# Amicus Curiae Brief — Hercules Inc. Inc. v. United States (Nos. 06-865, 06-1014, 06-853)

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URL: https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40386016_1925%3A4

## Record

- **Collection:** Supreme Court brief
- **Document type:** Amicus Curiae Brief
- **Published:** January 1, 2006

## Text

(2)

3

No. 06-865

LORE EN REE NE ORI A NERC

IN THE
Supreme Court of the United States

HERCULES INCORPORATED,

Petitioner,
Vv.

UNITED STATES OF AMERICA,
Respondent.
On Petition for a Writ of Certiorari

to the United States Court of Appeals
for the Eighth Circuit

BRIEF OF AMERICAN CHEMISTRY COUNCIL
AS AMICUS CURIAE IN SUPPORT OF PETITIONER

LiSE T. SPACAPAN LAN HEATH GERSHENGORN*
TRACI M. BRAUN JENNER & BLOCK LLP
JENNER & BLOCK LLP 601 Thirteenth Street, N.W.
One IBM Plaza Washington, DC 20005

Chicago, IL 60611-7603 (202) 639-6000

(312) 222-9350 ;
*Counsel of Record

Counsel for Amicus Curiae

S oeaiasasieeasiansheiiaasiiaed nema tainainaeadaaatmeemetemdamentemmnmematiemecamememeneamnamiannaamnatamemeay

i
CORPORATE DISCLOSURE

American Chemistry Council — The American
Chemistry Council is a trade association representing U.S.
chemical companies. The American Chemistry Council has
no publicly owned parent corporation, and no publicly owned
corporation-owns more than 10% of its stock.

ii

TABLE OF CONTENTS
CORPORATE DISCLOSURE ......ccesccosssscccocsersoveserersevecoesoesoes 1
PPE SE GREET EEGET E Gv evvecsossececerencenecessccossveosnescorenevencoeseees li
DERE SE FAR) A ERIIRE LD vsecevsesscerceseverserecnevovecovesnesesnsooees ill
SND SOE PEIRIE secscsevesssconssesereoreorenvevensvessequeevoneseves l
SUMMARY OF ARGUMENT. .............scssssssssssssesssecsesencenses 1
dei cceh vaedabarictsaregneneetwasnevenevsnvceteiooseneesane 4

1. COURTS RECOGNIZE THAT DIOXIN
EXPOSURE HAS NOT BEEN SHOWN TO CAUSE
IEE, 1s siceiacumisbiesubiseisavieversectetvivecarssavetereeetesseoeses cues 4

Il. THERE IS NO CONSISTENT PATTERN OF
ELEVATED CANCERS IN- STUDIES OF
INDUSTRIAL WORKERS EXPOSED TO DIOXIN.....8

Ill. STUDIES ON MILITARY PERSONNEL
EXPOSED TO DIOXIN CONSISTENTLY FAIL TO
DEMONSTRATE A CAUSAL LINK BETWEEN
SNEE HERE? GREW Esaeesccnsvcesoverssensseesesoversesnsecconeesoees 13

IV.EPA’S SCIENCE ADVISORY BOARD AND THE
NATIONAL ACADEMY OF SCIENCE HAVE
BOTH NOTED THE ABSENCE OF ANY
CONSISTENT, REPLICABLE PATTERN OF
INCREASED CANCERS IN THE
EPIDEMIOLOGY LITERATURE. ...........ccoccsscssseveessees 18

adler venicebuiaiesend<veubvnieeverneenstabveseoenvceneenes 20

ill
TABLE OF AUTHORITIES

CASES

In re “Agent Orange” Production Liability
Litigation, 304 F. Supp. 2d 404 (E.D.N.Y. 2004) ....4, 5, 9

In re “Agent Orange” Production Liability
Litigation, 373 F. Supp. 2d 7 (E.D.N.Y. 2005) ............06 7

In re “Agent Orange” Production Liability
Litigation, 611 F. Supp. 1223 (E.D.N.Y. 1985),
aff'd or other grounds, 818 F.2d 187 (2d Cir.

FOIE FD vsox\oietssicmesictanasohagiantiidsaienimmsetnimnieniaermaamilios 7, 12
In re “Agent Orange” Production Liability
Litigation, 818 F.2d 145 (2d Cir. 1987)........cesscseseeeeees 5,6
In re “Agent Orange” Production Liability
Litigation, 818 F.2d 187 (2d Cir. 1987)........:cesseseeeeeereees 6
In re “Agent Orange” Production Liability
Litigation, 996 F.2d 1425 (2d Cir. 1993)........ccsseceeseseeees 6

Chemical Weapons Working Group, Inc. v. United
States Department of the Army, 935 F. Supp.
1206 (D. Utah 1996), aff'd, 111 F.3d 1485 (10th

CE RED iialascatisciciciitabediiadasialas ie te es oe eee 7,8
Nehmer v. United States Veterans’ Administration,
712 F. Sapp. 14046 (C.D. Cal, 19G9) «2. cccccccvcsveccevevevenscosse 17
MISCELLANEOUS

Fatema Z. Akhtar et al., Cancer in U.S. Air Force
Veterans of the Vietnam War, 42 J. Occupational
& SAVE, GRE: 175 Cini iain 14, 15

K.M. Bodner, et al., Cancer Risk for Chemical
Workers Exposed to 2,3,7,8-tetrachlorodibenzo-
p-dioxin, 60 Occup. and Envtl. Med. 672 (2003).....12, 13

iv
Gregory G. Bond, et al., Update of Mortality
among Chemical Workers with Potential

Exposure to the Higher Chlorinated Dioxins, 31
Occupational Med. 121 (1989)..........qsscscssssrcsesessersoserees 9

Philip Cole, et al., Dioxin and Cancer: A Critical
Review, 38 Reg. Toxicology & Pharmacology
FI CI initcbsrtiticccsetecethe SE DEO ANI SRO 9, 10,11, 12

EPA, Dioxin Reassessment - on SAB Review of the
Office of Research & Development’s

Reassessment of Dioxin (2001).........:ccsscccssssesesessesensesees 19
Federal Judicial Center, Reference Manual on

Scientific Evidence (2d ed. 2000) ...........:.esesesseecsereseees 16
Alexandra Geusau, et al., Severe 2,3,7,8-

tetrachlorodibenzo-p-dioxin Intoxication:

Clinical and Laboratory Effects, 109 Envtl.

Health Persp. 865 (2001) .............::0000- sinikdieadaidasadaambuakune 8
Institute of Medicine, Veterans and Agent Orange:

CIT FOE GEG E i ivedescicevssccescsintetnstnicnnectnhieeaies 3, 15, 16
Institute of Medicine, Veterans and Agent Orange:

I Fe CD ititrccsnsinnsivedvovionscscnncuinninentnieiintiueiies 17

Institute of Medicine, Veterans and Agent Orange:
Health Effects of Herbicides Used in Vietnam

Int’| Agency for Research on Cancer, World Health
Org., IARC Monograph on the Evaluation of
Carcinogenic Risks to Humans (1997) ........:000:.cseeeeseeees 12

Manolis Kogevinas, Cancer Mortality in Workers
Exposed to Phenoxy Herbicides, Chlorophenois,
and Dioxins, 145 Am. J. Epidemiology 1061
EDIT Pivsckinesicisiccleicnistssivleskaiintaiondnncidaiuncdbdisananacienninssa 12

Vv

Junius C. McElveen, Jr. & Chris Amantea,
Legislating Risk Assessment, 63 U. Cin. L. Rev.
Rete ER CE Ro sicisiijiesvvincasaaiauinnsnensscndeoaneeeeNORRa i eoesbinstitts 17

Joel E. Michalek et al, The Air Force Health
Study: A Summary of Results, 54 Organohalogen
IE FIO COO Ds csciciscssvvtenisastesacsectaneetansssxdapernsess 14

National Research Council, Health Risks from
Dioxin and Related Compounds: Evaluation of
the EPA Reassessment(July 2006). ...........:2:00cecceeeee 19, 20

Marian Pavuk, et al., Prostate Cancer in US Air
Force Veterans of the Vietnam War, 16
J. Exposure Sci. & Envtl. Epidemiology 184
Sac ottisiacadepsletiniaseieiisseiccseumdiortenestaendidemtas 14-15

Science Application Int’] Corp., Air Force Health
Study Final Report, An _ Epidemiologic
Investigation of Health Effects in Air Force
Personnel Following Exposure to Herbicides —
2002 Follow-up Examination and Results (2005).......... 14

INTEREST OF AMICUS!

Amicus the American Chemistry Council (ACC)
represents the leading companies engaged in the business of
chemistry. ACC members apply the science of chemistry to
make innovative products and services that make people's
lives better, healthier and safer. The business of chemistry is
a $558 biilion enterprise and a key element of the nation's
economy. It is one of the nation’s largest exporters,
accounting for ten cents out of every dollar in U.S. exports.

Amicus and its members have a strong interest in
ensuring that the federal government’s regulation of
chemicals is based on the most accurate and up-to-date
scientific information regarding the effects of exposure to
chemicals and other products. It thus has a strong interest in
opposing actions such as those taken by the USS.
Environmental Protection Agency here that regulate the
disposal and treatment of chemicals without basing that
regulation on an adequate scientific foundation and without
subjecting that regulation to judicial review as Congress
intended. The American Chemistry Council participates
regularly in federal court litigation both as a party and as
amicus curiae.

SUMMARY OF ARGUMENT

The issues presented in the petition are of paramount
importance. As noted in the petition, the Environmental ~
Protection Agency (“EPA”) consistently applies a standard
potency factor for dioxin that effectively dictates the
remedial actions required at chemical disposal sites around
the country. That potency factor, however, has never been
subjected to notice-and-comment rulemaking. The EPA has

' No person or entity other than amicus and their counsel made a
monetary contribution to the preparation or submission of this brief.
Counsel of record for the parties have consented to the filing of this brief,
and letters of consent have been filed with the clerk.

2

thus never had to consider the full range of scientific
evidence that bears on the dioxin potency standard; nor has it
ever had to satisfy any level of independent judicial review in
holding to that factor.

That is of critical importance here because EPA has
its science wrong. Despite several decades of intensive
epidemiological research on populations of production
workers and military personnel who may have had high
exposures to dioxin, there is no scientific consensus that
exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (“TCDD” or
“dioxin”) causes soft-tissue sarcoma, non-Hodgkin’s
lymphoma, multiple myeloma, or any other cancer. To the
contrary, the best-designed studies fefute any assertion of
causation. Indeed, more than thirty years of serious scientific
analysis and scores of epidemiological studies have failed to
demonstrate even a consistent association between exposure
to dioxin and any particular cancer.

The federal courts examining the scientific literature
involving dioxin have consistently recognized the lack of
evidence showing a causal link between dioxin exposure and
cancer risks. Judge Weinstein, for example — who has
presided over 20 years of Agent Orange” litigation in the
District Court for the Eastern District of New York — has
repeatedly found that plaintiffs in that litigation lack
scientific support for their causation theories, and the Second
Circuit has consistently echoed those findings.

These court decisions are backed by science, not
speculation. For example, a recent Institute of Medicine
Report expressly disclaims any conclusions as to causation

. Agent Orange was a 50/50 mixture of two concentrated herbicides (2,4-
Dichlorophenoxyacetic acid and 2,4,5-Trichlorophenoxyacetic acid).
Neither is considered a carcinogen, but the latter contained trace amounts
of TCDD. Hence, the Agent Orange litigation, insofar as the claims are
based on cancer, indirectly focuses on TCDD.

3

and, moreove: + pressly recognizes that “it is impossible to
quantify the aegree of risk likely to be experienced by
veterans because of their exposure to herbicides in Vietnam.”
Institute of Medicine, Veterans and Agent Orange: Update
2004 at 17 (2005) (“2004 IOM Report”). Similarly, there is
no coherent and consistent evidence for a link between
dioxin and cancer risk in heavily-exposed dioxin production
workers. There is simply no substantial scientific support for
the hypothesis that dioxin causes cancer in humans.

Despite this uncertain evidence regarding highly
exposed persons, the EPA continues to employ a cancer
potency factor that is based on a linear, no-biological-
threshold model to extrapolate laboratory animal findings to
persons with the very lowest levels of dioxin exposure. This
model, which has been routinely criticized even by EPA’s
own Scientific Advisory Boards and other independent
scientific panels, assumes that, if a high exposure to
something increases cancer risk, then (1) there is no “safe” or
“threshold” exposure below which there is no cancer risk
(i.e., any exposure increases cancer risk) and (2) cancer risk
increases linearly with exposure. This model, however, is
not supported by the science. This is, in short, a situation in
which full notice-and-comment rulemaking followed by
judicial review would make a difference.

Moreover, the stakes are high, as this case
demonstrates. EPA applied its scientifically unsupported
standard to impose over one hundred million dollars in clean-
up costs on Hercules, and EPA itself has acknowledged that
dioxin-related litigation and regulatory response expenditures
have likely exceeded $100 billion. Given the stakes, EPA
may not cling to its no-threshold model and the resulting
potency standard while maintaining that the standard is
immune from all judicial review. Review by this Court is
thus appropriate.

4

ARGUMENT

I. COURTS RECOGNIZE THAT DIOXIN
EXPOSURE HAS NOT BEEN SHOWN TO CAUSE
CANCER.

EPA’s cancer potency factor is based on the flawed
premise that dioxin has been shown to cause cancer.
However, as recognized by a number of courts that have
examined the science behind dioxin, despite decades oi
litigation there has been no credible evidence presented even
in highly exposed persons that dioxin actually causes cancer.

The seminal decisions involving Agent Orange (and
thus dioxin) exposure have been issued by Judge Weinstein
in the Eastern District of New York. Judge Weinstein, more
than any other sitting federal judge, has been steeped in the
scientific literature associated with Agent Orange and dioxin
for well over twenty-five years and has been uniquely
situated to evaluate that literature as a result of handling that
consolidated Agent Orange litigation. While his recent
opinion, Jn re “Agent Orange” Production Liability
Litigation, 304 F. Supp. 2d 404, 424-42 (E.D.N.Y. 2004),
focuses primarily on how the government contractor defense
forecloses plaintiffs’ claims, in the course of that opinion, the
court offered a tentative assessment of plaintiffs’ claims that
their diseases — principally multiple myeloma and non-
Hodgkin’s lymphoma — resulted from their exposure to
Agent Orange while serving in the U.S. military in Vietnam.
Judge Weinstein noted that “[i]n earlier waves of such suits
in the 1970s, 1980s and 1990s, the courts concluded that
none of the available evidence would support a finding to’a
more-probable-than-not standard of causality between
exposure to Agent Orange and disease (except for a quickly

5

discoverable and curable form of skin irritation, chloracne).’”
Id. at 407. He went on to note that “[t]he scientific basis for
that conclusion of lack of any substantial proof of causality,
either general or specific to individuals, remains much the
same.” /d. (citing Institute of Medicine, Veterans and Agent
Orange: Update 2002 (2003)). This conclusion was based
on his continuing review of the scientific literature on dioxin
and Agent Orange in connection with the ongoing litigation
in In re “Agent Orange” Production Liability Litigation,
MDL No. 381.’

It is also in the context of this Agent Orange litigation
that the Second Circuit has gained considerable experience in
addressing the scientific causation issues. That court first
addressed the issue in 1987 when it affirmed the certification
and settlement of class actions brought in the initial wave of
Agent Orange litigation. See In re “Agent Orange”
Production Liability Litigation, 818 F.2d 145 (2d Cir. 1987).
Writing for a unanimous court, Judge Winter noted that “the
clear weight of scientific evidence casts grave doubt on the

* Chloracne is linked to dioxin exposure, but not exposure to the basic
herbicides.

* The docket sheet in the Agent Orange MDL reflects more than 150
entries from 1984 through 2005 describing scientific journals and articles
relating to Agent Orange and the health consequences of exposure that
Judge Weinstein has read and of which he has taken “judicial notice.”
Throughout the mid-1990s, for example, Judge Weinstein took notice of
reports such as the EPA Health Assessment Documents for
Tetrachlorodibenzo-p-Dioxin and Related Compounds on Oct. 21, 1994
(docket entry 14679); EPA Review Draft Documents for Public Review
for 120 day public review and comment (docket entry 14790); Estimating
Exposure to Dioxin-Like Compounds Volume 1 Executive Summary
(docket entry 14791); Health Assessment Document for 2,3,7,8 TCDD
and Related Compounds (docket entry 14792); Estimating Exposure to
Dioxin Like Compounds, Volume 11, Properties, Sources, Occurrences
and Background Exposures (docket entry 14794); and EPA Review Draft
Estimating Exposure to Dioxin Like Compounds (docket entry 14795).

6

capacity of Agent Orange to injure human beings,” Jd. at
149, and that “[e]pidemiological studies of Vietnam veterans,
many of which were undertaken by the United States,
Australian, and various state governments, demonstrate no
greater incidence of relevant ailments among veterans or
their families than among any other group.” Jd.; see also In
re “Agent Orange” Production Liability Litigation, 818 F.2d
187, 193 (2d Cir. 1987) (noting that “epidemiological studies
of those very personnel and their families fail to show that
Agent Orange was hazardous”). The Court observed that the
pertinent question was “‘What will Agent Orange do to
friendly personnel exposed to it?’” The epidemiological
studies provided an answer: “‘Nothing harmful so far as can
be told.’” Jd.

The Second Circuit revisited the issue in 1993, when
it affirmed Judge Weinstein’s conclusion that the initial
Agent Orange class settlement barred plaintiffs’ claims in the
so-called “second wave” of Agent Orange litigation. Jn re
“Agent Orange” Production Liability Litigation, 996 F.2d
1425 (2d Cir. 1993). Again speaking unanimously, the court
quoted scientific literature making clear that “‘[t]o date, there
has been no conclusive evidence that exposure to Agent
Orange is carcinogenic, mutagenic or teratogenic in humans.
Furthermore, no deaths attributable solely to exposure to
Agent Orange and its dioxin contaminant have been
reported.”” Jd. at 1437 (quoting 13B Arthur L. Frank,
Courtroom Medicine: Cancer § 25A.00, at 25A-4 (1992)).

The conclusions at that time were based in part on the
extensive scientific record that Judge Weinstein had
compiled and analyzed. In 1985, for example, Judge
Weinstein surveyed the evidence advanced by the plaintiffs.
Focusing in particular on epidemiological studies, Judge
Weinstein concluded that “[nJo acceptable study to date of
Vietnam veterans and their families concludes that there is a
causal connection between exposure to Agent Orange and the

7

serious adverse health effects claimed by plaintiffs.” Jn re
“Agent Orange” Production Liability Litigation, 611 F.
Supp. 1223, 1231 (E.D.N.Y. 1985), aff'd on other grounds,
818 F.2d 187 (2d Cir. 1987). The court concluded that there
was simply no “credible evidence of a causal link between
exposure to Agent Orange and the various diseases from
which [the plaintiffs] are allegedly suffering.” Jd. at 1229.

Judge Weinstein’s lengthy and scholarly opinion
addressing the claims brought by the Vietnam Association
for Victims of Agent Orange/Dioxin reflects the same
thorough grounding in the relevant scientific literature. See
In re “Agent Orange” Production Liability Litigation, 373 F.
Supp. 2d 7, 19, 22-23, 32 (E.D.N.Y. 2005) (discussing recent
scientific articles and explaining why they do not alter the
court’s conclusions as to lack of proof of exposure or
causation). He noted that “[p]roof of causal connection
depends primarily upon substantial epidemiological and other
scientific data, particularly since some four million
Vietnamese are claimed to have been adversely affected,”
and that plaintiffs’ “[a]necdotal evidence . . . can not suffice
to prove cause and effect.” /d. at 32. Although the case was
dismissed on other grounds, Judge Weinstein noted that
epidemiological studies regarding Vietnamese plaintiffs are
not available “with the richness of demographic and other
data published in the United States,” and he cited recent
articles suggesting that the existing body of epidemiological
literature was insufficient. /d.

Although Judge Weinstein has had the most
experience with such cases, his decisions do not stand-alone.
For example, in Chemical Weapons Working Group, Inc. v.
United States Department of the Army, 935 F. Supp. 1206
(D. Utah 1996), aff'd, 111 F.3d 1485 (10th Cir. 1977), an
environmental group sought an injunction to stop the U.S.
Army’s proposed operation of a facility to incinerate
chemical warfare agents, which would create TCDD as a

8

byproduct. Discussing the science on dioxin, the court noted
that “fa]lthough plaintiffs argue that any increase in the
levels of dioxin exposure is unacceptable, the danger
associated with relatively small increases is far from certain,
and the evidence presented by plaintiffs is insufficient to
support a finding that such danger is likely to be significant.”
Id. at 1213. The court also critiqued the assessment done by
Utah’s Department of Environmental Quality, noting that
“[uJltimately, the court finds that the Utah DEQ assessment
is intended to show an area of safety, not predict an actual
level of risk. Although plaintiffs have shown that the
assumptions applied in the State’s health risk assessment
may indicate a higher level of risk for some hypothetical
persons, this does not constitute a showing that there is an
actual risk to some person or persons posed by the emissions
levels predicted for the facility.” /d. at 1214. As a matter of
law, the court concluded that “the asserted risks of harm due
to dioxin exposure are too speculative to qualify as
irreparable harm to plaintiffs.” Jd. at 1215.
Il. THERE IS NO CONSISTENT PATTERN OF
ELEVATED CANCERS IN STUDIES OF
INDUSTRIAL WORKERS EXPOSED TO DIOXIN

Production workers exposed to dioxin in industrial
settings are generally considered to have the highest
documented exposures of any of the cohorts studied in the
epidemiological literature.” Most members of this group
were exposed during the course of their work in industrial
- plants. However, even for these high levels of exposure, the
results of the major epidemiological studies remain largely

* Higher exposure levels have been reported in rare instances of
intentional dioxin poisoning. See, e.g., Alexandra Geusau, et al., Severe
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) Intoxication: Clinical and
Laboratory Effects, 109 Envtl. Health Persp. 865 (2001).

9

negative, with occasional weak and inconsistent findings. In
fact, among humans, the only disease found to be causally
related to TCDD is chloracne, which is a reversible skin
condition that develops shortly after high levels of exposure
to dioxin. Jn re “Agent Orange” Production Liability
Litigation, 304 F. Supp. 2d at 407.° .

A relatively recent comp: hensive review article on
the evidence relating to the “hypothetical cause-effect
relationship” between 2,3,7,8-TCDD and cancer concludes
that “[t]he long-term accumulation of negative, weak, and
inconsistent findings suggests that TCDD eventually will be
recognized as not carcinogenic for humans.” Philip Cole, et
al, Dioxin and Cancer: A Critical Review, 38 Reg.
Toxicology & Pharmacology 378, 378 (2003). Cole et al.
examined the scientific research on dioxin from three
perspectives: (1) an analysis of the evidence available
through 1997, with emphasis on the review done by the
International Agency for Research on Cancer (IARC) in its
1997 Monograph 69, (2) a review of epidemiologic reports
issued after 1997 Monograph was published, and (3) an
evaluation of the EPA’s ongoing risk assessment. Cole et al.
concluded that “[ijt is clear from this review that the
evidence does not support the IARC’s classification of
TCDD as a Group | carcinogen. In fact, the evidence

* Indeed, studies done in worker populations who were exposed to dioxin
at sufficient levels to develop chloracne show “no clear evidence of a
causal association between any” cause of mortality and potential
occupational exposures to the higher chlorinated phenols, derivative
products, or the chlorinated dioxins.” See Gregory G. Bond, et al.,
Update of Mortality among Chemical Workers with Potential Exposure to
the Higher Chlorinated Dioxins, 31 J. Occupational Med. 121, 123
(1989); Cole et al., supra, at 383 (“Interestingiy, even chloracne has not
been associated with significant risks of cancer as would be expected if
moderate to high TCDD exposures were carcinogenic.”).

10

indicates that TCDD is not carcinogenic to human beings at
low levels and that it may not be carcinogenic to them even
at high levels. Cole et al., supra, at 386. The conclusion of
this recent, comprehensive review of the dioxin literature is
directly contrary to the EPA’s use of its no-biological-
threshold model, which is derived from the weak and
inconsistent findings for the most highly exposed industrial
worker cohorts, to fix a supposed level of cancer risk in
humans with low exposures—without any support in the ©
actual epidemiological literature for such low exposure
populations.

Cole et al. also addressed the question of how, “in the
absence of sufficient epidemiologic evidence, a conclusion of
human carcinogenicity was drawn.” /d. at 381.

There are four reasons why so much

attention has been focused on TCDD. First,

TCDD is the most toxic PCDD. Even

though toxicity and carcinogenicity are

different, the high toxicity of TCDD has

contributed to its overall notoriety. Second,

TCDD has been linked closely to a major

war (Vietnam) and to a major industrial

accident (Seveso), both of which attracted

widespread attention and __ increased
suspicion that TCDD imposes a risk of

cancer. Third, TCDD is an animal

carcinogen, although for tumor types that

bear little relationship to those allegedly

linked to it in humans. Generalizing to

humans from animals is fraught with

difficulty, and animal evidence is often not a

good predictor of human carcinogenicity.

Fourth, the original epidemiologic studies of

TCDD were represented as_ positive.

However, these early studies, all by Hardell

1]

et al., have not been confirmed by other
investigators. Nevertheless, it is difficult to
erase from the collective consciousness the
widely publicized early studies.

-

Id. at 381-82.

As aptly described by Cole et al., virtually the only
“science” behind the suspicion that TCDD may cause cancer
are the so-called “Hardell studies” conducted initially in the
lae 1970s by a _ group of Scandinavian
epidemiologists/oncologists. The Hardell studies were case-
control studies of pesticide applicators that focused on soft-
tissue sarcoma and malignant lymphoma. Importantly,
however, in the 20-plus years since these studies were
conducted, no other investigators have been able to replicate
the results, and contemporaneous case-control studies by
other investigators “uniformly produced non-significant
associations.” Cole et al., supra, at 383. Courts have also
recognized the limitations of the Hardell studies. Judge
Weinstein, after examining these studies in depth expressly
noted:

The parties, and especially plaintiffs, rely on

over one hundred epidemiological studies

not conducted by government officials and

as such not subject to the 803(8)(C)

exception. ... Most of the studies rely on

inapposite data and would be excluded

under Rules 401 to 403. Some of them on

industrial exposure have been recognized as

flawed. See, e.g., Palmer v. Nova Scotia

Forest Industries, 60 N.S.R. (2d) 271, 352-

53, 2 D.L.R. (4th) 397 (S.Ct. Nova Scotia,

1983) (Nunn, J.) (refusing to enter

injunction against spraying of 2-4-D, 2,4,5-

T-phenoxy herbicides in part because expert

12

studies, such as Hardell’s, showing alleged
adverse health effects were widely
recognized as flawed).

In re “Agent Orange” Prod. Liab. Litig., 611 F. Supp. at
1241 (emphasis added).

Studies of industrial workers further weaken any
suggested links between TCDD and cancer in humans. The
study by Manolis Kogevinas, Cancer Mortality in Workers
Exposed to Phenoxy Herbicides, Chlorophenois, and
Dioxins, 145 Am. J. Epidemiology 1061 (1997), which
involved “‘the largest overall cohort of 2,3,7,8,-TCDD-
exposed workers’” Cole et al., supra, at 381, (quoting IARC
Monograph at 161), found an overall relative risk of 1.1 Cole
et al., supra, at 381, (citing Kogevinas et al. at 144 (1997)).’

This lack of consistent evidence of increased cancer
risk associated with TCDD is further supported by the results
of a recent study examining the long-term mortality
experience of a cohort of 2187 male chemical plant
production workers. The cohort of workers, which was a
subset of the Kogevinas cohort, had previously been exposed
to substantial levels of dioxin prior to 1983. K.M. Bodner, et
al., Cancer Risk for Chemical Workers Exposed to 2,3,7,8-

” The Kogevinas study did show a slight, but statistically significant
increase in the rate of overall cancers associated with high-levels of

occupational exposure. As Cole et al. noted, however, it ts
unprecedented that a chemical would increase the risk of all cancers, but
not increase the risk of any specific cancer. “There is . . . no single

chemical that is known to cause cancer at many organ sites.” Cole et al.,
supra, at 380. Even the International Agency for Research on Cancer
(IRAC) acknowledged that “this lack of precedent for a multi-site
carcinogen without particular sites predominating means that the
epidemiology data must be treated with caution. . .” Int’l Agency for
Research on Cancer, World Health Org., /ARC Monograph on the
Evaluation of Carcinogenic Risks to Humans at 337, 338 (1997).

13

tetrachlorodibenzo-p-dioxin, 60 Occup. and Envtl. Med. 672-
75 (2003). The Bodner study was the most recent in a series
examining the cohort, and therefore has the most current
mortality statistics and involves the longest latency period. e
mortality rates were compared with both national figures and
with a pool of coworkers in unrelated production jobs. The
study showed that all cancers combined for this cohort were
at or below expected levels.* The Bodner study also noted
that workers who developed chloracne -- presumably the
workers who had the highest exposure levels generally -- had
very low all-cancer rates. The report concluded that
“{djespite some unanswered questions, we find no coherent
evidence that this cohort has an increased risk of cancer
collectively, or of any particular type of cancer that can be
attributed to dioxin exposure.” /d. at 675.
Iii. STUDIES ON MILITARY PERSONNEL
EXPOSED TO DIOXIN CONSISTENTLY FAIL
TO DEMONSTRATE A CAUSAL LINK
BETWEEN DIOXIN AND CANCER

The Air Force has spent hundreds of millions of
dollars following the health histories of the group of Vietnam
veterans who clearly were the most highly exposed
individuals during that conflict—the Operation Ranch Hand
personnel who loaded and sprayed Agent Orange. That
ongoing study of the Ranch Hand veterans has shown no
marked excess of cancer even now, thirty-five to forty years
after the exposure.”

Although the rates for soft tissue sarcoma and non-Hodgkin’s
lymphoma were greater than expected during the prior study period, the
rates of these cancers did not increase at the expected rate during the
update period.

The 2005 report of this study concludes that “the significant
associations between herbicide exposure or dioxin levels and the
likelihood of developing cancer were seen primarily for Ranch Hand

9

14

The Ranch Hand study examined veterans who
serviced, loaded, and flew the fixed-wing aircraft used for
herbicide spraying missions in Vietnam and compared them
to veterans who flew similar aircraft in Southeast Asia during
the time of the Vietnam War but never flew herbicide
missions and were not exposed to Agent Orange in their
missions. Elevated serum levels of dioxin confirmed that the
Ranch Hand group had been exposed to Agent Orange.
Logically, if one were to find an increased risk from Agent
Orange exposure in any group of Vietnam veterans, it would
first show up in the most heavily exposed Ranch Hand group.
However, study of the Ranch Hand veterans has not found
any cancer-related health effects caused by Agent Orange
exposure, see Joel E. Michalek et al., The Air Force Health
Study: A Summary of Results, 54 Organohalogen Compounds
396 (2001), and the overall cancer mortality rate is similar to
the comparison group, See Fatema Z. Akhtar ef al., Cancer in
U.S. Air Force Veterans of the Vietnam War, 42
J. Occupational & Envtl. Med. 123 (2004).'°

officers and Ranch Hands in the low dioxin category, which were the
lower-exposed subgroups, on average. Some of these associations also
may have been due to chance or to a lack of adjustment for a factor not
considered in these analyses.” Science Applications Int’l Corp., Air
Force Health Study Final Report, An Epidemiologic Investigation of
Health Effects in Air Force Personnel Following Exposure to Herbicides
~— 2002 Follow-up Examination and Results, 10-138 (2005).

'© Akhtar et al., supra, conducted a comparison of cancer incidence in a
cohort of Ranch Hand and Comparison veterans relative to the general
United States white population and found a positive association with
prostate cancer and melanoma in both groups of veterans. However,
some researchers question whether a comparison of these cohorts is
scientifically valid. Both melanoma and prostate cancer are frequently
undiagnosed for many years in the general population, leading to a
detection bias in favor of the Ranch Hand veterans. See Marian Pavuk, et
al., Prostate Cancer in US Air Force Veterans of the Vietnam War, 16
J. Exposure Sci. & Envtl. Epidemiology, 184, 188 (2006) (“Air Force

15

Similar findings were made in the most recent
Institute of Medicine (“IOM”) Report, which concluded that
“in general, it is impossible to quantify the degree of risk
likely to be experienced by veterans because of their
exposure to herbicides in Vietnam.” 2004 IOM Report at 17
(emphasis added); see also Id. at 7 (noting that the “lack of
adequate data on Vietnam veterans themselves makes it
difficult to reach conclusions about increased risk of disease
among Vietnam veterans”). The Report highlights the
inadequacy of the current state of the scientific record,
decrying “the lack of data on Vietnam veterans, the large
uncertainties about the magnitude of potential risk posed by
exposure to herbicides in epidemiologic studies, the
inadequate control for other important risk factors in many
epidemiologic studies, and the uncertainty about the nature
and magnitude of exposure to herbicides in Vietnam.” Jd. at
7. Indeed, far from reflecting a scientific consensus that
Agent Orange has caused cancer in Vietnam veterans, the
Report highlights the need “for additional scientific studies to
resolve continuing scientific uncertainties about the health
effects of the herbicides used in Vietnam and _ their
contaminants.” Jd. at 10.

For public policy reasons, Congress created a
program of compensation for Vietnam veterans without
requiring reliable scientific evidence of the health effects of
Agent Orange exposure. Pursuant to the Agent Orange Act
of 1991, the IOM was directed to “provide scientific
information for the Secretary of Veterans Affairs” to aid in
the implementation of the compensation program. Jnstitute
of Medicine, Veterans and Agent Orange: Health Effects of

veterans have been more closely followed than the general population and
underwent repeated medical examinations that may partly explain
excesses seen in that study.”); Akhtar et al., supra, at 133 (acknowledging
the potential for detection bias in the melanoma findings).

16

Herbicides Used in Vietnam at 227 (1994) (“1994 IOM
Report”). The IOM’s periodic reports — the first was
published in 1994, and the IOM has issued updated reports
every two years since — have done just that. The IOM,
however, has expressly disclaimed any intent to make
causation assessments, noting that its “charge was not] to
focus on questions of causation,” /d., and explaining that its
categorization of diseases was “based on ‘statistical
association,’ not on causality as is common in scientific
reviews,” Id. at 246; see also e.g., 1994 IOM Report at 7,
572; 2004 IOM Report at 7 (“As mandated by PL 102-4, the
distinctions among categories are based on statistical
association, not on causality.”). As the Federal Judicial
Center’s Reference Manual on Scientific Evidence explains,
however, “an association is not equivalent to causation”:

An association identified in an

epidemiologic study may or may not be

causal. Assessing whether an association is

causal requires an understanding of the

strengths and weaknesses of the study’s

design and implementation, as well as a

judgment about how the study findings fit

with other scientific knowledge.

Federal Judicial Center, Reference Manual on Scientific
Evidence 336-37 (2d ed. 2000) (footnote omitted)."!

'' The peril of conflating association with causation is not unique to the
dioxin context. In some early epidemiological studies, for example,
coffee drinking was associated with lung cancer. However, coffee
drinking used to be highly associated with smoking cigarettes, thus
smoking was a “confounding” variable. Once smoking was controlled
for, the association between coffee drinking and lung cancer disappeared.
See Junius C. McElveen, Jr. & Chris Amantea, Legislating Risk
Assessment, 63 U. Cin. L. Rev. 1553, 1581 (1995).

17

The vast gulf between association and causation has
been well established in the context of Agent Orange. As
described in Nehmer v. United States Veterans’
Administration, 712 F. Supp. 1404, 1407-08 (N.D. Cal.
1989), the Veterans Administration (“VA”) initially adopted
a causation standard to govern eligibility for disability
benefits under the Veterans’ Dioxin and Radiation Exposure
Compensations Standards Act of 1984. Applying that
standard, the VA denied more than 31,000 claims for
compensation in the first three years of the program. /d.
at 1408. That causation standard was declared invalid in
Nehmer, see id. at 1416-20, and was replaced with a standard
requiring only a “significant statistical association,” id. at
1420. Under that more relaxed standard, the VA has granted
thousands of claims and is paying hundreds of millions of
dollars in Agent Orange benefits.

The distinction between association and causation is
particularly significant in the present context because of the
congressional mandate to assess only the former. The IOM
thus considers the link between chemical exposure and
disease to be sufficient when “a positive association has been
observed between herbicides and the outcome in studies in
which chance, bias, and confounding could be ruled out with
reasonable confidence.” Institute of Medicine, Veterans and
Agent Orange: Update 2002 at 8 (2002) (“2002 IOM
Report”). “Several small studies that are free of bias and
confounding” may be sufficient evidence of an association
when the results are “consistent in magnitude and direction,”
Id. at 14, even if larger and more reliable studies fail to
replicate the small studies and even report results to the
contrary.

There is, in short, nothing even approaching a
“scientific consensus” that Agent Orange has caused cancers
in Vietnam veterans, and nothing in the IOM Report suggests
otherwise. As the record in the Agent Orange litigation

18

indicates, the Ranch Hand Study and the other studies of

Vietnam veterans “effectively rule out the possibility of

widespread health effects in Vietnam veterans due to Agent

Orange.”

IV. EPA’S SCIENCE ADVISORY BOARD AND THE
NATIONAL ACADEMY OF SCIENCE HAVE
BOTH NOTED THE ABSENCE OF ANY
CONSISTENT, REPLICABLE PATTERN OF
INCREASED CANCERS IN THE
EPIDEMIOLOGY LITERATURE.

In 1995, EPA’s Science Advisory Board (“SAB”)
issued a powerful critique of the agency’s Dioxin
Reassessment. Among other criticisms, the SAB stated that
“the presentation of scientific findings portrayed in the draft
document’s conclusions is not balanced vis-a-vis the possible
risks posed by exposure to dioxin, with a tendency to
overstate the possibility for danger.” JA18028. The SAB
further noted that the evidence “for the purported
mechanisms that link receptor binding to toxic effects in
humans” was “quite mixed,” making it “difficult to document
a dioxin-cancer relationship.” JA18066. Although the SAB
concluded that EPA had fairly summarized the findings,
strengths and weaknesses of the relevant epidemiological
studies, the SAB was quite firm in its additional conclusions
that “TCDD is not a complete carcinogen” and that the risk-
specific dose estimate supplied by EPA’s cancer potency
factor “is not supported by the available data.” JA18077,
18101.

In addition to the findings above, SAB recommended
that EPA revise the dioxin risk characterization and the dose-
response modeling chapters of its report.” Because of the

'? SAB also recommended that EPA develop of a new section on dioxin
toxicity equivalence factors (TEF).

19

complexity of the science issues related to dioxin, the SAB
suggested that the subsequent draft undergo an additional
level of review by independent external peer reviewers
before being brought back to the SAB for review.

In 2000, a revised reassessment was submitted to
SAB. Surprisingly, despite the prior criticism of its cancer
potency factor, EPA did not revise its flawed no-threshold
model. SAB was again critical of EPA’s dioxin risk
characterization, noting (1) the lack of consensus about the
strength of the epidemiological data suggesting that dioxin is
carcinogenic in humans; (2) the lack of consensus on a single
value for a dioxin potency factor; and (3) EPA’s failure to
assess non-cancerous affects to establish a reference dose
characterization. See generally, EPA, Dioxin Reassessment -
on SAB Review of the Office of Research & Development's
Reassessment of Dioxin 2-11 (2001). EPA undertook further
revisions. At this point, the Department of Agriculture,
concerned that enforcement of EPA’s cancer potency factor
could imperil large portions of the country’s food supply,
assembled an Interagency Working Group made up of
representatives from seven federal agencies that
recommended further review of EPA’s 2003 revision of the
Dioxin Reassessment. EPA then asked the National
Research Council (NRC), the operating arm of the National
Academy of Sciences, to convene an expert committee to
review independently EPA’s Reassessment. National
Research Council, Health Risks from Dioxin and Related

Compounds: Evaluation of the EPA Reassessment, at 9(July
2006).

The NRC strongly criticized EPA’s continued
reliance on the linear, no threshold model:

[SJelection of the default linear

extrapolation approach for carcinogenicity

emerged as one of the most critical decisions

in the 2003 Reassessment. The committee

20

concludes that EPA did not support its
decision adequately to rely solely on this
default linear model and recommends that
EPA add a scientifically rigorous evaluation
of a nonlinear model that is consistent with
receptor-mediated responses and the recent

NTP cancer bioassay _ studies. The
committee determined that the available data
support the use ofa __ nonlinear model,

which is consistent with receptor-mediated
responses and a potential threshold... .

Id. at 17.

Although the NRC made no effort to calculate a
cancer potency factor using a non-linear model, it seems
clear that any such calculation will yield a factor which will
be much lower than the 16-fold reduction that Hercules
proposed in the Administrative Records of this case. See,
e.g., JA17583 (proposing slope factor of 9,700 (mg/kg-day)
' using linear model and then-recent histopathology results),
JA17585 (noting that other nations had dramatically higher
Acceptable Daily Intake (ADJ) standards than EPA).
Moreover, a “nonlinear model” with “a potential threshold,”
means that there is some lower level of exposure below
which any cancer risk becomes insignificant. And, al] the
risk models leave open the ever-increasingly likely
possibility that dioxin does not cause human cancer even at
the highest levels of exposure.

CONCLUSION

The petition for a writ of certiorari should be granted.

Respectfully submitted,

LISE T. SPACAPAN IAN HEATH GERSHENGORN*
TRACI M. BRAUN JENNER & BLOCK LLP
JENNER & BLOCK LLP 601 Thirteenth Street, N.W.
One IBM Plaza Washington, DC 20005

Chicago, IL 60611-7603 (202) 639-6000

(312) 222-9350
* Counsel of Record

Counsel for Amicus Curiae

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Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40386016_1925%3A4. Public record. Not legal advice.