. MO.

7.

EQUAL OPPORTUNITY
(a) He O has, O has not, participated in a previous contract or subcontract subject either to the Equal Opportunity clause herein or
the clause originally contained in section 301 of Executive Order No. 10925, or the clause contained in Section 201 of Executive Order No.
11114; that he D has, D has not. filed all required compliance reports: and that representations indicating submission of required compliance
reports, signed by proposed subcontractors, will be obtained prior to subcontract awards. (The above representation need not be submitted in
connection with contracts or subcontracts which are exempt from the equal opportunity clause.)
(b| The bidder (or offeror) represents that (1) he O has developed and has on file, D has not developed and does not have on file, at
each establishment affirmative action programs as required by the rules and regulations of the Secretary of Labor (41 CFR 60-1 and 60-2) or
(2) he D has not previously had contracts subject to the written affirmative action programs requirement of the rules and regulations of the
Secretary bf Labor. (The above representation shall be completed by each bidder lor offerorl whose aid (offer! is $50.000 or more and who has
50 or more employees.)
Q

" ''CERTjFICATIQfjIS (Check ^co^eteaff applicable boxes of b/ocksl^

t u

.

^ ,,

^-

1.
BUY AMERICAN CERTIFICATE
The offeror certifies as part of his offer, that: each end product, except the end products listed below, is a domestic end product (as defined
in the clause entitled "Buy American Act"); and that components of unknown origin have been considered to have been mined, produced, or
manufactured outside the United States.
EXCLUDED CNO PRODUCTS

COUNTRY OF ORIGIN

Sundvd Form 33 Pag* 2 (REV. 3-771

AP~"0028

�2.

CLEAN AIR AND WATER (Applicable if the bid or offer exceeds $100.000 or the contracting officer has determined that orders
under ar, indefinite quantity contract in any year will exceed $100,000, or a facility to be used has been the subject of a conviction
under the Clean Air Act (42 U.S.C. 185?c8tcl(l)l or the Federal Water Pollution Control Act 133 U.S.C. 1319/cll and is listed by EPA.
or is not otherwise exempt.)
The bidder or offerer certifies as follows:
(a) Any facility to be utilized in the performance of this proposed contract O has, D has not, been listed on the Environmental
Protection Agency List of Violating Facilities.
(bl He will promptly notify the contracting officer, prior to award of the receipt of any communication from the Director. Office of
Federal Activities, Environmental Protection Agency, indicating that any facility which he proposes to use for the performance of the
contract is under consideration to be listed on the EPA list of Violating Facilities.
(c) He will include substantially this certification, including this paragraph (cl. in every nonexempt subcontract.

3.

CERTIFICATION OF INDEPENDENT PRICE DETERMINATION (Seepar. 18on SF 33-AI
(a) By submission of this offer, the offerer certifies, and in the case of a joint offer, each party thereto certifies as to its own
organization, that in connection with this procurement:
(1) The prices in this offer have been arrived at independently, without consultation, communication, or agreement, for the
purpose of restricting competition, as to any matter relating to such prices with any other offeror or with any competitor;
(2) Unless otherwise required by law, the prices which have been quoted in this offer have not been knowingly disclosed by the
offeror and will not knowingly be disclosed by the offeror prior to opening in the case of an advertised procurement or prior to award in the
case of a negotiated procurement, directly or indirectly to any other offeror or to any competitor; and
(3) No attempt has been made or will be made by the offeror to induce any other person or firm to submit or not to submit an
offer for that purpose of restricting competition.
&lt;b| Each person signing this offer certifies that:
(1) He is the person in the offerer's organization responsible within that organization for the decision as to the prices being
offered herein and that he has not participated, and will not participate, in any action contrary to (aid) through (a)(3). above; or
(2) (i) He is not the person in the offerer's organization responsible within that organization for the decision as to the prices
being offered herein but that he has been authorized in writing to act as agent for the persons responsible for such decision in certifying that
such persons have not participated and will not participate, in any action contrary to (aid) through (a)(3) above, and as their agent does
hereby to certify; and (ii) he has not participated, and will not participate, in any action contrary to &lt;a)(1) through (a)(3) above.

4.

CERTIFICATION OF NONSEGREGATED FACILITIES (Applicable to III contracts, (2) subcontracts, md (31 agreements with
applicants who are themselves performing federally assisted construction contracts, exceeding SW.OOO which are not exempt from the
provisions of the Equal Opportunity clause./
By the submission of this bid, the bidder, offeror, applicant, or subcontractor certifies that he does not maintain or provide for his
employees any segregated facilities at any of hit establishments, and that he does not permit his employees to perform their services at any
location under his control, where segregated facilities are maintained. He certifies further that he will not maintain or provide for his employees any segregated facilities at any of his establishments, and that he will not permit his employees to perform their services at any location,
under his control, where segregated facilities are maintained. The bidder, offeror, applicant, or subcontractor agrees that a breach of this certification it a violation of the Equal Opportunity clause in this contract. As used in this certification, the term "segregated facilities" means
•ny waiting rooms, work areas, rest rooms and wash rooms, restaurants and other eating areas, time clocks, locker rooms and other storage or
dressing areas, parking lots, drinking fountains, recreation or entertainment.areas, transportation, and housing facilities provided for
employees which are segregated by explicit directive or are in fact segregated on the basis of race, color, religion or national origin, because
of habit, local custom, or otherwise. He further agrees that (except where he has obtained identical certifications from proposed
subcontractors for specific time periods) he will obtain identical certifications from proposed subcontractors prior to the award of
subcontracts exceeding $10,00d which are not exempt from'the provisions'of the Equal. Opportunity clause; that he will retain such
certifications. In his files; and that he will forward .the'following notice to such proposed subcontractors (except where the proposed
subcontractors have submitted identical certifications for specific time periods!:"""
. .
. . .
' • Notice to prospective subcontractor* of requirement for certif icationj of nonsegregated f»cilitie«. '•'•

' - ' •• ' ; '.-'

. * Certification of Nonsegregated Facilities mutt be submitted prior'to the award of a subcontract exceeding $10,000 which is not
exempt from the provisions of the Equal Opportunity clause. The certification may be submitted either for each subcontract or for all
subcontracts during a period (if.,-quarterly; semiannually,-or annually). NOTE: The penalty for making false often is prescribed in 18
U.&amp;C1001.
=.,,. . . , . . . „ " . . , . - . - . ' . - ...-.1,.,..,1 ...
' r ...,..". : " :
•
''
•^

AMENDMENT NO

ACKNOWLEDGMENT OF AMENDMENTS
Tht olltior Kknowltdgn rtcupt 01 .amend- .
m«ni lo tht Solicitation &lt;or offers and rilattd
documtnu numMrid and dattd as fellowi:

v.';

'.• ^ ..

•.

WTE

' ':' '

- '

..• : :•• i.l •' 5-

AMENDMENT NO

.

'..

.'

•:.-... • • •

DATE

:

HOTS: Offers must set forth full, accurate and complete information as required by this Solicitation (including attachments!. The penalty
for making fa/st statements in offers is prescribed in 1SU.S.C. 1001.
'~
•
' •"''
^
SUnoird Form 33 P*o« 3 (BEV. 3-77T|

�SCHEDULE. Coniinutt-on
.

ITIMNO

SUPPLIES SERVICES

QUANTITY

Contractor will complete the quantitative
analysis for dioxin on twenty ( 0 specimens
2)
of human fat forwarded to him by selected
representatives of the Veterans Administration. Results of the assays will be forwarded to Lyndon Lee, K.D. V.A. Medical
Center, W shington, DC 20422

1
.

1

UNIT

UNIT PRICE

AMOUNT

sv

ADDITIONAL REQUIREMENTS

V.A. Form 10-1130 (Oct. 1978) is attached
hereto and incorporated by reference.

1
.

2.

This contract is subject to the Service Cootract act of 1965, As Amened (V.A. Form
10-1312, copy attached)

3.

'

This contract is subject to the provisions
of the Privacy Act (copy attached)
Travel and Perdiem (copy attached)

4
.

SPECIAL COlfDinoitS
Provisions for Payments; Invoices will cite
contract number and be nailed to:

1.

Contracting Officer ( 3 C
14)
DH&amp;S Supply Service
810 Vermont Ave., BH
Wasington, DC 20420
Term of Contract; Term of contract will run rom
date of acceptance by the V.A. through Septet)! er 30.
1979.

2.

•

Representative of the Contracting Officer: D . Lyndon Lee V.A. Media 1 Center
Wasington, DC has been designated as the repre entative of the contract ing officer
in furnishing technical guidance of the work t be perfo mei under this contract.

3.

Only the contracting officer it authorized to i take any «
(anents or c! ange&gt; which
will effect the price, quantity or quality of elivery t ena . All chanies oust be
authorized by the contracting officer within ti e scope e f h • authority in writing.
~

The contractor shall obtain all necessary lice ses and/o r pi raits requi: ed to perform
this work. He shall take all precautions nece sary to p roti ct persons i ad property
from injury or damage during the performance o this cor trai t. He shal be responsible for any injury to himself, employees, or others, as vei: as for any damage to
personal or public property' that occurs during the perfc *«pHi ce of this &lt; on tract
that is caused by his or hit employees ' fault r neglige ace

// this Schedule is Continued on SF 36. check here^ Q
• o.«. oovannmrr Mnrran orncz: tin o - MI-MI imn

SUndird form 33 P«g« 4 (REV. 3-77)

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                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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0163

Author

Hobson, Lawrence B.

°

Corporate Author
Report/Article Title Typescript: Fat Assays for Dioxin, December 14,1979

Journal/Book Title
Year
Month/Day
Color
Number of Imeges

D

3

Doscrlpton Notes

Wednesday, June 06, 2001

Page 1631 of 1688

�Fat Assays for Dioxin
Dioxin, the toxic contaminant of Agent Orange, is retained in body fat but it
has not been known how long it persists in human fat. Veterans who served in
Viet Nam were sometimes in contact with dioxin when Agent Orange was used as
an herbicide or defoliant. Batches of Agent Orange differed, however, in how
much dioxin they contained, some having none at all, and there is no way to
determine the content of any particular batch.
Aside from a very few armed forces personnel, troops were last exposed to
Agent Orange about ten years ago. The fat of the men would contain very
little, if any, dioxin so long after exposure even though the body
concentrates the substance there. Earlier chemical methods would not be
expected to detect the substance but recent advances in assay techniques
make it possible to identify and measure very small amounts of dioxinactually a few parts per trillion in the fat.
The Veterans Administration has undertaken a study to determine whether
dioxin can be detected in Viet Nam veterans and in Viet Nam era veterans
who did not serve in that country. To conduct this work, samples of
body fat were removed surgically from 20 volunteers who reported exposure
to Agent Orange in Viet Nam, from 10 volunteers who had not been there,
and 3 Air Force volunteers (identified as "Ranch hand") with recent known
exposure to Agent Orange. A highly skilled analytic chemist, without
knowing the source of each sample, assayed the fat using a two-part method.
The first part tentatively identified and measured the dioxin, specifically
TCDD; the second identified the TCDD more certainly and measured it more
precisely.
The methods used included careful extraction techniques, gaschromatography
and mass spectrometry with stable isotope identification of the substance.
The method as a whole is delicate, complicated, and still the subject of
study in itself. At present, 3 parts per trillion can be considered the
lower limit of detection.
The accompanying table summarizes the results as they are available today.
"Final Results" are those for samples in which both parts of the assay have
been completed; "Tentative Results" are for samples in which only the first
part of the method has been done to date and they cannot be considered
definite as yet.
As an additional check on the assay results, duplicate samples of some fat
specimens have been sent to an Environmental Protection Agency laboratory
that uses a somewhat different technique. No results are yet available
from these assays.

AP""CC55

�The results to date have shown that the assay used can detect and measure
dioxin in amounts as small as a few parts per trillion and that the substance
can be found in some persons whose last exposure was ten years or more
earlier. There is no evidence that the presence or the absence of dioxin
in body fat correlates with symptoms or abnormalities that could be caused
by the substance.
The study has made available an additional research tool that will be used
in further studies of Agent Orange. Until ill effects can be correlated
with the presence of dioxin, the assay has limited clinical usefulness. It
demonstrates now only that a person has at some time had contact with
substances containing dioxin. The contact may have occurred in fairly
recent non-military circumstances, however, since dioxin is found in
materials other than Agent Orange.

UH 1
*

12/U/79

,

�Final Results
22 Veterans
Viet Nam Service
Symptoms

3/12*

No Symptoms

3/4**

Total

6/16

No Viet Nam Service

1/6

. 1/6

Tentative Results***
12 Veterans
Viet Nam Service

No Viet Nam Service

Symptoms

3/7

0/1

No Symptoms

1/1

0/3

Total

4/8

0/4

* Numerator is number of veterans whose fat contained more than
2 parts per trillion above base line; denominator is total of
veterans in group
** All 3 of "positive" veterans were Ranch hand
*** Results of single unvalidated assay

AP""C057

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&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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°1633
Hobson, Lawrence B.

Corporate Author
ROPOrt/ArtiClB TltlB Typescript: brief overview of the study results, January
22, 1980

Journal/Book Title
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000

°

Month/Day
Color
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D

2

Descrlpton Notes

Wednesday, June 06, 2001

Page 1634 of 1688

�As you know, the Veterans Administration has undertaken a study
to find out whether it is possible, by the most sensitive tests known,
to detect and measure dioxin in the body fat of veterans exposed to
Agent Orange.

That study is completed and the results are fairly

definite.
Briefly 20 veterans who report that they were exposed to Agent
Orange in Viet Nam and who now have trouble they attribute to that
exposure volunteered to allow a surgeon to remove fat from their
belly wall for the test. Three Air Force officers who have worked
long and recently with Agent Orange but who have no ill effects
similarly volunteered. Another 11 veterans of the Viet Nam era who
were never exposed to Agent Orange agreed that surgeons could take
a sample of their fat as "control" when they performed a needed
operation. All these men gave informed consent for the procedure.
The 34 fat samples were tested by an independent, university
chemist who used the most sensitive method known to detect and
measure dioxin, the most toxic material in Agent Orange.

The

method, known as gas chromatography with high resolution mass
spectrometry, is still experimental, delicate and tempermental.
Despite difficulties with the equipment, the results are now
available.
The tests show that seven of twenty veterans with Viet Nam
service had dioxin in the small amounts of 3 to 89 parts per
trillion in their fat. Six others had even smaller amounts and
seven had no detectable dioxin at all. The three Air Force

�officers, none of whom had symptoms, had 3 or 4 parts per trillion.
One of the eleven controls with no known exposure to Agent Orange had
3 parts per trillion, three others had less and seven had none at all.
Environmental Protection Agency scientists using different but
similar tests on eight duplicate samples have confirmed that these
results are reasonable.
We can say then that there is a method to detect and measure
small amounts of dioxin in body fat but that it is difficult to do.
Further, it requires an operation to obtain a fat sample. The test
seems to be a research tool rather than a routine procedure.
The results suggest that a veteran who had contact with
Agent Orange in Viet Nam a decade or more ago may still have
minute amounts of dioxin in his fat but if the test fails to detect
these small amounts we cannot say that he had no such contact.
Similarly, it is unreasonable to say that the presence of
dioxin in the fat means that it causes any set of symptoms or, on
the other hand, that the absence of dioxin means that current
difficulties are not due to it.
One thing seems certain and that is that the "ticking time
bomb" idea is incorrect.

The amounts of dioxin found are far- too

small - even if all were released a once - to cause trouble in
any manner so far demonstrated. If exposure years ago to dioxin
is causing trouble today, it is not due to - and it isn't predicted
by - the presence of dioxin in the body fat so far as we know.

LBHOBSON ISA

1/22/80

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&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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01637

Author

Hobson, Lawrence B.

Corporate Author
RBpOrt/ArtiClB TltlB Typescript: TCDD (Dioxin) Content of Human Fat:
Progress Report, March 13,1980

Journal/Book Title
Year

000

°

Month/Day
Color

^

Number of Images

2

Doscrlpton Notes

Wednesday, June 06, 2001

Page 1638 of 1688

�TCDD (Dioxin) Content of Human Fat: Progress Report
The VA has undertaken a study to determine whether there is a method
that can detect minute amounts (in parts per trillion) of 2, 3, 7, 8
tetraclorodibenzo-para-dioxin (TCDD or dioxin) in the body fat of
persons claiming exposure to Herbicide Orange and those with no known
exposure.

Samples of fat were obtained by biopsy from 20 veterans

who believe they were exposed to the herbicide in Vietnam and 3 Air
Force officers with known close and more recent exposure.

Ten veterans

who denied exposure had fat biopsies during operations for other
disorders.

(An eleventh name was entered in the latter group but no

biopsy specimen was submitted.)

The gas chromatography = high resolution mass spectrometry used at
a university laboratory for the sensitive assay proved difficult with
the low concentrations encountered but the comparatively large biopsy
samples have allowed repeated assays. Duplicate extracts and biopsy
samples from 10 veterans were sent to the EPA laboratory which uses
a more discriminating gas chromatograph but a lower resolution mass
spectrometer.

Both laboratories assayed "blinded" samples; both

experienced difficulties with the new and delicate techniques.
Replication and equipment problems have delayed results.
At present, the assay problems have been resolved except for tv1
samples extracted and assayed by EPA scientists. These two gave
concentrations that far exceeded any other determinations, results

AP"""C085

�thought to be due to contamination.

Both laboratories are attempting

to resolve the discrepancy.

Simultaneously, the exposures to Herbicide Orange reported by the
20 Vietnam veterans are being evaluated to see whether they can be
assigned a relative value for the extent of contact.

This will allow

a comparison of assay results with exposure within the group.

The symptoms and signs of the Vietnam veterans have been reviewed
and the findings of their clinical chemistries are being tabulated.
Correlation of these with the assay results and the exposure
evaluations will then be sought.

The results to date can be tentatively interpreted as showing that
a method does exist to detect minute amounts of TCDD in body fat
but it requires samples so large that open biopsy is used and the
technique is still too difficult and slow for routine use. The method
remains at present a research tool for use with small groups.

TCDD has been detected both in individuals claiming exposure to
Herbicide Orange and in those with no known exposure.

Some in-

dividuals in both groups have no TCDD in the fat using methods that
can measure as little as one or two parts per trillion. No value
to date has been so great as one part per billion even in the two
samples with questionably large concentrations.

• 2—•
3/13/80 - LBHOBSON

AP~"'C'OS'l

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Hobson, Lawrence B.

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Ronort/ArtlCiO TltlU

Form:

Report of Contact, Fat Biopsies for Dioxin, March
18, 1980

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DOSCrlptOU NOtOS

Discusses a telephone conversation between Hobson
and a Mr. Schroeter (lawyer for Dow Chemical Co.)
regarding the study.

Wednesday, June 06, 2001

Page 1639 of 1688

�ttENTirtCATIOM NO* 1C, XC, SS, XSS

V, JC, etc.)

REPORT OF CONTACT
NOTE: TMtform mutt btfJUfd ml in ink or on typewriter,
«t it ttcomci m permment record In vetennt' foUen.

-WSTI

: NAME Of VET8WN (Tfft «r prmt)

Mr. Schroeter
ADMESS Of VfWtAN

Central Office
DATE Of CONTACT

3/18/80
TElfmONE NO. OF VETEKAN

CONTACTED

TYK Of CONTACT (Cluck)

AODM3S Of KKSOM CONTACTED

LJ HKSONAl
LJ TEtffHONE
TttEPHONC NO. Of KtSON CONTACTED

aATEMCNT Or MFOHMATIONttQMSTEDAND OMN

Biopsies for Dioxin
On March ISth Mr. Schroeter who introduced himself as a lawyer for DOW Chemical
Company in the current hearings for the EPA called to ask me some questions
about the fat biopsy study of Agent Orange. He said that he.was disturbed by
jthe press releases claiming that the fat biopsy completely invalidated some
"bt th6 stand taken by ouWV2,4,5-T. He asked me whether the figures of the
blqjlissay had been released and I told him that they had not and that the
Administrator had promised the congressional committees not to release the
study until 1t had been reviewed by the National Academy of Sciences and some
other groups. .
He asked me what conclusions we had revealed and I said that we had made public
the fact that there were individuals who had been in Vietnam and individuals
who toad not been in Vietnam who had very small amounts of TCDD in their fat.
There were also individuals who claimed exposure in Vietnam and some who had
not been 1n Vietnam who ted no dectable TCDD. He said this was pretty much
as he had understood the situation and asked how he could obtain the data when
they were released. I told him that I was certain that they would be given to
the press and that he could obtain notice there about as rapidly as elsewhere.
He asked whether he could call me after the data had been released and I said
certainly. No further action is needed at present.

DIVISION O« SCCTION

.RESEARCH AND DEVELOPMENT
FORM . . 0
JUL

i IV

OUSTING STOCKS Of VA fO*M )1»,
JUU »«74. WIU It USED-

,
or Research &amp; Development
0.U.5. G . P . O .

1978-261-143/1538

AP'""C117

�Concentration TCDD
Subject

Exposure*

TCDD
Presence

Gross I

Vietnam Service

1

- ****
- ****

5 (3)

EPA
(#2)

$ (JP

6

Gross II** EPA (.Gross
extract)
_
2

nd
8

- ****

5 (3)

9

- ***

nd (12)
nd (3)
nd (4)

10

11

+

12
16
35
23

+

(2)
(4)
(9)
(4)

2
nd

3 (1)
36 (3)

230

21
17

2
1

9 (3)

13

nd (0.2) nd

nd (2
nd (2

13

160

1

3 (2)

12

3 (0.6) 5

14

4 (3)

15

7 (4)

16

nd (4)
nd (8)

19

nd
nd

15)
3)

24

3
12 (4)
10 (3)

26

11

63 (6)
96 (10)

25

100

173

(1)

AP""Cll8

�Concentration TCDD
Subject

Exposure*

TCDD
Presence

Gross I

Gross II ** EPA (Gross
extra)

EPA
(#2) .

Vietnam Service (Continued)
27

nd (1 )
nd (6)

8 (6)

28

nd

3

29

7 5
nd (6
13 (5

30

9 (4)
nd (3

nd

4 (4)
5 (3)

5

5 (2)

4

4 (1)

2

6 (6)

4

9 (5)
4(4)

6
5

3(2)
-

2
nd

17

3(3)
4(3)

2
3

18

nd (4)

20

5(4)

34

—
8

Ranch Hand

2
3

***

4

3

10

Non-Vietnam - no exposure

5
7

21

_ ****

***

6(3)

20
5

8

3

12

5
2
_

6(3)
8(2)

31
32
33

***

3
_

nd(5)
4(4)

***

8

4(2)
7(4)

23

5

7(6)
14(7)

(2)

—

5

nd(3)

�No Biopsy
22

* Exposure as judged by veteran's statements
** Via the absolute intensity of 322
*** Cannot be considered positive because of poor validation (substance
detected probably not TCDD)
**** Cannot be considered positive because of poor validation and
contaminant removed on repeat of analysis

TCDD presence (+) or absence (-) evaluated by Dr. Gross;
+. indicates + if evaluated as 2.5:1 signal to noise ratio
- if evaluated as 3:1 ratio
Parenthetic figures are detection limits of individual assay

AP

C120

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  <item itemId="2669" public="1" featured="0">
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01639

Author

Hobson, Lawrence B.

Corporate Author
Report/Article TltlB Memorandum: Contract No. V101 (134)P-705, from
Lawrence B. Hobson to Director, Supply Service, March
20, 1980

Journal/Book Title
Year

0000

Month/Day
Color

n

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1

DeSCrlpton NotBS

Discusses budget increase for contract to University of
Nebraska-Lincoln, one of the laboratories where
analysis of samples was performed.

Wednesday, June 06, 2001

Page 1640 of 1688

�UNITED STATES GOVERNMENT

DATE: March 20, 1980
T0

FROM

Memorandum

Director, Supply Service (134)
Deputy ACMD for Research and Development (15A)

suBJ: Contract No. V101034)P-705
1. Contract No. V101(134)P-705 issued to the University of NebraskaLincoln under obligation no. S90068 for. $10,000 was exceeded by $6,500.
2. This error was due to originally believing that 20 samples were all
that were going to be available. An additional 13 samples were obtained
and sent for analysis. This was done in order to obtain more reliable
results and establish a broader base. Prior approval for increasing the
contract was not obtained due to unfamiliarity with VA contract procedures
by the person collecting these samples.
3. I am requesting the contract be increased at this time to cover these
additional samples. This will be charged to obligation no. S90068.

LAWRENCE B. HOBSON, M.D., Ph.D.

AP""'C083
Buy U .S. Savings Bonds Regularly on the Payroll Savings Plan

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01647

Author

Mobson, Lawrence B.

Corporate Author
Report/Article TltlB Typescript: Dioxin in Body Health and Health Status: a
Feasibility Study

Journal/Book Title
Year

000

°

Month/Day
Color

n

Numbor of Images

11

DOSCriptOD NOtOS

Study was presented before the Division of
Environmental Chemistry, American Chemical Society,
186th National Meeting, August 28-September 2,1983
(preprint exended abstract is included with typescript).

Wednesday, June 06, 2001

Page 1648 of 1688

�Dioxin in Body Health and Health Status:
A Feasibility Study
L. B. Hobson, L. E. Lee, M. L. Gross, and A. L. Young

Agent Orange, the defoliant used in Vietnam, contained
an average of about 2 parts per million of
2,3,7,8-tetrachlorodibenzo-para-dioxin or TCDD.

Since it is

extemely toxic for some animal species, it has been blamed
for a wide variety of medical problems by veterans who served
in Vietnam.
It was suggested that TCDD might remain concentrated in
the body's fat long after contact with it and serve both as a
cause of ill effects and as a marker to prove prior exposure
to Agent Orange.

It also became evident that improved

methods of gas chromatography and mass spectrometry would
allow detection of TCDD in amounts as small as a few parts
per trillion, a few picograms per gram of human fat.
In order to test the feasibility of using such assays,
the Veterans Administration undertook a pilot study with Dr.
Michael L. Gross of the Department of Chemistry, the University of Nebraska in Lincoln.

Three groups of men volunteered

to provide specimens of their fat:

twenty men, believing

that they had been exposed to Agent Orange in Vietnam and—
except for one man—experiencing medical problems submitted
to surgical biopsy of the abdominal wall.

A second group of

�ten veterans who were having operations anyway provided
specimens of fat from the body wall as control samples since
none had been in Vietnam nor had contact with Agent Orange.
A third group of three Air Force officers had worked with
TCDD or Agent Orange within the prior two years and one had
also been exposed to the defoliant in Vietnam.

They also

were biopsied.
To do this, VA surgeons removed 10 to 30 grams of fat
from the abdominal wall of the volunteers of the first and
last group using local anethesia.

In all instances

precautions were taken to avoid contaminating the specimens
with TCDD and to deliver them frozen to the assay laboratory.
I am not competent to discuss the methods of
extraction, gas chromatography and high resolution mass
spectrometry used by Dr. Gross.

Nor can I describe in detail

the techniques used by the chemists of the Environmental
Protection Agency who assayed 15 of the -specimens to confirm
Gross1 findings.

I am quite willing to believe that the

methods are delicate, exacting, and time-consuming.
Each volunteer had a medical work-up at the VA medical
center.

The military record of each "exposed" man was

examined to evaluate his exposure before the assay results
were available. The assays were conducted "blind" as well
since the chemist had only a code number for each specimen.
Estimating exposure to Agent Orange is generally a less

�than satisfactory procedure and the results must be viewed
sceptically.

We did divide, as best we could, the 20

"exposed" men into three subgroups:

the most likely exposed,

the least likely exposed, and an intermediate group with
possible but less definite exposure.
The results showed that it is indeed possible to detect
and quantify to some degree, at least, 2,3,7,8-TCDD in human
fat.

To be specific, it was present in fat from 13 of the 20

exposed veterans, from 9 of the 10 controls, and from all
three Air Force officers.

The amounts ranged from 3 to 99

parts per trillion with the two highest values in "most
likely exposed" veterans.

The third veteran in that group,

however, had no detectible TCDD and the heavily exposed Air
Force officer had only 6 parts per trillion.
It will be easier to review the results in graph form
(Slide I) than in a large table.

The front row of cubes
•

indicates the results from the most likely exposed
volunteers, the rear row of cubes refers to controls,

the

other two portray the possibly exposed and least likely
exposed groups.

Each cube stands for the highest value

obtained for one volunteer.

Only three individuals had more

than 15 parts per trillion and one of these was a control.
Most values were below 10 parts per trillion.
It is difficult in so small a sample to evaluate the
significance of an "outlier" such as the 99 parts per

�trillion, especially because of the intralaboratory, as well
as the interlaboratory, variability on replication.

It is

best to say only that a-larger series would have to be tested
with better documentation of exposure before any firm
conclusion can be drawn. This is especially true because two
recent small series, one in Canada and another in the United
States have found TCDD in fat samples from civilians, each
with a mean value of about 10 parts per trillion.

In Canada

one "outlier" of 130 ppt was discarded to arrive at that
mean.

The mean of our controls was 5.7^ 3.1 ppt, the mean

of the Vietnam veterans (except the "outlier") was 8.3^6.9.
In considering the clinical situations of the 20
"exposed" veterans, it must be kept in mind that all but one
volunteered because they had medical problems.
are a self-selected
Vietnam veterans.

Hence they

sample and are not representative of
The 19 men had a total of 36 diagnoses

ranging from the grave to the trivial. 'They are reasonably
typical of what can be seen in a large clinic serving a truly
sick population.

Thus, 8 men had minor skin problems, 4 had

blood vessel problems of high blood pressure or varicose
veins, 3 each had gastro-intestinal disorders, neuropsychiatric problems, benign tumors, joint diseases, or
reproductive disorders.

However, one of the benign tumors

was inside the skull, one man had sarcoidosis and another a
cancer, one was schizophrenic.

All of these are serious

�diseases.
I will show you the complaints, the diagnoses and the
TCDD values of only the most and least heavily exposed groups
in order to give you an idea of the results (Slide II).
First, please, notice the column of TCDD concentrations,
you can readily see, expecially for subject number 10, that
the assay presented some problems.

The "ND" indicates that

no TCDD was detected.
"S" stands for skin, "G-I" for gastrointestinal, "V"
for vascular, and so on.

Without going into detail, the

variability and the lack of relation to TCDD values is
obvious for both complaints and diagnoses.

One serious

illness—schizophrenia—was diagnosed in a man with 7 ppt
in his fat, the other—a cancer—was in a veteran with no
detectible TCDD.

Even a small series such as our 20 veterans

and 10 controls should reveal some correlation if these
levels of TCDD were associated with some one or two diseases
or groups of diseases.

There is no evidence of this.

There remains the question of whether the TCDD in the
body fat poses a threat to health, for example, if it were
all released into the blood within a very short time.

It is

most unlikely that there is any danger from this source.
TCDD concentrates in fat but even if all our soft tissues
contained 100 ppt, the blood concentration would only be 0.1

�microgram per kilogram of body weight, far below a dose
expected to endanger health.
At present, we do not recommend or provide an assay of
body fat for TCDD in order to determine whether a veteran was
exposed to Agent Orange or to evaluate his medical condition.
An operation is necessary to obtain a fat specimen, not
always a trivial undertaking.

The assay is difficult and

therefore expensive and, most important, the results of our
pilot study give no hope that useful information will be
obtained.
The assay unquestionably has value in research.

It

would be most desirable to follow the course of TCDD's
disappearance from fat after a known exposure to it.

It may

also help us detect suspected sources of TCDD in our civilian
environments but only on a very selective basis.

It is by no

means a practical screening procedure for occupational or
public health studies.

�Adipose Tissue Content of 2,3,7,8 - TCDD

5

10

15

20

35

100
Each cube represents highest assay

* A» Force Officer*

value for any one subject

2, 3. 7, 8 - TCDD (ppt)

�Fat Assay Results/ Complaints, and Diagnoses of Vietnam Veterans
Subject
Code

2,3,7,8-TCDD
(ppt)

Complaints

Diagnoses

Most heavily exposed
26
10
4*
19

63,99
12,16,23,35
6
ND,ND

S
G-I

None
V

S
S

None
V

Least heavily exposed
28
15
34
1
13

7,8
7
5
ND
ND

* - Air Force O f f i c e r
- Serious Diagnosis

None
N-P,R,V,S
N-P,S,V
CA
N-P

None
S
B-T
(CAJ
N-P,B- T

GEH

ND - Not detected

�Aiwn&lt;Acr
l*ror&gt;ehte&lt;l IWjfore the Division ot Environmental Chemistry
American Chemical Society
WaHhiivjton, D.C. Septcmlier, 1903
Uioxin in IVxiy Kal and Health Status: A feasibility Study
..-•• •'"'•'•"
/'/
L. B. llolxjon, L. K. Lee, M. L. Gross ancl A. t,. Youtvj
Arjent Oraivje ('rejects Office, Veterans Administration
810 Vernont Avenue, N.W.
Washington, D.C. 20420
Since 1978 there has been mounting concern over human exposure to 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDO). Much of this concern has been expressed by
veterans of the Vietnam war who believe that they were exposed to the
TCDO-oontaminated herbicide, 2,4,5-trichlocophenoxyacotlc acid (2,4,5-T), an
ingredient of Agent Orange, the major defoliant used by the United States Armed
forces In Vietnam.

During a 5-year period (com 1965 to 1970, the U.S. Air Force applied more than
40 million liters of Agent Orange containing more than 92 kg TCDO in South
Vietnam. Some two million American military personnel served t-yeac tours
during the same period. Many veterans of that era have reported medical
problems that they ascribe to exposure to Agent Orange. Their complaints have
ranged from tingling in the extremities to rare forms of cancer. Some veterans
have fathered children with birth defects and have suggested that the TCDO is
the cause. Accordingly, the Veterans Administration (VA) has initiated
extensive health studies of veterans exposed to Agent Orange and its dioxin
contaminant during the Vietnam Conflict.
Since TCDO is known to accumulate preferentially in the adipose tissue of
certain species of laboratory animals, it was suggested, early in the history of
the Agent Orange issue, that the analysis of human fat Cor TCDO might provide a
way to determine earlier Agent Orange exposure. A relation between the presence
of this substance health problems had also been suggested. Although methods for
TCDO analysis have Improved in recent years, no such study had been carried out
in humans with known exposure to herbicides containing this toxic contaminant.
Consequently the VA embarked on a small feasibility study to test the
methodology and to determine whether conclusions might be drawn regarding the
significance of the results. The study was carried out in three groups of adult
males as follows:
(1) Twenty Vietnam veterans all but one of whom claimed health problems
related to Agent Orange exposure and who volunteered for the fat
biopsy.
(2)

Three U.S. Air R&gt;cce officers with known heavy and relatively recent
exposure in connection with herbicide disposal operations but who did
not serve in Vietnam.

(3) Ten veterans with no service in Vietnam and no known exposure to
herbicides who were undergoing elective abdominal surgery and who
volunteered to serve as controls.
Methods; The procedure called for the removal of 10-30 grams of subcutaneous
adipose tissue from the abdominal wall. This was accomplished surgically under
local anesthesia. Precautions were token before, during an! after the procedure
91

AMERICAN CHEMICAL SOCIETY
Division of Environmental Chemistry
186th National Meeting
Washington, DC
August 28—September 2, 1983

Vol. 23 No. 2

SYMPOSIA
.

• Safe Drinking Water; The Impact of Chemicals on « Limited Resource
• Chlorinated Dioxins and Dibenzofurans in the Total Environment - II
• Acid Precipitation
• Recent Advances in Environmental Chemical Kinetics
• Organic Contaminant Behavior in the Subsurface Environment
• The Master Analytical Scheme for Organic Pollutants
• General Papers

�to avoid contamination by products, e.g., hexachlorophene, that could contain
TCDD. Specimens were collected In glass containers previously rinsed with
acetone and dried before use. All tissues were refrigerated during shipment bo
the assay laboratory, each of the volunteers had a medical history, physical
examination, and routine clinical chemistry. The details of military service in
Vietnam from the volunteer's report and his service record were examined to
evaluate his potential exposure to military herbicides using the dates, location
and nature of his service. Prom these a rough estimate of the likelihood of
exposure to TCDO was made without knowledge of the assay results.
The extraction and assay of all samples for TCDD were conducted at the
University of Nebraska, Midwest Center for Mass Spectrometry, Lincoln, Nebraska.
Approximately 5 to 10 grams of tissue were used, when available, for each
analysis. A known amount, generally 2 ng, of internal standard (either 37
C-2,3,7,8- TCDO or 13 C-2,3,7,S-TCDD) was added to the adipose tissue. The
sample was digested in alcoholic potassium hydroxide followed by extraction with
hexane to renove TCDD. The hexane extract was washed with concentrated sulfuric
acid, neutralized, dried and concentrated. The final stage of preparation
involved the use of three short-column liquid chromatography steps (silica gel,
alumina and Florisil). Gas chroinatography/hlgh resolution mass Spectrometry was
employed for quantitation of 2,3,7,8-TCDO and coeluting isomers. Signal
profiles were obtained at a mass resolution of 10,000 for ra/z 321.8936, the itost
abundant molecular ion for TCDD, and for the internal standard mass by signal
averaging for approximately 100 sec. commencing with the appearance of the
co-eluting internal standard 2,3,7,8-TCDO.
Extracts which contained materials giving signals greater than 2.5 times noise
at the exact mass of TCDD (i.e. 321.8936 + 0 0 2 ) over the Integration period
.00
discussed above were reanalyzed. For the~second analysis, signal profiles of
tn/z 321.8936 and m/z 319.8965 were nonitored over the elution period oC 2 3 7 8
,,,TCDO (determined by injection of standard solutions). A positive detection was
reported if signals were observed above the detection limit (2.5 times raise)
and if their intensity ratio was 1.0:0.78 + 0.10, which is consistent with the
presence of four chlorine atoms in the nolecule. Samples meeting all criteria
except the correct isotope intensity ratio have been considered to contain "not
detectable" levels of TCDO. Foe these samples, it was judged that the presence
of TCDD is not disproved by the observation of an incorrect isotope ratio at
these low concentrations; rather, the presence of TCDD is not confirmed.
Results; Of the twenty veterans who served in Vietnam, seven had no detectible
TCDD with the limit of detection at 2 to 6 part per trillion (ppt) . Another two
had detectible material that could not be validated as TCDD and the results for
one was considered equivocal because the measured value was only questionably
above the detection limit. Five of the ten remaining Vietnam veterans had TCDD
in amounts from 5 ppt to 7 ppt. three Vietnam veterans had TCDO in the amounts
from 9 ppt to 13 ppt. One individual had 63 and 99 ppt (average - 81 ppt) and
another had 23 and 35 ppt (average - 29
Of the ten control ("unexposed") veterans, four had TCDO identified in their fat
( , , and 14 ppt). Two other veterans had values low enough to be considered
677
equivocal and in three instances the detected material was not validated as
TCDO. The remaining veteran had no detectible TCDD.
One of the three Air Force officers with known exposure had no identified TCDD
in his fat. The unidentified substance in his case and the TCDD measured in the
other two officers was never more than 3 ppt above the limit of detection.

92

»\

�The clinical data were reviewed, seeking correlations between complaints or
diagnoses and the assay results. Within the group of twenty Vietnam veterans,
seven of them reported some health problems beginning in or during a tour of
duty in Vietnam. No two, however, reported the same symptoms. The remaining
thirteen veterans reported no illness in Vietnam although only one reported good
health at all times. Anong the nineteen veterans with current medical
complaints, symptoms and diagnoses varied widely without any common pattern.
Five had mental problems ranging from nervousness to schizophrenia and three had
experienced difficulties of reproduction, namely, spontaneous abortion by the
wives of two and congenital heart disease in the son of a third.
Pour of the seven veterans who reported difficulties while in Vietnam had no
TODO detected. The five veterans with mental problems included three without
detectible TCDO and three whose assays results were 5 to 7 ppt. Che of three
veterans reporting reproductive problems had no detected TCDO, one had doubtful
level and one had 7 ppt. Detectible TCDO in the body fat could not be
correlated with clinical chemistry findings. Similar results applied to the
controls i.e., veterans who did not serve in Vietnam.
The highest values for TCDO in adipose were found In two Vietnam veterans. Both
men had military records substantiating duties that involved the use of
TCDD-oontaminated herbicides in Vietnam. Other individuals, however, who
claimed extensive handling of herbicide in base perimeter operations had little
or no TCDO in their adipose.
Discussion; TCDO was found in some persons who reported exposure to Agent
Orange and in others who were never in Vietnam. On the other hand, some
veterans from Vietnam had no detectible TCDO and the same is true of veterans
who were never in Vietnam. The low level of TCDD in two Air Force officers and
its absence in another is of special interest since their exposure to TCDO is
certain and more recent than that of the veterans.
Among the twenty Vietnam veterans there was no uniformity of symptoms, either
Immediately after exposure, at the time of biopsy, or during the Intervening
period. N&gt; one symptom or group of symptoms was common to veterans with
detectlble TCDO in their fat. The presence of TCDD did not mean ill health nor
did its absence indicate good health, tb detailed statistical analysis was
attempted of this small pilot series.
The TCDO content in the fat was very small, not exceeding 100 ppt. Since TCDO
accumulates in fat more than in other tissue, the average body concentration
woald be much lower. Even if all tissues contained 100 ppt, however, the
concentration would be less than 0.1 mircogram per kilogram of body weight, a
value below the demonstrated toxic dose to threaten health.
Conclusions; The present assay for TCDO in fat tissue does not offer a
satistactdry routine test for exposure to Agent Orange, providing neither clear
evidence of contact with that specific defoliant nor of absence of such contact.
Moreover, the technique cannot be used to correlate body levels of TCDO and
medical conditions. The assay technique is difficult and not readily available,
fat'samples must be obtained by surgical biopsy and the source of any TCDO
detected is uncertain. The current assay method does provide a research tool
under proper conditions and for specific purposes, e.g., for determining the
rate of disappearance of TCDD after known exposure.

93

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                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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