1
15
86
-
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
094
Folder
The folder containing the original item.
2384
Series
The series number of the original item.
Series IV Subseries IV
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Source
A related resource from which the described resource is derived
Settimana 3
Date
A point or period of time associated with an event in the lifecycle of the resource
1984-03-01
Title
A name given to the resource
Il Verde Degli Alberi Lungo Vai Vignazzola
Subject
The topic of the resource
health studies
ecological recovery
-
https://www.nal.usda.gov/exhibits/speccoll/files/original/cad3267cb5be106cd2eadd6b51b80537.pdf
144a9fe99edccaec58d3ce77c9e660f3
PDF Text
Text
ItomD Number
°2292
Author
Corporate Author
Report/ArtlGlB TltlB Form: BSOB Medical Surveillance, NYS Department of
Health
Journal/Book Title
Yeer
Month/Day
Color
Number of Images
D
6
Dascrlpton Notes
Thursday, September 20, 2001
Page 2292 of 2293
�7
BSOB MEDICAL SURVEILLANCE
NYS Department of Health
Section II.
Interval History
Patient's Name_
ss#
Employer
Date of Birth:
Date of Exam:
During the past 8 or 9 months, since your first exposure to the Binghamton State
Office Building (BSOB) after the fire, (Feb. 5, 1981), have you have any of the
following:
YES
NO
UNKNOWN
(If yes, provide specific
details on comment page)
1.
Excessive weight loss (10 Ibs. or more)
2 . Excessive weakness
3.
Changes in coloration of the skin
p
D
D
Itching of the skin
4.
a
5 . Thickening or scaling of the skin
f 6 . Acne
7.
Inflamation of sweat glands
8.
Rash or dermatitis
9 . Headaches
10.
Dizziness
11.
Discharge or infection of the eye
12.
Swelling of eyelids
13.
Burning or pain in eyes
a
D
a
p
p
14 . Changes in vision
15.
Frequent coughing
16.
Trouble with breathing
17.
Heart trouble
18.
Loss of appetite
19.
Pain in abdomen
20.
Nausea or vomiting
21.
Changes in bowel habits
Jaundice
Hepatitis or liver problems
CC-323
a
a
P
a
p
a
a
D
Q
P
a
a
a
a
a
a
a
a
a
p
p
a
a
a
P
n
p
a
p
a
a
a
a
a
a
a
D
D
D
a
a
a
a
a
D
d
a
a
D
p
p
p
a
a
�ss#
Patient's Name
Interval History (continued)
YES
NO
UNKNOWN
(If yes, provide spec ifi
details on comment page
24.
Trouble with urination
25. Abnormality in menstrual cycle
(female only)
26. Pregnancy (females and wives of male workers)
27. Difficulty becoming pregnant
(females and wives of males)
^ 8
2 . Numbness in the extremities
29. Muscle pain
>^30.
Clumsiness of movement
31. Hearing difficulties
32.
Nervousness or sleep problems
33.
Cancer of any type
34.
Other noteworthy symptoms or illnesses
Please specify
•
BSOB - DOH p.2
CC-323
D
Q
n
a
n
a
n
D
a
P
D
a
a
a
a
D
a
LJ
a
a
a
D
r•*»
D
n
n
n
a
D
a
n
D
a
�SS#
COMMENT PAGE
Patient's Name
(1) Complaint Number
(2) Describe the Complaint in Greater Detail
(3) Duration of Complaint
From
(Month
-
(4) Was Patient Seen by a Physician
To
Year)
Yes
N
(Month
Year)
n °n
If yes -
A. Name of Physician
B.
Physician's Address
C.
Was a Diagnosis Established
Yes
No
If yes, what was the Diagnosis
D. Was Patient Hospitalized
If yes, Name of Hospital
Addre s s
Date of Admission
BSOB - DOH - P.3
CC-323
Yes
No
Don ' t Recall
�BSOB MEDICAL SURVEILLANCE - DOH
Section III.
PHYSICAL EXAMINATION
Patient's Name:__
Employer:
.. - ;
-
_Social Security #:
,
Date of Birth:
Date of Exam:
(a) Height (in.)
(b) Weight (Ibs.)
(d) Pulse
(e) Resp.
(f) BP
(g) Visual Acuity R
General Appearance:
Nl
d
(c) Temp.
or Distressed
Female { jWhite
Black
[]
~ Other
Skin - specify-if the following are present
Yes No
Yes No
a. Erythema
P.
g. Hyperpigmentation D
Q
D
b. Rash
h. Thickening
Q
P
D
c. Acne-like lesions D
i. Nail discoloration p
P
D
'd. Depigmentation
Q
p
j. Jaundice
m
e. Inclusion cysts
k. Spider angiomata p
D
D
f. Petechiae
Q
j-j
1. Ecchymosis
p
nu Other
p
Spec i fy:
•
Abn
n
a
a
a
a
If yes for a-m, specify location
and describe in detail:
Nl
n
Abn
n
4. Eyes Yes
a. Conjunc. injection
b. Eye discharge
c. Swelling of lids
d. Abnormal pigment
e. Other
n
Nl
n
Abn
5.
Liver and Abdomen
a. Hepatomegaly
b. Tenderness
c. Other masses
BSOB-DOH- p-4
CC-323
P
P
P
P ..
P
No
P
P
P
P
P
Yes
No
P
P
P
P
P
P
Specify:
cm. liver span
Specify:_
�Physical Exam (Continued)
Patient's Name
NL
D
a
a
Social Security #
Abn
C3 6
Neurological
a
a
a . Gait
b. Muscle strength - specify if decreased:
'Yes
No
I.
Distal wrist extensors
Q
Q
II. Ankle/toe Dors/Flexors
III. Deltoids
D
IV.
Hip Plexors
D
V.
Hip Extensors
Abn.
c . Abnormal movements
Specify :
Abn
a
a
a
n
D a
a a
R
R
R
R
a
a
a B
a L a
a
p .* n
L 0
L "Q
d . Coordination
fl n
a P
R
Specify:
Nl
Abn
a
Q
e. Reflexes: Biceps, Triceps, Patellar, Achilles, Bafoinski
indicate on diagram (0-absent, 1-sluggish, 2-*ctive,
3-very active, 4-clonus)
Nl
Abn
f,
P
a
Sensory system - specify if decreased
I.
II.
III.
IV.
No
Cranial nerves - specify any abnormalities
Nl
a
Yes
Touch
P
Pin Prick
D
Vibration (ankle)
Q
Position (great toe) m
If yes for I-IV, . specify
location
DDDD
'
Q
BSOB-DOH- p-5
cc-323
Ra
R a
R
R a
a
sfi
L
LD
n
�Patient's Name
.
Social Security #:
Physical Exam (Continued)
Nl
I—I
Abn
I—i 7. Head and neck - specify abnormalities:
I—I
i—I
8
D
CH
9>
D
D 10.
j~J
Q 11. Heart
Q
[D 12. Back
CD
D 13. Extremities
' *}odes
leasts
Lungs
14. Genitalia
(pelvic exam, optional)
15. Rectal
Yes
No
D
D
D
D
16. Recommendations and/or referrals
D
D
b.
"
c
Examiners,Signature
Comments:
BSOB-IDOH p,6
CC-323
�
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
090
Folder
The folder containing the original item.
2292
Series
The series number of the original item.
Series IV Subseries II
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Form: BSOB Medical Surveillance, NYS Department of Health
Subject
The topic of the resource
BSOB
PCBs
health studies
survey
-
https://www.nal.usda.gov/exhibits/speccoll/files/original/9a40182060c8221148d270c09a67141c.pdf
6d25ad4eae1cc8b2c351e8e150ee996c
PDF Text
Text
Item D Number
02291
Author
Corporate Author
Report/Article TltiO
Form:
Binghamton State Office Building PCB
Screening, [nd]
Journal/Book Title
Year
Month/Day
Color
Number of uneoes
D
5
Descrlpton Notes
Thursday, September 20, 2001
Page 2291 of 2293
�BINGHAMTON STATE OFFICE BUILDING
PCS SCREENING
()
1
Record # JJ_ J_
(2) Card # J__ J_
1 2
(4)
3
Date: Mo.
Day
(3) ID #
4
Yr.
9 10
11 12
__
;
5
6
7
8
(5) Exposure Status
13 14
15
I WOULD LIKE TO BEGIN BY ASKING YOU SOME BASIC QUESTIONS ABOUT YOURSELF.
BACKGROUND INFORMATION
(6)
Name
(7)
Soc. Sec.
(8)
Home address
(9)
Home phone:
ft
^
16 17 18 19 20 21 22 23 24
(10)
Work address
(11)
Work phone
(12)
Employer
(13)
Job title
(14)
Job description
(15)
Date of birth Mo
Code
25 26 27
Day
28
(16)
29
Yr.
30
31
32
33
Marital Status (read choices to respondent)
1 » Currently Married
2 = Currently Divorced 3 => Currently Separated
4 =* Currently Widowed 5 « Never Married 8 = Don't Know (DK) 9«=No Response (NR)
34
(THE INTERVIEWER COMPLETES THE NEXT TWO QUESTIONS C16 and 17) WITHOUT
ASKING THE RESPONDENT.)
(17)
Sex 1 = Male
2 =» Female
35
(18)
Race 1 • White
2 « Black
3 « Hispanic
4 - Other
36
THE NEXT SET OF QUESTIONS DEALS WITH YOUR ACTIVITIES IN OR
AROUND THE BSOB AT THE TIME OF THE FIRE (FEBRUARY 5, 1981)
AND AFTERWARDS.
�EXPOSURE
(If yes, complete below.
( 9 Were you in:
1)
Total f
of Times
88=DK 99=NR
1 = Yes 2 = No
8 = Don't Know (DK)
9 =>. No Response ( R
N)
(a) The BSOB (including
its basement and
37
sub-basement)
Q
H
(b) City Building
(including its
basement and
sub-basement)
57
If nof DKf or NR, skip to 20.)
Total #
of Hours
888=DK 999=NR
000=Less than 1
First Date
Mo. Day ?r.
88=DK 99=NR
Last Date
Mo. Day Yr.
88=DK
99=NR
Code
Activities
38 39
40 41 42
43 44 45 46 47 48
49 50 51 52 53 54
55 56
58 59
60 61 62
63 64 65 66 67 68
69 70 71 72 73 74
75 76
(ID)
Keypuncher - Start new card: 0
1
( ) County Building
c
(including its basement s sub-basement)
1
2
0
3
2
4
5
6
7
8
10 11
12 13 14
15 16 17 18 19 20
21 22 23 24 25 26
27 28
30 31
32 33 34
35 36 37 38 39 40
41 42 43 44 45 46
47 48
(d) Garage
29
Level
1
2
3
4
(Ask e only if answers
a through d are no.)
.st
= 1s"" Floor (Ground)
= Basement
= Sub-basement .
» Combination
8• = DK
(e) Only exposed to
materials outside
the buildings
50
51 52
53 54 55
56 57 58 59 60 61
49
9 = NR
62 63 64 65 66 67
68 69
�ID
- 3-
(If respondent was in BSOB, complete below.
(20)
If not, skip to 23.)
What sections of the BSOB were you in?
Floor
19=»Base
88»DK
Boom/Location
Code
20«Sub-B.
99=NR
(a)
70 71
72 73
74 75
76 77
(b)
(ID)
Keypuncher - Start new card:
0
1
1
2
0
3
3
4
5
6
7
8
(0
11 12
9 10
(21) Did you wear protective gear while you were in the BSOB?
1 » Yes
2 - No
8 « DK
9 » NR
13
(If yes, complete below. If no, DK, or NR, skip to 22.)
Code
(a) Type of gear:_
1415
(b) How often did you wear this gear while in the BSOB? (Read choices to respondent.)
1 = Always
2 « Usually
3 « Sometimes 4 = Rarely
8 = DK
9 « NR
16
(22)
Additional information regarding possible routes of exposure would also
be helpful... For example, despite protective gear or other precautionary
measures, do you believe that you may have been exposed for any reason
through the:
1 = Yes
2 - NO
8 » DK
9'» NR
(a) Skin
17
(b) Oral
18
(c) Nasal
19
(d) Eyes
20
Specify:
(e) Other
21
�- 4-
(23)
ID
Did you have any chemical exposures prior to the BSOB fire?
1 « Yes
2 • No
8 - DK
9 « NR
_^
22
(If yes, complete below. If no, DK, or NR, skip to 24.)
Code
Type of Exposure
23* 24
Earliest Yr.
of Exposure
88-DK 99-NR
Latest Yr.
of Exposure
88-DK 99-NR
2T26
(24)
27 28
Have you had any chemical exposures outside the BSOB since the fire?
1 » Yes
2 • NO
8 « DK
9 « NR
29-
(If yes, complete below. If no, DK, or NR, skip to 25.)
Code
Type of Exposure
30 31>
Latest Date
MO
of Exposure
88*DK 99«NR
(25)
Day
32 33
Yr. __,
34 35
36- 37'"
IN ORDER TO COMPLETE OUR STUDY, I ALSO NEED SOME INFORMATION CONCERNING YOUR
MEDICAL HISTORY AND HEALTH HABITS.
MEDICAL HISTORY
Before the time of the BSOB fire, did you have any of the following health
problems?
1 = Yes 2 » No
If yes, complete below. If no, DK, or NR, skip to 26.)
8 « DK
9 • NR
Date of Dx
Code
Specify
Month Year
88=DK 99=NR
(a)
Tumor or Cancer
38
55 56 57 58
59 60 61
63 64 6 " 66"
5'
67 68 69
70
(e)
51 52 53-
62
(d)
47 48 49 50
54
(c)
43 44 45
46
(b)
39 40 41 42
71- 72 73 74
Ts 76~77
Liver Problem
Neurological
Problems
Skin Problems
Unusual loss
of wt. of 10
Ibs. or more
Keypuncher - Start new card: £_ 1__ 0_ 4_
1 2 3 4
(f)
5 6 7 8
Code
Other medical
problems
10 11 12 13
�- 5-
(26)
ID _
Do you take any drugs or medication on a regular basis?
1 <» Yes
2
9
8 m DK
No
NR
Code
17
18 19 20
If yes, specify:
(27)
Do you have any allergies?
1 » Yes
8 - DK
2
9
No
NR
,2.1
If yes, specify5
HEALTH HABITS
(28)
Have you ever smoked any of the following tobacco products?
(If yes, go to corresponding section of 29. jf no, DK, or NR, skip to 30 )
1 = Yes 2 • No 8 • DK 9 « NR
(b) Cigars
(a) Cigarettes
(29)
(c) Pipes
26
25
27
Do you currently smoke:
(If yes, complete below.
Amount
If no, DK, or NR, skip to 29.)
00 - Less than 1
*• of Years
Cigarettes/Day
31 32
29 30
1 » Yes 2 » No
8 = DK 9 - NR
(a) Cigarettes
28
Cigars/Day
(b) Cigars
33
34 35
36 37
39~ 40
41 42
Bowls/Day
(c) Pipes
38
(If response is a fraction, round u£ to nearest whole number.)
(30)
Have you ever used any of the-following"alcoholic beverages?
1 » Yes 2 • No
(a) Beer
8 « DK 9 = NR
(b) Wine
43
(31)
44
(If yes, go to corresponding section of 31%)
(If no, DK, or NR, skip to 3ZJ
(c)Liquor/
Mixed Drinks
45
Do you currently use:
1 - Yes
8 « DK
2 » No
9 a NR
(a) Beer
46
(b) Wine
(If yes, complete below.
-amount
00 == Less than 1
12 oz Bottles, Cans ;
or Glasses/Wk
47 48
If no, DK, or NR, skip to 32)
# of Years
49 50
4 oz Glass/Wk
51
(c) Liquor/
Mixed Drinks 56
52 53
54 55
57 58
59 60
Drinks with ih oz
liquor/wk
(If respondent is a fraction, round up to nearest whole number.)
(32)
THIS CONCLUDES OUR INTERVIEW.
THANK YOU VERY MUCH FOR YOUR TIME AND EFFORT.
DO YOU HAVE ANY QUESTION I MAY HELP YOU WITH?
�
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
090
Folder
The folder containing the original item.
2291
Series
The series number of the original item.
Series IV Subseries II
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Form: Binghamton State Office Building PCB Screening, [nd]
Subject
The topic of the resource
BSOB
PCBs
health studies
survey
-
https://www.nal.usda.gov/exhibits/speccoll/files/original/d3ad60c02d08d45495a8b3d816e69edb.pdf
1c4c57e8cebd8897224e5f04911b2618
PDF Text
Text
Rom D Number
0229
Author
Silbergeld, Ellen K.
°
Corporate Author
Rnnnrt/Artlnln Tltta Typescript: Affidavit of Ellen K. Silbergeld, November
M
14, [1984]
Journal/Book Title
Year
Month/Day
Color
Number of Images
D
5
Descriptor) Notes
Thursday, September 20, 2001
Page 2290 of 2293
�AFFIDAVIT OF ELLEN K. SILBERGELD
Comes now Dr. Ellen K. Silbergeld who states as follows
under penalty of perjury:
1. In this Agent Orange litigation, I have previously had
the following involvement. I have prepared and reviewed an expert
summary which was filed with the Court concerning the substance of
my proposed testimony and certain supplements thereto.
a deposition in New York City on March 18 and 19, 1984.
I have given
I have also
prepared a 13 page affidavit which was an exhibit to Opt-Out Plaintiffs' Opposition to Defendants' Motion to Dismiss, or in the Alteri
native, for Summary Judgment. I wish to incorporate those statements,
testimony and affidavit by reference.
The matters set forth there-
in are all true and correct to the best of my personal knowledge.
2.
I understand that the primary focus of the government's
motion to dismiss is in the area of reproductive toxicity. This is
my particular field of specialization as a scientist, and I have devoted substantial professional time and effort in the area of the
reproductive toxicity of polycyclic halogenated hydrocarbons, of
which dioxin is a member.
3. Epidemiological/statistical evidence is related to the
understanding of facts in the case of an individual to the extent
that it can be demonstrated that the individual shares the characteristics (and exposures) of the epidemiological group (cohort) for
which the statistical evidence was derived.
This is the case in all
issues of medicine and science, and hence all such issues share this
common characteristic.
�4.
The criteria first enunciated by Bradford Hill for
determining the acceptability of epidemiological data are (1) replication, (2) strength of association, (3) temporal relationship,
(4) specificity, and (5) biological plausibility. Using these criteria as guides, it can be posited, based upon the data known and
available to date, that Agent Orange causes the diseases and effects
alleged by plaintiffs, particularly with respect to birth defects.
5.
In the area of replicability, there are as yet relative-
ly few studies.
However, it is worth noting that data from Seveso
(Bisanti, in press) are consistent with the CDC 1984 study and with
the Ranch Hand study.
All three studies report increases in certain
birth defects, notably minor malformations (including hemangiomas)-,
spina bifida, and cleft palate.
The Australian study is not apparent-
ly consistent with these findings; however, there was no attempt by
the Australian study to determine likelihood or intensity of dose,
so that it is very likely (based upon information from the Royal
Commission) that unexposed veterans were included in the exposed
group.
This would render any conclusions reached by the Donovon
study suspect and weak.
There also appears to be an excess of neo-
natal deaths reported in both the Ranch Hand, CDC, and Serveso
data.
6.
In the area of strength of association, there is not
presently a great deal of reliable information due to the absence
of quantifiable exposure data.
In the occupational studies, there is
insufficient evidence as to dose, incomplete collection of subjects
(Dow study), or insufficient numbers (Czech study; Seveso; Nitro
-2-
�study).
Strength of association is usually demonstrated as a func-
tion of dose response relationships.
There is some qualitative evi-
dence for dose response in the CDC study, but the absence of quantifiable exposure data is a definite obstacle here.
7.
In the area of temporal relationship, there is again
little data, but, what data there is from the Ranch Hand study, from
the CDC study and from some of the Seveso data are consistent with
temporal logic. The Ranch Hand II study looked at some veterans
before and after Southeast Asian service.
In this group, it could
be seen that there was an increase in the incidence of several malemediated reproductive effects, including anomalies.
The Seveso
study has also reported an increase in hemangiomas after the exploi
sion, an increase which has now been reversed after the passage of
additional time. (Bisanti).
The CDC study remarked, but did not de-
tial, that,in exposed veterans' families, there was a much higher
incidence of more than one child with a birth defect.
8.
In the area of specificity, there exists some of the
strongest reproductive toxicity data, although it has not been appreciated. No study has found that Agent Orange or dioxin exposure
in other circumstances increases the rate of all birth defects or
all types of reproductive toxicity.
Instead, the positive studies
(noted above) have found increases in only a few types of defects.
This is strongly suggestive of specificity and of a specific toxic
agent.
9.
In the area of biological plausibility, there is sub-
stantial evidence for male-mediated birth defects, miscarriages, toxic
-3-
�exposures, and other unfavorable outcomes expressed in children.
Dr. F. Stanley's statement for the Austrailian Royal Commission discusses such hypotheses in considerable detail. These include (1)
gametotoxic effects, (2) genetic effects, and (3) secretion of dioxin in seminal fluid. While this
latter possibility is dismissed
by Dr. Stein in her affidavit, it is known that lead can be secreted in seminal fluid, and Robaire's group at McGill is studying the
effects of seminal fluid cytostatic drugs on pregnancy outcome.
One
of the positive findings of the CDC study is of particular importance here:
the increase in childhood cancer in children of the .
exposed veterans.
Male exposures (occupational) have been demon-,
strated to be associated with increases in childhood cancers (Kantor,
and others).
To my knowledge, no other study has looked for child-
hood cancer specifically, although in Ranch Hand II the causes of
neonatal deaths are not described, the similarity between it and the
CDC study in this regard is striking.
10. Thus, looking purely at epidemiologic criteria, it can
be said that the two major United States studies of Vietnam veterans
document and add to the growing body of knowledge that dioxin exposure can and did cause adverse reproductive outcomes.
It is true
that there are gaps in our knowledge, but those gaps do not present
obstacles to the formulation of reasonably-based scientific opinions
on causation.
The major gaps are in the areas of strength of asso-
ciation and temporal relationship.
below.
-4-
The reasons for this, I address
�11.
As I noted above, there are frustrating gaps in our
scientific knowledge of the reproductive toxicity of dioxin.
Those
gaps are due to the failure to determine, monitor and record for posterity the amount of exposure of individual veterans at the time of
exposure.
The gaps are also due to the failure to test the exposed
servicemen for the presence of dioxin or its effects in their bodies
at and/or shortly after the time of their exposure, the failure to
keep meaningful medical records of post exposure symptoms, signs,
conditions, illnesses and diseases, and the failure to test the
Agent Orange product in animals and other lower forms of life prior
to spraying.
12.
Those failures to obtain and record pertinent data -
doomed scientific analysis to uncertainty and inconclusiveness in '
large part.
It is only by testing epidemiologically for specific
outcomes based upon refined exposure data that cause and effect relationships can be elucidated clearly.
The absence of such data here,
however, does not prevent the formulation of reliable, validly-based
scientific opinion as to causation ; it only makes the testing of such
hypotheses and the interpretation of available data more difficult.
13.
Nonetheless, the fact remains that there is reasonable
scientific data available upon which to formulate a valid opinion
that dioxin was the cause of adverse reproductive outcomes in children of servicemen exposed to it in Vietnam.
Ellen K. Silbergeld*
ELLEN K. SILBERGELD
*Dr. Silbergeld is presently out of the country as this
typed in final form (11/14). It was read to her in its
the evening of 11/13 and she approved it. The original
to her for signature and delivery to the Court upon her
this country.
_5_
affidavit is
entirety on
will be sent
return to
�
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Title
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Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
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Box
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090
Folder
The folder containing the original item.
2290
Series
The series number of the original item.
Series IV Subseries II
Dublin Core
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Creator
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Silbergeld, Ellen K.
Title
A name given to the resource
Typescript: Affidavit of Ellen K. Silbergeld, November 14, [1984]
Subject
The topic of the resource
BSOB
dioxin
congenital birth defects
health studies
-
https://www.nal.usda.gov/exhibits/speccoll/files/original/c2c00f58fb4fdfa7f0fc2780aaf14d95.pdf
d35a4b78d3f7300ed12152d0000b90e0
PDF Text
Text
Item e Number
02233
Author
Fitzgerald, Edward F.
Corporate Author
Report/Article Titto Typescript: Summary of Binghamton State Office
Building Medical Surveillance Program: Design and
Implementation, [nd]
Journal/Book Title
Year
Month/Day
Color
Number of Images
D
5
Descrlpton Notes
Thursday, September 20, 2001
Page 2288 of 2293
�SUMMARY OF BINGHAMTON STATE O F F I C E B U I L D I N G MEDICAL SURVEILLANCE PROGRAM:
DESIGN AND IMPLEMENTATION
Prepared by Edward F. Fitzgerald, PhD, and Susan" J. Standfast, MD, New
York State Department of Health
Protocol
A plan was established in June, 1981, to help assess the health consequences of the Binghamton State Office B u i l d i n g (BSOB) fire, which occurred
on February 5, 1981. It was proposed to extend and follow-up p r e l i m i n a r y
efforts conducted by the Broome County Health Department soon after the
fire. The New York State Department of Health administers the BSOB Medical
Surveillance Program and implements the protocol. The supervision and
d i r e c t i o n of the program, howevsr, is the r e s p o n s i b i l i t y of the National
I n s t i t u t e of Occupational Safety and Health (NIOSH).
The plan e n t a i l s a multi-stage process contigent upon an i n d i v i d u a l ' s
probable level of exposure. Anyone who entered the BSOB on or after the
date of the fire was requested to have a series of laboratory tests performed.
Physical examinations and interval medical histories were a d d i t i o n a l l y conducted on those persons who remained in the BSOB for at least 25 hours.
Laboratory tests were, al so offered as a p u b l i c service to those not in the
BSOB since the fire, but who had s i m i l a r tests performed per order of the
Broome County Health Department in February or March, 1981, because they
felt that they nevertheless may have been exposed to contaminants from the
BSOB.
The rationale for this schema is the b e l i e f that if health problems
did occur as a result of exposure to PCB, d i o x i n , or dibenzofurans released
by the fire, they would most probably be apparent among persons who actually
entered the BSOB, since contamination was largely an i n t r a - b u i I d i n g problem.
The l i k e l i h o o d of contamination should also increase w i t h duration of exposure, so the most intensive efforts are focused upon i n d i v i d u a l s who were
in the BSOB for 25 or more hours. A d d i t i o n a l consideration is being given
to a more sophisticated index of exposure, one which w i l l incorporate measures
of intensity (e.q., use of protective gear, date of exposure, floor and location of exposure) as well as duration.
The laboratory tests were performed at Binghamton General Hospital
(BGH), which is operated by United Health Services, Inc (UHS). They
involve a serum biochemistry profile of 20 analyses. Included were 1 i v e r
function tests linked to PCB exposure in the literature (e.g., SCOT and
GGPT), t r i g l y c e r i d e s , and a variety of other procedures. A complete blood
count with platelets and d i f f e r e n t i a l was also conducted. These tests are
nearly identical to those ordered by the Broome County Health Department
and performed at BGH on most of the 'program participants soon after the
fire. They w i l l provide for the examination of change in physiologic processes over time.
�The interval medical history cons i sted of the person's responses to
a nurse-administered questionnaire of 3^ symptoms which he or she may have
first experienced since the date of the fire. I l l u s t r a t i v e items included
skin rash, headaches, swollen eyelids, and other problems which may be
related to- PCB exposure, in addition to control items. The physical
examination was performed at Wilson Memorial Hospital in Johnson City by
licensed physicians board-certified or e l i g i b l e for certification in
internal medicine or family practice and employed by UHS. It focused
upon the skin, since chloracne and other dermatologic conditions have
been linked to PCB exposure in the literature. The nervous system was
also carefully examined, because PCB's may have neural and sensory effects.
The other organ systems, however, were a 1 so reviewed to complete the examination and to reassure the i n d i v i d u a l . The attending physician was encouraged to make recommendations or referrals for any conditions he detects. Referrals for dermatologic or neurologic disorders which the attending physician felt may be related to exposure to contaminants from
the BSOBweremade to specialists provided by NIOSH and the New York State
Department of Health. Al 1 other referral s were made through the workers ~personal physician.
The consulting physician for dermatologic conditions was Dr. Steven
Cohen. He is associated with the Occupational Skin C l i n i c of the Yale
University School of Medicine, and is well experienced in the diagnosis
of chloracne and other skin lesions associated with PCB exposure. Dr.
Jeffrey Ribner is a board-certified neurologist who maintains a practice
in Binghamton, and he provided neurologic consultations.
The protocol also provides for the determination of serum PCB levels.
Serum wassaved from all persons in the program and w i l l be sent to Hazelton
Raltech, Inc., in Madison, W l , a laboratory well-equipped and q u a l i f i e d in
the detection of PCB in human blood. The type of PCB under investigation
is Aroclor 1254, since this was the type contained in the transformer f l u i d
which was released, and the f ype idencified in the soot retrieved from the
BSOB for testing. Samples of serum saved from those drawn in February and
March, 1981, w i l l also be sent for analysis together with the follow-up
samples to provide for an investigation of change in serum PCB levels over
time. All samples w i l l be labelled so that the laboratory is unaware of
when they were drawn and the patient's exposure status. Control samples
w i l l be added without the laboratory's knowledge to provide q u a l i t y assurance,
and all analyses w i l l be conducted d u r i n g the same time period. This assessment of serum PCB levels w i l l provide important objective evidence of exposure, and w i l l be examined in relation to self-reported exposure, laboratory test results, and c l i n i c a l findings.
Program Participants
The most recent enumeration revealed that the target population consists
of 521 i n d i v i d u a l s (Figure 1), This total represents an increase of 42 from
the original estimate of '479. Three hundred and eighteen of this number
actually entered the BSOB during or after the fire. The remaining 203
persons were predominately those who worked in the adjacent City and County
Office B u i l d i n g s and felt that they were exposed through secondary sources.
�One hundred and eighty-five of the 318 persons who had entered the BSOB
remained there for at least 25 hours. This group included approximately
47 employees of the New York State Office of General Services who were
involved in the i n i t i a l clean-up, approximately 33 private electricians
who removed and replaced the destroyed transformer, and 48 professional
p o l l u t i o n control wo'rkers. The latter group are routinely exposed to
.toxic substances as a function of their occupation. Data w i l l be collected
from these i n d i v i d u a l s by their employer (New England Pollution Control
Company), and analyzed separately from the other persons in the program.
The effective size of the target population is therefore reduced to 473The 33 firemen who extinguished the fi.re were also considered e l i g i b l e
for p h y s i c i a l examinations. Although they were not in the BSOB for 25 or
more hours, they were exposed soon after the PCB's were released from the
transformer oil and w h i l e the chemicals were in a v o l a t i l e state. The
unique nature of their exposure warranted their inclusion in the group
receiving physical examinations.
Conduct of Examinations, Histories, and Labortory Tests
The program officially began in September, 1981, with the receipt of
budget approval for five staff positions and for maintenance and operation.
The worker l i s t s were reviewed and updated. Copies were sent to each
person's employer to notify the organization of the program and to assure
that the l i s t s were complete. NIOSH and New York State Department of
Health representatives held an informational meeting in Binghamton to
instruct the panel of examining physicians on the c l i n i c a l effects of
PCB exposure. Certified letters were sent to the workers informing them
of the arrangements and asking them to take part. The l i s t s of workers
were sent to the hospital to arrange for appointments, and the first
persons were scheduled for October 30, 1981.
The majority of physical examinations, interval medical h i s t o r i e s ,
and laboratory tests were completed by the end of January, 1982. The
numbers of examinations and h i s t o r i e s currently performed are 139, and,
for the laboratory tests, the number is 430. These totals represent
94% and 91%> respectively, of the persons e l i g i b l e for these services.
A d d i t i o n a l efforts were made to contact the non-participants and to
g a i n their cooperation. Saturday appointments have been offered to persons
who were unable to v i s i t the hospital for the necessary procedures during
the week. Seven of 14 dermatology and two of three neurology consultations have been performed. Serum samples are currently being prepared
for shipment to Hazelton Raltech for PCB analyses.
Conduct of Interviews
All persons in the program are also being interviewed. The information collected includes sociodemographic characteristics, pervious medical
problems, tobacco and alcohol consumption, medication currently used, and
a l l e r g i e s . The main purpose of the interview, however, is to gather data
concerning the exposure status of each i n d i v i d u a l . They are asked whether
�they entered the BSOB on or after the date of the fire, and if so, the
dates of their entry, the length of their stay, and their activities.
They are also queried concerning the floors of the BSOB they v i s i t e d ,
the use of protective gear, and l i k e l y routes of exposure. S i m i l a r
questions are posed concerning the surrounding C i t y and County B u i l d i n g s
and parking garage. The interview additionally contains the patient's
report of previous or subsequent chemical exposures.
This information is necessary to update, standardize, and extend
s i m i l a r data gathered by the Broome County Health Department last
February and March. Those who received physical examinations were
interviewed in Johnson City as they arrived for their examination and
interval medical history. The remaining patients are interviewed by
telephone from Albany. Approximately 250 interviews have been completed
to date, or more than 50% of those e l i g i b l e .
P u b l i c Servi ces
Copies of the results are sent to the personal physicians of the
persons in the program. The workers are sent letters asking them to
contact their physician and discuss the significance of the findings.
Informational brochures concerning the program and the health effects
of PCB's and dioxin are enclosed with t h i s correspondence. Persons
without a physician a re'referred to'the Broome County Health Department.
The New York State Health Department's Communications Office has compiled
a binder of materials relating to all aspects of the BSOB Project (cleanup, medical surveillance, environmental sampling, animal toxicity experiments, etc.), which is made a v a i l a b l e to the p u b l i c at l i b r a r i e s , the
SUNY campus, and other locations. Meetings have been held with the Broome
County Medical Society and other groups to inform them of the program.
A New York State Department of Health representative travels to Binghamton
from Albany twice a week to serve as a liason between the community and
the State Health Department and to answer quest-ions concerning the program.
Data Management and Analysis
The physical examinations, interval medical histories, and laboratory tests (including those conducted last winter by the Broome County
Health Department) have been coded, keypunched, and placed on computer
tapes. E d i t programs are being developed to detect errors in processing,
logical inconsistencies, duplicate or missing records, and other problems.
The interviews that have been completed are currently being coded and w i l l
shortly be ready for entry into the computer. A plan to analyze the
data is being developed for N I O S H , and w i l l be implemented by the New York
State Department of Health as soon as possible upon receipt,
sd
�Figure 1
Possible Exposure
(N - 521)
Exposure I n s i d e BSOB
(N = 318)
Exposure Outside BSOB
(N = 203)
L
i
Follow-up Blood Screen
Durat ion < 25 Hrs,
(N = 133)
Follow-up Blood Screen
Durat ion > 25 Hrs.
(N = 185)
Follow-up Blood Screen
Physical Exam
�
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
090
Folder
The folder containing the original item.
2288
Series
The series number of the original item.
Series IV Subseries II
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Creator
An entity primarily responsible for making the resource
Fitzgerald, Edward F.
Susan J. Standfast
Title
A name given to the resource
Typescript: Summary of Binghamton State Office Building Medical Surveillance Program: Design and Implementation, [nd]
Subject
The topic of the resource
BSOB
health monitoring
health studies
NIOSH
-
https://www.nal.usda.gov/exhibits/speccoll/files/original/d09e5018355eaded4005465213b014b7.pdf
3a158e8474d3ca4eea02973127471bbd
PDF Text
Text
Item D Number
°2287
Author
Schecter, Arnold
Corporate Author
ROpOrt/ArtlGlO TltlB Typescript: Transient Liver Pathology in Patients
Consuming Water from a Private Well Contaminated by
PCBs from a Submersible Water Pump, [nd]
Journal/Book Title
Year
Month/Day
Color
D
Number of Images
6
DOSCrlPtOll NOtBS
Typescript of article published in Chemosphere, 1987, vol.
16, no.1,pp.37-42.
Thursday, September 20, 2001
Page 2287 of 2293
�TRANSIENT LIVER PATHOLOGY IN PATIENTS CONSUMING WATER FROM
A PRIVATE WELL CONTAMINATED BY PC3s FROM A SUBMERSIBLE WATER PUMP
Arnold Schecter
Department of Preventive Medicine
Upstate Medical Canter
Clinical Campus
State University of New York
Binghamton, New York 13901
ABSTRACT
Submersible water pumps in private water wells have in some instances been found to
contain PCBs in their oil. When these pumps leak they may release PCSs into the drinking
water constituting a potential health hazard.
IHTROOUCTIOH
Since 1982, in New York State, and in Wisconsin, a number of private water wells,
usually in rural areas, have been found to be contaminated with PCBs. The source of this
contamination is thought to be submersible water pumps from several manufacturers where
PCBs were apparently, found in the oil of the pumps or in their capacitors. Although the
manufacturers deny Intentionally putting PCBs in these pumps, the presence of PCSs has been
documented by State and County Health Departments from 1982 through 1985 in Broome County
and adjacent areas in Upstate New York as well as in Wisconsin. PCB levels in drinking
water from these wells has been found to be as high as 57 times greater than State PCB
drinking water standards at this time. Whether significant health consequences occur
depends on the Ingested dose of specific PCS isomers with their usually coexisting
chlorinated dibenzofurans and less frequently coexisting chlorinated dibenzo-p-dioxins.
A medical case study with transiently elevated liver enzymes found in three members of a
family after ingestion of PCBs 1n their drinking water is presented.
FINDINGS
A family of three came to the Upstate Medical Center affiliated Faculty Practice
Occupational Medicine Clinic in Binghamton, New York, located at Binghamton General
�Hospital, with.complaints of feeling sick from documented ingestion of PCBs in their
drinking water for at least one week, with accompanying subjective, primarily central
nervous system, symptoms of discomfort, a feeling of generalized illness and "dizziness".
The family members had noted a chemical odor and a film on the water at times. A Health
Department investigation had determined that the source of PCBs and a chemical taste in their
water was a submersible water pump of a type shown in Figures 1 and 2, which had been
leaking. The pump in question, a Barnes pump from the Barnes Manufacturing Co. of Mansfield,
Ohio and Oakland, California, had detectable PCBs when tested by the State Health Depart{12}
ment.v ' ' Upon review of Health Department records, it was found that Peabody Barnes Pumps
were found to have PCSs which leaked in nine instances between 1982 and 1985. ' ' Some
pumps were found to have 2.5% PCBs in their oil, when tested by the State Health Department.
In the pump owned by the patients in this case study, there was a finding of 6.6 parts
per billion of PCBs in the drinking water. The leaking pump oil was found to have 630,000
parts per billion of PCBs. Analysis for polychlorinated dibenzofurans which so frequently
accompany PCBs was not performed.
Patients with PCS contaminated water noted bad odors, peculiar taste, a petroleum-like
taste, and a disorientation or "spaced out" feeling after drinking the water. Serum PCB
levels in the three patients followed by us, a mother, father and 12 year old son, seen
one month after the consumption of water contaminated with PCBs were quite low, below 2 ppb;
whereas serum PCB values for adults from this part of Upstate New York are usually about
5-10 ppb. The family's diet was somewhat unusual in that they usually ate "natural" foods,
usually vegetables, and also Ingested high levels of vitamins. Abnormal (elevated) liver
enzymes were found in blood tests performed on all three members of this family who ingested
the PCS contaminated water for an estimated one weak. These abnormal values, indicative of
liver damage, returned to normal levels within one month after the initial values were
documented, or two months after ingestion of water contaminated with PCBs, suggesting that
the acute injury was a transient one. No clinical or laboratory evidence of hepatitis
or drug induced liver damage was found. The patients recovered from their acute
medical problems but are being followed for possible delayed onset pathology.
New York State "Safe Drinking Water Guidelines" for PCBs is one part per billion.^
Water from wells contaminated by oil from these pumps, schematically diagramed in Figures 2,
3, and 4, have shown between .26 and 57 parts per billion, according to State records. '
Tests of the oil from the contaminated pumps have shown 630,000 to 24,000,000 parts per
billion of PCBs. Tests of the lubricating oil fn these pumps have shown that levels of
PCBs have been found in pumps more than 20 years old and as new as a 1982 model. To date
the brands of pumps Involved have been Barnes or Peabody Barnes, Reda and Myers, (2^
'
According to the Water Systems Council, Inc,, SOS of private well pumps are above
ground units and the remaining 50% are submersible units. Half are oil cooled and half
are water cooled. Census figures for 1982 describe 12,000,000 homes connected to private
wells in the U.S.A.^
By way of comparison, the U.S. Food and Drug Administration sets a 2 parts per million
PCB tolerance level for fish consumption. The P.O.A. recommends eating fish at this level
�Check valve
Radial bearing
Impellers
Pump Intake
Seal
Electric motor
Pressure equalizing tube
I Thrust and radial bearing
Fluid chamber
Fig. 2 - This schematic diagrams the internal components
of a submersible water pump.
Fig. 1 - A Health Department technician is shown holding
a PCB contaminated submersible water pump.
�\
150'OF DISCHARGE PIPE
WITH 2 - 90° ELBOWS
PUMP
Fig. 3 - A typical arrangement of a submersible water pump,
well, and pipe fixtures leading to a hone Is shown here.
�no more than once per week. ' A half pound or eight ounce serving of fish contaminated at
this limit would contain 500 nricrograms of PCBs.
win. SEAl
SlfjDC* V A L V E '
•
AI» INTAKE VAIVE !/•;.%
:.:••
if NO CHAIN is AVAIIA»U
MQTO»
\-J
Fig. 4 - This schematic depiction details the apparatus
immediately related to the pump and well.
Also, for comparison, if two liters of water at the New York state Drinking Water PCS
Guidelines are consumed for 70 years with a one part per billion PCS level this has been
calculated to lead to one additional cancer death per 10,000 persons according to State
(a)
Health Department calculations. '
Additional concern has been raised by an EPA study performed under contract by Versar,
Inc., of Springfield, VA, in 1980 which estimated that 1,100,000 wells may have PC8 capacitors in the well motors. ' This is different from the current findings of PCBs in the
oil of the motors or pumps themselves, rather than the capacitors.
�SUMMARY AND RECOMMENDATIONS
Submersible water pumps in private wells are widespread, especially in rural areas, and
may constitute a potential health hazard, especially if they contain PCSs with the usually
concomitant chlorinated dlbenzofurans and occasional chlorinated dibenzo-p-diox1ns. These
leaking pumps have been demonstrated to contaminate drinking water above levels considered
safe for human consumption, PCBs apparently were used in these pumps from at least three
known manufacturers at least in the United States without the admitted knowledge of the
l&\
presence of PCSs, except in the capacitors, by any party/ ' The extent of these contaminated pumps remain to be documented. To date the only incidents known to us are the nine
pumps 1n and around the Broome County, New York area, where the public and health department are especially sensitive to the possible presence of PCBs since the PCS, dloxtn and
furan contaminated State Office Building incident of February 1981, ' and In Wisconsin where
the Wisconsin Department of Natural Resources (WONR) has also detected PCB contamination in
private well water with submersible water pumps as the probable source. It is unclear as
to whether only the capacitors contain PCBs or whether the pump oil Itself, usually
pharmaceutical grade mineral oil, also contains PCBs. News releases to the public and a
notice to well drillers and installers have been issued 1n Wisconsin by the WONR. Further
sampling of lubricating oil from additional pumps and water from more wells 1s planned 1n
Wisconsin. However, the nationwide distribution of these pumps suggests that other Instances
will be documented when the possibility of PCB contamination exists in similar submersible
water pumps.elsewhere in the world. Because of the large number of such pumps In the United
States and worldwide, it is possible that these may constitute a potential human health
hazard. Further chemical testing of suspect pumps and water 1s Indicated and appropriate
medical evaluation of patients exposed to PCS contamination is Indicated, including routine
blood screening tests as well as blood PCB levels, serially'obtained wherever the possibility
of a transient elevation above the patient's baseline exists.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
Personal communication, Broome County Health Department.
Personal communication, Environmental Health Division, New York State Health
Department.
Mew York State Safe Drinking Water Guidelines, 1984.
The Sunday Press, Odato, J.M., July 7, 1985; The Evening Press. OdatO, J.M.,
July 8, 1985; Press & Sun-Bulletin, Odato, J.M., December 8 & 11, 1985.
U.S. Food and Drug Administration Guidelines for Consumption of PCB Contaminated
F1sh, 1982.
Woodcock, 8. and Powers, P., (Versar, Inc.), PCB Contamination of Well Water: An
Engineering Risk assessment, U.S. EPA Document EPA-570/9-SQ-OQ1, January 1982.
Schecter, A., Contamination of an Office Building in Blnghamton, New York by PCSs,
01ox1ns, Furans and Biphenylenes after an Electrical Panel and Electrical Transformer Incident, Chemosphere, 12, (4/5), 669-680, Pergamon Press Ltd., London,
1983.
�
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Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
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Box
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090
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2287
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Series IV Subseries II
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Schecter, Arnold
Title
A name given to the resource
Typescript: Transient Liver Pathology in Patients Consuming Water from a Private Well Contaminated by PCBs from a Submersible Water Pump, [nd]
Subject
The topic of the resource
BSOB
health studies
PCBs
water pollution
-
https://www.nal.usda.gov/exhibits/speccoll/files/original/166a877e1bf030dcaa423c05a3719e0b.pdf
681110039e22d9a0e4971ceb7786c4b3
PDF Text
Text
Item D Number
02269
Author
Gleit Alan
'
Corporate Author
Report/Article Tltte Typescript: Draft Summary Report of the Medical
Surveillance Program for the Binghamton State Office
Building Decontamination Project, August 7,1985
Journal/Book Title
Year
000
°
Month/Day
Color
Number oflmaflss
D
55
Doscrlpton Notes
Thursday, September 20, 2001
Page 2269 of 2293
�DRAFT
Summary Report of the
Medical Surveillance Program
for the Binghamton State Office Building
Decontamination Project
Prepared for
Versar New York, Inc.
By
Alan Gleit, Ph.D.
Versar, Inc.
P.O. Box 1549
6850 Versar Center
Springfield, Virginia 22151
Arnelle 6. Cohen, M.S.
Biometric Research Institute, Inc.
1401 Wilson Boulevard
Arlington, Virginia 22209
Kenneth H. Chase, M.D.
Washington Occupational Health Associates, Inc.
1120 - 19th Street, N.W., Suite 410
Washington, D.C., 20036
August 7, 1985
�Table of Contents
I.
Introduction
1
II.
Materials and Data Sources
2
A.
B.
Study Population
Health Data
2
2
C.
Exposure Data
4
III.
Methods and Procedures
7
A. Exposure Classification
7
B.
9
Statistical Tests
C. Methods for Reviewing Clinical Data
Statistical Results
14
A.
IV.
11
14
Descriptive Statistics
B. Correlation Analysis
16
C.
16
Cumulative Effect of Potential
Exposure
D.
Regression Analysis
19
E.
Discussion of Clinical Data
19
V.
Conclusion
24
VI.
References
26
Tables
Appendix:
Normal Ranges
�I. INTRODUCTION
As
a
result
Binghamton
State
polychlorinated
of
a
transformer
Office
Building
biphenyls
(PCBs),
and tetrachlorodibenzofurans
fire
on
(BSOB)
5
February
was
1981,
contaminated
tetrachlorodibenzodioxins
the
with
(TCDDs),
(TCDFs) apparently produced by the action
of the fire on the transformer fluid.
With the discovery of TCDD and
TCDF, the initial cleanup effort was halted, the building was shut down
as of 26 February 1981,
York
and an expert panel was convened by the New
State Department of Health on 3 April to define the conditions
under
which
clean-up
activities
building could occur.
BSOB decontamination
and
eventual
re-occupancy
of
the
The worker medical surveillance program of the
project forms a part of the health and safety
plans resulting from the recommendations of this panel.
The
purpose
threefold:
of
the
medical
surveillance
(1) to determine the medical suitability
in the BSOB cleanup,
program
has
been
for participating
(2) to periodically monitor the health status of
members of the cleanup crew, both present and future, and (3) to assess
the efficacy
values
for
of the health and safety
PCS
blood
levels
and
plan by establishing
pertinent
clinical
baseline
parameters-'-.
The objectives of this analysis are:
1.
To describe and summarize data collected during the
medical surveillance program for the cleanup of the
BSOB.
2.
To assess the health status of workers at risk of
hazardous exposure during the cleanup.
3.
To evaluate the efficacy of the protective equipment
and
safety procedures used
hazardous exposure.
to minimize
potentially
�-2II. MATERIALS AND DATA SOURCES
A.
Study Population
All persons entering
required
the BSOB as workers
to participate in the medical
participation
includes
an
entrance
or visitors have been
surveillance
examination,
program.
bi-monthly
Such
interval
evaluations, an annual examination, an exit examination and a follow-up
evaluation.
All
participants
are
identification numbers
based
project.
focuses
This
report
on
male.
their
on
Individuals
are
affiliation with
those
employees who
assigned
the overall
were
in the
building during the earliest phase of the cleanup, i.e. 29 September
1981
The
through 31 December 1983, when potential exposure was greatest.
total number
of
participants
for
whom
both exposure
data and
medical data were available during this time period is 193: 24 Versar,
23 Office of General Services, 139 Allwash contract workers, 3 Broome
County personnel, and 4 individuals designated as visitors.
The suitability of each worker
determined
at
the
entrance
to participate in the program is
examination.
Potentially
disqualifying
conditions for participation in the BSOB cleanup include:
dermatitis,
associated
liver
with
disease,
or
and
aggravated
other
by
conditions
potentially
alcoholism,
thought
hazardous
to
be
exposures.
Primary consideration was given to conditions that could interfere with
the
ability
to
use
protective
equipment
under
non-sedentary
work
conditions.
B.
Health Data
All health data are collected at the examination site, either in
Washington, D.C.
York.
or at Wilson or Lourdes
Hospital
in Binghamton, New
Blood chemistries are analyzed at one of three labs, depending
on the examination
site:
Bionetics laboratory, Wilson laboratory, or
Lourdes laboratory, respectively.
Plasma PCB specimens are split and
�-3shipped
to
each
of
the
following
labs:
Professional
Clinical
Laboratories (PCL) in Wilmington, Delaware and Biomedical Reference
Laboratories (BRL) in Burlington, North Carolina. The normal ranges
from these labs for PCB, SCOT, SGPT, GGTP, triglycerides,
and HDL cholesterol
a standard set of
Kenneth Chase of
(WOHA). Dr. Chase
cholesterol
are shown in Appendix A.
Results are recorded on
forms, as described below, and transmitted to Dr.
Washington Occupational Health Associates, Inc.
then delivers the forms, in batches, to Biometric
Research Institute, Inc. (BRI).
BRI has developed a system of processing forms that results in an
accurate and consistent data set. All forms are processed in batches.
Each batch is reviewed manually and any necessary coding is done. The
batch of forms is then keypunched and machine-verified.
After
keypunching, the data are listed by computer and data coordinators
check keypunching against the original form to identify keypunching
errors.
Errors identified in the visual check are corrected in the
computer file.
The objective of this first phase of data processing is
to ensure data are entered into the computer exactly as recorded on the
original forms by the physician.
The second phase of data processing involves computer listings of
the data to identify missing or out-of-range values. These listings
are reviewed at WOHA and
the corrected copy is returned to BRI.
Resolutions are entered into the system and the computer file is
updated. This data bank contains all available information from the
entrance, interval, annual, exit, and follow-up exams.
and
The entrance examination includes a complete medical, reproductive
occupational/environmental history as well as a comprehensive
physical
examination.
Baseline
laboratory
parameters
include
a
complete blood count with differential and platelet count, urinalysis,
chemistry profile (modified SMAC 20), chest x-ray, pulmonary function
tests, EKG, and plasma PCB level.
�-4All
participants
evaluations.
or
not
scheduled
for
bi-monthly
interval
These evaluations include a determination as to whether
there
evaluation,
are
a
has
been
any
determination
unusual
as
to
exposure
the
since
presence
the
of any
previous
unusual
or
unexplained symptoms, a determination as to the presence or development
of
any
pertinent
dermatologic
findings,
and
liver
function
'(alkaline phosphatase, total bilirubin, SCOT, SGPT, GGTP).
tests
Plasma PCB
levels are drawn on every other interval examination.
Annual examinations consist of all tests performed at the interval
evaluation plus repeat pulmonary function tests and a chest x-ray.
Exit evaluations include all of the procedures described under the
interval
evaluation
but
in
addition
include
serum
triglyceride,
cholesterol and HDL cholesterol levels and plasma PCB level.
A follow-up
examination
is performed approximately three months
following the exit examination and is identical in scope except that
plasma PCB levels are not included.
Another source of data for evaluating the potential health effects
of
participating
incident
in
reports".
the
decontamination
Workers
were
project
required
to
includes
complete
a
"medical
medical
incident report if they were feeling ill or if they felt that any of
their symptoms were potentially associated with their work in the BSOB.
The
safety
officer
on
site,
who
co-signed
these
reports,
was
responsible for noting any signs of skin contamination as well as any
other corroborating signs of illness.
C.
Exposure Data
As part of the overall health and safety plan, a comprehensive
industrial hygiene monitoring program was developed by Versar to assess
�-5contaminant control and worker exposure during the decontamination of
the BSOB.
These data are summarized and discussed in more detail in
periodic reports published by Versar2.
Industrial hygiene air samples
and
periodically
wipe
samples
have been
determine PCS levels.
surfaces
and
collected
and
analyzed
to
Sample selection sites were chosen to represent
locations inside
the BSOB with a high probability of
contamination or potential worker exposure.
According
industrial
to
Versar
hygiene
(Revised
sampling
26
January
program has
1983
indicated
report),
that the
"the
overall
level of control and containment of contamination is quite effective."
"The concentration of PCBs in the air within
BSOB
ranges
from
0.3
to
ug/m3
2.3
for
the upper floors of the
samples
with
measurable
concentrations except for one sample taken from the 18th floor men's
room in September 1982."
fire
occurred,
3
ug/m )."
A
shows
report
Only "the basement mechanical room, where the
consistently
dated
18
collected in the subbasement
higher
levels
(as
1983,
states
that
July
high
as
air
5.6
samples
area had PCB concentrations of 0.43 and
3
0.48 ug/m .
Routine wipe samples collected in selected areas depicted only one
problem area —
up
by
the floor near the wash water dump —
November
of
"samples collected
1982.
from
The
the
July
floors
contain PCB-1254 in the expected
1983
of
range
batch
the
which was cleaned
report
subbasement
states
and
that
Floor-1
of concentrations for
these
areas."
In addition, as part of a monitoring
program jointly conducted by
Versar and the New York State Health Department Center for Laboratories
and Research,
"air
times
the
within
dibenzofurans,
2,3,7,8-TCDF
samples collected
BSOB
have
been
dibenzodioxins
concentration
from
and
at 15 distinct locations and/or
analyzed
for various
o
j
biphenylenes ".
twelve
locations
chlorinated
"The
sampled
average
when
the
�-6-
building's internal air circulation system was operative was 15.0 ± 3.6
pg/m3". Eadon et al.3 developed a system for estimating 2,3,7,8-TCDD
equivalents, and determined that the relative toxicity for air samples
containing mixtures of chlorinated dioxins, furans and biphenylenes to
be equivalent to about 14 pg/m3 of 2,3,7,8-TCDD. This value was within
the range of suggested guidelines for re-entry into the building, as
established by the risk assessment of Kim and Hawley .
An additional, but unquantifiable source of potential exposure
data, is "exposure incident reports" filed by Allwash employees.
Workers were required to report all incidents of potential direct
contact with contaminated soot as well as any malfunction of their
protective equipment (e.g., tear in tyvek suit, tear in glove, or loss
of respirator seal) to the on-site health and safety officer. These
reports were then sent to Washington, D.C. where they were included in
the employee's permanent folder. It was anticipated that working in
sometimes cramped areas with bulky cleanup equipment would occasionally
result in a tear or dampening of the employee's disposable tyvek suit.
The usual procedure was to temporarily "break out" of their garmets,
undergo appropriate personal decontamination and cleaning if necessary,
and then change into a new suit and resume work. Workers were not
penalized or discouraged from filing these reports so it is felt that
this source of data is a fairly reliable means for evaluating the
efficiency of the protective equipment and safety procedures.
�— 7—
III.
A.
METHODS AND PROCEDURES
Exposure Classification
When
attempting to classify workers
by potential
occupational
exposure to hazardous substances, it is preferable to assess individual
exposure status rather than grouping employees by crude indices of
exposure, such as general job titles or place of employment.
especially
that the
This is
desirable if industrial hygiene monitoring data suggests
opportunities or routes of potential exposure differ
significantly between workers. In their initial status report for the
BSOB medical surveillance program, the State of New York and NIOSH
investigators created an exposure index score which was computed as a
multiplicative function of five factors:
location in BSOB, type of
activity, whether or not protective clothing was worn by workers,
number of hours in the BSOB, and the actual PCB air levels on various
dates in the BSOB-*. Each factor was weighted by a number reflecting
its relative magnitude, as determined from studies in the literature,
with "number of hours in the BSOB" being the most significant factor.
The feasibility of developing a similar index for workers involved
in the Versar medical surveillance program was investigated by on-site
toxicologists
and
industrial
hygienists.
The
following
factors
mitigate the ability to create a similar exposure index in this study
population:
(1) unlike the initial cleanup crew, all workers were
required to wear full-face respirators and protective clothing when in
the building in addition to taking other precautions to minimize
potential exposure-'-; (2) PCB air levels documented during this time
period (i.e., 9/81 - 12/83), were much lower than those during the
initial fire fighting and immediate cleanup phase^; and (3) although
there may be qualitative differences in the nature and opportunity for
�-8-
PCB exposure between individual workers or specific job duties, workers
in this study were known to rotate on various teams on a daily and
weekly basis and individual job assignments were not available to
confidently group workers on this basis. As part of the medical
surveillance and safety program administered by Versar, the total
number
of hours
actually
spent in the building was collected
on
everyone who entered the BSOB. After careful consideration, this
measurement was determined to be the best available indicator of
potential exposure.
Differential exposure due to type of activity is accounted for by
performing all analyses on two subsets of the population. One group
(N=129) is composed of the Allwash contract employees, workers who have
the greatest likelihood of contact with contaminated soot by virtue of
their
cleanup
activities
(e.g.
scrubbing
ceilings, vacuuming
fireproofing, etc.). The second group (N=64) is comprised of all
"other" participants in the cleanup project, namely Versar, O.G.S.,
Broome County personnel, visitors, and 10 Allwash employees working in
a supervisory capacity. The individuals
in this subset are
predominantly supervisors or short-term visitors whose exposure to
potentially toxic substances per hour spent in the building is likely
to be less than that of the Allwash employees.
Examination of the frequency distribution of number of hours in
the building indicates that reasonable cut-off points can be identified
to represent different exposure categories. The Allwash employees for
whom complete PCB data was available (100/129) were used to determine
these cut-offs.
They were then applied to the two subsets of the
population for statistical analysis.
�-9-
The
population naturally
divides itself
into three groups as
depicted in the histogram shown in Figure 1. These groups have the
following ranges: Group I, 0-400 hours; Group II, 401-979 hours; and
Group III, 980-3500 hours. These ranges hold true for the distribution
of Allwash workers, as well as Other participants (see Figure 2 and 3);
however, a substantial number of participants in the 200-500 hours
range did not have complete PCB data.
For the purpose of statistical
analyses, the "least-likely" exposure category will form Group I, Group
II will be comprised of the "less-likely" exposure group and Group III
will represent the "most-likely" exposure category. The distribution
of exposure category by study subset is depicted in Table 1. Within
each subset, approximately 50% of the population falls into the lowest
exposure category.
Table 2 shows the distribution of study
participants by job classification and exposure category.
B.
Statistical Tests
Adopting similar procedures to those utilized by the New York
State Health Department investigators, some analyses will preserve the
original scaling of hours spent in BSOB, while other analyses will
utilize the distinct exposure categorizations. The advantage of the
first approach is that it maintains the interval nature of the data
which is desirable for assessing time trends and dose-response
relationships. Categorization of potential exposure status by hours in
BSOB allows the use of group means to estimate the significance of
differences between potential exposure status, PCB blood levels, and
biochemical parameters. The data have been analyzed as follows: (1)
descriptive
statistics;
(2) correlation
analysis; (3) possible
cumulative effect of potential exposure; and (4) regression analysis.
Descriptive statistics
Descriptive statistics have been calculated to provide an overview
of the characteristics of the study population as a whole, as well as
by exposure category (as defined
above).
This
stage of
analysis
�-10includes frequency distributions of variables such as age, dermatogical
symptoms, and
history
of alcohol
abuse.
The
chi-square
test
of
association was used to assess significant differences between exposure
groups.
Plasma PCB values, biochemical parameters, and other continuous
variables being analyzed have been tested for normality.
Whenever
appropriate, log transformations of the data have been used. If
neither the original data nor the transformed data approached a normal
distribution, nonparametric methods were applied.
Correlation analysis
In order to evaluate whether potential exposure
to PCB
contaminated soot had subclinical effects on liver function, plasma PCB
levels were compared to the three most sensitive liver function tests,
i.e., SCOT, SGPT and GGTP.
The normal distribution and nonparametric
correlation coefficients between plasma PCB levels and each of these
parameters were analyzed for Allwash employees and Other participants
separately.
Correlation coefficients and probability values were
tabulated using the latest time interval possible.
Cumulative effect of potential exposure
The cumulative effect of potential exposure in the BSOB was
assessed in the following manner.
All analyses described were
performed twice: once for the subset of Allwash workers only, and once
for the subset of Other employees. This analysis compared baseline
values to values on the last exam, whether interval or exit, for each
particular subject by exposure category. Because of the small number
of Other employees, particularly in Group II, Group I and II were
combined for statistical purposes.
Ideally, Group II should have been
�-11combined with Group III, but because of the potential exposure in Group
III it was decided to report on them separately. Thus, for each
parameter considered, five distinct groups of individuals were analyzed
(three Allwash and two Other). The last visit date varies considerably
within the population; however, this method is most likely to assess
the highest cumulative dose. The null hypothesis being tested is that
the difference between the baseline and final test means in each
exposure category equals zero. The mean differences of each group were
statistically compared using paired t-tests.
Another analysis of the cumulative effect of potential exposure
evaluated possible differences in the final examination (interval or
exit) values for various parameters for the three groups of Allwash
employees
and
for
the
two groups
of
Other employees.
The
null
hypothesis being tested is that the mean level of the groups are all
equal. The analysis was performed both parametrically (Analyses of
Variance) and nonparametrically (Wilcoxon).
Regression analysis
Possible time trends in the PCB and biochemical measurements as a
function of the length of time t that individuals spent in the BSOB
were evaluated. For each participant, the final interval or exit
values were used as a proxy for the values when last in the building.
Linear regression was performed to determine
measurements were related to the time t.
C.
whether
these
final
Methods for Reviewing Clinical Data
The most reliable means of monitoring potential health effects is
prompt recognition and reporting of signs and symptoms of illness, both
by the worker himself in the form of self initiated medical incident
�-12reports (with appropriate follow-up) and by the examining physician at
the bi-monthly interval examination. This method identifies all cases
of frank toxicity as well as most cases of immediate concern, such as
grossly abnormal biochemical tests and any cases of elevated plasma PCB
levels.
As mentioned previously in the discussion of the medical
surveillance program, Dr. Chase periodically monitors summary reports
of all clinical data. During this process, employees with moderately
or significantly altered biochemical tests can be identified and
notified for further evaluation. Two employees who were identified as
having significantly altered liver function tests are discussed in
section IV.
Individual records of all 129 Allwash workers employed between 29
September 1981 and 31 December 1983 were reviewed and the symptoms and
signs listed on the medical incident reports were summarized. The
frequency of these symptoms can only be crudely compared to those
listed at the time of baseline examination because unlike the initial
survey, all workers were not asked a standard set of questions at a
given point in time. Instead, workers were instructed to complete a
medical incident report if they felt ill. Although in most cases,
these symptoms can reasonably be presumed to be associated with the
circumstances of their employment on the day the report was filed, it
is also necessary to keep in mind that Allwash employees, like everyone
else, develop seasonal colds and are involved in non-work related
accidents.
These conditions could be aggravated by being garbed in a
full-body
tyvek
suit
all
day
while
working
under
sometimes
environmentally stressful circumstances.
Similarly, individual records of all 129 Allwash workers were
examined, and all exposure incident reports were reviewed and
summarized. The safety officer on-site who was responsible for signing
off on exposure incident reports was obligated to note on the report if
�-13he saw evidence of coverall or skin contamination. The distribution of
Allwash employees filing exposure incident reports was then examined by
exposure category in an effort to determine if workers who quit or
spent few hours in the BSOB may have experienced more intensive
circumstances of exposure. These workers may have filed more incident
reports or may have reported more instances of direct contact.
Alternatively, it would reasonably be expected that workers who were
employed longer would naturally encounter more opportunities for
protective equipment failure. This comparison would also investigate
whether multiple exposure incident reports were filed by few or many
workers.
Many previous studies have demonstrated a positive correlation
between plasma PCB levels and age, length of employment (or exposure)
and intensity of exposure among workers exposed to PCB fluids.6>?>8 jn
lieu of personal PCB air levels, the relationship between the frequency
of exposure incident reports filed by Allwash employees was compared to
the PCB blood level. The hypothesis being tested is that those workers
who filed more exposure incident reports should have higher plasma PCB
levels. The chi square test was then used to test for a statistically
significant difference.
In an effort to identify those individuals thought to be at
highest risk of potential exposure, all Allwash employees who filed
twenty or more exposure incident reports were identified. Their latest
interval or exit laboratory tests were then examined to determine if
there was any evidence of liver toxicity in those individuals who
presumably were at highest risk for direct contact with contaminated
soot.
�-14IV.
STATISTICAL RESULTS
The results will be presented in five sections as described in the
rationale:
(A) descriptive statistics; (B) correlation analysis;
(C)
analysis of the cumulative effect of potential exposure; (D) regression
analysis; and (E) discussion of clinical data.
For Section A through
D, the results for Allwash employees and Other employees are presented
separately.
measurements
In
addition,
were several
two
participants
whose
liver
function
levels of magnitude larger than any others
were excluded from all analyses other than the descriptive statistics
so they would not skew the results.
These two cases are discussed in
Section E.
A.
Descriptive Statistics
The age distribution of Allwash
employees
(Table
3) reveals a
relatively young population, with 88 percent less than 35 years of age.
Only 2 percent of Allwash employees are 45 or older.
This pattern is
generally maintained among individuals in the middle and upper exposure
categories, in which 50 percent of the population is 15 to 24 years old
and 100 percent are younger than 45.
Group I, representing workers who
are least likely to be exposed to PCBs, is more diverse, having fewer
people under 25 (36%)
and over twice as many people age 35 or older
(18% vs. 7% and 3%) than does Group II or III.
Among Other employees (Table 4) most people were 25 to 44 years of
age (64%) with 14 percent under 25 and 22 percent age 45 or older.
The
largest variation among exposure categories occurs in Group II in which
all eight employees
small
number
of
(100%) are under
employees
under
25
35.
Group I has a relatively
(3%),
but
distribution is consistent with that of Group III.
the
overall
age
�-15-
The distribution of age by exposure category among Allwash
employees from whom exposure category was assessed (i.e., those with
complete PCB data) is similar to the subset of total Allwash employees.
This distribution is depicted in Table 5.
As mentioned previously, all employees were asked to complete a
detailed questionnaire at their entrance exam, before entering the
building, which focused on conditions thought to be associated or
aggravated by potentially hazardous exposures. It should be noted that
chloracne, a specific dermatological condition requiring a tissue
specimen and histological diagnosis that has been associated with
exposure to chlorinated hydrocarbons, was grouped with "acne" on the
original baseline questionnaire. Positive responses to this question
do not necessarily imply that some workers had documented chloracne at
the time of beginning work in the BSOB. Furthermore, it should be
appreciated that mere reporting of ever having a history of liver
hepatitis or dermatitis were not disqualifying conditions if they were
not active at the time of physical examination. Baseline symptoms
reported by the employee or examining physician were tested, using
Chi-square, for any association with exposure category. No significant
(p < .05) associations were found, i.e., the groups were about the same
prior to entering the BSOB.
Among Allwash employees, the most commonly self-reported symptoms
at the entrance exam (Table 6) were acne or chloracne in Group I (18%),
thickening in Group II (25%), and both skin irritation or burning and
acne or chloracne in Group III (18%). The baseline symptoms most
frequently reported at the entrance exam by the physician (Table 7)
were thickening in Group I (25%) and rash in Group II (32%) and III
(26%).
Among Other employees, rash was the most frequently self-reported
symptom at the entrance exam in Group I/II (17%). In Group III, rash
was tied with skin irritation or burning and acne or chloracne at 17
�-16-
percent each (Table 8).
Rash was the symptom most frequently reported
by physicians at the entrance exam in both exposure categories (Table
9) with 22 percent in Group I/II and 30 percent in Group III.
The case records of Allwash and Other employees in Group II and
III who reported history of any hepatic-related problems were evaluated
to
assess
their
impact
on
the
results.
The
presence
of
conditions
was not controlled for in the remaining
analyses
very
employees
those
few
reported
these
problems
and
these
because
who
did,
experienced them many years ago without recurrence.
All
participants
reporting
any
unusual
exposure
or
breach of
safety regulations, adverse health effects, or abnormal findings were
identified.
The
frequency
and
nature
of
these
complaints
are
summarized in the discussion of clinical data.
B.
Correlation Analysis
Plasma
PCB
levels
(separately
analyzed
at
PCL
and
BEL
laboratories) were tested for correlation with the three biochemical
parameters
SCOT, SGPT,
and
available time interval.
GGTP.
Data
were used
from the
latest
The possible association of these parameters
was evaluated using the normal Pearson correlation coefficient as well
as
the nonparametric Spearman
correlation coefficient.
results were statistically significant (p <
None of the
.05).
C.
Cumulative Effect of Potential Exposure
The
difference
statistically analyzed
the following
between
(paired
parameters:
baseline
and
final
measurements
t-test) within each exposure group for
plasma PCB (analyzed at PCL Lab and
Lab), SCOT, SGPT, GGTP, triglycerides, cholesterol and HDL.
on the entrance exam
was
was
subtracted from the value
BRL
The value
on the latest
interval or exit exam; therefore, when the mean difference is positive,
the value of the parameter increased over time and when it is negative,
�-17the value of the parameter decreased over time.
The results are
depicted in Tables 10 a & b to 17 a & b. The entrance and last exam
means are based on all available data; the mean difference is based on
results from the paired t-test, and so, may include fewer observations.
PCBs
Baseline and final values for plasma PCB levels were compared to
normal ranges obtained from the laboratories.
All values were within
the normal range; most values were at or below the minimal detection
limits. The ranges and means of PCB values for Allwash employees by
exposure group are as follows:
Exposure, lab
Entrance Exam
Range (Mean)
Last Exam
Range (Mean)
Group I, Pa
Group I, BRL
0 - 15 (5.85)
3 - 13 (5.09)
5 - 1 6 (5.44)
3 - 9 (4.83)
Group II, PCL
Group II, BRL
5 - 9 (5.19)
3 - 9 (4.19)
5 - 5 (5.00)
3 - 6 (3.44)
Group III, PCL
Group III, BKL
5 - 8 (5.09)
3 - 1 1 (4.30)
5 - 8 (5.12)
3 - 8 (4.24)
Plasma PCB values from the PCL Laboratory did not exhibit any
significant differences between baseline and final measurements. Of
the five average differences, however, three are negative, one is
"zero," and only one is positive (Group III Others) from baseline to
final measurements. Plasma PCB values from the BRL Laboratory showed
one significant difference
(Group
I/II Others).
All five of the
average differences were negative and two values (Allwash Group I and
II) were close to significantly (p = .06) negative. Thus, in general,
plasma PCB levels decreased for individuals in this study though, on
average, not significantly.
�-18Other Biochemical Parameters
Average baseline and final values for selected blood chemistry
parameters were compared to normal ranges obtained from the hospitals.
The group means for the liver enzyme parameters SCOT, SGPT, and GGTP
were always well within the normal range. Triglyceride levels were
slightly high for Group III Allwash employees (both baseline and final)
relative to the Bionetics Laboratory scale but were normal for the
Lourdes and Wilson Hospital scales.
Both baseline and final
cholesterol levels were slightly high for Other employees (Groups I/II
and III) relative to the Bionetics Laboratory scale but were normal for
the two hospital scales.
ranges.
The HDL levels were all within the normal
Values for SCOT, SGPT, triglycerides, and HDL did not exhibit any
significant differences between baseline and final measurements.
Average levels sometimes went up and sometimes went down.
GGTP levels changed significantly for Group III employees (both
Allwash and Others) as well as for Group II Allwash employees.
Individuals with high exposure, on average, had much lower values at
the end than at the beginning (mean difference of 12.83 and 9.53
lower). The differences for the other two groups did not exhibit any
consistent pattern.
In general, GGTP levels decreased for study
participants, especially for those with medium or large exposure.
Cholesterol
employees.
levels
changed
significantly
for Allwash
Group I
Allwash individuals with low exposure, on average, had much
lower (average decrease 9.44) cholesterol values at the end than at the
beginning. Also, the averages for all groups of Allwash employees went
down. Group III Others also decreased while Groups I/II Others groups
of Allwash employees went down. Group III Others also decreased while
Groups I/I1 Others remained the same, on average.
Thus, in general,
cholesterol levels declined for all study participants.
�-19Analysis of variance and Wilcoxon tests were performed on the
final measurement values for PCBs (from both labs), SCOT, SGPT, GGTP,
triglycerides, cholesterol, and HDL to determine whether
the mean
levels for the different exposure groups were the same. The only
significant ANOVA was for Allwash employees for PCBs from the BRL Lab.
Furthermore,
the mean levels do not vary linearly with length of
exposure. The only significant Wilcoxon Rank Sum Test result was for
GGTP among Allwash employees.
In addition, the means decrease as
exposure increases.
D.
Regression Analysis
To assess possible time trends in the PCB and biochemical data,
linear regression models were run using time in the BSOB as the
independent variable and final PCB levels (from both labs), SCOT, SGPT,
and GGTP as dependent variables. The only statistically significant
slope occurs for GGTP among Other employees (slope=-0.0003) showing a
slight decline in its level with time spent in the BSOB. Two other
values are almost significant (p=.07 level): these are for PCBs (BRL
Lab) for Others (slope=-0.0006) and SCOT for Others (slope=0.002). All
four slopes for PCBs are negative, both slopes for SCOT are positive,
and both slopes for GGTP are negative (one is significant).
E.
Discussion of Clinical Data
The frequency distribution of symptoms reported by Allwash
employees on the medical incident reports is summarized in Table 20.
The two most prevalent findings were complaints of feeling nauseous and
reports of blunt trauma and minor bruises. The latter findings are not
atypical of any group of industrialized workers.
Because the same
individual could have filed more than one report, or could have listed
more than one chief complaint on the same medical incident report, the
true prevalence of these symptoms among all workers within a particular
�-20-
exposure group cannot be determined.
feeling nauseous
among
34 workers
The reporting of 35 cases
of
in Group III may be attributed to
working longer hours under environmentally stressful conditions or may
be
a manifestation of
toxicity.
the cumulative effects of low level
chronic
In order to adjust for the differences in time spent in the
BSOB as well as differences In the size of the populations, a crude
index of the average number of reported cases per hour spent in the
BSOB was calculated and used to compare across groups.
By dividing the
number of cases of feeling nauseous in Group I and III (6 and 35) by
the average number of hours spent in the BSOB for these same groups
(184 hrs. and 1757 hrs.) it was determined that there were .033 cases
per hour reported for Group I compared to .020
for Group III.
The
results of similar calculations are shown in parentheses in Table 20.
This would suggest that spending longer time in the BSOB, and therefore
presumably at higher risk of potential exposure, is not
associated with a higher incidence of ill symptoms.
in which
the
Group
musculoskeletal pain.
III reports per
hour
were
necessarily
The only instance
clearly
higher
was
Most of these cases were due to low back pain
possibly associated with long hours in the cramped work conditions at
the BSOB.
The frequency distribution of all sources
reported
summarized
by
in
Allwash
Table
employees
21.
in
Clearly,
exposure
the
of equipment failure
incident
most
frequent
reports
is
source
of
"equipment failure" was tear in the outer layer of a glove or tyvek
suit.
If these incidents did not occur during a time when the worker
was actually involved in cleaning up of contaminated soot or were not
associated with evidence of skin or coverall contamination, then they
were listed as such in the incident report.
There were, however, a
total of 44 reported incidents involving the loss of a tyvek suit seal
and a total of 40 cases of a torn glove, all with evidence —
dampened or soiled skin —
of
of skin or coverall contamination.
usually
In all
these cases, however, workers underwent immediate decontamination
procedures and no cases of unresolving contact dermatitis or chloracne
�-21-
have been reported.
Table 21 also demonstrates that, in general, Group
III workers filed more reports in total; however, the number of reports
per hour spent in the BSOB was not higher.
Table 22A demonstrates that individual workers
more
likely
individuals
to
file
multiple
exposure
incident
in Group III were
reports.
Nineteen
in Group III filed 11 or more exposure incident reports.
Again, this occurrence is probably a reflection of the greater number
of hours spent in the BSOB.
In order to investigate the relationship between PCB blood levels
and length of potential exposure, PCB blood levels were compared to the
frequency of reporting potential contact with contaminated soot (Table
22b).
There is no evidence to suggest that the group of workers at
highest risk of exposure
levels.
more
to contaminated
soot had higher plasma PCB
To investigate this further, all those workers who filed 20 or
exposure
interval
incident
or exit
summarized
in
exam
Table
reports
were
identified
PCB blood levels
23.
and
All laboratory
and
their
latest
liver function studies
values
were
within
normal
limits.
As mentioned previously, two Allwash employees were identified who
had grossly abnormal
exit
examinations.
indicates
these
liver enzyme measurements at the time of their
Careful
evaluation
of
these
individuals'
cases
that their work in the BSOB was probably not a cause for
abnormalities.
Unfortunately,
neither
of
these
two
workers
reported for their three month follow-up exam, so it is unknown whether
these enzyme levels have since returned to normal.
Employee number
one is a 22 year
old white
male who had his
entrance examination
in January, 1982, and first entered the building
in February, 1982.
At that time his liver enzyme measurements
well within
IU/liter).
the normal ranges
(SCOT of
were
17 lU/liter and SGPT of 13
There was no indication at that time of any liver problems.
Values for these liver enzyme measurements remained relatively constant
on the interval examinations
on 24 March, 26 May, 3 August, and 28
�-22September 1982. The employee last entered the BSOB in November 1982.
During the time the employee was actively working in the BSOB he filed
numerous minor exposure incident reports, most of which were for torn
gloves and tyvek suit tears. During his March examination he did
report that there had been one incident in which he felt there was
potential for exposure. The exposure report for this incident stated
that charcoal and water had entered the employee's tyvek suit around
the wrists and that "some irritation was noted around the left wrist
and lower left abdomen, but subsided after showering". The examining
physician reported slightly red and swollen eyelids at the employee's
March interval examination but his exam was otherwise unremarkable.
The employee denied any subsequent instances of possible exposure
on his next three interval examinations as well as at the time of his
exit examination.
employee
did
During his exit examination on 12 January 1982 the
complain
of
itching
and
skin
irritation which
the
examining physician at that time described as dermatographia. Liver
enzyme measurements at this time were markedly elevated: SCOT 307
IU/1, SGPT 480 IU/1 and GGPT 184 IU/1. Plasma PCB blood levels as
measured by the Wilmington and Burlington laboratories were 5 and 3
ppb, respectively.
In view of the low PCB blood levels and no report
of possible direct contact with soot for at least 9 months prior to
developing these liver enzyme elevations, it is unlikely that these
abnormalities are the result of any hazardous exposures while working
in the BSOB. Elevated liver enzymes in this ratio are, however,
suggestive of infectious hepatitis which the employee could
developed in the 2 months since his last employment in the BSOB.
have
Employee number two is a 21 year old white male who had his
entrance examination in February, 1983, and first entered the building
in February. At that time his liver enzyme measurements were well
within the normal ranges (SCOT of 23 IU/1). There was no indication at
that time of any liver problems. Values for SCOT remained relatively
constant on the interval examinations in March and May 1983. Incidents
�-23-
with dust in his mask and torn gloves were reported at the May, 1983,
interval examination.
At that May examination the physician reported
no abnormal findings (including liver abnormalities).
the building in July, 1983.
He last entered
At the exit examination in August, 1983,
the value for SCOT jumped by a factor of fifteen to 446 IU/1.
The
employee's
and
Burlington
plasma
PCB
laboratories
levels
as
measured
by
the
Wilmington
were 5 and 7 ppb, respectively.
Although the
employee did report possible contact with some "dust" at the time of
the exit examination,
low plasma PCB levels and the absence of any
history of substantive exposures make it unlikely
was exposed to any hazardous substances.
that this employee
Significantly elevated SCOT
and slightly elevated SGPT liver enzyme values in the absence of any
other
abnormal
liver
function
tests
(e.g.,
bilirubin,
alkaline
phosphatase, GGTP) is frequently seen as a response to short term binge
alcohol comsumption.
�-24-
V. CONCLUSION
In conclusion, the results for specific biochemical parameters are
summarized and an overall explanation of the findings is presented.
Table 19 summarizes the statistically significant results.
o
PCBs (PCL Lab); The t-test indicated that in general there
was a tendency for the serum values to decline from baseline
to final examinations. The regressions indicated a general
decline of values with length of time in the BSOB.
o
PCBs (BRL Lab);
The results are similar to those found using
the BRL data but in this case are more pronounced and
sometimes significant.
o
SCOT; In general, the regressions indicated a slight rise in
values as the length of time increased in the BSOB. The
t-tests offered no clear pattern for possible changes within
groups.
o
GGTP; The t-test indicated a general trend for GGTP values
to decrease from baseline to final examination with
significant
decreases
for
the
high
and
medium
exposure
groups. The regression analyses also indicated a general
trend (significant for Others, suggestive for Allwash) for
lower final examination values for those with more hours in
the BSOB. Finally, the nonparametric Wilcoxon test showed a
significant decline in average GGTP values for the Allwash
employees with time spent in the BSOB (grouped data).
�-25o
Cholesterol; The t-test, in general, showed declining levels
from baseline to final examinations (significantly lower only
for low exposure Allwash employees).
o
SGPT, Triglycerides, HDL; Nothing even suggestive can be
said regarding these biochemical parameters based on our
analysis.
When evaluating the significance of these results, the following
must be considered.
First, even though there were statistically
significant findings, they may be of limited clinical importance due to
the fact that the mean level for every group and every parameter were
well within normal ranges.
Second, the transfer of these results to
other populations may be limited by the fact that the Allwash employees
(and to a lesser extent, the Other employees) were younger and
healthier than the average profile for American adult males. Third,
all statistical tests were performed at the 5% level so that chance
alone would dictate finding about 5% of the comparisons significant if
there were no real effects.
In conclusion, among the employees in this study for whom
protective equipment and safety procedures were used to minimize
potentially hazardous exposure, the health status of the workers was
not substantially affected, overall, by potential exposure to the toxic
contaminants in the BSOB.
�-26-
VI.
REFERENCES
1.
Versar New York Inc., 1981. General health and safety plan for
cleanup of Binghamton State Office Building.
2.
Versar New York Inc., 1983. Revised Summary Report. Industrial
hygiene monitoring to assess contaminant control and potential
worker exposure during cleaning of the Binghamton State Office
Building.
3.
Eadon G, Aldous K, Hilker D, O'Keefe P and Smith R. 1983.
Chemical data on air samples from the Binghamton State Office
Building. Unpublished data by the Center for Laboratories and
Research, New York State Department of Health.
4.
Kim NK and Hawley J. 1983. Revised risk assessment: Binghamton
State Office Building. Draft document by the Division of Health
Risk Control, New York State Department of Health.
5.
Fitzgerald EF, Melius JM, Standfast JJ, Janerich DT, Beckerman BS
and Youngblood LG. 1983. Status report for the Binghamton State
Office Building Medical Surveillance Program.
Division of
Community Health and Epidemiology, New York State Department of
Health.
6.
Smith AB et al. 1982.
Metabolic and health consequences of
occupational exposure to polychlorinated biphenyls
(PCBs).
British Journal of Industrial Medicine, 39:361-369.
7.
Maroni M et al. 1981. Occupational exposure to polychlorinated
biphenyls II, Health Effects.
British Journal of Industrial
Medicine, 38:55.
8.
Chase KH, Wong 0, Thomas D, Berney BW and Simon RK.
1982.
Clinical and metabolic abnormalities associated with occupational
exposure to polychlorinated biphenyls. Journal of Occupational
Medicine, 24:109-114.
�Figure 1
H I S T O G R A M OF NUMBER OF HOURS IN BSOB FOR A L I W A S H EMPLOYEES W I T H PC8 D A T A
(N=100)
FREQUENCY BAR CHART
FREQUENCY Group I t
1
2
0
0
0
0
3
0
0
4
0
0
Group II
5
0
0
6
0
0
7
a
0
0
0
0
Group
9
0
0
1 i
i
n 0
0
0
0
1
2
0
0
III
1
3
0
0
1
4
0
0
1
5
1
t>
0
0
0
0
1 1
7
0
0
8
0
0
1
9
0
0
2
0
0
0
EXPTIME MIDPOINT
2
1
0
0
2
2
0
0
2
3
0
0
2
4
0
0
2
2
5
6
0
0
0
0
2
7
0
0
2
8
0
0
2
9
0
0
3
0
0
0
3
1
0
0
3
2
0
0
3
3
3
3
0
0
4
0
0
5
0
0
�Figure 2
HISTOGRAM OF NUMBER OF HOURS IN BSOB FOH ALLWASH EMPLOYEES
<N=129)
FHEQUENCY BAR CHAPT
FREQUENCY
Group III
Group I
30
15
10
1
0
0
2
0
0
3
0
0
4
0
0
5
0
0
6
0
0
7
0
0
8
0
0
9
0
0
1
0
0
0
1 1
1 2
1
1
1
3
5
0
0
0
0
4
0
0
0
0
0
0
1
6
1
n
7
0
0
0
1 1
ft
0
0
9
0
0
2
0
2
1
2
2
0
0
0
0
0
0
E/PTIME MIDPOINT
2
3
0
0
2
4
0
0
2
5
0
0
2
2
6
0
0
7
0
0
2
8
0
0
2
9
0
0
3
0
0
0
3
1
0
0
3
2
0
0
3
3
0
0
3
3
4
5
0
0
0
0
�Figure 3
HISTOGRAM OF MUMdER OF HOURS IN BSOR FOR OTHER EMPLOYEES
(N=64)
FREQUENCY BAR CHART
FREQUENCY
Group I
Group II
Group III
30
20
15
.10
1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3
1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 H 9 0 1 2 3 < t b b 7 8 ' 3 0 1 2 3 4 5
O O O O O O O O O O O O O -O O O O O O O O O O O U O O O O O O O O O O
o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o
EXPTIME MIDPOINT
�Table 1
Distribution of Exposure Category by Study Subset
Subset
EXPOSURE
CATEGORY
Allwash with
PCB Data
//
()
%
Total Allwash
//
()
%
Other
#
()
%
Group I
46
(6
4)
67
( 52)
33
(52)
Group II
20
(20)
28
( 22)
8
(12)
Group III
34
(4
3)
34
( 26)
23
(6
3)
(100)
129
(100)
•64
TOTAL
100
(100) ,
�Table 2
Distribution of Study Participants
By Job Classification and Exposure Category
JOB
CLASSIFICATION
EXPOSURE
CATEGORY
SUBSET
Allwash
N
GO
OTHER
Other
N
()
%
Versar
TOTAL
N
(%)
N
()
%
O.G.S.
N
()
%
Misc.*
Supervisory
N
()
%
N
(%)
Group I
67
( 52) 33
( 52) 100 ( 52) 15
( 62)
9
( 39) 2
( 20)
7
(100)
Group II
28
( 22) 8
( 12) 36 ( 19)
4
( 17) 3
( 13) 1
( 10) 0
( 0)
Group III
34
( 26) 23
( 36)
5
( 21) 11
( 48)
( 70) 0
( 0)
(100)
(100)
7
(100)
TOTAL //(%)
129
(100)
64
(100)
57 ( 29)
193 (100)
24
* Includes 3 Broorae County personnel and 4 visitors
23
7
10
(100)
�Table 3
Age Distribution of Allwash Employees by Exposure Category
Exposure Category
Age (Yrs.)
Group 11
Group I
()
%
//
#
Total
Group III
()
%
(%)
if
f
()
%
15-24
24
(36)
14
(50)
17
(50)
55
. (42)
25-34
31
(46)
.12
(3
4)
16
(47)
59
(46)
35-44
10
-2
( 7)
2
0
1
( 0) .0
( 3) 1.3
2
(0)
(10)
45-54
(1?)
( 3)
( 2)
55-64
0
( 0)
0
( 0)
0
( 0) 0
( 0)
>65
0
( 0)
0
( 0)
0
( 0)
0
( 0)
TOTAL
67
(100)
2S
(100)
34
(100)
129
(100)
�Table 4
Age Distribution of Other Study Participants by Exposure Category
Exposure Category
Age (Yrs.)
Group II
Group I
//
()
%
15-24
1
( 3)
25-34
9
35-44
Group III
()
%
//
0
Total
()
%
//
()
%
(12)
(8
8)
7
(30)
9
(14)
(27)
1
7
5
(22)
21
(33)
14
(43)
0
( 0)
6
(26)
20
(31)
45-54
5
(15)
0
( 0) . 3
(13)
8
(12)
55-64
3
( 9)
0
( 0) 2
(9)
5
( 8)
>65
1
( 3)
0
( 0)
( 0) 1
( 2)
TOTAL
33
(100)
8
(100)
0
23
(100)
64
(100)
�Table 5
Age Distribution of Allwash Employees by Exposure Category
for Those with Complete PCB Data
Exposure Category
Age (Yrs.)
Group I
()
%
//
15-24
15
25-34
21
35-44
9
45-54
1
Group 11
//
( 33) 11
a)
( 55)
Total
Group III
()
%
//
17
16
43
( 43)
( 46)
55-64
0
9
( 20) 0
0
( 2)
0
( 0)
>65
0
( 0)
0
( 0)
0
( 0)
0
( 0)
TOTAL
46
(100)
20
(100)
34
(100)
100
(100)
( 45)
( 45)
( 0)
1
' ( 50)
()
%
//
( 0)
0
( 47) 46
( 3)
10
( 0)
1
( 0)
0
( 0)
0
( 1)
( 0)
( 10)
�Table 6
Frequency Distribution of Baseline Symptoms
Reported by Allwash Employees
According to Exposure Category
EXPOSURE CATEGORY
SYMPTOMS
Group I (N=67)
#
(%)
Group II (N=28)
#
(%)
Group III (N=34)
#
(%)
Skin irritation or burning
9
(13)
6
(21)
6
(18)
Rash
6
( 9)
3
(11)
3
( 9)
12
(18)
6
(21)
6
(18)
Thickening
9
(13)
7
(25)
4
(12)
Hyperpigmentation
3
( 4)
3
(11)
2
( 6)
Nail discoloration
2
( 3)
0
( 0)
2
( 0)
12
(18)
9
(32)
5
(15)
Acne or chloracne
Other dermatologic symptoms
Eye irritation or burning
4
( 6)
1
( 4)
3
( 9)
Eye discharge
2
( 3)
0
( 0)
2
( 6)
Swelling of eyelids
0
( 0)
0
( 0)
0
( 0)
Other ophthalmic symptoms
2
( 3)
2
( 7)
1
( 3)
Any history of liver dysfunction
2
(3)
0
( 0)
0
( 0)
Any history of hepatitis
2
( 3)
0
( 0)
0
( 0)
Any history of yellow jaundice
2
( 3)
0
( 0)
0
( 0)
Any history of alcohol abuse
1
( 1)
1
( 4)
2
( 6)
Other hepatic symptoms
2
( 3)
0
( 0)
2
( 6)
Persistent body odor
1
( 1)
0
( 0)
0
( 0)
History of hyperlipidemia
1
( 1)
0
( 0)
0
( 0)
History of cancer
2
( 3)
0
( 0)
0
( 0)
�Table 7
Frequency Distribution of Baseline Physical Findings
Reported by Physician for Allwash Employees
According to Exposure Category
EXPOSURE CATEGORY
PHYSICAL FINDINGS
Erythema
Rash
Group I (N=67)
#
()
%
1
12
Group II (N=28)
#
(%)
Group III (N=34)
//
()
%
( 1)
2
( 7)
2
( 6)
(18)
9
(32)
9
(6
2)
Chloracne
0
( 0)
1*
( 4)
0
( 0)
Hyper pigmentation
7
(10)
1
( 4)
1
( 3)
17
(25)
8
(9
2)
4
(12)
( 9)
1
( 4)
4
(12)
23
(68)
Thickening
Nail discoloration
Other dermatologic findings
6
36
(54)
19
(8
6)
Conjunctival Infection
3
( 4)
1
( 4)
0
( 0)
Eye discharge
0
( 0)
0
( 0)
0
( 0)
Swelling of lids
0
( 0)
0
( 0)
0
( 0)
Jaundice
0
( 0)
0
( 0)
0
( 0)
Hepatomegaly
1
( 1)
0
( 0)
0
( 0)
Other hepatic findings
0
( 0)
0
( 0)
0
( 0)
*This case was not confirmed by histological diagnosis or by a dermatologist.
�Table 8
Frequency Distribution of Baseline Symptoms
Reported by Other Employees
According to Exposure Category
EXPOSURE CATEGORY
SYMPTOMS
Group I/II (N-41) ; Group III (N-23)
#
#
()
%
()
Z
Skin irritation or burning
5
(12)
4
(17)
Rash
7
(17)
4
(17)
Acne or chloracne
5
(12)
4
(17)
Thickening
1
( 2)
0
( 0)
Hyperpigmentation
1
( 2)
0
( 0)
Nail discoloration
1
( 2)
0
( 0)
Other dermatologic symptoms
5
(12)
2
( 9)
Eye irritation or burning
4
(10)
0
( 0)
Eye discharge
1
( 2)
0
( 0)
Swelling of eyelids
1
( 2)
0
( 0)
Other ophthalmic symptoms
3
( 7)
1
( 4)
Any history of liver dysfunction
0
( 0)
0
( 0)
Any history of hepatitis
1
( 2)
0
( 4)
Any history of yellow jaundice
1
( 2)
0
( 0)
Any history of alcohol abuse
0
( 0)
0
( 0)
Other hepatic symptoms
0
( 0)
0
( 0)
Persistent body odor
1
( 2)
0
( 0)
History of hyperlipidemia
0
( 0)
0
( 0)
History of cancer
0
( 0)
1
( 4)
�Table 9
Frequency Distribution of Baseline Physical Findings
Reported by Physician for Other Employees
According to Exposure Category
EXPOSURE CATEGORY
PHYSICAL FINDINGS
Group I/II (N=41)
//
(%)
Group III (N-28)
#
(%)
Erythema
5
(12)
1
( 4)
Rash
9
(22)
7
(30)
Chloracne
0
( 0)
1*
( 4)
Hyperpigmentation
2
( 5)
1
( 4)
Thickening
3
( 7)
6
(26)
Nail discoloration
4
(10)
0
( 0)
19
(46)
4
(17)
Other dermatologic findings
Conjunctival Infection
2
( 5)
2
( 9)
Eye discharge
0
( 0)
0
( 0)
Swelling of lids
1
( 2)
1
( 4)
Jaundice
0
( 0)
0
( 0)
Hepatomegaly
0
( 0)
0
( 0)
Other hepatic findings
0
( 0)
0
( 0)
*This case was not confirmed by histological diagnosis or by a dermatologist,
�Table lOa
Plasma PCB Levels by Exposure Category
for Allwash Employees
Exposure Category
Plasma PCB
Level
(Lab=PCL)
Group I
Group III
5.85 (62)
5.44 (41)
-0.29
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
Group II
5.19 (27)
5.00 (19)
- 0.26
5.09 (33)
5.12 (33)
0.03
Table lOb
Plasma PCB Levels by Exposure Category
for Other Employees
Exposure Category
i
Plasma PCB
Level
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
*p <0.05
**p < 0 . 0 1
tAnalysis of Variance p <.05
ttWilcoxon p <.05
6.64 (33)
5.97 (29)
- 0.90
Group II
Group III
5.75 (8)
5.25 (8)
- 0.50
4.96 (23)
5.43 (23)
0.48
�Table lla
Plasma PCB Levels by Exposure Category
for Allwash Employees
Exposure Category
Plasma PCB
Level
(Lab=BRL)
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
5.09 ( 4
6)
4.83 (46) t
-0.73
Group II
4.19 (27)
3.44 (18) t
-0.94
Group III
4.30 (33)
4.24 (33) t
-0.06
Table lib
Plasma PCB Levels by Exposure Category
for Other Employees
Exposure Category
Plasma PCB
Level
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
*p <0.05
**p <0.01
t Analysis of Variance p <,.05
ft Wilcoxon p < . 0 5
6.52 (33)
5.62 (29)
-1.48
Group II
Group III
5.25 (8)
4.50 (8)
-0.75
5.36 (22)
4.57 (23)
-0.86
�Table 12a
SCOT Levels by Exposure Category
for Allwash Employees
Exposure Category
SCOT
Level
Group I
Group III
27.62 (67)
26.94 (67)
-0.68
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
Group II
26.78 (27)
24.67 (27)
-2.11
25.39 (33)
27.03 (33)
1.64
Table 12b
SCOT Levels by Exposure Category
for Other Employees
Exposure Category
SCOT
Level
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
*p < 0 . 0 5
**p< 0.01
tAnalysis of Variance p <.05
ft Wilcoxon p <.05
Group II
Group III
23.33 (33)
25.18 (33)
1.85
21.44 (8)
22.00 (8)
0.56
23.46 (23)
27.26 (23)
3.80
�Table 13a
SGPT Levels by Exposure Category
for Allwash Employees
Exposure Category
SGPT
Level
Group I
Group III
26.33 (66)
26.66 (67)
0.42
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
Group II
24.56 (27)
21.56 (27)
-3.00
19.39 (33)
22.09 (33)
2.70
Table 13b
SGPT Levels by Exposure Category
for Other Employees
Exposure Category
SGPT
Level
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
*p< 0.05
**p< 0.01
tAnalysis of Variance p <.05
ttWilcoxon p <.05
Group II
Group III
27.96 (33)
24.67 (33)
-3.29
19.31 (8)
20.50 (8)
1.19
21.55 (23)
22.70 (23)
1.14
�Table 14a
GGTP Levels by Exposure Category
for Allwash Employees
Exposure Category
GGTP
Level
Group I
27.47 (61)
31.15 (67)tt
4.20
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
Group 11
33.38 (26)
27.89 (27)tt
-5.88*
Group III
33.70 (30)
20.48 (33)tt
-12.83*
Table 14b
GGTP Levels by Exposure Category
for Other Employees
Exposure Category
GGTP
Level
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
*p <0.05
**p < 0.01
tAnalysis of Variance p <.05
ttWilcoxon p <.05
Group I
Group II
Group III
25.88 (32)
22.30 (33)
-3.50
17.30 (8)
19.00 (8)
1.70
26.53 (20)
16.87 (23)
-9.53**
�Table 15a
Triglyceride Levels by Exposure Category
for Allwash Employees
Exposure Category
Triglyceride
Level
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
Group II
Group III
122.19 (67)
116.91 (32)
14.03
104.63 (27)
73.29 ( 7)
-15.14
153.33 (33)
153.27 (15)
19.20
Table 15b
Triglyceride Levels by Exposure Category
for Other Employees
Exposure Category
Triglyceride
Level
Group I
Entrance Exam Mean (N)
. Last Exam Mean (N)
Mean Difference
*p <0.05
**p <0.01
tAnalysis of Variance p <.05
ftWilcoxon p <.05
113.27 (33)
109.13 ( 8)
-14.50
Group II
75.88 (8)
57.50 (4)
-16.25
Group III
131.57 (23)
113.17 ( 6)
-2.50
�Table 16a
Cholesterol Levels by Exposure Category
for Allwash Employees
Exposure Category
Cholesterol
Level
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
Group II
190.57 (67)
179.03 (32)
-9.44*
172.89 (27)
165.14 (7)
-15.00
Group III
•
193.00 (33)
189.35 (17)
-7.12
Table 16b
Cholesterol Levels by Exposure Category
„
for Other Employees
Exposure Category
Cholesterol
Level
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
*p <0.05
**p <0.01
t Analysis of Variance p <.05
tt Wilcoxon p <.05
Group II
Group III
218.82 (33)
199.50 ( 8)
-6.75
199.75 (8)
200.00 (4)
15.00
207.30 (23)
201.17 ( 6)
-9.33
�Table 17a
HDL Levels by Exposure Category
for Allwash Employees
Exposure Category
HDL
Level
Group I
49.10 (67)
49.22 (32)
-1.88
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
Group II
51.04
51.14
-5.43
(27)
( 7)
Group III
50.76 (33)
64.82 (17)
14.41
Table 17b
HDL Levels by Exposure Category
for Other Employees
Exposure Category
HDL
Level
Group I
Entrance Exam Mean (N)
Last Exam Mean (N)
Mean Difference
*p <0.05
**p <0.01
tAnalysis of Variance p <.05
ttWilcoxon p <.05
Group II
Group III
47.54 (33)
48.75 ( 8)
0.54
54.50 (8)
55.25 (4)
2.50
51.46 (23)
47.17 ( 6)
-1.67
�Table 18a
Summary of Regression Analysis for
Allwash Employees
Parameter
PCB (PCL lab)
PCB (BRL lab)
SCOT
SGPT
GGTP
Sample Size
Intercept
92
96
126
126
126
5.33
4.56
26.29
24.77
31.39
Slope
-0.0001
-0.0002
0.0003
-0.0006
-0.0054
Table 18b
Summary of Regression Analysis for
Other Employees
Parameter
PCB (PCL lab)
PCB (BRL lab)
SCOT
SGPT
GGTP
*p < .05
Sample Size
59
59
63
63
63
Intercept
5.88
5.55
23.99
23.03 .
22.25
Slope
-0.0003
-0.0006
0.0021
0.0005
-0.0031*
�Table 19
Summary of Statistically Significant Results (p < .05)
Name of Test
Paired t-test
Subset and Parameter
Sample Size
p Value
Allwash, Group I,
Cholesterol
Allwash, Group II,
GGTP
32
.0483
26
.0230
Allwash, Group III,
30
.0133
Others, Group I/II,
PCS (BRL)
37
.0374
Others, Group III
20
.0001
97
.0257
GGTP
GGTP
Analysis of
Variance
Allwash, PCB (BRL)
Wilcoxon Rank
Sura
Allwash, GGTP
127
.0333
Regression
Others, GGTP
63
.0424
�Table 20
Frequency Distribution of Symptoms Reported by
Allwash Employees on Medical Incident Reports*
According to Exposure Category
EXPOSURE CATEGORY
SYMPTOMS
t
Group I
(*
*)
#
Group II
(**)
#
Group III
(**)
Dermatological :
skin irritation/itching
acne/rash
0
1
( 0)
(.005)
1
0
(.002)
( 0)
2
2
(.001)
(.001)
Ophthalmological :
eye irritation/burning
2
(.011)
3
(.005)
9
(.005)
Respiratory:
dyspnea
chest pain
congestion
sore throat
0
0
0
0
(
(
(
(
0)
0)
0)
0)
1
1
0
0
(.002)
(.002)
( 0)
( 0)
3
3
4
3
(.002)
(.002)
(.002)
(.002)
2
9
(.011)
(.049)
3
0
(.005)
( 0)
4
33
(02
.0)
(.019)
0
( 0)
0
( 0)
25
(.014)
1
6
2
3
1
0
(.005)
(.033)
(.011)
(.016)
(.005)
( 0)
3
6
2
3
4
0
(.005)
(.009)
(.003)
(.005)
(06
.0)
( 0)
9
35
1
5
14
2
(.005)
(.020)
(.001)
(.003)
(08
.0)
(.001)
Musculoskeletal :
lacerations/ abrasions
blunt trauma/bruises
and minor accidents
musculoskeletal pain
Other :
dizziness/lightheadedness
nausea/vomiting
abdominal pain
heat stress/diaphoresis
headache
palpitations
*More than one report may be included for the same individual.
**Number of reports divided by average number of hours in BSOB for each group: 1=184,
11=634, 111=1757.
�Table 21
Frequency Distribution of Sources of Equipment
Failure Reported by Allwash Employees on Exposure Incident
Forms* According to Exposure Category
EXPOSURE CATEGORY
Group I
(*
*)
Group II
#
(**)
TYPE OF
EQUIPMENT FAILURE
#
Tear in Tyvek Suit with
Little Likelihood of Skin
Contact
17
(02
.9)
30
(.047)
74
(02
.4)
Dampening or Soiling
of Tyvek Suit with
No Break in Seal
11
(00
.6)
15
(04
.2)
70
(00
.4)
6
(.033)
12
(.019)
26
(.015)
18
(08
.9)
48
(06
.7)
128
(.073)
6
(.033)
12
(.019)
22
(.013)
Malfunction of Respirator
( . . , loss of seal)
ie
16
(.087)
25
(.039)
60
(04
.3)
Accidental or Deliberate
Removal of Respirator
10
(.054)
19
(00
.3)
26
(.015)
1
(05
.0)
1
(.001)
Tear in Tyvek Suit
with Evidence of
Skin Contact
Tear in Outer Layer
of Glove
Tear in Glove With
Evidence of Skin
Contact
Reported Safety Violation
with No Potential for
Direct Contact
0
(
0)
Group III
#
(*
*)
*More than one report may be included for the same individual.
**Number of reports divided by average number of hours in BSOB for each group:
11=634, 111=1757.
1=184,
�Table 22a
Distribution of Allwash Employees Filing
Exposure Incident Reports According to Exposure Category
Number of Allwash Employees
Number of Exposure
Reports Filed
Group I
Group II
Group III
5
60
15
5
6 - 10
6
10
11
11 - 30
1
3
19
0-
Table 22b
Relationship Between PCS Blood Levels*
and Frequency of Exposure Incident Reports Filed
by Allwash Employees
PCB Blood Level (ppb)
Frequency of Reported
Potential Contact
ND - 5
6-10
10-16
39
18
1
Occasionally (6 - 10)
12
9
0
Frequently (11 - 30)
17
4
0
Rarely (0 -
5)
*PCB blood levels are the highest values reported by either laboratory
at the time of exit exam or most recent interval exam.
�Table 23
Summary of PCB Blood Levels and Liver Function Tests
for those Individuals Filing More Than Twenty Exposure Incident Reports
ID #
# of Hrs.
in BSOB
ALK.
PHOS.
BILI
SCOT
SGPT
GGTP
PCB
(PCL)
PCB
(BRL)
_
3097
2157
44
1.1
22
18
25
3145
759
72
0.5
23
15
16
5
4
3159
2726
42
0.6
33
39
12
-
3
3217
1912
44
0.7
22
18
12
-
-
3269
1349
49
0.4
21
15
9
-
3
3289
1574
46
0.7
20
9
11
6
—
3
�Appendix A
Normal Ranges for Selected Biochemical Parameters
Parameter
Bionetics
Wilson
Lourdes
PCL
PCB (ppb)
N/A
N/A
N/A
0-20
0-30
SCOT (IU/1)
7-46
8-36
8-44
N/A
N/A
SGPT (IU/1)
0-50
2-32
3-38
N/A
N/A
GGTP (IU/1)
8-37
0-42
15-85
N/A
N/A
10-150
47-180
20-200
N/A
N/A
120-200
150-250
150-250
N/A
N/A
30-65
-
25-58
N/A
N/A
Triglycerides (mg/dl)
Cholesterol (mg/dl)
HDL cholesterol (mg/dl)
BRL
�
Dublin Core
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Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
089
Folder
The folder containing the original item.
2269
Series
The series number of the original item.
Series IV Subseries II
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Creator
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Gleit, Alan
Arnelle G. Cohen
Kenneth H. Chase
Title
A name given to the resource
Typescript: Draft Summary Report of the Medical Surveillance Program for the Binghamton State Office Building Decontamination Project, August 7, 1985
Subject
The topic of the resource
BSOB
health monitoring
health studies
-
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
086
Folder
The folder containing the original item.
2161
Series
The series number of the original item.
Series IV Subseries I
Dublin Core
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Okie, Susan
Source
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The Washington Post
Date
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April 18 1986
Title
A name given to the resource
Dioxin may Weaken Ability to Fight Disease
Subject
The topic of the resource
health studies
herbicide toxicology
human testing
-
Dublin Core
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Title
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Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
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Box
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086
Folder
The folder containing the original item.
2155
Series
The series number of the original item.
Series IV Subseries I
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Creator
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Finch, James A., Jr.
Description
An account of the resource
<strong>Corporate Author: </strong>Missouri Dioxin Task Force
Date
A point or period of time associated with an event in the lifecycle of the resource
October 31 1983
Title
A name given to the resource
Final Report of the Missouri Dioxin Task Force including Appendices
Subject
The topic of the resource
herbicide damage assessment
health studies
decontamination
clean-up standards
-
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
085
Folder
The folder containing the original item.
2154
Series
The series number of the original item.
Series IV Subseries I
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Description
An account of the resource
<strong>Corporate Author: </strong>Missouri Department of Social Services, Division Health
Date
A point or period of time associated with an event in the lifecycle of the resource
October 16 1983
Title
A name given to the resource
Two letters, a press release and the Executive Summary of the Progress Report: All items in regards to the Missouri Dioxin Health Studies and dated October 16, 1983
Subject
The topic of the resource
Missouri Dioxin Study
human exposure
health studies
-
https://www.nal.usda.gov/exhibits/speccoll/files/original/e25158f908501f63663937ff42c0eaa9.pdf
680b181aa029d79188de4519c54ef60f
PDF Text
Text
Item ID Number
01495
Author
Lathrop G. D.
Corporate Author
ROpOTt/ArtlClO TltlO Typescript: Chapter 5: The Epidemiology of Agent
Orange and its Associated Dioxin
Journal/Book Tltlo
Year
0000
Month/Day
Color
n
Number of Imaofls
29
DOSGPiptOn NOtOS
~""n's manuscript is a draft version of a chapter or section
from the following book: Agent Orange and its
Associated Dioxin: Assessment of a Controversy.
Young, A. L. and G. M. Reggiani, eds. New York:
Elsevier, 1988. This book is available in the NAL
collection, call no.: RA1242 T44 A3. This chapter
discusses health studies, the problems with conducting
viable epidemiological studies, and proposed
disease/conditions attributable to agent orange/dioxin.
Tuesday, May 15, 2001
Page 1495 of 1514
�CHAPTER 5
"IN THE FINAL ANALYSIS, THE EVIDENCE OF RISK FROM
THE COMPONENTS OF AGENT ORANGE MUST BE OBTAINED FROM THE
STUDY OF HUMAN POPULATIONS."
THE EPIDEMIOLOGY OF AGENT ORANGE
AND ITS ASSOCIATED DIOXIN
G. D. LATHROP
This chapter focuses on the realm of adverse human
health effects following exposure to Herbicide Orange and
TCDD. The many outstanding contributions of toxicologists
and pathologists have given a firm platform for clinical
concern, Clearly, TCDD is a remarkable, broad-ranged, profound cellular toxin that is, for reasons not fully understood, species specific (35). The key science questions
to resolve: is man among the affected species, and, if so,
what are the specific measureable attributable symptons, signs,
syndromes or diseases? The traditional difficulties in transitinning from the animal laboratory to the human laboratory
have been compounded, by the progressive array of special
interest groups, media representation, legal action, congressional
interest, and finally, legislative compensation. Young (36)
has aptly described this sequence as the "Crossroads of Science
and Social Concern." Now with the legal and compensatory
issues largely settled--i.n the absence of, or because of, the
absence of a science answer of causality—the broader questions
become: do we have a "cart before the horse" situation, and
if so, will the dioxin controversy serve as a model for
future solutions of environmental controversies?
Thus, it is appropriate to examine some of the root
causes of our slow and, perhaps now, inadequate science.
5: 1
�These fundamental science difficulties fall into the broad
categories of methodology, and operational and study circumstance, some of which are listed in Table 1.
Table 1. Fundamental Epiclemiologic Difficulties in the
Conduct: of Health Studies.
Precedence:
Lack of Definitive Acute/Chronic Diseases
D i s e a s e S p e ctr u m
Nonspecificity of Alleged Symptons
Rareness of Proposed Clinical Endpoirits
Limitations of Epidemiologic Methodology
Case Control vs. Cohort Studies
Study Sample Size
P o p ulution As c e r t a i nme n t
Sample Size™-Exposure Reversal
Pitfalls in Merging Cohorts
Exposure to TCDD
Latency
Proven vs. Probabilistic
Vietnam Misperceptlons
Assessment of Causal Inferences
M i s c 1 a s si f i ca ti o n
Bias
Confounding
Use of All Covariates
5: 2
�These science difficulties in the dioxin controversy
are magnified somewhat by the current state of the art and
science of the cpidemiologic process. Because of the great
advances in mathematical statistics in the past decade
vis-a-vis the essentially unchanged "artful" data collection
techniques in humans and human populations, epidemiology no
longer rigidly holds to the computer axiom of "Garbage In-Garbage Out," but may more pose a state of "Garbage In—Elegance
Out." The point is that the reviewer scientist should not
be mesmerized by the mathematical ingenuity, but must primarily
consider the fundamentals of data collection (source, accuracy,
etc.) and the study design before accepting a given study as
an important piece of work (6).
Further, all studies must be placed into the context of
the overall causal inference. As Moore (23) has nicely said
in the past, each dioxin study is part of the mosaic needed
for an overall scientific conclusion, since.each study is not
definitive in and of itself. This, of course, largely stems
from the facts that the epidemiologic process cannot prove a
negative association but can only attempt to bound it by
logical inference and that each study generally presents a series
of inherent methodologic flaws.
With this background in mind, let me return to the fundamental science difficulties of the dioxin controversy, focusing
on the science and operational issues rather than on specific
critiques of previous studies.
ORIGIN OF THE SCIENTIFIC ISSUE
In October, 1969, the first report was made of an increase
in congenital abnormalities following administration of 2,4,5-T
to pregnant rodents. Because of this report the Department of
Defense halted all aerial dissemination of 2,4,5-T containing '
herbicides in Vietnam during 1970, unfortunately lending
5; 3
�credence to the longstanding enemy propaganda claims of
chemical warfare (35), In 1973,the National Academy of
Sciences (NAS) conducted an in-depth assessment of the
forestry and ecologic implications of herbicide spraying in
American-held South Vietnam (24). Health studies -were not a
planned segment of the evaluation, nor could they be attempted
because of the wartime environment. In 1977, Maude DeVictor,
a Veterans Administration (VA) claims clerk at the Mines
Hospital in Chicago, noted a commonality of subjective complaints in Vietnam veterans (17). Prominent symptons centered
about the ncuro-asthenia complex, skin disorders, affective
disorders, and An increased frequency of birth defects. A
non-scientific association was made to Agent Orange exposure
in Vietnam and was quickly promulgated by the news media.
Initial inquiries to the Department of Defense and the VA
induced responses that proper scientific study of U.S. ground
personnel would be difficult or inappropriate because of the
difficulty in determining true exposure, a point later challenged by a Government Accounting Office (GAO) report (31). In
1979, the first of a series of Swedish case-control studies
suggested the additional endpoint of soft tissue sarcoma
(5,9,10). From the first involvement of veteran population
groups, both scientists and politicians quietly debated
whether the Agent Orange controversy had scientific merit,
or whether the issue was simply the flagship carrier of
veteran concern regarding their postwar treatment by the
American public. Also in 1979, the EPA Alsea Oregon study
suggested that miscarriages were associated with dioxin
exposure, but the study was quickly assailed for methodologic
difficulties (30).
From the period of 1980 to the present a great variety
of governmental and industry studies were initiated to
investigate both specific and generic proposed effects of
exposure to dioxin (1,4,7,8,12,16,18,19,20,21,29,32,34,37),
5: 4
�Thus, in relatively short order, the scientific issue trans itioned from animal toxicologic studies to social concern to
the proving ground of epidemio.log.ic studies.
STUDY COHORT ISSUES
Several key issues surrounding the study population guide
the use of a particular epidemiologic design. They include:
t*
Study Population Size
Determination of the Quality of Exposure
Single vs. Multiple Combined Study Populations
Rareness of the Proposed Clinical Conditions
The relationships of these parameters are depicted in
Figure I. Because of uncommon sustained exposure to dioxin,
discreet populations available for study are limited. Figure
II shows some of the traditional study groups and their crude
ranking of exposure relative to each other.
Figure I.
Formulation of the Epidemiologic Design.
Available Study Populations
(Type, Size).*-
Quality and Degree
*-0f Exposure
Epidemiologic
Study Design
and Methods
Clinical Endpoints of
Interest (type. Frequency)
Available Comparison/
Control Group
Sufficient Statistical
Power
5: 5
�Figure II.
The Exposure -Sample Size Quandary.
Oom.1
5: 6
�As a generality, the highest exposed groups represent
the smallest population sizes, and conversely, the lower
exposed groups contain the highest sample sizes. This exposurestudy size reversal is the first fundamental reason why ideal
epidcrniologic studies cannot be quickly formulated and conducted in the clioxin setting. Several other ramifications
of the exposure-sample size reversal are also apparent.
Small population groups often present ascertainment and location
difficulties, making them more amenable to study bias. If
the study focus is upon rare or uncommon diseases, small
population groups cannot be justifiably used because of a
lack of statistical power. Further, there is great temptation to merge (add) study cohorts as a mechanism of enhancing
statistical power. If the cohorts cannot be proven identical
with respect to quality and degree of dioxin exposure as well
as host parameters (age, sex, race, employment history, etc.)
an egregious error of dilution of the effect is likely (22).
Stated another way, a small borderline "positive" study might
be falsely converted to a negative study with higher stated
power and presumably, more scientific credibility. The
merging process has, in fact, been proposed by several
scientists (12) as a solution to the sample size dilemma;
it must be approached with great caution.
The type and frequency of the proposed clinical endpoints
under study have a. major influence on the overall epidemiologic
study design. Table 2 depicts the major signs and symptons of
Agent Orange and dioxin exposure both from a literature review
up to 1980 and a distillation of the VA's Agent Orange Registry
(32).
5: 7
�Table 2. Components of Selected Human Sympton/Signs Following
Exposure to Phenoxy Herbicides and/or TCDD.
NEURO-PSYCHJATRIC ABNORMALITIES
ASTHENIA
PERIPHERAL NEUROPATHY
Anxiety
Depression
•Fatigue
Apathy
Loss of Drive
Libido
Impotency
Sleeplessness
E motion a 1 Ins t a b :i. 1 i t y
Anorexia
Dizziness
Learning Disabi 1.ity
Hyporeflexia
Weakness
Paresthesias
Extremity Numbness
Myalgia
Gait .Disturbance
"Mild" Paresis
Chioracne
Porphyria Cutanea Tarda
Hyp e rp i gmen t a t i o n
Hirsutism (Body)
Alopecia of the Scalp
OTHER DISORDERS
RENAL DYSFUNCTION
Cholesterol
SCOT, SGPT, LDI1
Nausea
Vomiting
Diarrhea
Gastritis
ADD Pain
Flatulence
Proteinuria
Decreased Output
Tubular Degeneration
Glomerular Degeneration
Renal Glucosuria
Bradycardia
Tachycardia
Atrial Fibrillation
�From the perspective of the causal relationship, some
scientists have interpreted the wide array of signs and symptoms
as highly supportive of the animal studies and of the notion
that dioxin indeed induces multi-organ system effects. Other
scientists view the sympton complex as indicative of alternant
etiologies, including chance, bias, and social causes. In
formulating a suitable epidemiologic study, the above broad
based symptom complex poses formidable design issues. Most
of the alleged symptons are highly subjective in nature and
require sophisticated and detailed survey research (questionnaire) methods or laboratory testing for validation. The
reported, clinical signs are generally transitory following
acute exposure and thus could not be relied upon validly for
cross-sectional or follow-up studies. In addition, only the
sign of chloracne could be considered (and not strictly so)
as specific for dioxin exposure, while the rest are relegated
to nonspecific signs and symptoms (3). Wide clinical nets
must be cast to determine if attributable disease syndromes
or diseases exist. In the other extreme are the proposed
rare disease endpoints of soft tissue sarcoma and porphyria
cutanea tarda. Clearly, the rareness of these diseases precludes any active clinical attempt to describe them by crosssectional or prospective cohort designs. Thus, the second
fundamental cause of the dioxin complexity is the extreme
divergence between the alleged disease conditions (common
subjective vs. rare objective) with little middle ground available for powerful classic studies using multiple independent
designs,
The third fundamental reason for the science complexity
centers upon the true exposure circumstance of the study population. Since chloracne is the herald sign of dioxin exposure,
some scientists believe that chloracne is a requirement as a
precursor to the emergence of serious disease (28). The
epidemiologic viewpoint of this notion is somewhat contrary
5: 9
�and holds that chloracne is not a required precursor but is
merely a'point on the overall spectrum of illness. Further,
it is likely that the study of chloracne populations is simply
a focused study upon the higher exposed segment of the population, a process that is a traditional starting point in
occupational epidemiology (13,14,25). With respect to tHe
study populations of industrial workers, dioxin workers,
pesticide applicators, and the Air Force Operation Ranch.
Hand members, the exposure question is generally not "if,"
but "how much?" Exposure estimation has magnetic appeal to
the scientist because a demonstrated positive dose-response
relationship is one of the most convincing of the eight parameters used in establishing a cause-and-effect re 1 at ions hip,
For the above population groups, a variety of exposure
estimators are feasible; industrial hygiene data a,nd tiweweighted projections; occupational titles adjusted by personyears of employment; an average tinie-weighted experience in
dispensing herbicides. For industrial accident populations,
exposure indices derived from soil contamination levels or
concentric circle analyses are reasonable approaches.
However, for most Vietnam veterans and certainly the
general United States population, the exposure question is
"Did it occur, yes or no?" not "how much?" For these populations assignment of exposure is subject to overwhelming possible
bias or misclassification (15). More on this later for the
Vietnam veterans. Unfortunately, in epidemiology, most
exposure estimators do not pan out. Linear relationships
between the exposure estimator and the expected effects are
rare because of the variability in these measurements plus
such intervening factors as age, sex, race, and susceptibility.
Thus, the three fundamental difficulties of sample sizeexposure reversal, ascertainment of exposure, and the breadth
of alleged symptoms and disease are intertwined to produce a
5: 10
�science polemic of the first order, Since the ultimate
resolution depends upon the strengths and weaknesses Q£
scientific methodology, a, brief description of the
available epidemiologic designs is in order,
A hierarchal order of scientific sophistication
ges'ted by the type of study undertaken, and further
a relative contribution to the solution Of an issue.
ranking is displayed in Table 3,
A notable exception to this ordering is the
worth of well described case reports and case series to. e.xppsure.~
disease problems. Such efforts by tqxicologists , clinicians
and pathologists arc invaluable in defining acute disease and
are often instrumental in predicting chronic effects.
Similarly, uncontrolled .mortality or morbidity 'studies -mayprovide useful clues that merit inclusion in larger controlled
studies. Multiple design parameters can be enfolded into most
of the listed, types of studies and can be as convoluted and
complex as the circumstance and available funding allow. For
example, one Government study uses a nonconcurrent prospective
design with a mortality component and four referent groups,
a retrospective morbidity assessment, a cross-sectional
morbidity study, a 20-year follow-up study, all with both
matched pair and stratified analytic techniques; additionally,
this study possesses the opportunity of conducting embedded
case-control cancer studies and specialized comprehensive
fertility/reproductive efforts (19) . Most epidemiologic
studies in the dioxin arena, however, are less interlinked
and generally condensed to either case-control studies or cohort studies. The advantages and disadvantages of these
approaches are summarized in Table 4.
5: 11
�Table 3.
Science Assessment of Medical Studies.
Study Parameters
[De
Concurrent
Nonconcurrent
Conditions of Stydy
Type of Study
•Mwa<H>«lL.«.•,..««.. •-IUWWI-.P «,-.,-—» wnb,uun»u»b»
Case Report
Case Series
Literature Reviews
Mortality Studies
Uncontrolled, Controlled
Death Certificate vs.
Medical Record Confirmation
Cross -• Sect iona 1
Retrospective
Prospective
Morbidity Studies
Uncontrolled, Controlled
Follow-up Studies
Uncontrolled, Controlled
Experimental Studies
Natural, Planned
Matched
Randomized
Stratified
Table 4. Advantages and Disadvantages of the Conduct of
Case-Control and Cohort Epidemiologic Studies.
Cohort Study
Advantages:
F a s t, I n e xp e n s i v e
Tailormade for Rare Diseases
Easily Repeatable if Causal
Association Truly Present
Disadvantages:
Highly Subject to Bias
Often Difficult to Assess
the True Risk
Accurate Estimates of Risk
Biases Amenable to Control
Laborious, Time-consuming
Expensive
Cannot Practically Investigate
Rare Diseases
Difficult to Apply to Diseases
of Long Latency
5: 12
�As a brief review, the case-control stud/ begins wjvth
collection of, disease cases which a,re then assigne.d
controls; both-the cases and the controls are then
tively assessed for the presence or absence o,f tlxe e,.xjpqs,u;j>Q
or causative variable. This .method is the da,y>,tQr>day< WQrkn
horse used in epidemiology, and many articles and te^ts have,
highlighted, its applications and limitations. The case-control
method is quick, inexpensive, ideal for rare diseases, generally
repeatable, and often the only available technique that avoids
ethical barriers. Alternatively, this method is terribly
subject to bias, and in particular, respondent bias when the
exposure assignment is made. Most of the published dioxin
studies have used this method in one form or another, and
significant caution is required in the interpretation of
results. In contrast to the case-exposure sequence of casecontrol studies, cohort studies begin with exposed individuals
and a determined control or comparison group consisting of
non-exposed individuals; the entire cohort is then observed
forward in time from the point or points of exposure, and
disease conditions of interest are recorded. Because of the
extreme cost and the complexity of the data base, cohort
studies usually require government or industry support. The
advantages and disadvantages of the cohort method are almost
a point by point opposite of the case control technique.
The key feature is that for exposure scenarios like Agent
Orange and dioxin where there has been substantial media
coverage, respondent bias to the exposure circumstance may
well exceed the correction capacity of a cohort study. Overall, because of the relative shortcomings of each epidemiologic
method, a. series of studies using different methods and designs
are required to establish a causal relationship firmly. A
traditional study sequence is depicted in Figure III.
5: 13
�Figure III.
Case, Case
Series Reports
Traditional Epidemiologic Study Sequence.
Pilot/Vanguard
Effort
•mi-.ru
Case-Control
Study
tf.
Cohort
Study
M «• •» 4^-
Intervention
TriaJs/Programs
"—- —L ••"••"-'
• Full Hypothesis Testing
* Risk Assessment
Purpose: * Assess Siudy Feasibility
* Determine Case/Population
Parameters, Sampling Scheme
• Risk Management
• Formulate Medical/
Social/Legal Parameters
for Disease Prevention
Other CaseControl Studies
• Formulate Hypothesis
• Restricted Testing of Hypothesis
General emphasis points are: 1) pilot or vanguard efforts
are often, not desirable when the exposed study population size
V
is small so as to avoid "contamination" and eventual loss of
additional size to the full study, 2) initial case-control
studies are best used for hypothesis testing, and 3) causal
relationships are more accurately determined with the addition
o f co ho rt s tud i e s.
With the limitations of the epidemiologic process in mind
and recalling the three fundamental components of the science
knot, it: is now appropriate to assess the credence of the links
of specific diseases to exposure to Agent Orange and dioxin.
5: 14
�PROPOSED DISEASE/CONDITIONS ATTRIBUTABLE TO AGENT ORAKGE/DIOXXN
CHLORA.CNE:
Numerous clinical and. epidemiologic studies have unequivocally established the causal link between chloracne and
exposure to dioxin (13,14,25). There is no scientific debate
to this fact. However, chloracne is not specific to dioxin
exposure and may be induced by other compounds including the
dibenzofurans (34). The diagnosis is easily made in the acute
fulminate stage but may be exceptionally difficult in its
chronic form, often necessitating biopsy confirmation or the
examination by a dermatologist particularly astute with chloracne,
The disease may be diagnosed 30 years after onset in some
cases (28). The only difficulty presented by chloracne is
the differential diagnosis with adolescent acne in population
groups with low exposure. In such instances, as with. Vietnam
veterans, the diagnosis must be attempted by detailed questionnaire techniques, clinical examination with biopsy, or by
medical record review. This approach -may be confounded by
respondent bias as well as by a lack of contempoTaxy
clinical acumen. As mentioned previously, it may well be that
confirmed chloracne within the study population -may merely
represent a level of dioxin exposure that -merits farther
study for the emergence of other clinical conditions.
PROPHYRIA CUTANEA TARDA:
Porphyria cutanea tarda (PCT) is the most common form
of a rare class of diseases (porphyrias) affecting hemoglobin
metabolism. The porphyrias range in severity from life threatening hepto-dermatologic disease to subclinical illness. Their
classification and etiologies are complex. PCT may be caused
by hereditary factors, chronic alcoholism, exposure to diverse
chemicals, or combinations thereof. The causal association of
PCT and dioxin was made following two independent industrial
episodes in New Jersey and Czechoslovakia. Chloracne was also
a predominent sympton in both plants where pentachlorophenol
was produced. However, pure exposure to TCDD was far from
5: 15
�shown, and in retrospect, it is possible that confounding
exposures, particularly to the chlorinated benzenes, may
be implicated in the induction of the PCT cases (11). Thus,
definitive evidence of the role of TCDD must await additional
industrial circumstances or possibly the conduct of casecontrol studies. However, because of the known etiologic
role of other chemicals, the extreme rareness of PCT, and
the difficulty of respondent bias, it is unlikely that casecontrol efforts would generate clear-cut results to the satisfaction of the scientific community unless an international
comprehensive registry or data base is formulated.
SOFT TISSUE SARCOMA:
Soft tissue sarcoma (STS) is a generic malignant cancer
that actually embodies 1.10 distinct histologic subtypes found
in essentially all anatomic locations. The histologic differential diagnosis between sarcoma and carcinoma is often
difficult,and the variation between pathologists often leads
to substantial misclassification of the tumor. For this
reason, and as well demonstrated by Fingerhut et-al. (8),
histologic confirmation by an expert or expert panel is a
requirement to conduct a meaningful study of STS. The quick
approach of a case-control study using a death certificate
data base also presents the unusual problem of very significant
Linderascertainment of the sarcomas. Because of a quirk in
the medical coding system, up to 40 percent of the fatal
deep-seated sarcomas may be missed (8).
Due to the extreme rarity of STS, as exemplified by a
United States death rate of 0.07 percent, only the casecontrol method stands a reasonable chance to clarify the causal
association. The technique of merging industrial cohorts from
mortality studies or surveillance programs may also be
acceptable and provide useful data in the presence of marked
case clustering, provided that the previously mentioned merging
cautions are observed and that measurement of the cancer
patterns follows the merging process. While these techniques
5: 16
�may or may not be ultimately useful, the basic question of
biologic plausibility remains. According to some pathologists,
it is difficult to imagine how a single chemical could induce
multiply related cancers in a diversity of anatomic sites.
Such a phenomenon, if true, would run contrary to the classic
cancer-chemical models which now exist (e.g., mesothelioma
and asbestos; and polyvinyl chloride and brain tumors).
The association of STS and dioxin exposure was raised
by four Swedish reports beginning in 1979 (5,9,10). These
serial papers reveal slightly different study and referent
groups to obtain a "relative risk" of 5-6, impressive, to
say the least. However, all these studies used the casecontrol method, and serious questions are posed for the issue
of respondent or proxy respondent bias. In the view of some
workers, the methodologic weaknesses of the Swedish studies
render the association of STS and dioxin to the lowest
order. However, the association is fixed in the minds of
many, including Congress, and clearly, all dioxin scientists
will have to account for STS if their study population and
epidemiologic design permit.
Thus, because of STS diagnostic difficulties, underascertainment induced by the International Classification of
Disease (ICD-9) coding, and disease rareness which mandates
a case-control design, many more carefully conducted studies
will be required to resolve the suspected STS-dioxin
association.
FERTTLITY/REPRODUCTIVB ABNORMALITIES:
Fertility difficulties, fetal wastage, and overt birth
defects were alleged by Vietnam veterans to be caused by
exposure to Agent Orange. In terms of biologic plausibility,
there is no known human example or animal model to demonstrate
that male exposure alone can induce such effects. Four recent
5: 17
�epidemiologic studies have shown mixed results with respect
to these endpoints. The Dow Chemical Company study of workers
exposed to chlorophenols and dioxin largely showed negative
findings (29). For the parameters it attempted to cover, it
was a credible effort. The Center for Disease Control (CDC)
study of veterans and Vietnam veterans in the Atlanta, Georgia,
area also Largely revealed negative results, but it should
be noted that certain analytic procedures and statistical
assumptions merit additional review (4). The Australian
birth defects study, using a classic case-control design,
showed that a Vietnam veteran was at no higher risk of
fathering a defective child than a non-Vietnam veteran (1).
The Air Force Ranch Hand study, using a nonconcurrent prospective design with a physical examination component, determined
negative findings for most classic fertility/infertility
indices, severe and moderate birth defects, and both total
sperm counts and percent abnormal sperm (19). However, in
this latter study, for limited birth defects (e.g., birth
marks and skin tags), neonatal deaths, and physical handicaps,
the exposed group showed statistically significant excesses.
All findings were based upon subjective questionnaire data,
unverified by birth certificate or medical record reviews.
An overreporting bias was suggested in the data set, but it
was not fully analyzed. These baseline findings are the
subject of current intensive record verification and
follow-up; the findings should be published in late 1986.
Thus, with respect to fertility/reproductive abnormalities,
the preponderance of evidence is largely to the no-effect side,
but additional studies and follow-up are still indicated. It
is anticipated that the current CDC morbidity study being
conducted at the Lovelace Clinic and the first follow-up
Ranch Hand study at the Scripps Clinic will provide significant
clarifying data.
5: 18
�OTHER FINDINGS;
The Air Force Ranch Hand study noted the curious finding
of peripheral pulse deficits in the exposed group,
known mechanism to explain this effect (19)•
There is no
Of considerable
interest was a similar but statistically nonsignificant finding in the Times Beach morbidity study ( )
7.
The unpublished work of Ward has stimulated considerable
interest in the possible adverse effects of dioxin on the
immune system (33).
The Ranch Hand baseline study showed
no group differences with respect to B & T cell count and
functional tests but did reveal for the first time the profound effects of age and smoking upon these measurements
(19).
Additional assessments of these immune parameters are being
conducted in the Ranch Hand follow-up study as well as the
CDC morbidity study.
The discussion to this point has made several references
to the possible exposure differences to Agent Orange in
veteran cohorts.
Because this fundamental point will have
great bearing on the interpretation of future veteran study
results, a review of the exposure dilemma is in order.
THE EXPOSURE CONTROVERSY FOR VIETNAM VETERAN COHORTS
DIRECT EXPOSURE:
Since 1978, Vietnam veterans have alleged that they
received substantial direct exposure to Agent Orange via
aerial dissemination (OPERATION RANCH'HAND).
Media "docu-
mentaries" (best exemplified by Mr. Kurtis' Vietnam's Deadly
Fog [l/U ) , statements to the media by veterans and veteran
activist groups, and widely publicized Congressional hearings have presented a convincing scenario of significant
direct exposure, to the point, in fact, where the public and
jiiost scientists believe that military service in Vietnam is
equivalent to Agent Orange exposure.
5: 19
�Because this misperccption will have profound effects
in .the interpretation of ongoing or future studies, it is
important to balance the record. I believe that the following
statements accurately reflect the exposure circumstance in
Vietnam:
1.
U.S. ground personnel were only rarely directly exposed
to aerially dispersed Agent Orange because of the
related facts that:
a.
The Air Force fixed-wing aerial herbicide missions
were flown 4-6 weeks in advance of ajntlj^iplated ground
conflict (e.g., remote areas generally away from U.S.
troop concentrations Q2,3,s] ).
b.
Army commanders were included in the approval cycle
for all missions to improve mission effectiveness
and to restrict U.S. troop entry because of the
often intense fire cover provided by U.S. fighter
escorts.
2.
Some U.S. ground personnel were undoubtedly exposed to
Agent Orange via helicopter and backpacks used to spray
camp perimeters. On extremely rare occasions, a few
soldiers may have been exposed to Ranch Hand aircraft
in the process of experiencing emergency dumns of
herbicide. Many personnel may have been exposed to
contaminated soil, dust, water, and foodstuffs, but the
occurrence, extent, or relevance of such exposure is
unknown. The U.S. personnel who occasionally assisted
in herbicide loading operations were likely exposed.
Because of limitations in military records, precise
identification of any of the above persons is virtually
impossible.
3.
U.S. Air Force Ranch Hand personnel: pilots, navigators,
crew chiefs, and aircraft repairmen were substantially
5: 20
�exposed to Agent Orange and many other herbicides while
in Vietnam. It is crudely estimated that the average
annual exposure of an aircrew member was 1,000 times the
dose received by an unclothed man standing directly
beneath a low-flying spraying aircraft (19). Precise
quantitation of the exposure of a Ranch Hand member is
not possible, nor can relative exposure be determined
between occupational categories.
4.
Most U.S. servicemen in Vietnam were intentionally
exposed to aerially disseminated malathion in an effort
to quell the malaria problem. The malathion was dispensed by virtually the same fixed-wing aircraft that
sprayed Agent Orange (2). It is understandable why
many veterans honestly believe that they were sprayed by
these aircraft in Vietnam; they were. This fact precludes
questionnaire techniques to determine exposure because of
misclassification of the responsible aircraft.
5.
Because of a lack of chloracne in Ranch Hand personnel and
U.S. Army personnel, it is inferred that these populations
received substantially less exposure than industrial
populations (19).
PRO.B ABILISTIC EXPOSURE :
Following the Congressional mandate to conduct an epidemiologic study of U.S. ground personnel, significant scientific
energy was devoted to the clarification of the exposure issue.
The second GAO report on the Agent Orange issue suggested the
use of the HERBS tapes, a computerized chronicle of the map
coordinates of "spray on" and "spray off" points for each
herbicide mission (31). By calculating a time-distance
matrix of the soldier's headquarters location to the spray
line, a "likelihood exposure index" could be constructed
for each study and comparison subject, or alternatively,
5: 21
�the index could be used to determine the study and comparison
populations. This notion has transitioned in design through
the UCLA School of Public Health, the Department of Defense,
to the current Stollman and Stellman approach of a concentric
circle analysis (27). While I believe that these efforts
have been commendable and represent a valiant attempt, I
think they will eventually be shown to be without scientific
merit for several reasons:
1,
True direct exposure in Vietnam was a dichotomous
event, not a probabilistic event.
2,
Application of any probabilistic approach is made without
knowledge of the true misclassification rates of:
a.
b.
Designating an exposed person as unexposed and,
Designating an unexposed person as exposed.
Determination of these errors is not possible. It is
therefore not possible to calculate an overall required
study size to discern true specified group differences
(exposed, unexposed) at standardized alpha and 1-Beta
levels. Stated another way, such a study could not
validly assure the scientific community that it had the
ability to detect the putative effect at a given
frequency at a stated study size.
3,
The map coordinates cited in the HERBS tapes are largely
accurate, but many are inaccurate and based only on the
guesstimates of Ranch Hand pilots and navigators who were
under extreme combat or terrain-flying stress. Straight
line approximations or multi-leg zig-zag patterns can
only be viewed as gross approximations of many of the
missions in Vietnam. This error source can only be
adequately factored into the probabilistic approach by
the use of additional crude assumptions.
5: 22
�4.
The proximity of a given individual to an actual spray
mission the moment it was .flown as determined by a
review of Army battalion or company personnel records
represents a clear overreaching of the data source.
Errors implicit in such crude approximations are
incalculable.
The ultimate distillation of the probabilistic model(s)
is that it probably measures true direct exposure with the
same precision as a coin-flip. If it can do better, it is the
responsibility of the investigators to p_rove that point, and
in a clear and convincing way. Further, in the discussions
or writings of probabilistic methods, there is a noted
tendency to quickly drop the proper caveats of "probable,
likely, likelihood," etc., when discussing exposure, often
leading both scientists and lay readers into the unwarranted
shorthand assumption of true exposure.
The problems associated with specifying the true Vietnam
exposure scenarios and the likely interpretative problems
that will, arise from veteran studies should renew scientific
efforts to explore further study opportunities in industrial
or industrial accident populations.
AN OUTLOOK FOR DT.OXIN EPIDEMIOLOGY
The next five years will bring forth a variety of dioxin/
Agent Orange studies, predominantly of the case-control design.
Those cohort studies focusing on Vietnam veteran populations
will likely be well conducted, elegant, expensive, and considerably nagged by the exposure issue and interpretive
c o n s i cl e r a t i o n s .
The novelty of well conducted and large fat biopsy
studies should emerge, stimulating new discussions on the
dioxin half-life, mass spectroscopy, arid the relevance of
5: 23
�Vietnam exposure (37). As the causal relationship between
ch.loracne and clioxin is well established, few additional
studies should be published. Because of the confounding
effects of multiple industrial chemical exposures, chronic
alcoholism, and genetic contributions, plus the extreme
rarity of porphyria cutanea tarda, a cause-and-effect
relationship with dioxin will not be made unless registrybased international collaborative studies are conducted. The
prospect for consensus determinations on soft tissue sarcoma,
other cancers, excess generic mortality, fertility/reproductive abnormalities, neuroasthenia, psychological disturbances,
etc., is far more favorable than for PCX. However, the
entire resolution process will continue to be slow and
difficult, unfortunately lending further justification to
the social/legal solution of an issue that heretofore R
in the scientific domain.
5: 24
�REFBIUiN_C]GS
1.
Australian Veterans Health Studies, 1983. Case-Control
Study of Congenital Anomalies and Vietnam Service Qiirth
Defects Study). Report to the Ministry $oy Veterans'
Affairs, January, 1983. Australian Government Publishing
Services, Canberra, 127 pp.
2.
Buckingham, W.A. , Jr., 1982. Operation RANCH HAND. The
Air Force and Herbicides in Southeast Asia, 1961-1971.
Office of Air Force History, United States Air Force,
Washington, D.C. 253 pp.
3.
Crow, K.D. , 1981. Chloracne and its Potential Clinical
Implications. Cliiu_ E xpu Dcrmatol . 6 (3):243-257.
4.
Erickson, J.D., Mulinare, J. , McClain, P.W., et al., 1984.
Vietnam Veterans' Risks for Fathering Babies with Birth
Defects. J . Am . Me d i cal As s o c . 252:903-912.
5.
Erickson, M. , Harde.ll, L. , Berg, N.O. , Holler, T. , Axelson, 0.,
1981. Soft-Tissue Sarcomas and Exposure to Chemical Substances:
A Case-Referent Study. Br. J. Ind. Med. 38:27-33.
6.
Diamond, G.A. , and Forrester, J.S., 1983. Clinical Trials
and Statistical Verdicts: Probable Grounds for Appeal.
® • 98:385-394.
Talk, H., Stehr, P. A., Stein, G.F.., Sampson, E. J. , Donnell, H.D.,
Scliramm, IV. F., Webb, K. , Gedney, W.B. A Pilot Epidemiologic
Study of Health Effects Due to 2,3,7,8-Tetrachlorodibenzo
Dioxin (TCDD) Contamination in Missouri. Danbury Report "18:
Biological Mechanisms of Dioxin Action; Cold Springs Harbor
Laboratory, pp. 447-460, 1984.
Fingerhut, M.A. , Halperin, W.E., Honchar, P. A. , Smith, A. B.,
Groth, D.IL, and Russell, W.O. An Evaluation of Reports
of Dioxin Exposure and Soft Tissue Sarcoma Pathology in
U.S. Chemical Workers. Danbury Report 18: Biological
Mechanisms of Dioxin Action; Cold Springs Harbor Laboratory,
pp. 461-470, 1984.
5: 25
�9.
Hardell, I.,., and Sandstrom, A., 1979. Case-Control Study:
Soft-tissue Sarcomas and Exposure to Phenoxyacetic Acids
o r C h 1 o r o p h e n o 1 s . Br^J^ _Cance jr, 39:711-717.
10.
Hardell, L., 1981. Relation of Soft Tissue Sarcoma,
Malignant Lymphoma and Colon Cancer to Phenoxy Acids,
Chlorophenols and Other Agents. Scand^ J. WprkmEnvi:r_ cm.
HeaTth. 7:119-130.
11.
Hobson, L.B., April, 1983. Unpublished Report: Porphyria
Cutanea Tarda. Agent Orange Projects Office, Veterans
Adm i n i s t r a t i o n, W a s h i n g I; o n, D. 0.
12.
Honchar, P.A., and Halperin, W.E., 1981. 2,4,5-T,
Trichlorophenol, and Soft Tissue Sarcoma. Lancet, Jan.31:
268-269.
13.
Jirasek, L. , Kalensky, J., Kubec, K., 1973. Acne Chlorina
and Porphyria Cutanea Tarda. during the Manufacture of
He rb i c i de s . Ce_s k _._ Jte rma t£ 1. 48(5):306-315.
14.
Jirasek, L., Kalensky, J., Kubec, K., Pazderova, J., and
Lukas, E., 1974. Acne Chlorina, Porphyria Cutanea Tarda
•and Other Manifestations of General Intoxication during
the Manufacture of Herbicides. II. Cesic. DC^atol^.
49 (3) : 145-157.
15.
Kle.inbaum, D.G., Morgenstern, H. , and Kupper, L.L., 1981.
Selection Bias in Epidemiologic Studies. Am. J. _Ep_idemio 1.
113(4):452-463.
16.
Kogan, M.D., and Clapp, R.W. Mortality among Vietnam
Veterans in Massachusetts, 1972-1983. Massachusetts Office
of Commissioner of Veterans Services, Agent Orange Program:
Massachusetts Department of Public Health, Division of
Health Statistics and Research, January 18, 1985.
17.
Kurtis, B., 1978. "Agent Orange: Vietnam's Deadly Fog."
TranscrJ.pt of a television documentary aired March 12,
1978, WBBM-TV, Chicago, 111. 30 pp.
5: 26
�18.
Lathrop, G.D., Moynahan, P.M., Albanese, R.A., and Wolfe, W.H.
An Epidemiologic Investigation of H-alth Effects in Air Force
Personnel Following Exposure to Herbicides: Baseline
Mortality Study Results. Annual Report (Initial), United
States Air Force School of Aerospace Medicine, June 30, 1983.
19.
Lathrop, G.D., Wolfe, W.H., Albanese, R.A., and Moynahan, P.Mv
An Epidemiologic Investigation of Health Effects in Air Force
Personnel Following Exposure to Herbicides: Baseline Morbidity
Study Results. United States Air Force School of Aerospace
Me d i c i ne, F eb ruary 24, 1984.
Lamb, J.C., Moore, J.A., and Marks, T.A., Evaluation of 2,4dicblorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,3,7,8-tetrachlorobidenzo-pdioxin (TCDD) Toxicity in C57BL/6 Mice: Reproduction and
Fertility in Tratod Male Mice and Evaluation of Congenital
Malformations in their Offspring. National Toxicology
Program, Research Triangle Institute, Research Triangle Park,
N.C. Report No. NTP-80-44. 57 pp.
20.
21.
Lawrence, C.E., Reilly, A.A., Quickenton, P., Greenwald, P.,
Page, W.F., and Kuntz, A.J., 1985. Mortality Patterns of
New York State Vietnam Veterans.
279.
Am. J. Public Health, 75:277-
22.
Marshall, J.R., Priore, R., Graham, S., and Erasure, J,, 1981.
On the Distortion of Risk Estimates in Multiple Exposure
Level. Case-Control Studies. Am. J. Epidemiol. 113 (4) : 464-480.
23.
Moore, J.A., 1980. Report of the Agent Orange Working
Group Science Panel. Department of Health and Human Services,
Washington, D.C.
24.
National Research Council, 1974. The Effects of Herbicides
in South Vietnam: Part A. Summary and Conclusions. National
Academy of Sciences, Washington, D.C. AD-774-749.
25.
Reggiani, G., 1979. Estimation of the TCDD Toxic Potential
in the Light of the Seveso Accident. Arch. Toxicol. 2:291-302.
5: 27
�26.
Smith, A.H. , Pearce, N.E., Fisher, D.O., Giles, H.J.,
Teague, C.A. , and Howard, J.K., 1984. Soft Tissue Sarcoma
and Exposure to Phenoxyherbicides and Chlorophenols in New
Zealand. JNCL. 73:111-1.17.
27.
S tollman, J.M., and Stellman, S.D. Issues, Options and
Methodologies in the Determination of Exposure to PhenoxyHerbicides among Vietnam Veterans. Written Testimony
Presented to the United States District Court, Eastern
District of New York, February 20, 1985.
28.
Suskind, R.R., and Hertzberg, V.S., 1984. Human Health
Effects of 2,4,5-T and Its Toxic Contaminants. JAMA .
251:2372-2380.
29. . Townsend, J.C., Bodner, K.M. , Van Peenen, P.P., Olsen, R.D.
and Cook, 11. R, , 1982. Survey of Reproductive Events of
Wives of Employees Exposed to Chlorinated Dioxins. Am. J.
:U 115:695-713.
30.
U.S. EPA, 1979. Report of Assessment of a Field Investigation of Six-Year Spontaneous Abortion Rates in Three
Oregon Areas in Relation to Forest 2,4,5-T Spray Practice.
OTA/ EPA.
31.
U.S. General Accounting Office (USGAO) , 1982. VA's Agent
Orange Examination Program: Actions Needed to More Effectively
Address Veterans' Health Concerns. GAO/HRD-83-6 , October 25.
78 pp.
32.
Veterans Administration, Department of Medicine and Surgery.
Review of Literature on Herbicides, Including Phenoxy
Herbicides and Associated Dioxins. Volume I. JRB Associates:
1981.
33.
Ward, A.M., 1978. Investigations of the Immune Capability
of Workers Previously Exposed to 2 ,3,7 , 8-tetrachlorodibenzop-dioxin (TCDD) . Unpublished. Department of Immunology,
Hallamshire Hospital, Sheffield, U.K. 9 pp.
5: 28
�34. Wolfe, W.H., and Lathrop, G.D., 1983. A Medical Surveillance
Program for Scientists Exposed to Dioxins and Furans. Environ.
Scj.._Re_s^ 26:707-716.
35.
Young, A.L., Calcagni, J.A., Thalken, C.E., and Tremblay, J.W.,
1978. The Toxicology, Environmental Fate, and Human Risk
of Herbicide Orange and its. Associated Dioxin. USAF Occupational and. Environmental Health Laboratory Technical Report
No, USAF OEHLTR 78-92, 262 pp.
36.
Young, A.L., 1981. Agent Orange at the Crossroads of Science
and Social Concern. Report Number 2750-81, Air Command
and Staff College, Air University, Maxwell AFB, AL 36112.
63 pp.
37.
Young, A.L., Kang, U.K., Shepard, B.M., 1985. Chapter 13,
Rationale and Description of the Federally Sponsored
Epidemiologic Research, in the United States on the Phenoxy
Herbicides and Chlorinated Dioxin Contaminants. Keith, L.H.,
Rappe, C., and Choudhary, G. (Editors). Chlorinated Dioxins
and D.ibenzofurans in the Total Environment II. Butterworth
Publishers, Stoneham, Mass., 02180. 155-166.
5: 29
�
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Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
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056
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1495
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Series III Subseries II
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Lathrop G. D.
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Typescript: Chapter 5: The Epidemiology of Agent Orange and its Associated Dioxin
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health studies
chloracne
porphyria
soft tissue sarcoma
ao_seriesIII
-
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Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
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056
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1486
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Series III Subseries II
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Irey, Nelson S.
Florabel G. Mullick
Walter D. Foster
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Draft Copy of Vietnam Veterans and "Agent Orange": A Morphologic Study
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dioxin
health studies
AFIP
Agent Orange Registry
ao_seriesIII
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°1483
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Author
Corporate Author
ROpOTt/ArtiClO Title Typescript: Statement of Dr. Philippe Shubik, Senior
Research Fellow, Green College, Oxford University
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Descripton Notes
Tuesday, May 15, 2001
Page 1483 of 1514
�Statement of
Dr. Philippe Shubik
Senior Research Fellow
Green College
Oxford University
Ecclesiastes 3:22
Wherefore I
than that a
for that is
to see what
perceive that there is nothing better,
man should rejoice in how own works:
his portion: for who shall bring him
shall be after him?
Ecclesiastes 2:1
Then I looked on all the works that my hands had
wrought, and on the labour that I had laboured to
do: and, behold, all was vanity and vexation of
the spirit, and there was no profit under the sun,
Ecclesiastes 8:1
Who is as the wise man? and who knoweth the
interpretation of a thing? a man's wisdom maketh
his face to shine, and the boldness of his face
shall be changed.
�The historical background of a role for chemical carcinogenesis
in toxicology
The knowledge that chemical compounds or mixtures of
them might cause cancer originates from clinical studies of
occupationally exposed groups. The classic instance quoted
frequently in textbooks concerns the discovery that chimney
sweeps in England in the 18th century developed cancer of
the scrotum from prolonged exposure to soot begun in early
youth.
This observation by the English surgeon of note,
Percival Pott, stimulated many experimental studies at the
end of the 19th century and the beginning of the 20th. Various
research workers tried to reproduce this disease in laboratory
animals by painting solutions of soot and the related coal tar
on different laboratory animals. They were uniformly
unsuccessful until two Japanese research workers, Yamagiwa
and Itchikawa persisted in their studies and continued to
paint coal tar on the skin of the rabbit ear for many months.
These workers were not only persistent but were
fortunate to have chosen the right tissue in the right animal.
The factors involved in the success of this study have
influenced the design and interpretation of many of the routine
studies undertaken since that time. It is realized that it
is often difficult to obtain a positive finding even with a
chemical known to cause cancer in man. The dose, the route
of application and the species used as well as the length of
the experiment are" crucial factors in obtaining a valid result.
During the period between the discovery of the cancer
causing effects of coal tar and 1946 the subject of chemical
carcinogenesis was largely confined to two major areas of
investigation.
Firstly instances of occupational or so-called iatrogenic
(drug or treatment) induced cancers were investigated both in
human populations and the laboratory. Thus the causation of
human bladder cancer in the aniline dye industry was finally
elucidated when it was found initially that the chemical
20napthylamine caused the same type of cancer to occur in the
dog; this time the positive finding took up to 7 years of
administration of very large doses of the chemical to achieve.
This finding determined the future course of much of the
testing; the species, the time of the experiment as well as
the very high dose required added other factors to be taken
into account in determining the validity of studies.
In the instance of the coal tar observations it was
found that a single compound polycylic hydrocarbon, called
benzo(a) pyrene seemed to be the principle component
responsible to the cancer producing effect. (Subsequent
�- 2 studies have shown that it is probably that this is only one
of several similar compounds with this property; these many
years later this area still requires more work). It became
apparent that this compound usually abgreviated to B(a)P
was ubiquitous in the human environment. It occurs as the
result of combustion of organic matter and is found in small
quantities in polluted atmospheres, cigarette tobacco tars,
charcoal broiled meats, etc. The significance of these lower
levels in the causation of human cancer is anyone's guess.
In fact these so-called lower levels are, in the
instance of the charcoaled meats in the range of several parts
per million; with newer analytical methods this would be
considered to be a high level. Common sense contemplation
tells us that atmospheric pollution as seen in modern urban
environments is not a major factor in the current epidemic
of lung cancer; cigarettes are unequivocally a (if not THE)
major factor; yet there is usually more available B(a)P in
the polluted atmospheres.
Other cancer causing chemicals identified in the smoke
of the cigarette seem to be more likely candidates. Indeed
there are a large range of potent animal carcinogens present
in cigarette smoke including representatives of several
different chemical classes and radio-active particles. Thus
in the instance of the best established human carcinogen
affecting the general population the research worker is faced
with a mass of information and has not yet been able to sort
out the mechanism or precise factor(s) concerned. In this
instance it is, of course, possible to control the disease
by stopping smoking of cigarettes; it is not, however, possible
to introduce a "safe" cigarette with any degree of confidence.
Other practical aspects of research into the other
causes of cancer involved the demonstration that certain
medical procedures such as the use of certain diagnostic
procedures such as the use of a radioactive material,
Thorotrast, used for outlining parts of the body to be x-rayed
caused local cancers; naturally occurring hormones were found
to be able to cause certain kinds of cancer in animals and
this correlated well with observations in the human.
In the late 1920's a major event to have a considerable
effect on this era was the discovery that a food additive
known as "butter yellow" (chemically p-dimethylaminoazobenzene
[dab]) could give rise to liver cancers when fed to rats. This
finding was particularly influential in the development in the
1940's of routine testing of food additives for possible
cancer producing effects in animals. Butter Yellow (dab) was
no longer permitted for use even though there was no evidence
that it had had any effect on the cancer incidence in man.
�- 3 In the instance of a deliberately added food additive
no one wishes to know whether or not it was a human carcinogen;
it was felt more prudent to assume that it might be potentially
hazardous and to get rid of it. Since the use of this compound
was not particularly important economically this posed none
of the problems encountered later. Indeed this same dye was
used to colour chemical smoke for military purposes and it was
said by the late Dr. W.C. Hueper of the U.S. National Cancer
Institute on several occasions but without published figures
that no occupational hazard had been observed from massive
exposure to this compound in the U.S. arsenal. Even if this
were the case few would have advocated reintroducing this
compound in the U.S. arsenal. Even if this were the case
few would have advocated reintroducing this compound in the
food supply.
A second key incident was the testing of a proposed
pesticide then called 2-acetylaminofluorene in rats for a
two year period by a series of research workers in the U.S.
Department of Agriculture's research facility. This compound
proved to be a new kind of cancer producing agent giving rise
to many cancers in many different organ sites. As time has
gone on this chemical has proved to be an invaluable tool for
the research worker.
However the impact of this study was to result in the
beginning of long term routine testing of food additives and
pesticides notably in the U.S. regulatory agencies. This leads
us into the next era starting in the 1940's and I will deal
with this later.
The second major approach taken to research into chemical
compounds causing cancer subsequent to the discovery of the
effects of coal tar components was a major effort to try and
understand how these compounds worked. Needless to say this
effort continues and above all things it must be borne in mind
when considering the practical aspects of cancer control that
we still do not understand and the mechanisms of action of a
single causal factor of cancer and do not understand~iEhe nature
of cancer.Theories abound and some are based on enough facts
to be useful guidelines for preventive measures.
Studies into this field between 1920 and the end of
the 2nd World War took three distinct approaches; first a
series of compounds closely related to those first discovered
(B[a]P, or dab) were synthesized by able chemists and tested
in animals usually by painting them on the skin or injecting
them subcutaneously in the first case or feeding them in the
second instances. It was hoped that a clear cut relationship
between chemical structure and biological activity would be
established and that, from this, a mechanism of action would
be obvious. This logical idea was doomed to failure. For
these two decades it was firmly believed that only a very few
types of chemical structure had the capability of giving rise
to cancer and the older cancer research workers were quite
�- 4unprepared for the great onslaught when many new types of
compound were demonstrated to have somewhat similar activity.
The second approach was to study the metabolism or
these established cancer producing agents in animal systems.
The studies revealed that some compounds seemed to have to be
changed into other forms before they became active; this type
of study which is painstaking and long term still continues
and a large body of knowledge has been accumulated which has
both practical implications to control and can be counted
upon to play a major role in the eventual understanding of
mechanisms.
The third approach was the investigation of biological
and pathological factors affecting the process of cancer
induction. For example one scientists, Deelman, in the 1920's
found that he could greatly augment the effects of skin
application of coal tar by incising the skin simultaneously.
The healing would appeared to enhance the cancer producing
effects. This and a variety of other studies resulted in the
demonstration that at least for cancer induction in the skin
it seemed likely that a multiphased process was involved.
This has led to many studies on so-called "Initiation" and
"Promotion."
Other factors were found to inhibit the action of these
compounds and studies led to the discovery of many of the
modern chemotherapeutic drugs now in use. Much of this work
was stimulated by the discovery that mustard gas (also known
to be able to induce cancer) could inhibit cancer induction.
Many efforts were made to study the effects of different
routes of administration of chemicals and it was found that
this was of great significance; certain compounds active on
the skin had no apparent effect when administered by mouth and
visa versa. It was observed that many experimental rodents
developed tumours in the untreated state and that chemicals
could be seen sometimes to have a dual effect - both inducing
local cancers at the site of administration and "augmenting"
the incidence of some of these "spontaneous" cancers.
The distinction between these two effects still puzzles
the research workers and poses a major problem in the assessment of modern cancer bioassays in practical terms.
This early era involved the discovery that changes perhaps equatable with cancer - could be produced in tissue
cultures.
The knowledge that many species differences existed
was noted with interest and formed the basis for interesting
discoveries into mechanisms of action later on. A discovery
made accidentally by Oppenheimer at the end of this first
era, that inert plastics implanted under the skin of rodents
�- 5 caused cancer, gave rise to great confusion which, in truth,
has never been dissipated.
All the theories of chemical interactions being essential
for the production of cancer seemed to require revision. At the
same time it became apparent that certain results attributed to
specific chemicals might, in fact, be quite non-specific and
only a result of the physical nature of the material.
SUMMARY
The first era of the scientific study of chemical
carcinogens spanning the period from 1918 to the end of the
Second World War established a large base of knowledge that
several groups of chemicals could be shown to be responsible
for cancer in man and that these cancers could in most instances
be reproduced in animal models. The first inroads into understanding of mechanisms of action were made. At the same time
a series of other chemicals were found to be capable of
inducing different kinds of cancers in animal systems. It
started to be apparent that this characteristic of chemicals
was not as limited to a few types of chemical structure as
originally appeared.
The different end points possible in bioassays introduced
complexity that had not originally been anticipated.
THE PRESENT ERA
For the purposes of this discussion the present era
will date from the end of the Second World War, although in
truth major changes started taking place about 10 years later.
The first area of concern about the effect of chemicals,
and particularly new chemicals as potential causes of cancer
centered around the food additive and pesticide problem.
More food additives and more widespread use of pesticides
that resulted in residues in food appeared during this era
than perhaps altogether before that time.
Initially these chemicals were tested in a bioassay
that was designated as a 2 year chronic toxicity test. This
test was undertaken using the rat as the principal species
although some tests were done in mice. It was presupposed that
this test would uncover a variety of possible chronic effects
and there was no special emphasis placed on this test as one
for carcinogenesis.
The well known toxicologists, Barnes and Denz from the
U.K. believed such tests to be of little value and felt that
a subacute test of three months, if conducted properly, would
reveal the majority of toxic effects. Indeed their views
eloquently expressed in a review article in 1953 in advance
echoed some of our more modern attitudes.
�- 6 In the course of some of the earlier chronic toxicity
tests undertaken by the U.S. Food and Drug Administration many
subsequent findings were predicted. D.D.T., for example, was
found to be productive of liver tumours in mice; this was not
considered to be of practical importance at that time since
the tumors were all benign and only malignancies were thought
to be of relevance.
A variety of other food additives were found to augment
or induce various tumors in rodents and some were banned as
a result.
By the 1960fs it had become apparent that the primary
use of the chronic toxicity test was as a test for carcinogenesis and a survey of the literature reveals that little
else was detected in such studies.
In revising the Food Additives regulations in the
1960's the U.S. Congress took the far reaching and unusual
step of singling out carcinogenesis as a special form of
toxicity that required the regulatory agency to ban a compound.
The freedom of the regulator to make a value judgement was
removed. The regulation known as the Delaney amendment says,
in effect, that any food additive found to give rise to cancer
in man or in animal tests using an appropriate route of
administration shall not be used. This drastic regulation
was enacted after a considerable debate; a major factor in
its adoption was research undertaken in Germany by Druckrey
and his co-workers that had concluded that chemicals causing
cancer acted by a mechanism that was different from other
chemicals.
Whereas the cumulative effects of the majority of
chronic toxic effects were a result of an accumulation of the
chemical in question the effects of cancer causing chemicals
were visualized as an accumulation of irreversible changes in
the cells. There were several reasons for believing this to
be the case. The practical result of such a view of mechanisms
was that no tolerance level for such chemicals could be
determined; any dose whatsoever could be visualized as one
that produced an irreversible cellular change that potentially
could lead to cancer.
Although there is much validity in some of the deductions
drawn from some of these experiments it is also apparent that
tolerance levels for carcinogens are likely to exist.
Additionally the requirements of the Delaney amendment
assume tests for carcinogenesis to be much more easily
interpretable than is in fact the case. Since 1957 numerous
bioassays of chemicals for cancer induction have been made
and it is now quite apparent that many of these results are
extremely difficult to assess.
�- 7 In summary the Delaney amendment represents a gross
over-simplification; any detailed re-examination of this
legislation now would require a much more explicit statement
on the details of the animal studies.
The testing of food additives is emphasized since it
preceded the other uses of such tests and set the stage for
the use of these bioassays for chemicals of general environmental
interest, as well as extending the procedures used for evaluating
the potential toxicity of drugs.
A comparison of the problems associated with the toxicity
of drugs and of environmental contaminants illustrate almost
opposite ends of the spectrum in several regards. The drugs
are almost invariably administered in relatively high biologically
active doses whereas the environmental contaminants are usually
present at very low levels - often at levels that have only
recently become detectable because of the numerous advances
in analytical chemistry that have taken place. There is often
little or no knowledge of the effects of these very low doses;
they can only be inferred by theoretical extrapolation from
studies undertaken at much higher doses.
On the other hand the effects of the drugs are often
found at levels quite comparable with those used under therapeutic conditions. Drugs, however, are usually visualized as
useful, sometimes life saving, agents; environmental contaminant
chemicals, on the other hand are only seen as undesirable.
It is, therefore, the case that many drugs that are
clearly potential cancer producing chemicals (some even with
evidence obtained from human studies) are permitted for use
whereas some other chemicals, often pesticides, resulting in
contamination of the environment as parts per billion levels
only have been banned.
One of the clearest examples of this perhaps anomalous
situation is the instance of the oral contraceptives where
initial findings that liver tumors were induced on enhanced in
experimental rodents was considered irrelevant to human health
on the-basis that the endocrine physiology of the rodents was
not similar to the human. Subsequent epidemiological studies
revealed that these liver tumors did, in fact, occur in women
taking these drugs, albeit at very low incidence. This finding
has been ignored by regulators on the basis that the benefit of
the oral contraceptives outweighs this level of risk. It may
well be that this is an appropriate decision to have made for
society and unfortunate that such leeway is not available in
other instances.
�- 8 The bioassay of chemicals for possible carcinogenic
activity has proceeded particularly in the U.S. both in the
regulatory areas where food additives, pesticides and drugs
have largely been tested by manufacturers in order to obtain
the necessary rights to market these products. These requirements are commonly applied in a similar manner on a world
wide basis and many of these studies are carefully reviewed
by committees of the WHO and FAO such as the Joint Expert
Committee on Food Additives (JECFA) and the corresponding
committee on pesticide residues (JMPR). Both these committees
review procedures regularly and set approved levels for use
of these chemicals.
Although not bound in any way by such rigid and codified
procedures as those in inherent in the U.S. food laws the
philosophy inherent in the "Delaney amendment" has considerable
influence on the decision making of these international bodies.
More recently there has been a tendency to review this attitude
and there is now a clear desire to try and introduce a more
scientific and flexible judgement into these approaches.
The National Toxicology Program (N.T.P.) of the U.S.
has introduced another dimension into this problem. In this
program selected chemicals are, in essence, "screened" for
cancer induction in set tests in mice and rats; no account
is taken of use conditions in many of the tests performed so
far; thus the route of administration is not necessarily
determined by use conditions and dosage rarely takes use
conditions into account.
This approach has resulted in the accumulation of much
data showing some effect or another on tumor incidence in
rodents and the practical significance of this data has been
hotly debated. The assessment of such tests will be discussed
at greater length in the next section.
It is said that the protocols for these N.T.P. tests are
to be modified and to be made more relevant to use conditions
in the future.
SUMMARY
Certain specific product categories are now routinely
tested for carcinogenicity according to planned protocols.
Other more generalized long term animal tests are carried out
notably in the U.S. in large scale "screening" programs. Many
of the results obtained have been exceptionally difficult to
interpret in practical terms.
�- 9 Research patterns in chemical carcinogenesis:
1945-date
The first part of this era was concerned with following
up leads obtained in the three preceeding decades. Many new
classes of chemical carcinogen were discovered. Some of these
were more readily amenable to biochemical and molecular biological
study and thus more in-depth investigation of the interaction of
these compounds with cellular components has become possible.
Also newer techniques of cell biologists involving the
use of tissue cultures and of bacterial systems have played an
increasingly important role in such studies.
So far many of these interesting studies have not played
a major role in understanding the meaning of the practical
bioassays but it is not difficult to visualize a situation in
which much of this research may well play a role in elucidating
practical problems in the near future.
Since the early part of this century Bovari's theory
that cancer may be the result of a somatic mutation has been
considered possible. In the past decade a series of techniques
have been introduced for detecting mutations in various bacterial
and other systems. There have been those who have wished to
correlate this effect with chemical carcinogenesis; more recently
of such correlations have been shown to be less and less predictive,
A great deal of experimental work has been undertaken to
expand the concepts of "initiation" and "promotion" but so far
few basic mechanisms have been elucidated.
CURRENT VIEWS ON CRITERIA FOR EVIDENCE OF CARCINOGENICITY OF
CHEMICALS
Criteria for assessing evidence for the carcinogenicity
of chemicals were reviewed by a panel of the National Cancer
Advisory Board of the U.S. in 1977. In its introductory
statement this group stated that "The criteria that are
described are guidelines and not rigid, universal criteria.
The complexity of the problem dictates that the evaluation of
potential human hazards of a given agent must be individualized
in terms of the chemical and metabolic aspects of that agent,
its intended use(s), the data available at the time the decision
must be made, and other factors pertinent to the case under
consideration. Each case must considered on its own and the
criteria appropriate for one agent may not necessarily apply
to another."
This general statement of philopophy was accepted as
still valid by a more recent committee which has addressed
the same problems in an effort to update the situation. The
report of this committee that I had the privilege of chairing
will be published in the journal Science within the next few
weeks and a preprint of the article has been made available
to the Royal Commission.
�- 10 This article deals with problems in assessing evidence
derived from (1) Human studies, (2) Long term bioassays in
animals, (3) Short-term tests, (4) Mechanisms of carcinogenesis,
(5) Problems in extrapolation of experimental data, (6) the
overall assessment process.
The last section of this report is felt to be particularly
pertinent to present discussions and is recorded below:
The Overall Assessment Process
Chemical carcinogenesis is a rapidly moving field, and
great quantities of data have been accumulated during the past
decade. Even though an individual experiment may yield only
suggestive information, this information may be of considerable
importance when considered together with other data.
Clearly, when the primary source of data comes from
epidemiological studies in man, it may be possible to evaluate
a chemical and institute scientifically-based preventive
measures. However, even in the instances where data are
available from humans, the data must be supplemented with
information from other sources before a conclusion can be reached.
For example, toxicological evaluation of carcinogenicity
has classically relied upon long term in vivo studies as the
primary source of data. Such studies have been performed in
a routine manner, and evaluations have followed predetermined
formulas. This rote method is rapidly giving way to evaluations
that take into account findings from vitro tests, metabolism
studies, and biometric analyses as well as any other available
information. One of these methods alone cannot produce a
reliable estimate of a chemical's risk to man, but taken
together they provide an estimate with a high level of confidence.
Carcinogens act via different mechanisms, which results
in their having different magnitudes of risk to man. Even
though there is no basis for the exact extrapolation of risk
from experimental animal to man, current advances, if exploited
to the fullest, can provide a basis for distinguishing the
degrees of risk from different carcinogens. The scientific
criteria should be reviewed often, and scientific advances
should be fully adopted.
The scientific criteria should be reviewed often, and
scientific advances should be fully adopted.
The scientific characterization of human risks from
carcinogens involves the evaluation and integration of data
from nany disciplines. It requires scientific impartiality
to review all appropriate data, both negative and positive,
including statistical estimations of low-dose response.
Quantitative characterization of human risk requires scientific
experience and judgement. Because of the strengths and
�- 11 weaknesses of the data to be evaluated in the assessment of
human risk and the complexity of the problem, case-by-case
analysis is most appropriate.
Although it would perhaps be most reliable to quote
extensively from this report in other areas certain specific
matters can be dealt with in summary. Thus the report concurs
with the findings of a recent IARC worker who concluded that
although the distinction between carcinogens found to be
mutagenic in short term tests and those that are not in most
interesting it does not yet serve a purpose to divided
carcinogens into genotoxic and non-genotoxic types. This
does not preclude the use of knowledge of mechanisms in the
evaluation of specific carcinogens.
In certain situations, the particular mechanisms of
action of some carcinogens provide guidelines for preventive
measures. These situations include carcinogenic effects
directly related to the hormonal changes caused by certain
compounds and carcinogenic effects in the bladder caused by
compounds that induce bladder calculi. These carcinogenic
effects can be dealt with differently from those of compounds
that induce cancer without the apparent intervention of other
physiological or pathological factors.
In spite of the inability to derive a generic classification of carcinogens, chemical carcinogens can, in principle,
be divided into two types. One type gives non-threshold dose
responses, is stochastic in mechanism, and has some probability
of producing carcinogenic effects at any dose. The second type
gives threshold dose responses and, theoretically, has a noeffect level. A few chemicals can be placed, provisionally,
in one category or the other; but for the bulk of chemical
carcinogens, we are currently unable to discern in which compartment they fall. By dealing with chemicals case-by-case
and by studying mechanism, we can look forward to doing better
than this.
Individual Compounds
2, 4 dichlorophenoxyacetic acid (2,4-D)
2,4-D was reviewed by the IARC in 1977 (1) and again in 1982
()
2 . It is reported that there were studies in mice employing
a combination of gavage and dietary administration. ( ) The
3
butyl, isopropyl and isoctyl esters were also studies. These
1969 studies used high doses and lasted 78 weeks. These
studies were deemed to be inadequate as result primarily of
the small numbers of animals used.
It should be noted, however, that this was part of a
large study of many pesticides; one group in this study
recorded positive findings with DDT and this was considered
to be an adequate demonstration of carcinogenicity.
�- 12 Osborne-Mendel rats were fed for two years with diets
containing 4,25,125,625 or 1250 mg/kg 2,4-D ( ) This study
4.
has been variously reported. The original authors must be
awarded a prize for recording one of the most confused and
contradictory conclusions in the literature, namely "When
tumor incidence was analysed statistically a higher incidence
of tumors occurred in male rats fed 2,4-D at 1250 ppm, and
a trend toward increased tumor formation with log dose in the
female rats was noted. The raw data, however, support the
pathological interpretation that a carcinogenic effect of
2,4-D has not been shown." I would concur with this second
sentence rather than the IARC viextf that carcinogenicity "could
not be evaluated."
It should be noted that this study by Hansen et al has
been re-recorded in a most unusual and unorthodox manner by
Reuber (5). This paper is presented as if it were original
data; it is, however, merely a re-evaluation of the previous
study that concludes that carcinogenic effects were, indeed,
seen in several different organ sites. These conclusions are
not supported in any way by the data.
In one other study random bred rats are recorded as
having been fed one dose level; no increased tumor incidence
is recorded but this study cannot be interpreted on the basis
of recorded information. (4)
In the 1969 (3) study mice were tested subcutaneous
injection using doses of 215 mgm/kg/body weight in dimethyl
sulphoxide and observed for 78 weeks. This study was negative.
I believe that this negative finding must be viewed with
interest in the context of the controversial reports of
sarcoma occurrence in man. It cannot be denied that additional
animal data using contemporary standards might be useful in
the instance of this compound. Apparently such data will be
forthcoming. As matters stand it would be my conclusion that
2,4-D should be classified as non-carcinogenic in animal systems,
and therefore unlikely to be in humans.
2,4,5-trichlorophenoxyacetic acid
2,4,5-T was reviewed by the IARC in 1977(1) and 1982(2).
It was tested in a 1969 mouse study by a combination of gavage
and dietary administration (3) and was not found to be
carcinogenic. Identical comments made above for 2,4-D apply
to the evaluation of this study.
A further mouse study (6) is made difficult to critique
because of inadequate reporting by the authors and the use of
less commonly used strains of mice. The authors report that
2,4,5-T was found to be non-carcinogenic when administered
orally to mice of the XVII/G strain at levels of 80 ppm in the
diet. The 2,4,5-T was said to contain 0.05 ppm of several
dioxins that are listed.
�- 13 On the other hand it is reported that there was a
significant increase in tumor incidence in C3HF mice in this
same study. This contention is virtually impossible to check
since the tumors are classified into incidental tumors and
non-incidental tumors for purposes of evaluation. It is then
concluded that the incidence for non-incidental tumors is
significantly increased whereas the incidence of incidental
tumors is not. There is no precise listing in this paper of
which tumors were placed in which category and this statistical
manipulation of the data cannot be checked. My personal
conclusion from reviewing the data is that this was an entirely
negative study. In this instance, perhaps, it is safest to
conclude that this study does not add anything of consequence
one way or the other.
A parallel subcutaneous injection study in mice to that
recorded for 2,4-D was undertaken. The 2,4,5-T was also
administered as a single dose of 215 mg/kg body weight in
dimethyl sulphoxide and the mice observed for 78 weeks. This
study was again negative.
It is repeated continuously in IARC and other reports
that the evidence from studies with 2,4,5-T is inadequate and
does not permit a negative conclusion on carcinogenicity.
Whilst it is undoubtedly true that additional data might
permit a more definitive conclusion to be drawn the available
data certainly cannot just be dismissed.
In my view it indicates that it is most unlikely that any
further studies would find 2,4,5-T to be carcinogenic. Having
regard to the limited resources for testing for carcinogenesis
by long term animal investigations, I do not think this compound
should be accorded research priority over the many others
requiring much more urgent evaluation for public health purposes.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
There are three recorded studies claiming to demonstrate
some degree of carcinogenicity in TCDD. In the first of these
studies Kociba et al (7) reported that Sprague Dawley rats were
fed on diets providing 0.1.0.01 or 0.001 micrograms/kg/day for
two years. At the highest level of feeding they report an
increased incidence of hepatocellular carcinomas, and squamous
cell carcinomas of the lung, nasal turbinates, hard palate and
tongue. At the median level of 0.01 only lesions described
as hepatocellular nodules were observed. At the lowest level
no toxicity or neoplasms were reported. The authors of this
paper draw attention to the toxicity observed at the highest
level and suggest that this may have had an effect on the
carcinogenic effects observed.
�- 14 In a bioassay reported from the U.S. National Toxicology
Program (N.T.P.)(8) Osborne Mendel and B6C3F1 mice were given
TCDD by gavage for 104 weeks. The compound was administered
in a corn oil-acetone vehicle at doses of 0.01, 0.05 and 0.5
micrograms/kg/week to rats and male mice and 0.04, 0.2 and
2.0 micrograms/kg/we to female mice. It is reported that male
rats developed a significantly increased incidence of follicular
cell adenomas of the thyroid in the high dose group only and
that female rats developed an increased incidence of hepatocellular carcinomas was significantly increased at the two
highest dose levels.
The peer-review panel of the NTP was most critical of
the interpretation of this study and concluded that the liver
and thyroid tumors could well be attributed to the hepatoxicity
induced. It was also pointed out that the analysis of the
significance of the mouse liver tumors had not taken into
account the high levels of similar tumors reported in historical
controls of this strain of mice.
It is my view that an objective analysis of the NTP
study must dismiss it as flawed in design and interpretation.
It is surprising to note that the peer review group haveing
been scathing in their criticism finally agrees with the view
that this study has demonstrated the compound to be carcinogenic.
I would be unable to draw a similar conclusion.
The comparison of the NTP test and the Kociba et al
study is made difficult by the different modes of administration,
different strains of rat etc. It is difficult to dismiss the
findings of the Kociba study but one is puzzled by occurrence
of the tumors in the respiratory epithelium (lungs, nasal
sinuses, tongue) and their total absence in the NTP study.
It might be that there is a greater local exposure in the diet
study and it would be interesting to know this. The discrepancy
between these two studies demands added investigation.
The third study is an NTP study (8) in mice in which
TCDD was applied repeatedly to the skin of mice alone or
following a single initiating dose of the carcinogen
7,12-dimethylbenz(a)anthracene. The doses used were 0.005
micrograms per application in the females and 0.001 micrograms
per application in the males; acetone was the vehicle. The
higher doses female mice are said to have developed a
significant number of fibrosarcomas.
Once again, as in the previous study, the NTP group
was exceptionally critical of this study. The portion of the
study in which DMBA was administered first is disregarded
since no DMBA control alone was used. There was a dispute
amongst the reviewers as to the validity of the contention
that a significant number of fibrosarcomas had in fact been
induced. One reviewer felt that this finding should be
�- 15 "interpreted with caution" and that "an assessment of human
risk cannot be made." I would concur completely with this
review and do not believe that the data in this study provides
an adequate foundation for concluding that TCDD is a carcinogen
in this model system.
TCDD has been tested in a variety of so-called two
stage studies as both an "initiator" or as a "promoter." I
do not believe that these studies have provided any information
of practical significance to the assessment of TCDD as a
potential carcinogen.
Conclusion
In spite of considerable effort long term experimental
results obtained with TCDD present a confused picture. Only
one study has provided positive results that appear to be
incontravertible (7) but in view of the lack of confirmation
of this finding additional studies are required using the
same conditions as those employed in this study. The Dow
study even though not confirmed by NTP (perhaps as anxious
to confirm it as Dow was unhappy to conclude as it did) must
until explained leave TCDD in the very suspect compartment.
Picloram (4-amino-3,5,6-trichloropicolinic acid)
This compound was assayed in a standard U.S. National
Cancer Institute bioassay using Osborne Mendel rats and B6C3F1
mice. The rats were given 744 or 372 mgm/kg/day and the mice
fed either 640 or 320 mg/kg/day. Only the female rats were
reported to have had an increased incidence of benign liver
tumors. M. Reuber has reported that on re-reviewing this
study that there was an increased incidence of various malignant
tumors. The recent review of this literature by Clements
Associates, Inc., takes issue with the techniques used by
Reuber in selecting his material. It is not possible for me
to take a stand in this instance without additional information.
In view of the other characteristics of picloram - namely
that it appears not to be metabolized it seems unlikely that
it will prove to be carcinogenic in the study that is now
apparently underway. Judgement of the potential hazard from
this compound should await the completion of the new study.
Cacodylic acid - Dimethylarsinic acid
Althouth the only term study on this compound was
undertaken in 1969 by Innes et al (3) and has been deemed
inadequate, the compound was reported as negative. The
particular study must be viewed in the context of this overall
study in which several other compounds which including DDT
were reported to have been carcinogenic.
�- 16 From a biochemical standpoint cacodylic acid seems most
unlikely to be carcinogenic since it is a detoxification product
It would be quite inappropriate to equate the possible activity
of this compound with the inorganic arsenicals said to be
carcinogenic in man.
Malathion
This compound has been bioassayed in the U.S. by mouth
in rats and mice and has been pronounced non-carcinogenic.
The only suggestions to the contrary have not been based on
any data.
It would seem most unlikely that this compound poses a
potential carcinogenic hazard, and in my opinion its use as an
insecticide will cause no cancers in veterans.
DDT
DDT induces liver tumors readily in mice and less so
in rats and not at all in hamsters. There is a considerable
amount of work on the metabolism of this compound encouraged
by these interesting species differences.
There is a great deal of frustration present in many
of the toxicologists that several decades after the introduction
of this widely used, persistent and easily detectable compound,
no one is prepared to say whether or not it has proved to be
safe in man. My view is that if hazard were present there
should have been some indication of it by now.
Efforts to mount studies in which levels of DDT in
human fat are related to tumor incidences have foundered.
One can do no more than have a common sense opinion in this
instance; my personal view is that it is most unlikely that
DDT is a human health hazard in any respect.
Dapsone-4,4'-sulphonylidianiline
Of all the compounds included in the list for discussion
at the Royal Commission I would select Dapsone as the most
likely compound to pose a potential carcinogenic hazard.
This compound is an aromatic amine which has been found
to give rise to mesenchymal tumors of the spleen and thyroid
tumors in rats.
The exposure levels are of a much higher order of
magnitude from those encountered in dealing with herbicides
or pesticides. I recommend an epidemiological study of those
individuals exposed to this drug in Vietnam and a control
from who went to Vietnam who received other therapy.
�- 17 On present data I am unable to say whether dapsone is
actually carcinogenic in humans.
I was unable to locate any pertinent data on the possible
carcinogenicity or paludrine or primaquine and have no additional
comments.
Chlordane
This is another representative of the group of compounds
giving rise to hepatomas in mice; data in rats is inconclusive.
No epidemiological evidence is available. This compound is in
my view unlikely to be carcinogenic in humans.
Dieldrin
This chlorinated hydrocarbon, although more acutely
toxic than DDT, presents similar problems from the standpoint
of carcinogenesis. It enhances the incidence of hepatomas in
mice but is apparently inactive in rats and hamsters.
Lindane
This chlorinated hydrocarbon again gives rise to hepatomas
in mice; evidence in other species is said to be inconclusive.
It is in my opinion unlikely to be carcinogenic in humans.
Diazinon
This compound has been tested in a U.S. National Cancer
Institute bioassay and pronounced negative for carcinogenicity
in rats and mice.
I have been asked to speculate on the matter of possible
synergism between the various herbicides, pesticides, drugs
and possible environmental factors on any potential cancer
producing effects that may have occurred.
I can only respond that I have no knowledge of any studies
that would suggest that any of the agents involved have ever been
evaluated in any combinations to examine this possibility.
Neither am I familiar with any studies that would suggest
theoretically that such a possibility exists.
It should be remembered that the two unequivocally
established carcinogens to which Vietnam veterans were exposed
were cigarette smoking and sunshine. In addition it is my
understanding that a certain number of soldiers were exposed to
Hepatitis B virus which can certainly be considered to be at
least a co-factor in the occurrence of hepatocellular carcinoma.
The possible exposure of troops in Vietman to the naturally
occurring carcinogen, Aflatoxin, a product of fungal contamination and prevalent in Southeast Asia should also be considered.
�- 18 REFERENCES
1.
IARC Monographs Vol 15. 1977
2.
IARC Monographs Supplement 4.1982
3.
Innes, J.R.M. et al Journal of the National Cancer
Institute 42.1101-1114. 1696
4.
Hansen W.H. et al Toxicology and Applied Pharmacology
20.
122-129. 1971
5.
Reuber M.D.
31.203-218.
6.
Muranyi-Kovacs I, Rudali, G., and Imbert, I., Brit. J.
Cancer 33.626-633. 1976
7.
Kociba R.J. et al
46.279-303.
1978
8.
National Toxicology Program Technical Reports 209 and 201
The Science of the Total Environment
1983
Toxicology and Applied Pharmacology
�
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
056
Folder
The folder containing the original item.
1483
Series
The series number of the original item.
Series III Subseries II
Dublin Core
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Title
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Typescript: Statement of Dr. Philippe Shubik, Senior Research Fellow, Green College, Oxford University
Subject
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cancer risk assessment
health studies
herbicide toxicology
ao_seriesIII
-
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
055
Folder
The folder containing the original item.
1460
Series
The series number of the original item.
Series III Subseries II
Dublin Core
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Title
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Typescript: Scientific Issues and Agent Orange Exposure
Subject
The topic of the resource
dioxin
health effects
AOWG
health studies
ao_seriesIII
-
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Alvin L. Young Collection on Agent Orange
Description
An account of the resource
<p style="margin-top: -1em; line-height: 1.2em;">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.</p>
<p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p>
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Box
The box containing the original item.
055
Folder
The folder containing the original item.
1455
Series
The series number of the original item.
Series III Subseries II
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Typescript: Chapter 3: Studies Evaluating Human Exposure to Phenoxy Herbicides
Subject
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health studies
safety
protective clothing
ao_seriesIII