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27–173PDF 2017

EXAMINING THE SCIENTIFIC 

AND OPERATIONAL INTEGRITY OF 

EPA’S IRIS PROGRAM 

JOINT HEARING 

BEFORE THE

SUBCOMMITTEE ON ENVIRONMENT & 

SUBCOMMITTEE ON OVERSIGHT 

COMMITTEE ON SCIENCE, SPACE, AND 

TECHNOLOGY 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED FIFTEENTH CONGRESS 

FIRST SESSION 

SEPTEMBER 6, 2017 

Serial No. 115–26 

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 

DRAIN LAHOOD, Illinois 

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 

SUBCOMMITTEE ON ENVIRONMENT

HON. ANDY BIGGS, Arizona, Chair 

DANA ROHRABACHER, California 

BILL POSEY, Florida 

MO BROOKS, Alabama 

RANDY K. WEBER, Texas 

BRIAN BABIN, Texas 

BARRY LOUDERMILK, Georgia 

JIM BANKS, Indiana 

CLAY HIGGINS, Louisiana 

RALPH NORMAN, South Carolina 

LAMAR S. SMITH, Texas 

SUZANNE BONAMICI, Oregon, Ranking 

Member 

COLLEEN HANABUSA, Hawaii 

CHARLIE CRIST, Florida 

EDDIE BERNICE JOHNSON, Texas 

SUBCOMMITTEE ON OVERSIGHT

HON. DRAIN LAHOOD, Illinois, Chair 

BILL POSEY, Florida 

THOMAS MASSIE, Kentucky 

BARRY LOUDERMILK, Georgia 

ROGER W. MARSHALL, Kansas 

CLAY HIGGINS, Louisiana 

RALPH NORMAN, South Carolina 

LAMAR S. SMITH, Texas 

DONALD S. BEYER, Jr., Virginia, Ranking 

Member 

JERRY MCNERNEY, California 

ED PERLMUTTER, Colorado 

EDDIE BERNICE JOHNSON, Texas 
(III) 

C O N T E N T S 

September 6, 2017 

Page 

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

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

Opening Statements 

Statement by Representative Andy Biggs, Chairman, Subcommittee on Environment, Committee on Science, Space, and Technology, U.S. House of 

Representatives .................................................................................................... 4 

Written Statement ............................................................................................

Statement by Representative Suzanne Bonamic, Ranking Member, Subcommittee on Environment, Committee on Science, Space, and Technology, 

U.S. House of Representatives ............................................................................ 8 

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

Statement by Representative Darin LaHood, Chairman, Subcommittee on 

Oversight, Committee on Science, Space, and Technology, U.S. House of 

Representatives .................................................................................................... 12 

Written Statement ............................................................................................ 14 

Statement by Representative Donald Beyer, Ranking Member, Subcommittee 

on Oversight, Committee on Science, Space, and Technology, U.S. House 

of Representatives ................................................................................................ 15 

Written Statement ............................................................................................ 17 

Statement by Representative Eddie Bernice Johnson, Ranking Member, Committee on Science, Space, and Technology, U.S. House of Representatives .... 19 

Written Statement ............................................................................................ 21 

Witnesses: 

Dr. Kenneth Mundt, Principal, Ramboll Environ 

Oral Statement ................................................................................................. 23 

Written Statement ............................................................................................ 26 

Dr. James Bus, Senior Managing Scientist, Exponent 

Oral Statement ................................................................................................. 44 

Written Statement ............................................................................................ 46 

Dr. Thomas Burke, Professor, Bloomberg School of Public Health, Johns 

Hopkins 

Oral Statement ................................................................................................. 50 

Written Statement ............................................................................................ 52 

Discussion ................................................................................................................. 60 

Appendix I: Answers to Post-Hearing Questions 

Dr. Kenneth Mundt, Principal, Ramboll Environ ................................................. 80 

Dr. James Bus, Senior Managing Scientist, Exponent ......................................... 110 

Dr. Thomas Burke, Professor, Bloomberg School of Public Health, Johns 

Hopkins ................................................................................................................. 112 
Page

IV 

Appendix II: Additional Material for the Record 

Documents submitted by Representative Andy Biggs, Chairman, Subcommittee on Environment, Committee on Science, Space, and Technology, 

U.S. House of Representatives ............................................................................ 116 

Documents submitted by Representative Suzanne Bonamic, Ranking Member, 

Subcommittee on Environment, Committee on Science, Space, and Technology, U.S. House of Representatives ............................................................... 121 
(1) 

EXAMINING THE SCIENTIFIC 

AND OPERATIONAL INTEGRITY 

OF EPA’S IRIS PROGRAM 

Wednesday, September 6, 2017 

HOUSE OF REPRESENTATIVES, SUBCOMMITTEE ON ENVIRONMENT AND

SUBCOMMITTEE ON OSVERSIGHT, COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY, Washington, D.C. 

The Subcommittees met, pursuant to call, at 10:04 a.m., in Room 

2318 of the Rayburn House Office Building, Hon. Andy Biggs 

[Chairman of the Subcommittee on Environment] presiding. 
2 

LAMA!l S, SMI fH, fexas 

CHAIRMAN 

<tongrcss of tile 'tinitcd ~tatcs 

illotulc of 1Rcprcscntatiucs COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

2321 RAYBURN HOUSE OFFICE BUILDING 

WASHINGTON, OC 20515-6301 

Subcommittees on Environment and Oversight 

FOD!E BERNICE JOHNSON, '1 ex as 

RANKING MEMSFR 

Examining the Scientific and Operational Integrity of 

EPA's IRIS Program 

Wednesday, September 6, 2017 

10:00 a.m. 

2318 Rayburn House Office Building 

Dr. Kenneth Mundt, Principal, Ramboll Environ 

Dr. James Bus, Senior Managing Scientist, Exponent 

Dr. Thomas Burke, Johns Hopkins University 
3 

U.S. HOUSE OF REPRESENTATIVES 

COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

HEARING CHARTER 

August 31, 2017 

TO: Members, Subcommittee on Environment and Subcommittee on Oversight 

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

SUBJECT: Joint Subcommittee Hearing: "Examining the Scientific and Operational Integrity 

ofEPA's IRIS Program" 

The Subcommittee on Environment and the Subcommittee on Oversight of the 

Committee on Science, Space, and Technology will hold a joint hearing titled Examining the 

Scientific and Operational Integrity of EPA's IRIS Program on Wednesday, September 6, 2017, 

at 10:00 a.m. in Room 2318 ofthe Rayburn House Office Building. 

Hearing Purpose: 

The purpose of this hearing is to examine the U.S. Environmental Protection Agency's 

Integrated Risk Information System (IRIS) program. This hearing will focus on the scientific 

and operational integrity issues as they relate to the functionality and goals of the IRIS program. 

Witness List 

• Dr. Kenneth Mundt, Principal, Ramboll Environ 

• Dr. James Bus, Senior Managing Scientist, Exponent 

• Dr. Thomas Burke, Professor, Bloomberg School of Public Health, Johns Hopkins 

Staff Contact 

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

Chairman BIGGS. Good morning. Welcome to the Subcommittee 

on Environment and Oversight in the House Committee on Science, 

Space, and Technology, our hearing on ‘‘Examining the Scientific 

and Operational Integrity of the EPA’s IRIS Program.’’ 

I’m grateful to be back. Good to see so many back, and I know 

others will be coming, and I hope all of you had a productive work 

period in your districts. 

The Subcommittee on Environment and Oversight will come to 

order. Without objection, the Chair is authorized to declare recesses 

of the Subcommittee at any time. 

Welcome to today’s hearing titled ‘‘Examining the Scientific and 

Operational Integrity of EPA’s IRIS Program.’’ I recognize myself 

for five minutes for an opening statement. 

Welcome to our Subcommittee hearing titled ‘‘Examining the Scientific and Operational Integrity of EPA’s IRIS Program.’’ Today, 

we will hear from witnesses who are experts in the fields of epidemiology and toxicology and learn about their interactions with 

EPA’s IRIS program. The original purpose of IRIS was simply to 

identify and characterize the health hazards of chemicals that are 

found in the environment. However, this program has long suffered 

from a lack of scientific transparency and an inability to produce 

work in a timely manner. 

Even worse, IRIS appears to have been used by the previous Administration as cover for unjustified and unscientific regulatory action, something well outside of the scope of the program’s mandate. 

I’m far from the only one raising the alarm. In fact, both the National Academy of Science and the Government Accountability Office have been critical of the management of the IRIS program. 

In February of this year, GAO again included IRIS on its annual 

high-risk list, which identifies federal programs that have greater 

than normal vulnerabilities to fraud, waste, abuse, and mismanagement. 

In both 2011 and 2014, NAS made numerous recommendations 

for IRIS that have never been fully implemented. For example, 

NAS found that IRIS assessment methods and reporting continue 

to be a concern, especially in light of the extremely long process 

that IRIS takes to choose chemicals and complete its evaluations. 

Despite the numerous deficiencies that were highlighted in both 

the GAO and NAS reports, IRIS fails to show any sign of improvement. It is now the role of Congress, as the ultimate steward of 

taxpayer dollars, to carefully assess whether IRIS can even be 

salvaged. I myself remain very skeptical and simply cannot support 

the program in its current form. 

What I find most troubling is that IRIS may be providing conflicting or duplicative information and creating confusion for Americans regarding either the harm or lack of harm that any given 

chemical may possess. If that is indeed the case, IRIS poses a 

threat to the public’s trust and safety and simply cannot be allowed 

to continue to operate. 

I’m also deeply concerned by the fact that we can actually point 

to cases in which determinations by IRIS have been inappropriately used to make regulatory decisions. For example, the previous 

Administration took action against a chemical manufacturer in 

Louisiana based on a faulty IRIS determination, even though that 
5 

particular company was currently in compliance with all emissions 

regulations put forward under the Clean Air Act. Actions like the 

one initiated by IRIS in Louisiana do not inspire confidence in our 

federal agencies. 

This Committee is committed to ensuring that EPA uses the best 

available science. IRIS, it appears, has failed to use even passable 

science on many occasions, and what is so troubling is that even 

when IRIS administrators are alerted to this fundamental problem, 

they take absolutely no corrective action. 

We must also be committed to ensuring that EPA’s actions are 

based on the highest levels of scientific integrity. The fact that 

IRIS has been subjected to continued scrutiny of its scientific processes and continued requests for Information Quality Act reviews 

should send a clear signal that the program is failing and is in serious danger of irrevocably subverting its mission. 

All those concerns aside—and they are considerable—I am hopeful that the witnesses before us today can provide Congress with 

information to better inform actions that this Committee may take. 

We all want to ensure the protection of American citizens from the 

potentially harmful impacts of chemicals. If IRIS is the appropriate 

program to do that, we in Congress must ensure that it is properly 

organized and makes informed decisions. 

Moreover, we must ensure that IRIS efforts—the efforts of IRIS 

to evaluate chemicals are based on real-world threats, not theoretical ones. 

I would briefly take a moment to point out that the existence of 

or changes to the IRIS program would not have an impact on the 

continued effectiveness of EPA’s Risk Management program. 

I look forward to learning more from our distinguished panel 

today, and have no doubt that this will be a wide-ranging and fascinating discussion. I thank each of our witnesses for being here 

today. 

[The prepared statement of Chairman Biggs follows:] 
6 

COMMITTEE ON 

SCIENCE, SPACE, & TECHNOLOGY 

Lamar Smith. Chairman 

For Immediate Release 

September 6, 2017 

Media Contact: Thea McDonald 

(202) 225-6371 

Statement of Environment Subcommittee Chairman Andy Biggs (R-Ariz.) 

Examining the Scientific and Operational Integrity of EPA's IRIS Program 

Chairman Biggs: Good morning and welcome to today's joint subcommittee hearing, 

entitled "Examining the Scientific and Operational Integrity of EPA's IRIS Program." 

Today, we will hear from witnesses who ore experts in the fields of epidemiology and 

toxicology and learn about their interactions with EPA's IRIS program. 

The original purpose of IRIS was simply to "identify and characterize the health hazards 

of chemicals that ore found in the environment." However, this program has long 

suffered from a lock of scientific transparency and an inability to produce work in a 

timely manner. Even worse, IRIS appears to have been used by the previous 

administration as cover for unjustified and unscientific regulatory action, something 

well outside of the scope of the program's mandate. 

And I'm far from the only one raising the alarm. In fact, both the National Academy of 

Science and the Government Accountability Office have been critical of the 

management of the IRIS program. In February of this year, GAO again included IRIS 

on its annual "high risk" list, which identifies federal programs that have greater than 

normal vulnerabilities to fraud, waste, abuse, and mismanagement. 

In both 2011 and 2014, NAS made numerous recommendations for IRIS that have 

never been fully implemented. For example, NAS found that IRIS assessment methods 

and reporting continue to be a concern, especially in light of the extremely long 

process that IRIS takes to choose chemicals and complete its evaluations. 

Despite the numerous deficiencies that were highlighted in both the GAO and NAS 

reports, IRIS fails to show any sign of improvement. It is now the role of Congress, as the 

ultimate steward of taxpayer dollars, to carefully assess whether IRIS can even be 

salvaged. I myself remain very skeptical and simply cannot support the program in its 

current form. 

What I find most troubling is that IRIS may be providing conflicting or duplicative 

information and creating confusion for Americans regarding either the harm-or lack 

of harm-that any given chemical may possess. If that is indeed the case, IRIS poses a 

threat to the public's trust and safety and simply cannot be allowed to continue to 

operate. 
7 

I am also deeply concerned by the fact that we can actually point to cases in which 

determinations by IRIS have been inappropriately used to make regulatory decisions. 

For example, the previous administration took action against a chemical 

manufacturer in Louisiana based on a faulty IRIS determination, even though that 

particular company was currently in compliance with all emissions regulations put 

forward under the Clean Air Act. 

Actions like the one initiated by IRIS in Louisiana do not inspire confidence in our 

federal agencies. This Committee is committed to ensuring that EPA uses the best 

available science. IRIS, it appears, has failed to use even passable science on many 

occasions, and what is so troubling is that even when IRIS administrators are alerted to 

this fundamental problem, they take absolutely no corrective action. 

We must also be committed to ensuring that EPA's actions are based on the highest 

levels of scientific integrity. The fact that IRIS has been subjected to continued scrutiny 

of its scientific processes and continued requests for Information Quality Act reviews 

should send a clear signal that the program is failing and is in serious danger of 

irrevocably subverting its mission. 

All those concerns aside -and they are considerable- I am hopeful that the witnesses 

before us today can provide Congress with information to better inform actions that 

this Committee may lake. 

We all want to ensure the protection of American citizens from the potentially harmful 

impacts of chemicals. If IRIS is the appropriate program to do that, we in Congress 

must ensure that it is properly organized and makes informed decisions. Moreover, we 

must ensure that IRIS efforts to evaluate chemicals are based on real-world threats, not 

theoretical ones. 

I look forward to learning more from our distinguished witnesses and have no doubt 

that this will be a wide-ranging and fascinating discussion. 

### 
8 

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

time and recognize now the Ranking Member of the Environment 

Subcommittee, the gentlewoman from Oregon, for an opening statement. 

Mr. BONAMICI. Thank you very much, Mr. Chairman. 

Mr. Chairman, this Committee has a long tradition of examining 

the Environmental Protection Agency’s Integrated Risk Information System, or IRIS. The last time this Committee held a hearing 

on it was back in 2014, and at that hearing, I said that this Committee needs to allow the EPA to fulfill its mission of protecting the 

public’s health from environmental hazards. Producing assessments of chemicals that may cause harm to our constituents and 

our communities is critical to that mission. 

I am disappointed that today, this Committee is once again headed in the wrong direction. Rather than undermining important 

public health assessments, we should be supporting and in fact 

strengthening the EPA’s efforts to protect Americans from unsafe 

chemical exposure. Given that the Committee has not held a hearing on this issue in three years, it is troubling that today the Majority is calling two witnesses with clear interests in a particular 

outcome, but did not call the EPA or the GAO. This does not seem 

to me like a hearing to investigate how we can best protect our constituents’ health, which is what we should be doing, but instead an 

attempt to look for a basis for weakening or eliminating the IRIS 

program. That is unacceptable. 

It’s also perplexing that the Majority is hosting a hearing to emphasize industry-held criticisms of the IRIS program at a time 

when independent organizations that have investigated the IRIS 

program are citing its notable improvements. And Mr. Chairman, 

you said that IRIS has failed to show any signs of improvement, 

but just last week, the independent EPA Science Advisory Board, 

or the SAB, wrote a letter to Administrator Pruitt praising the 

progress of the IRIS program. That letter said, ‘‘The SAB has observed significant enhancements in the IRIS program over the last 

few years, with impactful changes over the past year, and marked 

progress over the past six months. The changes are so extensive 

and positive that they constitute a virtual reinvention of IRIS,’’ and 

I’ll repeat that last line: ‘‘The changes are so extensive and positive 

that they constitute a virtual reinvention of IRIS.’’ 

The work of IRIS is especially critical to protecting the health of 

our Nation’s children. The human health assessments developed 

through the program provide vital information that aids the EPA 

in its decision making, and also informs state and local governments and public health professionals. Fundamentally the IRIS 

program helps those tasked with protecting the public’s health to 

make the best decisions they can by using the best available 

science to determine the potential harmful effects of chemical exposures. That is precisely why this Committee has taken an interest 

in the activities of IRIS in the past, particularly when the program 

was not living up to its potential. 

In response to a request from Congress, the National Academies 

reviewed the IRIS program and released a report, two months prior 

to our 2014 hearing, which made recommendations for improvements that EPA should implement. What is the status of those rec-
9 

ommendations, what progress has the program made, and what improvements are still needed? Those are the questions we should be 

asking the EPA and the National Academies. Unfortunately, the 

Majority did not invite anyone from the EPA or the National Academies to offer any answers. 

Mr. Chairman, the IRIS program is too important for there not 

to be a thoughtful examination of its status and a fuller review of 

the recent progress it has made. This Committee has the important 

role of providing oversight of the Administration’s efforts in its jurisdiction. 

During the Obama Administration, this Committee held dozens 

and dozens of hearings investigating actions of the Administration, 

and the EPA, including the EPA Administrator, was here to answer. Yet, now that there is a Republican Administration, this 

Committee has failed to have a single hearing with any of the presidential appointments in its jurisdiction. 

During the Obama Administration, Administrator Pruitt testified 

in front of this Committee in his role as Oklahoma’s Attorney General and was highly critical of the EPA. Now that he is the EPA 

Administrator, the American people deserve the opportunity to 

hear his priorities for the EPA. This Committee must fulfill its 

duty of providing oversight of the agencies in its jurisdiction. 

Mr. Chairman, will you commit to holding a Full Committee 

hearing on a legislative day this year with EPA Administrator Pruitt? 

Chairman BIGGS. Is the gentlewoman done? 

Ms. BONAMICI. No, I’m asking, Mr. Chairman, will you commit 

to holding a Full Committee hearing on a legislative day this year 

with EPA Administrator Pruitt? He has not been before this Committee yet. 

Chairman BIGGS. Well, I appreciate you asking me a question in 

public that you’ve never broached with me in private, which I consider to be highly improper and highly unusual, frankly, and I’m 

happy to discuss with you in private. 

Ms. BONAMICI. Thank you, Mr. Chairman. 

And finally, Mr. Chairman, I ask that the letter from EPA’s 

Science Advisory Board, which I referenced earlier, be made a part 

of the record. 

Thank you, and I yield back. 

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

OPENING STATEMENT 

Ranking Member Suzanne Bonamici (D-OR) 

of the Subcommittee on Environment 

House Committee on Science, Space, and Technology 

Subcommittee on Environment 

Subcommittee on Oversight 

"Examining the Scientific and Operational Integrity of EPA's IRIS Program" 

September 6, 2017 

Mr. Chairman, this Committee has a long tradition of examining the Environmental Protection 

Agency's Integrated Risk Information System, or IRIS. The last time this Committee held a 

hearing on it was back in 2014. At that hearing, I said that this Committee needs to allow the 

EPA to fulfill its mission of protecting the public's healtb from environmental hazards. 

Producing assessments of chemicals that may cause harm to our constituents and our 

commtmities is critical to that mission. 

I am disappointed that, today, this Committee is once again headed in the wrong direction. 

Rather than undermining important public health assessments, we should be supporting and in 

fact strengthening the EPA's efforts to protect Americans from unsafe chemical exposure. Given 

tbat the Committee has not held a hearing on this issue in three years, it is troubling that today 

the Majority called two witnesses with clear interests in a particular outcome, but did not call the 

EPA or the GAO. This does not seem to me like a hearing to investigate how to best protect our 

constituent's health, which is what we should be doing, but instead an attempt to look for a basis 

for weakening or eliminating the IRIS program. That is unacceptable. 

It is also perplexing that the Majority is hosting a hearing to emphasize industry-held criticisms 

of the IRIS program at a time when tbe independent organizations that have investigated tbe 

IRIS program are citing its notable improvements. Just last week, the independent EPA Science 

Advisory Board - "the SAB" - wrote a letter to Administrator Pruitt praising the progress of the 

IRIS program. That letter said, quote 'The SAB has observed significant enhancements in the 

IRIS program over the past few years, with impactful changes over the past year, and marked 

progress over the past six months. The changes are so extensive and positive that they constitute 

a virtual reinvention ofiRIS." I will repeat tbat last line: "The changes are so extensive and 

positive that they constitute a virtual reinvention of IRIS." 

The work ofiRIS is especially critical to protecting the health of our nation's children. The 

human health assessments developed through the program provide vital information that aids the 

EPA in its decision making, and also informs state and local governments and public health 

professionals. Fundamentally the IRIS program helps those tasked with protecting the public's 

health to make the best decisions they can by using the best available science to determine the 

potential harmful effects of chemical exposures. 

That is precisely why this Committee has taken an interest in tbe activities ofiRIS in the past, 

particularly when the program was not living up to its potential. In response to a request from 
11 

Congress, the National Academies reviewed the IRIS program and released a report, two months 

prior to our 20 14 hearing, which made recommendations for improvements that EPA should 

implement. What is the status of those recommendations, what progress has the program made, 

and what improvements are still needed? Those are the questions we should be asking EPA and 

the National Academies. Unfortunately, the Majority did not invite anyone from EPA or the 

National Academies to offer any answers. 

Mr. Chairman, the IRIS program is too important for there not to be a thoughtful examination of 

its status and a fuller review of the recent progress it has made. This Committee has the 

important role of providing oversight of the Administration's efforts in its jurisdiction. During 

the Obama Administration this Committee held dozens and dozens of hearings investigating 

actions of the Administration, and the EPA was here to answer. Yet, now that there is a 

Republican Administration, this Committee has failed to have a single hearing with any of the 

presidential appointees in its jurisdiction. During the Obama Administration, Administrator 

Pmitt testified in front of this Committee in his role as Oklahoma's Attorney General and was 

highly critical of the EPA. Now that he is the EPA Administrator, the American people deserve 

the opportunity to hear his priorities for the EPA. This Committee must fulfill its duty of 

providing oversight of the agencies in its jurisdiction. 

Mr. Chairman, will you commit to holding a Full Committee hearing on a legislative day this 

year with EPA Administrator Pmitt? 

Finally, Mr. Chaim1an, I ask that the letter from EPA's SAB, which I referenced earlier, be made 

part of the record. 

Thank you. I yield back. 
12 

Chairman BIGGS. Thank you, Ms. Bonamici. Thank you. 

And now we’re going to recognize the Chairman of the Subcommittee on Oversight, Mr. LaHood, for his opening statement. 

Mr. LAHOOD. Thank you, Chairman Biggs, and good morning, 

and welcome to today’s Joint Subcommittee hearing on ‘‘Examining 

EPA’s Integrated Risk Information System Program.’’ 

Today, we will hear from expert witnesses highlighting various 

examples of why oversight of the IRIS program is critical to restoring scientific integrity to the agency. I would like to thank the witnesses in advance for their testimony today. 

EPA created IRIS in 1985 under no statutory authority, defining 

no safeguards, timelines, or binding requirements with which the 

program must adhere. EPA intended for the program to ‘‘foster consistency in the evaluation of chemical toxicity across the Agency.’’ 

However, since 2011 multiple reports have been issued raising 

glaring deficiencies in the program that to this day have gone 

unaddressed. As we will hear today from witnesses, there are many 

questions and issues that have been raised about IRIS assessments 

being based on sound science. There are multiple instances of the 

IRIS program relying on outdated or flawed studies to complete assessments, neglecting to obtain or use the scientifically critical raw 

supporting data related to risk assessments. Moreover, IRIS has 

failed to adapt mode-of-action science utilized by other offices within EPA, which we will hear today from Dr. Bus. 

More troubling, it appears that quasi-regulatory decisions have 

been based off the assessments completed by the IRIS program. 

The fact that many of these assessments may be faulty illustrates 

why oversight is so important to the function of our government. 

An accredited scientific body, The National Academy of Sciences, 

has raised serious questions and concerns about IRIS. The GAO 

has included IRIS on its biennial High Risk List since 2009, and 

this Committee sent EPA a letter last year raising similar concerns. These combined efforts have resulted in little, if any, improvement to the IRIS program. By holding this hearing today and 

diving deeper into the issue at hand, I hope to continue an oversight of the IRIS program to bring attention to the scientific integrity issues that need to be addressed here today. 

And Mr. Chairman, I would also add, I know a number of issues 

have been raised already here this morning. I would just mention 

that the Minority mentioned the EPA’s Science Advisory Board letter to Administrator Pruitt as evidence the IRIS program has been 

improved significantly. This letter was sent to Administrator Pruitt 

last Friday, September 1st, less than 36 hours after the Science 

Advisory Board meeting and two days after the public notice of today’s hearing. The Board was not tasked with providing official review or comment on the presentation highlighting changes to the 

IRIS program. It appears that the SAB recognizes that issues have 

existed in the past with regard to the IRIS program and that issues 

still persist currently. Given the speed with which this letter was 

sent, I find it difficult for the letter to carry much weight toward 

establishing any significant progress with the IRIS program. 

Moreover, this letter fails to provide for any meaningful scientific 

scrutiny of reviews completed in the past where scientific integrity 
13 

issues have been raised, which is one of the major issues with the 

program and why we are here today, Mr. Chairman. 

With that, I yield back. Thank you. 

[The prepared statement of Mr. LaHood follows:] 
14 

COMMITTEE ON 

SCIENCE, SPACE, & TECHNOLOGY 

Lamar Smith, Chairman 

For Immediate Release 

September 6, 2017 

Media Contact: Thea McDonald 

(202) 225-6371 

Statement of Oversight Subcommittee Chairman Darin LaHood (R-Ill.) 

Examining the Scientific and Operational Integrity of EPA's IRIS Program 

Chairman LaHood: Good morning and welcome to today's Joint Subcommittee 

hearing "Examining EPA's Integrated Risk Information System Program." Today, we will 

hear from expert witnesses highlighting various examples of why oversight of the IRIS 

program is critical to restoring scientific integrity to the agency. I would like to thank 

the witnesses in advance for their testimony today. 

EPA created IRIS in 1985 under no statutory authority, defining no safeguards, timelines, 

or binding requirements with which the program must adhere. EPA intended for the 

program to "foster consistency in the evaluation of chemical toxicity across the 

Agency." However, since 2011 multiple reports have been issued raising glaring 

deficiencies in the program that to this day have gone un-addressed. 

As we will hear from witnesses today, IRIS assessments are not based on sound science. 

There are multiple instances of the IRIS program relying on outdated or flawed studies 

to complete assessments, neglecting to obtain or use the scientifically critical raw 

supporting data related to risk assessments. Moreover. IRIS has failed to adapt "mode 

of action" science utilized by other offices within EPA. which we will hear more about 

from Dr. Bus. 

More troubling, it appears that quasi-regulatory decisions have been based off the 

assessments completed by the IRIS program. The fact that many of these assessments 

may be faulty illustrates why oversight is so important to the function of our 

government. 

An accredited scientific body, The National Academy of Sciences has raised serious 

questions and concerns about IRIS; the GAO has included IRIS on its biennial High Risk 

List since 2009; and this Committee sent EPA a letter last year raising similar concerns. 

These combined efforts have resulted in little, if any, improvement. By holding this 

hearing today and diving deeper into the issue at hand I hope to continue our 

oversight of the IRIS program to bring attention to the scientific integrity issues that 

need to be addressed. 

### 
15 

Chairman BIGGS. Thank you, Mr. LaHood. 

I now recognize the Ranking Member of the Subcommittee on 

Oversight, Mr. Beyer, for his opening statement. 

Mr. BEYER. Thank you, Chairman Biggs, and thank you, Chairman Biggs and Chairman LaHood, for this hearing. 

And I too must convey my disappointment with this hearing and 

the apparent purpose. I’m encouraged by my friend Chairman 

LaHood’s comments that he believes it’s the appropriate role for 

this Committee to have oversight of IRIS but this—I fear this isn’t 

a hearing about oversight. This is going to be a hearing about how 

to—not a hearing about how to improve the critical function of the 

EPA’s Integrated Risk Information System, not a hearing to actually determine the facts about the remarkable progress they’ve recently made. This appears to be a hearing for industry. 

The letter that the EPA’s Science Advisory Board wrote to EPA 

Administrator Pruitt last week touted the progress made by the 

IRIS program and its importance in protecting the public health. 

To quote: ‘‘The SAB members in attendance voted unanimously 

that I communicate to you their enthusiasm for the IRIS program’s 

progress.’’ However, the Majority has not invited anyone from the 

SAB or the National Academies of Sciences or the GAO or the EPA 

to testify about the significant improvements the program has 

made. And I don’t think that it undercuts the validity or the importance of the SAB’s letter to suggest that it was at least partially 

a reaction to the announcement of this hearing. Of course it was. 

When they saw this was coming up, they thought it was important 

to note all the progress that had been made. 

The Majority has instead chosen to ignore this progress and invite two industry scientists as witnesses, who undoubtedly criticize 

the IRIS program and the EPA in general, and despite assurances 

from Majority staff that this hearing is simply about hearing from 

stakeholders, the real intent seems to coincide with a call by industry to eliminate IRIS altogether. For example, if I could ask one 

slide to be put up? I note that our Chairman Biggs recently offered 

an amendment to H.A. 3354, the Appropriations Act of 2018, that 

would zero out all funding for EPA’s IRIS program, effectively abolishing it. 

I believe this hearing should be viewed in the larger context of 

what it actually is, which is another attack on the American 

public’s environmental health, another opportunity for industry 

consultants and industry-paid scientists to attempt to weakness 

the effectiveness of the EPA, the only federal agency charged with 

protecting the environment and the health of the American people. 

You know, whatever efforts this Administration takes to impede 

progress made to the EPA’s IRIS program, reduce its role in identifying harmful chemicals, or eliminate this program altogether, 

those efforts unfortunately fit neatly into the anti-science agenda 

already unveiled by this Administration. Since the Trump Administration came to office less than eight months ago, political appointees at EPA are now reviewing grants to conduct scientific 

studies, rather than actual scientists as has been the tradition 

through Democratic and Republican Presidents in the past. The 

EPA has withdrawn a data request to industry regarding methane 

emissions from the oil and gas industry, which is a growing and 
16 

dangerous problem. Administrator Scott Pruitt has made it known 

he wants more industry representatives on the Agency’s scientific 

advisory boards, an effort that will undermine the health and safety of the American public and damage the environment. Key positions at the EPA are now being filled with individuals with deep 

ties to industry, rather than qualified scientists or qualified public 

health experts. Senior federal officials and scientists have resigned 

in protest over the direction of the Trump Administration and the 

actions of the EPA Administrator, and the EPA and other federal 

agencies have scrubbed references to climate change from their 

websites and some federal offices have reportedly banned the use 

of the term. 

So it really disheartens me that the Science Committee is not investigating important scientific issues that have a real world impact on the health and safety of our citizens across the country, 

their exposure to chemical pollutants, and the human health implications of a warming climate. Rather, the Committee seems resolved to providing a forum for industry scientists to advocate for 

policies and procedures that will please the industries they work 

for, but cause harm to the environment and the public health of all 

Americans across the political spectrum. 

Thank you, Mr. Chairman. I yield back. 

[The prepared statement of Mr. Beyer follows:] 
17 

OPENING STATEMENT 

Ranking Member Donald Beyer (D-VA) 

ofthe Subcommittee on Oversight 

House Committee on Science, Space and Technology 

Subcommittee on Environment 

Subcommittee on Oversight 

"Examining the Scientific and Operational Integrity of EPA 's IRIS Program" 

September 6, 2017 

Thank you Chairman Biggs and Chairman LaHood. Unfortunately, I too must convey my 

disappointment with this hearing and the apparent purpose for this hearing. This is not a hearing 

about oversight. This is not a hearing about how to improve the critical function of the EPA's 

Integrated Risk Information System (IRIS) program. This is not a hearing constructed to actually 

detennine the facts about the problems this program has had in the past and the remarkable 

progress they have recently made. This appears to be a hearing for industry. 

The letter that the EPA's Science Advisory Board (SAB) wrote to EPA Administrator Scott 

Pruitt just last week touted the progress made by the IRIS program and its importance in 

protecting the public's health. The letter to Administrator Pruitt, written by the Chair of the SAB, 

said - quote: "The SAB members in attendance voted unanimously that I communicate to you 

their enthusiasm for the IRIS program's progress." However, the Majority has not invited anyone 

fi-om the SAB or the National Academies of Sciences or the Government Accountability Office 

(GAO) or the EPA to testifY about the significant improvements the program has made. 

The Majority has instead chosen to ignore this progress and invited two industry scientists as 

witnesses, who undoubtedly will criticize the IRIS program and the EPA in general. And despite 

assurances from Majority staff that this hearing is simply about hearing from "stakeholders" 

about the IRIS program, the real intent seems to coincide with a calling by industry to eliminate 

IRIS altogether. 

I would note that Chairman Biggs recently offered an Amendment to H.R. 3354 the 

Department of the Interior, Environment, and Related Agencies Appropriations Act of2018 that 

would zero out all funding for the EPA's IRIS program, effectively abolishing it. It appears that 

this hearing had a pre-determined outcome from the start, and was never intended to be a 

thoughtful examination of the EPA's IRIS program. It appears to be some sort of pre-text for 

eliminating the program altogether. 

I believe this hearing should be viewed in the larger context of what it actually is: another attack 

on the American public's environmental health, and another opportunity for industry consultants 

and industry-paid scientists to attempt to weaken the effectiveness of the EPA, the only federal 

Agency charged with protecting the environment and the health of the American people. 

Some Trump Administration officials have also called for eliminating the IRIS program, a move 

supported by some from industry and industry-friendly groups such as the Competitive 

Enterprise Institute (CEI). The efforts by these individuals and groups to eliminate, or drastically 
18 

curtail the budget and staff of IRIS, seem to be part and parcel of this Administration's war 

against the environment and science, and appears to be part of this hearing's agenda too. 

Whatever efforts this Administration takes to impede progress made to the EPA's IRIS program, 

reduce its role in identifying harmful chemicals, or eliminate this program altogether, those 

efforts fit neatly into the anti-science agenda already unveiled by this Administration. 

Since the Trump Administration can1e to office less than eight months ago: 

• Political appointees at EPA are now reviewing grants to conduct scientific studies, rather 

than actual scientists' as has been the tradition in the past. 

• The EPA has withdrawn a data request to industry regarding methane emissions from the 

oil and gas industry, which has been a growing and dangerous problem. 

• EPA Administrator Scott Pruitt has made it known he wants more industry 

representatives on the Agency's scientific advisory boards, an effort that will undenninc 

the health and safety of the American public and damage the environment. 

• Key positions at the EPA are now being filled by individuals with deep ties to industry, 

rather than qualified scientists or public health experts. 

• Senior federal officials and scientists have resigned in protest over the direction of the 

Trump Administration and the actions of EPA Administrator Scott Pruitt. 

• The EPA and other federal agencies have scrubbed references to climate change from 

their websites and some federal offices have reportedly banned the use of the term. 

It disheartens me that the Science Committee is not investigating important scientific issues that 

have a real world impact on the health and safety of citizens across this country, their exposure to 

chemical pollutants, for instance, and the human health implications of a warming climate. 

Rather, the Committee seems resolved to providing a forum for industry scientists to advocate 

for policies and procedures that will please the industries they work for, but cause harm to the 

environment and the public health of all Americans across the political spectrum. 

Thank you, I yield back. 
19 

Chairman BIGGS. Thank you, Mr. Beyer. 

I now recognize the Ranking Member of the Full Committee, Ms. 

Johnson. 

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

I too must say that I’m disappointed, but I’m really not surprised 

that we are holding this hearing today. Sadly, I have had to make 

this statement too many times in the last four years. 

How can we, in good conscience, title this hearing as an examination of the scientific and operational integrity of EPA’s IRIS program, when there is no one here from EPA here to testify? I don’t 

think we can. How do we conduct the necessary oversight for this 

program when the Government Accountability Office is not present 

to answer questions about their recent review of IRIS? I don’t know 

that we can. How are we serving the best interests of our constituents, and of all Americans, when the National Academies of 

Sciences is not present to discuss their report upon which the last 

three years. worth of reforms to IRIS were based upon? I don’t 

think we are. How can we have an honest discussion about this 

program while ignoring the key entities that have reviewed it and 

studied its recent improvements? I don’t think we can. 

I would also note that just last week the EPA’s independent 

Science Advisory Board—the SAB—sent a letter to EPA Administrator Scott Pruitt praising the progress the IRIS program has 

made. The letter said, in part, and I quote: ‘‘The Board commends 

the Agency for making such significant improvements over a short 

period of time. We are optimistic that the restructured IRIS program will strengthen the scientific foundations of risk assessment 

and protect the health and safety of the American public.’’ But we 

are not here to hear that today. Instead, the Majority has invited 

two industry scientists to voice their criticisms of IRIS. 

Let me be clear, industry perspectives should not be excluded 

from scientific discussions on environmental issues at the EPA, and 

they are not now and nor have they ever been. The current membership of EPA’s Science Advisory Board, for instance, includes representatives from the Dow Chemical Company, Procter and Gamble, and Exxon Mobil. However, I’m concerned that industry, the 

leadership of this Committee, and now this Administration, are 

seeking to let industry drive the science upon which critical decisions about protecting the public’s health and the environment are 

made. 

The current criticisms of the EPA’s IRIS program by industry 

highlight that point. We have seen this tactic used by industry before, and I’m sure that we’ll see it repeated in the future. 

Mr. Chairman, not only can we do better, we must do better. The 

American people deserve a Congress that is working for them, and 

with them, not against them, and certainly not for the interests of 

wealthy polluting industries. I hope that one day soon our Committee will be a forum for a balanced discussion on the critical 

issues under our jurisdiction. Unfortunately, today’s hearing falls 

well short of that mark. 

My last point—the response from the Majority to my statement 

may be that Minority Members are permitted to invite one witness 

to these hearings and that we could have invited anyone we wanted to, such as a representative of the EPA, the SAB or the GAO 
20 

or the National Academies. My response to that, Mr. Chairman is 

that I don’t believe it is the job of the Minority to do the Majority’s 

job for them. It is clear that all of those entities should be represented at today’s hearing, not just the single witness allocated for 

the Minority. If we are serious about conducting credible oversight 

of IRIS, I would hope that the Majority will commit to a follow-up 

hearing so that those voices may be heard. 

I thank you, and I yield back. 

[The prepared statement of Ms. Johnson follows:] 
21 

OPENING STATEMENT 

Ranking Member Eddie Bernice Johnson (D-TX) 

House Committee on Science, Space, and Technology 

Subcommittee on Environment 

Subcommittee on Oversight 

"Examining the Scientific and Operational Integrity of EPA 's IRIS Program" 

September 6, 2017 

Mr. Chairman, I am disappointed, but I am not surprised, that we are holding this hearing today. 

Sadly, I have had to make this statement too many times in the last four years. How can we, in 

good conscience, title this hearing as an examination of the scientific and operational integrity of 

EPA's IRIS program, when there is no one from EPA here to testify? We cannot. 

How do we conduct the necessary oversight of this program, when the Government 

Accountability Office (GAO) is not present to answer questions about their recent review of 

IRIS? We do not. 

How are we serving the best interests of our constituents, and of all Americans, when the 

National Academies of Sciences is not present to discuss their report upon which the last three 

years' worth of reforms to IRIS were based upon? We are not. 

How can we have an honest discussion about this program while ignoring the key entities that 

have reviewed it and studied its recent improvement~? We simply can't. 

I would also note that just last week the EPA's independent Science Advisory Board (SAB) sent 

a letter to EPA Administrator Scott Pruitt praising the progress the IRIS program has made. The 

letter said, in part and I quote: "The Board commends the Agency for making such significant 

improvements over a short period of time. We are optimistic that the restructured IRIS program 

will strengthen the scientific foundations of risk assessment and protect the health and safety of 

the American public." But we're not hearing from the SAB either. Instead, the Majority has 

invited two industry scientists to voice their criticisms of IRIS. 

Let me be clear, industry perspectives should not be excluded from scientific discussions on 

environmental issues at the EPA and they are not now, nor have they ever been. The current 

membership of EPA's Science Advisory Board, for instance, includes representatives from the 

Dow Chemical Company, Procter & Gamble, and Exxon Mobil. However, I am concerned that 

industry, the leadership of this Committee, and now this Administration, are seeking to let 

industry drive the science upon which critical decisions about protecting the public's health and 

the environment are made. The current criticisms of the EPA's IRIS program by industry 

highlight that point. We have seen this tactic used by industry before and I am sure we will see it 

repeated in the future. 

Mr. Chairman, not only can we do better, we must do better. The American people deserve a 

Congress that is working for them, and with them, not against them, and certainly not for the 

interests of wealthy polluting industries. I hope that one day soon our Committee will be a forum 
22 

for a balanced discussion of the critical issues under our jurisdiction. Unfortunately, today's 

hearing falls well short of that mark. 

One last point. The response from the Majority to my statement may be that Minority Members 

are permitted to invite one witness to these hearings and that we could have invited anyone we 

wanted to, such as a representative of the EPA, the SAB, GAO or the National Academies. My 

response to that, Mr. Chairman is that I don't believe it is the job of the Minority to do the 

Majority'sjob for them. It is clear that all of those entities should be represented at today's 

hearing, not just the single witness allocated to the Minority. If we are serious about conducting 

credible oversight ofiRIS, I would hope that the Majority will commit to a follow-up hearing so 

that those voices can be heard. 

Thank you. I yield back. 
23 

Chairman BIGGS. Thank you. I thank the gentlewoman. 

I want to now introduce our witnesses, the three with impeccable 

scientific backgrounds and expertise, and I’m grateful that each of 

you would take time to be here today. When you give your testimony, at some points you’ll get five minutes, and I’ll stand up and 

dance as you get close so you know you’re near the end. 

Dr. Kenneth Mundt is our first witness. He is the Principal at 

Ramboll Environ, where he serves as the Health Sciences Global 

Practice Area Leader and Director of Applied Epidemiology. Additionally, Dr. Mundt is an Adjunct Faculty Member at the University of North Carolina and the University of Massachusetts-Amherst. He received a bachelor’s degree from Dartmouth College and 

a Ph.D. in epidemiology from the University of North Carolina at 

Chapel Hill. 

Our next witness today is Dr. James Bus, Senior Managing Scientist at Exponent. Dr. Bus has over 23 years’ experience as a Consulting Toxicologist in the Toxicology and Environmental Research 

and Consulting Unit at the Dow Chemical Company and serves as 

an Adjunct Professor in the Department of Pharmacology and Toxicology at Michigan State University. He received a bachelor’s degree in medicinal chemistry and a Ph.D. in pharmacology from 

Michigan State University. 

And our final witness today is Dr. Thomas Burke, Professor at 

Johns Hopkins Bloomberg School of Public Health. Dr. Burke also 

serves as the Director of the Johns Hopkins Risk Sciences and Public Policy Institute. He received a master’s of public health from the 

University of Texas and a Ph.D. from the University of Pennsylvania. 

And I now recognize Dr. Mundt for five minutes to present his 

testimony. Dr. Mundt. 

TESTIMONY OF DR. KENNETH MUNDT, 

PRINCIPAL, RAMBOLL ENVIRON 

Dr. MUNDT. Good morning. 

Chairman BIGGS. You’re going to need to press the ‘‘talk’’ button. 

There you go. Thanks. 

Dr. MUNDT. Good morning. Thank you, Mr. Chairman. My name 

is Kenneth Mundt. I’m an Epidemiologist and Health Sciences 

Practice Network Leader at Ramboll Environ. 

My career has focused on evaluating health risks of chemicals, 

particularly in the workplace. Thank you and the Committees for 

the opportunity today to provide the highlights of a scientific evaluation of the 2010 IRIS Toxicological Review of Chloroprene that 

colleagues at Ramboll and Environ and I recently completed. Our 

evaluation of the IRIS review illustrates how important good 

science is to understanding human health risks and highlights 

some issues that need to be addressed. 

IRIS is responsible for evaluating the potential human health effects of chemical exposures. However, as noted, the IRIS review 

process has been criticized by expert panels of the National Research Council of the National Academy of Sciences. In particular, 

the NAS emphasized the importance of transparency and rigor in 

the IRIS review methods. Our evaluation of the IRIS review of 

chloroprene identified several scientific problems impacting the 
24 

evaluation of chloroprene as a human carcinogen, and leading to 

the derivation of an inhalation unit risk, or IUR, that is 156 times 

greater than the IUR we derived. 

The following were among the key scientific problems we found 

with that IRIS review. First, EPA failed to critically evaluate the 

quality of each epidemiological study of chloroprene-exposed workers, which resulted in giving equal weight to all studies, both good 

and bad. Suggestive positive associations were reported among the 

weakest studies with the greatest limitations. However, the largest 

and best study demonstrated no increased risk of liver or lung cancers. The NAS reviews provided guidance on study selection, methods for evaluating study quality, accounting for various forms of 

bias that impact study findings, and integrating evidence so that 

stronger studies are given greater weight. 

Second, the EPA ignored the strongest study’s conclusion: ‘‘Persons exposed to chloroprene or vinyl chloride at the levels encountered in the four study sites did not have elevated risk of mortality 

from any of the causes of death including all cancers combined and 

lung and liver cancers, the cancer sites of a priori interest.’’ In contrast, the IRIS review noted ‘‘Relative risk estimates for liver cancer while not statistically significant increased with increasing exposure indicating a dose response trend.’’ However, this trend also 

was not statistically significant and provides no evidence of increased risk. 

Third, and most importantly, EPA did not fully account for large 

and well-recognized differences between mice and humans. Mice 

appear to be far more sensitive to chloroprene than other animals, 

or even humans, which can be explained by differences in pharmacokinetics. Accounting for these differences using standard 

methods applied by EPA and IRIS reviews of other chemicals dramatically reduced the estimated IUR. 

Ultimately, applying standard EPA methodology and conservative assumptions we derived the revised IUR. Compared with 

ours, the EPA IUR was 156 times higher. Simply put, the EPA’s 

IUR is extremely large, scientifically implausible, and has significant real-world consequences. Correction of the IUR is especially 

critically given that it has prompted lawsuits and enforcement actions. 

Our critical review and integration of the published epidemiological and toxicological evidence on chloroprene also highlights the 

need to reconsider EPA’s classification of chloroprene. The IRIS review classified chloroprene as ‘‘likely to be carcinogenic to humans’’ 

based on five stated criteria. We determined that three of these criteria are not supported by a weight of evidence analysis, and a 

fourth, the structural similarities to other chemicals was not informative. It also underscores the importance of some of the improvement recommended by the NAS. 

As the Committee looks at how EPA can be expending resources 

more efficiently and how to improve the IRIS program as a whole, 

the chloroprene example may help identify specific areas where scientific and procedural flaws may be targeted and remedied. 

There’s nothing that precludes the EPA from using credible outside scientific resources to foster constructive scientific debate and 
25 

enhance their evaluation and decision-making capabilities. In doing 

so, EPA will better achieve justifiable scientific conclusions. 

Thank you. 

[The prepared statement of Dr. Mundt follows:] 
26 

The Committee on Science, Space, and Technology's Subcommittee on 

Environment and Subcommittee on Oversight of the U.S. House of 

Representatives 

September 6'h Hearing 

Examining the Scientific and Operational Integrity of EPA's Iris Program 

THE IRIS REVIEW PROCESS: 

CHLOROPRENE AND THE CRITICALITY 

OF GOOD SCIENCE 

Dr. Kenneth Mundt 

Dr. Sonja Sax 

Dr. P. Robinan Gentry 

Ramboll Environ US Corporation 

28 Amity Street, Suite 2A 

Amherst, MA 01002 

l;f+'*W!I ENVIRON 
27 

Written Testimony of Kenneth A. Mundt, PhD, FACE 

The IRIS Review Process: Chloroprene and the criticality of good 

science 

Overview 

2 

The US Environmental Protection Agency (EPA) Integrated Risk Information System 

(IRIS) compiles and evaluates available scientific studies to determine the potential 

for chemicals to cause human health effects, and to conduct risk assessments that 

indicate the exposure levels at which risk of health effects is increased. These 

evaluations are relied upon by federal, state, local as well as international regulatory 

and public health agencies. Therefore, the validity of the IRIS evaluations is 

paramount. Over the last decade the methods used in and ultimate quality of IRIS 

reviews have been criticized by numerous entities, most notably, by expert panels of 

the National Academy of Sciences (NRC 2011, 2014). 

EPA's 2010 IRIS Toxicological Review of Chloroprene (Final Report) (hereafter, "the 

2010 Review")' serves as one example where several o.f the more recent concerns 

expressed by two National Research Council (NRC) Committees of the National 

Academy of Sciences (NAS) can impact the quality of the scientific evaluation and 

lead to the derivation and publication of official risk numbers (intended to quantify 

the relationship between chloroprene exposure and the risk of human cancers), 

which in the case of chloroprene are not scientifically valid. For example, the 

Inhalation Unit Risk (IUR) that EPA published for chloroprene appears to be 156 

times greater than a more scientifically accurately derived value. Furthermore, EPA's 

extreme IUR for chloroprene - a chemical EPA did not even classify as a "known" 

human carcinogen due to uncertainty - is orders of magnitude higher than the IURs 

for other chemicals for which the integration of evidence demonstrates 

carcinogenicity in humans (such as benzene and vinyl chloride) and are classified as 

"known" human carcinogens. Clearly, EPA's IUR for chloroprene needs to be 

corrected. 

Based on a detailed critical evaluation of the 2010 Review conducted by Ram boll 

Environ US Corporation (Ramboll Environ), and sponsored by Denka Performance 

Elastomer LLC ("DPE"), several scientific errors and other problems were identified 

that likely gave rise to the extreme IUR value that EPA derived. The most important 

of these scientific issues include the following: 

• The 2010 Review failed to critically evaluate the quality of each of the 

published epidemiological studies on workers highly exposed to chloroprene 

and apparently gave equal weight to all studies regardless of quality. Workers' 

exposure to chloroprene is expected to be thousands of times higher than that 

of the general public. Suggestive associations are reported among the weakest 

studies (including studies from Armenia, Russia and China); in contrast, the 

stronger studies (primarily from the US and UK) do not demonstrate increased 

cancer risks. EPA noted: "In humans, significant increases in liver cancer 

1 U.S. EPA. IRIS Toxicological Review of Chloroprene (Final Report). U.S. Environmental Protection 

Agency, Washington, DC, EPA/635/R-09/0lOF, 2010. 
28 

Written Testimony of Kenneth A. Mundt, PhD, FACE 3 

mortality were observed in four occupational epidemiology studies (out of nine 

total studies)." The four studies did not include the highest quality study. 

• The 2010 Review ignored the conclusion of the highest quality and most 

informative epidemiological study published to date: "We conclude that 

persons exposed to chloroprene or vinyl chloride at the levels encountered in 

the four study sites did not have elevated risks of mortality from any of the 

causes of death examined, including all cancers combined and lung and liver 

cancer, the cancer sites of a priori interest" (Marsh et al., 2007a, 2007b). 

Rather, the 2010 Review highlighted out of context statistical results based on 

small subgroups of workers, even though none of the risk estimates was 

statistically significant (i.e., likely arose due to chance). EPA noted: "Relative 

risk estimates for liver cancer (while not statistically significant) increased with 

increasing exposure, indicating a dose-response trend." However, even the 

reported "trend" was not statistically significant (p=0.09). 

• The 2010 Review failed to properly account for large and well-recognized 

differences between mice and humans in deriving the IUR. The National 

Toxicology Program (NTP) conducted a study in which male and female mice of 

a specific strain, as well as male and female rats, were exposed to high 

concentrations of chloroprene. More tumors were observed in the exposed 

mice than the unexposed mice, and more in mice compared to rats, with the 

mouse data then used as the main data for estimating potential cancer risk to 

humans. However, scientific evidence providing significant and welldocumented physiological and metabolic differences between mice and 

humans were not fully considered. Furthermore, the effects driving the 

estimates of cancer risk (lung cancer observed in female mice) were not 

elevated with chloroprene exposure in experiments using rats or hamsters, 

suggesting that mice are not equivalent to humans and far more sensitive to 

chloroprene than other animals or humans. 

Ramboll Environ, using published data and standard EPA risk assessment methods 

that properly account for these large differences between female mice and humans 

(and that EPA has used in IUR calculations for other chemicals), derived a corrected 

IUR, demonstrating that the EPA IUR was overestimated 156-fold. Other quantitative 

evaluations in the 2010 Review (e.g., Reference Concentration) also are likely to be 

incorrect if the interspecies differences are not fully appreciated. 

As emphasized in reviews by prominent scientific committees, most notably those of 

the NAS (NRC 2011, 2014), significant improvements to the IRIS review methods 

and process are needed, including greater transparency. Additionally, fuller 

engagement of scientists most knowledgeable about the chemicals under review -

including those potentially funded by industry - would contribute to scientific quality 

and help identify and correct scientific errors before reviews are finalized. 

Regardless of future improvements, some IRIS Reviews that are in progress (e.g., 

formaldehyde) or have been finalized (e.g., chloroprene) need to be validated, with 

mechanisms for correcting past errors. Regulations and other decisions based on the 

erroneous IUR for chloroprene, for example, will not be based on sound science, and 

likely will have serious impacts. Scientifically, the magnitude of this difference 
29 

Written Testimony of Kenneth A. Mundt, PhD, FACE 4 

between the published and recalculated IUR is very large, and clearly warrants reevaluation and correction. 

Impetus for Rambo// Environ's evaluation of the 2010 Review 

In December 2015, EPA finalized and published the 2011 National Air Toxics 

Assessment (NATA), which indicated an extremely high off-site air pollution cancer 

risk from emissions of chloroprene from what is now DPE's Neoprene production 

facility in LaPlace, Louisiana. The NATA was derived based on the IUR from the 2010 

Review and the emission profile of the Neoprene facility. The NATA findings 

precipitated adverse public opinion, enforcement actions, and a class action lawsuit, 

all of which potentially have serious economic implications for DPE and the 

community. 

Immediately after the release of the NATA cancer risk conclusions, DPE asked 

Ramboll Environ to conduct an independent evaluation of the 2010 Review, including 

a critical review and synthesis of all relevant published epidemiological and 

toxicological literature, with a focus on validating EPA's cancer IUR as reported in the 

2010 Review. DPE recognized Ramboll Environ's scientific work and interaction with 

the IRIS program regarding the IRIS Draft Formaldehyde Toxicological Review, which 

was the focus of the NRC 2011 peer review and their criticisms of the IRIS process 

and methods. 

Highlights of the Ram boll Environ evaluation as of one year ago were presented to 

EPA on August 9, 2016 at an event EPA entitled, "IRIS Assessment of Chloroprene," 

and attended by 13 EPA representatives - including the Acting Director of EPA's 

National Center for Environmental Assessment (NCEA) and the Director of IRIS- plus 

three representatives of the Louisiana Department of Environmental Quality. 

Ramboll Environ's presentation to the group can be found at the following link: 

https://cfpub.epa.gov/ncea/iris2/events.cfm. A follow-up letter to Dr. Vandenberg is 

included as an Attachment. This letter highlights some of the difficulties encountered 

in seeking a correction of the 2010 Review. 

Subsequently, the full Ramboll Environ report was submitted to EPA as part of a 

request for correction, and is available at the following link: 

https://www.epa.gov/quality/rfc-17002. This report lays out the exact approach 

used in calculating an IUR for chloroprene using the best scientific methods used by 

EPA in other chemical evaluations, and considering the quality of the epidemiological 

and toxicological evidence used in evaluating chloroprene's carcinogenicity and risk 

numbers. 

Rambo// Environ's evaluation of the 2010 Review 

In the 2010 Review, EPA classified chloroprene as "likely to be carcinogenic to 

humans" and not the more definitive "known to be a human carcinogen," primarily 

based on EPA's recognition that the evidence was insufficient to classify it as a known 

human carcinogen. However, even classifying chloroprene as "likely to be 

carcinogenic to humans" was subject to and influenced by questionable 

interpretations of the published epidemiological and toxicological evidence. 
30 

Written Testimony of Kenneth A. Mundt, PhD, FACE 5 

Nevertheless, EPA proceeded to derive an IUR for chloroprene that is the 5th highest 

IUR (not including carcinogenic metals or coke oven emissions) EPA ever has 

developed, even among chemicals EPA or the World Health Organization's (WHO's) 

International Agency for Research on Cancer (!ARC) classifies as "known" or 

likely/probable human carcinogens. Specifically, the IUR for lifetime exposure to 

chloroprene derived by EPA is 5 x 10·4 per microgram per cubic meter (f.lg/m3 ). 

The chloroprene IUR is sufficiently large that EPA should have realized prior to 

publishing the 2010 Review that the value was anomalous. Despite the fact that the 

2010 Review underwent several peer-reviews, the large and obvious discrepancy 

between EPA's IUR for chloroprene and other IURs derived by EPA appears to have 

gone further unnoticed or unreported. The reasons for this are not clear, but call into 

question the quality of the peer-review process that IRIS has relied upon to draw 

conclusions regarding the potential for cancer risk in humans. 

The main objective for the Ram boll Environ scientific evaluation of the 2010 Review 

was to evaluate the IUR for chloroprene as derived by EPA, and to provide improved 

and transparent scientific methods, interpretations and risk calculations to facilitate 

scientifically justified corrections for EPA's consideration. 

The main elements of the Ram boll Environ assessment are presented below in four 

sections: Epidemiological Evidence; Toxicological Evidence; Chloroprene 

Carcinogenicity Classification; and, Deriving the Chloroprene IUR. 

Epidemiological Evidence 

A critical piece to understanding the potential cancer effects in humans from 

exposure to chloroprene is a rigorous evaluation of the occupational epidemiological 

literature. Workers involved in producing and directly using chloroprene are likely 

the most highly exposed individuals, and the occupational setting facilitates 

epidemiological methods for enumerating cohorts of workers, estimating levels of 

exposure and following workers over time to observe the rates at which various 

outcomes, including cancers, occur. The epidemiological evidence relevant to 

chloroprene carcinogenicity and that EPA correctly identified includes findings from 

occupational cohorts from the US, France, Ireland, Armenia, Russia and China. 

However, the 2010 Review of the epidemiological literature was methodologically 

irregular, particularly with respect to how individual study quality was assessed and 

weighted in the overall weight-of-evidence assessment. In fact, it is not clear 

whether EPA critically evaluated the quality of each of the published epidemiological 

studies on workers highly exposed to chloroprene and their respective cancer risks, 

and if so, the methods and rationale for how this was done were not transparent. 

For example, where suggestive positive associations are seen is among the weakest 

studies (including studies from Armenia, Russia and China); in contrast, the stronger 

studies (primarily from the US and UK) do not demonstrate increased cancer risks. 

The NRC recommendations regarding the IRIS review process (2011, 2014) 

underscore the importance of considering the quality of individual studies, giving 

greater weight to high-quality studies in the weight-of-evidence evaluation, and 

providing transparency in applying and documenting these methods. 
31 

Written Testimony of Kenneth A. Mundt, PhD, FACE 6 

A critical review of the same literature cited in the 2010 Review had already been 

published by Bukowski, as of 2009. The Table below is adapted from a similar table 

in that publication: 

Table: Quality Rankings for Cohort Studies of Cancer Risks from Occupational 

Chloroprene Exposure 

Marsh et al. (2007 a,b) Study Other Studies 

EPA Criteria North France- France- Kentuclcy1 

Ireland1 Louisianal- Mort* 1 Armenia2 

Incid**3 Russia4 

Clear objectives H* H H H H H·M H 

Comparison 

groups H H·M H·M M M M M·L 

Exposure H H H H M M L 

Follow-up H H·M H H·M M·L M-L M-L 

Case H H-M H·M H·M M M M ascertainment 

Control of bias H·M H-M H·M M M·L M M 

Sample size H H M L M·L L H·M 

Data collection H H H H M M M·L and evaluation 

Adequate H resoonse H H H M M M 

Documentation H H H H M·L M M of results 

Overall rank 1 2 3 4 5 5 5 11-bestl 

China5 

M 

L 

L 

M·L 

H·M 

M·L 

M·L 

M·L 

H·M 

L 

6 

Source: Bukowski 2009 * Mort= Mortality ** Incid=Incidence * Subjective estimate of study quality for each specific 

criterion H=high, M=medium, L=low; 1 Marsh et al. 2007; 2- Bulbulyan et aL 1999; 3- Colonna and Laydevant 

2001; 4- Bulbulyan et al. 1998; 5 Li et al. 1989 

From this evaluation of individual study quality, it is clear that the first four studies 

received predominately "high" or "high-medium" ratings, in contrast with the final 

four studies that received predominately "medium" or lower ratings (Bukowski 2009). 

The Marsh et al. study (2007a, 2007b) combined the data from these four highquality studies, and represent the most methodologically rigorous epidemiological 

evidence available to date. This study has the largest overall cohort size and the 

most rigorous follow-up, providing the greatest statistical power to detect an 

increased cancer risk should one exist. In contrast with the low-quality studies, the 

Marsh et al. study (2007a, 2007b) has the most comprehensive exposure 

assessment, including assessment and consideration of exposure to other 

occupational carcinogens (i.e., potentially confounding agents) such as vinyl chloride. 

Importantly, the Marsh et al. (2007a, 2007b) study reported no excess occurrence of 

lung or liver cancers among chloroprene exposed workers when compared to the 

general population reference group. For all exposed workers at all plants combined, 

observed liver cancer mortality was 72% of what would be expected based on rates 

in the unexposed general population (this is expressed by the standardized mortality 

ratio, or SMR). The comparable finding for all exposed workers in the largest plant 
32 

Written Testimony of Kenneth A. Mundt, PhD, FACE 7 

(Louisville) was 90% of expected. Both these values demonstrate no increased risk 

for liver cancer. By exposure sub-group, none of the SMRs was statistically 

significantly elevated, and three of the four were below 1.0 (the value when observed 

and expected are equal). Furthermore, there was no statistically significant trend of 

increasing risk with increasing exposure (see Figure). 

Uver Cancer RRs and SMRs by Cumulative CD Exposure, Louisville 

4.1-!iSJl !li!i!I-11\\U 

CUm (J.>I"''"lftl 

Mmlb<lt' of lib$""""" <JNI/is .thown abo.,. bM 

RRs. also adjusted forg<mdw 

lM.H 

Source: Figure from comments submitted by Andrea V. Malinowski to EPA, Docket ID No. EPA-HQ~ORD2009··0217, based on data from Marsh et aL 2007b 

For lung cancers - the cancer site that provided the highest incidence in the mouse 

and was hypothesized to be relevant to chloroprene exposure - the Marsh et al. 

study (2007a, 2007b) documented a statistically significant 25% deficit of lung 

cancer mortality for all plants combined. Specifically, the pooled study data observed 

112 fewer lung cancer deaths than would be expected based on unexposed 

population rates. Findings for each of the four individual plants were consistent (i.e., 

suggesting a deficit) although only one - Louisville, the largest plant - had a 

statistically significant deficit (89 fewer lung cancer deaths observed than expected). 

In contrast, EPA noted in the IRIS review that several studies reported higher SMRs 

for lung cancer among workers exposed to chloroprene, although few of the 

associations were significant and none of the studies controlled for confounding by 

smoking status, a strong indicator of lung cancer. 
33 

Written Testimony of Kenneth A. Mundt, PhD, FACE 8 

Nevertheless, EPA appears to have given no more weight to the most recent and 

rigorous epidemiological evidence (Marsh et al., 2007a, 2007b) showing no increased 

occurrence of liver and lung cancer than to the poorer quality Russian, Armenian, and 

Chinese studies, all of which had significant limitations. These limitations had been 

identified by others than Bukowski (2009). Rice and Boffetta (2001) conducted a 

review that included cohorts from the US (Pell 1978), China (Li et al. 1989), Russia 

(Bulbulyan et al. 1998) and Armenia (Bulbulyan et al. 1999) and noted significant 

methodological limitations in these studies, including unclear documentation for 

cohort enumeration, inadequate reference rates for standardized ratios, a lack of 

detailed histopathology of liver cancer cases, and limited or no information on 

potential co-exposures. They also remarked that the occupational chloroprene 

exposure assessment was poor for all published studies at that time, and the 

statistical power of the available studies was low due to the small number of 

observed cancers of interest. 

In addition to discounting the Marsh et al. (2007a, 2007b) study findings relative to 

the weaker evidence, EPA also appears to have misinterpreted the Marsh et al. 

(2007b) results. Specifically, the 2010 Review interpreted a statistical correlation 

between exposure level and liver cancer risk relative to a comparison subgroup 

where the comparison group exhibited anomalously fewer cancers than expected, 

creating the appearance of an increased risk in the higher exposure groups (see 

Figure). Specifically, note that the 2 observed liver cancer deaths represent less than 

half the expected number. In turn, using this as the referent or comparison group 

effectively inflates the other categories by a factor of 2.3. Furthermore, that there 

were only two liver cancer deaths in this category contributed to large instability in all 

categories due to chance alone, i.e., the impact of one fewer or one more liver cancer 

death in this category would spuriously generate conflicting results. 

The issues summarized here suggest that EPA's 2010 Review relied on incomplete 

evaluation and misinterpretation of the published epidemiological evidence. Properly 

evaluated, interpreted and weighted, the weight of epidemiological evidence does not 

demonstrate an association between occupational chloroprene exposure and 

increased incidence of liver or lung cancer. 

Separate from the evaluation of the 2010 Review, Ramboll Environ examined cancer 

incidence data from the Louisiana Tumor Registry, comparing rates for St. John the 

Baptist Parish where the DPE Neoprene plant is located, with those of the state of 

Louisiana. For all cancers combined, the rate in the five most recent years in St. John 

the Baptist Parish was 463.2, compared with 478.7 for the state of Louisiana, that is, 

cancer rates in St. John the Baptist Parish were about 3% below the state average. 

For lung cancers, the rate in St. John the Baptist Parish was 60.1 compared with 70.5 

for the state of Louisiana, that is, lung cancer rates in St. John the Baptist Parish are 

14.7% lower than the state average. Too few liver cancers have occurred in St. John 

the Baptist Parish to be publically reported. 2 Though these official data are at best 

an indirect indicator of a population impact of the OPE facility operations, they do not 

provide evidence that the parish in which the DPE facility operates has elevated 

cancer rates. 

2 https: II statecancerprofi les. ca nee r. g ov li ncidenceratesli ndex. ph p ?stateFI PS = 2 2&cancer= 

OOl&race=OO&sex=O&age=OOl&type=incd&sortVariableName=rate&sortOrder=default#results. 
34 

Written Testimony of Kenneth A. Mundt, PhD, FACE 9 

Toxicological Evidence 

As with the epidemiological studies, the toxicological evidence also should be 

evaluated in ways that adhere to EPA's own standard risk evaluation methodologies 

and conform to the NRC recommendations. The 2010 Review relied on the animal 

toxicological data as basis for deriving the chloroprene IUR, and specifically, the 

animal studies conducted by the National Toxicology Program (NTP 1998). Overall, 

this study, which included both mice and rats, demonstrated very little consistency 

across species in tumor incidence and tumor locations, but also demonstrated a 

unique sensitivity in a particular strain of female mice in which lung tumors appeared 

to be the most sensitive endpoint. Findings were specific to mice and not 

generalizable across the other animal species tested, including rats and hamsters. 

Given the striking differences in response in mice compared to other laboratory 

species, it is critically important to identify and evaluate possible differences in 

pharmacokinetics between animal species and to consider differences between mice 

and humans. The impact of this on the IUR is substantial, as discussed below. 

In addition to revisiting the reliance on the animal dataset for the estimation of the 

IUR, a more rigorous re-evaluation and integration of the cytotoxic and genotoxic 

evidence for chloroprene is needed, consistent with NRC (2011, 2014) 

recommendations. The Ramboll Environ evaluation of the published toxicological 

literature found that the evidence from these studies indicates that chloroprene acts 

through a different mode of action (MOA) than 1,3-butadiene, a structurally similar 

known human carcinogen, but used for comparison and to draw conclusions by EPA 

in the 2010 Review. Using the NRC (2011, 2014) recommendations as guidelines, 

review of chloroprene's genotoxicity profile appears to lack several attributes 

necessary to conclude that there is a mutagenic MOA. Instead, the evidence 

supports site-specific cytotoxicity as a more likely MOA. This contradicts EPA's 

conclusion that chloroprene acts via a mutagenic MOA, and alone inflated EPA's IUR 

by about 60%. 

Chloroprene Carcinogenicity Classification 

The 2010 Review determined that chloroprene was "likely to be carcinogenic to 

humans" based on EPA's conclusions of (1) statistically significant and dose-related 

information from the NTP (1998) chronic inhalation bioassay data demonstrating the 

early appearance of tumors, development of malignant tumors, and the occurrence of 

multiple tumors within and across animal species; (2) evidence of an association 

between liver cancer risk and occupational exposure to chloroprene; (3) suggestive 

evidence of an association between lung cancer risk and occupational exposure; (4) a 

proposed mutagenic mode of action (MOA); and (5) structural similarities between 

chloroprene and known human carcinogens, 1,3-butadiene and vinyl chloride. As has 

been demonstrated in this report, three of the five EPA conclusions are not supported 

by the weight of evidence, and the fourth-structural similarities-has been shown 

not to be informative, as the evidence available for the chemicals demonstrates 

different modes of action. 
35 

Written Testimony of Kenneth A. Mundt, PhD, FACE 10 

The Ramboll Environ evaluation of the 2010 Review demonstrated considerable 

misinterpretation of the available science to support the "likely to be carcinogenic to 

humans" classification. For example, the epidemiological evidence, based on an 

appropriate weight-of-evidence approach, fails to demonstrate clearly increased risks 

among exposed occupational groups and the general population, and a weak 

difference between exposed and unexposed workers reflecting a deficit among the 

least exposed. The claim that chloroprene is mutagenic is not supported by the 

overall evidence. Although there are structural similarities between chloroprene and 

1,3-butadiene or vinyl chloride, the toxicological evidence that supports possible 

modes of action demonstrates substantial differences between chloroprene, vinyl 

chloride, and 1,3-butadiene. Little discussion of critical uncertainties in relying on the 

mouse data from NTP (1998) to predict the potential for carcinogenic risk in humans 

is offered in the 2010 Review, given ample evidence of important pharmacokinetic 

differences between mice and other species. 

The weight-of-evidence evaluation supports a reclassification. Based on the limited 

evidence remaining to support the potential carcinogenicity of chloroprene, a more 

appropriate classification of chloroprene would be "suggestive evidence of 

carcinogenic potential." In any case, a clearer weight-of-evidence narrative is 

needed that addresses the current uncertainties. 

Deriving the Chloroprene IUR 

In the 2010 Review, EPA derived the current chloroprene IUR based on a number of 

assumptions that are not substantiated by the scientific evidence, contributing to 

overestimation of an already conservative risk estimate (i.e., one based on the most 

sensitive species, gender, and endpoint). Specifically, EPA based the chloroprene 

IUR on a composite estimate of risk based on multiple tumors observed primarily in 

mice, instead of relying on just the most sensitive endpoints in mice (lung tumors) 

which is consistent with standard EPA methods. EPA then assumed that the female 

mouse-based IUR was representative of continuous human exposure, and that lung 

tumors were a result of systemic rather than portal-of-entry effects; EPA also 

rounded up calculations at various stages of adjustment, and these were 

compounded. Finally, EPA applied an age-dependent adjustment factor (ADAF) 

based on insufficient data to support a claimed mutagenic MOA. All of these 

assumptions are not supported by the scientific evidence and contributed to 

unrealistic increases in the final IUR, as presented in the Ramboll Environ report 

submitted to EPA as part of OPE's Request for Correction. 

The most important correction of the IUR is that it should seek to be predictive of 

human response. At the time of the 2010 Review, Himmelstein et al. (2004a, 2004b) 

had published a paper that described a physiologically based pharmacokinetic (PBPK) 

model for chloroprene. The model provided a means to adjust the exposures 

associated with tumors in the mouse to corresponding human exposures, and the 

model integrates the available data that explain why the mouse is the most sensitive 

species and why humans would be comparatively much less sensitive to the effects of 

chloroprene exposure. The hypothesis that differences in pharmacokinetics are 

determinants of the observed species differences has been demonstrated for other 

chemicals reviewed by EPA, including vinyl chloride. In the 2010 Review, EPA 
36 

Written Testimony of Kenneth A. Mundt, PhD, FACE 11 

acknowledged that its results would be improved with the use of a PBPK model, but 

that all of the required data were not available. However, all of the quantitative data 

necessary to refine and verify the critical metabolic parameters for the existing peerreviewed PBPK model for chloroprene were published prior to the publication of the 

2010 Review. Since then, additional data have been published, and these newer 

findings further validate the model and its use in demonstrating consistency with the 

epidemiological evidence, and its use in deriving the chloroprene IUR (Thomas et al. 

2013, Yang et al. 2012, Allen et al. 2014). In particular, Allen et al. (2014) derived 

an IUR based on consideration of pharmacokinetic differences between mice and 

humans and estimated an IUR that was 100 times lower than EPA's value, using a 

method which integrates both the animal and human evidence. Importantly, 

consideration of the IUR reported by Allen et al. (2014) in comparison with IURs for 

known human carcinogens, such as vinyl chloride and 1,3-butadiene, is consistent 

with the stronger and more consistent epidemiological evidence of human 

carcinogenicity for these compounds compared to chloroprene. 

Ramboll Environ performed an updated analysis by applying the peer-reviewed 

published results from validated PBPK models (Yang et al. 2012) to arrive at an IUR 

that accounts for the known interspecies differences in pharmacokinetics. Standard 

EPA methodology and conservative assumptions were applied to estimate the 

potential cancer risks for chloroprene. The revised IUR is 1.1x 10·2 per ppm or 3.2 x 

10·6 per tJg/m3, which is of the same order of magnitude as the IUR derived by Allen 

et al. (2014), and which better reflects the scientific understanding of potential 

chloroprene cancer effects in humans. In contrast, the EPA derived an IUR for 

lifetime exposure to chloroprene of 5 x 10·4 per microgram per cubic meter (tJg/m3), 

a value approximately 156 times higher than what Ram boll Environ considers the 

best estimate using standard EPA methods and available data. The revised value 

also is consistent with the results from validated PBPK models and comparisons with 

other structurally relevant compounds, such as vinyl chloride and 1,3-butadiene, that 

are recognized as known human carcinogens. 

There is little scientific support for each of EPA's conservative assumptions and 

subsequent adjustments. Combining a fuller understanding of interspecies 

pharmacokinetic differences and validated PBPK models with the results from the 

strongest epidemiological data provides the scientific grounds for correcting the 2010 

IUR and calls into question the strength of the evidence to support a "likely to be 

carcinogenic to humans" classification. Similar adjustments should also be 

considered in estimating the chloroprene inhalation reference concentrations (RfC), 

as species- and strain-specific differences are noted. This will assure that policies 

and decisions resting on these toxicity values meet the test of sound science, 

transparent methods, and reproducible findings. 

Conclusions 

EPA's 2010 Review of chloroprene offers examples of several broader issues with the 

quality of IRIS Reviews including those of the NAS (NRC 2011, 2014), including 

evaluation of individual toxicological and epidemiological studies for quality, and 

transparency in weight-of-evidence integration to validly determine a chemical's 

potential carcinogenicity and derive accurate risk numbers. For chloroprene, the IUR 
37 

Written Testimony of Kenneth A. Mundt, PhD, FACE 12 

that EPA derived in the 2010 Review appears to be at least 100-fold inflated, and, 

based on a best-methods approach performed and documented by Ramboll Environ, 

over-estimated by as much as 156-fold. Risk assessments based on this IUR, such as 

the National Air Toxics Assessment, incorporate the overestimated value leading to 

grossly exaggerated human cancer risk predictions. This undoubtedly and 

unnecessarily triggers regulatory and legal action, as well as incites fear in the 

workers exposed to chloroprene, as well as those in the surrounding communities 

who may be exposed at much lower concentrations. 

As outlined above, the overestimation of the IUR is the product of several scientific 

shortfalls or errors, including misreading of the epidemiological evidence, the likely 

erroneous assumption that chloroprene is mutagenic, an under-appreciation and 

subsequent incomplete consideration of the large pharmacokinetic differences 

between the female mice and humans, as well as other issues. 

Scientifically, updating the IRIS Review of chloroprene is warranted, possibly 

including reconsideration of the carcinogenicity classification in light of a more 

accurate interpretation of the epidemiological evidence. However, and more urgently, 

a correction to the IUR is needed, based on the Ramboll Environ analysis provided to 

EPA in DPE's recent Request for Correction. The IUR published in the 2010 Review 

requires correction to address flaws that are consistent with the critique of the IRIS 

program by NRC. Specifically, an updated IUR should be based on the best available 

methodology as well as a valid, transparent, and systematic interpretation of the 

body of published evidence. Although there are variations in how IURs are derived, 

proper application of established EPA risk assessment methods - including the PBPK 

model to account for extreme interspecies differences should generate an IUR that 

is 100-150+ times lower than that published in the 2010 Review. The methods 

presented in the Ramboll Environ report could serve as a starting point, reducing the 

time and resources EPA otherwise would expend. 

Correction additionally is critical given that the IUR published in the 2010 Review is 

being used by EPA to support enforcement actions and underlies a class action 

lawsuit. The chloroprene example highlights deficiencies in the IRIS process that 

need to be addressed as soon as possible. 

Respectfully submitted, 

Kenneth A. Mundt, PhD, FACE 
38 

References 

Allen BC, Van Landingham C, Yang Y, Youk AO, Marsh GM, Esmen N, Gentry PR, 

Clewell III HJ, and Himmelstein MW. (2014). A constrained maximum likelihood 

approach to evaluate the impact of dose metric on cancer risk assessment: 

Application to b-chloroprene. Regulatory Toxicology and Pharmacology 70: 203-

213. 

Bukowski JA. (2009). Epidemiologic evidence for chloroprene carcinogenicity: 

Review of study quality and its application to risk assessment. Risk Analysis 

29(9): 1203-1216. 

13 

Bulbulyan MA, Margaryan AG, Ilychova SA, Astashevsky SV, Uloyan SM, Cogan VY, 

Colin D, Boffetta P, and Zaridze DG. (1999). Cancer incidence and mortality in a 

cohort of chloroprene workers from Armenia. International Journal of Cancer 

81( 1): 31-33. 

Bulbulyan MA, Changuina OV, Zaridze DG, Astashevsky SV, Colin D, and Boffetta P. 

(1998). Cancer mortality among Moscow shoe workers exposed to chloroprene 

(Russia). Cancer Causes and Control9( 4):381-387. 

Colonna M and Laydevant G. (2001). A cohort study of workers exposed to 

chloroprene in the department of Isere, France. Chemico-Biological Interactions 

135-136:505-514. 

Himmelstein MW, Carpenter SC, and Hinderliter PM. (2004a). Kinetic modeling of 

betachloroprene metabolism: I. In vitro rates in liver and lung tissue fractions from 

mice, rats, hamsters, and humans. Toxicological Sciences 79(1):18-27. 

Himmelstein MW, Carpenter SC, Evans MV, Hinderliter PM, and Kenyon EM. 

(2004b). Kinetic modeling of beta-chloroprene metabolism: II. The application of 

physiologically based modeling for cancer dose response analysis. Toxicological 

Sciences 79( 1): 28-3 7. 

Li SQ, Dong QN, Liu YQ, and Liu YG. (1989). Epidemiologic study of cancer 

mortality among chloroprene workers. Biomedical and Environmental Sciences 

2(2):141-149. 

Marsh GM, Youk AO, Buchanich JM, Cunningham M, Esmen NA, Hall TA, and Phillips 

ML. (2007a). Mortality patterns among industrial workers exposed to chloroprene 

and other substances: I. General mortality patterns. Chemico-Biological 

Interactions 166(1-3):285-300. 

Marsh GM, Youk AO, Buchanich JM, Cunningham M, Esmen NA, Hall TA, and Phillips 

ML. (2007b). Mortality patterns among industrial workers exposed to chloroprene 

and other substances: II. Mortality in relation to exposure. Chemica-Biological 

Interactions 166(1-3):301-316. 

NRC (National Research Council). (2014). Review of US EPA's Integrated Risk 

Information System (IRIS) Process. Washington, DC. National Academies Press. 

NRC (National Research Council). (2011). Review of the Environmental Protection 

Agency's Draft IRIS Assessment of Formaldehyde. Washington, DC: National 

Academies Press. 
39 

14 

NTP (National Toxicology Program). (1998). Toxicology and carcinogenesis studies 

of chloroprene (CAS No. 126-99-8) in F344 rats and B6C3F1 mice (inhalation 

studies). Public Health Service, U.S. Department of Health and Human Services; 

NTP TR-467. http://ntp.niehs.nih.gov/ntp/htdocs/L T)rpts/tr467 .pdf. 

Pell S. (1978). Mortality of workers exposed to chloroprene, Journal of 

Occupational Medicine 20:21-29. 

Rice JM and Boffetta P. (2001). 1,3-butadiene, isoprene, and chloroprene: Reviews 

by the IARC monographs programme, outstanding issues, and research priorities in 

epidemiology. Chemico-Biological Interactions 135-136:11-26. 

Thomas RS, Himmelstein, MW, and Clewell HJ III, Yang Y, Healy E, Black MB, and 

Andersen ME. (2013). Cross-species transcriptomic analysis of mouse and rat lung 

exposed to chloroprene. Toxicological Sciences 131(2): 629-640. 

doi: 10.1093/toxsci/kfs314 

U.S. EPA. IRIS Toxicological Review of Chloroprene (Final Report) (2010). U.S. 

Environmental Protection Agency, Washington, DC, EPA/635/R-09/010F, 2010. 

U.S. EPA. 2011 National Air Toxics Assessment (2015). U.S. Environmental 

Protection Agency, Washington, DC. https:/ /www.epa.gov/national-air-toxicsassessment/20 11-national-air-toxics-assessment 

Yang Y, Himmelstein MW, and Clewell HJ. (2012). Kinetic modeling of bchloroprene metabolism: Probabilistic in vitro-in vivo extrapolation of metabolism 

in the lung, liver and kidneys of mice, rats and humans. Toxicology in Vitro 

26:1047-1055. 
40 

15 

Attachment 
41 

@;fji§I:Ji4!1 ENVIRON 

John Vandenberg, PhD 

Director of Research at NCEA 

109 T.W. Alexander Drive 

Research Triangle Park, NC 27709 

Sent via e-mail 

RE: FOLLOW-UP TO THE MEETING AT RTP 

Dear Dr. Vandenberg, 

Thank you for setting up and orchestrating the "listening session" on Tuesday 

August gth, 2016 at your offices. Dr. Gentry and I appreciate the opportunity 

to presentthe findings from our independent review of chloroprene 's potential 

carcinogenicity, based on all available data and state-of-the-art methods for 

critically reviewing and synthesizing epidemiology, toxicology and mechanistic 

studies, and for integrating evidence .across these lines of inquiry. 

As discussed after our presentation of the science, we acknowledge and 

appreciate your explanation of the IRIS Program's resource constraints, the 

complex procedures in place for selecting substances for IRIS review or rereview, as well as what you described as the "full docket" of current and future 

IRIS reviews. Based on this feedback, we understand that the IRIS Program 

will not at this time undertake a new review of chloroprene - or consider any 

revisions to the risk numbers - primarily due to resource constraints. 

This, as you can understand, leaves our client, Denka Performance Elastomer, 

LLC (DPE), in a very difficult position, and unjustifiably so from a scientific 

standpoint. During our meeting, we outlined important new information 

demonstrating that an IRIS chloroprene IUR derived today would be vastly 

different and more compatible with other IURs for other chemicals. As we 

demonstrated during our meeting, properly employing validated PBPK models 

leads to an IUR for chloroprene that is more than 100-fold lower than the 

2010 IRIS value. In fact, the 2010 IRIS Review of Chloroprene astutely 

acknowledged this very flaw: "Ideally, a PBPK model for the internal dose(s) 

of the reactive metabolite(s) would decrease some of the quantitative 

uncertainty in interspecies· extrapolation; however, current PBPK models are 

inadequate for this purpose" (US EPA, 2010, Section 3) 1 The information and 

methods required for chloroprene now have been peer-reviewed, published1 

and validated, with similar models and methods applied by EPA in comparable 

risk evaluations (such as vinyl chloride). 

1 US EPA2010. Toxicological RevlewofChloroprene. In support of Summary Information on the 

Integrated Risk Information System. Washington, DC: U.S. Environmental Protection Agency. 

1/2 

ENVIRONMENT 

& HEALTH 

August23,2016 

Rambo!! Environ 

28 Amity Street 

Suite 2A 

Amherst, MA 01002 

USA 

T +1 413 8354350 

www.ramboll··environ.com 
42 

i;f,01:1i41"1 ENVIRON 

We also noted what we consider a misinterpretation of the body of epidemiological evidence, 

largely due to discounting the negative results published from the 2007 Marsh et al. study, 

which is also the strongest epidemiological study, in favor of results from much weaker studies. 

The integration of the entirety of epidemiological evidence supports the updated toxicology and 

mechanistic evidence indicating important and substantial differences between humans and 

mice, specifically in terms of metabolism, which are directly related to estimating the potential 

cancer risks for chloroprene. This no longer can be ignored. Taking the most up-to-date 

information into consideration in the context of using science to inform EPA policy and regulation 

is entirely consistent with the Agency's very public"mission statement" to ensure that "national 

efforts to reduce environmental risk are based on the best available scientific information." 2 

Without a commitment on the Agency's part to reexamine the 2010 IRIS assessment's IUR 

derivation in light of the new information, EPA and the Louisiana Department of Environmental 

Quality have advised DPE that it will be required to meet extremely stringent emissions limits, 

which may not be attainable, and that are not based on the best available science. We also have 

seen that the IUR is being used to inform important regulatory and other federal and state 

government actions, as well as public statements with respect to the possible cancer risks to 

people who live and work in the community in which our client's facility 1s located. 

Notwithstanding the IRIS Program's resource constraints, we genuinely look forward to any 

thoughts or ideas you or Dr. Cogliano might have with respect to how we might work 

collaboratively with you and the program office within EPA that is relying on the 2010 IRIS 

Assessment, to timely improve and update the IUR. The IUR for chloroprene (as well as actions 

that are derivative of that IUR) should be more in line with those of other substances, such as 

vinyl chloride, that provide stronger evidence than chloroprene of carcinogenicity in humans. 

We, too, will be exploring various available avenues, and will keep you informed. One possibility 

would be for us to file a requestfor correction (RFC). Our ultimate goal, as I initially mentioned 

to Dr. Cogliano when I f1rst approached him, is to improve the risk calculation based on currently 

available science and evidence-based processes, which have evolved since the completion of 

the 2010 C hloroprene Toxicological Review, and to do so in a way that creates the lowest 

demands on already limited resources. Thank you again, and I look forward to continuing our 

discussion. 

Yours sincerely 

Kenneth A. Mundt, PhD, FACE 

Health Sciences Practice Netv.ork Leader 

D +1 413 835 4360 

M +1 413 885 1345 

k m u ndt@ramboll.coiTt 

cc: Dr. Vincent Cogliano 

: https :/ /www.epa .gov/al:xl utepa/our- mission-and-what-we-do 

2/2 
43 

l;tJ#I:IfA' ENVIRON 

KENNETH A MUNDT 

Principal 

Dr. Kenneth Mundt is Ram boll's Global Health Sciences Practice 

Network Leader. He brings over 30 years of experience applying 

epidemiological concepts and methods to understand human health 

risks from environmental, occupational and consumer product 

exposures. 

Dr. Mundt specializes in the pragmatic interpretation of 

epidemiological evidence in evaluating disease causation and 

supporting science-based regulation and decision-making. 

Dr. Mundt served 11 years on the Graduate Faculty of the School of 

Public Health and Health Sciences, University of Massachusetts at 

Amherst. He received his PhD in Epidemiology at the University of 

North Carolina at Chapel Hill, and is a Fellow in the American College 

of Epidemiology. 

Epidemiological Studies 

Managed multidisciplinary teams in designing, conducting and 

interpreting occupational epidemiological studies of workers 

involved in rubber, porcelain, chemical and steel industries, as well 

as military and other professionals. 

Health Risks Evaluation and Communication 

Responded to observed and perceived health problems related to 

occupational, environmental and consumer product exposures. 

Teaching and Scholarship 

Frequent participant in scientific meetings, training courses, and 

litigation proceedings. Consistent publication record. 

Scientific Regulatory Support 

Provided scientific evaluation and support to various regulatory and 

policy processes, including oral and written testimony, statistical re· 

analysis of data from key studies, preparation of commentaries and 

technical communications, developing new research opportunities, 

critical review and meta-analyses of epidemiological evidence, 

integration of scientific evidence from diverse lines of inquiry, and 

organize and manage expert panels and topical symposia. 

Critical Reviews and Syntheses 

Comprehensively identified, systematically critically reviewed and 

synthesized the epidemiological literature on human health risks 

associated with numerous occupational, environmental and 

consumer product exposures. 

ENVIRONMENT 

& HEALTH 

Kenneth A Mundt 

kmundt@rarnboll.com 

+1 (413) 8354360 

Rambo!! Environ 

28 Amity Street 

Suite 2A 

Amherst, 01002 

United States of America 

PhD, Epidemiology 

University of North Carolina 

MS, Epidemiology 

University of Massachusetts 

MA, Englisll 

University of Virginia 

AB, English 

Dartmouth College 
44 

Chairman BIGGS. Thank you, Dr. Mundt. 

And now I recognize Dr. Bus for five minutes to present his testimony. 

TESTIMONY OF DR. JAMES BUS, 

SENIOR MANAGING SCIENTIST, EXPONENT 

Dr. BUS. Good morning. I am Dr. James Bus, and I’m a Toxicologist with the consulting firm Exponent. I will preface my comments by noting that the increasingly financially and other resource-constrained realities confronting our nation demands nothing less than a cost-effective, transparent and science-based evaluation and regulation of environmental chemicals. 

I will briefly highlight three major areas of concern with the IRIS 

program. First, IRIS has not effectively implemented the National 

Academy of Sciences recommendation that good risk assessment 

must start with good problem formulation. Second, IRIS use of 

chemical mode of action information to better inform its risk assessments is substantially flawed. And third, IRIS frequently does 

not effectively differentiate between the highest quality science and 

that of substantially lower quality in its evaluations. 

The National Academy has emphasized the importance of the 

question—what problems are we trying to solve?—as an absolute 

necessity for focusing the priorities of the IRIS program. Although 

IRIS has recently implemented problem formulation dialog with 

the public, the IRIS program has not effectively integrated this key 

concept into its overall prioritization processes. For example, 

human exposures to many, if not most chemicals, have been substantially reduced or constrained over the last several decades as 

a direct result of regulatory and/or industry product stewardship 

interventions, yet IRIS often overlooks this important progress as 

a screening mechanism to rule out the need for detailed evaluations. As is commonly said in the practice of toxicology, it is the 

dose that makes the poison. Thus, more realistic consideration of 

the relationships of human exposures to doses producing toxicity at 

much higher doses used in experimental toxicity studies must become a key consideration to answering the practical question of: do 

real-world exposures indicate a reasonable need for a detailed risk 

assessment evaluation? 

Turning to the second point of concern, and speaking as a toxicologist, extensive taxpayer investments into the toxicological 

sciences have yielded substantial advances in understanding how 

chemicals cause toxic effects in animals and in humans. Such mode 

of action information is essential to establishing the human health 

relevance of toxicity observed in cell or animal-based toxicity findings. In recognition of the value of mode of action science, the toxicology, risk assessment, and regulatory scientific communities have 

developed detailed frameworks for credible and transparent translation of these data into chemical risk assessments. While mode of 

action framework processes have long been included within EPA 

guidance procedures and are routinely and effectively used by the 

EPA’s Office of Pesticides, the IRIS program has yet to embrace 

their full practice. Thus, IRIS assessments consistently default to 

risk decisions that do not reflect the substantial added value of 
45 

mode of action science that has long been supported by taxpayer 

investments. 

Finally, the IRIS program has not implemented consistent criteria as have other EPA offices for appropriately waiting study 

quality as key to meaningful data integration. Too often, poorly 

conducted and/or described studies carry equal weight to those of 

far higher quality in the final risk decision. For example, the recent 

IRIS evaluation of trichloroethylene, a commercially important solvent, relied on published studies from a single university-based laboratory that were subsequently subject to three published error correction that still have not clarified the experimental findings. In 

addition, not only were the original data from these problematic 

studies not available for review by the EPA, the study findings also 

were not reproduced in two much higher-quality studies. In the 

case of trichloroethylene, the EPA decision to rely on the lowerquality study to drive the risk assessment has created additional 

environmental remediation costs potentially in the hundreds of millions to even billions of dollars. 

Thank you for the opportunity to share my personal perspectives 

on some of the more serious concerns that continue to plague the 

IRIS program. Although the IRIS program has recently introduced 

new evaluation tools aimed at improving the quality of its evaluation, the IRIS program, given its past reluctance to embrace substantive change, will be challenged to efficiently and effectively 

evolve into a program that meets the expectations of delivering 

timely, credible and science-based assessment of environmental 

chemicals. 

Thank you. 

[The prepared statement of Dr. Bus follows:] 

Chairman BIGGS. Thank you, Dr. Bus. 
46 

United States House of Representatives Hearing: "Examining the Scientific and Operational Integrity of 

EPA's IRIS Program", September 6, 2017, 2318 Rayburn House Office Building, Washington, DC. 

Committee on Science, Space, and Technology's Subcommittee on Environment and Subcommittee on 

Oversight. 

Oral presentation of James S. Bus, PhD DABT ATS, Exponent, Inc. (support provided by the American 

Chemistry Council) 

Good morning. I am Dr. James Bus, and I am a toxicologist with the consulting firm Exponent. I must 

preface my comments by noting that the increasingly financially and other resource-constrained realities 

confronting our nation demands nothing less than a cost-effective, transparent and science-based 

evaluation and regulation of environmental chemicals. 

I will briefly highlight three major areas of concern with the IRIS program. First, IRIS has not effectively 

implemented the National Academy of Sciences recommendation that good risk assessment must start 

with good problem formulation. Second, IRIS use of chemical mode of action information to better 

inform its risk assessments is substantially flawed. And third, IRIS frequently does not effectively 

differentiate between highest quality science and that of substantially lower quality in its evaluations. 

The National Academy has emphasized the importance the question "What problems are we trying to 

solve?" as an absolute necessity for focusing the priorities of the IRIS program. Although IRIS has 

recently implemented problem formulation dialog with the public, the IRIS program has not effectively 

integrated this key concept into its overall prioritization processes. For example, human exposures to 

many if not most chemicals have been substantially reduced or constrained over the last several 

decades as a direct result of regulatory and/or industry product stewardship interventions. Yet, IRIS 

often overlooks this important progress as screening mechanism to rule out the need for detailed 

evaluations. As is commonly said in the practice of toxicology, it is "the dose that makes the poison". 

Thus, more realistic consideration of the relationships of human exposures to doses producing toxicity 

at much higher doses used in experimental toxicity studies must become a key consideration to 

answering the practical question of: "Do real-world exposures indicate a reasonable need for a detailed 

risk assessment evaluation?" 

Turning to the second point of concern, and speaking as a toxicologist, extensive taxpayer investments 

in toxicological sciences have yielded substantial advances in understanding how chemicals cause toxic 

effects in animals and humans. Such mode of action information is essential to establishing the human 

health relevance of toxicity observed in cell- or animal-based toxicity findings. In recognition of the value 

of mode of action science, the toxicology, risk assessment and regulatory scientific communities have 

developed detailed frameworks for credible and transparent translation of these data into chemical risk 

assessments. While mode of action framework processes have long been included within EPA guidance 

procedures, and are routinely and effectively used by the EPA Office of Pesticides, the IRIS program has 

yet to embrace their practice. Thus, IRIS assessments consistently default to risk decisions that do not 

reflect the substantial added value of mode of action science that has long been supported by taxpayer 

investments. 

Finally, the IRIS program has not implemented consistent criteria, as have other EPA offices, for 

appropriately weighting study quality as key to meaningful data integration. Too often poorly 
47 

conducted and/or described studies carry equal weig~t to those of far higher quality in the final risk 

decisions. For example, the recent IRIS evaluation of trichloroethylene, a commercially important 

solvent, relied on published studies from a single university-based laboratory that were subsequently 

subject to three published error corrections that have still not clarified the experimental findings. In 

addition, not only were the original data from the problematic studies not available for review by EPA, 

the study findings also were not reproduced in two much higher quality studies. In the case of 

trichloroethylene the EPA decision to rely on the lower quality study to drive the risk assessment has 

created additional environmental remediation costs potentially in the hundred's of millions to even 

billions of dollars. 

Thank you for the opportunity share my personal perspectives on some of the more serious concerns 

that continue to plague the IRIS program. Although the IRIS program has recently introduced new 

evaluation tools aimed at improving the quality of its evaluations, the IRIS program, given its past 

reluctance to embrace substantive change, will be challenged to efficiently and effectively evolve into a 

program that meets expectations of delivering timely, credible and science-based risk assessments of 

environmental chemicals. 
48 

James Bus, PhD, DABT, Fellow ATS 

Senior Managing Scientist 

Professional Profile 

Dr. James Bus is a Senior Managing Scientist in Exponent's Health Science Center for 

Toxicology and Mechanistic Biology. Dr. Bus has over 35 years of toxicology experience 

focused on research and evidence-based literature analyses informing potential health risks 

associated with chemical and pesticide exposures. He offers chemical specific and strategic 

toxicology expettise addressing development, stewardship, and regulatory needs to individual 

industry clients and business cons01tia and government and non-governmental agencies. Dr. 

Bus provides expertise in design, implementation, and interpretation oftoxicity tests and mode 

of action and dose response/exposure evaluations fiuthering translation of toxicology findings to 

risk assessment. His expettise includes target-organ and endpoint-specific modes of action, and 

specific toxicity of chemicals including chlorinated organics, ethylene glycol and glycol ethers, 

aromatic derivatives benzene, styrene, aniline and others, and pesticides such as 2,4-D. His 

research interests include toxicokinetic mechanisms mediating dose-dependent expression of 

chemical toxicity. He has over 120 research and review publications and has received both the 

Achievement Award and Founder's Award from the Society of Toxicology in recognition of his 

research and leadership in toxicology. 

Dr. Bus' experience includes over 23 years as a consulting toxicologist in the Toxicology and 

Environmental Research and Consulting unit of The Dow Chemical Company. He previously 

held positions at the Upjohn Company, the Chemical Industry Institute of Toxicology, and as 

Assistant Professor of Toxicology at the University of Cincinnati. Across all of these positions 

he focused on providing consulting and research expertise in support of health risk evaluations 

of environmental and industrial chemicals and pesticide and phmmaceutical products. 

Dr. Bus has served as President of the Society of Toxicology, the American Board of 

Toxicology, and the Academy of Toxicological Sciences, and as a Director of the Intemational 

Union ofToxicology. He has served on various toxicology-related advisory Boards and Panels 

including: ILSI-HESI and ILSI Research Foundation; the American Chemical Council LongRange Research Strategic Science Team; both EPA ORD B'oard of Scientific Counselors and 

Chartered Science Advisory Board; theN ational Academy of Sciences Board on Environmental 

Studies and Toxicology; the National Institutes of Environmental Health Sciences/National 

Toxicology Program Board of Scientific CounselOJs (Technical Reviews Subcormnittee); the 

FDA National Center for Toxicology Research Science Advisory Board; and Board of Directors 

of the Hamner Institutes. In addition, Dr. Bus served on the Chemical Substances (TL V) 

Committee of the American Conference of Governmental and Industrial Hygienists, the 

Program Committee of the Toxicology Fmum, and advisory boards ofthe University of 

Michigan and Purdue University. He is an Adjunct Professor in the Department of 

Pharmacology and Toxicology at Michigan State University. 

08/17 
49 
50 

And now I recognize Dr. Burke for five minutes to present his 

testimony. 

TESTIMONY OF DR. THOMAS BURKE, PROFESSOR, 

BLOOMBERG SCHOOL OF PUBLIC HEALTH, JOHNS HOPKINS 

Dr. BURKE. Thank you for the opportunity to address the Subcommittees today. I’m Tom Burke, Professor at Johns Hopkins, and 

my views are my own. They don’t reflect the university. 

First, as a former Houstonian and graduate of the University of 

Texas School of Public Health in Houston, my thoughts are with 

all those impacted by Hurricane Harvey. 

This hearing is particularly timely as Texans work to recover, restore drinking water and housing, and evaluate the risks from contaminated floodwaters. 

Before joining Johns Hopkins, I worked on the frontlines as an 

environmental and health official for the State of New Jersey, serving three governors. I’ve also served on the National Academy of 

Sciences Board on Environmental Studies and Toxicology, the EPA 

Science Advisory Board, and the Board of scientific Counselors. 

From 2015 to 2017, I served as the EPA Science Advisor and Deputy Assistant Administrator for Research and Development. 

Now, the capacity to evaluate the hazards of toxic chemicals is 

essential to protecting our public health. It’s essential for agencies, 

public officials, and businesses alike to assure clean air and safe 

water, to respond to emergencies, and to protect our workers and 

communities. 

The EPA IRIS program is a cornerstone of our national public 

health capacity. IRIS is charged with the daunting task of synthesizing enormous amounts of scientific information to identify the 

potential for a chemical to cause adverse health effects. The program provides a consistent and comprehensive source of toxicity 

data, not just for agency programs but for the regions and state officials, business and industry, and the public. 

IRIS is not a regulatory program but the assessments provide essential scientific guidance for agency decisions. Not surprisingly, 

they’re controversial. Don’t like the regulation? Attack the science. 

There’s an important distinction between the IRIS assessment 

process and the ultimate risk management decision. The assessments provide insights on the magnitude of risks but they do not 

tell us what level of risk is acceptable nor do they tell us how to 

manage risk. Ultimately, the regulatory options are the responsibility of the program offices and the Administrator. 

Now, there are challenges to IRIS. The demand for information 

about the safety of chemicals is constantly growing. One of our 

greatest environmental challenges is the lack of basic information 

about health effects. The 2016 bipartisan Lautenberg Chemical 

Safety Act represents a great step forward but the key to the success will be the scientific capacity of EPA. 

Unfortunately, there are inherent scientific uncertainties in toxicology and epidemiology, as we’ve heard. They present difficult 

challenges to IRIS. For example, does cancer in a laboratory test 

animal mean that chemical will cause cancer in humans? If epidemiology studies give conflicting results, which one do we choose? 

Rigorous stakeholder and peer review is built into the IRIS process 
51 

and it’s essential for producing credible results and addressing uncertainties. 

Now, over the past few years there’s been great progress in improving IRIS. As was mentioned, the 2011 formaldehyde report 

presented a roadmap to improve the process by increasing transparency in the review of evidence. The 2014 follow-up report from 

the National Academies noted the progress. As has been already 

stated, the GAO and the EPA Science Advisory Board have also 

made note of the enormous forward progress that the program has 

taken. 

Now, in conclusion, EPA is a science-based agency. Ultimately, 

the success and credibility of EPA decision depends upon the quality and integrity of the science behind them. The core mission of 

EPA is to protect public health. IRIS has a unique and essential 

role in supporting that mission. 

I’d like to close on a personal note. I’d like to acknowledge the 

great people of IRIS and EPA Office of Research and Development. 

They’re dedicated public servants and world-class scientists. They 

take on the toughest environmental challenges we face from the 

dust of the World Trade Center and faucets of Flint to the toxic 

waters of Katrina and Harvey. They have worked selflessly to protect our Nation’s environment and public health. Our health depends on them; our health depends on the IRIS program. 

Thank you for the opportunity to speak with you today. 

[The prepared statement of Dr. Burke follows:] 
52 

Testimony of Thomas A. Burke, PhD, :tvfPH 

Jacob I and Irene B. Fabrikant Professor and Chair in Health Risk and Society 

Director, Risk Sciences and Public Policy Institute 

Johns Hopkins University 

Bloomberg School of Public Health 

U.S. House of Representatives 

Committee on Science, Space, and Technology 

Subcommittee on Environment and Subcommittee on Oversight 

Hearing on Examining the Scientific and Operational Integrity of EPA's IRIS Program 

September 6, 2017 
53 

Thank you for the opportunity to address the Subcommittees on Environment and 

Oversight at today's hearing on EPA's IRIS Program. I am Dr. Thomas Burke, Professor 

at the Johns Hopkins University Bloomberg School of Public Health. I am also Director 

of Johns Hopkins Risk Science and Public Policy Institute. 

First, as a former Houstonian and graduate of the University ofTexas School of Public 

Health, I want to express my deep sympathy for all those impacted by Hun-icane Harvey. 

Please know that I, and the public health community at Johns Hopkins and throughout the 

country, stand ready to assist in any way we can. This hearing is particularly timely, as 

Texas and Louisiana work to protect public health, restore safe drinking water, and 

evaluate the risks from contaminated floodwaters and chemical releases. 

I speak today as an individual, informed by a career devoted to public health and 

protecting our environment. Before joining the faculty at Johns Hopkins I worked as both 

an environmental and health official for the State ofNew Jersey, serving three governors, 

both republicans and democrats. I have served as a member of the National Academy of 

Sciences Board on Environmental Science and Toxicology, and a Member of the EPA 

Science Advisory Board and Board of Scientific Counselors. I also served as Chair of 

the National Academy of Sciences Committee on Improving Risk Analysis Approaches 

Used by the U.S. EPA. Perhaps most relevant to today' s topic, from January 2015 to 

January 2017 I served as the EPA Science Advisor and Deputy Assistant Administrator 

for the Office of Research and Development. 

2 
54 

The capacity to evaluate the hazards of toxic chemicals is essential to protecting our 

public health. It is essential for clean air and safe drinking water, for responding to 

emergencies, and protecting our communities from harmful exposures. It is equally 

essential for business, industry, and agl'iculture to provide safe products, protect workers, 

and preserve the safety of our food supply. 

The IRIS Program 

The EPA IRIS Program is a cornerstone of our national capacity to protect public health. 

IRJS, within the National Center for Environmental Assessment (NCEA), is charged with 

tht: daunting task of synthesizing enormous amounts of scientific information to identify 

the potential for a chemical to cause adverse health effects. The program was started in 

1985 to provide a consistent scientific source of toxicity data for the many program 

offices throughout the Agency and the broader regional and state environmental 

protection efforts. 

IRIS is not a regulatory program, but the assessments provide essential scientific 

guidance for Agency decisions. There is an important distinction between the IRIS 

assessment process and the ultimate risk management decision. They provide insights on 

the magnitude of risks---but they do not tell us what level of risk is "acceptable". Nor do 

they tell us how to manage or reduce risks. Ultimately, regulatory options are the 

responsibility of the program offices and the Administrator. 
55 

Challenges to IRIS 

The demand for infmmation about the safety of chemicals is constantly growing. 

Although the actual number is often debated, there are thousands of chemicals in 

commerce and in our environment. One of our greatest environmental challenges is the 

lack of basic information on the toxicity and health effects of these chemicals. The 2016 

bipartisan passage ofthe Frank R. Lauten berg Chemical Safety for the 21 '

1 Century 

Act represents a step fmward, but the key to success will be the scientific capacity of 

EPA. IRIS is essential to that capacity. 

The IRIS process includes weighing the scientific evidence that a chemical may cause 

adverse impacts such as developmental and reproductive effects or cancer. IRIS 

assessments can also be the starting point for many of the agency's most difficult and farreaching regulatory decisions about chemical pollutants. Not surprisingly, they are also 

controversial. 

Unfortunately, there are inherent uncertainties in toxicology and epidemiology studies 

that present difficult challenges to IRIS assessments. For example, does finding of cancer 

in laboratory test animals mean that exposure will cause cancer in humans? If 

epidemiology studies give conflicting results for an adverse health effect, which study do 

you choose to characterize the hazard? These vexing questions arc examples of the 

challenges faced by IRlS scientists charged with evaluating and presenting the evidence. 

Rigorous stakeholder and peer review is built in to the IRIS process and is an essential to 

4 
56 

producing credible results, addressing uncertainties, and explaining the scientific basis for 

conclusions. 

The IRIS program is challenging both from a management and science perspective. Over 

the past few years there has been a tremendous commitment to improvement. This 

progress is ret1ected in reviews by the National Academies of Science (NAS), the 

Government Accountability Office (GAO), and the EPA Science Advisory Board (SAB). 

The 2011 NAS review of the IRIS Draft Formaldehyde Assessment presented a roadmap 

to improve the process by increasing transparency and improving the systematic review 

and of evidence. ( 1) The follow up NAS repmt in 2014 credited the program for making 

steady progress in addressing the recommendations for improvement. The GAO also 

made recommendations for improvements and has recently noted the progress of the IRIS 

program. (2) Most recently, the EPA SAB expressed their strong support for the program 

in a letter to EPA Administrator Pruitt. The Board recognized the progress in responding 

to NAS recommendations, and noted significant "impactful changes" that "constitute a 

virtual reinvention ofiRIS". 

Conclusion 

EPA is a science-based agency. Ultimately the success and credibility ofEP A decisions 

depends upon the quality and integrity of the science behind them. The core mission of 

EPA is to protect public health. IRIS has a unique and essential role in supp01ting that 

mission, and the public health efforts of our states and tribes. 

5 
57 

I would like to close on a more personal note. During my time at the agency l came to 

know the great people ofEPA ORD and IRIS. They are dedicated and talented public 

servants and world-class scientists. Their work goes far beyond the tedium IRIS 

document preparation. They are there to take on the toughest environmental challenges 

we face. From the dusts of the World Trade Center and the faucets of Flint; to the toxic 

waters of Katrina and Harvey; they are there, working selflessly to protect our Nation's 

environment and public health. Our health depends on them. 

Thank you for this opp01tunity to speak with you today. 

I . National Academies of Science (20 II). Board on Environmental Science and 

Toxicology, Review of the Environmental Protection Agency's Draft IRIS's Assessment 

of Formaldehyde. Washington, DC: National Academy Press 

2. National Academies of Science (2009). Board on Environmental Science and 

Toxicology. Committee on Improving Risk Analysis Approaches Used by the U.S. 

Environmental Protection Agency. Scismce and Deci§ions Advancing Risk Assc_:!)~nent. 

Washington, DC: National Academy P!'ess. 

3. GAO (2017) Transforming EPA's Process for Assessing and Controlling Toxic 

Chemicals 

http://www.gao.gov/highrisk/transfortning epa and toxic chemicals/why did study#t=o 

Q 

4. EPA SAB (2017) Science Advisory Board comments on EPA's response to 

recommendations on the Integrated Risk Information System. Letter to Administrator E. 

Scott Pruitt, September 1, 2017. 

https://yosemite.epa.gov/sab/sabproduct.nsti'LookupWebReportsLastMonthBOARD/A9 

A9ACCE42B6AAOE85258!8E004CC597/$File/EP A-SAB-1 'Z.:::008.pdf 

6 
58 

Thomas A. Burke, Johns Hopkins University Bloomberg School of Public Health 

Thomas A. Burke, PhD, MPH, is the Jacob I and Irene B. Fabrikant Professor and Chair 

in Health Risk and Society at Johns Hopkins University Bloomberg School of Public 

Health, Department of Health Policy and Management. He holds joint appointments in 

the Department of Environmental Health Sciences and the School of Medicine 

Depatiment of Oncology. He is also Director of the Johns Hopkins Risk Sciences and 

Public Policy Institute. Dr. Burke was nominated by President Barack Obama to serve as 

EPA Assistant Administrator for the Office of Research and Development. From January 

2015 until January 2017 Dr. Burke was the EPA Science Advisor and Deputy Assistant 

Administrator for Research and Development. His research interests include 

environmental epidemiology and surveillance, evaluation of population exposures to 

environmental pollutants, assessment and communication of environmental risks, and 

application of epidemiology and health risk assessment to public policy. Before joining 

the University faculty, Dr. Burke was Deputy Commissioner of Health for the State of 

New Jersey and Director of Science and Research for the New Jersey Depatiment of 

Environmental Protection. In New Jersey, he directed initiatives that influenced the 

development of national programs, such as Superfund, the Safe Drinking Water Act, and 

the Taxies Release Inventory. Dr. Burke served as a member of the National Academy of 

Sciences Board on Environmental Studies and Toxicology. He was Chair of the National 

Academy of Sciences Committee on Improving Risk Analysis that produced the report 

Science and Decisions, and chaired the NAS Committee on Human Biomonitoring for 

Environmental Toxicants and the Committee on Toxicants and Pathogens in Biosolids 

Applied to Land. He also served on the NAS Committee on the Toxicological Effects of 

Methylmercury. He is a Fellow of the Society for Risk Analysis and a lifetime National 

Associate of the National Academies. He was Inaugural Chair of the Advisory 

Committee to the Director of the CDC National Center for Environmental Health and a 

member of EPA Science Advisory Board and Board of Scientific Counselors. Dr. Burke 

received his BS from St. Peter's College, his MPH from the University of Texas and his 

PhD in epidemiology from the University of Pennsylvania. 
59 
60 

Chairman BIGGS. Thank you, Dr. Burke, appreciate that. I appreciate the testimony of all of you, and I now recognize myself for 

five minutes to ask questions, and I’ll start with Dr. Mundt. 

Dr. Mundt, in your testimony, you talked about the National Air 

Toxic Assessment and the findings and impacts that those findings 

had, and I’m wondering, you mentioned specifically precipitated— 

the NATA findings precipitated adverse public opinion, enforcement actions and a class-action lawsuit, all of which potentially 

have serious economic implications for DPE and the community. 

Can you tell us what impact that had with—and how it relates to 

IRIS? 

Dr. MUNDT. Certainly. The NATA enforcement action requires an 

exposure standard which is unattainable, largely because it used in 

its calculations the inhalation unit risk that we believe is at least 

100-fold inflated from what the best scientific methods and processes would suggest. So I think the root of that particular problem 

arises with the erroneous derivation or the poor derivation of the 

IUR and then using it in a calculation to determine at what levels 

humans can safely be exposed. 

Chairman BIGGS. And I’ll continue with Dr. Mundt. The Science 

Committee has been committed to ensuring that the science of EPA 

is open and available to the American people, and that’s why we 

passed the HONEST Act, which would require science that EPA 

uses to make decisions to be publicly available. In your experience, 

does the IRIS program live up to that transparency in science? 

Dr. MUNDT. My experience with IRIS has been primarily with 

the chemicals chloroprene and formaldehyde. The reviews of both 

of those, at least the draft review for formaldehyde, were from 

2010. And of course, the NAS reacted also to the formaldehyde 

IRIS draft report identifying many of its problems. So I would say 

that yes, at least in 2010, there were significant problems that 

have led to more serious misinterpretations of the science and 

probably hardships for those who are impacted by those regulatory 

decisions. 

I hear a lot about progress being made and good intentions, and 

I look forward to seeing new IRIS assessments that have embraced 

all of those recommendations and quality improvements, but to 

date, I’m really focusing on what I have seen and what has been 

relied upon from some of the earlier IRIS assessments. 

Chairman BIGGS. And Dr. Bus, in your testimony, you indicated 

that IRIS frequently does not effectively differentiate between highest quality science and that a substantially lower quality in its 

evaluations. Can you tell us how that might impact the regulatory 

environment of EPA and how we distinguish between the highest 

quality science and the lowest quality? 

Dr. BUS. Certainly, and thank you for the question. With respect 

to quality assessments, there are a number of mechanisms and 

tools that have been used across the agency, not necessarily specific 

to IRIS but to other programs of the agency, that are available for 

rating the quality of the science. Also, the EPA has made extensive 

investment in terms of development of what they call good laboratory practices and setting up of guidelines for how chemicals should 

be tested. Those studies are generally regarded as having the highest quality. 
61 

But yet often when those studies are considered in the overall 

context of IRIS evaluation, you find as in the case of trichloroethylene, the default was to a study conducted by a single laboratory that turned out not to be reproduced under two conditions of 

studies conducted by good laboratory practices and using EPA 

guidelines for conduct of those studies. The implications of that obviously is incredibly important because depending on what science 

you use will make a big difference in terms of the outcome of the 

ultimate risk values that will be derived by the IRIS program, and 

that of course then ultimately drive the final risk assessment, 

which I mentioned in the case of trichloroethylene can translate to 

a very large economic impact. So in the case of trichloroethylene, 

there are many Superfund sites that had been remediated under 

the previous trichloroethylene remediation programs that had been 

regarded as now an acceptable point of remediation, with this new 

assessment conducted by trichloroethylene by the IRIS program, 

many of those sites now are facing reopening, each one of them 

costing in the range of several hundred thousand dollars to remediate to the new level identified by IRIS, and you spread that over 

the range of about a thousand additional sites that have been to 

have trichloroethylene associated with them, you can see the dollars add up very rapidly. 

But most importantly, that really brings home the message of 

why it’s important that the agency has the proper expertise and 

means and review to use the highest quality science because the 

implications are important. Thank you. 

Chairman BIGGS. Thank you. 

And now my time is expired and so I’ll recognize the gentlewoman from Oregon, Ms. Bonamici. 

Ms. BONAMICI. Thank you, Mr. Chairman, and thank you to the 

witnesses. 

Dr. Burke, I’m concerned about this Committee’s lack of diligent 

oversight of the agencies in its jurisdiction since President Trump 

took office in January. In your opinion, how could this Committee 

best provide constructive oversight of the IRIS program with the 

goal of protecting public health of the American people? For example, are there informative witnesses we would benefit from hearing 

from as we try to learn more about the IRIS program? 

Dr. BURKE. Thank you very much for the question, and yes, there 

are. IRIS has a daunting task, as I mentioned, and there are many 

members of the scientific community including the National Academy of Sciences, the Board on Environmental Studies, as I mentioned, that have been key to making sure IRIS documents may be 

the most scrutinized and peer-reviewed scientific documents the 

agency has ever produced. There is a tremendous review process, 

and there is a tremendous commitment to progress. We’ve seen a 

lot of change, as has been mentioned here, and I think you need 

to get the right kind of folks who have been involved in that 

change before you to really understand not just how important 

IRIS is but all the changes that have been made to solidify it, to 

listen to the comments of people like my colleagues here and to 

make sure the science is improved in a constant way. 

Ms. BONAMICI. Thank you, Dr. Burke. And continuing, the mission of the EPA is to protect human health and the environment, 
62 

and we know that, and you’ve served as a Science Advisor for EPA, 

and you’ve been an environmental public health professional your 

entire career, so I’d like to hear your opinion about the general direction now in this Administration with EPA Administrator Pruitt. 

Recently we’ve heard actions—we’ve heard about actions at the 

EPA that are raising serious concerns including barring EPA scientists from attending scientific conferences, censoring use of the 

word ‘‘climate change,’’ politicizing the allocation of scientific 

grants, rejecting the conclusion of EPA scientists in banning some 

harmful chemicals. So Dr. Burke, many anti-science actions seem 

to be driving decisions at the EPA, so will you please discuss the 

public health implications of that for individuals across the country 

in light of these actions. 

Dr. BURKE. Thank you for that question. It was a really comprehensive one. But I can address the public health issues and a 

concern of the public health community. Obviously there’s many 

great debates about the application of science. We hear this today 

in IRIS, but across the board, and I think it’s important that we 

follow the evidence. But what I’m concerned about in this quest for 

regulatory relief is that public health has been the collateral damage here, that we really have taken our eye off the ball and the 

primary mission of EPA. It’s a public health agency, and the 

science is there to provide the foundations of that public health 

agency. 

Ms. BONAMICI. Thank you very much, and I appreciate that. I’ve 

been on this Committee my entire time in Congress, and we’ve had 

many conversations about public health, and I share your concerns 

about losing focus on that important part of the EPA’s mission. 

And I wonder if you—since the time you started at the EPA in 

2015 and left earlier this year, how did the IRIS program change 

during your time with the agency during that period of time? 

Dr. BURKE. Thank you for that question too. As my colleagues 

know, I’ve been involved in the National Academy overview of— 

and oversight of the IRIS process, and I am aware that there have 

been historical problems in the presentation of evidence and the 

management, and I worked like crazy to make sure we have the 

best people, that we listen to the Academy, that we begin to address the issue of problem formulation, which actually was part of 

a report that I chaired at the Academy to improve the IRIS process, and so I worked to get the best people there, to make sure we 

have the best scientific applications of systematic review, to address many of the concerns that you heard today, and the program 

is on a wonderful, positive trajectory. 

Ms. BONAMICI. Thank you. I appreciate your work. 

Mr. Chairman, this hearing really seems incomplete without the 

participation of the EPA to answer questions about the IRIS program and how the Administration will prioritize the protection of 

health of the American people. There are many important environmental policies and public health issues that the Committee should 

be addressing: the effects of sea-level rise, ocean acidification, air 

quality—we’re experiencing that in my home State of Oregon right 

now with terrible wildfires—coastal resiliency efforts, the broad 

public health impacts of climate change, but this year the Committee has not hosted a single EPA official to testify about these 
63 

important matters. It’s unacceptable for this Committee to cede its 

jurisdiction and responsibilities to provide oversight of the federal 

agencies that are funded by our constituents. We should not go 

through an entire year without having an EPA official testify before this Committee, so I look forward to working with the Chairman and Chairman Smith. I hope we can get an Administration official to appear before this Committee as soon as possible. 

Thank you, Mr. Chairman. I yield back. 

Chairman BIGGS. The gentlewoman’s time is expired. 

The Chair recognizes Mr. LaHood. 

Mr. LAHOOD. Thank you, Mr. Chairman, and I want to thank the 

witnesses for your valuable testimony here today. 

Dr. Mundt, one of the intended steps in the IRIS process is independent expert peer review. I wanted to ask you, do you find that 

this peer review process adequately facilitates discussion from all 

relevant stakeholders, and particularly as you look at how IRIS utilizes or does not utilize independent third party? 

Dr. MUNDT. Thank you. I think peer review in general is subject 

to the quality of the individuals selected and the amount of energy 

and efforts that they put into that peer review. This is true for published literature as well. Journal articles are subject to peer review 

but the quality of that varies from individual to individual. 

I assume that the same is true with the IRIS program, that peer 

review panels have varied in terms of their quality, and maybe 

more specifically in terms of their expertise. I’ve found with formaldehyde and with chloroprene there to be inadequate peer review 

support on the epidemiological literature and its interpretation. So 

I think that can be remedied. I think, though, that it will require 

more systematic assignment of peer reviewers and perhaps even 

provide some standard expectations or guidance that those peer reviewers deliver upon so that obvious errors or bigger problems or 

questions of greater concern that deserve scientific debate can be 

identified earlier in the process and not only after the final drafts 

have been made public. 

Mr. LAHOOD. Thank you. And Dr. Bus, do you want to comment 

on that also? 

Dr. BUS. Thank you, and I would agree certainly that peer review is a very important aspect of the overall program, and one of 

the real challenges because peer review is often conducted by individuals from the scientific community who are essentially serving 

as a labor of love in terms of it’s not their full-time job requires 

that they have adequate time by way of example to prepare for 

these types of reviews. So I can describe a review if you want an 

illustration of has the agency and the IRIS program really learned 

its lessons in terms of valuing that input. Two reviews, which were 

just conducted 3 weeks ago, the actual materials of the entire two 

reports for them to review were presented to them just 4 weeks before they were scheduled to deliver their final opinion. In my mind, 

that’s woefully inadequately. 

Secondly, another example in terms of does the IRIS program, 

have they really understood that it’s important to value the input 

of outside comment to their overall assessment. The year before 

those same reviews were conducted, they actually correctly held a 

public session to solicit public input. At that time, their own invited 
64 

experts from the National Academy of Sciences indicated that the 

key endpoint that they were going to use for those evaluations definitely needed the consultation of an expert pathologist. One year 

later, this program was reviewed just 3 weeks ago by the EPA 

Science Advisory Board and it received severe criticism—this is a 

matter of public record—because the agency, the IRIS program had 

failed to follow up on that advice from their own National Academy 

consultant expert invited a year before. So that’s an example of 

where although the IRIS may be talking going down the correct 

road, they still have a lot of need to actually put that into action, 

and it’s not evident at least to date. Even as of events occurring 

just in the last several weeks that the IRIS program truly has reflected the advances that they are promoting and as claimed as 

successes, for instance, by way of to their presentation to the EPA 

Science Advisory Board. 

Mr. LAHOOD. Thank you, Dr. Bus. 

Dr. Mundt, I mentioned in my opening statement that IRIS is 

currently operating without specific statutory authority that would 

hold the program accountable. Do you believe IRIS would benefit 

from statutory guidance from Congress? And as a follow-up on 

that, what else can Congress do to help ensure toxicology risk assessment is reliable and transparent, particularly with the backdrop of the National Academy of Science’s study and also the GAO 

study? 

Dr. MUNDT. Thank you. I think it’s a challenging question, and 

the solution is not immediately apparent. However, scientists in 

general are striving for more or less one thing, that is, understanding the science and incorporating the best science, and so I 

think if statutory support for deriving the best science could work, 

then yes, of course, it would. But what this usually means is adequate time, as Dr. Bus mentioned, for proper review, the right scientists who are knowledgeable about the key topics, and also support for engagement, that is, all of the scientific interests and communities. I’m frequently referred to as an industry scientist but I’m 

really not. I’m an independent scientist looking at the science and 

often my understanding of the science is as great as anyone’s having looked deeply into it yet that is often not welcomed in the circles where these issues have been debated at EPA and specifically 

at IRIS. 

Mr. LAHOOD. Thank you. 

Thank you, Mr. Chairman. 

Chairman BIGGS. Thank you. 

The Chair recognizes the gentleman from Virginia, Mr. Beyer. 

Mr. BEYER. Mr. Chairman, thank you very much, and thank you 

all for the testimonies. It’s very interesting. 

Dr. Burke, Dr. Bus identified three problems with IRIS, and the 

first was that they don’t use—they’re not good with problem formulation, and perfect sense. Do real-world exposures indicate reasonable need for a detailed risk assessment evaluation. Do you agree 

with his assessment? Is there some reason why IRIS isn’t or 

shouldn’t be using that? 

Dr. BURKE. Well, first of all, IRIS has moved in the direction of 

starting with the right questions, and I think Dr. Bus rightly 

points out that there’s a need to ask the right questions, and now 
65 

that is built into the process. We don’t want to have a number 

pulled out of the air of some bright line of what an acceptable risk 

is without providing a context, but let’s go back to that example of 

TCE. TCE is probably one of the most pervasive environmental 

contaminants this world has ever seen from the drinking waters of 

Camp Lejeune to the Superfund sites all around the country. I personally have closed water supplies in New Jersey because TCE is 

such a pervasive environmental contaminant exposing millions of 

people. These are exactly the kinds of things that should drive our 

priority-setting process, drive our science, and drive our problem 

formulation. 

Mr. BEYER. It sounds like TCE would meet Dr. Bus’s test of realworld exposure demonstrating reasonable need. 

Dr. BURKE. Absolutely. 

Mr. BEYER. His second concern was that the IRIS program has 

yet to embrace the practice of mode of action information. Why 

have they been reluctant to do that? Do you agree that mode of action information is important? 

Dr. BURKE. Mode of action information is important, and understanding those mechanisms is part of a major investment the agency has made in our computational toxicology and advancing the 

science but it’s also important that we move ahead when we have 

evidence of a relationship to a health impact even though the mysteries of mode of action may not be there, and this is not just specific chemicals where we lack this information but we know in the 

complexities of multiple exposures in the environment and the way 

that the biology of the human works that this is a very challenging 

undertaking, and the challenge is, when you’re charged with protecting public health, when do you have enough information to 

move ahead to reduce exposure and to support the regulatory decisions of the agency? So he raises some very important points that 

have been raised by the National Academy of Sciences, but therein 

lies the inherent uncertainty of the science base for decision making, and we have to constantly try to improve that, and I think 

with mode of action, we are doing that. 

Mr. BEYER. Great. Thank you. 

Dr. Mundt, it’s nice to see a Dartmouth English major turns out 

okay. You had mentioned that there are large pharmacokinetic differences between mice and human beings. Is this an argument that 

we shouldn’t be doing mice experiments, animal experiments? It 

seems to me that most of my adult life, we’ve been measuring cancer stuff with smaller animals. 

Dr. MUNDT. Thank you. The answer is no, not at all. We should 

continue to use these very good experiments appropriately, but we 

have to—and as the previous two speakers have noted, there’s been 

great advances in understanding the way that chemicals cause disease. It turns out the way that chloroprene, for example, causes tumors in mice is very different from rats and hamsters and humans, 

and that can be taken into the computational toxicological developments now in hand. In fact, in 2010, EPA had access to those 

methods and chose not to use them, and that was one of the basic 

points of my written testimony. 

So yes, I think there’s full agreement here, and none of it suggests that we discontinue animal testing. We should probably re-
66 

duce animal testing to that which is most necessary but it does inform human health risks and can be used if properly extrapolated 

to humans for risk control and exposure control. 

Mr. BEYER. Thank you. 

Dr. Burke, a very quick political question. Who was President in 

1985 when IRIS was started? I’ll go on. That’s obvious. 

Dr. Bus, your third point was that who—that you need to use the 

highest quality science, and Dr. Mundt had the Bukowski chart. 

Who determines the highest quality science? 

Dr. BUS. Well, ultimately, obviously the IRIS program pulls together the science story as they believe it reflects the assessment 

for that compound being evaluated, but then it obviously is subjected to additional reviews by external parties including the 

science advisory panels as well as the external public such as members of the chemistry industry or other individuals interested or 

parties interested in that science. And then in the end, it is—it 

does come down to an issue of judgment although that judgment 

can be guided by, as I mentioned. There’s been extensive investment by the federal government to define what constitutes a highquality study, so we have a whole set of testing guidelines so that 

when we do toxicity tests in animals that they’re done according to 

an accepted protocol that the scientific community universally 

agrees is sensitive and adequate to evaluate that particular endpoint of concern. 

And then likewise, we have an additional wide set of guidelines 

called Good Laboratory Practices to make sure that as those studies are conducted, we’re keeping accurate records, and that if the 

additional other people interested in that science want to actually 

see the science record of that study, it will be available for them 

to scrutinize. That is one of the major problems that I certainly 

highlighted with the example of TCE where we have an example 

of the study that was driving the overall risk assessment for TCE 

was based on a study where the scientific records, the raw data, 

was not even available. The author admitted it was fundamentally 

lost so it couldn’t be—it could not be reobtained for re-analysis. But 

yet the other two studies conducted of much higher quality studies, 

there was a full study report conducted according to Good Laboratory Practice according to EPA guidelines that was available for 

complete detailed review by the scientific community. It’s those 

kinds of judgments that are really used to help differentiate what 

constitutes a high-quality study versus one of lesser quality studies, and in the end, it is a balancing act for sure, and it also has 

to deal with, well, how do the higher quality studies perform relative to the lower quality studies. So if you have a consistent pattern of high-quality study performance indicating one type of response but you have an outlier study where you’re—of uncertain 

quality that gives you a totally different response, that certainly 

weighs in terms of your ultimate decision as to how you would look 

at that science, so thank you for the question. 

Mr. BEYER. Thank you, Mr. Chairman. 

Chairman BIGGS. Thank you. The gentleman’s time is expired. 

Without objection, a letter from Denka Performance Elastomer to 

Administrator Pruitt requesting that EPA withdraw and correct its 

IRIS review for chloroprene is entered into the record. 
67 

[The information appears in Appendix II] 

Chairman BIGGS. I now recognize the gentleman from Kansas, 

Mr. Marshall 

Mr. MARSHALL. Yeah, good morning. I’m a physician and a biochemist, so this is actually a pretty exciting topic to me. It feels 

like I’m back in college again. 

I think my first question is for Dr. Mundt. Chloroprene is neoprene, and that’s one of your expertises. I think that you’ve been 

researching—I mean, obviously bathing your hands in these hydrocarbons is a little bit different than the different phases so I’m just 

very curious from a scientific standpoint how does IRIS or EPA 

deal with just whether the chloroprene is liquid, solid, vapor, and 

do they extrapolate the carcinogenic based upon perhaps the liquid 

phase compared to the synthetic—like our life jackets, I assume, 

are made out of neoprene, it looks like. 

Dr. MUNDT. Thank you. I’m not an expert on the chemistry here 

but I understand that chloroprene is the monomer or the building 

block of neoprene like vinyl chloride monomer makes polyvinyl 

chloride. The end product is stable, a very different product. 

The only epidemiological studies that looked at—reliably looked 

at worker exposure were those done or overseen by Gary Marsh, 

Dr. Marsh from the University of Pittsburgh. Most of those studies 

were in the United States. One was in Ireland. And they had quantitative exposure estimates of workers to chloroprene from the largest plant in Louisville. There’s the basis for what kinds of exposures humans can be exposed to. These are significantly higher 

than what might be anywhere outside of a plant. These are workers and probably the only people exposed to levels—— 

Mr. MARSHALL. But they’re not extrapolating the liquid product 

carcinogenic potential as opposed to the way the consumers are 

using it? 

Dr. MUNDT. Well, consumers are typically not exposed to this 

material. In the workplace, though, the workers were exposed to 

the vapor, so it’s in the air, and the risks are evaluated based on 

inhalation exposure. 

Mr. MARSHALL. The next question for Dr. Bus, if the EPA—if the 

EPA wants to revise or correct an IRIS assessment, does that ever 

happen, or how does the process work? 

Dr. BUS. Once an IRIS decision is closed, it can be reevaluated 

obviously because science changes with time. So the presumption 

would be that if a new piece of science came into the record that 

significantly impacted an existing IRIS review, that there should 

be a process available for reopening that IRIS record so that it 

could be revaluated in the context of that new science. One thing 

we certainly do know is the IRIS program reviews are not subject— 

although they’re subject to reviews by science advisory panels, 

they’re to subject to any legal review in the courtroom, at least as 

I understand it. 

Mr. MARSHALL. But practically speaking, does that happen? Does 

the EPA ever go back and look at them and make modifications to 

IRIS findings? 

Dr. MUNDT. With some of its older compounds, yes, they do come 

back as new science comes onto the table. My understanding is, 

they have revisited some of their evaluations. But it is a very chal-
68 

lenging process in terms of getting it to be reopened to be reevaluated. 

Mr. MARSHALL. Last question is about formaldehyde. I guess I’ll 

go back to Dr. Mundt. There were some concerns about transparency in years past when the IRIS reviewed formaldehyde. Has 

the EPA improved in your estimation of that transparency process, 

or what steps else need to be taken to help it be more transparent? 

Dr. MUNDT. I would say my interactions with EPA in the last 

couple of years regarding formaldehyde have been very professional, very cordial. There has been—we made a great effort to 

point out to IRIS all of the new science in the last six or seven 

years that has been published and is relevant to their evaluation. 

We have asked, however, for IRIS to identify what body of scientific papers are they relying on for the revised formaldehyde assessment, and that information has not been shared with us. 

Mr. MARSHALL. So they’re not being transparent at this point? 

Dr. MUNDT. I would say I can’t say that there is any source that 

I can go to say what is EPA considering today including some of 

the most recent science that contradicts some of the older science. 

Mr. MARSHALL. Did they give you any explanation why they 

won’t be more transparent or what’s going on? 

Dr. MUNDT. Not specifically. I’m assured that there are many 

changes underway but I was also told by Dr. Bahadori, now heading the NCEA program, that many of these changes will not have 

been implemented in time for the formaldehyde reissue or the finalization of formaldehyde. 

Mr. MARSHALL. I yield back. Thank you. 

Chairman BIGGS. Thank you. The Chair recognizes the gentleman from Florida, Mr. Crist. 

Mr. CRIST. Thank you very much, Mr. Chairman, and thank you 

to our panelists for being here today. 

I’m from Florida, as the Chairman noted, which means that obviously with the hurricanes that we’ve experienced in Texas and one 

that appears to be bearing down on my home state, these issues 

are in the forefront of my mind, so Dr. Burke, it leads me to a 

question for you. Can you explain to me and the Committee how 

IRIS risk assessments assist in disaster recovery and response, 

particularly related to hurricanes and flooding? 

Dr. BURKE. Sure, and I’ve been there as a state official on the 

front lines. I’ve worked as a federal official with the environmental 

leadership of all of the 50 states, and the IRIS program is there. 

We’re talking about the documents that those folks prepare today 

but I think what we’re not talking about is the scientific expertise 

at the IRIS program, the folks that are there when Corpus Christi, 

Texas, has a question about an inadvertent chemical contamination 

of their water supply and has to understand what the exposures 

might be and what the risks might be. They’re there when there’s 

a complicated mixture from a release. They’re there to provide in 

the case of Harvey, Region 6, our Dallas—or EPA’s Dallas office— 

excuse me, I don’t speak for EPA—but Region 6 with the expertise 

to understand how to take the samples, to understand the vulnerable populations, and to use the expertise of the IRIS program to 

really have a strong public health response to environmental disasters that are related to things like extreme weather. 
69 

Mr. CRIST. Would emergency responders be able to quickly and 

safely address the types of chemical spills that we’re seeing in the 

wake of Hurricane Harvey without these risk assessments? 

Dr. BURKE. Well, there are many ways that emergency responders need to get information, the first of which is understanding 

what’s on site and whether that’s reported and shared with the 

local communities, and that is not part of the IRIS program, but 

once things are known, IRIS is a reliable and important database 

that doesn’t just look at cancer in rats and things like that but also 

looks at the acute exposure risks, the lethal dose, the short-term 

doses, the neurological effects, the respiratory effects, the irritant 

effects that we’ve heard about recently in Texas, and so yes, IRIS 

is there. It’s a backstop for the states. It’s an important tool. 

Mr. CRIST. So it’s safe to say that timely chemical assessments 

are pretty important in helping communities and families recover 

from the unthinkable? 

Dr. BURKE. They’re essential. They’re absolutely essential. 

Mr. CRIST. Thank you, Dr. Burke. As you know, the Trump Administration has proposed to eliminate the IRIS program among 

other important science programs as well as significantly cut staff 

at the EPA. Will the EPA be able to handle the recovery and response efforts after Hurricane Harvey and now after Hurricane 

Irma with a reduced staff, and how would the elimination or 

downsizing of the IRIS program affect the long-term recovery of 

communities affected by storms and flooding? 

Dr. BURKE. Well, it will have a profound effect on our national 

capacity to respond to chemical exposures and understanding those 

risks, and the unique combinations. For instance, I worked on the 

toxic combinations of water and what was called the toxic gumbo 

of Katrina. These are challenging risk assessments that need to be 

supported by data and good exposure science, and this is the kind 

of expertise that you have uniquely in IRIS that goes well beyond 

just the toxic substances program or looking at industrial chemicals. It really supports every aspect of our public health efforts, and 

it’s really important to the state and local officials to have this resource, to have that number to call, to have those programs or the 

Office of Research and Development and IRIS there to support 

them. 

Mr. CRIST. Thank you very much. 

Thank you, Mr. Chairman. I yield. 

Chairman BIGGS. Thank you. 

The Chair recognizes the gentleman from California, Mr. Rohrabacher. 

Mr. ROHRABACHER. Well, thank you very much, and let me just 

note that we hear charges all the time from people who claim that 

we are politicizing science by basically supporting positions that 

are not acceptable to other people who believe that their positions 

are sacrosanct, I guess, and should not be questioned. 

As a young man, I remember very well the whole issue of 

cyclamates. Do you fellows remember cyclamates? That was the industry—the soda pop industry put enormous amounts of money 

into developing a new sweetener, and it was cyclamates, and they 

were—and they got into the drinks and then all of a sudden it was 

said that cyclamates caused cancer, and they had to pull this out. 
70 

It cost the equivalent of billions of dollars today when this whole 

thing—by the time it was finished, and then of course cyclamates 

were pulled out and then ten years later after a study, it was found 

that the cyclamates did not cause the cancer, and the Canadians 

had never abandoned cyclamates during that whole time. So we 

have to be very careful because those billions of dollars that were 

wasted in that particular instance could have been used for something else that was beneficial to us. For example, when the 

cyclamates were pulled out, I know that what came in was highfructose corn syrup instead, which may not cause cancer but my 

wife will not let me have anything that has high-fructose corn 

syrup in it. Now, whether or not that means because she’s afraid 

of getting fat or whatever it is, the bottom line is, the cyclamates 

would have been more healthy for me than the high-fructose corn 

syrup. 

So there is harm done by chemicals and there’s no doubt about 

that, and we should—and I’m very proud that Ronald Reagan 

signed this bill. I was working for Ronald Reagan at the time. I 

may have had something to do with the statement made on this 

issue years ago. 

But the harm done by cyclamates, or by chemicals and drugs, we 

also have to recognize there is a danger to be done by not permitting people to use beneficial chemicals and drugs that have had 

positive impacts on our lives, so we have to really be serious about 

it, and I would hope that the IRIS program is being serious about 

it and is not—does not succumb to what we have seen here over 

and over again as a politicalization of science, and it’s not a 

politicalization that comes from oh, we have to represent some 

major financial interest but instead it’s a politicalization where 

once an academe that something—and Ph.D.’s, I don’t know why 

they have this inclination but they’ve spent their life promoting a 

particular theory or they’ve come out and gotten grants on a particular theory and they will fight to the death to defend that theory 

even as more people come up and say well, that actually doesn’t fit 

with what we’ve newly discovered, and I believe that manmade 

global warming, the fight in that, people have been denied—over 

and over again we have seen this over the years—denied research 

grants but those who claim to be so open-minded and liberal about 

this, and they’ve been denied people if they have any question as 

to whether or not mankind is causing global warming. 

So one question. I know we’re running out of time here for my 

question. But the—we need to make sure that people are looking 

not just at the specific reaction to chemicals but also what is the 

threshold that someone—because we all ingest chemicals even natural chemicals all the time. The threshold is very important as well 

as the frequently of exposure, and are we being cautious enough to 

making sure that we do not take away the beneficial chemical results and chemical—things that chemicals can do for us? Are we— 

is that issue now being handled correctly by this program, or is this 

still a problem? And I just—for the whole panel. 

Dr. BUS. Thank you for that excellent question, and in fact, it 

really touches on the issue that Dr. Burke just touched on. The 

agency is called on on many occasions to deal with some very challenging issues such as events associated with hurricanes. That 
71 

means that the staff that they have needs to be put in the right 

place at the right time, and they certainly cannot be diverted to efforts that ultimately are really not proving, as you say, necessary 

to improving public health. 

Let me give you a practical example of that. There’s a compound 

that’s under review right now by the agency called ethyl benzene. 

This is an intermediate compound, 99 percent of which in terms of 

its total chemical production is used as a closed system intermediate for the production of styrene, so it’s a closed process. 

You’re not going to have much releases to the environment as the 

result of that use. The other process—the other exposures to ethyl 

benzene come from its natural component of gasoline, which of 

course is assessed by other means independent of the ethyl benzene 

that’s contained within it. It’s another very small component of 

mixed xylenes, which is a commonly used solvent, but again, mixed 

xylenes are assessed for their own toxic independently. 

So why is this important? Well, EPA has set off in terms of projecting, and this is as of just a couple of weeks ago, the IRIS program notified that they were going to continue forward with the 

evaluation of ethyl benzene in terms of developing an IRIS evaluation of it. That’s an extensive effort on their part which will consume staff time but yet over a year ago in a public problem formulation session, which was appropriately held for this compound, 

they were advised that this compound is a chemical intermediate 

all used in closed system production, and that its exposures, which 

have been monitored in the air across North America for many 

years, are less than one part per billion, which is the general air 

concentration associated with ethyl benzene, but here’s the kicker. 

In the case of ethyl benzene in terms of the animal toxicity studies, 

the primary endpoint of concern is liver tumors in rats that are 

seen with ethyl benzene but they occur only at a concentration of 

750,000 parts per billion. Now, I would argue when you look at 

that data set alone, you would say that particular compound might 

not be worthy where significant resource investment by the agency 

justifies evaluation of a compound for that concern, and that frees 

the agency up to make the types of information flow that’s necessary for the other critical elements that they’re challenged with 

dealing with on an everyday basis, as Dr. Burke has already mentioned. So it’s just one example that’s actually currently in progress 

today so it’s again another example of has the IRIS program truly 

learned and put into action what its words are versus where it’s 

walking the talk. At least from my perspective I have some real 

concerns that that isn’t the case. And the end result of it is, is just 

as you’ve just described. The necessary resources of the agency to 

truly protect public health, which I believe is exactly what they 

should be doing, are constrained when they’re not making wise decisions as to where best to put their time in terms of evaluating 

the science. 

Chairman BIGGS. Thank you, and the gentleman’s time is expired. 

The Chair recognizes the gentleman from Texas, Mr. Weber. 

Mr. WEBER. Thank you, Mr. Chairman. 

Dr. Burke, you said you spent some time in Houston. What part? 
72 

Dr. BURKE. Actually I was part of the downtown—I lived at the 

Texas Medical Center in student housing while I was pursuing my 

degree there, and part of the flood of 1976. 

Mr. WEBER. Oh, I got you. Well, don’t tell us how old you are 

now. 

Dr. BURKE. I’m pretty old. 

Mr. WEBER. You said in your written remarks ‘‘the capacity to 

evaluate chemicals is essential to public health.’’ 

Dr. Mundt, you wouldn’t disagree with that, would you? 

Dr. MUNDT. No, sir. 

Mr. WEBER. Dr. Bus, you wouldn’t disagree with that, would 

you? 

Dr. BUS. Absolutely—have to do that. 

Mr. WEBER. So I’m going to start back at the other end of the 

table. 

Dr. Mundt, have you ever known scientists to be wrong? 

Dr. MUNDT. Quite frequently. 

Mr. WEBER. Quite frequently? 

Dr. Bus, how about you? 

Dr. BUS. I would agree, but there are certainly processes now 

available to help resolve those disagreements among scientists. So 

for instance, I mentioned mode of action frameworks. They’re an 

excellent way to resolve those types of—— 

Mr. WEBER. I just want to make the point that scientists—well, 

let me get Dr. Burke in here first. Have you ever known scientists 

to be wrong? 

Dr. BURKE. I sure have. 

Mr. WEBER. Okay. So they’re not infallible. 

One of the problems that I see with the way the program is that 

the IRIS assessment is not reviewable by courts. Are you aware of 

that, Dr. Mundt? 

Dr. MUNDT. No, I’m not aware of that. 

Mr. WEBER. Dr. Bus? 

Dr. BUS. Yes. 

Mr. WEBER. Dr. Burke? 

Dr. BURKE. I’ll pass. 

Mr. WEBER. Let’s—— 

Dr. BURKE. I think that the regulatory application of IRIS is certainly consistently reviewed by the courts. 

Mr. WEBER. Let me say it this way then. If that were in fact the 

case, the process is not reviewable by courts, would that be problematic, Dr. Mundt? 

Dr. MUNDT. I have—— 

Mr. WEBER. I mean, if it’s not reviewable by courts, do you see 

that as a problem? 

Dr. MUNDT. I was going to say only if it’s wrong. If it’s right, 

then of course—— 

Mr. WEBER. That’d be great, but the courts—— 

Dr. MUNDT. —if we’re wrong, where can you then turn. 

Mr. WEBER. I got you. 

Dr. Bus, if it’s not reviewable by courts, is that problematic? 

Dr. BUS. It can be in certain circumstances, yes. 

Mr. WEBER. Dr. Burke? 
73 

Dr. BURKE. Again, I think the regulatory application is what the 

focus should be on, and my understanding is that is reviewable by 

courts, and very often are reviewed by courts. 

Mr. WEBER. Let me read something that I have here. A March 

2008 GAO report noted that EPA has not been able to ‘‘routinely 

complete critical IRIS assessments.’’ More recently, a 2011 NAS report found that EPA’s IRIS claims were not supported by its assessments, they were subjective, and that no clear scientific framework had been used by EPA to reach its conclusions. The NAS also 

stated that the IRIS program was deficient in meeting the benchmarks of objectivity, scientific accuracy, and transparency necessary to ensure high-quality and reliable assessments. Any of you 

all familiar with that report? Just a simple question. Dr. Mundt? 

Dr. MUNDT. Yes. 

Mr. WEBER. Dr. Bus? 

Dr. BUS. Yes. 

Mr. WEBER. Dr. Burke? 

Dr. BURKE. I assume that’s from the 2011—— 

Mr. WEBER. Okay. So does that sound problematic to you, Dr. 

Mundt? 

Dr. MUNDT. I’ve spent the last five, six years working on that 

issue with regard to formaldehyde. 

Mr. WEBER. To you, Dr. Bus, is that problematic? 

Dr. BUS. Very much so. 

Mr. WEBER. Dr. Burke? 

Dr. BURKE. Yes, and—— 

Mr. WEBER. Okay. Thank you for that. 

Let me go to my fifth question. Dr. Burke, you said that you had 

personally, I think, closed down some water plants in New Jersey? 

Dr. BURKE. Yes, sir. 

Mr. WEBER. Is that right? You need to come back to Texas. 

You also said that you felt like that the IRIS was critical in 

emergencies like hurricanes where they can be out there on the 

ground taking samples. Is that a fair recounting of what you said? 

Dr. BURKE. I think it’s—yes. 

Mr. WEBER. Are you familiar with the TCEQ in Texas, Texas 

Commission on Environmental Quality? 

Dr. BURKE. Yes, I am. 

Mr. WEBER. Are you aware that it is the second largest regulatory agency in the world second only to the federal EPA? 

Dr. BURKE. I wasn’t aware of that but I am familiar with it. 

Mr. WEBER. Right. Well, I can tell you, having served in the 

Texas legislature for two terms, four years—I was on the environment reg committee—I can tell you that’s a fact. 

Do you think the TCEQ would have a vested interest in having 

boots on the ground immediately in those areas and assessing 

those same kinds of situations? 

Dr. BURKE. Yeah, I think the state responsibilities are essential, 

and they have that role. 

Mr. WEBER. Okay. Well, I appreciate you all being here today. 

I think the statements, the evidence and the hearing kind of 

speaks for itself. Thank you, gentlemen. 

I yield back. 

Chairman BIGGS. Thank you. 
74 

The Chair recognizes the gentleman from Georgia, Mr. 

Loudermilk. 

Mr. LOUDERMILK. Thank you, Mr. Chairman, and thank all the 

members of the panel for being here. 

Dr. Burke, you mentioned that a member of the National Academy of Sciences, you’ve made recommendations for IRIS for certain 

reforms. Did I get that right? 

Dr. BURKE. Yes, a 2009 report. 

Mr. LOUDERMILK. Have they followed through with those reforms 

that you’ve recommended? 

Dr. BURKE. They are moving forward, yes, in a very responsive 

way but the reforms are challenging. There’re inherent uncertainties in the science, and very often a lack of scientific information 

that make it challenging, but I’m very satisfied and have been part 

of pushing them to do just that. 

Mr. LOUDERMILK. So those recommendations are 2009, 2017, 

they still haven’t implemented how much—are you projecting how 

long it’s going to take? 

Dr. BURKE. I can’t speak for how the program is going now but 

I know that it was a focus of my efforts to improve that program, 

and they have implemented tremendous improvement. 

Mr. LOUDERMILK. Okay. Thank you. 

Dr. Mundt, 2017, the GAO in their High Risk Report set out numerous recommendations for IRIS. Others have as well. To your 

knowledge, has EPA established timelines for the different stages 

of the assessment process since the GAO report? 

Dr. MUNDT. I’ve not seen any. 

Mr. LOUDERMILK. Okay. Dr. Bus, do you know? 

Dr. BUS. No. 

Mr. LOUDERMILK. Okay. I wouldn’t expect if in 2009 they haven’t 

made significant progress in the other recommendations. 

Dr. Bus, the 2017 GAO report also indicates that other EPA offices do not exclusively use IRIS assessments for information on 

toxicity. The use of alternative sources for toxicity information begs 

the question, are there in fact other sources better equipped to provide information IRIS assessments do not, and are these sources 

able to make up for IRIS shortfalls? So it appears that EPA doesn’t 

even use its own data. Are you aware of that? 

Dr. BUS. Most of the science that the EPA considers in terms of 

its chemical evaluations is science coming from other sources. They 

do have their own Office of Research and Development but the vast 

majority of the science that the ultimately end up incorporating 

into their assessment comes from either industry sources or from 

primarily the academic environment. So those are the primary 

sources of the science that they use. 

Mr. LOUDERMILK. I guess what is IRIS used for if EPA typically 

doesn’t use it? 

Dr. BUS. The primary purpose of IRIS is to pull together their 

IRIS evaluations, the objective of which is to develop what they call 

reference concentrations. So these are concentrations which they 

believe the public can be—the science says the public can be exposed to without reasonable concern for harm, and likewise, they 

also do cancer evaluations to say at what level of exposure is it acceptable where you might not be vulnerable to having cancer as a 
75 

consequence of exposure to this agent, and that’s where the debate 

often comes in with respect to IRIS evaluation because there the 

studies that you use as the basis for making those determinations 

for those key values, the reference concentrations and the reference 

doses and the cancer values are really what drive the regulatory 

action. 

So by way of example, Dr. Burke mentioned one of the things an 

emergency provider immediately would ask in the case of a chemical release associated with a hurricane by way of example, is there 

a reference—an acute reference concentration associated with this 

material. So if people happen to be exposed to the vapors or a first 

responder is exposed to the vapors, what do we know about the potential for that to cause that harm. So having that value is useful 

if you can measure it at the same time. 

Now, it’s also fair to say that the agency is not the only agency— 

and here’s another issue regarding redundancy. The National Academy of Sciences has an extensive battery of what they call acute 

emergency guidelines. That’s—they have an entire committee devoted to saying in these acute circumstances like chemical releases 

associate with these natural disasters, the first responders can consult the EGL values and to say what can we expect, you know, as 

a consequence of exposure to the first responders and then ultimately to the surrounding population as well. 

So not having the IRIS there for those acute responses is certainly covered by other areas in the risk assessment community, so 

for instance, the National Academy and their EGL values. 

Mr. LOUDERMILK. Dr. Mundt, is IRIS in need of major reforms 

or is it duplicative now that we have other resources like Dr. Bus 

just brought up? 

Dr. MUNDT. Well, the range of products IRIS produces is broad. 

It not only includes the reference concentrations but it’s one of the 

main organizations, the other being the National Institute for Environmental Health Sciences and the National Toxicology Program 

for classifying substances as carcinogenic. So there’s another area 

where there’s some redundancy. I think one of the other could do 

this but in every case it ought to be done well with high-quality 

science. So I don’t think that all of the functions of IRIS currently 

could be absorbed by other organizations. 

Mr. LOUDERMILK. But we do—— 

Chairman BIGGS. The gentleman’s time is expired. 

Mr. LOUDERMILK. —need major reform. 

Dr. MUNDT. It’s clear that there are major reforms underway because the problems have been recognized. Whether and at what 

rate they’ll be implemented is yet to be seen. 

Mr. LOUDERMILK. Thank you, Mr. Chairman. 

Chairman BIGGS. Thank you. 

The Chair recognizes the gentleman from California, Mr. 

Takano. 

Mr. TAKANO. Thank you, Mr. Chairman. 

Dr. Burke, good morning. 

Dr. BURKE. Good morning. 

Mr. TAKANO. Despite the vital function IRIS provides in assessing the public health dangers of chemicals and recent findings by 

both GAO and the Academies that EPA has made progress in im-
76 

proving the IRIS process, this Administration proposed to eliminate 

the program altogether. My first question is, why would that matter? As a former state environmental official and former EPA 

Science Advisor, you bring a unique perspective to the table regarding the usefulness of IRIS. How does the program help state and 

local officials, public health professionals and the public? But first 

answer the question of why would it matter? 

Dr. BURKE. Well, it matters tremendously to the frontline people 

in public health and environmental protection that we have a consistent source of information. I remember the chaos before 1983 

when the risk assessment process got started in 1985 when IRIS 

was established, and we risk returning to 50 different solutions. As 

strong as some states may be, I think the business community does 

not want 50 different solutions, 50 different numbers, and certainly 

the health effects aren’t different in the states. And so it would be 

a chaotic situation if that program were no longer there to respond 

to the Nation’s environmental chemical priorities. 

Mr. TAKANO. Well, what impact would eliminating IRIS have on 

EPA’s statutory obligations? 

Dr. BURKE. Well, the National Center for Environmental Assessment and the IRIS program really are the starting point for the 

science. EPA is only as strong as the science that supports its decisions, and EPA has very clear statutory authorities for clean air 

and clean water and the cleanup of hazardous waste. Each one of 

these is guided by science whether it’s for a cleanup value or a contaminant level for drinking water or an air quality standard. Without IRIS, without the scientific engines that support that mandate, 

I feel that EPA would fail to meet its public health responsibilities 

Mr. TAKANO. Well, based on these impacts, does it make it—does 

it make sense to reduce overall staff or monetary resources for the 

IRIS program? 

Dr. BURKE. Again, I think it’s an essential capacity for not just 

EPA but the Nation. Reducing that staff is very shortsighted, and 

I think would have profound effects not just on public health but 

on our business community as well. 

Mr. TAKANO. So it doesn’t make sense at all to reduce the staff. 

Dr. Burke, as you state in your testimony, the scientific peer review process is essential to producing credible results, addressing 

uncertainties, and explaining the scientific basis for conclusions. 

And contrary to what some of my Republican colleagues believe, 

the peer review process is a critical part of how we conduct science 

in this country and around the world. Could you expand on your 

testimony and describe for us exactly why peer review—why the 

peer review process is built into IRIS and why is it so essential? 

Dr. BURKE. Sure. Independent peer review is essential. All of the 

data, as was said by my colleagues here, that EPA uses is from the 

academic community, the scientific community, the industry community, and is peer reviewed prior to being part of this synthesis 

of information, but IRIS documents are subject to the highest levels 

of peer review, first through committees of the EPA’s Science Advisory Board, and very often for the high-profile, high-impact compounds or substances, the National Academy of Sciences, our highest level of scientific expertise in this country, and so it is essential 

to be independent and it is essential that it be reviewed with the 
77 

kind of scrutiny and the kind of updating that was suggested here 

today. 

But I have to mention one very important distinction between 

stakeholder input and scientific—independent scientific peer review. These are very different things, and sometimes we get confused about having stakeholders express their opinions on things, 

on the cost of regulations and things like that that is important but 

very different than the independence of the scientific review, and 

I fear that we may have gotten these things kind of crossed and 

what you see is a frustration on the part of stakeholders because 

they don’t like the answer. Because in my experience in 40 years, 

I have never seen a stakeholder industry come forward with their 

risk assessment and say EPA, you got it wrong, your number is 

way too high, this is bad stuff. It’s always recommending a more 

lenient approach with the public’s health. 

Mr. TAKANO. Thank you, Dr. Burke. 

Chairman BIGGS. Thank you. 

The Chair recognizes the gentleman from Texas, Mr. Babin. 

Mr. BABIN. Thank you, Mr. Chairman. I thank the witnesses as 

well. 

Dr. Bus, do IRIS assessments properly consider real-world regulatory and risk management implications of its hazard assessments? 

Dr. BUS. The risk management applications, if I understand it, 

is actually outside the domain of the IRIS program. Their intention 

is just—and their objective and their responsibility is to assess the 

science that ultimately then is translated for use by the risk managers. However, if that science is not pulled together in a way that 

represents the best reflection of the practice of that science, it will 

result in poor risk management decisions. So by way of example, 

I mentioned the trichloroethylene example. I’ll come back to that. 

The risk managers now are faced with the potential option of saying do we need to revisit all of the Superfund sites that had been 

resolved for trichloroethylene, do they need to be reopened now as 

a result of this reassessment conducted by the IRIS program. 

That’s how it flows into a risk management decision. 

Mr. BABIN. Okay. Thank you. Thank you very much. 

And then Dr. Mundt, does IRIS use a weight-of-evidence framework that incorporates all relevant and reliable data? 

Dr. MUNDT. This is one of the key criticisms that the earlier NAS 

committees identified, and I understand there’s efforts in place to 

move toward this. But in the two chemistries that I’ve been involved with for the last few years, it’s clear that that was not the 

case. The—especially epidemiological human health studies were 

all considered as equals where there were some that were considerably stronger and others that were considerably weaker. Preferentially, we tend to favor the results from studies that are well conducted, well documented, large numbers, strong exposure assessments and whatever they say, which should drive the assessment. 

Mr. BABIN. Okay. Thank you very much. 

One more question, and Dr. Bus, if you don’t mind, what steps 

in the current IRIS process are most troublesome to you? You’ve 

mentioned some already, but with chemical toxicity, does one proc-
78 

ess fit all or should it be tailored based on the type of chemical and 

the need for speedy assessment? 

Dr. BUS. You’ve put your finger on certainly several of the key 

issues. The ability to identify which compounds really need the attention of the agency to the degree of investment that they engage 

in with an IRIS evaluation certainly is important. The other area 

in which the IRIS program has struggled with mightily without 

coming to any effective resolution even as of the last several reviews that have just been released over the last—this summer, and 

that is, how to use mode of action science, and why is that important? The vast majority of the decisions that are made with respect 

to evaluating the health effects of chemicals arises from data flowing from animal toxicology studies because we simply don’t have 

often—I’m sure my colleague, Dr. Mundt, would agree—the horsepower in epidemiology necessarily to tease out those health effects 

so we rely on animal studies. But we also know animals are not 

little people, and that in some cases they don’t behave the same 

way biologically as do adults, and we can also—because we can put 

these animals in cages and give them any amount of chemical that 

we choose, we often use doses that are far disparate from realworld exposures, and now we recognize that doing that kind of 

science often can generate results that are fundamentally not 

quantitatively relevant to human risk. So the risk program has, I’ll 

have to admit, over its entire existence struggled mightily with the 

use of mode of action data, and I don’t believe you can hardly point 

to a single example where mode of action science despite the extensive investment in the scientific community paid for and generate 

that science where it’s ever been effectively used. 

Mr. BABIN. I understand. Thank you very much. 

I yield back the balance of my time, Mr. Chairman. 

Chairman BIGGS. Thank you. The gentleman yields. 

And now I thank the witnesses for your testimony. It’s very valuable, very insightful, very interesting today, and the members for 

their questions. The record will remain open for two weeks for additional comments and written questions from members. 

This hearing is adjourned. 

[Whereupon, at 11:45 a.m., the Subcommittees were adjourned.] 
(79) 

Appendix I 

ANSWERS TO POST-HEARING QUESTIONS
80 

ANSWERS TO POST-HEARING QUESTIONS

Responses by Dr. Kenneth Mundt 
81 

evaluations and interpretations to any legal company or government entity that is 

not engaged in any hate, terrorist or criminal activities. Therefore, it would be 

reasonable to assume that Ram boll Environ indeed provides professional 

scientific evaluations and interpretations to all legal, corporate, government or 

other entities. 

The nature of work performed by Ramboll Environ's Health Sciences Practice 

area includes, but is not limited to, primary research studies, critical reviews and 

syntheses of the published scientific literature, quantitative risk assessments, 

workplace health and safety evaluations, compliance audits, environmental 

assessments, and chemical and product registrations. 

b. Please provide identical information for the listed co-authors of your testimony, 

Dr. Sonja Sax and Dr. Robinan Gentry. 
82 

iil;.)#l:ii4!J ENVIRON 

P ROBINAN GENTRY 

Principal/Operations Director- Gulf Coast 

Dr. Robinan Gentry has over 25 years of experience in toxicological 

issues relevant in the determination of the potential safety or risk 

associated with exposure to chemicals in consumer products, 

pharmaceuticals or the environment. Over her career, she has been a 

principal investigator or contributing author for numerous safety and 

risk assessments for both government and industry. The purpose for 

a number of these assessments has been to incorporate innovative 

quantitative approaches in the determination of acceptable levels of 

exposure of humans to chemicals in the environment, 

pharmaceuticals and consumer products. She is a published author in 

the development of physiologically-based pharmacokinetic (PBPK) 

models and their application into both the cancer and non-cancer risk 

assessment processes. She has also been involved in projects using 

these types of models to investigate human variability by age and 

gender, and the potential impact of this variation on risk 

assessment. Her recent work includes projects that are aimed at 

understanding the mode of action of adverse effects in animals and 

the implications to human health, as well as the development of 

innovative approaches that rely upon in vitro data and incorporation 

of these data into the risk assessment paradigm. 

2015- Present 

Principal/Senior Toxicologist, Ramboll Environ US Corporation 

2011-2014 

Principal/Senior Toxicologist, ENVIRON International Corporation 

2001-2010 

Manager /Senior Toxicologist, ENVIRON International Corporation 

2001 

Vice President, IFC Consulting 

1997-2001 

Senior Project Manager, ICF Consulting 

1992-1997 

Project Manager, ICF Kaiser 

1989-1992 

Associate Scientist1 ICF Kaiser 

1987-1989 

Analyst, Clement Associates 

1/20 CV, P R0!3INAN GENTRY 

ENVIRONMENT 

& HEALTH 

P Robinan Gentry 

rqentry@ramboll.com 

+ 1 (318) 3982083 

Ramboll Environ 

3107 Armand Street 

Monroe, LA 71201 

United States of America 

Diplomate. American Board of 

Toxicology, 2002; recertified, 

2007, 2012 
83 

i;i'Ui:WIJ ENVIRON 

EDUCATION 

2008 

PhD, Toxicology 

Utrecht University, The Netherlands 

1992 

MS, Pharmacology /Toxicology 

Northeast Louisiana University, United States 

1987 

BS, Toxicology 

Northeast Louisiana University, United States 

COURSES/CERTIFICATIONS 

Diplomate of the American Board of Toxicology - DABT 

PROJECTS 

Risk Assessment Issues and Documents 

ENVIRONMENT 

& HEALTH 

Principal Investigator for a multi-year project evaluating integration of the available evidence, 

epidemiological, toxicological and mechanistic, regarding the potential for formaldehyde to cause 

cancer, specifically leukemias and nasopharyngeal cancer. 

Primary author of a publication evaluating the raw data from a study relied upon heavily by !ARC 

and the USEPA for establishing biological plausibility of leukemia resulting from exposure to 

formaldehyde. 

Served as the project manager on a work assignment to support USEPA in advancing the 

evaluation, development and application of PBPK models to be used in deriving IRIS toxicity values, 

including models for vinyl acetate, n-methylpyrrolidine, and acetaldehyde. 

Served as project manager and senior toxicologist for a work assignment to support USEPA.in the 

revision of chapters one through six of the Toxicological Review for Antimony and Compounds. The 

document shall provide a summary of the state-of-the-science pertaining to potential health effects 

from antimony and antimony compounds found in the environment. The document will also contain 

information necessary for the derivations of an oral reference dose (RfD), inhalation reference 

concentration (RfC), cancer slope factor and inhalation unit risk where feasible, as well as the 

information that will be used to assign a cancer weight-of-evidence (WOE) classification. The cancer 

assessment shall include an uncertainty analysis, and an appropriate classification and grouping of 

antimony compounds (considering their chemical, physical, biological and toxicological properties), 

for presentation of hazard and dose response analyses. 

Served as project manager and senior toxicologist for a work assignment involving the completion 

of the IRIS documentation of the carcinogenic potential and potency of methanol for the cancer 

assessment portion of the USEPA Methanol Toxicological Review. This project included the 

quantification of the potential carcinogenicity of methanol using dose-response modelling and 

documentation of uncertainty in these estimates. 

Served as project manager and senior toxicologist for project involving the development of chapters 

one through four of the IRIS Toxicological Review for Weathered Toxaphene. This project involved a 

comprehensive literature search and provided information that will be used to derive an RfD, RfC, 

cancer slope factor and inhalation unit risk (where scientifically feasible). This document will also 

present information used to assign the cancer WOE characterization for weathered toxaphene. 

2/20 CV, P ROB!NAN GENTRY 
84 

i;f4=1:1C111J ENVIRON ENVIRONMENT 

& HEALTH 

Served as project manager and toxicologist on a project for the American Chemistry Council (ACC) 

ACC to incorporate PBPK and other advanced approaches (e.g., Bayesian logic) in the conduct of 

quantitative dose-response analyses for compounds that act through receptor-mediated modes of 

action in order to harmonize cancer and non-cancer effects. The case study compound is DEHP and 

the initial phase was to discern a mode of action for the reproductive effects, enhance a PBPK model 

to describe the reproductive component, determine the common obligatory precursor and conduct 

the initial phase of dose-response modelling. 

Served as project manager and toxicologist for a project that involved conducting a review of the 

available in vitro studies of the interactions of arsenic species with genes and proteins involved in 

cellular control functions (e.g., DNA repair and redox control), as well as genomic/transcriptomic 

studies conducted with arsenic compounds. Possible biologically-based dose-response modelling 

approaches were explored and their suitability for an arsenic risk assessment evaluated. Additional 

data required to implement alternative modelling approaches was also be identified. Multipathway 

cancer modelling as a potential approach will also be investigated. 

Served as project manager and toxicologist on a project to assist the USEPA and the National Center 

for Environmental Assessment's Washington office with the development of an approach for the 

application of a PBPK model in both a cancer and noncancer risk assessment of 1,2-Dichloroethane 

(DCE). The approach was divided into two phases: an initial phase related to the evaluation of the 

existing PBPK model, and a second phase that involved the actual application of the model in the 

risk assessments for 1,2-DCE. 

Served as task manager for the development of revised drinking water criteria documents for radon 

and uranium, and an ambient water quality criteria document for methylmercury, for the Office of 

Water and the Office of Science and Technology. This contract involved a critical evaluation of the 

recent literature for a given chemical in order to summarize the studies in the appropriate section, 

but also to determine new studies that may be used in a quantitative manner for derivation of RfDs, 

RfCs, or cancer potency factors. Also served as task manager under the same contract for the 

development of the IRIS profile and support documentation for chloroform. 

Served as the principal investigator in a project for a private client that involved the application of 

benchmark modelling to effects observed in the parental generations of a two-generation 

reproductive study. This project involved the evaluation of the histological information for 

determination of data sets to be modelling, as well as the potential relevance of these datasets for 

human health risk assessment. 

Served as a co-investigator in the quantification of a margin of exposure and cancer slope factor, 

using existing kinetic and mechanism of action data, for a fungicide. This project involved the 

evaluation of the increases in the incidence of Leydig cell tumors observed in a two-year bioassay 

conducted with a fungicide in rats. The mode of action data collected for this chemical were 

reviewed, and based on this review, it was determined that the likely mode of action for this 

chemical was different in the rat and human. Therefore, for the risk assessment dose-metric 

adjustments for metabolic differences and for differences in response to LH stimulation (measured 

by testosterone production) were made, and a margin of exposure and cancer slope factor were 

quantified. 

Served as a co-investigator in the derivation of an alternative RfD for methylmercury, based on 

information available from fish-eating populations. Also participated in the development of a 

document detailing the methodology for peer-review. This innovative assessment involved the 

integration of Monte Carlo analysis, benchmark modelling and PBPK modelling. Played a key role in 

the identification of information for the development of distributions for the Monte Carlo analysis. 

3/20 CV, P ROBINAN GENTRY 
85 

l;f±Ui:liiAI ENVIRON ENVIRONMENT 

& HEALTH 

Served as a co-investigator in the development of a document evaluating the toxicological and 

statistical significance of three National Toxicology Program (NTP) bioassays conducted with nickel 

subsulfide, nickel sulfate hexahydrate and nickel oxide. The results of the NTP bioassays were 

explained from a mechanistic viewpoint using putative mechanisms of action described in the 

toxicological literature. Where appropriate, unit risk factors and cancer slope factors were derived 

using the results of the NTP bioassays as a basis. The potential impact of the NTP data on future 

allowable air concentrations was also considered. 

Worked on a consortium of universities and corporations to conduct a comprehensive, independently 

managed review and evaluation of existing Department of Energy (DOE) weapons complex risk 

assessments to track issues of public concern. Information provided by this consortium will be used 

by the DOE Office of Environmental Management and Office of Integrated Risk Management, as 

background in preparing a June 1995 report to Congress describing the risks associated with 

cleaning up weapons complexes. 

Served as a contributing author of toxicological profiles for the Agency of Toxic Substances and 

Disease Registry for radon, plutonium and DDT. Prepared a critical evaluation of the available 

toxicity data, including animal data and epidemiology data, and identification of effect levels. 

Susceptible populations and data gaps were also discussed. 

Served as a contributing author for the development of the drinking water criteria documents for 

several radionuclides (including uranium, alpha emitters and beta/gamma emitters). Critically 

reviewed and summarized the available animal data and human epidemiology data, including dose 

calculations and effect determinations. 

Served as a co-investigator in a project that involved the development of comparative potencies for 

polychlorinated biphenyls (PCBs). 

Served as the principal investigator in the development of a cancer potency estimate for Toluene 

diisocyanate. 

Served as the principal investigator for the development of benchmark dose estimates and cancer 

potency estimates using dose-response models for numerous private clients, for use in regulatory or 

litigation related issues. 

Served as the principal investigator in a project for the USEPA that involved the derivation of 

potency factors for addenda to 49 reportable quantity documents. 

Served as the principal investigator in the derivation of margins of safety and excess lifetime cancer 

risks for selected volatile organic chemicals (VOCs). 

Served as a co-investigator on a team writing and editing the carcinogenicity sections for addenda 

to 49 reportable quantity documents for the USEPA. 

Served as the principal investigator on the derivation of reproductive, developmental and fetotoxic 

RfD's for a new chemical, based on the laboratory testing of that chemical required for registration. 

Served as the principal investigator in the development of cancer potency estimates for 29 

chemicals under the Clean Air Act for the office of Air Quality and Planning Standards. 

Served as the principal investigator in the development of absorption factors for three chemicals 

based on the available literature to be used to adjust toxicity criteria values (RfDs and Ql *s). 

Served as a co-investigator in a quantitative risk assessment for the development of new 

permissible exposure limits (PELs) for cadmium, on behalf of OSHA. 

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Served as a co-investigator in the development of Appropriate Cleanup Performance Criteria 

(ACPCs) for selected chemicals in groundwater and soil for a client in Florida, as applied to a RCRA 

Clean Closure Equivalency Demonstration. 

Assisted the state of Minnesota in setting one-hour standards for VOCs in air. 

Risk Assessment Methods Research and Development 

Served as the manager of an ongoing project related to the development of a program to implement 

two-stage models for calculating the probability of nasal squamous cell carcinoma incidence and 

mortality in the rat due to inhaled formaldehyde. In addition, confidence limits on risk estimates are 

calculated and simulations carried out under various prescribed scenarios. 

Developed a report which provided a description of the practices, rationale, approaches and case 

studies of the production, evaluation and quantitative interpretation of PBPK modelling of genetic 

polymorph isms of drug metabolizing enzymes. This report was based on analyses, publications and 

workshop materials previously developed by ENVIRON staff. 

Served as the principal investigator in a project for ATSDR, in which the potential impact of 

pharmacokinetic and benchmark dose modelling in the development of minimal risk levels for 

noncancer health effects from chemicals was evaluated. The multi-year study demonstrated the use 

of these techniques for approximately 20 chemicals, and provided guidance on criteria for 

determining chemicals for which the application of the techniques should be given priority. 

Developed an advisory system to accompany TOX_RISK, a risk assessment software package 

developed by Clement International. This advisory system is intended to provide the non-risk 

assessor with information to assist in the conduct of the risk assessment and the interpretation of 

results. 

Served as the manager of a project that provided re-registration support for a pesticide. Critically 

evaluated the existing potency factor for this pesticide, and determined if the appropriate 

methodology and dose-response modelling techniques had been applied. 

Served as a co-investigator in a project conducted for the Office of Water Quality to investigate the 

use of the methodology reported in the newest USEPA Guidelines for Carcinogen Risk Assessment 

for the development of ambient water quality criteria for the protection of human health. This 

project involved the development of ED lOs for four chemicals, 2,4-dinitrotoluene, 1,3-

dichloropropene, hexachlorobutadiene and lindane. Also considered were the types of information 

needed to evaluate the possible underlying mechanisms of carcinogenicity and to distinguish 

between a linear or nonlinear mechanism of carcinogenicity. 

Managed a project involving a detailed review and critical analysis of the draft guidance documents 

prepared by the Office of Environmental Health Hazard Assessment for the determination of acute 

toxicity exposure levels for airborne toxicants, as well as the levels developed for five specific 

chemicals, including benzene, toluene, hydrogen sulfide, ammonia and nickel. 

Served as the principal investigator for a project that compared and contrasted the risk assessment 

methods used by USEPA for six chemicals, and the risk assessment of those same six chemicals, 

under California's Proposition 65. 

Served as a co-investigator in a project to evaluate the potential effects of partial lifetime exposure 

on the current methodology for risk assessment for the Office of Air Quality and Planning Standards. 

Served as a co-investigator in a critical review, for a private client, of an ambient air standard 

proposed by the state of Louisiana. This involved an evaluation of the current methodology for 

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deriving the proposed air standard and investigating alternative methodologies for deriving an air 

standard. 

Served as a co-investigator in the preparation of an advisory system and database program for 

weight-of-evidence assessments and quantitative risk assessments. 

Served as a co-investigator in the development the risk assessment methodology for the risk 

analysis part of a systems engineering analysis computer software program. 

Pharmacokinetics and PBPK Modelling 

Served as the principal investigator on a project to conduct work related to the development and 

application of a PBPK model in the evaluation of the kinetics of ethanol following occupational 

exposure. 

Provided litigation support in the application of a PBPK model for trichloroethylene to investigate 

blood concentrations of the parent and metabolite following various occupational exposure 

scenarios. 

Assisted a private client in the refinement of an existing PBPK model for dichloromethane for 

performing a cancer risk analysis. This work considered individual data from human exposures used 

by DiVincenzo and Kaplan (1981), and a modified PBPK model originally published by Andersen et 

al. (1987). The input data to the risk analysis was the rodent bioassay data as described in the 

current IRIS database on DCM, as well as human epidemiological data provided by the client. These 

analyses relied on Bayesian MCSIM statistical methods and incorporation of GST-T1 polymorph isms 

to calculate cancer risk. 

Served as manager on a project for Health Canada to develop a report addressing critical issues 

related to the use of PBPK modelling in risk assessment. 

Served as manager of a project assisting USEPA, National Center for Environmental Assessment, in 

the development of an approach for the application of a PBPK model in both a cancer and noncancer 

risk assessment of DCE. In the initial phase of this project, the uncertainties in an existing PBPK 

model for DCE were qualitatively evaluated, and a determination was made of how this model would 

best be applied to reduce or characterize uncertainties in high-to-low dose extrapolation and crossspecies extrapolation, including human and route-to-route extrapolation. The second phase involved 

the development of estimates of dose metrics for USEPA application using a revised PBPK model in 

cross-species and route-to-route extrapolation of cancer and non-cancer risk, and a quantitative 

uncertainty analysis. 

Served as manager of an ongoing project to provide support to the !LSI Children's Risk Assessment 

Framework Working Group. This support included compiling, reviewing and evaluating the available 

data on key physiological parameters for life stages (stages of functional maturation), from the 

perinatal period through adolescence, to develop a consistent and credible data set for PBPK 

modelling. These data have been integrated with rodent data in a pre-existent database. To explore 

the issues associated with trying to populate the database, several case studies were conducted on 

selected parameters (liver weight, liver blood flow, renal clearance and specific enzyme systems) to 

characterize the nature of available data, as well as data quality issues and specific data 

deficiencies. A common conclusion of the case studies was that, for the database to be useful, the 

data that are being incorporated must be critically evaluated with careful consideration given to data 

quality and representativeness. 

Served as project manager on a joint project with Toxicology Excellence for Risk Assessment (TERA) 

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related changes in physiological parameters of animals used in PBPK modelling. The review focused 

upon the parameters previously utilized in models of pregnancy and lactation in rats and mice, and 

covered the period from initiation of pregnancy (fetal parameters only} through early adulthood of 

the offspring. The ultimate goals of this work were to provide a state-of-the-science compilation of 

PBPK parameters; use the actual age-specific, strain-specific data, which reflect any age-specific 

differences in growth, to replace default algorithms; and identify data gaps for development of agedirected PBPK models. 

Served as a co-investigator in a project using PBPK models to explore the issue of sensitive 

sub populations. As part of this project, a PBPK "lifestage" model was developed in which simulations 

of the changes in tissue dosimetry over the entire lifespan, birth to 75 years, were been conducted 

for six environmentally relevant chemicals, covering the spectrum of chemical/physical properties. 

Two focused case studies were also conducted. One focused on the impact of differences in lung 

morphology and ventilation rate on both local and systemic toxicity as a function of the properties of 

the chemical. The other focused on the perinatal period, using PBPK models to evaluate in utero 

exposure via placental transfer versus exposure via lactational transfer, to demonstrate critical 

periods of exposure from a pharmacokinetic perspective. 

Served as a co-investigator in a project conducted for the American Chemistry Council on the 

application of a PBPK model in a risk assessment for acetone to estimate RfD. A PBPK model 

previously developed for isopropanol, whose major metabolite is acetone, was applied. 

Incorporation of a PBPK model into the derivation of the RfD and RfC for acetone allowed for a 

tissue-based approach rather than an external exposure-based approach, making it possible to 

derive an oral RfD from an inhalation study. In addition, the use oft he PBPK model enabled an 

assessment of the potential for acetone to produce any of the effects observed in the isopropanol 

studies, filling some of the data gaps for acetone. 

Worked on a team as a subcontractor to TERA, in conjunction with staff from the University of 

Georgia, to develop a harmonized PBPK model for trichloroethylene (TCE}. ENVIRON staff and 

University of Georgia staff had previously developed independent PBPK models for TCE. At the 

request of the US Air Force, this working group has been convened to develop a harmonized PBPK 

model for TCE, which will be taken through the peer consultation process by TERA. 

Served as a co-investigator in a project using PBPK modelling to investigate the potential impact of 

polymorphisms in genes that encode xenobiotic metabolizing enzymes. One goal of the project was 

to estimate the resulting variability in the activities of these enzymes and the incidence of different 

metabolism phenotypes in a population. The other was to develop an approach for the incorporation 

of these data into a standard risk assessment. Two case studies were conducted that focused on the 

metabolism of warfarin and parathion. 

Served as the principal investigator in the development of a PBPK model for multiple species, 

including rat, rabbit, monkey, dog and human. This project also included a noncompartmental 

analysis of the plasma data of the chemical of concern in rats, monkeys, rabbits and dogs. 

Served as a co-investigator in the development of a PBPK model for arsenic for EPRI. This model will 

be an extension of an existing model that will include the capability to simulate pharmacokinetics in 

the mouse. 

Served as a co-investigator in the development of a PBPK model for acrylic acid. This project 

involved not only a review of the toxicokinetic and toxicity information for acrylic acid, but also for 

esters of acrylic acid to provide direct empirical support for the selection of a duration adjustment 

factor. Responsible for the development of two manuscripts submitted for publication in a peerreviewed journal. 

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Served as a co-investigator in the development of a PBPK model for isopropanol for the Chemical 

Manufacturers Association. This project involved the extension of a previously developed rat model 

to develop a human model and to address reproductive/developmental effects observed in rats. In 

addressing these effects, the model has the capability to simulate internal dose metrics during a 

two-generation reproductive study. 

Served as the principal investigator of the available pharmacokinetic and toxicological data available 

for vinyl chloride for the development of a pharmacokinetic model for vinyl chloride assuming two 

saturable metabolic pathways, to be used by the USEPA in updating their cancer and noncancer risk 

assessments for vinyl chloride. 

Served as the principal investigator of the available toxicological data for TCE for the development 

of dose metrics for this data based on published pharmacokinetic information. 

Served as a co-investigator in a project aimed at making quantitative predictions of interindividual 

differences in susceptibility by using PBPK models. Initially, a systematic and comprehensive review 

of the literature was conducted to identify any quantitative information related to gender- or agespecific physiological and biochemical factors that could influence susceptibility to chemical 

exposure. These data were then organized from a pharmacokinetic perspective by process and 

chemical class to identify key factors likely to have a significant impact on susceptibility as it relates 

to internal target tissue dose. The next phase of this work consisted of using PBPK models to 

develop examples of approaches through the development of case studies. The goal of the case 

studies is to continue to develop a methodology that incorporates PBPK modelling to assess the 

likelihood that a chemical or class of chemicals may present an age- or gender-specific risk. 

Exposure Assessment Documents for Contaminants, Mixtures, Media- or Site-Specific Cases 

Conducted human health risk assessments for private clients at multiple properties in southern 

Louisiana that were historically or currently used for oil and gas exploration activities. Focus in some 

areas was to evaluate the impact that may have resulted to the subsurface soil and groundwater 

beneath closed pits used to store produced water. As necessary, this also involved the collection of 

biota samples (i.e., various species of fish, crabs, and oysters) from waterbodies close to selected 

properties to evaluate the potential impact to humans and ecological receptors from of biota. 

Provided technical support on a project involving the development of inhalation provisional advisory 

levels for the USEPA and National Homeland Security Research Center. 

Managed exposure assessments conducted to estimate the daily intake of anthraquinone from the 

ingestion of food products stored in paper/paperboard manufactured from pulp containing residual 

amounts of anthraquinone. This involved the estimation of the migration of anthraquinone from the 

paper/paperboard to the food which was ingested by a receptor, as well as dermal contact of the 

receptor to the paper/paperboard and inhalation of volatiles from the paper/paperboard. Estimated 

potential exposure via ingestion, dermal contact, and/or inhalation for several other products, 

including drilling mud and fire logs containing residual anthraquinone. 

Participated in the development and preparation of the environmental impact statement for the 

licensing of the first commercial uranium enrichment facility to be built in Louisiana, and prepared 

related sections of the Safety Analysis Report (Reg. Guides 4.9 and 3.25, respectively). The scope of 

this project included evaluation of environmental effects due to uranium isotopes which may be 

attributed to plant operation, coordination of multi-disciplinary teams to conduct environmental 

studies, and the establishment of protracted operational effluent and environmental monitoring 

programs. Issuance of the permit required QA/QC compliance with NQA-1 and USEPA protocols. 

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Reviewed the toxicokinetic data for arsenic and selected organic chemicals in drinking water and 

soil, in order to develop bioavailability factors to adjust for the difference in absorption of arsenic 

when contained in a soil medium by the oral route and the dermal route for use in a site-related 

human health risk assessment. 

Served as the principal investigator in the derivation of an action level for dermal contact with PCBs 

using methodology recommended in the 1986 USEPA Spill Policy Cleanup memorandum and 

incorporating site-specific information. 

Served as the manager of the human health portion of a multi-media risk assessment as part of the 

permit application process to burn hazardous waste as a fuel source at a sulfuric acid regeneration 

plant, consisting of two phases: a screening level assessment and comprehensive assessment. 

Served as the manager of the ecological portion of a multi-media risk assessment as part of the 

permit application process under the Screening Level Combustor Risk Assessment Guidelines 

developed by Region VI USEPA. 

Served as a co-investigator for several site-specific risk assessments and provided toxicological 

support for numerous other applied risk assessment projects at Superfund and other hazardous 

waste sites for both private and government clients. 

Served as a co-investigator in the toxicity assessment and risk assessment portions of an EIS for 

the state of California's Department of Transportation to advise.the state as they assess their 

vegetation management program. The risk assessment was conducted for 25 chemicals with both 

occupational exposure and exposure to the public by multiple pathways. 

Analysis, Document and Issue Paper Preparation 

Managed a project to provide support to the !LSI Children's Risk Assessment Framework Working 

Group. This support included compiling, reviewing and evaluating the available data on key 

physiological parameters for life stages (stages of functional maturation), from the perinatal period 

through adolescence, to develop a consistent and credible data set for PBPK modelling. 

Served as the project manager on a project for EPRI that involved conducting a review of the 

available in vitro studies of the interactions of arsenic species with genes and proteins involved in 

cellular control functions (e.g., DNA repair and redox control), as well as on genomic and 

transcriptomic studies conducted with arsenic compounds. 

Managed a project for Health Canada to determine an appropriate approach for providing a 

meaningful comparison of external acetone intakes to endogenously produced levels. 

Served as the project manager on a project to provide support to the !LSI Research Foundation in 

the development of a children's risk assessment framework case study on perchlorate to: illustrate 

the use of the framework, test the framework and suggest refinements or clarifications to facilitate 

further development. The work product will be a publication in the peer-reviewed literature. 

Served as the project manager on a project to aid in the development of age-specific PBPK models 

for experimental animals. This effort focused on generic physiological values, such as tissue weight 

(termed tissue volume in the context of PBPK modelling), intake (alveolar ventilation, food intake 

and water intake) and flows (blood flows to tissues, bile flow, creatinine clearance and glomerular 

filtration rate). To date, parameters for Sprague Dawley rats and mice of multiple strains have been 

collected and evaluated for data gaps and patterns. Using this database, we found that food intake 

in neonates does scale with approximately bw3/4. 

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Served as a co-investigator in a project that investigated the mechanism of action of acrylamide and 

the formation of mesothelial tumors of the scrotal tunica vaginalis in Fischer 344 rats. The potential 

relationship between these tumors and testicular Leydig cell tumors was also evaluated and the 

relevance to human health was determined. 

Served as a senior reviewer of data evaluation reports prepared for different types of toxicity 

studies, including reproductive/developmental toxicity and subchronic and chronic toxicity studies, 

in a project for the USEPA's Office of Pesticide Programs and Program for Toxic Substances (OPPTS). 

Developed two documents that reported the final histopathological results of two inhalation toxicity 

studies following several reexaminations of the initial histopathological results, an independent 

pathology laboratory and a pathology working group. 

Developed a document that summarized the applicable data for the determination of 

NOAELs/LOAELs for a select class of chemicals to be submitted to the state of California under 

Proposition 65. The data was selected from a comprehensive toxicological database containing 

extensive information regarding the health effects, environmental effects and environmental fate for 

the class of compounds. 

Participated in a toxicological review of data for a new drug. This included reviewing all toxicological 

data and supporting studies to discern putative mechanism of action of drug and relevance of this 

mechanism with regard to human health. This review was presented to the USFDA. 

Participated in a toxicological review of a fungicide for a private client. This included conducting a 

critical toxicological review of bioassay data, mutagenicity, metabolism and pharmacokinetic data to 

evaluate statistical and biological significance of animal bioassay, and the relevance of these data 

with respect to human health. 

Participated in the preparation of toxicological profiles for ATSDR. This included a review of the 

available toxicity data for radon, plutonium and DDT. 

Participated in a review of the current toxicological literature on PCBs, TCDDs and TCDFs to be used 

as an addendum to an existing document. 

Participated in a review of the literature on the reproductive toxicity of ethylene glycol and glycol 

ethers. 

Developed toxicological summaries for occupational exposure to 41 mixtures for a private client to 

be used as supporting documentation for the toxicity information section of the standard material 

safety data sheet. 

Conducted a critical review of the recently developed RfC for manganese, consisting of a review of 

the study upon which the RfC was based. The impact of the uncertainty factors used by the USEPA 

was also considered, as well as the consistency of the derivation of this value compared to RfCs 

developed from similar studies. Evaluated the impact on the RfC of incorporating the benchmark 

approach. 

Participated in a critical review of methylmercury data both in animals and humans to identify the 

endpoints of concern and to select the appropriate data for use in quantitative analyses. Evaluated 

the strength of the evidence based on consideration of all the data with regard to threshold, 

endpoints (discrete, continuous, or multivariate) and feasibility for modelling. Neurotoxicity in the 

developing fetus was also considered. Four data bases were created: studies with dose-response 

data that could be used in initial dose-response modelling work; studies with dose-response data 

expressed in terms of body burden or levels in various tissues or compartments that could be used 

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for dose-response modelling when used as part of a pharmacokinetic model; data on mechanism of 

action; and pharmacokinetic studies. 

Served as the principal author of nine data evaluation reviews (DERs) for the Office of Pesticide 

Programs (OPP) of the US EPA. 

Consumer Products/Pharmaceuticals 

Provided toxicological support on litigation issues related to the potential safety of second 

generation antipsychotics. 

Served as a co-investigator in the evaluation of the potential safety of multiple excipients used in 

the development of a new controlled-release drug to be administered in chronic pain management. 

Served as a co-investigator into the determination of systemic concentrations of PAHs following the 

use of coal-tar-containing shampoos in the treatment of skin disorders. Based on internal dose 

metrics, a safety assessment was conducted to evaluate the potential for adverse effects following 

therapeutic use. 

Served as a co-investigator in the development of a PBPK model for coumarin, a fragrance 

ingredient. This model was used to evaluate potential human health risk following dermal exposure 

to coumarin. The significance of this model is that is relies mainly on the use of in vitro data for 

development of metabolic parameters. 

Served as the principal investigator in a multi-year safety evaluation of the use of various personal 

care products and the determination of their compliance with California's Proposition 65. 

Served as the principal investigator for a project involving the application of a PBPK model in the 

determination of the relationship between the inhaled concentration of ethanol and the blood alcohol 

concentration (BAC). A comparison of the BAC achieved for a limited number of occupational 

scenarios, with BACs achieved following social alcohol consumption, has also been conducted. The 

goal of this project is to determine inhalation concentrations that may result in impairment or the 

potential for developmental effects in the offspring of exposed workers. 

Served as a co-investigator in the evaluation of the potential for adverse effects in children following 

exposure to lead in consumer products and residential settings. 

Conducted a critical review of the inhalation and oral literature for antimony compounds in order to 

select appropriate data to use in dose-response modelling to develop a no significant risk (NSRL) for 

California's Proposition 65. The metal was of concern because of its presence in consumer products 

developed by a private client. The data base was limited and a number of assumptions were made 

to develop the NSRL, all of which were clearly indicated. 

Served as a co-investigator in a quantitative risk assessment to address the issue of the presence of 

trace lead levels in calcium supplements. This investigation was conducted to determine if the 

current lead levels in calcium supplements exceeded the target internal dose associated with the 

NSRL developed by the state of California. This investigation considered the issue of comparative 

bioavailability for lead by the oral and inhalation routes, the influence of calcium and other minerals 

on that bioavailability, and the impact of pregnancy on calcium and lead bioavailability. 

Prepared and served as a QA reviewer for multiple toxicological data evaluation reviews (TDER) 

USFDA for studies submitted in support of a food additive petition. 

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Investigated and prepared information outlining the modes of action and potential health effects 

related to different atypical antipsychotic agents. In addition, provided toxicological support in the 

safety evaluation of the excipients contained in an extended release opiate compound. 

Applied PBPK models to determine potential blood concentrations of volatiles, including PCE, 

following various inhalation exposure scenarios. 

Applied pharmacokinetic principles to evaluate potential BACs over time related to insurance claims. 

Evaluated potential effects of lead in consumer products and residential settings on blood lead levels 

in potentially exposed children. 

Consumer Products/Proposition 65: Provided support in several cases for the review of the basis for 

Proposition 65 NSRLs, conducted product use-specific exposure assessments, conducted risk 

assessments and advised on warning requirements. This has included coal tar shampoos and 

acrylamide 

Provided support for Department of Justice Superfund litigation. 

Provided oversight in the organization of a science advisory panel to evaluate ongoing activities 

related to arsenic research. 

Siloxane-specific Experience 

Principal Investigator the development of aggregate global human health risk assessments for D4 

and Ds. The scope of the project included the development of an aggregated global human health 

risk assessment for D4 and Ds separately, that incorporates the requirements of risk assessments 

conducted by authoritative bodies worldwide. The assessments considered risk scenarios for 

workers, consumers, and the general population; contained a probabilistic exposure assessment to 

rank the exposure scenarios; and utilized an existing physiologically-based pharmacokinetic (PBPK) 

model for the dose-response assessment and calculation of Margins of Safety. 

Principal Investigator in the development of a Systematic Review of the science forDs to support a 

technically rigorous and representative approach to Risk-based Human Health Risk Assessment. 

The goal of the proposed project, which includes the development of a protocol for conducting a 

systematic review of the epidemiological and toxicological literature for Ds, will allow for the 

evaluation of the procedures anticipated by the USEPA in the evaluation of D5 in the IRIS process. 

Senior Scientist on a Ramboll Environ team that provided support in the development of dossier for 

Ds for submission to the EU Scientific Committee on Consumer Safety (SCCS). The toxicology of 

this substance was evaluated in full and human exposure was assessed using PBPK modelling and 

aggregate exposure models covering a range of cosmetics products used daily across the world. In 

addition to supporting the development of the dossier, Ram boll Environ staff also attended a 

meeting with the EU sees to address any questions related to the dossier. 

Participating in the development of case studies for D4 and Ds to estimate Kinetically-Derived 

Maximum Doses (KMDs). These doses both determination of systemic doses of parent compounds 

or metabolites, as well as the application of statistical methods to identify nonlinearities in external 

or internal dose, which are important in identifying a point at which nonlinearity is detectable. The 

identification of these nonlinearities can assist in the development of protocols for toxicity testing. 

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Principal on a project to revise the currently published PBPK model for D. and Ds based on recently 

available results from oral uptake studies. Refinement of the PBPK model will unify the D•/Ds 

models into a single description for assessing risks from cumulative exposure scenarios. 

Prepared manuscripts summarizing groups of studies performed to assess the potential toxicities of 

a variety of siloxanes, including fluids, gels and elastomers. 

Managed the development of a database containing abstracts and relevant toxicological studies to 

be submitted to the USEPA in response to an 8A data call-in for a number of siloxanes to satisfy the 

database requirement for TSCA, as well as the remaining studies conducted by the client. This 

project involved the review and abstracting of approximately 5,000 toxicological studies and the 

incorporation of these abstracts into a searchable database. 

PUBLICATIONS 

2017 

Does occupational exposure to formaldehyde cause hematotoxicity and leukemia-specific chromosome 

changes in cultured myeloid progenitor cells? 

Critical Reviews in Toxicology 47(7); 592-602; DOl: 10.1016/j.ecoenv.2017.04.048. 

Authors: Mundt KA, Gallagher AE, Dell LD, Natelson EA, Boffetta P, Gentry PR. 

2017 

Evaluation of triclosan in Minnesota lakes and rivers: Part II - human health risk assessment. 

Ecotoxicol Environ Saf 142:588-596; DO!: 10.1080/10408444.2017.1301878 

Authors: Yost U, Barber TR, Gentry PR, Bock MJ, Lynda II JL, Capdevielle MC, Slezak BP. 

2017 

A global human health risk assessment for octamethylcyclotetrasiloxane (04 ). 

Toxicology Letters 2017; DOI:10.1016/j.toxlet.2017.05.019 

Authors: Gentry R., Franzen A, Van Landingham C, Greene T, Plotzke K . 

2017 

Refinement of the oral exposure description in the cyclic siloxane PBPK model for rats and humans: 

Implications for exposure assessment 

Toxicology Letters 2017; DOl: 10.1016/j.toxlet.2017.04.002 

Authors: Campbell JL, Andersen M, Van Landingham C, Gentry R, Jensen E, Domoradzki JY,Ciewell III 

HJ 

2017 

A tissue dose-based comparative exposure assessment of manganese using physiologically based 

pharmacokinetic modeling-The importance of homeostatic control for an essential metal. 

Toxicology and Applied Pharmacology 322 (2017) 27-40; DO!: 010.1016/j.taap.2017.02.015. 

Authors: Gentry PR, Van Landingham C, Fuller WG, Sulsky SI, Green TB, Clewell III HJ, Andersen MA, 

Roels HA, Taylor MD, Keene AM. 

2016 

The need for transparency and reproducibility in documenting values for regulatory decision making and 

evaluating causality: The example of formaldehyde. 

Regulatory Toxicology and Pharmacology 2016; 81:512-521. 

Authors: Van Landingham C, Mundt KA, Allen BC, Gentry PR 

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Predicting lung dosimetry of inhaled particle borne benzo[a]pyrene using physiologically based 

pharmacokinetic modeling. 

Inhalation Toxicology 2016; 28(11) [Epub ahead of print]. 

Authors: Campbell J, Franzen A, Van Landingham C, Lumpkin M, Crowell S, Meredith C, Loccisano A, 

Gentry R, Clewell H. 

2016 

Systematic review in chemical risk assessment - A chemical industry perspective. 

Environment International 2016; 92-93: 574-577. 

Authors: Pease CK, Gentry RP 

2016 

A global human health risk assessment for Decamethylcyclopentasiloxane (OS). 

Regulatory Toxicology and Pharmacology 2015; 74(Suppl): S25-S43. 

Authors: Franzen A, Van Landingham C, Greene T, Plotzke K, Gentry R. 

2015 

Risk assessments for chronic exposure of children and prospective parents to ethylbenzene (CAS No. 

100-41-4). 

Critical Reviews in Toxicology 2015; 45(8): 662-726. 

Authors: Sweeney LM, Kester JE, Kirman CR, Gentry PR, Banton Ml, Bus JS, Gargas ML. 

2015 

A Preliminary Regional PBPK Model of Lung Metabolism for Improving Species Dependent Descriptions of 

1,3~Butadiene and its Metabolites. 

Chemico-Biological Interactions 2015; 238: 102-110. 

Authors: Campbell J, Van Landingham C, Crowell S, Gentry R, Kaden D, Fiebelkorn S, Loccisano A, 

Clewell H. 

2015 

Evaluation of gene expression changes in human primary lung epithelial cells following 24-hr exposures 

to inorganic arsenic and its methylated metabolites and to arsenic trioxide. 

Environmental and Molecular Mutagenesis 2015; [Epub ahead of print]. 

Authors: Efremenko AY, Seagrave J, Clewell HJ, Van Landingham c, Gentry PR, Yager JW. 

2014 

A constrained maximum likelihood approach to evaluate the impact of dose metric on cancer risk 

assessment: Application to P·chloroprene. 

Regulatory Toxicology and Pharmacology 2014; 70(1): 203-213. 

Authors: Allen BC, Van Landingham C, Yang Y, Youk, AO, Marsh GM, Esmen N, Gentry PR, Clewell HJ 

3rd, Himmelstein MW. 

2014 

Use of mode of action data to inform a dose-response assessment for bladder cancer following exposure 

to inorganic arsenic. 

Toxicology in Vitro 2014; 28(7): 1196-1205. 

Authors: Gentry PR, Yager JW, Clewell RA, Clewell HJ 3rd. 

2014 

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The impact of recent advances in research on arsenic cancer risk assessment. 

Regulatory Toxicology and Pharmacology 2014; 69(1): 91-104. 

Authors: Gentry PR, Clewell HJ 3rd, Greene TB, Franzen AC, Yager JW. 

2014 

ENVIRONMENT 

& HEALTH 

Potential occupational risk of amines in carbon capture for power generation. 

International Archives of Occupational and Environmental Health 2014; 87(6):591-606. 

Authors: Gentry PR, House-Knight T, Harris A, Greene T, Campleman S. 

2013 

Formaldehyde exposure and leukemia: Critical review and reevaluation of the results from a study that is 

the focus for evidence of biological plausibility. 

Critical Reviews in Toxicology 2013; 43(8): 661-670. 

Authors: Gentry PR, Rodricks JV, Turnbull D, Bachand A, Van Landingham C, Shipp AM, Albertini RJ, 

Irons R. 

2013 

Evaluation of gene expression changes in human primary uroepithelial cells following 24-hour exposures 

to inorganic arsenic and its methylated metabolites. 

Environmental and Molecular Mutagenesis 2013; 54(2): 82-98. 

Authors: Yager JW, Gentry PR, Thomas RS, Pluta L, Efremenko A, Black M, Arnold LL, McKim JM, Wilga 

P, Gill G, Choe KY, Clewell HJ 3rd. 

2012 

Physiologically based pharmacokinetic/toxicokinetic modelling. 

Methods in Molecular Biology 2012; 929: 439-499. 

Authors: Campbell JL Jr, Clewell RA, Gentry PR, Andersen ME, Clewell HJ 3rd. 

2011 

Challenges in the application of quantitative approaches in risk assessment: a case study with di-(2-

ethylhexyl)phthalate. 

Critical Reviews in Toxicology 2011; 41(S2): 1-72. 

Authors: Gentry PR, Clewell HJ 3rd, Clewell R, Campbell J, Van Landingham c, Shipp AM. 

2011 

Concentration- and time .. dependent genomic changes in the mouse urinary bladder following exposure to 

arsenate in drinking water for up to 12 weeks. 

Toxicological Sciences 2011; 123(2): 421-432. 

Authors: Clewell HJ 3rd, Thomas RS, Kenyon EM, Hughes MF, Adair BM, Gentry PR, Yager JW. 

2010 

Analysis of genomic dose-response information on arsenic to inform key events in a mode of action for 

carcinogenicity. 

Environmental and Molecular Mutagenesis 2010; 51(1):1-14. 

Authors: Gentry PR, McDonald TB, Sullivan DE, Shipp AM, Yager JW, Clewell HJ 3rd. 

2007 

A pharmacokinetic model of the intracellular dosimetry of inhaled nickel. 

Journal of Toxicology and Environmental Health, Part A 2007; 70(5): 445-464. 

Authors: Hack CE, Covington TR, Lawrence G, Shipp AM, Gentry PR, Yager JW, Clewell HJ 3rd. 

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2007 

ENVIRONMENT 

& HEALTH 

Research toward the development of a biologically based dose response assessment for inorganic arsenic 

carcinogenicity: A progress report. 

Toxicology and Applied Pharmacology 2007; 222(3):388-398. 

Authors: Clewell HJ, Thomas RS, Gentry PR, Crump KS, Kenyon EM, EI-Masri HA, Yager JW. 

2006 

Acrylamide: Review of toxicity data and dose~ response modelling for cancer and noncancer effects. 

Critical Reviews in Toxicology 2006; 36(6-7):481-608. 

Authors: Shipp A, Lawrence G, Gentry R, McDonald T, Bounds J, Macdonald N, Clewell H, Allen B, Van 

Landingham C. 

2006 

Revised assessment of cancer risk to dichloromethane: part I Bayesian PBPK and dose-response 

modelling in mice. 

Regulatory Toxicology and Pharmacology 2006; 45(1):44-54. 

Authors: Marino DJ, Clewell HJ, Gentry PR, Covington TR, Hack CE, David RM, Morgott DA. 

2006 

Revised assessment of cancer risk to dichloromethane II. Application of probabilistic methods to cancer 

risk determinations. 

Regulatory Toxicology and Pharmacology 2006; 45(1):55-65. 

Authors: David RM, Clewell HJ, Gentry PR, Covington TR, Morgott DA, Marino DJ. 

2006 

The use of Markov chain Monte Carlo uncertainty analysis to support a public health goal for 

perchloroethylene. 

Regulatory Toxicology and Pharmacology 2006; 47(1): 1-18. 

Authors: Covington TR, Gentry PR, Van Landingham CB, Andersen ME, Kester JE, Clewell HJ 3rd. 

2005 

Evaluation of physiologically based pharmacokinetic models in risk assessment: An example with 

perchforoethylene. 

Critical Reviews in Toxicology 2005; 35(5): 413-433. 

Authors: Clewell HJ, Gentry PR, Kester JE, Andersen ME. 

2005 

Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds. 

Journal of Toxicology and Environmental Health 2005; 68(5): 329-351. 

Authors: Gentry PR, Covington TR, Lawrence G, McDonald T, Snow ET, Germolec D, Moser G, Yager JW, 

Clewell HJ 3''. 

2004 

Evaluation of the potential impact of age- and gender-specific pharmacokinetic differences on tissue 

dosimetry. 

Toxicological Sciences 2004; 79(2): 381-393. 

Authors: Clewell HJ, Gentry PR, Covington TR, Sarangapani R, Teeguarden G. 

2004 

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& HEALTH 

Interspecies dose extrapolation for inhaled dimethyl sulfate: A PBPK model-based analysis using nasal 

cavity N7-methylguanine adducts. 

Jnahlation Toxicology 2004; 16(9): 593-605. 

Authors: Sarangapani R, Teeguarden JG, Gentry PR, Clewell HJ 3rd, Barton HA, Bogdanffy MS. 

2003 

Evaluation of the potential impact of pharmacokinetic differences on tissue dosimetry in offspring during 

pregnancy and lactation. 

Regulatory Toxicology and Pharmacology 2003; 38(1):1-16. 

Authors: Sarangapani R, Teeguarden JG, Gentry PR, Clewell HJ 3rd, Barton HA, Bogdanffy MS. Gentry 

PR, Covington TR, Clewell HJ 3rd. 

2003 

Evaluation of the potential impact of age- and gender-specific lung morphology and ventilation rate on 

the dosimetry of vapors. 

Inhalation Toxicology 2003; 1S(10): 987-1016. 

Authors: Sarangapani R, Gentry PR, Covington TR, Teeguarden G, Clewell HJ 3rd. 

2003 

Application of a physiologically-based pharmacokinetic model for reference dose and reference 

concentration estimation for acetone. 

Journal of Toxicology and Environmental Health, Part A 2003; 66(23): 2209-2225. 

Authors: Gentry PR, Covington TR, Andersen ME, Clewell HJ 3rd. 

2003 

Physiologically based pharmacokinetic modelling of arsenic in the mouse. 

Journal of Toxicology and Environmental Health, Part A 2003; 67(1): 43-71. 

Authors: Gentry PR, Covington TR, Mann S, Shipp AM, Yager JW, Clewell HJ 3rd. 

2002 

An approach for the quantitative consideration of genetic polymorphism data in chemical risk 

assessment: Examples with warfarin and parathion. 

Toxicological Sciences 2002; 70(1):120-139. 

Authors: Gentry PR, Hack CE, Haber L, Maier A, Clewell HJ 3rd. 

2002 

Genetic polymorphisms in assessing interindividual variability in delivered dose. 

Regulatory Toxicology and Pharmacology 2002; 35(2 pt 1):177-197. 

Authors: Haber LT, Maier A, Gentry PR, Clewell HJ 3rd, Dourson ML. 

2002 

Application of a physiologically-based pharmacokinetic model for isopropanol in the derivation of an 

RfD/RfC. 

Regulatory Toxicology and Pharmacology 2002; 36(1): 51-68. 

Authors: Gentry PR, Covington TR, Andersen ME, Clewell HJ 3rd. 

2002 

Review and evaluation of the potential impact of age and gender-specific pharmacokinetic differences on 

tissue dosimetry. 

Critical Reviews in Toxicology 32(5): 329-389. 

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&HEALTH 

Authors: Clewell HJ 3rd, Teeguarden J, McDonald T, Sarangapani R, Lawrence G, Covington T, Gentry R, 

Shipp A. 

2001 

Development of a physiologically based pharmacokinetic model of isopropanol and its metabolite 

acetone. 

Toxicological Sciences 2001; 63(2):160-172. 

Authors: Clewell HJ 3rd, Gentry PR, Gearhart JM, Covington TR, Banton MI, Andersen ME. 

2001 

Comparison of cancer risk estimates for vinyl chloride using animal and human data with a PBPK model. 

The Science of the Total Environment 2001; 274(1-3): 37-66. 

Authors: Clewell HJ 3rd, Gentry PR, Gearhart JM, Allen BC, Andersen ME. 

2001 

A hybrid computational fluid dynamics and physiologically based pharmacokinetic model for comparison 

of predicted tissue concentrations of acrylic acid and other vapors in the rat and human nasal cavities 

following inhalation exposure. 

Inhalation Toxicology 2001; 13(5): 359-376. 

Authors: Frederick CB, Gentry PR, Bush ML, Lomas LG, Black BA, Finch L, Kimbell JS, Morgan KT, 

Subramaniam RP, Morris JB, Ultman JS. 

2000 

Site-specific reference dose for methylmercury for fish-eating populations. 

Fuel Processing Technology 65-66:43-54. 

Authors: Clewell HJ 3rd, Crump K, Gentry R, Shipp A. 

2000 

Determination of a site~specific reference dose for methylmercury for fish-eating populations. 

Toxicology and Industrial Health 2000; 16(9-10): 335-438. 

Authors: Shipp AM, Gentry PR, Lawrence G, Van Landingham C, Covington T, Clewell H, Gribben K, 

Crump K. 

2000 

Development of a physiologically-based pharmacokinetic model of trichloroethylene and its metabolites 

for use in risk assessment. 

Environmental Health Perspectives 108(Suppl 2): 283-305. 

Authors: Clewell HJ 3rd, Gentry PR, Covington TR, Gearhart JM. 

2000 

Application of a hybrid CFD-PBPK nasal dosimetry model in an inhalation risk assessment: an example 

with acrylic acid. 

Toxicological Sciences 2000; 57(2): 312-325. 

Authors: Andersen A, Sarangapani R, Gentry R, Clewell HJ 3rd, Covington T, Frederick C. 

1999 

Requirements for a biologically realistic cancer risk assessment for inorganic arsenic. 

International Journal of Toxicology 18(2): 131-147. 

Authors: Clewell HJ 3rd, Gentry PR, Barton HA, Shipp AM, Yager JW, Andersen ME. 

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1999 

ENVIRONMENT 

& HEALTH 

Evaluation of the uncertainty in an oral reference dose for methylmercury due to interindividual 

variability in pharmacokinetics. 

Risk Analysis 1999; 19: 547-558. 

Authors: Clewell HJ 3rd, Gearhart JM, Gentry PR, Covington TR, Van Landingham CB, Crump KS, Shipp 

AM. 

1998 

Calculation of benchmark doses for reproductive and developmental toxicity observed after exposure to 

isopropanol. 

Regulatory Toxicology and Pharmacology 1998; 28: 38-44. 

Authors: Allen B, Berman D, Van Landingham C. 1998. Authors: Allen BC, Gentry PR, Shipp AM, Van 

Landingham CB. 

1997 

Investigation of the potential impact of benchmark dose and pharmacokinetic modelling in noncancer 

risk assessment. 

Journal of Toxicology and Environmental Health 1997; 52(6): 475-515. 

Authors: Clewell HJ 3rd, Gentry PR, Gearhart JM. 

1995 

Considering pharmacokinetic and mechanistic information in cancer risk assessments for environmental 

contaminants: Examples with vinyl chloride and trichloroethylene. 

Chemosphere 1995; 31(1): 2561-2578. 

Authors: Clewell HJ 3rd, Gentry PR, Gearhart JM, Allen BC, Andersen ME. 

ABSTRACTS 

2005 

Physiological parameters for early life stages. 

The Toxicologist 2005; 84(S-1): 261. 

Authors: Olin S, Clewell HJ 3rd, Gentry R, !LSI Working Group. 

2005 

Issues in the use of PBPK modelling in the development of cancer slope factors for perchloroethylene. 

The Toxicologist 84(S-1): 350. 

Authors: Kester KE, Gentry P, Covington TR, Clewell HJ 3rd. 

2002 

Evaluation of the potential impact of age- and gender-specific pharmacokinetic differences on tissue 

dosimetry. 

The Toxicologist 2002; 66(1-S): 251. 

Authors: Gentry R, Teeguarden J, Sarangapani R, Covington T, Lawrence G, McDonald T, Shipp A, 

Clewell l. 

2001 

Comparison of alternative exposure measures for evaluating the neurological effects of methylmercury in 

children. 

The Toxicologist 2001; 60(1): 19. 

Authors: Gentry PR, Clewell HJ 3rd, Shipp AM, Yager JW. 

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2000 

ENVIRONMENT 

& HEALTH 

Trichloroacetate tissue dosimetry and PPAR alpha~mediated liver cancer induction by trichloroethylene 

and perchloroethylene. 

The Toxicologist 2000; 54(1): 95. 

Authors: Barton HA, Gentry PR, Clewell HJ 3rd. 

2000 

Development of a physiologically-based pharmacokinetic (PB-PK) model and human health risk 

assessment for coumarin. 

The Toxicologist 2000; 54(1):109. 

Authors: Gentry R, Clewell HJ 3rd, Covington T, Wilson J. 

2000 

Investigation of the impact of benchmark and PBPK modelling on the derivation of MRLs. 

The Toxicologist 2000; 54(1):109. 

Authors: Clewell HJ 3rd, Gentry PR, Gearhart JM, Born SL, Lehman-McKeeman LD, Covington TR. 

2000 

Consideration of the potency classification of acrylamide (ACR) based on the incidence of tunica vaginalis 

mesotheliomas (TVMs) in male Fischer 344 rats. 

The Toxicologist 2000; 54(1): 272. 

Authors: Lawrence G, Gentry R, Clewell H, Shipp A. 

1999 

Development of a physiologically-based pharmacokinetic (PB-PK) model for isopropanol and acetone. 

The Toxicologist 1999; 48(1-S):144. 

Authors: Gentry R, Clewell HJ 3rd, Gearhart J, Covington T, Andersen M. 

1999 

Intracellular clearance of nickel compounds: An important determinant of carcinogenic potential. 

The Toxicologist 1999; 48(1-S): 333. 

Authors: Lawrence G, Shipp A, Clewell H, Gentry R, Gearhart J. 

1998 

Reevaluation of the current RfD for methylmercury. 

The Toxicologist 1998; 42(1-S): 225-226. 

Authors: Gentry PR, Shipp AM, Gearhart JM, Crump KS, Clewell HJ 3rd. 

1998 

Application of the risk assessment approaches in the USEPA proposed cancer guidelines to arsenic. 

The Toxicologist 1998; 42(1-S): 229 

Authors: Shipp AM, Clewell HJ 3rd, Crump KS, Gentry PR, Andersen ME. 

MEMBERSHIPS 

Society of Toxicology (SOT) 

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1;f4UI:Ifl!!l ENVIRON 

SONJA SAX 

Senior Environmental Health Scientist 

Dr. Sonja Sax is an environmental health scientist with over 15 years 

of exposure and health risk assessment experience. She has 

particular expertise in airborne gases and particles, and has 

performed indoor and outdoor air quality investigations, managed 

several large environmental projects, conducted critical evaluations of 

toxicology and epidemiology studies, and helped prepare technical 

and expert reports. Sonja has authored and co-authored several 

publications, presented her research and consulting work at various 

conferences and testified before scientific panels, including the Clean 

Air Science Advisory Committee (CASAC). Sonja earned an MS and 

doctorate in environmental health from the Harvard T.H. Chan School 

of Public Health, where she also served as a postdoctoral fellow. 

2016->>> 

Senior Environmental Health Scientist, Ram boll Environ 

2005-2015 

Senior Project Manager, Gradient 

Managed and worked on multiple projects related to evaluation of 

human exposures and health risks associated with environmental 

pollutants; routinely conducted air dispersion modeling and 

exposure assessments to support health risk assessments; 

reviewed and interpreted epidemiology and toxicology studies for 

use in preparing expert reports, peer-reviewed publications, 

regulatory comments, and risk communications. 

2003-2005 

Postdoctoral Fellow, Harvard School of Public Health 

Managed two large exposure assessment projects, developed study 

protocols, organized field studies, and managed staff. Additional 

duties included writing grants, analyzing data, and publishing 

manuscripts in peer-reviewed journals. 

1998-2003 

Research/Teaching Assistant, Harvard School of Public Health 

Designed, conducted, and managed a large air pollution exposure 

assessment study of inner-city teenagers in New York City and Los 

Angeles; measured and analyzed indoor, outdoor, and personal 

concentrations of volatile organic compounds (VOCs), carbonyls, 

PM2.5, and particle-associated metals. Teaching assistant for an 

introductory environmental health course. 

1/6 CV, SONJA SAX, lAST UPDATED 2016/2 

ENVIRONMENT 

& HEALTH 

Sonja Sax 

ssax@rambo!l.com 

+1 (413) 835-4358 

Ram boll Environ 

28 Amity Street 

Suite 2A 

Amherst, 01002 

United States of America 
103 

i;f4UI:WI!I ENVIRON 

1995 

Intern, Environmental Protection Agency 

ENVIRONMENT 

& HEALTH 

Analyzed health effects data to assess the impact of ozone concentrations on hospital admissions in 

Massachusetts. 

1994-1997 

Research Assistant, Harvard School of Public Health 

Proposed, designed, and implemented an indoor air quality study of a green community of homes. 

1991-1994 

Research Associate, Repligen Corporation 

Managed the peptide chemistry lab. Conducted research to improve the synthesis of peptides. Trained 

and supervised laboratory staff. 

EDUCATION 

2003 

SeD, Environmental Health Sciences 

Harvard School of Public Health 

1996 

MS, Environmental Health Management 

Harvard School of Public Health 

1991 

BA, Biological Chemistry 

Wellesley College 

LANGUAGE SKillS 

Spanish (mother tongue), English (mother tongue) 

EXPERIENCE HIGHUGHTS 

Critical Reviews and Syntheses 

Conducted an extensive literature search on the toxicity and health effects of several different chemical 

compounds including cobalt and cobalt alloys found in dental materials, diesel exhaust, carbon black, 

welding fumes, and sulfur dioxide. 

Systematic Reviews 

Conducted weight-of-evidence evaluation of cardiovascular and respiratory effects from exposures to 

ozone. Results of the critical evaluation of toxicology, epidemiology, and mode -of-action studies were 

published in several peer-reviewed manuscripts. 

litigation Support 

Contributed to the preparation of expert reports in litigation projects that involved a variety of different 

chemical exposures including volatile organic compounds (e.g., vinyl chloride), asbestos, carbon black, 

particulate matter, sulfur dioxide, and pesticides. 

2/6 CV, SONJA SAX, LAST UPDATED 2016/2 
104 

l;fiUI:JC4D ENVIRON 

Exposure and Risk Assessment 

ENVIRONMENT 

& HEALTH 

For numerous projects prepared technical analyses on exposures and potential health effects associated 

with various pollutants (e.g., particulate matter, sulfur dioxide, nitrogen dioxide, arsenic, and 

pesticides). Exposure assessments often included air dispersion modeling. 

Regulatory Comments 

Provided written and oral comments on several occasions to the Clean Air Scientific Advisory Committee 

{CASAC) on human exposure, epidemiology, toxicology, and mechanistic studies and their bearing on 

US EPA's National Ambient Air Quality Standards (NAAQS) for particulate matter and ozone. 

Indoor Exposure and Risk Assessment 

Conducted exposure and risk assessments of residential exposures to various chemicals including 

formaldehyde from wood products, vapor intrusion of tetrachloroethylene, exposures to mercury from 

wallboard and concrete, and exposures to flame retardants from various indoor sources. 

PUBUCA TIONS 

2015 

Particle size distributions of lead measured in battery manufacturing and secondary smelter facilities and 

implications in setting workplace lead exposure limits. 

Journal of Occupational and Environmental Hygiene (Submitted) 

Authors: Petito Boyce C, Sax SN, Cohen JM 

2015 

Are the Elementsofthe Proposed Ozone National Ambient Air Quality Standards Informed by the Best 

Available Science? 

Regulatory Toxicology and Pharmacology 72(1): 134-140 

Authors: Goodman JE, Sax SN, Lange SS, Rhomberg LR 

2015 

Providing Perspective for Interpreting Cardiovascular Mortality Risks Associated with Ozone Exposures. 

Regulatory Toxicology and Pharmacology 72(1): 107-116 

Authors: Petito Boyce C, Goodman JE, Sax SN, Loftus CT 

2015 

Rethinking Meta-analysis: Applications for Air Pollution Data and Beyond. 

Risk Analysis 35(6):1017-1039 

Authors: Goodman JE, Petito Boyce C, Sax SN, Beyer LA, Prueitt RL 

2015 

Ozone Exposure and Systemic Biomarkers: Evaluation of Evidence for Adverse Cardiovascular Health 

Impacts. 

Critical Reviews in Toxicology 45(5):412-452 

Authors: Goodman JE, Prueitt RL, Sax SN, Pizzurro DM, Lynch HN, Zu K, Venditti FJ 

2014 

Weight-of-evidence Evaluation of Short-term Ozone Exposure and Cardiovascular Effects. 

Critical Reviews in Toxicology 44(9):725-790 

Authors: Goodman JE, Prueitt RL, Sax SN, Lynch HN, Zu K, Lemay JC, King JM, Venditti FJ 

3/6 CV, SONJA SAX, LAST UPDATED 2016/2 
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l;lfUI:ii4!1 ENVIRON 

2014 

The dubious benefitsoffurtherozone reductions (Op-ed). 

ENVIRONMENT 

& HEALTH 

The Wall StreetJournal May 11, 2014 at http://online.wsj.com/news/articles/SB100014240527023041 

78104579536120366671620?mg=reno64-wsj 

Authors: Goodman JE, Sax S 

2014 

Weight-of-evidence Evaluation of Long-term Ozone Exposure and Cardiovascular Effects. 

Critical Reviews in Toxicology 44(9):791-822 

Authors: Prueitt RL, Lynch HN, Zu K, Sax SN, Venditti FJ, Goodman JE. 

2014 

Evaluation of adverse human lung function effects in controlled ozone exposure studies. 

Journal of Applied Toxicology 34(5):516-24 

Authors: Goodman JE, Prueitt RL, Chandalia J, Sax SN 

2013 

Letter re: article, 'Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular 

Effects.' 

Circulation 127(4):e432 

Authors: Goodman JE, Sax SN 

2013 

Letter to the editor Re: Air pollution and lung cancer incidence in 17 European cohorts: Prospective 

analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE). 

The Lancet Oncology 14(11):e439-40 

Authors: Sax SN, Zu K, Goodman JE 

2013 

Letter to the editor Re: Long-Term Residential Exposure to Air Pollution and Lung Cancer Risk. 

Epidemiology 25(1): 159 

Authors: Sax, SN, Goodman JE 

2013 

Letter re: Equivocal evidence for confounding effects of components of particulate matter on the 

relationship between ozone and mortality [letter]. 

American Journal of Epidemiology 177(12): 1460-1462 

Authors: Sax SN, Goodman JE 

2012 

Potential indoor air exposures and heatth risks from mercury off-gassingof coal combustion products 

(CCPs) used in building materials. 

Coal Combustion and Gasification Products 4:68-74 

Authors: Long CM, Sax SN, Lewis AS 

2011 

Human health hazards of exposure to new technology diesel exhaust (NlDE). 

Toxicologist- Supplement to Toxicological Sciences 120(Suppl. 2) 

Authors: Hesterberg TW, Long CM, Sax SN, Lapin CA, Bunn WB, Valberg PA, McClellan RO 

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i;ftj;t=IC41'1 ENVIRON 

2011 

ENVIRONMENT 

& HEALTH 

Non-chemical stressors and cumulative risk assessment: An overview of current initiatives and potential 

air pollutant interactions. 

International Journal of Environmental Research and Public Health 8(6):2020-2073. 

Authors: Lewis AS, Sax SN, Wason SC, Campleman SL 

2011 

Risk characterization of the brominated flame retardant decabromodiphenyl ethane in indoor dust. 

Toxicologist- Supplement to Toxicological Sciences 120(Suppl. 2):271 

Authors: Dodge DG, Pollock MC, Sax SN, Petito Boyce C, Goodman JE 

2010 

Letter re: Xue et al. (2010} article addressing probabilistic modeling of dietary arsenic exposure and 

dose. 

Environmental Health Perspectives 118(8). E-pub ahead of print doi: 10.1289/ehp.1002328. 

Authors: Petito Boyce C, Lewis AS, Sax SN, Beck BD, Eldan M, Cohen SM 

2009 

Human exposure to decabromodiphenyl ether, tetrabromobisphenol A, and decabromodiphenylethane in 

indoor dust. 

Journal of Environmental Protection Science 3:75-96 

Authors: Petito Boyce C, Sax SN, Dodge DG, Pollock MC, Goodman JE 

2009 

Non-cancer health effects of diesel exhaust (DE): A critical assessment of recent human and animal 

toxicological literature. 

Critical Reviews in Toxicology 39:195-227 

Authors: Hesterberg TW, Long CM, Bunn WB, Sax SN, Lapin CA, Valberg PA 

2008 

Probabilistic analysis of human health risks associated with background concentrations of inorganic 

arsenic: Use of a margin of exposure approach. 

Human and Ecological Risk Assessment 14:1159-1201. **Winner of the HERA Human Risk Assessment 

Paper of the Year Award in 2008. 

Authors: Petito Boyce C, Lewis AS, Sax SN, Eldan ME, Cohen, SM, Beck BD 

2007 

Trends in the elemental composition of fine particulate matter in Santiago, Chile, from 1998 to 2003. 

Journal of the Air & Waste Management Association 57(7):845-855 

Authors: Sax SN, Koutrakis P, Rudolph PA, Cereceda-Balic F, Gramsch E, Oyola P 

2006 

Integrating studies on carcinogenic risk of carbon black: Epidemiology1 animal exposures, and 

mechanism of action. 

Journal of Occupational and Environmental Medicine 48(12):1291-1307 

Authors: Valberg P, Long CM, Sax SN 

2006 

A cancer health risk assessment of a cohort of inner-city teenagers in New York City and los Angeles. 

Environmental Health Perspectives 114(10):1558-1566 

Authors: Sax SN, Bennett DH, Chillrud SN, Kinney P, Ross J, Spengler JD 

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i;fiUI:WD ENVIRON 

2005 

ENVIRONMENT 

& HEALTH 

Analysis of PM10, PM2.5, and PM2.5-10 concentrations in Santiago, Chile, from 1989 to 2001. 

Journal of the Air & Waste Management Association 55{3):342-351. 

Authors: Koutrakis P, Sax SN, Sarnat JA, Coull B, Demokritou P, Oyola P, Garcia J, Gramsch E 

2004 

Differences in source emission rates of volatile organic compounds in inner-city residences of New York 

City and Los Angeles. 

Journal of Exposure Analysis and Environmental Epidemiology 14:S95-S109 

Authors: Sax SN, Bennett DH, Chillrud SN, Kinney PL, Spengler JD 

2004 

Elevated airborne exposures to manganese, chromium and iron from steel dust in New York City's 

subway system. 

Environmental Science & Technology 38:732-737 

Authors: Chillrud SN, Epstein D, Ross JM, Sax SN, Pederson D, Spengler JD, Kinney PL 

2002 

Exposures to multiple air taxies in New York City. 

Environmental Health Perspectives llO(Suppl. 4):539-546 

Authors: Kinney PL, Chillrud SN, (Sax) Ramstrom S, Ross J 

OTHER ACTIVITIES 

Technical peer reviewer for the following Journals: 

Journal of the Air & Waste Management Association 

Journal of Exposure Science and Environmental Epidemiology 

Environmental Health Perspectives 

Atmospheric Environment 

Environmental Pollution 

MEMBERSHIPS 

Air & Waste Management Association (AWMA) 

Society for Risk Analysis (SRA) 

Society for Risk Analysis New England Chapter (SRA-NE) 

International Society of Exposure Science (ISES) 

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108 

2. Dr. Mundt, in your written testimony before the Committee you referenced a "detailed 

evaluation of the 2010 Review conducted by Ram boll Environ US Corporation" as a 

starting point for the EPA to begin a re-evaluation of its 2010 IRIS Toxicological 

Review of Chloroprene. 

a. Has this referenced "2010 Review" prepared by Ramboll Environ been 

published in a scientific journal? If so, please provide the citation to the journal 

article. 

Our technical report has not yet been published. We hope to publish a shorter 

version of the critical portions of the report. In the meantime, DPE is relying upon 

our technical review to assist them in addressing the EPA Clean Air Act review of 

the facility, and to assist the Request for Correction of the erroneous and 

scientifically unsubstantiated determinations from the 2010 Review, particularly 

the erroneous IUR. We consider our evaluation of the science to be independent 

and all conclusions to be our own and not guided or influenced by DPK 

b. If the ehloroprene paper has been published, was it peer-reviewed prior to 

publication? If so, please detail the process by which the paper was reviewed. 

Please see previous response. 

3. A June 26, 20171etter that Denka Performance Elastomer LLC ("Denka") sent to EPA 

seeks to have EPA "withdraw and correct" its 2010 IRIS toxicology review of 

chloroprene. In the letter, Denka leans heavily on the findings of a Ramboll Environ 

report, in which you served as lead author. Your report-Basis for Requesting 

Correction of the U.S. EPA Toxicology Review of Chloroprene-stated that Denka 

"asked Ramboll Environ to conduct an independent evaluation ofthe 2010 

[chloroprene] review." 

a. Was Ram boll Environ compensated by Denka for producing the aforementioned 

report? If so, please detail the compensation provided. Please also detail any 

other compensation or support Ram boll Environ received from any other 

company, organization, association, entity or individual for researching and/or 

producing this report. 

Yes. As stated in our written testimony, Ramboll Environ and DPE entered a 

business agreement whereby Ramboll Environ was provided usual fees for the 

performance of the scientific evaluation of the 2010 Review. No other entity has 

provided financial sponsorship. 

b. Was this report-Basis for Requesting Correction of the U.S. EPA Toxicology 

Review of Chloroprene-peer reviewed? If so, please indicate the association, 

organization, or entity who conducted this review. 

Our technical report has not yet been submitted to any scientific journal, and 

therefore has not undergone any formal peer-review. Should we submit some or 

all of the technical report for publication in a scientific journal, it will be subject 
109 

to such peer review. As noted above, our aim was to conduct an independent 

evaluation of the 2010 Review, specifically with respect to EPA's derivation of 

the IUR. Our report provides a detailed description of how standard conservative 

EPA risk evaluation methods and data inputs from peer-reviewed publications can 

be used to derive a scientifically sound IUR. It is important to reiterate that we 

used standard EPA methodologies, which EPA has used in the evaluation of other 

IRIS chemicals, and that our technical report transparently describes the 

methodology and assumptions used to derive the IUR following the 

recommendations from the NRC best practices. Importantly, the conclusions of 

the technical report are based on peer-reviewed publications that were published 

subsequent to the development of the 2010 Review. Certainly EPA may elect to 

use alternative assumptions and/or methods; however, any IUR that fully and 

properly considers the known large differences between the way mice and 

humans process chloroprene will be much closer to the one we calculated than to 

the one published by EPA in 2010. Our comparison of the potential cancer risks 

based on our estimated IUR to the results from epidemiological studies indicates 

that it is more consistent with the epidemiological evidence than the EPA IUR 

that was published in the 2010 Review. 
110 

Responses by Dr. James Bus 

U.S. HOUSE OF REPRESENTATIVES 

COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

Subcommittee on Environment 

Subcommittee on Oversight 

Hearing Questions for the Record 

The Honorable Eddie Bernice Johnson 

Examining the Scientific and Operational Integrity of EPA's IRIS Program 

Questions for Dr •• James Bus 

1. In your written testimony, you acknowledge that you received "support" in preparing 

your testimony from the American Chemistry Council (ACC). Please detail the 

complete nature of that "support" provided by ACC, including names of the individuals 

who provided such "support" in the preparation of your testimony. This should include 

any financial support provided by the ACC, or any support, of any kind, provided by 

any other organization or individual regarding the preparation of your testimony. 

The first question posed inquired about the financial support 

provided by the American Chemistry Council ("ACC"). Through a 

contract with my employer, Exponent, the ACC provided financial 

assistance supporting my expenses associated with development and 

presentation of my comments. The expenses included both time and 

travel. Also, because I reside in Michigan, the ACC also made the 

requested copies of my testimony and accompanying biographical 

information and arranged for the delivery of those materials to 

congressional staff. 

My comments were entirely my own, and were based entirely on 

my professional experiences over many years of interactions with the 

IRIS program. My comments were not reviewed or approved by the 

ACC. The ACC provided me with background informational documents 

on the IRIS program, publicly available copies of the EPA NCEA 

presentation to the Chartered EPA SAB, and the ensuing SAB letter to 

Congress reflecting its observations on progress ofthe EPA IRIS 

program. 

2. Many of the studies you have conducted while employed at Exponent have been funded 

by industry. Please provide a list of the specific companies, associations, or other entities 

that have funded, or otherwise supported, your research efforts since you joined 

!707670.000. !543 
111 

Exponent in May 2013. Please also include a brief description of the nature of each 

research effort. 

The second question posed asked me to identify the specific companies, 

associations or other entities that have funded or supported my research efforts since May 

of2013. Due to contractual obligations, Exponent cannot release the names of its clients 

for which I have provided consulting services without the permission of those clients. As 

noted in my Exponent curriculum vitae, based on my extensive and broad experiences in 

toxicology, my consulting activities include provision of 

... chemical specific and strategy toxicology expertise addressing 

develop, stewardship, and regulatory needs to individual industry clients 

and business consortia and government and non-governmental agencies. 

Dr. Bus provides expertise in design, implementation, and interpretation 

of toxicity tests and mode of action and dose response/exposure 

evaluations furthering translation of toxicology findings to risk 

assessments. 

In connection with the publications that appear on my curriculum vitae (an updated copy 

of which is enclosed), funding sources are disclosed in the publication as required by the 

publisher. 

1707670.000- 1543 
112 

Responses by Dr. Thomas Burke 

U.S. HOUSE OF REPRESENTATIVES 

COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY 

Subcommittee on Environment 

Subcommittee on Oversight 

Hearing Questions for the Record 

The Honorable Eddie Bernice Johnson 

Examining the Scientific and Operational Integrity of EPA's IRIS Program 

Questions for Dr. Burke 

1. How would you respond to those who suggest that IRIS assessments and the IRIS 

process should be reviewable through the judicial system? Is there an appropriate 

role or the courts to play in ensuring both EPA, and the IRIS process meet their 

regulatory obligations? How would that role differ from inserting judicial review in 

the IRIS process itself, and what, if any, consequences could there be from inserting 

such judicial review? Do you believe, for instance, that this sort of judicial review 

could impact the scientific integrity of the IRIS process? 

I feel that judicial review is not appropriate, since IRIS is not a regulatory or policy 

process. IRIS synthesizes scientific evidence. Independent peer review of the science is 

the most appropriate form of review to assure the quality of the science. The transparency 

of the process is also enhanced by interagency review, the stakeholder and public 

comment process. There is an appropriate and important role for the courts in assuring 

that EPA is meeting their regulatory obligations. Judicial system review of EPA 

regulatory decisions has proven to be important in assuring that the Agency is complying 

with the law and meeting its responsibilities in protecting health and the environment. 

While I would need more specific information on how judicial review might be inserted 

in the IRIS process before answering, I am concerned that may have a number of 

unintended and costly consequences. Consequences might include major delays in 

identifying evaluating risks to human health, deterioration of the scientific excellence, 

integrity, and independence ofiRIS, discouragement or even intimidation of scientists, 

and increased costs to EPA, the courts, as well as chemical manufacturers and other 

industries and organizations that may be a party to such judicial review. A key principle 

of scientific integrity is freedom from outside interference. Judicial review could invite 

interference throughout the process, from the selection of chemical for assessments to the 

determination of adverse effects from exposure. 

2. Both the 2008 Government Accountability Office (GAO) report and the 2011 

National Academies of Sciences (NAS) report reviewing and suggesting changes to 

the IRIS program were discussed during the hearing. However, more recent reviews 
113 

conducted by both GAO and the Academies would appear to be more relevant to 

discussing the current state of the IRIS program. 

• How should the 2008 and 2011 reviews be considered when evaluating the current 

status of the IRIS program and the more recent GOA and NAS reviews? 

These reports are outdated and do not reflect the great progress that the IRIS program has 

made in recent years. While they were important in spurring the positive changes in the 

program, they no longer reflect the current methods, practices and leadership of the IRIS 

program. The more recent GAO and NAS reviews are more relevant and both reflect the 

continued progress and responsiveness of the IRIS program. 

• How would you respond to those who suggest that the IRIS program suffers from a 

deficiency in transparency? What is the process for ensuring transparency at IRIS 

particularly in the six years since the publication of the 2011 National Academies report? 

Again, this criticism likely reflects outdated reviews rather than the current program. The 

IRIS assessment process may have one of the most rigorous and open review processes in 

all of government science. The reports have multiple steps that include agency review, 

interagency science consultation, public comment, external peer review, revision and 

then further agency and interagency science discussion. In addition, the program releases 

preliminary materials during draft development including tables showing the results of 

pertinent studies. The Program also conducts bimonthly public science meetings 

providing opportunities for public comment, including web access to meeting to promote 

greater participation. These improvements were noted in the NAS 2014 review. 

3. What are some ofthe unforeseen consequences if chemical risk assessments 

conducted by IRIS were to be driven by industry interests, and more importantly, 

an industry sponsored chemical assessment was given the same weight and 

authority as independent scientific studies? 

IRIS does in fact often consider and include industry sponsored studies that have been 

published in the peer reviewed literature. The program depends upon he editorial staff of 

the peer reviewed journal to assure the quality and independence of the research. 

However, many industry-sponsored critiques of IRIS assessments are prepared by 

consultants without independent peer review or conflict of interest reporting. Clearly, 

these reports may introduce bias and financial conflict of interest and may lead to delays 

in finalizing reports and implementation of public health protections. 

4. EPA's IRIS program evaluates dozens and dozens of studies in its assessments of a 

chemical's risk to human health and the environment. However, not all studies are 

the same scientific quality and sometimes studies are authored by individuals that 
114 

have inherent financial or other conflicts-of -interests in the subject they arc 

reviewing. The American Chemistry Council (ACC), for instance, fund a large 

number of studies that examine the potential dangers of chemicals their member 

companies actually produce or distribute. Even though the scientists they fund to 

conduct these studies may be well qualified, how does EPA's IRIS program take 

into account the potential biases and conflicts of interest in evaluating these studies? 

As stated in the previous answer, El' A does consider many peer reviewed published 

industry-sponsored studies. The IRIS programs evaluates the quality of each study in its 

systematic review of the evidence base. In addition, the rigorous peer review of each 

assessment and the agency and public review also assist in identifying weaknesses or 

potential bias in studies. The quality of the science and the independence ofthe peer 

review, not the source of the funding, should be the driver of the assessment of the 

evidence. That said, it is essential to be diligent in identifying potential conflicts of 

interest throughout the process. 
(115) 

Appendix II 

ADDITIONAL MATERIAL FOR THE RECORD
116 

DOCUMENTS SUBMITTED BY SUBCOMMITTEE ON ENVIRONMENT CHAIRMAN ANDY

BIGGS
117 

Denka 

Denka Performance Elastomer 

The Honorable Scott Pruitt 

Administrator 

U.S. Environmental Protection Agency Headquarters 

William Jefferson Clinton Building 

1200 Pennsylvania Avenue, N.W. 

Mail Code: !lOlA 

Washington, D.C. 20460 

Denl<a Perfonnance Elastotner LLC 

560 Highway 44 

LaPlace, LA 70068 

June 26,2017 

Re: Request to Withdraw and Correct the 201 0 IRIS Review of Chloroprcne 

Dear Administrator Pruitt: 

I write on behalf of Denim Performance Elastomer LLC (DPE) in support of the request that the 

U.S. Environmental Protection Agency (EPA) withdraw and conect its Integrated Risk Information System 

(IRIS) Toxicological Review ofChloroprene (EPA/635/R-09/0JOF, 2010) (the 2010 IRIS Review). The 

ermrs in the 20 l 0 IRIS Review threaten the very survival ofDPE's Neoprene production facility in LaPlace, 

Louisiana (Facility). In particular, based on those errors and EPA's subsequent flawed determinations 

concerning the l'isks caused by Facility emissions, EPA is making stringent a it· pollution contml demands 

concerning the Facility that are technologically impossible to achieve. EPA must expeditiously apply good 

science in this matter in orde!' to alleviate the public's undue concet·ns about the risks associated with this 

Facility and to prevent furthet· significant damage to DPE's business. 

Key conclusions of the 2010 IRIS Review are not based on the best available science ot' sound 

scientific pi·acticcs. First, the 20 l 0 IRfS Review rejected the findings of the strongest available 

epidemiological study, which concluded that there is no increased risk of cancer in workers exposed to 

chloroprene (some of the study cohorts actually exhibited a lower risk of cancer than the control 

population). Rather than accepting the overall study conclusions, the 2010 IRIS Review relied on select 

statistically non-significant comparisons of cancer incidence rates among subgroups of the large•· 

epidemiology study to bolster its classification of chloroprene as "likely to be carcinogenic to 

humans." Second, the 2010 IRIS Review is flawed because it relied on labomtory animal studies, and then 

used the results for the most sensitive laboratory animal- female mice- as the basis for a sel'ies of overly 

conservative calculations to develop the human inhalation unit risk (IUR). Contraty to sound scientific 

practice, the 2010 IRIS Review ignored the known differences between humans and a select strain of female 

laboratory mice, and relied on results in those female mice to estimate an IUR for humans. Third, the 20 I 0 

IRIS Review gives chloroprene, which EPA designates only as a "likely'' and not a "known" human 

carcinogen, the fifth highest IUR estimate of any similar chemical, including known human carcinogens, 

in the IRIS database. DuPont, the former Facility owner, provided similar information and analysis to EPA 

in comments on the draft IRIS Review, which comments were rejected in 2010. DPE's Re<juest for 

Correction and the Ram boll Environ report provide new information and weight-of-evidence review not 

available in 20 I 0. 

Page I 
118 

[)enl<a 

Denka Performance Elastomer 

Dcnka Performance Elastomer LLC 

560 Highway 44 

LaPlace, LA 70068 

After EPA published the 2010 IRIS Review, the National Academies of Sciences' National 

Research Council (NRC) recommended major reforms in the IRIS process. Congress has repeatedly 

instructed EPA to implement the NRC's recommendations, and EPA has advised Congress that it is doing 

so. The 20 I 0 IRIS Review is plagued with flaws similar to those that gave rise to these refm·m initiatives, 

and it is extt·emely important that the 20 10 IRIS Review now be corrected in light of its scientific and 

procedural deficiencies. 

These issues are more fully explained in DPE's Request for Correction and in the supporting 

toxicological and epidemiological expert review prepared by prominent scientists with the consulting firm 

of Ram boll Environ: Drs. Kenneth Mundt, Robinan·ocntry, and Sonja Sax. Their report is entitled Basis 

for Requesting Con·ection of the US. EPA Toxicological Re1•iew ofChloroprene, dated June 2017 ("the 

Ramboll Environ Report," and attached hereto), The Ramboll Environ Report identifies multiple 

substantive errors in the 20 l 0 IRIS Review and demonstrates that if chloroprene is to be treated as a possible 

human carcinogen, the 20 I 0 IRIS Review establishes an IUR that is !56 times too high. 

By way of background, OPE acquired the Neoprene Facility fi•om DuPont on November I, 2015. 

Neoprene is a synthetic mbber utilized in a wide variety of applications, including laptop sleeves, 

orthopedic braces, electrical insulation, and automotive fan belts. OPE is the only manufacturer ofNeoprene 

in the United States. The Facility is a commercial mainstay of LaPlace, Louisiana. With an annual payroll 

of$33 million, DPB directly employs 200-250 people in manufacttll'ingjobs and regularly employs between 

125 and 150 contractors. OPE also has created 16 new corporate jobs. Additionally, DPE is investing and 

upgrading the Facility, including taking new measures to reduce its environmental footprint and improve 

its productivity and competitiveness. 

The base feedstock fot· Neoprene is chloroprene. The Facility's air pel'mits authorize it to emit 

chloroprcne, and the Facility operates in compliance with those permit limits. However, shortly after DPE's 

acqtiisition of the Facility, on Decembet· 17, 2015, EPA publicly released its 2011 National Ait· Toxics 

Assessment (NATA), which identified the Facility as creating the greatest offsite risk of cancer of any 

manufact,uring facility in the United States. The NATA findings concerning the Facility are based on the 

scientifically unwarranted and outdated 20 l 0 IRIS Review and the emission profile of the Facility. 

Following the public release of the NATA, EPA and the Louisiana Department ofEnvimnmental 

Quality (LDEQ) pressed OPE to reduce emissions to achieve an extraordinarily miniscule ambient air target 

concentration of0.2 ftg/m3 for chloroprene on an annual average basis (which is intended to reflect a 100 

in 1,000,000 rate of potential excess cancers in a population exposed to such concentrations continuously 

for 70 years). The 0.2 !Lg/m3 target is based on a risk assessment that applied the erroneous and scientifically 

unsubstantiated IUR fi·om the 20 I 0 IRIS Review, and the tat·get reflects more th~n a four thousand-fold 

reduction in the applicable Louisiana 8-hour ambient standard for chloroprene. Ramboll Environ's expett 

scientific opinion is that the appropriate risk-based ambient target should be 156 times larger or 31.2 )1g/m3• 

There is no agency rule or even proposed rule requiring the attainment of the 0.2 ftg/m3 tat·get, yet EPA has 

advised DPE, LDEQ, and the public that 0.2 ftg/m3 is the appropriate target. 

As a result of the flawed science embodied in the 2010 IRIS Review, and as a result of the NATA 

findings and the Facility's emission profile, OPE has suffered extraordinaty hardship in a number of ways. 

Page2 
119 

-

IJenl<a 

Denka Performance Elastomer 

Dcnka Performance Elastomer LLC 

560 Highway 44 

LaPlace,LA 70068 

First, despite DPE's concems about the science behind the 2010 IIUS Review, DPE is cummtly 

spending more than $18 million on new pollution controls. On January 6, 2017, DPE ente1'ed into an 

Administrative Order on Consent with LDEQ to reduce chloroprene emissions by approximately 85% 

below the level of the Facility's 2014 emissions. DPB estimates that the capital·cost of these emission 

reduction devices is approximately $1 & million, and the devices will cost hundreds of thousands of dollars 

per year to operate, Even though DPE is installing the most advanced air pollution controls available, it will 

still not be able to meet the stringent 0.2 [tg/m' target. 

Second, because the 2010 IRIS Review is flawed, EPA's very public announcements arising out of 

that Review and the NATA lmve created unnecessary public alarm. For example, after issuing the NATA, 

EPA created a public webpage specifically addressing DPE's chloroprene emissions.1 Moreover, 

environmental activists and plaintiffs' lawyers have had numerous meetings in the community about DPE, 

all based on the faulty assumption that 0.2j.lg/m3 is the "safe" level for chloroprene. Further, a local citiz<;n's 

group has formed and has been handing out misleading tlyers and protesting near DPB's Facility. The 

erroneous IUR in the 2010 IRIS Review and the resulting NATA findings have caused DPE enormous 

reputational damage, 

Third, as a result of the NATA findings, EPA Region 6 asked the National Environmental 

Investigations Centel' (NBIC) to investigate the regulatory compliance status of the Facility. NEIC sent a 

team of inspectors to the Facility from June 6-10, 2016, approximately seven months after DPB's 

acquisition. To be clear, DPE fl!lly respects the important function of the EPA in enforcing environmental 

requirements. It is simply a fact, however, Umt as a result of the erroneous JUR a1id the NATA findings, 

EPA has initiated an enforcement proceeding against DPE and has devoted an extraordinaty amount of 

resources fl·om the Department ofJustice, EPA headquarters, EPA Region 6, and NEIC to developing and 

pursuing the issues in the NEIC report. 

Finally, since acquiring the Facility in November of 2015, DPE's relatively small management 

team has been buffeted by continuous environmental regulatoJy demands resulting from the erroneous IUR 

and the NATA findings. In addition to Facility operation, DPE staff has been in non-stop meetings and 

negotiations with EPA and LDEQ. DPB's legal and consulting expenses have been enormous, in the 

millions of dollars. Underlying all ofthese expenses and burden~ on DPE is the erroneous IUR in the 20 I 0 

IRIS Review, as applied in the NATA risk assessment. 

DPE needs EPA's assistance in the expeditious application of good science to this matter. In 

meetings with EPA in 2016 concerning the need to correct the 2010 IRIS Review, EPA officials advised 

DPE that EPA's "queue is fhll". OPE respectfully requests that EPA review the science underlying the 20 I 0 

IRIS Review, withdraw the erroneous IUR, and develop a more accumte toxicological review of 

chloroprene. We are confident that the Ram boll Envil'on Report will lead you to these conclusions. Without 

See https:l/www.epa.gov/la/Japlace-louisiaua-backgt·ound-information. 

!'age 3 
120 

Denl<a Performance Elastomer LLC 

560 Highway 44 

LaPlace, LA 70068 

this relief, it is uncertain whether DPE will be able to reduce emissions sufficiently to satisfy agency 

demands, Ol' even continue operation. 

Sincerely, . 

~---------- President and Chief Executive Officer 

Denka Performance Elastomer LLC 

Page4 
121 

DOCUMENTS SUBMITTED BY SUBCOMMITTEE ON ENVIRONMENT RANKING MEMBER

SUZANNE BONAMIC
122 

The SAB has observed significant enhancements in the JRIS pwgram over the past few years, 

with impactful changes over the past year, and marked progress over the past J>ix months. The 

change.~ arc so extensive and positive that they constitute a virtual reinvention of lRlS. For 

example, it is now standard praetice for the program to engage stakeholders in an early scoping 

and problem formulation phase, thereby allowing stakeholders to provide important input at the 

very begiMing of the process. The program has fully adopted the principles of systematic 

review, and incorporated automation and publicly available software platforms to modernize the 

process. Finally, the IRIS documents are now more modular and structured to enhance 

transparency and reudabiHty. 

The SAB notes that no other federal entity performs the IRIS functions, and that JRJS help.~ 

ensure consistency in chemical assessments within the Agency and across the federal 

government. lRIS serves the needs of regions, states and tribes, who nf\en lack the ability to 

perform their own chemical risk assessments. llUS is also well-positioned to incorporate new 

evidence streams such as cell-based screening and computational methods into risk assessment, 

which will be a major advancement over the coming years. The Board commends the Agency for 

making such significant improvements over a short period of time. We are optimistic that the 

restructured llUS program will strengthen the scientific foundations of risk assessment and 

protect the health and safety of the American public. 

Enclosure 

(I) Roster of SAB Members 

Sincerely, 

lsi 

Dr. PeterS. Thome, Chair 

Science Advisory Board 

2 
123 

NOTICE 

This report has been written as part of the activities of the EPA Science Advisory Board (SAB), a public 

advisory group providing extramural scientific information and advice to the Administrator and other 

officials of the Environmental Protection Agency. The SAB is structured to provide balanced, expert 

assessment of scientific matters related to problems facing the Agency. This report has not beeri reviewed 

for approval by the Agency and, hence, the contents of this report do not necessarily represent the views 

and policies ofthe Environmental Protection Agency, nor of other agencies in the Executive Branch of the 

Federal government, nor does mention of trade names of commercial products constitute a 

recommendation for use. Reports ofthc SAB are posted on the EPA Web site at http://www.cr-a.gov/sab. 

3 
124 

CHAIR 

U.S. Environmental Protection Agency 

Science Advisory Board 

BOARD 

Dr. Peter S. Thorne, Professor and Head, Department of Occupational & Environmental Health, College 

of Public Health, University of Iowa, Iowa City, IA 

MEMBERS 

Dr . .Joseph Arvai, Max McGraw Professor of Sustainable Enterprise and Director, Erb Institute, School 

of Natural Resources & Environment, University of Michigan, Ann Arbor, MI 

Dr. Deborah Hall Bennett, Professor and Interim Chief, Environmental and Occupational Health 

Division, Department of Public Health Sciences, School of Medicine, University of California, Davis, 

Davis, CA 

Dr. Kiros T. Berhane, Professor, Preventive Medicine, Keck School of Medicine, University of Southern 

California, Los Angeles, CA 

Dr. Sylvie M. Bronder, Professor and Wickersham Chair of Excellence in Agricultural Research, 

Department of Agronomy, Purdue University, West Lafayette, IN 

Dr . .Joel G. Borken, Curator's Professor and Chair, Civil, Architectural, and Environmental Engineering, 

College of Engineering and Computing, Missouri University of Science and Technology, Rolla, MO, 

United States 

Dr . .Janice E. Chambers, William L. Giles Distinguished Professor and Director, Center for 

Environmental Health and Sciences, College of Veterinary Medicine, Mississippi State University, 

Starksville, MS 

Dr. Alison C. Cullen, Professor, Daniel J. Evans School of Public Policy and Governance, University of 

Washington, Seattle, W A 

Dr. Ana V. Diez Roux, Dean, School of Public Health, Drexel University, Philadelphia, PA 

Also Member: CASAC 

Dr. Otto C. Doering III, Professor, Department of Agricultural Economics, Purdue University, W. 

Lafayette, IN 

Dr. Joel J. Ducoste, Professor, Department of Civil, Construction, and Environmental Engineering, 

College of Engineering, North Carolina State University, Raleigh, NC 

Dr. Susan P. Felter, Research Fellow, Global Product Stewardship, Procter & Gamble, Mason, OH 

4 
125 

Dr. R. William Field, Professor, Department of Occupational and Environmental Health and Department 

of Epidemiology, College of Public Health, University of Iowa, Iowa City, JA 

Dr. H. Christopher Frey, Glenn E. Futrell Distinguished University Professor, Department of Civil, 

Construction and Environmental Engineering, College of Engineering, North Carolina State University, 

Raleigh,NC 

Dr. Joseph A. Gardella, SUNY Distinguished Professor and John and Frances Larkin Professor of 

Chemistry, Department of Chemistry, Collcge.of Arts and Sciences, University at Buffalo, Buffalo, NY 

Dr. Steven P. Hamburg, Chief Scientist, Environmental Defense Fund, Boston, MA 

Dr. Cynthia M. Harris, Director and Professor, Institute of Public Health, Florida A&M University, 

Tallahassee, FL 

Dr. Robert J. Johnston, Director of the George Perkins Marsh Institute and Professor, Department of 

Economics, Clark University, Worcester, MA 

Dr. Kimberly L. Jones, Professor and Chair, Department of Civil and Environmental Engineering, 

Howard University, Washington, DC 

Dr. Catherine J. Karr, Associate Professor - Pediatrics and Environmental and Occupational Health 

Sciences and Director- NW Pediatric Environmental Health Specialty Unit, University of Washington, 

Seattle, WA 

Dr. Madhu Khanna, ACES Distinguished Professor in Environmental Economics, Director of Graduate 

Admissions and Associate Director, Institute of Sustainahility, Energy, and Environment, Department of 

Agricultural and Consumer Economics, University of Illinois at Urbana-Champaign, Urbana, IL 

Dr. Francine Laden, Professor of Environmental Epidemiology, Associate Chair Environmental Health 

and Director of Exposure, Departments of Environmental Health and Epidemiology, Harvard T.H. Chan 

School of Public Health, Boston, MA 

Dr. Robert E. Mace, Deputy Executive Administrator, Water Science & Conservation, Texas Water 

Development Board, Austin, TX 

Dr. Clyde F. Martin, Horn Professor of Mathematics, Emeritus, Department of Mathematics and 

Statistics, Texas Tech University, Crofton, MD 

Dr. Sue Marty, Senior Toxicology Leader, Toxicology & Environmental Research, The Dow Chemical 

Company, Midland, Ml 

Dr. Denise Mauzerall, Professor, Woodrow Wilson School of Public and International Affairs, and 

Department of Civil and Environmental Engineering, Princeton University, Princeton, NJ 

Dr. Kristina D. Mena, Associate Professor, Epidemiology, Human Genetics and Environmental Sciences, 

School ofPublic Health, University of Texas Health Science Center at Houston, El Paso, TX 

5 
126 

Dr. Surabi Menon, Director of Research, Climate Works Foundation, San Francisco, CA 

Dr. Kari Nadeau, Naddisy Family Foundation Professor of Medicine, Director, FARE Center of 

Excellence at Stanford University, and Sean N. Parker Center for Allergy and Asthma Research at, 

Stanford University School of Medicine, Stanford, CA 

Dr. James Opaluch, Professor and Chair, Department of Environmental and Natural Resource 

Economics, College of the Environment and Life Sciences, University of Rhode Island, Kingston, RI 

Dr. Thomas F. Parkerton, Senior Environmental Associate, Toxicology & Environmental Science 

Division, ExxonMobil Biomedical Science, Houston, TX 

Mr. Richard L. Poirot, Independent Consultant, Burlington, VT 

Dr. Kenneth M. Portier, Independent Consultant, Athens, GA 

Dr. Kenneth Ramos, Associate Vice-President of Precision Health Sciences and Professor of Medicine, 

Arizona Health Sciences Center, University of Arizona, Tucson, AZ 

Dr. David B. Richardson, Associate Professor, Department of Epidemiology, School of Public Health, 

University of North Carolina, Chapel Hill, NC 

Dr. Tara L. Sabo-Attwood, Associate Professor and Chair, Department of Environmental and Global 

Health, College of Public Health and Health Professionals, University of Florida, Gainesville, FL 

Dr. William Schlesinger, President Emeritus, Cary Institute of Ecosystem Studies, Millbrook, NY 

Dr. Gina Solomon, Deputy Secretary for Science and Health, Office of the Secretary, California 

Environmental Protection Agency, Sacramento, CA 

Dr. Daniei 0. Stram, Professor, Department of Preventive Medicine, Division of Biostatistics, University 

of Southern California, Los Angeles, CA 

Dr. Jay Turner, Associate Professor and Vice Dean for Education, Department of Energy, Environmental 

and Chemical Engineering, School of Engineering & Applied Science, Washington University, St. Louis, 

MO 

Dr. Edwin van Wijngaarden, Associate Professor, Department of Public Health Sciences, School of 

Medicine and Dentistry; University of Rochester, Rochester, NY 

Dr. Jeanne M. VanBriesen, Duquesne Light Company Professor of Civil and Environmental 

Engineering, and Director, Center for Water Quality in Urban Environmental Systems (Water-QUEST), 

Department of Civil and Environmental Engineering, Carnegie Mellon University, Pittsburgh, PA 

6 
127 

Dr. Elke Weber, Gerhard R. Andlinger Professor in Energy and the Environment, Professor of 

Psychology and Public Affairs, Woodrow Wilson School of Public and International Affairs, Pr(nceton 

University, Princeton, NJ 

Dr. Charles Werth, Professor and Bettie Margaret Smith Chair in Environmental Health Engineering, 

Department of Civil, Architectural and Environmental Engineering, Cockrell School of Engineering, 

University of Texas at Austin, Austin, TX 

Dr. Peter J. Wilcoxen, Laura J. and L. Douglas Meredith Professor for Teaching Excellence, Director, 

Center for Environmental Policy and Administration, The Maxwell School, Syracuse University, 

Syracuse, NY 

Dr. Robyn S. Wilson, Associate Professor, School of Environment and Natural Resources, Ohio State 

University, Columbus, OH 

SCIENCE ADVISORY BOARD STAFF 

Mr. Thomas Carpenter, Designated Federal Officer, U.S. Environmental Protection Agency, 

Washington, DC 

7 
128 

Transforming EPA's Process for Assessing 

and Controlling Toxic Chemicals 

Why Area Is High 

Risk 

What GAO Found 

Transformmg EPA's Processes 

for Assessmg and Controlling 

Toxic Chemicals 

The Environmental Protection Agency's (EPA) ability to effectively 

implement its mission of protecting public health and the environment is 

critically dependent on assessing the risks posed by chemicals in a 

credible and timely manner. Such assessments are the cornerstone of 

scientifically sound environmental decisions, policies, and regulations 

under a variety of statutes, such as the Safe Drinking Water Act, the 

Toxic Substances Control Act (TSCA), and the Clean Air Act. EPA 

conducts assessments of chemicals under its Integrated Risk Information 

System (IRIS) program. EPA is also authorized under TSCA to obtain 

information on the risks of chemicals and to control those the agency 

determines pose an unreasonable risk. Because EPA had not developed 

sufficient chemical assessment information under these programs to limit 

exposure to many chemicals that may pose substantial health risks, we 

added this issue to the High-Risk List in 2009 as a government program 

in need of broad-based transformation. The Frank R. Lauten berg 

Chemical Safety for the 21st Century Act, enacted on June 22, 2016, 

provides EPA with greater authority to address chemical risks, but 

implementing it will take time. 

EPA has again met the criteria for leadership commitment, and its former 

administrator and top leadership publicly stated their focus on improving 

the IRIS program and implementing the 2016 TSCA reform legislation 

through its TSCA program. The agency has begun to align people and 

resources to address the current and future workload of these programs. 

For the IRIS program, EPA has partially met the criteria for capacity, an 

improvement over its previous rating, in part because it issued an IRIS 

Multi-Year Agenda in December 2015 that focused on the need for IRIS 

assessments over the next few years. EPA has again not met the criteria 

for capacity for its TSCA program, and with new TSCA authority, it is 

unclear if EPA has the people and resources to implement the new law. 

Overall, EPA needs to continue to determine for both the IRIS and TSCA 

programs if it has adequate capacity to resolve this high-risk area. EPA 

needs to work with Congress to ensure that the resources dedicated to 

IRIS and TSCA activities are sufficient to maintain a viable IRIS database 

of chemical assessments, and effectively implement TSCA reform 

activities. EPA has partially met the criteria for having a corrective action 

plan by issuing an IRIS Multi-Year Agenda. EPA has also partially met the 

criteria for having a corrective action plan by increasing its efforts to 

obtain chemical toxicity and exposure data, initiating chemical risk 

assessments, and reviewing certain new uses of chemicals, but it is too 

early to tell whether these actions will reduce chemical risks. EPA needs 

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What Remains to Be 

Done 

Integrated Risk 

Information System 

nansformlng EPA's Process for Assessing 

and Controlling Toxic Chemicals 

to continue to implement the TSCA reform legislation and define how it 

will implement corrective actions to assess and control toxic chemicals. 

EPA has now met the criteria for monitoring the IRIS program by finalizing 

the IRIS Multi-Year Agenda and other actions, including continuing to 

submit IRIS assessments for independent review to entities with scientific 

and technical credibility. EPA has not met the criteria for monitoring the 

TSCA program; to help ensure that the resources dedicated to TSCA are 

sufficient for effectively implementing the new law, EPA needs to institute 

a program to monitor and independently validate the effectiveness and 

sustainability of its initiative to use the new TSCA authorities. For the IRIS 

program, EPA has now partially met the criteria for demonstrated 

progress by, among other things, issuing five IRIS assessments since 

fiscal year 2015-as of January 19, 2017-and making three 

assessments available for public comment in fiscal year 2016 in 

preparation for an external peer review meeting associated with that 

particular assessment. For the TSCA program, EPA has not met the 

criteria for demonstrated progress. Both the IRIS and TSCA programs 

need to continue to implement corrective actions to resolve this complex 

high-risk area. 

Passing the Frank R. Lautenberg Chemical Safety for the 21st Century 

Act may facilitate EPA's effort to improve its processes for assessing and 

controlling toxic chemicals in the years ahead. The new law provides EPA 

with greater authority and the ability to take actions that could help EPA 

implement its mission of protecting human health and the environment. 

Continued leadership commitment from EPA officials and Congress will 

be needed to fully implement reforms. Additional work will also be needed 

to issue a workload analysis to demonstrate capacity, complete a 

corrective action plan, and demonstrate progress implementing the new 

legislation. 

We recommended that EPA periodically assess the level of resources 

that should be dedicated to the Integrated Risk Information System 

(IRIS) program to meet user needs and maintain a viable database. 1 

1GAO, Chemical Assessments: Low Productivity and New Interagency Review Process Umit the Usefulness and Credibility of E:PA 's Integrated Risk Information System, 

GA0-08-440 (Washington O.C: Mar. 7, 2008). 

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Transforming EPA'a Process for Assessing and Controlling Toxic Chemlcats 

EPA determined the types of IRIS assessments to conduct, based on 

the needs of EPA's Program Offices and other users, as reported in 

the IRIS Multi-Year Agenda and in deliberative documents provided to 

us in October 2016. However, EPA has not established a schedule for 

regularly revisiting its assessment of resource needs to ensure that 

priorities are consistent with user needs over time. 

We recommended two actions about EPA's time frames for IRIS 

assessments? First, we recommended that EPA assess the feasibility 

and appropriateness of the established time frames for each step in 

the IRIS assessment process, including whether different time frames 

should be established for different types of IRIS assessments. 

Second, should different time frames be necessary, we recommended 

that EPA establish a written policy that clearly describes the 

applicability of the time frames for each type of IRIS assessment to 

provide greater predictability to stakeholders. In July 2013, EPA 

issued what the agency described as enhancements to the IRIS 

process to address, in part, these priority recommendations. EPA 

developed two sets of timelines for the IRIS assessment process and 

provided us with detsils about them and its online chemical 

information tracking system; however, EPA needs to determine 

whether different time frames should be established. 

We recommended three actions encouraging transparency about the 

status of planned and ongoing IRIS assessments. 3 First, we 

recommended that EPA indicate in published IRIS agendas which 

chemicals it is actively assessing and when it plans to start 

assessments of the other listed chemicals. Second, we recommended 

that EPA update the IRIS Substance Assessment Tracking System 

(IRISTrack) including projected and actual start dates and other 

information, and to keep this information current. Third, we 

recommended that EPA publish the IRIS agenda in the Federal 

Register on an annual basis. In October 2016, EPA officials told us 

that they believed they had met the intent of these recommendations 

by publishing an IRIS Multi-Year Agenda in December 2015. 

However, EPA still needs to provide current and accurate information 

on chemicals that the agency plans to assess through the IRIS 

program for IRIS users on an annual basis. The Multi-Year Agenda 

does not identify projected start dates for new assessments, and 

2GAO, Chemical Assessments: Challenges Remain with E'PA 's Integrated Risk 

Information System Program, GA0-12-42 (Washington, D.C.: Dec. 9, 2011). 

3GA0-12-42. 

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Toxic Substances Control 

Act 

Transforming EPA's Proceq for Assessing and Controlling Toxic Chemicals 

therefore is not ensuring that current and accurate information on 

chemicals that EPA plans to assess through IRIS is available to IRIS 

users. Using the Federal Register to communicate these plans offers 

greater transparency to the public about the IRIS process than other 

forms of communication. 

We recommended that EPA develop a strategy to address the needs 

of its Program Offices and regions when IRIS toxicity assessments 

are not available4 Officials from select EPA offices stated that, in the 

absence of agency-wide guidance, they used a variety of sources, 

other than IRIS toxicity assessments to meet their needs, including 

toxicity information from other EPA offices, or other state or federal 

agencies. IRIS program officials also stated that there is no agencywide mechanism for EPA to ensure that chemicals without sufficient 

scientific data during one nomination period will have such information 

by subsequent nomination periods. We recognize that the 

development of EPA's Multi-Year Agenda, issued in December 2015, 

was a productive effort that EPA told us included an extensive 

evaluation of user needs. However, the agency does not have a 

strategy for addressing data gaps or have assurance that its efforts 

will be sustainable over time. EPA needs to address this priority 

recommendation by developing: (1) an agency-wide strategy that 

addresses coordination across EPA offices and with other federal 

research agencies to help identify and fill data gaps that preclude the 

agency from conducting IRIS toxicity assessments, and (2) guidance 

that describes alternative sources of toxicity information and when it 

would be appropriate to use them when IRIS values are not available, 

applicable, or current. 

After many years of congressional committees considering legislation 

aimed at reforming the Toxic Substances Control Act (TSCA), in June 

2016, Congress passed and the President signed the Frank R. 

Lautenberg Chemical Safety for the 21st Century Act, which gave EPA 

greater authority to improve its processes for assessing and controlling 

toxic chemicals. EPA and Congress need to continue to ensure that the 

resources dedicated to TSCA activities are sufficient to effectively 

implement the new law. 

4GAO, Chemical Assessments: An Agencywide Strategy May Help EPA Address Unmet 

Needs for Integrated Risk Information System Assessments, GA0-13-369 (Washington, 

D.C.: May 10, 2013). 

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Transfonnlng EPA's Process for Assessing 

and Controlling Toxic Chemicals 

We made three priority recommendations to address challenges EPA 

has faced obtaining toxicity and exposure data, banning or limiting the 

use of chemicals, and identifYing resource needs. 5 First, we 

recommended that EPA issue a rule to obtain toxicity and exposure 

data that chemical companies have submitted to the European 

Chemicals Agency. Second, we recommended that EPA issue a rule 

to obtain exposure-related data from processors. Third, we 

recommended that EPA develop strategies for addressing challenges 

associated with obtaining these data, banning or limiting the use of 

chemicals, and identifYing resource needs. Because EPA has used its 

authority to limit or ban only five chemicals since TSCA was originally 

enacted in 1976, in part, because it believed it didn't have enough 

information, we made these recommendations to address these 

concerns. The Frank R. Lauten berg Chemical Safety for the 21st 

Century Act, enacted on June 22, 2016, provides EPA with greater 

authority to address chemical risks, but implementing it will take time. 

With the implementation of the Frank R. Lautenberg Chemical Safety for 

the 21st Century Act, we believe EPA can make progress on these open 

recommendations. The act substantially revises TSCA and requires EPA 

to carry out numerous rulemaking and other activities within the next 2 

years. In early 2016, we started a review of the TSCA program. With the 

passage of TSCA reform, we decided to suspend our review and give 

EPA time to implement the new law. In October 2016, as part of our 

recommendation follow-up process, we reviewed information on the new 

TSCA provisions. EPA officials told us that with new TSCA authority, the 

agency is better positioned to take action to require chemical companies 

to report chemical toxicity and exposure data. The new law authorizes 

EPA to order companies to develop new information relating to a 

chemical as necessary for prioritization and risk evaluation. This authority 

may help EPA to gather new information, as necessary, to evaluate 

hazard and exposure risks. TSCA reform legislation offers promise for 

EPA implementation of our recommendations and bringing the agency 

closer to achieving its goal of ensuring the safety of chemicals. 

5GAO, Toxic Substances: EPA Has Increased Effolts to Assess and Control Chemicals 

but Could Strengthen Its Approach, GA0-13-249 (Washington, D.C.: Mar. 22, 2013). 

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Additional Details on 

What GAO Found 

IRIS 

Transformmg EPA's Processes 

for Assessmg and Controllmg 

TOXIC Chemicals 

EPA's Integrated Risk Information 

System 

SourO!!:GAOanalysls. j 2017HighRisklisiGAQ.l1-317 

Leadership Commitment 

Transforming EPA's Process for Assessing 

and Controlling Toxic Chemicals 

EPA has met the criteria for leadership commitment. In July 2013, the 

then-EPA Administrator demonstrated leadership commitment to the IRIS 

program by identifying action on taxies and chemical safety as one of her 

top seven priorities for the agency. EPA's IRIS database is intended to 

provide the basic information the agency needs to determine whether it 

should establish controls to, for example, protect the public from exposure 

to toxic chemicals in the air, in water, and at hazardous waste sites. 

"Taking action on taxies and chemical safety" was one of the prior EPA 

Administrator's priorities for meeting the challenge ahead-a priority that 

includes the IRIS program. In addition, EPA established an IRIS 

Executive Review Committee after the 2014 National Research Council 

report identified the need for quality management of IRIS assessments. 

According to internal EPA documents, the Executive Review Committee 

provides a mechanism for the National Center for Environmental 

Assessment-the center that houses the IRIS program-to endorse IRIS 

assessments prior to public release, and among other goals, serves to 

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Capacity 

Action Plan 

Transforming EPA's Process for Assessing 

and Controlling Toxic Chemicals 

provide a management-level review for consistency and quality control 

across assessments. Also, the Office of Research and Development's 

Deputy Assistant Administrator worked With other EPA Deputy Assistant 

Administrators in Program Offices, such as the Office of Water and 

Deputy Regional Administrators, to develop the IRIS Multi-Year Agenda. 

EPA's top leadership has also demonstrated support for improving the 

IRIS program by continuing to implement recommendations from us and 

EPA's Science Advisory Board, and suggestions from the National 

Academies. 

EPA has partially met the criteria for capacity, after not meeting the 

criteria in 2015. In May 2013, we reported that EPA had not recently 

evaluated the demand for IRIS toxicity assessments with input from users 

inside and outside EPA. In response to our report, EPA started work on 

an IRIS Multi-Year Agenda in the summer of 2013 and issued it in 

December 2015. According to EPA, the purpose ofthe agenda was to: (1) 

identify IRIS assessments currently underway and their status; (2) 

prioritize IRIS assessments that will be initiated over the next few years; 

and (3) evaluate assessment needs and develop an update process for 

existing IRIS values. Now that EPA has finalized the agenda, the agency 

is better informed about how many people and resources to dedicate to 

the IRIS program. 

We have reviewed internal EPA documents on the need for people and 

resources, and the IRIS program has started to determine if it has the 

capacity to address the issues it faces. Because of EPA's efforts to 

develop the Multi-Year Agenda, in October 2016, we closed a priority 

recommendation we made to EPA in 2008 for the program to determine 

the types of IRIS assessments to conduct on the basis of the needs of 

EPA's Program Offices and other users. EPA's actions are a good 

starting point for EPA's continued process for determining the types of 

IRIS assessments to conduct on the basis of the needs of EPA's Program 

Offices and others. 

EPA continues to partially meet the criteria for having an action plan to 

address measures we recommended, and has made progress. For 

example, by developing the IRIS Multi-Year Agenda and providing us with 

internal EPA documents, EPA has begun to document how the agency 

applies its selection criteria for IRIS toxicity assessments, including the 

circumstances under which Program Offices and Regions may or may not 

need an IRIS toxicity assessment-a priority recommendation we made 

in 2013 and closed in October 2016. As of October 2016, EPA officials 

told us that the agency evaluated user needs for toxicity assessments as 

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Monitoring 

Demonstrated Progress 

Transforming EPA's Process for ASsessing 

and Contro111ng Toxic Chemicals 

part of its process for developing the Multi-Year Agenda it issued in 

December 2015. EPA also indicated that the agency used six general 

criteria to inform the selection of chemicals for assessment or 

reassessment, and it documented this process in an internal working 

table as part of its process for developing the agenda. By beginning to 

document how it applies its IRIS selection criteria, the IRIS program can 

start to determine a corrective action plan that defines root causes and 

solutions to move the program forward. EPA needs to be as transparent 

as possible when applying the selection criteria so that IRIS stakeholders 

can know how EPA is choosing what assessments to start and why. 

EPA has met the criteria for monitoring the IRIS program-after partially 

meeting the criteria in 2015-byfinalizing the IRIS Multi-Year Agenda and 

other actions. Specifically, the program identified and evaluated demand 

for the number of IRIS toxicity assessments and resources required to 

meet users' needs-a priority recommendation we made in 2013 and 

closed recently based on internal documents provided by EPA. Moreover, 

EPA presented a plan for how the agency will implement the National 

Academies' suggestions for improving IRIS assessments in the "roadmap 

for revision" included in the National Academies' peer review report on 

the draft formaldehyde assessment. The National Academies' most 

recent report on the IRIS program, issued in May 2014, independently 

validates some of the corrective measures the program is implementing. 

EPA also created the Chemical Assessment Advisory Committee in 

January 2013, and uses it to provide continuing, consistent review of IRIS 

assessments and comment on implementing the National Academies' 

suggestions in specific IRIS assessments-a recommendation we made 

in December 2011 and closed in the fall of 2016. All of these actions 

demonstrated EPA's commitment to monitoring the IRIS program. 

EPA has partially mel the criteria for demonstrating progress in 

implementing corrective measures by taking actions, such as releasing 

the IRIS Multi-Year Agenda that publicly identifies the current and future 

IRIS assessments. As of January 19, 2017, EPA issued two assessments 

in fiscal year 2017, two assessments in fiscal year 2016, and one 

assessment in fiscal year 2015. In addition, EPA made three 

assessments available for public comment in fiscal year 2016 in 

preparation for an external peer review meeting associated with that 

particular assessment. 

The IRIS program has also demonstrated progress by establishing 

Slopping Rules, which, among other things, were implemented to 

increase flexibility to revise draft assessments as needed after hearing 

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TSCA 

Transformmg EPA's Processes 

for Assessmg and Controlling 

Toxic Chemicals 

Toxic Substances Control Act 

Leadership Commitment 

Transforming EPA's Process for Assessing 

and Controlling Toxic Chemicals 

the public's comments prior to peer review. EPA told us that the Stopping 

Rules also are important to the IRIS process to determine how to include 

new studies in an assessment without delaying the process or cycling 

through repeated revisions and re-revisions. 

Because of these actions, we closed a 2008 priority recommendation that 

demonstrated progress in implementing corrective measures. The 

recommendation called for EPA to conduct IRIS assessments on the 

basis of peer-reviewed scientific studies available at the time of the 

assessment, and develop criteria for allowing assessments to be 

suspe·nded to await the completion of scientific studies only under 

exceptional circumstances. Although EPA officials told us that the agency 

has not formally invoked the Stopping Rules in response to a request to 

delay an assessment to incorporate studies, they told us they apply the 

rules in their everyday work when deciding whether to include new 

studies at different points in the IRIS development process. EPA said they 

would characterize the Stopping Rules as public IRIS policies that are in 

place to avoid delay for the inclusion of new studies or analysis that they 

believe would not affect the assessment's conclusions. 

Over the past two decades, we reported that EPA had found much of 

TSCA difficult to implement-hampering the agency's ability to obtain 

certain chemical data or place limits on chemicals. For example, EPA has 

found it difficult to obtain adequate information on toxicity-that is, the 

degree to which the chemical is harmful or deadly-and exposure 

levels-the frequency and duration of contact with the chemical. Without 

this information, it is difficult for EPA to determine whether a chemical 

poses an unreasonable risk to human health or the environment, and 

then take any action necessary to regulate such chemicals. The Frank R. 

Laufenberg Chemical Safety for the 21st Century Act, which reformed 

TSCA, was enacted on June 22, 2016. The new law provides EPA with 

greater authority and the ability to take actions that could help EPA 

implement its mission of protecting human health and the environment. 

EPA continues to meet the criteria for leadership commitment because of 

the former EPA Administrator's explicit support for taking action on taxies, 

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Capacity 

Action Plan 

Monitoring 

Transforming EPA's Process for Assessing 

and Controlling Tqxic Chemicals 

including TSCA. In addition, the former Administrator and top leadership 

have expressed support for implementing TSCA reform. For example, the 

former Administrator said that, as with any major policy reform, this one 

includes compromises. But the former Administrator noted that the 

legislation should help EPA's mission to protect public health and the 

environment. 

As in 2015, EPA has not met the criteria for capacity because the agency 

has not yet issued a workload analysis which is needed to determine 

whether EPA's TSCA program has the capacity-people and resourcesto resolve the risk to the program. The TSCA reform legislation requires 

EPA to report to Congress by December 2016 on its capacity to 

implement certain aspects of the legislation, including carrying out 

chemical risk evaluations and issuing rules regulating specific chemicals. 

In January 2017, EPA issued a report in response to this deadline. The 

report estimates the costs of carrying out risk evaluations under the TSCA 

reform legislation and discusses actions underway or planned for 

increasing EPA's capacity to carry out these evaluations. The report does 

not, however, contain estimates of EPA's capacity for carrying out risk 

evaluations or promulgating associated rules. We have previously 

reported that EPA has found many provisions of TSCA cumbersome and 

time consuming to implement. It is currently unclear if EPA has the people 

and resources to implement the new law. We will continue to monitor the 

program to determine if progress is made and the criteria for capacity are 

met. 

EPA continues to partially meet the criteria for having an action plan. As 

we reported in 2015, EPA has increased its efforts to obtain chemical 

toxicity and exposure data, initiate chemical risk assessments, and review 

certain new uses of chemicals, but it is too early to tell whether these 

actions will reduce chemical risks. With new TSCA authority, EPA officials 

stated that the agency is better positioned to take action to require 

chemical companies to report chemical toxicity and exposure data. 

Officials also ststed that the new law gives the agency additional 

authorities, including the authority to require companies to develop new 

information relating to a chemical as necessary for prioritization and risk 

evaluation. Using both new and previously existing TSCA authorities 

should enhance the agency's ability to gather new information as 

necessary to evaluate hazard and exposure risks. 

As in 2015, EPA has not met the criteria for monitoring because it is too 

soon to determine whether EPA's approach to managing chemicals within 

the new TSCA authorities will position the agency to achieve its goal of 

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Demonstrated Progress 

Benefits Achieved by 

Implementing Our 

Recommendations 

Transforming EPA's Process for Assessing 

and Controlling Toxic Chemicals 

ensuring the safety of chemicals. We will continue to monitor the TSCA 

program as the agency implements this important legislation. 

As in 2015, EPA has not met the criteria for demonstrating progress, 

although it has recently begun implementing corrective measures to 

resolve this high-risk area. For example, the first TSCA reform reporting 

deadline directed EPA to publish in the Federal Register a list of mercury 

compounds that will be prohibited from export, not later than 90 days after 

the date of enactment. That reporting deadline was September 20, 2016; 

on August 26, 2016, EPA published a list of the mercury compounds that 

will be prohibited from export effective January 1, 2020. TSCA reform 

actions required by December 19, 2016, included the following topics and 

actions: (1) Risk Evaluations: EPA must ensure that risk evaluations are 

being conducted on 10 chemical substances drawn from the 2014 TSCA 

Work Plan; (2) Small Business: EPA must review, and potentially revise, 

its definitions of small businesses for reporting purposes after consulting 

·with the Small Business Administration; and (3) Congressional Report: 

EPA must submit a repoit to Congress regarding the agency's capacity to 

carry out risk evaluations and associated actions. 

According to EPA, the promulgation of these rules will better position the 

agency to increase the rate at which chemicals are evaluated for human 

and environmental health and safety. As of December 19, 2016, EPA had 

taken steps to respond to the December deadlines for risk evaluations 

and small business. Specifically, EPA has announced the first 10 

chemicals it will evaluate for potential risks to human health and the 

environment and published a Federal Register notice on Standards for 

Small Manufacturers and Processors. In January 2017, EPA took action 

in response to December deadline 3 by issuing a report: Initial Report to 

Congress on the EPA's Capacity to Implement Certain Provisions ofthe 

Frank R. Lautenberg Chemical Safety for the 21st Century Act. We will 

continue to monitor EPA as it implements this important piece of chemical 

legislation and determine if it is satisfying all the criteria for removal from 

the High-Risk List. 

EPA has taken actions to address many of our priority recommendations 

on chemicals management and Congress has used our work to support 

legislative deliberations. For example, EPA's efforts, such as developing 

the IRIS Multi-Year Agenda, addressed a number of our 

recommendations related to the IRIS program. EPA identified and 

evaluated demand for the number of IRIS toxicity assessments and 

resources required to meet users' needs, which was a priority 

Page427 GA0-17-317 High·Risk Seri&s 
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GAO Contact 

Related GAO 

Products 

Transforming EPA's Process for Assessing 

and Controlling Toxic Chemicals 

recommendation we made in 2013 and closed recently based on EPA's 

actions. 

Our work has also supported deliberations by Congress about TSCA and 

about strengthening EPA's ability to regulate chemicals. For example, as 

far back as 1994, we reported that Congress should consider setting 

specific deadlines for reviewing existing chemicals, which the new TSCA 

legislation would address because it requires EPA to establish a chemical 

prioritization process, and to initiate risk evaluations of high priority 

chemicals, among other issues. 

Our work since then has addressed a variety of chemical management 

policy matters for Congress. For example, in 2009, we testified that EPA 

does not routinely assess the risks of chemicals in commerce, and in 

2013, we testified about possible statutory changes to TSCA to give EPA 

additional authorities to obtain information, and shift more of the burden to 

chemical companies for demonstrating the safety of their chemicals. 

Finally, in 2016, Congress passed the Frank R. Lautenberg Chemical 

Safety for the 21st Century Act, which we found addresses key challenge 

areas we've identified previously. 

For additional information about this high-risk area, contact Alfredo 

G6mez at (202) 512-3841 or gomezj@gao.gov. 

Chemicals Management: Obse/Vations on Human Health Risk 

Assessment and Management by Selected Foreign Programs. 

GA0-16-111R. Washington, D.C.: October9, 2015. 

Chemical Assessments: Agencies Coordinate Activities, but Additional 

Action Could Enhance Efforts. GA0-14-763. Washington, D.C.: 

September 29, 2014. 

Chemical Regulation: Observations on the Toxic Substances Control Act 

and EPA Implementation. GA0-13-696T. Washington, D.C.: June 13, 

2013. 

Chemical Assessments: An Agencywide Strategy May Help EPA Address 

Unmet Needs for Integrated Risk Information System Assessments. 

GA0-13-369. Washington, D.C.: May 10, 2013. 

Page428 GA0·17-317 Hlgh.Risk Series 
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Æ 

Transforming EPA's Process for Assessing 

and Controlling Toxic Chemicals 

Toxic Substances: EPA Has Increased Efforts to Assess and Control 

Chemicals but Could Strengthen Its Approach. GA0-13-249. Washington, 

D.C.: March 22, 2013. 

Chemical Assessments: Challenges Remain with EPA's Integrated Risk 

Information System Program. GA0-12-42. Washington, D.C.: December 

9, 2011. 

Chemical Assessments: Low Productivity and New Interagency Review 

Process Limit the Usefulness and Credibility of EPA's Integrated Risk 

Information System. GA0-08-440. Washington D.C: March 7, 2008. 

Page429 GA0-17-317 High-Risk Series