# Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

> Briefs, arguments, decisions, and more.

URL: https://www.frixlaw.com/law-library/documents/crs%3AR40177

## Record

- **Collection:** Congressional research report
- **Document type:** CRS Report
- **Published:** April 29, 2009
- **Citation:** R40177

## Text

Environmental Exposure
to Endocrine Disruptors:
What Are the Human Health Risks?
-name redactedSpecialist in Environmental Policy
-name redactedSpecialist in Natural Resources Policy
April 29, 2009

Congressional Research Service
7-....
www.crs.gov
R40177

CRS Report for Congress
Prepared for Members and Committees of Congress

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Summary
In 2008, Congress banned the use in children’s toys and child care articles of several chemicals
known to disrupt normal development and reproduction of mice and rats. The legislation was a
response to accumulating scientific evidence supporting the hypothesis that exposure to certain
chemicals in consumer products and the environment might be adversely affecting human
reproduction, growth, development, or metabolism by interfering with endocrine systems. This
report summarizes the science underlying the environmental endocrine-disruptor hypothesis, and
describes congressional actions and related programs and policy issues at the U.S. Environmental
Protection Agency (EPA).
This report focuses on the potential human health effects of environmental exposure to endocrine
disruptors. The potential effects on fish and wildlife also are of concern. Scientists have
discovered many egg-bearing male (intersex) bass in the Potomac River, as well as intersex fish
of other species in other U.S. waters. Chemicals of interest include certain pesticides (e.g., DDT),
synthetic hormones administered to cattle and poultry, both prescription and over-the-counter
drugs and ingredients of some personal-care products (e.g.,triclocarban in antibacterial soaps),
naturally occurring plant hormones (e.g., in soy beans), industrial compounds (e.g.,
polychlorinated biphenyls (PCBs)), some dioxins, lead, mercury, cadmium, uranium, arsenic, and
organic compounds of tin. Potential sources of such chemicals include runoff from animal
feedlots and agricultural fields, wastewater discharges, industrial releases, and consumer
products. In the 111th Congress, H.R. 1145 would require each water resources research and
technology institute to conduct technical research on prevention and removal of contaminants of
emerging concern, including endocrine-disrupting compounds.
Support might be found for the hypothesis that chemicals in the environment are disrupting
human endocrine systems in the apparent increases in rates of certain cancers, reported declines
in sperm counts, and reported scientific evidence of increasing rates of some birth defects, thyroid
disorders, attention deficit disorder, premature births, and premature puberty. There appears to be
a worldwide increase in cases of testicular cancer, for which there is no clear cause. Any of these
effects could be linked to hormone disruption because they are hormone dependent and have been
chemically induced in experimental animals. However, scientifically demonstrating a cause-effect
relationship between environmental exposure to a particular chemical and human health effects is
difficult. Many scientists hypothesize that environmental levels of potential endocrine disruptors
are too low to influence human endocrine systems. Others argue that significant adverse effects
might result from long-term exposure to low levels of multiple endocrine disruptors.
Congress began investigating the presence and possible effects of endocrine disruptors in the
environment at a hearing in 1993. In 1996, Congress directed EPA to establish and implement an
endocrine-disruptor screening program for pesticides and drinking water contaminants. As of
April 2009, chemical screening under that program has not begun, and funding for the program
has declined, and legislators have expressed concern about the pace of program development.
However, EPA this month promulgated final rules establishing the list of 67 pesticide ingredients
and procedures that will be followed when the first set of testing orders is issued to
manufacturers. EPA has stated that orders will be issued during the summer of 2009. Once the
program is implemented, Congress might consider whether statutes and regulations provide
adequate authority and direction with respect to the influence of any findings of endocrine
disruption on the regulation of specific chemicals, chemical groups, uses, or products.

Congressional Research Service

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Contents
Background ................................................................................................................................1
Endocrine Disruptors ............................................................................................................1
Congressional and Administrative Attention ..........................................................................2
The Endocrine Disruptor Screening Program...................................................................3
Research Initiatives .........................................................................................................6
Scientific Evidence .....................................................................................................................7
Human Health Trends ...........................................................................................................7
Human Studies of Chemical Effects on Endocrine Systems ...................................................8
Animal Studies.................................................................................................................... 12
Fish............................................................................................................................... 13
Other Wild Vertebrates .................................................................................................. 15
Invertebrates ................................................................................................................. 16
Laboratory Rodents....................................................................................................... 17
Environmental Exposure to Potential Endocrine Disruptors................................................. 18
Policy Issues ............................................................................................................................. 20
Pace of FQPA Implementation ............................................................................................ 20
Welfare of Test Animals ...................................................................................................... 21
Regulation of Endocrine Disruptors..................................................................................... 21
Conclusion................................................................................................................................ 23

Contacts
Author Contact Information ...................................................................................................... 24

Congressional Research Service

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Background
Scientific reports of reproductive failure among migratory birds exposed to DDT during the
1950s provided some of the earliest evidence that chemical pollutants in the environment might
affect hormone-mediated processes in wildlife. 1 In 1996, several scientists brought the endocrine
2
disruptor hypothesis to public attention with the release of a book, Our Stolen Future. In the
same year, Congress directed the U.S. Environmental Protection Agency (EPA) to develop and
implement a program to screen all pesticides and suspect drinking water contaminants for
endocrine-disrupting potential. Ten years later, the screening program was not yet launched, when
scientists reported finding a large number of feminized male fish in the Potomac River and other
U.S. waters. In response, Congress held hearings and urged federal agencies to expedite related
research. In 2008, the National Toxicology Program issued a report indicating scientific concern
about fetal and child exposure to several chemicals with endocrine-disrupting potential. In the
same year, Congress enacted legislation banning those chemicals in children’s toys and child care
3
articles. H.R. 1523/S. 593 and S. 753 in the 111th Congress would regulate certain uses of
bisphenol A, another potential endocrine disruptor.
This report summarizes the science underlying the endocrine disruptor hypothesis, describes
congressional actions, outlines EPA’s efforts to implement legislation, and discusses some policy
issues that have been raised. The report is intended to support Congress as it considers legislation
to control potential endocrine disruptors and as it oversees EPA’s programs. With a few
exceptions, the report does not discuss in detail all of the various specific chemicals that might be
endocrine disruptors and particular source categories for such chemicals that might be in the
environment. Several CRS reports on specific chemicals and sources are referenced where
relevant.

Endocrine Disruptors
Endocrine disruptors4 are chemical compounds in drugs, food, consumer products, or the ambient
environment that can interfere with biological processes normally regulated by hormones within
animals. Physical development, growth, reproduction, and metabolism, for example, are
hormone-dependent processes that might be affected by exposure to endocrine disruptors. Some
endocrine disruptors exist naturally, for example, the phytoestrogens (or plant estrogens, which
are responsible for female sexual characteristics) in some plants. Others are the products of
human industry—for example, some pesticides and pharmaceuticals.

1
Hoffman, David J., Barnett A. Rattner, G Allen Burton, Jr., and John Cairns, Jr. (Eds.) 2003. Handbook of
Ecotoxicology. 2nd ed. Lewis Publishers: New York. p. 76.
2
Colburn, Theo, Dianne Dumanoski, and John Peterson Myers. 1996. Our Stolen Future: Are We Threatening Our
Fertility, Intelligence, and Survival? A Scientific Detective Story. New York: Penguin. 316 p.
3
The chemicals banned were di-(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), or benzyl butyl phthalate
(BBP). The ban was enacted through Section 108 of P.L. 110-314, the Consumer Product Safety Improvement Act of
2008.
4
The endocrine system includes the glands (e.g., thyroid, pituitary gland, pancreas, ovaries, or testes) and their
secretions (i.e., hormones), that are released directly into the body’s circulatory system (rather than through ducts). The
endocrine system controls metabolic rates, blood pressure, growth, development, aging, blood sugar levels, and
reproduction.

Congressional Research Service

1

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Some endocrine disruptors are similar in form and action to natural hormones; these are called
“hormone mimics.” The terms “environmental estrogen” and “xenoestrogen” are narrower,
referring only to those chemicals that mimic the action of the female sex hormones. (Similarly,
environmental androgens are chemicals that mimic the action of the male sex hormones.) Other
endocrine disruptors do not mimic, but block the action of hormones (for example, the antiestrogens or anti-androgens) or otherwise modify the synthesis, secretion, transport, binding,
action, or elimination of natural hormones. Some scientists prefer the more neutral but just as
inclusive term “endocrine modulators” over the better known term “endocrine disruptors.”
Exposure to high levels of certain manufactured chemicals in the environment has been shown to
harm insects, some vertebrate wildlife, 5 and aquatic life by influencing the normal activities or
effects of reproductive and other hormones. 6 There also is scientific evidence that relatively low
environmental levels of some chemicals may be harmful to the endocrine systems of fish and
wildlife, particularly when low chemical concentrations are continuous or bioaccumulate,
exposing animals higher on the food chain to greater chemical concentrations. Selected, peerreviewed studies are described and references are cited under the next major section of this report,
“Scientific Evidence.” Some scientists hypothesize that existing environmental levels of potential
endocrine disruptors also may be harming human health, but other scientists believe that current
levels of such chemicals in the environment are too low to exert significant adverse effects on
people.

Congressional and Administrative Attention
Congress began investigating the effects of endocrine disruptors in the environment at a hearing
7
in 1993. Among those testifying at that hearing were several researchers who later published
8
their findings in the book, Our Stolen Future. It summarized a number of studies by wildlife
biologists, epidemiologists, and other scientists, and hypothesized that endocrine disruption by
environmental pollutants might be responsible for increases in deformities and population
declines of amphibians, declining human fertility in various geographical regions, and reported
increases in human rates of breast, testicular, and prostate cancers, as well as endometriosis. In
9
the next few years, research produced evidence both for and against that hypothesis.
5
Generally, scientists have studied effects in vertebrates (animals with spines), especially amphibians, freshwater fish,
and mammals.
6
The pesticide industry has studied and exploited chemicals that can disrupt the endocrine systems of insects. For
example, synthetic juvenile hormone analogs control insect pests by interfering with the natural juvenile hormone,
which suppresses metamorphic change during molting and induces production of egg yolk protein during ovarian
development. The pesticides can act to enhance or obstruct these endocrine effects. Examples include phenoxyphenoxy
carbamate and methoprene. However, research on insects is not described below, because it appears to be less relevant
than research on vertebrates to the question of human health effects from environmental exposures. This is not meant to
imply that any adverse effects on beneficial insects (such as the honeybee) might not be important. It is simply beyond
the scope of this paper.
7
U.S. Congress. House of Representatives, Committee on Energy and Commerce, Subcommittee on Health and the
Environment. Health Effects of Estrogenic Pesticides. 103rd Cong., 1st Sess., Oct. 21, 1993. Washington, DC: U.S.
Govt. Print. Off. (1994) 185 p.
8
Colburn et al., 1996.
9
Initially, one of the most influential studies (“Synergistic activation of estrogen receptor with combinations of
environmental chemicals,” S.F. Arnold, D.M. Klotz, and B.M. Collins, et al., 1996, Science, v. 272, pp. 1489-1492)
was later retracted, when the authors were unable to replicate their results (McLachlan, J.A., 1997 “Synergistic effect of
environmental estrogens: report withdrawn,” Science, v. 277, pp. 459-463). The original report indicated that effects of
(continued...)

Congressional Research Service

2

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Congress continued to study the issue, and in 1996 concluded that there was a need to screen
pesticide chemicals and drinking water contaminants for their potential to disrupt endocrine
systems. A screening program was established by the Food Quality Protection Act (P.L. 104-170)
and the 1996 Amendments to the Safe Drinking Water Act (P.L. 104-182).

The Endocrine Disruptor Screening Program
The Food Quality Protection Act (FQPA) Section 408(p)10 directs EPA, not later than three years
after August 3, 1996, to require validated tests to determine the potential of pesticides to produce
effects in humans similar to those produced by naturally occurring estrogens or, at the discretion
of the Administrator, other endocrine effects in humans. The mandate covers all registered
pesticide ingredients, as well as other substances identified by the Administrator which might
have a cumulative effect together with pesticides and to which a substantial population may be
11
exposed.
The 1996 Safe Drinking Water Act Amendments (P.L. 104-182) authorize screening for endocrine
12
disruption potential of contaminants found in sources of drinking water. Under both statutes,
actual screening of chemicals for toxic effects is to be conducted by manufacturers of suspect
chemicals (or laboratories hired by manufacturers) following protocols approved by EPA. The
laws authorize EPA to take appropriate action to protect public health under existing statutory
authority if substances are found to have endocrine effects in humans.13
To help implement the new provisions, EPA organized the Endocrine Disruptors Screening and
Testing Advisory Committee (EDSTAC). This committee of scientists (some independent and
others representing various chemical manufacturers and distributors, chemical users, public health
advocates, environmentalists, and other stakeholder groups) assisted EPA in designing the
chemical screening and testing program. The committee’s recommendations, released October 5,
1998, were reviewed by a special peer review panel consisting of members of the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) Science Advisory Panel and the Science
Advisory Board. EPA generally accepted the EDSTAC recommendations and officially
“established” the Endocrine Disruptor Screening Program (EDSP) in 1998. Under this program,
pesticides and other chemicals would be screened using a battery of tests known as Tier 1 assays,
which are relatively inexpensive short-term tests. Chemicals that tested positive for possible
endocrine disruption in one or more Tier 1 assays would be subjected to one or more Tier 2
toxicity tests, to confirm or refute Tier 1 results, and if confirmed, to determine the dose of the
chemical that caused the effects. Tests would screen for effects on estrogen, androgen (hormones

(...continued)
combined exposure to two different pesticides could be greater than effects from an equivalent exposure to either of the
individual pesticides alone. However, synergy (as well as antagonism, in which effects are less than expected from
exposure to a combination of chemicals) has been demonstrated for other health effects of exposure to PCBs and
several pesticide formulations (Hook, G.E., and G.W. Lucier, 1997, “Editorial: Synergy, antagonism, and scientific
processes,” Environmental Health Perspectives, v. 105, p. 784).
10
See §405 of P.L. 104-170, amending §408 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 346a).
11
The EPA Office of Science Coordination and Policy website describes the statutory authority for the Endocrine
Disruptor Screening Program at http://www.epa.gov/scipoly/oscpendo/.
12
See §136 of P.L. 104-182, adding a new §1457 to the Safe Drinking Water Act (42 U.S.C. 300j-17).
13
Federal Food, Drug, and Cosmetic Act, as amended; 21 U.S.C. 346a(p)(6).

Congressional Research Service

3

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

responsible for male sexual characteristics), and/or thyroid systems. The thyroid hormones
regulate growth and development and the rate of metabolism.
Chemical screening for potential effects on endocrine systems has not yet begun, however,
because EPA has not finished selecting and validating toxicity assays. An Endocrine Disruptor
Method Validation Subcommittee (EDMVS) was formed in 2001 to advise EPA on how it should
select and evaluate the screens and tests to be developed. This process proved to be controversial,
particularly with respect to the role of animal experimentation and the validation of tests
involving live animals. Three years later, the Endocrine Disruptor Methods Validation Advisory
Committee (EDMVAC) was formed to replace EDMVS. This group assisted EPA as it identified,
developed, and validated the various methods for detecting potential endocrine disruptors.
In 2004 and 2005, the EDSP was reviewed and evaluated at EPA’s request by the independent
Board of Scientific Counselors (BOSC) for EPA’s Office of Research and Development. A
subcommittee of the BOSC prepared a final report, which is summarized in a peer-reviewed
publication14 and posted on the BOSC website. 15 The BOSC subcommittee concluded that the
goals and science questions of the endocrine disruptor screening program were appropriate, and
EPA’s progress on implementing the program was good, although challenges remained. The
subcommittee advised EPA to
•

strengthen its expertise in wildlife toxicology;

•

expedite validation of the tests;

•

take a leadership role in applying “omics” technologies (such as proteomics or
metabolomics);

•

maintain funding; and

•

“continue to sponsor multidisciplinary intramural research and interagency
collaborations.”16

The BOSC again reviewed the program in 2008.17 BOSC reported that the program
... exceeds expectations in progress to address concerns of the previous 2004 program
review. ... The [Endocrine Disrupting Chemicals Research Program] has taken under
consideration all recommendations of the previous BOSC review and those
recommendations not implemented were held in abeyance because of budgetary
constraints.18

14

Harding, Anna K., George P. Daston, and Glen R. Boyd, et al. 2006. Endocrine disrupting chemicals research
program of the U.S. Environmental Protection Agency: Summary of a peer-review report. Environmental Health
Perspectives, v. 114, n. 8, pp. 1276-1282.
15
Board of Scientific Counselors, Office of Research and Development, U.S. EPA. Endocrine Disrupting Chemicals
(EDC) Research Program Review, Final Report of the Subcommittee on Endocrine Disrupting Chemicals. March 4,
2005. Revised April 21, 2005, http://www.epa.gov/OSP/bosc/pdf/edc0504rpt.pdf.
16
Harding, ibid.
17

Board of Scientific Counselors, Office of Research and Development, U.S. EPA. Mid-cycle Review of the Office of
Research and Development’s Endocrine Disrupting Chemicals (EDCs) Research Program at the U.S. Environmental
Protection Agency, Apr. 16, 2008, http://www.epa.gov/OSP/bosc/pdf/edcmc0804rpt.pdf.
18
Ibid., Cover letter.

Congressional Research Service

4

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

The BOSC noted that
... the budget to support this program has been cut substantially. The budget has been cut 20
percent since 2003, with a 4 percent cut proposed for this year. Funds for extramural STAR
grants for EDC research were completely eliminated in 2005.19

Largely as a result of the constrained budget, BOSC found that wildlife toxicology and
epidemiology remain areas of weakness in EPA’s EDSP.20
EPA also worked closely with the Interagency Coordinating Committee on the Validation of
Alternative Methods (to identify and validate test methods that reduce animal use or suffering)
and the Organization for Economic Cooperation and Development (to ensure international
21
acceptance of the methods.) EPA’s independent Science Advisory Panel (established under the
Federal Insecticide, Fungicide, and Rodenticide Act) has completed peer review of validated Tier
1 assays and approved EPA’s initial test battery, but some chemical manufacturers continue to
object to several of the Tier 1 assays. In July 2008, the Center for Regulatory Effectiveness (a
public policy advocacy group) filed a “Request for Correction” on one of the assay validations
under the Agency’s Information Quality Guidelines (IQG), and Crop Life America, a trade group
for pesticide manufacturers, filed a petition to delay the EDSP orders to initiate testing. As a
result, EPA delayed the issuance of orders until 2009. In April 2009, it was announced that EPA
denied the Crop Life petition22 and announced that orders would be issued during the summer of
2009.
At the same time that it was developing toxicity assays, EPA established a process for prioritizing
and selecting chemicals to be screened. 23 In June 2007, EPA proposed a draft list of 73 chemicals
for initial screening.24 The comment period for the draft list ended February 11, 2008. In April
2009, after considering comments on this list of chemicals, EPA published in the Federal Register
the final list of 67 chemicals.25 The list included pesticide active ingredients, “selected based on
their relatively high potential for human exposure”26 and other chemicals produced in amounts
greater than one million pounds per year that also are used in pesticide products but which are
categorized as inert (that is, not active) pesticide ingredients. EPA’s website “EDSP Phases”
provides additional details about the process EPA used to select chemicals for screening.27

19

Ibid., p. 5.
Ibid., p. 6, 8.
21
U.S. Congress. House of Representatives. Committee on Government Reform. Ova-Pollution in the Potomac: EggBearing Male Bass and Implications for Human and Ecological Health. 109th Cong., 2nd Sess., Oct. 4, 2006.
Washington, DC: Govt. Printing Off. (2006) p. 25 (Testimony of Benjamin H. Grumbles).
22
Bill Pritchard, “EPA Rejects CropLife Request for More Study of Endocrine Disruptor Screening Program,” Daily
Environment Report, Apr. 16, 2009, p. A-2.
23
70 Federal Register 56449-56465, Sept. 27, 2005.
24
72 Federal Register 33486-33503, June 18, 2007.
25
74 Federal Register 17579-17585, Apr. 15, 2009.
26
70 Federal Register 56449-56465, Sept. 27, 2005.
27
EPA. EDSP Phases, http://www.epa.gov/endo/pubs/edspoverview/components.htm#4.
20

Congressional Research Service

5

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Late in 2007, EPA also solicited public comments about its proposed procedure for issuing orders
28
to manufacturers to conduct initial screening and for overseeing compliance with such orders.
The final version of these procedures was published in the Federal Register April 15, 2009.29
The House Committee on Government Reform held a hearing October 4, 2006, to learn about the
status of the EDSP and to examine the human and ecological health implications of the discovery
of egg-bearing male bass in the Potomac River. One year later, some Members of that committee
sent a letter to EPA Administrator Stephen L. Johnson asking him how EPA might speed up the
process of screening chemicals for endocrine effects, to provide a timetable for EDSP
implementation, and for explanations in response to specific questions about the process and
30
substance of the program as designed. EPA’s responses are posted on the Committee’s
31
website. The agency indicated that the list of chemicals, procedures, and peer review of Tier 1
tests should have been completed and Tier 1 test orders should have been issued to manufacturers
of the first 73 chemicals before mid-2008. An EPA website provides more information about
EDSP program development. 32

Research Initiatives
The hypothesis that existing environmental levels of chemical pollutants may be harming human
health by disrupting endocrine functions has been, and continues to be, hotly debated. At present,
there is no conclusive evidence to support this hypothesis.
Research interest is growing, and some epidemiological studies have found statistical associations
between human exposure and health effects that are consistent with the results of experiments
with animals, particularly with respect to potential effects on prenatal and infant development.
Research attention has focused on chemicals such as certain phthalates that are ubiquitous at low
levels in the air, surface water, and food, and at higher levels in many consumer products,
including medical devices and baby toys.33 Some other chemicals of potential concern include a
number of pesticides (e.g., DDT, lindane, and vinclozolin), medicinal drugs (especially synthetic
hormones), other synthetic compounds (e.g., nonylphenol, polychlorinated biphenyls (PCBs),
perchlorate), and some metals (e.g., lead, mercury, arsenic, and organotins). In recent years,
hundreds of studies have been conducted to determine possible health effects due to exposure to
34
components of plastics such as bisphenol A (BPA) and phthalates. EPA has posted an inventory
35
of endocrine research that it sponsors.
28
29

72 Federal Register 70842-70862, Dec. 13, 2007, http://www.epa.gov/endo/pubs/draft_policies_frn.pdf.
74 Federal Register 17560-17579.

30

Letter from Henry A. Waxman et al. to Administrator Johnson, Sept. 20, 2007, http://oversight.house.gov/
documents/20070920162537.pdf.
31
EPA. Responses to Questions from the House of Representatives, Committee on Oversight and Government Reform,
Chairman Henry Waxman, September 20, 2007, http://oversight.house.gov/documents/20071204153145.pdf.
32
EPA, Revised Policies and Procedures, http://www.epa.gov/scipoly/oscpendo/pubs/regaspects/.
33
For more information about phthalates, see CRS Report RL34572, Phthalates in Plastics and Possible Human
Health Effects, by (name redacted) and (name redacted).
34
For more information about BPA, see CRS Report RS22869, Bisphenol A (BPA) in Plastics and Possible Human
Health Effects, by (name redacted) and (name redacted).
35
EPA. Office of Research and Development. National Center for Environmental Research. Endocrine Disruptors
Research. Research Projects, http://es.epa.gov/ncer/science/endocrine/researchproj.html.

Congressional Research Service

6

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Many U.S. and other governmental and intergovernmental organizations are sponsoring and
coordinating research efforts to clarify the scope and severity of potential endocrine disruptor
effects.36 In the United States, work among federal public health and environmental agencies was
initially coordinated by the Endocrine Disruptor Working Group, which was established by the
National Science and Technology Council’s Committee on the Environment and Natural
37
Resources. However, this working group appears to have disbanded after 1999. Internationally,
the Organization for Economic Cooperation and Development (OECD) is developing harmonized
international test guidelines to detect endocrine disruptors.
In the 111th Congress, H.R. 1145 would require each water resources research and technology
institute, established under the Water Resources Research Act of 1984, to conduct technical
research on prevention and removal of contaminants of emerging concern, including endocrinedisrupting compounds, pharmaceuticals, and personal care products. This bill also would
establish a national interagency coordinating committee to plan and report to Congress on waterrelated research.

Scientific Evidence
Human Health Trends
Proponents of the hypothesis that environmental exposure to endocrine disruptors may be
affecting human health have pointed to apparent increases in U.S. and global rates of certain
cancers,38 reported declines in sperm counts in various nations,39 and scientific evidence of
increasing rates of type II diabetes,40 obesity (especially among children),41 some birth defects,42
36
EPA. Office of Research and Development. National Center for Environmental Research. Science Topics. Endocrine
Disruptors Research. Related Links, http://es.epa.gov/ncer/science/endocrine/relatedlinks.html.
37
For more information about this group, see the EPA website for the Endocrine Disruptor Research Initiative.
However, the workgroup does not appear to be active, http://www.epa.gov/endocrine/edrifact.html.
38
Hodgson, N.C., J. Button, and C.C. Solorzano, et al. 2004. Thyroid cancer: is the incidence still increasing? Annals
of Surgical Oncology, v. 11, n. 12, pp. 1093-1097.
Jemal, A., R. Siegel, and E. Ward, et al. 2008. Cancer statistics, 2008. CA: A Cancer Journal for Clinicians, v. 58, n. 2,
pp. 71-96.
Sedjo, Rebecca L., Tim Byers, and Ermilo Arrera, Jr., et al. 2007. A midpoint assessment of the American Cancer
Society challenge goal to decrease cancer incidence by 25% between 1992 and 2015. CA: A Cancer Journal for
Clinicians, v. 57, n. 6, pp. 326-340.
39
Rozati, R., P.P. Reddy, and P. Reddanna, et al. 2000. Xenoesterogens and male infertility: myth or reality? Asian
Journal of Andrology, v. 2, n. 4, pp. 263-269.

Aitken, R.J., N.E. Skakkebaek, and S.D. Roman. 2006. Male reproductive health and the environment. Medical Journal
of Australia, v. 185, pp. 414-415.
Travison, T.G., A.B. Araujo, and A.B. O’Donnell, et al. 2007. A population-level decline in serum testosterone levels
in American men. Journal of Clinical Endocrinology and Metabolism, v. 92, n. 1, pp. 196-202.
40
Lang, Iain A., Tamara S. Galloway, and Alan Scarlett, et al. 2008. Association of urinary bisphenol A concentration
with medical disorders and laboratory abnormalities in adults. Journal of the American Medical Association, v. 300, n.
11, pp. 1303-1355.
41
Hugo, Eric R., Terry D. Brandebourg, and Jessica G. Woo, et al., in press, “Bisphenol A at Environmentally
Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes,” Environmental
Health Perspectives, online Aug. 14, 2008, at http://www.ehponline.org/members/2008/11537/11537.pdf.
42
Centers for Disease Control and Prevention, Department of Health and Human Services. Hypospadias trends in two
(continued...)

Congressional Research Service

7

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

43

and other disorders. In some cases, these reported increases in rates of hormone-mediated
diseases or conditions may reflect improvements in diagnostic tools or reporting rates rather than
increased rates of disease. In other cases, disease rates may have increased in fact, but may be due
to medication use, smoking, or some other reason. However, in at least a few cases, increasing
exposure to chemicals in the environment seems to some a plausible hypothesis to explain an
increase in disease rates. Many developmental, reproductive, and carcinogenic conditions for
which increased incidences have been reported in humans are similar to effects that have been
44
observed in wildlife and fish exposed to endocrine disruptors.
Congress has indicated its interest in several recent health trends, including: reported declines in
45
certain nations in semen quality over the last few decades; increasing rates of deformities of
46
male reproductive organs before 1985, after which rates stabilized; and a worldwide increase in
the incidence of testicular cancer, for which there is no clear cause.47 Some researchers have
noted the similarity of these health concerns with effects seen in rats and mice prenatally exposed
to certain phthalates that act as anti-androgens. 48 One hypothesis is that human exposure to
combinations of phthalates and perhaps other ubiquitous endocrine disruptors might be
interfering with the development of baby boys, resulting in what is referred to as “testicular
dysgenesis syndrome.”49

Human Studies of Chemical Effects on Endocrine Systems
Except for strong poisons with clear, short-term effects on health, the effects of chemical
exposures on humans are difficult to demonstrate scientifically. Ethically, scientists cannot
manipulate levels of human exposure to a chemical if there is a chance that harm might result.
The alternative, so-called “natural experiments” (which compare the health of people with
accidental exposures to the health of people with no exposure), is rare because accidental
exposures of sufficient magnitude are few, and potentially contributing conditions (such as
exposure to other chemicals) are inadequately controlled. In particular, study of effects of lowlevel exposures to environmental chemicals is problematic, because the expected effects are
(...continued)
US surveillance systems. Press Release, Nov. 3, 1997, http://www.cdc.gov/media/pressrel/hypospad.htm.
43
Carpenter, D.O., Y. Shen, and T. Nguyen, et al. 2001. Incidence of endocrine disease among residents of New York
areas of concern. Environmental Health Perspectives, v. 109, Supp. 6, pp. 845-851.
Davis, Devra Lee, Pamela Webster, and Hillary Stainthorpe, et al. 2007. Declines in sex ratio at birth and fetal deaths in
Japan, and in U.S. whites but not african americans. Environmental Health Perspectives, v. 115, n. 6, pp. 941-946.
44
U.S. Environmental Protection Agency. 1997. Special Report on Environmental Endocrine Disruption: An Effects
Assessment and Analysis, EPA/630/R-96/012. p. 5.
45
Semen quality is based on ejaculate volume, sperm concentration, sperm motility, and sperm morphology.
46
Safe, S.H. 2000. Endocrine disruptors and human health: Is there a problem? An update. Environmental Health
Perspectives, v. 108, n. 6, pp. 487-493.
47
Safe, ibid.
48
Fisher, Jane S., S. Macpherson, and N. Marchetti, et al. 2003. Human “testicular dysgenesis syndrome”: a possible
model using in utero exposure of the rat to dibutyl phthalate. Human Reproduction, v. 18, n. 7, pp. 1383-1394.
Toppari, Jorma , John Chr. Larsen, and Peter Christiansen, et al. 1996. Male Reproductive Health and Environmental
Xenoestrogens. Environmental Health Perspectives, v. 104, n. S4, online at http://www.ehponline.org/members/1996/
Suppl-4/toppari.html.
49
For more information about phthalates, see CRS Report RL34572, Phthalates in Plastics and Possible Human
Health Effects, by (name redacted) and (name redacted)
.

Congressional Research Service

8

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

subtle and potentially affected by numerous conditions. Often, virtually everyone has been
exposed to the chemical being studied, and there are too few unexposed people to serve as a
control group for comparison.
Scientific studies have demonstrated the potential of hormones and some other chemicals acting
through hormone systems to harm human health, especially if the chemical exposure is highly
concentrated and occurs during fetal or infant development. For example, the role of naturally
occurring male and female sex hormones in the growth of prostate and breast cancer is well
established scientifically.50 Moreover, research has demonstrated that administration of the drug
diethylstilbestrol (DES), a strong, synthetic estrogen, to women early in their pregnancies greatly
increases risk that their daughters will develop vaginal cancer and reproductive abnormalities. 51
In addition, studies have documented a higher than normal incidence of genital tract
abnormalities in male babies following in utero exposure to DES.52
Some chemicals with effects on endocrine systems have therapeutic value. For example, sex
hormones are used to treat some forms of cancer. 53 There also is evidence that some plant-derived
endocrine disruptors54 (e.g., phytoestrogens prevalent in soy beans) may protect against disease.55
Some scientists argue that such evidence undermines the hypothesis that endocrine disruptors in
the environment are a threat to human health. Other scientists believe the evidence for therapeutic
effects only underscores the potency of hormonally active chemicals.
Numerous epidemiologic studies56 have found associations between environmental levels of
potential endocrine disruptors and effects on human development or health. 57 For example, a
50

See the National Cancer Institute website at http://www.nci.nih.gov.

51

Herbst, A., H. Ulfelder, and D. Poskanzer. 1971. Adenocarcinoma of the vagina: Association of maternal stilbestrol
therapy with tumor appearance in young women. New England Journal of Medicine, v. 284, pp. 878-881.
52
Mittendorf, R. 1995. Teratogen update: Carcinogenesis and teratogenesis associated with exposure to
diethylstilbestrol (DES) in utero. Teratology, v. 51, n. 6, pp. 435-445.
53
Huggins, Charles B. 1967. Endocrine-induced regression of cancers. Science, v. 156, n. 778, pp. 1050-1054.
Machtens, S., D. Schultheiss, and M. Kuczyk, et al. 2000. The history of endocrine therapy of benign and malignant
diseases of the prostate. World Journal of Urology, v. 18, n. 3, pp. 222-226.
54
Perhaps in this case, the term endocrine modulator is more appropriate.
55
Warri, A., N.M. Saarinen, and S. Makela, et al. 2008. The role of early life genistein exposures in modifying breast
cancer risk. British Journal of Cancer. v. 98, n. 9, pp. 1485-1493.
Vincent, A. and L.A. Fitzpatrick. 2000. Soy isoflavones: are they useful in menopause? Mayo Clinic Proceedings, v.
75, n. 11, pp. 1174-1184.
Lakshman, M., L. Xu, and V. Ananthanarayanan, et al. 2008. Dietary genistein inhibits metastasis of human prostate
cancer in mice. Cancer Research, v. 68, n. 6, pp. 2024-2032.
56
“Epidemiologic” studies examine groups of people to determine rates of occurrence of particular outcomes (health
effects) relative to varying levels of chemical exposure. Such studies rely on statistical methods to evaluate the
likelihood of hypotheses about relationships between exposures and outcomes (that is, dose-response relationships).
“Associations” are regular patterns between frequencies of particular health outcomes and changes in exposure levels.
Associations do not necessarily indicate a causal relationship, but there can be no causal relationship without an
association.
57
Ibarluzea, J.M., M.F. Fernandez, and L. Santa-Marina, et al. 2004. Breast cancer risk and the combined effect of
environmental estrogens. Cancer Causes and Control, v. 15, n. 6, pp. 591-600.
Mocarelli, Paolo, Pier Mario Gerthoux, and Donald G. Patterson Jr., et al. 2008. Dioxin exposure, from infancy through
puberty, produces endocrine disruption and affects human semen quality. Environmental Health Perspectives, v. 116, n.
1, pp. 70-77.
Sharpe, Richard M., and D. Stewart Irvine. 2004. How strong is the evidence of a link between environmental
(continued...)

Congressional Research Service

9

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

study of newborns in Spain reported data that suggested that the combined effects of
bioaccumulated estrogenic substances in the placenta played a role in the risk of male urogenital
malformations. 58 However, causality has not been (and possibly cannot be) clearly demonstrated
for any adverse health effect as a result of exposure to an endocrine disruptor at levels typically
present in the environment.
Most studies focus on a single chemical or closely related group of chemicals. For example, many
scientists believe that the same phthalates that are toxic to rats and mice would be able to cause
similar malformations in humans, because the male hormones affected by phthalates are
important to the normal development of the male reproductive tract in all species of mammals. A
few human studies have been conducted. 59 Some scientists have found that relatively low levels
of exposure to phthalates may be associated with health effects. A study published in 2005
provided the first evidence of subtle developmental effects in baby boys exposed prenatally to
breakdown products of certain phthalates, and these effects were similar to those seen in
experiments with rats and mice exposed to phthalates.60 A high exposure to one breakdown
product of a phthalate was found to alter the development (in a laboratory culture) of human fetal
testes and to reduce the number of germ cells.61 Nevertheless, human health effects of
environmental phthalate exposure have not been conclusively demonstrated. Additional research
is seen as needed to confirm or refute these findings of effects at environmental levels of human
exposure.
Recently, scientists have been advising that risk assessments should consider the combined effects
of chemical exposures. For example, studies with rodents suggest there may be additive effects of
multiple phthalate exposures.62 A recent report issued by the National Research Council

(...continued)
chemicals and adverse effects on human reproductive health? British Medical Journal, v. 328, , n. 7437, pp. 447-451.
58
Fernandez, Mariana F., Begona Olmos, and Alicia Granada, et al. 2007. Human exposure to endocrine-disrupting
chemicals and prenatal risk factors for cryptorchidism and hypospadias: A nested case-control study. Environmental
Health Perspectives, v. 115, Supplement 1 (December), pp. 8-14.
59
Main, Katharina M., Gerda K. Mortensen, and Marko M. Kaleva, et al. 2006. Human breast milk contamination with
phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environmental Health
Perspectives, v. 114, pp. 270-276.
Swan, Shanna H., Katharina M. Main, and Fan Liu, et al. 2005. Decrease in anogenital distance among male infants
with prenatal phthalate exposure. Environmental Health Perspectives, v. 113, n. 8, pp. 1056-1061.
60
Swan et al. 2005.
61
Lambrot, Romain, Vincent Muczynski, and Charlotte Lecureuil, et al. 2009. Phthalates impair germ cell development
in the human fetal testis in vitro without change in testosterone production. Environmental Health Perspectives, v. 117,
n. 1 (January), pp. 32-37.
62
Hotchkiss, A.K., L.G. Parks-Saldutti, and J.S. Ostby, et al. 2004. A mixture of the “antiandrogens” linuron and butyl
benzyl phthalate alters sexual differentiation of the male rat in a cumulative fashion. Biology of Reproduction, v. 71,
pp. 1852-1861.
Howdeshell, Kembra L., Vickie S. Wilson, and Johnathan Furr, et al. April 14, 2008. A mixture of five phthalate esters
inhibits fetal testicular testosterone production in the Sprague Dawley rat in a cumulative, dose additive manner.
Toxicological Sciences Advance Access. Reprint received from the author.
Rider, Cynthia V., Johnathan Furr, and Vickie S. Wilson, et al. 2008, A mixture of seven antiandrogens induces
reproductive malformations in rats. International Journal of Andrology, v. 31, pp. 249-262.
Crofton, Kevin M., Elena S. Craft, and Joan M. Hedge, et al. 2005. Thyroid-hormone-disrupting chemicals: evidence
for dose-dependent additivity or synergism. Environmental Health Perspectives, v. 113, n. 11, (November) pp. 15491554.

Congressional Research Service

10

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

concluded that there is a need to explore the additive effects of exposure to phthalates.63 Dr.
Andreas Kortenkamp has reviewed research on the effects of mixtures of endocrine-disrupting
chemicals and has called for additional, more systematic investigations of combinations of
endocrine disruptors.64
Human hormones other than sex hormones also might be affected by environmental chemicals. A
recently released study found that low-level human exposure to bisphenol A (BPA) inhibits the
release of adiponectin from adipose (fat) tissue. This result indicates a possible link of BPA to
diabetes, because adiponectin increases insulin sensitivity and helps regulate glucose
metabolism. 65 Because this study was well designed and controlled, its results are seen as
particularly interesting, but until it has been replicated by an independent team of scientists, any
conclusions are considered tentative.
Another chemical group that has been studied extensively is PCBs. Although the production and
use of PCBs has been strictly regulated since 1976, these chemicals are ubiquitous in the air,
water, soil, and many animal tissues due to their environmental persistence, tendency to
bioaccumulate in animal fat, and previous widespread use. Some PCBs are known to be
estrogenic. 66 In addition, PCBs may affect thyroid function,67 and there is evidence that fetal
exposure to PCBs affects cognitive development, but it is not known whether this toxicity is
related to thyroid or any other type of hormone disruption.68 In addition, some studies have found
63

Committee on the Health Risks of Phthalates, National Research Council. 2008. Phthalates and Cumulative Risk
Assessment: The Tasks Ahead. The National Academies Press, Washington DC, p. 6.
64
Kortenkamp, Andreas. 2007. Ten years of mixing cocktails: A review of combination effects of endocrine-disrupting
chemicals. Environmental Health Perspectives, v. 115, Supplement 1 (December), pp. 98-105.
65
Hugo, Eric R., Terry D. Brandebourg, and Jessica G. Woo, et al., in press, “Bisphenol A at Environmentally
Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes,” Environmental
Health Perspectives, online Aug. 14, 2008, at http://www.ehponline.org/members/2008/11537/11537.pdf.
66
Longnecker, M.P., W.J. Rogan, and G. Lucier. 1997. The human health effects of DDT
(dichlorodiphenyltrichloroethane) and PCBs (polychlorinated biphenyls) and an overview of organochlorines in public
health. Annual Review of Public Health, v. 18, pp. 211-244.
Brouwer, A., U.G. Ahlborg, and F.X. van Leeuwen, et al. 1998. Report of the WHO working group on the assessment
of health risks for human infants from exposure to PCDDs, PCDFs and PCBs. Chemosphere, v. 37, n. 9-12, pp. 16271643.
67
Ibid.
Turyk, M.E., H.A. Anderson, and S. Freels, et al. 2006. Associations of organochlorines with endogenous hormones in
male Great Lakes fish consumers and nonconsumers. Environmental Research, v. 102, n. 3, pp. 299-307.
68
Jacobson, J.L., and S.W. Jacobson. 1996. Intellectual impairment in children exposed to polychlorinated biphenyls in
utero [see comments]. New England Journal of Medicine, v. 335, n. 11, pp. 783-789.
Jacobson, J.L., and S.W. Jacobson. 1996. Dose-response in perinatal exposure to polychlorinated biphenyls (PCBs): the
Michigan and North Carolina cohort studies. Toxicology and Industrial Health, v. 12, n. 3-4, pp. 435-445.
Sagiv, Sharon K., J. Kevin Nugent, T. Berry Brazelton, et al. 2008. Prenatal Organochlorine Exposure and Measures of
Behavior in Infancy Using the Neonatal Behavioral Assessment Scale (NBAS). Environmental Health Perspectives, v.
116, n. 5, pp. 666-673.
Schantz, Susan L., John J. Widholm, and Deborah C. Rice. 2003. Effects of PCB exposure on neuropsychological
function in children. Environmental Health Perspectives, v. 111, n. 3, pp. 357-376.
Stewart, Paul, Jacqueline Reihman, and Edward Lonky, et al. 2000. Prenatal PCB exposure and neonatal behavioral
assessment scale (NBAS) performance. Neurotoxicology and Teratology, v.22, n. 1, pp. 21-29.
Stewart, Paul, Susan Fitzgerald, and Jacqueline Reihman, et al. 2003. Prenatal PCB Exposure, the Corpus Callosum,
and Response Inhibition. Environmental Health Perspectives, v. 111, n. 13, pp. 1670-1677.
Stewart, Paul W., Edward Lonky, and Jacqueline Reihman, et al. 2008. The Relationship between Prenatal PCB
Exposure and Intelligence (IQ) in 9-Year-Old Children. Environmental Health Perspectives, v. 116, n. 10, pp. 1416(continued...)

Congressional Research Service

11

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

an association between human PCB exposure and low sperm counts, undescended testes, altered
semen quality, lower age of onset of puberty, and shorter height at maturity.69
In recent years, Congress has expressed concern about the possible effects on thyroid function of
perchlorate, a common pollutant in drinking water and soil. Perchlorate is formed naturally but
also is manufactured for various products including explosives, fireworks, road flares, and solid
rocket fuel and often is associated in the environment with sites operated by the Department of
Defense. Perchlorate is known to disrupt the uptake of iodine by the thyroid, and health effects
associated with perchlorate exposure are expected to parallel those caused by iodine deficiency.
Iodine deficiency decreases the production of thyroid hormones, which help regulate the body’s
metabolism and growth. A key concern is that impairment of thyroid function in pregnant women
can affect brain development in fetuses and nursing infants and can lead to attention deficit
disorder, generally delayed development, and decreased learning capacity.70 Several studies have
found that at significantly higher levels of perchlorate exposure than the amounts typically
observed in the environment, thyroid changes occur in humans.71 However, a 2006 study by the
Centers for Disease Control and Prevention (CDC) of a representative sample of the general U.S.
population found that environmental exposures to perchlorate have an effect on thyroid hormone
levels in women who are deficient in iodine (and on levels of the pituitary gland’s thyroid
stimulating hormone in all women). (No effect was found in men.) Fully 36% of the 1,111 women
in this study were found to be iodine deficient.72

Animal Studies
The most compelling evidence for endocrine disruption due to environmental exposure to
contaminants has been obtained in aquatic systems, with most of the published literature based on
studies of fish. 73

(...continued)
1422.
69
Dhooge, Willem, Nicolas van Larebeke, and Gudrun Koppen, et al. 2006. Serum Dioxin-like Activity Is Associated
with Reproductive Parameters in Young Men from the General Flemish Population. Environmental Health
Perspectives, v. 114, n. 11, pp. 1670-1676.
Hauser, Russ, Paige Williams, and Larisa Altshul, et al. 2005. Evidence of Interaction between Polychlorinated
Biphenyls and Phthalates in Relation to Human Sperm Motility. Environmental Health Perspectives, v. 113, n. 4, pp.
425-430.
70
Zoeller, R. Thomas, Amy L.S. Dowling, and Carolyn T.A. Herzig, et al. 2002. Thyroid hormone, brain development,
and the environment. Environmental Health Perspectives, v. 110, Supp. 3, pp. 355-361.
71
Kelsh, Michael A., Patricia A. Buffler, and Jorge J. Daaboul, et al. 2003. Primary congenital hypothyroidism,
newborn thyroid function, and environmental perchlorate exposure among residents of a southern California
community. Journal of Occupational Environmental Medicine, v. 45, n. 10, pp. 1116-1127.
72
Blount, Benjamin C., James L. Pirkle, and John D. Osterloh, et al. 2006. Urinary Perchlorate and Thyroid Hormone
Levels in Adolescent and Adult Men and Women Living in the United States, Centers for Disease Control and
Prevention, in Environmental Health Perspectives, v. 114, n. 12, pp. 1865-1871. For more information about
perchlorate, see CRS Report RS21961, Perchlorate Contamination of Drinking Water: Regulatory Issues and
Legislative Actions, by (name redacted).
73
Jobling, Susan, Monique Nolan, and Charles R. Tyler, et al. 1998. “Widespread sexual disruption in wild fish,”
Environmental Science and Technology, v. 32, n. 17, pp. 2498-2506.

Congressional Research Service

12

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Fish
Feminization of male fish due to exposure to endocrine-disrupting chemicals in the environment
is an increasing concern.74 Fish appear to be useful as sentinels for the presence and possible
hazard of endocrine-disrupting chemicals in the aquatic environment, since they are currently the
only vertebrates for which the connection between environmental contamination and adverse
effects on health has been established in both field75 and laboratory76 studies. In addition, fish are
exposed to any contaminants in their aquatic habitats through skin absorption, food ingestion, and
dissolved gas absorption across the gills. Aquatic food chains often are long, relative to terrestrial
food chains, so bioaccumulation potential may be greater. The aquatic environment is especially
well suited for these studies as it is the ultimate sink for many natural and anthropogenic
compounds released into the environment.
Feminization of male fish collected from British rivers near the effluent from wastewater
treatment plants alerted the scientific community to the potential hazard of endocrine-disrupting
chemicals (specifically, synthetic female hormones) in the environment.77 Feminization of males
was confirmed by the presence of eggs in the testes and vitellogenin (a protein in the yolk of
eggs, usually made only by females) in the blood of male fish. (While manufacture of
vitellogenin by males is clearly abnormal, it is not clear whether these males are impaired in their
ability to reproduce.) More recently, marine fish populations in the English Channel and in Tokyo
Bay have shown evidence of feminization.78
In the United States, studies have found feminized male fish in diverse locations. For example,
there is a report of complete sex reversal of male salmon in the state of Washington.79 Others have

74

However, feminization and any resulting effects on fish populations are not the only concerns. Another potential
effect might be immune system changes and perhaps greater susceptibility to infections and other diseases. It was fish
kills and skin lesions on a number of fish species in the South Branch of the Potomac River that prompted the Blazer et
al. (2007) study of smallmouth bass which is described below.
75
Folmar, Leroy C., George R. Gardner, and Martin P. Schreibman, et al. 2001. Vitellogenin-induced pathology in
male summer flounder (Paralichthys dentatus). Aquatic Toxicology, v. 51, pp. 431-441.
Folmar, Leroy C., Nancy D. Denslow, and Vijayasri Rao, et al. 1996. Vitellogenin introduction and reduced serum
testosterone concentrations in feral male carp (Cyprinus carpio) captured near a major metropolitan sewage treatment
plant. Environmental Health Perspectives, v. 104, pp. 1096-1100.
Harries, J.E., D.A. Sheahan, and S. Jobling, et al. 1997. Estrogenic activity in five United Kingdom rivers detected by
measurement of vitellogenesis in caged male trout. Environmental Toxicology and Chemistry, v. 16, pp. 534-542.
Jobling, Susan, Monique Nolan, and Charles R. Tyler, et al. 1998. Widespread sexual disruption in wild fish.
Environmental Science and Technology, v. 32, pp. 2498-2506.
76
Panter, Grace H., R. S. Thompson, and John P. Sumpter. 1998. Adverse reproductive effects in male fathead
minnows (Pimephales promelas) exposed to environmentally relevant concentrations of the natural oestrogens,
oestradiol and oestrone. Aquatic Toxicology, v. 42, n. 4, pp. 243-253.
77
Jobling, Susan, Monique Nolan, and Charles R. Tyler, et al. 1998. Widespread sexual disruption in wild fish.
Environmental Science and Technology, v. 32, n. 17, pp. 2498-2506.
78
Gross-Sorokin M.Y., S.D. Roast, and G.C. Brighty. 2006. Assessment of feminization of male fish in English rivers
by the Environment Agency of England and Wales. Environmental Health Perspectives, v. 114 (Supplement 1), pp.
147-151.
79
James J. Nagler, Jerry Bouma, and Gary H. Thorgaard, et al. 2001. High incidence of a male-specific genetic marker
in phenotypic female Chinook salmon from the Columbia River. Environmental Health Perspectives, v. 109, n. 1, pp.
67-69.

Congressional Research Service

13

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

reported intersex trout in Rocky Mountain National Park and Glacier Park,80 hornyhead turbot in
southern California,81 and white sucker in Boulder, CO.82
In spring of 2004, scientists found a high prevalence of feminized smallmouth bass in the South
Branch of the Potomac River, which drains a rural area of West Virginia.83 Water samples in the
area detected a number of known endocrine disruptors with estrogenic activity including several
pesticides, a degradation product of industrial phenols, and two polybrominated diphenyl ethers
(PBDEs), but the study authors concluded that a combination of contaminants probably was
responsible for the observed effects on fish. 84 Recent research has demonstrated that mixtures of
estrogenic chemicals can act in combination, exerting adverse effects on fish even when each
component is present at a level below the threshold level for producing such effects.85 Fish were
also taken from several other rural sites in West Virginia that were characterized by low human
population and low intensity agriculture. At these sites scientists found a lower prevalence of
feminized bass.86 In contrast, in a more heavily populated and more intensely agricultural part of
Virginia, 80 to 100% of male bass taken from the Shenandoah River were feminized.87 The
cellular responses to ethynylestradiol (the bioactive component of contraceptive pills) that lead to
feminization have been documented.88
Androgenic substances (i.e., substances with an effect similar to that of male sex hormones) also
have been detected in environmental samples, especially in pulp mill effluents, and studies have
linked such effluents to masculinized female fish.89 Although both androgenic and estrogenic
effects have been observed in fish, estrogenic activity appears to be more ubiquitous and hence

80
National Park Service. News release, Feb. 26, 2008. “Airborne contaminants study released: Measurable levels
detected in twenty western U.S. and Alaska National Parks.” p. 2.
81
Renner, Rebecca. 2009. Sex-changing fish: caused by contamination or nature? Environmental Science &
Technology, Article ASAP, Publication Date (Web): January 14, 2009, http://pubs.acs.org/doi/abs/10.1021/es8036912,
visited Jan. 21, 2009.
82
Vajda, Alan, Larry Barber, and James L. Gray, et al. 2008. Reproductive disruption in fish downstream from an
estrogenic wastewater effluent. Environmental Science & Technology, v. 42, n. 9, pp. 3407–3414.
83
Blazer, V.S., L.R. Iwanowicz, and D.D. Iwanowicz, et al. 2007. Intersex (testicular oocytes) in smallmouth bass from
the Potomac River and selected nearby drainages. Journal of Aquatic Animal Health, v. 19, pp. 242-253.
84
Ibid., p. 250.
85
Brian, Jayne V., Catherine A. Harris, and Martin Scholze, et al. 2007. Evidence of estrogenic mixture effects on the
reproductive performance of fish. Environmental Science & Technology, v. 41, n. 1, pp. 337-344.
86
Ibid.
87
Ibid.
88
Filby, A.L., K.L. Thorpe, G. Maack and C.R. Tyler. 2007. Gene expression profiles revealing the mechanisms of
anti-androgen- and estrogen-induced feminization in fish. Aquat. Toxicol. 81(2):219-231.
89
Larsson, D.G., M. Adolfsson-Erici, and P. Thomas. 2006. Characterization of putative ligands for a fish gonadal
androgen receptor in a pulp mill effluent. Environmental Toxicology and Chemistry, v. 25, n. 2 (Feb.), p.419-427.
Galloway, Brendan, K.R. Munkittrick, and S. Currie, et al. 2000. Examination of the cumulative responses of slimy
sculpin (Cottus cognatus) and white sucker (Catostomus commersoni) collected on the Saint John River downstream of
a pulp mill, paper mill, and sewage discharges. Society of Environmental Toxicology and Chemistry (SETAC), p. 255,
SETAC: Nashville, TN.
Larsson, D.G.J., H. Hallman, and L. Forlin. 2000. More male embryos near a pulp mill. Environmental Toxicology and
Chemistry, v. 19, n. 12, pp. 2911-2918.

Munkittrick, Kelly R., M.E. McMaster, and M.R. Servos, et al. 2000. Secondary sex characteristics and gonadal size in
white sucker (Catostomus commersoni) during modernization at a pulp mill. In: 6th International Symposium on the
Reproductive Physiology of Fish (1999), (ed. Bergitta Norberg), Bergen, Norway.

Congressional Research Service

14

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

better studied. 90 Moreover, the presence of estrogenic substances in some U.S. rivers and streams,
especially near outfalls from wastewater treatment plants, has been well documented. 91
The significance of the numerous observations of feminized male fish for the sustainability of
wild populations was unknown until recently. The results of a study in the Experimental Lakes
Area of northwestern Ontario, Canada, demonstrated that sustainability might be adversely
affected by endocrine-disrupting chemicals. Chronic exposure of fathead minnow in one lake to
low concentrations92 of the potent synthetic estrogen 17α-ethynylestradiol (EE2) nearly
extinguished this population after only two years.93 EE2, which is the most common component
of birth control pills, is often found in wastewater plant effluent and has been found in U.S.
surface water at concentrations ranging from 0.1 to 5.1 ng/l. 94 Academic scientists working
together with pharmaceutical company scientists have derived a predicted no-effect concentration
for EE2 of 0.35 ng/l for aquatic life in general.95

Other Wild Vertebrates
Reproductive or developmental problems potentially resulting from hormone exposure have been
observed in other wild vertebrate species, especially fish-eating species, including birds (such as
gulls, terns, ospreys, eagles, and pelicans), polar bears,96 Florida panthers,97 alligators,98 river
90

Bayley, Mark, Jacob R. Nielsen, and Erik Baatrup. 1999. Guppy sexual behavior as an effect biomarker of estrogen
mimics. Ecotoxicology and Environmental Safety, v. 43, pp. 68-73.
Bjerselius, Rickard, K. Lundstedt-Enkel, and K.H. Olsen, et al. 2000. Estrogen in food or water severely [a]ffect the
male goldfish (Carassius auratus) sexual behavior. In: 6th International Symposium on the Reproductive Physiology of
Fish (1999), (ed. Bergitta Norberg), Bergen, Norway.
Jobling, Susan, D. Sheahan, and J.A. Osborne, et al. 1996. Inhibition of testicular growth in rainbow trout
(Oncorhynchus mykiss) exposed to estrogenic alkylphenolic chemicals. Environmental Toxicology and Chemistry, v.
15, pp. 194-202.
Nash, J.P., D.E. Kime, and L.T. Van der Ven, et al. 2004. Long-term exposure to environmental concentrations of the
pharmaceutical ethynylestradiol causes reproductive failure in fish. Environmental Health Perspectives, v. 112, n. 17,
pp. 1725-1733.
Kramer, V.J., S. Miles-Richardson, and S.L. Pierens, et al. 1998. Reproductive impairment and induction of alkalinelabile phosphate, a biomarker of estrogen exposure, in fathead minnows (Pimephales promelas) exposed to waterborne
17b-estradiol. Aquatic Toxicology, v. 40, pp. 335-360.
Matthiessen, P. 1998. Effects on fish of estrogenic substances in English rivers. In: Principles and Processes for
Evaluating Endocrine Disruption in Wildlife, (ed. R. Kendall, et al.) pp. 239-247, Pensacola, FL: SETAC Press.
Panter, Grace, R. S. Thompson, and John P. Sumpter. 1998. Adverse reproductive effects in male fathead minnows
(Pimephales promelas) exposed to environmentally relevant concentrations of the natural oestrogens, oestradiol and
oestrone. Aquatic Toxicology, v. 42, n. 4, pp. 243-253.
91
Campbell, Chris G., Sharon E. Borglin, and F.Bailey Green, et al. 2006. Biologically directed environmental
monitoring, fate, and transport of estrogenic endocrine disrupting compounds in water: A review. Chemosphere, v. 65,
p.1265-1280.
92
The concentrations were 5-6 nanograms of EE2 per liter of water (ng/l), which also may be expressed as 5-6 parts per
trillion (ppt).
93
Kidd, Karen, A., Paul J. Blanchfield, and Kenneth H. Mills, et al. 2007. Collapse of a fish population after exposure
to a synthetic estrogen. Proceedings of the National Academy of Sciences, v. 104, n. 21, pp. 8897-8901.
94
Campbell et al. op cit.
95
Caldwell, Daniel J., Frank Mastrocco, and Thomas H. Hutchinson, et al. 2008. Derivation of an aquatic predicted noeffect concentration for the synthetic hormone, 17α-ethinyl estradiol. Environmental Science & Technology, v. 42, pp.
7046-7054.
96
Braathen, Marte, Andrew E. Derocher, and Oystein Wiig, et al. 2004. Relationships between PCBs and thyroid
(continued...)

Congressional Research Service

15

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

otters,99 and mink.100 In addition, there is growing evidence for effects of environmental exposure
to endocrine disruptors in marine mammals.101 The accumulation of persistent chlorinated organic
chemicals, such as PCBs, in seals and dolphins has been well documented, 102 and research
indicates that the thyroid hormone system in harbor seals is “highly sensitive to disruption by
environmental contaminants,” particularly by PCBs.103 Laboratory studies of a beluga whale
protein that is key in many endocrine-disrupting effects (the aryl hydrocarbon receptor) reveal
that the protein binds strongly to dioxins and PCBs. This may increase the likelihood that toxic
responses can be elicited by contaminants in the environment.104
However, as is the case with humans, cause-and-effect relationships are difficult (or impossible)
to show experimentally for marine mammals, because direct toxicity testing is precluded by
logistical, legal, and ethical constraints.

Invertebrates
There is evidence of endocrine effects in some marine invertebrates. Ambiguous genitalia have
been found by the EPA in Maine bivalves, allegedly due to herbicides. 105 Reproductive
impairment has been noted in some species of snails exposed to very low amounts of tributyltin
(TBT), a constituent in anti-fouling paints used on boats. This chemical causes female snails to
(...continued)
hormones and retinol in female and male polar bears. Environmental Health Perspectives, v. 112, n. 8, pp. 826-833.
97
Facemire, Charles F., Timothy S. Gross, and Louis J. Guillette, Jr. 1995. “Reproductive impairment in the Florida
panther: nature or nurture?” Environmental Health Perspectives, v. 103, Supp. 4, pp. 79-86.
98
Guillette, Louis J., Timothy S. Gross, and Denise A. Gross, et al. 1995. Gonadal steroidogenesis in vitro from
juvenile alligators obtained from contaminated or control lakes,” Environmental Health Perspectives, v. 103, n. 4, pp.
31-36.
99
Grove, R.A., and C.J. Henny. 2008, Environmental contaminants in male river otters from Oregon and Washington,
USA, 1994-1999. Environmental Monitoring and Assessment, v. 145, pp. 49-73.
100
Golub, Mari S., James M. Donald, and Joe A. Reyes. 1991. Reproductive toxicity of commercial PCB mixtures:
LOAELs and NOAELs from animal studies. Environmental Health Perspectives, v. 94, pp. 245-253.
101
Cooper, Ralph L., and Robert J. Kavlock. 1997. Commentary: endocrine disruptors and reproductive development: a
weight-of-evidence overview. Journal of. Endocrinology, v. 152, n. 2, pp. 159-166.
Ross, Peter S. 2000. Marine mammals as sentinels in ecological risk assessment, Human and Ecological Risk
Assessment, v. 6, pp. 29-46.
102
Watanabe, M., K. Kannan, and A. Takahashi, et al. 2000. Polychlorinated biphenyls, organochlorine pesticides,
tris(4-chlorophenyl)methane, and tris(4-chlorophenyl)methanol in livers of small cetaceans stranded along Florida
coastal waters, USA. Environmental Toxicology and Chemistry, v. 19, n. 6, pp. 1566-1574.
Reddy, M.L., J.S. Reif, and A. Bachand, et al. 2001. Opportunities for using Navy marine mammals to explore
associations between organochlorine contaminants and unfavorable effects on reproduction. Science of the Total
Environment, v. 274, n. 1-3, pp. 171-182.
103
Tabuchi, Maki, Nik Veldhoen, and Neil Dangerfield, et al. 2006. PCB-related alteration of thyroid hormones and
thyroid hormone receptor gene expression in free-ranging harbor seals (Phoca vitulina). Environmental Health
Perspectives, v. 114, n. 7, pp. 1024-1031.
104
Jensen, Brenda A., and Mark E. Hahn. 2001. cDNA cloning and characterization of a high affinity aryl hydrocarbon
receptor in a cetacean, the beluga, Delphinapterus leucas. Toxicological Sciences, v. 64, n. 1, pp. 41-56.
105
Van Beneden, R.J., G.R. Gardner, and N.J. Blake, et al. 1993. Implication for the presence of transforming genes in
gonadal tumors in two bivalve mollusk species. Cancer Research, v. 53, pp. 2976-2979.
Van Beneden, R.J. 1996. Comparative studies of molecular mechanisms of tumorigenesis in herbicide-exposed
bivalves. In: Interconnections between Human and Ecosystem Health (eds. R. DiGiulio and E. Monosson), Chapman
and Hall Ecotoxicology Series, London, England, pp. 29-43.

Congressional Research Service

16

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

grow male reproductive organs in addition to normal female ones, a condition called “imposex.”
When this condition becomes severe, affected females cannot function as females or as males; the
resulting reproductive failure caused severe population declines in some species. While the use of
TBT in anti-fouling paints has been severely restricted in the United States (P.L. 100-333,
Organotin Antifouling Paint Control Act of 1988) and European countries, it remains in use in
other parts of the world.

Laboratory Rodents
In laboratory experiments with rodents, there is clear evidence that exposure to some endocrine
disruptors affects the development of reproductive organs and causes tumor development. For
example, one study found that exposure of newborn mice to genistein (a naturally occurring plant
estrogen) at a level “within the range to which humans may be exposed in soy-based infant
formulas” caused effects that would impair fertility in every exposed mouse, but in no unexposed
mouse. 106 In addition, uterine cancer occurred in about one-third of the exposed mice, but not in
the unexposed mice.107 (An expert panel of the National Toxicology Program’s Center for the
Evaluation of Risks to Human Reproduction found in 2006 that the results of rodent studies were
sufficient to conclude that genistein produces reproductive and developmental toxicity in
offspring of rodents, 108 but another expert panel report concluded that evidence was insufficient to
demonstrate that soy formula would or would not produce such effects.109)
Some on-going studies of developmental effects in rats have found effects on the reproductive
organs from very low levels of exposure to DES, bisphenol-A, an ingredient in some plastic, and
other substances.110 Other studies found no effects.111 The resulting controversy has prompted
some scientists to note that the design of laboratory studies often has contributed to the confusion,
because statistical measures were not employed to ensure adequate power to detect subtle
effects.112 In 2001, an expert workshop to evaluate the data on low-dose effects of endocrine
disruptors concluded that biological effects have been shown to occur following exposure to

106
Newbold, R.R., E.P. Banks, and B. Bullock, et al. 2001. Uterine adenocarcinoma in mice treated neonatally with
genistein. Cancer Research, v. 61, n. 11, pp. 4325-4328.
107
Ibid.
108

U.S. Department of Health and Human Services, National Toxicology Program, Center for the Evaluation of Risks
to Human Reproduction. 2006. NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of
Genistein. NTP-CERHR-GENISTEIN-06.
109
National Toxicology Program, Center for the Evaluation of Risks to Human Reproduction. 2006. NTP-CERHR
Expert Panel Report on the Reproductive and Developmental Toxicity of Soy Formula. NTP-CERHR-SOY
FORMULA-06.
110
U.S. Department of Health and Human Services (HHS), National Toxicology Program, Center for the Evaluation of
Risks to Human Reproduction, “NTP-CERHR Monograph on the Potential Human Reproductive and Developmental
Effects of Bisphenol A,” NIH Publication No. 08-5994, September 2008, 321pp, at
http://cerhr.niehs.nih.gov/chemicals/bisphenol/bisphenol.pdf.
111
Ibid.
112
Scholze, Martin, and Andreas Kortenkamp. 2007. Statistical power considerations show the endocrine disruptor
low-dose issue in a new light. Environmental Health Perspectives, v. 115, Supp. 1, pp. 84-90.

Congressional Research Service

17

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

some estrogenic compounds at very low levels. 113 The question remains whether those effects
would adversely affect rodent health, however.114

Environmental Exposure to Potential Endocrine Disruptors
Concern about possible human or wildlife hormone disruption has been fueled by the limited
information that is available about levels of potential hormone disruptors in the environment. It is
known, however, that some potential endocrine disruptors are heavily used and, in some cases,
released to the environment. For example, pesticides such as DDT and dieldrin, now banned, still
are found in many rivers and streams.115 Wastewater effluent from sewage treatment plants
contains many potential endocrine disruptors, including synthetic (pharmaceutical) hormones.116
The U.S. Geological Survey has found synthetic hormones in U.S. streams.117 Concentrated
animal feeding lots are another potential source of environmental contamination. 118 Other
potential endocrine disruptors are prevalent in certain foods, such as soy-based milk substitutes,
because soy beans contain phytoestrogens (i.e., isoflavonoids such as genistein) at relatively high
levels.119 Some argue that the high phytoestrogen concentrations in food far exceed
concentrations of endocrine disruptors in the environment, implying that environmental
exposures are likely to be relatively insignificant.120 Others say this conclusion is not necessarily
justified, because it is based on a comparison of apples with oranges, or rather a mixture of
isoflavonoids and other phytohormones with a mixture of synthetic industrial compounds,
including pharmaceuticals and other chemicals, each of which may exert a different biological
effect and be more or less potent at various concentrations.
Data collected during the National Health and Nutrition Examination Survey indicates that most
people in the United States are exposed to various potential endocrine disruptors that are in
widespread use. Bisphenol A was detected in more than 90% of the surveyed population.121 In
113

National Toxicology Program’s Report of the Endocrine Disruptors Low Dose Peer Review. (2001) National
Toxicology Program, U.S. Department of Health and Human Services, http://ntp.niehs.nih.gov/ntp/htdocs/liason/
LowDosePeerFinalRpt.pdf.
114
That is, the effects observed are not known to be adverse. For example, at certain very low doses fetal exposure to
bisphenol-A produces enlarged prostates in male rats, but it is not clear that an enlarged prostate is an adverse health
impact.
115
National Park Service. News release, Feb. 26, 2008. “Airborne contaminants study released: Measurable levels
detected in twenty western U.S. and Alaska National Parks.” p. 2.
116
Liney, Katherine E., Josephine A. Hagger, and Charles R. Tyler, et al. 2006. Health effects in fish of long-term
exposure to effluents from wastewater treatment works. Environmental Health Perspectives, v. 114, Supp. 1, pp. 81-89.
EPA. Expanded investigations of pharmaceuticals in fish tissue, http://www.epa.gov/waterscience/ppcp/studies/fishexpand.html.
117
Kolpin, Dana W., Edward T. Furlong, and Michael T. Meyer, et al. 2002. Pharmaceuticals, hormones, and other
organic wastewater contaminants in U.S. streams, 1999-2000: A national reconnaissance. Environmental Science &
Technology, v. 36, n. 6, pp. 1202-1211.
118
Durhan, Elizabeth J., Christy S. Lambright, and Elizabeth A. Makynen, et al. 2006. Identification of metabolites of
trenbolone acetate in androgenic runoff from a beef feedlot. Environmental Health Perspectives, v. 114, Supp. 1, pp.
65-68.
119
The isoflavonoids appear to exert both estrogenic and anti-estrogenic effects which are not completely understood.
120

Easterbrook, Gregg. 1999. Another phony health scare. Science fiction. New Republic, v. 221, Aug. 30, 1999, pp.
20-22.
121
For more information about bisphenol A, see CRS Report RS22869, Bisphenol A (BPA) in Plastics and Possible
Human Health Effects, by (name redacted) and (name redacted).

Congressional Research Service

18

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

addition, the survey found almost universal American exposure to low levels of the most common
phthalates, usually multiple phthalates.122 Women tend to have greater exposure than men, but
children appear to be the group most exposed to di-(2-ethylhexyl) phthalate (DEHP), dibutyl
phthalate (DBP), and benzyl butyl phthalate (BBP). Studies of amniotic fluid have also
documented exposure to multiple phthalates for human fetuses. 123 More generally, babies may be
the most heavily exposed group.124 Children may be exposed to such chemicals through their
mothers’ blood prenatally, through breast milk, or by eating certain foods.125
Release of a chemical to the environment and even proof of exposure to the chemical do not
necessarily lead to toxic effects, even for vulnerable populations of animals or people. Some
believe that available data are reassuring, because known potential disruptors of endocrine
function generally are present in the environment at very low levels. 126
On the other hand, there are no measurements at all of environmental concentrations for most
chemicals in the environment, some of which might be affecting hormones. Some known
hormone disruptors, such as phthalates or bisphenol A, are ubiquitous at low levels, raising the
question of long-term effects and possible additive or synergistic effects with continual
exposure. 127 Of particular concern are chemicals designed to be biologically active in humans or
in pests that are released to the environment. Synthetic hormones are an obvious example. Birth
control compounds, synthetic estrogen for postmenopausal women, and synthetic thyroid
hormone are three common contaminants of wastewater. Other chemicals, such as PCBs and
some dioxins, are persistent in the environment and are known to bioconcentrate in the food
chain.
Knowledge about the range of potential health effects in immature, as well as mature wildlife and
humans, and actual exposure measurements are needed to accurately assess risks. Existing data
sometimes support conflicting views, leading to controversies about the extent to which people
generally are exposed to endocrine modulators, whether very low levels of exposure potentially
could affect human health, and whether exposure to very low levels of chemicals in the
environment currently is affecting reproduction, fetal development, or other hormone-dependent
functions in animal or human populations. Nevertheless, a panel convened by the National
Academy of Sciences concluded in 1999:
122

Ibid.
Silva, M.J., J.A. Reidy, and A.R. Herbert, et al. 2004. Detection of phthalate metabolites in human amniotic fluid.
Bulletin of Environmental Contamination and Toxicology, v. 72, pp. 1226-1231.
124
Wormuth, Matthias, Martin Scheringer, and Meret Vollenweider, et al. 2006. What are the sources of exposure to
eight frequently used phthalic acid esters in Europeans? Risk Analysis, v. 26, n. 3, pp. 803-824.
125
For more information about phthalates, see CRS Report RL34572, Phthalates in Plastics and Possible Human
Health Effects, by (name redacted) and (name redacted).
126
Scientists disagree about whether it is likely that animals or people would experience adverse effects of exposure to
very low doses of chemicals with the potential to disrupt endocrine function. Detailed arguments for and against the
hypothesis of low-dose effects are provided in Richter, C.A., et al. 2007, In vivo effects of bisphenol A in laboratory
rodent studies, Reproductive Toxicology, v. 24, n. 2, pp. 199-224; and Willhite, C.C., et al., 2008, Derivation of a
bisphenol A oral reference dose (RfD) and drinking-water equivalent concentration, Journal of Toxicology and
Environmental Health, Part B, Critical Reviews, v. 11, n. 2, pp. 69-146.
127
National Academy of Sciences 1999. Hormonally Active Agents in the Environment, National Academy Press,
Washington, DC.
U.S. Environmental Protection Agency. 1997. Special Report on Environmental Endocrine Disruption: An Effects
Assessment and Analysis, EPA/630/R-96/012.
123

Congressional Research Service

19

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Environmental [hormonally active agents] probably have contributed to declines in some
wildlife populations, including fish and birds of the Great Lakes and juvenile alligators of
Lake Apopka, and possibly to diseases and deformities in mink in the United States, river
otters in Europe, and marine mammals in European waters. Such contaminants, along with
inbreeding, might have contributed to the poor reproductive success of the endangered
Florida panther and the increased embryonic mortality of the snapping turtle in the Great
Lakes.128

Policy Issues
Pace of FQPA Implementation
Environmental, consumer, and public health advocacy groups accuse EPA of “dragging its feet”
in implementing many provisions of the Food Quality Protection Act (FQPA), including the
mandate to establish an endocrine disruptor screening program. The Natural Resources Defense
Council (NRDC) and six California-based public interest groups alleged in a lawsuit filed August
3, 1999, in the U.S. District Court for the Northern District of California that delays had caused
EPA to miss FQPA deadlines.129 On January 19, 2001, EPA and NRDC agreed to settle the
lawsuit. The settlement agreement states that endocrine disruptor screening would begin no later
than spring 2004.130 That did not occur.
Although grower groups and the pesticide industry have echoed complaints about delays in
overall FQPA implementation, they also have complained that EPA is proceeding too fast,
jeopardizing the scientific basis for decisions about the screening program. Several test protocols
approved for use in the screening program have been inadequately validated, according to these
stakeholders. Since chemical producers would conduct the actual screening of chemicals, they
want to ensure that screening requirements established by EPA would be cost-effective in
identifying potentially hazardous pesticides rather than wasteful of company resources. Thus,
they generally would prefer relatively quick and inexpensive screens to quickly rule out (or at
least delay) the need to pursue testing of chemicals that are less likely to pose health risks. This
approach would allow time for additional, and perhaps improved, test methods to be validated.
Public health advocates would prefer more thorough testing of a larger number of chemicals, to
ensure that all potentially hazardous substances are identified and quickly regulated.
Some scientists are concerned about adopting and implementing a program at this time to screen
chemicals for endocrine effects, because the field of study is so new and developing rapidly.
Almost certainly, better tests will be developed as scientists gain understanding of the endocrine
systems, how they develop, how they respond to variations in hormone levels, and how they
might be disrupted. On the other hand, most scientists appear optimistic about the value of
screening chemicals with the methods that are being developed, as long as they are validated prior
to being employed on hundreds, if not thousands, of chemicals.
A key question then is how flexible the adopted program should be: Would it be allowed to
evolve quickly in response to new knowledge?
128

National Academy of Sciences, op cit., p. 7.
Natural Resources Defense Council v. U.S. Environmental Protection Agency, No. C993701CAL, Jan. 19, 2001.
130
Ibid.
129

Congressional Research Service

20

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Welfare of Test Animals
Traditional methods of toxicity testing often involve administration of measured doses of
chemicals to groups of laboratory animals (usually rodents), which are then observed for health
effects. Test animals may be affected in a positive way (if the chemical at the administered dose
improves health), unaffected, mildly adversely affected, severely adversely affected, or even
killed by the administered dose. If they survive (which generally is the scientifically preferable
result), they may be sacrificed (i.e., killed) at some future date to permit inspection of internal
tissues, or they may be allowed to live a normal lifespan. In some cases, test animals are allowed
to reproduce, so that any adverse health effects on the reproductive process or on offspring may
be observed. Standard scientific protocols generally require the use of groups of animals for such
tests, so as to permit statistical analysis of the results. For example, many tests require the use of
25 or 50 rats of each gender at each dose level.
Animal welfare advocates are concerned that a large number of animals might be sacrificed for
the Endocrine Disruptor Screening Program, and they have questioned the value of such tests for
assessing human health risks. They argue that alternatives to animal tests exist, and that others
should be developed, both to improve the predictive value of the tests for human health and to
protect the animals that otherwise might suffer or die. Others contend that animal models provide
valuable information about the potential human health effects of chemical exposure, and animal
welfare is protected by laboratory guidelines for their care. Alternative test methods for many
kinds of effects have not been developed, it is argued.
For several years, federal agencies have been evaluating alternative methods for screening
chemicals for toxicity, which would require the use of fewer laboratory rodents or other animals
than are required using traditional toxicity tests. Alternative toxicity testing methods exist, but
their results are more difficult to interpret, in terms of what they might mean for human health,
and few are used routinely by federal agencies. The 103rd Congress established the Applied
Toxicological Research and Testing Program within the National Institute of Environmental
Health Sciences (NIEHS), in part, “to develop and validate assays and protocols, including
alternative methods that can reduce or eliminate the use of animals in acute or chronic safety
testing, ... to establish criteria for the validation and regulatory acceptance of alternative testing[,]
and to recommend a process through which scientifically validated alternative methods can be
accepted for regulatory use” (P.L. 103-43, Section 1301(a)). To implement the program, NIEHS
established an ad hoc Interagency Coordinating Committee on the Validation of Alternative
Methods (ICCVAM). The 106th Congress made ICCVAM a permanent interagency coordinating
committee (P.L. 106-545). EPA is a member of this committee.

Regulation of Endocrine Disruptors
If EPA determines through the endocrine disruptor screening program or some other program that
a chemical poses a risk to public health due to its effects on endocrine systems, the agency is
authorized to act under its existing legal authorities. The authorities available to EPA that are
likely to be most relevant to the protection of public health from toxic chemicals derive primarily
from the Safe Drinking Water Act, the Federal Water Pollution Control Act, the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), and the Toxic Substances Control Act.131
131

For brief summaries of these laws, see CRS Report RL30030, Clean Water Act: A Summary of the Law, by (name re
dacted); CRS Report RL31921, Pesticide Law: A Summary of the Statutes, by (name redacted); CRS Report
(continued...)

Congressional Research Service

21

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

Alternatively, EPA may refer a substance to another agency for action. For example, EPA might
suggest that the Food and Drug Administration or the Occupational Safety and Health
Administration regulate the use of particular chemicals to reduce risks.
Because many chemicals that may be endocrine disruptors have a variety of uses and may be
released to the environment at several stages in their lifecycles, multiple agencies are likely to
have a stake in their regulation. In such cases, any overlapping or inconsistent risk assessments,
guidelines, or regulations are likely to spark controversies. For example, EPA and FDA at one
time published risk assessments for mercury and guidance for consumers of fish containing
mercury that appeared to be inconsistent. The resulting controversy was quelled only when the
two agencies issued a joint communication. Some in Congress might be expected to urge
coordination of agency efforts to avoid such controversies. Cooperation among agencies also
might lead to more cost-effective regulation, an objective of President Obama and many
Members of Congress.
Another concern due to multiple uses and releases of chemicals and divided authorities for
regulating them might be that risks could be under-estimated and thus under-regulated if they
were assessed for each source of exposure and each exposed population individually, rather than
aggregated from all sources, combined with risks from chemicals with similar effects, and
calculated cumulatively over time. This is a particular concern when the health effects of
exposure are not immediate or not obvious, as might be the case for certain reproductive or
developmental effects. This situation arguably occurred with respect to phthalates: it was the
cumulative risk assessment conducted by the interagency National Toxicology Program that
caused scientists to express concern about possible consequences of exposure to phthalates from
multiple sources for infants and fetuses. Scientists’ concern prompted Congress to require action
by regulatory agencies.
Congress might wish to evaluate whether agencies are adequately assessing cumulative and
aggregate risks. Various groups of scientists have called for increased use of cumulative risk
assessments.132 Congress has acted in the past to require cumulative and aggregate risk
assessments for pesticides, when it enacted the FQPA. The Kid-Safe Chemicals Act (H.R. 6100/S.
3040) in the 110th Congress would have extended that requirement to other chemicals.
The nature of endocrine disruption may challenge would-be regulators. Disruption may consist of
enhancement or inhibition of effects that vary widely within populations of humans and wildlife.
Under some circumstances, disruption of a hormonally regulated process even may be beneficial.
Moreover, endocrine disruption may not fit the traditional model of the relationship between
increasing chemical exposure and effects, and effects may vary depending on the timing of
(...continued)
RL31243, Safe Drinking Water Act (SDWA): A Summary of the Act and Its Major Requirements, by (name redacted);
and CRS Report RL31905, The Toxic Substances Control Act (TSCA): A Summary of the Act and Its Major
Requirements, by (name redacted). These and other environmental laws also are summarized in CRS Report
RL30798, Environmental Laws: Summaries of Major Statutes Administered by the Environmental Protection Agency
(EPA), by (name redacted) et al.
132
Committee on Improving Risk Analysis Approaches Used by the U.S. EPA, National Research Council of the
National Academies. 2008. Science and Decisions: Advancing Risk Assessment. Prepublication Copy. Washington
DC: The National Academies Press. p. 9.
Committee on the Health Risks of Phthalates, National Research Council of the National Academies. 2008. Phthalates
and Cumulative Risk Assessment: The Tasks Ahead. Washington, DC: The National Academies Press. 142 p.

Congressional Research Service

22

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

exposure and other factors. Early indicators of endocrine disruption may not be considered
adverse. At what point might regulators intervene, and under what authority? Some laws might
require substantial evidence of severe effects prior to agency action, while others might authorize
action when risks are less certain. Congress may consider whether statutes provide agencies with
appropriate authority and directives for regulating endocrine-disrupting chemicals.
Congress might also consider whether agency budgets are adequate to support appropriate levels
of research and regulatory activity. Within the context of the overall federal budget, funding for
research, chemical screening programs, and regulatory activity, in the view of some, should be
proportionate to congressional concern about the potential risks to human or animal health posed
by endocrine disruptors.
In the 111th Congress, H.R. 1145 would require each water resources research and technology
institute, established under the Water Resources Research Act of 1984, to conduct technical
research on prevention and removal of contaminants of emerging concern, including endocrinedisrupting compounds, pharmaceuticals, and personal care products. This bill also would
establish a national interagency coordinating committee to plan and report to Congress on waterrelated research. In addition, H.R. 1145 would direct an interagency committee to evaluate the
adequacy of funding levels and the distribution of funding across agencies. The bill would
authorize to be appropriated to the National Oceanic and Atmospheric Administration for
coordination and outreach activities $10 million through 2014.

Conclusion
Chemicals with the potential to disrupt endocrine systems are frequently present in the
environment, particularly in rivers and streams, and in some consumer products. Exposure to high
levels of some of these chemicals has been shown to harm insects, some vertebrate wildlife, and
aquatic life by affecting reproductive and other hormone-dependent processes. In controlled
laboratory experiments, some scientists have found that relatively low levels of certain chemicals
harm the endocrine systems of fish and wildlife, particularly when exposure is continuous,
chemicals bioaccumulate, or animals are exposed simultaneously to several chemicals with
similar effects. Fish studies provide the most compelling evidence that endocrine disruption
might be occurring due to environmental exposures to contaminants. Reproductive or
developmental problems potentially resulting from hormone exposure also have been observed in
birds, polar bears, Florida panthers, alligators, river otters, mink, and marine invertebrates.
Some scientists have hypothesized that existing environmental levels of chemical pollutants
might be harming human health by disrupting endocrine functions. They point to increased rates
of certain human health problems, demonstrated harm to human endocrine systems when people
have been exposed to high levels of certain chemicals, and epidemiologic studies that have found
statistical associations between exposure to environmental levels of potential endocrine disruptors
and diabetes, malformations, sexual function, cognitive development, thyroid function, and other
potentially hormone-mediated effects. The environmental endocrine disruptor hypothesis is
disparaged by other scientists, because known potential disruptors of endocrine function generally
are present in the environment at very low levels, especially compared to the levels of hormones
that are naturally present in the human body, as well as in some of the plants that humans eat.
Many scientists who are not convinced there is an environmental problem nonetheless are
concerned about the issue, because there are no measurements at all of environmental
concentrations for most chemicals, people are known to be exposed to low levels of multiple

Congressional Research Service

23

Environmental Exposure to Endocrine Disruptors: What Are the Human Health Risks?

environmental contaminants with endocrine-disrupting potential for which potential cumulative
effects have not been assessed, and some studies suggest the public health consequences of
exposure might be significant.
Congress might be asked to consider various issues connected to the endocrine disruptor
hypothesis. In 1996, Congress mandated chemical screening for endocrine-disrupting potential.
The screening program has not yet been launched, and some argue that it should not be launched
until the complete test battery is validated. Others are concerned about the extent to which EPA
might rely on animal experimentation in its screening program. Once the program is
implemented, Congress might consider whether statutes and regulations provide adequate
authority and direction with respect to the influence of any findings of endocrine disruption on
the regulation of specific chemicals, chemical groups, uses, or products.

Author Contact Information
(name redacted)
Specialist in Environmental Policy
[redacted]@crs.loc.gov, 7-....

Congressional Research Service

(name redacted)
Specialist in Natural Resources Policy
[redacted]@crs.loc.gov, 7-....

24

EveryCRSReport.com
The Congressional Research Service (CRS) is a federal legislative branch agency, housed inside the
Library of Congress, charged with providing the United States Congress non-partisan advice on
issues that may come before Congress.
EveryCRSReport.com republishes CRS reports that are available to all Congressional staff. The
reports are not classified, and Members of Congress routinely make individual reports available to
the public.
Prior to our republication, we redacted names, phone numbers and email addresses of analysts
who produced the reports. We also added this page to the report. We have not intentionally made
any other changes to any report published on EveryCRSReport.com.
CRS reports, as a work of the United States government, are not subject to copyright protection in
the United States. Any CRS report may be reproduced and distributed in its entirety without
permission from CRS. However, as a CRS report may include copyrighted images or material from a
third party, you may need to obtain permission of the copyright holder if you wish to copy or
otherwise use copyrighted material.
Information in a CRS report should not be relied upon for purposes other than public
understanding of information that has been provided by CRS to members of Congress in
connection with CRS' institutional role.
EveryCRSReport.com is not a government website and is not affiliated with CRS. We do not claim
copyright on any CRS report we have republished.

---

Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/crs%3AR40177. Public record. Not legal advice.