Thank you for that introduction. I'm delighted to be here to talk about exciting progress being
made at EPA in protecting men's reproductive health from environmental hazards.
On behalf of EPA Administrator Carol Browner, I would like to thank all of the sponsors of this
important conference -- the National Institute of Environmental Health Sciences/Superfund Basic
Research Program, Mount Sinai School of Medicine, the New York Academy of Medicine, the
National Institute for Occupational Safety and Health and the Agency for Toxic Substances and
Disease Control -- for helping us move forward together to link science, risk assessment, and
public policy in protecting male reproductive health. I'm looking forward to learning a great deal
from the program's presentations.
Based on what we have learned over the past 20 years, it is becoming clearer -- thanks to the
work of Theo Colborn and her coauthors in the landmark book, Our Stolen Future, as well as
many other researchers who amassed the pieces of the puzzle -- that some hazardous substances
-- such as some pesticides, dioxin and PCBs -- that persist in the environment, biomagnifying and
bioaccumulating in fatty tissues as they move up the food chain, affect endocrine systems and how
our hormones function. These endocrine disrupting chemicals have been linked to developmental
and reproductive effects in animals and humans worldwide. They present a significant concern for
men's reproductive health. We have reports of increases in adverse male reproductive effects
worldwide, such as higher incidences of testicular cancer, reduced sperm quality and quantity, and
increases in hypospadia -- and all of these may be linked to endocrine disrupting chemicals.
The fact is that endocrine disruptors confront us all with disturbing questions, ranging from the
health of ecosystems to the health of our children and future generations. Women face important
concerns including reduced fertility and sterility. We have few definitive answers and few
protections in place against the thousands of chemicals that may have endocrine disrupting
potential.
Our mission here is to work toward developing an international research strategy to better
understand the effects of these and other environmental agents on male reproductive health. I am
happy to have the opportunity today to talk with you about the program EPA will propose to
screen initially as many as 15,000 chemicals for their potential to disrupt human endocrine
systems, and that will require additional screening and testing for many of those chemicals. I will
also be talking about other EPA activities -- such as implementing the 1996 Food Quality
Protection Act -- that are enabling us to learn more about and to better protect against exposures
to chemicals that can compromise male reproductive health and fertility.
But first I would like to place our current efforts in context -- how has EPA over more than two
decades dealt with the protection of reproductive health, and, in particular, male reproductive
health? I think that most of us know that historically EPA has focused much of its energy on
evaluating the carcinogenic risks posed by hazardous substances, as well as on relatively gross
effects, such as liver damage, and in the case of air pollution, on pulmonary effects. This intense
targeting of carcinogenic effects was due in large part to the way that we have conducted risk
assessments. Generally, we have looked at the entire spectrum of an agent's adverse effects, but
our evaluation of risk has been and still is based on the most sensitive endpoint. And because, as
you know, our cancer model had until recently assumed that there was no safe level for a
carcinogen and that a linear dose-response curve existed, the great tendency was to believe that
by protecting against carcinogenic effects, we would also protect against other health effects. This
thinking certainly predominated -- and together with society's deep concern about cancer --
reinforced our reliance on looking at cancer as an endpoint.
We can, nevertheless, look back and see that since its inception, EPA has been evaluating
developmental and reproductive effects in its pesticide program and that by the mid-80s, the
practice had spread throughout the agency. Moreover, EPA has contributed significantly on a
worldwide scale to developing state-of-the art testing and developing risk assessment guidelines
for reproductive risks, and has taken a number of major regulatory actions based on protection
of reproductive health, including banning pesticides for the primary purpose of protecting male
reproductive health.
Many of EPA's statutes and programs -- such as air, water and hazardous waste -- are authorized
to protect for effects that include reproductive effects. However, only the Toxic Substances
Control Act, or "TSCA," and the Federal Insecticide, Fungicide and Rodenticide Act, or
"FIFRA," give the agency authority to require the production of test data for chemicals. Together
these statutes give EPA authority more than 78,000 thousand chemicals. But EPA's authority to
require companies to submit test data and to regulate substances has always been far greater
under FIFRA, which requires companies to submit test data on which EPA makes a decision on
whether to register a pesticide use and to assign a tolerance level for the pesticide's residue on
food. To get test data on industrial chemicals under TSCA, the agency must first show that the
chemical is of concern or that there is widespread exposure and the data is inadequate to assess
the chemicals.
During the '70s and '80s, EPA took emergency actions to ban and eventually cancel at least four
pesticides where serious threats to male reproduction were involved -- 1,2-dibromo-3-chloropropane, or DBCP, in 1977; chlordecone, or Kepone, in 1977; dinoseb in 1986, and
ethylene dibromide, or EDB, in 1983.
I would like to tell you the story about one of them -- DCBP. It is the most toxic pesticide to the
human male reproductive system that we have encountered. Its effects were first suspected after
wives of men working in a pesticide manufacturing plant had attended several baseball games
together where they discussed similar difficulties conceiving. As it turned out, workers at the
factory who were tested had sperm counts ranging from low to zero. Some of the men eventually
regained normal or near normal sperm counts. Unfortunately, DBCP is not an example of good
risk management. Data was available in the literature since 1961 indicating that DBCP caused
testicular atrophy in rats, guinea pigs and rabbits. Later, studies revealed that this potent toxicant
also induced adverse genetic, endocrine and possibly secondary sex gland effects in the male
reproductive system.
In 1984, EPA expanded its small number of scientists devoted to evaluating developmental and
reproductive effects. The influx of new scientists came after Administrator William Ruckelshaus
made reproductive research a priority and called for the development of reproductive risk
assessment guidelines. Many of those scientists today comprise the agency's highly expert core
group working on reproductive health. My sense is that they would tell you that while their work
has been very much a part of the regulatory process, it sometimes may have played a less
prominent role than they think was warranted by the animal and human health effects data.
Test Guidelines and Risk Assessment Guidelines
As for testing and research, it was not until 1982 that EPA had in place its first testing guidelines
for both reproductive and developmental effects for pesticides and industrial chemicals. The
developmental and reproductive test guidelines, a product of consensus decisionmaking, were
widely recognized and used by other federal agencies, as well as the scientific community at large.
In 1986 EPA issued draft guidance on how developmental toxicity should be evaluated to
determine risks to humans, and in October of 1996 completed the more than a decade-long effort
to develop final reproductive toxicity risk assessment guidelines. These were also the result of a
process aimed at reaching scientific consensus. EPA's Assessment Guidelines for Reproductive
Toxicity today remain the only ones worldwide and are relied on extensively in here and
internationally.
We have also completed a major revision of both the developmental and reproductive testing
guidelines, and are now in the process of ensuring that they are harmonized internationally
through the test guideline program of the Organization of Economic Cooperation and
Development (OECD).
EPA's development of reproductive toxicity testing and risk assessment guidelines has been a
major task. As I mentioned, the effort goes back more than a decade, and it clearly reflects
increased attention to and concern about hazardous substances' effects on reproductive health.
These guidelines have also been a springboard, enabling us -- as we knew would be necessary --
to begin providing the added protections to fetuses, infants and children required by the 1996
FoodQuality Protection Act.
Research
And in the last few years, our improved ability to measure sperm counts and determine sperm
quality has helped us to take a quantum leap in the type of research we are conducting. We have
moved from looking at effects of fertility/ infertility to looking at more subtle reductions infertility. Underway at EPA is an epidemiological study in which we have data that allows us to
predict changes in fecundity based on semen quality parameters. Eric Clegg, the project leader,
will be talking about it later in the program. Preliminary results of another study conducted,
which was conducted in the Czech Republic, indicate an association between high levels of air
pollution and degradation in sperm quality. Later you will be hearing about this collaboration
between the Czech Ministry of the Environment and EPA. With us from the Ministry is Jiri
(pronounced Uri) Rubes as well as EPA collaborators Sally Perreault-Darney and Sherry Selevan.
We are also preparing a state-of-the-science report on the environmental causes of prostate
cancer, which is being led by EPA's Thomas Crisp .
Endocrine Disrupters
The 1996 Food Quality Protection Act was a major step in moving to protect the health of our
children as well as our reproductive health. With this law and Safe Drinking Water Act
Amendments, EPA was given the green light to pursue and expand work to deal with endocrine
disruptors, work which it had already begun.
The Food Quality Protection Act mandates that EPA develop and carry out a comprehensive
screening program for all pesticides -- specifically for estrogenic effects -- and authorizes
screening for other endocrine effects. The 1996 Amendments to the Safe Drinking Water Act
authorize EPA to include in its endocrine screening program any chemical found in drinking water
sources to which substantial numbers of people may be exposed.
These are the first statutes since enactment of the 1976 Toxics Substances Control Act that
authorize EPA to require chemical testing -- an essential tool for helping us get answers on
endocrine disruptors.
The statutory timetable for action directs EPA to propose a screening program by August 1998.
The Agency is to implement the screening program by August 1999 and report back to Congress
by the year 2000.
Anticipating the legislation, on May 15, 1996, EPA sounded out many of the major stakeholders
involved. The resounding response was for a collaborative, participatory process. They urged
that EPA establish an advisory committee under the Federal Advisory Committee Act.
Resolving issues through a federal advisory committee has important advantages. The process is
public and, therefore, transparent. It brings in outside expertise. It helps ensure that all views in
controversial issues are represented. It promotes consensus and reduces the potential for future
litigation.
In this spirit, on October 16, 1996, EPA established the Endocrine Disrupter Screening and
Testing Advisory Committee. EDSTAC -- as it is called -- is comprised of approximately 40
members. They include scientists and other representatives from: EPA and other federal agencies;
state government; chemical, pesticide, and consumer product industries; water providers; worker
protection and labor organizations; national environmental groups; environmental justice
organizations; public health groups; and academia.
EPA asked the committee to make recommendations on a scientifically defensible strategy for
selecting and setting priorities for chemicals for screening and testing. We sought advice on a
process for identifying new and existing screening tests for validation. We also asked for the
committee's views on a set of available screens for early application and when to use them and
how to determine the need to go beyond screening.
The task set was difficult and the process itself has been time-consuming and far from easy. But I
was extraordinarily encouraged by the level and seriousness of effort that has been put into
accomplishing it, and I would like to publicly express my thanks to each EDSTAC member.
In terms of scope, the committee quickly concluded that the program should consider both human
and ecological effects. It should include not only estrogenic but also anti-estrogenic, androgenic,
anti-androgenic effects, and effects on the thyroid. It also should consider single compounds and
mixtures.
EDSTAC developed a conceptual framework to organize the process and resolve issues. It
begins with obtaining and analyzing existing information for the purpose of sorting and priority
setting for all of the pesticides and chemicals in commerce and contaminants found in drinking
water sources, with a particular focus on those produced in produced in volumes greater than
10,000 pounds per year.
Priority setting will be based on existing data including toxicology and metabolism data,
epidemiology and field studies, structure-activity relationships, production and use data,
monitoring data, and fate and transport data, as well as statutory and regulatory mandates.
Obtaining and analyzing these existing data would lead to sorting and priority-setting of chemicals
under the framework. Next would come screening of chemicals and, in turn, chemical testing,
hazard assessment, evaluation of exposure and risks, and, if indicated, regulatory action.
The Food Quality Protection Act directs that the screens used in determining endocrine activity be
validated. The committee gave us guidance on the validation status of each assay and on a
program to validate the screening battery. Validation means that the tests need to give
reproducible results over time and in the same and different laboratories, and they need to be
predictive in target populations.
The purpose of screening is to identify chemicals for testing. For screening, the committee
recommended that both in vitro and in vivo assays will be included. Testing will identify effects of
concern and provide dose-response data that will form the basis of EPA's hazard assessment.
A range of issues have been discussed -- from how to ensure that chemicals that get a low priority
for screening and testing are not removed from consideration altogether to how to test and assess
complex mixtures for which there is little or no information.
EDSTAC took a very practical approach to these issues. They recognized that we tend to focus
attention on chemicals for which some hazard information is known. So they established separate
prioritization tracks for high production volume high exposure chemicals for which little effects
data are available and chemicals about which endocrine-system relevant hazard data are available.
They also established a separate track for chemicals nominated from the public. EDSTAC
recognized that chemicals that appear insignificant on a national basis might give rise to high local
exposures. So citizens can use Toxics Release Inventory data or other information to identify
chemicals of specific concern to them. Some chemicals from each of these tracks would be a high
priority for screening. Thus chemicals within tracks will compete for testing in the first phase of
the screening program, the second phase, and so forth.
For mixtures, EDSTAC is recommending that a few mixtures related to special exposure concerns
be tested. These might include a mixture of chemicals frequently found in breast milk,
phytoestrogens in infant formula, and a mixture of pesticides commonly used around the home,
for example.
The screening battery recommended by EDSTAC is comprised of three in vitro assays and four in vivoassays. The screen is designed so that each estrogen, androgen and thyroid endpoint is
capable of being detected in at least two assays. We will thus have a high degree of confidence
that substances which test negative in the screens do not pose a risk of interfering with estrogen,
androgen, or thyroid hormones in humans or wildlife. Substances testing positive in the screening
tier will be tested in a multigeneration rodent study and in bird, fish and amphibian assays
involving exposure to the egg and the full reproductive cycle of one or more generations.
EPA will continue to wrestle with some of these issues and others as we implement EDSTAC's
recommendations -- issues such as having too few validated assays, particularly for non-mammalian species; the significance of low-dose effects and their implications for testing, and
how the weight-of-evidence approach will be used to determine if a chemical is an endocrine
disruptor.
In May EPA's Scientific Advisory Panel and Science Advisory Board, two federally chartered
committees that oversee EPA's major science products and our scientific work, met to discuss
EDSTAC's recommendations. Comments at the meeting were supportive of the approach
EDSTAC would like EPA to follow. The same panel will formally review EPA's screening and
testing program, which will be proposed this August.
Using EPA's authority under the FIFRA and TSCA to require testing can take time, especially in
the context of the procedural hurdles under TSCA. Therefore, acceptance of the committee's
work is critical. If real scientific consensus is achieved on a viable screening and testing
framework, industry would probably use it to get on with the job of evaluating endocrine activity
of chemicals in advance of any regulatory action.
Yet, the subject of endocrine disruptors is highly controversial. EPA's Science Policy Council's
interim position, approved last year, recognizes the potential for adverse impacts on human health
and the environment associated with exposure to endocrine disruptors. It also recognizes that
there currently is little knowledge of, or agreement on, the extent of the problem but that wildlife
effects are more certain than human effects.
The Agency considers endocrine disruption a mode of action that has the potential to lead to
adverse effects. These may include carcinogenicity, reproductive and developmental effects, and
neurobehavioral effects.
As I mentioned, we are concerned about risk to children, other vulnerable individuals, and
ecosystems. We are committed to implementation of research and testing strategies to fill critical
data gaps, and we will take regulatory action when sound scientific information and public policy
dictate.
Lack of data is the major problem. There are a number of activities underway to help advance the
state of the science. EPA's Office of Research and Development is carrying out a $14 million
research program to implement the Agency's national research strategy to determine the nature
and magnitude of health and environmental effects associated with exposure to endocrine
disruptors. The research strategy is available on the internet at:
www.epa.gov/ORD/WebPubs/final. EPA's Special Report on Environmental Endocrine
Disruption: An Effects Assessment and Analysis gives an overview of the state of the science.
The report, which draws on Agencywide expertise, also is available on the Internet at:
www.epa.gov/endocrine.
EPA is helping to fund the work of an expert committee of the National Academy of
Sciences/National Research Council to develop a scientifically based approach to improve the
assessment of the significance of endocrine disruptors.
We are confident that the upcoming endocrine disruptor screening and testing program will afford
new protections for adults' reproductive health, as well as for the health of our children. As you
know, the Clinton Administration has been dedicated to the protection of children. EPA
Administrator Carol Browner has launched a series of steps aimed at better protecting children's
environmental health. In 1995, the Administrator directed that all Agency programs explicitly
evaluate potential hazards to children in their risk assessment. EPA created its first Office of
Children's Health Protection to ensure that job is accomplished. The new office is headed by my
colleague, Dr. Phillip Landrigan, who is also a professor at Mt. Sinai's School of Medicine and
who will be speaking this afternoon.
So families could better protect themselves their children, the Agency expanded consumer right-to-know information by nearly doubling the number of chemicals on the federal Toxics Release
Inventory whose releases to the air, water, and land must be reported each year. We went on to
add many pesticides to the Toxics Release Inventory and broadened the types of industries that
must report. And one year ago, President Clinton signed an historic Executive Order to reduce
environmental health and safety risks to children. It requires federal agencies, for the first time, to
ensure that their standards take special risks to children into account.
Food Quality Protection Act
The 1996 Food Quality Protection Act, or "FQPA," is landmark legislation, reflecting this
Administration's dedication to protecting children. The law, which overhauled pesticide
regulation, was passed unanimously by Congress and vigorously supported by the Administration.
Congress had received a clear message from American citizens -- they wanted safe food and they
wanted to protect their children from pesticides in their food, water, homes and communities.
On the scientific side, the law directly responded to the National Academy of Sciences' 1993
report, "Pesticides in the Diets of Infants and Children." NAS concluded that infants and children
may have significantly different exposures and/or responses to pesticides than adults and that
pesticide laws should be revised to strengthen protections for children.
The new food law incorporated many of the NAS's recommendations and is significantly
changing the way pesticides are regulated.
Under the new food quality law, a patchwork of standards was replaced by a single standard that
says EPA must have "reasonable certainty" that each pesticide use it allows will cause "no harm."
For the first time, when we make a decision on a use or residue tolerance level, we must now take
into account the combined exposures from residues in all foods, plus exposures from pesticides in
drinking water as well as residential and lawn use. Prior to FQPA, generally we only considered
residues on food.
Another very important change is that we must now also account for the risks a pesticide may
pose cumulatively with other substances that share a common mechanism of toxicity, or, in other
words, that act in a similar way in the body to cause an adverse effect.
And on top of this we must add a 10-fold safety factor to account for the special sensitivities of
infants and children and incomplete data with respect to exposure and toxicity. This is in addition
to the usual 100-fold safety factor we traditionally added to account for differences between test
animals and humans and for variations in humans' sensitivities. We can eliminate or reduce this
added 10x safety factor only if we make a finding that reliable and complete data indicate a lesser
factor will be safe for infants and children.
EPA must also consider all available information on in utero effects, and we have proposed a set
of criteria to determine the chemicals that will require in utero testing, which has been reviewed
by our a scientific review panel.
Two other requirements have dramatically changed the timing and substance of our decisions:
Congress has prohibited EPA from considering benefits in setting tolerances for any new
pesticide; it only allows us to consider benefits in maintaining existing tolerances and then only in very limited circumstances. Under previous law, EPA was often required to balance risks with benefits.
And Congress set a 10-year schedule for EPA to review nearly 10,000 existing tolerances for
pesticide residues on food. So decisions will be coming very quickly. Over the next two years,
EPA will review the first third -- or about 3,300 tolerances -- that pose the greatest hazards. The
first group of 228 pesticides includes the organophosphate, carbamate and organochlorine classes,
as well as chemicals that may be human carcinogens.
Most of these provisions became effective on August 3, 1996, the day the law was signed by
President Clinton. Since then, EPA has been racing to implement a streamlined and more
protective, but far more scientifically complicated pesticide program. One of our challenges has
been developing -- in cooperation with the scientific community and our other stakeholders --
risk assessment methods needed to implement the new requirements.
Some of this work had begun prior to enactment of the new law. As I mentioned, EPA had
already begun to revise the critical developmental and reproductive toxicity testing guidelines. We
lengthened the duration of dosing, which will help to better identify effects in the male
reproductive system which are often more sensitive in the later stages of development and we
added additional endpoints to evaluate sperm and male reproductive organs.
As a result of the law's new requirements, over time you will be seeing some of the current -- and
least safe -- pesticide uses replaced by safer ones or non-chemical alternatives, such as integrated
pest management and biologically engineered pesticides.
When major new regulatory decisions begin having impacts in the real world, stakeholders have
legitimate concerns about how decisions are made. The Food Quality Protection Act is is
certainly no exception and indeed is under attack from all sides. Vice President Gore has outlined
a set of principles for implementing the law. EPA will work with the Department of Agriculture
and outside stakeholders to ensure that implementation of law is based on sound science and is
transparent, so the decisionmaking process readily understood. The Vice President also asked that
we consult with our stakeholders and ensure a smooth transition for growers. EPA has
established a federally chartered committee to receive input from stakeholders on how to
implement the new tolerance setting requirements, and our Science Advisory Panel has reviewed a
number of scientific questions on our approach to 10x.
The first group of pesticides with a common mechanism that we are reviewing are the
organophosphates. They are used by millions of homeowners for insect control and used widely
on food crops. Already, it is clear that the reassessment of tolerances for organophosphate
pesticides may eliminate many of their uses. Information on pesticide use patterns and
alternatives to organophosphate pesticides will be critical. We will need that information to decide
which uses should be allowed and which uses could be curtailed, and to enable the "public
interest" to guide our choices. I hope that in the coming months and years as the impact of the
Food Quality Protection Act becomes felt in agribusiness, you will support this law and encourage
its very strong incentives for agribusiness to find safer alternatives to many of our high-risk
pesticides.
Screening Chemicals
Because of the Food Quality Protection Act, w
