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                    <text>Item ID Number

01532

Author

Lee L ndon

' y

Corporate Author
Report/Article TltlB TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in Body Fat
of Vietnam Veterans and Others (Draft)

Journal/Book Title
Year

000

°

Month/Day
Color

n

Number of Imaoos

14

Descrlpton Notes

Wednesday, June 06, 2001

Page 1633 of 1688

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VA FORM
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�TCDD (2,3,7,8-tetrachlorcKiLbenzo-p-dioxin) in Body Fat of Vietnam
Veterans and Others

-^y

Authors *

Lyndon E. Lee, M.D. , Philip Donahue, M.D. , Herbert B. Greenlee, M.D. ,
Carlos R» Mota, M.D. , William Schumer,M.D. , and Paul A, Thomas, Jr., M.D.
Veterans Administration Medical Centers; Washington, D.C.; West Side,
Chicago, II; Hines II; Lincoln, NE; West Side, Chicago, IL; and North
Side, Chicago, IL.
The past three years have seen a mounting concern over exposure to the
defoliant 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), an ingredient of
Herbicide Orange used by the Uhited States Armed Forces in Vietnam from
1965 to 1971. At least some lots of 2,4,5-T contained a contaminant, 11
2,3,7,8-tetrachlorodibenzo-p-dioxin, also called TCDD or simply "dioxin .
This substance is highly toxic to animals (1,2) and has been claimed to
produce chronic and delayed adverse effects among American veterans who
served in Vietnam.
- ,
*

TCDD accumulates preferentially._in""the body fat of experimental animals
(3) and man ( 4 ) . It has been jbos tula ted to remain in adipose tissue for
years and to threaten damage ;if .released by reduction in the amount of
that tissue (5).
/"
Analytic methods to identify and measure TCDD have improved in recent
years, enabling the Veterans Administration to investigate whether TCDD
can be detected in the body fat of veterans who were presumably exposed
to Herbicide Orange and in the fat of other veterans without known
exposure to the herbicide. Three Air Force officers with more recent and
better reported exposure to TCDD were tested as well.
Twenty veterans who believe that they were exposed to Herbicide Orange in
Vietnam volunteered to have 10 to 30 grams of fat removed from their
abdominal walls. Another ten veterans without known contact agreed to
have a similar specimen of subcutaneous fat removed during an otherwise
necessary abdominal operation. Three Air Force officers who volunteered
for biopsy had been intimately involved with the destruction of Herbicide
Orange, two years earlier, had had other frequent contacts with the
herbicide, and had used TCDD in the laboratory.
The biopsies were conducted with care to avoid contamination by products
containing TCDD. The specimens were collected in glass containers
previously rinsed with acetone and refrigerated until use.

vx-;

The methods of extraction and of gas chroma tography - mass spectrography
have been described by Gross (6). Ten specimens of the thirty-three were
assayed as well in a second laboratory using slightly different
techniques. The assays in both were conducted without knowledge of which
specimens came from exposed and which from non-exposed men.

�Each of the twenty exposed volunteers provided information about his
military service with details of his exposure to toxic substances in
Vietnam or elsewhere. A medical history, physical examination, and
routine clinical chemistry were obtained, although the values of the
latter are not available in some instances. Service records were
available%as well. The clinical data were reviewed, seeking correlations
between them and the assay results. The details of military service in
Vietnam from the volunteer's report and his service record were examined
in order to evaluate his likely exposure to Herbicide Orange using the
dates, location, and nature of his service. From what is known of the
times and places of Herbicide Orange usage a rough estimate of the likelihood of exposure was possible. This evaluation was made without
knowledge of the assay results.
Results. The assay results are reported in Table I. Detailed
tabulations of the results and comparisons with those from the second
laboratory are given by Gross (6). It should be noted that where the
assay is indicated as negative despite an apparently detectable amount of
TCDD, the chemist was unable to identify the measured substance as TCDD.
In such cases, contamination with small quantities of some other,
unidentified substance is likely (6).
One of the three Air Force officers with known exposure to TCDD 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 parts
per trillion above the limit of detection.
Of the twenty veterans from Vietnam, seven (numbers 1,9,13,16,19,27 and
30) had no detectable TCDD with a limit of detection at 2 to 4 parts per
trillion; another two (numbers 6 and 8) had detectible material that
could not be validated as TCDD and one (number 14) could be considered
equivocal because the measured value was so low as to be questionable.
The ten remaining men had TCDD identified anct measured in amounts from 3
parts per trillion with a limit of detection ofc&gt; 2 parts (number 11) to 96
or 100 parts per trillion with 10 parts limit of detection (number 26).
Only one other (number 10) had a TCDD value greater than 7 parts per
trillion above the limit of detection. ^ • ^
Of the 10 unexposed veterans, two (numbers 20 and 23) had TCDD identified
in their fat; neither had nore than 6* parts per trillion above the limit
of detection. Two other veterans (numbers 17 and 23) had values low
encught to be considered equivocal and in five instances (number
5,7,21,31, and 33) the detected material was not validated as TCDD. The
remaining veteran (number 18) had no detectible TCDD with a limit of
detection of 4 parts per trillion. No specimen was submitted for the
assigned number 22.
Table II presents data relevant to the exposure in Vietnam to Herbicide
Orange. Group A is composed of the three volunteers (numbers 10, 19, and
26) were judged to be most heavily exposed to the -defoliants. Their
duties in Vietnam involved handling the chemicals at a tijne and under
circumstances when few precautions were taken to avoid contact or
'ingestion.

^1'V

�The five veterans comprising Group B are judged to have had relatively
little likelihood of exposure to Herbicide Orange either because their
location in Vietnam was removed from the areas sprayed (nunber 1, 15, and
34), because of the time of their Vietnam duty (numbers 13 and 28) or its
short duration (nunber 1), and because of a questionable description of
exposure (nunber 34). The remaining twelve Vietnam veterans appear to
have had an intermediate likelihood of exposure, i.e. between that of
Groups A and B and are not described in Table II.
Arong the most heavily exposed men are
the highest TCDD content in their body
had none detected. Two of the lightly
no detect ible TCDD but the other three

the two (numbers 10 and 26) with
fat but the other man (nunber 19)
exposed men (numbers 1 and 13) had
(numbers 15, 28 and 34) did have.

Table III summarizes the clinical information regarding all twenty
Vietnam veterans. Seven of them (numbers 9,13,15,26,27,29, and 30)
reported some health problems beginning during a tour of duty in Vietnam.
No two, however, reported the same symptoms which included probable
numbness and tingling; tingling and swelling of the hands and feet with
insomnia due to the pain; plantar warts; a rash on the legs with "jungle
rot" and occasional diarrhea; apparently generalized itching; amoebic
dysentery as well as pleurisy, weakness, and hypertension; and asthma
with cough and an intermittent rash on the flexor surface of the arms.
The remaining thirteen veterans reported no illness while in Vietnam
although only one reported good health at all times. Among the nineteen
veterans with medical complaints six (numbers 1,8,10,19,24, and 26)
suffered from conditions difficult to relate to toxic agents, namely
malignant astrocytoma; chronic ulcer after laceration of the hand;
plantar warts and a "stomach condition" without radiographic or chemical
evidence of disease; varicose veins; hemorrhoids, low back pain, and
palpable liver with a history of heroin use; and pruritis ani and
possible urticaria. Of the thirteen other veterans reporting
difficulties five reported mental problems ranging from nervousness to
schizophrenia and three had experienced difficulties of reproduction,
namely, spontaneous abortion by the^rwfes of two (numbers 11 and 15) and
congential heart disease in the h^f a third (number 16) .
Three of the seven veterans j £%&gt;orted difficulties while in Vietnam
had no TCDD detected; the fo~CHr, -others had 5 to 96 parts per trillion. Of
the six men whose medical cowplaints were difficult to relate to toxic
substances, three had no TCDD and three had 5 to 96 parts per trillion.
The category of five veterans with nental problems included two without
detectable TCDD and three whose assays results were 5 to 13 parts per
trillion. One of three veterans reporting reproductive problems had no
detected TCDD and the other two had levels of 3 and 7 parts per trillion.
The lack of relationship between detectable TCDD in the body fat and the
usual clinical chemical findings can be illustrated by the fact that none
of the men tested had abnormal values for total plasma protein, albumen,
thronboplastin, creatinine, or uric acid. The aspartate amino
transferase (SOOT) was slightly elevated (21IL/L or less) in three

•7s V. ••
.' ' V

�veterans without detectable TCDD in their fat and in two with 6 and 35
per trillion. One veteran with an elevation of 48 iq/L and another with
an increase of 190 IIJ/L of SCOT had no TCDD detected. Similar lack^
relationship between clinical chemistry and TCDD content is eviderf£, £oj
each test*
_._ y"':\^
Summary and Conclusions; As Gross (6) concluded, his method of gas
ohroma'tography-mass spectrcmetry is capable of detectingvand measuring
very small amounts of TCDD of human fat. The technique is, however,
difficult and delicate in its present form. It also requires enough
adipose tissue to necessitate surgical biopsy and this must be performed
under conditions that avoid contaminating the tissue with TCDD fran
extraneous sources.
The data indicate that TCDD can be found in some persons who report
exposure to Herbicide Orange and in others who were never in Vietnam and
know of no contact with the herbicide. On the other hand, some veterans
from Vietnam have no detectible TCDD 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 TCDD is certain and more recent than that of the veterans.
Information regarding pre- and post-service exposure to chemicals that
contain TCDD is too inadequate to allow more than speculation on other
sources of the material in the fat samples. TCDD has been found in a
substances other than Herbicide Orange or the 2,4,5-T in that mixture
(1). It is impossible', therefore, to be certain of the source of TCDD
found in any ofi ' the map in this study.
r
•;
&gt; .j.
v

\

• i.- ""

Because.of the difficulty and limited availability of the assay
techniques, the necessity for securing relatively large fat samples, and
the uncertainty of the source of the TCDD detected, the method described
here does not seem a satisfactory routine test for exposure to Herbicide
Orange nor acceptable evidence of contact with that specific defoliant
nor of the absence of such contact. It will provide a research tool
under proper conditions and for specific purposes, e.g. the study of the
rate of disappearance of TCDD after known exposure.
It should be noted that the amounts of TCDD measured in the fat are very
small, not exceeding 100 parts per trillion. Since the substance is more
concentrated in fat than in other tissues, the total body concentration
is even less.

�References:
(1)

Young, A.L., J.A. Calcagni, C.E. Thalkan, and 3.W. Tremblay. The
Toxicology, Environmental Fate and Human Risk of Herbicide Orange
and its Associated DioxLn. UEAF OEHL Technical Report TR-78-92.
1978,

(2)

Cattabeni, F., A. Cavallaro, and^G. Galli. Dioxin. Technical and
Chemical Aspects. Vol. 1 Monogr^^ of the Giovanni lorenzini
Foundation. New York. 1978t^YJ ^
,-'•»» t syjExT^
Gasiewicz, T.A. and RrA^^skl. 1978. Tissue distribution and
excretion of 2,3,7,8*(t^trachlorodibenzo-p-dioxin (TCDD) and effects
upon clinical parameters in the guinea pig. Fed. Proc. 37(3):501.

(3)

(4)

Reggiani, G. 1978. The estimation of the TCDD toxic potential in the
light of the Seveso accident. Presented at the 20th Congress of the
European Society of Toxicology, West Berlin.

(5)

Commoner, B. 1978. Interview on "Agent Orange: Vietnam's Deadly
Fog", WBBM-TV, Chicago"

(6)

Gross, M.L. 1980. Trace analysis of tetrachlorodibenzo-p-dioxin
(TCDD) in human adipose in publication.

�Table I. 1CDD in Hunan Fat Samples (after Gross (6))
Veterans with Military Service in Vietnam

Subject

TCDD
Presence

1

Neg. b

6

Neg.

b

8

Neg. b

9

TCDD Concentration3
(parts per trillion)
n/z 392:n/z 328
n/z 322

Meg.6

^jp*
11

nd (5)

5 (3)
5 (^X
nd (12)
nd (3)
nd (4)

^£\12 ^

Pos.

10

nd (11) C

23

4

&lt; &gt;

^4
*-.(\£

-d
2

2
nd

1
21
17
2
1

P^KN^'

3 (2)

Fos.

9 (3)

13

Neg.

nd (2)
nd (2)

14

Doubtful

4 (3)

4

12

'

13

15

Pos.

7 (4)

8

16

Neg.

nd (4)
nd (8)

-

19

Neg.

nd (15)
nd (3)

24

x^ &gt;^ Pos.

25
26

5 4
5 ((3))

3

Pos.

12 (4)
10 (3)

11

Pos.

63(6)
96 (10)

t3$
^i,J
^%V

-

100

�27

Neg.

nd (11)
nd (6)

28

R&gt;s.

8 (6)
7 (5)

29

R&gt;s.

nd

nd (6)
13 (5)

3

8
jtfr

Neg.

30

R&gt;s.

34

9 (4)
nd (3)

J
&lt;IJ4K

'&lt;%P^

nd

(5)

Air Force Officers
2

IbB.

5 (2)

4

3

Neg.b

4 (1)

2

4

R&gt;S.

6 (6) .,^k

4

Veterans with Military Service Ou ts i de^ie't ftain
5

Neg.b

9 (5)
4 (4)

6
5

7

Neg.e

3 (2)

2
nd

3 (3)
4 (3)

2
3

17

/.-.^Doubtful

18 „.&lt;;•;&gt;

Neg.

nd (4)

-

20 V"

Rxs.

5 (4)

5

21

Neg.e

6 (3)

2

23

R)S.

6 (3)
8 (2)

8

31

Neg.e

4 (2)

-

32

toubtful

nd (5)
4 (4)

5

7 (6)
14 (7)

5

33

Negf

�a.

n/z 322: m/z: 328" is value calculated from relative signafi^JiJtensities
at two mass spectrcphotoneter channels. "m/£ 322" is vefJu^from absolute
intensity of that channel.
&gt;«MJ;VV
^&amp;~~^^ \^,'

b.

Cannot be consic3ered positive because of poor validation (substance
detected probably not TCDD) and contaminant removed on repeat analysis.

c.

"nd" means "not detect^y.^
of TCDD.
&lt;£/*C

Value in parentheses is limit of detection

teV

d.
e.

Dash indicateaW5\assay performed.
^L!V positive because of poor validation (substance
Cannot be considered
detected probably not TCDD).

f.

"Doubtful" indicates that result wxild be considered positive at 2.5:1
signal: noise ratio negative at 3:1 ratio.

�Table III.

Immediate
Non- Service
Civilian
Symptoms
Exposures
Occupation '
Well Maintenance Chlorine; Chemo- Hone given
therapy, radion disability
ation

SUMMARY OF CLINICAL INFORMATION

Intermediate
Health
Lt. temperoparietal tumor;
"kidney condition"

Current
Positive Findin&lt;js
None

SUBJ:
1

*.
Age
31

6

31

Machine Keeper

Radiation tonsils 1950

None given

Acoustic j^nkr,

8

30

Constructionunemployed

tone - ETOH,
cocaine, marl
huana use

None given

Ma*reported
difficulty

Ulcer-after cut 2-3 mon.

9

30

Student

None

? Numbness &amp;
tingling

Rhinitis, "back
condition" - 1969

Numbness, tingling
Hostile - abdominal
fatigability, fever- tenderness, pharynx
yrs. "Psychiatric &amp; edema
sexual problems"

tone

10

30

Steel mill crane None
operator; studen

None given

Back pain, Chr.
otitis media,
plantar wart

"Stomach condition"

Plantar wart

11

32

Student; ConNone
struction worker

None given

Wife aborted at
3-4 mon - 2 1/2
years ago

Intermittent chest
None
pain &amp; dyspnea - 2 yr
Urinary frequency 2 yrs., Infertility

.*!*
^

Headaches - 1 1/2 yrs Thyroid nodule, facial Acoustic neurFacial pain
oma- 1979,
N. changes
thyroid nodule1976

12

Technical rep- None
resentative for
Clinical instru.
Company

30

None given

Current Symptoms
None

Butterfly facial
None jg
rash after r'TCH or
; anxiety - before
Vietnam as weLU*Jf

Diagnoses
'•iliynant
astrocytoma 1976

None

None

•

Butterfly rash on
face &amp; forehead

i
[

i
i

(

i

"i

Ulcer - L index finger Chronic ulceration

i

"

Comments

!
!

�SUMMARY OF CLINICAL INFORMATION

Civilian
Occupation

Ag.

Immediate
Symptoms

Non-Service
j Exposures

Intermediate
Health

Current Symptoms

Jumpy, small non-tendei none
axillary nodes

Construction

Prominent hila, disc
atelectasis

:
I

32

Mastectomy for
bynecomastia - 197 200X swollen lids &amp;
red conjunctiva;
nervousness, tingling
of fingers &amp; toes *
"several years".
periodic weakness
4
*&amp;i ^^^&gt;
Farm chemicals; None Qiysft^fc 'Kidney stone-1975; Chestpain; forehead
photographic;
v*»* Pleurisy &amp; pneumon a cyst; lipoma, mole,
2 wks; PPD pos.lawn fertilizer
hernia
&gt;$x
1969; blood in
stools

Diagnoses

School Teacher 1 (TP4 in service Plantar warts
'Heroin for 3 yr
1 4 yr. ago

29

&lt;$^T&lt;&gt;

33

1/5
Current
Positive Findings

Machine repair- Cleaning agents Rash on legs;
occasional
heavy ETOH
man
diarrhea;
jungle rot of
'
toe-nails &amp;
groin

Nervousness- late
Recurrent extremity
1972; wife aborted well ing- 10 yrs. ,
IX between 1969 &amp; "nerves", rash
1975; "nervous
&amp;f
breakdown"- 1972

Comments
i

Sarcoidosis,
inguinal herni;
lipoma cyst

Pigmented areas on It. Schizophrenia.
thigh and lower legs skin rash,
cnychomycosls

.v&gt;

. ^^ \

rtf^^
YM) 'a*

1
35

Piper fitter

None

None given

Son-congenital
heart dis. 1971

Dry cough- 3 wks. ,
foot problems-since
service

Lt. great toe contract none
ure; tenia pectis

51

Machinist (?)

None

None given

No Statement

Painful leg edema

Varicose veins

33

Tailor

34

Auto Mechanic

Varicose veins

Painful knee &amp;
Groin pain - few yrs. Hemorrhoids; Palpable hernia
[liver
leg swelling after low back pain
exercl se

i None. HeroinNone given
until 3 yr. ago
•

*

1

Insecticides

• Pain, swelling left IBP 150/100; arthoscopy
Recurrent dry
icholecystectomy. tenia
patches on back &amp; | knee-post-traumatic
iversicolor
shoulders; peptic
i
ulcer
j

None given

i

:
•

i

i

i

Arthritis.
chronic cholecystitis, fattj
liver, HBP,

�SUMMARY OF CLINICAL INFORMATION

Civilian
Occupation

Ag.

SUBJ:

33

26

Non-Service
Exposures

None given

None

Artist

Immediate
Symptoms

i

Intermediate
Health

Current Symptoms

Crampy abdominal
pain-4 yr. ago;
allergy to fish &amp;
IVP dye

Severe rectal itch-3
yr; generalized skin
itch occasionally
since 1968

Current
Positive Findings

Diagnoses

Perianal excoriated
lesion
*

Pruritis ani,
Possible urticaria

&lt;*t

27

32

None given
i
,
.

None

w^
•$&amp;

3

ItenjKjbur tingl- Still fingers &amp; toe Reynaud -like reaction Stiff fingers &amp; toes. none
iipgVK swelling Hematemesis; back (&amp; weakness of
bilateral limp
of hands &amp; feet pain
| extremities
1
insomnia from
pain

28

33

MAS (VA)

None

None given

29

30

Carpenter

None

None given

None

None Given

•
Oil Tank leader
Fireman

34

37

Carpenter

}

1

i

j

None

rimary light
oils-benzene,
toluene, etc.

•

-,

30

None

Amoebic dysentery; Early morning weakness None
pluerisy 2 mon in
normal by evening
BP 158/90
Vietnan; "weak"
before discharge;
HBP at discharge;
Crampy abd. pain1976' "Poly cystic
•kidney"
a
*'^
Repeated cough, ^Nervousness
^ •Intermittent pruritic Expiratory rhonchi
asthma worse (t*
«TV: r.ash'on flexor surface
evac. hos)
j
\ of arms-since Vietnam
W

1

30

None

None
Duodenitis

None

¥•*"

(Multiple, general iz Chr. anxiety, dyspnea Abdominal nodules
blurred vision; palpit (lipomata ?)
;ed lipomata
i
ations; chest pain,
stomach pain; facial
flushing, infraorbital
"water blisters" 1 eac
week, HBP

None

•8

Ccnrnen

Q.

�•^

SUMMARY OF CLINICAL INFORMATION
-

SUBJ:
2

Civilian
Occupation

*

Non-Service
Exposures

Intermediate
Health

Immediate
Symptoms

Current
Positive Findings

Current Symptoms

36

Farm d e f oliants

None

None

None

Mass ( ? )

36

3

USAF
USAF

Laborat .
insecticides

None

B r o n c h i e c t a s is ,

None

None

39

USAF

K^fc^. Organo-phosphatea ,
industrial
V-"v
HCOs

5

34

Unemployed

No record

1

40

Unemployed

No record

17

31

JNot r e p o r t e d

Gasoline &amp;

i

automot ive
chemicals

18

51

20

Mot recorded

48

21

lot recorded

federal
Employee

43

Not given

Not given
• •,
None

leftaxill

allergy
NCC a r e t h r l t l s ,
r t n a l stone ,
spastic colon

None

O c c a s i o n a l p e r l o r - None
bital acne-3yrs.t

None

m o l e - l i k e lesions

of a r m , g r o i n ,
penla
Not applicable

None given

None g i v e n

^•^\
Nolffc-^ jttven
Not applicable
.• *'l ;'• "'

None given

Not a p p l i - v P e l v i c
cable
1

s
*

Not a p p l cable
Not a p p l i cable

f r a c t i o n s Acute low back
pain.
Infertility
(past pelvic
fracture)

l U B P , a l l e r g y to
idyes
i

Rt . i n g u i n a l
hernia

Hernia
R e c t a l adenacarclnoma

Rt . v a r i c o s e vv . ;
Rt . leg a t r o p h y ;
Lumbar spabraA
i•
-* - ^ \ \ ^
\

Epigastric
her i&gt; la, a c u t e
leraboscral

sprain

Ca lc_ui~u I6»,»r t .
kLrfney i-,f

I n t e r m i t t e n t dematurla-9mon .

Kt. renal
ca l e u 1 us
Hypertension

'* •
["Back problems" Severe a b d o m i n a l &amp; S l i d i n g l l a t a l
;gout-12 y r s . ago b a c k p a i n
hernia; ureteral

U r e t e r o l 1th l a s t s ;

Hypertension
Not a p p l i cable

i
K n o w n non-f unc t l o n f N o n e
ing kidney

Not r e c o r d e d

Rt . , nonf unc t t o n i n g ,
mul t i c y r t i c
kidney

I
. .
1
.

Comments

penlc t llln

&lt; *\
4

Diagnoses

I

:

i

Ureterolithotomy

UreteroHthotomy
Nephoectomy

�GO

a,'

SUMMARY OF CLINICAL INFORMATION
SUBJ:

Civilian
Occupation

Agi

23

31

31

27

Non- Service
Exposures

i

Foreman meat
cutter

None given

Intermediate
Health

Immediate
Symptoms

i

Diagnoses

Comments

Not applicable

Duodenal ulcer. Exigastric pain,
(
Obesity
bronchial asthm
vomiting-tl/2 yr

Not applicable

Automobile acci Hipvpain
dent with right '•*&amp;'.
hip injury
&lt;?• V*

:Limit movement, rt. Traumatic
Kip fussion
nip. Abscess mandi- dislocation
ble
rt. hip;
ostionicrosis; anemia

£

Sheet-m^Sl
None , drug
J ma ch i nfe ' a{4e r- abuse

Current
Positive Findings

Current Symptoms

ator

^i^

Hiatus her- Nissen
nia &amp;
fundoreflex iso- olication
phagitis,
asthma

-33

43

Retired AF
and Marine

None

Not applicable

Dermatitis .left Sinus headaches,
foot; arthritis tics
chest 6 left
arm pains,
dyspenia 6-7yrs

Bilat, direct in
guinal hernia
Hemorrhoids

Left inguin Herniorrhapty
~ "~iernia

'.33

42

Manager-auto
repairs

None given

Not applicable

None given

None given

Cholelithia- Cholecystec
tomy
sis

None given

.

i

,
.

•
j
i
i
i
1
•

\
i
i

!

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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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              <elementText elementTextId="18879">
                <text>Lee, Lyndon E.</text>
              </elementText>
              <elementText elementTextId="18880">
                <text>Philip Donahue</text>
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                <text>Herbert B. Greenlee</text>
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                <text>Carlos R. Mota</text>
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                <text>Paul A. Thomas</text>
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                <text>TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in Body Fat of Vietnam Veterans and Others (Draft)</text>
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                <text>VA Dioxin Fat Assay Study</text>
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                    <text>Item ID Number

°1491

Author

Lee, Lyndon E.

Corporate Author
RBDOrt/ArtlClO TltlO Typescript: 2,3,7,8-Tetrachlorodibenzo-p-dioxin
(TCDD) in Body Fat of Vietnam Veterans and Other Men

Journal/Book Title
Year

000

°

Month/Day
Color
Number oflmaoos

n

is

Descripton Notes

Tuesday, May 15, 2001

Page 1491 of 1514

�2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in Body Fat
of Vietnam Veterans and Other Men

Lyndon E. Lee, M.D., Philip Donahue, M.D., Herbert B. Greenlee, M.D.,
Carlos R. MDta, M.D., William Schumer, M.D., Paul A. Thomas, Jr., M.D.,
and Lawrence B. Hobson, M.D., Ph.D.
Veterans Administration Medical Centers: Washington, D.C.; West Side,
Chicago, IL; Hines, IL; Lincoln, NE; West Side, Chicago, IL; forth Side,
Chicago, IL; and Veterans Administration Central Office, Washington, D.C.
Summary: TCDD in surgical biopsy specimens of fat from twenty
veterans (A) reporting Agent Orange exposure in Vietnam, ten veterans (B)
without Vietnam experience and (C) three Air Force officers recently
exposed to Agent Orange and TCDD. In A 10/20, in B 2/10, and in C 2/3 men
had detectable TCDD. The highest concentrations (in A) were 99 and 35
ppt.; none others exceed 12 ppt. Gas chromatography - mass spectrometry
currently cannot prove Agent Orange exposure.

The past three years have seen mounting concern over exposure to the
defoliant 2,4,5-trichlorophenoxyacetic acid (2,3,5-T), an ingredient of
Agent Orange used by the United States Armed Forces in Vietnam from 1965
to 1971. Some lots of 2,4,5-T contained small amounts of a contaminant,
2,3,7,8-tetrachlorodibenzo-p-dioxin, also called TCDD or "dioxin". TCDD
is highly toxic to animals (1) and has been claimed to produce chronic and
delayed adverse effects among American veterans who served in Vietnam.
TCDD accumulates preferentially in the body fat of experimental
animals (2) and man (3). It has been postulated that the compound remains
in adipose tissue for years and damages the individual who subsequently

�-2-

loses fat and mobilizes the substance (4). TCDD has a half-life of 30
days in the fat of rats (5) and guinea pigs (7) and 105 to 125 days in the
adipose tissue of cows ( ) No one has investigated the possibility that
7.
TCDD remains more than eight years in the fat of veterans who served in
Vietnam that long ago.
Analytic methods for identifying and measuring TCDD have been
improved in recent years so that it is possible to assay fat for
quantities as small as a few parts per trillion, i.e. a few pioograms per
gram or little more than 0.000000000001 gram of TCDD per gram of tissue
(8). Because results viere uncertain and the method complicated and
difficult, a pilot trial seemed more appropriate than a full-scale study
to determine whether the assay discriminates between veterans who were
exposed to Agent Orange a decade or so earlier and men who were not. The
study might also indicate whether specific symptoms were associated with
detectible TCDD in an individual's body fat.
Subjects: Three groups of men served as subjects and all signed
informed consents for biopsies. The smallest group of three Air Force
officers had handled Agent Orange in field tests or in disposal operations
and had worked with the herbicide and TCDD in a laboratory. All three
reported repeated contact with the chemicals and all had been exposed
within the prior two years.
The second and largest group of twenty volunteers was self-selected;
each believed that he was exposed to Agent Orange in Vietnam prior to 1971
and all but one claimed health problems as a consequence.

The exposure of

these men was recorded as they reported; tours of duty in Vietnam and
military classifications were obtained from service records.

�-3-

The third or control group of ten veterans contained volunteers with
no Vietnam servie and no known exposure to Agent Orange or related
chemicals. Their biopsies were obtained during otherwise necessary
abdominal operations.
Methods; Surgeons removed 10 to 30 grams of subcutaneous fat from
the abdominal wall under local anesthesia in the case of the 23 "exposed"
men. A similar specimen was removed during operation from each of the ten
"unexposed" controls. Precautions were taken before during and after the
procedure 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 to the assay laboratory.
The methods of extraction, gas chromatography, and mass spectrometry
are described by Gross (8) who performed the analyses. As he reports
a second laboratory assayed 15 of the 23 specimens using a somewhat
different technique; only Gross1 results are considered here in order to
maintain uniformity of the method used for all volunteers. The assays in
both laboratories were performed without knowledge of which specimens came
from "exposed" and which from "unexposed" men.
Each of the volunteers had a medical history, physical examination,
and routine clinical chemistry.

The clinical data were reviewed, seeking

correlations between them and the assay results. The details of military
service in Vietnam from the volunteer's report and his service record were
examined to evaluate his exposure to Agent Orange using the dates,
location, and nature of his service. From these a rough estimate of the
likelihood of exposure was made without knowledge of the assay results.

�-4-

Results; The assay results are reported in Table I. Details and
comparisons with those from the second laboratory are given by Gross (8).
Where the assay is indicated as negative despite an apparently detectible
amount of TCDD, the chemist was unable to confirm the identity as 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 parts
per trillion (3 picograms per gram) above the limit of detection.
Of the twenty veterans from Vietnam, seven had no detectible TCDD
with the limit of detection at 2 to 6 parts per trillion (ppt). toother
two (numbers 6 and 8) had detectible material that could not be validated
as TCDD and the results for two (numbers 11 and 14) were considered
equivocal because the measured value was only questionably above the
detection limit. Pour of the nine remaining Vietnam veterans had TCDD in
amounts from 5 ppt to 7 ppt. Five men had TCDD in concentrations above
those of the controls. One (number 26) had 63 to 99 ppt; another (number
10) had

to 35 ppt.

Of the ten "unexposed" veterans, two had TCDD identified in their
fat; neither had more than 8 ppt. Two other veterans (numbers 17 and 32)
had values low enough to be considered equivocal and in five instances the
detected material was not validated as TCDD. The remaining veteran had no
detectible TCDD. No specimen was submitted for the assigned number 22.
Veterans were divided into three groups on the basis of exposure in
Vietnam to Agent Orange. One contained the three volunteers (numbers 10
19 and 26) who were judged to be most heavily exposed. They included
handling the defoliant amoung their duties in Vietnam. Five other
veterans judged to have had little likelihood of exposure to Agent Orange

�-5-

either because their location was removed from the areas sprayed (numbers
1, 15 and 34), because the dates of their Vietnam duty (numbers 13 and 28)
or its short duration (number 1) reduced the chances of exposure, or
because the description of exposure was questionable (number 34). The
remaining twelve Vietnam veterans appear to have had an intermediate
likelihood of exposure, i.e. between that of the other groups.
Among the most heavily exposed men, two (numbers 10 and 26) had the
highest TCDD content in their body fat but the other man (number 19) had
no identifiable TCDD. Two of the lightly exposed men (numbers 1 and 13)
had no detectible TCDD but the other three did have.
Six of the twelve men judged to have had intermediate exposure were
ground combat troops; three had TCDD in their fat, three did not. Of the
six other veterans, two had detectible TCDD and three did not; one with a
doubtful level was a helicopter gunner who described some contact with
Agent Orange.
Table II summarizes the clinical information regarding all twenty
Vietnam veterans. Seven of them (numbers 9, 13, 15, 26, 27, 29 and 30)
reported some health problems beginning during a tour of duty in Vietnam.
ND two, however, reported the same symptoms. The remaining thirteen
veterans reported no illness in Vietnam although only one reported good
health at all times. Among 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 (numbers 9, 13, 15, 30 and 34) and three had experienced
difficulties of reproduction, namely, spontaneous abortion by the wives of

�-6-

two (numbers 11 and 15) and congenital heart disease in the son of a third
(number 16).
Pour of the seven veterans who reported difficulties while in Vietnam
had no TCDD detected; the other three had 7 to 99 ppt. The five veterans
with mental problems included three without detectible TCDD and three
whose assays results were 5 to 7 ppt. One of three veterans reporting
reproductive problems had no detected TCDD, one had a doubtful level, and
one had 7 ppt. Detectible TCDD in the body fat could not be correlated
with clinical chemical findings.
Discussion; Gross (8) concluded that his assay is capable of
detecting and measuring a few parts per trillion of TCDD in human fat.
The present technique is, however, difficult and delicate and may not be
free of error. The determinations require surgical biopsy, a minor
operation, performed under conditions that avoid contamination with TCDD.
TCDD has been found in substances other than 2,4,5-T (1).

It and

closely related chemicals could have been acquired by "exposed" and
"unexposed" veterans from the civilian environment long after they left
military service. There is no known source of TCDD, however, in the
surroundings of a steel mill crane operator and student nor of an artist,
the two men with the greatest concentrations of the compound. It is
impossible to determine when, in what amounts, and from what source the
subjects could have acquired TCDD.
TCDD was found in some persons who report exposure to Agent Orange
and in others who were never in Vietnam. On the other hand, some veterans
from Vietnam had no detectible TCDD 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

�TCDD is certain and more recent than that of the veterans.
flnong the twenty Veitnam veterans there was no uniformity of
symptoms, either immediately after exposure, at the time of biopsy, or
during the intervening period. No one symptom or group of symptoms was
common to veterans with detectible TCDD in their fat. The presence of
TCDD did not mean ill health nor did its absence indicate good health. ND
detailed statistical analysis was attempted of this small pilot series.
The TCDD content in the fat was very small, not exceeding 100 ppt.
Since TCDD accumulates in fat more than in other tissues, the average body
concentration would be much lower. Even if all tissues contained 100
ppt., however, the concentration would be 0.1 microgram per kilogram of
body weight, too far below the demonstrated toxic dose to threaten health.
Conclusions; The present assay for TCDD in fat tissue does not offer
a satisfactory routine test for exposure to Agent Orange, providing
neither clear evidence of contact with that specific defoliant nor of
absence of such contact. The assay technique is difficult and not readily
available, fat samples must be obtained by surgical biopsy, and the source
of any TCDD 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.

�-8-

References;
(1) Young, A.L., J.A. Calcagni, C.E. Thalkan, and J.W. Tremblay, The
Toxicology, Environmental Fate and Human Risk of Herbicide Orange and
its Associated Dioxin. USAF OEHL Technical Report TR-78-92(1978).
(2) Gasiewicz, T.A. and R.A. Neal, Fed. Proc. 37(3):501(1978).
(3) Reggiani, G., The estimation of the TCDD toxic potential in the
light of the Seveso accident. Presented at the 20th Congress of the
European Society of Toxicology, West Berlin (1978).
(4) Commoner, B.,

Hosp. Pract. 13(6):56(1978).

(5) Rose, J.Q., J.C. Ramsey, T.H. Vfentzler, R.A. Hummel and P.G. Gehring,
Tox. and Appl. Pharmacology 36:209(1976).
(6) Gasiewicz, T.A. and R.A. Neal, ibid. 51:329(1978).
(^) Exposure, Toxicity and Risk Assessment of 2,4,5-T/TCDD. Element
Associates Document prepared for Environmental Protection Agency Vol. 1, pages 1-36(1980).
(8) Gross, M.L., J.O. Lay, P.A. Lyon, D. Lippstreu, N. Kangas, R.L.
Harless, and A. E. Dupuy, Jr., In press (1981).

�-9-

Table I. TCDD in Human Fat Samples (after Gross (6))

Veterans with Military Service in Vietnam
TCDD

TCDD Cbncentration

Subject

Presence

(parts per trillion)

1

Neg.

6

TCDD

TCDD Cbncentration

Subject

Presence

(parts per trillion)

nd (5)b

28

Pos.

7 (5)

Neg.a

5 (3)

29

Pos.

13 (5)

8

Nsg.a

5 (3)

30

Neg.

nd (3)

9

Neg.

nd (3)

34

Pos.

5 (3)

10

K&gt;s.

12 (2)

Air Force Officers

16 (4)

2

Pos.

5 (2)

35 (9)

3

Neg.a

4 (1)

23 (4)

4

Pos.

6 (2)

11

Dfl.c

3 (2)

12

POS.

9 (3)

5

Neg.a

4 (4)

13

Neg.

nd (2)

7

Neg.d

3 (2)

14

Dfl.

4 (3)

17

Dfl.

4 (3)

15

Pos.

7 (4)

18

Neg.

nd (4)

16

Neg.

nd (4)

20

Pos.

5 (4)

19

Neg.

nd (3)

21

Neg.d

6 (3)

24

Pos.

5 (3)

23

Pos.

8 (2)

25

Pos.

12 (4)

31

Neg.d

7 (4)

26

Pos.

63 (6)

32

Dfl.

4 (4)

99 (10)

33

Neg.d

14 (7)

27

Neg.

nd (6)

Veterans with Military Service Ouside Vietnam

�-10-

a. Cannot be considered positive (Pos.) because of poor validation
(substance detected probably not TCDD) and contaminant removed on
repeat analysis.
b. "nd" means "not detectible". Value in parentheses is limit of
detection of TCDD.
c. "Doubtful" (Dfl.) indicates that result would be considered positive
at 2.5:1 signal: noise ratio negative at 3:1 ratio.
d. Cannot be considered positive because of poor validation (substance
detected probably not TCDD).

�TABLE II. SUMMARY OF CLINICAL INFORMATION

SUBJ:
1

6

Non-Service
Exposures

Immediate
Symptoms

Intermediate
Health

Chlorine; chemotherapy; radiation

None given*a' Temperoparietal

Radiation tonsils 1950

None given

Current Symptoms

None

tumor; "kidney
condition"
Acoustic tumor

Findings
and/or
Diagnoses
Malignant
astrocytoma-1976

Headaches; facial
pain

Acoustic
neuroma 1979;

thyroid
nodule 1976

8

Alcohol ,

None given

No reported
difficulty

Ulcer after cut

Numbness &amp;
tingling

Rhinitis; "back
condition"

Numbness, tingling;

cocaine, marihuana use
9

None fo)

Chronic
ulceration
of finger

Hostility;
fatigability; fever; abdominal

"psychiatric &amp;
sexual problems"
10

None

None given

Back pain; otitis

tenderness
pharyngeal
edema

"Stomach condition"

Plantar
wart

Intermittent chest
pain &amp; dyspnea:
urinary frequence infertility

None

None

Butterfly
rash on
face &amp;
forehead

media; wart

11

None

None given

Wife aborted at
3-4 months

12

None

None given

Butterfly facial
rash after
alcohol or
anxiety as before
Vietnam

(a) "None" indicates that record states a negative reply
(b) "None given" indicates that record indicates neither positive or negative reply

�TABLE II. SUMMARY OF CLINICAL INFORMATION

SUBJ:

Non-Service
Exposures

Immediate
Sjymptoms

13

Heroin for 3 yrs
4 yrs ago

Plantar
warts

14

Farm and photographic
chemicals; lawn
fertilizers

15

Intermediate
Health
Mastectomy for
gynecomastia 1978

Findings
and/or
Diagnoses

Current Symptoms
Swollen lids &amp; red
conjunctiva; nervousness; tingling of
fingers &amp; toes;
periodic weakness

Jumpy; small
non-tender
axillary
nodes

None given*b' Kidney stone 1975; pleurisy &amp;
pneumonia; PPD
pos. - 1969;
blood in stools

Chest pain; forehead
cyst; lipoma; mole;
hernia

Sarcoidosis;
inguinal
hernia; lipoma; cyst

Cleaning agents;
heavy alcohol
use

Rash on
Nervousness; wife
legs; occa- aborted; "nervous
breakdown" - 1972
sional
diarrhea;
"jungle rot"
of toe-nails
&amp; groin

Recurrent extermity
swelling; "nerves";
rash

Schizophrenia;
cnychomycosis;
pigmented
areas on
legs

16

None (a)

None given

Son-congen ital
heart disease 1971

Dry cough; foot problems since service

Lt. great
toe contracture; tenia
pectis

19

None

None given

No statement

Painful leg edema
veins

Varicose
veins

24

Heroin until
3 yrs ago

None given

Painful knee &amp;
leg swelling
after exercise

Groin pain; low back
pain

Hemorrhoids;
palpable
liver;
hernia

25

Insecticides

None given

Recurrent dry
patches on back
&amp; shoulders;
peptic ulcer

Pain, swelling left
knee, post-traumatic

Arthritis;
chronic
cholecystitis; fatty
liver; hypertension;
tenia versicolor

(a) "None" indicates that record states a negative reply
(b) "None given" indicates that record indicates neither positive or negative reply

�TABLE II. SUMMARY OF CLINICAL 1OTOPMATION

SUBJ;

Non-Service
Exposures

Immediate
Symptoms

Intermediate
Health

Findings
and/or
Diagnoses

Current Symptoms

26

None(a&gt;

None given^) Crampy abdominal
pain; allergy to
fish &amp; IVP dye

Severe rectal itch;
occasional generalized skin itch

Pruritis
ani;
possible
urticaria

27

None

Tingl ing,
swelling of
hands &amp;
feet; insomnia from
pain

Tingling of fingers &amp; toes
hematemesis; back
pain

Reynaud-like reaction; weakness of
extremities

Stiff fingers &amp; toes
bilateral
limp

29

None

None given

Amoebic dysentery; Early morning weakpluerisy in
ness, normal by
Vietnam; "weak"
evening
before discharge;
hypertension at
discharge; crampy
abdominal pain "Polycystic kidney"

30

Primary light
oils, benzene
toluene, etc.

Cough,
asthma made
worse

Nervousness

34

None

None given

Multiple, general- Chronic anxiety;
ized lipomata
dyspnea; blurred
vision; palpitations;
chest pain, stomach
pain; facial flushing; infraorbital
"water blisters";
hypertension

Duodenitis;
marginal
hypertension

Intermittent pruritic Expiratory
rash on flexor sur- rhonchi
face of arms
Abdominal
nodules
(possible
lipomata)

(a) "None" indicates that record states a negative reply
(b) "None given" indicates that record indicates neither positive or negative reply

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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>Lee, Lyndon E.</text>
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