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76–011 2012

ENDOCRINE-DISRUPTING CHEMICALS IN DRINKING 

WATER: RISKS TO HUMAN HEALTH AND THE 

ENVIRONMENT 

HEARING 

BEFORE THE

SUBCOMMITTEE ON ENERGY AND ENVIRONMENT 

OF THE

COMMITTEE ON ENERGY AND 

COMMERCE 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED ELEVENTH CONGRESS 

SECOND SESSION 

FEBRUARY 25, 2010 

Serial No. 111–99 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 


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COMMITTEE ON ENERGY AND COMMERCE 

HENRY A. WAXMAN, California, Chairman 

JOHN D. DINGELL, Michigan 

Chairman Emeritus 

EDWARD J. MARKEY, Massachusetts 

RICK BOUCHER, Virginia 

FRANK PALLONE, JR., New Jersey 

BART GORDON, Tennessee 

BOBBY L. RUSH, Illinois 

ANNA G. ESHOO, California 

BART STUPAK, Michigan 

ELIOT L. ENGEL, New York 

GENE GREEN, Texas 

DIANA DEGETTE, Colorado 

Vice Chairman 

LOIS CAPPS, California 

MICHAEL F. DOYLE, Pennsylvania 

JANE HARMAN, California 

TOM ALLEN, Maine 

JANICE D. SCHAKOWSKY, Illinois 

CHARLES A. GONZALEZ, Texas 

JAY INSLEE, Washington 

TAMMY BALDWIN, Wisconsin 

MIKE ROSS, Arkansas 

ANTHONY D. WEINER, New York 

JIM MATHESON, Utah 

G.K. BUTTERFIELD, North Carolina 

CHARLIE MELANCON, Louisiana 

JOHN BARROW, Georgia 

BARON P. HILL, Indiana 

DORIS O. MATSUI, California 

DONNA M. CHRISTENSEN, Virgin Islands 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

CHRISTOPHER S. MURPHY, Connecticut 

ZACHARY T. SPACE, Ohio 

JERRY MCNERNEY, California 

BETTY SUTTON, Ohio 

BRUCE L. BRALEY, Iowa 

PETER WELCH, Vermont 

JOE BARTON, Texas 

Ranking Member 

RALPH M. HALL, Texas 

FRED UPTON, Michigan 

CLIFF STEARNS, Florida 

NATHAN DEAL, Georgia 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

JOHN B. SHADEGG, Arizona 

ROY BLUNT, Missouri 

STEVE BUYER, Indiana 

GEORGE RADANOVICH, California 

JOSEPH R. PITTS, Pennsylvania 

MARY BONO MACK, California 

GREG WALDEN, Oregon 

LEE TERRY, Nebraska 

MIKE ROGERS, Michigan 

SUE WILKINS MYRICK, North Carolina 

JOHN SULLIVAN, Oklahoma 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

PHIL GINGREY, Georgia 

STEVE SCALISE, Louisiana 


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SUBCOMMITTEE ON ENERGY AND ENVIRONMENT

EDWARD J. MARKEY, Massachusetts, Chairman 

MICHAEL F. DOYLE, Pennsylvania 

JAY INSLEE, Washington 

G.K. BUTTERFIELD, North Carolina 

CHARLIE MELANCON, Louisiana 

BARON HILL, Indiana 

DORIS O. MATSUI, California 

JERRY MCNERNEY, California 

PETER WELCH, Vermont 

JOHN D. DINGELL, Michigan 

RICK BOUCHER, Virginia 

FRANK PALLONE, JR., New Jersey 

ELIOT ENGEL, New York 

GENE GREEN, Texas 

LOIS CAPPS, California 

JANE HARMAN, California 

CHARLES A. GONZALEZ, Texas 

TAMMY BALDWIN, Wisconsin 

MIKE ROSS, Arkansas 

JIM MATHESON, Utah 

JOHN BARROW, Georgia 

RALPH M. HALL, Texas 

FRED UPTON, Michigan 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

JOHN B. SHADEGG, Arizona 

STEVE BUYER, Indiana 

GREG WALDEN, Oregon 

SUE WILKINS MYRICK, North Carolina 

JOHN SULLIVAN, Oklahoma 

MICHAEL C. BURGESS, Texas 


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C O N T E N T S 

Page 

Hon. Edward J. Markey, a Representative in Congress from the Commonwealth of Massachussetts, opening statement ................................................... 1 

Hon. Cliff Stearns, a Representative in Congress from the State of Florida, 

opening statement ................................................................................................ 3 

Hon. John Shimkus, a Representative in Congress from the State of Illinois, 

opening statement ................................................................................................ 4 

Hon. Lois Capps, a Representative in Congress from the State of California, 

opening statement ................................................................................................ 4 

Hon. Gene Green, a Representative in Congress from the State of Texas, 

prepared statement .............................................................................................. 70 

Hon. Joe Barton, a Representative in Congress from the State of Texas, 

prepared statement .............................................................................................. 81 

Hon. Michael C. Burgess, a Representative in Congress from the State of 

Texas, prepared statement .................................................................................. 85 

WITNESSES

Hon. James P. Moran, a Representative in Congress from the Commonwealth 

of Virginia ............................................................................................................. 5 

Prepared statement .......................................................................................... 8 

Linda Birnbaum, Director, National Institute for Environmental Health 

Sciences ................................................................................................................. 13 

Prepared statement .......................................................................................... 16 

Answers to submitted questions ...................................................................... 100 

James Jones, Deputy Assistant Administrator, Office of Prevention, Pesticides 

and Toxic Substances, Environmental Protection Agency ................................ 24 

Prepared statement .......................................................................................... 26 

Answers to submitted questions ...................................................................... 115 

Gina Solomon, Senior Scientist, National Resources Defense Council ............... 31 

Prepared statement .......................................................................................... 34 

Answers to submitted questions ...................................................................... 130 

Christopher J. Borgert, President and Principal Scientist, Applied Pharmacology and Toxicology, Inc. .................................................................................. 51 

Prepared statement .......................................................................................... 53 

Answers to submitted questions ...................................................................... 144 

SUBMITTED MATERIAL

Statement of American Water Works Association ................................................ 88 

Statement of American Chemistry Council ........................................................... 92 

Statement of Hon. Louise M. Slaughter ................................................................ 98 


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ENDOCRINE-DISRUPTING CHEMICALS IN 

DRINKING WATER: RISKS TO HUMAN 

HEALTH AND THE ENVIRONMENT 

THURSDAY, FEBRUARY 25, 2010 

HOUSE OF REPRESENTATIVES, 

SUBCOMMITTEE ON ENERGY AND ENVIRONMENT, 

COMMITTEE ON ENERGY AND COMMERCE, 

Washington, DC. 

The Subcommittee met, pursuant to call, at 9:34 a.m., in Room 

2123 of the Rayburn House Office Building, Hon. Edward J. Markey [Chairman of the Subcommittee] presiding. 

Members present: Representatives Markey, Inslee, McNerney, 

Green, Capps, Matheson, Barrow, Moran, Stearns, Shimkus, Burgess, and Scalise. 

Staff present: Jackie Cohen, Counsel; Tracy Sheppard, Counsel; 

Melissa Cheatham, Professional staff; Michael Freedhoff, Professional staff; Peter Ketcham-Colwill, Special Assistant; Caitlin 

Haberman, Special Assistant; Earley Green, Chief Clerk; Jerry 

Couri, Minority Professional Staff; and Garrett Golding, Minority 

Legislation Analyst. 

OPENING STATEMENT OF HON. EDWARD J. MARKEY, A REPRESENTATIVE IN CONGRESS FROM THE COMMONWEALTH 

OF MASSACHUSETTS 

Mr. MARKEY. Welcome, ladies and gentlemen. Lately not a day 

goes by where the public is not reminded of the presence of toxic 

chemicals in the air we breathe and in the water we drink, and the 

potential harmful effect that these chemicals can have on public 

health and the environment. Just last week, a local newspaper 

warned that the Potomac River and other Mid-Atlantic rivers are 

awaste with toxins that may be responsible for bizarre deformities 

in fish, frogs, and other wildlife that come in contact with the contaminated water. This includes male fish that have begun growing 

female sexual organs and female fish that can no longer reproduce. 

W.C. Fields once said I never drink water because of the disgusting things that fish do in it. Well, today people wonder whether they should be drinking the water that comes out of their taps 

because of the disgusting things it is doing to the fish and possibly 

to them. There are serious concerns that the same chemicals that 

are responsible for these deformities in wildlife may also have similar effects in humans. They may be the culprit for the widespread 

increase in human disorders such as infertility, obesity, diabetes, 

and cardiovascular disease. These contaminants which fall under a 


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class of chemicals called endocrine disruptors are pervasively showing up in our Nation’s waterways including in water that millions 

of people rely on for drinking. 

For example, bisphenol-A BPA, which is used in many plastic 

containers and as a lining in canned food is associated with developmental and reproductive disorders in humans. To this end, the 

FDA recently announced that it is concerned about these health effects and I have got a bill to ban its use in food and beverage containers in hope that we can finally stop limiting our exposure. 

Tyclasin is another example of an endocrine disruptor which is 

used as an anti-microbial in hand soaps. Tyclasin has been shown 

to interfere with the development of the brain and nervous systems 

of laboratory animals, and I am concerned about the consequences 

on human health. I have asked both FDA and EPA what they plan 

on doing about evaluating and regulating Tyclasin’s widespread 

use. 

Perchlorate used as an ingredient in rocket fuel is pervasively 

showing up in drinking water all across the Nation. We are looking 

for that extra boost in the morning, but I would personally rather 

stick to a large cup of coffee. 

Massachusetts is one of the few states that regularly monitors 

perchlorate and has also set a statewide water standard for the 

contaminant. Exposure to this chemical during pregnancy can 

cause serious neurological deficits and could be one of the contributing causes of increased attention deficit disorders and other cognitive problems in our Nation’s children. 

All of these dangerous chemicals along with others whose health 

effects are less well known have been found by government scientists to be contained in our Nation’s surface water, ground water, 

and drinking water. In 1996, The Food Quality Protection Act and 

Safe Drinking Water Act amendments authorized EPA to screen 

for endocrine disruptors in sources of drinking water. 

In response to that statute, the EPA established the endocrine 

disruptor screening program designed to evaluate the safety of 

chemicals that might cause adverse health effects to the body’s endocrine system. EPA’s progress with this screening program has 

been slow, but late last year the first 67 chemicals designated for 

screening were announced, and the process of collecting information has finally begun. Given the advancements in science and 

technology that have occurred over the last decade, it is appropriate to reevaluate what we know about endocrine disruptors and 

assess the effectiveness of EPA screening program in identifying 

and evaluating the safety of endocrine disruptors found in sources 

of drinking water. 

I thank you for coming here today to the witnesses, and let me 

turn now to recognize the gentleman from Florida, Mr. Stearns, for 

an opening statement. 

Mr. STEARNS. Thank you, Mr. Chairman, and I ask unanimous 

consent that all members have 5 days for submission of their opening statements. 

Mr. MARKEY. Without objection. 


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OPENING STATEMENT OF HON. CLIFF STEARNS, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF FLORIDA 

Mr. STEARNS. And thank you for having this important hearing. 

Examining the science and the regulation of endocrine disrupting 

chemicals that I think all of us are concerned about. We all take 

this subject very seriously. There are some substances in the water 

that can pose real problems, and I want to know more about it. I 

think most members do. I would particularly like to welcome a constituent. Not oftentimes you have someone from your congressional 

district here. Dr. Christopher Borgert, the president and principal 

scientist at Applied Pharmacology and Toxicology Incorporated, 

which is located in my congressional district at the home of the 

University of Florida in Gainesville. Applied Pharmacology and 

Toxicology is one of the leading consulting firms that specializes in 

the pharmacological and toxicological effects of chemicals on living 

systems. And so I am honored to have a constituent with that kind 

of broad-based experience with us this morning. 

As the chairman mentioned, endocrine disrupting chemicals are 

natural chemicals that interfere with or mimic the hormones responsible for growth and development of an organism. Endocrine 

disrupting chemicals can be found in commonly used products such 

as personal care products, obviously soaps and cosmetics, industrial 

by-products, plastic, pesticides, and pharmaceuticals. As testing 

has become more sophisticated, minute traces of certain chemical 

substances suspected to be endocrine disruptors have been detected 

in surface water and drinking water supplies. These chemicals 

enter into our environment from various sources, obviously including industrial and municipal discharges, agricultural runoffs, and 

hospital residues. 

And while many researchers agree that field and laboratory studies of animals providing compelling evidence of the effect of these 

chemicals, the scientific community remains sharply divided of 

whether organic chemicals are responsible for increases of certain 

human cancers, diseases of the human reproductive system, the 

immune system, and the thyroid glands. Nevertheless, environmental advocates have increasingly pushed for the aggressive federal regulation of the substances. 

In 1996, Congress recognized that arbitrary, legislatively mandated regulation can bog EPA down and delay urgent public health 

needs. So to address this, the Safe Drinking Water Act amendments of 1996 replaced mandatory drinking water regulations with 

directions to EPA that it use simply deliberative rigorous and objective science in making any further rules on drinking water contaminant levels. EPA and the scientific community need to continue to study the occurrence and movement of endocrine-disrupting chemicals in our environment, and then EPA, not Congress, should set a standard that best protects the public health. 

So, Mr. Chairman, I thank you for this hearing, and we look forward to the witnesses this morning. 

Mr. MARKEY. We thank you. We thank the gentleman, and we 

have with us the gentlemen from Virginia—I am sorry. Chair recognizes the gentleman from Illinois, Mr. Shimkus, for an opening 

statement. 


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OPENING STATEMENT OF HON. JOHN SHIMKUS, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF ILLINOIS 

Mr. SHIMKUS. Thank you, Mr. Chairman. We need to just make 

sure that when we go down a route that that is—we are using high 

quality science whose results are repeatable, whose objective is not 

to answer questions for which we already have decided the answer. 

We have a tendency of doing that. 

We made some precautionary decisions in the toy bill, and that 

has just been one disaster after another. The whole debate on climate has just been a great exercise in how this climate-gate thing 

all unfolded. Science wanted the data to see if the projections by 

scientists were relevant and true. These scientists withheld data. 

They would not provide those. Under the Freedom of Information 

Act, we finally started getting the data. And guess what. 

Are the Himalayan glaciers melting in 35 years? We made a mistake. What about sea levels? That was a miscalculation. We have 

people walking away from or leaving the IPCC. We have the U.N. 

guy now stepping down. And why? Because we didn’t use science. 

We didn’t use the scientific method to put the bats on the table, 

put data on the table, and do the research to replicate these assumptions. So we have to be very, very careful that we don’t go 

down a route. 

This is the ‘‘Washington Post’’ Tuesday, February 23, ‘‘Replacing 

BPA cans gives foodmaker fits.’’ At the end of this, it says—they 

are talking about tuna. They spent thousands of dollars. Is it in the 

cutting board? Is it in the fish? Is it in the tuna itself? We don’t 

know. We are trying to figure it out. Let us use real science. Let 

us be able to replicate the data. Let us just don’t go on an emotional rollercoaster to impinge on our ability to create jobs in this 

America which increased regulations always does, and I yield back 

my time. 

Mr. MARKEY. The gentleman’s time has expired. The chair recognizes the gentlelady from California, Mrs. Capps, for an opening 

statement. 

OPENING STATEMENT OF HON. LOIS CAPPS, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF CALIFORNIA 

Mrs. CAPPS. Thank you, Mr. Chairman, and thank you for holding this hearing on the growing pandemics of endocrine related 

health disorders. Like you, I am very concerned about exposure 

that may be occurring through drinking water supplies. I am particularly concerned given the very pervasive nature of endocrinedisrupting chemicals, which are everywhere in our environment. 

Many of these chemicals are either unregulated or underregulated and include toxics, pesticides, even pharmaceuticals. As many 

of you, I spent my early professional years as a public health nurse. 

It is from this experience that I have been very mindful of threats 

to human health. While the Safe Drinking Water Act was successful at controlling some substances, it is clear that today’s contaminants of concern are not the pollutants of yesteryear. 

For example, there are currently 80,000 chemicals in use. This 

is a threefold increase from 1941 to 1995. 8,000 of these are known 

to be carcinogens. One would hope that all of these 8,000 cancercausing chemicals are somehow addressed under federal and state 


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laws, including the Safe Drinking Water Act. Shockingly, this is 

not the case. It seems that less than 300 chemicals have permitted 

limits. 

Today’s hearing provides us with an opportunity to ask why this 

is the case. It is not as if endocrine-disrupting chemicals are new 

issues of concern for either Congress or EPA. Through the Safe 

Drinking Water Act, Congress instructed EPA to develop a screening program to determine if certain chemicals disrupt hormones in 

humans. In the 14 years since this mandate was put in place, EPA 

has begun to test few chemicals under the program, despite the potential for these chemicals to cause great harm to individuals, especially to children and pregnant women. 

Today, I hope to hear about where these chemicals are coming 

from, what the impact to human and ecological health is, and what 

should and can be done to protect us from harm. So I do look forward to the testimony from our witnesses today on this very important hearing. And again I thank you for calling it to order, and I 

yield back. 

Mr. MARKEY. Thank you. Thank the gentlelady. We see no other 

members of the subcommittee seeking recognition for the purpose 

of making an opening statement. So we will turn to our witnesses, 

but we will begin first with our friend Congressman Jim Moran 

who has worked for many years on this issue and who has joined 

us here this morning. We welcome you to the committee, and we 

look forward to your testimony. 

STATEMENT OF HON. JAMES P. MORAN, A REPRESENTATIVE 

IN CONGRESS FROM THE COMMONWEALTH OF VIRGINIA 

Mr. MORAN. Mr. Chairman, thank you very, very much, and 

thank you for your leadership on this issue. And it is good to see 

my colleagues and friends Ms. Capps and Mr. Stearns. I first came 

to be concerned about this when we looked at the fish in the Potomac River. Now, this is just between northern Virginia and Washington, D.C., and almost 100 percent of the fish—they are smallmouth basses—are intersex. They are both male and female sexual 

organs. There is something wrong with that, and so we looked into 

what might be the cause. And invariably, we came back to endocrine disruptors. 

The problem is that the scientific research is inadequate to give 

us the kind of determination that we need to get, but we have the 

authority. Back in 1996, the amendments to the Safe Drinking 

Water Act call for EPA to ensure testing of chemicals with endocrine-disrupting effects. Congress directed the EPA to develop an 

endocrine-disruption screening program as part of the Food Quality 

Protection Act, as Ms. Capps suggested. Unfortunately, for a number of reasons—I will mention some of them—this program has not 

been effective. It has been deliberately delayed. Here we are 14 

years later, and over $100 million has been put into this program. 

And it wasn’t until October of this past year, just a few months 

ago, that EPA announced the availability of the national SAs and 

its testing guidelines for a limited number of chemicals. 

Chairman Markey, you have been monitoring the progress of the 

EPA and performing these studies, and you have been expressing 

your concern about the public’s exposure to these chemicals while 


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the issue continues to be studied. We can’t study it forever if we 

know that people are really suffering because we haven’t been able 

to come up with determinations on what is causing it. What is especially frustrating that, despite slow progress by the EPA, the 

science has continued to evolve through robust research by the scientific and academic communities through basically no help from 

the EPA who is charged with this work. 

And the work that the scientific community has done convincingly demonstrates a link between synthetic endocrine-disrupting 

chemicals and a number of disorders of the human endocrine system. It has seriously undermined the health of our Nation. It is 

costing hundreds of billions of dollars. Now, it is autism, hyperactivity disorder, asthma, juvenile and adult diabetes, juvenile cancer, osteoporosis, Parkinson’s, Alzheimer’s. What we know is that 

these disorders began to increase noticeably in the early 1970s 

when the first generation was exposed in the womb to post World 

War II synthetic chemicals. And they reach maturity, and that is 

when we see this phenomenal increase in these kinds of disorders. 

The endocrine disruptors were a fringe concept a decade ago. 

Now, they are accepted by the scientific community. But think of 

this, asthma rates have tripled in the past three decades. One in 

six American children has a developmental disorder. One in 59 

boys has autism. Cancer is the leading cause of death among children now. Primary brain cancer has increased by nearly 40 percent. We know about childhood obesity. One in two minority children develop diabetes. Testosterone levels have declined dramatically over the last 20 years. 

We have to be concerned about this. Something is happening, 

and it is happening on an accelerating pace. The scientific community is telling us that there is very likely a link to these dramatic 

increases in diseases in EDCs. What is happening, according to an 

environmental working group, that analyzed the umbilical cord 

blood that was collected from minority infants, they identified industrial compounds and pollutants that there were complex mixtures of compounds in each infant. And it shows that industrial 

chemicals cross the placenta in large numbers and contaminate babies in the womb. And it is that synergistic effect of these chemicals that is likely causing the problem. 

In November of this past year, the AMA said that the federal 

government needs to minimize the public’s exposure to endocrinedisrupting chemicals. So this is no longer a fringe issue. This is a 

very important issue for the entire Nation. But despite the profound improvements in scientists’ knowledge, the chemical industry, because of legislation that said that basically all the stakeholders have a veto if they choose to use it. 

The chemical industry, being one of those stakeholders, has been 

able to manipulate the process that has been undertaken by the 

Environmental Protection Agency so that they could produce results that were contrary to all of the research conducted by qualified endocrinologists that have found health consequences from 

EDCs. 

And through the process of buying up the stakeholders, EPA has 

been prevented from using the most appropriate modern protocols. 

That is the problem. EPA has not been able to conduct these exVerDate Mar 15 2010 08:22 Nov 08, 2012 Jkt 076011 PO 00000 Frm 00012 Fmt 6633 Sfmt 6633 E:\HR\OC\A011.XXX A011

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periments in the way that they know they need to. They have been 

conducting them in an outdated way. I won’t go into all the details 

because I suspect your speakers will describe it. But basically they 

use this dose response method. The dose establishes the poison. At 

higher doses, the effects are often nullified causing organs to stop 

producing more hormones and receptors. 

It is in low doses where the damage oftentimes occurs, but I will 

let the experts explain that. We have to be using modern, 21st century testing paradigms that recognize the unique subtle and complex properties that affects EDCs. I know that is what you want 

to be doing, Mr. Chairman. 

We need to be guided by the scientific community instead of 

stakeholders who we know have a major financial interest in not 

allowing EPA to be able to pursue the authority and charge that 

the Congress gave it. I don’t think I am going to get into the fact 

that EPA hasn’t done these studies properly, but the National Institutes of Environmental Health Sciences has the expertise and 

the objectivity. And you are going to hear from them. We strongly 

support them. 

For what it is worth, we have some role in the Environmental 

Appropriations Subcommittee. We want to do everything we can to 

support your efforts, Chairman Markey. This is a very important 

issue. It is affecting tens of millions of children across the country, 

and it is more than past time that we started doing the right thing 

in finding out the real impact of these EDCs and how we can get 

them out of the bloodstream of American society. 

So, Mr. Chairman, thank you very, very much for your leadership. I really do appreciate it. I appreciate the opportunity to add 

my two cents this morning. 

[The prepared statement of Mr. Moran follows:] 


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Statement of Rep. James P. Moran 

House Energy and Commerce Subcommittee on Energy and the Environment 

Hearing on Chemicals in Drinking Water 

Thursday, February 25, 2010 

Chainnan Markey, Ranking Member Upton, thank you for schcduling a hearing 

on an issue that is very important to me, the need to study and regulate endocrinedisrupting chemicals (EDCs). Extensive studies to date have shown a correlation between 

exposure to EDCs and all manner of adverse health effects. 

As you know, the 1996 amendments to the Safe Drinking Water Act called for the 

U.S. Environmental Protection Agency (EPA) to ensure testing of chemicals for 

endocrine disrupting cffects. In 1996, Congress also directed the EPA to develop an 

endocrinc disruption screening program as part of the Food Quality Protection Act. 

Unfortunately, for various reasons, EPA's EDC program has been plagued by delays. 

Here we are, fourteen years and over $100 million later, and it wasn't until October of 

2009 that EPA aImounced the availability of initial assays and testing guidelines for a 

limited number of chemicals. Chainnan Markey, you have been monitoring the progress 

of the EPA in performing these studies, and have expressed concern about the public's 

exposure to these chemicals while the issue continues to be studied. It is especially 

frustrating that, despite slow progress by the EPA, the science has continued to cvolve 

through robust research by the scientific and academic communities. 

This work convincingly demonstrates a disturbing link between synthetic EDCs and 

a number of disorders of the human endocrine system that is seriously undennining the 

health of our Nation. These disorders include autism, attention dcficit hyperactivity 

disorder, asthma, juvenile and adult diabetes, juvenile cancer, autoimmune diseases, 

obesity, osteoporosis, Parkinson's disease, and Alzheimer's dementia. These disorders 

began to increase noticeably in the early 1970s when the first generation exposed in the 

womb to post-World War II synthetic chemicals reached maturity. According to the 

Director orMount Sinai's Children's Environmental Health Center (CHIC). endocrinc 

disruptors were a fringe concept ten years ago. but now their significance is accepted by 

the scientific community. CEHC reports that: 

• Asthma rates have nearly tripled in the past three decades. 
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• One of every six American children has a development disorder (ADHD, 

dyslexia, mental retardation). 

• One in every 150 American children is now diagnosed with autism (the Centers 

for Disease Control have updated this to 1 in 101 children, and I in 59 for boys). 

• Cancer. after accidents. is the leading cause of death among children in the United 

States. 

Primary brain cancer increased by nearly 40% and leukemia increased by over 

60')'0 among children 14 years and younger from 1975 to 2004. 

Childhood obesity has quadrupled in the past 10 years. 

Other studies indicate: 

• 1 in 3 children and 1 in 2 minority children will develop diabetes; and 

• Age-independent declinc in testosterone levels has occurred over the past 20 years 

in American mcn. 

Something in the environment is making Americans sick in epidcmic proportions, 

and studies indicate a link to EDCs. Exposure to EDCs begins in the womb. A study 

commissioned by The Environmental Working Group analyzed umbilical cord blood 

collected from ten minority infants born in 2007 and 2008. The laboratories identified up 

to 232 industrial compounds and pollutants, finding complex mixtures of compounds in 

each infant. This research shows industrial chemicals cross the placenta in large numbers 

to contaminate babies in the womb. No one can predict the synergistic effects of these 

chemicals, or the impacts with repeated exposure over a lifetime. 

The Endocrine Society, comprising 14,000 hormone researchers and medical 

specialists in more than 100 countries, warned that "evcn infinitesimally low levels of 

exposure" to endocrine-disrupting chemicals may cause endocrine or reproductive 

abnormalities, particularly if exposure occurs during a critical developmental window. At 

its annual meeting in June 2009 the Society released a statement identifying exposure to 

endocrine disrupting chemicals as the issue of greatest public health concern to the 

Society. 

In November 2009, the American Medical Association Board of Delegates approved 

a resolution that called on the federal government to minimize the public's exposure to 

endocrine-disrupting chemicals. The measure was advanced by the Endocrine Society, 

the American Society for Reproductive Medicine and the American College of 

Obstetricians and Gynecologists. This is not just a national problem - the UN has also 

called upon members to undertake the study of endocrine disrupting chemicals. 

The cost of failure to act is enormous. The American Diabetes Association reports 

that the occurrence of diabetes is reaching epidemic proportions. The cost in the U.S. for 

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treating diabetes in 2007 was estimated at $116 billion. About one in every ten dollars 

spent on health care was related to diabetes. This is just one disease of the many believed 

to be attributable in part to endocrine disruptors. 

EPA's work has been at a glacial pace. Moreover, many question whether testing 

conducted under EPA's program will be as relevant or effective as it should be. Despite 

profound improvements in scientists' knowledge and understanding of endocrine 

disrupting chemicals, the chemical industry has been able to manipulate the process 

undertaken by EPA in order to produce results contrary to all of the research conducted 

by qualified endocrinologists that have found health consequences from EDCs. Through 

a process that requires the buy-in of stakeholders, including the chemical industry, EPA 

has been prevented from utilizing the most appropriate, modern protocols. 

Stakeholders, most notably the chemical industry, have vetoed all but outmoded 

study concepts, in effect using the fourteen years EPA has had to study EDCs to take a 

giant step backwards. For example, all endocrinologists would use a positive control to 

establish a baseline to compare to the effects of the studied chemical. The tests industry 

sponsor do not follow this protocol. More egregious, industry-sponsored studies use the 

dose-response method, known as "the dose establishes the poison." This means that the 

testing assumes the higher the dose, the greater the response. In fact, in the case ofEDCs, 

it is the small doses, such as the levels that occur in drinking water, that cause the effect. 

At higher doses the effects are often nullified causing organs to stop producing more 

hormones and receptors in target tissues to shut down. The dose/response is not a slope, 

but an inverted horseshoe curve. Nonetheless, industry studies have taken the results of 

high doses and concluded that with no response, the chemical poses no risk. 

We need to use a modern, 21 st century testing paradigm that recognizes the known 

unique, subtle, and complex properties and effects ofEDCs. Only then will we have 

accurate, practical data to inform appropriate and expeditious regulation of these 

chemicals. The experience of the last fourteen years has shown us that the regulatory 

agencies lack the ability or the integrity to conduct scientific investigations without 

interference by the industries they regulate. The scientific inquiry should be driven by 

scientists, not advisory panels stacked with industry experts who have an inherent 

conflict of interest. Once the scientific investigation is complete, and a clear link has 

been established between a chemical and its impact on human health, once science has 

spoken, I have no problem with the responsible regulatory agencies evaluating the risk 

and at that point working with the affected stakeholders to develop appropriate risk 

management strategies. 

Congress now has an opportunity to assess what has gone wrong in the past as far 

as developing an effective testing and screening program, and to ensure that steps are 

taken to move forward. Last year I, and several of our colleagues, introduced the 

"Endocrine Disruption Prevention Act of2009," legislation that will establish a muchneeded comprehensive research program and process to identify chemicals that interfere 

with human reproduction and development. More important, it will require regulatory 

agencies to come together and provide an appropriate public response to the scientific 

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findings, including identifying what actions they will take to protect humans from 

exposure to such chemicals. 

In this legislation science, not politics, will set the stage for determining the 

impact on these chemicals on human health. I propose that we authorize and fund 

additional efforts to study EDCs by an organization dedicated to research. Such studies 

should not be conducted by the regulatory component of EPA. Risk management 

considerations should only be made after risks have been identified through competent 

research. I believe that the National Institutes of Environmental Health Sciences 

(NIEHS) could provide the expertise and objectivity needed. NIEHS (or possibly EPA's 

Office of Research and Development) needs to undertake a comprehensive research and 

testing program, using the best available science, to identify chemicals with endocrine 

disruption potential. In addition, the process would include an independent expert panel, 

guided by the scientific research, to develop a list of the chemicals and evaluate the 

potential threat they pose. When the science has been developed, regulatory agencies like 

EPA. the Consumer Product Safety Commission (CPSC), and the Food and Drug 

Administration (FDA), need to coordinate a timely response to those scientific findings. 

Regulating such chemicals to reduce cxposure would be ideal; public outreach, so that the 

public can avoid exposure to such chemicals absent regulation, would also be beneficial. 

In any event, action will be based on sound, unbiased science. 

In 2009 we saw much debate on the issue of health care costs in America. Every 

coverage option developed carries with it enormous costs. One rarely-discussed 

approach to bringing down health care costs is increased attention to improving the health 

of Americans, particularly the most vulnerable, those that require extensive health care 

support, even from infancy. 

Let us not, ten years from now, be sorry that we did not take action sooner to 

prevent this health crisis. I urge my colleagues to support this important work. 

Thank you. 

4 
12 

Mr. MARKEY. Well, it is more than two cents, and since you are 

on the Appropriations Committee, you have a chance to put in a 

few more than that too. We thank you so much for your leadership 

on this issue over the years, and we thank you for coming here 

today. And I would like to partner with you as we go forward between our two committees to try to find a way that we can properly 

fund and properly regulate this incredible lies in disease that we 

know is related to something that we are doing to ourselves would 

cure most of the diseases that over the years have afflicted people. 

Now we have to deal with issues that we do it to ourselves, you 

know, that we just make decisions with regard to chemicals, with 

drugs, with alcohol, with overeating. These are things that here we 

have a chance, you know, just with preventative measures to protect against the diseases, and your leadership has been fantastic. 

The gentleman from Florida. 

Mr. STEARNS. You know I would ask the staff about your opening 

statement, and my good friend has been on this issue for some 

time. And I have heard you before, and I think many of us have 

gone down to the Chesapeake, and so we are a little bit aware of 

what happened. And then, of course, we look at the Potomac occasionally and see what happened there. Many of us sometimes go 

fishing on the Potomac, either part of fundraising events or just social events. And so it is disturbing. I live in Old Town. I go down 

to King Street where you were mayor of Alexandria, and sometimes 

you get alarmed. 

So I think it is an important issue. For all of us, I think the idea 

is there hard, repeatable science that can show this? Because we 

are asking the federal government to step in. So I think, Mr. Chairman, that is probably the crucial aspect to see that there is hard, 

repeatable science. Thank you. 

Mr. MARKEY. And we thank you again. We very much appreciate 

your work and your staff’s work on this issue. Now let us turn to 

our witness panel, and first of all, the subcommittee has received 

several letters and documents related to the subject matter. And I 

ask unanimous consent that the materials be included in the record 

without objection. 

[The information appears at the conclusion of the hearing.] 

Mr. MARKEY. We will turn to our first witness, Dr. Linda 

Birnbaum. She serves as the director of the National Institute of 

Environmental Health Sciences and the National Toxicology Program. She is a board-certified toxicologist and has served as a federal scientist for nearly 30 years. Dr. Birnbaum previously served 

for 16 years as director of the experimental toxicology division of 

the Environmental Protection Agency. We welcome you, Doctor. 

Whenever you feel comfortable, please begin. 


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STATEMENTS OF LINDA BIRNBAUM, DIRECTOR, NATIONAL INSTITUTE FOR ENVIRONMENTAL HEALTH SCIENCES; JAMES 

JONES, DEPUTY ASSISTANT ADMINISTRATOR, OFFICE OF 

PREVENTION, PESTICIDES AND TOXIC SUBSTANCES, ENVIRONMENTAL PROTECTION AGENCY; GINA SOLOMON, SENIOR SCIENTIST, NATIONAL RESOURCES DEFENSE COUNCIL; 

AND CHRISTOPHER J. BORGERT, PRESIDENT AND PRINCIPAL SCIENTIST, APPLIED PHARMACOLOGY AND TOXICOLOGY, INC. 

STATEMENT OF LINDA BIRNBAUM 

Ms. BIRNBAUM. Thank you. Mr. Chairman and distinguished 

members, I am pleased to present testimony on our current understanding and ongoing research on endocrine-disrupting chemicals 

or EDCs. My name is Linda Birnbaum. I am director of the NIEHS 

and the National Toxicology Program. 

Some endocrine disruptors are naturally occurring, but many are 

manmade substances that mimic or interfere with hormonal signals in the body and therefore alter the normal functions of tissues 

and organs. NIEHS has had a long-standing interest in these 

chemicals with its support for research dating back to the beginning of the institute in the 1960s. Over the past 50 years, we have 

seen increases in health problems such as breast and prostate cancer, ectopic pregnancies, undescended testicles, and a 42 percent 

decrease in sperm count. 

These findings along with observations of abnormal sexual development in frogs and fish and the widespread detection of endocrine-disrupting chemicals in our bodies lead NIEHS to increase its 

research on the effects of these chemicals on human health. 

The detection of numerous pharmaceutical agents and chemicals 

with endocrine-disrupting potential in surface waters around the 

country has raised concern about drinking water as a significant 

route of human exposure. 

I would like to emphasize four things about endocrine disruption. 

First, low dose. Our endocrine system works on tiny amounts of 

hormones that have significant biological effects. As a result, some 

chemical exposures, even at low doses, may disrupt the body’s delicate endocrine system and lead to disease. 

Second, wide range of health effects. Endocrine signals govern 

every organ and process in the body. That means when chemicals 

interfere with endocrine signaling, effects can be seen in many different conditions and diseases. 

Third, persistence of biological effects. We are finding that the 

health effects of exposure to endocrine disruptors can be observed 

long after the actual exposure has ceased. This is especially true 

when exposures occur during growth and development, processes 

that are very sensitive to endocrine regulation. 

Fourth, ubiquitous exposure. Because of widespread use as drugs 

and components of consumer products, chemicals with endocrinedisrupting activity are widely dispersed in our environment often 

at biologically effective levels, and exposure to humans is common. 

This is well-documented by the CDC National Exposure Report. I 

will give you a few examples regarding low dose. For some endocrine disruptors, biological changes can be seen at low but not at 


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high doses. This is different from the usual dose response curve 

which shows continually increasing responses with increases in 

dose. 

Low doses of BPA and EDC change brain structure, function and 

behavior in rats and mice exposed during critical periods of development. Regarding the broad range of health effects, early work on 

endocrine disruption focused on health problems such as reproductive cancers that were known to be hormonally sensitive. More recently, the universe of potential health effects has grown to include 

immune function, metabolism, brain development, and behavior. 

Animal studies have identified how exposure to environmental 

endocrine disruptors such as tributyltin, genistein and 

diethylstilbestrol can cause weight gain later in life. EDCs have 

also been linked to cancers, altered behavior, diabetes, immune 

dysfunction, reproductive dysfunction, and cardiovascular disease. 

Regarding the persistence of biological effects. Exposure to endocrine disruptors during development can result in profound 

changes in later life. Animal researchers recently discovered that 

EDCs can produce these latent effects by subtly altering the structure of the DNA molecules and chromosomes. These changes may 

affect gene expression for several generations. 

NIEHS is also conducting human studies on the latent effect of 

EDC exposure including studies of children showing behavioral, 

mental, and physical abnormalities who were exposed to phthalates 

or flame retardants before birth. 

Regarding ubiquitous exposure. The NTP is conducting a study 

of triclosan, an antimicrobial that is one of the most frequently detected water contaminants. Our understanding of the endocrinedisrupting chemicals has lead to new approaches for studying 

EDCs including research on whether mixtures of chemicals known 

to occur in drinking water impact development. 

Other novel approaches are being developed to characterize the 

potential for environment agents to perturb endocrine function. 

NTP’s high throughput screening initiative and Tox 21 partnership 

with EPA includes assays designed to assess activity of chemicals 

as hormonal targets. Initial results have shown that EPA and 

triclosan are among the most active of hundreds of chemicals tested so far. Such novel screening tests can be used for a basis for deciding whether to conduct more intensive animal studies. 

To ensure that our science is shared with those who need it, we 

are partnering with the agencies that use our research, and we are 

sponsoring scientific forums for sharing this information with affected communities and stakeholders. For example, our breast cancer and environmental research program distributes fact sheets for 

clinicians and the public on likely sources of EDC exposures. 

In conclusion, I believe this area of environmental health 

sciences to be of utmost importance. Our endocrine systems keep 

our bodies in balance, maintaining homeostasis and guiding proper 

growth and development. With NIEHS’s leadership, we are all 

learning more about how these finely-tuned systems are sensitive 

to unanticipated effects from chemical exposure. 

This information is critically important for creating effective 

strategies to ensure safe drinking water and the health of the 

American public. I welcome your questions. 


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[The prepared statement of Dr. Birnbaum follows:] 


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Testimony 

Before the Subcommittee on 

Energy and Environment 

Committee on Energy and Commerce 

United States House of Representatives 

Statement for hearing entitled, "Endocrine 

Disrupting Chemicals in Drinking Water: 

Risks to Human Health and the 

Environment" 

Statement of 

Linda Birnbaum, Ph.D., D.A.B. T., A. T .S. 

Director, National Institute of Environmental 

Health Sciences, National Institutes of Health, and 

Director, National Toxicology Program 

U.S. Department of Health and Human Services 

For Release on Delivery 

Expected at 9:30 a.m. 

February 25, 2010 
17 


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Mr. Chairman and distinguished members of the Subcommittee-I am pleased to appear before 

you today to present testimony on current understanding and ongoing research on endocrine 

disrupting chemicals (EDCs). I am Linda Birnbaum, the Director of the National Institute of 

Environmental Health Sciences (NIEHS), part of the National Institutes of Health (NIH), as well 

as of the National Toxicology Program (NTP). NIH and NTP are entities of the U.S. Department 

of Health and Human Services. 

Endocrine disruptors are naturally occurring or man-made substances that may mimic or 

interfere with the fimction of hormones in the body. Endocrine disruptors may turn on, shut off, 

or modify signals that hormones carry and thus affect the normal fimctions of tissues and organs. 

NIEHS has had a longstanding interest in these chemicals with its support for research dating 

back to the beginning of the Institute in the 1960s. 

Over the past fifty years, researchers observed increases in endocrine-sensitive health outcomes. 

Breast and prostatic cancer incidence increased between 1969 and 19861

; there was a four-fold 

increase in ectopic pregnancies (development of the fertilized egg outside of the uterus) in the 

U.S. between 1970 and 19872

; the incidence of cryptorchidism (undescended testicles) doubled 

in the U.K. between 1960 and the mid 1980s3

; and there was an approximately 42% decrease in 

sperm count worldwide between 1940 and 19904

• 

These observations, set against the numerous observations of abnormalities of sexual 

development in amphibians and fishS and the widespread detection of chemicals with endocrine 

disrupting properties in our bodies6

, have led NIEHS to increase its support for research on the 

effects of chemical exposures on the various endocrine systems. The detection of numerous 

pharmaceutical agents and chemicals with endocrine disrupting potential in surface waters 

around the country 7 has raised concern about drinking water as a significant route of exposure. 

There are four aspects of exposure to endocrine disruption which I want to emphasize: 

First, the effect of low doses. Normal endocrine signaling involves very small changes in 

hormone levels, yet these changes can have significant biological effects. That means subtle 

disruptions of endocrine signaling is a plausible mechanism by which chemical exposures at 

low doses can have effects on the body. 

Second, the wide range of effects. Endocrine signals govern virtua1ly every organ and 

process in the body. That means that when outside chemicals interfere with those systems, 

I Hoel DG et a!. JNatl Cancer Inst 84:313-320(1992) 

2 NederlofKP et al. MMWR 39:9-17 (1990) 

3 Group JRHCS. Br Moo J 293:1401-1404(1986) 

4 Carlsen E et a!. Br Med J 305:609-613(1992) 

S e.g., Reeder et aI., Environ Health Perspect 113(3) 261-265 (2005); Gross-Sorokin et aI., Environ Health Perspect 

114 (S-I):147-151 (2006) 

6 CDC, Fourth National Report on Human Exposure to Environmental Chemicals (2009), 

http://www.cdc.gov/exposurereport! 

7 USGS, Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams (2002); 

http://toxics.usgs.gov/pubsIFS-027-02/ 

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the effects can be seen in many different diseases and conditions - some of which we are just 

learning to recognize as the result of endocrine disruption. 

Third, the persistence of effects. We are rmding that the effects of exposure to endocrine 

disruptors can be observed long after the actual exposure has ceased. This is especially true 

for growth and development, processes that are very sensitive to endocrine regulation. The 

question of how these kinds of latent effects occur is an active area of investigation. 

Fourth, the ubiquity of exposure. Both naturally occurring and manmade substances can be 

endocrine disruptors. Some, e.g., arsenic and agricultural chemicals, are ubiquitous in the 

environment In addition to the growing use of hormonally-active pharmaceuticals that pass 

through the bodies of those taking them and end up in water treatment systems and surface 

waters, many of the chemicals that are being found to have endocrine effects are components 

of a wide range of consumer products, including some water bottles, cosmetics, sunscreens, 

and other personal care products. Substances applied to the skin can be directly absorbed but 

also end up getting washed off our bodies and into our water systems. As a result, chemicals 

with endocrine disrupting activity are widely dispersed in our environment, often at levels 

plausibly associated with biological effects; exposure to humans is widespread. 

Looking at these four points together, it is apparent that endocrine disruption is an important 

emerging public health concern. NIEHS is responding to the importance of this concern through 

our research investments, and we are starting to understand these health risks better, but there are 

still many gaps in our understanding. We are therefore gathering more information to help 

assess and manage EDCs appropriately. 

Here are some examples to illustrate the fIrst three of the take-home messages about endocrine 

disruption that I listed above. As for the fourth, I would point you to the Centers for Disease 

Control and Prevention's National Exposure Report8 for evidence of the widespread exposure to 

these chemicals. 

Regarding low dose: Early studies ofEDCs in sensitive animal models established examples in 

which no threshold dose could be detected; that is, effects were already apparent at the lowest 

doses tested.9 Moreover, there are some endocrine disrupting chemicals whose effects can be 

seen at low doses but not at high doses, in opposition to the usual dose-response curve familiar to 

toxicologists, which shows continually increasing responses with increases in dose. A 2007 

NIEHS-sponsored review of studies of in vivo effects of Bisphenol A (BP A), for example, 

identifIed evidence for effects of low dose exposure during development on subsequent brain 

structure, function and behavior in rats and mice. 10 

An NIEHS-funded group at the Dartmouth College Superfund Research Program discovered that 

arsenic can act as a potent endocrine disruptor. They have shown that arsenic profoundly affects 

the function of five steroid hormone receptors (the receptors for glucocorticoid, androgen, 

progesterone, mineralocorticoid, and estrogen hormones) as well as the function of related 

, See http://www.cdc.gov/exposurereportlpdfIFourtbReport.pdfformost recent version of the report. 

9 Sheehan DM et aI., Environ Health Perspect 1999 Feb;107(2):155-9 

10 Richter CA et a!., Reprod Toxicol 24 (2007) pp. 199-224 

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nuclear receptors for thyroid hormone and retinoic acid. I I These effects were observed at levels 

of 0.01 to 2.0 micromolars in cell culture and at or below 10 ppb in several animal models. They 

have also shown that arsenic has a significant effect on the ability of an activated hormone 

receptor to regulate gene expression, and that low level drinking water arsenic has strong, tissuespecific effects on expression of genes and proteins involved in the innate immune response in 

mouse lung. 12 They found that mice that were exposed to 100 ppb arsenic in drinking water had 

a significantly compromised response to HlNl influenza infection. 13 

Regarding the broad range of effects: As our understanding of mechanisms has grown, so has 

our recognition of the many ways these compounds interact with the body and the many health 

outcomes that are influenced. The early work on endocrine disruption started out focusing 

mostly on outcomes that were known to be sensitive to the effects of steroid hormones, such as 

cancers of the reproductive system, and on mechanisms that involved hormonal receptors located 

in the cells' nuclei. However, in addition to working through normal nuclear hormone receptors 

such as estrogen, androgen, thyroid, and retinoid receptors, we find that these molecules interact 

with many other kinds of receptors, such as membrane (non-nuclear) receptors, neurotransmitter 

receptors, enzymatic pathways involved in steroid biosynthesis and metabolism, and all the other 

mechanisms that enable hormone systems to do the work they need to do, which in turn enables 

the organism to function normally and react to changes. So the universe of potential health 

effects has grown commensurately to include non-reproductive cancers, immune effects, 

metabolic effects, and brain development and behavior, in addition to non-cancer abnormalities 

of the reproductive system, such as reproductive tract abnormalities, precocious puberty, 

disorders of fertility and fecundity, and endometriosis. 14 For example, endocrine control of 

glucose homeostasis can impact development of diabetes, obesity, and cardiovascular disease. 

Researchers have now identified model systems and mechanisms by which developmental 

exposure to EDCs such as tributyltin 15, genistein and diethylstilbestrol16 may potentially cause 

weight gain in animals later in life. NIEHS-funded researchers are working on understanding 

biochemical and physiological aspects of environmental contributions to obesity, and we expect 

this work to have an impact on the development of interventions and preventive strategies to deal 

with this huge public health issue. 

There are concerns about multiple possible health effects ofBPA exposure. BPA is a selective 

endocrine modulator with widespread human exposure. The Department's Food and Drug 

Administration (FDA) recently announced that it has some concem about the potential effects of 

BP A, partly based on the conclusions of the NTP-CERHR Monograph on Potential Human 

Reproductive and Developmental Effects of Bisphenol A (see summaryI7), which in tum built on 

the earlier consensus statement report from the expert panel workshop convened by the NIEHS18. 

While much of the exposure to BP A in hnmans occurs through the diet, other sources of 

" Davey IC et aI. Environ Health Perspect (2008) I 16:165-172. 

12 Kozul CD et a!. Environ Health Perspect (2009) II 7(7): I 108-15. 

13 Kozul CD et al. Environ Health Perspect (2009)117:1441-1447. 

14 Diamanti-Kandarakis et a!., Endocrine Reviews (2009) June;30(4):293-342 

IS Grun F, Blwnberg B. Endocrinology (2006) 147:S50-S55 

16 Newbold RR et a!. Mol Cell Endocrinol (2009) May 25;304{1-2):84-89 

" http://www·niehs.nih.gov!news!medialquestions!sya-bpa.cfin 

18 vom Saal et a!. Reprod Toxicol (2007)24:131-138 

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exposure include air, dust, and water. NIEHS invested approximately $20M in FY2009 to study 

health effects ofBPA exposure, including $IO.7M from ARRA funding. We have developed a 

program to assess differences in routes of exposure and metabolism across species, as well as the 

replication and expansion of experiments that linked BPA exposure to disease endpoints such as 

cancers, ADHD, obesity/diabetes/metabolic syndrome, immune dysfunction, reproductive 

diseases and dyfunctions, and cardiovascular disease. In addition, an NTP study is being 

conducted with FDA measuring the effects of long term exposures to a wide dose range of BP A 

in rats. 

Regarding persistence of biological effects: Because of the existence of special windows of 

susceptibility in developmental processes, we know that exposure to EDCs at very sensitive 

stages of development can result in profound changes in physiology and function that may not 

emerge clinically until much later in life. 19 The exposure itself may cease, but the developmental 

impact and the subsequent adverse effect have already been set in motion. NIEHS leads the 

cross-NIH effort to understand how exposure-related changes in an individual's epigenetic status 

in one stage of their life can affect the health of the individual in later stages of their lifespan. 

Epigenetics is one recently discovered mechanism by which EDCs can produce these latent 

effects by altering the three dimensional structure of the chromosomes. The addition of methyl 

groups to DNA and changes to the histone proteins in chromosomes alter gene expression, 

leading to effects that can persist not just through one lifetime, but potentially for generations. 

These delayed effects are the subject of a number of human studies funded by NIEHS. A group 

of researchers at Mt. Sinai School of Medicine recently reported that adverse behaviors of 

children aged 4-9 years (conduct or ADHD disorders) were associated with prenatal exposure to 

low molecular weight phthalates.2o Other scientists at Columbia University's Center for 

Children's Environmental Health (co-funded by NIEHS and the Environmental Protection 

Agency (EPA) examined cord blood exposure to polybrominated diphenyl ethers (PBDEs), 

which are ubiquitous flame retardants, and associations with neurodevelopment at ages 1-4 and 6 

years. Children with higher concentrations of specific PBDEs while in utero scored lower on 

tests of mental and physical development.21 Previous data linking these compounds to altered 

thyroid hormones and thyroid function might provide a plausible mechanism for these effects. 

The NIEHS Breast Cancer and Environment Research Program (co-funded with the NIH's 

National Cancer Institute) is investigating whether periods of susceptibility exist in the 

development of the mammary gland, when exposures to environmental agents may impact the 

breast and endocrine systems that can influence breast cancer risk in adulthood. It is examining 

the determinants of puberty in girls, integrating environmental, genetic, biologic, lifestyle, and 

socioeconomic factors, in recognition of the epidemiology linking breast cancer risk to pubertal 

maturation. A major area of study is the role of exposures to EDCs. Center scientists have 

measured 51 environmental agents and their metabolites in biospecimens from approximately 

19 Diamanti-Kandarakis et alia, Endocrine Reviews (2009) June;30(4):293-342 

20 Engel SM et al. Environ Health Perspect 20 I 0 Jan 8 {Epub ahead of print] 

21 Herbstman JB et al. Environ Health Perspeet 2010 Jan 4 {Epub ahead ofprintJ 

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1,190 girls. The data include the first report in children of high levels of a number of hormonally 

active chemicals such as enterolactone, benzophenone-3, and monoethyl-phthalate.22 

A separate follow-up study is now in progress in response to observations of high perfluoroalkyl 

compound (PFC) levels measured in a ge0FnPhiCally distinct subset of the Breast Cancer and 

the Enviromnent Research Center cohort.2 PFCs such as perfluorooctane sulfonate (PFOS) and 

perfluorooctanoic acid (PFOA) are of concern because of their presence in air, food, drinking 

water and human tissues, their persistence and long half-life, and their adverse effects on 

development in animal models. NIEHS is supporting numerous studies on these compounds. 

One of our intramural investigators is following up previous observations of an association 

between PFOS and PFOA and increased time-to-pregnancy (a measure of decreased 

fecundability).24 At the request of the EPA, the NTP initiated a large research program on this 

class of comrsounds that includes PFOS, PFOA and shorter and longer chain perfluoroalkyl 

compounds. 5 These studies include an evaluation of multiple aspects of post-natal development 

following exposure in utero and will provide a sound basis for assessing cumulative human 

health risks for these ubiquitous contaminants. 

New science to promote new understanding: Given our growing understanding of the myriad of 

cellular hormonal targets ofEDCs, new approaches have to be developed in order to characterize 

the potential for enviromnental agents to perturb endocrine function. NTP's high throughput 

screening initiative (HTS) and Tox21 partnership, in collaboration with EPA and the NIH 

Chemical Genomics Center,26 include multiple assays designed to assess activity of chemicals at 

hormonal targets. Initial results have shown that among the most active of hundreds of 

chemicals tested so far in these assay systems is BP A. Triclosan, an antimicrobial in hand soaps, 

toothpaste, cosmetics, and many other products, and one of the most frequently detected water 

contaminants, also exhibits endocrine activity in these tests and is one of the most active compounds 

across multiple assays.27 

By linking pre-existing and newly developed information on toxicological activity in whole 

animal studies of compounds registering as positive in these endocrine-relevant assays, we are 

able to explore the in vivo significance of signals picked up in HTS. As we move forward and 

develop and include additional assays for endocrine activity, HTS will help us decide which 

chemicals need further investigation. 

The NIP is employing in vitro and short term animal models to detect perturbations in endocrine 

function that can be used as a basis for deciding whether to conduct more rigorous long-term 

studies. Short term models are also being used to address questions of cumulative risk, that is, 

whether exposure to mixtures of similar compounds causes additive or synergistic (whole greater 

than the sum of the parts) effects. For example, through a collaborative arrangement with EPA's 

22 WolffMS et a1. Environ Health Perspect 2007, 115(1):116-121 

23 R2IES017176 PI: Susan Pinney, Univ of Cincinnati. Exposure biomarkers of poly flu oro alkyl compounds in 

r,rsons living in the Ohio River valley. 

, PI: Matthew Longnecker, NIEHS. Perfluorinated alkyls and fecundability. 

25 ht!Jl:llntp.niehs.nih.govlfileslPFOAConcept.pdf 

26 ht!Jl:lln!p.niehs.nih.govlgoI28213 

17 ht!Jl:/lwww.epa.gov/ncctJpractice community/categorv priority.hlml 

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Office of Research and Development, the NTP is conducting studies to evaluate effects on male 

reproductive endpoints for many combinations of phthalates to allow more precise comparisons 

of potency and a better understanding of cumulative risk for this class of compounds found in 

many plastics. 

The NTP is also planning new research relevant specifically to EDCs in drinking water. One set 

of studies will investigate the potential for mixtures of chemicals known to occur in drinking 

water to impact pre- and early post-natal development. These studies will focus on structurally 

dissimilar drugs and other industrial chemicals that perturb a common biological pathway, e.g. 

cholesterol and lipid metabolism. 

New information on endocrine activity has led the NTP to develop toxicological research 

programs on additional compounds such as bisphenol AF,28 used to make certain industrial 

polymers; butylparaben,29 a preservative used in cosmetics; oxybenzone,3o a sunscreen 

ingredient; and triclosan.31 The relevance of cosmetics, sunscreens and other personal care 

products to drinking water exposures has previously been highlighted. Endocrine activity is also 

of potential concern for herbal products taken as dietary supplements. NTP research programs 

on several of these, such as gum guggul, Dong quai, and valerian, includes evaluations of 

hormonal activity. 

In addition to generating new knowledge, we also need to make sure our science is shared with 

those who need to use it. This includes other Federal, state and local agencies as wen as 

communities and individuals. Many of our research efforts are done in partnership with the 

agencies who will be the consumers of the research. We have also supported some excellent 

scientific forums for sharing this information with government and non-government scientists. 

For example, the NIEHSINTP, along with other NIH components, FDA, CDC, the Agency for 

Toxic Substances and Disease Registry, EPA, the Society of Toxicology, the World Health 

Organization, and the European Environment Agency, recently sponsored a workshop on 

prenatal programming and toxicology entitled, "PPTOXII: Role of environmental stressors in the 

developmental origins of disease." The meeting, attended by 280 scientists, focused on the 

developmental origins of disease with the goal of stimulating collaborations in the area of effects 

of endocrine disrupting chemicals on developmental toxicity. We are also mindful of the need to 

keep dialog open with affected communities. In our Breast Cancer and Environmental Research 

Program, researchers have created public messages to convey information about endocrine 

disrupting chemicals and their potential role in the prevention and understanding of breast 

cancer, including fact sheets for clinicians and the public on likely sources of exposures. 

In conclusion, let me stress that I believe this area of environmental health sciences to be of the 

utmost importance. Our endocrine systems keep our bodies in balance, maintaining homeostasis 

and guiding proper growth and development. With NIEHS's leadership, we are learning more 

and more about how these finely tuned systems are sensitive to unanticipated effects from 

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Endocrine Disrupting Chemicals in Drinking Water 

House Energy and Commerce Subcommittee on Energy and Environment 

February 25,2010 

Page 6 
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chemical exposures. This infonnation is critically important for creating effective strategies to 

prevent disease and promote better health, as well as to ensure safe drinking water. 

Thank you for the opportunity to present infonnation on this important topic. I would be happy 

to answer your questions. 

Endocrine Disrupting Chemicals in Drinking Water 

House Energy and Commerce Subcommittee on Energy and Environment 

February 25, 2010 

Page? 
24 

Mr. MARKEY. Thank you, Dr. Birnbaum, very much. Our next 

witness, James Jones, who is Deputy Assistant Administrator of 

the Office of Prevention, Pesticides and Toxic Substances at the 

Environmental Protection Agency. He is responsible for managing 

the daily operation of the office which oversees the Nation’s pesticide, toxic chemical, and pollution prevention laws. He previously 

served as the director of the agency’s office of pesticide programs. 

We welcome you, sir. 

STATEMENT OF JAMES JONES 

Mr. JONES. Good morning, Mr. Chairman. 

Mr. MARKEY. Move that microphone in a little bit closer please. 

Mr. JONES. Good morning, Mr. Chairman and members of the 

subcommittee. I am Jim Jones, the deputy assistant administrator 

of EPA’s Office of Prevention of Pesticides and Toxic Substances. 

I appreciate the opportunity to appear before the subcommittee to 

provide an update on EPA’s endocrine-disruptor screening program 

and plans for its future implementation. 

The implementation of the EDSP is part of one of Administrator 

Jackson’s top priorities. To make significant and long-overdue 

progress in assuring the safety of chemicals. Issuing test orders for 

the generation of data to better understand potential endocrine effects is an important step in improving our ability to protect the 

public health and the environment from chemicals. 

The Food Quality Protection Act of 1996 required EPA to develop 

and implement a program to screen all pesticides for any effect in 

human that is similar to effects produced by naturally-occurring estrogen and such other endocrine effects as EPA may designate. 

Upon the recommendations of our advisory committee, the EDSP 

was expanded to include the assessment of androgen and thyroid 

hormone systems and effects on wildlife. The EDSP is a two-tiered 

screening program. Tier one is composed of a battery of 11 invitro 

and short-term invivo assays to identify chemicals that have the 

potential to interact with estrogen, androgen and thyroid systems. 

Chemicals that are positive in tier one would be subject to the tier 

two testing requirements. 

The purpose of the tier two test is to provide information that 

can be used as a risk assessment such as identification and characterization of adverse effects resulting from the interaction of the 

chemicals with the hormone system and exposure levels required 

to produce them in assays involving developmental life stages in 

whole animals. 

The validation of the tier one assays took far longer than anyone 

in EPA anticipated. Because of the many complexities of methods 

developed in the validation for such a large number of assays, validation of tier one assays took 10 years and is still ongoing for tier 

two assays. Validation of the tier two assays will be complete in 

2012. 

The good news is that the EPA has begun to issue test orders. 

The first list of chemicals for testing consists of 67 chemicals, 58 

pesticide active ingredient and 9 inert ingredients that are also 

high-production volume chemicals. 

EPA began issuing its first EDSP test orders in October of 2009, 

and it will issue the last test orders for list one chemicals this 


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week. A total of 750 plus test orders will have been sent to manufacturers of these 67 chemicals. EPA has created a database of the 

initial pesticides chemicals to be screened in the EDSP and has 

made this information available on EPA’s Web site. 

In addition to the EPA provisions that require the screening of 

all pesticide chemicals, the Safe Drinking Water Act amendments 

of 1996 provide EPA with the authority to test substances that may 

be found in sources of drinking water, to which a substantial population may be exposed. Right now, EPA is preparing a second list 

of no less than 100 chemicals, a draft of which will be released in 

the near term. 

The list two chemicals will be drawn from three sources: national 

primary drinking water regulations, the Contaminant Candidate 

List, CCL 3, and pesticides that are on the registration review 

schedule in the near term. The CCL 3 list is a list of contaminants 

that are currently not subject to any proposed or promulgated national primary drinking water regulations that are known or anticipated to occur in public water systems, and which may require regulation under the Safe Drinking Water Act. The CCL 3 list includes pesticides, other chemicals used in commerce, and disinfection byproducts and degredates. 

In summary, EPA is on track to obtain tier one endocrine screening data on several hundred chemicals within the next several 

years. Although it has taken a long time to develop the tests necessary for this program, we have begun to meaningfully implement 

the EDSP and allow to expand the universe of chemicals for testing 

beyond pesticides to include drinking water contaminants. 

Thank you for your continued interest in this program, and I 

would be happy to answer any questions. 

[The prepared statement of Mr. Jones follows:] 


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I ntrod uction 

TESTIMONY OF 

JAMES J. JONES 

Deputy Assistant Administrator 

Office of Prevention, Pesticides and Toxic Substances 

U.S. Environmental Protection Agency 

Before the 

Subcommittee on Energy and the Environment 

Committee on Energy and Commerce 

U.S. House of Representatives 

February 25, 2010 

Good morning Mr. Chairman, Ranking Member Upton and members of the 

Subcommittee. I am Jim Jones, the Deputy Assistant Administrator of the 

Environmental Protection Agency's (EPA) Office of Prevention, Pesticides, and 

Toxic Substances. I appreciate the opportunity to appear before the 

Subcommittee to provide an update on EPA's Endocrine Disruptor Screening 

Program (EDSP) and plans for its future implementation. 

Background 

The implementation of the EDSP is part of one of Administrator Jackson's top 

priorities--to make significant and long overdue progress in assuring the safety of 

chemicals in our products, our environment and our bodies. Issuing test orders 

for the generation of data to better understand potential endocrine effects is an 

important step in improving our ability to protect the public health and the 

environment from chemicals. 

The Food Quality Protection Act of 1996 (FQPA) required EPA to develop and 

implement a program to screen all pesticides for any "effect in humans that is 

similar to an effect produced by a naturally occurring estrogen and such other 

endocrine effect" as EPA may designate. Because endocrine disruption was on 

the cutting edge of science, shortly after the Act was passed, EPA formed the 

Endocrine Disruptor Screening and Testing Advisory Committee, composed of 

scientists from government, stakeholder organizations and academia, and 

charged it with providing advice on how to design a screening program for 

endocrine disrupting chemicals. Considering EDSTAC's diverse membership and 

expertise, EPA found its consensus compelling and scientifically rigorous. 

Therefore, EPA relied heavily on EDSTAC's advice and recommendations in 

developing the EDSP. 
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Developing the Program 

Upon the recommendations from EDSTAC, the EDSP was expanded to include 

assessment of the androgen and thyroid hormone systems and effects on wildlife. 

EDSTAC also recommended a two tier screening program. Tier 1 is composed 

of a battery of in vitro and short-term in vivo assays to identify chemicals that 

have the potential to interact with the estrogen, androgen or thyroid systems. 

Although EPA is still refining the process for evaluating Tier 1 results, chemicals 

that are positive in Tier 1 for potential endocrine effects would be subject to the 

Tier 2 testing requirements. The purpose of the Tier 2 tests is to confirm chemical 

interactions observed in Tier 1 screens, and provide information that can be used 

in risk assessment such as identification and characterization of adverse effects 

resulting from the interaction of the chemicals with the hormone system and the 

exposure levels required to produce them in assays involving developmental lifestages in whole animals. EDSTAC recommended a number of assays for EPA's 

consideration as potential Tier 1 screens and Tier 2 tests for detecting and 

characterizing endocrine disrupting chemicals. 

Validation of Tier 1 Protocols 

The FQPA requires the use of validated tests. The purpose of validation is to 

ensure that the tests are based on solid science and requires that the relevance 

and reliability of the assay be demonstrated, that is, that it truly measures what it 

is supposed to measure and that it does so consistently within and across 

laboratories. Validation of the assays comprising Tiers 1 and 2 was by far the 

biggest challenge facing EPA In fact, Tier 2 assay validation is still in progress. 

As recognized by EDSTAC, no assays were validated to detect or characterize 

endocrine disruptors when EPA began this task. From 2001 through 2006, EPA 

consulted with stakeholders and scientific experts through a series of advisory 

committees regarding the validation of Tier 1 assays. EPA is continuing to 

involve stakeholders by working through the Organization for Economic 

Cooperation Development (OECD) validation management workgroups. 

The validation of the Tier 1 assays took far longer than anyone at EPA 

anticipated. The validation process commenced with test method development. 

Many of these methods were developed or refined within EPA's own laboratories. 

Once the test protocols were developed and optimized, their reliability and 

relevance had to be demonstrated in studies conducted in parallel in multiple 

laboratories outside of EPA Through most of this process, EPA solicited 

stakeholders' and the public's views through the advisory committee process. 

This process has been used in the development and validation of 19 different 

Tier 1 and Tier 2 assays. Because of the many complexities of methods 

development and validation for such a large number of assays, validation of Tier 

1 assays took 10 years and is still ongoing for Tier 2 assays. Most of the testing 

in outside laboratories was performed under EPA's contracts and many assays 

were validated in conjunction with the Organization for Economic Cooperation 

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and Development to produce internationally harmonized test guidelines. Working 

with OECD has saved the Agency resources as it leveraged the efforts of other 

countries, and it promises to reduce testing costs since the data generated under 

the OECD test guidelines will be accepted by all member countries, reducing the 

likelihood that tests will be repeated to meet the differing regulatory needs of 

each member country. After the laboratory work and analysis was completed 

and approved by EPA, the entire body of work supporting validation of each 

assay was summarized and submitted to a panel of independent scientific 

experts for peer review. EPA chose the eleven assays for the Tier 1 battery 

based upon their performance in validation and their ability to complement one 

another. EPA's recommendations for the Tier 1 battery were reviewed by the 

FIFRA Scientific Advisory Panel in March 2008. Validation of the Tier 2 tests, 

including peer review, should be completed in 2012. 

Priority Setting and Development of Policies and Procedures 

There were two other key activities needed for implementation of the EDSP: the 

development of a process for selecting chemicals followed by the actual selection 

of chemicals for the first list, and the development of policies and procedures for 

issuing test orders to pesticide registrants and chemical manufacturers. The first 

list of chemicals was selected solely on the basis of exposure because other 

methods for incorporating endocrine-relevant toxicity information were not yet 

ready for use. The first list consists of 67 chemicals-58 pesticide active 

ingredients and 9 inert ingredients that also are high production volume 

chemicals. 

The Agency's policies and procedures instruct how the Agency will issue test 

orders and the obligations of test order recipients to respond. The Agency is 

allowing test order recipients 90 days (150 days if they group together to form a 

consortium) to cite or provide existing data or inform the Agency that they will 

conduct Tier 1 testing. Test order recipients have up to 24 months from the date 

of the orders to submit required Tier 1 test data. 

Recent Accomplishments 

EPA began issuing its first EDSP test orders in October 2009. It will issue the 

last test orders for List 1 chemicals this month. The test orders are not tailored for 

specific chemicals and will require the full battery of Tier 1 assays. However, test 

order recipients can either cite or provide existing data that they believe meet 

some or all of the requirements of the test order. The Agency is now receiving 

and evaluating the first of the responses to the test orders and will communicate 

its determination to recipients. Test orders, responses to test orders, and EPA's 

final determination of the required testing are being tracked on the EDSP website. 

Test order recipients have two years from the receipt of the test order to conduct 

required studies and submit the results to the EPA. The Agency will review the 

data on each chemical. When test data from all 67 chemicals have been 

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reviewed, EPA will conduct a scientific evaluation of the screening data and 

determine whether revisions to the battery should be made. 

Creation of a Database 

EPA has created a database of the initial pesticide chemicals to be screened in 

the EDSP and made this information available on EPA's website. The database 

includes the date a test order is issued and to whom; the due date for completing 

and submitting the data; the recipient's response to the order, including requests 

for extensions, if any; and a summary of the results of Tier 1 screening or Tier 2 

testing for each chemical listed. 

List 2 and Substances in Drinking Water 

In addition to the FQPA provisions that require the screening of all pesticide 

chemicals, the Safe Drinking Water Act Amendments of 1996 (SDWA) provide 

EPA with the authority to test substances that may be found in sources of 

drinking water to which a substantial population may be exposed. As instructed 

by the House Appropriations Committee1

, EPA is preparing a second list of no 

less than 100 chemicals, a draft of which will be released shortly. The List 2 

chemicals will be drawn from three sources: National Primary Drinking Water 

Regulations, the Contaminant Candidate List 3 (CCl 3), and pesticides that are 

on the reregistration schedule for 2007 through 2008. The CCl3 List is a list of 

contaminants that are currently not subject to any proposed or promulgated 

national primary drinking water regulations, that are known or anticipated to 

occur in public water systems, and which may require regulation under SDWA. 

The CCL3 list includes pesticides, other chemicals used in commerce, and 

disinfection byproducts and degredates. 

ToxCast 

Several years ago, EPA's Office of Research and Development began carrying 

out a large-scale experiment, called ToxCast TM , which is a part of the T ox 21 

program, to test a high throughput screening in vitro approach to identify potential 

toxicity of chemicals. The aim of ToxCast is to more efficiently screen thousands 

of environmental contaminants using a battery of in vitro assays and to prioritize 

chemicals for further testing based on the biological activity associated with 

molecular pathways leading to toxicity. EPA is exploring the use of ToxCast, 

other computational tools, and other data to assist with choosing those chemicals 

for future lists that show potential to interact with the endocrine system. Fiftyseven of the chemicals on List 1 for EDSP screening have been put through the 

I H. Rep. No. 180, III th Cong., 1st Sess. 105 (2009), http://frwebgate.access.gpo.gov/cgi. 

bin/getdoc.cgi?dbname= 1 11_ congJeports&docid=f:hrI80.lll.pdf#Page~ lOS. 

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ToxCast battery of assays. Once those chemicals have been tested through the 

EDSP Tier 1 battery, results can be compared. So for now, while ToxCast, at its 

current state of development will initially be used to help select chemicals for 

future Tier 1 screening lists, it is envisioned that eventually it may be able to 

replace, at least, some Tier 1 assays. For the current set of test orders, EPA will 

review ToxCast data along with the claims the order recipients submit. Data 

generated from Tier 1 assays on the first and second lists of chemicals will play 

an important role in advancing our understanding of the endocrine disrupting 

potential of these chemicals, refining the predictions made by ToxCast, and 

moving us toward the point where some lower throughput assays that still rely on 

using laboratory animals and some whole animal assays may be replaced by 

higher throughput, shorter term laboratory results combined with predictive 

methods. 

In summary, EPA is on track to obtain Tier 1 endocrine screening data on several 

hundred chemicals within the next several years. Although it has taken a long 

time to develop and implement the EDSP, we have developed and validated 

some useful tools and learned lessons that can be applied to other areas. 

Thank you for your continued interest in the EDSP. I will be happy to answer 

any questions. 

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31 

Mr. MARKEY. We thank you, Mr. Jones, very much. Our next witness is Dr. Gina Solomon, who is a senior scientist in the health 

and environmental program of the National Resources Defense 

Council, and is a specialist in adult internal medicine, preventative 

medicine, and occupational and environmental medicine. Dr. Solomon also serves as an associate clinical professor of medicine at 

the University of California at San Francisco where she is the director of the occupational and environmental medicine residency 

program and the associate director of the ECSF pediatric environmental health specialty unit. So we welcome you, Doctor. Whenever 

you are ready, please begin. 

STATEMENT OF GINA SOLOMON 

Dr. SOLOMON. Good morning, Mr. Chairman and members of the 

subcommittee. Thank you very much for the opportunity to testify 

today. You introduced me very well, but I also want to mention 

that I was on the EPA’s endocrine disruptor screening and testing 

advisory committee from 1996 to 1998 and was therefore involved 

in the early stages of the EDSP program. I now serve on the EPA 

science advisory board drinking water committee, and as such, 

have been involved in reviewing EPA’s efforts on drinking water 

contaminants. 

Some years ago, I was invited to speak at the Riverside County 

Medical Association. It is in southern California in an area where 

a chemical called perchlorate had recently been detected in drinking water. The local physicians were concerned, and I went and 

gave them a talk about the health data at that time on perchlorate, 

including the fact that perchlorate was known to block uptake of 

iodine into the thyroid gland and thereby disrupt the thyroid’s ability to create normal thyroid hormones. 

And I also reviewed the science on how subtle disruption of thyroid function in fetal or early neonatal life can permanently alter 

normal brain development. Finally, I described the multiple 

sources of perchlorate pollution in clean water contamination from 

rocket fuel and fireworks manufacturing, and I closed by sharing 

some of the latest monitoring data, which showed that 402 public 

water systems serving 40.8 million people in 27 states, the District 

of Columbia, and two U.S. territories had perchlorate in their treated water or in their water sources, and California had the largest 

number of systems with perchlorate detections, over 180 at that 

time. 

After my talk that day, an elderly physician in the audience 

stood up and explained that he had spent his entire career treating 

patients with thyroid disease in this community. And he said now 

we learn that something in the water supply may be contributing 

to this problem. What am I supposed to do about it? And more importantly, what am I supposed to tell my patients about it? He said 

should I tell them not to drink the water? 

And he further went on to say that he wasn’t a fan of big government, but in this case, he said, we need to get government involved 

to deal with this problem. And I agree with him because this is not 

something that health care providers and their patients can deal 

with alone. This is EPA’s job. 


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32 

Over 5 years have passed since the day when I spoke at that 

medical society, and although California and other states have 

taken some action on this known endocrine disruptor, EPA has still 

failed to act. Meanwhile, there are other chemicals that are known 

or suspected endocrine disruptors that have been turning up with 

increasing frequency in water. Studies by the U.S. geological surveys toxic substances hydrology program have revealed that an unsavory mixture of pharmaceuticals, steroid hormones, unregulated 

pesticides, flame retardants, rocket fuel chemicals, plasticizers, detergents, stain repellents in both surface water and ground water 

that we rely on for drinking. 

For example, the USGS surface water study found a median of 

seven and as many as 38 chemical contaminants in any single 

water sample. And among the chemicals that were most commonly 

detected in this national survey were many known and suspected 

endocrine disruptors, some pesticides, triclosan, alkylphenols and 

alkylphenol polyethoxylates, bisphenol A, phthalates and steroid 

hormones. And unfortunately so far, the response to these water 

findings has tended a bit more toward killing the messenger rather 

than acting on the message. Over the most recent years, funding 

for the USGS water monitoring programs, already small, has been 

reduced, resulting in major cutbacks in water quality sampling and 

less data to inform science-based decisions. 

Meanwhile, over a decade has passed since EPA has promulgated 

a single regulatory standard for a chemical contaminate in drinking water. Now there is a large and growing backlog of chemicals 

like perchlorate that still have no regulatory standard, and then 

there are others that were regulated over a decade ago whose 

standards are outdated and in need of revision. For example, one 

endocrine disruptor ethylate known as DEHP, which stands for 

dyethol hexophthalate, does have a maximal contaminate leveler in 

MCL in drinking water, but it is terribly outdated. 

Now, these phthalates like DEHP are used in an enormous range 

of products such as cosmetics, personal care products, vinyl, medical devices, inks and adhesives, and they are also used as inert ingredients in pesticides and until last year, were in plastic toys. 

National monitoring studies have reported phthalates in about 

10 percent of surface water samples taken. And these chemicals 

cause lower testosterone levels, decreased sperm counts and lower 

sperm quality in animals, and exposure to phthalates during development can cause malformations of the male reproductive tract and 

testicular cancer. Preliminary studies in humans also show abnormalities in male reproductive development. 

Mr. MARKEY. If you could sum up please. 

Dr. SOLOMON. Sure. The MCL for DHP was set in July of 1992 

and was based on gastrointestinal disturbances, nausea, and 

vertigo. It is not likely to protect against endocrine disrupting effects. Other chemicals like bisphenol A also have no MCLs at all. 

So in summary, there are numerous steps that EPA should be 

taking to implement testing under the endocrine disruptor screening program for priority drinking water contaminants, implementing aspects of the endocrine disruptor screening and testing 

advisory committee report that have been ignored, and improving 


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wastewater and drinking water treatment. So thank you very 

much. 

[The prepared statement of Dr. Solomon follows:] 


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TESTIMONY OF 

GINA M. SOLOMON, M.D., M.P.H. 

SENIOR SCIENTIST, NATURAL RESOURCES DEFENSE COUNCIL 

ASSOCIATE CLINICAL PROFESSOR, U.c. SAN FRANCISCO 

ASSOCIATE DIRECTOR, UCSF PEDIATRIC ENVIRONMENTAL 

HEALTH SPECIALTY UNIT 

ON BEHALF OF: 

NATURAL RESOURCES DEFENSE COUNCIL 

BEFORE THE U.S. CONGRESS 

COMMITTEE ON ENERGY AND COMMERCE 

SUBCOMMITTEE ON ENERGY AND THE ENVIRONMENT 

AT HEARING ENTITLED: 

ENDOCRINE DISRUPTING CHEMICALS IN DRINKING WATER: 

RISKS TO HUMAN HEALTH AND THE ENVIRONMENT 

FEBRUARY 25, 2010 
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Testimony of Gina Solomon 2/25110 

Thank you for the opportunity to submit testimony to this Committee. My name is Gina 

Solomon, and I am a Senior Scientist at the Natural Resources Defense Council (NRDC). 

NRDC is a not-for-profit environmental advocacy organization with over one million 

members and activists whose mission is to safeguard the Earth: its people, its plants and 

animals and the natural systems on which all life depends. In addition to my work at 

NRDC, I am an Associate Clinical Professor of Medicine at the University of California 

at San Francisco (UCSF) where I am the Director of the Occupational and Environmental 

Medicine Residency and Fellowship Program, and the Associate Director ofthe Pediatric 

Environmental Health Specialty Unit. I have subspecialty training and expertise in 

environmental medicine, and have done research, education, and advocacy for over 15 

years to protect people from contaminants in their food, air and drinking water, and from 

hazardous pesticides. 

I served on the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor 

Screening and Testing Advisory Committee (EDSTAC) from 1996-1998, the National 

Academy of Sciences Committee on Toxicity Testing and Assessment of Environmental 

Agents from 2004-2007, and the EPA Science Advisory Board Drinking Water 

Committee from 2004 through the present. My educational and professional credentials 

are supplied in the attached Curriculum Vitae. 

Endocrine Disruptors in Water: A Widespread Problem 

There are serious concerns about contaminants in our nation's drinking water and source 

waters. Fish have been found in numerous rivers, including the Potomac, with disrupted 

sexual development -- specifically feminized male fish. When this finding was first noted 

in England in the 1990's, I it was considered possibly a fluke. But what was once a 

localized, spotty observation is now being recognized as a widespread, pervasive 

phenomenon. Four months ago, scientists from the U.S. Geological Survey reported 

finding intersex fish in one third of sites surveyed in eight river basins (the Apalachicola, 

Colorado, Columbia, Mobile, Mississippi, Pee Dee, Rio Grande, and Savannah river 

basins)2 The problems were most severe in the Southeastern United States (sec 

Appendix I for a map of locations where intersex fish were found). 

The same kind of thing happened with deformed frogs: local observations in the Midwest 

led to the eventual realization that these amphibian abnormalities are widespread. A 

recent review by researchers at Yale University concluded that the mystery of these 

deformities remains unsolved. 3 Even the alligators in Florida's Lake Apopka with the 

famously tiny penises are not alone: research in other Florida lakes has revealed that the 

male deformities just keep turning Up.4 Essentially, wherever researchers look, they are 

finding problems with sexual development in wildlife. Now the question is: what does 

this mean for humans? Some scientists are concerned that increased incidence of cancer 

of the testis, prostate, and breast, along with increases in birth defects of the penis, might 

mean that humans arc not immune to the problems in our environment. 

Scientists have come up with a term to describe this general phenomenon: endocrine 

disruption. An endocrine disruptor is defined as "an exogenous agent or mixture of agents 

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Testimony of Gina Solomon 2/25/10 

that interferes or altcrs the synthesis, secretion, transport, metabolism, binding action, or 

elimination of hormones that are present in the body and are responsible for homeostasis, 

growth, neurological signaling, reproduction and developmental processes."s In other 

words, endocrine disruptors are chemicals that interfere with thc body's key signaling 

pathways, and they can cause harm, especially during fctal and early life development. 

Multiple contaminants are turning up in our nation's waterways, including in water 

millions of people rely on for drinking. Studies by the U.S. Geological Survey (USGS) 

have revealed an unsavory mix of pharmaceuticals, steroid homlOnes, unregulated 

pesticides, flame retardants, rocket fuel chemicals, plasticizers, detergents, and stain 

repellants in both the surface water and the groundwater wc rely on for drinking, and in 

our drinking water itself. 6 7 8 The USGS surface water study found a median of seven 

and as many as 38 chemical contaminants in any given water sample (sce Appendix 2 for 

morc details). Among the chemicals most commonly detcctcd in this national survey are 

known and suspected endocrine disruptors, including triclosan, alkylphenols and 

alkylphenol polyethoxylates, bisphenol A, and estriol. As a scientist, I wish I could tell 

you these chemicals are unlikely to be a problem at the concentrations measured. 

Unfortunately I can't tell you that, because my assessment of the data suggests a problem. 

Hcre's what I can tell you: wildlife populations are showing signs of harm, many of these 

chemicals are not eliminated by conventional drinking water trcatment, and mixtures of 

these chemicals arc present in our water supply. Although they are at low levels in water, 

hormones are known to have effects even in trace amounts. Furthermore, biomonitoring 

studies have detected these chemicals in our bodies. 9 Water is certainly not the only 

source of thesc chemicals, but trace amounts from one source add up with traces from 

other sourccs, and the sum total becomes a problem. The Endocrine Society evaluated the 

science on endocrine disruptors last year and concluded: 

The evidence for adverse reproductive outcomes (infertility, cancers, 

malformations)from exposure to endocrine disrupting chemicals is strong, and 

there is mounting evidence for effects on other endocrine systems, including 

thyroid, neuroendocrine, obesity and metabolism, and insulin and glucose 

homeostasis. J() 

The Endocrine Society is the premier professional organization devoted to research on 

hormones and the clinical practice of endocrinology, comprised of over 14,000 research 

scientists and physicians from over 100 countries. This statement has since been endorsed 

by the American Medical Association. The Amcrican Chemical Society just issued a 

similar statement with additional recommendations for: "More rapid advancement ofthc 

congrcssionally-mandated effort by the EPA, called the Endocrine Disruptor Screening 

Program (EDSP)." II 

There are two opportunities for action on this issue: First, many chemicals have never 

been adequately tested for their toxicity, and especially not for their endocrine effects; 

EPA's Endocrine Disruptor Screening Program which was supposcd to accomplish this 

goal has yet to live up to its promise; Second, some of the chemicals in our water supply 

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Testimony of Gina Solomon 2/25/10 

are known endocrine disruptors and can alter hormone function and disrupt development 

even when they are in very dilute concentrations, yet EPA has not yet taken action to 

appropriately regulate these hazards. 

EPA's Endocrine Disruptor Screening Program (EDSP): A Missed 

Opportunity 

In 1996, EPA created the Endocrine Disruptor Screening and Testing Advisory 

Committee (EDSTAC) in response to a Congressional mandate in the Food Quality 

Protection Act and authorization in the Safe Drinking Water Act Amendments of 1996. 

These laws specified that EPA: 

develop a screening program, !ising appropriate validated test systems and other 

scientijical(v relevant in/ormation, to determine whether certain substances may 

have all effect ill humans that is similar to an effect produced by a naturally 

occurring estrogen, or other such endocrine effect as the Administrator may 

designate. 

The laws required EPA to develop a screening program by August 1998, to implement 

the program by August 1999, and to report on the program's progress by August 2000. 

Unfortunately, EPA is now about a decade behind. 

EDSTAC was composed of representatives from industry, government, environmental 

and public health groups, and academia. The committee members were charged with 

developing consensus-based recommendations for a screening program that would 

provide EPA the necessary information to make regulatory decisions about the endocrine 

effects of chemicals. 

I served on the EDSTAC, and it was an intense experience. The Committee struggled 

under time pressure, and delivered a final report by the statutory deadline of August 

1998. 12 Over a period of 20 months, the committee fashioned a groundbreaking priority 

setting, screening and testing approach that encompasses the universe of chemicals in use 

today, evaluates a range of human health and ecological effects, and recommends a 

feasible, health-protective, approach: 

• The committee recognized that problems with endocrine disruption go beyond 

estrogen, and called for screening of chemicals for interference with male 

androgens, and with thyroid hormone. 

• The EDST AC recommended the use of new technology to rapidly pre-screen 

numerous chemicals to see if they interact with hormone receptors in vitro (in the 

"test-tube"). The committee recommended that this technology be used to rapidly 

evaluate the ten thousand most widely-used chemicals within one year. 

• Another new approach was a computer-bascd tracking system allowing 

infonnation about health effects and exposure to be collected in one placc to 

facilitate prioritization. Some people would be stunned that such a database 

didn't exist then, and still doesn't exist to this day. 

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Testimony of Gina Solomon 2/25/10 

• Finally, the committee urged EPA to accept nominations from the public of 

chemicals or chemical mixtures for expedited testing. This would allow workers, 

or impacted communities to press for more information about chemicals to which 

they are exposed. 

Unfortunately, the vision of the EDST AC was never realized. EPA missed deadline after 

deadline and became bogged down in an endless "do loop" of validation. It is 

discouraging to report that EPA scrapped the rapid "high-throughput pre-screen", has still 

failed to validate the definitive "tier 2" tests, and has never created the Endocrine 

Disruptor Priority Setting Database. The nominations process was also discarded, as was 

the Committee's unanimous recommendation to test six priority chemical mixtures 

(Table I). EPA finally implemented the program, over a decade late, when it issued the 

first test orders on October 29, 2009; only 67 chemicals are on the list for this first round 

of screening mostly pesticides, including a number of chemicals that are already wellknown endocrine disruptors. 13 What a wasted opportunity. Meanwhile tens of thousands 

of chemicals in daily use, in consumer products and even in foods, have not been tested, 

and contaminants continue to build up in our water supply. 

Table 1: EDSTAC Priority Chemical Mixtures 

a) Contaminants in human breast milk 

b) Phytoestrogens in soy-based infant formulas 

c) Mixtures of chemicals most commonly found at hazardous waste sites 

d) Common pesticide/fertilizer mixtures found in surface water 

e) Disinfection byproducts commonly found in drinking water 

f) Gasoline 

Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Final Report. pp. 4-49 - 4-51 

Section 136 of the SDW A Amendments states that: 

in addition to the substances referred to in (FQPA), the Administrator may 

provide for testing under the screening program authorized by (FQPA) for any 

other substance that may be found in sources of drinking water If the 

Administrator determines that a substantial population may be exposed to such 

substance. 

Unfortunately EPA has not yet used the authority granted by Congress under the SDW A, 

and has not prioritized drinking water contaminants for testing. 

The result of the decade of foot-dragging on testing chemicals for hormonal activity 

means that the vast majority of chemicals in our water supply and environment are 

"unknowns" when it comes to their hormonal effects. Due to the well-known flaws in the 

Toxic Substances Control Act (TSCA), almost all chemicals come onto the market with 

no toxicity information, and older chemicals remain untested too. The EPA Office of the 

Inspector General's report, released just last week outlines these problems clearly. 14 As a 

scientist, this absence of data appalls me. As a physician, it puts me in a position where I 

cannot counsel many of my patients because I don't have the data I need. 

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Testimony of Gina Solomon 2/25/10 

Known Endocrine Disruptors in Drinking Water: Regulatory Action 

Needed Now 

Not all chemicals are of unknown toxicity. Some chemicals have been tested and are 

already flagged as known endocrine disruptors. 1'd like to highlight three examples of 

such chemicals that are crying out for EPA action: perchlorate, plastic chemicals 

(including bisphenol A and phthalates), and steroid hormones. 

The SDWA requires EPA every five years to publish a list of currently unregulated 

contaminants that should be considered for potential regulation. EPA is then required to 

make a final determination about whether or not to regulate at least five of the 

contaminants identified on the Candidate Contaminant List (CCL). To date, the 

Candidate Contaminant List listing process has gone through 3 iterations, beginning in 

1998 with the publication ofCCLl and then CCL2 in 2005. CCLl contained 50 

chemical contaminants, including industrial organic chemicals, pesticides, and inorganic 

chemicals; in July 2003, EPA decided not to regulate any of the nine chemicals it 

evaluated on the CCL 1. CCL2 consisted of a subset of the chemical contaminants listed 

on CCLl; and in May 2007, EPA again decided not to regulate any of the 11 chemicals it 

considered from the CCL2. 

The CCL3, finalized on October 8, 2009, contains 104 chemicals or chemical groups. 

Several important endocrine disrupting chemicals are on this list, including perchlorate 

and several steroid hormones. Other important endocrine disruptors that are known to be 

water contaminants, such as bisphenol A and other phthalates, are not on the CCL3. Only 

one of the chemicals I'm going to talk about today - bis(2-ethylhexyl) phthalate - has 

been regulated by EPA under the SDW A - and it wasn't even regulated on the basis of 

endocrine disruption. 

Perchlorate 

Perchlorate has emerged as an important threat to drinking water sources over vast areas 

of the United States, with over 400 public water systems, large and small, reporting 

perchlorate in their water. As a result, millions of people are being exposed to this 

chemical in their drinking water. Perchlorate is on the EPA's Candidate Contaminate List 

3 (CCL3). It was also on the CCL2, and was the subject of an Unregulated Contaminant 

Monitoring Rule (UCMR). It has been a significant problem since the late-1990's, but 

unfortunately EPA has not even begun the process of setting a drinking water standard 

for this chemical. Individual states arc left to do the best they can, and the result is a 

wide-ranging patchwork of standards around the country, and many states with no 

enforceable drinking water standard. 

Perchlorate is a contaminant that comes from rocket fuel, fireworks, road flares, fertilizer, 

and other sources. It is known to interfere with the normal function of the thyroid gland. 15 

Iodine is needed by the thyroid in order to create thyroid hormones. Normally, iodine is 

transported into the thyroid gland through an energy-requiring mechanism called the 

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Testimony of Gina Solomon 2/25110 

sodium-iodide symporter. Perchloratc blocks this transport and prevents uptake of iodine 

into the gland, therefore interfering with the production of these vital honnones, 

A decrease in circulating thyroid honnone during gestation or the first year oflife can 

result in neurodeveiopmental abnormalities leading to permanent brain dysfunction. 16 

Many studies have shown subtle but lasting deficits in cognitive function, languagc, 

hearing, behavior, attention span, and vestibular function (balance) in those that had 

early-life or prenatal thyroid suppression. 17 

An NRDC analysis of available perchlorate data in 2005 showed that public water 

systems (PWS) in 27 states, the District of Columbia and two U.S. territories have 

reportcd detecting perchlorate in treated watcr or in their water sources, with 

concentrations ranging from 0.2 to 1,300 paIis per billion (ppb).18 Of 5,369 systems 

tested, 402 (7.5 percent) detected perchlorate in their water. California has the largest 

nnmber of systems with perchlorate detections, followed by Texas and Massachusetts 

(see Figure 1). These are also the states with the most perchlorate monitoring conducted 

to date. 

Figure 1: States with the largest number of water systems with perchlorate detections. 

~ n ~ ~ ~ 00 R ~ AA ~ ~ 

State 

The 402 systems that have found perchlorate serve 40.8 million people. 19 There was no 

remarkable difference between the trequency of perchlorate contamination in PWS that 

had groundwater as their primary water source and those that relied on surface water. 

Groundwater systems accounted for 60.9 percent of all systems sampled, and for 63.7 

percent of the systems with perchlorate. 

U.S. EPA, the U.S. Department of Defense (DoD) and state environmental agencies have 

identified at least 143 sites in 31 states and the District of Columbia where perchlorate 

releases have occurred, as well as an additional 281 sites in 45 states, one commonwealth 

and the District of Columbia where perchlorate or perchlorate-containing materials have 

been used, manufactured, or disposed. 2o DoD facilities account for 77 of the 143 known 

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Testimony of Gina Solomon 2125110 

release sites. Perchlorate releases have also been confirmed in eight federal facilities of 

other types, most of which belong to the Department of Energy (DoE). The remaining 58 

are currently non-federal or private sites. Most of these are owned by aerospace 

companies, defense contractors, and explosives or pyrotechnics manufacturers. 

EPA must set an enforceable drinking water standard for perchlorate that will protect 

pregnant women, children, and people with underlying thyroid disease or iodine 

deficiency. It is unconscionable that millions of people are drinking water contaminated 

with this known endocrine disruptor and remain unprotected. 

Plasticizers: Phthalates and Bisphenol A 

Phthalates are hormone-disrupting chemicals used in an enormous range of products, 

including air fresheners, plastic toys, cosmetic and personal care products (including 

fragrances and nail polish), vinyl, medical devices, inks and adhesives. They arc also 

used as food additives and as inert ingredients in pesticides. 

Phthalates arc known to interfere with the production of male reproductive hormones in 

animals and likely have similar effects in humans. 21 22 23 Their effects in animal studies 

are well recognized and include lower testosterone levels, decreased sperm counts and 

lower sperm quality. Exposure to phthalates during development can also cause 

malformations of the male reproductive tract and testicular cancer. Young children and 

the developing fetus are most at risk. 24 2S 

National monitoring studies have found one or more phthalates in over 10 percent of 

streams samplcd6 The only phthalate that has a drinking water standard is bis 2-

ethylhexyl phthalate (DEHP) which has a maximum contaminant level (MCL). 

Unfortunately the MCL was set in July 1992, and was based on potential to cause mild 

gastrointestinal disturbances, nausea, and vertigo, not on endocrine disrupting effects. 

The other phthalates have no drinking water standards at all. 

BPA, or bisphenol A, is a hormone-disrupting chemical used in making plastics and 

epoxy resins. BP A is used in the resin lining of all food and beverage cans. It is the 

building block of poly carbonate plastic and is used in a wide range of products, including 

clear plastic baby bottles and sippy cups, clear plastic water bottles, and other kitchen 

plastics such as measuring cups, drinkware and storage containers. BP A is also found in 

some dental sealants and fillings, medical devices, paints, epoxy adhesives and cash 

register receipts. 

In animal studies, BP A has been shown to mimic the female hormone estrogen. Exposure 

to this chemical early in life is associated with pre-cancerous changes in the mammary 

and prostate glands, as well as altered development of the brain, causing behavioral 

abnormalities and earlier onset ofpuberty26 Developmental exposure to BPA at low 

doses has also been associated with reproductive abnormalities such as lower sperm 

counts, hormonal changes, enlarged prostate glands, and abnormalities in the number of 

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Testimony of Gina Solomon 2125110 

chromosomes in eggs.27 It also has been associated with obesity and insulin rcsistance--

a condition that commonly precedes the development of diabetes. 28 

A study of Mississippi River water in Louisiana, which is used for drinking by the city of 

New Orleans, found numerous contaminants. Most relevant to our discussion today, 

monthly testing at the drinking water treatment plant in Jefferson Parish, Louisiana 

revealed detectable concentrations on bisphenol A in most of the samples. 29 The 

researchers in this study planned to determine if these widespread detections represented 

contamination from the laboratory, or contamination in the drinking water; no definitive 

results are available. 3o National groundwater sampling reported BPA in about 30 percent 

of groundwater samples7 

Both phthalates and bisphenol A are contaminants in wastewater. 18 of 19 wastewater 

samples tested in the San Francisco Bay Area contained at least one of three unregulated, 

widely-used endocrine disruptors- phthalates, bisphenol A, and triclosan. Two samples 

contained all three substances. 31 Despite sophisticated wastewater treatment, these 

chemicals were detected in treated waters discharged into the Bay and have also been 

detected in the Bay itself. 32 While wastewater treatment is extremely effective in 

removing biodegradable food and human waste, it was never designed to address this 

broad spectrum of unregulated chcmical pollution. 

There is no EPA drinking water standard for bisphenol A even though it is a known 

endocrine disruptor and a known water contaminant. Unfortunately this chemical is not 

even on the CCL3, so the likelihood of any appropriate EPA action to protect consumers 

from this chemical in drinking water appears small. Several states such as Minnesota, 

Washington and Connecticut, as well as major retailers such as Walmart and Target have 

taken action to eliminate phthalates and bisphenol A in children's products, and Congress 

banned phthalates in children's toys over a year ago. 

Steroid Hormones 

Studies of water sources around the U.S. have detected widespread contamination with 

steroid hormones. For example, a recent study in Pennsylvania collected data from 21 

locations in suburban, agricultural, and mixed suburban/agricultural areas. At least one 

steroid hormone was detected in every stream; two honnones, estrone and estriol, were 

detected at more than 80 percent of the sampling sites (see Figure 2).33 Potential sources 

of the hormones include municipal wastewater discharges, septic tanks, and animal 

manure. 

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Testimony of Gina Solomon 2125110 

Figure 2: Percent Detection of Steroid Hormones in Pennsylvania Surface Water 

Samples 

,,, ,.------------r-r----,-...,.,.-r------, 

"\!'I.....,~c-l 1T~.jlOt 11'.~_MfAI ....-wI 

Odorrkd ~h.J't.d lWr.h4h,,, 

An important source of hormonal contaminants in water is steroids used in livestock 

operations which contribute to widespread environmental contamination. Beef cattle 

raised in large feedlots are treated with anabolic steroids to promote the growth of 

muscle. One of the most common steroids used is a male sex hormone (androgen) mimic, 

trebolone acetate. Exposure to trebolone metabolites at concentrations as low as parts per 

trillion can cause masculinization of female fish and reduced fertility. 34 A recent study at 

an Ohio-based animal feeding operation with a capacity for 9,800 cattle found detectable 

concentrations of trebolone in the discharge from the facility at levels that were sufficient 

to induce gene expression associated with exposure to androgens. 34 Other research has 

found environmental androgens associated with masculinization in female fish living 

downstream of pulp and paper mills and concentrated animal feeding operations. These 

pharmaceuticals interfere not only with sex hormones but also with other hormonal 

systems including the thyroid gland, which is critical for proper growth and development 

of the brain during fetal growth, infancy, and childhood. 

Confined animal feeding operations (CAFOs; also known as "factory farms") are largescale producers of hogs, poultry, beef or dairy cows ~ typically housing from thousands 

to tens of thousands or even hundreds of thousands of animals. These facilities often treat 

the animals with hormones to promote growth, and they produce enormous amounts of 

waste, which pose significant challenges for storage and disposal. Hog waste, for 

example, is typically stored in open lagoons, roughly the size of football fields. Drier 

animal waste, such as "chicken litter," is stored in piles, often outside where rain can lead 

to runoff into nearby waters. After being stored, animal waste is typically spread on 

surrounding crop fields as fertilizer for crops. These "spray fields," as well as the lagoons 

and litter piles, are sources of pollution that can introduce hormones, and other 

contaminants into our waterways. 

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Testimony of Gina Solomon 2/25110 

Several important veterinary steroids that have been detected in drinking water are on the 

CCL3, including estriol, estrone, ethinyl estradiol, and mestranol. Some of these are also 

breakdown products of human pharmaceuticals. These are reasonable priority chemicals 

that deserve scrutiny and action. Trebolone acetate and its metabolites, are unfortunately 

not on the CCL3, even though they have been detected downstream of many animal 

feeding operations. 

Recommendations to Address the Problem of Endocrine Disruptors in 

Drinking Water 

Under the Safe Drinking Water Act and the Food Quality Protection Act, EPA has the 

authority and obligation to ensure the safety of our drinking water. EPA should: 

• Implement testing under the endocrine disruptor screening program for priority 

drinking water contaminants, including all chemicals on the CCL3, as well as 

other chemicals in pharmaceuticals and personal care products that have been 

detected by USGS in surface or groundwater. 

• Implement aspects of the EDSTAC report that have been ignored, such as 

creating the Endocrine Disruptor Priority Setting Database, integrating the HighThroughput Pre-Screen (or ToxCast) into the program for priority-setting, 

screening common mixtures, and inviting public nominations for testing; 

• Evaluate and identify wastewater and drinking water treatment practices for 

removing endocrine disrupting chemicals, including pharmaceuticals; 

• Work with other federal agencies and states to prevent or limit the use of 

hormones in agriculture. 

Congress needs to take additional steps to help address this issue, including: 

• Require EPA to prioritize and screen chemicals in drinking water, including 

mixtures, for endocrine disrupting effects; 

• Restore adequate funding for the USGS Toxic Substances Hydrology Program 

and the USGS National Water Quality Assessment Program (NAWQA), so more 

data are available on contaminants in source water and drinking water; NA WQA 

started with 500 sites in 1991, and has now been reduced to 113, of which only 12 

are monitored annually. 86 sites are monitored only once every four years; 

• Reform the Toxic Substances Control Act to require testing of chemicals for 

toxicity, and require EPA action to promptly regulate hazardous chemicals. 

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Testimony of Gina Solomon 2/25/10 

Appendix 1 

Results ofthe USGS Survey ofIntersex Fish in the United States, 1995-

2004 

Of the 16 fish specics rescarchers examined from 1995 to 2004, intersex was most 

common by far in small mouth and largemouth bass: a third of all male smallmouth bass 

and a fifth of all male largemouth bass were intersex (Figure 3). This condition is 

primarily revealed in male fish that have immature female egg cells in their testes, but 

occasionally female fish will have male characteristics as well. 

-Intersex small mouth bass were found in a third of male bass at almost half of the sites 

examined in the Columbia, Colorado, and Mississippi River basins. The percentage of 

intersex small mouth bass ranged from 14 to 73 percent at different sites. It was highest 

(73 percent) in the Mississippi River at Lake City, Minn., Yampa River at Lay, Colo. (70 

percent). Salmon River at Riggins, Idaho (43 percent), and the Columbia River at 

Warrendale, Oreg. (67 percent). 

-Intersex largemouth bass were found in nearly a fifth of the fish examined from the 

Colorado, Rio Grande, Mississippi, Mobile, Apalachicola, Savannah, and Pee Dee River 

basins; intersex was not observed in male largemouth bass from the Columbia River 

Basin. The percentage of intersex largemouth bass per site ranged from 8 to 91 percent 

and was most prevalent in the southeastern United States. The Pee Dee River at 

Bucksport, S.C., contained the highest percentage of intersex fish (91 percent), with high 

percentages occurring elsewhere on the Pee Dec too. Sixty percent of male bass 

examined at the Apalachicola River at Blountstown, Fla., were intersex, 50 percent in the 

Savannah River at Port Wentworth and Sylvania, Ga, 43 percent in the Savannah River at 

Augusta, Ga., and 30 percent in the Chattahoochee River at Omaha, Ga., and the Flint 

River at Albany, Ga. Lower percent intersex (10-25 percent) were found in bass from 

sites in the Mobile Rivcr in Alabama. 

-In addition, relatively high proportions of intersex largemouth bass were observed at 

three sites in the lower Rio Grande Basin including Rio Grande at Brownsville, Texas (50 

percent), Rio Grande at Falcon Dam, Texas (44 percent), and Rio Grande at Mission, 

Texas (20 percent). In addition, 40 percent of male largemouth bass from the Colorado 

River at Imperial Dam, Ariz. and at the Gila River at Hayden, Ariz., in the Colorado 

River Basin were intersex. 

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Testimony of Gina Solomon 2125110 

Figure 3: Locations where intersex small mouth bass and largemouth bass were 

found in the United States 

Source: Hinck JE, Blazer VS, Schmitt CJ, Papoulias DM, Tillitt DE. Widespread occurrence (If 

intersex in black hasses (l'vficropterus spp,)from u.s rivers, 1995-2004, Aquat Toxieo!. 2009 Oct 

19;95(J):60-70, 

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Testimony of Gina Solomon 2/25110 

Appendix 2 

Contaminants in Source Water in the United States 

The most common unregulated contaminants detected in surface water include steroid 

hormones, nonprescription drugs, insect repellent, detergent chemicals, disinfectants, and 

plasticizers; all of these chemicals were detected at 70 percent or more of sites tested. The 

concentrations of the steroids, detergents, and plasticizers were among the highest of all 

the emerging contaminants (Figure 4). Water used as source water for drinking water 

systems has a lower detection frequency of unregulated compounds (Figure 5). However 

steroid hormones and prescription drugs were found in more than 50 percent of surface 

water sources of drinking water, and groundwater sources in more than 20 percent of 

cases contained solvents, prescription drugs, fire retardant chemicals and plasticizers. 

Figure 4: Contaminants in U.S. Streams, 1999-2000 100 ~- ¥ ''''"'f"--'f'' T·~-·""l··'·"~"~ '1 ""'~'''l .. , ",., ,,~,.,~ 1''' 

r~ A 

Source: Kolpin DW. Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT. 

Pharmaceuticals. hormones. and other organic 'wastewater contaminants in u.s. streams. 1999-

2000: a national reconnaissance. Environ Sci Technol. 2002 Mar /5;36(6): 1202-11. 

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Testimony of Gina Solomon 2/25110 

Figure 5: Detections of organic wastewater compounds by general use category at 

surface- and ground-water sites. 

70 

60 

50 

30 

20 

o Surface-water sites; n=49 

• Ground-water sites; n=25 

Source: Focazio MJ, Kolpin DW, Barnes KK, Furlong ET, Meyer MT, Zaugg SD, Barber LB, 

Thurman ME. A national reconnaissance for pharmaceuticals and other organic wastewater 

contaminants in the United States--!!) untreated drinking water sources. Sci Tolal Environ. 2008 

Sep 1;402(2-3):201-16. 

REFERENCES 

1 Jobling S, Nolan M, Tyler CR, Brighty GC, Sumpter JP. Widespread sexual disruption in wild fish. 

Environ Sci Tech. 1998;32(17):2498-2506. 

, Hinck JE, Blazer VS, Schmitt CJ, Papoulias DM, Tillitt DE. Widespread occurrence of intersex in black 

basses (Micropterus spp.) from U.S. rivers, 1995-2004. Aquat Toxico!. 2009 Oct 19;95(1):60-70. 

J Skelly DK. Benard MF. Mystery unsolved: missing limbs in deformed amphibians. J Exp Zool B Mol 

Dev Eva!. 2009 Nov 30. [Epub ahead of print] 

4 Guillette LJ Jr, Gunderson MP. Alterations in development of reproductive and endocrine systems of 

wildlife populations exposed to endocrine-disrupting contaminants. Reproduction. 2001 Dec;122(6);857-

64. 

5 Based on Kavlock RJ, Daston GP, DeRosa C, Fenner-Crisp P, Gray LE, Kaattari S, Lucier G, Luster M, 

Mac MI, Maczka C, Miller R, Moore J, Rolland R, Scott G, Sheehan DM, Sinks T, Tilson HA. Research 

needs for the risk assessment of health and environmental effects of endocrine disruptors: A report of the 

U.S, EPA-sponsored workshop. Environ. Health Perspect. 104 SuppI4:715-740 (1996). 

15 
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Testimony of Gina Solomon 2/25/1 0 

6 Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT. 

Pharmaceuticals, honnones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a 

national reconnaissance. Environ Sci Techno!. 2002 Mar 15;36(6):1202-11. 

7 Barnes KK, Kolpin DW, Furlong ET, Zaugg SD, Meyer MT, Barber LB. A national reconnaissance of 

pharmaceuticals and other organic wastewater contaminants in the United States-oil groundwater. Sci Total 

Environ. 2008 Sep 1;402(2-3):192-200. Epub 2008 Jun 16. 

8 Focazio MJ, Kolpin DW, Barnes KK, Furlong ET, Meyer MT, Zaugg SD, Barber LB, Thurman ME. A 

national reconnaissance for pharmaceuticals and other organic wastewater contaminants in the United 

States-oIl) untreated drinking water sources. Sci Total Environ. 2008 Sep 1;402(2-3):201-16. 

9 Centers for Disease Control and Prevention. National Report on Human Exposure to Environmental 

Chemicals. Fourth Report, 2009. http://www.cdc.gov/exposurereporti. 

10 Diamanti-Kandarakis E et a!. 2009 Endocrine-Disrupting Chemicals: An Endocrine Society Scientific 

Statement. Endocrine Reviews 30(4):293-342. http://.'Y,,w.endosocicty.org!i9L1rn'!lsjs'i~ntijjcstaJgmcl1ts!upload!edc scientific statcnwntj'ldC (Visited February 22, 2010). 

''http://portal.acs.or,, po!:'-aLP.y_blic\VgbSitcipolicv!publicpoiicics!pro111otc cndocri11qliiruptoc~i~:J"U?J' 023 

441 (Visited February 22, 2010). 

12 h!.!Q:i!,,\V\\'.cp'L~ov;cndo,ipubsicdspo\'Cr\icwi!tnillmthJm (Visited February 21, 2010). 

13 !lttP:i!www~a,gov;l'Ildo!pubs;cdsp orders status 02 16 I.ll&ill (Visited February 21, 20 I 0). 

1. EPA Office of the Inspector General. EPA Needs a Coordinated Plan to Oversee Its Toxic Substances 

Control Act Responsibilities. Report No. 10-P-0066 February 17,2010. 

h.lli!/!www.cpa.(!ovi oi,,/rcports!2010l201 00217-1 O-P-0066.pdf (Visited February 21,2010). 

15 Benjamin C. Blount, James L. Pirkle, John D. Osterloh, Liza Valentin-Blasini, and Kathleen L. Caldwell. 

Urinary Perchlorate and Thyroid Hormone Levels in Adolescent and Adult Men and Women Living in the 

United States. Environmental Health Perspectives Volume 114, Number 12, December 2006. 

16 Zoeller RT. Thyroid toxicology and brain development: should we think differently? 

Environ Health Perspect. 2003 Sep;lll(l2):A628. 

17 Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, Vulsma T, Wiersinga WM, 

Drexhage HA, Vader HL. Low maternal free thyroxine concentrations during early pregnancy are 

associated with impaired psychomotor development in infancy. C1in Endocrinol (Ox!). 1999 

Feb:50(2): 149-55. 

18 Arizona Department of Environmental Quality (ADEQ), Perchlorate in Arizona: Occurrence Study of 

2004, Revised (December 2004); California Department of Health Services, Cali(ornia Drinking Water 

Data (April 2005); Massachusetts DEP, Perchlorate monitoring results [data provided by Drinking Water 

Program] (March 2005): U.S. Army Corps of Engineers (USACOE), Washington Aqueduct Perchlorate 

Data (2004); U.S. Environmental Protection Agency (U.S. EPA) Unregulated Contaminant Monitoring 

Data (January 2005); U.S. Government Accountability Office (GAO), Perchlorate: A System to Track 

Sampling and Cleanup Results Is Neede, (2005); and various Water Quality Reports (or Consumer 

Confidence Reports) and news articles for the City of Edmond, OK; City of Georgetown, TX; Las Vegas 

Valley Water District; New Mexico American Water Company; and Shreveport [Louisiana] Department of 

Operational Services. 

19 U.S. EPA, Sa(e Drinking Water In(ormation System (SDWIS). 

20 California Environmental Protection Agency State Water Resources Control Board, and Department of 

Toxic Substances Control, Joint Geotracker SWRCB and DTSC Perchlorate Confirmed Contaminant Site 

Data (2005); U.S. Department of Defense, DoD Perchlorate Occurrence Survey (2003): U.S. EPA, Known 

or Suspected Perchlorate Manufacturers/Users in US (April 2003); U.S. EPA, Known Perchlorate 

Releases in the u.s. (September 23, 2004; and December 10, 2004): U.S. EPA, Hazardous Waste Clean-up 

Information (CLU-IN) [citing Mayer, 2003]. Occurrence and Potential SOl/rces of Perchlorate Releases to 

the Environment as of April, 2003; U.S. EPA, STORET[database]; U.S. Government Accountability Office 

(GAO), Perchlorate: A System to Track Sampling and Cleanup Results Is Needed (2005): W.A. Jackson et 

aI., Distribution alld Potential SOl/rces o( Perchlorate in the High Plains Region or Texas: Final Report 

(2004) Texas Tech University Water Resources Center, prepared for Texas Commission on Environmental 

Quality. 

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Testimony of Gina Solomon 2/25110 

21 Kavlock, R., et al. (2002). "NTP Center for the Evaluation of Risks to Human Reproduction: phthalates 

expert panel report on the reproductive and developmental toxicity of butyl benzyl phthalate." Reprod 

Toxicol 16(5): 453-87. 

22 Kavlock, R., et al. (2002). "NTP Center for the Evaluation of Risks to Human Reproduction: phthalates 

expert panel report on the reproductive and developmental toxicity of di-n-butyl phthalate." Reprod Toxicol 

16(5): 489-527. 

2J Kavlock, R., et al. (2006). "NTP-CERHR Expert Panel Update on the Reproductive and Developmental 

Toxicity of di(2-ethylhexyl) phthalate." Reprod Toxieol 22(3): 291-399. 

2" Main, K. M., ct al. (2006). "Human breast milk contamination with phthalates and alterations of 

endogenous reproductive hormones in infants three months of age." Environ Health Perspect 114(2): 270-6. 

25 Swan, S., et al. (2005). "Decrease in Anogenital Distance Among Male Infants with Prenatal Phthalate 

Exposure." Environ Health Perspect 113: 1056-1061. 

26 National Toxicology Program, Center For The Evaluation of Risks To Human Reproduction, 

Reproductive and Developmental Effects of Bisphenol A. September 2008 NIH Publication No. 08- 5994. 

Available On line http://cerhLniehs.nih.gov/chemicals/bisphenol/bispheno1.pdf. 

,7 vom Saal, F. S., et al. (2007). "Chapel Hill bisphenol A expert panel consensus statement: integration of 

mechanisms, effects in animals and potential to impact human health at current levels of exposure." Reprod 

Toxicol 24(2): 131-8. 

28 Newbold, R., et a1. (2009). "Environmental estrogens and obesity." Molecular and Cellular 

Endocrinology 304( 1-2): 84-89. 

29 Zhang S, Zhang Q, Darisaw S, Ehie 0, Wang G. Simultaneous quantification ofpolycycJic aromatic 

hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and pharmaceuticals and personal care products 

(PPCPs) in Mississippi river water, in New Orleans, Louisiana, USA. Chemosphere. 2007 Jan;66(6):1057-

69. 

30 Boyd GR, Reemtsma H, Grimm DA, Mitra S. Pharmaceuticals and personal care products (PPCPs) in 

surface and treated waters of Louisiana, USA and Ontario, Canada. Sci Total Environ. 2003 JuI20;311(1-

3):135-49. 

31 htlP:i!www.ewg.org!water!downthcdrain (Accessed February 22, 2010). 

32 Oros DR. 2002. Identification and Evaluation of Previously Unknown Organic Contaminants in the San 

Francisco Estuary (1999-2001). RMP Technical Report: SFEI Contribution 75. Oakland, CA: San 

Francisco Estuarv Institute. 

33 Velicu M, suri R. Presence of steroid hormones and antibiotics in surface water of agricultural, suburban 

and mixed-use areas. Environmental monitoring and assessment. Volume 154 issue: 1-4 page: 349 -59, 

2009. 

H Durhan EJ, et al. Identification of metabolites oftrenbolone acetate in androgenic runoff from a beef 

feedlot. Environ Health Perspect. 2006 Apr;114 Suppl 1:65-8. 

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51 

Mr. MARKEY. Thank you, Dr. Solomon, very much. And our final 

witness, Dr. Christopher Borgert is the president and principal scientist of Applied Pharmacology and Toxicology Incorporated, a consulting firm that specializes in assessing the pharmacological and 

toxicological effects of chemicals on living systems. Dr. Borgert received his doctorates in medical science from the University of Florida College of Medicine. We welcome you, sir. 

STATEMENT OF CHRISTOPHER J. BORGERT 

Mr. BORGERT. Thank you, Mr. Chairman. 

Mr. MARKEY. If you can turn on the microphone and move it in 

closer please. There we go. Thank you. 

Mr. BORGERT. Thank you, Mr. Chairman. Thank you for giving 

me the opportunity to provide you my perspectives on this important issue. I come to you today speaking for myself. I don’t represent any particular entity, but I do come to you as a father and 

as a consumer, as a taxpayer, as an operator of small business, and 

a scientist with considerable background on this issue. 

And I too am very concerned about the chemicals that we use in 

commerce. I want to make sure that my family and my children 

and the people of Florida and all the people that come into contact 

with those chemicals are protected. That is a very big concern to 

me. That has been a large part of my work over the years. But I 

am most concerned that when we act, we do it based on solid 

science, science that is reliable and relevant for the purpose to 

which we put it. And what I would caution you about is that many 

of the decisions that are being urged to be made are being urged 

to be made on the basis of someone’s latest pet theory on what is 

causing certain human diseases, rather on solid, repeatable data. 

Let us remember that the diseases that were touted to be due 

to endocrine disruption a decade or so ago have shifted. So as some 

theories fall by the wayside, new theories replace them. These are 

theories. We don’t know what the punitive results of endocrine 

disruptors will be in a few years, and so I think it is very important that we use solid science. 

What do I mean by solid science? I mean science that comports 

with three very common sense tenets: that we know what we are 

measuring unequivocally and we know the precision of that measurement. These are very common sense rules. Number two, that we 

know our measurements are taken under controlled conditions that 

are relevant for the purpose we are putting them to. And third, 

that they are repeatable in independent hands. 

Now, the endocrine screening program that is at issue here has 

been through such a validation exercise, but let us be clear. That 

validation really was able to address only the first of my three tenets. So we now have some confidence that those assays measure 

what we believe they are measuring and we know something about 

the precision. But for some of the assays, that isn’t even entirely 

clear. 

Two of the assays, for instance, failed to produce negative results 

in a wide array of chemicals that we might expect to be negative. 

So we are not really sure that the results are relevant to the use 

we are going to put them to. We don’t know that they won’t simply 

move everything forward with positive results and a screen that 


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52 

doesn’t differentiate between what should be moved forward to tier 

two testing and what is a very low priority for tier two testing is 

rather useless. 

The EPA has issued test orders for 67 chemicals. Its science advisory panel back in 1999 advised that it do this, and we just heard 

that that will be complete in 2012. That will hopefully complete the 

validation exercise so that we will know the controlled conditions 

under which our measurements have to be made and whether they 

are relevant and useful for actually deciding which chemicals need 

to be tested and which are a lower priority. 

So my recommendation is to allow that science to occur, allow 

EPA the time, to give them the resources they need to formulate 

the criteria for moving chemicals forward based on the data, not 

based on the level of emotion and the latest concern, but based on 

the data. We don’t know what those data will be until they are collected. Allow that process to go forward, and I think that then we 

may emerge with science that we can rely on. And remember there 

are consequences to getting it wrong. 

Decisions about which chemicals are in commerce, if they are 

made based on a false notion of what the risks, the real risks are, 

can be the wrong decisions and actually not be precautionary. Bad 

decisions can imperil the public health and the environment rather 

than protect it. So there are consequences to getting it wrong. I 

urge you to give EPA the time to get it right. And thank you for 

your attention. I very much appreciate being able to provide my 

perspectives. 

[The prepared statement of Mr. Borgert follows:] 


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Testimony of 

Christopher J. Borgert, Ph.D. 

before the 

House Subcommittee on Energy and Environment 

"Endocrine Disrupting Chemicals in Drinking Water: 

Risks to Human Health and the Environment" 

Background and Expertise 

February 25, 2010 

Washington, D.C. 

I sincerely thank the Subcommittee for inviting me to testify. I am pleased to be given the 

opportunity to address you regarding endocrine disrupting chemicals and their potential human 

and environmental health risks. 

It has been almost 20 years since I first began tracking the scientific literature on the endocrine 

effects of environmental chemicals, and since then, I've devoted a significant portion of my 

professional career as a pharmacologist and toxicologist to this issue. 

My work generally involves evaluating the relationship between basic research discoveries and 

their application to real world problems, especially health risks posed by chemical substances. 

My expertise is typically sought by private individuals and firms who rely on an accurate 

understanding of the relationships between basic research and health risks to ensure the safety 

of products they bring to the marketplace. These are primarily manufacturers of industrial 

chemicals, pesticides, pharmaceuticals, cosmetics, dietary supplements, and other chemical 

substances, and their trade associations and legal counsel. 

Today, I am here of my own volition and represent only myself. My testimony is based on my 

my scientific training and expertise and my own experience with the issues at hand. 

I have given special attention to the subject of evaluating potential health risks posed by 

combined exposures to multiple chemicals, such as may occur from drinking water. As 

someone knowledgeable in these areas, I have been invited to advise govemmental agencies 

and organizations on such issues. 

In December of 2008, I addressed a workshop of the National Research Council investigating 

the issue of evaluating exposures and risks posed by mixtures of pharmaceuticals in the water 

supply. 

I've been a part of several working groups convened by professional and scientific societies 

interested in endocrine issues. From 1996 - 1998, I served on the Endocrine Disruptor 

Screening and Testing Advisory Committee (EDSTAC), which was the Federal Advisory 

Committee to EPA that initially devised and recommended the two-tiered endocrine screening 

and testing program that it has now begun to implement. 

I served on the EDSTAC as the representative for small business stakeholders, and I also 

served on the workgroup of that committee charged with evaluating and recommending the 

specific screening assays that comprise the Tier 1 Screening Battery. 
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Testimony of Dr. Christopher J. Borgert Page 2 of 6 

In keeping with the Congressional mandate for EPA to use validated test systems in 

constructing its screening program for estrogen-like effects in humans, the EDSTAC 

recommended to EPA that it undertake a formal validation program for the proposed screening 

and testing batteries. EPA did so, using the EDSTAC final report as its template. 

Since my EDSTAC experience, I have followed closely the EPA and OECD validation programs 

for the endocrine screening assays comprising the Tier 1 screening battery, now ordered to be 

conducted on an initial set of 67 chemicals. 

I have assisted various industries in following this validation program, and I also served on an 

OECD peer-review panel that evaluated the validation program for the uterotrophic assay, one 

of the mainstays of the endocrine screening battery. 

Just to make sure, you will remember that the Tier 1 battery of assays is intended to be a 

preliminary screen used to select items that could then be tested in the more specific Tier 2 

battery of tests. 

It is about this Tier 1 endocrine screening battery that I wish to focus my comments to this 

subcommittee, and my first objective is the most necessary clarification of some common 

misconceptions about the Tier 1 screening battery and the validation program conducted for the 

Tier 1 screening assays. 

Basic Scientific Principles are Applicable to Endocrine Screening 

Dispelling misconceptions is essential in order to see clearly what this endocrine screening 

program offers, and what it does not offer, and thus, to consider how the program might best be 

utilized. 

In order to do that, I will review some of the most basic tenets that validate scientific information 

so that the existing knowledge base on the endocrine screening battery, and on endocrine 

disruption in general, can be understood in its proper context. 

For data to be considered an established scientific observation, it must, at a minimum, conform 

to three fundamental tenets that have been well explained by Dr. Gio Gori, formerly Deputy 

Director of the Division of Cancer Cause and Prevention at the National Cancer Institute. These 

three tenets are simple, understandable, and undeniable, applying to the basic language of 

science that enables reliable measurement of the natural world. 

First, the identity and authenticity of scientific measurements must be verifiable within a defined 

range of precision. In other words, we must be able to demonstrate unequivocally that we have 

measured what we claim to have measured and that we know the margin of error on our 

measurements. 

Second, measurements and observations must not be confounded by extraneous factors and 

influences known to corrupt their accuracy and preCision. In other words, we must be able to 

demonstrate that our measurements are taken under well-controlled conditions. 

Third, the measurements and observations must be replicable in independent hands. In other 

words, other scientists using the same or similar methods must be able to repeat the results. 

These three tenets are common sense, but often become confused amidst the technical 

complexity and nuanced jargon of modern science, even by scientists. 
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Testimony of Dr. Christopher J. Borgert Page 3 of 6 

It is in the context of these simple, common-sense tenets that the opportunities and pitfalls of 

the endocrine screening program must be understood. This is also the context in which I 

explained to the National Research Council what valid methods exist for evaluating cumulative 

risks of pharmaceuticals in the water supply. 

Correcting Misperceotions Concerning Validation and Implementation of the EDSP 

Assays and the Tier 1 Battery 

First, regarding validation of the endocrine screening assays, validation and subsequent 

implementation of the EDSP has not been unreasonably delayed. 

While there is no disputing that validation programs for these assays have been protracted and 

have required more in-depth experimentation than initially envisioned by some individuals who 

served on EDSTAC, this lengthy process was completely predictable given the complex biology 

of the systems these assays were intended to measure. 

The TIer 1 endocrine screening battery includes 11 separate assays that range from single-day 

procedures conducted in the laboratory to multi-week assays requiring many experimental 

animals, large animal housing facilities, many personnel to care for and observe the animals, 

animal surgeons, and the evaluation of numerous tissues and organs by fastidious 

histopathological methods. 

Scientists who understand the process of scientific validation - i.e., that the results of the assay 

conform to the three tenets described above and are relevant to their intended purpose -

expected a much longer validation process due to the ambitious nature of the proposed 

endocrine screening program and the need to answer a number of important questions 

regarding the sensitivity and specificity of the individual assays and the battery as a whole, 

since the battery was intended to be interpreted as a unit. 

Unfortunately, because of time-constraints imposed on EPA by Congress, the Agency conducted 

the minimum validation work that might satisfy the Congressional mandate to use validated test 

systems so that screening could begin. 

The complexity of many of these assays and the novel uses to which they are being put in the 

Endocrine Screening Program - the detection of potentially weak hormonal activity for a broad 

array of diverse chemical types and molecular structures - fully accounts for the decade needed 

to complete even the abbreviated validation program that was conducted on these assays. 

It must be appreciated that neither EPA nor any scientist or scientific body is able to dictate the 

results of scientific research and the timeframe on which it will yield useable results. To my 

knowledge and from my perspective, EPA worked as rapidly as it could, taking advantage of 

cooperative efforts by the OECD and other international organizations, to conduct validation 

experiments and to adjust the experimental plan as necessary based on results of the studies 

as they were obtained. Some results enabled rapid progress; other results dictated abandoning 

initial approaches and evaluating alternatives instead. Scientific results simply cannot be forcefit to meet a predetermined schedule. 

Second, and perhaps more unfortunately, the endocrine screening battery, as a whole, 

has not yet been shown to be useful for its intended purpose. Because many of the 

assays are protracted and complex, the expedited validation programs were able to focus only 

on the ability of the individual assays to detect known positive and negative endocrine active 

compounds specific to each test. Only limited testing of unknowns was possible given the 
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Testimony of Dr. Christopher J. Borgert Page 4 of 6 

intense pressure on the Agency to implement the screening program rapidly. Moreover, the 

performance of the battery as a whole has been left unaddressed. 

Validation efforts for some of the assays, the pubertal male and female assays in particular, 

were unable to verify that the assays could yield negative results for a range of chemicals 

lacking endocrine activity. Indeed, the criteria for interpreting ambiguous results had to be 

modified in order to claim that these assays could yield a negative result for even one chemical. 

The assay protocols left standing at the end of the validation exercises, which have now been 

formalized as EPA test guideline series 890, leave unaddressed a number of technical problems 

that will complicate and confound the development of interpretive criteria for the individual 

assays as well as for the battery as a whole. 

In short, the validation process has provided increased confidence that we are measuring what 

we claim to measure with the endocrine screening assays, but the precision of some of those 

measurements is still uncertain, and the conditions under which extraneous factors might 

influence the measurements are not well controlled in all the assays. This makes tenuous the 

assumption that the screening battery will actually differentiate chemicals with the potential to 

interact with the endocrine system in definitive studies from those that do not. 

Presently, no one knows how useful the endocrine screening battery will be, as a whole, for 

predicting which chemicals should undergo definitive testing and which should be considered a 

low priority for further analysiS of endocrine effects. If the endocrine screening battery forwards 

everything to further testing, it has absolutely no utility whatsoever. 

EPA, on the advice of its Scientific Advisory Panel, has attempted to address this problem by 

ordering an initial phase of EDSP screening on 67 pesticide chemicals. The purpose of this 

approach is to evaluate the lier 1 assays and battery, as well as the Agency's policies and 

procedures, using a discrete set of chemicals. To be an effective approach, additional screening 

must await completion of the initial phase, at which time EPA would modify its assays, battery 

and procedures as necessary. 

Make no mistake; the status of the endocrine screening battery is analogous to a new but 

unproven clinical screening procedure. Assuming that a precautionary approach is without harm 

and that all important decisions will await the definitive test ignores the very real fact that life 

altering decisions are made daily on the basis of clinical screens. There are consequences to 

getting it wrong, even if it is only a screen and not the definitive test. 

In the same way, we might inadvertently presume great risk for relatively safe chemicals, and 

instead use riskier replacements, simply because some chemicals were assumed to be harmful 

based on highly publicized endocrine screening results. As a scientist who is also a father, a 

consumer and operator of a small business, I would like to know that products in commerce are 

evaluated on the basis of real risks, demonstrable by objective science, not upon hypothetical 

connections between screening results and serious diseases that are easily and conveniently 

sensationalized. 

Third, endocrine screening will not identify "endocrine disruptors." This issue concerns 

the predictive value of the endocrine screening battery and whether so called environmental 

endocrine disruptors have been unequivocally identified. Highly publicized statements have 

been made repeatedly over the years declaring that serious human diseases are known 

consequences of exposure to environmental endocrine disrupting chemicals. These 

speculations have often been made on the basis of epidemiological studies that used 

methodologies appropriate for hypothesis generation but wholly incapable of confirming putative 

associations or demonstrating causes. Interestingly, the list of human disease associated with 
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Testimony of Dr. Christopher J. Borgert Page 5 of 6 

endocrine disruption has shifted as initial speculations were debunked or severely tempered -

breast cancer related to chlorinated organic chemicals; reduced sperm counts related to higher 

chemical exposures in industrialized nations; feminized male fish in UK rivers caused by 

exposure to soaps and detergents - only to be replaced by newer and relatively less scrutinized 

speculations. Rather than convincing us by the sheer number of speculations that are based on 

hypothetical studies, the failure to reproducibly demonstrate these associations and to support a 

true causal role for chemical exposures should lead us to suspect them. 

There is a also a widely held misconception that the endocrine screening battery provides a 

sensitive means of identifying chemicals that may cause subtle health effects in the human 

population or in wildlife. Since those subtle effects have not been demonstrated, nothing could 

be more misrepresentative of what the screening battery can be expected to do. Indeed, the 

endocrine screening battery is intended to detect only chemicals that have the potential to 

interact with the endocrine system in live animals; it does not and cannot test for adverse health 

effects. 

Interaction with the endocrine system per se, i.e., positive results in the endocrine screening 

battery, does not signify that adverse endocrine effects are likely. The endocrine system is a 

homeostatic system that functions to maintain relatively consistent internal body conditions. An 

endocrine response is merely an indication that the system is working. The endocrine 

screening battery utilizes this responsiveness to screen chemicals for potential interaction with 

the system, but it does not determine whether the endocrine system is merely responding or is 

irrevocably perturbed by the chemical. The endocrine system is like a thermostat on a heating 

and air conditioning system; the fact that it turns off and on many times during the day does not 

signify that it is damaged, but merely that it is responding to changes in room temperature. 

Without knowing whether room temperature was properly controlled, it is impossible to conclude 

that the thermostat or heating system malfunctioned. 

In the same way, the endocrine screening battery cannot determine that a chemical poses a risk 

to human or environmental health, but merely indicates that some component of the endocrine 

system recognizes the presence of the chemical. A more thorough analysis - tier 2 tests - must 

be conducted to determine whether that potential interaction with the endocrine system leads to 

adverse effects. It may for some chemicals, but for many it might not, or if so, only at doses that 

far exceed doses that produce some other serious toxic health effect. In the latter case, 

adverse endocrine effects would never be observed. 

This last case underscores another reason the endocrine screening battery cannot be 

interpreted as indicating adverse effects: the extraordinarily and unrealistically high doses of 

chemicals that will be used in screening may elicit responses that could never occur at lower 

levels typically encountered in the environment. A similar conclusion, and others, have been 

explained in a recent publication by Dr. Richard Sharpe of the UK, who was one of the original 

voices of concern for the possible effects of environmental endocrine disrupting chemicals. 

These basic pharmacological and toxicological concepts of dose-response were at the core of 

my presentation to the National Research Council concerning risks posed by mixtures of 

pharmaceuticals in the water supply. These concepts have not been supplanted by hypothetical 

low-dose theories or by the speculation that mixture effects observable at high doses also 

operate and manifest adverse effects at low, environmentally relevant levels of exposure. 

Although good health trumps money in my value system, it is nevertheless important to 

recognize that endocrine screening is very expensive and should not be required of more than 

the initial 67 chemicals until its utility has been demonstrated. The costs of screening alone are 

on the order of 1 to 1.5 million dollars per chemical, but this figure does not account for the full 

cost to consumers who ultimately must bear the burden of funding the activities of the EPA and 
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Testimony of Dr. Christopher J. Borgert Page 60f 6 

Congress on this issue, nor does it include the costs of conducting tier 2 testing on chemicals 

that are false positives in the screens. Finally, such monetary figures fail to give due 

consideration to the tens of thousands of laboratory animals that must be sacrificed to conduct 

this screening, and the tens of thousands more that will be sacrificed in tier 2 testing. 

Four months ago, in October of 2009, EPA began issuing lier 1 test orders for 67 chemicals 

comprising pesticide active ingredients and inert ingredients in pesticide products. Many of 

these chemicals have already undergone the more extensive, long-term animal tests typical of 

tier 2 that are capable of defining adverse effects on reproduction and development in rodent 

species. Thus, it can only be hoped that the initial round of test orders will yield data upon 

which the predictive utility of the endocrine screening battery for adverse effects in laboratory 

rodents may finally be evaluated. 

Expanding the program within the first year of its implementation, as has been proposed, will not 

only be costly, but it will needlessly squander an opportunity to evaluate the data from the first 

67 chemicals screened and to improve the screening battery based on those results. In short, 

premature expansion carries great risk of getting the science wrong, with the consequence of 

poor decision-making that imperils rather than protects public health and the environment. 

From a scientific perspective, precious resources would be better directed toward evaluating the 

utility of the endocrine screening battery for identifying adverse endocrine effects in laboratory 

rodent tests, which are known to capture adverse effects on reproduction and development 

mediated by all physiologically relevant pathways, including endocrine disruption. 

Rather than expanding the program prematurely, this path would allow EPA time to determine 

the best criteria for moving chemicals from tier 1 screening to tier 2 testing based on the data, 

and to determine whether enhancements, deletions, or replacements for the current assays are 

needed. 

Without such a deliberate approach that relies on established scientific principles rather than on 

precautionary rhetoric and speculative hypotheses, the credibility of the endocrine screening 

program and the government agencies that drive it is likely to suffer. 
59 

Mr. MARKEY. Thank you, Dr. Borgert, and thank you for being 

here. That concludes testimony from our panel. Now we will turn 

to a question-and-answer period. The chair will recognize himself 

for a round of questions. 

I have introduced a bill to ban BPA in food and beverage containers in the past two Congresses, and recently the FDA announced that it had concerns about its health effects. It has also 

been found in 30 percent of groundwater sites sampled nationally. 

Dr. Birnbaum, the endocrine-disruptor screening program is intended to screen chemicals to see whether they are endocrine 

disruptors, but it seems to me that we already know that BPA 

qualifies. Do you agree with that? 

Ms. BIRNBAUM. I certainly support the recent decision of the EPA 

to suggest that they have some concern about the effects of BPA, 

which are based in large part upon the plethora of information that 

is being produced demonstrating that BPA is an endocrine 

disruptor and is associated with, at least potentially associated 

with a wide range of health effects. 

Mr. MARKEY. Dr. Jones—Mr. Jones, do you generally agree that 

if there is enough scientific data showing that a chemical is an endocrine disruptor that causes adverse health effects, that EPA 

shouldn’t have to screen it again and could use its authority to 

move straight to regulation? 

Mr. JONES. Well, I would generally agree that the agency would 

not need to do screening level assessments to determine whether 

it is an endocrine disruptor, BPA being a perfect example. We don’t 

think that that requires screening to understand whether it is. I 

don’t believe as a general matter we necessarily will therefore have 

enough information to go to regulation. I think that is the situation 

where we need to make sure we understand we can characterize 

the adverse outcomes of a compound before we can go to regulation. 

Now, that may not be true in all cases, but I think it would be 

an overstatement for me to say I think that we can go from we 

know it is a disruptor to regulation as a general matter. 

Mr. MARKEY. Dr. Solomon, since BPA is a known endocrine 

disruptor that is known to be in drinking water, do you think EPA 

should have included BPA on its list of chemicals to evaluate to 

consider whether a drinking water standard should be set for it? 

Dr. SOLOMON. Yes, I do. 

Mr. MARKEY. Could you expand on that briefly please? 

Dr. SOLOMON. BPA fits the criteria—clearly fits the criteria for 

a priority substance for regulation in drinking water because it is, 

a, known to be present in drinking water source waters, and, b— 

and actually in some studies in drinking water at the treatment 

plant, and, b, is a chemical that has very strong data on health effects at levels that are actually not that far off from what people 

are being exposed to today. Drinking water is not the only source 

of exposure, but it is certainly something that EPA can and should 

be controlling. 

Mr. MARKEY. OK, a recent press article, Dr. Solomon, suggested 

that EPA did consider including BPA on its list of chemicals of concern, which would put it into the regulatory process. But it was 

pulled off the list shortly after the chemical industry met with 

OMB. Do you think that EPA should decide which chemicals to 


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60 

evaluate using a process that is more transparent and gives more 

opportunities for all stakeholders to participate? 

Dr. SOLOMON. Yes, I believe it is extremely important for EPA 

to have more public involvement in the process, and the candidate 

contaminant list was not vetted until it was pretty much almost a 

done deal. And there were some significant concerns raised by 

members of the public and by the drinking water committee about 

the list itself and the chemicals that were not on and were on that 

list. 

Mr. MARKEY. Mr. Jones, what can you tell us about why BPA 

was not included on EPA’s list of chemicals of concern? 

Mr. JONES. Well, first, Mr. Chairman, I do want to point out it 

is a public record because what we submit to OMB is made public, 

and what comes back out of that process is public as well. And BPA 

was not on the list when it went to OMB, so a characterization that 

it was removed through that process would just not be accurate. 

My understanding is that BPA, when the agency did the CCL 3 

list, did not meet the criteria we had in terms of our understanding 

related to the known health effects associated with it. It is found 

in drinking water, but that the knowledge we had related to known 

effects associated with the compound, it did not meet the criteria 

that we use for listing chemicals under CCL 3. 

Mr. MARKEY. And back to you for a final question, Dr. Solomon. 

We often hear that the European Food Safety Authority thinks 

that BPA is safe and that we therefore don’t need to worry about 

it in this country. However, just a few days ago, the Danish parliament voted to ban BPA in children’s products, and a spokesperson for the European commission indicated it is looking at new 

scientific evidence. 

Do you agree with the European Food Safety Authority’s current 

policy on BPA? And if not, what did it get so wrong? 

Dr. SOLOMON. The European Food Safety Authority’s review of 

BPA was based on a fairly limited review of the data that focused 

on a number of the studies done by industry, and it unfortunately 

did not include many of the most important independent studies 

done by academics. And so, I am very pleased to see that the Danish authorities and that others, such as the Canadian government, 

have been reevaluating the science more fully, that the FDA is 

doing so as well because there is really a very extraordinary 

amount of science showing a serious concern related to health effects at low levels. 

Mr. MARKEY. Thank you, Dr. Solomon. Chair recognizes the gentleman from Florida, Mr. Stearns. 

Mr. STEARNS. Thank you, Mr. Chairman. Dr. Borgert, the chairman brought up this BPA, and he has made quite significant statements on it. In your opinion, should BPA be totally banned? I know 

it is omnipresent in very small quantities in everything from eyeglasses to liners in cans and everywhere. So I mean I will just give 

you a chance to respond since he has asked these three witnesses, 

what your opinion is. 

Mr. BORGERT. Well, thank you, sir. I have not formally reviewed 

all of the data on bisphenol A, but I know that it is still controversial among some. But I know that a number of well-qualified 

groups that have determined that at the levels people are exposed 


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to and that are in the environment in the food supply, et cetera, 

are present at levels that are unlikely to pose any significant 

human risk. And they do that not based on limited studies. They 

do that based on studies on comport with generally those three tenets that I explained. 

It is important not only that we look at the quality of the data, 

but we look at the quality of the methods we are using to select 

the relevant data. And so when you select the relevant data that 

are of high quality, you don’t come out with an answer that BPA 

is a significant health concern. You come out with a different answer, and many well-qualified groups have done that. 

So no, I think it would be a mistake to rush to regulation. I think 

we need to use the best science, and that science needs to be vetted 

not on the basis of stakeholder opinions but on good science. 

Mr. STEARNS. So in your opinion right now there has not been 

the scientific study done to totally ban it? Is that—— 

Mr. BORGERT. I don’t think the science would support that. 

Mr. STEARNS. OK, so it is your opinion that science would not 

support the total banning of the BPA as the levels we are using 

it today in America? 

Mr. BORGERT. Correct. 

Mr. STEARNS. Is that your opinion? And has there been any demonstrable evidence that in the levels we are using it, any science 

to show that it is harmful in the levels we have? Where is the people that are saying for the ban? Where are they getting their evidence to say it needs to be banned? You have a Scandinavian country saying they are banning it. So there must be some scientific 

evidence somewhere to back it up? 

Mr. BORGERT. Well, there are many, many studies conducted on 

BPA that can be used to raise concern. 

Mr. STEARNS. As well as to raise not concern. 

Mr. BORGERT. As well as to raise questions. 

Mr. STEARNS. Yes, so there are all studies across the spectrum 

is what you are saying? 

Mr. BORGERT. That is correct, but when we select the highest 

quality studies that are most relevant for the question, we don’t 

come up with the answer that it poses a risk and that it should 

be banned. 

Mr. STEARNS. Why do we use it so omnipresent everywhere? It 

is because it works in an efficacious way? 

Mr. BORGERT. Well, it is a plasticizer that enhances physical 

properties of the plastics. I am not a chemist who could—— 

Mr. STEARNS. No, I understand. 

Mr. BORGERT [continuing]. Explain that to you fully. But there 

are benefits to the products that are in the marketplace, and if we 

choose different alternatives, they may not confer the same benefits. We may actually incur real risks like bacterial infections, et 

cetera, if our products are less effective. 

Mr. STEARNS. Let me go to the heart now, the hearing we have 

here. So far, what chemicals are classified as proven endocrine 

disruptors in human? I mean that have been scientifically proven 

to be disruptors in humans? Do you know? 

Mr. BORGERT. Well, I haven’t prepared a list, and so I would 

hesitate to go on the record and provide one, but—— 


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Mr. STEARNS. Sixty-seven are being studied by the EPA. And 

then some of those have been pulled off. But I mean do you have 

a list in your own mind’s eye of the number of disruptors that actually could be classified? 

Mr. BORGERT. Well, no, and I think that is a large unknown at 

this point. 

Mr. STEARNS. So it is still unknown. I mean regardless of what 

we hear, testimony and so forth, but there is nobody that scientifically has classified as proven endocrine disruptors in any studies 

that affect humans. Is that true? 

Mr. BORGERT. Well, it is not that there are no chemicals that I 

think we could call endocrine disruptors. I think diethylstilbestrol 

is a classic example. I think that many of the drugs that we use 

today are used for their hormonal activity and that at that certain 

doses in certain people are certainly going to disrupt the endocrine 

system. 

I think that other chemicals in very high doses may be able to 

do that, but we have to consider two things: the dose and the potency. In other words, how much of it there is and how strong it 

really is. So doing animal studies where we give doses that may 

not reflect the human situation or the human physiology are not 

able to tell us whether a compound is an endocrine disruptor in humans. 

And I want to clarify that the endocrine disruptor screening program won’t do that for us either. It is a screen. It simply tells us 

which chemicals really deserve a close full-fledged definitive test 

and which are of lower concern. We don’t even know that the battery is going to be effective for that yet until the data from this 

first 67 comes in and we have time to digest it. 

Mr. STEARNS. OK, my questions are over. Based on what you are 

saying, we don’t—also the dosage at which they are damaging is 

very crucial is what you are saying. And that is part of this whole 

difficult challenge is to get a hold of, OK, this chemical is bad, but 

at what dosage is it bad? And that is probably what you are alluding to. Thank you, Mr. Chairman. 

Mr. MARKEY. Thank the gentleman. The gentleman’s time has 

expired. The chair recognizes the gentlelady from California, Ms. 

Capps. 

Mrs. CAPPS. Thank you, Mr. Chairman. I mentioned in my opening statement my background as a public health nurse. And working so many years as I did with my local public health department—and I know this to be the case amongst many public health 

agencies throughout our local communities across the country—this 

is a very important topic to our local health directors and 

facilitators. 

I want to ask several of you short questions, if I could, back and 

forth way. Mr. Jones, starting with you. I am concerned that the 

screens that EPA is using to test a very short list of possible endocrine disruptors will not even begin to capture the long list of 

chemicals being reported in drinking water supplies today. This is 

a bit of a repeat to what the chairman has already asked you, but 

I want to get it clearly on the record. 

Once an endocrine disruptor is identified through your screening, 

will that be adequate to regulate it? 


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Mr. JONES. The first step in the process is to screen for potential 

interactions with the endocrine system. Chemicals that come out of 

that process as positive will then go into a more in-depth testing 

regime that it is that information, a tier two test, that will give us 

the information that is necessary for regulating. 

Mrs. CAPPS. So after tier two, then you can regulate? 

Mr. JONES. That is correct. 

Mrs. CAPPS. How long does that process take usually? 

Mr. JONES. Going from today the 67 chemicals that have been 

tested up through having the results of the tier two test is going 

to be about five plus years. 

Mrs. CAPPS. Five years? 

Mr. JONES. That is correct. 

Mrs. CAPPS. That is remarkable. Dr. Solomon, what steps are 

necessary to determine if regulation is needed once an endocrine 

disruptor is identified through screening? You talked about this in 

your statement. 

Dr. SOLOMON. When an endocrine disruptor is identified, you 

know, I think there is a public health imperative to take action. 

Mrs. CAPPS. Immediately? 

Dr. SOLOMON. And so, you know, the EPA moves at its own pace, 

but it really needs to move quickly on these chemicals. And the 

ones that are known endocrine disruptors, that have been sort of 

sitting in the queue—— 

Mrs. CAPPS. Yes. 

Dr. SOLOMON [continuing]. Or even put back into the queue, for 

example, numerous phthalates that I would already classify as 

known endocrine disruptors are now going through the first tier of 

screening, entering 5 five-year process at a point when they actually should be gainfully heading toward regulation. 

Mrs. CAPPS. Well, you know, and the interesting thing is when 

the public knows, when the parents of the school kids I used to 

work with understand that there is a problem, they don’t want to 

wait 5 years. Their children will be adults by then, and the damage 

will have been done. So I hear your urgency. 

Back to you, Mr. Jones. Does the Safe Drinking Water Act provide EPA with the necessary mechanisms to regulate the chemicals 

being identified as endocrine disruptors? 

Mr. JONES. The Safe Drinking Water Act provides the necessary 

tools to do that. I will point out that the testing for endocrine disruption under the Safe Drinking Water Act was discretionary authority, which, I think, probably explains why it has not been—— 

Mrs. CAPPS. Do you believe it should be discretionary? 

Mr. JONES. I will leave that up to—— 

Mrs. CAPPS. OK. 

Mr. JONES [continuing]. Congress. We are now exercising our discretion, but it was discretionary in that we—— 

Mrs. CAPPS. I hear you. Back to you, Dr. Solomon. Do you think 

EPA has an effective mechanism to regulate the chemicals being 

identified as endocrine disruptors? And if you don’t, what should 

that mechanism be? 

Dr. SOLOMON. One of the problems with endocrine disruptors 

that came up was this issue of low doses, and EPA’s regulatory 

mechanisms in general are not very good at dealing with the kind 


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of unusual data where a chemical may have one set of effects at 

a high dose and a different set or even more severe effects at low 

doses at key periods of infant development. And this is really 

where we, you know, where the regulatory system stumbles. 

Mrs. CAPPS. And where groups like yours and Dr. Birnbaum’s 

can be perhaps useful in updating some of the procedures? That 

was a question kind of. 

Dr. SOLOMON. Yes, I certainly hope and believe that EPA is 

starting to look at these issues more seriously in all of the environmental media. 

Mrs. CAPPS. Dr. Birnbaum, I want to make sure that—because 

you have been nodding as I have been asking other questions. Does 

NIEHS have the capacity to provide the science and the protocols 

needed to regulate the chemicals being identified as endocrine 

disruptors? 

Ms. BIRNBAUM. NIEHS has a long-standing program in studying 

endocrine disruptors. In fact, in 2007, we convened a panel of over 

about 35 different experts from across the country and across the 

world looking, for example, at the issues of BPA. And the consensus of that panel was that BPA was an endocrine disruptor and 

was causing effects in multiple different animal species, not just 

rats and mice, and that there was evidence that there was at least 

the potential to cause those effects in humans. 

Since that time, the NTP Seer Panel has issued the report which 

again was an extensively peer-reviewed report involving many experts, which concluded that there was some concern for a number 

of developmental and reproductive endpoints including development neurological effects following exposure to BPA. 

At the same time, we have continued to fund additional work to 

look at the issues not only of BPA, but of many other endocrinedisrupting chemicals. So I would say that there are demonstrated 

endocrine-disrupting effects of a number of chemicals in humans. 

There are now several epidemiology studies that cannot prove causality but can demonstrate associations between, for example, BPA 

and developmental neurobehavioral changes in children between 

cardiovascular effects, between diabetes, for example. Again associations, but they are backed up by our animal studies. 

I think one point I would like to make is that we need to be careful when we talk about low dose. What I think many of us should 

be meaning when we talk about low dose are what are the levels 

that are present in people. So the epidemiology studies I referred 

to BPA, for example, are being seen in the general population. 

These are not necessarily high levels of exposure. 

And when you do animal studies, what you really need to understand is not how much you give the animal, not how much is in 

the drinking water, but how much is in the animal if you want to 

compare the effects in animals to the effects in people. And under 

those conditions, we often find that the puditive high-dose animal 

studies in fact are not high dose at all. 

Mrs. CAPPS. Thank you, Mr. Chairman, for allowing this to go 

forward. It appears to me, if I could just put these comments that 

the three of you have made together, that the scientific community 

in many resources in many settings has done a lot of studies that 

could be very useful to the EPA in terms of perhaps updating or 


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looking in more depth at what the sciences has out there and that 

would be very valuable for the public to have the benefit of. Thank 

you very much. 

Mr. MARKEY. The gentlelady’s time has expired. The chair recognizes Dr. Burgess from Texas. 

Dr. BURGESS. Thank you, Mr. Chairman. And, Mr. Chairman, 

just for a point of clarification, have you introduced a bill to ban 

the EPA or BPA? Because I was almost ready to sign on to your 

bill—— 

Mr. MARKEY. I know that the governor’s race in Texas is turning 

on that question, OK. It is amazing watching it from afar. 

Dr. BURGESS. Thank you for that clarification. Dr. Borgert and 

perhaps Dr. Solomon as well, Mr. Stearns was questioning you just 

a moment ago. We were kind of getting into the questions between 

dosage and potency, Dr. Borgert. Dr. Solomon, you were either nodding your head or shaking your head while that was going on. Did 

you have something you wanted to add to that discussion about the 

discussion of potency and dosage? 

We all know anything in the wrong dosage, water intoxication 

can happen. Water is generally regarded as safe, but there are people who are injured, and in fact, there have even been deaths from 

overdoses of just simply water. So what about this issue of dosage 

and potency? 

Dr. SOLOMON. Hormones are almost unique in the way that they 

act in our bodies because there are receptors on our cells that are 

basically sort of scanning our bloodstream for even minute traces 

of these hormones. And those receptors are primed basically hugely 

magnify the cellular and organ system response in our bodies to 

even slight hormonal fluctuations. 

So actually it is almost like a megaphone into the cells in our 

bodies when even a trace amount of a hormone enters our bloodstream, and that is true of natural hormones. It also is true of 

many endocrine disruptors. 

Dr. BURGESS. I don’t mean to interrupt, but I have only a short 

period of time. And you know how testy the chairman is with the 

person who sits immediately to his left. There is also a question of 

how rapidly that compound is metabolized in the body. Some are 

metabolized rapidly. Some will tend to have a cumulative effect. 

That may have been what Dr. Birnbaum was just referring to, that 

there are some things that will just sequester in the body and leave 

only more slowly. And, in fact, there may be populations where this 

behaves differently as we learn more and more about medicine. 

There may be people who are—I think this is some of the things 

we have learned about Gulf War syndrome and how quickly people 

are able to metabolize or not metabolize some of these organic 

phosphate compounds. So that is a lot of stuff to have to put into 

the equation. Dr. Borgert, did you want to say something about 

that? 

Mr. BORGERT. I do. Thank you. Potency is important, but it is potency at the receptor. And the hormone system is not unique in utilizing receptors. The neurological system uses the same concept. So 

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tems work. And it is the potency of the molecule of the drug or the 

chemical at that receptor that is important. 

I want to put this into perspective for you. A very fine study by 

a scientist, the group Katsenel and Bogens Group, not working on 

endocrine disruptors per se, but looking at steroid hormone receptors showed that testosterone can activate the estrogen receptor. 

Now, testosterone is the basic male hormone. It is not an estrogen, 

but at its very low potency at the estrogen receptor, but it can activate it. 

And so we need to consider these potency issues, and we need 

to remember that these low-dose theories are theories. In some instances, they may tell us that compounds are having adverse effects. In other instances, the import of those low-dose effects may 

be compensatory and adaptive and merely tell us that the system 

is working well to manage the tens of thousands of chemicals that 

we experience in our natural environment as well as the synthetic 

chemicals. Thank you. 

Dr. BURGESS. It has been a while since I have dealt with the biochemical aspects of this, but there are also places in the body 

where, in an extraglandular way, hormones can be produced in fat 

cells, for example. Estrogen can be—under the right circumstances, 

fat cells, adipose cells can produce estrogen if they are given the 

right precursors in the right setting. 

The reason I am bringing all this up is we passed a bill in the 

last Congress, H.R. 4040, the Consumer Products Safety Improvement Act, and the unintended consequences of that. The bill passed 

for the best of reasons. I voted for it. We passed that bill, and the 

unintended consequences have just been extremely disruptive for 

the American people that have to live under the legislation that we 

passed. 

I have motorcycle dealers who sell motorcycles that are designed 

for young people, youth motorcycles, which they are now not sure 

that they can sell because of the battery is taken out of the motorcycle and ingested, the lead levels, of course, would be horrendously high. And under the language of the bill, the lack of flexibility that we built into the language of the bill, I have motorcycle 

dealers in my district that tell me they have vast quantities of inventory that they can do nothing with. They can’t send it back. 

They can’t sell it. They can’t even sell parts to people who have 

previously purchased devices and come in for help. 

So it gets to your point, Dr. Borgert, about being so careful about 

this not wasting resources on chasing things that may be of minimal to no impact. But also then the downstream consequences of 

legislation are significant. There are some crystals that might have 

lead in them only if you pulverize them to a fine powder and ingest 

them. And, of course, the molars of a very young child are not capable of that level of grinding even if they were to ingest the rhinestone. There are multiple examples, and I have people through my 

office all the time who come and tell me about the bad things I did 

while I was trying to be protective of the public good with the 

CPSIA through this committee. You like you wanted to say something to that. 

Mr. BORGERT. Well, I just wanted to agree, and I wanted to summarize, I think, what you are saying is, you know, there is always 


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time after we realize we have made a mistake to go back and correct it. We have to do that. It is a shame there is often not enough 

time to be deliberative and get it right the first time. And I think 

we want to take that lesson here. 

Dr. BURGESS. Well, the other part of the lesson is with the 

change of administrations and the change of people at the Consumer Product Safety Commission, we haven’t made those changes. 

And we have left people hanging with either inventory that they 

cannot sell, resale shops that don’t know because of the level of 

lead testing we have required is not even available in some areas. 

Can we resell these books or toys? Libraries that don’t know if they 

can leave vinyl-covered books on their shelves. 

It is a huge problem that we created in this committee, and 2 

years later, we are not even talking about fixing any of those problems. And the agency now with a different head—and not that they 

are not good people—but the agency is focusing on new things and 

not looking at correcting the problems that we caused. 

This is one problem the Bush Administration didn’t cause. Yes, 

he signed the bill, but we caused the problem. And it has not been 

fixed. 

Can I just ask one additional question? With all the stimulus 

money we spent on computer IT, and you referenced a lot of the 

data, Dr. Birnbaum, that you have. Are you getting that stuff electronically in a place where you can search it and where those databases are actually going to be useful to you? Because you have collected a lot of data. You are continuing to collect a lot of data. But 

is it in a format that will actually be useful to us? 

Ms. BIRNBAUM. Thank you very much for the question. All the, 

for example, published studies are available electronically on the 

Web site. All the approximately $10 to $15 million that we are 

funding under the American Recovery and Reinvestment Act, all 

the information about what those studies are, who has conducted 

them, what these objectives are of those studies, are available on 

the usagovernment.recovery Web site as well as on our NIEHS 

Web site. And those results, as they come to fruition, will all be 

available for the general public. 

Dr. BURGESS. What sort of backlog do you have with putting data 

in there? 

Ms. BIRNBAUM. Excuse me? 

Dr. BURGESS. What sort of backlog do you have with putting the 

data in there? 

Ms. BIRNBAUM. It goes on almost as soon as it becomes available. 

Dr. BURGESS. The historical that has been collected. 

Ms. BIRNBAUM. All the historical data is currently available right 

now. 

Mr. MARKEY. OK, the gentleman’s time has expired. We thank 

the gentleman for identifying a problem that was not created during the Bush Administration. That is also very helpful, I think, historically. The chair recognizes the gentleman from California, Mr. 

McNerney. 

Mr. MCNERNEY. Thank you, Mr. Chairman. I am recovering from 

laryngitis so I don’t know if I have 8 minutes of voice or 9 minutes 

to compete with the gentleman from Texas, but I will give it a shot. 


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I am glad that he was as concerned about your testiness on this 

issue as he is. 

Mr. Jones, we have a town in my district, Morgan Hill, that has 

a large perchlorate spill in the region. Now, California has set pretty good standards for perchlorate, but there is no national standards in place. Do you think that would be a good idea to move forward with a national standard for perchlorate and other endocrine 

disruptors? 

Mr. JONES. Thank you, Mr. Congressman. The agency is going to 

make a determination this year as to whether or not we feel it is 

appropriate to establish an MCL, maximum contaminant level for 

perchlorate. That is referred to as a regulatory determination 

under the Safe Drinking Water Act, and in 2010, that decision will 

be made. 

Mr. MCNERNEY. Then your opinion is not to be given this morning? 

Mr. JONES. I am sorry. We are trying at EPA to coordinate better 

across our offices. I am actually not in the office that manages the 

Safe Drinking Water Act. I am in the office that manages the endocrine disruptor screening program, so although I am familiar with 

where the office of water is with respect to that determination. Because I am not intimately familiar with the facts around perchlorate, I think it would not be wise for me to offer an opinion on 

that. 

Mr. MCNERNEY. OK, thank you. Dr. Solomon, do you think the 

Safe Drinking Water Act worked effectively in regulating hazardous chemicals in drinking water? And if not—and I suspect that 

you are going to say that you don’t—do you have specific recommendations? 

Dr. SOLOMON. The Safe Drinking Water Act as amended in 1996 

required the creation of these various candidate contaminant lists. 

We are now on the third iteration, and in each case, EPA has gone 

through an extensive exercise to create the list and then has actually not taken any action to regulate any of the chemicals on these 

priority lists and has simply moved on to create another priority 

list. 

And so I am very much hoping that, you know, EPA will take 

action and start setting some regulatory standards on these chemicals. There is now well over 100 chemicals that have been identified as priorities, and, you know, on the CCL 3 as potential priorities. And a number of those really do need to move forward. 

Mr. MCNERNEY. So in other words, you don’t think they have 

been that effective so far and could be more effective? 

Dr. SOLOMON. Yes, EPA does have the authority to, you know, 

take the action that it needs to, but it is, you know, since it just 

needs to make a determination, it can, you know, on each of the 

previous CCL lists, the determination has just been that various 

chemicals did not need to be regulated. 

So it is very easy for the agency to avoid taking any action if it 

doesn’t want to take action. 

Mr. MCNERNEY. Thank you. Dr. Borgert, good morning. 

Mr. BORGERT. Good morning. 

Mr. MCNERNEY. You know I was a scientist or a mathematician 

in a past life. So I appreciate your comments about having repeatVerDate Mar 15 2010 08:22 Nov 08, 2012 Jkt 076011 PO 00000 Frm 00074 Fmt 6633 Sfmt 6633 E:\HR\OC\A011.XXX A011

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able science; however, I think the people in Morgan Hill would say 

there should have been precautions taken before they put the perchlorate in the ground even though they didn’t know it was an endocrine disruptor and a cancer-causing agent at that time. 

So my point is that when human health is at risk, when human 

health is on the line, we shouldn’t wait for permanent or absolute 

certainty. Absolute certainty in science is very, very hard to come 

by, and if we wait for absolute certainty, we are going to be dying 

from all kinds of problems. 

So I think we need to put some sort of risk into the consideration 

in making these kinds of decisions even though absolute certainty 

has not been achieved. Do you have a comment? 

Mr. BORGERT. Yes, I do. I couldn’t agree with you more that we 

need to be precautionary when we actually know what the risks 

are. But let me give you an example of what can happen when you 

think you know what the risks are and, in fact, you don’t fully appreciate them. 

Now, I think you gave us an example with perchlorate in the 

drinking water. And certainly I am not an engineer, but if there 

were good and valid methods, engineering methods for protecting 

against that, maybe those precautions should have been taken. 

But on the human health side, I want you to consider the example of dietary fat. There was a day when we thought fat was, you 

know, across the board a bad thing, and we tried to eliminate, 

many of us did, tried to eliminate fats from our diet. 

Today many of us take fish oil, which is a fat. With a little more 

reliable research and a little more understanding, we recognize 

that what we thought was a precautionary approach may actually 

have been harmful. It is not good to remove all the fat from your 

diet. Some are very beneficial. 

So sometimes you act with very good intentions to do what you 

believe is precautionary, and because you have rushed to judgment, 

you actually have done the opposite of what you intended. 

Mr. MCNERNEY. Well, I don’t know that we need to rush to judgment, Dr. Borgert, but I think we need to be precautionary when 

there is evidence, even association, that there is risk. I think we 

need to be precautionary and take steps ahead of time before the 

city of Morgan Hill has a $100 million cleanup on their hands and 

no company left again to do the cleanup. 

And I think across the board when there is evidence and associations of risk, we need to act accordingly. Mr. Chairman, I don’t 

have another 3 minutes of voice, so I am going to refer back to you. 

Mr. MARKEY. Thank you. William Shakespeare said that brevity 

is the soul of wit, and I think you got right at the heart of the matter, and we thank you for that. 

The gentleman from Texas, Mr. Green. 

Mr. GREEN. Thank you, Mr. Chairman. I would like to ask unanimous consent to place a statement in the record. 

Mr. MARKEY. Without objection, it will be so ordered. 

[The prepared statement of Mr. Green follows:] 


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Congressman Gene Green 

Subcommittee on Energy and Environment 

"Endocrine Disrupting Chemicals in Drinking Water: Risks to the Human Health and thc 

Environment" 

February 25, 2010 

Mr. Chairman, thank you for holding today's hearing on "Endocrine 

Disrupting Chemicals in Drinking Water: Risks to the Human 

Health and the Environment." 

Protecting our nation's drinking water supply from contaminants 

and microbiological diseases is of utmost importance to 

communities across the nation. 

Of particular growing concern is the presence of endocrine 

disrupting chemicals, or EDC's, and their potential health impacts 

on humans and wildlife. 

The prevalence ofEDC's in consumer products, food, 

pharmaceuticals, and the environment have led scientists and the 

federal government to evaluate the impact of EDC's on endocrine 

systems. 

Several studies have linked EDC's to increased birth defects, 

premature births, infertility, or even cancers. 

Increased levels of certain chemicals in the ambient environment 

have also led scientists to find abnormal impacts on insects and 

aquatic life, including the discovery of intersex fish species in the 

Potomac River. 

As a result of these concerns, Congress directed the Environmental 

Protection Agency (EPA) in 1996 to create an endocrine-disruptor 

screening program for drinking water and pesticide contaminants. 
71 


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2 

Surprisingly, it was not until October 2009 that the EPA issued the 

first test orders for the program, identifYing 67 chemicals to undergo 

Tier 1 testing. 

That same month, the EPA also published a list of unregulated 

drinking water contaminants that may require regulation under the 

Safe Drinking Water Act. 

I look forward to learning more from the EPA today about the status 

of these regulations and research on these chemicals. 

I also look forward to continue working through Congress to 

address the health and safety of our water supplies. 

That is why I am an original cosponsor of the Safe Drug Disposal 

Act of2009, introduced by my good friend and colleague Rep. Jay 

Inslee, which seeks to keep chemicals from prescription drugs -

including EDe's -- out of our drinking water supply. 

I also supported the Safe Drinking Water for Healthy Communities 

Act last Congress to set a time line for the EPA to set a national 

drinking water standard for perchlorate, a known EDC. 

Thank you Mr. Chairman. I look forward to the testimony this 

morning of our distinguished witnesses. 

I yield back the balance of my time. 
72 

Mr. GREEN. Dr. Solomon, this is for you and I would enjoy hearing other on the panel that has an opinion. Some have suggested 

that the present endocrine disruptors in drinking water isn’t really 

that alarming because the levels at which they are detected are so 

low. 

First, are there adverse health effects associated with low-dose 

exposure to these chemicals? 

Dr. SOLOMON. There are a few reasons why I am concerned about 

these chemicals in drinking water. One was actually raised by the 

chairman and other members of the committee, which is the fact 

that wildlife populations exposed to some of these source waters in 

which various low doses of endocrine disruptors are present are 

showing abnormalities such as the intersex fish seen in the Potomac River and in many other rivers and streams across the United 

States. 

I am also concerned because there are quite persuasive data 

showing that multiple chemicals can actually act together to create 

greater effects as mixtures or at least additive effects. And there 

are complex mixtures of various endocrine disruptors. As I mentioned in my testimony, up to more than 30 chemicals in a single 

water sample have been reported by the USGS. 

And in addition, I am concerned because of the remarkable sensitivity of hormone systems, not so much in the adult, where, as Dr. 

Borgert mentioned, there are some ability to sort of almost, you 

know, respond or buffer some alterations in hormones that occur, 

you know, transiently or even longer term, but in fetuses and infants where short-term alterations in hormones can actually have 

long-term effects on normal development. And so it is really those 

populations that I am most concerned about. 

Mr. GREEN. My second question, and again open it to the panel. 

What you are saying then is when someone is exposed to low doses 

from several different potential endocrine disruptors has a problem, 

so you answered the second question. Dr. Borgert or anyone else 

have a response to that question? 

Mr. BORGERT. Yes, I do. I think it is on point and raises an issue 

of one of the things that Dr. Solomon said. Mixtures are definitely 

an important area of research. I have devoted a large portion of my 

career to that, have several publications on it. About a year ago in 

December, I addressed the National Research Council on the issue 

of mixtures of pharmaceuticals in the water supply. 

And here again my message was similar. We need to rely on 

demonstrated scientific methods, and it hasn’t been demonstrated 

by any stretch of the imagination that these very low levels of 

chemicals with low potency actually have synergistic effects or even 

additive effects at the levels in the environment at which we encounter them. 

At higher levels, perhaps, but one of the rules of mixtures is 

what happens at one level and one ratio of components is not predictive of what happens at other levels and other ratios of those 

components. So we can’t make those extrapolations. And one of the 

things we know is it is incorrect to do that, so it is best not to do 

that. 

Mr. GREEN. Obviously we have a difference here from both our 

doctors. 


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Ms. BIRNBAUM. I would like to comment on that, if possible. 

Mr. GREEN. In fact, let me actually get you a question though. 

Obviously it has been suggested that although endocrine-disrupting 

affects animals, it has been demonstrated humans are better able 

to deal with low doses of chemicals without suffering adverse effects. Can you talk about the low dose issue earlier? And along 

with that, are humans any different from other animals that may 

consume drinking water? 

Ms. BIRNBAUM. Nature is inherently conservative, and the endocrine system is well conserved across from fish to amphibians to all 

the way up to mammals, and that includes us. There are numerous 

effects of endocrine effects in wildlife, not only fish, but for example 

amphibians, bird, and mammalian wildlife as well as beginning, we 

are seeing effects in people. 

I have to say that there is a great deal of data on mixtures at 

low environmentally-relevant concentrations for a number of different endocrine kinds of effects, effects on estrogens, effects on the 

androgen system, effects on the thyroid system, which demonstrate 

in animal models that additivity—at low concentrations again I am 

talking about. I am not talking about high levels. I am talking 

about low levels—appear to act in an additive fashion. So I think 

we have a real issue when we look at one chemical at a time instead of looking at multiple chemicals at low levels in the body at 

a time. 

Mr. GREEN. And again is there research being done now on the 

low level for multiple exposure? 

Ms. BIRNBAUM. Yes, there is. We are funding a great deal of research in that area, and I should mention that I have published extensively myself in this area of mixtures, and it is very important 

that you work at low levels because if you go to very high levels, 

I agree with Dr. Borgert that different things can happen. But you 

need to work at low levels. 

And we are funding work. For example, we are actually funding 

some studies right now at the Environmental Protection Agency’s 

Office of Research and Development to look at the interaction of 

multiple phthalates which have been shown to interact additively 

in blocking androgen action. 

Mr. GREEN. Thank you, Mr. Chairman. Any other response from 

anyone on the panel? 

Mr. BORGERT. Just one. I think we are using qualitative terms 

like low doses, and I think we have probably a difference of viewpoint on what is low. And I don’t think that it has been demonstrated that the levels of these chemicals to which humans are 

exposed are acting in an additive fashion. That is an unresolved 

question, and again my caution I think have stated. 

Mr. GREEN. Well, and again no matter what level we make the 

low dosage, the concern and the question was low dosage of a multiple number of endocrine disruptors in low dosage because we may 

not have a high dosage. But because of our lifestyle, we have multiple opportunities to have that. 

So thank you, Mr. Chairman. I know I have run out of time. 

Mr. MARKEY. Gentleman’s time has expired. Chair recognizes the 

gentleman from Louisiana, Mr. Scalise. 


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Mr. SCALISE. Thank you, Mr. Chairman. A couple of questions. 

First for Dr. Birnbaum. I think you had spoken or there was something written about your agency a few months ago that there were 

a number of research grants to university professors and others as 

part of the stimulus bill that, I think, totaled somewhere around 

$30 million. Primarily they were supposed to be used to conduct 

additional research on BPA. Can you tell me what processing criteria you used through the agency for the awarding of the grants 

and then also if you can give us an idea of how many new jobs 

were created by that stimulus money? 

Ms. BIRNBAUM. The stimulus money, we funded somewhere in the neighborhood of $10 to $15 million worth of research on BPA. 

The process that was used by NIH to give the stimulus money as 

part of our usual very, very extensive extramural peer review process. So some of the BPA work was funded under a special program 

coming from funding partly directly from our agency and partly 

from the office of the director, which is called the Challenge Program and the GO Program. And these were for high-priority needs 

to address health effects in the Nation. 

So that there was a request made for innovative research to address projects. The GO projects, known as the Grand Opportunity, 

were for projects. And in our agency, one of the topics that we put 

out was for understanding and expanding our knowledge base on 

BPA. 

We have funded 11 specific grants that are looking at the effects 

of BPA. These are effects looking at cancer, both prostate and 

mammary, but looking at the immune system, looking at developmental neurological effects, looking at cardiovascular effects and a 

variety of animal models. 

In addition, BPA has been in our sites for a number of years and 

in our regular extramurally-funded and peer-reviewed grants programs. We are looking at effects of BPA in human populations as 

well, and as I mentioned, one of the first results from that was recently published in the peer review literature, clearly needs to be 

repeated, but demonstrates an association between the mother’s exposure of BPA during her first trimester and neural behavioral effects in her children of 2 years of age. 

We are also funding ongoing studies with FDA to look at longterm effects in both rats and mice to BPA. We are also funding 

some studies in our intramural program in collaboration with outside investigators. 

Mr. SCALISE. I apologize for pulling back because I am limited on 

my time. 

Ms. BIRNBAUM. I was going to mention the—— 

Mr. SCALISE. But I did want to ask—and I don’t know if all those 

grants you were talking about, how much was stimulus money 

versus just regular department money. 

Ms. BIRNBAUM. About $10 to $15 million. 

Mr. SCALISE. So all that $10 to $15 million of stimulus money 

which was supposedly brought forward to create jobs, how many 

jobs were created with the $10 to $15 million of stimulus money? 

Ms. BIRNBAUM. Specifically with the BPA, I can tell you with the approximately $168 million of funding that NIEHS was allotted to 

send to the extramural community with the stimulus money, that 


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that has funded about 300 different grants. And we know that new 

jobs—I am not talking about continuation of jobs—but new jobs 

was about 436 new jobs. 

Mr. SCALISE. OK, and if you can get us the information on those 

new jobs. 

Ms. BIRNBAUM. We can get you more specifics. 

Mr. SCALISE. And specifically with the stimulus money portion, 

not your regular department. 

Ms. BIRNBAUM. I am just talking about—the 430 plus jobs—— 

Mr. SCALISE. Right, but we were told during the passage of the 

stimulus bill that there would be transparency in actually tracking 

the jobs created with that money, not with other money, with the 

stimulus money. I am just asking you for that transparency if you 

could get that to me. 

Ms. BIRNBAUM. I would be happy to provide it. 

Mr. SCALISE. Thanks. 

Ms. BIRNBAUM. I believe that is available—— 

Mr. SCALISE. Next question because I only have a minute left. 

During your written statement, you had mentioned that you try to 

ensure that focus on doing high-quality science or ensuring that its 

work adheres to the basic tenets of good objective science. Your 

statement didn’t mention that. What I am asking you is would you 

give us a pledge that when you are doing this work that you would 

only adhere to the basic tenets of good objective science since that 

wasn’t in your testimony? 

Ms. BIRNBAUM. Peer-reviewed science stands the nature of time, 

and our studies are undergoing extensive peer review both in the 

funding of studies, in the conduct of studies, and in the actual publication of studies. The NTP studies, which are funded are considered the gold standard for traditional toxicity kinds of testing. I 

think it is very important to understand that science is moving on, 

and the best studies of 20 and 30 years ago may not be the best 

studies. 

Mr. SCALISE. But would you base the decisions on the best 

science? 

Ms. BIRNBAUM. My studies are always based on the best study 

of all the peer-reviewed science. 

Mr. SCALISE. Thank you, and I yield back. 

Mr. MARKEY. Gentleman’s time has expired. The chair recognizes 

the gentleman from Washington State, Mr. Inslee. 

Mr. INSLEE. Thank you. I am just looking at an article from the 

Seattle Times. I am from Seattle. In 2007, it talked about fish, 

English sole, carrying something in their bodies not supposed to be 

there, a protein usually found only in female fish with developed 

eggs. And we found these chemicals, and the article quotes sources 

of suggestion that birth control pills, plastic bottles, detergent, 

makeup, and more chemicals from various sources may be associated with that protein. 

Dr. Birnbaum, first of all, I don’t understand this biology as well 

as I should. Is that protein that this article is referencing the 

chemical itself, or it is an expression or result of the presence of 

a chemical that causes that protein to be there where it shouldn’t 

be? 


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Ms. BIRNBAUM. You are talking about fatelegenin, which is a protein that is normally only present in female fish, and if the females 

are exposed to endocrine-disrupting chemicals, then in fact the 

males begin to produce fatelegenin. So just like in the Potomac 

River and parts of Puget Sound and many other waterways in our 

Nation, we are finding male fish that have eggs in their testes, and 

they are producing fatelegenin. 

Mr. INSLEE. And what is that mechanism? I don’t understand. 

You said if the female is—you mean the mother of the male? 

Ms. BIRNBAUM. No, these are the fish, female fish produce 

fatelegenin, which is a protein that actually goes into making the 

egg. It goes into the egg and provides nutrition for the baby, you 

know, the developing embryonic fish. Males, when exposed to environmental endocrine disruption, they begin producing fatelegenin, 

and they also begin making eggs. 

Mr. INSLEE. They pick it up from the water? 

Ms. BIRNBAUM. No, they get the endocrine-disrupting chemicals 

from the water or food particles in the water. But then they 

make—that is their response to the disruption. 

Mr. INSLEE. So is there a question about whether that is in fact 

occurring in our waters or not? Is that subtle science? 

Ms. BIRNBAUM. I think there is extensive evidence for the presence of male fish producing female responses. 

Mr. INSLEE. And is there any other hypothesis been suggested 

that it is other than endocrine disruptors that are causing this? 

Ms. BIRNBAUM. I don’t know of any. 

Mr. INSLEE. Does anybody in the panel have any other hypothesis as to what is causing this other than endocrine disruptors? 

Mr. BORGERT. I think it is important to understand what we 

mean when we say endocrine disruptors, and Dr. Birnbaum mentioned this, I believe, in her answer. But we don’t know exactly 

which chemicals might be doing that, for instance, and there have 

been instances where we again rush to judgment on similar findings of fatelegenin in male fish in the U.K. And based on those preliminary suspicions, a number of products were taken off the market because they were suspected endocrine disruptors. 

Turns out the most likely culprit was simply female hormones 

from human beings, and the water treatment plants were not up 

to snuff. They were not state-of-the-art, and they were not properly 

breaking down those compounds. Some of the compounds also may 

have been birth control pills. 

So it is important to recognize that when you see an effect, that 

doesn’t automatically tell you which chemicals might be involved. 

And so I think that is one of the critical questions. 

Mr. INSLEE. So is it—— 

Mr. BORGERT. Brings up another—well, I just wanted to make a 

quick point is that our analytical techniques are now thousands if 

not ten thousand-fold better than they were a decade or so ago. So 

what would appear to have been a perfectly clean water sample a 

decade ago now looks very contaminated, and that is simply because our analytical techniques are so much better. 

Mr. INSLEE. Well, I guess—— 

Mr. BORGERT. Finding what the cause is is not always easy. 


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Mr. INSLEE. What I am trying to get at is it relatively clear that 

the presence of maybe not specifically identified but generally defined as endocrine disruptors in our waterways are causing the 

presence of proteins in male fish that are not normally there. When 

I say normally meaning absent an industrial base that pollutes our 

water. Is that fairly well established, Dr. Birnbaum? I will just ask 

your opinion about that. 

Ms. BIRNBAUM. Absolutely. 

Mr. INSLEE. OK, Mr. Jones? 

Mr. JONES. Yes, I would agree with that. 

Mr. INSLEE. Dr. Solomon? 

Dr. SOLOMON. Yes, I would agree with that. 

Mr. INSLEE. And Dr. Borgert? 

Mr. BORGERT. Yes, I would agree that it can happen. I would 

have to disagree though that that is always the case. We don’t 

know of all the factors that might affect that, and in some instances, their habitat alterations for other effects that cause other 

effects that may lead to the same thing. I don’t think we have unraveled the story completely. 

Mr. INSLEE. But we don’t think it is sunspots, right? I mean we 

would agree we don’t think there are sunspots? That is a rhetorical 

question. 

Mr. BORGERT. I haven’t heard sunspots. 

Mr. INSLEE. Well, we have heard sunspots blamed for a lot of significant global activity. We just wonder if this is another one of 

them. Mr. Jones, can you give me sort of a lay answer that I can 

convey to my constituents on what percentage of chemicals that in 

the realm of possibility could be considered endocrine disruptors 

will be adequately tested by X date that we can tell our constituents that will have been receiving an appropriate level of the 

screening to determine whether or not they present a human 

health risk? Could you give me percentages by certain dates on the 

current track that we are on? 

Mr. JONES. The current track that we are on will take many 

years to tell you what that percentage is. The universe of chemicals 

in front of us include a thousand pesticides, and people throw 

around the number of 80,000 industrial chemicals. It is probably 

actually more in the range of 40,000. So we are talking about tens 

of thousands of compounds. Under current techniques, it will take 

many years to evaluate them all. We are working very hard with 

our colleagues in NAHS and some other agencies within the executive branch to develop alternative methods that will allow us to 

test thousands of chemicals in very short periods of time. 

That work, however, is not quite ready up to the task that we 

are seeking and that you are asking for. So I am hopeful that within the next 5 years those kinds of methods are available which will 

allow us to test thousands of chemicals in a matter of weeks as opposed to hundreds of chemicals in a matter of years. 

But that is still developmental. Under the existing framework 

that we have, it takes quite a while to even do the screening test, 

and we are talking about a universe of, as I said, upwards of 

40,000 chemicals that you would need to screen to be able to tell 

you which percentage—— 


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Mr. INSLEE. Very quickly. Probably be a decade before we have 

50 percent of these tests—— 

Mr. JONES. Absolutely. 

Mr. INSLEE. —concluded? Thank you. 

Mr. MARKEY. The gentleman’s time has expired. And just for 

clarification, Mr. Jones, earlier you told me that BPA was not on 

the list of chemicals that EPA was using to examine the purposes 

of setting drinking water standards. But I had asked you why EPA 

didn’t put BPA onto its chemicals of concerns action plan despite 

the data and the administrator’s statements regarding her concerns about the chemical. Can you clarify? 

Mr. JONES. Yes, and thank you for asking that. Going back to the 

CCL list part of my answer. 

Mr. MARKEY. What does CCL mean? 

Mr. JONES. The chemical contaminant list. That is the list of potential drinking water contaminants for regulation that was released last summer. It is not on that list; however, the work that 

is going on right now at the Food and Drug Administration, which 

we are working with them on, could ultimately lead to a different 

conclusion. So that work will inform future CCL lists. 

As it relates to BPA as an industrial chemical as opposed to a 

drinking water contaminant, the agency is planning on in the nottoo-distant future—and the administrator has spoken to this, and 

I think she actually testified yesterday at the appropriations hearing. That action plan is with the Office of Management and Budget 

right now going through interagency review, and we are hopeful 

that it will be publicly released in the very near future. So it could 

be on that last. Yes, it will be on that list. 

Mr. MARKEY. OK, it will be on that list. OK, that is important. 

OK, so we thank you all for coming here today. It is a very important hearing, and we thank anyone who has been watching this 

hearing on C–SPAN today. The endocrine system for human beings 

is really just our computer system. It is just a computer, and like 

a computer, if someone hacks in to a computer and drops in a new 

virus, it can cause a tremendous disruption to a computer. 

And there is one thing no one wants in America or in the world 

is for someone to hack in to their computer, for someone to add in 

a virus that can begin to disrupt it. No matter how small that virus 

might be, it is a big change in your relationship with the computer. 

Well, the endocrine system is the computer system, and that is 

why we are so concerned about it, that the more that the water, 

other avenues, that are used in order to disrupt the endocrine system, the computer system for human beings, you start to get these 

very significant or even minor changes in the body. And it can have 

very significant changes in the way in which people live. 

And so that is why it is so important, and since we are seeing 

significant changes over the last 30 or 40 years, whether it be, you 

know, autism or you go down the whole list, we are wondering 

what is happening? Why are we seeing so much larger identification of these problems in human beings? 

And so, you know, scientists are like the detectives. They look 

around. They see what could have hacked in to the human being. 

What is different? What is going into human beings that weren’t 


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going into human beings before especially as they affect children 

because that is when the system is most vulnerable? 

That is when a computer is most vulnerable, when it is brand 

new. You know it hasn’t quite developed all of its defenses yet. You 

haven’t added in all of the software packages that can defend, and 

so it is much more vulnerable to changes, OK. 

So that is why we are so concerned about it, and that is why I 

am concerned about BPA as it affects especially things that are 

close to children. That is what my legislation would be most concerned with, the kinds of things that children would be putting into 

their bodies because obviously that would have a more profound effect on the computer system of the body. 

So we thank you so much for your testimony here today, and in 

the weeks and months ahead, we are going to be pursuing this very 

aggressively. And I want to make sure that the right things are 

done in order to protect against the things which we think have a 

higher likelihood of having an impact especially upon children in 

our country. 

So we thank you all for your testimony, and I tell you what I am 

going to do. I am going to give each of you 1 minute to summarize 

what it is that you want us to remember about your testimony and 

would ask you to put it in as simple a language as is possible. And 

try to use as many monosyllabic words as you can in order to make 

it possible for us to in 1 minute understand what you are trying 

to tell us. We will go in reverse order of the opening statements, 

and Dr. Borgert—I am sorry as you are, I am sure, that Humphrey 

Bogart ever lived. That your name is constantly mispronounced. 

But we thank you, sir, for being here. Whenever you are ready, 

please begin. One minute. 

Mr. BORGERT. Well, thank you for that opportunity, sir. I would 

just leave you with one admonition, and that is to make sure that 

the information we gather is based on repeatable science, that is 

based on reliable science, that is based on relevant science, and 

that the data be evaluated for themselves for the relevance and reliability and repeatability and not merely over what can be suggested or hypothesized from that data, but what the data actually 

show. And I think that is very important in any decision-making 

process that will involve regulation because we risk actually imperiling ourselves rather than protecting ourselves with faulty information. 

Mr. MARKEY. OK, thank you. Dr. Solomon. 

Dr. SOLOMON. Yes, as was the case around the health effects of 

tobacco, there were many, many years through questions being 

raised and, you know, claims that the science was not totally clear 

yet. And it is always easy to do that kind of thing because science 

is never 100 percent crystal clear. But we do need to act based on 

the information we have, and major medicine societies such as the 

Endocrine Society and the American Medical Association have concluded, I actually quote ‘‘the evidence for adverse reproductive outcomes in fertility, cancer, malformations, from exposure to endocrine-disrupting chemicals is strong.’’ 

So we need to look at the conclusions of these important medical 

organizations and move to take action to protect human health. 

Thank you. 


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Mr. MARKEY. Thank you, Dr. Solomon. Mr. Jones. 

Mr. JONES. EPA is very worried about endocrine-disrupting 

chemicals not only in drinking water but in other media, and we 

are moving very aggressively in our testing program. Although, we 

are as frustrated as the committee is and many others of the public 

about how long it took to develop a testing schematic to evaluate 

chemicals for endocrine disruption. 

We have done that now, and that testing schematic is ready to 

be deployed. And we will be deploying it aggressively I think as 

evidenced by the first orders that have gone out in the last three 

months and our commitment here today to begin using the discretionary authority in the Safe Drinking Water Act to begin screening chemical contaminants in drinking water in the very near future. 

Mr. MARKEY. Thank you, Mr. Jones. Dr. Birnbaum. 

Ms. BIRNBAUM. Fish, frogs, birds, and mammalian wildlife are 

our canaries in the coalmine when we talk about endocrine disruption. The doses that are causing these effects when you look in the 

animals are many times comparable to the effects that we actually 

are measuring in humans, and we are finding that essentially the 

entire American population has these chemicals in their body. 

These chemicals are not associated with one health effect. They 

are associated with a multitude of health effects because what the 

hormones do is integrate everything in our body. They control development, and they control our normal way of life. Thank you. 

Mr. MARKEY. Thank you, Dr. Birnbaum, very much. So we thank 

all of you for being here. I think the lessons that were learned is 

that in order to ensure that drinking water is safe that we must 

make sure that the endocrine disruptor screening program robustly 

and aggressively tests chemicals to see which ones cause endocrinedisrupting health effects and that the screening program adapts its 

tests to take advantage of new scientific advances and that we 

move in a way that does so in a very rapid process because the 

EPA additionally must move forward to regulate known endocrine 

disruptors without conducting redundant and duplicative tests. 

When we have enough information, we are going to have to move 

because clearly there are families all across the country very concerned about the impacts, especially upon children. And as soon as 

we reach that level where we have enough evidence, I just think 

that we should err on the side of caution because some very significant things are happening amongst children in our country that we 

have not seen in previous generations. And we know it is related 

to this endocrine-disruptor issue. 

So we thank you all so much. We are going to be working very 

closely with you in the months ahead. This hearing is adjourned. 

[Whereupon, at 11:30 a.m., the Subcommittee was adjourned.] 

[Material submitted for inclusion in the record follows:] 


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Statement ofthe Honorable Joe Barton 

Hearing on Endocrine Disruptors and their Effects in Drinking Water 

Subcommittee on Energy and Environment 

February 25,2010 

Thank you for recognizing me to provide an opening 

statement and thank you for calling today' shearing 

on a topic that is increasingly getting media attention. 

Before I get to my remarks on the issue oftoday's 

hearing, I want to congratulate you, Mr. Chairman, 

and express my support for your efforts - in holding 

this hearing -- to remind certain committees in this 

Congress which committee has expertise and 

jurisdiction over drinking water programs. I think we 

do a pretty good job and we don't need the help of 

others to make a complicated process disjointed. If 

any House committee should be telling EP A what to 

do in the operation of its drinking water or chemicals 

programs, it should be this committee. 

As far as the issue of endocrine disruption goes, I am 

more than interested to hear about this subject and 

ferret out what the actual science on this matter is 

from creative suppositions that sound appealing. We 

need an environmental policy in this country that is 

predicated on high quality science, whose results are 

repeatable, and whose objective is not to answer 

questions for which we already have decided the 
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answer. If we are not using science to make 

decisions, we should be honest and transparent 

enough to tell the public that opinions and not the 

actual science are the real pillars behind these 

decisions. 

While I think there is enough data to suggest that 

there are substances that affect wildlife, I am much 

more skeptical about the universe of these substances 

that might translate to humans. I hope we will have a 

robust discussion to help inform us on that score. 

Further, if the route of exposure is drinking water, I 

think we need to be very clear that other actions, 

including waste and sewage management are 

appropriately factored into this equation concerning 

endocrine disrupting substances -- as well as the 

existing disinfection process used by today' s 

community water systems -- to examine whether 

doses worthy of concern, not just detection, exist and 

require action. 

We should find out today if public health trade-offs 

are being made based on decisions to eliminate 

chemical substances based upon minimal evidence 

and maximum uncertainty . We must ascertain 

whether politically popular substances are being 

focused on in this debate rather than ones required 

by the Safe Drinking Water Act - to be addressed 
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first because they present the greatest health threats 

and are present or are likely to be present in drinking 

water. 

We need to know that the Federal programs involved 

in this effort are using the funding we have given 

them in the most appropriate manner - that money is 

not being spent just to be spent and that a real plan is 

in place to obtain high quality results worthy of 

serious scientific scrutiny. Fundamentally, I think we 

should find out if these programs are focused on 

doing their statutory missions well rather than doing 

a lot of politically expedient things in a mediocre 

fashion. While I recognize that some are upset that 

certain Federal agencies haven't served them the 

results they wanted in the timeline they wanted, the 

fact is that high quality science takes time and we 

need to make sure those in charge are not hindered or 

blinded to ensuring high-quality, objective science 

answers questions to the best of its ability. 

From my work in this committee on the Toy Bill, I 

am familiar with the claims and counterclaims of 

what threats are really posed by various chemical 

substances. We made some decisions in that bill that 

sounded like a good idea at the time based on some 

interesting, but not overwhelming science, and the 

results have turned out to be a nightmare. We need 
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to make sure that we are more critical in asking 

questions about science underpinning various 

regulatory and legal policies before making the same 

mistakes. 

Mr. Chairman, I take this subject seriously. I think 

there are some substances that pose real problems. I 

am glad we have an expert panel to educate on this 

matter because I want to know more about how 

widespread of a problem we are facing. 

I thank you for yielding me this time and yield back 

the balance of my time. 
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Congressman Michael C. Burgess, M.D. 

Opening Statement 

Subcommittee on Energy & Environment 

Hearing entitled "Endocrine Disrupting Chemicals in Drinking 

Water: Risks to Human Health and the Environment" 

Thank you, Mr. Chairman. 

r think this is an important oversight hearing into the Environmental 

Protection Agency's process of monitoring and regulating certain 

chemicals which may be posing risks to human health via our drinking 

water systems. Having practiced medicine for 25 years before joining 

Congress, I made it a life-long mission to protect the health of those 

patients who came to me back home in Texas, and I believe I've 

continued that mission here. 

Chemicals have become a pervasive part of our daily lives the globe 

over for the past century. Indeed, chemicals have made our lives better 

in a plethora of ways, responsible for medications and anti-bacterial 

hand soaps, providing affordable consumer products, and serving as cost 
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effective pesticides, protecting crops and humans from such things as 

malaria-causing mosquitoes. 

However, the flip-side of any discussion on chemicals is the reality that 

certain chemicals in certain concentrations can indeed be harmful to 

human and animal health. We all know this. Utilizing chemicals to 

make our lives easier and safer comes with risks, and those risks must be 

balanced and weighed against the benefits the chemicals provide. This 

cost-benefit analysis can only be done after we are presented with solid, 

scientific findings as to the full harm any given chemical poses. 

The EPA is best positioned to provide us with these scientific findings, 

and indeed this task falls most squarely within EPA's mission. In 1996, 

Congress gave EPA the tools to look into which chemicals could be 

posing harm to our health. Yet here we are, 14 years later, and we all sit 

behind this dais, scratching our heads and wondering what EPA has 

been doing for the last decade. It's almost incredible how quickly EPA 

can make scientific findings on climate change, which to hear some 
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people tell it, will kill us all in the decades to come, yet has sat on its 

hands in regards to whether the chemicals we are exposed to in our 

everyday lives are going to kill us in a matter of months. 

I'm happy we are having this hearing, and I hope that shat comes out of 

it is that EPA will refocus its efforts on the true mission of the agency: 

protecting Americans in their everyday lives from harmful agents in the 

environment. EPA should leave saving the world to Congress. 
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Government Affairs Office 

NVV 

F 202 628 2846 

The Authoritative Resource on Safe Water co" 

Statement 

F 303.3470804 

awwa org 

for the House Subcommittee on Energy and Environment 

on Endocrine-Disrupting Compounds in Drinking Water 

February 25, 2010 

The American Water Works Association (AWWA) would like to offer some comments on the 

subject of endocrine-disrupting compounds (EDCs) and pharmaceuticals in water. AWWA is 

the world's oldest and largest association dedicated to safe water. Our utility members serve 

safe and affordable drinking water to more than 80 percent of the American people, 

Contrary to reports that characterize EDCs and pharmaceuticals in water as an entirely new 

issue, these substances were first reported in US waters by the U,S, Environmental Protection 

Agency (EPA) in 1975, The fact that more are detected today is a reflection of the increasingly 

sensitive analytical technology that allows us to identify and quantify diminishingly minute 

concentrations of these substances in water. 

AWWA believes the critical question we must address is not "Do they exist?" but rather, "At 

what concentration are these compounds harmful to human health?" Only then can we make 

intelligent, rational decisions that protect the health of this country's municipal water customers, 

AWWA is dedicated to protection of public health, Accordingly, we have intensively analyzed 

available information in the pursuit of ensuring the safety of the nation's water supplies, entirely 

without a federal mandate, In particular, we point to the research conducted by Dr. Shane 

Snyder, Research and Development Project Manager for the Southern Nevada Water Authority, 

The cities that participated in a study conducted by Dr. Snyder -- by submitting water samples 

for analysis -- did so in the absence of any regulatory requirement, being proactive and going 

well above and beyond the regulations in the interest of furthering understanding of this issue, 

Dr. Snyder's studies have been transparent, and have been published in open literature and 

frequently presented in public forums, As a scientist, Dr. Snyder strongly cautions that in order 

to provide meaningful information on EDCs and pharmaceutical compounds in water, scientists 

need both occurrence data and human health effects information, It is scientifically inadequate 

to communicate solely on what we can measure at any level without a frame of reference for 

what that means, 

AWWA has frequently been asked about the sources of these substances in our waters, We 

will not go into it here in detail, but will note that both nonpoint source runoff and sewage 

effluent from properly operated waste treatment plants may contain minute traces of these 

compounds, Some minute quantities of these products will pass through animals and humans 

who use them, and enter the waste stream, They are typically not completely destroyed or 

removed by waste water treatment processes, 
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A more central point about our studies is that the few EDCs and pharmaceuticals we did detect 

in US drinking waters occurred at unfathomably low concentrations, To illustrate that point, 

consider this: If Dr. Snyder's study had been constrained by the ability to find these compounds 

at parts-per-billion levels instead of delving into the parts-per-trillion range, none of them-not a 

single one-would have been found, 

This raises the critical question we suggested earlier: are we going to make decisions based 

upon our ability to find contaminants, or based upon protection of public health? AWWA can 

say with absolute certainty that, if the country regulates contaminants based upon detection 

rather than health effects, we are embarking on a futile journey without end. The reason is 

simple: Decades ago, we could only detect contaminants at parts per million levels, Years ago, 

we advanced to parts per billion, We are now able to detect compounds at the parts-per-trillion 

level, and are breaching the parts-per-quadrillion boundary in some cases, The truth is that the 

concentrations of EDCs and pharmaceuticals found in water supplies are millions of times lower 

than a medical dose. Consider that the highest concentration of any pharmaceutical Dr. Snyder 

detected in US drinking waters is approximately 5,000,000 times lower than the therapeutic 

dose. This concentration is difficult to perceive, so consider these analogies. This 

concentration is roughly equivalent to y, of an inch in the distance between the earth and the 

moon, or in terms of time, this concentration would be equivalent to approximately one second 

in approximately 750 years, Based upon Dr. Snyder's four-year study of the heaHh relevance of 

trace EDCs and pharmaceuticals, using the highest concentrations found and the most 

conservative safety factors to protect susceptible populations such as infants and pregnant 

women, one could safely consume more than 50,000 eight-ounce glasses of this water per day 

without any health effects, Dr. Snyder's report, "Toxicological Relevance of EDCs and 

Pharmaceuticals in Drinking Water," published by the Water Research Foundation, 2008, 

concluded that the concentrations of EDCs and pharmaceuticals studied are on orders of 

magnitude lower than would pose a public health threat. We are not suggesting that this is the 

final, definitive study on this issue; in fact, we urge Congress to support further health effects 

research, 

That said, the Safe Drinking Water Act already has established processes for identifying and 

regulating drinking water contaminants to protect human health, The Candidate Contaminant 

List and the Unregulated Contaminant Monitoring Rule are appropriate processes that entail 

great scientific rigor. We caution against regulating EDCs and pharmaceuticals any differently 

than the scores of contaminants currently covered by the Safe Drinking Water Act, because in 

reality they are no different. Our decision as humans to improve and extend our lives by using 

pharmaceuticals dictates that some infinitely small amount of these products can and will make 

their way into the environment. The fact that we can detect trace contaminants does not alone 

imply risk, 

With regard to removing these compounds through treatment, Dr. Snyder's team tested the 

effectiveness of a diverse array of water treatment technologies on removal of pharmaceutical 

compounds, and to be certain. some technologies are more effective than others, However, 

back to the pinnacle question: is use of these treatment technologies going to be warranted to 

protect public health, because there are environmental and societal costs associated with using 

them. In an age where we are concerned about greenhouse gas emissions and energy 

efficiency, is it wise to dictate energy-intensive water treatment systems when there is no 

evidence of public health benefits? Additionally, there is a looming crisis related to aging water 

infrastructure that will require a vast financial investment by utilities, Should that be set aside so 

treatment to remove all concentrations of a compound is achieved? 
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So what should we do? A'vVWA believes the following steps make sense, 

First, this issue does highlight the need to better protect America's sources of drinking water 

from various sources of contamination, 

Second, clearly there is a pressing need for additional research on this issue, We understand 

there are concerns about the effects such chemicals have within the natural environment, as 

well as human health, We recommend that we focus on research related to health effects from 

trace EDCs and pharmaceuticals with a lesser emphasis on occurrence, in order to determine 

whether there is in fact a problem to solve, 

Our additional recommendations are spelled out in more detail below: 

1. EPA should work with states, water and wastewater utilities, and the agricultural community 

to minimize contamination of source waters by EDCs and pharmaceutical products as well as 

other contaminants. 

It is imperative that the nation do a better job of protecting its waters, and especially sources of 

drinking water. from contamination, We have said previously that there is an imbalance 

between the enforceable controls on point sources, such as Publicly Owned Treatment Works. 

and the far less rigorous programs used to limit non point sources of pollution, such as 

agricultural runoff, Congress may wish to evaluate this issue to assure that all sources of 

pollution are equitably contributing to the protection of the nation's waters. 

2, We urge support for proper pharmaceutical disposal programs to reduce the flushing of 

pharmaceutical products into sewage systems to the greatest degree possible, while 

recognizing that this addresses only a small part of the problem, 

Although more research would be needed to accurately characterize this issue, we believe it is 

likely that more pharmaceuticals end up in the environment after passing through animals and 

humans than after flushing unused products, However, some unused pharmaceutical products 

are undeniably flushed into waste streams, contributing to the problem but also offering an 

opportunity to make reductions in the pollutant loading through a "pollution prevention" 

approach, We urge support for pharmacy "take back" programs that make doing the right thing 

obvious and convenient for consumers. 

3, Elevate EPA's drinking water health effects research budget so that it is at least equivalent to 

the air pollution health effects research budget. Even though this Subcommittee does not 

appropriate funds, we ask you to support this increase. 

To date, no peer-reviewed published research has found ill effects on humans from EDCs and 

pharmaceuticals in the environment at the trace levels we have seen in drinking water. 

However, drinking water providers would like to see more research on this matter, so that we 

can either take appropriate action to address an actual health risk if there is one, or reassure the 

public that there is not one. Treatment to completely remove all traces of pharmaceuticals from 

drinking water wi!! be very expensive, and our customers have a right to expect that we will only 

undertake the investment necessary to do this - and increase their utility bills to pay this 

expense - if doing so addresses an actual health risk. 
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We also specifically support 1) a dedicated authorization in the Research Title of the Agriculture 

Reauthorization bill for collaborative research between the drinking water community and the 

agriculture industry on ways to limit contaminants from entering water supplies; and 2) a 

dedicated research authorization to support decisions on contaminant listing and rulemaking by 

EPA's Office of Ground Water and Drinking Water. These funds should be used to focus 

research on priority drinking water areas of concern, 

4. We should continue to rely upon EPA's science-driven Contaminant Candidate List (CCL) 

process to identify candidates for new drinking water standards. 

Though at times this process appears to move slowly, a methodical, science-based process is 

necessary for determining which contaminants need to be regulated, so that we focus on actual 

risk and on the higher risks first. The standard-setting process detailed in the Safe Drinking 

Water Act is sound, and setting standards through a science-driven process gives the public 

confidence that the regulations they pay for are necessary, reasonable, and protect public 

health, An increase in human health effects research, as mentioned in Item 3 above, would 

improve this process. 

5, We should continue to rely upon the Unregulated Contaminant Monitoring Rule (UCMR) for 

deciSions concerning testing and reporting to customers about contaminants that are not 

currently regulated, 

EPA employs a comprehensive and science-based approach to determining which unregulated 

contaminants utilities should monttor for, and what utiltties should say about these contaminants 

(if detected) to their customers. It is appropriate to use this kind of science-based process to 

determine which, if any, additional currently unregulated contaminants utilities should 

investigate. 

AWWA stands ready to work with Congress to improve the country's understanding of these 

complex issues. 

### 

Contacts: 

Tom Curtis 

Deputy Executive Director for Government Affairs 

202 628-8303 

Greg Kail 

Director of Public Affairs 

303734-3410 
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merican. 

Chemistry 

Council 

February 25. 20 I 0 

The Honorable Edward J. Markey 

Chairman, Subcommittee on Energy and Environment 

Energy and Commerce Committee 

United States House of Representatives 

Washington. D.C. 20515 

The Honorable Fred Upton 

Ranking Member. Subcommittee on Energy and Environment 

Energy and Commerce Committee 

United States House of Representatives 

Washington. D.C. 20515 

Dear Chairman Markey and Ranking Member Upton: 

The House Subcommittee on Energy and Environment is scheduled to hear testimony 

today from several witnesses concerning potential risks trom "endocrine disruptors" in 

drinking water. The American Chemistry Council (ACC). a national trade association 

representing 140 member companies which employ 800.000 workers, requests that 

ACe's perspectives on this issue be entered into the hearing record. 

In 1996. in response to public concern that some substances may interfere with endocrine 

processes in humans and wildl ife, Congress directed the EPA, to develop a screening 

program. using appropriate validated test systems and other scientifically relevant 

infonnation~ for evaluating the potential of substances to induce honnone-related health 

effects. I The Food Quality Protection Act (FQPA) mandated the screening of pesticide 

chemicals and gave EPA authority to require screening of certain other substances. It 

also required EPA to "take action" as appropriate. on substances found to have an 

endocrine effect on humans. under existing statutory authority available to EPA. Shortly 

aner passing the FQPA. Congress also passed an amendment to the Safe Drinking Water 

Act (SDWA) that gave EPA authority to test (in accordance with the FQPA provisions) 

for endocrine effects, substances that may bc found in sources of drinking \vater if EPA 

determines that a substantial population may be exposed to such substance. 2 

A fier these laws were enacted, it quickly became apparent, as the resuit of a stakeholder 

advisory process conducted by EPA. that the scientific complexity of the endocrine 

system and the technical difficulties of screening and testing chemicals for endocrine 

disruption would be major challenges. EPA assessed the current state ofthe science and 

found that there were few, ifany, scientifically valid screens and tests available to study 

the potential endocrine activity of chemical substances. Therefore EPA initiated an 

1 Food Quality Protection Act of 1996. 21 115.C 346(a)·§408(p 1 2 Safe Drinking Water Act Amendments of 1996, 42 U.S.c. 300j·17 

americanchemistry.com'" 13OCiWilson Boulevard. Arlington. V.,,> 222091 (701) 741.5000 ~;,) 
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The Honorable Edward J. Markey 

CI he I lonorable fred Upton 

February 25, 20 I 0 

Page 2 

extensive research and development program, composed of both basic and applied 

research\ to develop. standardize and validate the necessary endocrine test methods for its 

Endocrine Disruptor Screening Program (EDSP). The EPA has expended over $100 

million dollars since 1996 on this joint applied- and basic-research enort. 

The American Chemistry Council (ACq has played a conslructive role in the Agency's 

development ofthe EDSP. Our goals have been to see the EDSP implemented as quickly 

and efiiciently as possible and in a manner consistent with the law, the science and ACe 

members' commitment to the safe manufacture, transport, usc and disposal of chemicals. 

To those ends) ACe has consistently supported increased funding for the Agency~s 

research and laboratury sludies to develop, standardize and validate the screening and 

testing methods required for the EDSP. ACC also has sponsored technical studies to 

supply netAled data for endocrine test dcvclopment and validation, and has participated 

with thc broader scientific and stakeholder communities on EPA '5 standardization and 

validation advisory committees. further, ACe has spon')oreJ scientific research on the 

endocrine hypolhesi~ through its Long-Range Research lnitiative. 3 

These actions demonstrate that with respect to endocrine disruption, as w'jth any potential 

chemical risks, ACe members take these concerns seriollsly. ~'e have committed 

substantial resourccs and expertise to make sure that there are well established 

scientifically robust methods for assessing endocrine activity and adverse eft-eets. and that 

thcre are well established regulatory processes to act on this scientific information. 

Having confidence in the scientific infonnation is critical. as this i~ the necessary 

foundation for assuring that chemicals and the products of chemistry are lIsed safely and 

effectively. 

A related key principle is that we must harness advances made in science and technology 

in our laws and regulations. Many emerging technologies like computational toxicology. 

molecular tools and computer modding hold greal promise for improving how we screen 

chemicals for endocrine activity_ ACe very actively supports the development orthese 

promising techniques. To date, however. they haven't ~en shown to meet the scientific 

standards of reliability. sensitivity and :-.pe-Cillcity. While some emerging technologies 

may be nearing the point of use. they are not there yet. But as ne\v technologies are 

proposed to be integrated into EPA's endocrine screening program, they must be 

appropriately validated so that their results can be relied upon and replicated by different 

labs. They mu~t be shown to measure what they purport to measure and do so ,,,,,ith an 

acceptable degree of accuracy. Doing so ,vill provide regulatory certainty and ensure 

protection of human health and the environment. 

3 i1ti:': .... \\11) :;'_~l<:L· ~';.;: 1: i ~·:,p.'l [!J-o-! .~;1i),dJ1D~~(i~>~ 

l'ilr': \\ \\ \\ .a'lh .. "'j':::'-Ih.:il(. T i .... I,·:. II ::'"-<2<11"\:1' 
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The Honorable Edward .I. Markev 

The Honorable Fred Upton . 

February 25, 20 I 0 

Page 3 

The importance of basing regulatory decisions on the best science cannot be overstated. 

Decisions not based on the best science and on established risk asses':>rnenl and 

management procedures can misallocate limited resources and limit the use of safe 

chemicals, and create potentially unnecessary public health concerns. In an attachment to 

this statement is a more in..cJepth discussion of three additional science topics that arc 

important in your subcommittee's consideration of the enducrine issue in the context of 

the Sate Drinking Water Act. These topics address: a) mechanism of action and adverse 

eftects~ b) e1Tects mediated by endocrine pathways that are addressed in outcomes from 

toxicity tests: and c) the "Iow dose" hypothesis. (See Attachment A.) 

EPA bas begun issuing endocrine test orders for certain pesticide ~hemicals and has also 

been charged by Congress to begin to idenlify certain drinking water contaminants for 

endocrine screening. ACe welcomes the opportunity to comment on the Agency's 

criteria for identifying drinking V'later contaminants for endocrine screening. Vv'e 

understand that if after screening and testing, EPA finds that certain substances pose 

adverse effects via endocrine mechanisms, EPA has existing authority to take actions to 

protect public health. This was the case in 1996 when Congress passed the endocrine 

screening requirements under the FQPA and the SO\VA amendments. anJ is still the case 

today. 

Finally, it is important to note that ACe supports improvements to the US chemical 

management framework to ensure the safety of chemicals in commerce today. To that 

end. ACe is on record calling for Congress to modernize the Toxic Substances Control 

Act, which is the primary federal law regulating chemicals in comrnerce~ including 

chemicals that may be tound in drinking water. ( call your attention to ACe's principles 

for modernizing TSeA fur your infonnation.4 

Ace and its members look fOf\\I"ard to \vorking with you and the entire Committee as 

di5.cussions around the endocrine issue continues. If we can provide any additional 

intonnation on ACe's perspective.;,; on this or rdated topics, please contact me. 

Sincerely, 

Cal Dooley 

President and CEO 
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Discussion of Additional Scientific Topics 

Relevant to Endocrine Disruption Issuc 

Attachment A 

Regulation of Endocrine Disruptors Must Be Based on Adverse Effects: It is important to 

recognize that the concept of "endocrine disruption" encompasses both an endocrine mechanism 

of action and adverse health effects. Finding that a chemical may interact with a component of 

the endocrine system does not necessarily mean that an adverse effect will ensue. Given the 

right dose and timing of exposure, almost anything - including everyday food - can, and often 

does, elicit an endocrine system mediated response that can be observed at a mechanistic or 

biochemical level. It is important to understand that natural variations in hormone levels and 

reversible or transient changes that are not considered adverse have been well documented. The 

concept of "endocrine disruption" applies only when two criteria are met: demonstration that I) 

the primary biological mechanism of action is via an endocrine system pathway and 2) adverse 

health effect(s) are directly caused by a substance's interaction with that pathway. Mechanistic 

information alone is insufficient to evaluate the potential health significance of exposure to 

chemicals. Certain interactions or responses will be within the range of normal homeostatic 

response, and these are not adverse effects. 

This is why, under the EPA's Endocrine Disruptor Screening Program (EDSP), Tier I screening 

(which will identifY the potential for a substance to interact with the endocrine system, i.e. a 

mechanistic response) cannot be the basis of regulation. The EDSP Tier 2 testing, which 

determines the potential for adverse effects, and delineates the dose response for such effects. 

provides the needed data for hazard evaluation. This is a well recognized principle clearly 

articulated by the EPA's Endocrine Disruptor Screening and Testing Advisory Committee and 

subsequently codified by EPA in the Agency's EDSP. When hazard data are coupled with 

exposure data, the ensuing risk assessment provides the quantitative benchmark needed to 

evaluate the potential health significance of exposures. including exposures via drinking water 

pathways. This approach is consistent with the well-established scientifically sound procedures 

for assessing and managing risks that EPA employs under the SDWA to set national healthbased standards for drinking water. Regulation should continue 10 be based on adverse effects, 

dose response and risk assessment. 

Effects Mediated by Endocrine Disruption Pathways Are Covered in Outcomes from 

Toxicity Tests: It is also important to point out that even if specific endocrine screening has not 

yet been conducted on certain compounds, hazard identification based on observable outcomes 

from apical toxicity tests (i.e., outcomes such as pathologic states indicative of disease 

conditions) covers all modes of action, including endocrine pathways. As noted above, endocrine 
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disruption is not a distinct toxicological hazard per se, but a mode of action (MoA) of toxicity 

that could potentially result in a hazard, typically manifesting in the reproductive system. 5 

ACC members are committed to develop, produce and put into the marketplace products that are 

both beneficial and safe for humans and the environment. Accordingly, science-based 

evaluations of chemicals arc necessary both to determine efficacy and safety for intended uses. 

In this regard. the toxicity information developed by ACC members as part of the High 

Production Volume Challenge Program, as well as other programs, is directly relevant to 

evaluating risks to children's health, including potential effects mediated by endocrine pathways, 

because it includes: I) identification and definition of possible hazards upon all major organ 

systems from both acute and repeated exposures; 2) detection of potential hazards arising from in 

utero exposures; 3) evaluation of potential of a substance to affect reproduction; and 4) 

evaluation of the potential of a substance to damage DNA. Acute toxicity studies are most 

critical to assure correct packaging, labeling and handling to prevent poisoning incidents. 

Developmental and reproductive toxicity studies are most relevant for assessing risks that could 

affect normal prenatal and postnatal growth, development and maturation. It is these endpoints 

that are of most concern for endocrine disruption. 

For evaluating the potential of a substance to eause adverse effects via endocrine-mediated 

pathways, a weight of evidence approach is considered to be the best scientific means to assess 

and integrate the range of available toxicity information. This approach considers not just the 

EDSP Tier I screening assays, but also the results of all other existing, relevant and validated 

toxicity tests such as subchronic, reproductive toxicity, and developmental studies. With this 

scientific analysis, in particular the laboratory toxicity studies investigating dose response of 

adverse health effects, there is assurance that the most relevant and best available science is used 

as a basis for regulatory decision making and setting health-based environmental standards. In 

such a weight of evidence evaluation, objective criteria are first employed to determine data 

quality and study reliability, and then a systematic evaluative process is applied for assessing the 

overall weight of the evidence for the postulated mode of action and dose response of adverse 

effects. In this way all relevant toxicity data can be comprehensively reviewed, given 

appropriate weight, and integrated in a manner that provides a robust, biologically plausible 

understanding of the potential hazards and health risks that exposures to a substance could pose. 

Status of Scientific Debate ou the "Low Dose Hypothesis": In the late I 990s, some scientists 

asserted that environmental exposure to compounds that could mimic hormones were capable of 

causing effects in lab animals at "low doses" and that these effects had not been detected earlier 

because the standard toxicology studies had been performed at high doses. This is the so called 

"low-dose" hypothesis - that low doses produce certain effects that are not seen at high doses. 

There has been a considerable number of comprehensive, expert panel, reviews of this 

hypothesis over the last 10 years. In his comprehensive review of the scientific literature, Dr. 

5 ECETOC report TR106 "Guidance on IdentifYing Endocrine Disrupting Effects Technical Report No. 106, 

Brussels, June 2009. 

2 
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Michael Kamrin, emeritus prOfessor of Michigan State University, reached a clear finding that, 

"Based on the evidence, it is concluded that these "low dose" effects have yet to be established, 

that the studies purported to support these cannot be validly extrapolated to humans, and the 

doses at which the studies have been performed are significantly higher than the levels to which 

humans are exposed" (International Journal ojToxicology, 26:13-23, 2007). 

The U.S. EPA in 2002 also carefully considered the entire body of scientific information 

available on the "low dose" hypothesis and concluded, "Until there is an improved scientific 

understanding of the low-dose hypothesis, EPA believes that it would be premature to require 

routine testing of substances for low-dose effects in the Endocrine Disruptor Screening Program. 

See: hHp:!/\\ \\\\ ,epa.goy 'endoipubs/edll1\S,'lowdosepolic) .pdf: 

The media coverage ofthe scientific debate around the "low dose" hypothesis has been 

confusing and has tended to continue to "stir the pot" on this question. Therefore, it's important 

to clarifY that at the present time, a considerable body of credible scientific evidence leans 

against the "low dose" hypothesis and therefore against changing the way chemicals should be 

tested in the endocrine program. This is the scientific process at work. The call to stay true to 

the scientific method and follow the data rather than "strong convictions" was most recently 

demonstrated in a statement from one of the leading researchers on endocrine disruptors, Dr. 

Richard Sharpe, on the recent studies published by EPA's lab showing no such "low dose" 

effects. See: hllp:/!lOxsci ,oxJordjournals.orgiegi/col1!ent/fuIlIl14i I! I 

EPA's endocrine research lab recently published results of their studies focusing on very early 

stages of life in rodents and that found no such "low dose" effects on the brain, reproduction or 

development, and concluded that this lack of effects confirms "other robust, well-designed, 

properly analyzed multigenerational studies" «Toxicological Sciences 114(1), 133-148 (2010». 

This research by EPA scientists has been described in the leading scientific toxicology journal as 

"unequivocal and robust and are based on a valid and rational scientific foundation" See: 

http://toxsci.oxfordjournals,org/egilcontenti/tili/ 114/] II 

Based on the totality of this information, ACC believes that the overall weight of the scientific 

evidence clearly indicates there is no need to change the toxicity testing dose-setting approach or 

risk assessment methods because: I) the low-dose findings have not been demonstrated 

consistently across different studies of the same substance in independent laboratories; 2) the 

findings are not consistent for all substances with similar mechanisms of action; and, 3) the 

biological significance of the reported low-dose effects is scientifically uncertain, in particular 

with respect to relevance of such effects, if any, to adverse effects upon health of the organism. 

3 
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COMMITIEE ON RULES 

CHAIRWOMAN 

WA$Hl'lmON OHICE 

2469 RAYIl\If!'J BlJllD:r.a 

WA$H,r<C;ToN, D.C. 20515·3221 

1202) 225·3615 

LOUISE M. SLAUGHTER 

CONGRESS OF THE UNITED STATES 

28TH D1STRICC NEW YORK 

February 25,2010 

The Honorable Louise M. Slaughter 

Statement for the Record 

3120 FEDERAL BUILDING 

100 STATE STREET 

ROCHESTER. NY 14$14 

(565) 23<'·4850 

465 MAIN STREET, SUITE 105 

BUFFALO, NY 14203 

(716}B53·5813 

1910 PINE AVENUE 

NIAGARA FALLS, NY 14301 

Submitted to the Committee on Energy and Commerce 

Energy and Environment Subcommittee 

"Chemicals in Drinking Water" 

Mr. Chairman, 

Mr. Chairman and members of the Committee, I would like to thank you for taking the time to 

hold this hearing on this important subject, as well as for giving me the opportunity to submit my 

remarks for the record. 

A few years ago, I participated in a study conducted by the Environmental Working Group to 

find out what toxic substances I have been exposed to throughout my life. My stunning test 

results showed literally hundreds of chemicals pumping through my vital organs every day. 

These chemicals include PCBs that were banned decades ago, as well as chemicals like Teflon 

that are currently under federal investigation. The study also tested ten newborn babies and 

found that on average, each one had some 200 chemicals in their blood at the time of birth. The 

fact that we have children coming into this world already polluted and at the same time, do not 

know what the effects of that pollution will be on their mental and physical development, is both 

bad policy and immoral. We must test chemicals before they go onto the market, not qfier they 

get into our bloodstreams. 

Over the last 30 years, the U.S. has seen a steep rise in the occurrence of breast cancer, childhood 

cancers, testicular cancer, juvenile diabetes, attention deficit disorder, learning disabilities, 

thyroid disorders, cognitive impairment, autoimmune disorders, and genital deformities. Autism 

cases alone rose 210 percent between 1987 and 1998. For years, the evidence has mounted that 

these increases are associated with endocrine disruptors in our water, yet research on this 

connection remains limited, particularly on the impact of these chemicals on women and on how 

long-term, low-dose exposure to environmental pollutants impacts children at critical stages of 

development. 

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"',...". 
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Endocrine disruptors are widely used in agriculture, industry and consumer products. Some also 

enter the water supply when estrogens in human urine - compounded when a woman is on birth 

control- pass through sewagc systems and then through water treatment plants. These 

endocrine disruptors have complex effects on the human body, particularly during fetal 

development of males. In the past several years scientists have began to suspect that the large 

increases in numbers of genital deformities among newborn boys is being caused by endocrine 

disruptors. For example, up to 7 percent of boys are now born with undescended testicles, and up 

to I percent of boys in the United States are now born with hypospadias, in which the urethra 

exits the penis improperly. 

Endocrine disruptors can have equally devastating effects on females. It is now well established 

that DES, a synthetic estrogen that was given to many pregnant women from the 1930s to the 

1970s to prevent miscarriages, caused abnormalities in thc children. Evidence demonstrataes that 

girls born to those women have been more likely to develop misshaped sexual organs and cancer. 

Researchers also suspect that the disruptors can cause early puberty in girls, which greatly 

increases their likelihood of developing breast cancer as adults. Recent research shows that the 

risk that a 50-year-old white woman will develop breast cancer has soared to 12 percent today, 

from I percent in 1975, and that younger people also seem to be developing breast cancer. As 

Nicholas Kristof asked in a recent New York Times column, "What ifbreast cancer in the United 

States has less to do with insurance or mammograms and more to do with contaminants in our 

water or air?" This is an alarming prospect that demands immediate congressional attention, and 

an drastically enhanced research program. 

While the Environmcntal Protection Agency's (EPA) Endocrine Disruptor Screening Program 

(EDSP) should bc commended for their screening of substances found in sources of drinking 

water for their endocrine disruption potential, research into the specific health effects that 

endocrine disruption has on human growth and development is still severely limited. To fill this 

void I have reintroduced H.R. 4160, the Environmental Hormone Disruption Act, which would 

establish a new research program within the NIH's National Institute of Environmental Health 

Sciences (NIEHS) focused on how endocrine disruptors influence the development and 

progression of diseases. The clinical research conducted by the NIEHS would allow for a more 

comprehensive program investigating the specific health impact of hormone-disrupting 

chemicals. This rcsearch would serve to compliment and supplement the work done by the EPA, 

Currently, about 100,000 chemicals are registered for use in the United States, 90 percent of 

which have never been fully tested for their impact on human health. Without a doubt, it is 

critical that we act now to identify other endocrine disruptors being ingested every day by 

pregnant women and young children that could have similarly devastating effects on their growth 

and development. 

Mr. Chairman, thank you again for the opportunity to submit my remarks for the record, and I 

look forward to working together. 
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QUESTIONS SUBMITTED FOR THE RECORD 

HEARING ENTITLED, 

"ENDOCRINE DISRUPTING CHEMICALS IN DRINKING WATER: 

RISKS TO HUMAN HEALTH AND THE ENVIRONMENT" 

SUBCOMMITTEE ON ENERGY AND ENVIRONMENT 

COMMITTEE ON ENERGY AND COMMERCE 

UNITED STATES HOUSE OF REPRESENTATIVES 

FEBRUARY 25, 2010 

Linda Birnbaum, Ph.D. 

Director, National Institute of Environmental Health Sciences 

National Institutes of Health 

and Director, National Toxicology Program 

U.S. Department of Health and Human Services 

Questions for the Record 

The Hon. Edward J. Markey 

1. In your testimony you mentioned that the potential health effects oj endocrine disrupting 

chemicals are much broader than just reproductive issues. Could you detail some oJthese other 

potential health impacts and "\1:hat we know about chemical causation? 

Response: The NIEHS has a research program to understand the role of exposures to 

environmental chemicals during development (in utero and the neonatal period) in the etiology 

of disease. The data in animal studies at environmentally relevant doses show that 

developmental exposures to a variety of chemicals with endocrine disrupting activity for just a 

few days can result in increased susceptibility to numerous diseases later in life, some with latent 

periods of a year of more. 12345 Examples of diseases that have been associated with 

developmental exposures to chemicals, at low environmentally relevant doses in experimental 

1 Miller KP, Gorgeest C, Greenfeld C, et al. In utero effects of chemicals on reproductive tissues in females. Toxicol 

Appl Pharmacol 2004;198:111-l31. 

2 Heindel J: Role of exposure to environmental chemicals in the development of reproductive disease and 

dysfunction. Semin Reprod Med 2005;24:168-177. 

'Bern B. The Fragile Fetus. Colborn TA, ed. Princeton, NJ: Princeton Scientific Publishing Co., 1992 

4 Newbold RR, Heindel JJ. Developmental exposures and implications for early and latent disease. In 

Environmental Impacts on Reproductive Health and Fertility, Woodruff TJ, lanssen 5J, Guillette U, and Guidice lC, 

eds. Cambridge Press, 2010, pp 92-102 

s Newbold RR, Heindel JJ, Developmental origins of health and disease: the importance of environmental 

exposures. In Early Life Origins of Human Health and Disease, Newnham JP, Ross MG, eds. Basel, Karger 2009, pp. 

41-50 
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animals, include: weight gain (obesity)6; attention deficit hyperactivity disorder (ADHD)'; 

behaviors 910; allergic diseases and asthma I I 12; infertilityl3; premature puhertyl4; hrea~tI5, 

prostate 16 and uterine cancersl7 ; cardiovascularl8 diseases. These results are in controlled animal 

studies, although the mechanism hy which the exposure causes the observed result is not clear. It 

is interesting that in these studies developmental exposures to endocrine disrupting chemicals at 

environmentally relevant doses in animal models for just a few days during development can 

6 Newbold RR, P"dill"-S,,nks E, Jefferson WN, Heindel JJ. Effects of endocrine disruptors on obesity. Int J Androl 

2008;31(2):201-208. 

7 Colborn, 1. Neurodevelopment and endocrine disruption. Environ Health Perspect 2004;9(112):944-949. 

8 Chung, YW, Nunez AA, Clemens LG. Effects of neonatal polychlorinated biphenyl exposure on female sexual 

behavior. Physiol Behov 2001;74:363-370. 

9 Palanza P, Moreilini F, Parmigiani 5J vom Saal FS. Prenatal exposure to endocrine disrupting chemicals: effects en 

behavioral development. Neuroscience & Behavioral Reviews 1999 Nov;23(7):1011-1027. 

10 Gioiosa L, Fissore E, Ghirardelli G, parmigiani S, Palanza p, Developmental exposure to low-dose estrogenic 

endocrine disrupters alters sex differences in exploration and emotional responses in mice. Horm Behav 2007 

Sep;52(3):307 -315. 

" Narita S, Goldblum RM, Watson (5, Brooks EG, Estes DM, Curran EM, Midoro-Horiuti T. Environmental 

estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators, Environ Health 

Perspect 2007 Jan;115(1):48-52. 

n Guo TI, Auttachoat W, Chi RP. Genistein enhancement of respiratory allergen trimetaliitic anhydride-induced IgE 

production by adult B6C3F1 mice following in utero and postnatal exposure. Toxieol Sci 2005 Oct;87(2):399--408. 

13 Hung-Shu C, Anway MD, Rekow 55, Skinner MK: Transgenerational epigenetic imprinting of the male germ-line 

by endocrine disruptor exposure during gonadal sex determination. Endocrino/2006; 147:5524-5541. 

14 Blanck HM, Marcus M, Tolbert PE, Rubin C, Henderson AK, Hertzberg VS, Zhang RH, Cameron L. Age at menarche 

and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl. Epidemiology 2000 

Nov;11(61:641-647. 

15 Durando M, Kass l, Viva J, et al: Prenatal bisphenol A exposures induce preneoplastic lesions in the mammary 

gland in Wistar rats. Environ Health Perspect 2007; 115:80-86. 

16 Prins GS, Tang WY, Belmonte J, Ho SM. Developmental exposure to bisphenol A increases prostate cancer 

susceptibility in adult rats: epigenetic mode of action is implicated. Ferril Steril2008; 89(Suppl. 2):e41. 

17 Newbold RR, Bullock BC, Mclachlan JA. Uterine adenocarcinoma in mice following developmental treatment 

with estrogens: a model for hormonal carCinogenesis. Cancer Res 1990; 50:7677-7681. 

18 Melzer, D, Rice NE, Lewis C, et al. Association of urinary bisphenol A concentration with heart disease: evidence 

from NHANES 2003/06. PLOS One 2010;5(1)e8673:1-9. 

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increase the incidence of many diseases that have increased in humans in the last 40 years 

obesity, ADHD, asthma, and cancer. 

Weare working to understand the mechanism whereby a chemical can have a latent effect 

long after the exposure. The data indicate that the developmental time frame is extremely 

sensitive to alterations in the epigenetic system that controls which genes are tumed on and off at 

particular times in order to form different cells and tissues. Thus, the current hypothesis under 

study in our research programs is that developmental chemical exposures alter epigenetic 

programming, leading to altered gene expressi()n, which leads to altered protein expression in 

cells that persists throughout life, causing increased susceptibility to disease later in life. Most of 

this work is in animals, but we are also funding some humau research, looking at epigenetic 

changes. If this hypothesis is not disproven, in the future, once we better understand how to 

translate the results from the animal studies to humans, it may be possible to measure the 

epigenetic changes and usc them as biomarkers of increased susceptibility to disease later in life. 

which can lead to the development of intervention strategies. 

A critical aspect ofthis work is the hypothesis that disease starts during development and 

thus can be potentially prevented by reducing exposures during development. l9 20 This paradigm 

will help to changc the focus from intervention once someone has the disease, to disease 

prevention, which is more cost effective and supports a healthier population. 

At present, much of the data comes from animal studies. but there are a growing number of 

human studies that show associations of exposures to environmental chemicals during 

development to childhood diseases like obesity2l, behavioral problems22, asthma23 , and 

cancer2425 It will take longer to be able to link developmental exposures to adult-onset discases 

as the populations need to be followed for many decades. 

19 Grun F, Blumberg B. Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in 

the obesity crisis. Rev Endocr Metab Discrd 2007;8:161-171 

20 Heindel JJ, vom Saal FS. Role of nutrition and environmental endocrine disrupting chemicals during prenatal 

period on the aetiology of obesity. Mol Cell Endocrino!' 2009 May 25;304:90-6 

2: Baillie-Hamilton PF. Chemical toxins; a hypothesis to explain the global obesity epidemic. J Altern Complement 

Med 2003;348(16): 1527-1536. 

22 Colborn T. Neurodevelopment and endocrine disruption. Environ Health Perspect 2004;112(9):944-949. 

23 Dietert, RR and ZelikDff JT. Early-life environment, developmental immunotoxicology, and the risk of pediatric 

allergic disease including asthma. Birth Defects Res (Part 8) 2008;83:547-560. 

24 National Institutes of Health (NIH) DES Research Update, NIH Publication No. 00-4722. Bethesda, MD, 1999 

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We are currently focusing on exposures to a single agent during development, but in the 

future we expect to develop initiatives to examine exposures to mixtures of chemicals, which is 

more similar to the exposures that humans actually experience. All studies noted here use 

environmentally relevant doses. 

2. There are some scientists that suggest that although endocrine disrupting effects in animals have 

been demonstrated. humans are better able to deal with the low doses o.lchemicals without 

suffering adverse effects. Can you respond to that? 

Response: Certainly, there is widespread agreement that extrapolation of rodent data to humans 

must be done with caution. There are a variety of factors that influence the effects caused by 

endocrine disrupting substances: age (e.g., prenatal, postnatal, child); species and strain 

differences in susceptibility; gender differences; variation in study protocol, endpoints evaluated, 

and data analysis; and the endocrine disrupting substance being evaluated. 

Controlled animal studies show that low doses of endocrine disrupting chemicals can cause 

adverse effects in rodent models.26 27 28 29 Since there are numerous variables associated with 

understanding the levels that cause adverse effects in humans and how humans mayor may not 

vary from rodents in handling endocrine related stresses, additional information is needed to 

understand how humans are able to deal with low doses ofthesc substances. We do not know 

how humans compare to animal models in their sensitivity to endocrine disrupting chemicals; 

however, the suggestion that humans are better able to deal wlth exposures to endocrine 

disrupting chemicals has yet to be firmly demonstrated. 

25 Smith AH, Marshall G, Yuan Y, Ferrecdo C, liaw J, von Ehrenstein as, Steinmaus C, Bates MN, Selvin S. Increased 

mortality from lung cancer in young adults following exposure to arsenic in utero and early childhood. Environ 

Health Perspect 2006;114:1293-1296 

26 Durando M, Kass L, Viva J, et al: Prenatal bisphenol A exposures induce preneoplastic lesions in the mammary 

gland in Wi star rats. Environ Health Perspect 2007; l1S:80-86. 

27 Prins GS, Tang WY, Belmonte J, Ho SM. Developmental exposure to bisphenol A increases prostate cancer 

susceptibility in adult rats: epigenetic mode of action is implicated. FertilSteril2008; 89(Suppl. 2):e41 

28 Heindel JJ, vom Saal FS. Role of nutrition and environmental endocrine disrupting chemicals during prenatal 

period on the aetiology of obesity. Mol Cell Endocrinol. 2009 May 25;304:90-6 

19 Smith AH, Marshall G, Yuan Y, Ferreccio C, Liaw J, von Ehrenstein as, Steinmaus C, Bates MN, Selvin S. 

Increased mortality from lung cancer in young adults following exposure to arsenic in utero and early childhood. 

Environ Health Perspect 2006;114:1293-1296 

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3. What evidence do we have of the presence of endocrine disruptors in sources of drinking water? 

Response: There are several strong lines of evidence to support the presence of endocrine 

disruptors in sources of drinking water including direct measurement of compounds and indirect 

evidence of endocrine disruptor activity provided by biological indicators. 

Numerous studies give direct evidence for the presence of endocrine disruptors in sources of 

drinking water in the U.S30 31 and throughout the world (e.g., Spain32; South Korea3\ A range 

of precise analytical techniques are required to detect endocrine disruptors in water because the 

compounds arc generally present at trace levels (i.e., nanogram/Liter or below) and have diverse 

chemical properties that affect analysis34. The most common analytical techniques employed to 

measure endocrine disruptors in water are gas chromatography and liquid chromatography, each 

coupled with tandem mass spectrometry (LC-MS/MS and GC-MS/MS). For example, Benotti et 

al. (2009) recently published the results of a survey to detect the presence of 51 compounds 

(including 25 endocrine disruptors and 20 phannaceuticals) in both source water and treated 

drinking water from 19 drinking water treatment plants across the U.S. The most frequently 

detected endocrine disruptors in the study were atrazine, estrone, nonylphenol, and linuron; all of 

which were also detected in treated water with the exception of estrone35 . Government agencies 

such as the U.S. Geological Survey,36 as well as local municipalities such as the city of Ann 

30 Kolpin, D. W., E. T. Furlong, et al. (2002). Pharmaceuticals, hormones, and other organic wastewater 

contaminants in U.S. streams, 1999-2000: a national reconnaissance. Environ Sci TechnoI36(6): 1202-11 

" Benotti, M. J., R. A. Trenholm, et al. (2009). Pharmaceuticals and endocrine disrupting compounds in U.S. 

drinking water. Environ Sci Technol 43(3): 597-603 

32 Carballa, M., F. Om ii, et a!. (2004). Behavior of pharmaceuticals, cosmetics and hormones in a sewage treatment 

plant. Water Res 38(12): 2918-26 

33 Yoan V, J. Ryu, et aL (2010). Occurrence of endocrine disrupting compounds, pharmaceuticals, and personal care 

products in the Han River (Seoul, South Korea). Sci Total Environment 408(3):636-43 

34 Comerton, A. M., R. C. Andrews, et al. (2009). Practical overview of analytical methods for endocrine-disrupting 

compounds, pharmaceuticals and persona! care products in water and wastewater. Philos Transact A Math Phys 

Eng Sci 367(1904): 3923-39 

35 Benotti et alia., 2009. 

36 Chambers DB, Leiker TJ (2006). A Reconnaissance for Emerging Contaminants in the South Branch Potomac 

River, Cacapon River, and Williams River Basins, West Virginia, April-October 2004. Accessed at 

http://pubs.usgs.gov/of/2006/1393/pdf/ofr20061393.pdf on March 26, 2010. 

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Arbor,37 have also published studies on the presence of endocrine disruptors in source waters 

and/or drinking water. 

A number of researchers have utilized aquatic animals as biological indicators of the 

presence of endocrine disruptors. Animals serve as indicators because they have a well 

characterized biological response to an endocrine compound. These animals can be housed in 

water to test whether or not the water contains a sufficient quantity of endocrine disruptors to 

trigger the biological response. The production ofvitellogenin (a yolk protein not normally 

produced by males) in male fish is one biological indicator that has been used in a number of fish 

studies of endocrine disruptors38. Fish and aquatic crustaceans have been used as indicator 

species because they can be housed directly in water where endocrine disruptors may be a 

concern, such as in the effluent trom waste water treatment plants 3940 for recent exanlples). 

Numerous studies demonstrate the presence of endocrine disruptors in sources of drinking water 

by either direct measurement of compounds or indirect evidence from biological indicators. 

4. In your testimony you mention that some endocrine disrupting chemicals can have profound 

effects at "sensitive stages of development". Can you please clarifj' what constitutes a "sensitive 

stage "? 

Response: Any period of rapid development is sensitive to disruption. The periods when 

organogenesis (the actual development of the organs) and differentiation (establishing organ 

function) are occurring are known to be especially sensitive.41 

37 Skadsden JM, Rice BL, Meyering DJ (2004). "The Occurrence and Fate of Pharmaceuticals, Personal Care 

Products and Endocrine Disrupting Compounds in a Municipal Water Use Cycle: A Case Study in the City of Ann 

Arbor,1I Accessed at 

http://www .a2gov.org/ government/publicservices/water _ treatment/Docu ments/E ndocrineDisru ptors.pdf on 

March 26, 2010. 

38 Marin, M. G. and V. Matozzo (2004). "Vitellogenin induction as a biomarker of exposure to estrogenic 

compounds in aquatic environments." Mar Pollut Bull 48(9-10): 835-9. 

39 Barber, L. B., K. E. Lee, et al. (2007). "Reproductive responses of male fathead minnows exposed to wastewater 

treatment plant effluent, effluent treated with XAD8 resin, and an environmentally relevant mixture of alkylphenol 

compounds." Aquat ToxicoI82(1): 36-46. 

40 Verslycke, T., A. Ghekiere, et al. (2007). "Mysid crustaceans as standard models for the screening and testing of 

endocrine-disrupting chemicals." Ecotoxicology 16(1): 205-19. 

41 Reproductive and Developmental Toxicology· ed K.S. Korach, Marcel Dekker, NY, 1998. 

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5. In your testimony, you also indicate {hat some endocrine disruptors have the ability 10 alter DNA 

structure. Please describe how this may influence genetic predisposition of certain diseases? 

Response: Epigenetic mechanisms are cellular regulatory processes that influence the 

expression of genes without affecting DNA base sequences. Thus, while the DNA itself still 

maintains the genetic coding sequence, other changes such as addition of extra atoms has an 

effect on whether a set of genes gets turned on or off. Other modifications can occur to the 

chromatin, which is the highly organized protein package around the DNA in the chromosome; 

these modifications can also affect gene expression. 

For example, a recent study in yellow agouti mice demonstrated that maternal exposure to 

BPA shifted the coat color of the offspring by decreasing methylation in a controlling portion of 

the DNA sequence upstream of the coat-color gcne. 42 In the same study, maternal dietary 

supplementation with either folic acid or a phytocstrogen (genistein) inhibited the ability of BP A 

to reduce DNA methylation in a rodent model. These and other results highlight the importance 

of this growing area of research for our ability to understand how endocrine disrupting chemicals 

exert their effects, and how these alterations, which occur during development, may persist into 

adulthood. 

These modifications are independent of the actual DNA sequence of the gene, so they are not 

equivalent to what we usually think of as "genetic predisposition" which resides in the DNA 

sequence. However, we are only beginning to scratch the surface in our understanding of how 

various types of "predispositions" and susceptibilities actually work at the cellular and molecular 

leve1. 

The Hon. Joe Barton 

1. In your testimony, you state: "chemicals with endocrine disrupting activity are widely dispersed 

in our environment, often at levels plausibly associated with biological effects; exposure to 

humans is widespread" Does your use of the word "plausibly" indicate you are unsure and this 

is an educated guess at best, or has causation been established between the condition and the 

chemical? 

Response: Causation has been established in the laboratory setting for a wide variety of 

endocrine disrupting chemicals (EDCs) and consequent biological effects. Since people are 

42 Dolinoy DC, Huang D, Jirtle RL Maternal nutrient supplementation counteracts bisphenol A-induced DNA 

hypomethylation in early development. Proc Natl Acad Sci USA 2007 Aug 7;104:13056-61 

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exposed to many different chemicals in their daily lives, the same certainty of causation is hard 

to establish for humans, but when you detect in humans a level of exposure which has been 

reliably demonstrated to cause adverse effects in laboratory animals, 1 consider it to be plausible 

that that level of exposure is having an effect on human health as well. 

2. The CDC previously testified that the mere detection of a substance in a bio-monitoring test is 

not an indication that any disease or other effect will result. Do you agree with the CDC on this 

point? ljnot, why? 

Response: I agree that the mere detection of a substance in a bio-monitoring test is not by itself 

proof that any disease or other effect wi II result. 

3. Please describe what you consider to be suffiCient types of data needed tofairly evaluate 

chemicals. 

Response: Over the past several decades, our understanding of the effects of environmental 

chemicals has grown considerably. As our knowledge base grows, the baseline for what 

constitutes sufficient information also changes. Years ago, toxicity testing evaluated high dose 

effects and focused on overt toxicity. Animal testing and human epidemiological studies have 

demonstrated that these early testing strategies are inadequate. This is particularly the case for 

endocrine disrupting chemicals. For example, test guidelines used in the 1970's and 1980's for 

developmental endpoints focused on teratogenicity. These studies would not have detected low 

dose endocrine effects. Even the multigenerational reproductive studies had weak power to 

evaluate low dose effects43 Traditional rodent cancer bioassays start exposures while the 

animals are adults and are continued for two years. 

At a workshop sponsored by the National Toxicology Program, entitled National Toxicology 

Program Hlorkshol' 011 Hormonally Induced Reprodllclive Tumors-Relevance ojRodcnr 

Bioassays, one of the conclusions was that this exposure period is inadequate to evaluate 

hormonally induced tumors4

.!. In response to this workshop, the National Toxicology Program 

has modified their bioassays to begin exposures in lItero and continue exposures for two years. 

43 Hotchkiss AK et aI., Fifteen years after "Wingspread"--environmental endocrine disrupters and human and 

wildlife health: where we are today and where we need to go. Toxicol Sci. 2008 Oct;105(2):235-59. 

44 Thayer KA and Foster PM. Workgroup report: National Toxicology Program workshop on Hormonally Induced 

Reproductive Tumors - Relevance of Rodent Bioassays. Environ Health Perspect. 2007 Sep;l1S(9):1351-6. 

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This new exposure paradigm is consistent with human exposures to environmental chemicals. 

because, for most environmental chemicals, humans arc exposed from "cradle to grave:' 

In addition, where older bioassays simply tested for the endpoint of cancer, there are a 

variety of non-cancerous diseases that have rapidly inereascd over tbe past several decades 

including autism, ADHD and metabolic syndrome. Very few chemicals have been evaluated for 

developmental neurotoxicity and the potential for metabolic syndrome, as the bioassays to 

conduct the evaluations were not available. For many outcomes. the perfect bioassay has yet to 

be developed. 

With our current understanding of the toxicity of endocrine disruptors and other 

environmental chemicals. an adequate testing protocol should include "cradle to grave" 

exposures, to evaluate neurodevelopmcntal, reproductive, and immunological effects in addition 

to cancer. It is clear that these tests would have significant cost and time constraints. Tbis is 

why the National Toxicology Program, in collaboration with the US EPA, is developing a 

biochemical- and cell-based "high throughput" screening program, called Tox21. It is hoped that 

this screening program will provide some insights into the potential adverse effects of 

environmental exposures. The results from these high-throughput screens will lead to more 

targeted testing of specific environmental chemicals. We envision that tbis approach would 

guide our testing to the most appropriate animal model. including the potential use of novel 

transgenic animals that serve as better models for specific human diseases. 

Finally, recent advances in pharmacokinetic studies allow for more accurate species 

extrapolation of the absorption, distribution, metabolism and elimination of chemicals. Toxicity 

testing must continue to advance and incorporate new technologies. 

-I, Your testimony in support of low dose theory refers to rats that were susceptible to illness al100 

parts per billion of arsenic. Today '5 Federal drinking water standard is 10 parts per billion, or 

JlIO,h orthe rat dosage you cited. Please explain the relevance oryour example considering the 

disparity in subject. weight. and dosage. 

Response: With regard to subject disparity, it is noted that mice and humans show similar 

arsenic metabolism and biokinetics.45 4647 In terms of comparing effects between humans and 

45 Carter, D.E., Aposhian, H.V., Gandolfi, A.J., 2003. The metabolism of inorganic arsenic oxides, gallium arsenide, 

and arsine: a toxicochemical review. Toxicol. Appl. Pharmacol. 193, 309-334. 

46 Styblo, M., Drobna, Z., Jaspers, I., Lin, S., Thomas, D.J., 2002. The role of biomethylation in toxicity and 

carcinogenicity of arsenic: A research update. Environ. Health Perspect. 110, 767-771. 

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mice, one study indicates that humans arc far more sensitivc to arsenic than rodents, making the 

mouse a conservative model in this one experiment.48 

To address the disparity in weight between humans and mice, it is important to consider 

internal dose, i.e., the measure of a chemical in the blood stream. Waalkes reports that mice 

must consume 100 to 200 times greater inorganic arsenic concentration in drinking water to 

achieve similar blood levels to that of humans.49 Although we cannot say at this time how 100 

ppb arsenic in drinking water given to mice for 5 weeks directly corresponds quantitatively to a 

given human exposure, the Waalkes research supports the theory that this applied dosage to a 

mouse would achieve an internal dose relevant to arsenic exposures at or below the current 

drinking water standard. 

In tenns of the relevancy of the applied dose, the internal dose resulting from a 100 ppb dose 

to a mouse is relevant to possible human exposures to arsenic found in sources of drinking water 

in the U.S. The US EPA has estimated thatthc number of US residents who are exposed to 

excess arsenic in drinking water may be as high as 1.4 million Americans. Higher levels of 

arsenic tend to be found more in ground water sources than in surface water sources (i.e., lakes 

and rivers) of drinking water. The demand on ground water from municipal systems and private 

drinking water wells may cause water levels to drop and release arsenic from rock formations. 

Compared to the rest of the United States. western states have more systems with arsenic levels 

greater than EPA's stamlard of 10 parts per billion (ppb). Parts of the Midwest and New England 

have some systems whose current arsenic levels are greater than 10 ppb, but more systems with 

arsenic levels that range from 2-10 ppb. While many systems may not have dctectcd arsenic in 

their drinking water above lO ppb, there may he geographic "hot spots" with systems that may 

have higher levels of arsenic than the predicted occurrence for that area. 50 

In a recent study, researchers at Dartmouth College gave mice drinking water containing 100 

ppb arsenic then exposed them to a combination offlu viruses including HINI. The effects were 

severe: all arsenic treated mice died while those in the control group recovered. In their next 

phase of research, they will repeat the in vivo study with lower doses (including the lO ppb 

47 Aposhian. H.V., Zakharyan. R.A., Avram, M.D., Sampayo-Reyes, A., Wollenberg, M.L., 2004. A review of the 

enzymology of arsenic metabolism and a new potential role of hydrogen peroxide in the detoxication of the 

trivalent arsenic species. Toxico!. Appl. Pharmacal. 198, 327-335. 

48 Waalkes, M. P., Liu, J., and Diwan, B. A : Transplacental arsenic carcinogenesis in mice. Toxico!. Appl. Pharmacol. 

222: 271-280, 2007. 

so EPA Web Site. "Basic Information About Arsenic Regulations" 

http://water.epa.gov/lawsregs/rulesregs/sdwa/arsenic/Basic-Information.cfm 

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level)51 The gene and protein expression studies relating arsenic to endocrine disruption and 

immune suppression showed marked effects at 0.1 ppb in laboratory based experimental 

studies.52 53 (one-hundredth oftbe drinking water standard). 

5. In a September 21. 2009 letter to FDA Commissioner Hamburg. a group (~fresearchers led by 

Dr. R. Thomas Zoeller of the University of Massachusetts-Amherst wrore that they had "serious 

concerns with the FDA 's toxicity studies for BPA " and that it was "troubling thai the FDA is 

proposing to spend such a large amount of money on sllch a well-researched chemical." The 

letter additionally called the ongoing National Centerfor Toxicological research's (NCTR) work 

with rats "a serio liS wasle of time and money." The group further opined that there was 

"sujjicient research and independent review available for the agency to make a decision." Yet. 

later that same year. many of the signalories onlhe Zoeller letter received NIEHS grants to 

conduct even more studies onlhe effects of BPA. the very chemical cited by the Zoeller group as 

needing no further study. Please explain why NIEHS would invest millions of dollars in testing 

by individuals who have publicly opined no/urther research is necessary. 

Response: The NIEHSfNTP decision to fund more research on BPA was based on interactions 

with FDA officials who, notwithstanding the arguments made in the September 21. 2009, letter 

to FDA Commissioner Hamburg, believed that there were still significant data gaps that needed 

attention bcfore regulatory action would be appropriate. The NTPfNCTR initiative specifically, 

and the NIEHS grants program more generally, were designed to fill data gaps that were 

identified by the NTP and independently by the FDA during the course of their respective 

reviews of the BPA literature. Research was designed to assess the following: (I) develop 

infOlmation on the comparable amonnts of active circulating BP A in the bloodstream of neonatal 

and adult rats and non-human primates; (2) develop further rodent studies that specifically 

focused on developmcntal exposures and diseases later in life; (3) provide more complete dose 

responses for all experiments, including internal dose measurements of free (active) and 

51 Kozul, Courtney D., Kenneth H. Ely, Joshua W. Hamilton, and Richard I. Enelow. 2009a. Low·dose arsenic 

compromises the immune response to influenza A infection in vivo. Environmental Health Perspectives 117:1441-

1447. dOi:l0.1289/ehp.0900911 

"Barr, Fiona D., Lori J. Krohmer, Joshua W. Hamilton, and Lynn A. Sheldon. 2009. Disruption of histone 

modification and CARMI recruitment by arsenic represses transcription at glucocorticoid receptor-regulated 

promoters. PioS ONE 4(8):e6766. doi:1O.1371/journal.pone.0006766 

53 Davey, 1.e, Athena P. Nomikos, M, Wungjiranirun, J. Sherman, l. Ingram, C. Satki, Jean P. Lariviere, and Joshua 

W. Hamilton. 2008. Arsenic as an endocrine disruptor: arsenic disrupts fetinoic acid receptor-and thyroid 

hormone receptor-mediated gene regulation and thyrOid hormone·mediated amphibian tail metamorphosis. 

Environmental Health Perspectives 116:165,172. doi:l0.1289!ehp.l0131 

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conjugated BPA (inactive); (4) in collaboration with academic investigators, examine multiple 

overlapping endpoints that address actual disease endpoints rather than early predictors of 

disease or disease susceptibility; (5) use larger number of animals per group (when justified); (6) 

assess both males and females; and (7) develop more data to support areas with some hut 

insufficient data, including weight gain, behavior, breast and prostate cancer, reproduction, 

fertility, and puberty. 

The NIEHS funded 10 grants from this initiative. At the time offunding the NIEHS was not 

aware of the letter. However, we fund the best science based on our review system and data 

needs; thus, this letter would not have affected any funding decisions. 

6. In the section entitled "New Science . . , your written testimony described the initial results of BP A 

testing as significant. Is it wise to announce experiment results before the full experiment and 

analysis is complete? 

Response: The results cited in my testimony were complete and have been announced and 

published by EPA scientists in a peer reviewed journal.S4 They were referred to as "initial 

results" because they were the product of the first phase of the ToxCast program. Phase I 

profiled over 300 well-characterized chemicals (including BPA) in over 400 high-throughput 

endpoints. "Initial" was not intended to imply "incomplete." 

7. You testified the "NTP is also planning new research relevant specifically to EDCs in drinking 

water. One set of studies will investigate the potential for mixtures of chemicals known to occur 

in drinking water to impact pre- and early post-natal development. " In the spirit offiscal 

restraint and consistent with the President's message of making tough budget choices, do you 

plan 10 consult with Dr. Borgert and liAS on their work that has already addressed this matter? 

Response: With regards to drinking water and mixtures, there is little science on which to base 

an assessment of cumulative risks posed by mixtures of the myriad of substances 

(pharmaceuticals, disinfection by-products, industrial chemicals) in drinking water that could 

adversely affect developing organisms. Plans for research on substances nominated to the 

National Toxicology Program (NTP) are developed by NTP scientists in consultation with a 

variety of inputs, including both government and non-government scientists. 

54 Judson RS et al. (2010) In vitro screening of environmental chemicals for targeted testing prioritization - the 

ToxCast project. Environ Health Perspect 118:485-92 

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In developing its research programs, the NTP works with other federal agencies to ensure its 

efforts are not duplicative and meet regulatory and public health needs. Once a draft research 

concept is developed, it is reviewed in a public meeting by the NTP's Board of Scientific 

Counselors, to ensure that it is scientifically justified, mission-related and appropriate in scope. 

Comments are solicited via the Federal Register, and any public commenter is afforded time to 

provide comments on the proposed research plan if they so wish or they may submit wTitten 

comments if they prefer. It is then subsequently reviewed by members of the NTP executive 

committee. These reviews are taken into consideration by NTP management when setting both 

scientific and fiscal priorities for research and testing in subsequent fiscal years. In addition, 

NTP often sends the draft concepts to additional experts with specific expertise to ensure the 

most robust review of these concepts. In this case we will ensure that Dr Borgert receive 

notifications of the meetings where these concepts are being reviewed so that he may have 

opportunity for comment. 

8. You testified "there was an approximately 42% decrease in sperm count worldwide between 

1940 and 1990." Yet. the World Health Organization's comprehensive review of endocrine 

disruptions concluded that global reductions in human semen quality over time are related to 

increasing exposure to estrogenic. antiandrogenic (identify unknown). or other as yet 

unidentified chemicals, during critical phases of testicular development. Based on the weight of 

evidence WHO concluded: 

For outcome, the evidence is judged to be weak. A global trendfor declining semen 

quality is not supported by current data. Some studies show declines in certain regions 

or cities, whereas others have not found a decline. suggesting there may be regional 

trends but not a global trend There is no evidence relating to the strength of the 

hypothesis because of the lack of exposure data. There are no human data to support an 

EDC-related mechanism. 

Please explain the basis of your disagreement with the WHO. 

Response: There is no substantive disagreement with the WHO. My testimony cited the 1992 

paper to justify the research we have done on endocrine disrupting chemicals (EDCs) over the 

past years. In their 2002 report, WHO states that "a number of studies report a decline (since the 

1930's) in human sperm quality in several countries" and that there arc important variations in 

sperm count, although studies are hard to compare and have been retrospective 55 The 2009 

55Damstra T, Barlow 5, Bergman A, et aI., eds, (2002). "Global Assessment of the State-of-the-Science of Endocrine 

Disruptors." Accessed at http://www.who.int/ipcs/publications/new issues/endocrine disruptors!en!index.html 

on March 26, 2010. 

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Scientific Statement of the Endocrine Society56 also refers to reports of declining sperm count in 

Denmark and other countries contributing to the hypothesis of environmental contaminants being 

hamlful to reproduction. WHO's analysis points out that tbe lack of data about levels of 

exposure in humans has made it difficult to judge the strength of the hypothesis of EOC 

causation - this is distinctly different from stating that there is no effect from EOCs. That is why 

NIEHS believes this is an important area for research. 

9. Dr. Borgert testified that high-quality science consists a/science that is based on: verifiable 

measurements with sutJiciently small error rates: well controlled measurements whose 

interpretation is not confounded by extraneous influences: and results that are repeatable by 

independent scientists. Please state whether you agree with this assessment. If you disagree, 

please explain/he basis a/your disagreement. 

Response: I agree that the listed items are elements of a good study, but with the understanding 

that no study involving living organisms can be exactly duplicated and that in human studies 

(essential to our health and well-being) we can never achieve "well-controlled measurements 

whose interpretation is not confounded by extraneous int1uences'". High-quality science consists 

of the results from state-of-the-art studies that build incrementally to a consensus-a consensus 

that is rarely 100 percent. 

56 Diamanti-Kandarakis et al. (2009) Endocrine-disrupting chemicals: an Endocrine Society scientific statement. 

Endocrine Reviews, 30(4):293-342 

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D C, 204GO 

The Honorable Henry A. Waxman 

Chairman 

Committee on Energy and Commerce 

U,S, HOllse of Reprcsclltatives 

\\·ushington. D.C 20515 

Dear Chainnan \Va.\man: 

Thank you for the opportunity \(' respond to qnestions lor the rcc\wd that fellowed the 

February 25 hearing <lll Endocrine Disrupting Chemicals in Drinking Wuter, I hope this 

int'(mnatio!l will be useful to you and the members of the Committee. 

If you ha\'e any further questions, please contact me or your staff may contact 

Christina J, \1oody in my otTie," at 202.56-+'02(1). 

Sincerdy,7 , , 

AlTin R. Ganes<ln 

Deputy Associate Administrator 

Anncbment 
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Lmlocrinc Disrupting Cbcmieab in Drinking \\at(,L 

Risks to I Itlman J kaith and tbe hlyirnnl1lcnt 

I It'll';" C\l!l1111ittcc (l11 Energy and C(ll11llllcrCl' 

I dJrllar: 15, ~OJ() Hearing Date 

.lim'!one," ReSI'(lI1Sl'S lothe 

Questions t(Jr the Record 

Response to the HOllorahJc Ethnlrd J. \larke\ 

\ [mhe; I. ])0 :on belie,-c that Fl' ,\ has the personnel and resources to el1sure that the end('erinc 

disllIptor screening program can carry out its intcmkd purpose': If not, please claborate un \\'hat 

restlurees might be needed, 

\Jarkey 1 Rt'sponsc: In the Office of Chemical Safl'ty and Pollution PrcHntion (OCSPP), 

EPA (,llITt'lItly has cnough rcsources and persollnel ill the Endocrinc Disruptol' Screening 

Program. 

\larhc) 2, In y()ur testimony, you stat", that the \'alidation Url<:~ts cn,ure that th~y arc based (\!l 

;\,lid scicllce and thai they measure \\hal the\' arc intcndcc!lo measure. 

\ larkc\' ':::a. It is Illy understanding that there arc some rodent strains that arc unu,uall: Sl'!lsiti\ c 

to certain endocrine disruptor" and other,; that arc unusually insel1siti\'c \Yhen testing [(1r 

.cnti,)crinc' di,nlptillIl in animal sY,lcms is it neces:.;ar: to tak" in((l consideration \ ariatitlll in 

sellsi!!"it\' to endocrine disruplOrs that occurs in different wdent -.train,;': Illl\\ \\uLllli a scienti,l 

determine the sensitivity ur a wdcnt strain to a particular hormonal stimulus') Should scientists 

c'stahlish this baseline sens1ti\ i(y lIsing a kno\\'n ~lIdocrinc disruptc'r prior tll (estill!; an UllKll(1\\ll 

COllli't11111d Ill!' endocrine disruption? 

\larl;ey 2 and 2a Response: EPA has been cOllcerned for mall" years about the jlossibilit~, 

Ihn! rat strains Illay haH' different sellsitivities to l'ndocrinc di>ruptors, In 2002 it 

commissioned a cO!llprehensi\ (' literature >l.'llI'Ch and report on the eff,'ct of strain and 

sJlecics Oil the mammalian assays being considered for the TicI'I Battery of the Endocrine 

Disruptol' Screening Program. As part of the preparation of the n'port. the contractor 

submitted a draft fOl' I'cyiew hy an external fe\je" er. The final/'cpol't and the external 

re,jewcr's comments ha\C beclI on the EnSp \Yell site since tht, sUlllmer of 2003 

(h It P ://,,\\ w .cpa.gm Isd poly/oscpend o/pu bs/p rognt m/" h itcpa pel', h tm). 

The conclusiull that EPA reached on the hasis of this rniew is that whil!, SOllie strains llla~ 

hc lllore scnsitiYC than others for individual endpoints, there is no single strain that is most 

scmitiH' OH'1'l11l ill tht' assays with multiple !!ndpoints. The ntcmal reviewer suggested 

that seYcr'll strains be testet! simultaneouslY to provide a helt,'" chanet' uf minimizing 

sensitivity issues, There arc problems with this rc('ommcndatioll. First. as the peer 

rni,'\Hr noted, it would take suhstantial additiunal rcseardl to identify which strains to 

usc. ScrOllt). it would he sub,tllntial1: more costly (hotlt in dollat·~ and numbers of live 

animals) to les( multiple ;.trains. While the rCYiewcr suggested that a !'c!lm'cd number of 

llllimais of each of lIlultiple strains could bt~ used to keep the totaillum/wr of animals in the 
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,tudy !llllllagcahlc, such lill approach relies on the assumptioll that the SHille dose 11.'\ cis 

would he aPPl'opl'iatc in all of the strains used, \\ilhou( :,ueh an assumptioll, data could 

not be pooled across the strains, The assumption is not justil1ahlc due to strain differences 

in ratcs of meta holism, sizes. etc, 

EPA stated a prdcrcncc for a particular strain of rat because it has data sho" ing that th:lt 

strain works corn:rtly and identifies endocrine disl'uptors. If additiol1all'tscarch shows 

that a different strain 01' set of stnlins is comistcntly more scnsith'e, the test guidelines may 

he changed appropriately. The Agency bdicws it is better to begin testing for endocrine 

disl'llptor's now with a strain that has repeatedly' been demonstrated to he sensitive enough 

to detcct kno"n endocrine disl'llptOl's tlHlll to wait for all optimal stnlill or sct of str'ains to 

he identified. 

\ lark..:\' 2h, Del Y"ll ;;p-.:cify in y"ur lL"l (\["ders the strain or .1l1illlUl ,\!' cdl t> pc llw\ must be usccl 

ill a particular assay to ensure consish:ncy across labor:!lorit's" If so, plcase elaborate, and if 1]"\. 

\\hy not. sincc using a eli n(,)'cnt ,train c(lldd kad to "idely \'lll') ing and inc"l1sis\Cnl results" 

\larl,cy 2b Respouse: SOlm' t{'st guidelincs sJlecify exactly the strain of animal or cell t~ pc 

that must he used. For nalllpk, the steroidogenesis assay requires that H295R cells be 

used. That Cl'lIline has characteristics that make it uniquely suitllhle to eyaluate the entire 

metaholk path of stcl'oidogcnc,is and without using that particular ('ell Hue the assay 

cannot work In other assays, ho\\ c\ cr, a preference for an animal strainl'ather than a 

strict requirement is ginn, This is usually' heC<lIlSC strain is only one of man~' factors that 

clin affect the outcome of the stud)'. lind may not bl' among till' most important Yadahlcs. 

Studies using litllc-lwowl1 strains or str'ains known to be inappropriate arc lil,ely to he 

considered "other scientifically relevant information" rat he!' than information from a 

"yalidated" assay, and consrqllcntly subJect to signifklllltly gr~atl'r scrutiny. If a 

lahorator~' presents dala showing that the n:sults of a screening assay have not been 

compromised h~ nse of a llOll-prcfen'cd strain, the study may jll'oyj(k infol'Illatioll that can 

l"llT~' signific,mt weight in an (>nrall evaluation of the chemical. 

\brkc: 2c. It is l1l:- understanding thm rennin animal rood and housing cqllipm..:l1t cOlltain 

chemicals thm can act ;1S endocrinc disruptors and can subsc:qucntly intcrtCn.: \\ ith aSS3:-'S that me 

d(:~ignl.?(l to JO(Jk ~lt a b,lrn1pnal endpoint. Du ) 0\1 ~pecit'y in ) Ollr test ord~rs the type (,)f (('rod ~tnd 

housing proct..'dur~'s that arc ncc('~sar: in t)rJ~r tp 111inJmil.c cl)l1tmninmi(ln fnH1l1i1':se sources 

ami to ensure cOl1sistcnc" across IaboH!wrks') If su, pleasl' elaborate, and i l' oN, II'by 11,)!, ,ince 

thi5 \ (lriahilit\ can lead 1O in\,\1Jbi,;tcllt l'cslilLc," 

\Iarkcy 2c Respollse: The test guidelincs contain provisions to restrict usc of materials in 

feed and housing equipment thllt may interfere with the ability to detect endocrine 

disntptol'S. For example, the lise of polycarbonatc watcl' hottles fO!' rat studies is 

prohibited sincl' water in prolonged contact with aged and distressed polycllriJoll:ltC has 

been shown to have the potcntial to be estrogenic, Similarly, the fish and frog assays 

sJlcdfY that glass aquaria arc to he used, EPA docs not restrict use of materials if thc~' 

"el'e judged not to June any bearing on the ontcome of the study, For c:\amplc, usc of 

fl()l~ carbonate l'ag('s for rats is not prohihited since the cages arc not cX[l('cted to he in 
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contact with wat.::,· for a prolongl'd period of timc, In the caSl' of rat feed. the Ienl of 

natural phmt-bllset! estrogens has heen capped at a IcYClthat does not intcrfl'l'c ,yith the 

H"UItS of a screening assay. Howeycl", EPA "ccognizes that there ma~' be compounds 

present in feed and hOllsing l'quipml'l1t that nH\~' haH tudocl"inc cffccb hut \\c an' simpl~ 

una" arc of thelll, 

\larKc), 2d, \\'hal can )OU say about the accuracy ofa study cksign.:d w cnl1uClk ,,!Jctlh,T a 

c~rlain Su,;pcckd endocrine di,rul'wr call,C, adYcr,,, health erCcets in an animal ,train if that 

,am!" chose as its modd ~111 animal strain that is cOl1sickrcd highl\ ins.:nsiliw to h"rnl,'nai 

slimu!i'.' 

\larkey 2d Response: If an animal strain \\I,re highly iuscnsitiH 10 hnnllonal stimuli. weak 

endocrine disruplol's might nut be identified ('iHTectly b~' assays that use that strain, 

Howevel'. usc of II pntatinJy suhoptimal strain might be justifiablt' if data show that it 

correctly identifies known "cak endocrine <iisl'uptors. and if no other ,trllin 01' set of 

strain> lUIS been ,hown to he more sensitive. It should he remembered that strain is ()Ill~' 

one factor amollg many that aff{',! the oul('OIll{' of HII assay. and ma~ 1101 he the most 

important one. 

\lark.:) ~", \\'hcll dcsi~ning ::ISS.," j(lr bUlh the I icr i and Tier" prowellls, i:, a positiyc relc:\ant 

h(lnnnnal cOl1trnl. sllch as cstrGg~'n 1.)1' l(,~lo:-\tcn)ne. U=,L't! ill Y(?rit\ tb .. ' rdc'"<'H1(C and 

r(,spl)n::;i\·('n\?~s or th~ a:-;say'? It' 111-)1. \\"hy nor.) 

\Iarke)' 2e Response: Positive controls han: hel'n used (01' llre Iwing used) in the validation 

for the TicI' 1 and Tiel' 2 protocols, [n addition. cOllcurrent positin controls are required 

to ht, run in paralld with the te>! chemical inllHlny of Ihl' Tier I assays. II ow (,"1'1" positive 

COil trois arc not required in certain rcsotlrcc-intensin assays that detect multiple potential 

Il1cctUlnisms of {'ndocrinc activity, For example. running estradiol in the puhertal fernak 

assay as a posithc contl'olmight help ensure that chcmkals that act similarl~ to estradiol 

would he i{klltificd but would not help to enslin' that chemical> that arc anti-estrugenic, 

that interfere with stl'l'oidogCllcsis, 01' that interferc with thyroid horlllone al'tiyit~, "uull! 

be identified. Including positiH coutnJls for each of the' applicable mechanisms would 

reqnire severa! differcnt positiw clIntl'o}s to he run ,itllultancollsl~ "jth a singlt' It's! 

chemical. Ideally. a positive control would have to he included for cstrugCllici~ through 

the estrogen receptor. anti-estrogenicity through the estrogen I'ct'cptor, androgcnicity 

through the androgen receptor. alltial1dl'ngel1icit~ through the androgen receptur. 

<lromatase inhibition. interference with SI{'l'oidogl'IH:Sis, and the l1Jany mechanisms hy 

which thYl'oid function {'oult! be affeded each time a test chemical is tested. This would 

add signit1canl ,'0,( and lIS(' of animals, The Agcnc~' helicHs that the performance criteria 

included ill slich complex studies will heJp to ensure that the stlld~ is run COITt'Ctly. 

\brKc'" 'I', I lnw \\'j1l1hc results I'rom i'll,itj\l; cPlltr,,1 c'xjlcTiment inl1uencc' C!JIKcntrJti(lllS oi'lc'c;t 

dh..'lnil\lb thal aI'\,..' thc;d ill the TiL'r 2 d():'.\.~ r(,:sp(!I1'-;t~ ~l:-;:<IY:<' 

\Iad,c,' 21' Hesjlol1se: H.{'sults from positiYC fontr!)J experiments in TicI' J assays arc not 

('xpectl'd to illl1ucllec l'ollC('ntration:. of test chl'lllieal, that an' used in the Tiel' 2 dose-
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response assays. Appropriate dose lrnls arc almost without exception chcl\lic~lI-specific so 

it g{,lIcrall~ is not aelyisahle to set dose le\ds based Oil a diffcn:nt "hemicHI (viz., the positin 

control ill a Tier 1 llssa~). Presumably. il prclimill:ll'~' c!ose-nmge stud~' aud/or data from 

the Tier 1 pullertaI, fish. and frog assays for each specifk chemical would influence the 

selection nl' the dose kYCIs fnr tht, Tier 2 assays for that chemical. 

.\ kirk.:'\ 3, I h'ccnth \\ {'Ok Ieners to both FD .. \ and CP,\ about triclo,;an. \\hicb i, us.:d illl11al1~ 

consulller l'rndud, - ti'O!l1 haud Sl)ap to clItting buards de:<pik qUc'stiolls abt,U! \\ hether it \Yorks 

J;ll! ]'c11"ntial I'or elld,'crinc disrcIj,ting c'fl'"ds, Tridnsa:l ha, als(l b~en round in ncar!: GO"" or 

l. ,S, strcams!. and the CDC dCl1lonstrarcd it w be contain .... d in the' urine 01'75"" L1fAI11c:rjc:ll1'~, 

FDA reccntly responded t" Illy tener. and ,tated that it is "FD, \', (lpininl1 that c':-:isling data raise 

yalid concern;; about the eneet d' rCllctiti\'c ,lail: human ""!,,,sure ltl 1116" anti:;,'Pli( 

in~r('di('nlS.·· 

\larkey 3a, Do you think trich),r1l1 sh,'uld be s(!'"end unLkr the EncllKrinc Disrupto!' Sc:rcening 

Pn.grrul1 or dll:, lOU ht'lie\ e thaI the c,\isting (10m could be suflicicllt to either accelerate the 

sc!'eening process or Illlm:: straight to Cllilsicieratioll Il)j' regulation lInder the Safe Drinking \\'ater 

,\cr,' Pica,,, I;:\plain Y"Ul' rc'SP(lll'C, 

:\Iarkey 3a Response: 

The Agcnc~' uses its Contaminant Candidate List (CeL) and Rcgulalor~ l)cterlninations 

processes to cnrluatc unregulated cuntaminants for pott'ntiai n'guiatio!lnnder SD\VA. A~ 

noted in the response to your .January 5, 2010 letter. EPA puhlishcd Oll!' third eCL (or 

eeL 3) Oil October 8, 2()09. This list includes unrcguiaH'd contaminants that arc known or 

anticipated to OC,'UI' in puhlic water systems and may require regulatioll I1ndel' SD\\,A. In 

uncloping CeL3, EPA considered the hest a\'ailable occurrence and health effects dala to 

evaluate a unh'ersc of approxiIllatcl~' 7.500 contaminants and subseqm'ntly idcntitkd a li,t 

of 116 contaminants that presented the greatest puhlic health cuneI'i'll for drinking water. 

While EPA cYllluated tridosall a, part of tlw uniYCl'sc of 7.:100 contaminants, the Agency 

dct{'rmined that it did not present as great a pulllie health concern (for dl'inking \\ ater) as 

other contaminants that "ere selected for the final eel. 3. 

EYCll if the Ag{.'llcy had listed tricloSllll on eCL.', in (Ink!' to determine \\ helher to n'gulatc 

a cont,lIninant \\Hh a national pI'illlar!' drinking water n'gulatioll (,\PD\YHj, section 

1-i12(h) of SJ)W..\ requires that EPA mak(' an affinnati\e finding for ,Ill three of the 

follo\\ing statutory criteria: (1) The contaminant Illay ha\C an adn:l'sc effect on the he'llth 

of persons; (2) The contaminant is known to occur 01' there is a suhstantiallikclihood that 

the contaminant II ill occnr in publk \\ atel' systems with a frequency and at leycls of puhlk 

health cOllcern; and (3) In the sole judgment offhl' Administrato!', rt'gulHlion of sud I 

contaminant presents a meaningful opportunity for health risl( reductioll for pCl'sons 

s('ned by public water s~'stcms. In th,' case of tridosall. the Agency would not have 

sufticicnt information for finished drinking \\lIter to add!'"ss tht· second and third statutory 

critt'ria. 

However, EPA is conducting seyeral tests Oil triclos<ln as part of its research p!'ognlm. Thl' 

Agency helicH's that th{'sc data will provide useful information 011 tit,· potcntial of tricloslln 
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to affect the endocrine system and believes that thc results of this testing will provide the 

Agency with important information regarding the further testing needs for triciosan. EPA 

will contiuue to cVllluate unregulated conhlminants such liS tricloslIn and will utilize an~' 

ne\\, !'clcv'llIt data that might l"equi!'c the Agenc~' to issue an EDSP test order for triclosan 

or reconsider placing this contaminant on future CCLs and/or future regulation, 

\Iarkey 3b, It is estimated that 95~o of the lIses oftriclosan (found in numerous COl\Sltll1Cl' 

products) are disposed of in residential drains and are consequently found in sources ofwateL3 

When EPA re-eyaluated triclosdn for usc as a pesticide did it tak(~ into consideration cUlllulmiw 

exposures that come fi'ol11 products that tall under FDA's jurisdiction? ,\rc EPA's risk 

assessments based on this total public exposure',' If !lO\. why nor. SilKC FI'A is cilarl'cd with 

ensuring that drinking \\ ater is safe to drink irrcSpCCliyc of the source of the contamination of the 

drinking \\ater') 

:\'lal'key Jb Response: EP A's I'c-evaluation of triclosan for use as a p<'sticidc considercd all 

potential exposures to the general public resulting from EPA and FDA regulated uses. 

EPA '5 risk assessment is based on the total exposure from all IIses that ma~ co-uccur 

including an~' contribution from contaminated drinking wllter. The total exposures from 

all sources of triclosan were del'ivcd from the :'\ational Health ami :'\utrition Surycys 

(:,\HA\,ES) hiologicalmonitoring data. l'iHA:'\ES is a nationally rcpr'csentativc hiological 

(urine) surny offhe general public, captul'ing their dail~' routines/exposures such as 

consumptioll of drinking water, EPA views the :,\HA:,\ES monitoring data as the most 

reliable and rcprescntati\'C llssessment of total exposures that co-occur including daily use 

products as well as to other sOUl'ees of triclosan contamination such as drinking "ateI', 

\'larkey 3c, Currently, under 1.:1'.'\ regulations products treated "itll triclosan to protect the 

product itself such as a clIlting board. for example - arc not subject to the lu\\' requiring that the 

products be labekd as containing lriciosan, Gin!l1 the health concerns with triclosan. do you 

think that the public should be notified \,'hen a product contains tric!osan. regardk,s of whm type 

of product it is'? Why or why not'? 

:\Iarkey 3c Response: EPA '5 pesticide regulatioIls cxempt "tl'cated articles" from FIFRA 

requirements, Sec -10 CFR 1:52.25(a). A "treated al'ticle" is any product which has been 

treated with an EPA-rcgistcl'cd pesticide to protect the product and for which no other 

pesticidal claims are mmle, For eXllmple, many paints, sealants, paperboard products, and 

plastic products (e.g., ,howel' curtains) contain pesticides in order to prCH'nt the growth of 

mold 01' mildew in or on the pl'Oducts. Before approving a pesticide fOl' such materials 

preseryatiye use, EPA carefully assesses the potential risks resulting frolll such USt'. This 

assessment indudcs cOllsideration of the possible expoSlIl'e a consumer, who uses the 

jll'Oduct, might experience, The Agency ",ill not approve a pesticide fOl' materials 

preservative uses if there is a risk to consumers who handle Jll'oducts treated with the 

pesticid£'. EPA's assessment of the materials prcscrvatiYC lIses of tricIoslIJI concluded that 

except for usc in paint as an in-cllil prcsel'YatiH, they did Ilot pose a risk to consumers wlto 

would come into contact with products treated with triclosan, 

Howenr. EPA determined that there 

were risks for the fIlaterial preservative usc of tric\osan ill paint as an in-can prcscn ath c. 

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Therefore, EPA did not re-register the paint usc. Had EPA reached a ditTrrcnt conclusion 

for tilt' othlT material prcsenatin~ uses, r"ther than requiring labeling of tn~atcd products, 

we wonld have disallowed the llse of triclosan as a materials pl'cselTatin. In sum, so long 

as a pesticide used in consumer products <IS a materials pn~scl'\atin~ is registered and its 

use complies" ith its EPA-approycd directions for lise and the t!'(,<lted articles exemption. 

EPA docs not thinl, there is any need to rcquirl' a separate registration or labeling of 

products treated with such pesticide. As new information becomes llyailahle on the 

hazards and leYcls of exposure to tricloSHn, EPA will worl, with rOA to evaluate the safety 

of allu.,es of triclosan. If there are llses of tricloSlln liS a pesticide that do not mel'! thl.' 

safety standard, EPA will take the appropriate regulatory action to prohibit thos,' IIses. 

I{espouse to the HOllorablc .Joe Barton 

Barton 1 a. 110\\' much h~\s tht [1','\ sp~nt to datc·) 

Barton I aResponsc: Th(' Endocrine Disruptor Screening Program ill the Office of 

Chemical Safety and Pollution Prcycntion (OCSPl') has total obligations of approxilllatd~ 

S88.9\1 anti 189.1 FTE from FY 1999 through the end OfSCCOlld quarter ofFY 2010. :'\otc 

that this total ohligation alllount rO!· the Endocrine Disrupter Screening Program of 

oesP!' docs nM include funds obligated through EPA's Office of Research and 

Dcye!opment for endocrine disf'uptor research whkh includes the dC\elopmcnt of some 

~crecJling assays. 

Banon I h. Is it lru~ lhat LP,-\ swff at one j)oil1l lil,)ughl chemicals might be' ,crecncd umkr 1h" 

EDS]' for a" little ;15 $:;0 pcr chemica]·: 

Barton I h Response: We do not believe that the estimate that chemicals could b~ S(TCCl1cd 

for 5:;0 pCI' chemical clime from EPA. There were two sets of hc·arings held in 1991 and 

1993 as a prelude to the passage of the FQPA. Although we have !lot rescal'ched the 

hearing records. it is our belief that this estimate \\ as proYidcd hy one of the witnesses who 

testified that a single in yitro screen to detcct estrogen receptor bindill~ (the E-Scrcl'n) 

could he l'O!Hillctcd for S50 (lcr chemical. EDSTAC and other experts did not reganl this 

simpll'. single assay approach to screening to he scientifically adequate to (klcc! dlcmicals 

with the potential to affect the cndo,Tine syst('m. 

Barkm J c. lei illruc lhat 1110st eSlimak:; clIlTc'llll) put the (,,1St of Ihc Ticr ] iCsling battery 31 

S50(J.(loO to S 1 million per ch<:micaJ') 

BartOli 1 c Response: Two estimates of la\)oratOl:' costs hayc been performed, one 

commissioned by the American Chemist!: Council (A(T) in 2003 and one hy EPA in 2009. 

Additional information was submittcd by the ACe as comments on the fCR.' EPA 's stlld~' 

titled "LahonItOl: Testing of Chemicals for Endocrine Disruption Potential-Analysis of 

2008. C,)I11111(;nb fin FPr\· s Infnrm.uit'n C(lllecth111 R .. 'qll~$t dcy;;'!\)pl..'d f~)J' the Agent') ." I·I)SP. Dock.:t 

o :md FP\.IIQ-:'007-J\l8J-OIlI.'.:' 

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'larket Factors" lVas dcsi"ncd. in pill't, to provide contclllporar~' co,t estimate, from 17 

Iah,watories for conducting the most recent protocols for the I! '","('en in" a,sa~s in the 

EnS}, Tier I battlT~, 

EPA', study rcport indicated a median estilllated cost to rondue! the 11 assays was 

S5~2,~97 per chemical. Since there \\ as a lar"e variation in the cost estimates 1Il1lflng 

lai.Jorntorics··El'A. 's study report indkatl'd a minimulll of S2,B,000 and maximulll of 

S9.t 1. 750 pn chcmi<'lIl .. till' nll'dian was reported to briter cOll\cy tht, information, The 

highc~,t and lowest eust estimates for all ill vitro assay, Inn' provided by two lahonltories, 

In addition, in 2007. EPA published calculation.' for paperwork burden mll! cos,," for data 

gent'ration activities (Information Collection Request. ICR) ,'elated to conducting II 

screcning assa~s in the EDSP Tier I hatter~' for the f'il'st list of 67 chemicals to Ill' ~crcencd 

(Dod,('t # El'A-HQ·OPI'T·1(81). In Attachment F of the supporting doculllentation. the 

llwrage cstimat('d cnst to ,'ol1lluct the II assays wa, S.t0.t,315 pCI' chemical. The 2003 

SlIl'\'ey. conducted hy Applied Pharmacolo"y and Toxicology.,loL (APT) and funded hy 

ACC was the basis foJ' EPA's cost estimates for eight of the slTecning assays ill th,' ICR, 

The APT sUlTey included II laboratories ami draft protocols mailahle at tit,' time for ER 

and .\R binding. Steroidogenesb, Aromahlsc, Ctuotrophk (o\'aricclOll1izeci), Hushhergcr 

and Female and :\lalc Puhertal a,slIY:S, EPA adjw'ted the AJ'T sun ey cost c<;tilllates by all 

inl1atioll factor of 1.1.t, Since the Human ER 'I'l'anscl'iptional ActiYlltion. Amphibian 

",'tamorphasis and Fish Short-tel'lI! Reproductioll screening lhsa~'s estimates \1 ere not 

included in the initial APT surn-y. EPA cost estimates wert' !lased Oil professional 

judgment and the cm!s the A!!ellc~ inculTcd during assay yalidation IAmphihian 

\INalllol'phosis and Fish Short·term Repl'odm'tion), 

Although median and nl('lln cost estimates frolll EPA's estimates ill 2009 and 2tHl7. 

rcspectiycly, are !lot directly comparahle, the fIll'dian estimate fO!' thl' 2009 EPA study ,,,as 

app/'(',imlttcl~' SIIl.nOIl to S21l.000 higher for most indhidmll assays tlHlll the mean cstimatt' 

for the same assays in the 2(){)7 EPA ICR. Apart from reporting the median versus mean. 

the discrepancy nHl~ he due, in Il,!rt, to older Hrsus lIe\\ er Ycr,iol)s of the protocol>; and 

e(uuomic changes bel" een 2ml7 and 2009, 

1~,lI1on ld. Iflh"s.; c"pens.; c,timatcs ,we nccurGlc. inligbt llfthat c'''pcnsc, \\hy would EPA not 

iirs! c\a\l"llc e"isting (bw before taking <'ther ,teps! 

Harton Id Response: Rt'cipicnis ofilte EDSP Test Orders for the initial screening of 

chcmicals h<lYC thc option to suhmit or cite existing data (induding citing data prc\'iousl~ 

suhmitted to the Agcnc~ ) that the:,' beline h rck'\ ant to one or more of the assays specitkd 

in the Test Orcll'I', I'll{' Agency" ill revic" this Oth('I' Scientifically Relevant Information 

that may be suilmilH'd h\ ('ith('r the test order ndpicnt or till' publit, in liell of thc TicI' 1 

hattc!'~, Tflt, po!kics and 11I'ocNIurcs the Agclle.l' adopted for initial sen'clling lind!:!' tht, 

EnS!' n'commcnd that the Te,t Onkr rcdpicnt or otlll'l' parties. provide lin cxplanation of 

the releYllllCl' of an~' citnl e.,i,ling data to the It'st order as well as a rationale for \\ hy tht,~ 

hclil'Y c the information is Of' is not sufficient to ,atisf)' part 01' all of the Tit!' 1 ordel'. These 

polkks and p!'occtiHl'cs provide for the usc of information that is consistent with a!lol' part 
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of the battery or lIlay also inforlll the outcoUles that the battery seeks to evaluate. In this 

manner, the Agency will only require needed data. 

Barton 2. Dr. [3,)rgen tc:;tified that .:-"panding the endocrin.: testing program hefore the 

ef!,,<:liwness of its ksting system can bc cyaluated Ill)\lld be an incflkimt u,e oftaxpa\'er 

n:s\)urc:~s> Please stuc \yh(,lhc'r y\H'! agree t)f dis~!gr('c \\ ilb this statcl11('nL 

Barton 2 Response: EPA accl'ptct! tht· recommendatiun of the 1999 r~\icw of the proposed 

EDSP hy a .loint Subcommittee offhe Science .\(I\·isory Board and FIFR.·\ Scientific 

.\dyisul')" Panel to limit the number uf chemicals in the first list to 50-100 chcmicllb lind 

review the results bd'ore issuing II second list. This" as a cautious approach and prudent 

when it appeared that snch a lis! could he isslled and data l'cceind by 2005. Howt'Hr, the 

yalidlltioll of assays has takcn far longcr than EPA or l\ll~'OIlC else anticipated. The current 

Tir!' 1 battcQ' was reviewed h,\ the SAP ill 'J,wch 2008 and found to he 'Hkquate to detect 

substances" ith estrogen, androgen, and th:HOid acti\' it~·. EPA belicHs the hatter,..' will 

produce sufficiently valuable data and that further delays in testing should not be madc. 

Barton 3. Do: ou agree that there are real II'orid CO!lSeqlicllc':S that will accompany the results of 

the endocrine screenin1-' batte!":. and ifs(). doesn't Ihat make it all the more importal1llhm the 

tests ar..: precis.: ::mel rdi:lbk': 

Hal·ton 3 Response: EPA agrees that issuing test orders wbich J'cquire J'el'ipicnts to <'ollliud 

the endocrine screening battery has rcal world consequences. \Ve also agJ'ce that it is 

important therefore for the tests that comprise the hattcr~' to IH' scientifically reliabk' for 

their intended Pllrpose. Based Oil the cxtellshc, multi-yellr effort to vlIlidate the assays 

lIsed ill the endocrine screening battery, we concluded that the (c,ting method" we arc 

requiring meet the statutory standard of being "appropriate validated tests s~'stel1ls." The 

independent, c~perts on the FlFRA Scientific Advisury Panl'! who reviewed the battery in 

\larch 2008 agreed \\ ith EPA's conclusion. 

I3art(lll -I. Ylllll",tillc·,j the "lirst list p["chemicals \\as selected sold: (\11 the basis ni"c'xpnsur'· ... 

E:\pl)SUr,,~ is an impt)rlalll c(ln~id""'wtion but h\l\\' many l)j' the sdc'ctl?d chemical:-. arc hit'h rj~k 

chemicals for the Purl""(,' t1!"lhis pn;~\ral11'.' 

Barton -l Response: EPA is not prepared to identify any of the 67 chemicals on its initillilist 

of suhstllnces undergoing EDSP screening as "high risk chcmkals," ''"hen we hcg,lIl to 

idcnrif~' substances for this list, scientists had not developed an approach for sc;Wng testing 

priorities based on the potcntilll of a test snbstalll'c to he an endocrine disruptor (although 

we aI'C aware of promising research that may pro\'idc priority setting tools ill the future). 

Therefore, EPA lIsed cxposure-hasl'd criteria to select chemicals for the initiailist. We 

hayc repeatedly stated that the inclusion of a chemical Oil the initial list does not indicate 

that the chemical has tbe potential to disrupt the endocrine system. Rather, we will use the 

r('suits of the TicI' 1 battery to characterize the potential of suhstances to interact with the 

cndocl'ill(' sysll'm, and where llpprupriate, the results of Tier 2 assays (0 define the 

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relationship hl'tHCCll dose and rc~ponse. \\'ith slIch information. EPA can assess the 

potential risl,5 posed by human exposure to cndocrine-disrupting chemicals. 

Bartol! 5, Do lb~ test urders lelr T i"r I C('llsiSl or d "cookie-cUIter"' or "elllc-,izc'-lits-aU" 

dl'Jlwach'l 1l'no1. \\,11\'" Could thL qualil\ olTPXs rLsults!>c impact~cl by this kind l'i'appwadl'.' 

Bart()n 5 Rcsp()m'e: :\0. thl' test orders for thc EnSp Tier I nssays require that recipients 

perform allil TicI'I assays lInless tile respondent has ju;.tification equally informatin: as 

that" hich II ould he pro\'ided by conducting a particular EDS!' Tier I assay (in other 

II on!s, they hayc other scientificall~ rrlnani information that call illform determinations 

Ihnt would be gt'llcrated IhrOllgb a Ticl' I assl1~). It i., the responsibility of the respondent 

to pl'o\'idc <;ignificant justification that the' Tier I assay has heen satisl1ed ill full ill ordcl' to 

ensure the data needed to flllfilithc Tier I assay !·cquircmcllts. 

nar1<in 6, 'I he stalUhln language oCS~clion 1.f~7 orth~ Sal;; Drinking \Yakr ,\ct requirc:s EI' .. \ 

tl) h,"st "ubslancc~J that 111ay b(' 1n drinking \\~nt:r :'t'UfCc:-\ i!'a ~Ub:;.;t.lntial pC!ptl!~ti(\n i~ l~~p{)sl'd, 

Yet. Y(llll' kSlimOll) ,Wt", tlut EPA is colJ1piling a li:,t of 1 00 ch~l1licals pursuant ttl !lPl1-

s1alli!\1ry n:p()rl langlLtgc, 

Thrt(\ll 6a, \\'ouIJ any ,,1' lh~ 100 chemical> lll't IllL~t the 'latu[nry crileria (11' th~ Safc Drinking 

\\' ate'r ,\cl': 

Barton 6a Response: The House Report for H.R. 29%. which accompanied the FY 2010 

llPl'l'Oprintions, for EPA directs the Agency to "publbh" ithin one ~ ear of enactment 11 

second list Orn') less than 100 dH~ll1icals for sCI'rcning that includes drinking waleI' 

contaminllnts. slIch ,IS haiogclIllted organic chemicals, dioxins. flame retardants (I'BDFs. 

FCBs. I'FCs). plastics (BFA), pharmaceuticals and personal care products, and iSSIH,' 25 

orden pcr ~ car for Ill<' {('>ting of thl'S(, (~hcl1licals." 

EPA has already issued test onlet's for 67 pesticide chemicals and bdiews that it h 

important to continue testing additional substances for potential cnlioninc disrupting 

acthity. Wl' arc currcntly dcveloping our second list of approximately 100 chemicals and 

expect to invite public COllllllent on the list within the IJe\t sCHn,1 months and begin issning 

Il'st orders later this ~ ~ar. Onlers requil'ing testing of additional chemicals must he 

anthorized under our existing statutory authoritic's. which include sectioll 1-157 of the Safe 

Drinking \Vater Act (SDWA) and s{'ction -I08(p) of the Federal, Food, Drug, and Cosmetic 

Act (FFnC\). SOllie of the chemicals proposed for the sl'cond list" ill he Ill'stidde 

ingredients. and \Ie" ould rel~ on section -I08(p) of FFDCl,. as the authority to issue test 

onkrs for these chemicals. TIll' rt'lllaining chemicals IJrOIH"cd for the second list \I ill he 

drinking" at,'!' contnminanls. For them. Wt' would rdy 011 scction 1-157 of SD'YA, which 

n'qllires EPA to make eel'lain findings hcfon: i'Suing the test ordl'l's, 

I\mwn (,11, \\ iI\ ell'''' 1<1',\ ilHc'nd h) include pe:,ricici", tlil a llOIh\a\UI(lIY lisllhat Ih~ ag.:ncy 

jlt\:'\ il,lU~I~ ct'!nc1udcd JiLl ntJl ll1ccl tl1L~ mininHl!l1 ((mc,-'-rn erik-ria [t) lllL'ril lislillf:;. \';11 eer ::? 
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Barton 6h Response: As noted above, EPA helieves it is important to evaluate chemicals, 

including pesticides. for potential for endoninc disrupting acti\ity. We ban a statutory 

mandate to scrcenaH pesticide chemicliis under se('fion -l08(p) of FFDCA. Iuaddition to 

the initial list of 67 pesticides for" hich we have aln~ad~' issued test orders, we plan to usc 

our slat\ltol'~' authority under section ./08(p) of FFDC\ to issue test orders for any othn 

pesticides that arc included on our second list. ~ote tbat some of the pesticides on the 

second list ma~ also he drinking watrr contaminants as well. 

Barlcln 7, Plcas2 c\pbin 1\ hcthcr IlllKIi of the l'r(lbkl11 of tile presence of !hc,,~ suhstances in 

surfa.:e \Yakr.; could be soh'cd \Iitl! bwer \\':lSle Wilier trcatnKnl tcdmiqncs, 

Barton 7 Response: 

The rffee/heness of tcchnoiugi('s in remo\ing the (lotentially wide I"llnge of chemicals that 

may hI: EDCs has not heen fully studied, Howc\cl\ gcnually the more ad":liIccd the 

treatment tecllllolo~', the greatel' the removal of chemical contaminants, :\Iany factors 

impact the type of treatment that is appropriate for a publid~' owned \Yllste water 

treatment works (POT") These include thc source and t~'pc of contaminants in tlit' wllste 

stream, the size of the cOlllnllll1it~' sened by the POTW, and the cost of the treatlllent 

tcchnolog.\' to thc community sen cd. A portion of EPA's cndocrine disrufltOI' researcb 

budgrt is devoted to studying the effectiYClless of wastewater treatment trchnologies to 

rCl1lO\C chemical contaminants. 

Barton 8, Hasn't it beell 1::1'/\' s appwnch to conduct scn:ening of an initial list of ch"micals to 

kst the pert0rm:lnc.: of'I'; Ti"r 1 screening ban..:r;-·) Doesn't El',\ 1l('C'd to :lmlit the results oftlla1 

screening bel\lre it umkrtakcs ndditional screening') 

Barton 8 Response: The purpose of the scrcening of chemicals on the initial list is to 

generate data that will be used to determine "hether or not those chemicals haY(' till: 

potential to interact with the endocrine Systl'lll. It is not specifically designed to test the 

hattery; howcwr, cOllsistent "ith the 1999 SAB/SAP's recommendation, EPA \\ ill wnt/uct 

an analysis of the dahl tn determine how' the different assays \yurkcd in COllcert with each 

other, compare thl' resnlts ,\ ith Part 158 data and with the To\Cast data to determine tbe 

correlatioll of the Tox('ast assays "'ilh the EDSI' results. ToxCast has been dcnlopcd since 

2005. The comparison of ToxCast results with the results of the Tic,' 1 hattery is all 

importallt slep in determining tht' potential ofT(nCast, and to understand whether the 

relevant TO:l.Cast ass"ys provide the relmbility and reproducibility required for chemical 

screening. Determining how \\ ell the assays wO!'k as Plll't of the batte!)' as a whole would 

allow EPA to optimize the batte!'y by diminating assa~ s that provide needless rcdllndanc~ 

01' flag others for impru\cment or replacement. Ideally, this analysis would he conducted 

before EPA issued additional test ordel·s. 

Bartoll 0, In 1099, EPX, Science ,\dyisnry Bc)ard (S,\B) and I::PA':. Science: ,\d\isnr) Pand 

(SAP) l\~COl1llllend"d Ihat [Po'\ conduct all initial phase ofscr..:.:ning orSfl to 100 substances, 

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Bartoo 9n, Pkas~ CXplaillth.: bibis t<)1' tilat I'CCDIllIl1Cnciatit111, induding \Iilether tll"l'e \\"r" 

e<)l1eerllS that til..: a'Sil: s or balkry might nOl perform ,)<; hoped, Pkasc furth,'l' explain til" S,,\ P' s 

:.p~ci lie ClJlll\ .. Tns. 

Bartun 9a Re,ponsc: The S,\1' report notes; "The Subcommittee supports thc proposal to 

dewlop a two-phaH' program for endocrine dbruptor scrt'clling and testing (EOST). 

Furthcl', a formal rccYaiualioll of the screening and testing proc('ss at regnlar intc!'\'ais 

should be part of the program, The purposes of this rccy,lluatioll IlI'ocrss would he to 

CYalliatc the cffcctiHncss of the protocols initially adopted fIJI' screening and testing and to 

adopt lit'" protocol; in clIses when none clirrently exist for idelltif~·ing cndocrill<' 

aitnations or thl' effects of those alterations. Adoption of new SCI'cellS and tests should also 

mean the elimination of pn.'\ious, less useful ones." 

Barton 9b, Please: slate whdher 1"1':\ has undertaken the SAP-l'ccnl11l11(.'mkd pilas<.'d approach by 

ordering sCl'L'ening oj' an initial list oj' 67 l)(.'stieick d)cmicais, 

Barton 9h Response: As stated in -,e\'ernl Federal Regis!t,!, Ilotices, 1':1'.\ is following the 

1999 SABfSAI"s "c,'ol11mCndat\olls to screen 50-Hili chcmicab and review the results. That 

rc\ic\\ is projected to occlir in 2013 after all of til(' data haw been submitted and rt'yicwcd 

hy thl' :\gcl1l'Y' !IOWCHI'. [P,\ is also following the directive in the Appt'opriation 

Committee report that a second list of no Ic~s than 100 dlemkals be puhlislJ('d by October 

31.2010 and that the Agency issuc a minimum of 25 orders per year. 

BnrtllJlC)L'. I'kast: S\a,C "hetb"r FPA bclic\cs it ll1a~ lind itl1cccss~ll': h) modif\ S(\111e riel'] 

screens and the TI S balleT) ~IS a result "i' inillJ'lnati<ll1 itllhtains li'om screening the initial list lIr 

chemicals. 

lbrtllll 9ci, Pleas\.' stalc I,bdlcr it is jlos,ibk lhill the riel' 1 balkr\ 11la: not be cfl'ccti\ c for 

ckterll1ining \\ hich chemicals lll:l\' interact \\'itll th" cnd()crinc syslL.'m. Pkasc also cxpJainthc 

basis of Fl':\'s col1clu,ioJl .. , 

Barton gei Rcspomc: EPA belie"cs, and the SAP re1ic\\ ill 2008 COIlCUlTl'd, that the baltcr~ 

"ill perform ils cssential fUllction IG identify chemicals that intenlct with the estrogen, 

androgen and thyroid hormone systems. EPA docs 1I0t anticipate any serious problems 

with any ofthc assa~ s in till' bal1uy, but acknowledges IIUlt there is ah, <1:-'$ the possibility 

of unforeseen problems that did not show up during validation. Please note that the 

yalidation process has lwen HI'" ri1~()n.u" and EPA has carefully ;;ought to hllhlllec the 

need for ,alidation with the >talulol'Y mandate to require it'sling. 1':1',,\ is developing 

potcntial l'('placcmen! assay;; and \yill phase in n('\\ el' trl'imologies as th"y arc "alidatNI. 

This is cHnsistent with the SAP recomllJendations; "In sUlllmary. the proposed set of Ti,'!' I 

assays arc appropriate (0 Ill'gin screening for disrllptors of the lestrogen, androgen, and 

thyroidl EAT i\"\es, Ho\\(', LT. srHral assa~'s do not I'elll'csmt the run-en! statc of tile 

,eicllce, or tbe proposed screens do !lot fully address maJor modes of action and should bl' 

npda(('d and C'l.tcnticd as soon :lS possible. The E1':\ sholild consider this set of a,says to he 

a work in jlr0t:n'ss, The Panel ex peds that the EP,\ will ('ontjulle to de, dop, rl'i'ilJ('. and 

l'CYil'" the batt('I·~'. '\cw endocrinc disruptnl's and fie,\" merhanisllls of at'fion arc likely to 

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be renaled in the future requiring that the current Tier 1 as,a~'s be modified and new ones 

deYeloped and yalidated," 

Banon llcii. Please SWlt' \\"Iwthcr it is possible EPA may tind it necessary tn signiticamiy ll1odij~ 

some assays and the hallcr\. 

Barton 9di Response: Otht,!' than replacement of a>says with Ilewer technolog~', EPA docs 

not anticipate significallt modifications: hIm e\"Cl', as noted EPA is prepared to do so if this 

is warranted, EPA also intends to explore additional areas recomlllended hy the 

Appropriatioll Cummittee such as the adrenal axis, The adrenal axis is the adrenal, the 

h~polhalitlnus and pituitary glands and (hdl hut'monc;" 

BIliWIl 9d. Pkbe ,1:[t(: "hether 1-:1',\ drafted ilexi!>!.: il11pklllclltatic,n polic\ and procedures ia, 

c1pp<"cd ttl a rllicll1akingll.'111hc' ha,is that the agcllC\ might need 1<.ll11odil) ti1nsc plllicies alhi 

l'I"Occ'durc..; ill rc"polbC t(' information il gatbers in implementing the Iirst pha,c 1'1' screening. 

Harton 9<1 Response: EPA chose 110t to use rulemaking to codify its policies and procedures 

so that their ll1odifil'ation could he ll10re expeditions if\\arrantcd hy the experience with 

the fil's! group of 67 chcmicals 

Bartl111 9c, Please cXl'i3in how the: bc'l1elits (\1' a phased screening approach can be it LP,\ docs 

not (lIYaits \he results 1 "rcening before undel1aking additional screening. 

EPA is pl'ocl'eding with the .second list hef'ore the analysis of the results from the first list 

Clln be conducted; howcycl', what EPA learns frolll the tirst and second lists will bc' 

reneetcd into lIlodifications to tht' EDSP, if appropriate, and applied to subsequent lists, 

Rather than a )'igidl~' scqut'ntial approach, EPA is adopting a rolling 'lpproach to 

impl'osclllcnt of the EDS!', 

Barlon 9.::[, Pkasc slate \\ hether 1:1'.\ has identified all i,;slIe,; that might arise during screening. 

Barton 9ci Response: EPA made a ~ood faith effort to identify the most important issues 

that arc likcl~ to ;lrisc during screening, and to prepare for them, However, there "'111 he 

no guarantee that all illlportant bsnes hayc heen anticipated, 

Barton 'kii. Plcase state ifFP,·\ has already dctc:rmined \\'hctl1cr or nN it \\illl11odit~ its lier 1 

~bsa:, and bau\.'r) 

Barton 9cii Response: As noted abon, EPA plans to eyalnate l1eWel' technologies that lIlay 

provide significant ,ulqllltages on!' sOllle of the oldet' technologies, Howe\"cr, until 

validation is complete and the Agency can be certain that such technologics provide 

cquil alent or hetter informatioll. a decisioll to modify the existing Titr I assays and battery 

would he inappropriate, 

8;1n011 Ill. Pkase stme: \\hctllcr. in 1999, the EP,\ Science ..\(I\isory Plmci (S.\P) stated \\il11 

respect to :\cgati\'c Control ,\gcnls. "There is a need to ddll1c and agree on St'me !legali\"<;; 

- 11 -
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contr,,1 ,rgents for I endocrine disruptor! as,ay yalitiation, . \s:iay spl'cilicit) II ill not be capable (If 

a5scs~n1cnt unkss su('h ag('nts ('an be Inadc ayailabk l~)r g~lh."ral study," 

Hartoll I () Response: The sentcnces cited lIPlwar in the S.\P's "Rc\icw of the EPA's 

propm.cd cmirollll1cntal endocrine di;.ruptor :in-cening I'rognlll1" rck:lscd in 1999. 

Bart\)11 lOa, 1'1",15\: s\att' \\hethel' rP-\ has established and run ncgatih' c()]111'(\1 agents in som..: ,,1' 

the EDSl' Ti"r I scrcening assa~s, 

Bartoli lOa Response: EPA has estahlished and run ncgath C coulro! agents in sonlt' of the 

EnS!' TiCI· I screening assa~'s. For example, iil till' estrogen l'en'ptor binding llssa~, 

octyltriethoxysilane has becn estahlished as a negatiH control agent. All of the Tier I 

assa~'s wen' successfully tcst,'d "ith ncgati\'C chemicals pl'io!" to the issuance of test orders. 

Howen'f, during the yalidation program. the chemical selected as the Ilcgath'c chemical for 

the puhcrtals showed SOllie effc"ts on the endocrine system. i.e .• it was Ilot nc[,!:atiYC. This 

raised cOllcerns I"cgarding the spt'cificity of these ass:!! s. 

Barwn lOb, I'kasc "Ule' \\he'thl."l' ill \ larch ~ilm( the S .. \P l\)Jd I 1', \ .. ',\ nt:gati,'c Cllmwl 

substance(s) has !lot be'en idcntilic'd It)1' 1h" pubertal assn:s and lhis stands as a major iilllilation 

ttl lile Tkr I balkr;," 

Barton ]()h Respomc: In SAP 'linutes 'io. Z008-()3 ",\ set of scicntific issues heing 

considered h~ the Ell\irollmcntal Protection '\l!enc~' regarding: the Endocrine Dismptor 

Screening Pl"Ogmm (EnSP) pl"Oposed tier 1 S(Tl'('nin[,!: Battery" tI'ansmitted to EPA in .Julle 

ofZ()()8 the SAP "mtl' as follows: "Althou[,!:h the Panel found that the battery of assays 

presented would selTe as all adequate stl"cen for estrogenic, androgenic and thyroid 

hormone disruptors. a number of n:commendatinlls were made for modifications of the 

assays and for further research. Among those arc the following: ... 7 . ..\ ncgatiYC ,·ontrol 

suhstancc(s) ha, !lot been idcntilkd fOl' til(' pubertal assays. This stands as a maJor 

limitation to the Ticl" I battery and morc compounds should be (est cd ... :' 

The follow-uJl to this ronccrn was stated in the I·,sponse to qllcstion lOa. 

Barton I (ie, l'kasc slate whether the .. \geney has rdClb<:d 1\)r independent peer. [IS \\'e11 as puhlie. 

rc\-je\\ ~tudiL'S of j lH\l1-cndpcri]1l.:? acti\ c. ne~ali\'~ (ol1tl'nI agent in thCSL pubertal assays. 

BartOl! J()c RCS[HJIlSC: As of ,\latTh 22, 2010 the Agency has tlut ~ct n'lm,scd for 

independent peer review its c\'idence that a chemical that has HOIl-endocrine toxicity does 

not necessarily haH' effects on the l'ndocrinc s~'stem. The study. which has been complttcd, 

is acti\el~' bdng prepared for suhmission to a lwn-n'\,icwed journal. 

llarll)1l IOd, Pkasc stalc (\kther the ,\g<.:nc\ has neglected h) heed the r1Cilicc ,,(the S,\!'. ,lIlel if 

Sl). pkasc l'''plaill \\ hv, 

Harton lOd Rl'spoll<,e: Tilt' Agmcy has !lot Ilcglt-cted to heed tilt' ,1(1\ icc of the SAP. The 

SAP call1'lI for additiotlalre~\':trch. EPA i;; preparing for publication the !"c,lIlts of:t 

I..' 
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research study which addrcsse, the SAP's conccm llbout the lack of a nega!i\ C l'ontrol in 

the pullertal assays, 

EPA also notes the difficulty offillding a chemical that is ,llread~ "known" to he negatiY<' 

and that can be used to test whether the pubertal assll:'s give the "correct" (negative) 

response, \\ hen no Yltlidated endocrine assays that tcst the breadth of endocrine 

l1l('chanisms coycrcd h~' the pubertal assays ,we available. That is, there is no llcccptcd 

assay to cOlllpare the results of the pubertal aS~illys to, Ccrtainl~' there are chemic'lls" hich 

a1'e kno" II to he negatiH for specific mechanisms such as estrogen receptor binding or 

aromalasc inhibition, hut the [lubertal assays test for effects that might he due to any of 

scnl'al different mechanisms and that may be modifil'd hy the complexities and possihle 

interactiollS across multiple pathways of a living organism, Thus the negarive control 

chcmicals that arc used in mechanism-specific assays and test-tube assays cannot he said to 

he "known" to he negativc for all endocrine pathways tcsttd by tbe pubertal assays, 

Bart(\n I (k Pkase slatC' the re:lse'!1ing behind EPA's decision t(1 require these a%a: s despite the 

nc:ed 1,)1' specificity as (11lC of (ile core ckm,'llb 01' cstabli,;/1ing a Sckl11iiically \'alid ass:!,. 

BartOli IOe Respollse: Since there arc no compounds that arc "known" to he negative for 

all of the endocrine mechanisms tested by the pubertal assays in a complex [iying o rgllll is 111 

lUld that could, thus, SCI've as chemicals to lest the specificity of the pubertal assa~'s, EPA 

has t'('Iicd on thc fact that certain chemicals arc negali\'(, for one mechanism or another to 

show that the puhertal assays arc specific, A thyroid-artin' compollnd could rCllsollahl~' be 

eX\lected to hc ncgatin' for estrogenic 01' androgenic effects (although thel'(' is some cr'osstalk alllong the syst(,lllsj, and "ice wrsa lind indeed this is sho\yn to be true when using thc 

pubc,rtal assays. Propylthiouracil, for eXllmple, showed cleal' effects (Ill the thyroid in the 

puhertal fl:ll1alc assa~' at a dose level that did not han 1111 cff('ct 011 the reproductive axis. 

COllversel~', ctltynyl estradiol showed clear effects 011 the n?productiYe llxis but 110 effect on 

the thyroid system. TIl(' pubertal assa~ s clearly do not give positiH results fOl' all 

endpoints for all chcmicals, as lllight be ('xpected jf the pubertal assays respoIHkd 10 

general stress rather than to endocrine-specific mcch,lIlisll1s and it was on this basis that 

EPA del'i(kd to inclIHk' the pubertal assa~s in the b.ltter~' proposed to the SAP, As noted 

aboH, EPA's Office of Rescardl and DCHlopmcnt continued to search for a chemical that 

would he gl'ncl'all~' toxic hut dcyoitl of all eff,'cls on the endocrine system, 

Barton 101~ Picase stall: the rationule 1(11' EP,,,"s ,it:ci,inl1 not to li.)lkm thc S\P 

rccol1l1nendations. Pkas;; c;;plain I\ll: assays which 111JY not be ahle to distinguish endocrine 

'lcti\ it" 1'1',)111 \11her type" of toxi,:ity ,h,)ulcl be includ"ct in the endocrine s<:r"ening ballery if the 

purpose oCtlla! ballery is te) idenljl~ substances with the potential to interact \1 ith components of 

th~ cndc1crin..: S) st;:n1. 

Barton IOf RespOllse: As explained ahove, El'A has followed till' SAP recollll11endations. 

The fish screening assay contains lIpical endpoints snch as fecundity which has caused somc 

l'Onerl'll llmong stakeholders 'rho argue that the screens should only measure endpoints 

specific to cndocrine disruption, However, consistent with the recolllmendations of its 

mhisory cOlllll1itt{'cs, EPA decided to inl'lude some apical endpoints as not all endocrine 

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mode;; ()f actioll can Ill' t'llptul'cd "itllOut thl'lIl. While other t~ pes of t()xicit~ ma~ also 

affect fccllIldit~ .. the Imllcl-:'- a;; a wlwlc can he used tn distinguish effects that arc endocrine 

related from those arising from other mod('s of action. 

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March 31, 2010 

Committee on Energy and Conul1erce 

2125 Raybum House Office Building 

Washington, DC 20515-6115 

NATURAL RESOURCES DEFENSE COUNCIL 

Dear Chainnan Markey, Rep. Barton, and Members of the Committee: 

I am pleased to respond to the additional written questions posed by Chainnan Markey 

and Representative Barton in follow-up to my testimony before the Subcommittee on 

Energy and Environment on February 25, 2010. My original testimony focused on 

"Endocrine Disrupting Chemicals in Drinking Water: Risks to Human Health and the 

Environment". I expressed serious concems about the documented presence of chemical 

contaminants in source water in the United States. The decade-long delay in the 

implementation of the EPA Endocrine Disruptor Screening Program (EDSP) has resulted 

in a huge backlog of chemicals that have not been tested for endocrine disrupting effects, 

including many COl1U110n drinking water contaminants. Furthenl1ore, EPA has failed to 

take regulatory action under the Safe Drinking Water Act (SDW A) to protect the public 

from chemicals that have been tested and found to be endocrine disruptors, and that are 

known to be contaminants in drinking water. In my testimony, I offered a number of 

recommendations to help address these problems, including: 

• Implementing testing under the endocrine disruptor screening program for priority 

drinking water contaminants, including all chemicals on the CCL3, as well as 

other chemicals in phannaceuticals and personal care products that have been 

detected by USGS in surface or groundwater. 

• Implementing aspects of the EDST AC report that have been ignored, such as 

creating the Endocrine Disruptor Priority Setting Database, integrating the HighThroughput Pre-Screen (or ToxCast) into the program for priority-setting, 

screening common mixtures, and inviting public nominations for testing; 

• Evaluating and identifying wastewater and drinking water treatment practices for 

removing endocrine disrupting chemicals, including phanl1aceuticals; 

• Preventing or limiting the use ofhonnones in agriculture. 

• Requiring EPA to prioritize and screen chemicals in drinking water, including 

mixtures, for endocrine disrupting effects; 

• Restoring adequate funding for the USGS Toxic Substances Hydrology Program 

and the USGS National Water Quality Assessment Program (NA WQA), so more 

data are available on contaminants in source water and drinking water; NA WQA 
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Gina M. Solomon, M.D., M.P.H. responses to qucstions 3/3112010 

started with 500 sites in 1991, and has now been reduced to 113, of which only 12 

are monitored annually. 86 sites are monitored only once every four years; 

• Reforming the Toxic Substances Control Act (TSCA) to require testing of 

chemicals for toxicity, and require EPA action to promptly regulate hazardous 

chemicals. 

Responses to follow-up questions from Chairman Markey arc presented below. 

1. In your testimony, you state that certain endocrine disrupting chemicals are 

present in our water supply, albeit at low levels. 

a. Are there documented health effects associated with low dose exposures to 

endocrine disrupting chemicals? If so, can you describe them? 

Yes, peer-reviewcd scientific publications have found health effects from low dose 

cxposures to endocrine disrupting chemicals. "Low doses" are defined here as exposures 

that are occurring at or below current levels of exposure in the human population. 

Endocrine disrupting compounds such as bisphenol A I, phthalates 2

, and some 

pesticides3

.4 have been associated with a wide array of adverse health effects after low 

dose exposurcs. Many of these studies have been done in laboratory animals, but 

emerging research has found evidence of similar haml in non-human primates and 

humans. 

Low doses ofbisphenol A (BPA) have been associated with precancerous lesions in the 

prostate and mammary gland (breast), alterations in brain development causing 

behavioral abnormalities, reproductive harm including earlier onset of puberty, uterine 

fibroids, and abnormal numbers of chromosomes in oocytes (female eggs)5. Recent 

studies in non-human primates and human epidemiological studies have found effects 

similar to those seen in animal studies after low dose BP A exposure. These include 

interference with the treatment and progression of breast canccr6

• 

7

, prostate cancerS, 

altered development of the brain causing changes in behavior 9.10, alterations in hormone 

signaling in fat tissue 11.12 and cardiovascular disease 13. Low doses ofphthalates have 

been associat7

? with allergic responses,:: worsening of as~hma, altered de:el?pme?t of 

male gemtals " Impaired semen qualIty ,and alteratIOns m toddler behavIOr . Fmally, 

mixtures ofphthalates and other anti-androgenic chemicals including some pesticides, 

have been found to have additive effects such that exposures to the mixture cause harm 

where exposures to the individual chemicals at the same doses cause no harm 18 . 

b. Why is the dose-response for endocrine disrupting chemicals different than 

other toxic chemicals? 

It is a well-recognized and accepted physiological phenomenon that hormones naturally 

occurring in the human body (endogenous hormones), are regulated by feedback loops 

which respond to small changes in circulating hormone levels, receptor binding, and 

metabolism or breakdown of hormones. Therefore, low levels of endogenous hormones 

have very different, and sometimes opposite, effects than high levels of a hormone. These 

2 
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Gina M. Solomon, M.D., M.P.H. responses to questions 3/3112010 

feedback loops respond to very small changes in concentration, in the parts-per-trillion to 

part-per-billion range, but are potent enough to bring about ovulation and other physical 

changes each month in a women's reproductive cycle and the profound changes that 

occur during puberty. Therefore, it is not surprising that chemicals in the environment 

that interfere with the endogenous honnones in a human body can have differing effects 

at low versus high levels of exposure. Furthennore, laboratory studies which rely on 

dosing animals with high doses of an endocrine disrupting chemical, will not adequately 

predict the effects oflow doses of exposure. 

c.If endocrine disruptors exert their effects at what are considered minute 

dosages. can a dose that is low enough to be considered safe ever be determined? 

Risk assessments currently done by federal agencies such as the EPA do not adequately 

address endocrine disruptors because they do not consider mixtures, low dose effects, or 

background exposures, and therefore have not been adequately protective of the most 

susceptible populations. The National Academy of Sciences (NAS) recently issued two 

important reports which called on EPA to consider mixtures, background exposures and 

susceptible populations for improvements in chemical risk assessments - especially for 

endocrine disrupting chemicals. 1920 The NAS also recommended that EPA move away 

from the assumption that there is a threshold for non-cancer adverse effects. 

Although endocrine disruptors pose a challenge to risk assessment, thc NAS clearly 

cOlmnunicated that the challenge can be met with updates and improvements to the 

current risk assessment process. In some cases, there may be no safe level of exposure to 

a chemical or group of chemicals, but these chemicals can also be addressed using 

existing approaches. For example, there is a broad scientific consensus that there is no 

safe level of exposure to lead, so there has been a decades-long effort to reduce or 

eliminate sources oflead exposure. As a result of exposure reduction efforts, CDC 

biomonitoring data have documented a dramatic reduction in blood lead levels in the U.S. 

over the past few decades. Endocrine disruptors - like lead - are chemicals that can have 

health effects at low doses. Regulatory approaches to assess population risks and to 

reduce cxposures as mueh as feasible can successfully protect human health and the 

environment from these chemicals. 

d. What do we knml' about the effects of being simultaneously exposed to 10lV 

doses of several different endocrine disruptors? 

Mixtures ofphthalates and other anti-androgenic chemicals including some pesticides 

have been found to have additive effects such that exposures to the individual chemicals 

at doses shown to cause no harm have been found to cause hann when combined in a 

mixture 21 . Furthennore, there are a number of environmental chemicals which mimic 

thyroid homlOne and also can be expected to exert additive or synergistic effects when 

combined in a mixture. 22 The National Academy of Sciences (NAS) recently issued a 

report underscoring the importance of evaluating groups of chemicals that cause the same 

adverse outcome, such as altered male genital development caused by mixtures of antiandrogens including phthalates, or neurodevelopmental hann caused by thyroid honnone 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/3112010 

disrupting chemicals. 23 The NAS stated that basing chemical safety evaluations on just 

one chemical at a time or ignoring other modes of action which contribute to the same 

outcome "may lead to considerable underestimation of risks to the developing fetus." 

2. In your testimony, you state that you served on EPA 's Endocrine Disruptor Screening 

and Testing Advisory Committee. The committee submitted its final report to EPA in 

August 1998 with a number ojrecommendations. 

a. Which oj these recommendations did EPA jail to implement? 

I) EPA failed to implement the "high-throughput pre-screen (HTPS)" for estrogen and 

androgen receptor binding and transcriptional activation. This rapid screen was 

envisioned as important for priority-setting, and for rapid detection of chemicals that may 

be endocrine disruptors via a receptor-based mechanism. The EDST AC envisioned using 

the HTPS to scrcen 10,000 chemicals per year. 

2) EPA has not yet validated the "tier 2" tests, so it is possible that chemicals which test 

positive in the current round of testing may still not have sufficient data for regulatory 

action even after the testing is done. 

3) EPA never created the Endocrine Disruptor Priority Setting Database which was 

envisioned as a way for the information on exposure and potential endocrine hazard of 

chemicals to be gathered together in one place in a publicly accessible fonnat. 

4) EPA has not developed a strategy for screening mixtures of chemicals for endocrine 

effects, including the six priority mixtures identified by the EDST AC. Two of the 

EDSTAC priority mixtures related to drinking water: common pesticide/fertilizer 

mixtures found in surface water, and disinfection byproducts commonly found in 

drinking water. 

5) EPA has not yet implemented the recommended nominations process to allow 

members of the public to recommend chemicals for priority testing. 

6) EPA has not proposed testing chemicals other than pesticides and pesticide inerts, even 

though the EDST AC explicitly recommended that all chemicals be prioritized for 

potential screening. 

b. Which oj the recommendations listed in question 2a do you think EPA should 

still incorporate into the screening program.? 

The public nominations process, and screening of priority mixtures are still very 

important and should be implemented. The most important recommendation that still 

remains to be implemented, however, is the recommendation to prioritize, screen, and test 

a broader universe of chemicals than just pesticides. For example, drinking water 

contaminants should also be tested under the EDSP. 

c. What additional recommendations do you have to improve the Endocrine 

Disruptor Screening Program? 

The ToxCast program is implementing approaches similar to the HTPS. EPA should 

integrate endocrine disruptor screening approaches from the ToxCast and Tox21 efforts 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/31/2010 

with the EDSP to improve prioritization and expand the number of chemicals screened. 

EPA should also create a public database that contains endocrine-related data - as well as 

data gaps - on a broad universe of chemicals. 

3. Over a decade ago, the EPA adopted a battery of validated experimental assays 

(called Tier 1) for the endocrine disruptor screening program. 

a. Do you think the EPA should regularly update its screening assays to 

incorporate advances in sensitivity, accuracy. reliability, reproducibility. or 

efficiency? 

Yes, EPA should regularly update its screening assays to incorporate advances in testing 

approaches and also to pursue four major objectives outlined by the National Research 

Council: (1) to increase 'throughput' so more chemicals can be screened, (2) to enhance 

the depth of infonnation for risk assessment by incorporating more endocrine effects and 

a broader range of doses, (3) to reduce animal use, and (4) to reduce COSt. 24 Newer 

techniques are being developed that allow screening of chemicals using in-vitro methods 

and non-mammalian approaches. These should be run in parallel with the current EDSP 

screens until it is clear that they are reliable enough to replace some or all of the current 

screens. This will allow continuous improvement in the program without further delaying 

implementation of the EDSP. 

b. What recommendations do you have to ensure that the adopted screening 

protocols are SCientifically valid? 

The National Research Council, in their report entitled "Toxicity Testing for the 21 st 

Century," rccommended running newer assays in parallel with current testing methods 

until there is sufficient experience with the newer assays, and sufficient confidence using 

these results in priority-setting and risk assessment, that the newer assays can smoothly 

replace the older ones. 25 

4. Are there chemicals that have been listed on any of EPA's Candidate Contaminant 

Lists, for which you believe there is enough information about their endocrine disrupting 

effects that further Tier 1 screening under EDSP is not necessary? If so. which ones? Are 

the health effects associated with any of these chemicals suffiCiently well-understood such 

that Tier 2 screening under EDSP is also unnecessGlY? Ifso, which ones? 

Several important veterinary steroids that have been detected in drinking water are on the 

CCL3, including estriol, estrone, ethinyl estradiol, and mestranoL Some of these are also 

breakdown products of human pharmaceuticals. Perchlorate is also on the CCL3. The 

CCLl and CCL2 list contain several additional well-understood endocrine disruptors 

including linuron, triazine herbicides, and organotin compounds. These are chemicals 

whose endocrine disrupting effects are well-characterized. There is no need for additional 

screening or testing of these chemicals. In my opinion, regulatory determinations for 

these chemicals can (and should) be made based on currently-available toxicity and 

pharmacological information. 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/31120lO 

Responses to follow-up questions from Rep. Barton are presented below. 

1. You are critical on (sic) the speed at which EPA has moved the Endocrine Screening 

Program along. Please tel/me what is the exact amount of time that it takes to 

produce high-quality science? 

Congress gave EPA a reasonable timeline for creation and implementation of the EDSP; 

two years to create the program and an additional year for implementation. EPA met the 

deadline for creation of the program, but missed the implementation deadline by more 

than a decade. The explanation the Agency offered for failure to meet the Congressional 

deadline was that the validation process was ongoing. It is puzzling to many scientists 

and to the members of the Endocrine Disruption Screening and Testing Advisory 

Committee (EDSTAC) that validation of these particular assays took so long. The 

EDST AC envisioned that EPA could complete the validation within the allotted year. 

Most of the assays used in the EDSP are ones that have been in widespread scientific use 

and have achieved broad scientific acceptance for many decades. For example, the 

receptor binding assays and the Hershberger assay have all been in common scientific use 

since the early 1970's, and the uterotrophic assay had been in broad scientific use for 

more than 80 years at the time of the EDSTAC report. These assays were not new 

science, and represented well-established and well-understood scientific tests for 

hormonal effects. For such assays, a decade-long validation process makes no scientific 

sense. 

2. You testified that an "unsavory mix" of such substances like pharmaceuticals, 

hormones, pesticides. flame retardants, and plasticizers have beenfound in the 

nation's waterways. Many of these substances are not just vital to human health-like 

pharmaceuticals and often hormones- but many are mandated by law for safety. How 

do you respond? 

As a physician I am distressed at the implication that because some pharmaceuticals and 

hormones may be prescribed to some individuals to treat speeific diseases, widespread 

exposure to the entire popUlation might somehow be "vital to human health". I have 

never preseribed a drug to a patient who doesn't need it. To do so would be malpractice, 

and could result in serious harm. For drugs sueh as antibiotics, overuse and resulting 

environmental contamination has been linked to the very dangerous problem of antibiotic 

resistant bacteria. In tact, the CDC has an ongoing campaign to prevent antibiotic 

resistance and has highlighted numerous dangerous human diseases that have been linked 

to this problem. 26 The problem is not limited to antibiotics. Synthetic homlOnes that 

might benefit some adults at some times in their lives are known to hann developing 

infants. Many pesticides, flame retardants, and plasticizers have well-documented 

adverse health effects. I am not aware that any of these chemicals are "mandated by law 

for safety" in drinking water. 

3. While it is a good goal to reduce toxic exposures in the environment. should the u.s. 

Government stop requiring the use offlame retardants in consumer products like 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/3112010 

mattresses, forniture, and clothing? In the absence of alternatives, should we stop 

mandating the use of the chemicals that make our cars safer and more impact resistant 

and our children's bike helmets more protective and shatter-proof? 

To my knowledge, the U.S. Government does not require the use of toxic flame 

retardants, nor does it mandate the use of any specific chemicals to make cars and bike 

helmets safer. Instead, there are flame retardancy standards and safety standards for some 

consumer products. These standards can be met in various ways, such as through the use 

of naturally flame-resistant materials or design changes. For example, Apple was the first 

electronics manufacturer to announce a commitment to remove all chlorinated and 

brominated chemicals, including flame retardants, from their products and as one 

example of a design change has replaced the polycarbonate housing of its laptop 

computers with an aluminum alloy. As a result of these and many other design changes, 

many Apple products such as the iPhones and iPods, as well as their computers, are free 

ofbrominated flame retardants. 27 Seagate, the largest disk drive manufacturer in the U.S. 

has eliminated chlorine and bromine-based chemicals from a line of new disk drives. 

Furniture companies such as Herman Miller and lKEA also have pledged to replace toxic 

flame retardants with safer alternatives. 28 

I certainly hope that my testimony did not imply that consumer safety protections should 

be eliminated. Instead, the goal is to eliminate contamination - such as of our drinking 

water supply and to encourage innovation in the chemical industry to adopt "green 

chemistry" approaches. It is certainly within the range of modem science to ensure 

product safety without needing to use toxic chemicals or produce environn1ental 

contamination. 

4. Your testimony of (sic) is highly critical of BPA. IfBPA is so dangerous, why have 

countries like Israel and the EU reversed their bans on the substance, stating 

unequivocally that its use is perjectzy safe? 

Neither Israel nor the EU have ever temporarily banned BPA or reversed a ban on BP A. 

The Israeli Health Ministry advises parents to throwaway baby bottles that have been in 

use for over a year and those that have cracks or scratches. The Israeli Health Ministry 

has said that it is watching recommendations on BPA from relevant organizations abroad 

and is working with the Israel Standards Institution to produce a standard for baby bottles 

and related plastic products. 29 An extensive search failed to find any documentation of 

the alleged statement that "unequivocally ... its use is perfectly safe". I would be very 

interested in seeing documentation of this statement. 

In Europe, the French Food Safety Agency (AFSSA) is pursuing a new safety assessment 

of BPA with the European Food Safety Authority (EFSA).30 Meanwhile, the French 

govefllll1ent is moving to ban BPA in baby bottles. 31 A spokesman for the French 

enviromnental health research institute Reseau Environnement Sante, said the French 

Senate had taken "a big step forward" by voting in favor of the ban. He called for it to 

"go a step further and vote to ban BP A from all food containers used by mothers that 

could cause foetuses and breast fed babies to be contaminated by the chemical".32 On Feb. 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/31/2010 

9,2010, the Danish Parliament voted to ban bisphenol A in products aimed at children 

under three years old and called on the Danish government to press for a European 

Union-wide moratorium on the use and sale of food contact materials with BP A. The 

resolution urges the govermnent to ask other member-states to implement national bans 

and support an EU-wide ban. 

The Canadian Ministry of Health has determined BP A is a "chemical of concern" and has 

banned the use of BP A in baby bottles and is restricting use in fornmla cans. 33 In 

addition, the U.S. FDA has recently changed its opinion on the safety ofBPA in our food 

supply and has expressed "some concern" for the impacts of developmental exposure to 

BPA. FDA is encouraging thc development of safer alternatives and has public 

information on its website about how to avoid BP A exposure. 

5. You cite studies that allegedly show exposure to BP A is so dangerous that it is linked 

to cancer and brain abnormalities. 

a. What was the route of exposure for the BP A dosage? 

Laboratory studies that have found evidence of a predisposition to cancer or brain and 

behavioral abnormalities have dosed the animals via subcutaneous injection during 

critical windows of development such as in the womb (prenatal) or early in life 

(neonatal). Independent peer-reviewed research has demonstrated that during these 

critical windows of development, the capacity to breakdown or metabolize BP A is not 

developed and therefore, the route of administration has not been found to change 

circulating levels of BP A. 34 

In the 2008 report of the National Toxicology Program's (NTP) Center for Evaluation of 

Risks to Human Reproduction on BP A, the NTP wrote the following regarding route of 

administration of BP A in animal studies: 

"Taken together these data indicate that, compared to adults at a given dose, 

neonatal rats (and presumably mice) metabolize bisphenol A more slowly and 

suggest that differences in circulating levels of free bisphenol A arising from oral 

and subcutaneous routes of administration as a result of "first-pass metabolism" 

are reduced in fetal or infant animals compared to adults." and "While more 

research in this area is warranted, data from studies where bisphenol A was given 

by subcutaneous injection were considered as useful in the NTP evaluation as oral 

administration when treatment occurred during infancy when the capacity to 

metabolize bisphenol A is IOW.,,35 

b. Assuming the animal tested is identical inform and substance to a human. 

is that a normal route of exposure for BPA? 

For fetuses in the womb the route of exposure will be through BPA transferred from the 

mother's blood. Administration ofBPA in laboratory animals via the subcutaneous route 

of exposure to the mother will result in identical transplacental exposure to the fetus. 

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c. Generally speaking, are there studies that suggest that BP A is not harnifit/? 

Most industry-funded studies have not found evidence of harm. These studies have had 

flaws, including not looking at endpoints that have been described for BP A toxicity such 

as precancerous lesions in prostate tissue or behavioral abnormalities and the studies 

reportedly contained inconsistencies in the reporting of animal data. 36 One new study by 

US EPA scientists has also found no evidence of hann in laboratory rats. 37 However, this 

study has also been criticized for using a strain of rat that is relatively insensitive to 

estrogen and estrogen-mimicking chemicals such as BP A. 38 

d. If so, what is the ratio o.lstudies that allegedly demonstrate danger to those 

studies that support its safe use? 10 percent to 90 percent that it is unsafe? 

25 to 75 percent unsafe? 50-50? 90 percent to 10 percent? 

In an analysis of the BPA literature published in 2005, there were 115 published studies 

concerning low-dose effects of BPA. Ninety-four of these (about 82 percent) reported 

significant effects. 39 Since this publication, there have been many more research studies 

on BP A and the overwhelming weight of evidence continues to demonstrate that BP A 

causes a wide array of adverse effects in a number of animal models, including nonhuman primates. In addition, there is an emerging body of research in humans which is 

consistent with the evidence of hann seen in the animal studies. 

6. Dr. Robert David Utiger, one of the leading thyroid doctors in the country, testified 

last Congress that Americans live in an iodine sujficient country. He jilrther testified 

that "there is a potent mechanism - increased TSH secretion by the pituitary glandto compensatejor thyroid hormone deficiency"; that supplementing the human diet 

with iodized salt was a cheap and easy way of adding enough compensatory iodine to 

the diet for iodine deficient persons; and that prenatal vitamins should include iodine. 

This testimony was consistent with the findings of the National Academ:v of Sciences 

and the American Thyroid Association, both of which preceded and postdated the 

CDC study cited in your testimony. Please explain your contradictory conclusion that 

a regulatory solution is necessary to address iodine deficiency. 

Among women of reproductive age in the United States, the median urine iodide (UI) 

level was 139 microg/L according to the 2003-2004 National Health and Nutrition 

Examination Survey. 15 percent of women had a UI level <50 microg/L, and NonHispanic blacks in this group had a lower UI level than other racial/ethnic groupS.40 In 

contrast, the World Health Organization (WHO) considers that a median urinary iodine 

(UI) concentration of 150-249 microg/L indicates adequate iodine intake in pregnant 

women. 41 Therefore, according to WHO criteria, the median iodine intake in U.S. women 

is low and 15% of U.S. women have outright iodine insufficiency. I agree that iodized 

salt is a positive public health measure and also agree that pregnant women may 

sometimes require supplementation (although excessive iodine can also be a health 

hazard so this approach would need to be employed with caution). None of this, however, 

should be used to countenance contamination of drinking water with industrial chemicals 

that are known to interfere with normal thyroid function. The widespread contamination 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/3112010 

of drinking water in the U.S. with a chemical perchlorate that is known to block the 

thyroid gland, is reckless and dangerous to health. Additional iodine supplementation, if 

indeed it were pursued in a widespread manner, would not obviate the need to control 

human exposure to a chemical such as perchlorate. 

7. Your testimony was velY critical of the Toxic Substances Control Act. You stated 

that we need more testing and that we do not know anything about new chemicals. 

a. Please provide specific examples of how section 5 ofTSCA has been a 

failure. 

Section 5 of TSCA deals with new chemicals that are entering the market. The EPA 

Office oflnspector General (OIG) reported in February of this year on EPA's 

implementation ofTSCA. 42 The report concluded that: 

"EPA does not have integrated procedures and measures in place to ensure that 

new chemicals entering commerce do not pose an unreasonable risk to human 

health and the environment. We found that EPA's New Chemicals Program had 

limitations in three processes intended to identifY and mitigate new risks 

assessment, oversight, and transparency. The program is limited by an absence of 

test data and a reliance on modeling because TSCA does not require up front 

testing as part of a Premanufacture Notice (PMN) submission." 

Specifically, according to EPA data, 67% ofPMNs contain no test data, 85% ofPMNs 

contain no health data, and more than 95% ofPMNs contain no ecotoxicity data. Because 

manufacturers are not required to provide such data under Section 5 ofTSCA, EPA does 

not have the information it needs to deternline if new chemicals are safe. 43 

b. Many observers believe EPA's ChAMP program made progress in 

plugging information gaps. Please state whether you agree with this 

statement. and ifnot, why not. 

EPA's Chemical Assessment and Management Program (ChAMP) was created to 

implement commitments that the United States made at the Security and Prosperity 

Partnership of North America (SPP) Leaders Summit, in August 2007. The United States 

agreed to complete screening-level chemical prioritizations and initiate action as 

appropriate by 2012 on an estimated 6,750 chemicals. The chemicals include High 

Production Volume (HPV) chemicals, and Medium Volume Production (MPV) 

chemicals - in other words, all chemicals manufactured or imported at over 25,000 

pounds per year. The program had potential for generating important hazard data on 

thousands of chemicals. Unfortunately, it came up short. 

Serious concerns have emerged over both the quality and completeness of data for many 

HPV chemicals. EPA's own accounting indicates that data gaps remain in about 30% of 

the supposedly final HPV submissions it has reviewed, and an analysis by the 

Environmental Defense Fund identified even more. 44 The foundation of the HPV 

Challenge was that companies were to provide a hazard data set specified through an 

international consensus process as the minimum amount of data needed to conduct a 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/3112010 

screening-level hazard assessment for a chemical. The fact that serious data gaps remain 

call into question EPA's ability to characterize hazards of these chemicals even at a 

screening level. 

ChAMP generated flawed risk decisions that prematurely exonerated hundreds of 

chemicals, despite inadequate data on exposure and hazard. It also caused EPA to fail to 

meet its promise to characterize the hazards of all sponsored HPV chemicals in a timely 

manner - and to clearly identify gaps in the quality and completeness of the data received 

under its voluntary program. It is one thing for EPA to identify as high-hazard those 

chemicals where, despite the data gaps, available data demonstrate high toxicity. It's quite 

another for EPA to effectively exonerate chemicals as low-hazard or low-priority when 

not even a bare-minimum data set is available for them. 45 

ChAMP has been superseded by the comprehensive approach to enhancing the Agency's 

current chemicals management program announced by Administrator Lisa Jackson on 

September 29,2009. 

c. Please explain why the EPA should not wait for the results of the initial 

screen of certain chemicals before imposing massive new testing 

requirements on these and other chemicals? 

Over the past half-century, tens of thousands of chemicals have been introduced onto the 

market and many of these have become widespread in our environment. As a physician, I 

frequently see patients who are exposed at work or in their community to chemical 

contaminants and who have health concerns that may (or may not) be linked to those 

exposures. I frequently seek infonnation on the toxicology of these chemicals and very 

often find that the infornlation I am seeking does not exist. It is difficult or impossible for 

a physician to advise a patient about potential links between their illness and chemical 

exposures if there are no data on which to base the advice. I cannot, in good conscience, 

tell a patient that there is no harm associated with a chemical that has not been tcstcd. On 

the other hand, I cannot, in good conscience, advise them to change their lifestyle, change 

their job, or move out of their home without a solid basis for doing so. That is one reason 

why I believe that chemicals that are in our environment, homes, products, and 

workplaces should be tested for safety. My experience is but one example of how having 

public access to good data on all chemicals in commerce is of usc, not only to EPA, but 

to many other sectors of our society, including companies seeking to make betterinformed choices about the chemicals and products they make, use, sell or buy 

I hope that this additional information is useful to the Conunittee as it continues its 

deliberations on these important public health issues. 

Sincerely, 

~~?n Gina M. Solomon, M.D., M.P.H. 

Senior Scientist 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/3112010 

1 vom Saal, F. S., B. T. Akingbemi, et al. (2007). "Chapel Hill bisphenol A expert panel consensus 

statement: integration of mechanisms, effects in animals and potential to impact human health at current 

levels of exposure." Reprod ToxicoI24(2): 131-8. 

, Swan, S. H. (2008). "Environmental phthalate exposure in relation to reproductive outcomes and other 

health endpoints in humans." Environ Res 108(2): 177-84. 

3 Gray, L. E., Jr., J. Ostby, et al. (2001). "Effects of environmental antiandrogens on reproductive 

development in experimental animals." Hum Reprod Update 7(3): 248-264. 

4 Ralph, JL, M-C Orgebin-Crist, J-J Lareyre and CC Nelson. 2003. Disruption of androgen regulation in the 

prostate by the environmental contaminant hexachlorobenzcne. Environmental Health Perspectives 

III :461-466. and 

5 vom Saal, F. S., B. T. Akingbemi, ct al. (2007). "Chapel Hill bisphenol A expert panel consensus 

statement: integration of mechanisms, effects in animals and potential to impact human health at current 

levels of exposure." Reprod ToxicoI24(2): 131-8. 

6 LaPensee, E. W., T. R. Tuttle, et al. (2009). "Bisphenol A at Low Nanomolar Doses Confers 

Chemoresistance in Estrogen Receptor-a-Positive and -Negative Breast Cancer Cells." Environ Health 

Perspect 117(2): 175-180. 

7 Dairkee SH, Scok J. Champion S Sayeed A. Mindrinos M. Xiao W, Davis RW, Goodson WHo Bisphenol 

A induces a profile of tumor aggressiveness in high-risk cells from breast cancer patients. Cancer Res. 2008 

Apr 1;68(7):2076-80. 

'Hess-Wilson, J. K., S. I.. Webb, et al. (2007). "Unique bisphenol A transcriptomc in prostate cancer: 

novel effects on ERbeta expression that correspond to androgen receptor mutation status." Environ Health 

Perspect 115(11): 1646-53. 

Wetherill, Y. B., J. K. Hess-Wilson, et al. (2006). "Bisphenol A facilitates bypass of androgen ablation 

therapy in prostate cancer." Mol Cancer Ther 5(12): 3181-3190. 

9 Braun,.I. M., K. Yolton, et al. (2009). "Prenatal bisphenol A exposure and early childhood behavior." 

Environ Health Perspect 117(l2): 1945-52. 

10 Nakagami, A., T. Negishi, et al. (2009). "Alterations in male infant behaviors towards its mother by 

prenatal exposure to bisphenol A in cynomolgus monkeys (Macaca fascicularis) during early suckling 

period." Psychoneuroendocrinology 34(8): 1189-97. 

l! Ben-Jonathan, N., E. R. Hugo, et al. (2009). "Effects ofbisphenol A on adipokine relcase from human 

adipose tissue: Implications for the metabolic syndrome." Mol Cell EndocrinoI304(1-2): 49-54. 

12 Hugo, E. R., T. D. Brandebourg, et al. (2008). "Bisphenol A at environmentally relevant doses inhibits 

adiponectin release from human adipose tissue explants and adipocytes." Environ Health Perspect 116(12): 

1642-7. 

13 Lang, I. A., T. S. Galloway, et a!. (2008). "Association of Urinary Bisphenol A Concentration With 

Medical Disorders and Laboratory Abnonnalities in Adults." JAMA 300(11): 1303-1310. 

14 Yanagisawa, R., H. Takano, et al. (2008). "Effects of mate mal exposure to di-(2-ethylhexyl) phthalate 

during fetal and/or neonatal periods on atopic dennatitis in male offspring." Environ Health Perspect 

116(9): 1136-41. 

15 Swan, S. H. (2008). "Environmental phthalate exposure in relation to reproductive outcomes and other 

health endpoints in humans." Environ Res 108(2): 177-84. 

16 Hauser, R., 1. D. Meeker, et al. (2006). "Altered semen quality in relation to urinary concentrations of 

phthalate monoester and oxidative metabolites." Epidemiology 17(6): 682-91. 

17 Swan, S. H., F. Liu, et al. (2009). "Prenatal phthalate exposure and reduced masculine play in boys." Int J 

Androl2009 Nov 16. [Epub ahead ofprintl. 

18 Rider, C. V., V. S. Wilson, et al. (2009). "Cumulative Effects of In Utero Administration of Mixtures of 

"Antiandrogens" on Male Rat Reproductive Development." Toxicol PathoI37(l): 100-113. and Hauser, 

R., P. Williams, et al. (2005). "Evidence of interaction between polychlorinated biphenyls and phthalates in 

relation to human spenn motility." Environ Health Perspect 113(4): 425-430. and Howdeshell, K. 1.., V. S. 

Wilson, et al. (2008). "A Mixture of Five Phthalate Esters Inhibits fetal Testicular Testosterone Production 

in the Sprague-Dawley Rat in a Cumulative, Dose-Additive Manner." Toxico!. Sci. 105(1): 153-165. 

19 Phthalates and Cumulative Risk Assessment The Task Ahead, The National Academies Press, 

Washington, DC, 2008. http://books.nap.edu/catalog.php')record id= 12528. 

20 Science and Decisions: Advancing Risk Assessment, National Academies Press, Washington, D.C. 2008. 

http://dcls.nas.edll/dcls/viewreport.cgiOid~5545. 

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Gina M. Solomon, M.D., M.P.H. responses to questions 3/3112010 

2) Rider, C. V., V. S. Wilson, et al. (2009). "Cumulative Effects ofln Utero Administration of Mixtures of 

"Antiandrogens" on Male Rat Reproductive Development." Toxicol PathoI37(l): 100-1l3. and 

Hauser, R., P. Williams, et a1. (2005). "Evidence of interaction between polychlorinated biphenyls and 

phthalates in relation to human spenn motility." Environ Health Perspect 113(4): 425-430. and 

Howdeshell, K. L., V. S. Wilson, et a1. (200S). "A Mixture of Five Phthalate Esters Inhibits Fetal Testicular 

Testosterone Production in the Sprague-Dawley Rat in a Cumulative, Dose-Additive Manner." Toxico!. 

Sci. IOS(l): 153-165. 

22 Zoeller RT. "Environn.!9lllil chemicals impactiml the thvroid: targets anp consequences." 

Thyroid. 2007 Sep; 17(9):811-7. 

23 Phthalates and Cumulative Risk Assessment The Task Ahead, The National Academics Press, 

Washington, DC, 200S. hllJh'Lbooks.nal'~£9ulcatalog.!lliP."record id=12528. 

24 Toxicity Testing for Assessment of Environmental Agents: Interim Report. National Academies Press, 

Washington, DC, (2006). 

25 Toxicity Testing for the 21" Century: A Vision and a Strategy. National Academies Press, Washington, 

DC, (2007). 

26 hltp:ilwww.cdc.gov/drugresislancc/discascs.htm. 

27 : Greening Consumer Electronics: Moving Away from Bromine and Chlorine. Clean Production Action, 

October, 2009. http://www.cleanproduction.org/library!GreeningConsu111erElcctronies.pdC 

28 Clean Production Action, Safer Products Program. 

http://www.clcanproduction.org/Saicr.About.furniture.php, accessed March 30, 2010. 

29 Don't Use Old Baby Bottles, Ministry Warns. Jerusalem Post, January 22, 2008. 

http://www.jpost.comIHomeIArtic1e.aspx··id= I 0889. 

30 "Bisphenol A: AFSSA recommends the development of new assessment methods." 5 February 2010 

http://www.afssa.fr/. 

3J Senat Communique. La commission des affaires sociales demande la suspension de la commercialisation 

des biberons [abriques a base de Bisphenol A. March 24, 2010. 

bttp:1 Iwww.scnat.fi.lpressc/cp20 I 00324,btml. 

32 French Senate backs proposal to ban BPA in baby bottles: Health research institute calls for greater 

control of plasticizer, Chemical Watch, March 26, 2010. http://chemicalwatch.com/3532. 

33 Health Canada news release: http://www.hc-sc.gc.ca/ahc-asc/media!nr-cpi 200912009 t06-eng.php 

34 Taylor, J. A., W. V. Welshons, et a!. (2008). "No effect of route of exposure (oral; subcutaneous 

injection) on plasma bisphenol A throughout 24h after administration in neonatal female mice." Rcprod 

ToxicoI25(2): 169-76. 

35 Chapin, R. E., J. Adams, et a!. (2008). "NTP-CERHR expert panel report on the reproductive and 

developmental toxicity ofbisphenol A." Birth Defects Res B Dev Reprod ToxicolS3(3): 157-395. 

36 Milwaukee Sentinel Journal, April 11,2009. "Consortium rejects FDA claim ofBPA's safety." 

http://www.jsonline.comiwatchdogiwatchdogreports/42S58807.html 

37 Ryan, B. c., A. K. Hotchkiss, et a!. (2010). "In Utero and Lactational Exposure to Bisphcnol A, In 

Contrast to Ethinyl Estradiol, Does Not Alter Sexually Dimorphic Behavior, Puberty, Fertility, and 

Anatomy of Female LE Rats." Toxico!. Sci. 114(1): 133-14S. 

38 Yom SaaL et a!. 2010. "Flawed Experimental Design Reveals the Need for Guidelines Requiring 

Appropriate Positive Controls in Endocrine Disruption Research." Toxieo!. Sci published February 17, 

20 I O. http://toxsei.oxfordjoul1lals.org/cgi/reprint/kfg048v l.pdf 

39 vom Saal, F. S. and C. Hughes (2005). "An extensive new literature concel1ling low-dose effects of 

bisphenol A shows the need for a new risk assessment." Environ Health Perspect 113(8): 926-33. 

40 Caldwell KL, Miller GA, Wang RY, Jain RB, Jones RL. Iodine status of the U.S. population, National 

Health and Nutrition Examination Survey 2003-2004. Thyroid. 2008 Nov;lS(ll):1207-14. 

4) Zimmermann MB. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on 

the offspring: a review. Am J Clin Nutr. 2009 Feb;89(2):668S-72S. 

42 Office oflnspector Genera!. EPA Needs a Coordinated Plan to Oversee Its Toxic Substanees Control Act 

Responsibilities. Report No. 10-P-0066. February 17,2010. 

hHp:llwwlV.epa.gov/oig/rep911s/20 1 (l/20 1.00217-1 0-P-0066.pdf. 

43 http://b Jogs. edforgfnanotechno logv! 2009.'04! 16! epas-new-chemical s-program-tsea-dealt -epa-a -verypoor-hand!. 

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44 Denison R. ChAMP: No! exactly a heavyweight. April 20, 2009. 

http://blogs.edf.org/nanotechnology/2009!04/20/champ-not-exactly-a-heavyweightl. 

45 Denison R. (How) Can ChAMP get back on track? May 7, 2009. 

http://blogs. edf. org/nanotechnology /2 009 10510 7 ibow-can-champ-gct -back -on-track/ 

14 

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Borgert Follow-up Responses page 1 of 28 

The Honorable Edward J. Markey 

1. In limine, LLC has you listed as a scientific and technical advisor for health and exposure 

based litigation claims. 

a. What is the nature of your work for In limine, LLC? 

b. In the course of your work of In limine, LLC, have you done work for any companies that 

have been sued for exposing people to endocrine disruptors or other toxic substances that 

resulted in an out of court settlement or case dismissal? Please list all such companies. How 

much have you been compensated for your work for these companies? 

c. Have you ever testified in court as an expert witness for a defendant in a product liability 

claim involving endocrine disruptors or other toxic substances? Please list all such 

companies. How much have you been compensated for your testimony for such 

companies? 

Dear Chairman Markey: 

Thank you for your follow-up questions. Your questions signal an interest, and perhaps a 

familiarity with my writings on the subject of conflict of interest in scientific discourse (Borgert, 

2007a, 2007b). Your question raises an issue of great importance, and one on which Congress 

could demonstrate real leadership if they so choose. 

As you know, absolutely alien to the precepts of good science, participation in peer-review 

panels for the US. EPA and other federal agencies now requires disclosure of compensated and 

non-compensated employment, consulting, grants, expert witness testimony, stocks, bonds, real 

estate, business interests, patents, trademarks, royalties, and financial liabilities, for the 

reviewer, spouse and dependent children, meaning that the worthiness of individuals to publish 

in most journals or to participate in the government agency peer-review process is being judged 

on the basis of affiliations, sources of funding, and the financial assets of one's family rather 

than on actual scientific merit. 

I believe you should know, this cuts at the epistemological foundation of scientific reasoning and 

at the very precept that distinguishes science from any other form of inquiry in the quest of 

factual knowledge. The reasons are abundantly clear to anyone who knows the difference 

between scientific methods and political consensus. Science elevates observation over the 

observer, but outside of science no objective method exists for judging observations, and so the 

observer becomes of paramount interest. Outside of science, professional and personal 

affiliations, funding, experience, employment, and social status establish credibility and fitness 

to partiCipate, to opine, and to proclaim. Outside of science, consensus is achieved subjectively 

through the dialectic persuasiveness of the participants, by compromise, by vote, and even by 

the diktat of strident minorities. 

In stark contrast, the observing scientist is only an accessory in the acquisition of scientific 

evidence, where the facts are asked to first speak for themselves in order to enhance objectivity. 

The method of science randomizes, double-blinds the identity of treatments, measures, controls 

for biases and confounders, tests probabilities, and replicates in order to remove the individual 

observer as far as possible from the process of observation and interpretation. In science, 

provisional consensus is achieved only as the range of interpretations narrows, consistent with 

an increasingly broad and probative data set; compromise and vote are anathema. By these 

precepts science has proved itself time and again, accruing myriad benefits to lifestyles, public 

health, and the environment. 
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Borgert Follow-up Responses page 2 of 28 

Admittedly, complete removal of bias from the observer - in effect, a completely controlled 

experiment or interpretation - is impossible, In fact, the central, and perhaps the only argument 

of scientific discussion is about how well controlled the measurements and experimental 

conditions might be, and how thoroughly and unequivocally the interpretations are supported by 

the data. 

To this end, information technology now enables unprecedented transparency of the scientific 

process: the details of experimental design, data collection, methods of analysis, and criteria for 

interpretation. Laboratory notebooks, raw data, and the statistics used can be posted online for 

thorough review and replication by anyone. Similarly, peer-reviews for governmental agencies 

and testimony before Congress could be conducted according to guidelines for systematic 

review, with all details posted online. Such transparency is bound to thwart bias far better and 

more honorably than any conflict of interest or financial disclosures. Data transparency would 

definitely enhance the scientific merit of any report, peer review process or testimony. 

Conversely, experimental data and scientific interpretations cannot be factually improved or 

weakened by irrelevant disclosures of political and financial affiliation. 

I urge Congress to take this opportunity to improve the science used in regulatory decisionmaking by advocating transparency of the scientific process and the data rather than irrelevant 

disclosures about the scientist, and by inSisting that government agencies do the same. To do 

otherwise is to accede to the invidious doctrine of anti-science interests, bent on deciding issues 

by ad hominem arguments rather than by testable facts. Journals, funding agencies, peerreview bodies, and especially Congress, should abandon demands that focus the debate more 

on the politics of the science or scientists and instead embrace accessible and verifiable data 

and transparent methods as the exclusive determinants of scientific merit. 

I am concerned that to do otherwise may pave a wide road to corrupting science into a process 

where personalities are prominent, data are relegated to rhetorical sound bites, subjectively 

derived consensus is praised, and the loudest voices rule. I believe the progress of valid 

science and its ability to offer improvements to public health and the environment depend upon 

these choices. 

To the specific details of your question, a) the purpose of In Limine, LLC is to explain to the 

Courts the very fundamental tenets of science that I explained to your Subcommittee both 

verbally and in my written testimony. b) In Limine, LLC has not been retained to do any work for 

any entity, and thus, no income has been received. c) I have testified in court approximately 30 

times in my career. A list of these is attached. Some of these, but not all, involved product 

liability issues; some, but not all, involved industrial chemicals or pesticides; many involved 

prescription medications. I do not recall testifying with respect to a specific claim of "endocrine 

disruption." I cannot be more specific because I do not maintain a list of the companies 

involved, other than would appear in the style of the case, nor whether I was retained by the 

defense or the plaintiff, nor do I track my income according to the nature of the projects. 

References 

Committee on Publication Ethics, 2005. The COPE Report, available from: <h!.tp;iL\V\V\Wlliblica!i.Qm;ll;j.c~illl:~kL 

~!s/20051>. 

Drazcn. 1.M., Curfman. G.D., 2002. Financial associations of authors. N. Eng. J. Med. 346 (24), 1901-1902. 

James.A., Horton, R., Collingridge, D., McConnell, J., Butcher, J., 2004. The Lancet's policy on conflicts of 

interest-2004. The Lancet 363, 2-3. U.S. Office of Govemment Ethics. 2007. Confidential Financial Disclosure 

Form (OGE Form 450). <ht!p.:il\Yll\".gSog~,gol"iPilgeJ>!fQIn,"L.Jlab.'-().therct()cs! 

.L1Oforrll'-..]2.\lJ:LLmhcr pg3.html#Anchor-OG- 13588>. Other conflict of interest!financial disclosure guidance and 
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Borgert Follow-up Responses page 3 of 28 

form templates can be found on the web at the following locations: Food and Drug Administration - financial 

disclosure for clinical investigators bJ1P.;jj\V\V~~:,fda.gov!c~h:hLd~~0ill~ii.hkLfLniln£i~tillt:.mJ and lmn://www.fda.-gQ..Yi 

Q£Lw~.t~1ncejfjnam;iahlis.html, - procedure for committee members, consultants, and experts Jllip~w\\.J.Y.fda,gQYI ocl 

advisory/conftictofinterest/policies.html; Environmental Protection Agency - Peer Review Handbook hli.p....:!i 

.~~'_l'L&P~LgnYjo~!!L~/2peerr~y, htm: National Science Foundation-Grant Policy Manual, Grantee 

Standards hlli);!lW\\~\\:,n.'iLgm:i!Iui1<JDlanililJ:iJ'g12m!li.J1Jjgpm5.is.!l: The National Academies (NAS, NAE, 10M, 

NRC) - Conflict of Interest Policy h1wJlw\\'\\'o[Lational;lcademje~.orgL£j,2.il.lDsJ.~\.:.htmJ; and the National Institutes of 

Health-ConRiet of Interest Infonnation 

bJ:tp;[!,gEm:b£nihoRQY!-.Wll1.'iPDfuf£DiL. Zaza. S" Wright-De Aguero, L.K., Briss, P.A., Truman. B.l., Hopkins, 

D.P., Hennessy, M.H., Sosin, DM.,Anderson, L., Carande-Kulis, V.G., Teutsch, S.M., Pappaioanoll, M., 2000. Data 

collection instru- ment and procedure for systematic reviews in the guide to community preventive services. Am. J. 

Prevo Med. 18 (Suppl. 1),44-74. 

The Honorable Joe Barton 

I. Dr. Birnbaum testified there are four aspects of exposure to endocrine disruption, In these 

four aspects, she relates what could be "plausible." Please state your opinion on whether 

this is a good way to conduct science or make regulatory determinations, 

The concept of biological plausibility involves the application of deductive and inductive 

reasoning to biological data. Biologically plausible conclusions are, in essence, reasonable 

speculations based on available data, but this is an inherently subjective process and should not 

be confused with objectively verifiable scientific facts. A set of objectively verifiable scientific 

facts typically invites further hypothesis generation such that the blurring of scientific fact with 

further hypothesis generation enjoys an easy relationship in basic research. Within the 

research context, however, it must be kept in mind that most hypotheses turn out to be wrong. 

Even hypotheses that are not completely rejected upon rigorous testing must typically undergo 

tortuous corrections and refinements in order to remain viable. This is a healthy process for 

basic research, but in my opinion, it is a wasteful and potentially dangerous way to make 

regulatory determinations. The lack of biological plausibility can substantially weaken a 

scientific hypothesis or conclusion, but should not be used to imply that a particular hypothesis 

or conclusion is established or even likely to be correct. Rather than react in a regulatory 

setting to biologically plausible speculation, I would prefer to know that the risks being regulated 

are real, and therefore, that their mitigation will produce measurable improvements to public 

health and the environment. 

2, Please state whether in your opinion there is enough high-quality science to justifY a "low 

dose" theory of regulation. 

Unequivocally, there is insufficient valid science to justify a "low dose" theory of regulation. In 

fact, the so-called 'low-dose' theory has not been formulated with sufficient clarity to even be 

scientifically testable. Many different concepts have been used, in a confused and inconsistent 

fashion, to advance the so-called "low-dose" theory, some of which are inconsistent with one 

another and perhaps even contradictory. What can be said with certainty is that toxic effects 

produced by chemicals at high doses may be very different from the effects, if any, produced at 

lower doses, and that the subtle effects produced at low doses may not be toxic effects but 

rather adaptive and compensatory responses of the organism. 
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3. Modem science and technology allows us to more easily detect increasingly subtle changes 

in the human body. Please explain whether a subtle change in human functioning based on 

external factors necessarily means something negative has happened. 

As mentioned in answering the previous question, subtle effects produced at low doses may not 

be toxic effects but rather adaptive and compensatory responses of the organism. To expand 

briefly, the great challenge to toxicology as I see it is to discover the fundamental differences 

between subtle adverse effects and responses that merely reflect a successful compensation or 

adaption to the presence of an external factor. So that the concepts can be understood in the 

broader biological context, please indulge a non-chemical example. Bacterial and viral 

infections can adversely affect humans in many ways and are a significant cause of morbidity 

and mortality, even in advanced societies. However, we have learned in recent decades that 

some exposure to infectious bacteria and viruses are actually necessary for normal 

development of a healthy and resilient immune system. Some research even suggests that a 

very low exposure to infectious agents in early life might weaken the immune system in its 

important role in preventing cancer. Clearly, all immunological responses in a child do not lead 

to harm; the challenge is to understand more clearly which responses signal that the immune 

system is responding normally to bacterial and viral exposures versus those that portend illness. 

This is not to suggest that exposures to environmental chemicals is necessary for normal 

development. However, just as not all immunological responses portend illness, all responses 

to chemical exposures do not portend toxicity. 

Among the various biological systems, the endocrine system best exemplifies this principle. 

Because the endocrine system is one of the body's principal homeostatic systems, enabling the 

body to maintain a consistent internal environment in the face of ever-changing external 

influences, it by design responds to exposures in the environment from chemicals, light, sound, 

heat, and a myriad of other social and external factors. These endocrine responses are not 

mostly adverse; instead, they indicate that the endocrine system is detecting external influences 

and is responding appropriately to maintain an internally consistent environment. The challenge 

for endocrine toxicology, and thus, for the EPA's EDSP, is to properly differentiate endocrine 

responses that are adaptive and compensatory from those that are adverse. Failure to do so 

increases the likelihood that regulatory actions based on a presumption of precaution will be as 

ill-informed, ineffective, and potentially damaging to public health as they are well-intentioned. 

4. You testified EPA "conducted the minimum validation work that might satisfy the 

Congressional mandate." Please explain this comment. 

In the 1996 Food Ouality Protection Act (FOPA), Congress required EPA to use "validated test 

systems" in screening chemicals for the ability to cause estrogen-like effects in humans. I 

believe the stipulation to use validated test systems was wise and apparently intended to avoid 

potentially unreliable and ineffective screening. The FOPA, however, gave the Administrator of 

EPA discretion to screen for additional hormonal activity beyond estrogen. Rather than develop 

a screening program that would satiSfy the explicit mandate of FOPA, EPA took a much broader 

view and devised a screening battery to include three hormones and their antagonists. This 

could be seen as a six-fold expansion of the explicit requirement, and it necessitated EPA 

proposing to use some assays that were relatively little known and untested for screening 

purposes. Validation of such a screening battery was sure to be more expensive, more 

complex, and require much more time than had EPA focused on meeting the explicit 

requirement of FOPA as rapidly as possible in the most scientifically rigorous way. Interestingly, 

many who exhorted EPA to be expansive in its screening program subsequently criticized the 
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Agency for failure to rapidly issue test orders to screen. The pressure to implement clashed 

with the requirement to validate the assays, and so EPA did the best they could to respond to 

both pressures. In truth, many scientists acknowledge that adequate validation of the Endocrine 

Screening Battery (ESB) awaits results for the first 67 chemicals placed under test order, as 

EPA has simply not been given sufficient time to develop a full validation data set prior to issuing 

these current test orders. 

5. Please state whether you believe the minimum validation work for the EDSP would satisfy 

most scientists. Please also state whether the minimum validation work provides a good 

discriminator for what should move on to the next level. 

I cannot credibly say what most scientists would find satisfactory, but having served on the peerreview panel for the OECD validation program for the uterotrophic assay - one of the key assays 

in the ESB - I know that some scientists who are quite knowledgeable about validation 

procedures consider the level of validation for the EDSP assays to be inadequate. 

I discussed three tenets of scientific validity in my testimony; using those tenets as a guide, the 

validation results for the various EDSP assays reveals a varied degree of validation. We can 

verify what we are measuring within a defined degree of precision for most of the eleven EDSP 

assays, and for many, we have identified and can control the confounding factors that influence 

the measurements. For some of the assays, we have reasonably sufficient data to know how 

consistently results from these assays can be replicated by independent SCientists, in other 

words, we have data on inter-laboratory variability. However, for other assays, none of those 

tenets are particularly well characterized. The battery as a unit has not been subjected to a 

round of overall validation. Thus, no one can say how effectively the battery discriminates 

between chemicals that actually show adverse endocrine effects on further testing versus those 

that do not. Furthermore, EPA has not yet defined the criteria for interpreting the screening 

battery so that it is effective and efficient in making this discrimination. Since more extensive, 

tier-2-level data have already been generated under current pestiCide regulations for the first 67 

chemicals now undergoing endocrine screening, it is hoped that the performance of the 

screening battery can be evaluated once the screens are completed. This will involve 

comparing the screening results with the already-available tier-2-level testing data to determine 

interpretive criteria will allow adequate prediction of tier 2 results. 

6. You testified the endocrine screening program detects potentially weak hormonal activity 

for certain chemicals. 

a. Please state whether the reliability of this method concerns you given that most of the assays 

were intended for potent hormonal activity. 

The 11-assay screening battery is intended to be able to detect even weak hormonal activity. 

Some of the types of assays included in the battery have a history of reliable use in screening 

for potential new pharmaceuticals, but this purpose, of course, seeks to identify compounds that 

have high potency. This does not mean that the screening assays will be useless for detecting 

compounds that have weak potency, but neither does it assure us the assays are reliable for 

that purpose. It does, however, underscore the importance of validating the assays and 

determining their specificity, sensitivity, and predictive value. In my view, EPA should be given 

the time, resources, and encouragement to complete this process before insisting that more 

chemicals be screened using a battery that is as yet uncharacterized. 
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b. Please explain what the significance of "weak hOlmonal activity" is for human health and the 

envirorunent. 

Medical science has not yet determined the significance of weak hormonal activity for human 

health. As was heard during the subject Congressional hearing, there is much speculation that 

serious human diseases and malformations arise because of exposure to weak hormonal 

activity. Even though some are firmly convinced of these speculations, and choose to state their 

views as if the science were settled, it is far from settled. The science on this issue is in the 

hypothesis-generation phase, and it must be recognized that the hypotheses on this subject 

have been shifting for about two decades without definitive confirmation that any chemical, or 

mixture of chemicals with weak hormonal activity causes disease in humans at environmentally 

relevant levels of exposure. In my view, there are overwhelming data that call into question the 

endocrine disruption hypothesis, particularly regarding chemicals with weak hormonal activity, 

but the science is not completely settled in the negative either, as it is nearly impossible to 

establish a negative premise. 

c. Please state the rate of false positives from this type of screening. 

This is indeed a critical question, but it cannot be answered with available data. The answer 

awaits data emerging from the results of the first 67 chemicals to be screened. Without those 

data, one can only speculate that the incidence of false positives will be very high. A few simple 

statistical concepts illustrate how high it could be. 

In most biological assays, we find it acceptable if no more than 5% of the observed responses 

are positive due to chance alone, I.e., a false positive rate of 5%. The probability of observing at 

least one false positive result among several independent assays rises with the number of 

assays according to the following simple statistical formula: 1-(1-p)", where p is the false 

positive rate for each individual assay and n is the number of assays to be conducted. Thus, 

even if each assay in the endocrine screening tier has a false positive rate of only 5%, the 

probability that at least one assay the 11-assay endocrine screening battery will give a false 

positive result would be expected to be about 43%. Some assays in the ESB measure several 

independent endpoints, so the true probability of at least one assay in the battery giving a false 

positive result could be even higher. Thus, if a positive result in any of the assays is deemed to 

render the endocrine screening battery positive for that chemical, then half or more of the 

chemicals screened would be expected to give a false positive result. 

Furthermore, because two of the assays have failed to yield a clear negative result for any 

chemical, it is unclear whether anything will be deemed negative, and so all substances 

screened could be declared candidates for further testing. This is why it is critical to complete 

the validation exercise that will allow EPA to establish a set of interpretive criteria that provide a 

reasonable level of discrimination. 

7. Isn't the real concern here dosage? Even watcr can bc fatal in high enough dosages. Don't 

you think it's important that we take the time to understand if these chemicals can have an 

adverse affect on humans, and at what dosages before we make sweeping and potentially 

damaging, Federal regulations? 

Yes, dosage is the critical issue for any toxic effect, and yes, at what dosage chemicals might 

have an adverse effect on humans is the critical issue for regulation of chemicals to which 

humans may be exposed. It is important to recognize, however, that our current regulatory 

testing paradigm does not require that a real risk to human health is ever demonstrated in order 
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for EPA to impose regulations. Instead, human risk is inferred from any adverse effect in a 

rodent or other mammalian test species, unless that adverse effect can be demonstrated to be 

irrelevant for human physiology. i.e., that the physiological differences between humans and the 

test species are understood in such detail that it is clear the effect could not occur in humans. 

This is a very conservative approach in that many risks to humans are assumed without any 

actual human evidence, but this is the prevailing policy based on prioritizing precaution over 

accuracy. My statements are not meant to disparage that policy, but merely to point out that the 

policy is conservative and must not be confused with actual scientifically demonstrable risks. 

EPA has rightly and consistently stated its intent to make a determination of adverse endocrine 

effects and dose-response On the basis of tier 2 testing, and explicitly not on the basis of tier 1 

screening. If this intent can be realized, then the screening program, once fully validated, might 

serve its intended purpose. Unfortunately, regardless of how well-intentioned EPA might be, 

inaccurate publicity regarding the purpose and predictive power of endocrine screening can 

result in products being displaced from the market on the basis of public perception rather than 

fact. A review of the video of the Subcommittee Hearing gives testament to this phenomenon: 

even though Mr. Jones and I clarified that the endocrine screening battery cannot identify 

endocrine disruptors, and that the determination of adverse effects will be made after tier 2 

testing, other witnesses and members of the subcommittee continually made reference to 

'endocrine disruptors' being identified by the 'endocrine screening battery'. 

8. Please describe the importance of potency of a substance in relation to its presence or dose. 

Please explain whether the EPA's tests appropriately consider this factor in your opinion. 

Potency refers to the strength of a chemical for producing a particular biological effect. For 

example, the greater the potency of a pain-reducing drug, the less of it is required to eliminate 

the sensation of pain. The endocrine screening battery is not designed to determine the 

potency of a chemical, but simply to determine whether at any achievable dose, the chemical 

might interact with a component of the endocrine system. Some of the screening assays are 

performed in test-tube systems utilizing just one component of the endocrine system - either a 

hormone receptor or a particular enzyme - while others measure changes in specific tissues or 

hormone levels in a test species, either rats, frogs, or fish. The effects measured in these 

endocrine screens are not necessarily adverse effects. Thus, potency for producing adverse 

endocrine effects is not measured by the endocrine screening assays, but will be determined in 

tier 2, where adverse effects in test species are measured. This two-tiered screening and 

testing program would appropriately consider potency for single chemicals if conducted as it 

was designed (see answer to previous question). 

Cumulative risk assessment is the area in which EPA procedures may not appropriately 

consider potency. Please refer to question #13. 

9. You testified that we risk replacing relatively safe chemicals with riskier ones. Please 

describe with what other chemicals or in what other circumstances you have seen this 

occur. 

As I explained during my testimony, the concept behind this statement is that we often attempt 

to eliminate all risks irrespective of whether they are demonstrable risks or only theoretical risks, 

and we suffer an increasing tendency for failing to distinguish between real and hypothetical 

risks and benefits. Consequently, our proclivity for precaution may render us vulnerable to real 

adverse health consequences, or resistant to real health benefits, in order to avoid theoretical 

risks. During my oral statements, I used the example of eliminating all fats from our diets just a 
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few decades ago on the mistaken belief that all dietary fat contributed to the risk of coronary 

artery disease. We now know that some fats are actually beneficial, and many doctors now 

advise patients to consume supplements containing fish oil and other omega fatty acids. The 

examples are too numerous to list, but two prominent examples illustrate the concepts. 

In the 1990s, Peru suffered new outbreaks of cholera. In many locations, poorly sanitized water 

became a vector for the disease. Thousands of people died and many more were hospitalized. 

Many of these infections, and some deaths were likely preventable had public health authorities 

not feared theoretical cancer risks posed by chlorine disinfection of water supplies, and based 

on that fear of a hypothetical risk, increased risks of contracting cholera and its very real 

adverse health consequences. An articie by Fred Reiff, extracted from the American Chemistry 

Council website <http.//www.americaochemistry.com/s chlorine/sec content.asp? 

CID-1195&DID=4489&CTYPEID=107>, explains the details. 

The Precautionary Principle Under Fire: Detractors Continue to Challenge 

Chlorination as a Safe Water Solution for Developing Nations 

By Fred Reiff 

Former PAHO official, Fred Reiff, recounts his experiences battling chlorine misinformation 

during the Latin American cholera epidemic of the 1990s. 

Despite data supporting chlorine's highly beneficial impact on clean water supplies and public 

health, claims persist that the potential risks of chlorination outweigh the public health value of 

water disinfection. To me this is comparable to watching the third sequel of a grade Z science 

fiction movie about a monster that won't die. A case in point is a Greenpeace report currently 

posted on the organization's website asserting that DBP concerns had no bearing on the spread of 

disease during the 1991 cholera epidemic that began in Peru and was propagated to almost all 

countries of Latin America. From personal experience I can confirm that these claims are utter 

nonsense. I am concerned that such disinformation and half truths might be accepted as fact, 

resulting in otherwise avoidable disease, suffering, death, and economic impact on the poor 

people of developing countries. 

Why am I qualified to respond? From 1981 through most of 1995, I was an official in the Pan 

American Health Organization/World Health Organization (PAHO) in a position that offered a 

very unique vantage point. During this period I was responsible for disseminating the WHO 

drinking water quality guidelines and fomenting the adoption or updating of national drinking 

water quality standards.l also was responsible for managing the United Nations Global 

Environmental Monitoring Programs for Water (for the Americas), the development and 

promulgation of environmental interventions in disaster preparedness and relief, and the 

development of appropriate technology for treatment of both potable and waste water. I also 

served on PAHO's management task force that was formed for the prevention and control of 

cholera. This level of involvement provided many opportunities for both overall and close-up 

monitoring of the status of water supply disinfection and its effectiveness as a public health 

measure in prevention and control of waterborne diseases in all Latin American and the 

Caribbean countries before, during, and after the introduction of cholera in Peru in 1991. 
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For many years prior to the cholera outbreak, PAHO had been promoting the disinfection of 

community water distribution systems and other delivery systems for water for human 

consumption. Primarily through its Center for Sanitary Engineering and Environmental Science 

(CEPIS) in Lima, Peru, PAHO collaborated in pilot and demonstration projects for virtually all 

disinfection methodologies in various countries to ascertain their relative disinfection efficiency, 

cost effectiveness, and practicality for various cultural and economic situations. Some of them 

worked well and others were failures. Everything considered, chlorination was almost always 

found to the most reliable and cost effective. 

Until the cholera outbreak erupted in Peru in January-February of 1991, the acute and deadly 

diarrheal disease had not been prevalent in the Americas since the early 1900's. Immediately 

upon verification of its presence, PAHO began organizing workshops to infornl the appropriate 

officials of the countries of Latin America (and later Caribbean countries) of the seriousness of 

this disease and its potential to become an epidemic. We shared the most effective and advanced 

technologies to detect the pathogen, how to diagnose and treat the disease, the tried and proven 

methodologies that have been used to prevent cholera, public education strategies, and the 

epidemiological efforts and methodologies to track and understand the propagation of the 

disease. 

Simultaneously, PAHO headquarters directed each of the PAHO Country Offices to advise health 

and water agencies to take measures to continuously chlorinate all water distribution and 

delivery systems. For the population not connected to public water systems, special programs 

were developed to promote the disinfection of water at the household level. In addition, 

treatment of the waste products of cholera victims with lime was recommended before its 

discharge to the sewer systems Of the environment, and a list of all preventi ve measures to be 

taken by officials and individuals were provided to all appfopriate officials. Chlorination was 

recommended, not only because all of the countries were familiar with this technology, but also 

because chlorine products were readily available and chlorination was the least costly of the 

disinfection methodologies. And, most importantly, chlorine is very effective in killing or 

inactivating Vibrio cholerae, the pathogen of this disease as well as pathogens associated with 

almost all other waterborne diseases. 

Shortly after this directive was issued, I was surprised to Jearn that some local PAHO officials 

werc encountering pockets of resistance to chlorination from a number of health officials, both in 

Peru and in other countries. I was specifically told that the reason was their concern for 

chlorination by-products, especially trihalomethanes. This concern had its origin in press releases 

and published scientific studies widely disseminated by environmental agencies in the developed 

countries. I traveled to Peru and other countries and personally met with the health officials and 

even heads of water agencies who expressed their concern directly (0 me; some even believed 

that they might be subjected to a lawsuit if they chlorinated or raised the level of chlorine in their 

water supplies. I also met other concerned health officials in various cholera workshops and 

symposiums sponsored by PAHO. Most surprising of all was the discovery that even officials in 

small towns were aware of disinfection by-products and their alleged negative health effects. It 

was pointed out to all that when the cholera pathogen is present in a water supply, the risk of 

contracting the disease is immediate, and that a resulting epidemic conld cause thousands of 

deaths. In contrast, the hypothetical health risk posed by trihalomethanes in levels in excess of 
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those recommended by WHO (and EPA) was one extra death per 100,000 persons exposed for a 

period of 70 years, Unfortunately, some of these well-meaning, but ill-informed officials had to 

experience the immense proportional difference in risk before accepting this reality. 

Debates over the relative significance of the drinking water pathway for cholera in comparison to 

other pathways also impeded the rapid implementation of drinking water chlorination. Routes 

that can be taken by cholera include food, beverage, and ice that have been processed or prepared 

with contaminated water, unhygienic food handlers, produce that is eaten raw but which has been 

irrigated with cholera contaminated water, filter feeding shellfish harvested in sewage 

contaminated water, and casual person-to-person contact. Both practical experience and studies 

have proven that even if cholera is initially introduced through a pathway other than drinking 

water, the waterborne pathway will soon be activated unless drinking water is disinfected 

continuously with an adequate level of disinfectant and measures are taken to prevent 

recontamination before its consumption. A cholera contaminated distribution system is without 

doubt the most efficient way to transmit this disease. 

It should be noted that throughout the first four years of this epidemic the countries with the 

highest percentage of continuously and adequately chlorinated water systems had no secondary 

transmission of cholera, even though the disease was introduced into these countries. Also 

countries that quickly implemented chlorination were able to bring the epidemic under control. 

There was also an obvious inverse correlation between the percentage of the population 

receiving chlorinated water and the incidence of new cases of cholera. In one country with 

excellent long-term epidemiological surveillance in place, it was found that after implementation 

of measures to prevent cholera, there was also a significant reduction in typhoid fever and 

infectious hepatitis. 

Conversely, those countries that were not able (for whatever reason) to implement chlorination of 

water supplies on a timely basis, suffered recurring annual epidemics until a sufficient percentage 

of the population had developed immunity, preventing further epidemic propagation of the 

disease. Typically there were a number of reasons for delay in implementing widespread 

chlorination of drinking water supplies. However, no obstacle was harder to overcome than the 

incorrect perception of risks posed by disinfection by-products relative to the very real and 

deadly threat of cholera. 

To reduce the spread of cholera in areas of abject poverty where household were not connected 

to water distribution systems PAHO worked in concert with the U.S. Centers for Disease Control 

and Prevention (CDC) and the University of North Carolina to develop, test, and 

microbiologically and epidemiologically monitor the results of a methodology to purify the 

available water at the household level. The end result was chlorination of the household water in 

containers that were specifically designed to preclude subsequent contamination during storage 

and use. The annual cost of this intervention was found to be less than $2.00 per family, the 

major cost being the container. The annual cost of the calcium hypochlorite was less than fifty 

cents per family. Not only did this prove effective for Latin America but it also led to global 

health organizations adopting this or similar programs as a viable interim health measure for 

developing countries in Africa and Asia. 
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Since the cholera outbreak of 1991, many nations have embraced what is known as the 

"Precautionary Principle", a protocol acknowledging that uncertainty is inherent in managing 

emerging risks. The thrust of public health management in the principle is to take steps to reduce 

potential harm, even when uncertainties remain. Yet a true precautionary approach also means 

that you do not do away with a proven health intervention. This concept was clearly stated by Dr. 

Carlyle Macedo, Director of PAHO in his address to the 1992 International Conference on the 

Safety of Water Disinfection, Balancing the Chemical & Microbiological Risks sponsored by the 

International Life Sciences Institute. 

"In developing countries, the primary public health concern for water supplies should remain 

preventing them from becoming an efficient vehicle for the widespread transmission of enteric 

diseases. This concern should not be overshadowed in any way in our efforts to also address the 

tertiary concern of minimizing the relatively small risk stemming from disinfection by-products ... 

The high incidence of diseases that are related to water supply and sanitation are primarily a 

reflection of the social and economic inequities and marginalization that unfortunately still exist 

in our hemisphere. Basically the people that suffer the mostfrom these diseases have sofew 

ecollomic resources that all but the simplest and least expensive of interventiolls to reduce their 

risk of exposure to the many waterborne pathogens are beyond their means. Under such 

circumstances the disinfection of drinking water with chlorine at the household level, is usually 

the most viable and cost-effective public health intervention available. To cause these people to 

abandon chlorination is not only unwise, but cruel, if the alternative is beyond their economic 

and technical means. Unless there is a simple alternative at an affordable cost, these people 

should not be frightened away from chlorinating their water. This will only increase their 

suffering and decrease their life expectancy." 

To protect public health, par1icularly in developing regions, applying the precautionary principle 

requires use of practical. affordable technologies and a realistic balancing of known and 

uncertain risks. 

Fred M. Reiff, an engineer, is a former official of the Pan American Health Organization/World 

Health Organization. He retiredfrom that organization in 1995 but continues to serve as an 

independent international consultant. 

To read the Greenpeace report "Cholera and Chlorine" please refer to the following link: 1l.l.tr.:11 

archi ve .greel}peacc .org:lto xi cslreportsl c hoi erachlorine .pdf 

A second example comes from my own publications. One of the recurring concerns of modern 

mothers is whether it is safe to breast feed their infants. Given the enormous public attention 

given to synthetiC chemical contaminants that can be detected in our bodies, it is not surprising 

that some women have avoided breast-feeding because of the theoretical risks from these 

chemicals, Some of these chemicals are putative endocrine disruptors. Despite the theoretical 

health effects of putative endocrine disrupting chemicals that may be present in human milk, the 

epidemiological and clinical data reveal clear benefits of breast feeding. In a paper published in 

Environmental Health Perspectives, a journal of the National Institute of Environmental Health 

Sciences (Environmental Health Perspectives, 111(8): 1020-1036.), I and co-authors wrote: 
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Borgert Follow-up Responses page 12 of 28 

Clinical data currently available indicate a health benefit to offspring for 6 

weeks of breast- feeding. At present, there is no evidence that infants 

breast-fed for more than 6 weeks suffer more adverse health effects, 

hormonally medi- ated or otherwise, than infants receiving infant formulas 

or other sources of nutrition. Effects similar to those observed following 

high-dose exposure to potent estrogens-e.g., in utero exposure to DESto the best of our knowledge, have not been associated with breast-feeding or other sources of infant nutrition. Thus, the epidemiologic and clinical 

studies con- ducted to date suggest that breast-fed infants suffer no 

adverse estrogen-related health effects. Given that much of the data on 

breast-fed infants was collected several decades ago when levels of 

persistent contaminants in humans were likely higher than at present, 

particularly in countries such as the United States where the use/release of 

many of these chemicals has been banned or restricted (LaKind et al. 2001; 

Westphal 1986), estrogenic risks to infants from consumption of human 

milk should be considered de minimis. 

Furthermore, in a publication summarizing the conclusions of an expert panel on human milk 

surveillance convened at the Milton S. Hershey Medical Center, Pennsylvania State University 

College of Medicine, Hershey, PA (Journal of Toxicology & Environmental Health Part A, 65: 

1929-35), my co-authors and I wrote: 

The panel strongly supports the scientific and public health value of studies 

on environmental chemicals in human milk. However, it is even more 

strongly emphasized that the mere presence of an environmental chemical 

in human milk does not necessarily indicate that a health risk exists for 

breast-fed infants. The accumulated data overwhelmingly supports the 

positive health value of breast-feeding infants. 

10. You testified the "perfonnance of the battery as a whole has been left unaddressed." Please 

explain this statement and its implications. 

The ESB was intended to be conducted and interpreted as a battery of assays, not as a set of 

single, independent assays. To date, validation exercises have focused on the performance of 

the individual assays. Although a necessary step, validating the individual assays does not 

answer whether the battery as a whole is useful for discriminating between chemicals that need 

further testing because they exhibit real potential to interact with the endocrine system versus 

those that do not. Ultimately, some combination(s) of results among the various assays may be 

discriminative, but we will not know what the interpretive criteria must be until more data is 

available. It is hoped that the information necessary to develop such criteria will emerge from 

results of the first 67 chemicals to undergo screening. Until we know whether the battery can be 

interpreted in a way that produces an effective screen, i.e., a means of separating the chemicals 

that need no further analysis from those that do, we have no idea whether the ESB is effective, 

If the ESB improves neither the sensitivity nor the efficiency of testing chemicals, then it is 

merely a burdensome process for both industry and EPA, and ultimately the public. 

11. You testified the criteria for interpreting ambiguous results was modified so that such results 

could be interpreted as negative. Please describe how the criteria were modified and the 

significance of those modifications. 
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My statement relates to the way a maximum tolerated dose was defined for the pubertal assays 

As background, it is important to appreciate that endocrine tissues and organs can be affected 

in some of the endocrine screening assays by pathways that are not endocrine-related. 

Therefore, correct interpretation of the results relies on disceming effects that occur via 

endocrine activity from those that are secondary to other effects. For example, a small change 

in body weight is known to affect the weights of endocrine tissues measured as indicators of an 

endocrine effect in these assays. 

EPA typically requires reproductive toxicity assays and assays for other specific effects to be run 

at a 'maximum tolerated dose' (MTD), which is defined as the highest dose that fails to produce 

general toxicity and which fails to alter terminal body weights by 10 percent or more. EPA 

initially selected 2-chloronitrobenzene, but the initial results were positive for endocrine activity 

and it was obvious that a new negative control compound would be needed. At this time, EPA 

had done several studies with hydroxyatrazine. Interestingly, the EPA found hydroxyatrazine 

positive in an early pilot study with the female pubertal assay in 2003 (Laws et aI., 2003. 

Toxicological Sciences 76, 190-200). One of the primary effects of hydroxyatrazine is kidney 

histopathology, which is not a typical MTD endpoint. These endpoints (kidney histopathology 

and clinical chemistry values) were not included as MTD targets in the EPA's inter-laboratory 

validation studies for the pubertal assays, which were reported in 2005-2006. However, in their 

Integrated Summary Reports for the pubertal assays, EPA identified kidney histopathology and 

changes in clinical chemistry values as potential endpoints for determining the MTD in the 

pubertal assays, and in 2008, carried these endpoints into the test guideline. To the best of my 

knowledge, EPA's Integrated Summary Reports for the pubertal assays are the first mention of 

these endpoints as possible MTD targets. EPA's current hydroxyatrazine negative control data 

set from the pubertal assays the are not publicly available, however, it is my understanding that 

a manuscript is in preparation and will be submitted for publication soon. 

12. You testified that a positive result in the endocrine screening battery is not necessarily 

indicative of adverse effects. Please describe other instances, if any, where the presence of a 

substance has not been proven to have an impact. 

The examples of chemicals that can be present in the human without portending adverse 

consequences are too numerous to begin to list, but a few examples illustrate the general 

principle. Human physiology itself gives numerous examples of chemicals whose presence 

alone poses no toxic risk at all. Chromium and magnesium are metals used industrially, are 

toxic pollutants, and are normally found in humans. Their mere presence in humans does not 

portend adverse effects. In fact, small amounts of magnesium and chromium are necessary for 

normal physiological functioning, and recently, concem has been raised that modem diets may 

provide insufficient levels of chromium. Even arsenic is believed to be necessary in trace 

amounts in the human diet; larger amounts have been used medicinally to cure infections, 

though with toxic side effects; higher doses are lethal and have been used as poison. Organic 

chemicals may also be present without implying adverse effects. Ethanol is the type of alcohol 

contained in alcoholic beverages and is known to be toxic and lethal at sufficient doses. Yet, 

low levels of ethanol are detectable in healthy, non-drinking subjects as a by-product of normal 

metabolism and these low levels have no toxicologic or medical significance. Formaldehyde is 

produced in the human liver as a product of normal metabolism and is found in the blood in low 

levels, yet at high concentrations in the air, formaldehyde is toxic and corrosive to the 

respiratory tract. 
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13. You referred to your presentation to the NAS concerning mixtures of chemicals in drinking 

water and their potential effects on human health and the environment. Please explain the 

significance of your assessment of the valid science on this matter. 

My presentation to the NAS' explained the scientific basis for my evaluation of methods used in 

assessing risks of mixtures in drinking water, also known as assessing risks for cumulative 

toxicity, or cumUlative risk assessment. That basis included the three fundamental tenets of valid 

scientific evidence I explained in my testimony to this subcommittee. I further explained that 

current recommendations for performing cumulative risk assessment make the assumption that 

all chemicals capable of producing a particular effect, irrespective of their potency, will add 

together in producing that effect. This assumption relies on extrapolating data collected at 

relatively high doses, where effects are observable and where toxicity from multiple chemicals 

may be cumulative, to doses below which any measurable effect occurs and at which the 

concept of cumulative toxicity is questionable speculation, at best. Such approaches also rely 

on the assumption that the mechanisms by which chemicals produce effects at high doses also 

occur at much lower doses, but simply produce a lesser magnitude of effect. Current 

approaches ignore the substantial evidence that contradicts these questionable assumptions, 

which I explained in my presentation. 

The general concept can be explained by an analogy to density, mass, and buoyancy, where 

density is analogous to potency, mass to dose, and buoyancy to whether or not a particular 

biological effect occurs in a human. Although one can weigh a ton of closed cell foam on the 

same scales as one can weigh a ton of iron, their weights will not be additive when put to sea. 

In fact, the iron will sink but the foam will float, irrespective of the mass weighed, and closed cell 

foam will counteract the sinking of iron if placed in the same vessel. 

During my oral comments to this subcommittee, I gave the example of testosterone, the 

principal male sex hormone, activating the human estrogen receptor with a potency similar to 

that reported for some putative environmental estrogens including the synthetic chemicals 

bisphenol A and methoxychlor, among others. Yet, no serious endocrinologist would decry the 

estrogenic risks of testosterone; although testosterone truly possesses the ability to activate the 

estrogen receptor, its potency at the estrogen receptor is too low to have an estrogenic impact 

in the presence of estradiol, the principal female sex hormone. 

14. Please state whether in your opinion the screening tests are faulty because of the minimum 

validation. Please also state whether Congress should prohibit minimum validation testing or 

otherwise mandate what validation standards must be met for future regulatory assessment. 

Validation is a process that helps to ensure that an assay or test is not faulty. Since validation of 

the endocrine screening battery is incomplete, it would be premature for me to say that it is 

faulty. I believe that mandating extensive testing before the battery of assays has been fully 

validated is a faulty process. 

Regarding validation standards, I believe it was wise of Congress to require validated tests 

systems for the endocrine screening battery, and this should be a routine requirement for 

1 Considerations for Single Chemical Versus Mixture Risk Assessment: Concepts and Caveats. National 

Academies of Science, National Research Council, Board on Environmental Studies & Toxicology, 

Workshop on Pharmaceuticals in Drinking Water, December 11-12, 2008. Washington, DC. 
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Borgert Follow-up Responses page 15 of 28 

assays used in regulatory decision making. Although it may be difficult for Congress to mandate 

detailed validation requirements that would apply in all circumstances, the three tenets I 

described in my testimony could be used as a general guide, as these apply to all areas of 

scientific inquiry. To briefly reiterate, 1) the identity and authenticity of scientific measurements 

and observations must be verifiable within a defined range of precision and relevant to the 

question at hand; 2) the measurements and observations must not be confounded by 

extraneous factors and influences known to corrupt their accuracy and precision; and, 3) the 

measurements and observations must be replicable in independent hands. Technical details for 

fulfilling these simple requirements could be left to the appropriate Agency, but this would help 

to standardize and enforce the use of high quality science in regulatory activities. 

15. Please slate your opinion on whether the screening test results for the 67 chemicals cUlTently 

undergoing the endocrine screening battery should be validated before moving forward with 

a second set of test orders. 

Yes; I believe it is essential to provide EPA the time and resources it needs to fulfill validation for 

the individual endocrine screening assays as well as the endocrine screening battery as a unit 

before more test orders are issued. Here, it is important for Congress to appreciate that 

scientific investigation, including assay validation, cannot be placed on a time schedule and that 

particular outcomes cannot be dictated. Congress may desire that a new set of assays be 

proved valid and that the validation be accomplished within a particular time frame, but the data 

that emerge may support both, only one, or neither objective. 

16. You testified that some of the assays used in the endocrine screening program are used in 

"novel" ways. Please explain this statement. 

My statement referred primarily to the fact that many of the assays in the ESB have a long 

history of reliable use to screen for chemicals that have high endocrine potency. EPA's 

endocrine screening battery utilized these assays to detect chemical that may have very low 

endocrine potency. Whether all of these assays are useful for discriminating chemicals with low 

versus no potency remains to be determined. 

17. Please explain whether or not children are always more sensitive to chemicals and drugs. 

Children are not always more sensitive to drugs and chemicals than adults, however, they may 

be more sensitive to some drugs and chemicals. The oft-quoted phenomenon of critical 

windows of sensitivity is real, especially during development, but this does not apply to all 

chemicals or drugs, nor to all effects of chemicals and drugs. Whether or not a child is more 

sensitive than adults depends on a variety of factors, including the age of the child at issue, the 

tissues and pathways affected by the drug or chemical, the way the drug or chemical is 

absorbed into the body, the way the drug or chemical is metabolized by the body, the way the 

drug or chemical and its metabolites are distributed in the body, the way the drug or chemical is 

eliminated from the body, and other factors. 

18. You testified that the endocrine screening program will not identifY endocrine disruptors. 

Please explain this statement. Please also define what an endocrine disruptor is. 
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As a Plenary member of EDSTAC (Endocrine Disruptor Screening and Testing Advisory 

Committee), the the Federal Advisory Committee convened by the U.S. Environmental 

Protection Agency to provide advice in meeting the endocrine screening mandates of the 1996 

Food Quality Protection Act (FQPA) and the 1996 amendments to the Safe Drinking Water Act 

(SWDA), I argued a common-sense definition of "Endocrine Disruptor' in response to the 

Assistant Administrator of EPA's proposed definition of the term. Her definition was as follows: 

"The EDSTAC defines an endocrine disruptor as an exogenous chemical 

substance or mixture that alters the function(s) of the endocrine system 

and thereby causes effects at the level ofthe organism, its progeny, and 

populations or subpopulations of organisms. The EDSTAC considers 

endocrine disruption to reflect mechanisms of action which (among others) 

may lead to adverse outcomes including, for example, carcinogenic, 

reproductive, or developmental effects that need to be routinely considered 

in reaching regulatory decisions." 

I argued: 

1. The literature held out as support for the endocrine disruptor hypothesis 

is unfailing in its assertion that endocrine disruption is an adverse effect. 

Especially the writings of those individuals who now insist that "adverse" 

NOT be included in the definition are precisely the publications that warn 

most strongly that endocrine disruption IS adverse. I cannot fathom why 

Congress would have mandated screening and testing unless they were led 

to believe that endocrine disruptors were producing adverse effects in 

wildlife and humans. Certainly, I would not have spent the time and effort I 

have spent serving on this committee and on two of its workgroups had I 

believed that our charge was to design a screening and testing program for 

effects that might be merely adaptive and compensatory. 

2. Surely, whoever coined the term "endocrine disruptor" was aware that 

"disruption" is a "morphologic defect": 

disruption: a morphologic defect resulting from the extrinsic breakdown of, 

or intereference with, an originally normal developmental process. 

[Dorland's Illustrated Medical Dictionary, 27th Edition, 1988. WB. 

Saunders Company, Philadelphia.] 

disruptive: bursting apart; rending. [Dorland's Illustrated Medical 

Dictionary, 27th Edition, 1988. WB. Saunders Company, Philadelphia.] 

I could find no reference to "adaptive" or "compensatory" changes in any 

definition of any form of the word "disrupt" in any dictionary I consulted. 

3.. Therefore, to define an "endocrine disruptor" as a chemical that 

produces anything other than defects or adverse effects would make the 

EDSTAC appear to be contradictory and perhaps, intellectually dishonest. I 

fear that if such a definition emerges with consensus, the credibility of this 

committee becomes immediately suspect. I will not sign-on to such a definition. 
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Please remember that while the committee has made considerable 

progress without a firm consensus definition of endocrine disruptor (Tim 

Mealey, stated 49 times since October, 1997), 'the definition of what we are 

addressing ultimately sets the standard against which our report will be 

judged.' If we have not addressed a meaningful subject, or if our screens 

and tests do not match our definition, then we will not fare well in either 

the peer or public review. 

4. The argument was made that the EDSTAC's draft definition does include 

the word "adverse", and so my concerns are met. This is thoroughly 

unconvincing to me. One has only to read and reason clearly to see that the 

EDSTAC's draft definition does not specify that endocrine disruption is an 

adverse effect; rather, the draft definition merely allows that endocrine 

disruption MAY lead to adverse effects. The EDSTAC must have a definition that requires the effect to be both endocrine mediated and 

adverse; otherwise, we must also state clearly that endocrine disruptive 

effects may as likely be meaningless to human health and the environment. 

The draft definition gives one the option to be intellectually honest and 

consistent, but does not require it. Perhaps that makes grade in 

Washington D.C., but it's not my standard, and I hope it is not the 

EDSTAC's. 

5. While it may be difficult to determine that an observed effect is clearly 

adverse, this should not confuse our definition of endocrine disruptor (the 

section on Weight Of Evidence is the appropriate place for discussion of 

this difficulty). When it is unclear whether or not a specific effect is adverse, 

this is due to limitations of scientific knowledge rather than an inability to 

know what we are looking for. An analogy is cancer: there is no question 

that cancer is an abnormal and unhealthy population of cells; sometimes, 

however, a pathologist may be uncertain as to whether or not a particular 

cell is abnormal. This has not confused the field of oncology into defining 

cancer as a loose collection of mechanisms or as simply an effect that 

either mayor may not be abnormal and unhealthy. 

6. The consistent and intellectually honest thing for the EDSTAC to do is to 

define endocrine disruptor as a chemical that produces adverse effects or 

defects through endocrine mechanisms (I'm paraphrasing). The Europeans 

have thought clearly and accurately on the term "disruptor", despite the fact 

that English is not the first language of many Europeans. I would be 

embarrassed to concede that we are unable to do as well. The following 

definition is similar to the European definition, but puts endocrine function 

first to convey emphasis, and is close to an earlier definition the EDSTAC 

considered. I propose that the EDSTAC adopt the following definition: 

"An endocrine disruptor is an exogenous substance that changes endocrine 

function and causes adverse effects in an intact organism or its progeny, 

or in populations or subpopulations of organisms. " 

Please note that the I use "adverse effect" instead of "morphologic defect" 

because the latter term may imply to some an excessively restrictive 

page 17 of 28 
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Borgert Follow-up Responses 

meaning. In the spirit of compromise, I can accept that "adverse effect" 

is a broader term that would include and is consistent with "defect': even 

though the medical definition of "disruption" specifies "morphologic 

defect". 

page 18 of 28 

I stand by this analysis today, and I believe my arguments have been upheld by the OECD and 

in general by the scientific community. Therefore, identifying "Endocrine Disruptors" requires 

demonstrating adverse effects produced by an endocrine mechanism. 

The benefit of an additional decade of research since EDSTAC substantiates that the 

most accurate, complete, and clear definition of "endocrine disryptor" is "a chemical or 

other factor that causes adverse effects in an organism or its progeny as a consequence 

of altering endocrine function." 

EPA has consistently stated, as was emphasized by Mr. Jones at the February hearing before 

this subcommittee, that adverse effects are not determined in tier 1 (endocrine screening), but in 

tier 2 (definitive testing). The screening tier was intended to identify interaction of a chemical 

with components of the endocrine system; it was not designed to determine whether that 

interaction results in any deleterious change in the animal. Many of the endocrine screens are 

in vitro ('test tube') assays that do not necessarily reflect what will occur in an organism. Thus, 

it is erroneous to state or imply that endocrine screening will identify endocrine disruptors 

19. Please state whether the risks of additive or synergistic estrogenic effects in humans from 

drinking water have been evaluated, and if so, what those risks are. 

Humans may be exposed to estrogenic substances in drinking water that are natural estrogens 

excreted by humans and other animals and from plant materials, or that are synthetic estrogens 

from medications and other products. By far the most potent of these are the natural estrogenic 

hormones and estrogen medications. Human risks of additive estrogenic effects have recently 

been evaluated in a study authored by scientists from the pharmaceutical industry (Caldwell et 

al., 2010) and published in Environmental Health Perspectives, the journal of the National 

Institutes of Environmental Health Sciences. This study compared the potential doses of natural, 

synthetic and total estrogens from drinking water to normal dietary intake of estrogens and to 

four independent estimates of the acceptable daily intake of estrogens derived from toxicology 

studies. 

The acceptable daily intake is a level at which there is no reasonable concern for adverse 

human health effects. Calculating the ratio of different received doses gives the 'margin of 

exposure' for the exposures to various classes of estrogen. The ratio of a received dose to the 

acceptable daily intake dose gives the 'margin of safety' indicating how much difference exists 

between the received dose and the dose that would raise no reasonable concern for adverse 

health effects. The margins of exposure and safety calculated for the various ciasses of 

estrogens in the Caldwell et al. study are additive because comparisons to the acceptable daily 

intake levels were made on the basis of the total doses of natural estrogens, synthetic 

estrogens, and total natural and synthetic estrogens, rather than on a chemical-by-chemical 

basis. 

The results of this comparison indicate that children's exposures to synthetic estrogens from 

drinking water are from 730 to 480,000 times lower that their exposure to background levels of 

naturally occurring estrogens in milk, and a child's total estrogen exposures from drinking water 
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Borgert Follow-up Responses page 19 of 28 

are about 150 times lower than exposures from milk. Adult margins of exposure from 

estrogens in drinking water compared to total natural dietary estrogen intake are about 2-fold 

less than for children based on natural estrogens in milk. Margins of safety for of an adult's 

exposure to total prescribed estrogens in drinking water vary from about 135 to greater than 

17,000 depending on the acceptable daily intake used in the comparison. Margins of safety for 

total estrogens in drinking water are approximately 2-fold lower than for prescribed estrogens, 

indicating the increased estrogenic load in drinking water that is contributed by natural sources 

of estrogen. For young children, margins of exposure range from 28 to 5,120 for total 

estrogens, including both prescribed and naturally occurring sources in drinking water 

depending on the acceptable daily intake used in the comparison. In sum, the consistently large 

margins of exposure and margins of safety strongly suggest that prescribed and total estrogens 

that may potentially be present in drinking water in the United States are not causing adverse 

health effects in children or adults. 

The potential for synergistic effects cannot be estimated directly because synergistic effects are, 

by definition, effects produced by a mixture of chemicals that exceed the effects that would be 

expected based on the individual chemicals. In other words, it is not possible to predict the 

unpredictable. Nonetheless, the fact that no credible demonstration of significant synergistiC 

estrogenic effects has been published in the peer-reviewed literature suggests that such effects 

are highly unlikely. The Single example of a significant estrogenic synergy, published just a few 

months before passage of the 1996 Food Quality Protection Act, was retracted due to lack of 

reproducibility, and was ultimately believed to involve scientific fraud. The study was not funded 

or in any way connected with industry; rather, the authors had ties to large universities and the 

National Institutes of Environmental Health Sciences. 

20. You testified that you do not believe the scientific evidence warrants a ban on bisphenol-A. 

Please provide information to support this conclusion. Please also state whether BPA has 

been tested for endocrine disruption, and if so, please identifY the results. 

The conclusion that scientific evidence does not support a ban on BPA is not simply my belief: 

Regulatory agencies around the world have extensively assessed the science on BPA and 

concluded that BPA is safe for use in currently approved applications. Not a single one of the 

eleven regulatory agencies that have examined the science on BPA concludes that it there 

should be an "across the board" ban on BPA; indeed they have determined that BPA is safe for 

use in food contact products: 

U.S. Food and Drug Administration (August 2008, February 2009, January 2010) 

European Food Safety Authority (January 2007, July 2008, October 2008) 

European Commission Risk Assessment (June 2008) 

Swiss Federal Office of Public Health (February 2009) 

French Food Safety Authority (November 2008) 

Dutch Food and Consumer Product Safety Authority (November 2008) 

Danish Environmental Protection Agency (October 2008) 

German Federal Institute for Risk Assessment (January 2010) 

Food Standards Australia and New Zealand (January 2010) 

Japanese National Institute of Advanced Industrial Science and Technology 

(November 2005) 

Health Canada (October 2008, July 2009) - A 2008 proposal to ban polycarbonate 

baby bottles in Canada was based on precaution; the Canadian scientific 

assessment concluded that exposure is below levels that pose a risk 
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Borgert Follow-up Responses page 20 of 28 

Even Health Canada acknowledges that, despite its precautionary ban on baby bottles, the low 

levels of BPA to which humans are exposed are well below those that could cause health 

effects. In its October 2008 announcement of the conclusion of a screening risk assessment on 

BPA, the Canadian government noted: "The current research tells us that the general public 

need not be concerned. In general, most Canadians are exposed to very low levels of 

bisphenol A, therefore, it does not pose a health risk." 

Clearly, my conclusion that the scientific evidence does not support a ban on BPA is consistent 

with conclusions reached by numerous independent global regulatory agencies that have 

extensively assessed the full body of scientific research and determined that human exposure to 

BPA is low and that BPA is safe for use in current applications. 

With respect to the question whether BPA has been tested to determine whether it is an 

endocrine disruptor, the answer is yes. Tests have been performed and the results show that 

BPA is not an endocrine disrupter. As you know, there are a range of screening assessments 

and tests that EPA is proposing under the EDSP program. Under a screening assay, such as 

the utertrophic assay, BPA is weakly estrogenic (about 10,000 times less potent than ethinyl 

estradiol); however, when tested for adverse effects on endocrine modulated endpOints such as 

reproduction, development and sexually dimorphic behavior, BPA has not shown effects. 

With respect to reproduction and development, there are three statistically powerful, 

multigeneration reproduction and development studies that have been conducted in rats and 

mice under protocols validated by the OECD and EPA. The three studies independently show 

that BPA does not adversely affect reproduction or development; collectively they provide very 

strong corroboration that BPA does not disrupt the endocrine modulated functions of 

reproduction or development. Tyl et al. (2002b); Tyl et al. (2008b) and Ema et al. (2001) 

With respect to neurobehavioral effects, such as sexually dimorphic behavior, two recent highquality, robust and statistically powerful studies provide scientific evidence that there are no low 

dose neurobehavioral effects with BPA and no evidence of non-monotonic dose-response 

curves. 

One study - Ryan et al. (2009) funded and conducted by the United States Environmental 

Protection Agency -- examined whether maternal exposure to low oral doses of ethinyl estradiol 

and BPA would affect the age of puberty, reproductive function or sexually differentiated 

behaviors. The study showed that while the oral contraceptive ethinyl estradiol altered 

reproduction, development and behavioral endpoints, BPA did not affect any of those functions. 

The lack of effect of BPA on female and male rat offspring after oral exposure to low doses in 

the EPA study is consistent with the lack of adverse effects on growth, vaginal opening, fertility 

and fecundity of low doses in several other robust, well-designed, high quality multigenerational 

studies (Cagen et. AI. 1999; Ema et al. 2001; Tinwell et al. 2002; Tyl et al. 2002). 

The second study, Stump et al. (2010), which exposed pregnant rodents to a wide range of BPA 

dietary doses from low to high, concluded that BPA had no effects on brain development or 

behavior in their offspring that had been exposed to BPA in utero throughout development. The 

study was funded by industry and conducted by a highly qualified independent third-party 

laboratory. 

In addition to the high-quality scientific studies noted, as discussed more fully in my answer to 

question 21, there are multiple comprehensive reviews of the scientific literature on BPA, which 

conclude that the weight of the scientific evidence does not support the low dose hypothesis. 

For example, Goodman et al. (2008), an extensive, comprehensive review of the science on 

reproductive and developmental toxicology, concluded: "The weight of evidence does not 

support the hypothesis that low oral doses of BPA adversely affect human reproductive and 

developmental health." 
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Borgert FOllow-up Responses page 21 of 28 

21. You testified that well-qualified scientific panels have evaluated the low dose theory of 

bisphenol-A and potential risks to humans from its use in products, and that these panels have 

determined that no unreasonable risk is posed. Please explain those reviews and provide 

relevant documentation. Please also state whether foreign governments have assessed BPA as 

an endocrine disrupter. 

As stated in my testimony, a number of well-qualified panels, both in the United States and in 

foreign countries, have evaluated the low dose hypothesis as it relates to claims that BPA has 

endocrine effects at doses far below levels previously determined to be safe using wellestablished toxicological procedures and principles. The panels have also examined the lowdose hypothesis claim that the dose-response relationship is "non-monotonic", which means 

that health effects may only be observed at low doses while much higher doses result in no 

effects. This theory is contrary to a fundamental principle of toxicology - "the dose makes the 

poison." As detailed further below, all these well-qualified panels have determined that the lowdose hypothesis is not proven and that no unreasonable risk is posed by BPA. 

Panels in the United States 

U.S. National Toxicology Program Low Dose Endocrine Review 

In 2000, the U.S. National Toxicology Program (NTP), U.S. Environmental Protection Agency 

and the U.S. National Institute of Environmental Health Sciences cosponsored an independent 

scientific peer review of the evidence for and against "low-dose endocrine disruptor" effects. 

The peer review included both a Statistics Subpanel, which evaluated the experimental design, 

data analysis and interpretation of results, and a Bisphenol A Subpanei, which reviewed the 

then available studies on BPA. The Bisphenol A Sub panel found that low dose effects from 

BPA were not demonstrated: 

'}:\s a group these studies are very consistent, the conclusions are supported by 

appropriate statistical analyses, and the Statistics Subpanel confirmed the lack of BPA 

effects for the studies .. . " and "Collectively, these studies found no evidence for a lowdose effect of BPA, despite the considerable strength and statistical power they 

represent, which the subpanel considered especially noteworthy." 

The Bisphenol A Subpanel's overall conclusion stated: 

"There is credible evidence that low doses of BPA can cause effects on specific 

endpoints. However. due to the inability of other credible studies in several different 

laboratories to observe low dose effects of BPA, and the consistency of these negative 

studies, the Subpanel is not persuaded that a low dose effect of BPA has been 

conclusively established as a general or reproducible finding. In addition, for those 

stUdies in which low dose effects have been observed, the mechanism(s) is uncertain 

(i. e., hormone related or otherwise) and the biological relevance is unclear. " 

Based on its review of the NTP's report the U.S. Environmental Protection Agency, issued a 

statement that they viewed low-dose as still a "hypothesis" that had not been proven. As a 

result, EPA further stated, "it would be premature to require routine testing of substances for 

low-dose effects." 

Harvard Center for Risk Analysis 

In 2004, the Harvard Center for Risk Analysis impanelled a group of 8 experts to review the 

scientific literature and to evaluate whether the studies supported a conclusion that BPA 
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produces low dose developmental or reproductive effects, "The panel found no consistent 

affirmative evidence of low-dose BPA effects for any endpoint." Gray et ai, 2004, in Human and 

Ecological Risk Assessment. 

Subsequently, a subset of the same scientists were brought together in 2006 and again in 2008, 

in an 8 expert panel to review the scientific studies that had been published subsequent to the 

initial review, They considered the rigor, power, corroboration, universality, proximity, relevance 

and coherence within and among the studies to weigh the evidence, The 8 experts collectively 

found in 2008 that: 

'Thus, the weight of the evidence does not support the hypothesis that low doses of 

BPA are associated with developmental or reproductive effects in humans," See 

Goodman et aI, 2008 in Critical Reviews in Toxicology; see also Goodman et ai, 2006 in 

Critical Reviews in Toxicology, 

National Toxicology Program/Center for Evaluation of Risks to Human Reproduction Report 

(September 3, 2008) 

In 2008, the CERHR 12 member, independent panel conducted a comprehensive study-bystudy review of all available literature on SPA, (Relevant literature was identified by search of 

the PubMed (Medline) and Toxline databases through February 2007,) In their overall 

conclusions, the CERHR panel noted that it spent considerable time and effort "to interpret and 

understand the inconsistent findings reported in the "low dose" literature for bisphenol A" They 

went on to say that: 

"Every chemical that produces low dose cellular and molecular alteration of endocrine 

function also produces a cascade of effects increasing in severity resulting in clearly 

adverse alterations at higher doses, albeit the effects can be different from those seen at 

low doses, With these endocrine disrupters, but not BPA, the low dose effects are often 

causally linked to the high-dose adverse effects of the chemical, , , , 

Hence, the failure of SPA to produce reproducible adverse effects via a relevant 

route of exposure, coupled with the lack of robustness of the many of the low 

dose studies (sample size, dose range, statistical analyses and experimental 

design, GLP and the inability to reproduce may of these effects {or] any adverse 

effect strains the credibility of some of these study results, , " The lack of 

reproducibility of the low dose effects, the absence of toxicity in these low-dose-affected 

tissues at high-doses, and the uncertain adversity of the reported effects lead the panel 

to express "minimal" concern for reproductive effects," (CERHR report, Chapin et ai, 

2008 at 382), 

NTP/CERHR said that for neural and development endpoints the evidence was insufficient to 

reach a conclusion and that "it is not clear that the reported effects constitute an adverse 

toxicological response," Two recent studies, Ryan et al. 2009 and Stump et al. 2010, provide 

additional evidence to show that SPA does not have low dose effects on neural or development 

endpoints, 

Ryan et ai, 2009, a recent study by EPA researchers further confirms that claims of low dose 

endocrine effects from SPA are not proven, 

"The National Toxicology Program rated the potential effects of low doses of BPA on 

behavior and central nervous system (eNS) as an area of "some concern," whereas 

most effects were rated as of "negligible" or "minima/" concern, However, the number of 

robust studies in this area was limited, The current study was designed to determine if 
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Borgert Follow-up Responses page 23 of 28 

maternal exposure to relatively low oral doses of EE2 or BPA in utero and during 

lactation would alter the expression of well-characterized sexually dimorphic behaviors 

or alter the age of puberty or reproductive function in the female Long-Evans rat 

offspring . .... The lack of effect of BPA on female and male rat offspring after oral 

exposure to low doses in our studies is consistent with the lack of adverse effects on 

growth, VO, fertility, and fecundity of low doses of BPA in several other robust, welldesigned, properly analyzed multigenerational studies (Cagen et al., 1999; Erna et al., 

2001; Tinwell et al., 2002; Tyl et al., 2002)." Ryan et al. 2010 in Toxicological Sciences. 

Ryan et al. 2010 and the low dose hypothesis was the subject of a recent commentary in 

Toxicological Sciences by Richard M. Sharpe ofThe Queen's Medical Research Institute in 

Edinburgh, UK. Dr. Sharpe stated: 

"Ryan et al (2009) and other similarly detailed studies in rodents more or 

less close the door on the possibility that bisphenol A is an environmental 

chemical to be concerned about because of its ER-mediated estrogenic 

activity. . . . I recognize that this statement will run counter to the strong 

convictions of some, but I base it on objective, scientific principles of 

evaluation. Bisphenol A has put one of these principles firmly under the 

spotlight, namely, the almost complete inability for different laboratories to 

reproduce the same results . .. If an earlier result cannot be reproduced in a huge study conducted in a scientifically rigorous manner, as exemplified by 

Ryan et al. (2009), then the original result fails one of the golden rules that 

govern scientific research. When that happens repeatedly, as is the case 

with bisphenol A, then there can be no logical, scientifically based reason 

for continuing to espouse that the original results are the only ones that are 

correct, rather the converse." RM. Sharpe, "Is It Time to End Concerns 

over the Estrogenic Effects of Bisphenol A?," in Toxicological Sciences 

(2010) 

CA Proposition 65 

On July 15, 2009, the eight member Developmental And Reproductive Toxicant (Dart) 

Identification Committee examined the low dose studies and unanimousely determined that 

BPA does not meet the criteria for developmental or reproductive effects under CA Proposition 

65. 

." 

Food and prug Administration 

The Food and Drug Administration August 14, 2008 a Draft Assessment of Bisphenol A for Use 

in Food Contact Applications represents the collective views of the FDA scientists who reviewed 

250 references, including those that claimed to show low dose effects. FDA noted that "based 

on all available evidence, the present consensus among regulatory agencies in the United 

States, Canada, Europe, and Japan is that current levels of exposure to BPA through food 

packaging do not pose an immediate health risk to the general population, including infants and 

children. " 

Panels in Europe 

EC Scientific Committee for Toxicity, Ecotoxicity and the Environment 

The European Commission completed a comprehensive risk assessment on BPA, in 2003, 

which was updated in 2008. The EU Risk Assessment includes a review of evidence for and 

against low-dose effects and which concludes that the low doses of BPA to which humans are 

exposed are not a risk to human health. See http://ecb.jrc.ec.eurooa.eu/home.oho? 

CONTENU=!DOCl.Jf\~.ENTSiExi$ting-Chemicais/RISK_AsSESS.MENTiAODENOUM 
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The European Commission's Scientific Committee on Toxicity, Ecotoxicity and the Environment, 

independently reviewed the 2003 Risk Assessment Report (June 19, 2002) and stated: 

"[A] number of studies using non-standard protocols have reported effects of bisphenol 

A administration on development using substantially lower doses than the studies 

performed according to testing guidelines. The RAR critically describes the many 

weaknesses (lack of repeatability. problems with experimental design and statistical 

evaluation, poor reporting) of the low dose studies. The CSTEE agrees with the 

conclusion of the RAR that there is no convincing evidence that low doses of bisphenol 

A have effects on developmental parameters in offspring and remarks that effects 

observed are not adverse." See iltto://ec. GUfooa. eu/ileaitilioil_risk/committees/sct/ 

sc(_ qpin(ons,,",," en.htm 

The CSTEE further remarked, "a number of high quality studies on the reproductive and 

developmental effects of bisphenol A are already available and do not support low-dose effects. " 

Ibid 

European Food Safety Authority 

The European Food Safety Authority Panel on Food Additives, Flavourings, Processing Aids 

and Materials in Contact with Food (EFSA), which is made up of 21 independent scientific 

experts from across the EU, comprehensively evaluated the studies on toxicity, metabolism and 

pharmacokinetics, and dietary exposure in 2006 and updated its evaluation in 2008. EFSA 

"considered that low-dose effects of BPA in rodents have not been demonstrated in a robust and 

reproducible way, such that they could be used as pivotal studies for the risk assessment." 

Panels in Canada 

Health Canada 

Similar to other agencies that have reviewed the evidence, Health Canada chose the 

multigeneration studies in rats and mice as the basis for their overall conclusions. Health 

Canada's views on low dose studies, in particular on neurodvelopmental and behavior studies, 

also are similar to the views of other government agencies and expert panels. 

"While collectively these studies provide evidence that exposure to bisphenol-A during 

gestation and early postnatal life may be affecting neural development and some 

aspects of behavior in rodents, the overall weight of the evidence was considered limited 

from the perspective or rigour (e.g. study design limitations such as conduct of 

behavioral assessments as a single time point), corroboration/consistency (limited 

consistency of studies) and biological plausibility (e.g. certain studies involve use of a single dose, lack of dose response relationship). These limitations make it difficult to 

determined actual significance of findings to human health risk assessment." See 

Screening Assessment for the Challenge, Phenol, 4,4" -(1-methylethylidene)bis-

(Bisphenol A), Health Canada 2008 at p. 73. 

Panels in Japan 

Japanese Ministry of Economy. Trade and Industry 

In 2002, the Japanese Ministry of Economy, Trade and Industry released a hazard assessment 

of BPA conducted by its experts. In regard to low dose effects, the Ministry stated: 

"Though it is necessary to collect further information on so-called 'low dose effects' 

represented by BPA from academic point of view, it seems unnecessary to take any 

specific measure other than the above, considering the view expressed by NTP Low 
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Dose Effect Panel that the low dose effect of BPA at present is a phenomenon observed 

under considerably limited experimental conditions and it is hardly considered to be the 

general phenomenon. " 

Japanese Ministry of Health. Labor and Welfare 

The Japanese Ministry of Health, Labor and Welfare has also recently released a report from an 

expert review committee that has been evaluating the potential risks of endocrine disrupting 

substances (MHLW, 2002). After evaluating experimental reports on low-dose endocrine 

disruption, the expert committee concluded, "no reproducible experimental results have been 

obtained, and at this point of time, it is doubtful whether we can conclude that there are 

endocrine disrupting effects in the low dose range." 

Conclysion 

In conclusion, the hypothesis that BPA has endocrine effects at low doses that are not seen in 

traditional high dose studies has been thoroughly tested with a series of comprehensive, 

carefully conducted studies, all of which have been repeatedly reviewed by various expert 

panels - both government and independent. Those review show that the low dose studies have 

not been replicated and that the large-scale studies validated protocol studies, which have 

examined a range of doses from low to high, do not show low dose effects. The weight of 

scientific evidence provided by these studies and reviews by scientific experts clearly supports 

the safety of BPA and provides strong assurance that exposure to low doses of BPA does not 

raise human health concerns. 

22. Are pesticides and other chemicals currently evaluated for endocrine disruption, or does that 

type of evaluation only occur if the chemical is included in the EPA's endocrine screening 

program? 

Many chemicals are evaluated for potential endocrine activity irrespective of the EP!\s 

endocrine screening battery, and irrespective of regulatory requirements per se. The high 

production volume chemical (HPV) program in the U.S. and the REACH initiative in Europe 

include toxicity tests that capture certain endocrine-mediated effects. EPA's more established 

Series 870 OPPTS test guidelines, which are required for all pesticides marketed in the U.S., 

include evaluations in multiple mammalian and non-mammalian studies that provide both direct 

and indirect data on ability of a pesticide to cause adverse endocrine-mediated effects. These 

studies are conducted according to well-validated and well-documented protocols and conform 

to the EPA's Good Laboratory Practice Standards (GLP). In a paper published in 1997 entitled 

"FIFRA Subdivision F testing Guidelines: are these tests adequate to detect potential hormonal 

activity for crop protection chemicals? Federal Insecticide, Fungicide, and Rodenticide Act" 

Stevens and co-authors addressed the applicability of other tests required under FIFRA to 

provide data meeting the objectives of the EDSP Tier 1 screening battery. Their analysis is 

consistent with the view that potential endocrine disruption is well characterized for pesticides 

irrespective of the endocrine screening battery. 

FIFRA-required tests include sub-chronic and chronic toxicity studies in rats, mice and dogs, 

developmental toxicity studies in rats and rabbits, and reproduction studies in rats. Such 

studies evaluate a wide array of estrogen-, androgen- and/or thyroid-sensitive tissues and 

evaluate potential endocrine-mediated responses such as reproductive parameters (e.g. mating, 

fertility, and gestational indices), estrous cyclicity, sperm parameters, and histological alterations 

in a variety of endocrine controlled tissues, (e.g. epididymides, testes, ovaries, uteri, thyroid, 

adrenals, pituitary). Many of these endpoints are the same or very similar to those required in 

the endocrine screening assays, but they are evaluated over a much longer time frame. Over 

and above what the endocrine screening assays assess, these other FIFRA requirements 
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Borgert Follow-up Responses page 26 of 28 

include evaluation of fetal and pup development assessed by measuring endpoints related to 

growth, survival, and sexual development, and many studies include additional endpoints such 

as hormone levels, Endocrine-related effects are also evaluated in representative wildlife 

species, including fish and birds, Metabolism studies in rats, poultry, ruminant animals and fish 

characterize the absorption and excretion of the pesticide over time and help to identify any 

metabolites of concern, In short, the extensive toxicity profile generated on pesticides to meet 

the FIFRA requirements provides more complete and definitive information about a pesticide's 

potential to interfere with the endocrine system than the endocrine screening battery is able to 

provide, 

23, You mentioned during the hearing that male fish can produce the female protein vitellogenin 

in response to human estrogen in the water, Can you characterize the relative importance of 

chemical endocrine disruptors compared to human estrogens in causing this effect? Does this 

effect prevent the fish from reproducing? 

I acknowledged that the egg protein vitellogenin, normally expressed in female fish, can be 

produced in male fish exposed to estrogenic chemicals in the water. However, in contrast to the 

other witnesses who testified at the hearing, I noted that viteliogenin in male fish is not 

necessarily an indication of exposure to endocrine disrupting synthetic chemicals in the water, 

but can more likely indicate exposure to estradiol from human urine in the water, Furthermore, 

and in contrast to other witnesses, I noted that vitellogenin in male fish was not specific for 

exposure to estrogens and might reflect habitat factors or factors other than endocrine 

disruption, The presence of vitellogenin in male fish does not portend impaired reproductive 

capacity and does not prevent fish from reproducing, More detail substantiating these and other 

points are provided below, 

First, as I stated during the hearing, early speculation by researchers in the United Kingdom that 

synthetic chemicals (detergents and other industrial chemicals) were responsible for the 

presence of vitellogenin in male fish captured downstream of sewage treatment plants turned 

out to be incorrect. These same researchers later found that the estrogenic activity was due to 

hormones in human urine, Human hormones are the most abundant and among the most 

potent estrogens found in water supplies, therefore, human hormones are indeed of highest 

relative importance generally (see answer to question #19), 

As I further noted during the hearing, the critical question is whether adverse effects are 

produced, not whether vitellogenin is found in male fish, Summarizing their study, Mills et al. 

(Environ Health Perspect. 2003 Jan;111(1):93-100)" reported: 

The gene for vitel/ogenin, an egg yolk protein precursor, is usual/y silent in 

male fish but can be induced by estrogen exposure, For this reason, 

vitellogenin production in male fish has become a widely used indicator of 

exposure to exogenous estrogens or estrogen mimics in the aquatic environment. The utility of this indicator to predict impacts on fish reproductive 

success is unclear because information on the relationship between male 

plasma vitel/ogenin and reproductive end points in male and female fish is 

limited, In the research reported in this article, we investigated whether the 

presence of male plasma vitel/ogenin is a reliable indicator of decreased 

reproductive success in mature fish, '" Results sUfJgest that male plesma 

vitel/ogenin expression is not a reliable indicator of male reproductive 

dysfunction in adult cunner exposed to estrogens for 2-8 weeks during their 
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Borgert Follow-up Responses 

reproductive season. at least in relation to capacitv to produce motile sperm 

or fertilize eggs. [emphasis added] 

page 27 of 28 

Furthermore, as I stated during my testimony, the science on endocrine disruption is not settled, 

as other witnesses implied, but remains hypothetical. A summary of the critical review by Mills 

and Chichester (Review of evidence: are endocrine-disrupting chemicals in the aquatic 

environment impacting fish populations? Sci Total Environ. 2005 May 1 ;343(1-3):1-34) supports 

my contentions: 

In this paper, evidence from the current literature is presented that 

addresses either of two questions: 1) do EDCs in the aquatic environment 

have the potential to impact the reproductive health and survival of various 

fish species, and 2) are EDCs in the aquatic environment actually impacting 

the reproductive health and sustainability of indigenous populations of fish? 

Overall data from laboratory experiments support the hvpothesis that 

EDCs in the aquatic environment can impact the reproductive health of 

various fish species but evidence that EDCs in the aquatic environment are 

actuallv impacting the reproductive health and sustainability of indigenous 

fish populations is less convincing The scarcity of evidence linking impacts 

of environmental EDCs with changes in reproductive success of indigenous 

fish populations may reflect a critical need for a dependable method or 

indicator to assess reproduction of fish in situ. In addition, more studies that 

investigate whether fish populations routinely exposed to EDCs in situ are 

experiencing changes in population structure are needed. LiD.fs.iD.g 

endocrine disruption and reproductive impairment with an ecological/v 

relevant impact on the sustainability of real fish populations remains with 

few exceptions, an open challenge [emphasis added] 

Finally, results of even more recent research substantiate my contention that habitat and other 

factors are potential causes of supposed endocrine disruption in fish (Trubiroha et al.: Naturallyinduced endocrine disruption by the parasite Ligula intestinalis (Cestoda) in roach (Rutilus 

rutilus). Gen Comp Endocrinol. 2010 Apr 1 ;166(2):234-40), but that these other factors are 

rarely researched because it is easier to sensationalize effects of chemicals. 

Fish represent the most frequently used vertebrate class for the 

investigation of endocrine disruption (ED) in wildlife. However, field studies 

are complicated by exposure scenarios involving a variety of anthropogenic 

and natural influences interfering with the endocrine system. One natural 

aspect rarely considered in ecotoxicological studies is how paraSites 

modulate host physiology. Therefore, investigations were carried out to 

characterise the impacts of the parasitic tapeworm Ligula intestinalis on 

plasma sex steroid levels and expression of key genes associated with the 

reproduction in roach (Rutilus ruti/us), a sentinel species for wildlife ED 

research . ... In summary, the present results provide basic knowledge of the 

endocrine svstem in L. intestinalis-infected roach and clearly demonstrate 

that parasites can cause ED In fish. [emphasis added] 

These researchers also note that vitellogenin (VTG) production in male fish is not always an 

indication of exposure to estrogenic chemicals, but may have a normal physiological role in 

immunity. 
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VTG has generally been claimed to be a female-specific protein but, 

nevertheless, an increasing amount of data show that VTG or its mRNA is 

also present at low levels in male fish which were not exposed to 

oestrogenic compounds (Bowman et al., 2000; Rod- gers-Gray et al., 

2001). As Lake Mueggelsee is located upstream of sewage discharging 

areas (Massmann et al., 2004), it seems vel)' unlikely that the levels of VTG 

mRNA detected in male roach are caused by anthropogenic pollution. In 

addition, samplings of several hundreds of roach from Lake Muegge/see 

(2006-2009) re- vealed only a negligible incidence of testicular oocytes 

(unpublished data). Since in roach, the occurrence of intersex phenomena 

has been demonstrated to be the best predictor of exposure to oestrogenic 

compounds (Jobling et al., 2006), this further confirms that low levels of 

hepatic VTG mRNA are constitutively expressed in male roach even at 

unpolluted sites. Recent findings show that in fish, VTG functions as a 

pattern recognition receptor and exhibits opsonic activity, suggesting that 

VTG plays a role in innate immunity of oviparous vertebrates independent 

of gender (Li et al., 2008; Liu et al., 2009). 

o 

page 28 of 28