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

(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.

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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

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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

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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

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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