U.S. GOVERNMENT PUBLISHING OFFICE

28–933PDF WASHINGTON : 2018

IN DEFENSE OF SCIENTIFIC INTEGRITY: 

EXAMINING THE IARC MONOGRAPH PROGRAMME 

AND GLYPHOSATE REVIEW 

HEARING 

BEFORE THE

COMMITTEE ON SCIENCE, SPACE, AND 

TECHNOLOGY 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED FIFTEENTH CONGRESS 

SECOND SESSION 

FEBRUARY 6, 2018 

Serial No. 115–46 

Printed for the use of the Committee on Science, Space, and Technology 

( 

Available via the World Wide Web: http://science.house.gov 
(II) 

COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

HON. LAMAR S. SMITH, Texas, Chair 

FRANK D. LUCAS, Oklahoma 

DANA ROHRABACHER, California 

MO BROOKS, Alabama 

RANDY HULTGREN, Illinois 

BILL POSEY, Florida 

THOMAS MASSIE, Kentucky 

JIM BRIDENSTINE, Oklahoma 

RANDY K. WEBER, Texas 

STEPHEN KNIGHT, California 

BRIAN BABIN, Texas 

BARBARA COMSTOCK, Virginia 

BARRY LOUDERMILK, Georgia 

RALPH LEE ABRAHAM, Louisiana 

DANIEL WEBSTER, Florida 

JIM BANKS, Indiana 

ANDY BIGGS, Arizona 

ROGER W. MARSHALL, Kansas 

NEAL P. DUNN, Florida 

CLAY HIGGINS, Louisiana 

RALPH NORMAN, South Carolina 

EDDIE BERNICE JOHNSON, Texas 

ZOE LOFGREN, California 

DANIEL LIPINSKI, Illinois 

SUZANNE BONAMICI, Oregon 

AMI BERA, California 

ELIZABETH H. ESTY, Connecticut 

MARC A. VEASEY, Texas 

DONALD S. BEYER, JR., Virginia 

JACKY ROSEN, Nevada 

JERRY MCNERNEY, California 

ED PERLMUTTER, Colorado 

PAUL TONKO, New York 

BILL FOSTER, Illinois 

MARK TAKANO, California 

COLLEEN HANABUSA, Hawaii 

CHARLIE CRIST, Florida 
(III) 

C O N T E N T S 

February 6, 2018 

Page 

Witness List ............................................................................................................. 2 

Hearing Charter ...................................................................................................... 3 

Opening Statements 

Statement by Representative Lamar S. Smith, Chairman, Committee on 

Science, Space, and Technology, U.S. House of Representatives ..................... 4 

Written Statement ............................................................................................ 6 

Statement by Representative Eddie Bernice Johnson, Ranking Member, Committee on Science, Space, and Technology, U.S. House of Representatives .... 8 

Written Statement ............................................................................................ 10 

Minority Staff Report ....................................................................................... 12 

Statement by Representative Frank D. Lucas, Committee on Science, Space, 

and Technology, U.S. House of Representatives ............................................... 32 

Written Statement ............................................................................................ 35 

Statement by Representative Suzanne Bonamici, Committee on Science, 

Space, and Technology, U.S. House of Representatives .................................... 37 

Written Statement ............................................................................................ 39 

Witnesses: 

Dr. Anna Lowit, Senior Science Advisor, Office of Pesticide Programs, Environmental Protection Agency 

Oral Statement ................................................................................................. 42 

Written Statement ............................................................................................ 44 

Dr. Timothy Pastoor, CEO, Pastoor Science Communications 

Oral Statement ................................................................................................. 55 

Written Statement ............................................................................................ 57 

Dr. Jennifer Sass, Senior Scientist, Natural Resources Defense Council 

Oral Statement ................................................................................................. 62 

Written Statement ............................................................................................ 64 

Dr. Robert Tarone, (retired) Mathematical Statistician, U.S. National Cancer 

Institute and Biostatistics Director, International Epidemiology Institute 

Oral Statement ................................................................................................. 77 

Written Statement ............................................................................................ 79 

Discussion ................................................................................................................. 89 

Appendix I: Answers to Post-Hearing Questions 

Dr. Anna Lowit, Senior Science Advisor, Office of Pesticide Programs, Environmental Protection Agency .............................................................................. 106 

Dr. Timothy Pastoor, CEO, Pastoor Science Communications ............................ 107 

Dr. Jennifer Sass, Senior Scientist, Natural Resources Defense Council ........... 113 

Dr. Robert Tarone, (retired) Mathematical Statistician, U.S. National Cancer 

Institute and Biostatistics Director, International Epidemiology Institute .... 116 
Page

IV 

Appendix II: Additional Material for the Record 

Documents submitted by Representative Suzanne Bonamici, Committee on 

Science, Space, and Technology, U.S. House of Representatives ..................... 122 

Documents submitted by Representative Paul Tonko, Committee on Science, 

Space, and Technology, U.S. House of Representatives .................................... 139 

Documents submitted by Representative Jerry McNerney, Committee on 

Science, Space, and Technology, U.S. House of Representatives ..................... 213 

Documents submitted by Representative Donald S. Beyer, Jr., Committee 

on Science, Space, and Technology, U.S. House of Representatives ................ 214 

Documents submitted by Representative Lamar S. Smith, Chairman, Committee on Science, Space, and Technology, U.S. House of Representatives .... 220 
(1) 

IN DEFENSE OF SCIENTIFIC INTEGRITY: 

EXAMINING THE IARC MONOGRAPH 

PROGRAMME 

AND GLYPHOSATE REVIEW 

TUESDAY, FEBRUARY 6, 2018 

HOUSE OF REPRESENTATIVES, 

COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY, 

Washington, D.C. 

The Committee met, pursuant to call, at 10:06 a.m., in Room 

2318 of the Rayburn House Office Building, Hon. Lamar Smith 

[Chairman of the Committee] presiding. 
2 

LAMAR S. SMITH, leJCas 

CHAIRMAN 

EDDIE BERNICE JOHNSON, Texa$ 

RANKING Mf,::MBER 

Q:ongrtss of tht tinittd ~tatrs 

!louse of 'RQJrcscnmtiucs 

COMMITIEE ON SCIENCE, SPACE, AND TECHNOLOGY 

2321 RAYBURN HoUSE OFFICE BUILDING 

WASHINGTON, DC 20515'-6301 

(202) 225'-6371 

www.science.h.ouse.gov 

Full Committee 

.I_n Defense of Scientific Integrity: Examining the /ARC 

Monograph Programme and Glyphosate Review 

Tuesday, February 6, 2018 

!O:OOa.m. 

2318 Rayburn House Office Building 

Witnesses 

Dr. Anna Lowit, Senior Science Advisor, Office of Pesticide Programs, 

Environmental Protection Agency 

Dr. Timothy Pastoor, CEO, Pastoor Science Communications 

Dr. Jennifer Sa~, Senior Scientist, Natural Resources Defense Council 

Dr. Robert Tarone, (retired) Mathematical Statistician, U.S. National 

Cancer Institute and Biostatistics Director, Intemational Epidemiology 

Institute 
3 

U.S. HOUSE OF REPRESENTATIVES 

COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

HEARING CJIARTER 

Tuesday, February 6, 2018 

TO: Members, Committee on Science, Space and Technology 

FROM: Majority Staff, Committee on Science, Space, and Technology 

SUBJECT: Full Committee Hearing: "In Defense of Scientific Integrity: Examining the !ARC 

Monograph Programme and Glyphosate Review" 

The Committee on Science, Space and Technology will hold a hearing titled In Defense 

of Scientific Integrity: Examining the /ARC Monograph Programme and Glyphosate Review on 

Tuesday, February 6, 2018, at 10:00 a.m. in Room 2318 of the Rayburn House Office Building. 

Hearing Purpose: 

The purpose of the hearing is to examine the scientific underpinnings, principles, and 

procedures at the International Agency for Research on Cancer's (IARC) Monograph 

Programme. This hearing will use the review of glyphosate by both IARC and the 

Environmental Protection Agency (EPA) as a case study. 

Witness List 

Dr. Anna Lowit, Senior Science Advisor, Office of Pesticide Programs, Environmental 

Protection Agency 

• Dr. Timothy Pastoor, CEO, Pastoor Science Communications 

• Dr. Jennifer Sass, Senior Scientist, Natural Resources Defense Council 

• Dr. Robert Tarone, (retired) Mathematical Statistician, U.S. National Cancer Institute 

and Biostatistics Director, International Epidemiology Institute 

Staff Contact 

For questions related to the hearing, please contact Majority Staff at 202-225-6371. 
4 

Chairman SMITH. The Committee on Science, Space, and Technology will come to order. Without objection, the Chair is authorized to declare recesses of the Committee at any time. 

Welcome to today’s hearing entitled ‘‘In Defense of Scientific Integrity: Examining the IARC Monograph Programme and 

Glyphosate Review.’’ 

I recognize myself for five minutes for an opening statement, and 

then I’ll recognize the opening—I mean the Ranking Member as 

well. 

Today, we will examine the U.S. taxpayer-funded IARC Monograph Programme and its assessment of the herbicide glyphosate, 

more commonly known as Roundup. We must ensure that the underlying science behind assessments that influence policy and the 

public is based on sound science. The American people deserve to 

know the truth about which substances are safe and which ones 

pose a risk. Glyphosate is the most widely used herbicide in the 

world. Americans and people across the globe rely on these crops 

for high quality, affordable food. 

There are real repercussions to IARC’s unsubstantiated claims, 

which are not backed by reliable data. Labeling requirements will 

drive costs up for farmers and consumers and create unjustified 

public fear. IARC’s irresponsible handling of data does real harm 

to job creators and the public’s view of the scientific process. 

Agencies such as IARC have a responsibility to adhere to the scientific method and evaluate all relevant scientific studies, weigh 

the evidence, and come to a conclusion that can be reproduced. Following the scientific method also means forming a conclusion only 

after all data has been considered. 

According to information gathered by the Committee, there appear to be serious problems with the science underlying IARC’s assessment of glyphosate. The news media recently revealed evidence 

of data deletion and manipulation of draft assessments before final 

publication. IARC’s conclusion about glyphosate relied only on data 

that was favorable to its conclusion and ignored contradictory data. 

In its assessment, IARC did no direct evaluation of glyphosate’s 

effect on humans, no evaluation whatsoever. Specifically, IARC appears to have intentionally omitted data that showed glyphosate 

does not cause cancer. It’s no surprise that the Monograph Programme has refused to publish any of its draft assessments. If 

there is nothing to hide, why the secrecy? 

The manipulation of scientific data and lack of transparency is 

not the only defect in IARC’s glyphosate assessment. Besides altering the data used in the assessment, the Monograph Working 

Group failed to consider the most significant study on human exposure to glyphosate. The Agricultural Health Study, which was a result of a collaboration of several federal agencies such as the National Cancer Institute, National Institute of Environmental Health 

Sciences, and the Environmental Protection Agency presented information they had collected on over 50,000 humans. Aaron Blair, 

the Chair of the Monograph Programme at the time, admitted in 

a deposition that the study would, quote, ‘‘altered IARC’s analysis,’’ 

end quote. However, this study was not considered by IARC. 

In 2015, IARC published its findings on glyphosate, categorizing 

the herbicide as ‘‘probably’’ causing cancer. It has become apparent 
5 

that the Monograph on glyphosate uses nothing more than cherrypicked science created by those who have a financial stake in the 

resulting conclusions. 

The Monograph Programme is alone in its determination that 

glyphosate poses a cancer threat. Both the EPA and EFSA, a European regulatory agency, have reviewed glyphosate and determined 

that the chemical is unlikely to cause cancer. Last December, the 

EPA released a draft Human Health Risk Assessment evaluating 

the potential of glyphosate to cause cancer. The EPA body of research was then evaluated by a Scientific Advisory Panel composed 

of experts appointed during the Obama Administration. The EPA’s 

draft assessment reviewed IARC’s glyphosate Monograph and came 

to the conclusion that glyphosate is unlikely to cause cancer. 

The Committee has written several letters expressing concerns 

about the lack of sound science and biases found in IARC’s program. When asked to provide a witness for this hearing, IARC Director Wild refused to attend. No doubt he could not defend IARC’s 

glyphosate findings. The selective use of data and the lack of public 

disclosure raise questions about why IARC should receive any government funding in the future. 

[The prepared statement of Chairman Smith follows:] 
6 

COMMITTEE ON 

SCIENCE, SPACE, & TECHNOLOGY Lamar Smith, Chairman 

For Immediate Release 

February 6, 20 I B 

Media Contacts: Thea McDonald, Brandon VerVelde 

(202) 225-6371 

Statement by Chairman Lamar Smith (R-Texas) 

In Defense of Scientific Integrity: Examining the /ARC Monograph 

Programme and Glyphosate Review 

Chairman Smith: Today we will examine the U.S. taxpayer-funded !ARC Monograph 

Programme and its assessment of the herbicide glyphosate, more commonly known as 

Roundup. We must ensure that the underlying science behind assessments that influence 

policy and the public is based on sound science. 

The American people deserve to know the truth about which substances are safe and which 

ones pose a risk. Glyphosate is the most widely used herbicide in the world. Americans and 

people across the globe rely on these crops for high quality, affordable food. 

There are real repercussions to !ARC's unsubstantiated claims, which are not backed by 

reliable data. Labeling requirements will drive costs up for farmers and consumers and 

create unjustified public fear. IARC's irresponsible handling of data does real harm to job 

creators and the public's view of the scientific process. 

Agencies such as IARC have a responsibility to adhere to the scientific method and evaluate 

all relevant scientific studies, weigh the evidence, and come to a conclusion that can be 

reproduced. Following the scientific method also means forming a conclusion only after all 

data has been considered. 

According to information gathered by the committee, there appear to be serious problems 

with the science underlying !ARC's assessment of glyphosate. The news media recently 

revealed evidence of data deletion and manipulation of draft assessments before final 

publication. 

!ARC's conclusion about glyphosate relied only on data that was favorable to its conclusion 

and ignored contradictory data. In its assessment, !ARC did no direct evaluation of 

glyphosate's effect on humans. Specifically, IARC appears to have intentionally omitted 

data that showed glyphosate does not cause cancer. 

It's no surprise that the Monograph Programme has refused to publish any of its draft 

assessments. If there is nothing to hide, why the secrecy? 

The manipulation of scientific data and lack of transparency is not the only defect in !ARC's 

glyphosate assessment. Besides altering the data used in the assessment. the Monograph 

Working Group failed to consider the most significant study on human exposure to 

glyphosate. 
7 

The Agricultural Health Study (AHS), which was a result of a collaboration of several fedeqJI 

agencies such as the National Cancer Institute (NCI), National institute of Environmental 

Health Sciences (NIEHS) and the Environmental Protection Agency (EPA), presented 

information they had collected on over 50,000 humans. Aaron Blair, the chair of the 

Monograph Programme at the time, admitted in a deposition that the study would have 

"altered !ARC's analysis." However, this study was not considered by IARC. 

In 2015, IARC published its findings on glyphosate, categorizing the herbicide as "probably" 

causing cancer. It has become apparent that the Monograph on glyphosate uses nothing 

more than cherry-picked science created by those that have a financial stake in the 

resulting conclusions. 

The Monograph Programme is alone in its determination that glyphosate poses a cancer 

threat. Both the EPA and EFSA, a European regulatory agency, have reviewed glyphosate 

and determined that the chemical is unlikely to cause cancer. 

Last December, the EPA released a Draft Human Health Risk Assessment evaluating the 

potential of glyphosate to cause cancer. The EPA body of research was then evaluated by 

a Scientific Advisory Panel (SAP) composed of experts appointed during the Obama 

administration. The EPA's draft assessment reviewed !ARC's glyphosate monograph and 

came to the conclusion that glyphosate is unlikely to cause cancer. 

The committee has written several letters expressing concerns about the lack of sound 

science and biases found in !ARC's program. When asked to provide a witness for this 

hearing, IARC Director Wild refused to attend. No doubt he could not defend !ARC's 

glyphosate findings. 

The selective use of data and the lack of public disclosure raise questions about why IARC 

should receive any government funding in the future. 

### 
8 

Chairman SMITH. That concludes my opening statement, and the 

Ranking Member, the gentlewoman from Texas, is recognized for 

hers. 

Ms. JOHNSON. Thank you very much, Mr. Chairman. 

Chemicals have the potential to greatly improve our quality of 

life when developed and produced in a responsible manner. However, when produced or proliferated irresponsibly or without sufficient understanding of their potential impacts, chemicals can pose 

a grave and significant risk to every one of us. 

Unfortunately, by the time we realize the harm being caused by 

unsafe exposure to such toxic chemicals, the damage has often already been done, and we’re left regretting the fact that there might 

have been preventative actions we could have taken to protect ourselves if we had a better understanding of the hazards. If we knew 

then what we know now, would we have filled our homes, schools, 

businesses, hospitals with asbestos? Would we have supported the 

widespread installation of lead pipes to provide us with our daily 

drinking water? Most Americans who have had to suffer or who 

have seen their children and other loved ones suffer through the 

adverse health effects of exposures to dangerous chemicals would 

likely say no, of course not. 

The chemicals we are discussing today—glyphosate—is already 

one of the most widely used chemicals in agriculture. For example, 

it is the key ingredient in Monsanto’s herbicide Roundup that has 

helped farmers get greater yield of corn and other agriculture products. However, the widespread prevalence of glyphosate has raised 

serious concerns about its toxicity and potential cancer-causing 

properties. 

That is why the work done by independent chemical assessment 

organizations like the World Health Organization and its International Agency for Research on Cancer is so critical to protecting 

the public health of—those organizations evaluate without prejudice or concern about profits, the health habits—hazards and risks 

posed by exposure to toxic chemicals. By contrast, there’s been extensive documentation of efforts by the chemical industry to bias 

the science and public perception of their chemicals to protect their 

financial interests rather than the public health. If we are truly interested in defending scientific integrity, we should be doing more 

than simply hearing from the industry-friendly scientists. 

As my colleagues may be aware, the EPA’s Office of Inspector 

General has been investigating allegations that Monsanto attempted to influence officials at the Environmental Protection 

Agency who were central to EPA’s own review of glyphosate, as 

well as potential collusion by those officials with Monsanto. If this 

Committee really wishes to do oversight in defense of scientific integrity, those allegations would certainly seem to be worthy of our 

attention. However, I am not holding my breath that the majority 

will undertake such an investigation. 

Mr. Chairman, chemical companies will continue to innovate and 

manufacture chemicals that seek to improve human life, and I support their initiatives in doing so. But such innovations should not 

come at the cost of human health. That is why the work of independent organizations like IARC is so important and why we in 
9 

Congress should be supporting that work rather than attempting 

to undercut it. 

The minority staff has produced a staff report that documents 

some of the tactics Monsanto has used to undermine this IARC 

Monograph and scientific findings and glyphosate in general, and 

I’m attaching this report to my statement. 

I thank you, Mr. Chairman, and I yield back. 

[The prepared statement of Ms. Johnson follows:] 
10 

OPENING STATEMENT 

Ranking Member Eddie Bernice Johnson (D-TX) 

House Committee on Science, Space, and Technology 

"In Defense of Scientific Integrity: 

Examining the !ARC Monograph Programme and Glyphosate Review" 

February 6, 2018 

Mr. Chairman, chemicals have the potential to greatly improve our quality oflife, when 

developed and produced in a responsible manner. However, when produced or proliferated 

irresponsibly or without sufficient understanding of their potential impacts, chemicals can pose a 

grave and significant risk to every one of us. Unfortunately, by the time we realize the harm 

being caused by unsafe exposure to such toxic chemicals, the damage has often already been 

done, and we are left regretting the fact that there might have been preventative actions we could 

have taken to protect ourselves if we had a better understanding of the hazards. 

If we knew then, what we know now, would we have filled our homes, schools, businesses, and 

hospitals with asbestos? Would we have supported the widespread installation oflead pipes to 

provide us with daily drinking water? Most Americans who have had to suffer, or who have seen 

their children and other loved ones suffer, through the adverse health effects of exposures to 

dangerous chemicals would likely say!!!!' of course not. 

The chemical we are discussing today, glyphosate, is already one of the most widely used 

chemicals in agriculture. For example, it is a key ingredient in Monsanto's herbicide Roundup 

that has helped farmers get greater yields of com and other agricultural products. However, the 

widespread prevalence of glyphosate has raised serious concerns about its toxicity and potential 

cancer causing properties. 

That is why the work done by independent chemical assessment organizations, like the World 

Health Organization and its International Agency for Research on Cancer (IARC), is so critical 

to protecting the public health as those organizations evaluate, without prejudice or concern 

about profits, the health hazards and risks posed by exposure to toxic chemicals. By contrast, 

there has been extensive documentation of efforts by the chemical industry to bias the science 

and public perception of their chemicals to protect a financial interest rather than the public 

health. 

If we are truly interested in defending scientific integrity, we should be doing more than simply 

hearing from industry-friendly scientists. As my colleagues may be aware, the EPA's Office of 

Inspector General has been investigating allegations that Monsanto attempted to influence 

officials at the Environmental Protection Agency (EPA) who were central to EPA's own review 

of glyphosate as well as potential collusion by those officials with Monsanto. If this Committee 

really wishes to do oversight in defense of scientific integrity, those allegations would certainly 

seem to be worthy of our attention. However, I'm not holding my breath that the Majority will 

undertake such an investigation. 
11 

Mr. Chairman, chemical companies will continue to innovate and manufacture chemicals that 

seek to improve human life, and I support their initiative in doing so. But such innovations 

should not come at the cost of human health. That is why the work of independent organizations 

like the IARC is so important, and why we in Congress should be supporting that work rather 

than attempting to undercut it. 

The Minority Staffhas produced a staff report that documents some of the tactics Monsanto has 

used to undermine the IARC monograph and scientific findings on glyphosate in general. I am 

attaching this report to my statement. 

Thank you. I yield back. 
12 

[The Minority Staff Report follows:] 

Spinning Science & Silencing Scientists: 

A Case Study in How the Chemicallndusi1JI Attempts to Influence Science 

Minority Staff Report 

Prepared for Members of the 

Committee on Science, Space & Technology 

U.S. House of Representatives 

February 2018 
13 

Introduction 

Background 

TABLE OF CONTENTS 

Glyphosate Levels in the U.S. 1992-2015 (Map) 

Key Players 

Monsanto's IARC Battle Plan 

Ghostwriting 

Orchestrate Outcry 

Establish Front Groups 

Silence Scientists 

Conclusion 

Page 1 

Page 1 

Page 3 

Page4 

Page 5 

Page 6 

Page 11 

Page 14 

Page 15 

Page 17 
14 

Introduction. On February 6, 2018, the Committee on Science, Space, and Technology is 

scheduled to hold a hearing entitled, "In Defense of Scientific Integrity: Examining the !ARC 

Monograph Programme and Glyphosate Rel'ieH·. "The chemical glyphosate is a herbicide most 

commonly found in Monsanto's commercial weed-killer Roundup. Committee Chainnan Lamar 

Smith scheduled this hearing after months oflctter writing criticizing the !ARC review of 

glyphosate and examining the EPA's actions on glyphosate. Many of the criticisms contained in 

the Committee's letters regarding !ARC mimic criticisms that the chemical industry has leveled 

on the !ARC process. Since these industry talking points are apparently the basis for both a 

Congressional investigation as well as a Committee hearing, Minority Committee Staff have 

written this staff report to better infonn the Committee Members about the chemical industry 

tactics which have ultimately produced these industry talking points. The report necessarily 

focuses on the Monsanto Company due to their primary role in inventing, selling, and marketing 

glyphosate and glyphosate resistant seeds. This report is based in no small part on documents 

that have been made publically available due to ongoing third-party litigation with Monsanto. 1 

These newly released public documents have revealed in an unprecedented manner the tactics of 

the chemical industry in attacking public health science related to their products. 

Background. In March 2015, the World Health Organization's (WHO's) International 

Agency for Research on Cancer (!ARC), based in Lyon, France, released a hazard assessment 

that found glyphosate to be "probably carcinogenic to humans." In December 2017, the EPA 

released a draft human health risk assessment that concluded, "glyphosate is not likely to be 

carcinogenic to humans." There are significant differences between these two types of 

assessments because they attempt to evaluate different questions. According to !ARC, "A cancer 

'hazard' is an agent that is capable of causing cancer under some 

circumstances, while a cancer 'risk' is an estimate of the 

carcinogenic effects expected from exposure to a cancer hazard." 

As more scientific data is gathered and analyzed to more fully 

understand the impacts of giyphosate on human health, it is 

important for the science to lead the way, and for industry and 

politicians to remain on the sidelines. But that has not happened. 

There is significant evidence that Monsanto launched a 

disinfonnation campaign to undem1ine !ARC's classification of 

glyphosate as a probable carcinogen. A multi-district litigation 

court case against Monsanto regarding potential adverse health 

consequences of exposures to glyphosatc has revealed hundreds 

of pages ofintemal Monsanto e-mails, memorandums, and other 

records that clearly show Monsanto engaged in a decades-long concerted effort to fend off any 

evidence suggesting potential adverse human health effects from glyphosate and more recently to 

undermine !ARC's findings. They ghost wrote scientific articles on glyphosate, established front 

groups to help amplify their anti-IARC message and scientific evidence they did not like, and 

they attempted to silence scientists who reached conclusions questioning glyphosate's safety. 

Baum, Hedlund, Aristei & Goldman, accessed here: 
15 

While there are divergent conclusions between IARC and other science agencies, including the 

EPA, regarding the potential human health hazard of glyphosate, even Monsanto's own scientists 

acknowledged in internal e-mails that Roundup, the glyphosate containing weed-killer that 

Monsanto sells, does cause damage. "Glyphosate is OK, but the formulated product causes the 

damage," one Monsanto researcher wrote in an email. 2 "You cannot say that Roundup is not a 

carcinogen," wrote another Monsanto toxicologist. "We have not done the necessary testing on 

the formulation to make that statement."3 What we do know is that the use of glyphosate has 

exploded across the United States and around the world since it first came on the market in 1974. 

In the U.S. alone its use has grown from 11 million pounds in 1987 to nearly 300 million pounds 

in 2016. Recent studies have also shown that it is prevalent in the U.S. food supply from crackers 

and cookies to honey and wine. Several studies have also shown that glyphosate is detectible in 

around 90% of the U.S. population. · 

This report describes some of the tactics Monsanto has used to control the public debate about 

glyphosate as well as the scientific studies that have been conducted to assess its potential harm. 

These efforts appear aimed at corrupting and disrupting any honest, thorough and complete 

scientific evaluation of glyphosate and its potential adverse impact on the public's health. 

2 Email from William Heydens to Donna Farmer and Richard Dirks, Subject: "RE: European Commission 

Endocrine Disrupters developments (l)," April25, 2002, accessed here: http://baumhedlundlaw.com/pd£'monsantodocuments/37-Monsanto-Executive-Admits-Studies-Demonstrate-Formulated-RounduP::Does-the-Damage.pdf. 

'Email from Donna Farmer to Monsanto employees, Subject: "RE: Agitation against Roundup," Nov. 22, 2003, 

accessed here: http:/lbaumhedlundlaw.comlpd£'monsanto-documenL'I27-Internal-Monsanto-Email-You-CannotSay-That-Roundup-is-not-a-Carcinogen.pdf. 

2 
16 

Glyphosate use in the United States from 1992 to 2015 

(Source: U.S. Geological Survey4

) 

Estimated Agricultural Use for Glyphosate, 1992 

j/;~\: 'li'~l'~ \ 

'' i !' .'' ,, i 

,-, 

," l' :" "'~~ 

,, 

' 

E~tiii'Nited use on , l \ 

agricutturalland. an pounds per square mUe 

Q<45Z 

--45:!·Z112 

-Z113·B806 

->86.C6 

C]No estm!lted use 

EPest·Low 

Estimated Agricultural Use for Glyphosate, 2015 (Preliminary) 

·-;\ EPesi·LOW 

~~ ;.,.._;: . ,_.,.,_ 

i:~~'~ ,• ' 0 ~ \:,~ • 

. :1. . ,•!Jr! 

-~~. 

'' 

I / "' 

·~· ... ·:q_ Estlrnated u1e on . '; ' \, · · 

agrteunurat land, In 

pounds per square mil& 

0•4.52 

lilllH2·21.12 

lllll21.13·8806 

••••. 06 

c:J No estJmated use 

4 Glyphosate use in the U.S. 1992: 

https://water.usgs.gov/nawqa!pnsolusage/maps/show map.php?yeat= 1992&map-GL YPHOSATE&hilo=H; 

Glyphosate use in the U.S. 2015: 

https://water.usgs.gov/nawga/pnspiusage/mapsishow map.php?yeat=20!5&map-GL YPHOSATE&hilo=H 
17 

MONSANTO~ Key Players. The individuals listed below are some 

of the key players mentioned in the internal Monsanto emails and records cited in this report. Brief descriptions 

of their affiliation with Monsanto and their activities 

surrounding glyphosate are summarized below. 

• John Acquavella: Former Monsanto Company Scientist, Paid Monsanto Consultant. 

Currently works as a Consultant/Professor Clinical Epidemiology, Aarhus University. 

• Bruce Cbassy: Professor Emeritus at the University of Illinois Department of Food Science 

and Human Nutrition and Monsanto grant recipient. Chassy helped organize writing campaigns 

to scientific journals criticizing studies on glyphosate at Monsanto's request and runs a nonprofit called Academics Review that Monsanto reportedly helped to establish to provide an 

"independent" voice supporting glyphosate and other issues of interest to Monsanto. 

• Donna R. Farmer: Monsanto's lead toxicolo~ist and a Monsanto employee since 1991. 

• A. Wallace ("Wally") Hayes: Fonner Editor-in-Chief for Vision and Strategy at Food and 

Chemical Toxicology journal, which, during his tenure, published and retracted the Seralini 

rat study. Reportedly was paid $16,000 by Monsanto in a consulting contract. 

• William F. Heydens: Currently Monsanto's Product Safety Assessment Strategy Lead. 

• Larry Kier: Former Monsanto toxicologist. Authored, "Review of genotoxicity studies of 

glyphosate and glyphosate-based formulations," which found glyphosate posed no risk to humans. 

• David J. Kirkland: Monsanto contractor who was a co-author with Larry Kier on the study 

"Review of genotoxicity studies of glyphosate and glyphosate-based formulations." 

Henry Miller: Stanford Hoover Institution fellow and former contributor to Forbes.!n 2015, 

Miller published a Forbes article critical of !ARC that was solicited-and largely ghostwritten 

-by Monsanto. Forbes cut ties with Miller and retracted his articles when they discovered his 

failure to disclose ties with Monsanto. 

• Dr. James Parry was a Geneticist at Swansea University in the United Kingdom who was 

hired by Monsanto in 1999 to evaluate the genotoxicity of glyphosate. Monsanto refused to 

conduct additional tests at his request and attempted to "move him from his position." 

• Eric Sachs: Monsanto Science and Policy lead since 2005; botanist and plant geneticist. 

• David A. Saltmiras: Fonner Monsanto Company Toxicology Manager and author on the socalled Greim Study that refuted animal data indicating glyphosate's carcinogenicity. 

• Gilles-Eric Serallni. French molecular biologist who conducted a study that found rats fed 

glyphosate-tolerant corn treated with Roundup had an increased risk of developing tumors. 

The study, published in the journal Food and Chemical Toxicology, was retracted by journal 

editor 1111d Monsanto contractor A. Wallace Hayes. 

4 
18 

Monsanto's IARC Battle Plan. Prior to IARC's March 2015 classification of 

glyphosate as a Group 2A agent that was "probably carcinogenic to humans," Monsanto knew 

that the existing scientific evidence regarding potential ill-health effects from exposure to 

glyphosate was not on their side, according to their own internal e-mails. In October 2014, 

Monsanto scientist William Heydens wrote in an e-mail with the Subject hearing "IARC 

Evaluation of Glyphosate," "[W]hile we have vulnerability in the area of epidemiology, we also 

have potential vulnerabilities in the other areas that IARC will consider, namely, exposure, 

International Agency 

Research on Cancer 

genetox, and mode of action ... " 5 

By February 2015, a battle plan to confront what they 

suspected would be bad news for glyphosate was already 

underway. 6 ''We should assume and prepare for the outcome 

• 

of a 2B rating (possible human carcinogen); a 2A rating 

~ - ~ World Health (probable human carcinogen) is possible but less likely." 

~ il Organization Glyphosate received the 2A rating by IARC. According to 

~ several key records unsealed in the multi-district litigation 

against Monsanto, including the company's "Preparedness and Engagement Plan for IARC 

Carcinogen Rating of Glyphosate," dated February 17, 2015, Monsanto was ready for a fullborne defense of glyphosate when IARC released its Monograph on glyphosate in March 2015.7 

The Monsanto attack plan included efforts to "amplifY" their message that glyphosate was safe 

pointing to industry-sponsored studies and industry-placed news stories. They sought to generate 

industry "outrage" over what they thought would be a 2B rating. They had plans to address these 

"new allegations" regarding the potential hazard of glyphosate and to "neutralize" the impact. 

They also sought to "amplify" the ''positive" message about glyphosate's safety via social media 

platforms including Twitter and Facebook. They turned to industry trade groups, such as 

Crop Life and industry front groups, such as Genetic Literacy Project and Academics Review as 

platforms of support for industry spokespersons. They also sought third-party experts to "blog, 

op/ed, tweet and/or link, repost, retweet, etc." They were planning an onslaught of actions to help 

undermine IARC and to embolden their justifications to dismiss IARC's scientific findings. They 

have carried out that battle plan in a consistent and very aggressive manner ever since. 

Separately from Monsanto's attacks on IARC they have also tried to wield their influence at the 

Environmental Protection Agency (EPA) as well. In some instances, they have objected to key 

scientists sitting on EPA science panels reviewing glyphosate's safety. There have also been 

questions about other tactics. In May 2017 the EPA's Office of Inspector General opened "an 

investigation into reports that an EPA employee may have colluded with Monsanto to conduct a 

biased review of glyphosate," according to the IG's letter announcing the investigation.8 

s Email from William Heydens to Monsanto employees, Subject: "IARC Evaluation ofGiyphosate," October 15, 

2014, accessed here: http:/lbaumhedlundlaw.com/pdfi'monsanto-documents/35-Monsanto-Admits-Companv-FacesIssues-in-Epidemiology-Exposure-Genotoxicity-and-Mode-of-Action.pdf 

6 Monsanto internal document, "Glyphosate: IARC," (also referred to as the Monsanto !ARC Battle Plan by the 

media) February 23,2015, accessed here: http:/lbaumhedlundlaw.com/pdflmonsanto-documents/72-DocumentDetails-Monsantos-Goals-After-IARC-Report.pdf 

1 Ibid. 

8 See: Tiffany Stecker, "Watchdog May Find EPA-Monsanto Links on Pesticides Routine," Bloomberg Energy & 

Environment Report, June 8, 2017, accessed here: https://www.bna.com/watchdog-may-find-n73014453069/ 

5 
19 

Ghostwriting. Internal Monsanto e-mails show that Monsanto scientists "ghost wrote" 

scientific journal articles on glyphosate. It is clear from these e-mails, revealed in court 

documents, that ghostwriting articles on glyphosate was a concerted effort by the company. 

Monsanto scientists wanted to both steer the scientific studies away from identifying potential 

adverse human health effects from exposure to 

glyphosate and they wanted other "independent" 

scientists listed on these studies to provide the aura 

of objectivity and independence. 

Monsanto did this on several occasions. The 

internal e-mails show a clear and consistent attempt 

by some Monsanto scientists to obfuscate their 

roles in writing, directing and funding glyphosaterelated studies. Equally disturbing are examples 

where they attempted to bury scientific study 

results that did show potential adverse effects from 

glyphosate exposures. Many of these e-mails 

portray Monsanto scientists as Jess interested in 

discovering if glyphosate and Monsanto's herbicide 

Roundup could have toxic effects and more interested in developing studies that showed no 

potential ill health effects and had the veneer of independence and objectivity. The e-mails and 

other records unsealed in the Monsanto court case regarding Roundup have begun to pull back 

the curtain on those claims and the company's extraordinary efforts to discredit the scientific 

conclusions made by IARC on glyphosate and to undermine the reputation of the science agency. 

Ghostwriting Greim. In 2015, Monsanto anticipated, based on the scientific evidence that was 

publicly available, that IARC would classifY glyphosate as either a Group 2B agent (possibly 

carcinogenic to humans) or Group 2A agent (probably carcinogenic to humans). In preparation, 

they sought to publish new papers countering the animal data used by IARC, which ultimately 

concluded in March 2015 that glyphosate was a Group 2A agent, "probably carcinogenic to 

humans." In an email between Monsanto scientists Bill Heydens and Donna Farmer, they discuss 

what became known as the "Greim paper" - a 20 15 study published in Critical Reviews in 

Toxicology whose listed authors include Helmut Greim and David Saltmiras.9 In the ernails, they 

contemplate paying for a study to combat problematic findings, but determine a cheaper option 

would be to "ghost-write the Exposure Tox & Genetox sections ... [and] add Greim and Kier or 

Kirkland to have their names on the publication, but we would be keeping the cost down by us 

doing the writing and they would just edit & sign their names so to speak."10 The paper, 

published in March 2015 with Greim as the lead author, concluded: "After almost forty years of 

commercial use, and multiple regulatory approvals including toxicology evaluations, literature 

9 Greim H, Saltmiras D, Moster! V, Strupp C, "Evaluation of carcinogenic potential of the herbicide glyphosate, 

drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies," Critical Reviews in 

Toxicology, March 2015, accessed here: https://www.ncbi.nlm.nih.gov/pubmed/25716480. 10 Email from William Heydens to Donna Fanner, cc David Saltmiras and other Monsanto employees, Subject: "RE: 

!ARC Planning," February 19, 2015, accessed here: https://www.baumhedlundlaw.comlpdf!monsantodocumenl'li'Emaii-Correspondence-Wherein-William-Heydens-Suggests-Experts-Could-Edit-and-Sign-TheirNames-to-Scientific-Paoer.pdf. · 

6 
20 

reviews, and numerous human health risk assessments, the clear and consistent conclusions are 

that glyphosate is oflow toxicological concern, and no concerns exist with respect 

to glyphosate use and cancer in humans." That conclusion dismissed or ignored multiple other 

studies that have questioned 

glyphosate's safety. 

Multiple internal Monsanto records 

show that whatever role Greim had in 

the study, Monsanto scientists were 

clear that they were in charge and 

conducted the bulk of the work on the 

paper. One internal Monsanto powerpoint slide says Monsanto could use 

Greim and one or two other external 

authors on the paper they envisioned 

but that the "Majority of writing can be 

done by Monsanto, keeping OS$ 

down."11 David Saltmiras, a Monsanto 

scientist who was a co-author with 

Greim on the paper, wrote a 

description of his work for Monsanto 

in August 2015 labelled "Glyphosate 

Activities." He wrote that he "ghost 

wrote cancer review paper Greim et a!. 

(2015)." 12 

The Greim paper became a focal point 

of Monsanto's objections to IARC, 

with the company claiming that if it 

had been considered, the classification 

of glyphosate would have been 

different. While the definition of 

ghostwriting often differs from this 

situation- typically meaning that the 

E-mail from Monsanto's William Heydens 

to Donna Farmer and cc'd to David 

Saltmiras, et. al., February 19, 2015. 

Subject: RE: IARC Planning 

"A LESS EXPENSIVE/MORE PALATABLE 

APPROACH MIGHT BE TO INVOLVE 

EXPERTS ONLY FOR THE AREAS OF 

CONTENTION, EPIDEMIOLOGY AND 

POSSIBLY MOA [MODE OF ACTION] 

(DEPENDING ON WHAT COMES OUT OF 

THE IARC MEETING), AND WE GHOSTWRITE THE EXPOSURE TOX & GENETOX 

SECTIONS. AN OPTION WOULD BE TO 

ADD GREIM AND KIER OR KIRKLAND TO 

HAVE THEIR NAMES ON THE 

PUBLICATION, BUT WE WOULD BE 

KEEPING THE COST DOWN BY US DOING 

THE WRITING AND THEY WOULD JUST 

EDIT & SIGN THEIR NAMES SO TO SPEAK. 

RECALL THAT IS HOW WE HANDLED 

WILLIAMS KROES & MUNRO, 2000."6 

true author is unnamed- Monsanto itself referred to this process as "ghostwriting" multiple 

times. In addition, e-mails from Monsanto scientists show that this was not the first time they had 

"ghostwritten" a journal article on glyphosate. One e-mail says that Monsanto scientists had also 

11 Monsanto internal presentation, "Proposal for Post-IARC Meeting Scientific Projects DRAFT," May II, 2015, 

accessed here: https://www.bamnhedlundlaw.com/pdfimonsanto-documents/Monsanto-Prooosa!-for"/o20Post-IARCMeeting-Scientific-Projects.ndf. 

12 David Saltmiras custndial document, "Glyphosate Activities," August 4, 2015, accessed here: 

http://baumhedlundlaw.comlpdfimonsanto-documentsll8-Monsanto-Scientist-Admits-to-Ghostwriting-CancerReview-Paper.pdf. 

7 
21 

ghostwritten an article and had the 

independent scientists simply edit and sign 

their names to the paper back in 2000. 13 

Too close for comfort. On the other 

extreme, Monsanto, at times, has sought to 

have former Monsanto scientists distance 

themselves from Monsanto's scientific 

studies to maintain the charade of 

independence they have attempted to 

convey on Monsanto-directed research. In 

2015, after the release of the IARC 

monograph on glyphosate, Monsanto put 

together a supposedly independent "expert 

panel review" to dispute the IARC 

classification. Their effort to bury 

Monsanto ties to the panel was complicated 

by a retired Monsanto scientist who was 

E-mail from William Heydens (Monsanto 

scientist) to John Acquavella 

(retired Monsanto scientist), 

November 3, 2015, 1:49 p.m. 

Subject: Re: Glyphosate Expert Panel Poster 

at 2015 SRA Annual Meeting 

"I THOUGHT WE DISCUSSED PREVIOUSLY 

THAT IT WAS DECIDED BY OUR 

MANAGEMENT THAT WE WOULD NOT BE 

ABLE TO USE YOU OR LARRY AS 

PANELISTS/AUTHORS BECAUSE OF YOUR 

PRIOR EMPLOYMENT AT MONSANTO ... " 

E-mail from John Acquavella 

(retired Monsanto scientist) to 

William Heydens (Monsanto scientist), 

November 3, 2015, 2:55 p.m. 

now consulting for the company, John 

Acquavella. He objected to his name 

being omitted from a poster listing the 

names of authors and experts on that 

panel. Heydens responded to his 

objection by explaining that 

management ''would not be able to use 

your or Larry [Kier] as Panelists I 

authors because of your prior 

employment at Monsanto." Acquavella 

was blunt in his response, writing back, 

"I don't think that will be okay with my 

panelists. We call that ghost writing 

and it is unethical." 14 

Subject: Re: Glyphosate Expert Panel Poster 

at 2015 SRA Annual Meeting 

"I DON'T THINK THAT WILL BE OKAY WITH 

MY PANELISTS. WE CALL THAT GHOST 

WRITING AND IT IS UNETHICAL.l11° 

"Email from William Heydens to Donna Farmer, cc David Saltmiras and other Monsanto employees, Subject: "RE: 

!ARC Planning," Feb. 19,2015, accessed here: httos://www.baumhedlundlaw.com/odl7monsanto·documents/Email-

~ 

Correspondence-Wherein-William-Heydens-Suggests-Experts-Could-Edit-and-Sign· Their-Names-to-ScientificSee: Gary M.Williams, Robert Kroes and Ian C.Munro, "Safety Evaluation and Risk Assessment of the Herbicide 

Roundup and Its Active Ingredient, Glyphosate, for Humans," Regulat01y Toxicology and Phmmacology, 

Volume 31, Issue 2, April2000, Accessed here: 

https:/ /wv.w.sciencedirect.com/sciencelarticlelpii/S0273230099913 715'?via%3Dihub; 

Despite the evidence in the Monsanto e-mails some of the independent scientists mentioned by Monsanto regarding 

the "ghost writing" of articles have said they would never do such a thing. See: Warren Cornwall, "Update: After 

quick review, medical school says no evidence Monsanto ghostwrote professor's paper/• Science Magazine, March 

23, 2017, accessed here: ht\ll:iiwww.sciencemag.org/news/2017/03/update-after-quick-review-medical-school-savsno-evidence-monsanto-e.hostwrote. 

14 Emails between John Acquavella, William Heydens, and Donna Farmer, Subject: "John, Gtwhosate Expert Panel 

Poster at 2015 SRA Annual Meeting,''Nov. 3 6, 2015, accessed here: http:i/baumhedlundlaw.com/pdllmonsantodocuments/6-Monsanto-Consultant-Protests-Ghostm-iting.odf. 
22 

The next day Acquavella writes that he 

"can't be part of deceptive authorship 

on a presentation or publication" and he 

schools his former Monsanto coworkers in the ethics of authorship by 

including excerpts of the International 

Committee of Medical Journal Editors 

(ICJME) recommendations regarding 

authorship. 15 

Two days later Monsanto's Heydens 

attempts to backtrack and set the record 

straight after a phone call with 

Acquavella and Donna Farmer. He 

describes this whole episode as a "huge 

misunderstanding around authorship."16 

E-mail from John Acquavella 

(retired Monsanto scientist) to 

William Heydens (Monsanto scientist), and 

cc'd to Donna Farmer 

November 4, 2015, 

Subject: Re: Glyphosate Expert Panel Poster 

at 2015 SRA Annual Meeting 

"YOU GUYS KNOW ME. I CAN'T BE A PART 

OF DECEPTIVE AUTHORSHIP ON A 

PRESENTATION OR PUBLICATION. PLEASE 

NOTE THE ICJME GUIDELINES BELOW THAT 

EVERYONE GOES BY TO DETERMINING 

Ultimately, a later email indicates that WHAT IS HONEST/ETHICAL REGARDING 

Monsanto listed Acquavella as an AUTHORSHIP." 1o 

author. In fact, the abstract, "Expert 

Panel Review of the Carcinogenic Potential of the Herbicide Glyphosate," as published in the 

Society for Risk Analysis' 2015 Annual Meeting also included Williams, Greim, Kier and 

Kirkland, who Monsanto scientists had named in internal e-mails as individuals they had or 

E-mail from Erich Sachs to various other 

Monsanto employees, including Donna Farmer 

and David Saltmiras, 

February 24, 2015 

Subject: Re: Opportunity: Glyphosate and IARC 

JOHN V AND I TALKED TO HENRY MILLER TODAY. 

HENRY AGREED TO AUTHOR AN ARTICLE ON 

FORBES. COM JOHN WILL WORK WITH A TEAM 

INTERNALLY TO PROVIDE A DRAFT AND HENRY 

WILL EDIT/ADD TO MAKE IT HIS OWN. THE 

ARTICLE CAN BE LIVE SAME DAY IT IS COMPLETED. 

believed they could ghost 

write scientific studies on 

glyphosate for, although 

Monsanto scientists would do 

the bulk of the writing. 17 

Hiring journalists to 

discredit IARC. 

In Monsanto's effort to 

discredit IARC, they sought 

to recruit writers to publish 

pieces echoing their criticisms 

oflARC's process. In 

February 2015, one month 

before IARC published their 

glyphosate monograph that 

found glyphosate to be a 

"probable human carcinogen," Monsanto scientist Eric Sachs reached out to Henry Miller, a 

"Ibid. 

!6 Ibid. 

17Society for Risk Analysis 20!5 Annual Meeting Abstracts, Dec. 6-10,2015, Arlington, Virginia, see page 136, 

Williams, GM, et. al., "Expert Panel Review of the Carcinogenic Potential of the Herbicide Glyphosate," accessed 

here: http://www.sra.org/sites/defaultlfiles/pd£1events/ Abstracts%20?0 I 5.pdf 

9 
23 

Forbes contributor and a Medical Doctor and Fellow in Scientific Philosophy and Public Policy 

at Stanford University's Hoover Institute, a conservative think tank. Sachs prompted Miller on 

the desired content of the article, writing, "Ideally, your article would precede the IARC 

decision. Why not set the table with the weight of scientific evidence before IARC convenes? 

Then, regardless of what they do, your article will set the state for a science-based response." 18 

Miller agreed- and, after a follow-up email, requested a "high quality draft" from Monsanto. 19 

Officials at the company quickly got to work and provided Miller with a draft that was posted on 

the Forbes website largely unchanged. The article was published on March 17, 2015, with the 

title: "March Madness from the United Nations."20 

When this ghostwriting was discovered, Miller was fired by Forbes. In a statement to Retraction 

Watch, a Forbes representative said: "All contributors to Forbes. com sign a contract requiring 

them to disclose any potential conflicts of interest and only publish content that is their own 

original writing. When it came to our attention that Mr. Miller violated these terms, we removed 

all of his posts from Forbes. com and ended our relationship with him.'m 

18 Email from Eric Sachs to Henry Miller, Subject"Opportunity: Glyphosate and IARC," Feb. 23, 2015, accessed 

here: http://baumhedlund1aw .com/pd£'monsanto-documents/21-Intema!-Monsanto-Email-Detailing-CompanyEffort-to-Preemptively-Criticize-IARC-Ahead-of-Giyphosate-Report.ruif. 

Pull quote citation: Email from Eric Sachs to Donna Farmer, David Saltmiras, and other Monsanto employees, Feb. 

24, 20!5, link above. 19 Email from Henry Miller to Eric Sachs, Subject: "Re: !ARC Outcomes, Process, and Response," March 12, 2015, 

accessed here: http:/lbaumhed!und1aw.com/pd£'monsanto-documents/22-lntema1-Emai1-Demonstrating-MonsantoGhostwriting-Artic1e-Criticizing-IARC-for-Press.pdf. 

20 Henry Miller, "March Madness from the United Nations," Forbes, March 17, 2015, accessed here: 

https://web.archive.org/web/20 170220012 554/https:/www.forbes.com/siteslhenrvmiller/20 15/03/20/marchmadness-from-the-united-nations/#21 e08J ee2e9. 21 Andrew P. Han, "Unearthed emails: Monsanto connected to campaign to retract GMO paper," Aug. 10, 2017, 

Retraction Watch, accessed here: http://retractionwatch.com/20 17/08/1 0/unearthed-docs-monsanto-connectedcampaign-retract·gmo-paper/ 

10 
24 

Orchestrate Outcry. Henry Miller, whose clandestine ties to Monsanto got him removed 

as a contributor at Forbes, co-authored a piece on Forbes. com in September 2012 with Bruce 

Chassy, the former head of the Department of Food Science and Nutrition at the University of 

Illinois at Urbana-Champaign. Cbassy too has opaque ties to Monsanto. 22 He received funds 

·~ from Monsanto for research through the University of 

~ Illinois and he would l~ter ?e recruited to. defend it/: . Monsanto on the chemtcal mdustry webstte GMO 

... ~~ ~ , , ~· ~ Answers23 and established a non-profit website called 

.tj? ~ i.,.~ i J: Academics Review with Monsanto's assistance.24 The 

~!· j · j * 1

' .. ' ' article Miller and Chassy wrote for Forbes critiqued a 

_ . \ ' ( study of glyphosate by French microbiologist Gilles1 

~. 1\lJ "' 1 Eric Seralini in the journal Food and Chemical 

..l Toxicology (FCT) that found that the glyphosate 

·. containing herbicide Roundup and genetically modified 

glyphosate-resistant com caused tumors in rats. 25 

This spelled trouble for Monsanto's 

Roundup Ready crops. Monsanto was 

tipped off about the publication of the 

Seralini paper by FCTs Editor in Chief 

for Vision and Strategy, Wally Hayes. 

On September 26,2012 Monsanto 

scientist David Saltmiras sent an e-mail 

to colleagues and wrote: "Wally Hayes 

(FCT Editor in Chief) called me this 

morning in response to my voice mail 

yesterday. He expressed concern that to 

date he has only received links to 

blogs, web postings, media releases, 

etc. and no formal letters to the Editor" 

regarding the Seralini article. 26 He 

needed more. 

E-mail from Monsanto's Eric Sachs to 

David Saltmiras, William Heydens, et. al., 

September 26, 2012. 

Subject: RE: letters to the Editor? 

"I TALKED TO BRUCE CHASSY AND HE 

WILL SEND HIS LETTER TO WALLY HAYES 

DIRECTLY AND NOTIFY OTHER SCIENTISTS 

THAT HAVE SENT LETTERS TO DO THE 

SAME. HE UNDERSTANDS THE 

URGENCY.'122 

22 Tom Philpott, "These Emails Show Monsanto Leaning on Professors to Fight the GMO PR War," Mother Jones, 

Oct. 2, 2015, accessed here: https://www.motheriones.com/food/2015/10/monsanto-professors-gmo-pr/. 

2l "A University oflllinois Professor Joins the Fight," Sept. 5, 2015, New York Times, accessed here: 

https://www.nvtimes.com/interactive/2015/09/05/us/document-chassy.html 

24 Stacy Malkan, "Monsanto Fingerprints Found All Over Attack On Organic Food," Dec. 6, 2017, Huf!Post, 

accessed here: https://www.huffingtonpost.com/stacy-malkan/monsanto-fingernrints-fou b 10757524.html; 

"Academics Review- About," accessed here: http://academicsreview.org/about-academic-review/ 25 Gilles-Eric Seralini et al., "Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically 

modified maize," Food and Chemical Toxicology, Sept. 19,2012, accessed here: httos:l/ac.els· 

cdn.com/S0278691512005637/I-s2.0-S027869!512005637-main.pdf? tid=58dOdbl O-Oa9c-lle8-b8f6-

00000aacb35f&acdnat=l517852905 42d9615555402636b3cd425628eb849f. 26 Email from David Saltmiras to Eric Sachs, William Heydens, and other Monsanto employees, Subject: "Letters to 

the Editor?", Sept. 26,2015, accessed here: http://baumhedlundlaw.com/pdflmonsanto-documents/7-MonsantoPersonnei-Discusses-Pian-Seeking-Retraction-of-Serlani-Glyphosate-Study.pdf. 

Pull quote citation: Email from Eric Sachs to Monsanto employees, Sept. 26,2012, link above. 

ll 
25 

Internal Monsanto records show that Monsanto started aggressively attempting to attack the 

Seralini paper through third-parties. Monsanto began working their network of scientists. 

Monsanto's Daniel Goldstein to Monsanto 

sc1ent1st Eric Sachs, September 28, 2012 

Subject: RE: Slides~ Seralini Publication 

"I WAS UNCOMFORTABLE EVEN LETIING 

SHAREHOLDERS KNOW WE ARE AWARE OF 

THIS LTE .... IT IMPLIES WE HAD SOMETHING 

TO DO WITH IT-OTHERWISE HOW DO WE 

HAVE KNOWLEDGE OF IT? •••• 

WE ARE BEING ASKED TO KEEP INTERNAL 

CORRESPONDENCE DOWN ON THIS 

SUBJECT."24 

Monsanto scientists were 

encouraging and soliciting third 

parties to criticize the Seralini 

paper and call out flaws in hopes 

of putting enough pressure on the 

FCT journal to retract the study. 

One of the people they turned to 

was Bruce Chassy who wrote to 

Hayes complaining about the 

Seralini paper. But some 

Monsanto scientists worried 

because they did not want their 

fingerprints on any public 

campaign to retract the paper. 

"We should not provide 

ammunition for Seralini, GM 

critics and the media to charge 

that Monsanto used its might to 

get this paper retracted," wrote Monsanto scientist Eric Sachs.27 Others agreed, including 

Monsanto's Daniel Goldstein, who wrote: "We are being asked to keep internal correspondence 

down on this subject."28 

While Monsanto's quiet third-party efforts seemed to help, there was something else working in 

Monsanto's favor. Wally Hayes, the FCTeditor who was also a professor at the Harvard School 

of Public Health had apparently signed a consulting agreement on August 21, 2012, with 

Monsanto just before the Seralini paper dispute heated up. A letter dated September 7, 2012 from 

Monsanto to Hayes, just three weeks before Hayes and Saltrniras began talking about the Seralini 

paper, was identified as an "Authorization Letter" to the August 21, 2012 Consulting Agreement. 

The letter said that Hayes' services in setting up a Latin America South Toxicology Expert 

Panel, slated to begin on September 7, 2012, would pay him $400 an hour, not to exceed $3,200 

per day, for a total of$16,000. David Saltmiras was listed as Monsanto's representative for the 

project.l• 

The Seralini paper was officially retracted by Hayes and FCT in 2013.30 Hayes told the New 

York Times that he had not been under contract with Monsanto at the time of the retraction and 

was paid by the company only after he left the journaL "Monsanto played no role whatsoever in 

27 Ibid. 28 Email from Daniel Goldstein to Eric Sachs and Yong Gao, Subject: "RE: Slides- Seralini Publication," Sepr. 28, 

2012, accessed here: http:/lbaumhedlundlaw.com/pdllmonsanto-document<;/I4-Monsanto-Emails-ConfirmingUndisclosed-lnvolvement-in-Successfui-Retraction-of-Serlani-Study.ndf 

29 "Authorization Letter to Consulting Agreement dated August 21,2012, between Prof. A Wallace Hayes and 

Monsanto Company," Aug. 21,2012, acces.•ed here: http:/lbaumhedlundlaw.com/ndllmonsanto-documents!IOMonsanto-Consulting-Agreement-with·Food-and-Chemicai-Toxicology-Editor.pdf. 

30 Andrew Pollack, "Paper Tying Rat Cancer to Herbicide Is Retracted," New York Times, Nov. 28, 2013, accessed 

here: http://www.nvtimes.com/20 13/11/29/bealth/paper-tying-rat-cancer-to-herbicide-is-retracted.html. 

12 
26 

the decision that was made to retract," he told the newspaper. "It was based on input that I got 

from some very well-respected people, and also my own evaluation," he said.31 

Meanwhile, Monsanto's Saltimiras's own "business performance" plan for FY2013 touts his 

own success in these efforts. "Successfully facilitate numerous third party expert letters to the 

editor which were subsequently published, reflecting the numerous significant deficiencies, poor 

study design, biased reporting and selective statistics employed by Seralini," Saltmiras wrote in 

his reviewY The website Retraction Watch noted however, "An FCT investigation found no 

evidence of fraud, misconduct, or gross error, [in the Seralini paper], which are required by 

Committee on Publication Ethics (COPE) guidelines for retraction; however, FCT cited COPE 

guidelines in their retraction notice anyway."33 

31Danny Hakim, "Monsanto Emails Raise Issue oflnfluencing Research on Roundup Weed Killer," New York 

Times, Aug 1, 2017, accessed here: https:/lwww.nytirnes.com/2017108101/businesslmonsantos-sway-over-researchis-seen-in-disclosed-emails.html. 

J> Internal Monsanto document by David Saltmiras, "FY2013," Aug. 20,2013, accessed here: 

htm:llbaumhedlundlaw.comlpdflmonsanto-documents/8-Monsanto-Scientist-Admits-to-leveraging-Relationshipwith-Food-and-Chemical-Toxicology-Joumal.pdf. 

33 Andrew P. Han, "Unearthed emails: Monsanto connected to campaign to retract GMO paper," Retraction Watch, 

Aug I 0, 2017, accessed here" http://retractionwatch.com/20 17/08/1 0/unearthed-docs-monsanto-connectedcampaign-~tract-gmo-paper/. 

13 
27 

Establish Front Groups. Media reports have pointed to several seemingly independent 

non-profit groups as having close ties to Monsanto. Some were reportedly established with 

assistance from Monsanto in order to serve as a platform to confront scientific findings revealing 

potential health hazards from glyphosate while concealing 

Monsanto's direct involvement. 1bis confront-and-conceal 

approach is nothing new. These tactics have been used by the 

tobacco industry, energy sector and chemical companies. They 

often have innocuous-sounding names - for instance, the 

Campaign for Accuracy in Public Health Research (CAPHR), 

which is run by the American Chemistry Council (ACC). In 

this case, the ACC has not attempted to hide their ties with 

CAPHR and even announced its launch in January 2017. The 

organization's primary target is IARC.34 The group's initial 

press release said: "In particular, CAPHR will seek reform of 

the International Agency for Research on Cancer's (IARC) 

Monographs Program, which evaluates the carcinogenic 

hazard of substances and behaviors."35 

Other front groups are more 

secretive. Academics Review was 

co-founded by Bruce Chassy. The 

site was founded in January 20 I 0 to 

"ensure that sound science is widely 

and easily available." It describes 

itself as "an association of academic 

professors, researchers, teachers and · 

credentialed authors from around 

the world" who "stand against 

falsehoods, half-baked assertions 

and theories or claims not subjected 

to this kind of rigorous review."36 

What it does not reveal are the close 

ties between Chassy and Monsanto. 

But one e-mail exchange between 

Monsanto's Eric Sachs and Chassy 

shows Monsanto was interested in 

using the site to its advantage as 

long as it was able to hide its 

involvement. "The key will be 

E-mail from Monsanto's Eric Sachs to Bruce 

Chassy, co-founder of Academics Review. 

November 30, 2010 

"YOU AND I NEED TO TALK MORE ABOUT THE 

"ACADEMICS REVIEW" SITE AND CONCEPT. I 

BELIEVE THAT THERE IS A PATH TO A PROCESS 

THAT WOULD BETTER RESPOND TO 

SCIENTIFIC CONCERNS AND ALLEGATIONS .... 

FROM MY PERSPECTIVE THE PROBLEM IS ONE 

OF EXPERT ENGAGEMENT AND THAT COULD 

BE SOLVED BY PAYING EXPERTS TO PROVIDE 

RESPONSES .... THE KEY WILL BE KEEPING 

MONSANTO IN THE BACKGROUND SO AS NOT 

TO HARM THE CREDIBILITY OF THE 

INFORMATION." 33 

34 Campaign for Accuracy in Public Health Research, "!ARC," accessed here: 

http://campaignforaccuracyinpublichealthresearch.com/iarc/. 

" American Chemistry Council, "ACC Launches Campaign to Promote Credibility in Public Health Research," Jan. 

25, 2017, accessed here: https:l/www.americanchemistrv.coffi/Media!PressReleasesTranscriptsl ACC-newsreleases/ACC-Launches-Campaign-to-Promote-Credibi!itv-in-Public-Health·Research.html. 

36 Academics Review, "Purpose, .. accessed here: htto://academicsreview.orglabout-academic-review/purnose/. 

14 
28 

keeping Monsanto in the background so as not to harm the credibility of the information," wrote 

Sachs.37 

Silence Scientists. Monsanto and other large corporate interests use multiple tactics in 

their attempts to delay regulations, deter the publication of scientific findings that endanger their 

corporate profits, and degrade scientific institutions, such as IARC, that are independent and a 

ALL QUIET 

ON THE 

SCIENCE 

FRONT 

threat to an industry's influence and a challenge 

to their disinformation campaigns. Sometimes 

they also attack specific scientists who are 

independent and pose a potential threat to their 

objectives and activities as a result of their 

scientific studies, interests or integrity. 

Dr. Peter Infante, a renowned and highly 

respected epidemiologist, has been the victim of 

industry attacks for four decades due to his solid 

scientific findings on the cancer-causing 

properties of chemicals such as formaldehyde 

and benzene and arsenic. In the early 1980s, when he was a senior official at the Occupational 

Safety and Health Administration (OSHA) the House Science Committee held a hearing on the 

"Proposed firing of Dr. Peter Infante by OSHA" due to pressure on OSHA from the 

Formaldehyde Institute.38 The oversight hearing was led by then Representative AI Gore, and 

OSHA eventually backed down from its attempt to fire Dr. Infante. More recently it has been the 

glyphosate industry Jed by CropLife America, the national trade association that represents the 

manufacturers, formulators and distributors of pesticides, that has gone after Dr. Infante. 

In 2016, Dr. Infante was selected as a Member of the Environmental Protection Agency's 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) 

on the Evaluation of the Human Carcinogenic Potential ofGlyphosate. In October 2016, 

CropLife sent a Jetter to the EPA citing concerns about the SAP,39 specifically citing Dr. 

Infante's participation. The Crop Life Jetter stated that Dr. Infante had biases against industry and 

should therefore be removed from the Panel. Dr. Infante sent a rebuttalletter40 to the EPA as did 

the Center for Food Safety defending Dr. Infante.41 However, prior to the December 2016 

meeting of the SAP, EPA officials removed Dr. Infante from the SAP on glyphosate without 

37 Email from Eric Sachs to Bruce Chassy, Subject: "Questions," Nov. 30,2010, accessed here: 

httos:l fwww.usrtk. org!wp-content/uploads/20 1610 1/Sachs-AR.pdf. 38 "Proposed Firing of Dr. Peter Infante by OSHA: A Case Study in Science and Regulation," Subcommittee on 

Investigations and Oversight of the Committee on Science and Technology, U.S. House of Representatives, July 16, 

1981, accessed here: https:flhabel.hathitrust.org/cgilpt'?id-mdp.390 15082337588;view= I up:seq-8. 39 Letter from CropLife to EPA, Oct. 12,2016, accessed here: http:/1191hmtlpr08amfq62276etw2.wpengine.netdnacdn.comlwp-content!uploads/20 1610 1/CLA-Comments-on-SAP-Disqua!ification-1 0-12-16 .pdf. 

"'"Comment submitted by Peter F. Infante, Consultant, Peter F. Infante Consulting, LLC," Regulations. goY, Oct. 21, 

2016, accessed here: https://www.regulations.gov/document?D=EPA-HO-OPP-2016-0385-0439. 41 Comment submitted by Center for Food Safety to EPA, "RE: Scientific Advisory Panel meeting on glyphosate's 

carcinogenic potential," Dec. 12,2016, accessed here: http:ffwww.centerforfoodsafetv.orgffileslglyphosate-sapinfante-letter--cfs-12-12-16 02026.pdf. 

15 
29 

explanation.42 At Scott Pruitt's EPA, where he has intentionally removed independent scientists 

from the Agency's science advisory boards so that he can stack them with more industry-funded 

scientists, this was not a tremendous surprise, but one that is disappointing nonetheless. 

E-mail from Monsanto's Donna Farmer, 

Aprill7, 1999 (recipients unknown) 

Subject: Meeting Minutes 

"DR. PARRY CONCLUDED ON HIS 

EVALUATION OF THE FOUR ARTICLES 

THAT GLYPHOSATE IS CAPABLE OF 

PRODUCING GENOTOXICITY BOTH IN 

VIVO AND IN VITRO .•• IN ORDER TO 

MOVE DR. PARRY FROM HIS POSITION 

WE WILL NEED TO PROVIDE HIM WITH 

THE ADDITIONAL INFORMATION AS 

WELL AS ASKING HIM TO CRITICALLY 

EVALUATE THE QUALITY OF All THE 

DATA INCLUDING THE OPEN 

LITERATURE STUDIES .... MARK WILL 

ALSO EXPLORE HIS INTEREST (IF WE 

CAN TURN HIS OPINION AROUND) IN 

BEING A SPOKESPERSON FOR US FOR 

THESE TYPE OF ISSUES." 39 

Dr. James Parry. It is important to 

understand that Monsanto's aggressive 

tactics regarding its efforts to defend 

glyphosate and its highly successful 

product Roundup have been going on for 

decades. Like so many chemical-based 

products, however, as scientific evidence of 

potential worry accumulate, the potential 

threat to the commercial viability and 

sustainability of the product can grow. It is 

clear from the substantive documents that 

have come to light recently that Monsanto 

has been fending off those sorts of threats 

for many years. 

In the past, Monsanto has even sought to 

silence their own scientists, when they 

discovered evidence of potential adverse 

human health effects from exposures to 

glyphosate. Back in 1999, Monsanto's 

contracted scientist, Dr. James Parry, a 

geneticist at Swansea University in the 

United Kingdom, was one of them. 

Monsanto hired Parry to evaluate the 

genotoxicity of glyphosate, and, to their 

disappointment, Parry concluded that 

"glyphosate is capable of producing 

genotoxicity both in vivo and in vitro by a 

mechanism based upon the production of oxidative damage.'"'3 Disturbingly, internal Monsanto 

e-mails show that Monsanto scientists contemplated ways to ''move Dr. Parry from his 

position•>44 regarding the toxicity of glyphosate. Parry also signed a secrecy agreement with 

Monsanto in April 1999. The contents of the agreement are not known, but it does not appear 

that Dr. Parry ever published his findings regarding glyphosate's genotoxicity. 

42 "Panel Member Roster, Federal Insecticide, Fungicide, and Rndenticide Act Scientific Advisory Panel, Open 

Meeting, December 13-16, 2016," Regulations.gov, Nov. 28, 2016, accessed here: 

https://www. regulations.gov/document?D=EP A-HQ-OPP-20 16-0385-0454. 

''Email from Donna Farmer to unknown recipients, Subject: "Meeting Minutes 2/25," Aprill7, 1999, accessed 

here: http://baumhedlundlaw.com/pdflmonsanto-documents/38-Email-Sbows-Former-Monsanto-Expert-ConfumedBiolooical-Plausibilitv-of-Glyphosate-as-Carcinogen.pdf. 

.wlbid. 

16 
30 

As part of Parry's review, he 

suggested additional studies into the 

genotoxicity of glyphosate. 

Monsanto was opposed to funding 

these additional studies, however, 

and Bill Heydens expressed his 

disappointment in the Parry review 

in an email to colleagues and 

expressed the importance of finding 

a pro-glyphosate advocate. This was 

important, he wrote, because 

Monsanto was "currently very 

vulnerable in this area" regarding the 

genotoxicity of glyphosate. "We 

want to find/develop someone who is 

E-mail from Monsanto's William Heydens to 

Erik Jacobs, et. al., AprillO, 2001 

Subject: RE: Propachlor sample request 

"DATA GENERATED BY ACADEMICS HAS 

ALWAYS BEEN A MAJOR CONCERN FOR US 

IN THE DEFENSE OF OUR PRODUCTS •.•. 

CONSIDER THE RAMIFICATIONS OF A 

POSITIVE RESPONSE ON EUROPEAN AND 

US REGISTRATIONS." 42 

comfortable with the genetox profile of glyphosate/Roundup and who can be influential with 

regulators and scientific outreach operations when genetox issues arise," added Heydens.45 

In 2001, Parry reached out to Monsanto again to obtain a sample of another herbicide, 

Propachlor, so he could conduct studies on it. Monsanto employees disagreed on how to handle 

this request. Mark Martens supported providing the samples, so as to "keep prof Parry happy 

which will make him a good proponent of glyphosate." Bill Heydens, however, had concerns. 

"Data generated by academics has always been a major concern for us in the defense of our 

products," he wrote.46 

Conclusion. The incidents and tactics outlined in this report are, unfortunately, not 

surprising when it comes to the chemical industry. These same tactics were employed by the 

chemical industry with regards to lead and a host of other chemicals. They also mimic the 

tobacco industry's efforts to muddy the science surrounding the health effects of smoking. These 

efforts have been thoroughly documented, perhaps most notably in David Michaels book, 

"Doubt is Their Product: How Industry's Assault on Science Threatens Your Health," and in 

"Merchants of Doubt," by Naomi Oreskes and Erik M. Conway. These industry efforts 

oftentimes only come to light through disclosure of internal industry documents through the 

discovery process during litigation. The disclosures made during tobacco litigation revealed the 

inner workings of the "science for hire" industry and industry's tactics to undercut legitimate 

science. Likewise, this report relies heavily on documents which have been publically released in 

the ongoing litigation with Monsanto. That litigation is ongoing, and many documents and 

deposition transcripts remain under court seal. As these documents continue to be released to the 

public, more revelations about industry tactics and influence will undoubtedly come to light. 

45 Email from William Heydens to Mark Martens, Larry Kier, and Donna Farmer, Subject: "RE: Parry report," Sept. 

16, 1999, accessed here: https:llwww.baurnhedlundlaw .com/pdf/monsanto-documents/Email-from-WilliamHeydens-Monsanto-Vulnerable-{)n-Gene-Tox-After-Parry.pd f. 46 Email from William Heydens to Mark Martens and other Monsanto employees, Subject: "RE: Propachlor sample 

request," ApnliO, 2001, accessed here: https://www.baumhedlundlaw.com/pd£'monsanto-documents/EmailExchange-Responding-to-Dr-James-Parrv-Request-to-Test-Propachlor-Monsanto-Herbicide.pdf. 

17 
31 

Given the public policy implications of the IARC and EPA reviews of glyphosate (and other 

chemicals), staff wanted to ensure that Members had the most up to date information conceming 

the troubling industry led efforts to discredit the IARC process and exert undue influence at the 

EPA. 

18 
32 

Chairman SMITH. Okay. Thank you, Ms. Johnson. 

Mr. WEBER. Mr. Chairman? 

Chairman SMITH. Yes, the gentleman from Texas, Mr. Weber. 

Mr. WEBER. If I may, I have reservations about entering this report into the record. This Committee received the minority’s report—staff report late last night and has not had sufficient time to 

completely review this report for factual accuracy. I am aware at 

this time—— 

Ms. JOHNSON. I didn’t—oh, sorry. 

Mr. WEBER. —of at least one statement of questionable accuracy. 

It’s on page 15 and 16. The minority’s report appears to suggest 

that the current EPA Administrator Mr. Scott Pruitt was somehow 

involved in the December 2016 decision to remove Dr. Peter 

Infante from EPA’s Science Advisory Panel to review glyphosate. 

Mr. Chairman, Dr. Infante was removed during the SAP during 

President—from the SAP during President Obama’s term while 

Gina McCarthy was the Administrator. And since Greg Pruitt was 

sworn in February 17, 2017, there really is no rational basis to justify this claim. So I hope the minority will be able to explain that 

statement. 

I yield, Mr. Chairman. 

Chairman SMITH. Thank you, Mr. Weber. 

Ms. JOHNSON. Mr. Chairman? 

Chairman SMITH. And the gentlewoman from Texas is recognized. 

Ms. JOHNSON. I did not request unanimous consent. I simply said 

I will be attaching the report to my statement. 

Chairman SMITH. I think Mr. Weber’s point was that it contained 

something that was not accurate and not factual and we hope you’ll 

take a look at that. 

Ms. JOHNSON. I hope everyone will take a look at it. 

Chairman SMITH. Okay. Well, Mr. Weber went into some detail 

as to what was inaccurate, and we’ll look forward to your response 

later on. Thank you, Ms. Johnson. Thank you, Mr. Weber. 

The gentleman from Oklahoma, the Vice Chairman of the Committee, Mr. Lucas, is recognized for an opening statement. 

Mr. LUCAS. Thank you, Chairman Smith, for holding this hearing 

on the important topic of scientific integrity of the International 

Agency for Research on Cancer’s Monograph Programme. I look forward to hearing from our panel of expert witnesses this morning 

and want to thank them for their voluntary appearance before this 

Committee. 

First recognized by the World Health Organization in 1965, 

IARC began as a French initiative to find and root out cancer both 

in France and around the world. In pursuit of this goal, one of 

IARC’s many endeavors was the identification and classification of 

known carcinogens. This has come to be known as the Monograph 

Programme. While the effort at the time represented the best modern understanding of cancer and the environmental causes, the 

methods of IARC’s Monograph Programme have remained largely 

unchanged over the years, even as our understanding of cancer has 

evolved. 

This has caused IARC to reach conclusions that not only create 

unnecessary fear in people, but in some cases causes IARC to reach 
33 

conclusions that are contradictions to the best available science. 

This is unfortunate in any scientific program but is completely unacceptable in one in which the United States, through the NIH and 

through NIEHS, provides the majority of the funding. This is even 

more true when IARC’s conclusions are then utilized as the basis 

of regulations, for instance, in places such as California of products 

like Roundup that contain glyphosate. 

In 2015, the IARC Monograph Programme categorized 

glyphosate as ‘‘probably carcinogenic to humans.’’ As Chairman 

Smith explained, IARC’s glyphosate Monograph contained substantial portions of alterations and deletions, it appears, to aid the 

Monograph in drawing a particular conclusion. 

While the appearance of agenda-driven manipulation is troubling 

on its own, it’s even more so when considering that IARC’s final 

conclusion is not only on the fringe of the scientific world but is 

completely and totally by itself. The respected scientific bodies such 

as the Environmental Protection Agency, the European Food Safety 

Agency, or IARC’s own parent body, the WHO, has repeatedly 

found there to be no risk posed to humans when glyphosate is used 

as directed. Yet, the IARC Monograph Program persists, reviewing 

and labeling over 900 substances as ‘‘possible’’ or ‘‘probable’’ carcinogens over the past 40-plus years, while the only labeling—only 

labeling one as noncarcinogenic. 

IARC’s explanation for all this is that they simply assess hazard 

and not risk; therefore, the actual probability that these substances 

cause cancer cannot be gleaned from their Monographs. If left unchallenged, this would excuse IARC’s bad behavior and give a de 

facto blessing to their refusal to bring their scientific methods into 

the modern age. This kind of shoddy work is unacceptable from any 

scientific body, let alone one funded by the American taxpayer. 

The modern agricultural revolution, of which glyphosate and 

other IARC-labeled ‘‘carcinogenic’’ herbicides have played an enormous role, has helped feed the world and enabled struggling nations to grow and gain a footing on the world stage. All of this, 

however, is threatened by IARC’s flawed scientific analysis. Far too 

often, farmers, ranchers, and small businesses find themselves on 

the receiving end of burdensome regulations like those that stem 

from IARC’s misleading assessments. We should be working to reduce the burdens of these hardworking Americans, not funding the 

growth of them. 

And when a federal or international agency makes decisions that 

have the potential to directly and negatively impact American citizens, we in Congress have a duty to ask questions to address the 

concerns of our constituents. Similarly, when a federal or international agency utilizes American tax dollars to reach conclusions 

that directly contradict the overwhelming majority of scientific 

knowledge, we have a duty to ask how they came to that conclusion. 

This Committee has, on several occasions, attempted to gain a 

greater understanding of IARC’s decision-making process. Unfortunately, the Committee’s simple request for IARC to provide a witness to testify on the Monograph Programme has been met with resistance. The pursuit of an awesome goal like the eradication of 

cancer should not, cannot, prevent us from asking questions re-
34 

garding the processes and methods utilized to reach a certain conclusion. Simply because an organization has a commendable goal 

should never mean the conclusions it draws are beyond reproach. 

I look forward to hearing from our witnesses today not only 

about the problems in the methods and procedures of the IARC 

Monograph Programme, of which there are many, but also about 

the fixes they believe that can be made to bring the Monograph 

Programme back into line with modern science. 

And with that, Mr. Chairman, I yield back the balance of my 

time. 

[The prepared statement of Mr. Lucas follows:] 
35 

COMMITTEE ON 

SCIENCE~ SPACE~ & TECHNOLOGY Lamar Smith. Chairman 

For Immediate Release 

February 6, 2018 

Media Contacts: Thea McDonald, Brandon VerVelde 

(202) 225-6371 

Statement by Vice Chairman Frank Lucas (R·Okla.) 

In Defense of Scientific Integrity: Examining the /ARC Monograph 

Programme and Glyphosate Review 

Vice Chairman Lucas: Thank you, Chairman Smith, for holding this hearing today on the 

important topic of the scientific integrity of the International Agency for Research on 

Cancer's (IARC) Monograph Programme. !look forward to hearing from our panel of expert 

witnesses this morning and want to thank them for their voluntary appearance before this 

committee. 

First recognized by the World Health Organization (WHO) in 1965, IARC began as a French 

initiative to find and root out cancer both in France and around the world. In pursuit of this 

goal, one of !ARC's many endeavors was the identification and classification of known 

carcinogens. This has come to be known as the Monograph Programme. 

While the effort at the time represented the most modern understanding of cancer and its 

environmental causes, the methods of !ARC's Monograph Programme have remained 

largely unchanged over the years, even as our understanding of cancer has evolved. 

This has caused IARC to reach conclusions that not only create unnecessary fear in people, 

but, in some cases, even causes IARC to reach conclusions that contradict the best 

available science. 

This is unfortunate in any scientific program, but is completely unacceptable in one where 

the United States, through the NIH and NIEHS, provides the majority of funding. This is even 

more true when !ARC's conclusions are then utilized as the basis for regulation in California of 

products, like Roundup, that contain glyphosate. 

In 2015, the IARC Monograph Programme categorized glyphosate as "probably 

carcinogenic to humans." As Chairman Smith explained, !ARC's glyphosate monograph 

contained substantial portions of alterations and deletions, it appears, to aid the monograph 

in drawing a particular conclusion. 

While the appearance of agenda-driven manipulation is troubling on its own, it is even more 

so when considering that !ARC's final conclusion is not only on the fringe of the scientific 

world, but is completely and totally by itself. 

Respected scientific bodies such as the Environmental Protection Agency, the European 

Food Safety Agency or the !ARC's parent body, the WHO, have repeatedly found there to 

be no risk posed to humans when glyphosate is used as directed. Yet. the IARC Monograph 
36 

Program persists, reviewing and labeling over 900 substances as "possible" or "probable" 

carcinogens over the last 40-plus years all the while only labeling one as non-carcinogenic. 

IARC's explanation for all this is that they simply assess hazard and not risk, therefore the 

actual probability that these substances cause cancer cannot be gleaned from their 

monographs. If left unchallenged, this would excuse IARC's bad behavior and give a de 

facto blessing to their refusal to bring their scientific methods into the modern age. This kind 

of shoddy work is unacceptable from any scientific body, let alone one funded by the 

American taxpayer. 

The modern agricultural revolution, of which glyphosate and other !ARC-labeled 

"carcinogenic" herbicides have played an enormous role, has helped to feed the world and 

enabled struggling nations to grow and gain a footing on the world stage. All of this, 

however, is threatened by IARC's flawed scientific analysis. 

Far too often, farmers, ranchers and small businesses find themselves on the receiving end of 

burdensome regulations, like those that stem from IARC's misleading assessments. We should 

be working to reduce the burdens of these hardworking Americans, not funding the growth 

of them; and when a federal or international agency makes decisions that have the 

potential to directly and negatively impact American citizens, we in Congress have a duty to 

ask questions and address the concerns of our constituents. 

Similarly, when a federal or international agency utilizes American tax dollars to reach 

conclusions that directly contradict the overwhelming majority of scientific knowledge, we 

have a duty to ask how they came to that conclusion. This committee has, on several 

occasions, attempted to gain a greater understanding of IARC's decision-making processes. 

Unfortunately, the committee's simple request for IARC to provide a witness to testify on the 

Monograph Programme has been met with resistance. 

The pursuit of an awesome goal like the eradication of cancer should not, and cannot, 

prevent us from asking questions regarding the processes and methods utilized to reach a 

certain conclusion. Simply because an organization has a commendable goal should never 

mean the conclusions it draws are beyond reproach. 

I look forward to hearing from our witnesses today not only about the problems in the 

methods and procedures of the IARC Monograph Programme, of which there are many, but 

also about the fixes they believe can be made to bring the Monograph Programme back in 

line with modern science. 

### 
37 

Chairman SMITH. Thank you, Mr. Lucas. 

And the gentlewoman from Oregon, the Ranking Member of the 

Environmental Subcommittee, is recognized for her statement. 

Ms. BONAMICI. Thank you, Mr. Chairman. I’m glad we’re having 

this hearing today about the chemical review process. 

Ranking Member Johnson is correct. For too long industries’ influence on this process has endangered the public’s health and 

safety. Today, there is an assault on independent scientists and 

independent scientific organizations by the Trump Administration 

particularly by the Environmental Protection Agency. It is important that we review the methods and tactics that industry has used 

to influence this Administration and attack independent scientific 

organizations like the World Health Organization’s International 

Agency for Research on Cancer or IARC. 

This hearing today will focus on IARC’s hazard assessment of 

glyphosate, a key ingredient in Monsanto’s Roundup broad-spectrum herbicide used to kill weeds and grasses. In 2015, IARC determined that glyphosate was probably carcinogenic to humans. 

Other reviews, including a draft Human Health Risk Assessment 

released by the EPA in December, concluded that glyphosate is not 

likely to be carcinogenic to humans. Part of that discrepancy may 

be because these reviews have investigated different issues. 

IARC conducts hazard assessments while EPA conducts risk assessments. According to IARC, a cancer hazard is an agent that is 

capable of causing cancer under some circumstances while a cancer 

risk is an estimate of the carcinogenic effects expected from exposure to a cancer hazard. Although there seems to be some confusion about these distinct scientific procedures of analysis and the 

science on this issue still appears unsettled, the attacks by the 

chemical industry to discredit individual scientists and scientific organizations such as IARC is not. 

Internal Monsanto records show that company employees have 

ghostwritten scientific journal articles on glyphosate, attempted to 

orchestrate a public outcry over IARC’s glyphosate findings, and 

have targeted specific independent scientists for attack. At a time 

when most of us are sensitive to the cries of fake news the Monsanto records show in their own words that they have sought to 

amplify positive messages about glyphosate on social media, neutralize the impact of the IARC decision on glyphosate, and to use 

industry front groups as a platform for IARC observers and industry spokespersons. 

Attempts by industry to mischaracterize the scientific debate appear intended to undercut the scientific evidence regarding the possible dangers of glyphosate and its potential impact on human 

health. We must make sure any chemical review is not undone by 

undue corporate influence or misleading scientific studies. 

This is all the more important when the chemicals under review 

are so widely used. Glyphosate has been used as an herbicide in 

the United States since 1974, and its use in the United States has 

grown from 11 million pounds in 1987 to nearly 300 million pounds 

in 2016. Since its introduction in the United States 1.8 million tons 

of glyphosate have been applied across the country, and 9.4 million 

tons of glyphosate has been used on crops around the world. Recent 

studies have shown that this widescale use of glyphosate has had 
38 

an impact on our food supplies and communities. Glyphosate has 

been detected in crackers, cookies, cereals, as well as in organic 

honey and oatmeal. 

Chemical exposures, just like exposures to asbestos or lead or 

other potentially toxic substances, occur regardless of whether we 

sit on the left or the right of a particular political issue. The public 

health implications of these exposures are felt by all Americans 

and all people. That is exactly why an independent scientific review 

that is not unfairly or surreptitiously influenced by industry is necessary. We need to come to conclusions regarding the scientific evidence concerning glyphosate’s potential impact on human health in 

a transparent and complete manner. 

I look forward to hearing the testimony of our witnesses today, 

and I’m glad Dr. Jennifer Sass from the Natural Resources Defense 

Council is here. More than six years ago, Dr. Sass wrote a report 

titled ‘‘The Delay Game: How the Chemical Industry Ducks Regulation of the Most Toxic Substances.’’ It’s important that the Committee hear her perspective on these issues. 

[The prepared statement of Ms. Bonamici follows:] 
39 

OPENING STATEMENT 

Ranking Member Suzanne Bonamici (D-OR) 

of the Subconunittee on Environment 

Committee on Science, Space & Technology 

"In Defense of Scientific Integrity: Examining the !ARC Monograph Programme and Glyphosate 

Review" 

February 6, 2018 

Thank you. Mr. Chairman. 

I am glad we are having this hearing today on the chemical review process. Ms. Johnson is correct; 

for too long industry's influence on this process has endangered the public's health and safety. 

Today, there is an assault on independent scientists and independent scientific organizations by the 

Trump Administration, particularly the Environmental Protection Agency. It is important we review 

the methods and tactics that industry has used to influence this Administration and attack 

independent scientific organizations like the World Health Organization's International Agency for 

Research on Cancer (IARC). 

This hearing will focus on !ARC's hazard assessment of glyphosate, a key ingredient in Monsanto's 

Roundup broad-spectrum herbicide used to kill weeds and grasses. In 2015, IARC determined that 

glyphosate was "probably carcinogenic to humans." Other reviews, including a draft human health 

risk assessment released by the EPA in December concluded that "glyphosate is not likely to be 

carcinogenic to humans." Part of that discrepancy may be because these reviews have investigated 

different issues. IARC conducts hazard assessments while EPA conducts risk assessments. 

According to IARC, "A cancer 'hazard' is an agent that is capable of causing cancer under some 

circumstances, while a cancer 'risk' is an estimate of the carcinogenic effects expected from 

exposure to a cancer hazard." · 

While there seems to be confusion about these distinct scientific procedures of analysis, and the 

science on this issue still appears unsettled, the attacks by the chemical industry to discredit 

individual scientists and scientific organizations such as !ARC is not. 

Internal Monsanto records show they have ghost written scientific journal articles on g!yphosate, 

attempted to orchestrate a public outcry over IARC's glyphosate findings, and have targeted specific 

independent scientists for attack. At a time when most of us are sensitive to the cries of"fake news," 

the Monsanto records show in their own words they have sought to "amplify" "positive" messages 

about glyphosate on social media, "neutralize" the impact of the IARC decision on glyphosate, and to 

use industry front groups as a "platform for IARC observers and industry spokesperson[s]." 

Attempts by industry to mischaracterize the scientific debate appear intended to undercut the 

scientific evidence regarding the possible dangers of glyphosate and its potential impact on human 

health. We must make sure any chemical review is not undone by undue corporate influence or 

misleading scientific studies. 
40 

This is all the more important when the chemicals under review are so widely used. Glyphosate has 

been used as an herbicide in the United States since 1974 and that its use in the U.S. has grown from 

II million pounds in 1987 to nearly 300 million pounds in 2016. Since its introduction in the U.S. 

1.8 million tons of glyphosate have been applied across the country and 9.4 million tons of 

glyphosate has been used on crops around the world. 

Recent studies have shown that this wide scale use of glyphosate has had an impact on our food 

supplies and communities. Glyphosate has been detected in crackers, cookies and cereals, as well as 

in organic honey and oatmeal. 

Chemical exposures, just like exposures to asbestos or lead, or other potentially toxic substances 

occur regardless of whether you sit to the left or the right of a particular political issue. The public 

health implications of these exposures are felt by all Americans, and all people. That is exactly why 

an independent scientific review that is not unfairly or surreptitiously influenced by industry is 

necessary. We need to come to conclusions regarding the scientific evidence concerning glyphosate's 

potential impact on human health in a transparent and complete manner. 

I look forward to hearing the testimony of our witnesses today, particularly Dr. Jennifer Sass from 

the Natural Resources Defense Council (NRDC). More than six years ago, Dr. Sass wrote a report 

titled: "The Delay Game: How the Chemical Industry Ducks Regulation of the Most Toxic 

Substances. "I think it is important that the Committee hear her perspective on these issues. 

Thank you Mr. Chairman. I yield back. 
41 

Ms. BONAMICI. And before I yield back, Mr. Chairman, I have 

three responses from Dr. Christopher Wild, the Director of IARC, 

responding to inquiries you made late last year. In summary, Dr. 

Wild provides factually supported rebuttals to criticisms you and 

others have made about the IARC glyphosate Monograph, and I 

ask that these documents be made part of the record. 

Chairman SMITH. Without objection. 

[The information appears in Appendix II] 

Ms. BONAMICI. And I yield back the balance of my time. Thank 

you, Mr. Chairman. 

Chairman SMITH. Thank you, Ms. Bonamici. And I’ll introduce 

our witnesses now. Our first witness today is Dr. Anna Lowit, Senior Science Advisor in the Office of Pesticide Programs at the Environmental Protection Agency. Dr. Lowit has been a toxicologist in 

OPP’s Health Effects Division since 1998. During this time, she has 

provided expert technical advice and guidance on issues related to 

toxicity, testing human risk assessment, and science policy issues. 

She was elected co-Chair of the Interagency Coordinating Committee on the Validation of Alternative Methods, a committee of 

representatives from 16 federal agencies that require, generate, or 

disseminate toxicological and safety testing information. In January, she was named the recipient of the Society of Toxicology’s 2018 

Enhancement of Animal Welfare Award. Dr. Lowit received her 

master’s of science and Ph.D. in environmental toxicology from the 

University of Tennessee. 

Our next witness is Dr. Timothy Pastoor, CEO of Pastoor Science 

Communications. In addition, he is President of the Health and 

Environmental Science Institute, a D.C.-based nonprofit organization. With over 30 years of international experience, Dr. Pastoor 

has been involved with fundamental toxicity testing, mode-of-action 

research, and Human Health Risk Assessment. For the majority of 

his career, he led toxicology and risk assessment experts in the 

conduct of safety, health, and environmental studies to assess risk 

to humans and the environment. He retired in 2015 and founded 

the company Pastoor Science Communications, LLC, centered 

around his passion for advancing sound science. Dr. Pastoor received a Ph.D. in toxicology from the University of Michigan. 

Our third witness is Dr. Jennifer Sass, Senior Scientist at the 

Natural Resources Defense Council. She is also a professorial lecturer in the Environmental and Occupational Health Department 

at George Washington University. In her work with the NRDC, Dr. 

Sass brings a highly specialized expertise in U.S. chemicals policy. 

She has published peer-reviewed journals on the regulation of toxic 

chemicals and emerging contaminants such as nanomaterials. Dr. 

Sass earned a master’s degree and a Ph.D. in anatomy and cell biology from the University of Saskatchewan Canada and has done 

postdoctoral work in toxicology at the University of Maryland. 

Our final witness today is Dr. Robert Tarone, a Biostatistics Director at the International Epidemiology Institute for 14 years before retiring in 2016. Previously, he was a mathematical statistician at the U.S. National Cancer Institute and a professor in the 

Department of Medicine at Vanderbilt University. During his career, Dr. Tarone has provided statistical assistance to a wide variety of laboratory and clinical researchers, including investigators in 
42 

the field of immunology, DNA repair, and cancer-prone inherited 

diseases. He received his bachelor of science, master’s of arts, and 

Ph.D. all in mathematics from the University of California Davis. 

We recognize and appreciate and welcome you all. And, Dr. 

Lowit, if you will begin. 

TESTIMONY OF DR. ANNA LOWIT, 

SENIOR SCIENCE ADVISOR, 

OFFICE OF PESTICIDE PROGRAMS, 

ENVIRONMENTAL PROTECTION AGENCY 

Dr. LOWIT. Good morning, Chairman Smith, Ranking Member 

Johnson, and the rest of the Members of the Committee. My name 

is Anna Lowit. I serve as a Science Advisor for EPA’s Office of Pesticide Programs. I have a Ph.D. in environmental toxicology and 

have worked in the area of pesticide risk assessment and toxicology 

for nearly 20 years. 

EPA regulates the manufacture and use of all pesticides in the 

United States and establishes maximum levels for pesticide residues in food, safeguarding the Nation’s food supply, workers, and 

the general public. 

In addition to evaluating new pesticides before they can enter 

the market, EPA reevaluates existing pesticides at least every 15 

years under a program known as registration review. EPA must 

complete registration review for more than 700 pesticides by October 1 of 2022. In 2017, EPA evaluated more than 120 pesticides 

using the risk assessment process. 

Glyphosate, commonly known as Roundup, was initially registered by EPA in 1974. Glyphosate is one of the most widely used 

herbicides in the United States with about 270 million pounds of 

active ingredient applied annually. Glyphosate is used on a large 

number of crops, primarily corn and soybean, and is commonly 

used by homeowners. 

Registration review for glyphosate was initiated in 2009 using 

the statutory registration review process applied to all registered 

pesticides. As part of this process, several types of assessments 

have been initiated, including evaluations of human health, ecological risk, carcinogenicity, endocrine disruption, and risk to pollinators. The assessments are subject to extensive technical review 

and public comment throughout the review process. 

EPA released the draft Human Health and Ecological Risk Assessments in December of 2017. Glyphosate is considered to have 

little to no hazard when exposure is to the skin or when inhaled. 

Effects in laboratory animals were only seen through ingestion at 

very high doses. In the case of glyphosate, the Human Health Risk 

Assessment was developed with conservative exposure assumptions. Even with these conservative assumptions, no risk to humans, including infants and children, were identified. This conclusion showing no risk to humans is consistent with risk assessment 

findings in other countries and by international organizations such 

as Canada and the European Food Safety Authority. 

Glyphosate was also subject to endocrine screening. Based on 

weight-of-evidence considerations, there’s no convincing evidence of 
43 

potential interaction with estrogen, androgen, or thyroid pathways, 

and no additional endocrine related studies are considered necessary. 

In 2016, EPA conducted a comprehensive analysis of all the 

available laboratory animal carcinogenicity, mutagenicity, and epidemiology data to inform the human risk—the human cancer-causing potential of glyphosate. EPA presented its evaluation to the 

FIFRA Scientific Advisory Panel and received the panel’s recommendation in March of 2017. The Agency’s cancer issue paper 

was updated to incorporate revisions, and based on the comprehensive analysis of all available data and reviews, EPA concluded that 

glyphosate is not likely to be carcinogenic to humans. 

While the draft Human Health and Ecological Risk Assessments 

are already publicly available on EPA’s website, the official public 

comment period for the draft risk assessments and supporting 

science evaluations will soon be announced in the Federal Register. 

EPA will evaluate the public comments and, if needed, will revise 

the risk assessments and then issue a proposed interim decision for 

public comment. If necessary, the proposed interim decision may 

include labeling changes and other risk mitigation measures. After 

public comments on the proposed interim decision are received and 

evaluated, EPA will issue an interim decision. EPA plans to complete a final decision after an endangered species assessment is 

complete. 

Thank you for the opportunity to testify today, and I’m looking 

forward to questions from you and the Members. 

[The prepared statement of Dr. Lowit follows:] 
44 

TESTIMONY OF 

ANNA B. LOWIT 

SCIENCE ADVISOR, OFFICE OF PESTICIDE PROGRAMS 

U.S. ENVIRONMENTAL PROTECTION AGENCY 

BEFORE THE 

HOUSE COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

February 6, 2018 

Good morning Chairman Smith, ranking Member Johnson and members of the 

committee. My name is Anna Lowit. I serve as the Science Advisor in the Office of Pesticide 

Programs of the U.S. Environmental Protection Agency. I have a Ph.D. in Environmental 

Toxicology from the University of Tennessee and have worked at the EPA since 1998. In my 

role as Science Advisor, I provide advice and guidance to senior management and staff 

concerning toxicity testing, risk assessment, and science policy issues of national and 

international importance related to pesticides. 

The EPA regulates the manufacture and use of all pesticides in the United States and 

establishes maximum levels for pesticide residues in food, thereby safeguarding the nation's food 

supply, workers, and the general public. The EPA implements the Federal Insecticide, Fungicide, 

and Rodenticide Act (FIFRA); the Pesticide Registration Improvement Act (PRIA); and key 

parts of the Food Quality Protection Act (FQPA) and Federal Food, Drug, and Cosmetic Act 

(FFDCA), along with the Endangered Species Act. Under these statutes, new pesticides and new 
45 

uses of existing pesticides are evaluated before they can enter the market. In addition, existing 

pesticides are re-evaluated at least every 15 years to determine whether they continue to meet the 

standard for registration. This program is known as registration review. 1 The EPA must complete 

registration review by October I, 2022, for all pesticides registered as of October I, 2007. 

The process the EPA uses for evaluating the potential for human health and ecological 

effects of a pesticide is called risk assessment. The EPA uses the risk assessment process 

established by the 1983 National Research Council in the report on "Risk Assessment in the 

Federal Government: Managing the Process."2 This process is widely used across the federal 

government and considers how toxic a chemical may be, what exposures may occur to a 

chemical, and the issues and uncertainties associated with a calculated risk. In fiscal year 2017, 

the EPA evaluated more than 120 pesticides using the risk assessment process. 

The EPA's Office of Pesticides Programs is a science driven organization, employing 

more than 300 scientists. To evaluate the hazard of pesticides effects, we employ toxicologists, 

epidemiologists, botanists, and biologists. To evaluate the exposure of pesticides, the office 

employs industrial hygienists, chemists, physical scientists, agronomists, geologists, 

hydrologists, and environmental engineers. The office has entomologists and microbiologists 

who ensure the products we register are efficacious. The EPA also has statisticians, 

mathematicians, computer scientists, and experts in the Geographic Information System to 

support predictive modeling approaches. Our scientists work together in interdisciplinary teams 

1 See https://www.epa.gov/pesticide-reevaluationlregistration-review-process 2 National Research Council. 1983. Risk Assessment in the Federal Government: Managing the Process. 

Washington, DC: The National Academies Press. Available at https://doi.org/10.17226/366. 

2 
46 

to evaluate the complex science associated with pesticide risk assessment. Our scientists also 

routinely work with risk managers and attorneys to support science based decision making in 

accordance with the relevant statutes. Within the limits defined by federal statutes, we also 

consider the benefits of pesticides to users, growers, and to society. 

Scientists in the EPA's Office of Pesticides Programs work collaboratively with other 

program offices and regions within the EPA such as the Office of Water, the Office of Air, and 

the Office of Children's Health Protection. We engage with and depend upon input from the 

agency's Office of Research and Development to help solve some our most challenging science 

issues. In addition, the EPA's scientists are involved in projects with states and other federal 

agencies such as the U.S. Department of Agriculture, the Food and Drug Administration, the 

National Institute for Environmental Health Sciences, the U.S. Geological Survey, and the 

Centers for Disease Control and Prevention on numerous topics. The agency is involved 

internationally with at the Organisation for Economic Co-operation and Development (OECD) 

and the World Health Organization (WHO) to support harmonization and advancing risk 

assessment science. The EPA's methods are broadly accepted on an international basis. Many 

countries have adopted the methods developed and used by the EPA. 

Under FIFRA, the EPA requires substantial amounts of toxicology and exposure data to 

be collected and submitted for pesticide registration. For example, numerous studies involving 

laboratory animals are conducted on a variety of pesticidal effects such as cancer and systemic 

toxicity .. The FQP A requires specific consideration of the potential for infants and children to be 

sensitive to pesticides. Accordingly, the EPA requires testing on developmental toxicity and 

3 
47 

reproductive toxicity and often specific evaluations on neurotoxicity and brain development. 

Multiple species are tested, namely rats, mice, dogs, rabbits, birds, fish, plants, bees and other 

insects. These tests range in their duration of exposure from a single day up to the entire lifetime 

of the laboratory animal and are conducted in different routes of exposure such as oral, dermal, 

inhalation. 

Risk is not only a function of the toxicity of a chemical, it is also related to exposure that 

can occur due to its use. The EPA quantifies exposure to all facets of the U.S. population by 

considering diet and drinking water, as well as from other possible contact with pesticides both 

in the general population and as part of their job. The EPA also considers exposure in the 

environment to various plant and animal species. Many types of diverse data are required to 

evaluate such exposure patterns. These include monitoring of pesticide users (e.g., occupational 

exposure), behavioral information (e.g., dietary intake patterns), data intended to quantifY how 

pesticides behave in the environment (e.g., chemical fate, transport, and persistence), as well as 

data to quantify what pesticides could end up in food (e.g., residue from crops where a pesticide 

is applied). These data requirements are found in 40 CFR Part 158. 

To ensure data quality and consistency, the EPA has standard guidelines for how testing 

is to be conducted. The EPA's test guidelines are largely harmonized with those established 

internationally by the OECD. Harmonized test guidelines reduce the burden on chemical 

producers and conserve scientific resources, including reducing use of laboratory test animals 

while maintaining a thorough evaluation of the toxicity profile of pesticides. 

4 
48 

The EPA strives for transparency in our scientific analysis. Our science policies, 

guidance documents, and guidelines have been through peer review and public comments, and 

are publicly available. The agency's scientists develop independent, objective evaluations of 

studies sponsored by pesticide registrants and those available in the open scientific literature. The 

EPA's science reviews are publicly available in the federal docket and the agency's scientists 

routinely give presentations to the public and to other scientific experts. The EPA frequently 

meets with stakeholders, including industry, growers, non-governmental organizations, and 

states, on numerous issues pertaining to pesticides. 

The EPA uses a tiered approach to conduct risk assessment in order to focus its efforts on 

areas where additional refinement is needed. This is practical from both a regulatory and 

resource perspective, as it allows the EPA and the regulated community to focus on critical 

issues and refine as needed, and conserves resources. In this approach, the EPA starts with highly 

conservative risk assessment then adds refinement as appropriate. For example, when dietary 

intake is evaluated, the EPA might assume the entirety of a particular crop is treated using the 

maximum allowable amount of pesticide when crops are not actually produced this way. As a 

refinement, information related to how much of a particular crop is treated could be considered. 

Amounts in food close to the point of consumption, such as sampled from a grocery store, is 

another refinement. 

Glyphosate (commonly known as Roundup®) was initially registered by the EPA in 

1974. Glyphosate acid and several related glyphosate salt compounds are also registered 

pesticides. Glyphosate is one of the most widely used agricultural pesticides in the United States, 

5 
49 

with approximately 270 million pounds of active ingredient applied annually (2011-2015). 

Glyphosate is used on a large number of agricultural crops, primarily glyphosate-resistant com 

and glyphosate-resistant soybeans. Glyphosate also makes up 40 percent of the total pounds of 

herbicides sold in the U.S. residential consumer market for use on lawns and turf. Other 

important uses are direct uses in aquatic systems and rights-of-way for total vegetation control. 

Registration review for glyphosate was initiated in 2009. As mentioned above, the EPA 

has a statutory registration review process that is being applied to all registered pesticides, 

including glyphosate, involving evaluation of significant amounts of scientific information. As 

part of this process, several types of assessments have been initiated including evaluations of 

human health, ecological risk, carcinogenicity, endocrine disruption, and risk to pollinators and 

endangered species. The assessments are subject to extensive technical review and public 

comment at several time points throughout the review process. 

The EPA released the draft human health and ecological risk assessments on December 

18, 2017.3 The EPA's human health review evaluated dietary, residential/non-occupational, 

aggregate, and occupational exposures. Glyphosate is considered to have little to no hazard when 

exposure is to the skin and when it is inhaled. Effects in laboratory animals were only seen 

through ingestion at high doses. In the case of glyphosate, the human health risk assessment was 

developed with high end assumptions known to be overestimates of exposure. However, even 

with these assumptions, no risk to humans, including infants and children, were identified. This 

conclusion about showing no risk to humans is consistent with risk assessment findings in other 

3 See https://www.epa.gov/ingredients-used-pesticide-products/draft-human-health-and-ecological-risk-assessmentsglyphosate. 

6 
50 

countries and international organizations such as Canada, Australia, and the European Food 

Safety Authority. 

As required under the FFDCA, glyphosate was subject to endocrine screening as part of 

the EPA's Endocrine Disruptor Screening Program (EDSP). The EPA received and reviewed all 

the required Tier I assay data. Based on weight of evidence considerations, there is no 

convincing evidence of potential interaction with the estrogen, androgen or thyroid pathways, 

and no additional EDSP related studies are considered necessary. 

In 2015, the International Agency on the Research for Cancer (IARC) released its final 

conclusions that glyphosate is "probably carcinogenic to humans (Group 2A)."4 In 2016, the 

EPA conducted a comprehensive analysis of all the available laboratory animal carcinogenicity, 

mutagenicity, and epidemiology data to inform the human carcinogenic potential of glyphosate. 

In December 2016, the EPA presented its evaluation to the FIFRA Scientific Advisory Panel 

(SAP). The EPA received the SAP's recommendations in March 2017. The agency's cancer 

issue paper was updated to inc01porate revisions based on the SAP's report. Based on the 

comprehensive analysis of all available data and reviews, the EPA concludes that glyphosate is 

"not likely to be carcinogenic to humans." The EPA's cancer classification for glyphosate is 

based on a weight of evidence evaluation in accordance with the agency's 2005 Guideline for 

Carcinogen Risk Assessment.5 The dataset considered by the EPA included studies submitted for 

registration of glyphosate, as well as studies identified in the open literature as part of a 

systematic review. 

4 See http://monographs.iarc.fr/ENG/Monographs/volll2/monoll2-IO.pdf. 5 See https://www.epa.gov/risk/guidelines-carcinogen-risk-assessment. 

7 
51 

There are some fundamental differences between the IARC review and the EPA's review 

of glyphosate. For instance: 

• IARC only considers data that has been published or accepted for publication in the 

openly available scientific literature. As a result, IARC only considered I 0 laboratory 

animal cancer studies whereas the EPA includes 14 laboratory animal cancer studies in 

its evaluation; 

• IARC does not consider exposure and only bases its decision on the hazard of a chemical 

where the EPA considers exposure as a critical component of the cancer evaluation; 

• !ARC's conclusion is inconsistent with the international community, where the EPA's 

conclusion that glyphosate is "not likely to be carcinogenic to humans," is consistent 

with other countries and international organizations including: Australia (2013), Canada 

(2015), Japan (2016), New Zealand (2016), the European Food Safety Authority (EFSA) 

(2015), Germany (2014), the European Chemicals Agency (ECHA) (2017) and the Joint 

Food and Agriculture Organization of the United Nations (FAO)/WHO Meeting on 

Pesticide Residues (JMPR) (2016). 

On November 9, 2017, the National Cancer Institute, which is part of the National 

Institutes of Health (NIH), published a new epidemiology study entitled "Glyphosate Use and 

Cancer Incidence in the Agricultural Health Study". 6 The Agricultural Health Study (AHS) is a 

prospective cohort of more than 57,000 licensed pesticide applicators in Iowa and North 

Carolina. The results of this new study, which has a longer follow up period than previously 

6 JNatl Cancer Inst. 2017 Nov 15. doi: 10.1093/jnci/djx247, available at 

https:/ /www.ncbi.nlm.nih.gov/pubmed/29155 945. 

8 
52 

available evaluations of the AHS cohort, provide additional strong support for the agency's 

conclusion that glyphosate is "not likely to be carcinogenic to humans." 

In an ecological risk assessment, the EPA evaluates the potential that exposure to 

pesticides may cause harmful effects to non-target organisms. The effects can be direct, such as 

fish deaths from a pesticide entering waterways, or birds do not reproduce normally after 

ingesting contaminated fish, or indirect, such as a bird that can't reproduce because the plant it 

requires for nesting has been stunted by pesticide exposure. Specific to glyphosate, the 

ecological risk assessment indicates that there is potential for effects on birds (surrogates for 

reptiles and terrestrial-phase amphibians), mammals, and terrestrial and aquatic plants but not 

fish (surrogates for aquatic-phase amphibians) or aquatic invertebrates. Available data show low 

toxicity for honeybees and other terrestrial invertebrates. 

While the draft human health and ecological risk assessments are already publicly 

available on the EPA website7

, the official public comment period for the registration review of 

the draft glyphosate risk assessments and supporting science evaluations will soon be announced 

in the Federal Register. Once announced, this will begin the official public comment period 

which is anticipated to last for 60 days. After public comments are received on the risk 

assessment, if needed, the EPA will revise its risk assessments and issue a Proposed Interim 

Decision for public comment. If necessary, the Proposed Interim Decision will include proposed 

labeling changes and other risk mitigation measures. After public comments on the Proposed 

Interim Decision are received and evaluated, the EPA will issue an Interim Decision. The EPA 

7 See https://www.epa.gov/pesticides/epa-releases-draft-risk-assessments-glyphosate. 

9 
53 

plans to complete a Final Decision after an evaluation of risks to pollinators and an endangered 

species assessment is complete. In addition, the EPA plans to initiate endangered species 

consultation with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service 

by 2020. As mentioned earlier, registration review must be completed by 2022. 

In sum, the EPA has a statutory registration review process that is being systematically 

and transparently applied to glyphosate and all other pesticides reviewed by EPA. The EPA's 

pesticide risk assessments are based upon science and are subject to extensive science technical 

review and public comment. Draft risk assessments on glyphosate for human health and 

ecological effects are publically available at this time. 

Thank you for the opportunity to testify today. I will be happy to answer any questions 

you and the other members may have. 

10 
54 

Anna B. Lowit, Ph.D., received her Ph.D. in Environmental Toxicology from the University of Tennessee 

in 1998. Dr. Lowit has worked on pesticide risk assessment for nearly 20 years. Dr. Lowit currently serves 

as the Science Advisor in the U.S. Environmental Protection Agency's Office of Pesticide Programs. Dr. 

Lowit is currently one of the co-chairs of Interagency Coordinating Committee on the Validation of 

Alternative Methods and leads multidisciplinary teams on a variety of cross cutting topics. She also has 

experience in cumulative risk assessments, science integration along multiple lines of evidence, and 

improving the use of quantitative approaches in human health risk assessment. 
55 

Chairman SMITH. Thank you, Dr. Lowit. 

And Dr. Pastoor? 

TESTIMONY OF DR. TIMOTHY PASTOOR, 

CEO, PASTOOR SCIENCE COMMUNICATIONS 

Dr. PASTOOR. Chairman Smith—good morning, Mr. Chairman, 

Ranking Member Johnson, and the distinguished Members of this 

Committee. Thank you for inviting me to this important hearing on 

a very important subject. 

I am representing myself and nine other co-authors of a paper 

that we wrote. These are individuals that are—that come from the 

private sector and the public sector, professors that come from both 

the United States and the European area, as well as retired senior 

scientists from the United States EPA. 

My testimony today is going to focus on the scientific process 

that IARC uses, which the nine authors that I co-authored the 

paper with have concluded is badly outmoded and in need—in bad 

need of significant revision or termination. The reason is because 

the program uses an antiquated and irrelevant hazard classification scheme to simply declare a substance to be carcinogenic or not 

and provides no context about when, why, or how that substance 

might actually cause that effect. 

Let me illustrate it this way. I would imagine that most of the 

people in this room have consumed water or food or both that contained a substance that IARC Monographs Programme has declared to be carcinogenic. How does that make you feel? Well, the 

problem with that is that it’s a simple declaration about something 

that is in your food that could cause cancer. What I’m talking 

about is caffeic acid. Caffeic acid is found in a number of foods that 

we eat every day that are part of a healthy diet, including things 

like grapes, apples, blueberries, lemons, oranges, and it goes on. 

And oh, by the way, caffeic acid is also part of the cup of coffee that 

I have in front of me today. Declaring that caffeic acid is a carcinogenic substance is really of no help when you just state it that way. 

It needs to have context. 

As a toxicologist, I’m frequently asked by family and friends 

what it means when they hear something is declared to be possibly 

or potentially carcinogenic. What they want to know is how likely 

is that to happen to me, my family, my friends. It’s an important 

subject. My answer is always the same. It depends on how potent 

the chemical is, the substance is, and how much exposure is required to cause that effect. 

Let’s take potency first. Unfortunately, the IARC Monograph 

Programme fails to provide the crucial context of potency and instead lumps highly potent substances like plutonium, sulfur mustard, and neutron radiation in the same cancer classification as 

processed meat and salted fish. Clearly, there’s a difference, but 

the IARC Monographs Programme fails to account for potency. 

My wife is a registered nurse and an integrative healer who likes 

to use plant-based remedies. When I tell her that aloe vera and 

ginkgo biloba are classified by IARC as possibly carcinogenic, she 

rolled her eyes and said—oh, and by the way, they’re classified in 

the same category with fuel, oil, and gasoline, she simply kind of 

rolled her eyes back and say, ‘‘No, that can’t be.’’ 
56 

Such a classification scheme defies common sense, and yet IARC 

has maintained this hazard classification scheme for well over—in 

nearly half-a-century. Along with neglecting the important feature 

of potency, IARC Monographs Programme also fails to account for 

potential exposure. Why is that important? Because the central 

tenet of toxicology is the dose makes the poison. And the best way 

of giving you a good analogy of that is aspirin. A little bit of aspirin 

is not going to do anything. A couple tablets of aspirin will relieve 

your headache, and a bottle of aspirin can kill you. But where 

IARC stops is labeling something as being able to kill you. What 

good is that information without the context of benefits and dose? 

Nearly all 21st-century regulatory processes such as Dr. Lowit 

described just previously account for potency and exposure in their 

evaluation and therefore the likelihood that an adverse effect like 

cancer could occur. It’s known as risk assessment. However, the 

IARC Monograph Programme is not risk-based and instead is stuck 

in a hazard classification scheme created a half-a-century ago with 

no consideration of potency or exposure. 

In addition to being out of step with 21st-century science, the 

IARC Monograph Programme has also lost credibility because of 

serious flaws in process. I’m here to talk about the science, not the 

process, but that is a concerning issue. 

Outdated science and flawed process are not without consequence. Telling you that IARC has pegged caffeic acid as a carcinogenic substance in your food and coffee does nothing other than 

sow fear and uncertainty, which is unhelpful and irrelevant at best 

and irresponsible at worst. The IARC Monograph Programme 

needs to be either significantly reformed or abolished. 

Thank you very much, Mr. Chairman. 

[The prepared statement of Dr. Pastoor follows:] 
57 

Testimony of 

Timothy Pastoor, PhD, DABT, ATS 

(Biography at end of testimony) 

Pastoor Science Communications, LLC 

To 

The U.S. House of Representatives 

Committee on Science, Space, and Technology 

Hearing Title: 

In Defense of Scientific Integrity: Examining the IARC Monograph Programme and Glyphosate Review 

February 6, 2018 
58 

Change or Abolish the !ARC Monograph Program 

The International Agency for Research on Cancer Monographs' program is an antiquated review process 

that is based on the state of scientific knowledge a half a century ago. It has done little to keep up with 

advances in science and the protection of human health in the intervening years. While cancer 

classification systems such as !ARC's may have served a useful purpose when they were created, they 

are as irrelevant today as the telegraph or 8-track tape player. They provide little to no useful 

information and do more to confuse the public- and policy makers-- than to protect public health. 

In addition to being out of step with 21" century science, the IARC Monograph program has lost 

credibility because of serious flaws in its process. Lack of transparency and accountability in this once 

venerable program have led to numerous allegations of questionable ethical practices, undisclosed 

conflicts of interest, and opinions that run counter to worldwide scientifically-based consensus 

conclusions. 

Outdated science and flawed process are not without consequence. Declarations by the Monograph 

program have sown unnecessary fears about useful and safe products and deflected enormous 

resources away from useful investments in public health. The science and process of the IARC 

Monograph program needs to be either significantly reformed or abolished. 

Why is the IARC Monograph program so out of step with advanced health protection agencies such as 

the US EPA, Health Canada, the European Food Safety Authority (EFSA), and the United Kingdom 

Committee on Carcinogenicity, just to name a few? There are several reasons articulated in a 

publication' co-authored by myself and nine other senior scientists from academia, government, and 

private enterprises, but the primary issue is that the program fails to consider key factors such as 

potency and potential human exposure in its declarations of carcinogenicity. 

Back in the 161

h century, Paracelsus noted that "the dose makes the poison." He understood that 

anything anything at all- at a high enough dose is poisonous, but at a low enough dose that same 

substance will be completely harmless. The same holds true for substances that could possibly cause 

cancer. Many things that could cause cancer at extremely high doses are harmless at levels likely 

encountered by human beings. 

IARC simply ignores this essential fact. As a result, it lumps bacon, sausage, sulfur mustard gas, and 

plutonium together in the same category, Group 1, as definitely carcinogenic. !ARC makes this 

declaration based on its confidence in the information it reviews and NOT on the likelihood that a 

particular substance has the potency or levels of human exposure that would cause cancer. Many of its 

conclusions are based on long-term, multi-year dosing of animals with unreasonably high amounts of a 

substance -well beyond what a human will ever be exposed to. Despite the absurdity of this kind of 

test, !ARC nonetheless declares a substance to be carcinogenic. This approach is now being realized as 

1 This testimony focuses on the !ARC Monographs program and not on the broader !ARC institution, which is highly 

respected as a key center for cancer research and awareness. References in this text to "!ARC" should be inferred 

as the IARC Monographs program. 2 Boobis, A.R., et al., Classification schemes for carcinogenicity based on hazard-identification have become 

outmoded and serve neither science nor society, Regulatory Toxicology and Pharmacology (2016), 

http:/ I dx.do i .org/10.1016/j. yrtp h .2016.10.014 

Timothy Pastoor, PhD, DABT, ATS Page 2 ofS 
59 

untenable and disconnected with 21" century science, modern public health protection, and 

communication of appropriate health practices. 

In fact, if one were to take IARC seriously, there would be little if anything we could eat because many of 

the foods that contribute to what is universally considered a healthy diet would be suspected as causing 

cancer. To give just a few of many possible examples, take caffeic acid, which IARC classified as a Group 

2B carcinogen, and which is found in a wide variety of fruits, vegetables and other foods, including 

grapes, apples, wine, blueberries, lemons, oranges, beets, broccoli, cabbage, carrots, cauliflower, 

lettuce, kale, onions, peas ... not to mention coffee. And that's the short list. What do we do with a 

declaration that caffeic acid is a "possible human carcinogen"? 

Or take acetaldehyde in bread and the popular plant-based remedies, ginkgo biloba and aloe vera, all of 

which are also classified by IARC to be group 2B, "possibly carcinogenic to humans." 3 

This kind of classification has almost zero informational value if, as IARC does, it ignores the allimportant considerations of potency and exposure. Potency is important because it is the "punch" or 

power a substance has to induce a carcinogenic effect. Exposure is important because it considers how 

much of a substance we are likely to be exposed to under any reasonable scenario in the real world. This 

is an absolutely key element in limiting adverse effects. There are a wide variety of substances that may 

be labeled as carcinogenic based on high-dose, long-term studies, but in real life we could never 

consume enough or be exposed to enough to suffer adverse consequences. 

How much is too much? This is the central question. In our personal lives, we spend considerable parts 

of our day considering that very question on so many critical issues. How much sugar should I put in my 

coffee? How much coffee should I drink today? Should I have~ beer or two or more? What might be 

too much? Yet this important consideration is absent in IARC cancer classifications. 

let's take sunlight, for instance, which IARC classifies in Group 1 ("carcinogenic to humans"). We should 

indeed consider the adverse consequence, or hazard, we might encounter from too much sunlight, i.e. 

sunburn or skin cancer. The solution is not to simply stay inside all day. Sunlight is also important in 

enabling the body's production of Vitamin D. 4 So do we make the decision about going outside ONLY 

considering the adverse consequences, or hazard, in mind? Or do we make a rational decision and 

control our overall exposure maybe wear a hat-- and enjoy ourselves in the meantime. 

What we are doing when we quantify how much is too much is the same as what risk regulators must do 

in setting permissible levels of exposure. Risk assessors use this same procedure with chemicals: what is 

the hazard and how much exposure is too much? Declaring that a chemical causes cancer or is an 

endocrine disruptor is only half the story. The other half is declaring the amount that could cause that 

adverse effect and setting limits that protect the public from being exposed to too much. This is what is 

know'n as a "risk assessment." 

Regulatory agencies around the world follow this straightforward "risk assessment" technique to protect 

public health. The United States Environmental Protection Agency has very clear guidance on how it 

identifies a chemical hazard, quantifies potential exposure, and manages risk. The policies and 

3 https:/ /monographs. iarc. fr /ENG/Ciassification/CiassificationsAip haOrder. pdf 4 at least 50% of the world's population suffers from Vitamin D insufficiency, which can lead to increased mortality 

(htt ps:/ /www. ncbi. nlm. nih .gov I pmc/articles/P MC3356951/) 

Timothy Pastoor, PhD, DABT, ATS Page 3 of 5 
60 

procedures to do so have been developed over the years, and have evolved as scientific knowledge has 

evolved and deepened since the inception of the USEPA in the early 1970's. The USEPA and other 

national and international risk-based health protection agencies have kept up with the science and are 

continuing to develop better ways to identify hazards of chemicals and couple that knowledge with 

exposure science. Science marches on. 

Unfortunately, the IARC Monographs program has not kept up. Originally established a half century ago 

to identify agents that CAN cause cancer, the IARC Monograph program stops at what is called "hazard 

identification." It provides a simple yes/no and then, if yes, a classification category (1, 2A, 2B, 3, or 4), 

depending on the degree of confidence for a causal link to cancer (not, as many assume, the degree to 

which an agent is likely to cause cancer). I ARC still uses this outmoded scheme despite advances in the 

sciences that have illuminated better ways to understand and regulate potential cancer-causing agents. 

The program must shift from a "hazard-only" scheme to a process that incorporates potency and 

exposure, and expresses its conclusions in risk assessment terms. 

Furthermore, the IARC Monographs program, with its antiquated classification system, has taken on the 

evaluation of extremely well studied and carefully regulated chemicals such as glyphosate. At best this 

is a duplication of effort and at worst is an opportunity to sow confusion in the public's mind. 

Along with being a scientifically antiquated program, serious questions have been raised about the 

integrity of !ARC's process. Any agency whose evaluations are used to influence public health decisions 

must be transparent and fully accountable to the public. If this committee and the member countries of 

IARC do not address the numerous allegations of questionable ethical practices, undisclosed conflicts of 

interest, and lack of transparency, then the scientific reforms suggested here will be irrelevant. 

There are certain basic standards of accountability, transparency, and simply good science on which 

IARC presently falls short that should be the guideposts for any effective reform of the monograph 

process. These include: 

o Selecting working group and other advisory members with necessary expertise, 

regardless of affiliation; 

o Declaring the affiliation and potential conflicts of interest of all participants; 

o Considering ALL available data; 

o Providing a clear explanation why certain data are or are not included in the review; 

o Adhering to the principles of systematic review, such as those described by The National 

Toxicology Program's Office of Health Assessment and Translation (OHAT) and Cochrane 

Consumer Network; 

o Fully communicating the results of the agency's review in a timely manner; 

o Including the opinions of all reviewers and the degrees of consensus and dissent. 

In conclusion, the IARC monograph program served its purpose 50 years ago to flag substances, 

including chemicals, that may be of concern. But it is now outmoded. Every effort must be made to 

bring their review process up-to-date with advances in scientific knowledge, focus on those substances 

not otherwise well regulated, and communicate that process openly and accurately to the public. The 

alternative is to abolish the program. 

Timothy Pastoor, PhD, DABT, ATS Page 4 of 5 
61 

Biography 

Timothy Pastoor, PhD, DABT, ATS 

Dr. Pastoor obtained his PhD in toxicology from the University of Michigan, is certified by the 

American Board of Toxicology (DABT) and is a Fellow of the Academy of Toxicological Sciences 

(ATS). Dr. Pastoor is president of the Health and Environmental Sciences Institute (HESI) and is a 

Board member of the International life Sciences Institute (ILSI) and the American Council on 

Science and Health (ACSH). Dr. Pastoor retired in 2015 from 5yngenta as Principal Scientist and 

founded the company Pastoor Science Communications, LLC that is centered around his passion 

for sound science, communicated well. 

Dr. Pastoor has over 35 years of international experience in fundamental toxicity testing, mode 

of action research, and human health risk assessment. For most his career, including positions 

with DuPont, ICI, Zeneca, Novartis, and Syngenta, Dr. Pastoor led toxicology and risk 

assessment experts in the conduct of safety, health, and environmental studies to assess risk to 

humans and the environment. In those roles, he was involved in toxicological research projects 

and product development and was frequently asked to interact with media, community groups, 

legislators, and regulatory agencies. He is a frequent lecturer on toxicology and risk assessment 

subjects. 

In his "retirement" Dr. Pastoor has remained actively engaged in science, toxicology, risk 

assessment, and science communication. He is also finding time to. help the University of North 

Carolina develop the Professional Science Masters program in toxicology. As founder and CEO 

of Pastoor Science Communications and through his role as HESI president, he is leading global 

groups from academia, government, and corporations in developing consensus on difficult 

scientific issues. 

Tim is an avid fly fisherman and photographer, and hopes his knees allow him to continue 

playing tennis for many years to come. 

********************* 

Abstracted biography for introductions: 

Dr. Pastoor obtained his PhD in toxicology from the University of Michigan, is certified by the 

American Board ofToxicology (DABT), is a Fellow of the Academy of Toxicological Sciences 

(ATS), and is president of the Health and Environmental Sciences Institute (HESI). Dr. Pastoor 

retired in 2015 from Syngenta as Principal Scientist and founded the company Pastoor Science 

Communications, LLC that is centered around his passion for sound science, communicated 

well. 

Timothy Pastoor, PhD, DABT, ATS Page 5 of 5 
62 

Chairman SMITH. Thank you, Dr. Pastoor. 

And Dr. Sass? 

TESTIMONY OF DR. JENNIFER SASS, 

SENIOR SCIENTIST, NATURAL RESOURCES DEFENSE COUNCIL 

Dr. SASS. Thank you very much for the opportunity to speak to— 

before this Committee today about this very important topic of scientific integrity, the IARC Monographs, and the important evaluation of glyphosate. I very much appreciate coming before you today. 

I’ve been employed for 17 years at NRDC, the Natural Resources 

Defense Council, and I have advanced degrees in anatomy and cell 

biology with specific expertise in environmental health, developmental biology, neurobiology, and molecular biology and am also familiar with the Pesticide Office operations that Dr. Anna Lowit is 

Science Advisor before because on many, many occasions I’ve testified either with written or oral comments are both to the Pesticide 

Office following their review of pesticides and registration, including glyphosate. In addition, I’ve represented NRDC for over a decade on stakeholder advisory panels to the Pesticide Office so have 

participated as a public and stakeholder member in those processes. 

I also have knowledge of the IARC practices, having been invited 

to a meeting, a week-long meeting to look at arsenic and water disinfection byproducts by the Chair at the time the Chief of the 

Monograph Programme Dr. Jerry Rice, who is a colleague of Dr. 

Tarone’s. There have been two Chairs since then, and the current 

Chair, Dr. Kurt Straif, was also working at the Monograph Programme during that time, so he brings with his leadership continuity to that program and to IARC’s commitment to environmental public health and scientific excellence. 

IARC has undertaken over 1,000 substances for evaluation, including important ones like asbestos, tobacco smoke, secondhand 

smoke, diesel exhaust, formaldehyde, vinyl chloride and arsenic, 

methylene chloride benzene, and many others. There—many of 

these—not all of them, but many of them also come with people— 

stakeholders that have deep economic interests in these substances, and although there have been many, the Director Dr. 

Christopher Wild of IARC right now stated that the pressure that 

IARC has received in response to listing glyphosate as a probable 

human carcinogen group 2A has resulted in unprecedented coordinated efforts to undermine the evaluation, the program, and the organization. 

These efforts are largely sponsored and coordinated by the 

agrochemical industry that sought to support its own regulation— 

its registration and approval of glyphosate in the United States 

and around the world, to defend itself in litigation against farmers 

that were once Monsanto customers and are now cancer patients, 

and to prevent the labeling of glyphosate-containing products as a 

carcinogen in the State of California, which would inform the public. 

Dr. Jonathan Samet called these strategies that could be traced 

to the playbook of the tobacco industry to discredit findings related 

to active and passive smoking. And I would characterize them the 

same way. 
63 

This hearing is part of a kickoff that happened a few months 

after the IARC Monographs were made public where an article in 

The Hill was published asking for exactly this, for the stripping of 

funding for the IARC Programme by Dr. Bruce Chassy, who failed 

to acknowledge that he was funded by Monsanto. 

As far as the science goes, IARC did not ignore relevant studies. 

They included all the relevant studies, including the Agriculture 

Health Study and other review articles that they looked at that 

were sponsored by many—many were sponsored by Monsanto or 

the agrochemical industry, as well as published articles. But the 

key with IARC is that they need to be publicly available. It doesn’t 

necessarily have to be published but publicly available. How else 

can they verify the findings? 

In contrast, EPA’s 2017 assessment did rely on some of these review articles that—where the underlying studies were not made 

public. And I know the Dr. Tarone is going to talk about some of 

those. I would ask Dr. Tarone how long it took him to evaluate the 

underlying data and studies in those because the Greim, et al., for 

example, was only provided 30 days before the IARC meeting, so 

there’s no way it could have been properly evaluated based on a review article. 

The IARC has been following systematic methods that are improved worldwide, and in conclusion, I would like to say that, fundamentally, this hearing is about the ability of a public health 

agency to call a carcinogen a carcinogen even if that carcinogen 

makes a huge amount of money for powerful corporations. 

Thank you. 

[The prepared statement of Dr. Sass follows:] 
64 

J. Sass, NRDC Feb 2018 

NRDC 

~ NATURAL RESOURCES DEFENSE COUNCIL 

Testimony of Jennifer Sass, Ph.D., Senior Scientist 

Natural Resources Defense Council 

Healthy People & Thriving Communities Program 

US House Committee on Science, Space, and Technology 

Full Committee Hearing- In Defense of Scientific Integrity: 

Examining the IARC Monograph Programme and Glyphosate Review. 

Washington, D.C., February 6, 20181 

Tuesday, February 6, 2018- !O:OOam 

2318 Rayburn House Office Building 

1 https :/I scie nee. ho use.gov /legis latio n/hea rings/full-committee-hearing-defense-scientific-integrityexamining-iarc-monograph 

1 
65 

J. Sass, NRDC Feb 2018 

Introduction 

Thank you for the opportunity to speak before this Committee on this very important topic of 

Scientific Integrity, the IARC Monographs, and Glyphosate. 

I have been employed full-time as a Senior Scientist with the Natural Resources Defense Council 

{NRDC) since 2001. I have advanced degrees in Anatomy and Cell Biology, with specific 

expertise in developmental biology, neurobiology, molecular biology, and environmental 

health. In my position with NRDC, I am responsible for reviewing the science underlying many 

of the federal regulations of industrial chemicals and pesticides. I have published over forty-five 

articles in peer-reviewed scientific journals, including many pertaining to pesticide hazards and 

regulations. 

I developed an understanding of U.S. pesticide regulations and of the operations of the EPA 

Office of Pesticide Programs through various activities. On numerous occasions, I have provided 

written and oral testimony to the Pesticide Office on the registration of dozens of pesticides, 

including glyphosate. Additionally, I represented NRDC for over a decade as an active member 

of the EPA/U.S. Department of Agriculture {USDA) Pesticide Program Dialogue Committee 

{PPDC), a stakeholder committee that provides feedback to the Pesticide Office on various 

issues related to pesticide regulatory, policy, and program implementation issues. Through my 

years of work on the PPDC, from 2001 to 2013, I also served on issue-specific PPDC workgroups 

to provide more in-depth perspectives and advice on pesticide issues, including input on 

strategic approaches for implementation of the Food Quality Protection Act {FQPA). 

I also have knowledge of the policies and practices of the International Agency for Research on 

Cancer {!ARC), having read and referenced many IARC chemical assessments over almost two 

decades. In 2002, when IARC was reviewing styrene {Volume 82) I was publicly critical of !ARC's 

practice at the time of allowing financially-conflicted scientists to participate as voting members 

of the Committee. In response, the Chief of the Programme at that time, Dr. Jerry Rice, invited 

me to attend a week-long meeting at which IARC would review arsenic and some drinking 

water disinfection bypro ducts {Volume 84). I attended as an observer {non-voting), and was 

given full access to observe the Working Group and its sub-discipline groups, as well as join 

participants for meals, etc. Dr. Rice was correct, I was extremely impressed with the scientific 

rigor of the process and the output. While I continued to advocate for financially-conflicted 

individuals to be prevented from voting, I acknowledged even then that Dr. Rice was right to be 

proud of the Monograph Programme's scientific work, then and even more so now. I have not 

participated in any IARC Monograph meetings since that one single time. There have been two 

Chiefs of the Monograph Programme since Dr. Rice, with the current one, Dr. Kurt Straif, having 

worked for the Monograph Programme under both his predecessors. Dr. Straif's leadership 

brings continuity to !ARC's commitment to environmental public health and scientific 

excellence. 

2 
66 

J. Sass, NRDC Feb 2018 

IARC has undertaken the evaluation of over 900 substances including asbestos, tobacco smoke 

and later second-hand smoke, diesel exhaust, formaldehyde, vinyl chloride, viruses, carbon 

nanotubes, arsenic, methylene chloride, benzene, and about nine hundred others. IARC 

assessments inform global cancer prevention strategies. 

Because of its scientific excellence and its scientific and regulatory relevance, IARC enjoys 

overwhelming support from the global scientific and medical community. A few years ago, 124 

scientists and health professionals from diverse scientific disciplines, from around the world coauthored a published account of the last forty years of IARC Monographs, noting the 

Programme's role in identifying carcinogenic substances to inform policies and practices that 

prevent harm and save lives (Pearce et al, 2015). 

In a published review on the industry-led criticisms of the IARC Monographs, Dr. Jonathan 

Samet, a prestigious medical professor and frequent Chair of National Academies committees, 

writes, "the types of concerns raised about the /ARC monograph program are also archetypical 

of strategies for creating 'doubt' about scientific evidence that has policy implications. Such 

strategies can be traced to the 'playbook' of the tobacco industry for discrediting findings 

related to active and passive smoking (14,15). One tactic has been to question the processes 

used to draw causal inferences and the integrity and potential conflicts of interest of those 

doing so. The /ARC processes are robust and transparent and as concluded by Pearce and his 

123 colleagues, not flawed and biased." (Samet 2015)2 

In my testimony I address a few examples of those tobacco-industry tactics applied to 

glyphosate, and the agrochemical industry attack on the IARC Monographs. 

Agrochemicallndustry Opposition 

IARC Director Christopher Wild stated that his Agency has experienced "unprecedented, 

coordinated efforts to undermine the evaluation, the program and the organization" in 

response to listing glyphosate in 2015 as a probable human carcinogen (Group 2A). 3 These 

efforts are largely sponsored and coordinated by the agrochemical industry that has sought to: 

support glyphosate registration and approval; defend itself against litigation claims by 

thousands offarmers that were once Monsanto Co. customers and are now cancer patients; 

and, prevent labeling of glyphosate-containing products as a carcinogen in the State of 

California. 

2 Samet JM. The IARC monographs: critics and controversy. Carcinogenesis. 2015 Jul;36(7):707-9. 

https:/ /academic.oup.com/ carcin/article/36/7 /707/1800366 3 IARC briefing paper Jan 2018 http://governance.iarc.fr/ENG/Docs/BriefingGCSC FINAL 29012018.pdf 

and IARC webpage on glyphosate: https://www.iarc.fr/en/mediacentre/iarcnews/2016/glyphosate IARC2016.php 

3 
67 

J. Sass, NRDC Feb 2018 

Today's hearing supports the agrochemical industry agenda to discredit and ultimately defund 

IARC. In September 2015 the New York Times reported that emeritus food professor Bruce 

Chassy received funding from Monsanto Co. to lobby the EPA to block regulation of GMO 

products.4 Almost a year later Chassy wrote an opinion-editorial in The Hill, "NIH needs public 

examination after giving millions to rogue UN agency".5 However, Chassy's editorial failed to 

disclose his work with Monsanto Co., instead identifying himself only as, "a researcher at the 

NIH for 21 years before moving to the University of Illinois at Urbana-Champaign as a 

department head and assistant dean, and is now professor emeritus of Food Science and 

Human Nutrition." What Chassy failed to disclose is that the nonprofit he runs called Academics 

Review received $300,000 from the Monsanto Co.-funded trade group BIO in both 2014 and 

2015. This industry money is the majority of Academics Review's funding and Chassy runs it 

with his wife.6 

What I've touched upon here is only a small part of the well documented public relations 

campaign to soften up public opinion about the agrichemical industry and create a venue to 

pressure agencies to block regulations, and try to discredit and silence public health and 

scientific institutes that may show some harm from their profitable products. 

IARC Response 

IARC has ably defended itself from all substantive criticisms in public documents, letters to this 

Committee which are publicly accessible on the IARC website, or in other public reports. 7 

Additionally, over 100 non-industrv scientists across many scientific and medical disciplines and 

from dozens of public Universities and Institutes in the US and worldwide- including myselfhave expressed confidence generally for the IARC process and specifically in the IARC 

Monograph for glyphosate (Portier et al 2016).8 

4 Food Industry Enlisted Academics in G.M.O. Lobbying War, Em ails Show. Eric Lipton. Sept 5, 2015. NY 

Times. https:/ /www. nyti mes. co m/20 15/09/06/ us/food -industry-en listed -a ca de m ics-in-g mo-lo bby ingwar-emails-show.html 

5 Bruce Chassy. The Hill. 10/24/16. http://thehill.com/blogs/pundits-blog/healthcare/302484-nih-needspublic-examination-after-giving-millions-to-rouge-un 

6 Paul Thacker, 07/21/2017. The Progressive. http://progressive.org/magazine/how-the-biotechindustry-cultivates-positive-media/ 

7 1ARC briefing paper Jan 2018 http://governance.iarc.fr/ENG/Docs/BriefingGCSC FINAL 29012018.pdf 8 Portier CJ, Armstrong BK, Baguley BC, Baur X, Belyaev I, BelleR, Belpoggi F, Biggeri A, Bosland MC, 

Bruzzi P, Budnik LT, Bugge MD, Burns K, CalafGM, Carpenter DO, Carpenter HM, L6pez-Carrillo L, Clapp 

R, Cocco P, Consonni D, Co mba P, Craft E, Dalvie MA, Davis D, Demers PA, DeRoos AJ, DeWitt J, 

Forastiere F, Freedman JH, Fritschi L, Gaus C, Gohlke JM, Goldberg M, Greiser E, Hansen J, Hardell L, 

Hauptmann M, Huang W, Huff J, James MO, Jameson CW, Kortenkamp A, Kopp-Schneider A, Kromhout 

H, Larramendy ML, Landrigan PJ, Lash LH, Leszczynski D, Lynch CF, Magnani C, Mandrioli D, Martin FL, 

Merler E, Michelozzi P, Miligi l, Miller AB, Mirabelli D, Mirer FE, Naidoo S, Perry MJ, Petronio MG, 

Pirastu R, Portier RJ, Ramos KS, Robertson LW, Rodriguez T, R66sli M, Ross MK, Roy D, Rusyn I, Saldiva P, 

Sass J, Savolainen K, Scheepers PT, Sergi C, Silbergeld EK, Smith MT, Stewart BW, Sutton P, Tateo F, 

4 
68 

1. Sass, NRDC Feb 2018 

I will add my own perspective here. 

The IARC Monographs have clearly described published guidelines called the "Preamble to the 

Monographs". 9 The guidelines describe the separate criteria for reviewing evidence from 

animal studies, epidemiologic information, and mechanistic data, and then integrating the data 

into an overall evaluation. All evaluations are made by Working Groups of experts, and have 

included over 1,200 scientists from over 50 countries. Scientific data is evaluated in subgroups, 

and then by all members of the Working Group in a plenary session, where revisions and 

extensive discussions often occur. There are also procedural guidelines for ensuring 

transparency, and for identifying and managing conflicts of interest and stakeholder 

involvement. Government, industry, NGO observers, and others can attend the Working Group 

meetings; the glyphosate meeting was attended by Monsanto Co. and other agrochemical 

industry representatives as observers. 10 

For its glyphosate assessment, IARC identified 17 scientific experts from 11 countries (Volume 

112, 2017).11 A list of Working Group candidates is posted in advance of the meeting, along 

with their disclosure of relevant financial conflicts, and public comments are invited. In advance 

of the meeting, Working Group members are asked to review an often very large stack of 

scientific papers relevant to each person's area of expertise, and provide a draft summary for 

discussion at the in-person meeting. 

All information used for the evaluation must be published or otherwise publicly available with 

enough detail to enable independent scientific examination. For this reason, some Monsantosponsored review articles were left out, where the underlying studies cited in the review article 

were not available to the Working Group or to the public. For example, Greim et al (2015), a 

review article of animal toxicology that was sponsored and co-authored by Monsanto Co., is 

discussed in the IARC monograph, but was not relied upon because the studies in the paper 

were not publicly available.U 

Terradni B, Thielmann HW, Thomas DB, Vainio H, Vena JE, Vineis P, Weiderpass E, Weisenburger DD, 

Woodruff TJ, Yorifuji T, Yu IJ, Zambon P, Zeeb H, Zhou SF. Differences in the carcinogenic evaluation of 

glyphosate between the International Agency for Research on Cancer (!ARC) and the European Food 

Safety Authority (EFSA). J Epidemiol Community Health. 2016 Aug;70(8):741-5. doi: 10.1136/jech-2015-

207005. Epub 2016 Mar 3. 9 http:/ /monographs.iarc. fr/E NG/Preamble/index.php 10 Participants for the IARC Monograph Volume 112. https://monographs.iarc.fr/ENG/Meetings/voll12-

participants.pdf 

11 http:/ I monographs. ia rc. fr /E NG/M onogra phs/vol112/index. ph p 12 Greim H, Saltmiras D, Mostert V, Strupp C. Evaluation of carcinogenic potential of the herbicide 

glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies. Crit 

Rev Toxicol. 2015 Mar;45(3):185-208. 

Helmut Greim also chaired a 'scientific panel' funded by auto companies to respond to the 20051ARC 

evaluation of diesel exhaust. Greim's panel conducted studies on monkeys at a lab in Albuquerque New 

Mexico, exposed them in a chamber to diesel exhaust. However, the studies were rigged because the 

5 
69 

J. Sass, NRDC Feb 2018 

IARC has been criticized by Dr. Tarone, also a paid Monsanto Co. consultant, arguing that IARC 

could have used, "A supplement to the review paper [that] contains summary pathology tables 

for each ofthe rodent studies reviewed". 13 But, summary tables are not original studies, and do 

not provide the detail necessary for an independent examination, and thus the Working Group 

could not independently verify the conclusions. Similarly, the IARC Monograph determined that 

a Monsanto-sponsored review of genotoxicity studies by Kier and Kirkland (2013) also "did not 

meet the criteria for data inclusion as laid out in the Preamble to the IARC Monographs" 

because the original studies were not available publicly available. IARC requires information to 

be publicly available as a requirement for full transparency of how the Working Group came to 

its conclusions. In addition, peer reviewed publications and reports contain enough detail on 

the study materials, methods, and results so that peer reviewers and readers can 

independently evaluate the study quality, including any possible confounders and biases. 

In stark contrast to IARC, the 2017 EPA glyphosate assessment acknowledges that, "data and 

summaries provided in Greim eta! (2015) and Kier and Kirkland (2013)14 were relied upon for 

the current evaluation" (EPA 2016, 2017). Thus, EPA relied upon a Monsanto-sponsored 

summary of a Monsanto-sponsored study that EPA could not independently scrutinize- the full 

studies are not available to the public and do not even seem to have been made available to 

EPA. In a small footnote, EPA identified that all review articles except one "were funded and/or 

linked to Monsanto Co. or other registrants." 15 

On occasion, the Monographs have been wrongly accused of a bias towards too readily 

classifying a substance as carcinogenic. However, to date the IARC Monographs have evaluated 

over 1,000 agents, all with at least enough cancer data to support a nomination for 

consideration. Yet, only 120 are classified as known human carcinogens (Group 1) and only 

about 80, including glyphosate, as probable human carcinogens (Group 2A).16 That makes a 

total of 200 agents, only about 20 percent, that are classified in the strongest two categories. 

The overwhelming majority of agents that have been reviewed by IARC- about 80 percentare classified as either possibly carcinogenic to humans (Group 2B, 300 agents) or not 

classifiable (Group 3, 500 agents). The third category- not classifiable- has far more entries 

than any other single class, and even more than the first two combined (Group 1 and 2A). Thus, 

cars in the chambers were using the "cheating" device that reduced emissions. In addition to bad 

science, it was also unethical, given that it is completely unnecessary to test monkeys in a chamber, 

when people are walking around exposed to these diesel fumes every day. The study was never 

published, but was widely criticized and the story reported in the NY Times. 

htt ps :/ /www. nytim es.com/20 18/0 1/25/wo rid/ e u rope/volkswagen -d iese 1-em issio ns-mo nkeys. ht ml 13 Tarone RE. On the International Agency for Research on Cancer classification of glyphosate as a 

probable human carcinogen. Eur J Cancer Prev. 2018 Jan;27(1):82-87. 

https :/ /www .ncbi. nlm. nih.govfpu bmed/27 552246 14 Kier LD, Kirkland DJ. Review of genotoxicity studies of glyphosate and glyphosate-based formulations. 

Crit Rev Toxicol. 2013 Apr;43(4):283-315. Review. https://www.ncbi.nlm.nih.gov/pubmed/23480780 15 EPA 2017 glyphosate cancer assessment. See Page 22 and Footnote 11. 16 http:/ /monogra phs.iarc.fr/ENG/Ciassification/index.php 

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J. Sass, NRDC Feb 2018 

the data do not support a bias towards classifying chemicals in the higher groups; in fact, most 

are determined to have too little data to classify. 

There has been public criticism by Monsanto Co. and some Majority Members ofthis 

Congressional Committee that a member of the glyphosate Working Group, Dr. Aaron Blair, 

withheld a pre-publication update of the National Cancer Institute Agricultural Health Study 

(AHS), and, further, that if the Working Group had been provided with this update, then it 

would have altered the final classification of glyphosate as a Group 2A probable human 

carcinogen.U That story was reported in Reuters, and subsequently shown by former Reuters 

reporter and veteran journalist Carey Gillam to contain critical factual errors, and to have been 

orchestrated by Monsanto Co .. 18 The misleading Reuters story relies on court documents 

obtained from Monsanto Co., and quotes Monsanto Co. consultant Bob Tarone as an 

"independent" expert not associated with Monsanto Co. Dr. Blair himself states that his 

opinions held at the IARC meeting has not changed, which IARC pointed out in a response letter 

to this Committee.19 

The IARC Director, Dr. Christopher Wild, responded in a letter to this Committee that in fact the 

AHS is a decades-long prospective epidemiologic study, with "incremental updates published 

periodically," all of which were included by the IARC Working Group in the Monograph.20 Since 

the previous AHS reports did not identify an association between non-Hodgkin lymphoma (NHL) 

and glyphosate, and the most recent incremental update, in 2017, also did not identify such an 

association, then it's hard to see how the recent update alters the previous reports. In addition, 

the recent update was not published until 2017, a full 2.5 years after the meeting of the IARC 

Working Group, indicating that it was unpublished at the time of the meeting. 

It is also inappropriate to argue that null studies can even nullify completely unrelated studies 

that are positive, that do report a link to NHL or other cancers. As if, just because you don't 

have cancer, my cancer goes away. That isn't the way science works, and it isn't the way cancer 

works either. The updated AHS report does not call into question the IARC conclusions, which 

are based on many studies across multiple disciplines, including studies sponsored by 

Monsanto Co. 

lost or buried in much of the reporting of the recent update of the AHS study is that the study 

did find some evidence of a possible association between glyphosate and another type of blood 

cancer called acute myeloid leukemia (AML). The AHS study authors warn that, "Given the 

17 See letter from Reps. Lamar Smith, Andy Biggs, and Frank Lucas to IARC Director Dr. Christopher Wild. 

December 8, 2017. http:/ /governance.iarc.fr/ENG/Docs/SST _IARC12082017.pdf 18 htt ps:/ /www. huffing! on post.com/ entry/mons a nto-s pin-doctors-target -ca nee r -scientist-inflawed_us_594449eae4b0940f84fe2e57 

19 1ARC letter January 11, 2018, referencing a videotaped deposition of Dr. Blair, March 20, 2017. 

http://governance.iarc.fr/ENG/Docs/CPWild_Smith_Biggs_lucas_20180111.pdf 

20 See response from Dr. Wild to the Committee on Science, Space and Technology, January 11, 2018. 

http://governance.iarc.fr/ENG/Docs/CPWild_Smith_Biggs_lucas_20180111.pdf 

7 
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J. Sass, NRDC Feb 2018 

prevalence of use of this herbicide worldwide, expeditious efforts to replicate these findings are 

warranted". 21 The increase risk of AML was over 2-fold higher in highest exposed applicators 

compared with the never exposed applicators. The possible link with leukemia should be very 

concerning to the public and particularly to pesticide applicators, because AML is a very serious 

fast-growing cancer, with only about one-quarter of the people that have it surviving longer 

than 5 years. The EPA 2017 Cancer Assessment acknowledges these new data, but considers 

them too limited and simply says it will continue to follow the literature. 22 

In summary; the Monograph process: relies only on publicly available studies of sufficient detail 

for a peer assessment, including both industry and non-industry studies; follows a systematic 

review approach using internationally agreed upon best practices; is the consensus product of a 

Working Group of non-IARC experts; invites observers including industry stakeholders to attend 

all aspects of the Working Group meetings including sub-groups and plenary voting sessions; 

will report in the Monographs if there is a significant dissenting perspective among Working 

Group members (there was no such dissent on the glyphosate finding); does not alter any 

findings or conclusions that are not agreed to during the meeting of the Working Group. 

EPA Glyphosate Cancer Assessment- Process Problems 

The EPA Pesticide Office seems to have a questionable and non-transparent process for 

conducting its pesticide cancer assessments. Perhaps most alarming are revelations of a 

disturbing level of communication and collaboration between Monsanto Co. and senior EPA 

official Jess Rowland, who headed up the EPA Cancer Assessment Review Committee for 

glyphosate and many other pesticides. Monsanto Co. internal emails made available by U.S. RTK 

reveal that Rowland told a Monsanto Co. employee in 2015 that he would try to prevent the 

Department of Health and Human Services from conducting its own glyphosate hazard 

assessment, which then came to pass. Monsanto Co.'s regulatory liaison commented in a 2015 

email that Rowland "could be useful as we move forward with ongoing glyphosate defense," 

and Rowland has since left EPA. The concerns of collusion sparked an investigation by the EPA 

Inspector General that is still ongoing.23 

EPA's Pesticide Office seems to be failing the test of public scrutiny for its policy decisions as 

well. The Scientific Advisory Panel (SAP) that reviewed the 2016 assessment disagreed with 

EPA's classification of "not likely to be carcinogenic to humans' at doses relevant to human 

health risk assessment. First, the SAP agreed that the Pesticide Office had inappropriately 

21 Andreotti G, Koutros S, Hofmann JN, Sandier DP, Lubin JH, Lynch CF, Lerro CC, DeRoos AJ, Parks CG, 

Alavanja MC, Silverman DT, Beane Freeman LE. Glyphosate Use and Cancer Incidence in the Agricultural 

Health Study. J Natl Cancer lnst. 2017 Nov 9. https:/ /www.ncbi.nlm.nih.gov/pubmed/29136183 22 Revised glyphosate issue paper: evaluation of carcinogenic potential. EPA Office of Pesticide 

Programs. December 12, 2017. Section 3.5.2 (1), p. 53 23 Paul Thacker. Huffington Post. 06/06/2017. https://www.huffingtonpost.com/entry/epa-inspectorgeneral-probing-collusion-with-monsanto_us_59372108e4b0aba888b99dca 

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J. Sass, NRDC Feb 2018 

conflated a hazard statement (not likely to be carcinogenic) with a risk characterization (at 

doses relevant to risk assessment) without having conducted an exposure and risk assessment. 

24 Second, most of the SAP members supported the stronger classification of "suggestive 

evidence of cancer". Third, the SAP had concerns that the Pesticide Office had failed to follow 

its Agency-wide Cancer Guidelines in ways that biased the conclusions towards the least 

protective "not likely" classification. The SAP's report is in agreement with EPA's Office of 

Research and Development (ORD), including that the Pesticide Office had inappropriately 

dismissed cancer evidence by failing to conduct a systematic review and that a "not likely" 

cancer descriptor was inappropriate and inconsistent with the tumor evidence. 25 

Both the 2016 and 2017 glyphosate cancer assessments follow a systematic review process 

being developed by EPA's Office of Chemical Safety and Pollution Prevention (OCSPP). This 

office, known as the Toxics Office, is now under the management of Nancy Beck, a chemical 

industry lobbyist prior to her recent political appointment at EPA. Dr. Beck's previous foray into 

developing risk assessment guidelines was a failure, as evidenced by the National Academies 

conclusion that the draft government-wide risk assessment bulletin which she authored while 

at the Office of Management and Budget (OMB) was "fundamentally flawed" and the 

unprecedented recommendation for its withdrawal (NAS 2007). 26 

The systematic review approach used by EPA in the glyphosate cancer assessment is 

inconsistent in critical ways with best practices, and recommendations of the National 

Academies (NRC 2014; NRC 2017). 27 The approaches used in OCSPP do not meet the standard 

of transparency and public review of the IRIS program, which recently received praise from 

EPA's Science Advisory Board (SAB): "The program has fully adopted the principles of 

systematic review .. .it is now standard practice for the [IRIS] program to engage stakeholders in 

an early scoping and problem formulation phase, thereby allowing stakeholders to provide 

important input at the very beginning of the process." 28 It is unclear why the Pesticide Office is 

not coordinating with the IRIS program to share resources, save time, and implement the IRIS 

systematic review process that has been developed with public and stakeholder input, and 

favorable review by the National Academies and SAB. 

24 SAP meeting, December 2016. P. 80,86-87. https://www.epa.gov/sites/production/files/2017-

03/ documents/ december _13-16 _ 2016 _ fi na I_ report_ 03162017. pdf 25 Summary of ORD comments on OPP's glyphosate cancer assessment, December 14, 2015. 

https ://us rtk. org/wp-co nte nt/ u ploads/20 17/03/ ORDcom m entsonO P Pglyphosate.pdf 26 Available at http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordiD=l1811 27 National Research Council. 2014. Review of EPA's Integrated Risk Information System (IRIS) Process. 

Washington, DC: The National Academies Press. https://doi.org/10.17226/18764 

National Academies of Sciences, Engineering, and Medicine. 2017. Application of Systematic Review 

Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals. 

Washington, DC: The National Academies Press. https://doi.org/10.17226/24758. 28 Science Advisory Board comments on EPA's response to recommendations on the Integrated Risk 

Information System. September 1, 2017. EPA-SAB-17-008. Available at: 

https ://yosemite .epa .gov /sa b/SABP ROD UCT. NSF /RSSRecentAdditionsBOARD / A9A9ACCE42 B6AAO E85 25 

818E004CC597 /$File/EPA-SAB-17 -008.pdf 

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J. Sass, NRDC Feb 2018 

Instead, the EPA's glyphosate cancer assessment is being conducted according to a purported 

systematic review process that has not been subjected to public and stakeholder engagement, 

or peer review. Further, it veers from the National Academies and IRIS best practices in several 

important ways, all of which are promoted by the chemical industry,29 and favor industry 

outcomes: 

• preferentially relying on Guideline studies, which are conducted by the regulated 

industry to support the approval of its products; 

• preferentially relying on studies following so-called Good Laboratory Practices (GLP), 

which are required by industry product-testing labs to prevent malfeasance and 

misconduct; 

• over-emphasizing the requirement to understand the mechanism of toxicity, so that 

many studies of adverse effects in people are dismissed because the mechanism of 

disease is not fully understood; 

• using methods to score studies that score guideline and GLP studies higher; 

• misusing a 'weight of evidence' (WOE) approach to pit studies that find adverse effects 

against studies that don't, to dismiss the effects studies. 

The EPA Pesticides Office leans on all of the above chemical industry tactics to dismiss the 

following evidence that EPA acknowledges would support a "suggestive" classification for 

glyphosate (EPA Cancer Assessment, Section 6.6.2, p. 141-142): 

• Non-statistically significant non-Hodgkin's lymphoma (NHL) across studies, and in a 

meta-analysis sponsored by Monsanto Co. {Chang and Delzell2016)30 that, according to 

EPA, found results similar to I ARC (EPA Cancer Assessment, p. 64); 

• Limited evidence of a possible exposure-response relationship between glyphosate 

exposure and NHL in case-control studies; 

• A statistically significant trend in tumors in several animal cancer studies, and two 

studies with statistically significant tumor incidence at the highest doses tests, 

compared with concurrent controls; 

Evidence of genotoxic effects in a limited number of tests including damage to DNA and 

chromosomes. 

In each of the cancer evidence streams summarized by EPA above- human, animal, and cellular 

studies- there were also studies that didn't find a link between glyphosate and cancer, or 

29 Rick Becker comments on behalf of the American Chemistry Council on Data Quality in Toxicology 

Studies: A key element in systematic review for evaluating chemical risks. March 20, 2013. Submitted to 

the National Toxicology Program. 

https :/I ntp. niehs. nih .gov I ntp/ ohat/ eva lu at ion process/presentations/ rna rc h2013 /becke r201303 20 _ 508. 

pdf 

3

° Chang ET, Delzell E. Systematic review and meta-analysis of glyphosate exposure and risk of 

lymphohematopoietic cancers. J Environ Sci Health B. 2016;51(6):402-34. 

10 
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J. Sass, NROC Feb 2018 

glyphosate and cellular damage that could lead to cancer. 31 Most prominent among these noeffect studies are the industry-sponsored review articles of Greim et al (2015) and Kier and 

Kirkland (2013) that are heavily cited in EPA's cancer assessment, but dismissed by IARC 

because the underlying studies were not published or otherwise publicly available. 

The Pesticide Office concludes that, "In summary, considering the entire range of information 

for the weight-of-evidence, the evidence outlined above to potentially support the 'suggestive 

evidence of carcinogenic potential' descriptor are [sic] contradicted by other studies of equal or 

higher quality and, therefore, the data do not support this cancer classification descriptor." 

(page 142) The Pesticide Office therefore concludes that, ''The strongest support is for 'not 

likely to be carcinogenic to humans'. "(page 143). The OCSPP systematic review as applied to 

the glyphosate cancer assessment leads to the inclusion of systemic flaws that make the 

glyphosate assessment biased toward industry, inconsistent with best practices identified by 

the National Academy, unreliable and unprotective of human health. 

Only one agent has ever been classified by IARC in the lowest category, Group 4, probably not 

carcinogenic. The chemical is caprolactam, used in nylon and plastics (Volume 39, 1999). This is 

because, in accordance with the IARC guidelines, to classify a chemical into Group 4 requires 

affirmative evidence of lack of carcinogenicity, as opposed to simply a lack of evidence. The U.S. 

EPA Cancer Guidelines apply similarly stringent criteria to classify a substance as "not likely to 

be carcinogenic to humans", that is, "when the available data are considered robust for 

deciding that there is no basis for human hazard concern" (Guidelines, p. 2-57). such as, "animal 

evidence that demonstrates lack of carcinogenic effect in both sexes in well-designed and wellconducted studies in at least two appropriate animal species (in the absence a( ather animal ar 

human data suggesting a potential far cancer effects)." Against the requirements of its own 

guidelines, this is the category into which EPA has now placed glyphosate. We would welcome 

a committee hearing to more closely examine the scientific and procedural integrity of the 

Pesticide Office's assessment of glyphosate health risks. 

Conclusion 

Fundamentally, this hearing is about the ability of a public health agency to call a carcinogen a 

carcinogen, even if it makes a huge amount of money for a powerful corporation. Of course, 

even without IARC, or IRIS, (or the National Toxicology Program's Report on Carcinogens), the 

cancers will still occur- with their obvious terrible toll on individuals, families, health care 

costs, and the economy- but the suffering will be in vain because the tumors won't be 

counted, and the causes won't be tracked. IARC Monographs are considered essential for 

31 1n some cases, the Pesticide Office tried to cast doubt on the glyphosate cancer evidence by: using a 

different statistical method (pair-wise instead of trend tests); comparing tumor evidence with historical 

laboratory records of control animals instead of control animals within the same experiment (some with 

lab records over 10 years old); or discounting the tumors in the high dose groups (EPA 2017 pages 141-

142). 

11 
75 

J. Sass, NRDC Feb 2018 

informing cancer prevention strategies and effective public health decision-making around the 

world. 32 As several cancer assessment experts recently wrote, "the interference by economic 

interests in cancer evaluations conducted by public heath institutions do not bode well for the 

free flow of scientific information that informs and protects the public and workers from clear 

risks of cancer". 33 Are we willing to sell out the public's right to know about harmful chemicals 

in the places we work, live, and play, just so that Monsanto Co. can sell more glyphosate? 

Thank you for the opportunity to address this Committee. 

Respectfully, 

32 Lorenzo Richiardi, Benedetto Terracini; International Agency for Research on Cancer. The first 50 

years, International Journal of Epidemiology, Volume 45, Issue 3, 1 June 2016, Pages 967-968, 

https:/ /doi.org/10.1093/ije/ dyv331 33 Infante PF, Melnick R, Vainio H, Huff J. Commentary: !ARC Monographs Program and public health 

under siege by corporate interests. Am J lnd Med, online 3 February 2018. DOl: 10.1002/ajim.22811. 

http://onlinelibrary.wiley.com/doi/10.1002/ajim.22811/full 

12 
76 

J. Sass Short Professional Biography: 

Jennifer Sass is a Senior Scientist at the Natural Resources Defense Council (since 2001), an 

environmental non-profit organization. She also holds a position as part-time faculty at George 

Washington University Milken School of Public Health (since 2008). Sass is a Board Member of 

the NIEHS National Toxicology Program Board of Scientific Counselors (since 2016). Sass is an 

Authorized GreenScreen Practitioner {2016). Sass is well versed in environmental health science 

and policy particularly pertaining to the US review and regulation of chemicals including 

pesticides, nanomaterials and emerging contaminants. She has published overfour dozen 

articles in peer-reviewed journals. She regularly provides testimony and scientific briefings for 

the U.S. Congress and participates in stakeholder and expert scientific federal advisory 

committees. She holds BSc, MSc, and PhD (1998) degrees from the University of Saskatchewan, 

College of Medicine, Department of Anatomy and Cell Biology, and a Post-Doctoral Certificate 

(2000) from the University of Maryland, College of Medicine, Program in Human Health and the 

Environment. 
77 

Chairman SMITH. Thank you, Dr. Sass. 

And Dr. Tarone. 

TESTIMONY OF DR. ROBERT TARONE, 

(RETIRED) MATHEMATICAL STATISTICIAN, 

U.S. NATIONAL CANCER INSTITUTE 

AND BIOSTATISTICS DIRECTOR, 

INTERNATIONAL EPIDEMIOLOGY INSTITUTE 

Dr. TARONE. Good morning. My European Journal of Cancer Prevention paper differs from most of the published criticisms that you 

may have seen in the press and elsewhere of the IARC glyphosate 

classification. My paper critiques the deliberations of the working 

group completely on IARC’s terms. 

I accept that IARC is evaluating hazard rather than risk, that 

the IARC criteria for determining hazard are reasonable and that 

the body of studies relied upon by IARC is sufficiently complete to 

provide a valid assessment of glyphosate. My critique concludes 

that the IARC classification of glyphosate as a probable carcinogen 

resulted from a flawed and incomplete evaluation of the very rodent cancer studies that they relied upon. 

Although the working group concluded that there was sufficient 

evidence that glyphosate was an animal carcinogen, I conclude that 

a proper summary of the rodent studies would have difficulty supporting even the conclusion that there is limited evidence that 

glyphosate is an animal carcinogen. And I just want to discuss 

briefly one of several examples in which exculpatory rodent data 

were excluded by IARC. 

IARC concluded that glyphosate caused cancer in animals primarily on the basis of two studies in CD- mice. In the first study, 

groups of 50 male and female mice were fed diets with—containing 

increasing dose levels of glyphosate for two years. The original 

study report noted a positive trend in renal adenomas in male 

mice. The tumor counts were 0,0,1,3 at increasing dose levels, and 

this corresponds to a P value of .019 based on an exact test for 

dose-response. 

Additional pathological examination of renal tumors in this study 

revealed one new adenoma in an unexposed mouse, and three of 

the original renal tumors were upgraded from adenomas to carcinomas. So for the final tumor counts after pathology review, they 

were 0,0,1,2 for carcinomas, P value of .063, and 1,0,1,3 for carcinomas and adenomas combined, P equals .065. 

Now, these marginally significant findings were considered to be 

particularly consequential by the IARC working group because of 

the alleged extreme rarity of such tumors in CD–1 mice, and it was 

concluded from this study and the study alone that glyphosate 

caused renal tumors in male mice. 

Now, there was no a priori expectation that glyphosate should 

cause kidney tumors, and ordinarily such a small increase in tumors would not be considered especially noteworthy since around 

20 organs and tissues are typically evaluated in each rodent study. 

Nonetheless, even that small observed increase would be of concern 

if there was also evidence of an increase in renal tumors for female 

mice in that same study. Thus, I was surprised to see that the fe-
78 

male data were not reported with a remarkable sentence stating, 

quote, ‘‘No data on tumors of the kidney were provided for female 

mice.’’ 

IARC has been evaluating rodent studies for over 40 years and 

is aware that the renal tumor rates for female mice would’ve been 

provided in the same report that provided the male tumor rates. 

IARC’s staff should’ve been highly motivated to acquire these 

tumor rates. I obtained the female tumor rates for my review of 

glyphosate rodent studies in the journal Critical Reviews in Toxicology. This is the Greim, et al., paper that Dr. Sass referred to. 

For females, no renal tumors were observed, so there was no evidence of an increase in kidney tumors for female mice exposed to 

the same high levels of glyphosate as males. But even though there 

was no evidence that glyphosate caused renal tumors in female 

mice in this study, the working group still might have argued for 

a sex-specific effect if there was evidence of such an effect in the 

second CD–1 mouse study they relied upon. But inexplicably, in 

spite of devoting three—and I apologize for the—there’s an error in 

the printed comments; it’s three not two paragraphs to the discussion of renal tumors observed in the first mouse study, there is no 

mention at all of kidney pathology in the one paragraph devoted 

to the second mouse study, which is simply astounding. IARC staff 

should’ve been highly motivated to acquire the renal tumor rates 

from the second study because of the male results in the first 

study. 

The renal tumor rates for the second study were also provided 

in a review paper. For males, the renal tumor counts at increasing 

glyphosate exposure level were two, two, zero, and zero, and this 

is P equals .042, but for an inverse association, decreasing tumor 

rates with increasing exposure level. And it’s also noteworthy that 

two of these supposedly extremely rare renal tumors were observed 

in the unexposed mice in this study. Taken together, these two 

studies provide no evidence whatsoever to support the conclusion 

that glyphosate causes renal tumors in male mice, contrary to the 

working group conclusion. And for completeness no tumors were 

observed for female mice in the second study. 

In conclusion, my published paper notes other instances in which 

rodent tumor rates that supported the conclusion that glyphosate 

caused tumors were included in IARC deliberations while tumor 

rates from those same studies that did not support that conclusion 

were excluded. The systematic exclusion of exculpatory evidence is 

inexcusable, particularly when it’s practiced by an influential 

source such as the IARC Monograph Programme. My paper was 

published online in August of 2016, and not one of the specific 

claims of data exclusion in that paper has been refuted. And reports since my paper was published and depositions of key working 

group members related to lawsuits filed against Monsanto have 

fully substantiated the facts presented and questions raised my 

paper. 

[The prepared statement of Dr. Tarone follows:] 
79 

Comments on the IARC classification of glyphosate as a probable human 

carcinogen 

Committee on Science, Space and Technology 

February 6, 2018 

Robert E. Tarone, PhD 
80 

The IARC Monograph Working Groups evaluate three types of evidence in 

assessing the potential carcinogenicity of an agent; animal carcinogenicity studies, 

epidemiologic studies of cancer risk in humans, and "mechanistic and other 

relevant data". For each of the first two categories (animal and human studies) 

the evaluation leads to a conclusion that there is sufficient evidence of 

carcinogenicity, limited evidence of carcinogenicity, inadequate evidence of 

carcinogenicity, or evidence suggesting lack of carcinogenicity. The evaluation of 

mechanistic and other relevant data is not as formalized, and there is some 

subjectivity in how this evaluation contributes to the final carcinogen 

classification. The overall classification of an agent depends largely on the 

summary conclusions regarding the strength of evidence from the animal studies 

and the human studies. Of particular importance with regard to my European 

Journal of Cancer Prevention paper on the glyphosate classification, if the 

Working Group concludes that there is sufficient evidence that the agent is an 

animal carcinogen then the agent will be assigned to Group 28 (possibly 

carcinogenic to humans), Group 2A (probably carcinogenic to humans), or Group 

1 (carcinogenic to humans). 

In explaining occasional differences between IARC classifications and those 

of other regulatory bodies worldwide, IARC often notes that its Monograph 

Program evaluates cancer hazard rather than cancer risk. The following 

paragraph is from page 2 of the current Preamble to every published Monograph. 

A cancer 'hazard' is an agent that is capable of causing cancer under some 

circumstances while a cancer 'risk' is an estimate of the carcinogenic effects 

expected from exposure to a cancer hazard. The Monographs are an exercise 

in evaluating cancer hazards, despite the historical presence of the word 'risks' 

in the title. The distinction between hazard and risk is important, and the 

Monographs identify cancer hazards even when risks are very low at current 

exposure levels, because new uses or unforeseen exposures could endanger 

risks that are significantly higher. 

This distinction could provide a plausible explanation for why the conclusion in 

IARC Monograph 112 on the carcinogenic potential of glyphosate differed from 
81 

that of other bodies (e.g., the EFSA and JMPR, both of which concluded that 

glyphosate exposure from food consumption was not likely to be carcinogenic), 

but my paper points out a more basic problem with the IARC glyphosate 

classification. 

Additional questions have been raised about the IARC glyphosate 

deliberations, including the selection of studies IARC chose to rely upon in 

evaluating glyphosate (IARC has stricter criteria for selecting studies than many 

regulatory bodies) and the makeup of the Working Group (e.g., the inclusion of an 

invited specialist affiliated with the Environmental Defense Fund). These issues 

are not considered in my paper. My paper critiques the deliberations of the 

Working Group that evaluated glyphosate on IARC's terms. I accept that IARC is 

evaluating hazard rather than risk, that the IARC criteria for determining 

carcinogenic hazard are reasonable, and that the body of studies relied upon by 

IARC is sufficiently complete to provide a valid assessment of the carcinogenic 

potential of glyphosate. My critique concludes that the IARC classification of 

glyphosate as a probable carcinogen was the result of a flawed and incomplete 

evaluation of the very rodent cancer studies that IARC relied upon. Although the 

Working Group concluded that there was sufficient evidence that glyphosate was 

an animal carcinogen, I conclude that a proper summary of the rodent studies 

relied upon by IARC would not even support the conclusion that there is limited 

evidence that glyphosate is an animal carcinogen. Without the conclusion that 

there is sufficient evidence that glyphosate is animal carcinogen, the IARC criteria 

would not have supported the overall classification of glyphosate as a probable 

human carcinogen. 

IARC concluded that there was sufficient evidence that glyphosate caused 

cancer in animals, primarily on the basis of two studies in CD-1 mice. In the first 

study, groups of 50 male and female CD-1 mice were fed diets containing 0, 1000, 

5000, and 30000 parts per million glyphosate over a two year period. The original 

study report noted a positive trend in renal tubule adenomas in male CD-1 mice. 

The tumor rates were 0/49, 0/49, 1/50, and 3/50 at increasing dose levels 

(p=0.019). The US EPA requested additional pathological examination of renal 

tumors in this study, including the convening of a Pathology Working Group. One 
82 

additional renal tubule adenoma was discovered in the unexposed control group, 

and three of the original renal tubule tumors were upgraded from adenomas to 

carcinomas. Thus the final tumor rates after the pathological review for 

carcinomas were 0/49, 0/49, 1/50, and 2/50 (p=0.063), and for carcinomas and 

adenomas combined were 1/49, 0/49, 1/50, and 3/50 (p=0.065). These 

marginally significant findings were considered particularly consequential by the 

IARC Working Group because of the alleged rarity of such renal tumors in CD-1 

mice, and it was concluded that this study showed that glyphosate caused renal 

tubule tumors in male CD-1 mice. 

There was no a priori expectation that glyphosate should cause kidney 

tumors, and ordinarily such a small increase in tumors with increasing dose level 

would not be considered especially noteworthy, particularly since around 20 

organs and tissues are typically evaluated pathologically in rodent carcinogenicity 

studies. Nonetheless, even the small observed increase would be of concern if 

there was also evidence of an increase in renal tubule tumors for female mice in 

the same study or for male or female mice in the second CD-1 mouse study relied 

upon by IARC. Thus, the following sentence from the glyphosate chapter of 

Monograph 112 in the discussion of the first CD-1 mouse study is remarkable: "No 

data on tumours of the kidney were provided for female mice." IARC has been 

evaluating rodent carcinogenicity studies for over 40 years, and is aware that the 

renal tumor rates for female mice would have been provided in the original study 

report that provided the male tumor rates. IARC staff should have been able to 

acquire the female tumor rates. In fact, they should have been motivated to 

acquire the female renal tumor rates because of the male results. I obtained the 

female renal tubule tumor rates for the first CD-1 mouse study from a review of 

glyphosate rodent studies published in Critical Reviews in Toxicology (Greim et al., 

2015). For females the tumor rates were 0/50, 0/50, 0/50, and 0/50. That is, 

there was no evidence from female mice exposed to the same high levels of 

glyphosate for an increase in kidney tumors. The review paper by Greim et al. 

was discussed briefly in the summary of the Working Group deliberations in 

Monograph 112, but the review and its accompanying supplemental material 

were, for the most part, discounted. 
83 

Even though there was no evidence that glyphosate caused tumors in 

female CD-1 mice in this study, the Working Group still might have argued for a 

sex-specific carcinogenic effect, particularly if there was evidence of such an 

effect in the second CD-1 mouse study relied upon by !ARC. Inexplicably, 

however, in spite of devoting two paragraphs to the discussion of renal tubule 

tumors observed in first CD-1 mouse study, there is no mention whatsoever of 

kidney pathology in the one paragraph of the Monograph 112 glyphosate chapter 

devoted to the second CD-1 mouse study. Again, !ARC staff should have been 

motivated to acquire the renal tumor rates from the second study because of the 

male results from the first study. No explanation has been offered by !ARC for 

this disturbing omission of relevant kidney tumor data. The renal tubule tumor 

rates from the second study were also provided in the supplemental material of 

the Greim et al. review paper. Male and female mice were exposed to dose levels 

slightly lower than those in the first CD-1 mouse study, and for males the renal 

tubule tumor rates at increasing glyphosate exposure level were 2/50, 2/50, 0/50, 

and 0/50 (p=0.042 for an inverse association with glyphosate dose level). That is, 

while a marginally significant increase in renal tubule tumors was observed for 

males in the first mouse study based on small numbers of tumors, a marginally 

significant decrease in renal tubule tumors was observed in the second mouse 

study based on small numbers. It should also be noted that two of the 

supposedly extremely rare renal tumors were observed in the unexposed mice in 

this study. Taken together these two studies provide no evidence whatsoever to 

support the conclusion that glyphosate causes renal tumors in male mice. For 

female mice in the second study the tumor rates were 0/50, 0/49, 0/50, and 0/50. 

Thus, there is no evidence from the two mouse studies relied upon by the 

Working Group that glyphosate causes renal tumors in male or female mice. 

My published paper notes other instances in which rodent tumor rates 

which might support a conclusion that glyphosate is associated with tumor risk 

were included in the Monograph 112 glyphosate deliberations, while tumor rates 

from the same studies that do not support an association between glyphosate 

exposure and tumor risk were excluded. Such systematic exclusion of exculpatory 

evidence is outrageous, particularly when it is practiced by an influential source 
84 

such as the IARC Monograph Program. My paper was published online in August 

of 2016, and not one of the claims in the paper has been refuted. In addition to 

critiquing the Monograph 112 Working Group summary of rodent studies I also 

raised questions about the summary of epidemiologic studies by the Working 

Group. Publications since August 2016 and depositions of key Working Group 

members relating to lawsuits filed against Monsanto after the IARC glyphosate 

classification was announced in March of 2015 have substantiated the facts 

presented, and questions raised, in my paper. 

I have no conflict of interest whatsoever with regard to glyphosate or 

Monsanto. Since my retirement in June of 2016 I have received no payment for 

any of my continued scientific efforts. No payment was received for writing the 

European Journal of Cancer Prevention paper, nor was I requested by anyone to 

write the paper. The decision to write the paper was mine alone, after I 

discovered the serious scientific errors made by IARC in the glyphosate 

deliberations. Nobody else contributed in any way to the writing of the paper. 

References 

Greim H, Saltmiras D, Mostert V, Strupp C (2015). Evaluation of carcinogenic 

potential of the herbicide glyphosate, drawing from tumor incidence data from 

fourteen chronic/carcinogenicity rodent studies. Crit Rev Toxico/45:185-208. 

Tarone RE (2018). On the International Agency for Research on Cancer 

classification of glyphosate as a probable human carcinogen. Eur J Cancer Prev 

27:82-87 
85 

OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) 

BIOGRAPHICAL SKETCH 

Provide the following infonnation for the Senior/key personnel and other significant contributors. 

Follow this format for each person. DO NOT EXCEED FIVE PAGES. 

NAME: Tarone, Robert Ernest 

eRA COMMONS USER NAME (credential, e.g., agency login): TARONER 

POSITION TITLE: Biostatistics Director 

EDUCATION!TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, 

include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) 

DEGREE Completion 

INSTITUTION AND LOCATION (if Date FIELD OF STUDY 

applicable) MMIYYYY 

University of California, Davis B.S. 06168 Mathematics 

University of California, Davis M.S. 06169 Mathematics 

University of California, Davis Ph.D. 06/74 Mathematics 

A. Personal Statement 

I have extensive experience in providing statistical direction and analysis in a variety of areas of medical 

research that are relevant to the goals of the numerous and varied proposed investigations of determinants of 

disease in the Southern Community Cohort Study. As a Mathematical Statistician at the National Cancer 

Institute I was heavily involved in providing statistical assistance to a wide variety of laboratory and clinical 

researchers, including investigators in the fields of immunology, DNA repair, and cancer-prone inherited 

diseases. In addition, I was involved in the design, conduct and statistical analysis of several large scale 

observational studies, including the AL TS trial of HPV testing to detect cervical cancer, the nationwide NCI 

case-control study of electromagnetic fields and childhood leukemia risk, the prospective Agricultural Health 

Study, and the NCI case-control study of cell phones and brain tumor risk. I have also had extensive 

experience, while at the International Epidemiology Institute and Vanderbilt University Department of Medicine, 

in the conduct of retrospective and prospective cohort studies to evaluate potential health risks in numerous 

areas of environmental and occupational epidemiology. In summary, my record of statistical collaboration in 

productive laboratory and epidemiologic research demonstrates that I am well qualified for my role in the 

proposed project. 

1. Signorello L.B., Cai Q., Tarone R.E., Mclaughlin J.K. & BlotW.J. (2009). Racial differences in serum 

cotinine levels of smokers. Dis Markers 27(5):187-92. PMID: 20037205 

2. Lipworth L., Mumma M.T., Cavanaugh K., Edwards T.L., lkizler T.A., Tarone R.E., Mclaughlin JK, Blot WJ. 

(2012). Incidence and predictors of end stage renal disease among low income blacks and whites. PLoS 

One 7(1 0): e48407. PMID: 23110237 

3. Lipworth, L., Fazio S., Kabagambe E.K., Munro H., Nwazue B.C., Tarone R.E., Mclaughlin J.K., Blot W .J. 

& Sampson U.K. (2014). A prospective study of stalin use and mortality among 67,385 blacks and whites in 

the Southeastern United States. Clin Epidemiol1 9(6):15-25. PMID: 24379700 

4. Sonderman, J.S., Munro H.M., Blot W.J., Tarone, R.E. & Mclaughlin, J.K. (2014). Suicides, accidents, and 

other external causes of death among blacks and whites in the Southern Community Cohort Study. PLoS 

One 9(12):e114852. PMID: 25486418 
86 

B. Positions and Honors 

Positions and Employment 

1971 -74 Associate in Biostatistics, Department of Epidemiology and Preventive Medicine, UCD, Davis, CA 

1974-76 Staff Fellow, Division of Cancer Cause and Prevention, National Institutes of Health, Bethesda, 

MD 

1976- 93 Mathematical Statistician, Division of Cancer Etiology, National Institutes of Health, Bethesda, MD 

1993- 02 Chief, Statistical Research and Applications Section, Division of Cancer Epidemiology and 

Genetics, National Institutes of Health, Bethesda, MD 

2003- 12 Professor, Department of Medicine, Vanderbilt University, Nashville, TN 

2002- Biostatistics Director, International Epidemiology Institute, Rockville, MD 

Other Experience and Professional Memberships 

1969 - 71 Medical Corpsman, United States Army 

1974- American Statistical Association 

1983- International Statistical Institute {elected member) 

~ 

1979 

1983 

1992 

1999 

2001 

Public Health Service Special Achievement Award 

Fellow, American Statistical Association 

National Institutes of Health Director's Award 

Division of Cancer Epidemiology and Genetics Exemplary Service Award 

National Institutes of Health Merit Award 

C. Contribution to Science 

1. I have derived and published a number of statistical methods for a variety of problems arising in biomedical 

research. These include non parametric tests for censored survival data, methods for testing for 

heterogeneity of odds ratios across several strata, a method for combining relative risk estimates from 

multiple strata or studies, tests incorporating information on historical control tumor rates in animal 

carcinogenesis bioassays, estimation methods for identifiable contrasts in age-period-cohort analyses of 

disease rates, and statistical methods for the analysis of in vitro cell survival data from colony forming 

assays. 

a. Tarone, R.E. & Ware, J. {1977). On distribution-free tests for equality of survival distributions. 

Biometrika, 64:156-60. 

b. Tarone, R.E. {1982). The use of historical control information in testing for a trend in proportions. 

Biometrics, 38:215-20. 

c. Tarone, R.E .. Scudiero, D.A. & Robbins, J.H. {1983). Statistical methods for in vitro cell survival 

assays. Mutat Res, 111 {1 ):79-96. PMID: 6621576 

d. Tarone, R.E. & Chu, K.C. {1996). Evaluation of birth cohort patterns in population disease rates. 

Am J Epidemiol, 143(1 ):85-91. PMID: 8533751 

2. Although ecologic analyses disease rates, either over time or across geographic areas, must be interpreted 

cautiously, a number of my publications have developed methods for strengthening inferences from such 

analyses. Application of these methods has provided evidence that breast cancer rates in U.S. women 

decreased for women born after 1945, that changes in cigarette smoking can be detected in lung cancer 

rates in early adulthood {20-34 years of age), and that decreases in prostate cancer and breast cancer 

death rates were partly a result of early detection via PSA testing and mammography screening, 

respectively. 

a. Tarone, R.E. & Chu, K.C. {1992). Implications of birth cohort patterns in interpreting trends in 

breast cancer rates. J Natl Cancer Ins!, 84{18):1402-10. PMID: 1512791 

b. Grauman, D.J., Tarone, R.E., Devesa, S.S. & Fraumeni, J.F. Jr. {2000). Alternate ranging methods 

for cancer mortality maps. J Nail Cancer Ins!, 92(7):534-43. PMID: 10749908 

c. Jemal, A., Chu, K.C. & Tarone, R.E. (2001 ). Recent trends in lung cancer mortality in the United 

States. J Nail Cancerlnst, 93(4):277-83. PMID: 11181774 
87 

d. Chu, K.C., Tarone, R.E. & Freeman, H.P. (2003). Trends in prostate cancer mortality among black 

men and white men in the United States. Cancer, 97(6):1507-16. PMID: 12627516 

3. A long-standing interest in the control of the false-positive error rate in medical research has led to several 

publications, on both the methodologic and the philosophic issues involved in reducing the publication of 

false-positive results. The publications document the magnitude of the problem and provide guidance on 

reducing the probability of reporting false-positive findings. 

a. Tarone, R.E. (1990). A modified Bonferroni method for discrete data. Biometrics, 46(2):515-22. 

PMID: 2364136 

b. Boffetta, P., Mclaughlin, J.K., LaVecchia, C., Tarone, R.E., Lipworth, L. & Blot, W.J. (2008). 

False-positive results in cancer epidemiology: a plea for epistemological modesty. J Nat! Cancer 

lnst, 100(14):988-95. PMC2467434 

c. Joannidis, J.P.A., Tarone, R. & Mclaughlin, J.K. (2011 ). The false positive to false negative ratio in 

epidemiologic studies. Epidemiology, 22(4):450-6. PMID: 21490505 

d. Mclaughlin JK, Tarone RE. False positives in cancer epidemiology. Cancer Epidemiol Biomarkers 

Prev 2013;22(1):11-15. PMID: 23118145 

4. I have been involved in the design and analysis of numerous cohort studies to evaluate the impact of 

lifestyle, environmental or occupational risk factors on disease risk. These studies have resulted in 

numerous publications on a wide variety of both disease endpoints and risk factors. 

a. Alavanja, M.C., Samanic, C., Dosemeci, M., Lubin, J., Tarone, R., Lynch, C.F., Knott, C., Thomas, 

K., Hoppin, J.A., Barker, J., Coble, J., Sandier, D.P. & Blair, A. (2003). Use of agricultural 

pesticides and prostate cancer risk in the Agricultural Health Study cohort. Am J Epidemiol, 

157(9):800-14. PMID: 12727674 

b. Sigurdson, A.J., Doody, M.M., Rao, R.S., Freedman, D.M., Alexander, B.H., Hauptmann, M., 

Mohan, A.K., Yoshinaga, S., Hill, D.R., Tarone, R., Mabuchi, K., Ron, E. & Line!, M.S. (2003). 

Cancer incidence in the US radiologic technologists health study, 1983-1998. Cancer, 97(12):3080-

9. PMID: 12784345 

c. Lipworth, L., Sonderman, J.S., Mumma, M.T., Tarone, R.E., Marano, D.E., Boice, J.D. Jr. & 

Mclaughlin, J.K. (2011 ). Cancer mortality among aircraft manufacturing workers: an extended 

follow-up. J Occup Environ Med, 53(9):992-1007. PMID: 21866047 

d. Sonderman, J.S., Munro, H.M., Blot, W.J., Tarone, R.E. & Mclaughlin, J.K. (2014). Suicides, 

accidents, and other external causes of death among blacks and whites in the Southern Community 

Cohort Study. PLoS One, 9(12):e114852. PMC4259484 

Complete List of Published Work In MyBibllography: 

http://www.ncbi.nlm.nih.gov/sites/myncbi/1v0ivVFklq95f/bibliograpahy/48692470/public/?sort=date&di 

rection=ascending 

D. Research Support 

Ongoing Research Support 

2R01 CA092447-10 (Blot, Signorello) 

NIH/NCI 

Southern Community Cohort Study 

09/30/01-08/31/16 

The major goal of this project is to investigate the causes of racial disparities in the occurrence of cancer in 

the southern United States. 

Role: Co-Investigator 

5P50CA098131-12 (Arteaga) 

NIH/NCI 

09/17/13-08/31/18 

Spore In Breast Cancer- Project 3 (Identification of Prognostic Factors for Triple Negative Breast Cancer) 
88 

Project 3: The proposed two-year study will be supported by the current cycle of the breast cancer SPORE 

grant, with subsequent replication of findings to be sought within the NBHS and SCCS populations as part 

of research for the planned renewal of the SPORE grant. 

Role: lEI PD/PI 

Completed Research Support 

5 U01 CA137026-02 (Boice) 

NIH/NCI 

08/01/10-07/31/15 

Cancer Mortality among Military Participants at U.S. Nuclear Weapons Tests 

To evaluate the risk of radiation-induced cancers and quantify the risk in terms of low-dose radiation 

received gradually from external exposures and from inhaled or ingested radionuclides in fallout among 

military participants at aboveground nuclear weapons tests in Nevada and the Pacific testing areas. 

Role: Statistician 
89 

Chairman SMITH. Thank you, Dr. Tarone. 

Dr. Lowit, in your testimony you mentioned that when mice were 

injected with large doses of glyphosate that some did manifest 

symptoms of cancer-like conditions but that when the mice were 

just exposed to glyphosate, there was no effect. There were no 

symptoms. It seems to me that that’s a huge difference. No one is 

suggesting that humans be injected with large doses of glyphosate. 

Why is it that IARC doesn’t acknowledge the distinction between 

high doses that are being injected and simple exposure or inhalation, which has not resulted in any cancer-like symptoms? And it 

seems to me that they are intentionally misleading the American 

people, and maybe they have some kind of a vendetta against 

chemical companies, but why or how do you explain the lack of 

honesty and openness and transparency by IARC? 

Dr. LOWIT. So thank you, Chairman Smith, for that question. So 

I’m sorry if my South Carolina accent comes out. So it’s ingest, so 

I—through the oral route, not inject through the—— 

Chairman SMITH. Okay. Ingest—— 

Dr. LOWIT. Ingest through the oral route. 

Chairman SMITH. Okay. 

Dr. LOWIT. So I apologize for that lack of clarity. 

Chairman SMITH. But my—— 

Dr. LOWIT. So the question is—so I think it’s important that— 

I’m not going to comment on the value of the IARC process. I can 

tell you that EPA has been fully transparent in our evaluation. Our 

draft issue paper was reviewed by the Scientific Advisory Panel. In 

fact, the transcript from that meeting is publicly accessible. We’re 

now looking forward to public comment on our white paper for the 

cancer. 

Chairman SMITH. Any—was that—I didn’t understand that. It’s 

just a statement as to why you think they have been less than 

transparent? 

Dr. LOWIT. I think that’s—I’m not going to debate the transparency of IARC. 

Chairman SMITH. Okay. 

Dr. LOWIT. What we have done at EPA whereas in cases where 

IARC has looked at review articles, we’ve acquired the raw study 

reports, so we’ve been able to look at information. The full study 

reports for IARC cannot do that. 

Chairman SMITH. I’m just curious. When you talked about large 

doses of ingestion by the mice, how much are you talking about? 

A large percentage of their body weight or how much were they— 

did they ingest? 

Dr. LOWIT. So in terms of toxicology studies, often studies—and 

with glyphosate are in the ingestion of hundreds of milligrams per 

kilogram per day and what we define as the limit dose. Internationally, most regulatory organizations recognize 1,000 milligrams per kilogram per day as international standard for the limit 

dose. And in most—in many cases, glyphosate studies are actually 

done at that limit dose—— 

Chairman SMITH. Okay. 

Dr. LOWIT. —which is why we conclude there’s very little hazard. 

Chairman SMITH. And it’s very unlikely that any human would 

ingest anything near to that equivalent amount? 
90 

Dr. LOWIT. Oh, no. 

Chairman SMITH. Okay. Dr. Pastoor, you pointed out—and I was 

going to highlight as well—that I think IARC has found that something like 999 out of 1,000 substances created cancer. Only one was 

deemed to be probably not cancer-causing. Do you think that their 

process is flawed, their investigations are flawed, and do you think 

they have predetermined conclusions they’re trying to reach? 

Dr. PASTOOR. They may or may not. I can’t really comment in 

particular on glyphosate. I’m not here representing a critique or a 

defense of glyphosate. But what I would say is that there is a flaw 

in their scientific process. When you don’t take into consideration 

potency—which, Chairman Smith, you just brought up—is that if 

a significant portion of a body weight of an animal is being overwhelmed with a particular chemical, whether it’s glyphosate or 

anything else, and you’re declaring something to be carcinogenic, 

that’s erroneous science. That’s offsetting. That’s misinforming the 

public, and it doesn’t serve any process and it’s actually more 

harmful than helpful. 

Chairman SMITH. Okay. I agree. And I like that phrase ‘‘erroneous science.’’ I’m going to adopt it in this case and maybe in 

other instances as well. 

Dr. Tarone, you wrote a paper in 2016 and you came to the conclusion that IARC’s designation of glyphosate was a result of a, 

quote, ‘‘flawed and incomplete evaluation of experimental evidence.’’ What is the general scientific community’s response been to 

that paper? And what was IARC’s response? 

Dr. TARONE. There’s been surprisingly little response actually. 

I’ve been amazed. 

Chairman SMITH. Okay. 

Dr. TARONE. But with regard to IARC, I mean, this paper has 

gone through an incredible—I mean, it’s the weirdest experience 

I’ve ever had in 44 years of publishing in peer-reviewed journals. 

And it’s—I mean, I just—really, it’s stunning. But IARC did eventually submit a letter to the journal responding to my paper, and 

I received this in January of 2016. And—no, 2017, I’m sorry, and 

I responded to their letter. And I assumed that both letters would 

be published in the journal along with the paper. IARC’s letter was 

not responsive to any of the specific criticisms I raised. 

Chairman SMITH. Okay. 

Dr. TARONE. They complained about, you know, ‘‘Who wrote— 

who paid you to do this and what role did they play in writing and 

editing the paper?’’ They raised technical issues about what constitutes a research study and that this wasn’t a research study, but 

they didn’t deal with any of the specifics. 

Chairman SMITH. Okay. 

Dr. TARONE. And for some reason neither letter was published, 

and I’ve never been fully clear about why. 

Chairman SMITH. Okay. 

Dr. TARONE. I don’t know. I can’t figure out why that happened. 

Chairman SMITH. The point being IARC was not responsive to 

the substance of your—— 

Dr. TARONE. Not to the substance, and as I said, nobody has specifically refuted any of the claims that I’ve made about the exclusion—— 
91 

Chairman SMITH. Okay. 

Dr. TARONE. —of rodent studies that should have been included. 

Chairman SMITH. Okay. Thank you, Dr. Tarone. That concludes 

my time. 

And the gentlewoman from Texas, the Ranking Member, Ms. 

Eddie Bernice Johnson, is recognized for her questions. 

Ms. JOHNSON. Thank you very much, Mr. Chairman. 

Let me precede my question with this statement. I don’t believe 

any company puts anything on the market that they knowingly 

know that it harms people. I think it’s like the little book Who 

Moved My Cheese? Sometimes, it’s hard to change when you find 

out what the facts are. And so—and every company that has any 

respect for itself is going to defend itself when it can. 

But I want to ask Dr. Sass. Can you discuss the importance of 

keeping the development of scientific assessments on chemicals 

such as glyphosate and other toxic chemicals free from undue influence by industries or others? An example is what are the consequences if chemical risk assessments are driven by industry, and 

more importantly, if industry-sponsored chemical assessments are 

given the same weight and authority as truly independent scientific 

studies? 

Dr. SASS. Thank you. I would like to comment on that, and I 

think that glyphosate is a perfect example of where that’s happening because we can really see the difference in when you have 

an IARC assessment, which is a public health agency of the World 

Health Organization that links it to some level of carcinogenicity 

probably carcinogenic in humans. And then you have—based—including on Monsanto’s studies and other studies supported by the 

registrant, and then you have agencies that are calling it not likely 

carcinogenic, EPA, which is a regulatory agency. 

And I want to talk about some of those differences because the 

impact on public health is severe potentially. First of all, Mr. 

Smith’s comment about the doses that there—that they were— 

that—well, what Anna suggested what—that they were at high 

doses, I want to talk about the limit dose for a quick second because it has a toxicological definition, and these studies did not exceed it. So an arbitrary 1,000 mgs per kg per day was not what 

IARC used. They used a toxicological definition. And these studies 

didn’t exceed it at the high dose, so they should have been included. 

Dr. Pastoor’s statement referencing 16th century Paracelsus 

medicine, to then criticize IARC being half-a-century behind is just 

ridiculous. Paracelsus did say the dose makes the poison, and 

there’s a lot of truth in that, but that’s not the whole truth. The 

truth is that what’s being missed here is considering vulnerable 

populations potentially. We need to protect the EPA, and regulatory agencies need to be able to protect the whole population, 

so—including pregnant women and children, elders, people with 

preexisting diseases and chronic diseases, people that are high-end 

users or highly exposed in—as well as the Keith Richards of the 

world. We need to bracket all of those people and protect them. 

And, Dr. Tarone, I do have some answers for the exclusion of 

those rodent data, but primarily, they weren’t available to IARC 

and IARC relies on public data. The data sets were huge. They 
92 

were hidden in appendices. The IARC only had it 30 days in advance. But in addition, had IARC had those data, it would have 

likely come up with an even stronger link to cancer because there 

was even more tumors than Dr. Greim, the author of that review 

article, had revealed. Those have all come to light now through 

EFSA, so the European Food Safety Authority. They’ve been reanalyzed separately by non-industry scientists. And we now know that 

there’s data that also show tumors in the animals linking to malignant lymphomas and hemangiosarcomas, which, Dr. Tarone, I 

think you didn’t analyze. I think you may have focused on the kidney tumors only. 

So, in addition, Dr. Greim, the author of that paper, is not only 

of questionable scientific integrity for failing to report all those tumors but also ethical potential as well. He’s the main author in 

some diesel emissions studies that put monkeys into chambers 

being reported in the New York Times right now. So—— 

Dr. TARONE. Can I respond? 

Mr. LUCAS. [Presiding] Dr. Tarone, would that be appropriate for 

the Ranking Member? 

Ms. JOHNSON. Yes. 

Mr. LUCAS. It’s her time. Please respond. 

Dr. TARONE. Well, it’s totally incorrect to say that IARC should 

not have acquired those data because if—and I want to say something about the Greim paper. I relied on the Greim paper only for 

the data. They included supplemental tables with that review 

paper that included the underlying basic tables of tumor rates from 

every study that they reviewed. So I was not relying on Greim, et 

al., for their conclusion in any sense. I was only relying on it for 

the data. 

Dr. SASS. Well, the summary tables can be used, and EPA had 

those data for years, probably decades and didn’t ask for the underlying data, so to blame IARC for not having gotten it in 30 

days—— 

Mr. LUCAS. The gentlelady’s time is expired. 

The Chair would note to my colleagues we now have a series of 

three votes underway that, once the votes are over, we will return 

and continue this hearing. And with that, the hearing will stand 

in recess subject to the call of the Chair. 

[Recess.] 

Mr. LUCAS. This full Committee hearing of the Science Committee is reconvened. I will return to regular order, and I believe 

I was the next one in line to ask questions, so I’ll recognize myself 

for five minutes. 

And with that, I turn to Mr. Tarone. Would you care to expand 

and explain a little bit more about your analysis of the Monograph 

112 program and all those issues? 

Dr. TARONE. Yes. I specifically want to answer a couple of issues 

that Dr. Sass raised. First with regard to hemangiosarcomas, I did 

consider hemangiosarcomas, and it in fact is one of the examples 

in which IARC excluded exculpatory data. In the second mouse 

study where they did not discuss renal tumors, they emphasized 

the finding in hemangiosarcomas that Dr. Sass referred to. And 

there were four hemangiosarcomas in the highest dose group, and 

that was all—none in the other three groups. 
93 

But in the first mouse study, the one where they spent three 

paragraphs on renal tumors, they didn’t mention 

hemangiosarcomas, so it’s the same thing that happened with renal 

tumors. So—and it turns out that in that study there was one 

hemangioma in the low-dose group and one hemangiosarcoma in 

the mid-dose group and none in the highest-dose group. And by the 

way, that highest-dose group, glyphosate was three percent of the 

diet that they ate for every day for two years. It’s an incredibly 

high dose. So you would have—if what they saw in the second 

study was a true high dose effect, you would have expected to see 

it in the first study. And—but again that was not even mentioned 

in the IARC Monograph. 

And Dr. Sass also raised the issue of the accuracy of the tumor 

rates that I got from the supplemental tables in the Critical Reviews in Toxicology paper. And in fact, as I pointed out at the end 

of my comments, everything in my paper has in fact been substantiated by things published since, including comments submitted to 

the EPA glyphosate SAP by Chris Portier, who was the scientific 

expert for the IARC working group. And his comments were presenting his statistical analysis of all of the rodent studies that EPA 

was considering. And they considered many more than IARC, but 

they also considered all the studies that IARC relied upon. 

If you look at his tables upon which his analysis was based, in 

every case in which I indicated in my paper that IARC had excluded tumor rates, those tumor rates are in those tables in the 

comments he submitted to EPA. They were included in his EPA 

analysis, which is an admission that they should have been included in the IARC analysis. Moreover, they were exactly the rates 

that I reported that I got from the supplementary tables in the 

Greim, et al., review. So certainly, Christopher Portier now thinks 

that those rates are okay. 

Mr. LUCAS. Thank you, Doctor. 

Dr. Pastoor, could you visit with us for a moment about the ways 

in which the current Monograph Programme classification system 

on carcinogenicity might be outdated? Expand on that, please. 

Dr. PASTOOR. Well, the primary reason that it’s outdated and 

outmoded and needs to either be scrapped or considerably revised 

is because they stick with a hazard classification system. All they 

do is declare something as being carcinogenic or not. Modern 21stcentury risk-assessment-oriented regulatory programs such as 

what Dr. Lowit has described with the United States EPA uses 

that risk-based system to put hazard in context of risk: how much 

would cause that effect; what is the potency of that particular 

chemical? IARC was created over—nearly 50 years ago, and they 

really haven’t progressed beyond the point of only classifying 

things by its carcinogenicity but not putting it in the context of 

risk. 

Mr. LUCAS. Thank you. I think with that now I will yield back 

and turn to—I think in the next order would be the gentleman Mr. 

Tonko for five minutes for questions. 

Mr. TONKO. Thank you, Mr. Chair. And welcome, everyone. 

This hearing has been framed around the need to uphold scientific integrity standards in publicly funded research. If that is a 

serious concern for this Committee, then I implore us to take up 
94 

H.R. 1358, which I’ve authored, the Scientific Integrity Act. This 

Congress has a duty assigned directly to this Committee to ensure 

that public or publicly funded science is conducted, reviewed, communicated to the public and incorporated into policymaking transparently and free from distorting political, ideological, financial, or 

other undue influence. 

Public science informs national policy on everything from pesticides to power grids. Our nation’s cities and States need credible 

information to prepare for climate change. Our families deserve to 

know if unsafe chemicals are being sprayed on their food, dumped 

in their water, or added into the products they buy. As representatives, we need to reach conclusions on these high-stakes questions 

based on rigorous independent scientific facts, not predetermined 

opinions. We have a duty to ensure that political interference of the 

scientific process and attacks on the work of federal scientists do 

not get in the way of our responsibility to safeguard our public 

health and our national security. 

The rules and norms of our public science are standards that 

have made America a leading light in the global scientific community for decades. We have seen those standards being actively and 

deliberately eroded over the past year. Scientists should always be 

held to the highest ethical and professional standards. In return, 

it is our job to uphold standards that ensure scientists are not impugned for reporting their impartial findings. 

The Scientific Integrity Act restores our baseline for scientific 

independence by requiring every federal agency that funds or conducts scientific research to establish clear scientific integrity standards and set basic requirements for how the agency will adhere to 

those principles. 

Science is not about getting the results you want. Scientific integrity is about ensuring a process and atmosphere in which the 

science leads us to real, unvarnished results. The issue we should 

be focused on is whether glyphosate is safe, and finding the answer 

to this question is too important for us to let this be a partisan 

issue. These are chemicals that people have in their homes. This 

is on the food our children eat. We should be able to trust that the 

science we rely upon to make public health decisions is not being 

distorted or manipulated. 

While the tactics used by industry to influence science may have 

dramatic negative consequences on the independence and credibility of scientific review boards or advisory panels, the real victims 

of this kind of designed ignorance are everyday people. Without 

credible science to determine safe levels of exposure, millions of 

people around our country will be at risk. 

Dr. Sass, how do science agencies like IARC function in order to 

protect the public health? 

Dr. SASS. Thank you. IARC and other public health institutes 

put out very credible information about the potential hazards of 

chemicals and other substances. After reviewing all the data, 

IARC, for the glyphosate assessment, brought experts from all over 

the world from multiple different countries. They have different 

areas of expertise. They all come together as a working group. 

They—all of the discussion of all of the data—publicly available 

data is done in front of everybody. There’s a plenary session where 
95 

people get to also discuss what the different subject matter experts 

have come up with in their area. 

And the result of these very credible, transparent, publicly generated hazard assessments is to then support potentially risk assessments but also to support nonregulatory or even non-risk-related decisions that can be made, for example, not only by government regulatory agencies but also by forward-thinking companies 

and businesses looking to work with safer or less toxic or less hazardous chemicals are starting to replace it in their products. 

There’s retailers that care about this. There’s a whole area of green 

chemistry that’s very interested in this, and of course medical professionals, occupational health experts, all of these people care 

about understanding the hazard of materials even if they don’t— 

haven’t—there hasn’t been a full risk assessment to understand potency and dose-response and the other things that come afterwards. 

Mr. TONKO. And why is it important that independent bodies review chemicals for potential exposure risks? 

Dr. SASS. Well, all the available data should be looked at. I believe that, but that’s also what the agencies believe and it’s what 

IARC did. Many of the studies that relied on were supported or 

sponsored by the regulated industry, and that’s fine. That’s normal. 

That happens. But there are systematic review procedures for reviewing and evaluating confidence in those studies on a lot of different parameters. And if all of those different parameters aren’t 

available to do a proper robust review and assessment of the confidence, then it’s more difficult. 

And so we should—instead of a priori making decisions about 

what data is in or out of the pot, it should all be looked at and reviewed, which is what IARC did. 

Mr. TONKO. Thank you. Mr. Chair, I have several documents 

which I would like included in the record, including the Monsanto 

battle plan, laying out their preliminary attack on IARC, the IARC 

preamble defining the roles of working group members and participants, a list of participants from the IARC glyphosate Monograph, 

commentaries by several scientists on the strength of the IARC 

glyphosate evaluation, the FIFRA Science Advisory Panel report 

from December 2016 concluding that EPA did not follow its own 

guidelines for carcinogen risk assessment in evaluating glyphosate, 

and a letter from the United Nations special rapporteur stressing 

how essential the work of the National Institute of Environmental 

Health Science is to protecting human rights. 

Mr. LUCAS. Without objection. 

[The information appears in Appendix II] 

Mr. LUCAS. And the gentleman’s time is expired. 

Mr. TONKO. Thank you, Mr. Chair. 

Mr. LUCAS. The Chair now turns to the gentleman from Texas, 

Mr. Babin, for five minutes. 

Mr. BABIN. Thank you, Mr. Chairman. I appreciate it. And thank 

you to the witnesses for being here. 

Dr. Anna Lowit, if you don’t mind, the EPA’s risk assessment 

process explicitly includes opportunities for experts who did not 

contribute to the assessment to review and comment on a draft of 

the scientific analysis, is that correct? 
96 

Dr. LOWIT. That’s correct. 

Mr. BABIN. Okay. The EPA’s risk assessments like the one on 

glyphosate developed by the Office of Pesticide Programs are also 

subjected to rigorous independent peer review. Is that correct? 

Dr. LOWIT. So EPA’s cancer evaluation has been subject to the 

FIFRA Scientific Advisory Panel. That’s true. 

Mr. BABIN. Okay. As I understand it, the National Academies, 

which is similar to IARC, develops reports by expert panels and 

has outside peer reviews and evaluate each and every report to ensure scientific accuracy. However, unlike EPA and NAS, IARC 

Monographs do not employ any independent outside peer reviews. 

Instead an IARC Monograph working group collaborates behind 

closed doors to select studies, analyze data, and reach conclusions. 

So without any public engagement or independent scientific peer 

review, the working group acts hand-in-hand with IARC staff as 

judges, juries, and executioners. Clearly, these IARC procedures 

fall well short of meeting 21st-century standards for transparency 

and scientific credibility. And I would like to know if you agree 

with that. 

Dr. LOWIT. So what I can answer is EPA’s transparent approach, 

that our cancer evaluation was reviewed by the FIFRA—excuse 

me—Scientific Advisory Panel. The transcript from that meeting is 

actually publicly available. Our document is now available for public—will be open for public comment. It’s been released on our 

docket, and so our process is quite transparent. 

Mr. BABIN. Do any of the other witnesses agree with that statement? Now, let me repeat it. Without any public engagement or 

independent scientific peer review, the working group acts hand-inhand with IARC staff as judge, jury, and executioner. IARC procedures fall well short of meeting 21st-century standards of transparency and scientific credibility. Would you other three agree with 

that? Dr. Pastoor? 

Dr. PASTOOR. Yes, I would generally agree with that. I think 

IARC needs to be brought up to the standards of transparency that 

is exhibited by the United States EPA. 

Mr. BABIN. Okay. Thank you. Dr. Sass? 

Dr. SASS. I disagree because the meetings are open at IARC. Observers are invited. Monsanto was present. Other regulatory interests can also be present, so they’re public in that sense that anybody who wants to be present can. 

And I also want to point out that EPA’s Scientific Advisory Panel 

review of the ‘‘not likely’’ classification didn’t agree with that classification. 

Mr. BABIN. Dr. Tarone? 

Dr. TARONE. Yes, I wouldn’t agree completely with the statement, but what I believe is that right now the Monograph Programme appears to think they have—they’re accountable to no one, 

so I do need—I do think that they need to be brought in and show 

some accountability to somebody. The fact that they did what they 

did with the glyphosate working group, I mean, that should not 

happen. The exclusion of exculpatory rodent studies many times, 

there’s just absolutely no way that should happen, so I would just 

like to see more accountability. 
97 

Mr. BABIN. Absolutely. Okay. Is it scientifically proper to redo a 

peer-reviewed study’s data analysis with a different statistical 

analysis than was originally used for the study and then use this 

reanalysis without first ensuring that it undergoes robust independent peer review? Dr. Lowit? 

Dr. LOWIT. So the first half of your question is about reevaluating scientific data, and I would agree with that statement, that 

that is actually part of an independent evaluation of those data is 

often to reevaluate the statistics. And EPA has actually in fact 

redone some of the statistics for the glyphosate cancer evaluation. 

Mr. BABIN. Okay. 

Dr. LOWIT. The second part of your question is about peer review. Peer review is important, and in the case of the cancer evaluation, we did have our statistics evaluated as part of the Scientific 

Advisory Panel. 

Mr. BABIN. Thank you very much. 

And Dr. Tarone, could I ask you that question? 

Dr. TARONE. I have no problem with people doing independent 

different types of statistical analysis, although, you know, it does 

have to be peer-reviewed because sometimes you can pull tricks, 

you know, get the result you want. I mean, there’s a lot of data 

dredging, p-hacking it’s sometimes called that goes on. So peer review is essential, though, when you’re evaluating multiple different 

types of statistical analyses. 

Mr. BABIN. Absolutely. And my time is expired, Mr. Chairman. 

Thank you. 

Mr. LUCAS. The gentleman’s time is indeed expired. 

The Chair now recognizes the gentleman from California, Mr. 

McNerney, for five minutes. 

Mr. MCNERNEY. Well, thank you, Mr. Chairman, and I thank the 

witnesses. 

Dr. Sass, have you ever heard the term chemical trespass? 

Dr. SASS. Yes, I have. It’s when you find a chemical in—usually 

an industrial chemical not naturally occurring in your body that 

you didn’t give permission for it to be there. 

Mr. MCNERNEY. So do you think that term applies to our hearing 

this morning? 

Dr. SASS. I do and not just to glyphosate but certainly 

glyphosate. I mean, my guess is that there’s not many people in the 

United States that are unexposed to glyphosate because of how 

widespread its use is. It’s almost 300 million pounds annually, and 

every—in agriculture, and every one of those pounds are put out 

onto our fields, our food supplies, get into our rivers and streams 

and drinking water, sources of drinking water. 

Mr. MCNERNEY. Well, some studies claim that human exposure 

to glyphosate has increased by 500 percent in 25 years. What kind 

of risks are associated with this kind of proliferation of exposure? 

Dr. SASS. So we don’t understand the risks, and that’s one of the 

things that I think that EPA, you know, should be doing is taking 

on a proper risk assessment after a proper hazard assessment 

where they acknowledge that there’s a carcinogenic risk and then 

do a proper slope factor. There’s proper mechanisms to do that. But 

the increase is being shown in people’s urine, and we’re—so we 

know that for sure. And that’s why I think that there’s probably 
98 

no unexposed population, that we’re exposed on a daily or routine 

basis. 

Mr. MCNERNEY. Is it also present in mother’s milk? 

Dr. SASS. It is. It’s widespread and it’s—because it’s water-soluble, it is present in all those fluids. 

Mr. MCNERNEY. So even the youngest members of our society are 

being highly exposed to this chemical? 

Dr. SASS. It is, and that’s what brings up this dose poison fallacy, 

this 16th-century, you know, dose poison thing is that although it 

is true that, you know, we can’t be poisoned if we don’t dose ourselves, that’s true if we’re not exposed, it’s also true that there’s 

vulnerable populations. And how each of us react to those are differently—are very different so that a pregnant woman or a reproductive-age man or woman might be much more vulnerable to certain effects, reproductive effects, for example. Or if we’re exposed 

to a carcinogen when we’re young while our tissues are developing 

and growing and taking in—as they take in nutrients taking in 

those toxic chemicals, that could be a much more damaging time. 

And then the health impacts can be hardwired into the system, 

whereas, for example, if I’m exposed to a dose of lead, I have probably no reaction to the same dose of lead that could cause irreparable permanent harm in a developing child. 

Mr. MCNERNEY. Thank you. Some folks are critical of the World 

Health Organization, and other folks are critical of the EPA’s risk 

assessment. Can you explain how those assessments differ? 

Dr. SASS. Sure. I mean, primarily, for some reason the—a lot of 

the criticism which I think isn’t fair is on whether IARC considered 

some studies that actually weren’t available to it at the time. And 

my only answer is they’ve got to look at publicly available data. 

That’s a rule they made in advance. Industry knows that in advance. If it wants to get those studies to them in advance, they 

could have done so. The chemicals are nominated. They have plenty of time to do that if they want to. The—fundamentally, though, 

some of the ways they’re looking at it are, for example, EPA is not 

looking at the high-dose tumors. The animals have tumors at high 

doses, but there’s no other indication of toxicity to the animals at 

those doses, so there’s no real reason not to consider those tumor 

effects to be real or valid. Like I say, instead of using an arbitrary 

number, to actually use toxicological ways of assessing whether 

those doses should be considered. So that’s one important thing is 

to consider those doses. 

The other thing is to—when you look at it, does there have to 

be a clear dose-response? EPA is throwing out data if there wasn’t 

an—increasing tumors with increasing doses in every study, for example, and that’s not appropriate because many reasons. One is 

that we don’t—we—animals react differently, so you have to use 

your statistics to do that. EPA has used a certain statistical test. 

I argue some different statistical tests. The EPA cancer guideline 

says EPA should use whichever one provides the most health-protective outcome. 

Mr. MCNERNEY. Thank you. Mr. Chairman, I have an article 

published this morning by the POLITICO describing the European 

Parliament’s decision to create a special committee to investigate 

potential failings in the EU system for reviewing pesticides such as 
99 

glyphosate. The committee will look at whether the European Commission followed appropriate regulations and avoided conflict of interest when it decided to renew the license for another five years. 

I would like to introduce this story for the record. 

Mr. LUCAS. Without objection. 

[The information appears in Appendix II] 

Mr. MCNERNEY. Thank you. And I yield back. 

Mr. LUCAS. The gentleman yields back. 

The Chair now turns to the gentleman from Arizona, Mr. Biggs, 

for five minutes. 

Mr. BIGGS. Thank you, Mr. Chairman. I appreciate all the witnesses being here today. 

And I’ll start with Dr. Pastoor. You touched on your testimony, 

but I’d like you to expand if you would on additional examples besides glyphosate that were perhaps classified in a misleading way 

by IARC. 

Dr. PASTOOR. Well, you know, the—what I was trying to get at 

in my testimony is that things like caffeic acid, arachidonic, these 

are chemicals that we find in our diet naturally. And by just simply 

declaring them to be carcinogenic is not helpful to the American 

public. They need some context with that. And my criticism of 

IARC is they don’t provide that kind of context. 

Mr. BIGGS. And so—still with you, Dr. Pastoor. The—you’ve described that as a misleading way to classify these potential hazards, and you’ve advocated for a risk assessment as opposed to hazard assessment. And I thought—and I don’t want to misinterpret, 

but I thought I heard Dr. Sass refer to this kind of dose-level-type 

thing as being 16th-century—a 16th-century approach. Do you 

want to rebut that? 

Dr. PASTOOR. I definitely do. I think it’s absolutely as true as it 

was in the 16th century. And the best example I can give is the 

one I gave earlier on aspirin is that the dose makes the poison. It’s 

just as good at a low—in fact, the actual statement by Paracelsus 

in the 16th century was that the difference between a medicine and 

a poison is the dose. Aspirin is a good example of that. Two tablets 

will relieve your headache. A bottle full of it will kill you. That’s 

the dose makes the poison. It’s as true today as it was back in the 

16th century and long before that. 

It’s important to realize that because in some of these studies 

that are being cited here, whether it’s glyphosate or otherwise, 

these are animals that have been packed full of some of these 

chemicals for a lifetime. And I’m probably one of the few people in 

this room that’s actually conducted those very studies. And they go 

on for two years. They’re given to animals at the maximum dose 

that they can get, and even though Dr. Sass refers to the animals 

not having any adverse effects, they’re getting as much as three 

percent of their diet of that particular chemical. That’s outrageous. 

It’s something that no human would ever see, and the results are 

meaningless and not useful in the context of risk assessment and 

communication of that information to the American public. 

Mr. BIGGS. And, Dr. Lowit, I want to just ask you quickly—I 

don’t want my time to totally expire here, but the EPA sets tolerance levels for residue of glyphosate, and you’ve talked about the 

actual exposure to chemicals, not simply ask if a chemical could 
100 

ever be a carcinogen. And EPA takes a different approach than 

IARC. Why does EPA take the approach it takes? 

Dr. LOWIT. So EPA is a risk-based organization, which is consistent with federal statute and largely for the reasons that Dr. 

Pastoor just explained, that it is important to assess not only the 

hazard but the exposure of a particular chemical. And it is at that 

intersection of hazard and exposure where we understand risk. 

And our job is to understand risk to the American people. 

Mr. BIGGS. And I’m going to close out here by just covering a couple of statements. We’ve heard one of—previous questioners—when 

he was giving his statement prior to asking question says we don’t 

want the, quote, ‘‘science we rely on is not distorted or manipulated,’’ close quote. He didn’t want that—our science to be distorted 

or manipulated. And additionally, the idea of independent bodies 

look at this—we want independent bodies to be looking at these 

types of chemicals and potential hazards to us. 

But what if there is a conflict of interest? And I’m going to introduce—Mr. Chairman, without objection, I’d like to introduce a letter written in 2002, 15 years ago or so, by one of our panelists Dr. 

Sass where she noted that IARC’s working groups are made behind 

closed doors, no transcripts of the deliberations are publicly available. Most significant, the voting of the working group members is 

never made public. This lack of transparency and lack of public 

oversight makes peer review impossible. 

In the letter that we received back from Dr. Wild, at this point 

there’s no indication that any of the processes have changed in the 

last 16 years, and thus, I’m very concerned about IARC and their 

processes in this issuing these monologues and—or, excuse me, 

Monographs. And with that, Mr. Chairman, I introduce that letter. 

Mr. LUCAS. Without objection. 

[The information appears in Appendix II] 

Mr. LUCAS. The gentleman yields back the balance of his time? 

Mr. BIGGS. I do, thank you. 

Mr. LUCAS. And the gentleman—or the Chair now turns to the 

gentleman from Colorado, Mr. Perlmutter, for five minutes. 

Mr. PERLMUTTER. Thanks, Mr. Chair. 

And, Dr. Sass, I’m just going to ask you a pretty open-ended 

question. I’ve been able to sit through some of this testimony. Obviously, there’s some very different approaches and opinions just listening to the last 15 minutes. So are there some issues that you 

think really need to be brought out in more detail? And if so, what 

are they? 

Dr. SASS. Thank you. With regards to the IARC 2002 letter, 

which I point out is quite a long time ago, at that time that was 

three Chiefs of the Monograph Programme ago, and at that point 

we were concerned that they were allowing people with financial 

conflicted—conflicts of interest to be part of the voting working 

group. And since then, they have established conflict guidelines 

that are world-renowned. They’re very well-respected, they’re very 

well-implemented, and those kinds of things are well-tracked and 

well-reported, and so there’s a comfort level. And so those issues 

are not—have not been relevant for a long time. 

As far as the differences between the two assessments, it really 

is a difference between whether you’re doing the hazard only and 
101 

then going to risk assessment or whether you’re conflating them together. And IARC is a hazard only. They just say whether there’s 

an association with cancer or not, and then if you want to do a risk 

assessment or deregulatory actions, those things will come differently. 

I do not understand why the EPA is not going through its process to develop a slope factor and a dose response and a potency estimate and instead just doing—calling it not likely, dismissing 

quite a lot of evidence of tumors. 

And you’re wrong about Dr. Portier. He’s actually updated his tables, and there’s quite a few tumors there, which I would be happy 

to submit or have someone else—have him submit to the record 

that have been disregarded. 

What I don’t understand is why the Pesticide Office is working 

with the EPA’s Office of Chemical Safety and Pollution Prevention, 

which is the science policy office, which is headed by Dr. Nancy 

Beck, a former chemical industry lobbyist, to implement a systematic review procedure for its data that was reviewed by the National Academies in 2007 and was called fundamentally flawed, 

something the National Academies have never called anything before, instead of, for example, working with the EPA IRIS program, 

the Integrated Risk Information System program, which is in the 

Office of Research and Development, the science office of EPA, and 

which could work with them to develop potency estimates and slope 

factors and then a risk assessment at that point. 

Mr. PERLMUTTER. So—let me see. So the real difference here is 

one is just sort of purely data-driven in determining, you know, 

whether or not there’s potential carcinogens, and then there’s kind 

of a political and, you know, policy decision being made as to, okay, 

it’s risky, it’s not, the dose is okay, the dose is not okay, but it’s 

problematic to begin with, but we’ve looked at it on behalf of the 

EPA and the country and say, you know, this is okay, but there’s 

a problem. Is that—am I off? 

Dr. SASS. No, you are spot on. 

Mr. PERLMUTTER. Okay. Well, then with that, I’m going to yield 

back. 

Mr. LUCAS. Before the gentleman yields back, would he yield to 

the doctor from the EPA for a comment? 

Mr. PERLMUTTER. Sure. Which—yes. 

Mr. LUCAS. Dr. Lowit. 

Dr. LOWIT. Thank you for that. So I just think it’s important that 

we make sure the record is accurate. The Office of Pesticide Program is actually part of the Office of Chemical Safety and Pollution 

Prevention. And in fact Dr. Sass’ comments about systematic review and the IRIS program are inaccurate. The IRIS program, as 

publicly discussed in many venues in the last year, is actually moving to a systematic review which is the recommendations of the 

National Academies of Sciences. So EPA’s evaluation is consistent 

with the National Academies. 

Mr. PERLMUTTER. Dr. Sass, do you have a comment on that? 

Dr. SASS. Yes, there’s two different systematic reviews happening 

within EPA and parallel. One is being developed by Dr. Nancy 

Beck, a former ACC American Chemistry Council lobbyist until 

very recently, and one is being developed by the scientist within 
102 

the IRIS program. The IRIS program, it doesn’t prioritize or preferentially treat industry-supplied data, whereas the other systematic review does. For example, guideline studies—GLP it’s called, 

good laboratory practices, which were developed for industry studies specifically to stop them from lying and cheating about their 

data. If you apply systematic review properly, you would look at all 

the data with the same rules. 

Mr. LUCAS. The gentleman’s time is expired. 

Mr. PERLMUTTER. My time is expired. I yield back to the Chair. 

Mr. LUCAS. And on that note, the Chair is going to turn to the 

gentleman from Louisiana, Mr. Higgins, for five minutes. 

Mr. HIGGINS. Thank you, Mr. Chairman. I thank the panelists 

for appearing before us today. 

We have certainly challenging issues in front of us regarding 

what’s real and what’s not. We all want to protect the American 

people from unnecessary harm, but we also want to move forward 

with sound science as we do so. So this is a bipartisan effort, and 

I’m quite sure that the scientists before us and the experts that 

have testified before us and have met with us in our offices agree 

that we have a common goal here. The American farmer feeds the 

world. 

And the studies that I’ve read, including EPA reports and various other research documents, use verbiage like ‘‘most likely’’ and 

‘‘probable’’ and ‘‘potentially increased risk’’ regarding the primary 

chemical within Roundup. It’s a herbicide used to increase crop 

yield. 

So I clearly recall a few years ago the rumor that plastic bottles 

cause cancer. It was widespread. Now, we all drink from plastic 

bottles. I’ve never seen a colleague eat the bottle. 

So the usage of Roundup in reality on farms across America and 

in households is used very carefully because it’s very expensive. 

They use computerized dispersion on large farm machinery to carefully disperse the stuff. Protective clothing is worn. 

So I would say that a hungry child that the American farmer 

feeds across the world by the compassion and generosity of our nation, Mr. Chairman, a hungry child is concerned about the—overcoming that hunger at that moment with food provided by the 

American farmer, as opposed to most likely, probable, or potentially 

increased risk of cancer sometime down the line. 

So I have a question. You said something, Dr. Lowit, very interesting earlier. You stated that EPA conducted its assessment of 

glyphosate with conservative risk assumption. Can you please clarify for us what that means? What is a conservative risk assumption? 

Dr. LOWIT. So as a measure to be resource efficient in our risk 

assessment process, we use a tiering process when we evaluate exposure. Our tier 1 assessments use high-end estimates that are 

health protective and often even compound those assumptions together. And in the case of glyphosate we’ve done a health protective tier 1 level for—in most cases—assessment that uses health 

protective conservative assumptions and came to the conclusion, 

despite those conservative assumptions, that there’s no risk to humans, including infants and children. 
103 

Mr. HIGGINS. Would you recommend changes to the IARC to 

make this program—in this program to ensure transparency and 

reliable reporting to the public that you’re attempting to inform? Is 

there some improvement or streamlining of the scientific process 

where data can be shared amongst perhaps conflicting conclusions 

by various scientists, including scientists from other—from organizations from other nations? Can there be more transparency and 

inclusion of scientific data so that we can come to a conclusion? Because, you know, the loss of Roundup would definitely hurt the production of crop yield across the world, and there’d be an immediate 

impact felt worldwide. So do you have suggestions on how to improve the process so we can arrive at the truth ultimately? 

Dr. LOWIT. So EPA is not bound by our IARC conclusions, as 

noted in my testimony. We’ve come to the conclusion that 

glyphosate is not likely carcinogenic to humans, and that’s similar 

to many other nations in the world, including our Canadian colleagues and the European Food Safety—— 

Mr. HIGGINS. European colleagues. I concur. 

Dr. Sass, could you add to that? 

Dr. SASS. Well, the European assessment is being investigated 

because it’s been shown that they took the first draft from Monsanto and they barely redlined it. So I don’t think that should be 

held up as the high bar. 

And as far as transparency and the use of glyphosate, I just 

think a proper risk assessment should be done. And what’s happening here is that the EPA is doing the hazard assessment calling 

it not likely without doing the slope factor and the risk assessment 

I’m guessing because it favor Monsanto’s interest for selling it 

abroad. 

Mr. HIGGINS. Do you recommend that Roundup be pulled from 

the market? 

Dr. SASS. No, that has not been our recommendation. 

Mr. HIGGINS. Thank you. Mr. Chairman, I yield back. 

Mr. LUCAS. The gentleman yields back. 

The Chair now recognizes my neighbor from the great State of 

Kansas, Dr. Marshall, for five minutes. 

Mr. MARSHALL. Well, thank you, Chairman. And I guess I would 

start by—you had a standing joke with my pastor, and every week 

he would ask me, ‘‘Does coffee cause cancer this week, Doc?’’ And 

I would say, ‘‘Well, I hope not’’ because I usually had a cup of coffee 

in my hands. So I just continue to be amazed. I’m reading this and 

I see that IARC, once upon a time, actually said it was a carcinogen, so that shocks me. 

I’m also a little bit surprised to see that the United States has given $48 million to IARC, which is located in Lyon, France, a 

beautiful place by accounts of all the paintings I’ve seen of that 

area, but I’m not sure why we’re spending American dollars over 

there. 

You know, to go to my question, I’ll start with Dr. Pastoor, the 

first one. Obviously, there’s a big difference between hazard and 

risk, and on its webpage, IARC contends that it does not make a 

judgment about risk. So IARC says it does not make a judgment 

about risk. However, on the front page of its Monograph, it states 

that it evaluates carcinogenic risk to humans. This seems really 
104 

misleading. I’m a biochemist. I’m a physician. You can go down the 

dirt here a little bit if you want to, but if it’s not saying—talking 

about making judgment regarding to risk, saying something is carcinogenic is exactly declaring it’s a risk. Can you help me understand this better? 

Dr. PASTOOR. Representative Marshall, thank you for that question because that’s core to the testimony that I’m giving today, and 

that’s that the difference between the word hazard and risk is absolutely crucially important because if a patient comes to you and 

says, ‘‘Well, what should I do about caffeic acid?’’ or caffeine or 

whatever they’re asking you about, you have to put that in context, 

minimize your exposure or avoid it altogether, whatever it is. 

What IARC does is stops with half a loaf, half of the description. 

They’re just saying it’s carcinogenic and leaves it at that point. It 

is not a risk assessment. It’s simply a hazard assessment. That’s 

not useful. It’s actually injurious. It’s also I think irresponsible, and 

I think it’s harmful to the American public. 

Mr. MARSHALL. And one of our jobs here in Congress is to 

prioritize the dollars we do have on research. And in Kansas we 

have big issues with the sugarcane aphid, with the wheat mosaic 

virus. I mean, to me, prioritizing monies for those would seem to 

be—take precedent over this. 

I’ll go to Dr. Lowit with my next question. I think just to hammer this point home, explain to me the EPA—so I’m new to Congress. How does the EPA make its assessment? Is it hazards only? 

When you determine what chemicals are safe or not, do you use 

just the hazard assessment or how do you do it? 

Dr. LOWIT. So, consistent with federal statute, EPA does risk assessments, so we evaluate both the hazard and the exposure and 

then evaluate them together. 

Mr. MARSHALL. Does that often lead to a—are there examples of 

some chemicals that are a hazard only and—as opposed to a risk 

as well? 

Dr. LOWIT. As a general rule, no. EPA does risk assessment, not 

hazard assessment. 

Mr. MARSHALL. Okay. Thank you. I yield back. 

Mr. LUCAS. The gentleman yields back. I believe everyone’s had 

an opportunity for questions. 

Does the Ranking Member have any concluding comments? 

Ms. JOHNSON. I don’t. Thank you. 

Mr. LUCAS. The Ranking Member does not. 

The Chair simply wishes to thank our panel for being here and 

to express our appreciation for the insights gained today. Obviously, this is a subject matter that we will continue to delve into 

with great depth. 

And in particular to our fellow public official from the EPA, I appreciate the challenges you’re caught between. 

With that, the record will remain open for two weeks for additional written comments and written questions from the Members. 

This hearing is adjourned. 

[Whereupon, at 12:32 p.m., the Committee was adjourned.] 
(105) 

Appendix I 

ANSWERS TO POST-HEARING QUESTIONS
106 

ANSWERS TO POST-HEARING QUESTIONS

Responses by Dr. Anna Lowit 
107 

Responses by Dr. Timothy Pastoor 

HOUSE COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

"In Defense of Scientific Integrity: Examining the IARC Monograph Programme and 

Glyphosate Review" 

Dr. Timothy Pastoor, CEO, Pastoor Science Communications 

Questions submitted by Rep. Lamar Smith, Chairman, 

Committee on Science, Space, and Technology 

In 2003, Dr, Sass stated that "all deliberations of the IARC working group are made 

'behind closed doors,' and that no transcripts of the deliberations are publicly available. 

Most significant, the voting ofthe working group members is never made public, This lack 

of transparency, and lack of public oversight makes peer-review impossible." Dr. Sass 

explained that the statement was made many years ago, and she no longer held those 

criticisms after being invited to a Monograph Programme meeting. 

1. Has the !ARC Monograph Programme changed it.~ practice.~ .~ince 2003 in a way that 

makes the quoted statement no longer applicable? 

The IARC Monograph Programme 1 has not changed in any substantive way that would make 

their process any more transparent. In fact, modest changes since 2003 have done more to 

ensconce their practices and have made the deliberation table smaller and, in effect, moved the 

table to a darker room. Along with the scientific shortcomings pointed out in a paper2 that I coauthored with nine other scientists, Dr. Sass's criticisms ofthe Monograph Programme's closeddoor policies, including lack of transcripts and voting records as well as public oversight was 

true in 2003 and is still true today. 

Observing lARC's working practices up close should have verified that the Programme is 

actually designed to be closed. Whether or not this is deemed to be an acceptable practice, the 

Programme has been diligent in clearly describing procedures that carefully selects what the 

Programme considers acceptable meeting participants, shields them from data and 

communication not provided by the Programme, and keeps deliberations closely guarded. This 

process is part of the Programme's Preamble and has been reconsidered and reaffirmed since 

2003. 

1 My comments are related to IARC's Monograph Programme and do not necessarily refer to IARC on the whole. I 

will refer to the !ARC Monograph Programme as either "the Monograph Programme" or "the Programme". 2 Boobis, A.R, Cohen, S., Dellarco, V., Doe, J.E., Fenner-Crisp, P.A., Moretto, A., Pastoor, T.P., Schoeny, R., 

Seed, J., Wolf, D.C., Classification schemes for carcinogenicity based on hazard-identification have become 

outmoded and serve neither science nor society, Regulatory Toxicology and Pharmacology (2016), 

http://dx.doi.org/l 0.1 016/j.yrtph.2016.1 0.014 
108 

Central to Dr. Sass's 2003 criticism is peer review, which means that the output of the Working 

Group should be reviewed by scientists outside of the Programme. Peer review is fundamental 

in scientific deliberations; however, the Programme does not solicit or consider review of its 

conclusions by the public even though Advisory Groups have requested some form of public 

input3. Any scientific deliberation with the scope and impact of the !ARC Monograph 

Programme should be reviewed, just like any manuscript that may be published in a journal, and 

the additional viewpoints of the reviewers carefully considered. For example, the US EPA put 

in place processes for expert input, discussion, and transparency that should be guideposts for 

revising the Monograph Programme. Dr. Sass's 2003 criticism was valid then as it is now. 

The Programme has been challenged to consider a broader slate of experts on the Working 

Group4

, including those from the private sector with valuable in-depth knowledge on a particular 

substance. This request has been consistently rebuffed for fear of bias. Whereas bias is a 

legitimate concern, clear acknowledgements of orientation and potential conflicts would offset 

this concern and augment the Working Group with important and constructive input. 

Furthermore, such invited experts should be given an opportunity to draft sections of the 

monograph that pertain to their expertise. Currently, that is not the case. Invited experts and 

observers are kept at arm's length. Dr. Sass's invitation as an observer was strictly that: to 

observe, but not participate. If she or others have specific and valuable capabilities and 

knowledge regarding a particular substance, they should be allowed full participation or, at the 

very least, opportunities for input on data and draft monographs. 

Given that there is no record of voting, as pointed out by Dr. Sass, and because only "consensus" 

conclusions are published, there is no way to discover whether consensus is a majority vote 

(with minority opinions) or truly an agreement among the experts. The Programme would 

benefit greatly by having votes made public and the voices of dissenting experts made known. 

One way of doing so would be to have a minority report. However, neither the votes nor 

minority opinions are made public. 

Whereas the Monograph Programme convenes experts of international standing and has 

articulated its procedures, there is much that could be done to improve the legitimate concerns 

'From: !ARC Monographs on the Evaluation of Carcinogenic Risks to Humans INTERNAL REPORT 05/001 

Report of the Advisory Group to Recommend Updates to the Preamble to the !ARC Monographs 4-6 MAY 2005: 

"6c. Public comments on first drafts. There was a request that first drafts should be completed well before the 

meeting and placed on the !ARC website for public comment [ECETOC!IISRP]. Another commenter noted that 

since first drafts are sent to Observers, they should also be made available to others who request them [Huff]." 4 Manolis Kogevinas: " ... !ARC is obsolete regarding the openness of the evaluation procedures. It would be 

impossible to establish procedures similar to those used by the USEPA, but measures should be taken to identify 

interested parties and to allow the expression of their views. This later could be done through the presence of a few 

partners at the meeting in Lyon (say corresponding to a max of I 0-20% of the number of voting members in the 

working group), and also procedures that allow the submission of written comments to the working group even if 

not present." From: !ARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Advisory Group to 

Recommend Updates to the Preamble, Lyon, France: 4-6 May 2005, Comments from recent meeting chairs and 

subgroup chairs on the 1991 version of the Preamble. 
109 

expressed by Dr. Sass 15 years ago. To that end, I include relevant text from my February 6, 

2018 testimony, which articulates the essential elements of transparency and integrity: 

Along with being a scientifically antiquated program, serious questions have been raised about 

the integrity of !ARC's process. Any agency whose evaluations are used to influence public 

health decisions must be transparent and fully accountable to the public. If this committee and 

the member countries of IARC do not address the numerous allegations of questionable ethical 

practices, undisclosed conflicts of interest, and lack of transparency, then the scientific reforms 

suggested here will be irrelevant. 

There are certain basic standards of accountability, transparency, and simply good science on 

which IARC presently falls short that should be the guideposts for any effective reform of the 

monograph process. These include: 

o Selecting working group and other advisory members with necessary expertise, 

regardless of affiliation; 

o Declaring the affiliation and potential conflicts of interest of all participants; 

o Considering ALL available data; 

o Providing a clear explanation why certain data are or are not included in the 

review; 

o Adhering to the principles of systematic review, such as those described by The 

National Toxicology Program's Office of Health Assessment and Translation 

(OHAT) and Cochrane Consumer Network; 

o Fully communicating the results of the agency's review in a timely manner; 

o Including the opinions of all reviewers and the degrees of consensus and dissent. 
110 

Dr. Sass referred to "systematic review" and stated that there are two versions being 

developed. 

2. What is "systematic review," why is it important, and how should the !ARC 

Monographs Programme use it? 

Systematic review is a well-defined, stepwise process to acquire, select, and evaluate a broad 

array of data for decision making. Perhaps the best-defined process was developed by the Office 

of Health Assessment and Translation (OHAT) of the United States National Toxicology 

Program5

• The "Handbook" is based on other, similar processes such as Cochrane Collaboration, 

Navigation Guide, GRADE Working Group, CAMARADES, SYRCLE6

• All of these processes 

seek to collect ALL information, transparently evaluate the scientific and contributory value of 

each study and draw conclusions that are scientifically and procedurally credible. 

Although the Monograph Programme has considered systematic review, the Programme has 

shown little evidence of employing it. In a 2014 Advisory Group review 7

, the Programme 

considered incorporating systematic review in its procedures. However, the Programme's 

Preamble has not been revised to reflect this sentiment and the practices of the Programme give 

no evidence that such a structured and transparent process has been put in place. I am not aware 

of one, much less two, versions of systematic review being developed by the Programme. 

OHAT's process is illustrated in "Figure!" and "Figure 3", which are reproduced from the 

OHAT handbook. Three notable points can be seen in these figures: one is that public comment 

is a feature of each stage of the systematic review. As stated in my answer to Rep. Smith's first 

question, peer review and public input is fundamental to robust scientific review. 

5 Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review 

and Evidence Integration 6 Footnote taken from the OHAT Handbook: 

GRADE Working Group- Grading of Recommendations Assessment, Development and Evaluation (short GRADE) 

Working Group began in the year 2000 as an informal collaboration of people with an interest in addressing the 

shortcomings of present grading systems in health care. 

CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies) 

provides a supporting framework for groups involved in the systematic review and meta-analysis of data from 

experimental animal studies. As of December 2014, CAMARADES has five global national co-ordinating centres: 

University of Edinburgh, Florey Institute of Neuroscience & Mental Health, Radboud University Nijmegen Medical 

Centre, University of California San Francisco and Ottawa Hospital Research Institute. 

SYRCLE (SYstematic Review Centre for Laboratory animal Experimentation) was officially founded in 2012. 

SYRCLE 

focuses on the execution of SRs of animal studies towards more evidence-based translational medicine. 7 !ARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Internal Report 14/002, Report of the 

Advisory Group to Recommend priorities for !ARC Monographs during 2015-2019, 7-9 April2014; Section 2.2. 
111 

Second, studies and data from a broad range of sources, not just published studies, are 

considered and are evaluated for quality before being used. By evaluating for quality, the 

studies are given proper weight in deriving conclusions. 

Third, as shown in "Figure 3", the OHAT process integrates exposure into the evaluation to give 

proper context to the toxicological conclusions so that a "level of concern" can be 

communicated. Combining toxicological conclusions with exposure is risk assessment, which is 

the way hazard data (toxicity) is given proper context in communicating to the public the 

likelihood an effect may occur in human populations. Unlike all major human health regulatory 

agencies, the !ARC Monograph Programme is hazard-based and not risk based. The Monograph 

Programme titles itself as evaluating carcinogenic risks to human when in fact it does not. It is a 

hazard identification process, stopping at the toxicological conclusions, providing no context of 

exposure or 1isk. As I stated in my testimony, this is confusing and unhelpful to the public and 

decision makers who need scientists to describe the potential impact on their lives from 

substances as diverse as plutonium, red meat, or aloe vera. 

The Monograph Programme should adopt systematic review procedures, such as the OHA T 

process, and should revise the Preamble and working practices to reflect such adoption. 

Figure 1. Evaluation Process for OHAT Monographs.. 

Plan for Evaluation Conduct Evaluation 

Peer Review 

and Publish OHAT 

Monograph 

The use of systematic methods is in the evaluation plannlng and conduct phases and consists of Steps 1-7 (Rooney et al. 2014) 

• federally chartered advisory group 

... not included in state-of-sc.ienc:e evaluation or expert panel workshop report 
112 

Figure 3. Systematic Review in the Context of an OHAT Hazard Identification or Level of Concern 

Conclusion 

ADME ; absorption, distribut1on~ metabolism, excretion 

•NTP is currently updating the NTP approach tor reaching level of concern conclusions {expected 2016/2017} 
113 

Responses by Dr. Jennifer Sass 

HOUSE COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

"ln Defense of Scientific Integrity: Examining the IARC Monograph Programme and 

Glyphosate Review" 

Dr. Jennifer Sass, Senior Scientist, Natural Resources Defense Council 

Questions submitted by Rep. Suzanne Bonamici, Ranking Member, 

Subcommittee on Environment 

Dr. Sass, the chemical industry has a long history of attempting to influence the scientific 

conversation around its products and their potential health dangers, and it appears that 

Monsanto has engaged in a campaign to influence the dialogue surrounding glyphosate. 

Unfortunately, we seem to hear daily reminders of just how dangerous misinformation and 

misdirection can be. 

1. How has Monsanto attempted to influence the classification of glyphosate, while 

attempting to conceal their own involvement in those actions? 

Monsanto appears to have undertaken a public relations and lobbying campaign to undermine 

the !ARC's scientific work. The industry-led criticisms of the IARC Monographs are part of a 

public relations campaign documented in internal Monsanto documents made public as a result 

of court proceedings. These documents are available at the USRTK.org public website 1 and 

summarized in part in the report by the Minority Staff of the House Science Committee, 

"Spinning Science and Silencing Scientists: A Case Study in How the Chemical Industry 

Attempts to Influence Science". 2 These efforts include: 

• Monsanto supported websites such as Genetic Literacy Project and Academics Review 

to give the false impression that non-industry third parties are defending the safety of its 

cancer-causing products and attacking IARC's credibility and conclusions. 3 The websites 

failed to disclose ties to Monsanto;• 

• Monsanto sponsored academics to publish papers in scientific journals defending 

glyphosate's safety, and attacking IARC's credibility and conclusions;5 

1 USRTK.org documents at https://usrtk.org/wp-contentiuploads/20 17 /03/0RDcommentsonOPPglyphosate.pdf 2

https://usrtk.orglwp-contentiuploads/2018/02/REVISED-FINAL-Minority-Staff-Report-on-Glyphosate2.6.20 18.pdf 3 For example, Genetic Literacy Project. See https://gmo.geneticliteracyproject.org/FAQ/is-glyphosate-roundupdangerous/. Also see Academics Review website: http://academicsreview.org/20!5/03/iarc-glyphosate-cancerreview-fails-on-multiple-fronts/ 

4 https://usrtk.org/hall-of-shame/jon-entine-the-chemical-industrys-master-messenger/ 

5 https://www.npr.org/sections/thesalt/20 17/03/15/52025 0505/emails-reveal-monsantos-tactics-to-defendglyphosate-against-cancer-fears 
114 

• Monsanto worked with European and US officials at EFSA and USEP A to develop 

glyphosate assessments that deny a link between glyphosate and cancer, following the 

same talking points as Monsanto and citing Monsanto-sponsored reports. 6 

These attack strategies are aggressively promoted by corporate chemical trade organizations that 

include Monsanto among its members: the International Life Sciences Institute 7 (representing 

food manufacturers); CropLife America International 8 (representing Agrochemical 

manufacturers); and the American Chemistry Counci19 (representing chemical manufacturers) 

that was dubbed "The Cancer Lobby" by NY Times columnist Nicholas Kristof. 10 

The chemical industry attack on IARC has also been described in a scientific journal publication 

authored by Dr. Jonathan Samet, a prestigious medical professor and frequent Chair of National 

Academies committees as," ... archetypical of strategies for creating 'doubt' about scientific 

evidence that has policy implications. Such strategies can be traced to the 'playbook' of the 

tobacco industry for discrediting findings related to active and passive smoking." 11 

2. If Monsanto, and other chemical companies, can routinely succeed in manipulating 

the scientific record, what does that mean for scientific bodies like !ARC or EPA's 

IRIS program, and most importantly for the public's health and safety? 

Americans rely on objective public policy to protect them from hazards in their environment. 

Unbiased chemical assessment provided by bodies like WHO-IARC and EPA-IRIS have been 

instrumental in providing credible scientific information about chemical hazards. This 

information is used to support regulatory measures to limit or prevent harmful chemical 

exposures, as well as non-regulatory interests such as innovative green chemistry strategies, 

medical and health providers, reduced risk product formulators and manufacturers, retailers, and 

consumers. Manipulation of the scientific record by private or political interests will block the 

potentially lifesaving information from reaching the public for policy or even individual 

consideration. 

6 https://www .nrdc.org/experts/jennifer-sass/monsanto-mouthpieces-house-science-committee-epa-eu-efsa 7 http://ilsina.org/about-us/membership/ 

'https://monsanto.cornlcompany/partnershipsiq/is-monsanto-in-any-way-affiliated-with-croplife-international/ 

9 https://www.americanchemistry.com/Membership/MemberCompanies/ 

10 NYTimes Oct 6, 2012. http://www.nytimes.com/20 12/1 0/07/opinion/sunday/kristof-the-cancer-lobby.html 11 Jonathan M. Samet: The IARC monographs: critics and controversy, Carcinogenesis, Volume 36, Issue 7, I July 

2015, Pages 707-709, https://doi.org/1 0.1 093/carcinlbgv062 
115 

Dr. Sass, after the IARC decision, California's Office of Environmental Health Hazard 

Assessment (OEHHA), decided to include glyphosate on the state's list of products known 

to cause cancer. That listing would require Monsanto to include a warning label on its 

product. Monsanto is suing to stop the labeling requirement. 

3. With everything you know about glyphosate, wouldn't it be better for consumers to 

have that information before they decide to purchase and use the product? Don't our 

communities and families deserve to know exactly what chemicals they are spraying in 

their parks and backyards? 

In additional to sound federal policy, Americans must make individual decisions to protect 

themselves from environmental hazards. These decisions are only effective when informed by 

objective science that is free of financial influence and clearly conveyed to the consumer. 

Indeed, there is nothing new about using labels to help the public make informed decisions. 

Labels based on independent science are already used to reduce poor health outcomes related to 

nicotine consumption, household chemical interactions, or fetal impacts related to alcohol 

consumption. 

When science clearly indicates risks to human and environmental health- such as the case with 

glyphosate, the public must be informed of those risks as a way to make prudent decisions and to 

lower future societal costs. The health risks posed by glyphosate include potentially elevated 

risks of blood cancers such as non-Hodgkin lymphoma (NHL) and possibly also acute myeloid 

leukemia (AML). AML is a very serious fast-growing cancer, with a five-year survival rate of 

only 27%. The Agricultural Health Study found a possible association at the 90% confidence 

level. The IARC Working Group identified epidemiologic studies from the US, Canada and 

Sweden that reported an elevated risk of non-Hodgkin lymphoma (NLH), a type of blood cancer, 

associated with exposure to glyphosate, even after adjusting for exposure to other pesticides. 

Most Americans would likely want to know if a chemical that they are using in their 

communities, homes and around their families are associated with any form of cancer or other 

adverse health outcomes. 

We cannot let Monsanto's attack on IARC over glyphosate set a precedent. Allowing vested 

interests to successfully control and censor the science that raises concern about the safety of 

their products will encourage other manufacturers of harmful chemicals to attack science rather 

than improving their products and providing meaningful information to protect their customers. 
116 

Responses by Dr. Robert Tarone 

HOUSE COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

"In Defense of Scientific Integrity: Examining the IARC Monograph Programme and 

Glyphosate Review" 

Dr. Robert Tarone, (retired) Mathematical Statistician, U.S. National Cancer Institute and 

Biostatistics Director, International Epidemiology Institute 

Questions submitted by Reo. Lamar Smith Chairman 

Committee on Science Space, and Technology 

Aaron Blair, the chair of the IARC working group on glyphosate knew of exculpatory 

epidemiological data from the Agricultural Health Study, but did not share that knowledge 

with other working group members. An advanced draft of the updated AHS was 

circulating between its authors in early 2013 and they published a subset of the data in 

2014 without the inclusion of herbicide data- a decision you described in your 2016 paper 

as "difficult to comprehend or justify." The study was finally published in December 2017. 

1. Given your extensive history of over 300 scientific publications, your direct experience 

with publishing data from the AHS, and the state of the draft manuscript in 2013, why 

do you believe it took AHS this long to publish this most recent data? 

I remain puzzled by the failure of the AHS investigators to include the herbicide results in their 

2014 PLoS One paper. The main reason I have seen given in the press for the exclusion of 

herbicides is that the paper was getting too long, but I don't buy that explanation. PLoS One is 

an online publication and the instructions for the authors clear! y state that there is no restriction 

on paper length or the amount of data presented (e.g., the number of tables or figures in a paper). 

As noted in my European Journal of Cancer Prevention paper, the previous similar AHS 

publications (i.e., looking at one disease and exposure to various pesticides) had all included 

pesticides from all four classes (i.e., herbicides, insecticides, fungicides, and fumigants), even 

though most, if not all, of the previous papers were published in print journals for which there 

are page restrictions. The fact that herbicides constituted the class of pesticides excluded from 

the 2014 PLoS One paper is particularly difficult to understand. The March 2013 draft 

manuscript was clearly intended for a print journal (there were supplementary tables that were to 

be published online - a common practice now for most print j oumals ), and the primary tables to 

be included in the text of the print paper were restricted to only 16 pesticides- those for which 

the authors judged there to be strong a priori evidence for an association with NHL. Ten of 

these sixteen prioritized pesticides were herbicides, so the authors went from focusing primarily 

on herbicides (because of prior evidence) in the Spring of2013 to excluding all herbicides in the 

Fall of2014. The 2017 paper was restricted to glyphosate, so the AHS investigators have still 

not published the results for NHL risk and the other 17 herbicides. David Spiegelhalter was 

quoted in the June 14,2017 Reuters article on the AHS draft papers as concluding that none of 

the herbicides showed evidence of an association with NHL, an assessment that I agree with. 

Investigators sometimes fall in love with their favorite hypotheses, and the focus on herbicides 

in the March 2013 draft paper is consistent with my perception that many AHS investigators 
117 

believed it likely that herbicides were responsible for increased NHL risk in Midwest fanners. 

Perhaps they were so disappointed in the negative herbicide results that they excluded them from 

the 2014 PLoS One paper, hoping that with the accrual of additional NHL cases from longer 

follow-up some ofthe herbicide results might tum positive. 

This is not explicitly an IARC problem, because the IARC criteria require that deliberations of 

Working Groups be restricted to data from published papers. The AHS is so well known and 

respected, however, that one would think that an exception might have been made in the 

glyphosate deliberations, particularly since Aaron Blair was the Working Group chairman and 

could have presented the updated AHS results for glyphosate and NHL during deliberations. 

This would have required a departure from strict IARC criteria, however, so I view this as 

primarily an AHS problem 
118 

In your testimony you alleged that a scientific publication summarizing rodent study data 

(Greim et al.) was provided to IARC staff 30 days prior to the working group meeting and 

that this was too late for data to be reviewed adequately. Records made available as part 

of ongoing litigation demonstrate that IARC staff were alerted to the availability of Greim 

et al. on the day it became available online, which was also the data submission deadline 

for the monograph working group. Additionally, the chair of the animal data subgroup 

for the monograph stated that he did not receive a copy of Greim et al. prior to the 

Monograph 112 meeting and therefore did not have time to incorporate the data into the 

monograph. 

2. Based on these facts, does the inability to consider Greim et al. appear to be a problem 

with the timing of when /ARC staff received the publication or with the delay by /ARC 

staff in providing the publication to the animal data subgroup? 

I have never alleged anything (in testimony or in my paper) about whether the Greim et al. paper 

was received by IARC in a timely fashion. What I know about the Monograph 112 Working 

Group deliberations on glyphosate comes from my reading of the glyphosate chapter in 

Monograph 112. It was Dr. Sass who alleged in her testimony that the Greim et a!. paper was 

only provided 30 days prior to the Working Group meeting and that this was too short a time for 

it to be reviewed adequately. I have assumed that since the IARC Monograph 112 Working 

Group cited in the reference list, deliberated upon, and discussed the Greim et al. paper in the 

Glyphosate chapter that it had met all IARC criteria for inclusion in Monograph 112 Working 

Group deliberations. The Working Group discounted the paper, but if anyone on the Working 

Group or on !ARC staff had taken the time to read it they would have seen that the summary 

tumor data from all rodent studies (including all those relied upon by IARC) were made 

available in supplementary online tables. The fact that the Greim et al. paper might have been 

provided too late for careful review does not absolve IARC staff or the Working Group members 

from the responsibility of doing a thorough and careful evaluation of those rodent studies that 

IARC relied upon in the glyphosate deliberations. How is it possible that they could devote 

three paragraphs to discuss male renal tumors in the first CD-1 mouse study, but then not even 

discuss renal tumor pathology in the one paragraph devoted to the second CD-1 mouse 

study? Similarly, how could they emphasize a high dose male finding for hemangiosarcomas in 

the second CD-1 mouse study, but not even mention hemangiosarcomas in the discussion of the 

first CD-1 mouse study, in which the mice were exposed to even higher glyphosate levels than in 

the second mouse study? IARC has been evaluating rodent tumor studies for over 40 years and 

IARC staff knew that there were renal tumor data from the second mouse study and 

hemangiosarcoma data from the first mouse study. It is inconceivable that IARC staff could find 

only the renal tumor data for male mice from the first CD-1 mouse study and only the 

hemangiosarcoma data for male and female mice from the second CD-I mouse study. All 

relevant tumor data should have been provided to the Working Group members for consideration 

in their deliberations. Including only tumor data that supported the conclusion that glyphosate 

causes tumors in mice while excluding tumor data from the very same studies that refuted that 
119 

conclusion was inexcusable, scientiftcally unjustifiable, and renders the IARC classification of 

glyphosate as a possible human carcinogen invalid. 

(121) 

Appendix II 

ADDITIONAL MATERIAL FOR THE RECORD
122 

DOCUMENTS SUBMITTED BY REPRESENTATIVE SUZANNE BONAMICI

DR. WILD LETTER (JANUARY 11, 2018) 
123 

The Honourable Lamar Smith, the Honourable Andy Biggs & the Honourable Frank Lucas Page 2 

Ref.: Rq69/2·USA; IM0/75/2·112 11 January 2018 

aflegation that Dr Portier unduly influenced the Working Group and the consensus evaluation 

reached does not, to my knowledge, have any factual basis. 

Regarding Dr Portier's activities subsequent to this meeting, !ARC does not have any official 

relationship through which to influence such activities and can bear no responsibility for them. You 

additionally refer to Dr Portier having chaired a "glyphosate Advisory Group••, but there was no 

such group. What Dr Portier chaired, in April 2014, was the "Advisory Group to Recommend 

Priorities for IARC Monographs during 2015-2019". This Advisory Group comprised 21 members 

from 13 countries and recommended over 80 different agents for JARC to consider for evaluation 

over the five-year period mentioned, one of which was glyphosate. The IARC Secretariat took the 

decision on the five agents to be reviewed at the Monograph meeting in March 2015. 

With respect to the Agricultural Health Study (AHS), it Is important to recognize that this is a 

prospective study that has been ongoing since the 1990s in two US States (Iowa and North 

Carolina). Publications about the AHS date back more than 20 years6

, and incremental updates 

are published periodically. It is therefore incorrect that "the study was just recently published for 

the first time"7

• Even the most recent publication, appearing in 2017 - some 30 months after the 

Monograph evaluation of glyphosate- is not a "final" publication, as the study is ongoing. 

At the time of the Working Group's 2015 classification of glyphosate, several peer-reviewed 

publications from the AHS were available6• As the AHS is a large and well-conducted study, it was 

one of the key ones evaluated by the Working Group. The AHS is mentioned in the IARC 

Monograph on glyphosate2, counter to any suggestion that It "should have been mentioned''10 but 

was not. In fact, in the Monographll, the published AHS results are tabulated, described in text, 

and analysed as part of the Working Group's meta-analysis of non-Hodgkin lymphoma risk. 

At the time of the IARC evaluation, the AHS did not report an association between non-Hodgkin 

lymphoma and glyphosate. However, this null finding in the AHS did not outweigh the positive 

associations found in other epidemiological studies. The Working Group took this into account in 

concluding that there is "limited'' 12 evidence of carcinogenicity in studies of cancer in humans. 

While it Is accurate that "much of the research relied upon by the Monograph was on animals"13, 

it should be noted that the classification of glyphosate in Group 2A is also based on this "limited' 

evidence of cancer in humans, inclusive of the AHS, as well as on the "strong evidence that 

glyphosate causes genotoxicity"14• 

The latest publication from the AHS, in 2017, is an incremental update with a longer time of followup that includes more cancer cases. Consistent with the prior results Included In the IARC 

Monograph, the newly published AHS update did not find an association between non-Hodgkin 

lymphoma and glyphosate. New data on increased leukemia risk with glyphosate exposure in the 

5 letter from Hon. Lamar Smith, Hon. Andy Biggs and Han. Frank Lucas to Dr ChrtstopherWlld (Dec 8, 2017). 

'See Alavanja et al. (1996). Agricultural Health Study, Environ Heallh Perspecl,104(4):362--9, as cited In the !ARC MpnograQh on 

~-

7 Letter from Hon. Lamat Smith, Hoo. Andy Biggs and Hoo. Frank lucas to Dr Christopher Wild (Dec 8, 2017). 

• See IARC Monograph on g!vphosate: IARC Working Group on the Evaluation of Carcinogenic Risk to HtJmans (2017). Some 

Organophosphate Insecticides and Herbicides. international Agency for Reseatch on Cancer, lyon, France. 

http:/fmonograohsJarc fr/ENG/Monographs/vol112/indax.php 

'ld. 

10 Letter from Hon. Lamar Smith, Hon. Andy Biggs and Hon. Frank Lucas to Dr Christopher Wild (Dec 8, 2017). 

11 See IARC Monograph on glyohosate· IARC Working Group on the Evaluation of Carcinogenic Risk to Humans (2017). Some 

Organophosphate Insecticides end Herbicides. International Agency lor Research on Cancer, lyon, France. 

http://monographs.lar<:.fr/ENGIMOO<lqraphs/vo!112flndex.php 

12 As specified fn IARC (2.006). Preamble to the IARC Monographs. b!tp:/lmgnoaraplls.larc.fr/ENG/Preamble/ 

13 Leller from Hoo. Lamar Smith, Hen. Andy Biggs and Han. Frank Lucas to Dr Christopher Wnd (Dec 8, 2017). 

H See !ARC Monograph on glypllosate; IARC Working Group on the Evaluation of Carcinogenic Risk to Humans (2017). Some 

Organophosphate lnsecticldas and Herbicides. International Agency for Research on Cancer, Lyon, France. 

hltp:l/monoaraphs.larc.friENG/Monographslyol1121in<fex,pbp 
124 

The Honourable Lamar Smith, the Honourable Andy Biggs & the Honourable Frank Lucas Page 3 

Ref.: RC/69[2-USA; IM0/75/2-112 11 January 2018 

AHS were not, however, available to the Working Group in 2015. Because the IARC Monograph 

classification reflects the consensus view of an independent expert Working Group, based on a 

systematic review of ail publicly available studies, it is Inappropriate to speculate about how new 

data from one study (including on increased leukemia risk) might change that expert opinion. 

With regard to the quotation of Dr Aaron Blair, this appears selective and therefore is prone to 

misinterpretation. As a whole, the testimony given by Dr Blair does not support any change in the 

classification of glyphosate. To the contrary, when asked, "Has anything you've been shown .by 

Monsanto's lawyers In the 3 hours and 40 minutes that he questioned you changed the opinions 

that you had at the /ARC meeting about glyphosate and non-Hodgkin lymphoma?', Dr Blair 

answered, "No"15 • 

With respect to the confidentiality of deliberative documents, we note that reports from the US 

National Research Council routinely indicate that, "the review comments and draft manuscript 

remain confidential to protect the integrity of the deliberative process." 16 The European Food 

Safety Authority (EFSA) differs from the US National Research Councll on several key procedural 

aspects, including not publically disclosing the identity of the peer reviewers and the meeting 

attendees. EFSA also differs from other international agencies (including !ARC) with respect to 

some transparency issues, including "public access to data used In determining scientifically 

significant conclusions that affect po/icy''17, and the reliance on draft materials developed by those 

with vested interests. Options to improve transparency and conflict of interest disclosure in EFSA 

decisions are currently being explored18• 

The Monographs, in full agreement with the principles of transparency and importance of "public 

access to data used In determining sclentlflcally significant conclusions that affect policy'12, rely 

on published research, and do not cite unpublished or "secret data•. !ARC invites scientific 

stakeholders, in limited numbers, seeking to balance participation "from constituencies with 

differing perspectives" to participate In its meetings. All participants at Mmiograph meetings have 

full access to the draft documents and discussions, and may be recognized to speak. As publicly 

announced two months In advance of the meeting on glyphosate, !ARC included various 

Observers, Including from Monsanto, noting their disclosed conflicts of interests. However, only 

the Working Group of independent experts drafts the critical reviews and evaluations. Individuals 

with real or perceived conflicts of Interest of any kind may not draft text that pertains to the 

description or interpretation of cancer data. 

Finally, like the US National Research Council, the IARC Monographs assure the integrity of the 

process by maintaining confidentiality of draft documents and of the scientific peer review 

comments. !ARC's practices are also consistent with the Joint Meeting on Pesticide Residues 

(JMPR) (jointly administered by the FAO and WHO), which evaluated glyphosate in 2016, 

particularly with regard to the confidentiality of draft and deliberative documents, the determination 

of conclusions and decisions by consensus from all participants, and the adoption of the final 

report by the "entire Meetlng"19• 

In all, the rigorous published procedures followed in every Monograph meeting reflect !ARC's 

close adherence to the highest principles of transparency, independence and scientific integrity. 

15 Videotaped deposition of Aaron Earl Blair, PhD. March 20, 2017. MDL No. 2741, Case No. 16-md-0271-VC. United States District 

Court, Northern Dlslrtct of California. 

" Review of the Environmental Protection Agency's Draft IRIS Assessment of Formaldehyde (2011 ). 

b!tos-Hwww ncbi nlm.njh goy/books/NBK2082?7/' Review of EPA'slnlejjra!ed Risk Information System (IRIS) Process (2014). 

https:/t,mw.ncbi.nlm.nih.qovlbooksiNBK2300741; · 

17 Letter from Han. Lamar Smith, Hen. Andy Biggs and Hen. Frank Lucas to Dr ChrtstopherWIId (Dec 8, 2017). 18 See https://ww.H,efsa.eurcoa.euten!corporatefpubnndependencepolicy171 026 19 See http·I/WWW'.whoJoVfoodsafety!pubHcationsfjmpr guidance document 1 odf?ua=1 
125 

The Honourable Lamar Smith, the Honourable Andy Biggs & the Honourable Frank Lucas Page 4 

Ref.: RC/69/2-USA; IM0/75/2"112 11 Januaiy 2018 

This approach has permitted the Monographs to thoroughly evaluate many important agents, 

Including tobacco, hepatitis and human papilloma viruses, alcohol, air pollution and radiation, 

providing a foundation for many effective cancer control measures. 

In this regard, I wish to acknowledge the valuable support of the US National Institutes of Health 

and our other sponsors. We recognize the importance of awards such as the one to the 

Monographs Programme in enabling scientific excellence at !ARC, and also that such awards are 

only merited based on successful scientific peer review of the sponsor. In respect of oversight and 

accountability, the Programme is also responsive to !ARC's governing bodies (Scientific 

and Governing Councils) and to the international scientific community. Accordingly, each 

!ARC scientific Section is subject to in-depth external peer-review on a five-year cycle 

with a panel comprised of JARC Scientific Councll Members and additional subject-specific 

external scientists further Information about the governance of IARC is available at 

http://www.iarc.fr/en/abou!lgovernance.php. These scientific peer reviews have had an essential 

role in maintaining the scientific excellence of JARC, as reflected in an independent assessment, 

based on scientific bibllographlc analysis, placing !ARC in the top 2% of medical research 

organizations worldwidew. 

While assuring you of my commitment to the oversight and accountability of the Agency to its 

funding sponsors, its governing bodies and the international scientific community, l remain 

available to respond to further questions you may have about the IARC Monograph Working Group 

evaluation of glyphosate. Without prejudice to !ARC's willingness to facilitate your review by 

voluntarily responding to reasonable and substantiated requests for information received from 

appropriate authorities, !ARC would be grateful if the House Science Committee would take all 

necessary measures to ensure that the immunity of the Organization, its officials and experts, as 

well as the inviolability of its archives and documents, are fully respected. 

Yours sincerely, 

Christopher P. Wild, PhD 

Director 

zo See http• 1/www exce]Jencemapnjng net/ 
126 

DR. WILD LETTER (NOVEMBER 20, 2017) 

International Agency for Research on Cancer 

World Health 

Organization 

150 cours Albert Thomas 

69372 Lyon cedex 08, France 

Office of the Director 

Tel.: +33 4 72 73 85 77 

Fax: +33 4· 72 73 85 64 

E-mail: dlrector@iarc.fr 

http://www.larc.fr 

Ref.: RC/69/2-USA; IM0/75/Z-112 

CPW/rrg 

Dear Congressmen Smith and Biggs, 

The Honourable Lamar Smith 

Chairman 

Committee on Science, Space, and Technology 

and 

The Honourable Andy Biggs 

Chairman 

Subcommittee on Environment 

Congress of the United States 

House of Representatives 

2321 Rayburn House Office Building 

Washington, DC 20515-6301 

United States of America· 

E-mail: c/o joseph.brazauskas@mail.house.gov 

· &jullya.grlgoryan@mail.house.gov 

20 November 2017 

I refer to your letter dated 1 November 2017. I am pleased to provide a written response to the 

issues you raise about the Monographs programme of the International Agency for Research on 

Cancer (IARC). In replying, I note that this information is given without prejudice and does not 

constitute a waiver of the immunities and inviolability of archives enjoyed by the World Health 

Organization (WHO) and IARC. 

The IARC Monographs are consensus evaluations developed by Working Groups of independent 

experts, free from vested Interests. As IARC explained to the reporter cited in your letter, changes 

made to draft documents are the result of deliberation between Working Group members and for 

this reason are not attributable to any particular scientist. For all Monograph evaluations, drafts 

prepared over the months prior to a meeting form the basis of open and detailed scientific debate 

during the eight-day meeting In Lyon and are modified by the Working Group as a result. The 

final Monograph evaluation represents the scientific consensus of the whole Working Group and 

does not have individually authored sections. IARC staff {secretariat to the meeting) do not draft 

or revise the Monograph text, which Is the preserve of Working Group members. 

During the Monograph meeting in March 2015 at which glyphosate was evaluated, Dr Christopher 

Portier was an Invited Specialist. Invited Specialists do not serve as meeting chair or subgroup 

chair, nor do they draft text that pertains to the description or interpretation of cancer data, or 

participate in the evaluations. In April 2014, when Dr Portier chaired the Advisory Group to 

Recommend Priorities for !ARC Monographs 2015-2019, he did not have any contractual 

relationships with litigation lawyers relating to glyphosate nor any other declared activities that 

could be considered as creating a real or perceived conflict of interest. The Advisory Group 
127 

The Honourable Lamar Smith and the Honourable Andy Biggs 

Ref.: RC/69/2-USA; IM0/75/2·112 

Page 2 

20 November 2017 

comprised 21 members from 13 countries and their recommendations were published in The 

Lancet Onco!ogf and on the IARC website2• 

In the interests of transparency, the IARC Monographs are based on independent scientific review 

of published research and not on the basis of unpublished or "secret data" unavailable publicly. 

According to this principle and as requited by Its Preamblel, the IARC Monograph on glyphosate1 

did not Include any unpublished information on the Agricultural Health study {AHS). Therefore, it 

Is false to assert that Dr Blair was In a position to withhold critical Information from IARC, about 

the AHS or any other unpublished study, for that matter. The Working Group did consider the 

published report from the AHS. 

This same principle of independent scientific review and verification explains differences between 

a draft document and the published Monograph text referred to by Ms Kelland. Most of these 

differences specifically relate to a review article5 co-authored by a Monsanto scientist and which 

has been the subject of investigative reporting concerning "ghost-writing''~>. The draft Monograph 

document seen by Ms Kelland reported the conclusions of the authors of this review article. During 

the Monographs consensus meeting, the Working Group considered that Information In the review 

article and its supplement was insufficient for independent evaluation of the individual studies and 

the conclusions reached by the Monsanto scientist and other authors. As a result, the draft was 

revised, and the text in the publlshed Monograph Is the consensus opinion of the Working Group. 

Nevertheless, the Monograph factually describes the review article and the reported findings (see 

pages 34-35 and 4D-41). 

Draft and deliberative materials are not made public, in order to protect the Working Group 

scientists from interference by vested Interests. The position of IARC and the WHO concerning 

the public release of deliberative documents, or records of deliberative scientific discussions, is 

consistent with .standard practice in scientific committees. Individual Working Group members 

contacted IARC to express concerns when being pressed to respond to allegations about the 

scientific debate that took place during the Monograph meeting. In this light, IARC Issued a 

reminder to all parties not to pressure or intimidate scientists in relation to their role as Working 

Group members7• 

Draft documents are available, however, to all scientists attending the Monograph meetings, 

including Observers from industry. IARC was pleased to welcome various scientific Observers to 

the glyphosate Monograph meeting, Including from Monsanto. The Monsanto Observer was 

quoted In the media as saying: "The meeting was held in accordance with IARC procedures. 

Dr Kurt Straif, the director of the Monographs, has an intimate knowledge of the rules in force 

and Insisted that they be respected."8 

'Strait K eta/. {2014). Future priorities for the IARC Monographs. Lancet Oneal, 15, 683-684. 

http://www.thelancet.comliournalsllanonclarticte/PIIS1470-2045%2814%2970168-8/fulltext 

2 !ARC (2014). Report of the Advisory Group to Recommend PrloriUes for !ARC Monographs during 2015-2019. 

http://monographs.larc. fr/ENG/PublicaUonsllnternrep/14-002.pdf 3 IARC (2006). Preamble to the IARC Monographs. http://monographs.larc.fr/ENG/Preamble/index.php, 

4 IARC Working Group on the Evaluation of Carcinogenic Risk to Humans {2017). Soma Organophosphate 

Insecticides and Herbicides. http:l/monooraphs.larc.fr/ENG/Manographs/vol112/index.php 

• Greim H el a/. (2015). Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence 

data from fourteen chronic/carcinogenicity rodent studies. Grit Rev Toxlcol, 45, 185--208. PMID:25716480 6 http:l/abonnes.lemondeJr/planetelartlcle/2017/10/04/monsanto-papers-deslnformatlon-organlsee-autour-duglyphosate 5195771 3244.html; http://www europarl.europa.eu/cmsdata/1291201PH%20Giyphosate Gil!am.pdf; 

https:l/www.bloomberg.com/news/ar\lcles/2017-08-09/monsanto-was-lts-own-ghostwrlter-for-some-safety-revlews 

7 hltp:l/www.iarc.fr/en/media-centreliarcnews/2016/qlypbosate IARC2016.php 8 http:/]abonnes.lemonde.fr/planetelartlcle/2017/10118/glyphosate-monsanto-tente-une-dernlere-man-uvre-poursauver-le-roundup 5202606 3244.html 
128 

The Honourable Lamar Smith and the Honourable Andy Biggs 

Ref.: RC/69/2-USA; IM0/75/2-112 

Page 3 

20 November 2017 

In summary, the cancer hazard classifications made by the !ARC Monographs are the result of 

scientific deliberations of Working Groups of independent scientists, free from conflicts of Interest. 

The resulting Monograph represents the Working Group's consensus conclusions, based on their 

critical review of the published scientific literature, agreed upon by all Working Group members in 

plenary sessions. The principles, procedures and scientific criteria that guide the evaluations are 

described in the Preamble to the IARC Monographs. 

Although IARC is not in a position to provide witnesses for any potential hearing, I welcome this 

opportunity to respond to your various points and In so doing to correct repeated 

misrepresentations of the Monographs promoted by some sections of the media over an extended 

period of time. You would also both be welcome to visit the Agency and to pose your questions 

directly to me and my staff. 

The Agency remains committed to Its work to reduce the ever growing burden of cancer 

worldwide. 

Yours sincerely, 

Christopher P. Wild, PhD 

Director 
129 

IARC RESPONSE TO CRITICISMS OF THE MONGRAPHS AND GLYPHOSATE EVALUATION

IARC response to criticisms of the Monographs and the glyphosate evaluation 

Background 

Prepared by the IARC Director 

January 2018 

Since the evaluation of glyphosate by the !ARC Monographs Program in March 2015, the 

Agency has been subject to unprecedented, coordinated efforts to undermine the 

evaluation, the program and the organization. These efforts have deliberately and 

repeatedly misrepresented the Agency's work. The attacks have largely originated from 

the agro-chemlcal industry and associated media outlets. They have taken place in the 

context of major financial interests relating to: a) the relicensing of glyphosate by the 

European Commission; b) hundreds of litigation cases in the USA brought by cancer 

patients against Monsanto, claiming that their malignancies were caused by glyphosate 

use; c) and the decision by the Californian Environmental Protection Agency to label 

glyphosate as a carcinogen. 

In response to the misrepresentations, the Agency has sought to provide a clear account 

of its actions, including keeping its governing bodies Informed of developments. Many of 

the relevant documents have been posted in the public domain on the IARC Governance 

website1 and on dedicated glyphosate webpages2

• !ARC scientists have responded to 

industry-funded critiques appearing in scientific journals by published letters to journal 

editors. Given its limited capacity, IARC has not tried to develop an extensive media 

campaign to present its position, or to counter all industry-sponsored attacks In the media. 

However, in selected and important cases, !ARC has addressed the false claims in the 

media 2

• 

IARC response to criticisms of the Monographs and the glyphosate evaluation 

A number of quite specific and oth~r rnore general criticisms have been aimed repeatedly 

at the glyphosate evaluation and the wider Monographs program. Many criticisms in the 

media originate from one Reuters journalist; another source is a March 2015 article that 

1 http:/kovernance.iardr/ENG/infocouncils.php 

2 http://www.iarc.fr/en/media-centre/iarcnews/2016/glvphosate IARC2016.php 

1 
130 

Forbes' since removed from their website, ending their relationship with the author amid 

revelations in the New York Times that the article was ghostwritten by Monsanto. A 

number of these criticisms were included subsequently in two letters to the IARC Director 

from the US House of Representatives Committee on Science, Space and Technology4

• 

) . 

IARC did not edit parts of the glyphosate Monograph to achieve a particular outcome 

• The Reuters journalist5 obtained a draft of parts of the glyphosate Monograph from 

Monsanto and compared the draft with the final, published version of the Monograph. On 

this basis the journalist claimed IARC had selectively edited the text to favor an evaluation 

of glyphosate as "probably carcinogenic to humans". The majority ofthe highlighted 

differences were related to a review article co-authored by a Monsanto scientist, which 

has been the subject of Investigative reporting concerning "ghost-writing". The Agency 

rejected the false claims published by Reuters•. 

• The Working Group considered that information contained in the review article was 

insufficient to allow independent scientific evaluation. As a result, the draft text was 

revised by the Working Group; the text in the published Monograph is its consensus 

opinion. 

• For all Monograph evaluations, the drafts prepared over the months prior to a meeting 

form the basis of open and detailed scientific debate during the eight-day evaluation 

meeting In Lyon and are modified by the Working Group as a result. 

• Changes made to the draft documents are the result of deliberation between Working 

Group members and are not attributable to any particular scientist. 

• !ARC staff (secretariat to the meeting) do not draft or revise the Monograph text, which is 

the preserve of Working Group members. 

Data from the Agricultural Health Study (AHSl were not deliberately excluded from the 

Monograph 

3 https://www,nytimes.com/2017/08/01/b usiness/monsa ntos-sway-over-res·ea rch-i s-seen-in • 

disdosed-emalls.html 

4 http://governance.la rc. fr /ENG/Oocs/CLSBiggs-IARC 01112017 .pdf; 

http:ljgovernance.larc.fr/ENG/Oocs/CPWIId-LSmith&ABiggs.pdf; 

http:l/governance.!arc.fr/EN G/Oocs/SST IARC12082017 .pdf 

http:l/governance.iarc.fr/ENG/Docs/CPWild Smith Bjggs Lucas 20180111.pdf 5 https://www .reuters .com/investigates/specia I-re po rt/who-Ja rc-glyphosate/ 6 http:ljwww.iarc.fr/en/media-centre/iarcnews/pdf/IARC Response Reuters October2017.pdf 

2 
131 

• One suggestion made in media reports is that results from the AHS were withheld from 

the !ARC Monograph evaluation and that recent results would have led to a different 

evaluation7 • Monsanto lawyers obtained draft scientific manuscripts of the AHS as a result 

of calling the Principal Investigator of the AHS, Dr Aaron Blair to testify in litigation 

hearings in the US. !ARC rejected the claims publicly'!. 

• The AHS Is a prospective study that has been ongoing since the 1990s and publications 

date back more than 20 years, with incremental updates published periodlcally. For the 

2015 classification of glyphosate, several peer-reviewed publications from the AHS were 

available and included in the evaluation. At the time of the Monograph evaluation the 

latest AHS publication did not report an association between non-Hodgkin lymphoma and 

glyphosate. However, this null finding did not outweigh the positive associations found in 

other epidemiological studies. 

• The most recent analysis from the AHS only became available in 2017- 30 months after 

the Monograph evaluation- and was consistent with the prior results included in the 

Monograph, except that new data on increased leukemia risk with glyphosate exposure 

were not available to the Working Group in 2015. 

• Because the Monograph classification reflects the consensus view of the Working Group, 

based on a systematic review of all publicly available studies, it is inappropriate to 

speculate about how new data from one study might change that expert opinion. 

• The lengthy court testimony given by Dr. Blair does not support any change in the 

classification of glyphosate consequent to the latest AHS publication. To the contrary, 

when asked, "Has anything you've been shown by Monsanto's lawyers in the 3 hours and 

40 minutes that he questioned you changed the opinions that you had at the IARC meeting 

about glyphosate and non-Hodgkin fymphomar, Dr. Blair answered, "No"." 

!ARC Monograph evaluations are transparent and open to scrutiny 

• The suggestion has been made that !ARC's Monograph evaluations lack t~ansparency10 

because the draft documents are not made available and changes to drafts are not 

ascribed to specific Working Group members. 

7 https://www.reuters.com/investigates/special-report/glvphosate-cancer-data/ 

8 http:ljgovernance.iarc.fr/ENG/Docs/IARC responds to Reuters 15 June 2017.pdf 9 Videotaped deposition of Aaron Earl Blair, PhD. March 20, 2017. MDL No. 2741, Case No. 16-md· 

0271-VC. United States District Court, Northern District of California. 10 https://www.reuters.com/article/us-health·cancer-iarc-exclusive/exclusive-who-cancer-agency· 

asked-experts-to-withhold-weedkiller-documents-idUSKCN12P2FW 

3 
132 

• Draft and deliberative materials are not made public, in order to protect the Working 

Group scientists from Interference by vested interests. The position of IARC and WHO 

concerning the public release of deliberative documents, or records of deliberative 

scientific discussions, is consistent with standard practice in scientific committees. 

• For example, the Monographs approach is in line with the US National Research Council; 

reports from the US National Research Council routinely indicate that, "the review 

comments and draft manuscript remain confidential to protect the Integrity of the 

deliberative process." 11 

• !ARC's practlces are also consistent with the Joint M~eting on Pesticide Residues (JMPR) 

Oolntly administered by the FAO and WHO), which evaluated glyphosate in 2016, in 

particular with regard to the confidentiality of draft and deliberative documents, the 

determination of conclusions and decisions by consensus from all participants, and the 

adoption of theflnal report by the "entire Meetlng".12 

• It is noteworthy that Monograph meetings are open to scientific stakeholders in order to 

balance participation 7rom constituencies with differing perspectives"J3 • All participants 

have full access to the draft documents and discussions. For example, the meeting on 

glyphosate included an Observer from Monsanto and a Representative from the US 

Environmental Protection Agency (EPA). The Monsanto Observer was quoted in the media 

as saying: '7he meeting was held in accordance with /ARC procedures. Dr Kurt Strait, the 

director of the Monographs, has an intimate knowledge of the rules in force and insisted 

that they be respected. "14 

IARC has a strong rationale for inclusion of only publicly available studies In Monograph 

evaluations 

• The Monographs have been accused of selective use of scientific studies ("cherrypicking"15) because Working Groups consider only reports available in the public domain, 

identified and documented through the systematic assembly and review of all publicly 

available and pertinent studies, as specified in the Monographs Preamble. This practice is 

11 Review of the Environmental Protection Agency's Draft IRIS Assessment of Formaldehyde (2011) 

https://www.ncbi.nlm.nih.gov/books/NBK208227/: Review of EPA's Integrated Risk Information 

System {IRIS) Process {2014) https://www.ncbi.nlm.nih.gov/books/NBK230074/ 12 http://www.who.int/foodsafety/publicatlons/impr guidance document 1.pdf?ua-1 13 http://monographs.larc.fr/ENG/preamble/currenta5participants0706.php 

14 http://www.lemonde.fr/planete/article/2017/10/18/glyphosate-monsanto-tente-une-dernlereman-uvre-pour-sauver-le-roundup 5202606 3244.html 

15 https://www. n atu re.co m/n ews/wldely-use d -he rblc Ide-lin ked-to-ea ncer-1.17181 

4 
133 

criticized because It excludes studies conducted by Industry when these are publicly 

unavailable. 

• The Monographs do not exclude research conducted by industry per se. Where industryconducted studies are published In scientific journals they are considered, if available in 

sufficient detail to allow independent scientific review. Under the same conditions, the 

Monographs also take account of industry-conducted research in summary form or if 

placed in the public domain by national regulatory agencies; 

• The need for industry-conducted studies to be publicly accessible is in fine with the 

existing (e.g. European Medicines Agency) or developing (e.g. European Food Standards 

Agency) policies of other international agencies. 

• Consistent with the above principles and as required by its Preamble, the glyphosate 

Monograph did not consider any unpublished information on the AHS (see above). 

However, as already mentioned, the Working Group did include published reports from 

theAHS. 

• IARC follows Its current practice In order to enable others to scrutinize the basis of its 

decisions rather than relying on appeals to authority or trust. This transparency is 

fundamental to the scientific process. 

Monograph Working Group members who evaluated glyphosate were free from conflict of 

interests 

• Another suggestion is that the Working Group evaluation of glyphosate was unduly 

influenced by Dr Christopher Portier16, who was an Invited Specialist at the meeting17• It is 

· suggested that Dr Portier had contractual commitments to US law firms involved in 

glyphosate litigation at the time of the Monograph meeting. 

• · IARC is not aware of any contractual relationship existing between Dr. Portier and 

litigation lawyers relating to glyphosate at the time of the Monograph meeting in March 

2015, when glyphosate was evaluated. However, IARC did take account of other real or 

apparent conflict of interests declared by Dr. Portier, specifically his part-time role with 

the Environmental Defense Fund. On this basis, IARC invited his participation in the 

meeting as an Invited Specialist and his declared conflict of interest was made public on 

the IARC Monograph website two months in advance of the glyphosate evaluation. 

16 https://www.reuters.com/investigates/special-report/health·who-iarc/ 17 http://governa nce.la rc.fr /ENG/Docs/SST 1ARC12082017.pdf 

5 
134 

• Or. Portier had full access to draft documents and discussions during the meeting, and was 

recognized to speak at the meeting. However, as an Invited Specialist, Dr. Portier was not 

a member of the Working Group that was responsible for the critical reviews and 

evaluations developed during the meeting, Including the work performed in sub-groups 

assessing the epidemiology, animal bioassays or other relevant mechanistic data. 

• !'lone of the 16 Working Group members· or any other meeting participant (including the 

Observer from Monsanto, other ObseNers, and the US EPA Representative)· signaled any 

attempt at undue Influence by Dr. Portier. 

• A related suggestion has been that Dr Portier influenced the original decision to evaluate 

glyphosate18 through chairing the April 2014 meeting of the "Advisory Group to 

Recommend Priorities for IARC Monographs during 2015-2019". However, this Advisory 

Group comprised 21 members from 13 countries and recommended over 80 different 

agents for IARC to consider for evaluation over the five-year period mentioned, one of 

which was glyphosate. The I ARC Secretariat took the dedsion on the five agents to be 

reviewed at the Monograph meeting in March 2015. · 

IARC evaluates only agents that have some evidence of carcinogenicity 

• Some critics say the Monographs program finds "everything causes cancer" ~ because of 

nearly 1000 agents evaluated only one has been categorized in Group 4, "probably not 

cardnogenic to humans". 

• The criticism is misleading because the Monographs do not select at random the agents 

evaluated for carcinogenicity. Instead, in the interest of efficiency and according to the 

Preamble to the Monographs, "Agents are selected for review on the basis of two main 

criteria: (a) there is evidence of human exposure and {b) there is some evidence or 

suspicion of carcinogenicity." 

• IARC puts out a public call for agents to be reviewed and establishes the "Advisory Group 

to Recommend Priorities for I ARC Monographs" to propose priorities for evaluation of 

agents based on the criteria mentioned above. 

• Despite this careful selection of agents, in reality around half (502 of 1003) of the 

Monograph evaluations resulted in agents being classified in Group 3 ("not classifiable as 

to its carcinogenicity to humans"); just 12% of all agents evaluated (120 of 1003) are 

10 https:Uwww.reuters.com/investigates/special-report/health-who-iarc/ 19 1bid. 

6 
135 

Group 1 ("carclnogenlc to humans"} and a further 38% (380 agents} fall into Group 28 

{"possibly carcinogenic to humans") or 2A ("probably carcinogenic to humans"}. This is far 

from the finding everything is carcinogenic. 

Monograph evaluations take account of "real-world" exposures by evaluation of 

epidemiological stydies 

• A charge levelled at theMonographs is that evaluations are divorced from the "real world" 

i.e. are made without taking account of realistic human exposures. 

• However, epidemiological studies are a central part of Monograph evaluations and, by 

definition deal with people exposed in daily life, including at work. The studies frequently 

consider the gradient of risk observed with different levels of exposure. One part of the 

Monograph evaluation is specifically dedicated to describing the circumstances under 

which human exposure occurs and at what levels. 

• In addition, when considering sclentific evidence of carcinogenicity including biological 

mechanisms, the Working Groups place special emphasis on whether the observations are 

relevant to humans. 

• In light of occurring ("real world"} human exposures, Working Groups synthesize evidence 

In humans, animals and other model systems In reaching overall conclusions. 

The Monographs program re-evaluates an agent when a substantial addltlonal body of 

scientific evidence becomes available 

• As a science-driven process, the Monographs program has a responsibility to re-evaluate 

an agent when a significant additional body of evidence becomes available. However, this 

has led to updates being labelled as a "retraction"20 if the classification changes, as when 

coffee was re-evaluated in 2016. The implication that if an evaluation changes then all 

evaluations are open to doubt not only misrepresents the Monographs but 

misunderstands science. Science is not static; evidence accumulates and understanding 

evolves, thus enabling updated evaluations. 

20 https://oversight.house.gov/wp-content/uploads/2016/09/2016.09-26·JEC-to-Collins-NIH-IARCFundlng-due-10·10.pdf 

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• In practice, by far the most frequent change In classification after re-evaluation is that the 

agent goes into a higher group (e.g. Group 2A to 1). The fact that most re-classifications 

move into a higher group is an objective indicator that the Monographs do not overstate 

the strength of available evidence but are in fact conservative in nature. 

• A scientifically updated classification is not, therefore, equivalent to a retraction. Rather, 

re-evaluation is the sign of a strong, science-driven program responding to scientific 

progress. 

The Monograph evaluations group agents according to the strength of evidence of 

ca rcinogenidtv, not their potency 

• The Monograph evaluation results in a classification based on the strength of evidence 

that an agent causes cancer or not. In other words, It is a measure of how confident the 

Working Group is that this agent causes cancer in humans. 

• The Monograph evaluations do Include consideration of the level of exposure (dose) 

associated with the risk of developing cancer (response) and strong dose-response 

relationships corroborate the confidence that a particular agent is a cause of the cancers 

observed. However, this potency ofthe agent I.e. how many cancers it causes at certain 

exposure levels, is not the basis of classification. 

• Consequently agents with different potencies can be placed in the same classification 

group. For example, various forms oftobacco, plutonium, diesel engine emissions, 

hepatitis viruses and processed meat all have sufficiently strong evidence to classify them 

In Group 1. The distinction between strength of evidence and magnitude of effect is 

highlighted in media communications and on the Monographs website in order to make 

this distinction dear21• 

IARC Monographs Identify carcinogenic hazards and do not include a risk assessment 

• The IARC Monographs identify carcinogenic hazards i.e. those agents having the potential 

to cause cancer under some circumstances. This has led some to downplay the relevance 

of hazard identification22 and even to suggest the exercise is without value. 

21 http://monographs.larc.fr/ENG/News/O&A ENG.pdf 

22See internet archive 

(https://web.archive.org/web/20170220012554/https://www.forbes.com/sltes/henrymlller/2015/03 

/20/march-madness-from-the-united-nations/#6d5581212e93. best viewed with Microsoft Edge 

8 
137 

• The IARC Monographs program is explicit about the difference between hazard 

identification and risk assessment on its website23• 

• In fact, identifying carcinogenic hazards is a crucially important and necessary first step in 

risk assessment and management; it should be a "red flag" to those charged with 

protecting public health. 

• Revealing that an exposure is a threat (or hazard with a Group 1, 2A or 28 classification} 

should trigger elther immediate remedial action (e.g. bans, as with asbestos or access to 

artificial tanning salons for young people, or labelling of carcinogenic hazards) or further 

evaluation of the scale of the risk (risk assessment) in order to set the levels of exposure a 

particular society is willing to accept (e.g. control measures in occupational settings; 

acceptable levels of airborne pollutants, or food contamination by pesticides, etc.). 

• In contrast to hazard identification, the specific exercise of risk assessment typically 

involves extrapolation beyond the observed data, employs a variety of statistical models 

and Is based on anticipated levels of exposure and background cancer incidence rates that 

are often specific to a population or region. 

• Following risk assessment, decisions on managing risk encompass social, economic and 

political considerations. For the above reasons,IARC defers risk assessment and risk 

management to national and international bodies, restricting itseffto provision of hazard 

identification as a scientific foundation to those subsequent steps. 

• This area of debate brings into sharp relief the different and often imprecise ways the 

word risk is used and understood. A quantitative examination of the elevated risk 

associated with a given exposure is an integral part of hazard identification, as a support to 

causal inference. But this differs from the statistical exercises of quantitative risk 

assessment described above. 

There is clear value in IARC and WHO liaising closely In future exercises of ha>:ard 

identification and risk assessment and as mentioned in Section II of this document, 

discussion is in progress. 

IARC evaluations make use of the latest scientific data and methodologies 

• The I ARC Monographs pioneered and continue to be a leader worldwide in objective, 

systematic cancer hazard evaluations. 

and Safari browsers), as cited in https://www.nytimes.com/2017/08/01/business/monsantos-swayover-research-is-seen-ln-dlsdosed-emails.html. 

"http:ljmonographs.iarc.fr/ENG/News/Q&A ENG.pdf 

9 
138 

• Authoritative reviews, including by the National Research Council of the US (NRC, 2011, 

2014, 2018)24, have heralded !ARC's review and evaluation methodology, citing it as 

exemplary and recommending it as one potential model for adoption by US national risk 

assessment programs. 

• Additionally, the IARC Monographs data integration process has been adapted to other 

systematic review methodologies25• 

• The Monographs Program has received funding from the NCI/NIH USA for over thirty 

years. The most recent proposal received a score close to the best possible in the current 

NIH evaluation system. This rating therefore reflects a very high scientific esteem for the 

programme on the side of the independent reviewers. 

• The Monographs program undergoes scientific review by a Review Panel (composed of 

IARC Scientific Council members and external experts), most recently (in 2014) receiving 

the highest possible ran kings for performance (Outstanding) and fit with the Agency's 

mission (Perfect). 

• A subsequent IARC Monographs Advisory Group concurred with the Scientific Review 

Panel in supporting the current system of selection and use of experts for the cancer 

hazard evaluations, accompanied by strict management of conflict of Interests. The 

Advisory Group also encouraged the Program to disseminate the findings of the 

evaluations as broadly as possible to the scientific and technical community, pollcymakers 

and the general public. 

• In consideration ofthis valuable peer review input, and also taking into account positive 

peer review by the US NCI, the Programme remains committed to conducting reviews that 

are scientifically rigorous, respected, and free of conflict of interests. 

"'Review of the Environmental Protection Agency's Draft IRIS Assessment of Formaldehyde (2011). 

https://www.ncbi.nlm.nih.gov/books/NBK208227/: Review of EPA's Integrated Risk Information 

System (IRIS) Process (2014). https:ljwww.ncbi.nlm.nih.gov/books/NBK230074/; 

Using 21st Century Science to Improve Risk-Related Evaluations (2018). 

https://www.ncbi.nlm.nih.gov/books/NBK424983/ 

25 Environ Health Perspect. 2014 Oct; 122{10): 1007-1014. doi: 10.1289/ehp.1307175: Environ Health 

Perspect. 2014 Jul;122(7):711-8. doi: 10.1289/ehp.1307972 

10 
139 

DOCUMENTS SUBMITTED BY REPRESENTATIVE PAUL TONKO

COMMENTARIES BY SCIENTISTS ON IARC GLYPHOSATE EVALUATION
140 

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of glyphosate. The study had a null 

finding for NHL (RR 1.1, 0.7-1.9) with 

no apparent exposure-response relationship in the results. Despite potential 

advantages of cohort versus case-control 

studies, the AHS had only 92 NHL cases 

in the unadjusted analysis as compared to 

650 cases in a pooled case-control analysis from the USA7 In addirionJ the 

median follow-up time in the AHS W:tS 

6.7 years, which is unlikely to be long 

enough to account for cancer latency.-'1 

The RAR classified all of the casecontrol studies as 'not reliable/ because, 

for example, infotmation on glyphosare 

exposure, smoking status and/or previous 

diseases had not been assessed. In most 

cases, this is contrary to what is actually 

described in the public~tions. 

Well-designe~ case-control studies are 

recognised as strong evidence and rou· 

tinely reJied on for hazard evaluations? 10 

The !ARC WG carefully and thoroughly 

evaluated all availahle epidemiology data, 

considering the strengths and weaknesses 

of each study. This is key to determining 

that the positive associations seen in the 

case-control studies are a reliable indica· 

tion of an association and not simply due 

to chance or methodological fla.ws. To 

provide a reasonable interpretation of the 

findings, an evaluation needs to properly 

weight studies according to quality rather 

thQn simply count the number of positives 

and negatives. The two meta-analyses 

cited in tbe IARC Monogn1ph11 are excel· 

lent examples of objective evaluations and 

show a consistent positive association 

between glyphosate and NHL 

The final condusion5 {Addendum 1, 

p.21) that "there was no unequivocal evidence for a clear and strong association of 

NHL with glyphosate'" is misleading. 

IARC, like many other groups, uses three 

levels of evidence for human cancer data. 1 

Sufficient evidence means 'th.at a causal 

relationship has been established' between 

glyphosate and NHL BfR'.s conclusion is 

equivalent to deciding that there is not 

sufficient evidence. Legitimate public 

health concerns arise when (causality is 

credible', that is1 when there is limited evi· 

derrce of carcinogenicity. 

EVIDENCE FROM ANIMAL 

CARCINOGENICITY STUDIES 

EFSA concluded ~No evidence of carcinogetlicity was confirmed by the majority of 

the experts (with the exception of one 

minority view) in eith.er rats or mice due 

to a lack of statistical significance in pair· 

wise comparison tests, lack of consistency 

in multiple animal .studies and slightly 

increased incidences only at dose levels at 

or above the limit dose/maximum toler~ 

ated dose (MTD), lack of preneoplascic 

lesions and/or bei11g within historical 

control range•. The IARC WG review 

found a significant positive trend for renal 

rumours in male CD* 1 mice, 12 a rare 

mmour} although no comparisons of any 

individual exposure group to the control 

group were statistically significant. The 

WG also identified a significant positive 

trend for hemangiosarcoma in male CD·1 

mice, 13 ag<1in with no individual exposure 

group significantly different from controls. FinaUy, the WG. also saw a signifi· 

cant increase in the incidence of 

pancreatic islet cell adenomas in two 

studies in male Sprague-Dawley rats. 14- 16 

In one of these rat studies, thyroid gland 

adenomas in females and liver adenomas 

in male& were also increased. By the !ARC 

review criteria, 1 this constitutes sufficient 

evidence in animals. 

The IARC WG reached this condusion 

using data that were publiclY available in 

sufficient detail for independent scientific 

evaluation (a requirement of the IARC 

Preamble 1

). On the basis of the BfR 

Addendum, it seems th.ere were thtee additional mouse studies and two additional 

rat studies that were \mpubHshed and 

available to EFSA Two of rhe additional 

studies were reported to have a significant 

trend for renal tumours, one in CD-1 mice 

(Sugimoto. 18-Month Oral Oncogenicity 

Study in Mke. Unpublished, designated 

ASB2012-11493 in RAR. 1997), and one 

in Sw.iss·~bster mi<.:e (Unknown. A 

chrollic {eedi11g study of g!yphosate 

(roundup technical) in mlce. Unpublished, 

designated ABS2012-11491 in RAR. 

2001}. One of these studies (Sugimoto. 

Unpublished, 1997) also reported a significant trend for hemangiosarcoma. The 

RAR also reported two studies in CD-1 

mice showing significant trends for malignant lymphorna {Sugimoto. Unpublished, 

1997; Unknown. G/yphosate Ji!chnkal: 

Dietary Cardnogerrcity Study in 

the Mouse. Unpublished, designated 

ABS2012-11492 in RAR. 2009). 

The RAR dismissed the observed trends 

in ntmour incidence because there are no 

individual treatment grcmps that o:re significantly different from controls and 

because the maximum observed response 

is reportedly within the range of the his· 

torical control dat~ (fable 5.3-1, p.90). 

Care must be taken in using historical 

control data to evaluate animal carcino~ 

genidty data. In virtually all guidelines,1 17 18 scientific reports 19 and 

publications10-23 on this issue, the recom· 

mended first choi~ is the use of concurrent tontrols and trend tests, even in the 

EC regulations cited in the RAR 18 (see 

p.375). Trend tests are more powerful 

than pairwise comparisons, particularly 

for rare tumours wher:e data are sparse. 

Historical control data should be frotn 

studies in the .same time frame, for the 

same animal strain, preferably from the 

same laboratory or the same supplier and 

preferabJy reviewed by the same pathologisL 17 " While the EFSA final peer 

review4 mentions the use of historical 

contiol data from the original laboratory, 

no specifics are provided ·and the only 

referenced historical control data14 are in 

me BfR addendumf One of the mouse 

s.tudies12 was dearly done before this his· 

torical control database was developed, 

one study (Sugimoto. Unpublished, 1997) 

used Crj:CD~1 mice rnther than Crl:CD·l 

mic~ and one study13 did not specify the 

substrain and was reported in 1993 (proh· 

ably started prior to 198B). Hence, only a 

single study (Unknown. Unpublished, 

2009} use.d the .same mouse strain as the 

cited historical controls, but was reported 

more man 10 years after the historical 

control data set W<lS developed. 

The RAR dismissed the slightly 

increased tumour incidences in the .studies 

considered because they occur:red "only at 

dose levels at or above the limit dose/ 

maximum rolerated dose (MTDY', and 

because there was a lack of preneoplastic 

lesions. Exceeding the MID is. demonstrated by an increase in mortality or 

other serious toxicological findings at the 

highest dose, not by a slight reduction in 

body weight. No sedous toxicological 

findings were reported at the highest 

doses for the mouse studies in the RAR. 

While some would argue that tbese high 

doses could cause cellular disruption (eg,. 

regenerative hyperplasia) leading to 

cancer, no evidence of this was reported 

in any study. Finally, a lack of preneoplastic Jesiom for a significaot neoplastic 

finding is insufficient reason to discard the 

finding. 

MECHANISTIC INFORMATION 

The BfR Addendum dismisses the !ARC 

WG finding that 'there is strong evidence 

that glyphosate causes genotoxidty' by 

suggest~ng that unpublished evidence not 

seen by the IARC WG was overwhelm· 

ingly negative and that, since the reviewed 

studies were not done under guideline 

principles) they should get less weight. To 

mainmin transparency, !ARC reviews only 

publicly available data. The use of confi~ 

dential data submitted to the BfR makes it 

impossible for any scientist not associated 

with BfR to review this conclusion. 

Further weakening their interpretation, 

Portier CJ, eta/, 1 EpidemioJ Community Healfh Mooth 2016 Vol 0 No 0 
141 

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the BfR dld not jndude evidence of 

chromosomal damage from e"J)osed 

humans or human cells that were highM 

lighred in Tables 4.1 and 4.2 of the !ARC 

Monograph 3 

The BfR ·confirms (p.79) that the 

studies evaluated by the !ARC WG on 

oxidative sU.ess were predominantly posiM 

tive but does not agree that this is strong 

support for an oxidative stress mechanism. They minimise the significance of 

these .findings predominantly because of a 

Jack of positive controls in some :studies 

and because many of the studies used glyphosate formulations and not pure glyphosate. In contrast) the WG concluded 

that (p.77) ~strong evidence exists that 

glyphosote, AMPA and glyphosate-based 

formulations can induce oxidative stress,, 

From a scientific perspective, these types 

of mechanistic studies play a key role in 

distinguishing between the effects of mix~ 

tures, pure substances and metabolites. 

Finally, we strongly disagree that data 

from studies published in the pee.r--

reviewed literature should automatically 

receive less weight than guiddine studies. 

Compliance with guidelines and Good 

Lllboratory Practice does not gu-arantee 

validity and relevance of the study design, 

statistical dgour and attention to sources 

of bias. zs 26 The tnajotity of research after 

the initial marketing approval, including 

epidemiology studies, will be conducted 

in research· laboratories using various 

models to address spedfic issues related to 

toxicity, often with no testing guidelines 

available. Peer~reviewed and published 

find~gs have great value in understanding 

mechanisms of carcinogenicity and should 

be given appropriate weight in an evalu~ 

arion based on study quality, not just on 

compliance with guideline rules. 

GENERAL COMMENTS Sci~nce moves forward on careful evaluations of data and a rigorous review of 

findings, interpretations and conclusions. 

An jmportant aspect of this pr01:ess is 

transparency and the ability to question or 

debare the findings of others. This ensures 

the validity of the results and provides a 

strong basis for decisions. Many of the 

elements of transparency do not exist for 

the RAR.5 For example, citations for 

almost all references, even those from the 

open scientific literature, have been 

redacted. The abltity to objectively evaluate the findings of a scientific repm:t 

requires a complete list of cited supporting evidence. As another example, there 

are no authors or contributors listed for 

eitbe.~; document, a requirement for publi~ 

cation in virtually all sdentific journals 

where financial support, conflicts of inter~ 

est and affiliations of authors are fully dis~ 

dosed. This is in direct contrast to the 

!ARC WG evaluation listing all authors, 

all publi..:.--:ations and public disclosure of 

pertinent conflicts of interest prior. to the 

WG meeting.27 

Several gllidelines have been devised for 

conducting careful evaluation and analysis 

of carcinogenicity data, most after con~ 

sultation whh scientists from around the 

world, Two of the most widely used 

guidelines in Europe are the OECD guid~ 

nnce on the conduct and design of 

chronic toxicity and carcinogenicity 

studies17 and the European Chemicals 

Agency Guidance on Commission 

Regulation (EU) No 286/2011;18 borh are 

cited in the RAR. The methods used for 

historical controls and trend analysis are 

inconsistent with these guidelines. 

Owing to the potential public health 

impact of glyphosate, which is an extensively used pesridde, it is essential that all 

scientific evidence relating to its possible 

cardno'genicir:y is publidy accessible and 

reviewed transparently in accordance with 

established scientific criteria. 

SUMMARY 

The !ARC WG concluded that glyphosate 

is a 'probable human carcinogen', Putting 

it into IARC category 2A due to sufficitmt 

evidence of carcinogenicity in animals, 

limited evidence of carcinogenicity in 

humans and strong evidence for two carcinogenic mechanisms. 

~ The JARC WG found .an association 

between NHL and glyphosate bssed 

on the av~ilable human evidence, 

~ The !ARC WG found significant carcinogenic effects in laboratory animals 

for tare kidney tumows and heman~ 

giosarcoma in two mouse studies and 

benign rumours in two rat studies. 

I> The !ARC WG concluded that there 

was strong evidence of genotoxicity 

and oxidative stress for glyphosate, 

entirely from publidy available 

~:esearch, including findings of· DNA 

damage in the peripheral blood of 

exposed humans. 

The RAR concluded' (Vol. 1, p.l60) 

that 'dassilicatiou and labelling for carcinogenesis is not warranted' and 'glyphosate is devoid of genoto:xic potential'. 

• EFSA .. classified the 'human evidence 

as •very limited' and then dismissed 

;my association of glyphosare with 

cancer without cleat explanation or 

justification. 

~ Ignoring established guidelihes cited in 

their report, EFSA dismissed evidence. 

of renal tumours in three mouse 

Portier CJ. eta!. J Epidemic/ Community Jle.Gith Month 2016 Vol 0 No 0 

studies. hemangiosarcoma in two 

mouse studies and malignant lymphoma in two mouse studies, Thusl EFSA 

incorrectly discarded aU findings of 

glyphosate~induced cancer in animals 

as chance occurrences. 

• EFSA ignored important laboratory 

and human mechanistic evidence of 

genotoxicity. 

1> EFSA confirmed that glyphosate 

induces oxidative stress but then, 

having dismissed all other findings of 

possible carcinogenicity} dismissed this 

finding on the grounds that oxidative 

stress alone is not sufficient for carcinogen labelling. 

The most appropriate and scientifically. 

based evaluation of the cancers reported 

in humans and laboratory animals as well 

as supportive mechanistic data is that glyphosate is a probable hummt carcinogen. 

On the basis of this conclusion and in the 

absence of evidence to the contrary, it is 

reasonable to conclude that glyphosate 

formulations should also be considered 

likely human carcinogens. The CLP 

Criteria18 (fable 3.6.1, p.371) allow for a 

similar classification of Category 1B when 

there are 'studies showing limited evidence o{ carcinogenicity in humans 

together with limited evidence of carcinogenicity in experimental animals'. 

In the RAR, almost no weight is given 

ro studies from the published literature 

and there is an over-reliance on nonpublicly available industry .. provided 

studies using a limited set of as::~ays that 

define the minimum data necessary for 

the marketing of a pesticide. The IARC 

WG evaluation of probably carcinogenic 

to humllns accurately reflects the results of 

published scientific literature on glypho· 

sate and, on the lace of it, unpublished 

studies to which EFSA refers. 

Most of the authors of this commentary 

previously expressed their concerns to 

EFSA and others regardlng their review of 

glyphosare20 to which EFSA has published 

a reply. 29 This commentary responds to 

the EFSA reply. 

The views expressed in this editorial are 

the opinion of the authors and do not 

imply an endorsement or support for 

these opinions by any organisations to 

which they are affiliated. 

Author affiUatlons 1

Envlronmentaf Health Consultant Thun, Switzerland 1

The Uni'10<slty of sydney, Sydl1ey, New South Walos, Austratia 

lTtJe Unlversity of Auckland, Auckland, New- Zealand 4

ChariM University Medk.lne Berlin, Bedin. G~y 5

cancer Research Institute. Bratislava, Slovak. Republic SSorboone Universites. UPMC Univ Paris 06, UMRlll27, Roscoff, france 
142 

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7

CesareMaltoni cancel Research Center, Bentivog!1o 

~~~':}f!alancer Prevention and Rt!search, 

U"""hyofFioreoc~ Italy 9Unlversity of !Uinois at Chlcago, Chkago, Illinois, USA 10National Cancer Research Institute, San Martino-lST Hospkal, Genoa, Italy 1 Un~sity of Hamburg. Hamburg, Germany 12STAMI, Nationol Institute of Occupational Health, 

0<~. NO!Way 13Sdencecorps, Lexington, Massachusetts, USA 141nsUtuto de Alta lnvestigad6n. Ufllve.rsidad de Ti:uapa<:a, Mea~ Chile 151nstitule for Heakh -and the Envirooment Uhiversity at 

Albany, Rensselaer, New York, USA 16Toxkologist Maplewood, Minnesota, USA 17Nationallnstitute of PubrJC Health, Cueroavaca, 

Morelos,Mexico 188ostoll Unlverstty School of Public Health, Boston, 

Massachusetts, USA 

'~Department ol Public ~alth, Clinical and Molewlar 

Medidne, University of Cagllarl, Cagl!ari, Italy 

1Dtlepartmell1 of PreventNe Medidoe, fondazione 

lRCCS Ca' Granda Os.peda!e Maggiore Polidinico, 

MUan.lta~ 

Hoepartment of Environment and Primary Preventioo, 

lstltutoSuperiore di SanltA, Rome, Italy 

~nvlronmental Defense Fund, Amlin, Texas, USA 11Center for Environmental and Occupalional Health, 

Uhivefsity of Cape TONn, Cape Town, South Afrka 14Environmental Health Trmt, Jad:son Hole, ~ing, 

USA and~ Hebrew University Hada~h Schoo! of 

Medidne, Jerusalem, Israel. 25Dalla Lana Sdlool of Publlc Health, Unlver$ity of 

Toronto, Canada 

~nt of Environmental and Occupatlooal 

Health, o ..... l UniYe!sity, Philadelphia, Penn>}lvania, 

USA 

27Brody School of Medicine, tast Carolina University, 

Greenville, Nonh Caronna, USA 281kpartment <~f Epidemiology, J.azio Regional Health 

Sezvke, Rome, Italy 29Universlty of loulsVl11e School of Medicine, louisviKe, 

Kentucky, USA 

"School ol Pubhc Health, C~atln Univeolty, Perth, 

Western Australia. Australia 31Department of Envlronmentalloo:icology, The 

lWver:sity of Queensland, Bfisbane, Au5tralla 310epartment of Population Health Sdences, Virginia 

Tech, Blacksburg, Vlr~nla, USA 33Paris Descartes. University, France 34Epi,Con!'.Uit GmbH, Musweiler, Germany 3

S0anlsh Canter Sodely Researc:h Center, Copenhagen, 

Denmark 

36Unlwr.sity Hospital, Oro.bra, Sweden 37B.klstatistics Branch, Netherlands Cancer ln~tute. 

Amsterdam, The Netherlands 38Facutty of Department of Occupational and 

Environmental Health, Pel:.tng Univ School of Publrc 

He~th, lleljing, China 39Natlooallns1ltute for Environ.11tmtal Health Sciences, Res~arth Triangle Pari; North Carolina, USA 40UnM!Ilfty of Florida, Gainesville, Rorlda, USA 41CWJ Consulting, UC, Cape Cora~ Ftorlda, USA 

""lns~tt.ltl' of Environment, Health and Societies, Brune:! 

University london, London, UK 43Divislon of Biostatisti<S,. German Canc:er Research 

Center, lie!d@)berg. Germany 

Mlru~tute for Risk Ass.es:sment Sdeoces, Utre<ht 

University, Utre<ht, The Netherlands 45Nationaf Council of Scientific and Technological 

Research, Natiooal University of La Plata,. 

Argentina 

46Amhold Institute for Global Health. kahn School of 

Medidne at Mount Slnal, New York. USA 

-'~ Department of Pharmacology, Wayne State University 

School of Medicine, Detroit Michigan, USA 

48Department of Bio~enc!!s., University of Helsinkt 

Helsinki, finland 49Department of Epideml<~!ogy, University of Iowa, Iowa 

esearchCenter,Ben!i~lio. 

~~~;.~}fo~ ~%phot<~nlcs, lancarter University, UK 

S3Department of Prevention, Ocrupal:ional Health Unit. 

National Health SeMce, Padua, Italy 54Department of Epidemiology lazio Region, Rome, 

Ita~ 

550ccupatfonal and Environmental Epidemiology Unir, 

ISPO-Cancer PrevenUon and Researd! Institute. Flanmce, ltal1 

SGoalla Lana School of Public Heahh, University of 

Toronto, Canada 57Unit of Cancer Epidemiology, University of Twln and 

CPO-Piemonte, Torino, Italy 

.

580epartment of Envlronmflltal and OcOJPatlona! 

Health Sdenres,. City University of NEMI York School of 

Pubfk Health, USA 

~chool of Nurs:ing and Public Health, Unlversity of KwaZulu-Natal, Durban, Soutll Africa 60D~artment of Environmental and Ocrupatkmaf 

H.alth, Milken ln>tirute School of Public Health, TOO Ge.orge Washington University. Washington DC, 

USA 

51Health and Envlronment·Department of Prevention, 

local Heallh Aulho!jty...fmpo!i, Aotence, Italy 52Departmer1t of Biology and Blot&hnology "Charles 

DarNin". Sapienza Rome University, Italy 

IBDepartment of Environmental Sder'KeS, School of the 

Coast &: Erwironment, Loulsiana State Unlversicy, Baton 

Rouge, los Ange~ USA 64Center for Appfied GeneUcs and Gffiamic Medidne, 

University of Arizona Health Sciences, Tucson, Arizona, 

USA · 651owa Superfund Research Program and the 

Interdisciplinary Gr.lduate Ptogram in Human 

Toxkolo!)Y, UniVersity of Iowa., Iowa Clly, Jowa, US.4 

btJ.center for Res~n:h h1 Heallh, Work. and Erwironl"l'l:@flt 

(CI"STA}, National Alltonomous University of Nicaragua 

~~~~=~~~d ~~C:~:allh Institute, Associated 

lnstitl!te of the University of Basel, Basel Switzerland 

"coRege of Veterinary Medicine, Mississippi State 

University, Mississippi State, USA 69Department of Environmental and Oa:upati<Jna! 

Health, Floridalntemationa! University, Miami, florida, 

USA 

7

00epanment of Veterinary kltegratlve Biosdences, Texas A&M Univasity. CoiJege Station, Tecxas, USA 71Farulty of Medkine-, Univmlty of 5ao Paulo, sao 

Paulo, Brazil 12Natur~l Resourtes Def!!flse Council and George 

Washington University, Washlngton DC, USA 71Nanosafety RiSearch Centre, Finnish lnstlrute of 

Occupational Health, Helslnkl finland 7"Radbllud lnstiMe for Heallh Sciences, Radboud 

University Medica! Center, Nijmegen, The Netherlands 7

:>Department of Pathology, University of Alberta, 

Edmonton, Alberta, Canada 76Department of Environmental Health Sciences, Johns Hopkins Bloomberg S<.hool of Public Health, B:altlmore, 

Maryland, USA · 77School of Public Health. University of Cafifomia, 

Berkeley, Caltfornia, USA 711Faru1ty of Medidoe. Uni'versity of New Sooth Willes,. 

Randwlck. New South Wale~ Australia 7

-'Program on Reproductive liealth and tM 

Environment. University <~f California, San flandsco, 

CaRfornia, U.SA 80lstituto dl Ge<ISO!inze e Gearisors.e (CNR), Padova, 

Italy 

81 Universlty of Torino, Torino, Italy 

82German Cancer Rese.arch Center, Heide!~rg and 

Faadty of Pharmacy, Heidelberg University, Germany 83fred Hutchinson Cancer Researth Center, Uni'Ver:sity 

of Washington, Sl:!attle, Washiflgton.. USA 84Fa.culty of Public Health. Kuwait UnM!crlty, Kuwait 

City,Kllwait 

S.5Department of Pubr~~: Health ScienCl!s, Medical 

University of South Carolina. Charleston, South Carolina, USA 86Department of Emfromnental Epidemiology, Imperial 

College london, london, UK 87Department of Research, Cancer Registry of Nornay, 

lmtftute of Population-Bastd Cancer Research, Oslo, 

Norway; Depa/UTI(!nt of Community Medicine, Faculty 

of Health Sclef\Ces, Unlver$ity of Tronsm, The Ardk 

University of Norway, TromSII!, Norway; Department of 

Medical Epidemiology and Slostatistia., Karolimka 

lnstitutet. Stockholm. Sweden; and Genetic 

Epidemiology Group, Folkhlilsan Research Center, 

Hefsinld, Finland. 88Depanment of Patflology, City of Hope- Medical center, Dtlarte. Ca6fomfa, USA 89Progr<~m on Reproductive Heallh and theEnvironment, Unive~ty of California, San Francisco, 

USA 

"okayama Unlversily, Okayam~ Japan 91!nstitute of Nanopraduct Safety Res~arc:h, Hoseo 

U.,lty, Asan, The Repubic of Ko~a 92University of Padua, Padova, Italy 930epartment of Pre~ntioo and Evaluation, leibnizlnstltute for Prevention ReSI!arch and Epidemiology, 

B~n,Gennany 

"College of Pharmacy, UniYe!sity of South florida, 

Tamp~ Florida, USA 

Contributon All authors to this commentary have 

participated in Its development and approve the content MCB, FF, lf, CWJ, HI(, TR. MKR, IR and CS 

were all partidpants in the IARC WG. CJP was an 

Invited Specialist in the IARC WG. Many of the 

remaining authors have also served on !ARC Working 

Groups that did not penain to glyphosate. 

Comp!!ting interests CJP, MTS and ODWare 

providing advke to a US law fum involved in 

glwhosate litigation. CJP also works part~tlme for the 

Envlronmenral Defense Fund on issues not related to 

pesUcldes, 

Provenance and peer review Commissioned; 

externally peer reviewed. 

(;) 

OPEN ACCESS 

Open Access This Is an Open Ar.cess att!ded"!Strlbuted in accordance with the Creative Commoos Attribution Non <ommerdal {CC BY~NC 4.0) licerue, 

whkh permfts others to distribute, rii!ml~ adapt. buUd 

upon this wM: non-commerdaUy, and Jk:er5e their 

derlvatNe works en different terms, provided the 

OJiginal work is properly dted .and the use b: non~ 

commercial. See: hnp:l/creativ&ommon..s.orgllia:nse~ 

by-nd4.01 

To dte Portier CJ, Armstrong BK. Ba.guley BC. eta/. J EpidemkJ1 Community Health Pubtished Online first 

!please lndurle Day Month Year! dol: 10.1136/j«h· 

2015·20700S 

I fp/demlol ComtriUili/y Health 20t6;0:1-5. 

d~:10.1136!jech·2015·207005 

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A. Section 508-confQrman.t HTMl verslon.Qfthls ankl@-

lsa'\laJr.abfeathttpJ/dx.doJ,orgf10.12B9/ehp.tii09l49. Commentary 

IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans 

Environmental Health Perspectives • VOLUME 1231 NUNB.f.R61June 2015 507 

• 
147 

• Pearce et al. 

BACKGR.OUNO: Reocndy, the International Agency for Research on U:ncer (IARq Programme for the 

Ev.drution of Quodnqgcnic Rhks to Human' Jw been altldud foruvcral of Us evatuadOlls, ~:~ud abo for 

the approach llftd to pedonn th~ ~u:ulons, Some crltlcs ha't'! dalnud that &llum oCIARC Woddng 

Groups to recogohc mrdy weaknes.Je5. "!Ad b)as:es ofWo~g Group meMbe.rs lua.ve led to .lnappropcla~ 

dud~tlon of a n~ber ol asents.u tardno~lc: to h~~ll.· . ' 

0B~~t1he autlwa of thb ~01ent!Uy are ldentist.J from vadow dlsdpflnes tclev.ant'to the identification and hiWUd mllllltlon of human catdn~getu. We examined ctltldarns of the IARC claS&llicatlon 

pr~Keu: to determine the validity of these wncerns. Here, we prtsent the r¢SUIU of that examination, 

revJcw the blttor:y ofiAnC ~.oduadom, and derulbe how the. IARC: ~valuati~nJ are pcrform~d, 

DJ.SCUSSto& We concluded that thue r«ent crltld~l are llRWn$dng. lbe proudure.s employed by 

IAllC ro ustmble Working Gro!lps of .sdentl$ts from ~e yarktua dhcipllnes and th~ ted!lliques followed 

to .I'!Wlew the Jl~t!lle and pufortll buard ISSCSSmtht or \ilrioU$ age:DU provide I baJanted ~V;tluaflon 

and an .11ppr~rla~ Jrtdiwlon of t:h.e weight of the nldence. Some dlsagn::c:mens: by individual $dentists 

to some ~m~luatloru; b not e'ridence of proUS!! &UUN. The- cnWw pro£1:511 ~u been modlfied ovn tlme and 

wW undoubredJy be altered in the future to imp row tM proccu. Any proceS5' can ln. theoiJ' be improV!:d, 

llltd ~ would 'up port continued review and lmpronment o£ tht!. lARC proceue~. Thi.t doer not m.eau, 

however, tlat the cumnt pf(Jcedl!.les are flawed. 

CoNCWSIONS: The !ARC Monogra.phs·ha't'e made, and continue to make, major contribution:!" to the 

fodentlfi.c WKieiplnnlng for rodctal actlom to Jroprove the publk's heahh. 

CrrAUON: Peat~ N. Blair A, V1nels P. Ahrens W, AndeRm A. Anto JM, Arm~trong DK, Baocardll M. 

DeliiUd FA. Derrington A, Bemwl PA. Birnbaum LS, Brownson RC, .Bucher JR, Can.tot KP, CaRib E, 

Chettie JW, Chrlstlanl DC, Cocco P, Coggon D, Comba P, Dcmer.ll PA. Dement JM, Douwu J, E1sm EA, Engel LS, Fnuke RA, Remlns LE. Retdler T, Foutham E, Pomsriere F, Frenn.d·Beytne R. 

Ftltst.hi L, Gcrln M, Goldberg M, Grandjea:n P, Grimsrud TK, Gustavs:~on P, Halnes A, Hartge P, 

HazumJ, Hauptmilnll M, Hudtrik D, Hemmlnld K. Hernon D, Hertz-Plcdottl) l, Hoppln JA. Hulf J, }an"holm B, Kang D, Kan:gu MR. Kjaerhelm K. K)uua H, Lg!!Ylna.s M, K:rlebd. D, K:rUteawn P, 

Kromhout H, Laden F, Lebailly r. LeM:uteu G, Lubin jH, Lfuch. CF, Lynge E. •t Mannetjc A, 

McMichad. AJ, McLaughlin JR. Marrett L, Manuul M, Merchant JA. Meder E, Merlem F, MiUer A, 

Mlll:IPE, MonJI)n R, NonfbyKC, OlshanAP, P-~ME.PerenPP, Pr:nyMJ, PesatoriAC, PlnutuR,. 

Porta M, Pukk:da E, llkr C, IUthudson DB, Rltrer 1., Wn B, Ronckeu CM, Rmhton L, Rustcdd JA, .Rusyn I, Samn JM, Sandler DP, de Sanjo!>'t S, Sdternhllmmer E, Senlori Conan.llnl A. Selns N, Shy C, 

Siem1atycld J, Sllnm1an DT, Shnoo11to L, SmJr:h AH, Srnkh MT, SplneiU JJ, Spln MR, Stallone~ L, 

Stayner LT, SNcnlahd K, StcnuJ M, Stewart DW, Ste\Vlln PA, Syman.tkl E. Ternt.elui B, Tolbert PE. 

Valllio H, Vena J, Vermeulen R. Ykton CG, Ward EM, Weinberg CR. Webenbw-gu 0, Weuellng C, 

\V'e!derp;an E, Z,.bm SH. 2015, !ARC Monographs: 40 yean of evaluating carcinogenic hu:11rds to 

humans. Enrlron Health Penpect 123:507-!Sl<i; http:/ldx.doi,oq¥10.1289/ebp.l409149 

Introduction 

Importam advances in human health have 

come. from the recognition of t"lealth hazards 

and tl1e development of policy actions to 

address dtcm (Browruon et al. 2009; Espina 

et al. 20J3J Samet 2000). Government and 

nongovernmental organizations use expert 

pands. to review the ~dentific literature 

and to assess Its relevance to public health 

policies. Scientific expem ue charged wirh 

reviewing the quality and quantity of the 

scientific eviden(:e and providing sdendfi(: 

inrerpretatiom of the evidence that underpin · 

a range ofhealth policy dedsions. 

The !ARC Monvgraph1 on the EV111untion 

of Carcinogcllic Risks to Humans of the 

International Agency for Research on Dncer 

(IARC) are a prominent cumple of such 

an expen review process. The goal of the 

Monograpb Prognmme is ro asst'!s carcino~ 

genic hazards from occupational, environ~ 

mental, and lifestyle exposures and agents, 

thus providing an mential step in the socieral 

decision~nuking process to identify and 

~hen control carcinogenic hazards< For these 

evaluations, IARC assembles groups of sdcn~ 

tis~ with a range of relevant sdentllic: expet· 

rise (caUed "Working Groups") to review and 

assess the quality and strength of evidence 

from informative publications and perform a 

h:nard evaluation to asse:u rhe.likclihood that 

the agents of concern pose a c<~.ncer hazard 

to humans (Tomads 1976). IARC h"s used 

this approach for four decades, sin~ the first 

Monograph in 1972 (lARC: 1972). Although 

widely accepted internationally, there 

have been criticisms of the dassificatlon of 

particular agenn in the past, and more recent 

criticisms have been directed at the general 

approach adopted by IARC for such evalua~ 

lions (Boffetta et al. 2009; Epidemiology 

Monitor 2012; Joannidis 2005; Kabat 2012; 

McLaughlih etal. 2010, 2011}. 

The Mouographs are widely used and 

rcferem:ed by governmeD.U, prgartizations, 

and the public arotmd the world; therefore, 

it is critical that Working Group conclusions 

be dear and transparent. In addition to the 

actual evaluation, a major contribution of 

the Monographs ls the 3S$embly of relevant 

literature and Its dissemination to rhe public. 

We recognize that no system of -=valuation is 

perfect, h is important to foster continuing 

improvement of the mcthGds used by IARC 

and other bodies that review scientific 

evidence. The IARC prot:ess itself has been 

modified from Ume to time (e.g., addition of 

specific cYaluation of mechanistic data and 

greater usc:: of fonnal mcu-analyses and datapooling approaches). Indeed. as recently as 

Aprll 2014, the IARC Monographs program 

has been a subJect of a rcvlcw by the Advisory 

Group to recommend pdorides for !ARC 

Monographs during 2015-2019 {Straif 

et al. 2014). The Advisory Group has made 

a number of recommendations on further 

improvcmenu in the Monographs process 

specificafly related to conflict of.interest, 

transparcncy1 and the use of the: systematic 

review procedures in data gathering and 

evaluation. Thus, possible changes ro the 

ptoeC!IS are periodically con~dered by IARC 

Addreu. oouetpot1dt:lltt: toN. Pearce, llip~ftOleut of Medical Smtlstlcs, L!u~oll School of Hygiene 3ml Tropical MW:Idn~, ~ppel St., L:Jndon WCIE 7HT, Uni1nl Kingdom, 

TckpJt(lln~·: 44·20-7958-8151. E-malh udl.p-:arce@lshttn.ac.uk Thbwodt wllsronductcd with no d!rct:r funding, bur was s\lpponed in pan hy the Inu .. •mm·:~l Resr:m:h Program of !he NIH {MCJ ~1\d NIBHS). 

n.~ vic\n: cxp~ed :~re tho5e af the :llllhi'IU and de> 110t ne<."d.S:ui!y·feBw rhe oaidal "Ylc:ws of the UnJIUrmed Servku Unift'~ity of d1~ Ha.lth Sclem~c:s. th~ De~tntnt nf 

Dcfemc. or th~ U.S. Food and Orug.Admioi.~tr:u!on. 

M. Stcou! it cmpl~Jyed by E:tposurc As#utFKnt Appllauloru LLC (Arlington, VA, USJ\). P. Stew~ ill em}•loy~-d by Stcw:t.n .Expas~~ Aw:ssm~n!S LLC (.\rlingroa, VA. USA), 

S.ll. Zahm i:& employed by Shdia Zahm Coruu!dng {Hermon, ME, USJ\.), and she h~ so:rvcd :u an ~~lleR witlles.! fur dK: plaintiff$ It! U,S, lillgation invoMng polydlL:uinmd hlphenyb and non-Hodgkin lympho~rn~. J. Huffh:.s s~rvn:t u :111 aputwitMs.s &or pl:\lntlffs bt U,S, litigation liJYolving upamres ta :~~:rybmid~ 11.nJ to styr~ru: .and cuc~oenldty. 

B. Amutrong mslimnc-dy Ikputy Dirw:nroflARC (l99l-1993),:mdJ. Huff and H. V~ioio l.~w l'reviau!.ly St:rved a' head of rhc IARC Mouoguplu Pro,~:mm. Mwt (but not all) otht a11tbou ~~ scrwe-d on IARC Mooogr2ph Watldng grouJn, <~M .~ever;~! have worked for IARC in tho:. p;~n. Although P.' Demui b Director of ll Dcpntme1U rhat hu 

td~rch and consnlhtllcy .:onrr:rcn with industry (ind1.dlng perrochemkid, plastks.lron, and st~d, 211d other cb~niatl.), "~well as gownunental, privat~, and uonpr001 ~gencl~. 

hoe l1:u no affilluion with industry. he has ,~rvro in ltltlyas an nprn ln mcUicallqpl ca.= IRvr>holllg d.atos o;poruf~ 111<.! asbest05·lnduccd disea.u:: and prep:ued reporu (>n caustion. ~00 df~gn<uh of asb<ttOS-tdatcd diwrdm tor wun:s. D. Chrht:lani, J. Dement, lind A. Smirh baY~: :served ~s expertwiiiKlSel' in U.S. Jitiga.tionlllvolvjng :ubc.'ltoi o:pwure an.d dilellte ou~otnd, Including (;lf!Cer, E. Foutb.ttn b a Senior Rcn:a.rch Fellow at the lntcmational PtC\'Citdon ~tem::i1 Innlrurt. P, Comba, P. f'OWcitu-, E. Meder, F. Merlctti, 

R. Plr.mu, B. Tenadnl, and P. YtneU hn-e act«! as: c:nn~tt(;lntt to pro~cuton and Judga loa number (If cGuu c:.ue trials. P, Mlrcr has reaivcd romp!'ns;atlan ;u 11. caruulwu tQ the 

AFl-ctO 2nd the UAW 111 $ltppon oflklptl\lll. E. \Vd..ktp<\iS is atm:ntly ~member of 1he !ARC Sciemific Council, lhe other atnhors dedan: they lu.v.e no attua:l or potelttial 

cumpetingfinanti:lllnttrun. 

~ivM: 14 S!:!ptc.Jnbcr 2014; Arn:ptcd: 20 febrtr.~ry- 2015; Advance I'ublimion: 24 February 20l$; Final. Publiouiat~: l Juu~ 2015. 

508 VOWME 1231 NUM!!ER 61 June 2015 • Environmental. Health PerspecHves 
148 

governing groups (Scientific Council and 

Governing Council} a,nd Advisory Groups. 

Here. we focus on current IARC proce.s5es 

and practices bec11use these hav~ been the 

focus of recent criticisms. 'The -authors of this 

Commentary ate scientists from a wide: range 

of disciplines who are invoJved in designing· 

and conducting studies that provide data 

used in huard evaluations, such as thooe 

performed by !ARC. Many {but not .ill) of us 

have served on TARC Monognph Working 

Groups, but none arc current IARC staff. We 

lint discuss the history of !ARC, and describe 

how the IARC evaluations are performed in 

order to foster evidence~based poHcy. We 

then describe why unbiased evaluations, 

based on the evidence and free of conllicts 

of interest, are necessary for pullllc health 

decision making. Flnally, we dlscws the 

recent crltldsms of the !ARC approach. 

The IARC Monographs 

History of tb~ IARC Mo,ngraphs. Shortly 

after IARC's establishmenr, its parent entity, 

the World Health Organization (WHO}, 

asked IARC to prepare a list of agents known 

l'o cause cancer in hwuans. IARC recognized 

the need for a system:tdc process ro determine 

which agen~ should be listed. Such a proceu 

was bunched in 1972 by Lorenz.o T omatis, 

then Chief of the Division of Carcino~nidty 

of !ARC rromatis 1976). !ARC Is fund«! by 

the governments of 24 countriu that have 

decided to become members, in addition to 

compeddve grants from funding agencies. 

The JARC Monograph Programme is 

mainly funded h)' the U.S. N11tion:1l Cancer 

Irudtute through a rene\vabfe grant .subject 

to peer review of the program. Other sources 

of n;tcrn:t.l funding have included the 

European Commission Directorare-General 

of EmplQymem, Social Mfairs and Equal 

Opponunitie.s; the U.S. National Institute of 

Environmental Health Sciences; and the U.S. Environmental Protection Agency. 

The IARC process antetiues current 

system-:t.dc review methods, but anticlp-:t.ted 

some of them, for example, with regard ro 

transpan=nt litemture identification. In the 

!ARC process, Agenu are asse.s.sed for carcinogenic hazan.l o.nd autgned to one of live categodes, ranging from carcinogenic to humans 

to probably not carcinogenic ro humans 

(Appendix 1}. 1he das:~i6cation categories are 

de$Cribed in the preamble to the Monographs 

(IARC 2006). Carcinogenic hazard identification rd~!n to an as.ses.sment of whether an agent 

c:tuses cancer. Haz:trd identification does not 

predlct the magnitude of cancer risb under 

spcdfic conditions; this can be determined only 

with appropriate exposure-response information (Nation-al Research Coundl2009). 

7ht JARC Mb'nograp!J pro«Jt, The process 

for the preparation of ~n IARC Monograph 

is dearly described in the Preamble, which is 

published as part of each Monograph (e.g., 

IARC 2014.1), It starts with the nomination 

of ~ndid:ate agena. Nominations come frotn 

national reglllatury agencies, scieltd:ns, and 

stakeholders, including public health profe~­

slonah, experts in environmental or occu~ 

pational hygiene, Industry repres:entatins, 

and private citizens. It is important to note 

that anyone (including private citizens) can 

p:mkipatc in the nomination process. The 

Monograph Programme convenes meetings 

of special Advisory Groups (C{)mposed of 

exrernat scientists that posses.s a bmad range 

of relevant profasiona1 sldlb) to review agents 

nomiuted for evaluation and ro suggest 

!ARC priodi:ies for such reviews (Ward er al. 

2010). Announcements of a m-iew are made 

on the IARC weNite (http:!/monographs.iarc. 

fr/ENG/Meetingsl). For example, in 2013 

IARC sought nominations for agents to be 

""luotoo 1n 201~2019 (!ARC 2014b). An 

Advisory Group revkwed the nominated 

llgents :tnd exposures~ added several new ones, 

and di.scL1SSI:Ii the priotitie.; fur each. 

llu: IARC staff makes the 6nal selection 

of ageots fot review by taking into account 

the prcvaleltce and intensity of exposure (of 

both occup:ation:U groups and the general 

population) and availability of sufficient 

Htt:tature fOr an cwlnarion of carcinogenicity, 

as well a.s .advke from the Advisory Groups. 

The large majority of evaluations concern 

specific compounds, but there are also monographs on Y:l.rious occupations or industries, 

for example, aluminum production, insecticide applkators, 6rc6ghten, mAnufacture of 

le<tther goods, leather tanning and processing. 

welding, painters, petroleum refining, and 

pulp and paper manufacturing. Some indi~ 

vidw.l exposures that occur in these settings: 

have also br:en eva.luated. 

The next step Is the selection of members 

of the Working Group (WG). IARC staff 

review th(: literature to Identify Working 

Group candidates :tnd spedalisrs In relevant 

are::u: of expertise; they also .seek names 

of pos~!ible candidates from the scientific 

community and advisory groups. The list of 

potential members, including disclosure of 

relevant conAic~ of inteR"st, is posttd on the 

IARC website (http://monographs.iarc.fr/ 

ENG/Meetings/) before the WG is convened, 

and anyone can send comments. Members 

are typically scientists who have conducted 

research rdevattt to the agent under review, 

but not necess;uily on the speclfl.c agent. 

Selection procedures are evaluared yearly by 

the Scientific an~ the Governing Counclls. 

The IARC Section of Monographs also 

has: an external Advisory Board, made op 

of independent sc;ientists, that periodically 

peer reviews its activities. In addirion to 

Working Group members, invited specialists, 

Envltonmental Health Perspectives • VOtuMf 1231 NUMifR 61 June 2015 

!ARC Monographs 

representatives of health agencies, stakeholder 

observers, and the !ARC Secretariat also 

attend meetings. 

The responsibility of the Working 

Group is to review the literature before the 

Monograph meeting, dlscu.u rhe liter-ature 

at the mr:etlng. and then classify whether an 

agent is carcinogenic, probably cardnoge.nk, 

possibly carcinogt':nic, not dasslfiabl~, or 

probably not carcinogenic ro humans .(see 

Appendix. 1}. Worldng Group members 

are also cesponslble for writlng the IARC 

Monograph, which must both review the 

litel'a.ture :and explain why the Working 

Group came to their speci6c conclusions. 

The procedures used to evaluate the scientific evidence are described in the Preamble 

to the Mouogr.:tphs {IARC 2006). lt is 

important to stress thar on1y Working Group 

members conduct the acu~D.I evaluation (Wild 

and Cogliano 2011; Wild and Straif 2011), 

!ARC staff facilitate the evaluation proct:$5 and 

ensure that the procedures desc~Jhed in rhe 

Preamble are followed; however, they do not 

determine rh< outoome.s. 

1ARC assessments of eardnogenidty 

are based on, and necessuily lim!red to, 

scientific evidence: available at the tl me 

of the review. The evldence comes from 

epidemiologic studies, animal bioass:ays, 

pho.rmacoiUnetidmechanistic experiments, 

and surveys ofhum:m exposure. The aim is 

to include aU relevant papers on cancer in 

humans ;,tnd expcrimenr-.~:1 animals that h:t.ve 

been published. or accepted for publication, 

in peer-revirwed scientific journals and also 

any publicly aY:Iilable government or agency 

doc.."UU1ents that provide dat:t on the circum~ 

stances and extent of human exposure. To 

that end, the search of the literature tako a 

comprehensive approach. Papers that are 

found not to provide=. useful evidence can be 

excluded later in. the process. IARC staff 6r.st 

we previow IARC Monographs (if available}, 

darabHe searches wlng relevant coc:t strings, 

and contact with lnve,<;tlgators In the fidd ro 

idendfy porenrially rdev:rnt nmerial. Thw:, the 

inida1 :aMCJTlbly of the literature Js performed 

by indi'Viduais who arc not engaged in the 

actual evaluation. Worldng Group members 

are then aSJligned vadou~ writing tasks and 

are insttucted to perform their own liceratur._ 

searches to identify any further papers that 

might have,been missed. In addition, all of the 

papers rusembled by IARC :are made available 

to the full Working Group before they meet. 

and any member can rerommen4. other papers 

not previously identified that tbey think should 

be considered. Finally, papers can be recommended by nakeholder representatives before 

or during the Working Group meeting. 

At the meeting of the Working Group, 

rhe assembled docume.nrn an= reviewed and 

swnmarizcd by discipline-related ntbgroup.s.. 

509 

• 
149 

• Pearce et al. 

However, any member of the Working Group 

h:u ae;cess to all of the assembled lircramre. 1he 

summaries are distributed to aU subgroupsJ and 

information from all disciplines is: discu~ in 

plenary KS!ions prior m auigning the agent$ to 

a specific: carcinogenidty category. 

Ekcawe new flndings continually emerge 

in d1e lirerature, agents are reconsidered whc:11 

!ARC and IARC Advisory Groups judge 

iliat there is :ruffidcnt addition~ information 

iliat might alta a previous n-:tluation, lhw:, 

conclusions regardlng. human cardnogenidty 

of particular substances may change as new 

evidence becomes av:ttlablc. For some agents, 

this reevaluation has. resulted in progrcs~ 

sian toward greater ceru,!nty regarding thei.r 

human carci.noge,i~idcy, whcrea<~ for others 

the progress has been moved toward less 

certainty. Such movemcnn are expected in 

au open, tramparent, and evidcnce~bMed 

process. A comprehensive update of all 

Group 1 carcinogens was recently accom~ 

plished in Volume 100 A through F (http:/f 

monographs.larc.frfENG/Monographs/ 

PDFslind<x.php). 

Usually, several agents are evaluated in a 

single meeting las.ting more th:m 1 week. After 

discussing the evidence fully, the Work1ng 

Gwup members follow the published !ARC 

procedures for combining information from 

epidemiologic srudies and bioass:ays to arrive 

at a prefiminaty classification (IARC 20l4a), 

Mechomistic d:aa are then comktem{ ln order 

to determine whether they warrant a change 

from the preliminary dassifkation. The 

Working Group ilicn wtcs on the final determin:uion. Many votes :are unanimous, but QD 

occasion some reviewers may favor a higher 

or lower ranking than the majority. When 

there is dissent, alternative interpretations 

and ilidr underlying r~oning arc somctirnc.s 

reported in ilie rationale for ilic evaluation if 

the dissenters feel their point of view is not 

sufficiently addressd in the monograph. 

Comider11tio'1 of tbe totality of the 

evlden~e. !ARC Working Groups make 

every effort to provide full and tr;tnsp:arent 

documentation of what evidence was 

assembled, how it wa.~ cV"J.IUatcd, and which 

papers were most important for rhe hazard 

evaluation. Coosequently, the monographs 

arc often quite lengthy, containing many 

evidence tables [see, for example, the recent 

monograph on trichloroethylene (IARC 

2014c)1, Evaluations involve consider-.uion 

of all of the known relevant evidence: from 

epidemiologic, animal, ph2rmacokinetic/ 

mechanistic, and exposure studies to assess 

cancer haurd in hum•J.fls. Information on 

human exposure is not form·J.Jiy graded as 

part of the overall assessment or carclnogenk 

hazard; however, dtese data make a critical 

contribution to the process hy charac~ 

terlzing the tinting, duration, and levels or 

510 

exposure in the population, and in evaluating 

the quality of the exposure assessment in 

epidemiologic .stu<lies. 

Doubts and ctitidsrns have sometimes 

been expressed about the relative welghu 

attributed to evidence from individua1 disciplines to the assessment of cancer hazards to 

humans; however, each discipline provides. 

important evidence toward the overa11 evaluatlon of causality -ao:ording ro the Bradford 

Hill consider:ations (Hill 1965). 13ccawe the 

totality of the evidc:nce is considered, defi~ 

dcndcs in one discipline are ofren offset by 

suengtlu in another. For example, epldemio~ 

logic stud1c.s may focus on population-relevant 

exposures~ whereas findings from anim~l 

experiments usua1ly involve higher expo.tures 

bttt arc le.~~S susceptible to confounding. 

long~term :animal bioassays :md mecha· 

nisric studies provide ctidcal in&umation on 

the cap:~dty of an agent to produce. cancer 

ln mammalian systems, includJng hmnans, 

and to contribute to decisions that would 

lead to better protection of human health. 

Bioas.say.s arc the backbone of regulatory 

science because they provide the opportunity to rigorously eva1uate potential ha7.ards 

before there l.s widespread human exposure. 

Bloassays and mechanistic studies arc some--

times criticized ror employing exposure routes 

and doses that In most instances humans 

would not experience, although experimenta1 

dose categories sometimes approach exposure 

levels found In occupational situations, There 

is evidence that carcinogenicity In human and 

animaJ smdks is ofren concortlant, although 

data may differ a.~ to the affected cancer site 

(Haseman 2000; Maronpor et a!. 2004; 

Tomath 2002). A major effort ro evaluate 

the concordance between animal and human 

results is currently under way; two Working 

Grnups we~ convened at IARC in 2012, :and 

a systematic evaluation of the correspondence 

becwttn human and animal data 'va.s undertaken (a report is not yet publicly available). 

Criticisms of theiARC Process 

IARC Monographs arc widely used to 

identify potential carcinogenic hazards to 

humans and serve as reference documents 

summarizing the literarun: on many di.lfercnr 

agents. In rece.ut years, however, lnd1vidu-.1ls 

have criticized both ilic classification of indi~ 

vidual agents as we!l as the genttJ.l evaluative 

approach {Bolfen:a et al, 2009; Epidemiology 

Monitor 2012; Kabat 2012; McLaughlin 

et al. 2010) 2011). We discuss four of these 

criticisms below. 

Critid.JmJ (Jf epidemiol9gy. Some of the 

criticisms of the IARC process have occurted 

in the context of more general criticisms 

of epidemiology OJS a science {Kabat 2008); 

these were discwsed in detail by Blair et al. 

{2009). Potentia1 methodological we;tknesses 

for observational ephiemlologic studies are 

weU recognized :and can he found in any 

epidemiologic textbook (Cbeckoway ec al. 

2004; Rothman et al. 2008), Most studies 

are subject ro one or more methodological 

limitatiQnS, but this does not necessarily 

lnvaHd.ne their findings (Blair et aJ. 2009). 

[n facr, the value of epidemiologic studies has 

b~n .shown by ilic idcnti6carion of a nwnbcr 

of wdl-c.nabllshed human carcinogens, 

including tobacco, asbestos, benu:ne, hex-a~ 

valent chromium, and some viruses, ln 

multiple studies. Some ctitia also argue that 

small or nQnexistent he;d.ili rMa are unjustifi~ 

ably highlighted and hyped by rese11rchers who 

have a vested interest in continued research 

funding and the need to publish to benefit 

their careers (Boffetta ct al. 2008;. Kabat 

2008; M<Laugl~in" ~. 2010, 201!; T•ube. 

1995). However, such overstated results are 

unlikely to exert much of an influence in a 

Monngraph becau:se [ARC evaluations arc 

based on the totality of the evidence. The 

problem would have to occur in multiple 

studies, and the Working Group would h~ 

to be unable to identifY It or be unwilling to 

weigh such studiCJ appropriately. Incorrect 

positive conclusions regardlng carcJnogcniciry 

may also occur in reviews of multiple studies 

because of publication bias, which may 

selectlvdy popula~ the literature only wirh 

"po.titive" findings. Howevt:r, once a topic is 

recognized as scientifically important, ttports 

on rdevant studi(S wlll be: published regardless 

of the findings, ro publication bias. is mainly a 

concern for newly arising is.wes. To evalllate 

tbc porcnrlal for publication bias, Working 

Groups consider whether stronger negative 

studie& {both in terms of design and sample 

size) have emerged after publication of an 

lnltial duster of smaller and/or weaker positive 

studies, Funnd plot.! help in the auessment 

of bias relating to sample size and publica~ 

rion blas {Borenstein ct al. 2009), In contr~t, 

there arc no cnablished statistical techniques 

co clearly charncuril.e smngth Qf design. 

One of the distinctive features of epide~ 

mlology is thar criticism and sdf~critidsm 

are firmly embedded in the disdpline. A 

great deal of work has been done on devd· 

oping methods for critical appraisal (Elwood 

2007) and for asse.sdng the likely strength 

and direction of possible biases (Rothman 

et a!. 2008). Epidemiologists and other 

members on Working Groups routindy use 

various approaches to assess possible bias in 

srudy deslgn and ana1ysis when weighing the 

strengths of di~nt studies. 

'!he issue of false positi11es. Epidemiology 

specifically has been criddu:d for a tendency 

to produce false-positive results (i.e,, individual study assocb.tlons not home our by 

tbe weight of the evidence) or to preferen· 

tlally report positive findings ov.c:r llegative 

vrn.uMe 1231 HUMBER 61 June 2015 • Environmental Health Perspectives 
150 

or Inconclusive Hndings (i.e., publication 

bias) (Boffetta et aL 2008t 2009: Joannidis 

2005; Kabat 2012; McLaughlin and Tarone 

2013). This criticism has been mon often 

applied to potential false positives front 

individual studies, but it has been inferred 

that this problem may also apply to overaU 

hazard evaluations, which usc findings from 

mu[tlple :;:tudies. We will consider each of 

the.seissllC!inturn. 

False~positive findings may occur by 

chance, particularly when many combinations 

of exposures and health outooma have been 

cxamin~d in a single .srudy without strong 

prior expectations of assod:.tdon; this happens 

often, for example, in genome~wlde associa~ 

tion i'itUdies where thou:mnds of gene-disease 

associations are C"'aluatJ:O:d, Chant.-e, of oourse, 

operates in all disciplines and in both observational and cxpcrimcmal srudies. However, 

there are wcll~known sradstlcal techniques 

to reduce the probabi!iry of declaring chance 

findings as "positive" (ROlhman et at 2008), 

Independent replication, however, is the most 

convincing way of checking for "chance" 

findings; hazard evaluations, such al those 

conducted by IARC Working Groups, rely 

hellvily on reproducibility in independent 

studies and also interpret data following 

BndfurdHill pdnclpl« (H!U 1965). 

Fals:e negatives are more difficult to 

address, and perhaps they occur more 

frequently than &lse positives because of low 

statistical power, nondiffercntial misdas:-

siflcation of o:.posure and/or outcome. Md 

incomplete foUow-up, whidl tends to reduce 

the observed difference in risk between 

the exposed and noncxposcd populations 

(Ahlborn et al. 1990; Blair ct al. 2009; 

Grandjean 2005; Rothman et a!. 2008), A 

new poslri~ :uwcla.t!on stimulates research, 

wher":as studies .finding no auociatioons tend 

tu stifle fi.trthet work. 

There are clifficulrics in conducting 

epidemiologic studies of agent.t rhat are rela~ 

dvdy "weak" carcinogens, or for stronger 

carcinogens where exposure is very low 

because bi:as and confoundlng. can obscure 

weak positive a..~odations (Mi\cMahon et al. 1981). Ju gencril, weak carcinogens and low 

levds of exposure re.sult in a smaller "signal~ 

to~noise'' ratio making the real signa! more 

difficult to detect. Although the id.enriflcation of small relative risks ro humans p(lses 

special chatlenges to sdentiflc research, the 

refinement of study designs, improvements 

in methods t;tf nposure aue.umu.t, and the 

use of biomarkers have helped to address the 

problems (e.g., newer studies on the effects 

of air pollution, the growth in opportuni~ 

~::~s)o (:;~~i~c J.e~~i).v;:~~l:nstit~::~~::: there is less of a problem, For example, in 

occupational studies, exposures and relative 

risks may be higher while dtffe.rences in 

Ufa:tyle fact{)rs between different groups of 

workers are smal!e.r (Cha:koway et al. 2004); 

thus., any confounding by nonoccupational 

factors is likely to be weak, even from potent 

causes of cancer such as cignette smoking 

(Sjemiatycki et a!. 1988}. Of course, the 

interpretation of such s.tudles is enhanced 

when rherc is lUpporting evidence from bioas~ 

S'afs and/or mechanisric studies. 

False~posidve and false-negative findings 

in indivldual studies may ariSe by chance 

or bias, including bias due to confounding 

(Rothman et :al. 2008). How~ver, the .ewJuaN 

tion of multiple independent epidemiologic 

studies from various geogr:~phlc locations, 

involving a variety of srudy dC.'Iigns, as w~U as 

evidence from cxperimema1 studies, reduces 

the pouibllity that false-positive findings Cmm 

any individual nudy influences the overall 

cv'd!uation process, Some studies may have 

greater influence than others because of meth~ 

odological strengths and/or large sample size. 

The usc of information from a variety of study 

designs reduces the Ukdibood of false-positive 

evaluations because it is un1ikdy that the .same 

bta~ will occur in multiple studies based on 

different populations under different .study 

designs, Moreover, apparendy conflicting 

results from epidemiologic studies do not 

nea:ssarily indicate that some are false positive 

o.r false negative. This might, for exampJe, 

rdlecr differences in levels of exposure or 

susceptibility to the effects of expolure 

(effect modiAcation). Finally. judgment by 

rl1c Working Group is nm based exclusively 

on epidemiologic studies but usually also 

on results from laboratory and mechanistic 

studies rbat provide further evidenc-e and. 

biological coberencc. For the Monographs 

rhat evaluate cardno~nk hazard$ associated 

with specific occupations or industries. rbe 

cxp~rcs ofinrerest usually Involve a complex 

mixture of chemicals. For the.~e evaluations, 

most Information wmcs from epidemiologic 

ltudies, although exposures to individual 

\!gents occurring at these workplaces may have 

been evaluated in ocperimental studies. 

Disc(}tJtnt with IARC M(}nograph 

proce:~us, lhc IARC Monogr4ph evaluation 

process h:~s been criticized and it has been 

alleged that "a number of scientists with 

direct experience oflARC have felt compelled 

to dissociate rhe111.5elves from the agency's 

approach to evaluating carcinogenic hazards" 

{Kabat 2012). This Is a serious charge. 

However, the author of this claim provided 

no evidence to support rhc charge that a 

"number of sciendsu-" have dissociated them~ 

selves from the process) no.r has there been 

any indlc.ation of how many ~dcntisu have 

taken this step, or for what reason. In sCience, 

we expect sweeping statemc:ntl sucb as this to 

be appropriately docurnemed. We hllve nor 

Environmental Health Perspectives • VOLUM£ 1231 NUMtEII. 61 June 2015 

lARC Monographs 

been able ro ldentlfr any credibll" support fur 

rhJs contention. 

There is art IARC Governing Council 

and a Scientific lAuncil to provide oversjght 

and guidance to tbe agency. 11te Governing 

Counctl represents. the participating states 

and sets general !ARC policy. It appoints the 

lARC DJrcctor and mr:mbc~ of the Scientific 

Council. The latter are independent &cientisrs 

who are selected to provide scientific exper~ 

rUe and not as represenrad'lt".$ of the member 

states. They serve fOr 4 years and $Cn'e without 

pay. The voting members of Monograph 

Working Groups are not employed by lARC, 

and they perfOrm this ta.-dc without financial. 

compensation. There have been 111 volumes, 

including sb: separate documents under 

Volume 100. -and three Supplements. Over 

the years, a! the number of publications fur 

each agent to be evaluau:d incredSed, the size 

ofWorking Groups has increased. Early iu d1e 

process they were somethnes as small as 10, 

but now they sometimes include as many as 

30 scientists. We esdmate that over the emire 

Monograph series, approximately t,500 sden~ 

dsts h:we :ietved as Working Group members, 

and of course many .scientists have alro served 

on the Advisory Groups, Sdenrifk Council, 

and Govemlng Cowtcil. Thus, if e:veo. a small 

percentage of these scientists were disenchant«l with the IARC process, ir wOLdd rc.sult 

1n a oonsidecablc number of such individuals 

and should be e-J.sy ro docurn~t. To l:Je t~en 

seriously, the "dissociation" criticism needs 

to be supported by documented information 

da:cribing dte number of sci~ntists who have 

taken this action. 

Criti&isms of spulflc f!PJZiulltiom. Some 

criticisms of the 1ARC pwcess rdate to 

spocific agents, where it is asserted that the 

hazard evaluations or category 28. 2A, or 1 

are not supported by the scientific liter,~.turt:. 

In rhe 11 I volumes of the Monographs 

produced over the four decades since 1971, 

970 agents have been considered, 114 

{lZ%} have been dasslflcd as carcinogenic 

tG humans (Group 1), 69 (7%) as probably 

carcinogenic (Group 2A), 283 (29%) as 

possibly carcinogenic (Group 28), 504 (52%) 

as not classifiable regarding their cardnoge~ 

nicicy (Group 3), and 1 ( < 1 %) as probably 

not carcin(lgcnic to humans (Group 4}. 11\us, 

~en fpr this highly select group of agents 

(i.e,, those selected for ev::aluation because 

there wa5 some concern that they might be 

Cltdnogenic}, more than one~h:tlf were "not 

d:usiliable" or "'probably not carcinogenic," 

and a further 29% were placc::d into the 

category of posslbly cardnogenic to hum::ans. 

This distribution, based on nearly 1,000 ev-al~ 

u:~ti{)oo in which fewer than one in five agents 

were classified as carcinogenic o.r pfobabty 

<:arcinogcnlc to humans, doei not support a 

condwion that the process is heavlly biased 

511 

• 
151 

Pearce et at 

toward classifying agenu as carcinogenic 

(Boffitta et al. 2009; !Ubat 2012). 

lh~ monographs fOr formaldehyde, coffee, 

DDT. and radiofrequency electromagnetic 

r.tdladon ha~ been cited u. aamplc:s of problematic evaluations by rome (Kabat 2012) 

(Ol.mong these, only formaldehyde was classified \lS known to be carcinogenic to huOiaflS 

(Group 1) by an IARC Working Group). 

These are Important agenrs. However, to 

accept the charge that lARC evaluations arc 

fundament~IIy biased, one has to a.u:\1me 

that the sclentist5 who were members of the 

Wotking Groups were incapable of appropriately evaluating weaknesses .in the data, 

or rhat they distorted the evaluative process 

because of personal biases. In our experience, 

neither of these assertion.s is correct, Di~sent 

among ~dentists is not unusual in any area 

of science. It is a mengrh of the scientific 

process. 'TI1e IARC process capitalizes on this 

by bringing scientists from different disciplinet together in one room to evaluare the 

Htemture and to teach a reasoned conclusion. 

Diftl:rences of opinion occur among Wodcing · 

Group members. These differences, hawev.=:r, 

typicatly involve disputes related to auignment to adjacent d~slficatkm categories. It is 

instructive that there~ no instanc~s in which 

a catcinogcn classifkd at the Gtoltp 1 level 

by one Working Group has been reveued 

by another. The recent review of all Group 1 

ag«:ms forVolwne 100 provided ampleopporw 

tunio/ to reverse sucll previous cla.ssUicatioQS', 

but none occurred. Every scientist coUld 

probahly name il substance that has hccn 

reviewed by IARC that they might personally place in n different category from that 

assigned by the W1:1rking Group, but this is 

one opinion against the collective wimom and 

process of the: Working Group. 

Ct-itidnn$ of th~ ~6mpositio, .of the 

1/Jorkin.g p·oups. The composition of the 

Working Groups· h.as also been criticized 

{Erren 2011; McLaughlin er al. 2010, 

2011); it has been argued that members of 

the Worldng Groups who have conducted 

research on the agents under evaluation have 

a ve-S"ted interest in advancing their own 

rCSC"J..ch te.!iults in the deliberations. This criti~ 

dsm has been addressed din:ctly by Wild and 

colleagues (Wild and Cogl1a.~1o 2011; Wild 

and Straif 2011) from IARC, and we know 

of no evidence to suppnct this contention. 

Even if .rome scientists on the Working Group 

have performed research on some of the agents 

being considered, they make up a minorio/ of 

the Working Group because ~era1 agt=nrs .a.tt 

usU<11ly evaluated in a sing1e meeting, so the 

number of Working Group members who 

have conducted research oa any one agent 

i..s typically small. Our experience has been 

that having some scientists who are knowledgeable about the stndics of the agent under 

5!2 

evalt.11tion (and can therefore answer technical 

queries) and ntheu from different, but rdated, 

fidds provittes a knowledgeable and balanced 

mix of scientific backgrounds for a thoughtful 

ev;duarion of the literatun::. 

Working Group members do not receive 

:my fee for their wruk, but they are paid travd 

expcn.ses, and there ls some prestige aswci-

:ated with service on an !ARC Monograph. 

However, most sdendsu asked to serve on 

IARC Working Groups have al~dy achieved 

some me-.»:ure of sdentific stature, and there 

Is no reason why thb should bias their evaluation in one direction or th.e other. Jn addition, 

Appendix 1: Classification Categories for the Overall Evaluation 

f~r the IARC Monographs (IARC 2006) 

Grou:p 1: The agent is &4rrinogmic to humnm. 

This category is used when there is suffichmt evidence Qf carcinog'enicity ln huinans. 

Exceptionally, an agent may be pbci!d in this category when evidcr1ce of carcinogenkity in 

hwnans is Jess than sufficient but there is suffi.cie.n~ evidence of carcinogenicity in experimental animals and strong evidence in exp~ hwna.IlS that dle <tgent acts th!Ough a rdevant 

mechanism of carclno~nidty. 

Group 2. 

This category induda agents for which, at one extreme, the dcgttt of evidence of carcinogenicity in humans is a1mosr tujfidmt, as wdl :u those fur which, at the other f!x:rremc. there 

are no human data but for which there is evitlena: of cardrmgeniclo/ in experimenml animals. 

Agent$ are assigned to either Group 2A (prohnbly r:aninogenir: lo hmnttm) or Group 28 

(}tmibly cdrdnogenk to humam) on the ba:s:b of epidemiological and experimental evidence 

of carcinogcn.iclty and meclwtistic and other relev;mt data. The terms probably r:41'Ci11f}gmic 

and pouibly mrr:inogenic have. no qu.:mtltatlve significance and are used simply as desctipton: 

of different levels of evidence of human carcinog~clty, with probably cllrrinogmi< signifying a 

higher level of evid~ce than possibly mrrinogmk. 

Group 2A: 'lhe agent is prohably &ardnogmic to humans. 

This category iJ used when theri: is limitrd ~ide nee of c4rrinogmidty ln humans and sriffidcnt 

evidroce of n1reinogmicity ln expedmental animals. In some cases, an agent m<1y be classified 

in thi.i categoty \vhcn thne is iiJilrktjuntr f'Vitlcncc of cilrcinogmidt:,y in hwnans wd Jrifjicienr 

evidence of Mrcinogmkity in experimemal animals :and strong evidence th-at the carcinogenesis is metliated hy a mechanism that also operates in hum:ms. Ex.ceptionally, ;m agent 

may be dauified in this categoty solely on the hasis of limitr::tl f!ViJeHa of cttrriJIIWRkiJy ln 

hum;;ns. An agent may be as.dgned to this category tf tt clearly belongs, based on me.:hanistlc 

considerations, to a class of agents for which 9-n~ or mon: members have been classified in 

Group 1 or Group 2A. 

Group 28: The agent is prnslb/y carclnogeulr: to hllflltms, 

This category is used fur agents for whicll there is limited evltlente of t;r!Yc-iPogmkiJy in hwnans 

;md less than sufficient ~vidtnce of rrtrcin~nicity In expc:rimcnraJ animals, It may a1.ro be used 

when there is intldeiJUII~ ~idenrr of carcinogenicity in humans but there is sufficimt cuidena 

of .-nrcinogmidty In experimental animals. In some instances, an agent for which there is 

il:rttkqutt:e roidenct: ofi:arcinog~nic#y in humans and leiS than sufficimf tllidence of tardtur 

genirity in experimental animals together with $Upporting evidence from mechanistic and ather relevant da.ta may be pbctd in thJs group. An agent may be classified ln this category 

solely on the basis of StrQng evidence hom mechanist;ic and other rde"(;J..lt data. 

Group 3: The agent is not cWdfoble tU to Jts carcino~nicity /o humans. 

This category is wed most commonly for agenrs fnr which the evidence of a~inogeniciry is 

imtdttjwtte in hum::ans and inttde1Jtlttte oc limireJ in experimental animals. 

Exceptionally, agents for which the evidence of cardnogenlciry Is inndquate in humans 

but mfficimt in experimental animals may be placed in this category when there is 

strong evidence that the mechanism of carcinogenicity in opairnental :tnitnah does not 

operate In hum:ms. 

A genu that do nat fall into :my orher group are aloo placed in rhls category. 

An evaluation in Grou:p 3 is llot ~ det~nnination of nonCardnogenicity or overall safety. 

It often means that futther research is needed, especially when exposures are widespread or 

the cancer data are (Onsistent with dl~ring lnterpreratlons. 

Graup 4: 1he agent is probnbiJ 11ot cttnitJOgeiJ/c to humans. 

This category i5 used for agents for which there is roitktue suggatlng lnr:k of rm~inogmir:lty in 

humans and in experimental animals. In some Instances, ag'ents fur which there is indtkqutttc 

nFidmce of mrcinogt:flidt:,y In humans hut ~~~itknce mggating k:tr:k of ctJrcimwmicity In experimental anim11ls, consistently and strongly $Upponed by a broad range of m~chanlstic and 

other rdevant datl, may be classified In this group. 

VOWME 1231 HUMBfR 61June 2015 • Envhonmental Health PeBpectlves 
152 

IARC stricdy requires rhat any conflict of 

intcrcm be divulged, and doa not allow those 

with confticn of interest to serve on Working 

Groups, although nonvoting observers who 

rnay h:a.ve confllcrs. of imerest are able to attend 

the Working Group meetings. 

Conclusions 

For more than four decades the !ARC 

Monograph Programme h~.s provided evalua~ 

dons of cancu ha:zardi to humans from many 

different exposures and agents. These arc: often 

the first eya{uations of new and emergiDg 

threats to public health ant!, coruc:quendy, 

are subject to intense scrutiny. Although these 

Muations'are widely respected and used by 

many organb.arions, institutions:, companies, 

and government agende3 to improve the 

public's health, !ARC has recently been subject 

to criticism over conclwions on spttific agents, 

the p-rocess that leads to such coatcluslons, 

and membership of the Working Groups. 

Debate and criticism facilitate ,df~correction 

and a check on the validity in sdence. We 

are concerned, however, that the criticisms 

expreued by a vocal minority regt~rding the 

evaluations of a few agents may promote the 

denigration of a process th-at has; ;erved the 

public and public healdt well for many decade-s 

fiu reasons that are not supported by data. 

There h:u been very broad in'Vol'llemcnt 

of the scientific community in the IARC 

Monograph Programme rhrough partici~ 

pation in the Working Groups and service 

on the IARC Governing and SdentHlc 

Councils and ad hoc Advisory Board for 

the Monograph Programme. The long list 

of Kiemists wbo ar-e coauthors of this paper 

attests to the strong support that IARC has 

In the sdend6c community. Many exposures. 

that IARC h:u evaluated have ;~lso- been 

indepenJently evaluated by other institutions, such ru: the U.S, National Toxicology 

Program (http:s:/lnrp.niehs.nih.gov/); U.S. 

E,wlroruno:.ntal Prot«don Agency (http:// 

www.ep:a.gov/); Natiou:a.l Academy o-f 

Sciences (http://www.nasonline.org/); the 

American Confet·enct: of Governmental 

In-dustrial Hygienists (ACGIH) Threshold 

Limit Values and Biological Exposure Indices 

(Imp:/ /www.acgih.org/); the Nordic Experr 

Group for Criteria Documentation of 

He;:alth Risks from Chemicals (http:f/www. 

av.sclarkiv/negf)i Institute of Occupation:tl 

Medicine (http:/fwww.iom~world.org/); 

World Cancer Research Fund/American 

Insthute for Cancer Research (WCRF/ 

AICR} Expert Reports; European Chemicals 

AgenC)" (https:l/echa.europa.cu); Swedish 

Criteri:a. Group for Occupational Standard.s 

(2013); California Office ofEnvironmellt:~l 

Hazard Asse~ment (Proposition 65; http:!/ 

oehh:1..ca.gov/ prop65/background/ p65 plain. 

hun!); Health Can-ad-a Bureau of Chemic:~.! 

Safety {bup://www.hc-sc.gc.ca/ahc~a.scl 

brattch-dirgcn/hpfb¥dgpsa/fd-da/bc.s-bscl 

inde~·eng.php); Sde:ntiflc Committee on 

Occupational Exposure Limits (SCOEL). 

Euiopcan Commlss.lon, Employment, Social 

Affairs and Incluliion (http:J/ec,europa.eu/ 

sociillmain.jsp?calld=l48&lang1d::.cn&lntPa 

geld .. 684); European Food Safety Autboriry 

(EFSA 2013); and European Chemicals 

Agency (ECHA; http:/fccha.europa.eu/). 

Assessments from these groups typically come 

to condwions similar to those from JARC. 

This further indicates broad agreement within 

the sclendfk community regarding evldence 

on carcinogenicity In the scientific literature 

and exp:a.nds the numher of scienti.ns who 

do not have a "vested interest" but who have 

generally agreed with those conclusions. 

Disagreement with the: conclusions in an 

!ARC Monograph for an individual agent is 

not evidencr: for a failed or biased approach. 

Some disagreement' about the carcinogenic 

hazard of imponant agent$ seems inherent to 

tbe scientific enterprise and is unavoidable at 

early stages of the hazard evalll:l.don, where 

lARC usually operates. Because the evaluadoru are not-and $bnu1d not be-static, it 

is difficult to sec bow such assessments could 

be addressed any di.lkrently, Sl.lbstances now 

unive.rsaUy recognb:~ as human c~rcinogens 

(e.g., tobacco, asbestos} at one time went 

dtrough a quite lengthy period of contentious 

deb are (Michaels 2006, 2008). ky proce-ss. 

can in theory be improved with fair :a.nd 

corntrucdve cdticbm; appropriate rcvic:m may 

take place from time to time, :and we would 

support continued review and improvement 

of the IARC proce.ssc.s. However, as a group of 

international scientists, we have looked Qlrefully at the recent charges of flaws and bias 

in the hazard ev:a1uatioru by IARC Working 

Groups. and we have runcludtd char the m:ent 

criticisms are unfair and uncocstmctive. 

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VOlUME' 1231NUMBEII61 June 2015 • Environmental Health Perspectives 
154 

Actepted: 27 November 2017 

001: 10.10021ajlm.22811 

COMMENTARY WILEY IBIIJll:lJi§JI 

Commentary: IARC Monographs Program and 

public health under siege by corporate interests 

Peter F. Infante DrPH1® I . Ronald Melnick PhD2 I Harri Vainio MD3 I James Huff PhD4 

t Peter F. lnfi!lnte Consulting, LLC, Falls 

Churth, Virginia 

2 Ronald Melnick Consulting. LLC, North 

Logan, Utah 

~Dean , Faculty of Public Health. Kuwalt 

Unlverstty, Kuwait, Hawalli 

4 Jal!les f-luff Consultlng, Durham, North 

Caronna 

Correspondence 

Peter F. Infante, Peter F. Infante Coruu!tlng. 

llC, 200 S. Oak Street, Falls Church, VA 

22046. 

Ematl: p!nfante@starpowet.net 

Funding lnformat!on 

No funding 

1 I INTRODUCTION 

The International Agency for Research on Cancer (IARC) evaluates. eauses. of cancer 

With help from independent international experts in an open and trll~sparent rnal111~r· 

Countries, research and reg~latory agenCies, and other organizations adopt !ARC 

ey'aru~ti~n; for communlcat!on of hullla~ cancer hazards, a~d for stia~gles ~~ p;eveni . 

cancer .. Sderitlsts worldwide eridon;e !ARC cancer evaluations and Process. Those with . 

.econo,ntc Interests, however, challe~geiARC's cancer evaluations, m<;~st recently for .. 

giyphosaie and red and processed meats, and.are conducting.• campaign including 

intervention from US Congressional ·Representatives. to .discredit.· !ARC's review. , 

process and to· undermine .financial support~a carnpaifln· intimidating to IARC ·ahd 1 

Wor~ing Gro~p membe;s,Challenie~ to ~ciel1tific Interpretations serve to. advance 

~cie~ce and $hould be resplved by sclentifi~ experts who do n8t have confli~ of 

interest. Such lnterferenc~does not bode weti lorthe free flo.-of scientific lnfonnatio~· .i 

that informs and protects the publlcfrom risks of cancer. 

KEYWORDS . 

~ancer prevention, corporat~ {nfluen¢e, glyphosate; I.ARC rnon9g.raphs, 1)10tl;S3nto, roundl!P 

The International Agency for Research on Cancer [IARC) was 

established In lyon, France In 1965 as a specialized cancer research 

agency of the Wor1d Health Organi:tatlon, with founding members 

Germany, France, Italy, United Kingdom, and United States. Cl.lrrentfy, 

IARC has 25 member countries. Since 1970 the IARC Monographs 

Program, created by Lorenzo Tomatis, MD, has been evaluating 

chemical substances, agents, exposure circumstances, and lifestyle 

factors for evidence of carcinogenicity. IARC Monographs provide a 

unique and valuable objective International health service to evaluate· 

and lnform the publ!c about cancer ha2ards. IARC Working Group 

{WG} meetings held in lyon, France, thrlce a year, are comprised of 

Independent sdentists from throughout the wor1d, providing a truly 

international perspective. Meetings are openly transparent and 

members are vetted ror conflicts of interest. The primary objective 

of the Program Is to publfsh In the 1orrn of ager1t/substance~oriented 

Monographs, critical reviews and scientlffc evaluations written by an 

international WG of experts on evidence of carcinogenicity for a wide 

range of human exposures. IARC staff coordinates the process and 

provides scientific and materiel! support to WGs. The authors of this 

commentary have participated In the IARC Monographs Program 

meetings. Also, Harri Va!nlo and James Huff have served as Chiefs of 

the IARC Monographs Program. 

Levels of evtdence for an agent causing cancer are agreed upon by 

WG members as detailed In !ARC Monographs,1'

2 and shortlyafterWG 

meetings are concluded, summary evaluations wlth supporting 

evidence are published In lancet Oncology. Monographs report on 

human cancers observed with available measures of exposures as an 

integral part of hazard characterization, the initial .step in the risk 

assessment process, but do not ordinarily perform quantitative doseresponse risk a'l:sessrnents that extend beyond the range of observed 

data. Countries and research and regulatory agendes adopt JARC 

classifications for communication of potential human cancer hazards,3 

and for developing strategies to control and prevent cancer. lnstllut!O'I'l a.twllich the·wl!lrk W3s perfOrmed': The work: was nGt performed ;tan 

Institution. 

Am) lnd Med. 2018;1-5. wUeyonllnellbrary.com/journal/aJ!m © 2018 Wiley Perlodlcals, Inc. I 1 
155 

2 I lrMIIIitlll WILEY·------------------IN_FA_NT_E_"_"-

In Monographs Volumes 1~120, IARC evaluated available 

experimental, epldemioioglca!, and mechanistic evidence of carclno· 

genidty for lARCs 1003 agents.1 The selection process for agents 

reUes upon publi.shed scientific findings Indicating human exposures 

and potential cancer risk based on studies in humans and experimental 

animals along with information on mechanlsm.4 .S Agents without 

evidence of carcinogenicity and human exposure are not selected for 

review. Centered on these selection factors, one would a priori expect 

a slgnlficant perceotage of agents reviewed and evah.Jated to provide 

evidence of cardnogenldty. Categorical results for 1003 evaluations 

are:6 Group 1 "carcinogenic to humans," 120 agents; Group 2A 

,.probably cafcinogenic to humttn5,- 81; Group 29 11possibly carcino~ 

genk to humans," 299; Group 3 "not classifiable as to Its 

carcinogenicity to humans," 502; Group 4 "probably not carcinogenic 

to humans1 1. Based on selection criteria, it Is thus surprising that only 

..... 20% of agents/exposure drcumstances reviewed are classlfled as 

human carcinogens or probable human carcinogens. 

Likewise, selection of chemica[s for animal cancer testlng by the 

US National Toxicology Program based on widespread human 

exposure, and not suspicion of carcinogenic activity, 7 resulted In 

only 6.8% of substances giving positive cancer results In two species 

{one requfrement for IARC sufficient evldence of cancer In experl~ 

mental animals}. These results further support the observation that the 

slightly higher percentage of c:arclnogens identified In !ARC reviews Is 

a reflection ~f the chemical selection crlterta. Yet, despite this 

selection bias for agents that demonstrate evidence of carcinogenicity, 

only 120 of 1003 IARC agents (12%} evaluated were considered 

unequivocally carcinogenic to humans~ addlng those 81 agents 

evafuated by IARC WGs as "probably carcinogenic to humans" still 

results in only 20%; while 50% of <~gents evaluated bY !ARC were not 

classifiable as to their carcinogenicity to humans. Nonetheless, in light 

of this low percentage of agents revfewed, evaluated, and considered 

to be carcinogentc by JARC, the American Chemistry Council {ACC), a 

trade association which promotes the interests of US chemical 

companies has voiced its opinion that !ARC Is "dubious and misleading" 

In classifying potential cardnogens.8 ACC and its consultants further 

crltlcl&-:e IARC for misleading the public by over-evaluating agents that 

cause cancer in humans,9

•

10 

We mention two !ARC Monographs that have recently received 

considerable attention: red and processed meats11 and glyphosate 

{two other chemicals evaluated at the same meeting as 2A dlazinon 

and malathion, engendered no t:riticlsm).12 1n October 2015, after an 

8-day meeting, an Independent !ARC WG of 22 scientists from ten 

countrles concluded consumption of"processed meatn is Rcarclnogenic 

to humans" based on sufficient evident:e for colorectal cancer from 

epidemiology studies; and "consumption of red meat'* is "probably 

carcinogenic to humans" based on credible studies showing assodations with colorectal, panneatic,. and prostate cancers. Dlfferences in 

these evaluations center on strength of avallabfe ep!demtologlcat 

evidence: consumption of processed meat was classified as Group 1 on 

suffldent evidence In humans, whereas consumption of red meat was 

classified as Group 2A on substantial epidemiological data and strong 

mechanistic evidence. Sig11lflcantly, the IARC WG 11assessed more than 

800 epidemiological studies that Investigated the association of cancer 

wlth consumption of red meat or processed meat in many countries, 

from several continents, with diverse ethnicitles and diets.d1

•

13 {Note: 

the IARC definition of sufficient eytdence of carcinogenicity to humans 

signifies "a causal relationship has been established between exposure 

to the agent and human cancer." Limited eyldence ofcarclnmrenicifyto 

humans means that "a positive association has been ob£erved between 

exposure to the agent and cancer for which a causal interpretation ls 

considered by the Working Group to be credible, but chance, bias Ol" 

confounding could not be ruled out wlth reasonable confidence.111•

6 

Glyphosate was discovered In 1970 and brought to the market in 

1974 by Monsanto under the trade name Roundup. Glyphosate, a 

broad-spectrum herbicide, currently the highest production volume 

of all herbicides, Is promoted and sold worldwide by many 

agrochemkal companies. In different solution strengths and with 

various adjuvants, under dozens of trade names, as more than 750 

glyphosate products.r~ In March 2015, after an 8-day meeting, an 

independent IARC WG of 17 scientists from 11 countries concluded 

glyphosate, an herbicide widely used to control weeds In nonagricultural and agricultural settings primarily on ~netically~ 

engineered crops, wa-s "proba-bly carclnogenlc to humans• [2A1 based 

on sufficient evidence of cardnogenklty in experimental animals and 

limited evidence of cancer in humans for non-Hodgkin lymphoma. In 

addition, there was 5trong evidence that glyphosate operates through 

two key char-acteristics of known human carcinogens: exposure to 

glyphosate or glyphosate--based formulations is genotoxic based on 

studies Jn human cells In vitro and studies in experimental animals, and 

strong evidence that glyphosate, glyphosate-based formt.J1ations, and 

amlnomethylphosphonic add {major metabolite} Induces oxidative 

stress In experhnental animals, and In studies of humans cells In 

vitroP·14 Some have questioned this concluslon,15•

16whereas 94 

international independent scientists agreed with and support IARC's 

evaluation for glyphosate17 as do others.1

S.19 Further, IARC. the 

German Federal Institute for Risk Assessment (BfR}, and the European 

Food Safety Authority (EFSA) found Increases of tumors in seven 

carcinogenicity studies In mice and rats.2°However, BfR and EFSA 

opined five rea!ions for dismissing these carcinogenic effectS', using a 

"weight of evidence~ (WOE} approach. Clauslng20 and dauslng eta!, at 

however, have adequately challenged the validity of the BfR and EFSA 

approach, and their five WOE reasons for dismissing evidence of 

carcinogenicity. 

Regarding the worldwide credibiUty and public health value of 

IARC Monographs, 124 scientists with expertise in chemical carcinogenesis have praised and endors~d the !ARC Monographs for the 

transparency of their rev lew process and !ARC's impartial high quality 

evaluations in identifying cancer hazards in the environment and 

workplace.22 IARC allows observers and representatives from 

government agencies, Industry and oth.er organizations to attend 

and participate tn WG meetings• however, they are not permltte.d to 

vote on evaluations of carcinogeoictty. 

For the past 47 years, IARC Monographs have contributed to 

improving public health by providing evldence~based unbiased expert 

evaluations to identify carcinogens and to support cancer prevention 
156 

~IN~FA_NT~E_u_M·----------------------------------------VVJLEYIIiillill 1

3 

and controf.22 Nonetheless, vested-interest critldsms of IARC cancer 

evaluations,10 supported by pro-Industry consultants,23-

25 have 

centered partiadarly on the scientific credibility of IARC evaluations. 

Pointedly, In response to lARC evaluatlons for red and processed meat 

and glyphosate, the ACC Initiated a Campaign for Accuracy tn Public 

Health Resean;h (CAPHR} with the proclaimed alm •to promote 

credible, unbiased, and transparent science" to assist public health and 

policy makers in thetr evaluation and interpretation of evidence for 

cancer causation.9 The ACC fur1her states "!ARC's Monographs 

Program suffers from persistent scientific and process df!.'flclendes 

that result in public co-nfusion and misinformed po!lcy-maklng." Yet, 

most of the authoritative SOW1:e.S cited in an article critical of the fARC 

Monographs Program1.o appear to have conducted research or 

consultations that has been supported by industry,23•

24 Monsanto, 

through membetshlp In the ACC, has lobbied extensively, and paid 

scientists to author papers on the safety and continued use of 

glyphosate,25- 28 and that contradict the findings of !ARC despite 

recognized human health hazards. McCfellen,27 as editor of Critical 

Reviews in Toxicology, has published 10 arttdes dea~ng with 

glyphosate and health effects; most dispute IARC's conclusions in its 

evaluation of glypho~te or otherwise conclude that glyphosate's rlsk 

is minimal, or non-exfstent.2 6.29-

37 These authors have been 

supported/funded directly or indirectly by Monsanto, the primary 

producer of glyphosate and products containing this active ingredient. 

Additionally. Monsanto has sent a threatening Jetter of intimidation to 

I ARC staff.38 Ominously, EPA staff has been accused of collusion with 

Monsanto to downgrade the health ha~ards of g!yphosate.39- 41 

Ironically, from recenUyrekased_documents, Monsanto thoughtthelr 

herbicide would indeed fit into the IARC category of either 11possibly," or 

"probably carcinogenic to humans~ long before the .IARC Monographs 

revlew meeting and yet mounted a campaign to criticize !ARCs 

eva!uation.42•

43 Further, a Monsanto Internal confidential memorandum 

.states "And while we have vulnerablHty In the area of epidemiology, we 

also have potential vulnerabilities In the other areas that JARC wnl 

consider, namely, exposure, genetox, and mode of action ... If there is a 

force working against glyphosate, there is ample fodder to string together 

to help the cause {presumably to make glyphosate/Roundup viewed as 

safe]" even though it is not scientifically just1fled Tn its purest form.l>42 

The ACC has lobbied US Congress to invesUgate !ARCs revlew of 

glyphosate, 44 Now, because of successful lobbying, US Congressional 

Republicans are questioning the credibility of !ARC Monographs and 

funding from the US National Institutes of Health (NIH). They further 

question the ability of EPA to objectively evafuate the carcinogenicity 

of glyphosate because one staff member participated in the !ARC 

review as a WG member, A slx~page letter from the Chairman of the 

Committee on Oversight and Government Reform45 to Francis Collins, 

Director, NIH, questions NIH support for !ARC Moriographs, and 

requests a briefing on NIH funding to such "foreign" entitles In fight of 

!ARC's cancer evaluations being inconsistent with other entities, 

particu!arfv on red meats, proCessed meats, and glyphosate. 

Additionany, an eight-page fetter4"' from the chair of The 

Committee on Science, Space, and Technology to Gina Mccarthy, 

Administrator. US Envlronmental Protection Agency, admonishers her 

for EPA staff members .apparent rote in the !ARC Monograph WG's 

evaluation of glyphosate. Congressman Smith expressed concern that 

"activists" working both within and outside of EPA might derail the EPA 

preliminary evaluation of glyphosate16~an evaluation not yet finalized 

that is contradictory to the IARC conclusion on the probable 

carcinogenicity of glyphosate. Further, Kelland, 47 a defender of 

Monsanto, has contacted IARC g1yphosate Working Group members 

and has accused IARC of altering the Working Group's evaluation. 

IARC48 has rebutted these accusations. Further,congresstonal hearings 

are being considered to Investigate !ARC and the Monographs Program 

evaluation process and requests have been made for !ARC to provide 

names. of potential witnesses.49 The Director of IARC h.as responded to 

the Inquiry of Smith and Blggs,so but declined to provide witnesses for 

any potential congressional hearing. The response from IARC50 

apparently did not satisfy Congressman Smith et a!5 t. who continue to 

question the integrity of the IARC Monographs Program, US funding for 

the program, and to again request that I ARC provide names of potential 

witnesses. Such tactics are intfmlda.ting to IARC, to I ARC Working Group 

members, and to research and regulatory agencies reliant on !ARCs 

science-based cancer causation evaluations. 

Potential inconsistencies or relevant chatfenges in scientific 

interpretation often serve to advance science and should be resolved 

by scientific experts who do not have a conflict of interest in these 

evaluations, and certa1nly not by politicians with vested interests who 

lack understanding of the strength of sdenttflc evidence supporting or 

opposing a particular scientific determination. 

The interferences by economic Interests In cancer evaluations 

conducted by public health lnstitutions'!i2•

53 do not bode well for the 

free flow of scientific fnformation that informs and protects the public 

and workers from dear risks of cancer. 

AUTHORS' CONTRIBUTIONS 

All authors partidpated In the conception. design, analysis, Interpretation of the work .and in the revision of drafts, and all authors agreed 

with the final version of the commentary, PFI and JH participated in 

the acqui.sitlon of ~e documents Included in the analysis and the 

first draft, and are accountable for the accuracy and integrity of the 

documents cited ln the report. 

ACKNOWLEDGMENTS 

Martyn T. Smith, PhD, School of Public Heatth, University of California 

at Berkeley provlded comments on the manuscript. 

FUNDING 

The authors report that there was no funding source for the work that 

resulted in the article or the preparation of the article. 

ETHICS APPROVAL AND INFORMED CONSENT 

The work Wa.5 not performed at an institution. 
157 

4 I ··-· WILEY"-----------------INF_ANT_,_""· 

DISCLOSURE (AUTHORS) 

Or. James Huff reports that he has been retained as e)(pertconsu!tant 

on longwterm animal bioassays of glyphosate in litigation for plaintiffs. 

All other authors report no conftlcts of Interest. 

DISCLOSURE BY AJIM EDITOR OF RECORD 

Steven 8. Markowitz declares that he has no conflict of interest in the 

review and publication dedsion regarding this article. 

DISCLAIMER 

None. 

ORCID 

Peter F. Infante (!!) ht!p://orcid.org/0000·0001·5350·0154 

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https:// dol.org/10.1002/ajim.22811 
159 

FIFRA SCIENCE ADVISORY PANEL REPORT DECEMBER 2016 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MAR 1 6 2017 

MEMORANDUM 

OFFICE OF 

CHEMICAL SAFETY AND POLLUTION 

PREVENTfON 

SUBJECT: Transmission of Meeting Minutes and Final Report of the December 13-16, 2016 FIFRA 

SAP Meeting Held to Consider and Review Scientific Issues Associated with EPA's 

Evaluation of the Carcinogenic Potential ofGiyphosate 

TO: Rick P. Keigwin, Jr. 

FROM: 

THRU: 

Acting Director 

Oflicc Pesticides Programs 

Steven M. Knott. M.S. 

Acting Executive Secretary 

FIFRA SAP Staff 

Oflice of Science Coordination and Policy 

StanleyBarone.Ph.D. ~~ ........ ~~ } 

Acting Director ,_ ... -. --...-0 ,._ --- U 

Oflice of Science Coordination and Policy 

Please find attached the meeting minutes and final report of the December 13-16, 2016 Federal 

Insecticide. Fungicide, and Rodenticide Act (FIFRA) Scientific Advisoty Panel (SAP) open public 

meeting held in Arlington, Virginia. This report addresses a set of scientific issues associated with EPA's 

evaluation of the carcinogenic potential ofglyphosate. 

Attachment 
160 

cc: 

Wendy Cleland-Hamnett 

Louise Wise 

Stan Barone 

Arnold Layne 

Delores Barber 

Marietta Echeverria 

Michael Goodis 

Yu-Ting Guilaran 

Steve Knizner 

Robert McNally 

Wynne Miller 

Jaqueline Mosby 

Dana Vogel 

Gregory Akerman 

Jeff Dawson 

Anwar Dunbar 

AnnaLowit 

Cathy Milbourn 

Monique Perron 

Linda Strauss 

OPP Docket 

FIFRA Scientific Advisory Panel Members 

Marion F. Ehrich, PhD, DABT, ATS 

David A. Jett, PhD 

James McManaman, PhD 

Joseph Shaw, PhD 

Sonya K. Sobrian, PhD 

FOP A Science Review Board Members 

Kenny Crump, PhD 

Laura C. Green, PhD, DABT 

Eric S. Johnson, MB; BS (MD), PhD, MPH, DTPH 

Barbara L. Parsons, PhD 

Kenneth Portier, PhD 

Aramandla Ramesh, PhD 

Elizabeth A. (Lianne) Sheppard, PhD 

Emanuela Taioli, MD, PhD 

Daniel Zelterman, PhD 

Luoping Zhang, PhD 
161 

FIFRA Scientific Advisory Panel 

Meeting Minutes and Final Report 

No. 2017-01 

A Set of Scientific Issues Being Considered by the 

Environmental Protection Agency Regarding: 

EPA's Evaluation of the Carcinogenic Potential of Glyphosate 

December 13-16, 2016 

FIFRA Scientific Advisory Panel Meeting 

Held at the EPA Conference Center, 

One Potomac Yard 

Arlington, Virginia 
162 

TABLE OF CONTENTS 

NOTICE ....................................................................................................................................................... 3 

PANEL ROSTER ........................................................................................................................................ 5 

TABLE OF ACRONYMS .......................................................................................................................... S 

INTRODUCTION ..................................................................................................................................... 10 

PUBLIC COMMENTS ............................................................................................................................ 12 

EXECUTIVE SUMMARY ...................................................................................................................... 14 

DETAILED PANEL DELIBERATIONS AND RESPONSE TO CHARGE ...................................... 23 

TABLE I: OVERVIEW OF THREE META-ANALYSES OF GLYPHOSATE EXPOSURE AND NHL, PLUS 

INDIVIDUAL STUDIES AND EFFECT ESTIMATES ................................................................................ 45 

TABLE 2: LANKAS, 1981 (MRJD 00093879) ·RAT TESTICULAR INTERSTITIAL TUMORS- MALES AND 

CORRESPONDING DATAANALYSIS ................................................................................................. 58 

TABLE 3: META-ANALYSIS AS ONE POSSIBLE APPROACH TO A POOLED ANALYSIS· EXAMPLE PROVIDED 

IN PUBLIC COMMENTS CONTRIBUTED BY DR. CHRISTOPHER PORTIER (EPA-HQ-OPP-2016-0385-

0449] ............................................................................................................................................... 59 

REFERENCES .......................................................................................................................................... 90 

APPENDIX 1-WRITTEN SUBMISSIONS TO DOCKET NO. EPA-HQ-OPP-2016-0385 ............ 96 

2 
163 

NOTICE 

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), Scientific Advisory 

Panel (SAP) is a Federal advisory committee operating in accordance with the Federal Advisory 

Committee Act and established under the provisions of FIFRA as amended by the Food Quality 

Protection Act (FQP A) of 1996. The FIFRA SAP provides advice, information, and 

recommendations to the Agency Administrator on pesticides and pesticide-related issues 

regarding the impact of regulatory actions on health and the environment. The Panel se!Ves as 

the primary scientific peer review mechanism of the Environmental Protection Agency (EPA), 

Office of Pesticide Programs (OPP) and is structured to provide balanced expert assessment of 

pesticide and pesticide-related matters facing the Agency. Food Quality Protection Act (FQP A) 

Science Review Board members serve the FIFRA SAP on an ad hoc basis to assist in reviews 

conducted by the Panel. These meeting minutes and final report have been written as part of the 

activities of the FIFRA SAP and represent the views and recommendations of the FIFRA SAP 

and do not necessarily represent the views and policies of the EPA, or of other agencies in the 

Executive Branch of the Federal government. Mention of trade names or commercial products 

does not constitute an endorsement or recommendation for use. The meeting minutes and final 

report do not create or confer legal rights or impose any legally binding requirements on the EPA 

or any party. In preparing the meeting minutes and final report, the FIFRA SAP carefully 

considered all information provided and presented by the EPA, as well as information presented 

in public comments. 

These meeting minutes and final report ofthe December 13-16, 2016 FIFRA SAP meeting 

held to consider and review scientific issues associated with EPA's evaluation of the 

carcinogenic potential of glyphosate were certified by James McManaman, Ph.D., FIFRA SAP 

Chair and Steven Knott, M.S., Designated Federal Official. The minutes and final report are 

publicly available on the SAP website (https://www.epa.gov/sap) under the heading of 

"Scientific Advisory Panel Meetings" and in the public e-docket, Docket Identification Number: 

EPA-HQ-OPP-2016-0385, accessible through the docket portal: https://www.regulations.gov. 

Further information about FIFRA SAP reports and activities can be obtained from its website at 

https://www.epa.gov/sap. Interested persons are invited to contact Steven Knott, Designated 

Federal Official, via email at knott.steven@epa.gov. 

3 
164 

SAP Minutes and Final Report No. 2017-01 

A Set of Scientific Issues Being Considered by the 

Environmental Protection Agency Regarding: 

EPA's Evaluation of the Carcinogenic Potential of Glyphosate 

December 13-16,2016 

FIFRA Scientific Advisory Panel Meeting 

Held at the EPA Conference Center 

One Potomac Yard 

Arlington, Virginia 

James McManaman, Ph.D. 

FIFRA SAP Chair 

FIFRA Scientific Advisory Panel 

MAR 1 6 2017 

4 

Steven Knott, M.S. 

Designated Federal Official 

Office of Science Coordination and 

Policy, EPA 

Date: 

MAR 1 61017 
165 

PANEL ROSTER 

FIFRA SAP Chair 

James McManaman, PhD 

Professor and Chief 

Section of Basic Reproductive Sciences 

Department of Obstetrics & Gynecology, Physiology & Biophysics 

University of Colorado, Denver 

Aurora, CO 

Designated Federal Official 

Steven Knott, MS 

US Environmental Protection Agency 

Office of Science Coordination & Policy 

FIFRA Scientific Advisory Panel 

EPA East Building, MC 7201M 

1200 Pennsylvania Avenue, NW 

Washingtoq, DC 20460 

Phone(202)564-0l03 

Fax (202) 564-8382 

Knott.steven@epa.gov 

FIFRA Scientific Advisory Panel Members 

Marion F. Ehrich, PhD, DABT, ATS 

Professor, Pharmacology and Toxicology 

Department of Biomedical Sciences & Pathobiology 

Virginia-Maryland College of Veterinary Medicine 

Blacksburg, VA 

David A. Jett, PhD 

Director, National Institutes of Health CounterACT Program 

National Institute of Neurological Disorders and Stroke 

National Institutes of Health 

Bethesda, MD 

Joseph Shaw, PhD 

Associate Professor 

School of Public and Environmental Affairs 

Indiana University 

Bloomington, IN 

5 
166 

Sonya K. Sobrian, PhD 

Associate Professor 

Department of Pharmacology 

Howard University College of Medicine 

Washington, DC 

FOP A Science Review Board Members 

Kenny Crump, PhD 

Private Consultant 

Ruston, LA 

Laura C. Green, PhD, DABT 

President and Senior Toxicologist 

Green Toxicology LLC 

Brookline, MA 

Eric S. Johnson, MB; BS (MD), PhD, MPH, DTPH 

Professor, Department of Epidemiology 

University of Arkansas for Medical Sciences 

Little Rock, AR 

Barbara L. Parsons, PhD 

Research Microbiologist 

Division of Genetic and Molecular Toxicology 

National Center for Toxicological Research 

US Food and Drug Administration 

Jefferson, AR 

Kenneth Portier, PhD 

Vice President 

Statistics and Evaluation Center 

American Cancer Society 

Atlanta,GA 

Aramandla Ramesh, PhD 

Associate Professor 

Department of Biochemistry & Cancer Biology 

Meharry Medical College 

Nashville, TN 

Elizabeth A. (Lianne) Sheppard, PhD 

Professor and Assistant Chair of 

Environmental and Occupational Health Sciences 

University of Washington 

Seattle, WA 

6 
167 

Emanuela Taioli, MD, PhD 

Director, Institute for Translational Epidemiology 

lcahn School of Medicine at Mount Sinai 

New York, NY 

Daniel Zelterman, PhD 

Professor of Public Health (Biostatistics) 

Department of Biostatistics 

Yale School of Medicine 

New Haven, CT 

Luoping Zhang, PhD 

Professor in Toxicology 

School of Public Health 

University of California, Berkeley 

Berkeley, CA 

7 
168 

TABLE OF ACRONYMS 

ACRONYMS ·.· .})~SCRIPTION .. ... ·. " 

AAF 2-Acetylaminoflourene 

AHS Agricultural Health Study 

AIDS Acquired Immunodeficiency Syndrome 

AOP Adverse Outcome Pathway 

ATS Academy of Toxicological Sciences 

BW Body Weight 

CASAC Clean Air Science Advisory Committee 

CDK Cyclin-dependent kinase 

CI Confidence Interval 

CNV Gene Copy Number Variation 

DABT Diplomate of the American Board of 

Toxicology 

DNA Deoxyribonucleic Acid 

EFSA European Food Safety Authority 

FACE Fellow of the American College of 

Epidemiology 

FAO Food and Agriculture Organization 

FDA Food and Drug Administration 

FIFRA Federal Insecticide, Fungicide, and 

Rodenticide Act 

FQPA Food Quality Protection Act of I 996 

FRSC Fellow of the Royal Society of Chemistry 

GM Genetically Modified 

HIV Human Immunodeficiency Virus 

HL Hodgkin's Lymphoma 

!ARC International Agency for Research on Cancer 

IP Intraperitoneal 

JMPR Joint FAO/WHO Meeting on Pesticide 

Residues 

MM Multiple Myeloma 

MOA Mode of Action 

MRJD EPA OPP Master Record Identification 

Number 

MTD Maximum Tolerated Dose 

NHL Non-Hodgkin's lymphoma 

NIOSH National Institute for Occupational Safety and 

Health 

NRC National Research Council 

NTP National Toxicology Program 

OCSPP EPA Office of Chemical Safety and Pollution 

Prevention 

8 
169 

AC;RONVM.'l DES( ON. .... ;. 

OECD Organization for Economic Cooperation and 

Development 

OPP Office of Pesticide Programs 

OR Odds Ratio 

OSHA Occupational Safety and Health 

Administration 

RR Relative Risk 

SAP FIFRA Scientific Advisory Panel 

SAS Statistical Analysis System 

SCE ! Sister Chromatid Exchanges 

USDA United States Department of Agriculture 

US EPA or EPA United States Environmental Protection 

Agency 

WHO World Health Organization 

8-0H-dG 8-hydroxy-2' -deoxyguanosine 

9 
170 

INTRODUCTION 

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory 

Panel (SAP) has completed the meeting minutes and final report ofthe SAP meeting regarding 

scientific issues associated with EPA's evaluation of the carcinogenic potential of glyphosate. 

Advance notice of the SAP meeting was published in the Federal Register on July 26,2016 (81 

FR48794). 

Glyphosate is a non-selective, phosphonomethyl amino acid herbicide registered to control 

weeds in various agricultural and non-agricultural settings. Labeled uses of glyphosate include 

over 100 terrestrial food crops as well as other non-agricultural sites, such as greenhouses, 

aquatic areas, and residential areas. Use of glyphosate in the United States and globally has 

increased over time, particularly with the introduction of glyphosate-resistant crops; however, 

usage has stabilized in recent years due to the increased number of weed species becoming 

resistant to glyphosate. Glyphosate is currently undergoing Registration Review, which is a 

program where all registered pesticides are reviewed at least every 15 years as mandated by the 

Federal Insecticide, Fungicide, and Rodenticide Act. 

Recently, several international agencies have evaluated the carcinogenic potential of 

glyphosate. In March 2015, the International Agency for Research on Cancer (IARC), a 

subdivision of the World Health Organization (WHO), concluded that glyphosate was "probably 

carcinogenic to humans" (Group 2A). Later, in November 2015, the European Food Safety 

Authority (EFSA) concluded that glyphosate was unlikely to pose a carcinogenic hazard to 

humans. In May 2016, the Joint Food and Agriculture Organization (FAO) I WHO Meeting on 

Pesticide Residues (JMPR), another subdivision of the WHO, concluded that glyphosate was 

unlikely to pose a carcinogenic risk to humans from exposure through the diet. 

Recently, EPA collected and analyzed a substantial amount of data informing the 

carcinogenic potential of glyphosate and utilized its draft "Framework for Incorporating Human 

Epidemiological & Incident Data in Health Risk Assessment'' (EPA, 201 0) to assess its potential 

carcinogenic hazard. The draft framework provides the foundation for evaluating multiple lines 

of scientific evidence and includes two key components: (i) Problem formulation and (ii) Use of 

the mode of action/adverse outcome pathway (MOA/ AOP) frameworks. A comprehensive 

analysis of data on glyphosate from submitted guideline studies and the open literature was 

performed. This included epidemiological, animal carcinogenicity, genotoxicity, metabolism, and 

mechanistic studies. Guideline studies were collected for consideration from the toxicological 

databases for glyphosate and glyphosate salts. A fit-for-purpose systematic review was conducted 

to obtain relevant and appropriate open literature studies with the potential to inform the human 

carcinogenic potential of glyphosate. Furthermore, the list of studies obtained from the 

toxicological databases and systematic review was cross-referenced with recent internal reviews, 

review articles from the open literature, and international agency evaluations (i.e., IARC, EFSA, 

andJMPR). 

Available data from epidemiological, laboratory animal carcinogenicity, and genotoxicity 

studies were reviewed and evaluated for study quality and results to inform the human 

carcinogenic potential of glyphosate. Additionally, as described in the draft "Framework for 

Incorporating Human Epidemiological & Incident Data in Health Risk Assessment," the 

10 
171 

multiple lines of evidence were integrated in a weight-of-evidence analysis using the modified 

Bradford Hill Criteria considering concepts such as strength of association, consistency of 

observations, dose response, temporal concordance, and biological plausibility. 

The focus of this SAP meeting was on soliciting advice from the Panel on the evaluation 

and interpretation of the available data for each line of evidence and the weight-of-evidence 

analysis, as well as how the available data inform cancer classification descriptors per the 

Agency's 2005 Guidelines for Carcinogen Risk Assessment. The Agency's evaluation is 

summarized in an Issue Paper entitled: Glyphosate Issue Paper: Evaluation of Carcinogenic 

Potential, EPA's Office of Pesticide Programs, September 12, 2016 (EPA, 2016a). 

During the FIFRA SAP meeting, US EPA personnel provided the following presentations 

(listed in order of presentation): 

Welcome and Opening Remarks- Jack Housenger, Director, Office of Pesticide Programs 

Introduction- Dana Vogel, Director, Health Effects Division, Office of Pesticide Programs 

Overview of Glyphosate Registration and Carcinogenic Potential Evaluation- Monique 

Perron, SeD, Health Effects Division, Office of Pesticide Programs 

Systematic Review and Data Collection Methods- Gregory Akerman, PhD, Health Effects 

Division, Office of Pesticide Programs 

Data Evaluation of Epidemiology Studies - Monique Perron, SeD, Health Effects Division, 

Office of Pesticide Programs 

Data Evaluation of Animal Carcinogenicity Studies- Anwar Dunbar, PhD, Health Effects 

Division, Office of Pesticide Programs 

Data Evaluation of Genetic Toxicity- Gregory Akerman, PhD, Health Effects Division, Office 

of Pesticide Programs 

Data Integration and Weight-of-evidence Analysis Across Multiple Lines of EvidenceMonique Perron, SeD, Health Effects Division, Office of Pesticide Programs 

11 
172 

To view the entire FIFRA Scientific Advisory Panel Meeting Minutes and Final 

Report (No. 2017-01), visit https://www.epa.gov/sites/production/files/2017-03/documents/december—13-16—2016—final—report—03162017.pdf 
173 

IARC PREAMBLE

WORLD HEALTH ORGANIZATION 

INTERNATIONAL AGENCY FOR RESEARCH ON CANCER 

/ARC Monographs on the Evaluation of 

Carcinogenic Risks to Humans 

PREAMBLE 

LYON, FRANCE 

2006 
174 

CONTENTS 

A. GENERAL PRINCIPLES AND PROCEDURES ................................................................ ! 

1. Background ...................................................................................................................... ! 

2. Objective and scope .............................................. : .......................................................... 2 

3. Selection of agents for review .......................................................................................... 3 

4, Data for the Monographs ................................................................................................. 3 

5. Meeting participants ......................................................................................................... 4 

6. Workingprocedures ......................................................................................................... 5 

B. SClENTIFICR:EiVIEW ANDEVALUATION .......................................................... : ......... 6 

1. Exposure data ................................................................................................................... 7 

2. Studies of cancer in humans ............................................................................................ 8 

3. Studies of cancer in experimental animals ..................................................................... 12 

4. Mechanistic and other relevant data .............................................................................. 15 

5. Summary ........................................................................................................................ 18 

6. Evaluation and rationale ................................................................................................ 19 

References ............................................................................................................................. ~ .. 23 

Amended January 2006 

Last update September 2015 
175 

PREAMBLE 

2 

3 The Preamble to the !ARC Monographs describes the objective and scope of the 

4 programme, the scientific principles and procedures used in developing a Monograph, 

5 the types of evidence considered and the scientific criteria that guide the evaluations. 

6 The Preamble should be consulted when reading a Monograph or list of evaluations. 

7 

8 A. GENERAL PRINCIPLES AND PROCEDURES 

9 l. Background 

10 Soon after IARC was established in 1965, it received frequent requests for advice on the 

11 carcinogenic risk of chemicals, including requests for lists of known and suspected human 

12 carcinogens. It was clear that it would not be a simple task to summarize adequately the 

13 complexity of the information that was available, and IARC began to consider means of 

14 obtaining international expert opinion on this topic. In 1970, the IARC Advisory Committee 

15 on Environmental Carcinogenesis recommended • ... that a compendium on carcinogenic 

16 chemicals be prepared by experts. The biological activity and evaluation of practical 

17 importance to public health should be referenced and documented.' The IARC Governing 

18 Council adopted a resolution concerning the role of IARC in providing government 

19 authorities with expert, independent, scientific opinion on environmental carcinogenesis. As 

20 one means to that end, the Governing Council recommended that IARC should prepare 

21 monographs on the evaluation of carcinogenic risk of chemicals to man, which became the 

22 initial title of the series. 

23 

24 

25 

26 

27 

In the succeeding years, the scope of the programme broadened as Monographs were 

developed for groups of related chemicals, complex mixtures, occupational exposures, 

physical and biological agents and lifestyle factors. In 1988, the phrase 'of chemicals' was 

dropped from the title, which assumed its present form, !ARC Monographs on the Evaluation 

of Carcinogenic Risks to Humans. 

28 

29 

30 

Through the Monographs programme, IARC seeks to identify the causes of human 

cancer. This is the first step in cancer prevention, which is needed as much today as when 

IARC was established. The global burden of cancer is high and continues to increase: the 

31 · annual number of new cases was estimated at 10.1 million in 2000 and is expected to reach 

32 15 million by 2020 (Stewart & Kleihues, 2003). With current trends in demographics and 

33 exposure, the cancer burden has been shifting from high-resource countries to low- and 

34 medium-resource countries. As a result of Monographs evaluations, national health agencies 

35 have been able, on scientific grounds, to take measures to reduce human exposure to 

36 carcinogens in the workplace and in the environment. 

37 The criteria established in 1971 to evaluate carcinogenic risks to humans were adopted by 

38 the Working Groups whose deliberations resulted in the first 16 volumes of the Monographs 

39 series. Those criteria were subsequently updated by further ad-hoc Advisory Groups (IARC, 

40 1977, 1978, 1979, 1982, 1983, 1987, 1988, 1991; Vainio eta!., 1992; IARC, 2005, 2006). 

41 

42 

43 

The Preamble is primarily a statement of scientific principles, rather than a specification 

of working procedures. The procedures through which a Working Group implements these 

principles are not specified in detail. They usually involve operations tl1at have been 
176 

2 IARC Monographs 

1 established as being effective during previous Monograph meetings but remain, 

2 predominantly, the prerogative of each individual Working Group. 

3 2. Objective and scope 

4 The objective of the programme is to prepare, with the help of international Working 

5 Groups of experts, and to publish in the form of Monographs, critical reviews and evaluations 

6 of evidence on the carcinogenicity of a wide range of human exposures. The Monographs 

7 represent the first step in carcinogen risk assessment, which involves examination of all 

8 relevant information in order to assess the strength of the available evidence that an agent 

9 could alter the age-specific incidence of cancer in humans. The Monographs may also 

10 indicate where additional research efforts are needed, specifically when data immediately 

II relevant to an evaluation are not available. 

12 In this Preamble, the term 'agent' refers to any entity or circumstance that is subject to 

13 evaluation in a Monograph. All the scope of the programme has broadened, categories of 

14 agents now include specific chemicals, groups of related chemicals, complex mixtures, 

15 occupational or environmental exposures, cultural or behavioural practices, biological 

16 organisms and physical agents. This list of categories may expand as causation of, and 

17 susceptibility to, malignant disease become more fully understood. 

18 A cancer 'hazard' is an agent that is capable of causing cancer under some circumstances, 

19 while a cancer 'risk' is an estimate of the carcinogenic effects expected from exposure to a 

20 cancer hazard. The Monographs are an exercise in evaluating cancer hazards, despite the 

21 historical presence of the word 'risks' in the title. The distinction between hazard and risk is 

22 important, and t11e Monographs identify cancer hazards even when risks are very low at 

23 current exposure levels, because new uses or unforeseen exposures could engender risks that 

24 are significantly higher. 

25 In the Monographs, an agent is termed 'carcinogenic' if it is capable of increasing the 

26 incidence of malignant neoplasms, reducing their latency, or increasing their severity or 

27 multiplicity. The induction of benign neoplasms may in some circumstances (see Part B, 

28 Section 3a) contribute to fue judgement iliat the agent is carcinogenic. The terms 'neoplasm' 

29 and 'tumour' are used interchangeably. 

30 The Preamble continues the previous usage of the phrase 'strength of evidence' as a 

31 matter of historical continuity, although it should be understood that Monographs evaluations 

32 consider studies that support a finding of a cancer hazard as well as studies that do not. 

33 Some epidemiological and experimental studies indicate that different agents may act at 

34 different stages in the carcinogenic process, and several different mechanisms may be 

35 involved. The aim of the Monographs has been, from their inception, to evaluate evidence of 

36 carcinogenicity at any stage in the carcinogenesis process, independently of the underlying 

37 mechanisms. lnformation on mechanisms may, however, be used in making the overall 

38 evaluation (IARC, 1991; Vainio eta!., 1992; !ARC, 2005, 2006; see also Part B, Sections 4 

39 and 6). As mechanisms of carcinogenesis are elucidated, IARC convenes international 

40 scientific conferences to determine whether a broad-based consensus has emerged on how 

41 specific mechanistic data can be used in an evaluation of h1Jman carcinogenicity. The results 

42 of such conferences are reported in IARC Scientific Publications, which, as long as they still 

43 reflect ilie current state of scientific knowledge, may guide subsequent Working Groups. 

44 Although the Monographs have emphasized hazard identification, important issues ~ay 

45 also involve dose-response assessment In many cases, the same epidemiological and 

46 experimental studies used to evaluate a cancer hazard can also be used to estimate a dose-
177 

PREAMBLE 3 

1 response relationship. A Monograph may undertake to estimate dose--response relationships 

2 within the range of the available epidemiological data, or it may compare the dose--response 

3 information from experimental and epidemiological studies. In some cases, a subsequent 

4 publication may be prepared by a separate Working Group with expertise in quantitative 

5 dose--response assessment. 

6 The Monographs are used by national and international authorities to make risk 

7 assessments, formulate decisions concerning preventive measures, provide effective cancer 

8 control programmes and decide among alternative options for public health decisions. The 

9 evaluations of IARC Working Groups are scientific, qualitative judgements on the evidence 

10 for or against carcinogenicity provided by the available data. These evaluations represent 

11 only one part of the body of information on which public health decisions may be based. 

12 Public health options vary from one situation to another and from country to country and 

13 relate to many factors, including different socioeconomic and national priorities. Therefore, 

14 no recommendation is given with regard to regulation or legislation, which are the 

1 5 responsibility of individual governments or other international organizations. 

16 3. Selection of agents for review 

17 Agents are selected for review on the basis of two main criteria: (a) there is evidence of 

18 human exposure· and (b) there is some evidence or suspicion of carcinogenicity. Mixed 

19 exposures may occur in occupational and environmental settings and as a result of individual 

20 and cultural habits (such as tobacco smoking and dietary practices). Chemical analogues and 

21 compounds with biological or physi'cal characteristics similar to those of suspected 

22 carcinogens may also be considered, even in the absence of data on a possible carcinogenic 

23 effect in humans or experimental animals. 

24 The scientific literature is surveyed for published data relevant to an assessment of 

25 carcinogenicity. Ad-hoc Advisory Groups convened by IARC in 1984, 1989, 1991, 1993, 

26 1998 and 2003 made recommendations as to which agents should be evaluated in the 

27 Monographs series. Recent recommendations are available on the Monographs programme 

28 website (http://monographs.iarc.fr). IARC may schedule other agents for review as it 

29 becomes aware of new scientific information or as national health agencies identify an urgent 

30 public health need related to cancer. 

31 As significant new data become available on an agent for which a Monograph exists, are32 evaluation may be made at a subsequent meeting, and a new Monograph published. In some 

33 cases it may be appropriate to review only the data published since a prior evaluation. This 

34 can be useful for updating a database, reviewing new data to resolve a previously open 

35 question or identifying new tumour sites associated with a carcinogenic agent. Major changes 

36 in an evaluation (e.g. a new classification in Group 1 or a determination that a mechanism 

37 does not operate. in humans, see Part B, Section 6) are more appropriately addressed by a full 

38 review. 

39 4. Data for the Monographs 

40 Each Monograph reviews all pertinent epidemiological studies and cancer bioassays in 

41 experimental animals. Those judged inadequate or irrelevant to the evaluation may be cited 

42 but not summarized. If a gi-oup of similar studies is not reviewed, the reasons are indicated. 

43 Mechanistic and other relevant data are also reviewed. A Monograph does not necessarily 

44 cite all the mechanistic literature concerning the agent being evaluated (see Part B, Section 
178 

4 !ARC Monographs 

1 4). Only those data considered by the Working Group to be relevant to making the evaluation 

2 are included. 

3 With regard to epidemiological studies, cancer bioassays, and mechanistic and other 

4 relevant data, only repnrts that have been published or accepted for publication in the openly 

5 available scientific literature are reviewed. The same publication reqUirement applies to 

6 studies originating from IARC, including meta-analyses or pooled analyses commissioned by 

7 IARC in advance of a meeting (see Part B, Section 2c). Data from government agency reports 

8 that are publicly available are also considered. Exceptionally, doctoral theses and other 

9 material that are in their final form and publicly available may be reviewed. 

10 Exposure data and other information on an agent under consideration are also reviewed. 

11 In the sections on chemical and physical properties, on analysis, on production and use and 

12 on occurrence, published and unpublished sources of information may be considered. 

13 Inclusion of a study does not imply acceptance of the adequacy of the study design or of 

14 the analysis and interpretation of the results, and limitations are clearly outlined in square 

15 brackets at tl1e end of each study description (see Part B). The reasons for not giving further 

16 consideration to an individual study also are indicated in the square brackets. 

17 5, Meeting participants 

18 Five categories of participant can be present at Monograph meetings. 

19 (a) The Working Group is responsible for the critical reviews and evaluations that are 

20 developed during the meeting. The tasks of Working Group Members are: (i) to ascertain that 

21 all appropriate data have been collected; (ii) to select the data relevant for the evaluation on 

22 the basis of scientific merit; (iii) to prepare accurate summaries of the data to enable the 

23 reader to follow the reasoning of the Working Group; (iv) to evaluate the results of 

24 epidemiological and experimental studies on cancer; (v) to evaluate data relevant to the 

25 understanding of mechanisms of carcinogenesis; and (vi) to make an overall evaluation of the 

26 carcinogenicity of the exposure to humans. Working Group Members generally have 

27 published significant research related to the carcinogenicity of the agents being reviewed, and 

28 IARC uses literature searches to identify most experts. Working Group Members are selected 

29 on the basis of (a) knowledge and experience and (b) absence of real or apparent conflicts of 

30 interests. Consideration is also given to demographic diversity and balance of scientific 

31 findings and views. 

32 (b) Invited Specialists are experts who also have critical knowledge and experience but 

33 have a real or apparent conflict of interests. These experts are invited when necessary to assist 

34 in the Working Group by contributing their unique knowledge and experience during 

35 subgroup and plenary discussions. They may also contribute text on non-influential issues in 

36 the section on exposure, such as a general description of data on production and use (see Part 

37 B, Section 1). Invited Specialists do not serve as meeting chair or subgroup chair, draft text 

38 that pertains to the descriptio,n or interpretation of cancer data, or participate in the 

39 evaluations. 

40 (c) Representatives of national and international health agencies often attend meetings 

41 because their agencies sponsor the programme or an; interested in the subject of a meeting. 

42 Representatives do not serve as meeting chair, or subgroup chair, draft any part of a 

43 Monograph, nr participate in the evaluations. 

44 (d) Observers with relevant scientific credentials may be admitted to a meeting by IARC 

45 in limited numbers. Attention will be given to achieving a balance of Observers from 

46 constituencies with differing perspectives. They are invited to observe the meeting and 
179 

PREAMBLE 5 

1 should not attempt to influence it. Observers do not serve as meeting chair or subgroup chair, 

2 draft any part of a Monograph, or participate in the evaluations. At the meeting, the meeting 

3 chair and subgroup chairs may grant Observers an opportunity to speak, generally after they 

4 have observed a discussion. Observers agree to respect the Guidelines for Observers at !ARC 

5 Monographs meetings (available at http://monographs.iarc.fr). 

6 (e) The IARC Secretariat consists of scientists who are designated by IARC and who 

7 have relevant expertise. They serve as rapporteurs and participate in all discussions. When 

8 requested by the meeting chair or subgroup chair, they may also draft text or prepare tables 

9 and analyses. 

10 Before an invitation is extended, each potential participant, including the !ARC 

11 Secretariat, completes the WHO Declaration of Interests to report financial interests, 

12 employment and consulting, and individual and institutional research support related to the 

13 subject of the meeting. IARC assesses these'interests to determine whether there is a conflict 

14 that warrants some limitation on participation. The declarations are updated and reviewed 

15 again at the opening of the meeting. Interests related to the subject of the meeting are 

16 disclosed to the meeting participants and in the published volume (Cogliano el al., 2004). 

17 The names and principal affiliations of participants are available on the Monographs 

18 programme website (http://monographs.iarc.fr) approximately two months before each 

19 meeting. It is not acceptable for Observers or third parties to contact other participants before 

20 a meeting or to lobby them at any time. Meeting participants are asked to report all such 

21 contacts to IARC (Cogliano eta/., 2005). 

22 All participants are listed, with their principal affiliations, at the beginning of each 

23 volume. Each participant who is a Member of a Working Group serves as an individual 

24 scientist and not as a representative of any organization, government or industry. 

25 6. Working procedures 

26 A separate Working Group is responsible for developing each volume of Monographs. A 

27 volume contains one or more Monographs, which can cover either a single agent or several 

28 related agents. Approximately one year in advance of the meeting of a Working Group, the 

29 agents to be reviewed are announced on the Monographs programme website 

30 (http://monographs.iarc.fr) and participants are selected by IARC staff in conSultation with 

31 other experts. Subsequently, relevant biological and epidemiological data are collected by 

32 IARC from recognized sources of information on carcinogenesis, including data storage and 

33 · retrieval systems such as PubMed. Meeting participants who are asked to prepare preliminary 

34 working papers for specific sections are expected to supplement the IARC literature searches 

35 with their own searches. 

36 

37 

38 

39 

40 

41 

42 

43 

44 

Industrial associations, labour unions and other knowledgeable organizations may be 

asked to provide input to the sections on production and use, although this involvement is not 

required as a general rule. Information on production and trade is obtained from 

governmental, trade and market research publications and, in some cases, by direct contact 

with industries, Separate production data on some agents may not be available for a variety of 

reasons (e.g. not collected or made public in all producing countries, production is small). 

Information on uses may be obtained from published sources but is often complemented by 

direct contact with manufacturers. Efforts are made to supplement this information with data 

from other national and international sources. 
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6 !ARC Monographs 

1 Six months before the meeting, the material obtained is sent to meeting participants to 

2 prepare preliminary working papers. The working papers are compiled by IARC staff and 

3 sent, prior to the meeting, to Working Group Members and Invited Specialists for review. 

4 The Working Group meets at IARC for seven to eight days to discuss and finalize the 

5 texts and to formulate the evaluations. The objectives of the meeting are peer review and 

6 consensus. During the first few days, four subgroups {covering exposure data, cancer in 

7 humans, cancer in experimental animals, and mechanistic and other relevant data) review the 

8 working papers, develop a joint subgroup draft and write summaries. Care is taken to ensure 

9 that each study summary is written or reviewed by someone not associated with the study 

10 being considered. During the last few days, the Working Group meets in plenary session to 

11 review the subgroup drafts and develop the evaluations. As a result, the entire volume is the 

12 joint product of the Working Group, and there are no individually authored sections. 

13 !ARC Working Groups strive to achieve a consensus evaluation. Consensus reflects broad 

14 agreement among Working Group Members, but not necessarily unanimity. The chair may 

15 elect to poll Working Group Members to determine the diversity of scientific opinion on 

16 issues where consen:ms is not readily apparent. 

17 After the meeting, the master copy is verified by consulting the original literature, edited 

18 and prepared for publication. The aim is to publish the volume within six months of the 

19 Working Group meeting. A summary of the outcome is available on the Monographs 

20 programme website soon after the meeting. 

21 B. SCIENTIFIC REVIEW AND EVALUATION 

22 The available studies are summarized by the Working Group, with particular regard to the 

23 qualitative aspects discussed below. In general, numerical findings are indicated as they 

24 appear in the original report; units are converted when necessary for easier comparison. The 

25 Working Group may conduct additional analyses of the published data and use them in their 

26 assessment of the evid~nce; the results of such supplementary analyses are given in square 

27 brackets. When an important aspect of a study that directly impinges on its interpretation 

28 should be brought to the attention of the reader, a Working Group comment is given in square 

29 brackets. 

30 The scope of the IARC Monographs programme has expanded beyond chemicals to 

31 include complex mixtures, occupational exposures, physical and biological agents, lifestyle 

32 factors and other potentially carcinogenic exposures. Over time, the structure of a Monograph 

33 bas evolved to include the following sections: 

34 1. Exposure data 

35 2. Studies of cancer in humans 

36 3. Studies of cancer in experimental animals 

37 4. Mechanistic and other relevant data 

38 5.Summary 

39 6. Evaluation and rationale 

40 In addition, a section of General Remarks at the front of the volume discusses the reasons 

41 the agents were scheduled for evaluation and some key issues the Working Group 

42 encountered during the meeting. 

43 This part of the Preamble discusses the types of evidence considered and summarized in 

44 each section of a Monograph, followed by the scientific c1iteria that guide the evaluations. 
181 

PREAMBLE 7 

1. Exposure data 

2 Each Monograph includes general information on the agent: this information may vary 

3 substantially between agents and must be adapted accordingly. Also included is information 

4 on production and use (when appropriate), methods of analysis and detection, occurrence, 

5 and sources and routes of human occupational and environmental exposures. Depending on 

6 the agent, regulations and guidelines foruse may be presented. 

7 (a) General information on the agent 

8 For chemical agents, sections on chemical and physical data are included: the Chemical 

9 Abstracts Service Registry Number, the latest primary name and the IUPAC systematic name 

10 are recorded; other synonyms are given, but the list is not necessarily comprehensive. 

ll Information on chemical and physical properties that are relevant to identification, occurrence 

12 and biological activity is included. A description of technical products of chemicals includes 

13 trade names, relevant specifications and available information on composition and impurities. 

14 . Some of the trade names given may be those of mixtures in which the agent being evaluated 

15 is only one of the ingredients. 

16 For biological agents, taxonomy, structure and biology are described, and the degree of 

17 variability is indicated. Mode of replication, life cycle, target cells, persistence, latency, host 

18 response and clinical disease other than cancer are also presented. 

19 For physical agents that are forms of radiation, energy and range of the radiation are 

20 included. For foreign bodies; fibres and respirable particles, size range and relative 

21 dimensions are indicated. 

22 For agents such as mixtures, drugs or lifestyle factors, a description of the agent, 

23 including its composition, is given. 

24 Whenever appropriate, other information, such as historical perspectives or the 

25 description of an industry or habit, may be included. 

26 (b) Analysis and detection 

27 An overview of methods of analysis and detection of the agent is presented, including 

28 their sensitivity, specificity and reproducibility. Methods widely used for regulatory purposes 

29 are emphasized. Methods for monitoring human exposure are also given. No critical 

30 evaluation or recommendation of any method is meant or implied. 

31 (c) Production and use 

32 The dates of first synthesis and of first commercial production of a chemical. mixture or 

33 other agent are provided when available; for agents that do not occur naturally, this 

34 information may allow a reasonable estimate to be made of the date before which no human 

35 exposure to the agent could have occurred. The dates of first reported occurrence of an 

36 exposure are also provided when available. In addition, methods of synthesis used in past and 

37 present commercial production and different methods of production, which may give rise to 

38 different impurities, are described. 

39 The countries where companies report production of the agent, and the number of 

40 companies in each country, are identified. Available data on production, international trade 

41 and uses are obtained for representative regions. It should not, however, be inferred that those 

42 areas or nations are necessarily the sole or major sources or users of the agent. Some 

43 identified uses may not be current or major applications, and the coverage is not necessarily 
182 

8 !ARC Monographs 

1 comprehensive. In the case of drugs, mention of their therapeutic uses does not necessarily 

2 represent current practice nor does it imply judgement as to their therapeutic efficacy. 

3 (d) Occurrence and exposure 

4 Information on the occurrence of an agent in the environment is obtained from data 

5 derived from the monitoring and surveillance of levels in occupational environments, air, 

6 water, soil, plants, foods and animal and human tissues. When available, data on the 

7 generation, persistence and bioaccumulation of the agent are also included. Such data may be 

8 available from national databases. 

9 Data that indicate the extent of past and present human exposure, the sources of exposure, 

10 the people most likely to be exposed and the factors that contribute to the exposure are 

11 reported. Information is presented on the range of human exposure, including occupational 

12 and environmental exposures. This includes relevant findings from both developed and 

13 developing countries. Some of these data are not distributed widely and may be available 

14 from government reports and other sources. In the case of mixtures, industries, occupations or 

15 processes, infortnation is given about all agents koown to be present. For processes, 

16 industries and occupations, a historical description is also given, noting variations in chemical 

17 composition, physical properties and levels of occupational exposure with date and place. For 

18 biological agents, the epidemiology of infection is described. 

19 (e) Regulations and guidelines 

20 Statements concerning regulations and guidelines (e.g. occupational exposure limits, 

21 maximal levels permitted in foods and water, pesticide registrations) are included, but they 

22 may not reflect the· most recent situation, since such limits are continuously reviewed and 

23 modified. The absence of information on regulatory status for a country should not be taken 

24 to imply that that country does not have regulations with regard to the exposure. For 

25 biological agents, legislation and control, including vaccination and therapy, are described. 

26 2. Studies of cancer in humans 

27 This section includes all pertinent epidemiological studies (see Part A, Section 4). Studies 

28 of biomarkers are included when they are relevant to an evaluation of carcinogenicity to 

29 humans. 

30 (a) Types of study considered 

31 Several types of epidemiological study contribute to the assessment of carcinogenicity in 

32 humans - cohort studies, case-control studies, correlation (or ecological) studies and 

33 intervention studies. Rarely, results from randomized trials may be avaHable. Case reports 

34 and case series of cancer in humans may also be reviewed. 

35 Cohort and case-control studies relate individual exposures under study to the occurrence 

36 of cancer in individuals and provide an estimate of effect (such as relative risk) as the main 

37 measure of association. Intervention studies may provide strong evidence for making causal 

38 inferences, as exemplified by cessation of smoking and the subsequent decrease in risk for 

39 lung cancer. 

40 In correlation studies, the units of investigation are usually whole populations (e.g. in 

41 particular geographical areas or at particular times), and cancer frequency is related to a 

42 summary measure of the exposure of the population to the agent under study. In correlation 

43 studies, individual exposure is not documented, which renders this kind of study more prone 
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PREAMBLE 9 

1 to confounding. In some circumstances, however, correlation studies may be more 

2 informative than analytical study designs (see, for example, the Monograph on arsenic in 

3 drinking-water; IARC, 2004). 

4 In some instances, case reports and case series have provided important information about 

5 the carcinogenicity of an agent. These types of study generally arise from a suspicion, based 

6 on clinical experience, that the concurrence of two events - that is, a particular exposure and 

7 occurrence of a cancer - has happened rather more frequently than would be expected by 

8 chance. ·case reports and case series usually Jack complete ascertainment of cases in any 

9 population, definition or enumeration of the population at risk and estimation of the expected 

10 number of cases in the absence of exposure. 

II The uncertainties that surround the interpretation of case reports, case series and 

12 correlation studies make them inadequate, except in rare instances, to form the sole basis for 

13 inferring a causal relationship. When taken together with case-control and cohort studies, 

14 however, these types of study may add materially to the judgement that a causal relationship 

15 exists. 

16 Epidemiological studies of benign neoplasms, presumed preneoplastic lesions and other 

17 end-points thought to be relevant to cancer are also reviewed. They may, in some instances, 

18 strengthen inferences drawn from studies of cancer itself. 

19 (b) Quality of studies considered 

20 It is necessary to take into account the possible roles of bias, confounding and chance in 

21 the interpretation of epidemiological studies. Bias is the effect of factors in study design or 

22 execution that lead erroneously to a stronger or weaker association than in fact exists between 

23 an agent and disease. Confounding is a form of bias that occurs when the relationship with 

24 disease is made to app,ear stronger or weaker than it truly is as a result of an association 

25 between the apparent causal factor and another· factor that is associated with either an 

26 increase or decrease in the incidence ofthe disease. The role of chance is related to biological 

27 variability and the influence of sample size on the precision of estimates of effect. 

28 In evaluating the extent to which these factors have been minimized in an individual 

29 study, consideration is given to a number of aspects of design and analysis as described in the 

30 report of the study. For example, when suspicion of carcinogenicity arises largely from a 

31 single small study, careful consideration is given when interpreting subsequent studies that 

32 included 1hese data in an enlarged population. Most of these considerations apply equally to 

33 case-control, cohort and correlation studies. Lack of clarity of any of these aspects in the 

34 reporting of a study can decrease its credibility and the weight given to it in 1he final 

35 evaluation of the exposure. 

36 Firstly, the study population, disease (or diseases) and exposure should have been well 

37 defined by the authors. Cases of disease in the study population· should have been identified 

38 in a way that was independent of the exposure of interest, and exposure should have been 

39 assessed in a way 1hat was not related to disease status. 

40 Secondly, the authors should have taken into account- in the study design and analysis 

41 - other variables that can influence the risk of disease and may have been related to the 

42 exposure of interest. Potential confounding by such variables should have been dealt with 

43 either in the design of the study, such as by matching, or in the analysis, by statistical 

44 adjustment. In cohort studies, comparisons with local rates of disease may or may not be 

45 more appropriate than those with national rates. Internal comparisons of frequency of disease 

46 among individuals at different levels of exposure arc also desirable in cohort studies, since 
184 

10 IARC Monographs 

1 they minimize the potential for confounding related to the difference in risk factors between 

2 an external reference group and the study population. 

3 Thirdly, the authors should have rep01ted the basic data on which the conclusions are 

4 founded, even if sophisticated statistical analyses were employed. At the very least, they 

5 should have given the numbers of exposed and unexposed cases and controls in a case6 control study and the numbers of cases observed and expected in a cohort study. Further 

7 tabulations by time since exposure began and other temporal factors are also important. In a 

8 cohort study, data on all cancer sites and all causes of death should have been given, to reveal 

9 the possibility of reporting bias. In a case-control study, the effects of investigated factors 

I 0 other than the exposure of interest should have been reported. 

11 Finally, the statistical methods used to obtain estimates of relative risk, absolute rates of 

12 cancer, confidence intervals and significance tests, and to adjust for confounding should have 

13 been clearly stated by the authors. These methods have been reviewed for case-control 

14 studies (Breslow & Day, 1980) and for cohort studies (Breslow & Day, 1987). 

15 (c) Meta-analyses and pooled analyses 

16 Independent epidemiological studies of the same agent may lead to results that are 

17 difficult to interpret. Combined analyses of data from multiple studies are a means of 

18 resolving this ambiguity, and well-conducted analyses can be considered. There are two types 

19 of combined analysis. The first involves combining summary statistics such as relative risks 

20 from individual studies (meta-analysis) and the second involves a pooled analysis of the raw 

21 data from the individual studies (pooled analysis) (Greenland, 1998). 

22 The advantages of combined analyses are increased precision due to increased sample 

23 size and the opportunity to explore potential confollnders, interactions and m6difying effects 

24 that may explain heterogeneity among studies in more detail. A disadvantage of combined 

25 analyses is the possible lack of compatibility of data from various studies due to differences 

26 in subject recruitment, procedures of data collection, methods of measurement and effects of 

27 unmeasured co-variates that may differ among studies. Despite these limitations, well28 conducted combined analyses may provide a firmer basis than individual studies for drawing 

29 conclusions about the potential carcinogenicity of agents. 

30 IARC may commission a meta-analysis or pooled analysis that is pertinent to a particular 

31 Monograph (see Part A, Section 4). Additionally, as a means of gaining insight from the 

32 results of multiple individual studies, ad-hoc calculations that combine data from different 

33 studies may be conducted by the Working Group during the course of a Monograph meeting. 

34 The results of such original calculations, which would be specified in the text by presentation 

35 in square brackets, might involve updates of previously conducted analyses that incmporate 

36 the results of more recent studies or de-novo analyses. Irrespective of the source of data for 

37 the meta-analyses and pooled analyses, it is important that the same criteria for data quality 

38 be applied as those that would be applied to individual studies and to ensure also that sources 

39 of heterogeneity between studies be taken into account. 

40 (d) Temporal effects 

41 Detailed analyses of both relative and absolute risks in relation to temporal variables, 

42 such as age at first exposure, time since first exposure, duration of exposure, cumulative 

43 exposure, peak exposure {when appropriate) and time since cessation of exposure, are 

44 reviewed and summarized when available. Analyses of temporal relationships may be useful 

45 in making causal inferences. In addition, such analyses may suggest whether a carcinogen 
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PREAMBLE 11 

1 acts early or late in the process of carcinogenesis, although, at best, they allow only indirect 

2 inferences about mechanisms of carcinogenesis. · 

(e) Use of biomarkers in epidemiological studies 

4 Biomarkers indicate molecular, cellular or other biologic"al changes and are increasingly 

5 used in epidemiological studies for various purposes (IARC, 1991; Vainio et al., 1992; 

6 Toniolo eta/., 1997; Vineis et al., 1999; Buffler eta/., 2004). These may include evidence of 

7 exposure, of early effects, of cellular, tissue or organism responses, of individual 

8 susceptibility or host responses, and inference of a mechanism (see Part B, Section 4b). This 

9 is a rapidly evolving field that encompasses developments in genomics, epigenomics and 

10 other emerging technologies. 

11 . Molecular epidemiological data that identify associations between genetic polymorphisms 

12 and interindividual differences in susceptibility to the agent(s) being evaluated niay 

13 contribute to the identification of carcinogenic hazards to humans. If the polymorphism has 

14 been demonstrated experimenta1ly to modify the functiona:l activity of the gene product in a 

15 manner that is consistent with increased susceptibility, these data may be useful in making 

16 causal inferences. Similarly, molecular epidemiological studies that measure cell functions, 

17 enzymes or metabolites that are thought to be the basis of susceptibility may provide 

18 evidence that reinforces biologica:l plausibility. It shOuld be noted, however, that when data 

19 on· genetic susceptibility originate from multiple comparisons that arise from subgroup 

20 analyses, this can generate false-positive results and inconsistencies across studies, and such 

21 data therefore require careful evaluation. If the known phenotype of a genetic polymorphism 

22 can explain the carcinogenic mechanism of the agent being evaluated, data on this phenotype 

23 may be useful in making causal inferences. 

24 (f) Criteria for causality 

25 After the quality of individual epidemiological studies of cancer has been summarized 

26 and assessed, a judgement is made concerning the strength of evidence that the agent in 

27 question is carcinogenic to humans. In making its judgement, the Working Group considers 

28 several criteria for causality (Hill, 1965). A strong association (e.g. a large relative risk) is 

29 more likely to indicate causality than a wea:k association, a:lthough it is recognized that 

30 estimates of effect of small magnitude do not imply lack of causality and may be important if 

31 the disease or exposure is common. Associations that are replicated in several studies of the 

32 same design or that use different epidemiological approaches or under different 

33 circumstances of exposure are more likely to represent a causa:l relationship than isolated 

34 observations from single studies. If there are inconsistent results among investigations, 

35 possible reasons are sought (such as differences in exposure), and results of studies that are 

36 judged to be of high quality are given more weight than those of studies that are judged to be 

37 methodologically less. sound. 

38 If the risk increases with the exposure, this is considered to be a strong indication of 

39 causality, although the absence of a graded response is not necessarily evidence against a 

40 causal relationship. The demonstration of a decline in risk after cessation of or reduction in 

41 exposure in individuals or in whole populations also supports a causal interpretation of the 

4 2 findings. 

43 A number of scenarios may increase confidence in a causal relationship. On the one hand, 

44 an agent may be specific in causing tumours at one site or of one morphological type. On the 

45 other, carcinogenicity may be evident through the causation of multiple tumour types. 

46 Temporality, precision of estimates of effect, biological plausibility and coherence of the 
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12 IARC Monographs 

1 overall database are considered. Data on biomarkers may be employed in an assessment of 

2 the biological plausibility of epidemiological observations. 

3 Although rarely available, results from randomized trials that show different rates of 

4 cancer among exposed and unexposed individuals provide particularly strong evidence for 

5 causality. 

6 When several epidemiological studies show little or no indication of an association 

7 between an exposure and cancer, a judgement may be made that, in the aggregate, they show 

8 evidence of lack of carcinogenicity. Such a judgement requires firstly that the studies meet, to 

9 a sufficient degree, the standards of design and analysis described above. Specifically, the 

10 possibility that bias, confounding or rnisclassification of exposure or outcome could explain 

11 the observed results should be considered and excluded with reasonable certainty. In addition, 

12 all studies that are judged to be methodologically sourid should (a) be consistent with an 

13 estimate of effect of unity for any observed level of exposure, (b) when considered together, 

14 provide a pooled estimate of relative risk that is at or near to unity, and (c) have a narrow 

15 confidence interval, due to sufficient population size. Moreover, no individual study nor the 

16 pooled results of all the studies should show any consistent tendency that the relative risk of 

17 cancer increases with increasing level of exposure. It is important to note that evidence of 

18 lack of carcinogenicity obtained from several epidemiological studies can apply only to the 

19 type(s) of cancer studied, to the dose levels reported, and to the intervals between first 

20 exposure and disease onset observed in these studies. Experience with human cancer 

21 indicates that the period from first exposure to the development of clinical cancer is 

22 sometimes longer than 20 years; latent periods substantially shorter than 30 years cannot 

23 provide evidence for lack of carcinogenicity. 

24 3. Studies of cancer in experimental animals 

25 All known human carcinogens that have been stUdied adequately for carcinogenicity in 

26 experimental animals have produced positive results in one or more animal species (Wilbourn 

27 et al., 1986; Tomatis et al., 1989). For several agents (e.g. aflatoxins, diethylstilbestrol, solar 

28 radiation, vinyl chloride), carcinogenicity in experimental animals was established or highly 

29 suspected before epidemiological studies confirmed their carcinogenicity in humans (Vainio 

30 et al., 1995). Although this association cannotestablish that all agents that cause cancer in 

31 experimental animals also cause cancer in human.s, it is biologically plausible that agents for 

32 which there is sufficient evidence of carcinogenicity in experimental animals (see Part B, 

33 Section 6b) also present a carcinogenic hazard to humans. Accordingly, in the absence of 

34 additional scientific information, these agents are considered to pose a carcinogenic hazard to 

35 humans. Examples of additional scientific information are data that demonstrate that a given 

36 agent causes cancer in animals through a species-specific mechanism that does not operate in 

37 humans or data that demonstrate that the mechanism in experimental animals also operates in 

38 humans {see Part B, Section 6). 

39 Consideration is given to all available long-term studies of cancer in experimental 

40 animals with the agent under review (see Part A, Section 4). In all experimental settings, the 

41 nature and extent of impurities or contaminants present in the agent being evaluated are given 

42 when available. Animal species, strain {including genetic background where applicable), sex, 

43 numbers per group, age at start of treatment, route of exposure, dose levels, duration of 

44 exposure, survival and information on tumours (incidence, latency, severity or multiplicity of 

45 neoplasms or preneoplastic lesions) are reported. Those studies in experimental animals that 

46 are judged to be irrelevant to the evaluation or judged to be inadequate (e.g. too short a 
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PREAMBLE 13 

1 duration, too few animals, poor survival; see below) may be omitted. Guidelines for 

2 conducting long-term carcinogenicity experiments have been published (e.g. OECD, 2002). 

3 Other studies considered may include: experiments in which the agent was administered 

4 in the presence of factors that modify carcinogenic effects (e.g, initiation-promotion studies, 

5 co-carcinogenicity studies and studies in genetically modified animals); studies in which the 

6 end-point was not cancer but a defined precancerous lesion; experiments on the 

7 carcinogenicity of known metabolites and derivatives; and studies of cancer in non-laboratory 

8 animals (e.g. livestock and companion animals) exposed to the agent. 

9 For studies of mixtures, consideration is given to the possibility that changes in the 

10 physicochemical properties of the individual substances way occur during collection, storage, 

11 extraction, concentration and delivery. Another consideration is that chemical and 

12 toxicological interactions of components in a mixture may alter dose-response relationships. 

13 The relevance to human exposure of the test mixture administered in the animal experiment is 

14 also assessed. This may involve consideration of the following aspects of the mixture tested: 

1 5 (i) physical and chemical characteristics, (ii) identified constituents that way indicate the 

16 presence of a class of substances and (iii) the results of genetic toxicity and related tests. 

17 The relevance of results obtained with an agent that is analogous (e.g. similar in structure 

18 or of a similar virus genus) to that being evaluated is also considered. Such results may 

19 provide biological and mechanistic information that is relevant to the understanding of the 

20 process of carcinogenesis in humans and may strengthen the biological plausibility that the 

21 agent being evaluated is carcinogenic to humans (see Part B, Section 2f). 

22 (a) Qualitative aspects 

23 An assessment of carcinogenicity involves several considerations of qualitative 

24 importance, including (i) the experimental conditions under which the test was performed, 

25 including route, schedule and duration of exposure, species, strain (including genetic 

26 background where applicable), sex, age and duration of follow-up; (ii) the consistency of the 

27 results, for example, across species and target' organ( s ); (iii) the spectrum of neoplastic 

28 response, from preneoplastic lesions and benign tumours to malignant neoplasms; and (iv) 

29 the possible role of modifying factors. 

30 Considerations of importance in the interpretation and evaluation of a particular study 

31 include: (i) how clearly the agent was defined and, in the case of mixtures, how adequately 

32 the sample characterization was reported; (ii) whether the dose was monitored adequately, 

33 particularly in inhalation experiments; (iii) whether the doses, duration of treatment and route 

34 of exposure were appt·opriate; (iv) whether the survival of treated animals was similar to that 

35 of controls; (v) whether there were adequate numbers of animals per group; (vi) whether both 

36 male and female animals were used; (vii) whether animals were allocated randomly to 

37 groups; (viii) whether the duration of observation was adequate; and (ix) whether the data 

38 were reported and analysed adequately. 

39 When benign tumours (a) occur together with and originate from the same cell type as 

40 malignant tumours in an organ or tissue in a particular study and (b) appear to represent a 

41 stage in the progression to malignancy, they are usually combined in the assessment of 

42 tumour incidence (Huff et al., 1989). The occurrence of lesions presumed to be preneoplastic 

43 may in certain instances aid in assessing the biological plausibility of any neoplastic response 

44 obseJYed. If an agent induces only benign neoplasms that appear to be end-points that do not 

45 readily undergo transition to malignancy, the agent should nevertheless be suspected of being 

46 carcinogenic and requires further investigation. 
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14 !ARC Monographs 

{b) Quantitative aspects 

2 The probability that tumours will occur may depend on the species, sex, strain, genetic 

3 background and age of the animal, and on the dose, route, timing and duration of the 

4 exposure. Evidence of an increased incidence of neoplasms with increasing levels of 

5 exposure strengthens the inference of a causal association between the exposure and the 

6 development of neoplasms. 

7 The form of the dose---response relationship can vary widely, depending on the particular 

8 agent under study and the target organ. Mechanisms such as induction of DNA damage or 

9 inhibition of repair, altered cell division and cell death rates and changes in intercellular 

10 communication are important determinants of dose-response relationships for some 

11 carcinogens. Since many chemicals require metabolic activation before being converted to 

12 their reactive intermediates, both metabolic and toxicokinetic aspects are important in 

13 determining the dose---response pattern. Saturation of steps such as absorption, activation, 

14 inactivation and elimination may produce non-linearity in the dose---response relationship 

15 {Hoe! et al., 1983; Gart et al., 1986), as could saturation of processes such as DNA repair. 

16 The dose---response relationship can also be affected by differences in survival among the 

17 treatment groups. 

18 {c) Statistical analyses 

19 Factors considered include the adequacy of the information given for each treatment 

20 group: {i) number of animals studied and number examined histologically, (ii) number of 

21 animals with a given tumour type and (iii) length of survival. The statistical methods used 

22 should be clearly stated and should be the generally accepted techniques refmed for this 

23 purpose {Peto eta!., 1980; Gart et al., 1986; Portier & Bailer, 1989; Bieler & Williams, 

24 1993). The choice of the most appropriate statistical method requires consideration of 

25 whether or not there are differences in survival among the treatment groups; for example, 

26 reduced survival because of non-tumour-related mortality can preclude the occurrence of 

27 tumours later in life. When detailed information on survival is not available, comparisons of 

28 the proportions of tumour-bearing animals among the effective number of animals (alive at 

29 the time the first tumour was discovered) can be useful when significant differences in 

30 survival occur before tumours appear. The lethality of the tumour also requires consideration: 

31 for rapidly fatal tumo11rs, the time of death provides an indication of the time of tumour onset 

32 and can be assessed using life-table methods; non-fatal or incidental tumours that do not 

33 affect survival can be assessed using methods such as the Mantel-Haenzel test for changes in 

34 tumour prevalence. Because tumour lethality is often difficult to determine, methods such as 

35 the Poly-K test that do not require such information can also be used. When results are 

36 available on the number and size of tumours seen in experimental animals (e.g. papillomas on 

37 mouse skin, liver tumours observed through nuclear magnetic resonance tomography), other 

38 more complicated statistical procedures may be needed (Sherman eta!., 1994; Dunson et al., 

39 2003). 

40 Formal statistical methods have been developed to incorporate historical control data into 

41 the analysis of data from a given experiment. These methods assign an appropriate weight to 

42 historical and concurrent controls on the basis of the extent of between-study and within43 study variability: less weight is given to historical controls when they show a high degree of 

44 variability, and greater weight when they show little variability. It is generally not appropriate 

45 to discount a tumour response that is significantly increased compared with concurrent 

46 controls by arguing that it falls within the range of historical controls, particularly when 

47 historical controls show high between-study variability and are, thus, of little relevance to the 
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1 current experiment. In analysing results for uncommon tumours, however, the analysis may 

2 be improved by considering historical control data, particularly when between-study 

3 variability is low. Historical controls should be selected to resemble the concurrent controls 

4 as closely as possible with respect to species, gender and strain, as well as other factors such 

5 as basal diet and general laboratory environment, which may affect tumour-response rates in 

6 control animals (Haseman eta/., 1984; Fung eta/., 1996; Greim eta/., 2003). 

7 Although meta-analyses and combined analyses are conducted less frequently for animal 

8 experiments than for epidemiological studies due to differences in animal strains, they can be 

9 useful aids in interpreting animal data when the experimental protocols are sufficiently 

10 similar. · 

11 4. Mechanistic and other relevant data 

12 Mechanistic and other relevant data may provide evidence of carcinogenicity and also 

13 help in assessing the relevance and importance of findings of cancer in animals and in 

14 humans. The nature of the mechanistic and other relevant data depends on the biological 

15 activity of the agent being considered. The Working Group considers representative studies 

16 to give a concise description of the relevant data and issues that they consider to be 

17 important; thus, not every available study is cited. Relevant topics may include 

18 toxicokinetics, mechanisms of carcinogenesis, susceptible individuals, populations and life19 stages, other relevant data and other adverse effects. When data on· biomarkers are 

20 informative about the mechanisms of carcinogenesis, they are included in this section. 

21 These topics are not mutually exclusive; thus, the same studies may be discussed in more 

22 than one subsection. For example, a mutation in a gene that codes for an enzyme that 

23 metabolizes the agent under study could be discussed in the subsections on toxicokinetics, 

24 mechanisms and individual susceptibility if it also exists as an inherited polymorphism. 

25 (a) Toxicoldnetic data 

26 Toxicokinetics refers to the absorption, distribution, metabolism and elimination of agents 

27 in humans, experimental animals and, where relevant, cellular systems. Examples of kinetic 

28 factors that may affect dose-response relationships include uptake, deposition, biopersistence 

29 and half-life in tissues, protein binding, metabolic activation and detoxification. Studies that 

30 · indicate the metabolic fate of the agent in humans and in experimental animals are 

31 summarized briefly, and comparisons of data from humans and animals are made when 

32 ·possible. Comparative infmmation on the relationship between exposure and the dose that 

33 reaches the target site may be important for the extrapolation of hazards between species and 

34 in clarifying the role of in-vitro findings. 

35 (b) Data on mechanisms of carcinogenesis 

36 To provide focus, the Working Group attempts to identify the possible mechanisms by 

37 which the agent may increase the risk of cancer. For each possible mechanism, a 

38 representative selection of key data from humans and experimental systems is summarized. 

39 Attention is given to gaps in the data and to data that suggests that more than one mechanism 

40 may be operating. The relevance of the mechanism to humans is discussed, in particular, 

41 when mechanistic data are derived from experimental model systems. Changes in the affected 

42 organs, tissues or cells can be divided into three non-exclusive levels as described below. 
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16 JARC Monographs 

1 (i) Changes in physiology 

2 Physiological changes refer to exposure-related modifications to the physiology 

3 and/or response of cells, tissues and organs. Examples of potentially adverse 

4 physiological changes include mitogenesis, compensatory cell division, escape from 

5 apoptosis and/or senescence, presence of inflammation, hyperplasia, metaplasia and/or 

6 preneoplasia, angiogenesis, alterations in cellular adhesion, changes in steroidal hormones 

7 and changes in immune surveillance. · 

8 (ii) Functional changes at the cellular level 

9 Functional changes refer to exposure-related alterations in the signalling pathways 

10 used by cells to manage critical processes that are related to increased risk for cancer. 

11 Examples of functional changes include modified activities of enzymes involved in the 

12 metabolism of xenobiotics, alterations in the expression of key genes that regulate DNA 

13 repair, alterations in cyclin-dependent kinases that govern cell cycle progression, changes 

14 in the patterns of post-translational modifications of proteins, changes in regulatory 

15 factors that alter apoptotic rates, changes in the secretion of factors related to the 

16 stimulation of DNA replication and transcription and changes in gap--junction-mediated 

17 intercellular communication. 

18 (iii) Changes at the molecular level 

19 Molecular changes refer to exposure-related changes in key cellular stmctures at the 

20 molecular level, including, in particular, genotoxicity. Examples of molecular changes 

21 include formation of DNA adducts and DNA strand breaks, mutations in genes, 

22 chromosomal aberrations, aneuploidy and changes in DNA methylation patterns. Greater 

23 emphasis is given to irreversible effects. 

24 )'he use of mechanistic data in the identification of a carcinogenic hazard is specific to the 

25 mechanism being addressed and is not readily described for every possible level and 

26 mechanism discussed above. 

27 Genotoxicity data are discussed here to illustrate the. key issues involved in the evaluation 

28 of mechanistic data. 

29 Tests for genetic and related effects are described in view of the relevance of gene 

30 mutation and chromosomal aberration/aneuploidy to carcinogenesis (Vainio et al., 

31 1992; McGregor et al., 1999). The adequacy of the reporting of sample 

32 characterization is considered and, when necessary, commented upon; with regard to 

33 complex mixtures, such comments are similar to those described for animal 

34 carcinogenicity tests. The available data are interpreted critically according to the end35 points detected, which may include DNA damage, gene mutation, sister chromatid 

36 exchange, micronucleus formation, chromosomal aberrations and aneuploidy. The 

37 concentrations employed are given, and mention is made of whether the use of an 

38 exogenous metabolic system in vitro affected the test result. These data are listed in 

39 tabular form by phylogenetic classification. 

40 Positive results in tests using prokaryotes, lower eukaryotes, insects, plants and 

41 cultured mammalian cells suggest that genetic and related effects could occur in 

42 mammals. Results from such tests may also give information on the types of genetic 

43 effect produced and on the involvement of metabolic activation. Some end-points 

44 described are clearly genetic in nature (e.g. gene mutations), while others are 

45 associated with genetic effects (e.g. unscheduled DNA synthesis). In-vitro tests for 
191 

PREAMBLE 17 

1 tumour promotion, cell transformation and gap-junction intercellular communication 

2 may be sensitive to changes that are not necessarily the result of genetic alterations 

3 but that may have specific relevance to the process of carcinogenesis. Critical 

4 appraisals of these tests have been published (Montesano et al., 1986; McGregor et 

5 al., 1999). 

6 Genetic or other activity manifest in humans and experimental mammals is 

7 regarded to be of greater relevance than that in other organisms. The demonstration 

8 that an agent can induce gene and chromosomal mutations in mammals in vivo 

9 indicates that it may have carcinogenic activity. Negative results in tests for 

10 mutagenicity in selected tissues from animals treated in vivo provide less weight, 

11 partly because they do not exclude the possibility of an effect in tissues other than 

12 those examined. Moreover, negative results in short-term tests with genetic end-points 

13 cannot be considered to provide evidence that rules out the carcinogenicity of agents 

14 that act through other mechanisms (e.g. receptor-mediated effects, cellular toxicity 

15 with regenerative cell division, peroxisome" proliferation) (Vainio et al., 1992). 

16 Factors that may give misleading results in short-term tests have been discussed in 

17 detail elsewhere (Montesano eta!., 1986; McGregor et al., 1999). 

18 When there is evidence that an agent acts by a specific mechanism that does not involve 

19 genotoxicity (e.g. hormonal dysregulation, immune suppression, and formation of calculi and 

20 other deposits that cause chronic irritation), that evidence is presented and reviewed critically 

21 in the context of rigorous criteria for the operation of that mechanism in carcinogenesis (e.g. 

22 Capen et al., 1999). 

23 For biological agents such as viruses, bacteria and parasites, other data relevant to 

24 carcinogenicity may include descriptions of the pathology of infection, integration and 

25 expression of viruses, and genetic alterations seen in human tumours. Other observations that 

26 might comprise cellular and tissue responses to infection, immune response and the presence 

27 of tumour markers are also considered. 

28 For physical agents that are fonns of radiation, other data relevant to carcinogenicity may 

29 include descriptions of damaging effects at the physiological, cellular and molecular level, as 

30 for chemical agents, and descriptions of how these effects occur. 'Physical agents' may also 

31 be considered to comprise foreign bodies, such as surgical implants of various kinds, and 

32 poorly soluble fibres, dusts and particles of various sizes, the pathogenic effects of which are 

33 a result of their physical presence in tissues or body cavities. Other relevant data for such 

34 materials may include characterization of cellular, tissue and physiological reactions to these 

35 materials and descriptions of pathological conditions other than neoplasia with which they 

36 may be associated. 

37 (c) Other data relevant to mechanisms 

38 A description is provided of any structure-activity relationships that may be relevant to 

39 an evaluation of the carcinogenicity of an agent, the toxicological implications of the physical 

40 and chemical properties, and any other data relevant to the evaluation that are not included 

41 elsewhere. 

42 High-output data, such as those derived from gene expression microarrays, and high43 throughput data, such as those that result from testing hundreds of agents for a single end44 point, pose a unique problem for the use of mechanistic data in the evaluation of a 

45 carcinogenic hazard. In the case of high-output data, there is the possibility to overinterpret 

46 changes in individual end-points (e.g. changes in expression in one gene) without considering 

47 the consistency of that finding in the broader context of the other end-points (e.g. other genes 
192 

18 !ARC Monographs 

with linked transcriptional control). High-ouq)ut data can be used in assessing mechanisms, 

2 but all end-points measured in a single experiment need to be considered in the proper 

3 context. For high-throughput data, where the number of observations far exceeds the number 

4 of end-points measured, their utility for identifying common mechanisms across multiple 

5 agents is enhanced. These data can be used to identify mechanisms that not only seem 

6 plausible, but also have a consistent pattern of carcinogenic response across entire classes of 

7 related compounds. 

8 (d) Susceptibility data 

9 Individuals, populations and life-stages may have greater or lesser susceptibility to an 

10 agent, based on toxicokinetics, mechanisms of carcinogenesis and other factors. Examples of 

11 host and genetic factors that affect individual susceptibility include sex, genetic 

12 polymorphisms of genes involved in the metabolism of the agent under evaluation, 

13 differences in metabolic capacity due to life-stage or the presence of disease, differences in 

14 DNA repair capacity, competition for or alteration of metabolic capacity by medications or 

15 other chemical exposures, pre-existing hormonal imbalance that is exacerbated by a chemical 

16 exposure, a suppressed immune system, periods of higher-than-usual tissue growth or 

17 regeneration and genetic polymorphisms that lead to differences in behaviour (e.g. addiction). 

18 Such data can substantially increase the strength of the evidence from epidemiological data 

19 and enhance the linkage of in-vivo and in-vitro laboratory studies to humans. 

20 (e) Data on other adverse effects 

21 Data on acute, subchronic and chronic adverse effects relevant to the cancer evaluation 

22 are summarized. Adverse effects that confirm distribution and biological effects at the sites of 

23 tumour development, or alterations in physiology that could lead to tumour development, are 

24 emphasized. Effects on reproduction, embryonic and fetal survival and development are 

25 summarized briefly. The adequacy of epidemiological studies of reproductive outcome and 

26 genetic and related effects in humans is judged by the same criteria as those applied to 

27 epidemiological studies of cancer, but fewer details are given. 

28 5. Summary 

29 TI1is section is a summary of data presented in the preceding sections. Summaries can be 

30 found on the Monographs programme website (http://monographs.iarc.fr). 

31 (a) Exposure data 

32 Data are summarized, as appropriate, on the basis of elements such as production, use, 

33 occurrence and exposure levels in the workplace and environment and measurements in 

34 human tissues and body fluids. Quantitative data and time trends are given to compare 

35 exposures in different occupations and environmental settings. Exposure to biological agents 

36 is described in terms of transmission, prevalence and persistence of infection. 

37 (b) Cancer in humans 

38 Results of epidemiological studies pertinent to an assessm~nt of human carcinogenicity 

39 are summarized. When relevant, case reports and correlation studies are also summarized. 

40 The target organ(s) or tissue(s) in which an increase in cancer was observed is identified. 

41 Dose-response and other quantitative data may be summarized when available. 
193 

PREAMBLE 19 

(c)Cancer in expedmental animals 

2 Data relevant to an evaluation of carcinogenicity in animals are summarized. For each 

3 animal species, study design and route of administration, it is stated whether an increased 

4 incidence, reduced latency, or increased severity or multiplicity of neoplasms or 

5 preneoplastic lesions were observed, and the tumour sites are indicated. If the agent produced 

6 tumours after prenatal exposure or in single-dose experiments, this is also mentioned. 

7 Negative findings, inverse relationships, dose-response and other quantitative data are also 

8 summarized. , 

9 (d) Mechanistic and other relevant data 

10 Data relevant to the toxicokinetics (absorption, distribution, metabolism, elimination) and 

11 the possible mechanism(s) of carcinogenesis (e.g. genetic toxicity, epigenetic effects) are 

12 summarized. In addition, information on susceptible individuals, populations and life-stages 

13 is summarized. This section also reports on other toxic effects, including reproductive and 

14 developmental effects, as well as additional relevant data that are considered to be important. 

15 6. Evaluation and rationale 

16 Evaluations of the strength of the evidence for carcinogenicity arising from human and 

17 experimental animal data are made, using standard terms. The strength of the mechanistic 

18 evidence is also characterized. 

19 It is recognized that the criteria for these evaluations, described below, cannot encompass 

20 all of the factors that may be relevant to an evaluation of carcinogenicity. In considering all 

21 of the relevant scientific-data, the Working Group may assign the agent to a higher or lower 

22 category than a strict interpretation of these criteria would indicate. 

23 These categories refer only to the strength of the evidence that an exposure is 

24 carcinogenic and not to the exterit of its carcinogenic activity (potency). A classification may 

25 change as new information becomes available. 

26 An evaluation of the degree of evidence is limited to the materials tested, as defined 

27 physically, chemically or biologically. When the agents evaluated are considered by the 

28 Working Group to be sufficiently closely related, they may be grouped together for the 

29 purpose of a single evaluation of the degree of evidence. 

30 (a) Carcinogenicity in humans 

31 The evidence relevant to carcinogenicity from studies in humans is classified into one of 

32 the following categories: 

33 Sufficient evidence of carcinogenicity: The Working Group considers that a causal 

34 relationship has been established between exposure to the agent and human cancer. That 

35 is, a positive relationship has been observed between the exposure and cancer in studies 

36 in which chance, bias and confounding could be ruled out with reasonable confidence. A 

3 7 statement that there is sufficient evidence is followed by a separate sentence that identifies 

38 the target organ(s) or tissue(s) where an increased risk of cancer was observed in humans. 

39 Identification of a specific target organ or tissue does not preclude the possibility that the 

40 agent may cause cancer at other sites. 

41 Limited evidence of CMci11ogenicity: A positive association has been observed between 

42 exposure to the agent and cancer for which a causal interpretation is considered by the 
194 

20 IARCMonographs 

1 Working Group to be credible, but chance, bias or confounding could not be ruled out 

2 with reasonable confidence. 

3 Inadequate evidence of carcinogenicity: The available studies are of insufficient quality, 

4 consistency or statistical power to permit a conclusion regarding the presence or absence 

5 of a causal association between exposure and cancer, or no data on cancer in humans are 

6 available. 

7 Evidence suggesting lack of carcinogenicity: There are several adequate studies covering the 

8 full range of levels of exposure that humans are known to encounter, which are mutually 

9 consistent in not showing a positive association between exposure to the agent and any 

10 studied cancer at any observed level of exposure. The results from these studies alone or 

11 combined should have narrow confidence intervals with an upper limit close to the null 

12 value (e.g. a relative risk of 1.0). Bias and confounding should be ruled out with 

13 reasonable confidence, and the studies should have an adequate length of follow-up. A 

14. conclusion of evidence suggesting lack of carcinogenicity is inevitably limited to the 

15 cancer sites, conditions and levels of exposure, and length of observation covered by the 

16 available studies. In addition, the possibility of a very small risk at the levels of exposure 

17 studied can never be excluded. 

18 In some instances, the above categories may be used to classify the degree of evidence 

19 related to carcinogenicity in specific organs or tissues. 

20 When the available epidemiological studies pertain to a mixture, process, occupation or 

21 industry, the Working Group seeks to identify the specific agent considered most likely to be 

22 responsible for any excess risk. The evaluation is focused as narrowly as the available data on 

23 exposure and other aspects permit. 

24 (b) Carcinogenicity in experimental animals 

25 Carcinogenicity in experimental animals can be evaluated using conventional bioassays, 

26 bioassays that employ genetically modified animals, and other in-vivo bioassays that focus on 

27 one or more of the critical stages of carcinogenesis. In the absence of data from conventional 

28 long-term bioassays or from assays with neoplasia as the end-point, consistently positive 

29 results in several models that address several stages in the multistage process of 

30 carcinogenesis should be considered in evaluating the degree of evidence of carcinogenicity 

31 in experimental animals. 

32 The evidence relevant to carcinogenicity in experimental animals is classified into one of 

33 the following categories: 

34 Sufficient evidence of ca1'ci11ogenicity: The Working Group considers that a causal 

35 relationship has been established between the agent and an increased incidence of 

36 malignant neoplasms or of an appropriate combination of benign and malignant 

37 neoplasms in (a) two or more species of animals or (b) two or more independent studies 

38 in one species carried out at different times or in different laboratories or under different 

39 protocols. An increased incidence of tumours in both sexes of a single species in a well40 conducted study, ideally conducted under Good Laboratory Practices, can also provide 

41 stifjicient evidence. 

42 A single study in one species and sex might be considered to provide stifficient evidence 

43 of carcinogenicity when malignant neoplasms occur to an unusual degree with regard to 

44 incidence, site, type of tumour or age at onset, or when there are strong findings of 

45 tumours at multiple sites. 
195 

PREAMBLE 21 

1 Limited evidence of carcinogenicity: The data suggest a carcinogenic effect but are limited 

2 for making a definitive evaluation because, e.g. (a) the evidence of carcinogenicity is 

3 restricted to a single experiment; (b) there are unresolved questions regarding the 

4 adequacy of the design, conduct or interpretation of the studies; (c) the agent increases the 

5 incidence only of benign neoplasms or lesions of uncertain neoplastic potential; or (d) the 

6 evidence of carcinogenicity is restricted to studies that demonstrate only promoting 

7 activity in a narrow range of tissues or organs. 

8 Inadequate evidence of carcinogenicity: The studies cannot be interpreted as showing either 

9 the presence or absence of a carcinogenic effect because of major qualitative or 

10 quantitative limitations, or no data on cancer in experimental animals are available. · 

11 Evidence suggesting lack of carcinogenicity: Adequate studies involving at least two species 

12 are 11vailable which show that, within the limits of the tests used, the agent is not 

13 carcinogenic. A conclusion of evidence suggesting lack of carcinogenicity is inevitably 

14 limited to the species, tumour sites, age at exposure, and conditions and levels of 

15 exposure studied. 

16 (c) Mechanistic and other relevant data 

17 Mechanistic and other evidence judged to be relevant to an evaluation of carcinogenicity 

18 and of sufficient importance to affect the overall evaluation is highlighted. This may include 

19 data on preneoplastic lesions, tumour pathology, genetic and related effects, structure20 activity relationships, metabolism and toxicokinetics, physicochemical parameters and 

21 analogous biological agents. 

22 The strength of the evidence that any carcinogenic effect observed is due to a particular 

23 mechanism is evaluated, using terms such as 'weak', 'moderate' or 'strong'. The Working 

24 Group then assesses whether that particular mechanism is likely to be operative in humans. 

25 The strongest indications that a particular mechanism operates in humans derive from data on 

26 humans or biological specimens obtained from exposed humans. The data may be considered 

27 to be especially relevant if they show that the agent in question has caused changes in 

28 exposed humans that are on the causal pathway to carcinogenesis. Such data may, however, 

29 never become available, because it is at least conceivable that certain compounds may be 

30 kept from human use solely on the basis of evidence of their toxicity and/or carcinogenicity 

31 in experimental systems. 

32 The conclusion that a mechanism operates in experimental animals is strengthened by 

33 findings of consistent results in different experimental systems, by the demonstration of 

34 biological plausibility and by coherence of the overall database. Strong support can be 

35 obtained from studies that challenge the hypothesized mechanism experimentally, by 

36 demonstrating that the suppression of key mechanistic processes leads to the suppression of 

37 tumour development. The Working Group considers whether multiple mechanisms might 

38 contribute to tumour development, whether different mechanisms might operate in different 

39 dose ranges, whether separate mechanisms might operate in humans and experimental 

40 animals and whether a unique mechanism might operate in a susceptible group. The possible 

41 contribution of alternative mechanisms must be considered before concluding that tumours 

42 observed in experimental animals are not relevant to humans. An uneven level of 

43 experimental support for different mechanisms may reflect that disproportionate resow·ces 

44 have been focused on investigating a favoured mechanism. 

45 For complex exposures, including occupational and industrial exposures, the chemical 

46 composition and the potential contribution of carcinogens known to be present are considered 

47 by the Working Group in its overall evaluation of human carcinogenicity. The Working 
196 

22 JARC Monographs 

1 Group also determines the extent to which the materials tested in experimental systems are 

2 related to those to which humans are exposed. 

3 (d) Overall evaluation 

4 Finally, the body of evidence is considered as a whole, in order to reach an overall 

5 evaluation of the carcinogenicity of the agent to humans. 

6 An evaluation may be made for a group of agents that have been evaluated by the 

7 Working Group. In addition, when supporting data indicate that other related agents, for 

8 which there is no direct evidence of their capacity to induce cancer in humans or in animals, 

9 may also be carcinogenic, a statement describing the rationale for this conclusion is added to 

10 the evaluation narrative; an additional evalu,ation may be made for tins broader group of 

11 agents if the strength of the evidence warrants it. 

12 The agent is described according to the wording of one of the following categories, and 

13 the designated group is given. The categorization of an agent is a matter of scientific 

14 judgement that reflects the strength of the evidence derived from studies in humans and in 

15 experimental animals and from mechanistic and other relevant data. 

16 Group 1: The agent is carcinogenic to humans. 

i 7 This category is used when there is s1if.ficient evidence of carcinogenicity in humans. 

18 Exceptionally, an agent may be placed in this category when evidence of carcinogenicity 

19 in humans is less than slif.ficient but there is sufficient evidence of carcinogenicity in 

20 experimental animals and strong evidence in exposed humans that the agent acts through 

21 a relevant mechanism of carcinogenicity. 

22 Group 2. 

23 This category includes agents for which, at one extreme, the degree of evidence of 

24 carcinogenicity in humans is almost sufficient, as well as those for which, at the other 

25 extreme, there are no human data but for which there is evidence of carcinogenicity in 

26 experimental animals. Agents are assigned to either Group 2A (probably carcinogenic to 

27 humans) or Group 2B (possibly carcinogenic to humans) on the basis of epidenriological 

28 and experimental evidence of carcinogenicity and mechanistic and other relevant data. 

29 The te1ms probably carcinogenic and possibly carcinogenic have no quantitative 

30 significance and are used simply as descriptors of different levels of evidence of human 

31 carcinogenicity, with probably carcinogenic signifying a higher level of evidence than 

32 possibly carcinogenic. 

33 Group 2A: The agent is probably carcinogenic to humans. 

34 This category is used when there is limited evidence of carcinogenicity in humans and 

35 slif.ficient evidence of carcinogenicity in experimental animals. In some cases, an agent 

36 may be classified in this category when there is inadequate evidence of carcinogenicity in 

37 humans and sufficient evidence of carcinogenicity in experimental animals and strong 

38 evidence that the carcinogenesis is mediated by a mechanism that also operates in 

39 humans. Exceptionally, an agent may be classified in this category solely on the basis of 

40 limited evidence of carcinogenicity in humans. An agent may be assigned to Ibis categmy 

41 if it clearly belongs, based on mechanistic considerations, to a class of agents for which 

42 one or more members have been classified in Group 1 or Group 2A. 
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PREAMBLE 23 

Group 2B: The agent is posdbly carcinogenic to humans. 

2 This category is used for agents for which there is limited evidence of carcinogenicity 

3 in humans and less than sufficient evidence of carcinogenicity in experimental animals. It 

4 may also be used when there is inadequate evidence of carcinogenicity in humans but 

5 there is sufficient evidence of carcinogenicity in experimental animals. In some instances, 

6 an agent for which there is inadequate evidence of carcinogenicity in humans and less 

7 than sufficient evidence of carcinogenicity in experimental animals together with 

8 supporting evidence from mechanistic and other relevant data may be placed in this 

9 group. An agent may be classified in this category solely on the basis of strong evidence 

10 from mechanistic and other relevant data. 

11 Group3: The agent is not classifiable as to its carcinogenicity to humans. 

12 

13 

14 

15 

16 

17 

18 

19 

20 

21 

22 

23 

24 

25 

26 

27 

28 

29 

30 

31 

32 

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34 

35 

36 

37 

38 

39 

40 

41 

42 

43 

44 

This category is used most. commonly for agents for which the evidence of 

carcinogenicity is inadequate in humans and inadequate or limited in experimental 

animals. 

Exceptionally, agents for which the evidence of carcinogenicity is inadequate in 

humans but suffzcient in experimental animals may be placed in this category when there 

is strong evidence that the mechanism of carcinogenicity in experimental animals does 

not operate in humans. 

Agents that do not fall into any other group are also placed in this category. 

An evaluation in Group 3 is not a determination of non-carcinogenicity or overall 

safety. It often means that further research is needed, especially when exposures are 

widespread or the cancer data are consistent with differing interpretations. 

GJ'oup4: The agent is pl'Obably not carcinogenic to humans. 

This category is used for agents for which there is evidence suggesting lack of 

carcinogenicity in humans and in experimental animals. In some instances, agents for 

which there is inadequate evidence of carcinogenicity in humans but evidence snggesting 

lack of carcinogenicity in experimental animals, consistently and strongly supported by a 

broad range of mechanistic and other relevant data, may be classified in this group. 

(e) Rationale 

The reasoning that the Working Group used to reach its evaluation is presented and 

discussed. This section integrates the major findings from studies of cancer in humans, 

studies of cancer in experimental animals, and mechanistic and other relevant data. It 

includes concise statements of the principalline(s) of argument that emerged, the conclusions 

of the Working Group on the strength of the evidence for each group of studies, citations to 

indicate which studies were pivotal to these conclusions, and an explanation of the reasoning 

of the Working Group in weighing data and making evaluations. When there are significant 

differences of scientific interpretation among Working Group Members, a brief summary of 

the alternative interpretations is provided, together with their scientific rationale and an 

indication of the relative degree of support for each alternative. 

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18 Shennan, C.D., Portier, C.J. & Kopp-Schneider, A. ( 1994) Multistage models of carcinogenesis: an 

19 approximation for the size and number distribution oflate-stage clones. Risk Anal., 14(6), 1039~1048 

20 Stewa~ B.W. & Kleihues, P., eds (2003) World Cancer Report, Lyon, !ARC 

21 Tomatis, L., Aitio, A, Wilbourn, J. & Shuker, L. (1989) Human carcinogens so far identified. Jp11. J. Cancer 

22 Res., 80,795-807 

23 Toniolo, P., Boffetta, P., Shuker, D.E.G., Rothman, N., Hulka, B. & Pearce, N., eds (1997) Application of 

24 Biomarkers in Cancer Epidemiology (!ARC Scientific Publications No. 142), Lyon, !ARC 

25 Vainio, H., Magee, P., McGregor, D. & McMichael, A., eds (1992) Mechanisms of Carcinogenesis in Risk 

26 Identification (!ARC Scientific Publications No. 116), Lyon, !ARC 

27 Vainio, H., Wilboum, J.D., Sasco, A.J., Partensky, C., Gaudin, N., Heseltine, E. & Eragne, I. (1995) 

28 [Identification of human carcinogenic risk in TARC Monogt'aphs.] Bull. Cancer, 82, 339-348 (in French) 

29 Vineis, P., Malats, N., Lang, M., d'Errico, A., Caporaso, N., Cuzick, J. & Boffetta, P., eds (1999) Metabolic 

30 Polymorpllisms and Susceptibility to Cancer (!ARC Scientific Publications No. 148), Lyon, !ARC 

31 Wilbourn, J., Haroun, L., Heseltine, E., Kaldor, J., Partensky, C. & Vainio, H. {1986) Response of experimental 

32 animals to human carcinogens: an analysis based upon the !ARC Monographs Programme. Carcinogenesis, 

33 7, 1853-1863 

34 
200 

LETTER FROM UN SPECIAL RAPPORTEUR

PAI.AIS OilS NA11DNS • 1211 a•NHVA 10, SWtrZERlANO. 

www,obt:br..orll• 1F.l..: -t"l22'9l7"9000•1:Ax~ NI22IJ179008• F.·MA.fl: rctifs1Q'QI)olt¢1U".IN'8 

Mandate of the Specialltnpporteur on the Implications for lmmnn rights of the imvironmeutally 

sound management and disposal of hazardous substances nnd wastes 

RGFERBNC'E; SPMJU!l;MQIR 

29 January 2018 

Dear Sirs, 

1 have the honor to address you in my capacity as Special Rappti1teur on the 

implications for human rights of the environmentally sound management and disposal 

ofhnzardous substances and wastes, pursu.ant to Human Rights Council resolution 

36/15. I write in reference to your letter Of 17 January 2018 addressed to the Inspector 

Geneml and the Acting Secretary of the U.S. Department of Health & Human Services.1 

In this letter, you infonn that the Congressional Committee on Science, Space 

and Technology is conducting oversight of the activity of Dr. Linda Bimbaum, director 

of the U.S. National Institute of Environmental Health Sciences (NIBHS). The oversight 

relates to an article co-authored by Dr. Birnbaum and Dr. Liza Gross, in the scientific 

journal PLOS Biology, a highly selective peer-revieWed publication. You indicated 

your suspicion that Dr. Birnbamn might have violated the U.S. Anti-Lobbying Act by 

encouraging citizens "to petition the Government to make ce1tain poli~;y decisions." The 

letter underlines this statement: "Closing tho gap between evidence and policy will 

require that engaged citizens, both scientists and nonscientists, work to ensure our 

government officials pass health-protective poliCies based on the best available 

scientific evidence," 

In this regard, I would like to take this opportunity to express my deep concern 

regarding what I believe may be an attempt to intimidate a highly respected scientist for 

her contribution to a scientific journal. The article in question contained no sped fie . 

policy guidance that could suggest lobbying or any signal of conflict of interest. Ratller, 

it simply insisted on the need for policies and norms to be fully grounded in the best 

possible scientific evidence, and for the public to engage in debates regarding how the 

U.S. Government fultllls its obligation to protect the public from exposures to toxic 

chemicals, pollution and other hazardous substances. 

Encouraging citizen engagement, as done by Drs. Bimbaum and Gross, does not 

articulate a "certain" policy outcome. Rather, it promotes fundamental human rights, 

1 Availa!:>le at http://bit.ly/2E5qRnS and http://hit.ly/2G!Dk6E 

The Honorable Lamar Smith 

U.S. House of Representatives 

Chaim1an of the U.S. House Committee on Science, Space and Techno.logy 

The Honorable Andy Biggs 

U.S. House of Representatives 

Chairman of the U.S. House Sub-Committee on Environment 
201 

PAGEl 

including the right to take part in the conduct of public affairs, which the United States 

of America has recognized. Public participation is core component of democracy, and 

central to environmental governance. Indivisible from the right to participation is the 

right to information and freedom of expression, which Drs. Birnbaum and Gross 

promote and exercise in their article. 

Last year, I reported to the U.N. Hl.!man Rights Council that '!the ability to 

protect the human rights to life and to health [from hazardous substances] and.to realize 

the right to the benefits of sdentific progress and its applications hinges upon the ability 

to translate evidence into protective laws and policies."2 I noted that extreme delays in 

the translation of evidence of hazard and risk into protective measures have banned the 

public, drawing on well-documented examples from the United States of America. I 

emphasize to you that State's duty to protect the rights to life, health and physical 

integrity from toxic and otherwise hazardous substances must be reflected in the 

adoption, implementation and enforcement of adequate Jaws and policies regarding such 

substances. 3 

The work ofNlEHS is essential to protecting human rights, including the rights 

of children, who are arguably the most at risk of health impacts n:om exposure to toxic 

chemicals and pollution. ln 2016, I reported to the U.N. Human Rights Council on the 

urgent need of all States to better protect children from exposure to pollution and toxic 

chemicals. 4 The gap between what is required under international human tights law, and 

the protections afforded by_ Governments based on current scientific knowledge 

continues to diverge. And, race and poverty continues to be major factor in the 

disproportionate levels of exposure by children of color and low-income communities. 

I encourage you and your Congressional colleagues to explore opportunities to 

support the crucial work ofNIEHS in advancing human rights. Ensuring laws and 

policies adequately protect everyone-lich or poor, young or old-from exposure to 

h!)Zardous substances an obligation of States, which flows naturally from international 

human rights law. 5 While the United States of America remains the only country in the 

world that is not Party to the U.N. Convention on the Rights ofthe Chlld, it is a 

signatory and thus obligated not to defeat its object and purpose. 

l A/HRC/36/41 available at: 

http://www.ohcbr.org/EN/Issues!Environment/ToxicWastes/Pnges/Annual.aspx 

3 I note two ongoing cas~ of delayed implementation ofU.S. toxic chemical laws 

https://eaJ.1hjustice.orglsites/defaultlfiles/f1.1es/Pet%20for"/o20Rev·Prioritization%20Rule.pdf 

and bttps://earthjustice.org/sites/default/files/files/Peto/o20for%20RevRisk%20Eval%20Rule.pdf 

4 A/HRC/33/41 available at: 

http://www.ohcbr.org/EN/Issues!Environment!foxicWastes/Pages!Annual.aspx 

~ See e.g. human rights to life and to the highest attainable standard of health, which are 

enshrined at the Universal Declaration of Human Rights (respectively articles 3 for and 2S), and 

further developed by the U.N. Convention on the Right of the Child (respectively articles 6 and 

24). 
202 

Considering the public relevance Of this debate and its direct relation to the work 

I conduct as a ·special Rapporteur, I have decided to send this open letter in a spirit of 

cooperation. The letter will be posted ill the w~bpage of the mandate. 

I remain at your disposal to further discuss the reasons for the concerns stated in 

this letter and my work on the implications for human rights ofthe environmentally 

sound management and disposal ofhaz<lL'dous substances and wastes. 

Please accept, dear Sirs, the assurances of my highest consideration. 

BaskufTw1cak 

Special Rapporteur on the implications for human rights of the cnvirorunentully sound 

management and disposal of hazardous substances and wastes 

cc: Hon. E: D. Hargan, Acting Director, U.S. Dept. of Health and Human Services 

Hon. D. R. Levinson, Inspector General, U.S. Dept. of Health and Human Services 

Hon. E. Bcmice Johnson, Ranking Member, U.S. House Committee on Science, 

Space and Technology 

Han. P. D. Ryan Jr., Speaker of the U.S. House of Representatives 
203 

LIST OF PARTICIPANTS IN GLYPHOSATE PROGRAM

IARC Mo11og1'aplts 011 tlte Evaluatio11 ofCarci11ogmic Risks to HumaM 

VOLUME 112: SOME ORGANOPHOSPHATE INSECTICIDES AND HERBICIDES: 

DIAZINON, GLYPHOSATE, MALATHION, PARATHION, AND TETRACHLORVINPHOS 

Lyon, F•·ance: 3-10 March 2015 

LIST OF PARTICIPANTS 

Working Group Members and Invited Specialists served in their individual 

capacities as scientists and not as representatives of their government or any 

organization with which they ,are affiliated. Affiliations are provided for 

identification purposes only. 

Members 

Isabelle Baldi, University of Bordeaux, France 

Aaron Blair, National Cancer Institute, USA [retired] (Overall Chair) 

Gloria M. Calaf, Tarapaca University, Chile 

Peter P. Egeghy, U.S. Environmental Protection Agency, USA1 (Unable to attend) 

Francesco Forastiere, Regional Health Service of the Lazio Region, Italy (Subgroup Chair, 

Cancer in Humans) 

Lin Fritschi, Curtin University, Australia (Subgroup Chair, Exposure) 

Gloria D. Jahnke, National Institute ofthe Environmental Health Sciences, USA 

Charles W. Jameson, CWJ Consulting, LLC, USA (Subgroup Chair, Cancer in Experimental 

Animals) 

Hans Kromhout, Utrecht University, The Netherlands 

Frank Le Cmieux, European Chemicals Agency, Finland 

Matthew T. Martin, U.S. Environmental Protection Agency, USA 

John McLaughlin, University of Toronto, Canada 

Teresa Rodriguez, National Autonomous University of Nicaragua, Nicaragua (Unable to 

attend) 

Matthew K. Ross, Mississippi State University, USA 

Ivan I. Rusyn, Texas A&M University, USA (Subgroup Chair, Mechanisms) 

Consolata Maria Sergi, University of Alberta, Canada 

Andrea 't Mannetje, Massey University, New Zealand 

Lauren Zeise, Califomia Environmental Protection Agency, USA 

Invited Specialists 

Christopher J. Portier, Agency for Toxic Substances and Disease Registry, USA [retiredf 

1 Peter P Egeghy received "in kind" support and reimbursement of travel expenses of on average less than 

US $2.000 per year dul'ing the last 4 years from participation in meetings sponsored by the American 

Chemistry Council, an industry trade association for American chemical companies, and the Health and 

Environmental Sciences Institue (HEST), a nonprofit scientific research organization based in Washington 

and funded by corporate sponsors. 

2 Christopher J P01tier receives a part-time sala1y from the Environmental Defense Fund, a United Statesbased nonprofit environmental advocacy group. 
204 

IARC Monographs on t/.e Evaluation of Carcinogenic Risks to Humans 

VOLUME ll:Z: SOME ORGANOPHOSPHATE INSECTICIDES AND HERBICIDES: 

DIAZINON, GLYPHOSATE, MALATHION, PARATHlON, AND TETRACHLORVINPHOS 

Lyon, France: 3-10 March 2015 

Representatives of national and international health agencies 

Amira Ben Amara, National Agency for Sanitary and Environmental Product Control, 

Tunisia (Unable to attend) 

Catherine Eiden, U.S. Envit·onmental Protection Agency, USA (Unable to attend) 

Marie-Estelle Gouze, for the French Agency for Food, Environment and Occupational Health 

and Safety, France 

Jesudosh Rowland, U.S. Environmental Protection Agency, USA 

Observers 

Mette Kirstine Boye Jensen, for Cheminova NS, Denmark3 

Bean·ice Fervers, for the Leon Berard Centre, France 

Elodie Giroux, University Jean-Moulin Lyon 3, France 

Thomas Sorahan, for Monsanto Company, USA 4 

Christian Strupp, for the European Crop Protection Association, Belgium5 

Patrice Sutton, for the University of Califomia, San Francisco, Program on Reproductive 6 ' Health and the Environment, USA 

IARC secretariat 

Lamia Benbrahim-Tallaa, Section of !ARC Monographs 

Rafael Carel, Visiting Scientist, University of Haifa, Israel, Section of !ARC Monographs 

Fatiha El Ghissassi, Section of !ARC Monographs 

Sonia EI-Zaemey, Section of the Environment and Radiation 

Yann Grosse, Section of !ARC Monographs 

Neela Guha, Section of !ARC Monographs 

Kathryn Guyton, Section of /ARC Monographs (Responsible Officer) 

Charlotte Le Cornet, Section of the Environment and Radiation 

Maria Leon Roux, Section ofthe Environment and Radiation 

3 Mette Kristine Boye Kristensen is employed by Cheminova AJS, Denmark, a global company 

developing, producing and marketing crop protection products. 

4 Tom Sorahan is a member of the European Glyphosphate Toxicology Advisory Panel, and received 

reimbursement of travel cost from Monsanto to attend EuroTox 2012. 

6 Christian Strupp is employed by ADAMA Agricultural Solutions Ltd, Israel, a producer ofDi11zinone 

and Glyphosphate. 

6 Patrice Sutton's attendance of this Monographs meeting is supported by the Clarence E. Heller Charitable 

Fo1mdation, 11 philanthropic charity with 11 mission to protect and improve the quality of life through 

support of pl'ograms in the environment, human health, education and the arts. 
205 

!ARC Monographs on the Evaluation of Carcinogenic Risks to Humans 

VOLUME 112: SOME ORGANOPHOSPHATE INSECTICIDES AND HERBICIDES: 

DIAZINON, GLYPHOSATE, MALATHION, PARATHION, AND TETRACHLORVINPHOS 

Lyon, France: 3-10 March 2015 

Dana Loomis, Section of IARC Monographs 

Heidi Mattock, Section of IARC Monographs (Editor) 

Chiara Scoccianti, Section of !ARC Monographs 

Andy Shapiro, Visiting Scientist, Section of !ARC Monographs 

Kurt Strait; Section of IARC Monographs (Section Head) 

Jiri Zavadil, Section of Mechanisms of Carcinogenesis 

NOTE REGARDING CONFLICfS OF INTERESTS: Each participant submitted WHO's 

Declaration of Interests, which covers employment and consulting activities, individual 

and institutional research support, and other financial interests. Participants identified as 

Invited Specialists did not serve as meeting chair or subgroup chair, draft text that pertains 

to the description or interpretation of cancer data, or participate in the evaluations. The 

Declarations were updated and reviewed again at the opening of the meeting. 

NOTE REGARDING OBSERVERS: Each Observer agreed to respect the Guidelines for 

Observers at IARC Monographs meetings. Observers did not serve as meeting chair or 

subgroup chair, draft any part of a Monograph, or participate in the evaluations. They also 

agreed not to contact participants before the meeting, not to lobby them at any time, not to 

send them written materials, and not to offer them meals or other favours. IARC asked 

and reminded Working Group Members to report any contact or attempt to influence that 

they may have encountered, either before or during the meeting. 

Posted on26 January 2015, updated 19 October 2016 
206 

MONSANTO’S IARC BATTLE PLAN

Monsanto's IARC Battle Plan 

The two documents attached have been referred to jointly by the 

media as Monsanto's IARC Battle Plan. Monsanto, based on the 

publicly available scientific evidence, assumed that glyphosate 

would receive a ''possible'' (2B Classification) or ''probable" 

(2A Classification) rating from IARC. On March 20, 2015, 

IARC released its Glyphosate Monograph labelling the chemical 

"probably carcinogenic to humans," a· class 2A rating. 

The first document was produced on February 23, 2015 and 

outlines· various tasks to combat the upcoming release of the· 

IARC Monograph on Glyphosate. 

The second document is dated February 17, 2015 and is titled: 

HPreparedness and Engagement Plan for !ARC Carcinogen 

Rating of Glyphosate. "It provides a list for Pre~IARC and PostIARC activities coordinated by Monsanto for the chemical 

industry, non-profit gi'oups widely repmted to be front groups 

for industry, and other third;..party experts to combat the IARC 

rating for Glyphosate. Notably, the documents suggest a social 

media campaign against IARC through Facebook, Twitter and 

third-party expert blogs, op-eds, links, tweets and retweets. 

These documents made available through litigation against 

Monsanto regarding its glyphosate-containing herbicide 

Roundup provide a window on the tactics used to combat 

scientific evidence that is unfavorable to glyphosate. 1 

1 The two documentll att~ched we1·e obtained via th~ law firm ofBaum Hedlund Aristei Goldmllll and can be found 

here: 

~ 

http:/lbawnhedlundlaw.com{pdf/monsanlo·documents02-Document-De!ajls-Monsantas-Goa)s-After-1AR:C- . 
207 

Draft Feb 23, 2015 

The lnternatiDnal Agency tor Researcb on Canc.er(IARCJ, part of the World Health Organization, coordlnllte$ -and 

conducts bolh eplde.mloJoe;lcaland laboratory research Into the cau~ of human carteer. Jt abo evaluates the 

cardnogenlc potential of lndMdual substances based only on publfcl\f' aval'lable lnl'otmatton. White glyphosate has 

been a low prlodtyfor evaluation by !ARC for more than two decades, It was nomlnaled for rcvTew .I!!.. mid· 

tl!!l1.2014. 

AlterlearnJngoftha M~~klttion ofplypbMl)tq.form1QWfn September, the regulatoryteam'slnmal 

f«lH Wlll:spubllshllls safety studies tlmt were not yet in the public dornaln. All re:seuch had to be publ!shedJtt 

.i!.ru2lm.f2!~qo by Feb. 3, 2015 to be considered In the ha5 shared lhe$e 

ret:cnt publlcatlonswith !AR~ ar\d Is continuing to share d!recttywltfl 

"TI'Ie lnternatlo-m!Ageney for Reseuch on Cancer 

(!ARC) ls th.espectaUted cancer agency ofth~ World 

HealthOrganlzatloo" 

Monsanto Companyconndentlal · Page f PAGE J of ( NUMPAGES J 

Con!ldenllal· ProdUced Subject to Protective order MONGLY02913526 
208 

Draft Feb 2a, 2015 

Monsanto Companvconfldentlal Page{ PAGE} of( NUMPAGES J 

ConfldenUal· Produced Subject to Protective Order MONGLY02913527 
209 

Prell Feb 23,2016 

Glyphosate: IARC 

~-·---- ·s,.-h.,-,-=~M=m-:-:..,c:,-::g.,:-:-(IWI=to-t,-,-,,-E:.,C""'oe;;ff;'~C't~"'~,..,<l"'ve--l"Klm=u'"nk"----lf------ Fac.ebo~lc} gl content Heather McClurg 

Prepare key Man.sartto fnsure strons, FH 

spokespeople eonslstentMON KellyCiauss 

mtss~ng 

Communlu.te to emp!oylfl. 

Yl:aHcmallandconne.:tlon 

arlll;le 

Post-Dec!don/Postlfl 

WcakofMer.ch lmplementaUonofCri$IS 

f·U Plan,asnecwar)' 

Marth 10 Outreadl to key stakeholders 

(ut!Hzed!scusslongukle} 

Ra!seaware11eSS 

andlnor;ulate 

el'llployees 

::a.,,.,ff., MarchlD Outreach to grower groups Kim Magln 

{lltiiJUI:d!scu.sslongulde-, IAcollcagues 

~~-------1~~7.~=!=~~k~~.~~=~g~~~Kn~WPOO~In~UL_4H 'o~m~k=nukiM~--~------~ 

@Posting 

@)Postlng 

@Posting 

@Posting 

regu!ator:s of daclslonj gain Regional Rt\ 

ad!veStJ.PPOrt 

Publish I amplifY blog past on 

the meaning of the IA.RC 

ruRng 

AddlARCstaternenttoweb 

Publish ConnocUon arl)da for 

em loyees 

OUtreacll tollg med!a 

Ensure MON POV 

/neutrallteSM 

Ensurl'!. MON POV 

I neottt~llze: SM 

EnsureMONPOV 

KlrnUnk 

Cllaflal-ord 

Heatt!erMe.ct_urg . 

Kye!Ricbard 

JaclynPo!lnow 

E11sure MON POV John Combe~t 

In coverage 

See Attachment A: CommUI'Ilcatkm.s Plan 

~RNAl (Giypbosata tsnot cardnogenlc) 

@EPA concluded tn 2-013 that "'gfyphosate does Mt ~e a Catl(er risk to humans"' ( HYPERLINJ< 

"hllp:l/.vwtt.ro9u!'"lons.govf' ~ "ldocumantDelaii;D=EPA-HQ-OPP-2012-0132-000!1' 1 (§I EPA groups gJypbosate In the lowed category f 1 lndicatlng:gfVphosate does not: pose b cancer rfsk to 

h!lmansll!trul/.mw!.eiH!.ggy/opp:srrd1fweeWrat!on/6EDslfuct$l)(!ts/0178fncl: pdf 

• FA0..117 Dllet giyphosatecausacancer?[ HYPERUNK 

"htlp:llwww.monsanto.comlglyphosate/pageWglyphosate~frequently..asked-que&tlona.aspx~ \1 

• ~~~;::!nder Glyphosate: No evidence of~arclnogentcit){L f1XP§B.~!~!5.-"" ~--- ---~-~ ..,. .... ~·f~;;;ijk7j~~f.i;;~ihlk!s~n"Xed'~~-.. ) 

*hllp:/IW\WI.monsanto.com/gtyphosate/Doc:wnents/no·CVidOnce:of-oareTnogan!O'ify':pdf'] 

OJseover.tom { HYPERUNK "h1tp://d~ver.rnonsanto.comfconvarsatlonlqll(l~tlonhlr&·yoU·ready. 

to-be-hald-areountab!e·for·the-many-dlsea!les'-wh!OO-ara·oaussd-by-your-po!~orw;uch-as-leaky. 

aut-svndrome-and-eancef'1 

Monsanto Company Conlide:nUal ,Page-{PAGE]Ilf(NUMPAGES) 

Confidenllal· Produced Subject to Protective Order MONGL Y02913528 
210 

Dran Feb 23, 2016 

MoiUanto compa.nyconOdentlal Page{PACE}of(NUMPAGES) 

Confldenllal· Produced Subject to Protective Order MONGLY02913529 
211 

Draft Fab 23, 2015 

ATTAtKMENT A; PREPAREDNESS AND ENGAGEMENT PLAN 

FORfARCCARONOGEN RA.TIN:G OF GLYPHOSATE . 

last flpdoled: Februol)l J.l,. 2025 

OBJECliVES FOR PREPAREDNES.S& ENGAGEMENT 

· • Protect the reputation ai'ICII<TO of Roundup by communicating the safety Of glyphasatt! 

Amplify .s~l~:~.nce><~'!d Information to prevel1t unfounded clalms from becomtnB popular oplnluh 

• rrovkle cover for r.egl.llatoryagentles tG continue making re-regl.stratlon decisions based on stlen<:e 

Regulators 

• Stakeholders. 

Farm.erCIJ:Itomers 

STRA1EG1ES/TACHCS 

'1. Amplification of Sclllntlftc Studies 

Support the de>Riopmerrt of three. nQW papers cut efyphosate fociJsed on epldemto!OfiVilMd toldcology 

Work with 1\PSA ahdStrattgtc Communi~Utll'l$ to amplifY eJotlstlng studiE!s and new paper~ 

o. AUthors work directly with sc1entlne:Jaurnals to Issue fll"-fh and news releases o" new bod!e.s of work 

o RPSA poots blog from fft.st-p.e.f$0n vlewpoW. of MO/"Isanto's Davfd S<~ltmlras, to-author of-one ofthe 

glypho,sate tanoor papors , -

o .share resou(c.I!.S Sr'ld content with Monsanto key regions to amplify the message globally 

2, Inform f lnocu!ahl/ !ngase Industry r>artners . 

• D~!!lop a "toolkit" contalntng kay Information and resource.~: -

o ldentll'y any messngeshortcomlngs and address through updiltl:!s to 1'1\0I"Isanto.corn.fglyphosate and 

through US11nd EU blogposts 

• Work w!th RPSA, Stakeholder Outleac:;fl T~r.~.tn 1ndusby Affairs, Gcrvemment Affa1rs, US Dus.!rw.ss .. Global 

CE and ftegu!atOJYtearw:, ell:, to engage Industry partners 

o l!!r.1;. crop Ufe International f Euro~n Crop Protactlon Assodatlotl / GMO An$wen/ BIDldentlfycommlttees that are ~t to eng;tgl!! 

o :!.!!!li. Andernlcs (AgBJothatter), Blofortlfled.. Seru:e About Sdence, Genetic Literacy Projeet, 

Acadernks Review 

n Il!!.fu Alert (ood companies via S!Bkeh.okfer£ngagemoot ttl am (IFICJ GMA. Cfl) for -cnoculatJon 

strategv'' to pn:rVldlili early educatfon on slypho.sate resldua leveb,. describe scle.nce-based studlet 

versus agenda-driven hy-potheses 

o ~lnoallatekevgro~erass1'K.kl.t~ 

3. Addrsss New AI!Wtlon3 

• Respond qulc:;kly and pubJ!ca.l!y tQ new PlE!Udosele!'cet=onter !!tudfes 

• Jd~>ntlfy f request tll!rd~party experts to blog, op/ed, tweetan.d/ar !Ink, repos-t retw.eet etc, 

EQSN{!Bf 

4. Orduii.Jttnta Outcry wfti11AnC Paclslon .. March 10,2015 

tt\tfustry-conduets robust media I saclal ml!dla autreach an process and outcome 

o ISenseAboutSeiefl.te?} leads Industry re3pan5e and pravldes pfatform for IARC observer~ lWld 

indUS"tr'{spo~$person 

o CU and othal' aS:Saclntlons l:s.soe press releases 

Monsanto Company Confithmtlal PagetMGE:]of[NUMPAGES I 

Confldenllel • Produced Subject to Protective Order MONGL Y02~13530 
212 

Draft Feb 23, 2015 

o lolnt Glyphmate Task£orce publlshes press release1 li!ltC!t ,~:)fined bylooders of each manufacturerln 

North Amertca and Europea Push opinion leadElrle:ttcr to key dallynewsp!lpt!r on cfay of !ARC rulfng wllh assi10tmce: of Potomilt 

Gr()Up 

• Monsanto raspoodswfth:rtron,s reactlvestatemel\t o Distribute video and audlo responses: t<11AA.C deelslon 

o Addmss madla Jnqulrlcls with oampanyglyphotalbJpokesperson 

o UtOI:.l:e. M011santo cha,nnels (web, FB. Twltter1 blog, etc) to provklo Mcnsant.o POV 

o Cotpolilte Ensagement team patka11es Industry and Monsanto responsas1 then dlstrfbtJtes via em aU 

to "'2.0 most !nrluentlal ag medla outlets au ass print, radio and TV 

5. !ngaifa ll:asulstoJy Agendu 

• Growet assoclatlons/ growers write resufators w!th an appeal thtit thev remain focused on tile sdel'!c~ 

.not the poUUcallythai'B9d declston by !ARC 

Monsanto Company Con0rlent1111 Paae (PAGE j of[ NUMPAGES J 

Confidential- Produced Subject to Protective Order MONGLY02913531 
213 

ARTICLE SUBMITTED BY REPRESENTATIVE JERRY MCNERNEY

Reply-To: POLITICO subscriptions <replyfe8b137376620c7a77-11634 73 HTML-637934647-13763l9-

0@politicoemail.com> 

By Simon Marks. 

02/06/2018 08:24AM EDT 

The European Parliament today agreed to create a special 

committee to investigate potential failings in the ED's system for 

renewing pesticides such as glyphosate. 

Approved during a plenary session in Strasbourg, the committee 

will present recommendations to the European Commission on 

how to change EU law to ensure that the science used to prove a 

substance's safety is not aligned too closely with industry. The 

move comes after the U.S. agri-giant Monsanto was accused last 

year by activists and lawmakers of undue influence over the 

scientific literature that went into proving the safety of 

glyphosate, the active ingredient in its Roundup herbicide. 

Policymakers are also looking at the possibility ofcreating a 

special fund - financed by industry but run by the European 

Food Safety Authority- in order to increase the independence 

of scientific research on the safety of pesticide substances. 

The committee will investigate conflicts of interest "at all 

levels" and look at whether the Commission followed 

regulations when making the decision to renew glyphosate's 

license for another five years. 

This article first appeared on POLJTICO.EU on Feb. 6, 2018. 
214 

DOCUMENTS SUBMITTED BY REPRESENTATIVE DONALD S. BEYER, JR. 

APAMT POSTER GERONA) 
215 

HRI GLYPHOSATE STUDY SUMMARY RESULTS

a W/ Health Research Institute 

Laboratories 

February 2, 2018 

The Honorable DonaldS. Beyer, Jr. 

Ranking Member 

Subcommittee on Oversight 

Committee on Science, Space & Technology 

Dear Representative Beyer, 

Health Research Institute is collaborating with researchers at the University of California San Diego to 

measure human environmental exposure to glyphosate. We test urine samples provided by participants 

using LC/MS instrumentation, the gold standard in analytical chemistry. 

Our analytical capacities are routinely evaluated by a third-party, in de pendent proficiency testing program 

We passed the most recent proficiency test with a high degree of accuracy. 

We plan to submit the results of our glyphosate environmental exposure study for peer-reviewed 

publication later this year. Results, to date, that you may find of interest include: 

1078 people have been tested, from October 2016 to today. 

923 people (86%) had detectable levels of glyphosate. 

155 people (14%) had no detectable levels relative to our limit of detection of 0.03 parts per billion. 

The average level of glyphosate in the urine of study participants is 0.46 parts per billion. 

The top 10 percentile had an average of 2.74 parts per billion. 

The levels in North Americans tested in the study are 120% higherthan levels found in a similar 

study in Europe (Hoppe, 2013). 

People who consume non-organic oats had twice the glyphosate levels as those who do not. This 

may be due to the agricultural practice of desiccation, or drying, of the oat crop with glyphosate 

prior to harvest. 

People who consume the most organic foods have one quarter the glyphosate levels as those who 

consume the least organic foods. 

P.O. Box 370 • Fairfield, lA 52556 

www.HRILabs.org 

641-552-6258 
216 

The Honorable Donald S. Beyer, Jr. 

February, 2, 2018 

Page 2 of 2 

People who consume the most vegetables per day have half the glyphosate levels as those who 

consume the least vegetables. 

People who consume the most meals outside of their homes had the same glyphosate levels as 

those who consume most of their meals at home. 

People who use glyphosate on their yards or farms have 80% higher glyphosate levels than those 

who do not use glyphosate. 

We hope you find these statistics helpful. Please let us know if you have any questions. 

Sincerely, 

John Fagan, PhD 

Chief Scientist 
217 

GLYPHOSATE TEST RESULTS

Health Research Institute 

Laboratories 

Specimen Type: urine 

Client: Don Beyer 

Authorized Person: Don Beyer 

Sample. Weight I Volume: 30 ml 

Residue: 

Glyphosate 

AMPA 

Effective Glyphosate Level 

Glyphosate 

AMPA 

level: Units: 

0.31 ppb (ng/ml) 

Trace ppb (ng/ml) 

0.31 ppb (ng/mL) 

LOQ = 0.25 ppb, LOD = 0.03 ppb 

LOQ = 0.25 ppb, LOD = 0.04 ppb 

Report Number 

Report Date 

50002386- 20180202 

2018-02-02 

HRI Labs Sample No.: 50002386 

Receipt Date: 2018-(]2-01 

Test Date: 2018-02-(]1 

Shipment Temp: Ambient 

Terms: "Trace" is betw-een LOD and LOQ 

"Not Detected" is less than LOD 

Effective Glyphosate level calculated according to Food and Agriculture Organization {FAO) method where 

total glyphosate residue is the sum of the weight of glyphosate + 1.5 x the weight of its metabolite AMPA. 

Effective glyphosate levels above the LOQ are normalized using specific gravity. 

~t:~W) Dr. John Fagan, Chief Scientist 

P.O. Oox 370 

Fairfield, lA 52556 

+1641-552-6258 

CLIA ID #1602122655 

This test was developed and its perform::~nce characterlstics determined by Health Research Institute. lt has not been cleared or approved 

by the US Food and Drug administration (FDA). The FDA has determined that such tle;:~rance or approvals are not necessary. Th[s laboratory 

1:. registered under the Clinical Laboratory Improvement Amendments act of 19$8 (CLIA-88) to pNfo<m high comp!e}(ity dinica! testing. 

This test report is not to be reproduced, ~xccpt in full, without wr-itten approval of the laboratory. 

Pagel of1 
218 

STUDY ON GLYPHOSATE USE EXPOSURE IN HUMANS 2017 

Letters 

RESEARCH LETIER 

Excretion of the Herbicide Glyphosate 

in Older Adults Between 1993 and 2016 

The herbicide Roundup is sprayed onto genetically mod~ 

Hied crops and applied as a desiccant to most small nongenetically modified grains. Use of this herbicide has in~ 

creased since 1994 when genetically modified crops were 

introduced in the United States. Glyphosate, the primary in~ 

gredient in the herbicide, is found in these crops at harvest.1 

Environmentalexposurethroughdietaryintakeofthesecrops 

has potential adverse health effects and can be assessed by 

measuring urinary excretion.2·4 We measured excretion lev~ 

els of glyphosate and its metabolite aminomethylphos~ 

phonic add {AMP A) in participants from the Rancho Bernardo 

Study (RBS) of Healthy Aging. 

Methods I The RBS, established in 1972, is a prospective study 

of 6629 adults older than 50 years residing in Southern 

California. 5 As of 2016, approximately 1000 participants 

were active (the primary reason for loss to follow~up was 

mortality). Of those 1000 participants, 112 had routine morning spot urinary biospecimens obtained at each ofS clinic vis· 

its that took place from 1993 to 1996 and from 2014 to 2016. 

One hundred of these 112 were randomly selected for this 

study, which was approved by the University of California, 

San Diego, institutional review board. AU participants gave 

written infurmed consent. 

Samples were analyzed using high~ performance liquid 

chromatography coupled with mass spectrometry. Limits of 

detection (LOD)were 0.03 pg!L for glyphosate and 0.04 pg!L 

fur AMPA; assays were linear up to SOpg/L.Analyses were nor~ 

malized to each sample's specific gravity, thereby accounting 

Abbrevi~tions: AMPA, amlnomethylphosphonlcadd; LOD, limit of detection. 

" Participants with levels below the LDO had v~l:ues set ~t 0. 

bThe LCD was 0.031Jg/L for glyphosate ~nd 0.041Jg/l for AMPA. 

1610 JAMA October 24/31,2017 Volume 318. Number16 

for dilution or concentration effects due to variability in wa~ 

ter intake and age~related or other differences in renal func~ 

tion. Changes overtime in the proportion ofsamplesabovethe 

LODwere assessed using generalized estimating equation models to account for the dependency of observations in re~ 

pe.ated measures. A 2-sided significance threshold was set 

at less than .OS. Statistical analyses were performed using 

R (R Foundation), version 3.3.2. 

Results I Among the 100 participants in this study, the mean 

age in 2014-2016 was 77.7 years (SD, 6.6} and 60% were 

women. These values were not different from the 112 with 

urine specimens but were older than the entire group of 

1000 active participants in the RBS (mean age, 71.7 years 

[SD, 12.0]) (P < .001). 

The mean glyphosate level increased from 0.024 pg/L 

in 1993-1996 to 0.314 ~g/1 in 2014-2016, and reached 

0;449 Jl!l/L in 2014-2016 for the 70 participants with le,.,ls 

above the LOD (Table 1). Mean AMPA levels increased from 

0.008 pg/L in 1993-1996 to 0.285 pg/L in 2014-2016, and 

reached 0.401 }.lg/L in 2014~2016 for the 71 partidpants with 

levels above the LOD. 

The prevalence rates of glyphosate samples above the 

LOD increased significantly over time, from 0.120 (95% Cl, 

0.064-0.200) in 1993-1996 to 0.700 (95% Cl, 0.600-0.788) 

in 2014-2016 (Wald statistic " 80.5; P < .001) (Table 2). 

The pre,valence of AMPA samples above the LOD increased 

significantly from 0.050 (95% Cl, 0.016-0.113) in 1993-1996 

to 0.710 (95% Cl, 0.611-0.796) in 2014-2016 (Wald statistic = 103; P < .001). 

Discussion l Mean glyphosate and AMPA levels and the pro~ 

portion of samples with detectable levels increased over 

jama.com 

© 2017 American Medical Association. All rights reserved. 

Downloaded From: by a Johns Hopkins University User on 01/2412018 
219 

Table 2. Urinary Excretion Prevalence Rates ofGiyphosate 

and AMPAAmong Rancho Bernardo Study Participants Sampled 

Between 1993 and 2016 

PreviJ;Ience~te{95%CI)a 

Years Gtyphosate AMPA 

1993·1996 0.120 0.050 

,~0:06~·0.200) '(0.016.0.113) 

1999·2000 0.300 -1)~150 

(0:~~~-0-'!00) (0.08_~·-0.23_5~ 

2001·2002 0.430 0.430 {0.331·0.533} (0.331·0.533) 

2004:200s 0.390 0.400 (0.294-0.493) (0.303·0.503) 

2014·2016 0.700 "ii7i0""-'" (0.600·0.788) (0.611-0.796) 

Abbreviation: AMP A. aminomethylphosphonic acid. 

aPvaluewaslessthan.OOl. 

time. A 2015 review ofnonfarmer US and European adults 

reported mean urinary glyphosate levels of 1.35 1-Lg/L and 

0.215 J,lg/L, respectively. 6 The values observed in this study 

fall within this range and were higher than in European 

adults. Animal and human studies suggest that chronic expo· 

sure to glyphosate-based herbicides can induce adverse 

health outcomes.3 Animals consistently fed an ultra-low dos· 

age of the herbicide with a 50-ng/L glyphosate concentration 

show hepatotoxicity consistent with nonalcoholic fatty liver 

disease and its progression to steatohepatosis.4 In July 2017, 

in accordance with the Safe Drinking Water and Toxic 

Enforcement Act of 1986, the state of California listed 

glyphosate as a probable carcinogen. 

Limitations of this study include that the cohort lived in 

Southern California, which might have different exposures than 

other states, only a subset of RBS participants were studied, 

urinary levels represent recent exposure, urinary-specific gravityis reduced with age, and data on clinical outcomes were not 

evaluated. Future studies of the relationships between chronic 

glyphosate exposure and human health are needed. 

Paul J. Mills, PhD 

Izabela Kania»Korwel, PhD 

John Fagan, PhD 

Linda K. McEvoy, PhD 

Gail A. Laughlin, PhD 

Elizabeth Barrett-Connor, MD 

Author Aff"iliatfons! Family Medicine and Public Health. University ofCaHfornla, 

San Diego. La Jolla (Mills. Laughlin); Health Research Institute Laboratories. 

FairfieJd.Jowa(Kania-Korwe!.Fagan);Radio!ogy,Univel'5ityofCalifornia. 

San Diego. La Jolla (McEvoy); Family Medidne. Internal Medicine. and Public 

Health, University of California, San Diego. La Jolla {Barrett-Connor). 

Accepted for Publkatlon: July 31.2017. 

Corresponding Author: Paul J. Mills. PhD, University of California, San Diego, 

9SOO Gilman Dr. La Jolla, CA 92093·0725 (pmills@ucsd.edu). 

Author Contributions: Dr Mills had full access to all of the data in the study 

andtakesresponsibilltyfortheintegrityofthedataandtheaccuracyof 

thedataana!ys.is 

Qll'lO!pt and design: Mills, Laughlin. 

Ar:quisition,analysls,orinterpretationafdata:AIIauthors. 

Droftlf19ofthemanuscript:Mills,Fagan. 

Critical re~isiOfl of the manuscript fodmportant lntellecruol am tent: All authors 

srotistirnlano/ysis:MI!ls.Fagan. 

jamacom 

Obtained funding: Mills, McEvoy, Barrett-Connor. 

Adminlstrotive, technk:ol. D( materia/sUpport: Korwel. Fagan. Laughlin. 

supervision: Mills, Fagan, Barrett-Connor. 

letters 

Conntctoflnterest Disclosures: All authors have completed and submitted the 

!CMJE Form for Disclosure of Potential Conf!;cts of Interest. Dr McEvoy 

reportedreceivinggrantfundingfromtheNatlonal1nstitutesofHealth. 

No other dlsdosures were reported. 

Fundirlg/Support: The RallCho Bernardo Study was funded by grant AA021187 

from the National Institute on Alcohol Abuse and Alcoholism, grantsAG026507 

and AG007181 from the National !n~itute on Aging, and grant 01(31801 from 

the National Institute of Diabetes and Di~stive and l<idney Diseases. 

Additional support for this study was provided by the Solomon Dutk.l Fund 

in the New York Community Trust. !he Caroline Young Foundation, 

andtheWestreichFoundation. 

Role of the Funder/Sponsor: The funders had no role ill the design and 

conductofthestudy;collection,management,analy5is.andinterpretation 

ofthedata;preparation.review,orapproV<!Iofthemanuscript;anddecislon 

tosubmitthemanuscrlptfurpublication. 

1. B"hnT. Cuhra M. Traavik T, Sanden M. fil.&<lnJ, Prlmicerio R. Compositional 

differences in !;Oybeans on the market. Food Chern 2014J53.207-215. 

2. von Soosten D. Meyer U, Hiither L, etaL Excretion pathways 

andruminaldisappearallU!ofglyphosateanditsdegradationp!'oduct 

aminomethylphosphonlc add In dairy cows. J Dairy Sci. 2016;99(7).5318-5324. 

3. Myers JP. Antoniou MN. Blumberg B. eta I. Concerns over use of 

g!yphosate-based herbicides and risks associated with exposures.fnviron Heu/rtr. 

2016.1519. 

4. Mesnage R, Renney G, seralinl GE, Ward M. Antoniou MN. Multiomics reveal 

nonak:ohollcfattyliverdi..easeinratsfol!owlngchronicel(posuretoanultra·low 

doseofRoundupherbicide.SdRep.2017;7.39328. 

5. Barrett-Connor E. The Ranci'm Bernardo Study, Glob Heart. 2013.B(2l. 

6. Niemann l. Sieke C. Ph!il R, Solecki R. A attica! review of glyphosat~ findings 

in human urin~ samples and comparison with the exposure of operators and 

consumers.J Fur Verbrauchersdlutz Leb. 2015;10:3·10. hnps./l!ink.springer.com 

/artide/10.1007/500003-014·0927·3. Accessed Septeml>er 13.2017. 

COMMENT & RESPONSE 

Prediabetes Prevalence in China 

To the Editor Mr Wang and colleagues1 estimated that the overall prevalence of prediabetes was 35.7% among Chinese adults 

in 2013 and concluded that the difference from previous estimates may be due to an alternate method of measuring 

hemoglobin A1c (HbA1c). The previous estimate by Xu et aJ2 in 

2010 was 50.1% (52.1% in men and 48.1% in women). 

However, the study by Wang and colleagues might still 

have overestimated the prevalence of prediabetes in China. 

In a nationally representative sample of 46 239 adults in 

2008, the prevalence of prediabetes was 15.5% (16.1% among 

men and 14.9% among women),3 In contrast, the prevalence 

of diabetes in the 2008 study was 9.8%, which is close to the 

10.2% in the current study, Wang and colleagues used HbA1c 

levels as the criterion for prediabetes. Although the increased 

prediabetes prevalence could be due to improved sensitivity 

of screening with HbA1c measurement, the increase from 

15.5% in 2008 to 35.7% in 2013 is suspect. 

Wang and colleagues used HbA~c levels of5.7% to 6.4% to 

diagnose prediabetes, as recommended in the United States. 

However, this criterion, developed in the US population, has 

not been validated in a Chinese population. In addition, a 

study on the relationship between HbA1c level and the oral 

glucose tolerance test among Chinese adults found that the 

accuracy of HbA1c measurement for detecting diabetes 

JAMA October 24/31,2017 Volume 318, Number 16 1611 

© 2017 American Medical Association. All rights reserved. 

DownloadOO From: by a Johns Hopkins Uni-versity User on 0112412018 
220 

LETTER SUBMITTED BY CHAIRMAN LAMAR SMITH

0 CAIVIPAIG~J FOR /1CCURACY IN 

PUBLIC HEALTH RESEARCH 

OALITION 

The Honorable Lamar Smith 

Chairman 

February 19,2018 

Committee on Science, Space, & Technology 

2409 Rayburn House Office Building 

Washington, DC 20515 

The Honorable Frank D. Lucas 

Vice Chairman 

2405 Rayburn House Office Building 

Washington, DC 20515 

The Honorable Eddie Bernice Johnson 

Ranking Member 

2468 Rayburn House Office Building 

Washington, DC 20515 

Re: House Science, Space, & Technology Committee hearing- "In Defense of Scientific 

Integrity: Examining the IARC Monograph Programme and Glyphosate Review" 

Dear Chairman Smith, Vice Chairman Lucas, and Ranking Member Johnson: 

The Campaign for Accuracy in Public Health Research (CAPHR) Coalition' applauds the House 

Science, Space, & Technology Committee (Committee) for holding a hearing on the 

International Agency for Research on Cancer's (IARC) troubled Monographs Program (or 

Program) on February 6, 2018. The Coalition commends the Committee for acknowledging that 

fundamental changes need to be made to address the Program's flawed scientific approach and 

lack of transparency. The CAPHR Coalition fully supports the Committee's continued oversight 

of the !ARC Monographs Program, especially given ongoing U.S. funding. 2 

We recognize much oflARC' s work makes important contributions to public health. However, 

we have serious concerns with the Monograph Program's processes for gathering and analyzing 

studies, evaluating various lines of evidence, integrating evidence from mechanistic studies 

1 Members of the CAPHR Coalition are: American Chemistry Council, American Petroleum Institute, Chemistry 

Industry Association of Canada, CropLife America, National Association of Manufacturers, Society of Chemical 

Manufacturers & Affiliates, Styrene Information & Research Center, and United States Council for International 

Business. 

2 The l).S. government funds most of the IARC Monographs Program, providing it with approximately $1 million 

each year, which is in addition to the $1.8 million for the U.S.'s !ARC membership contribution and other U.S. 

grants. 

www.caphr.com 
221 

CAMPAICN FOR 1\CCUR!1CY I;'J 

PUBLIC HEALTH RESEARCH 

01\liTION 

including determining human relevance of animal studies, peer engagement, public engagement, 

peer review processes and the practices IARC uses to promote Monograph conclusions. We also 

reinforce the active role the U.S. government plays in promoting sound science and evidencebased policy at home and abroad. In particular, we note the Resolution from the 70th World 

Health Assembly in May 2017 "to enhance the coordination between !ARC and other parts of 

WHO on assessments of hazards and risks, and on the communication of those assessments." 

The CAPHR Coalition advocates for modernizing !ARC's Monographs Program through greater 

transparency and balanced assessments that produce credible conclusions. The Monographs 

Program- which evaluates cancer hazards, not risks- has been criticized by leading scientists 

and regulators for its lack of transparency, frequent conflicts of interest, questionable carcinogen 

classifications, and misleading communications. Additional concerns regarding the Program 

have been raised and reinforced by numerous credible and independent experts, including efforts 

to suppress and omit relevant data and manipulation of outcomes when designating carcinogenic 

classifications. 

Recent announcements from IARC have caused confusion for the general public. !ARC's 

classifications of some substances have contradicted the U.S. government's own findings or have 

resulted in the need for explanatory communications to concerned members of the public. Such 

discrepancies result from !ARC's limited assessment of cancer hazard, unlike the practices of 

most regulators worldwide, including the U.S. Environmental Protection Agency (EPA) that 

conduct thorough risk-based assessments. Due to their focus on hazard assessment, !ARC's 

assessments can also contradict those of other WHO entities- such as the Joint FAO/WHO 

Meeting on Pesticide Residues (JMPR)- further contributing to public confusion. 

The Coalition believes that the six principles for reform delineated below, if implemented, would 

strengthen the integrity of the Monographs Program's processes and ensure that !ARC updates 

the methods and assumptions of the Monographs Program to reflect modem scientific practices, 

rather than the outdated approaches it has relied on since the program was established in 1969. 

The following are the CAPHR Coalition Principles for Reform of the Monographs Program: 

I. Consider a Substance's Risk, Not Just Hazard 

Though !ARC uses the word "risk" in its monograph titles, it does not consider the actual risk of 

developing cancer based on exposure under real world circumstances. Rather, the Monographs 

Program considers only a substance's hazard: whether the substance could cause cancer in 

humans under any circumstances, such as doses and exposure levels far beyond what is typical. 

Unfortunately, this distinction is not widely known or understood, leading to significantly 

misinterpreted conclusions. Instead, the Program's identification of substances as carcinogens 

must no longer ignore the essential elements of dose and exposure. Without this context, 

!ARC's monograph conclusions are of little value in real world settings, and instead create 

www.caphr.com 
222 

CJ\MPAIGf\o FOR l\CCUI\ACY IN 

PUBLIC HEALTH RESEARCH 

COALiliON 

potential adverse consequences in areas including health, safety, and nutrition in both developed 

and developing countries. This context should be provided when !ARC publishes and promotes 

its findings to tbe media and other stakeholders to prevent confusion. 

2, Require Reliance on Weight of Evidence 

Currently, !ARC monographs do not consider the full weight of the scientific evidence. 

Currently, the Program which considers only selected findings, ignores conflicting evidence, and 

fails to fully consider the quality of individual studies. Instead, when making determinations in 

its monographs, the Monographs Program should give the most weight to those studies that are 

of the highest quality and greatest relevance to humans. A weight of the evidence approach 

evaluates each relevant study for its strengths and limitations before its conclusions are used as 

part of the review. 

3. Establish Standard Criteria for Selecting Studies 

!ARC monographs also regularly rely on poor quality studies as the basis of conclusions. To 

remedy this, the Monographs Program should establish clearly defined, transparent criteria for 

assessing the quality and reliability of studies for its monographs. It is currently unclear how the 

Program determines which studies it will consider and which it will disregard. 

4. Increase Transparency, Utilize Input from Stakeholders, and Employ Independent 

Scientific Peer Review 

The !ARC Monographs Program consistently lacks transparency. The Program can address this 

concern by openly engaging with and allowing participation from stakeholders during 

monograph development, including meetings with industry experts. !ARC should clearly 

articulate in its monographs how it considered stakeholder input and provide stakeholders an 

opportunity to comment on a draft monograph. 

Currently, each Monograph is developed by a Working Group comprised of scientists appointed 

by !ARC. The Working Group reviews studies and data, conducts analyses, and then relies on 

their expert opinion to arrive at their conclusions, which are then published. This process, wbich 

may have been permissible in tbe 1960's when the Monograph Program was initiated, allows the 

Working Group to both conduct and review their own scientific work. In 20 I 8, this process does 

not comport with best scientific practices, wherein independent scientific peer review is now a 

fundamental precept of credible and transparent scientific analyses, even for analyses, 

conclusions and reports generated by expert groups, such as those of the U.S. National 

Academies. 3 Therefore !ARC should develop and implement an independent scientific peer 

review process for the Monographs. 

3 http://national~academies.org/studyprocess/index.html#st4 

www.caphr.com 
223 

Æ 

CAfviPAICN FOI? MCUf\1\CY IN 

PUBLIC HEALTH RESEARCH 

Oi'ILITION 

5. Explain Conflicts of Interest 

The IARC Monographs Program has a history of suffering from conflicts of interest. To rectify 

this recuning issue, !ARC should disclose all conflicts of interest among the Monograph 

Program participants and advisors to its working groups, not just those affiliated with industry. 

For example, !ARC has not disclosed instances when its advisors and monograph working group 

members from tbe academic or NGO community may have a personal or professional stake in 

tbe outcome of the monograph. 

6. Improve Monograph Releases 

Currently, !ARC releases a summary of a new monograph immediately after tbe Program makes 

a carcinogenic determination; however, the full monograph with supporting evidence is not 

immediately released and may not be released for years. Rather, !ARC should release all 

monograph information at one time and do away with its current practice of releasing short 

summaries of the Monograph Program's findings months before supporting information is made 

public. !ARC's current publication practice fails to provide the evidence and exposure levels 

used to support its classifications of substances as carcinogenic, causing misunderstanding by 

media and the public. 

In conclusion, !ARC monographs cause significant public confusion, unwarranted marketplace 

de-selection, and regulatory action despite being of questionable relevance, as the monographs 

do not reflect actual risks. Therefore, !ARC must make key improvements to its Monographs 

Program to enhance tbe credibility and utility of its findings and prevent further public 

misunderstanding of its conclusions. 

We appreciate the opportunity to provide comments. If the CAPHR Coalition can provide any 

additional information, please contact Alexa Burr (Alexa Burr@americanchemistry.com or 202-

249-6425). 

Sincerely, 

(J.L. '/~(. 1/U.t ..... 

Alexa Burr 

CAPHR Coalition 

www.caphr.com