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

CRS Report for Congress
En vironmental Exposure t o Endocrine Disruptors:
What Are t he Human Health Risks?
Linda-Jo Schierow
Specialist in Environmental Po licy
Specialist in Natural Resources Po licy
Resources, Sc ience, and Industry Division

Congressional Research Service ˜ The Library of Congress

Environmental Exposure to E ndocrine Disruptors:
What Are the Human Health Risks?
Ex posure t o certain environmental pollutants m ay disrupt the human endocrine
system causing adverse effects o n d evelopm ent, growth, reproduction, metabolism,
or other hormone-dependent processes, according t o s ome s cientists. Although t here
is no conclusive evidence to support t his hypothesis, evidence is m ount i n g, and
researc h i n t e rest i s growi n g. C h em i cal s o f pot ent i al concern i ncl ude cert ai n
pesticid e s ( e . g., DDT or lindane), medici nal d rugs (e.g., synthetic hormones),
naturally occurring plant hormones (e. g. , i n s oy beans), and industrial compounds
(e.g., polychlorinated biphenyls (PCBs)), som e di ox i n s, l ead, m ercury, arseni c, and
o rganotins. Potential s ources of such chemicals i nclude wastewater dischar g e s ,
industrial releases, and consumer products . R esearch is being conducted t o i dentify
the range of potential h ealth effects and vulnerable animal s pecies (perhaps including
humans), s ensitive periods of development, and chemicals with endocrine-disrupting
Proponents o f t h e h ypothesis t hat envi ronmental ex posure t o endocrine
disruptors m ay be affecting human health poi nt t o apparent i n creases i n U.S . rat es o f
certain cancers, reported d e c l i n es in sperm counts i n v arious nations, and some
sci ent i fi c evi d ence of i n creasi n g rat es o f som e bi rt h d efect s, t h yroi d d i s orders,
attention d eficit disorder, p remature birt hs, and premature puberty. There appears t o
be a w orl d wi de i n crease i n cases of t est i cul ar cancer , f o r whi ch t here i s no cl ear
cause. T he reason for repor t e d i n creases i n rat es o f o t h er cancers h as not been
determined: s uch i ncreas es may reflect improvements i n diagnostic tools or reporting
rather than increases in disease. Res ear ch on trends in male fertility has p roduced
inconsistent results. In s ome nations, research found a d ecline i n s perm quality over
the l ast few decades and i ncreasing rates of deformities o f m ale reproductive o rgans
until 1985 after which rates apparently stabilized. Any of these effect s c o u l d b e
l i nked t o horm one di srupt i on, because t h ey are h o r m o n e m edi at ed, but such l i nks
have not been established. Although h igh doses of some chemicals h ave b een shown
to affect hormonal processes i n people, sometimes beneficially and sometimes
adversel y, many scientists believe that envi ronmental l evels o f potential d isruptors
are t oo low t o i nfluence human endocrine systems. The effect of long-term ex posure
to low l evels of m ultiple endocrine disruptors is a key question for scientific research.
Research interest is spurred b y evi d e n c e t h a t t he endocrine systems o f s ome
wildlife, es peci ally fish, are being affect ed by environmental pollutants , the
ubiquitous presence of some potential horm one disruptors i n t he environment at l ow
levels, l ack of scientific understanding of endocrine chemistry, and l ack of ex posure
Congress has m andated chemical screening t o assess the potential of pes ticides
and d ri nki ng wat er cont am i n ant s t o affect horm one syst em s. As evi d ence
accumulates, legi slators m ay decide to increase o r d ecrease funding for t he endocrine
disruptor screening p ro gr a m , o r t o ex p an d its requirements t o i nclude additional
chemicals o r hormone functions. This re port p rovides references to additional
sources of information. It will be updated as t he issue warrants.

Background ..................................................1
Endocrine Disruptors .......................................1
Congressionaland AdministrativeAttention .....................2
Current Research Initiatives ..................................3
ScientificEvidence ............................................4
HumanHealthTrends ......................................4
Human Evidence of P otential C hemical Tox i city to
Endocrine Systems .....................................4
AnimalEvidence ..........................................6
Environmental Ex posure t o P otential Endocrine Disruptors ........10
PolicyIssues .................................................12
PaceofFQPAImplementation ..............................12
WelfareofTestAnimals ...................................13
Legi slation i n t he 107 th Congress .................................14
AdditionalResources ..........................................14

Environmental Exposure to Endocrine
Disruptors: What Are the Human H ealth
Endocrine Disruptors. Endocrine disruptors”1 are chemical compounds in
drugs, food, consumer products, o r t he ambi ent environment t hat can interfere with
i n t ernal bi ol ogi cal proces ses o f ani m al s t h at norm al l y are regul at ed by t h ei r
hormones. Developme n t , growth, reproduction, and m etabolism, for ex ample, are
hormone-dependent processes t hat m i g h t be affected by ex posure t o endocrine
disruptors. Some endocrine disruptors ex i st naturally, for ex amp l e, the
phytoestrogens i n s ome p lants. Others are t he products of human indu s t r y – e.g.,
som e pest i ci d es and pharm aceut i cal s.
Some endocrine disruptors are similar i n form and action t o n atural hormones;
thes e are called “hormone mimics.” The terms “environmental estrogen” and
“x enoestrogen” are n arrower, referring only t o t hose chemical s t hat mimic the action
of the female s ex hormone estrogen. Other endocrine disruptors d o n o t m imic, but
otherwise m odify the s ynthes is, s ecretion, transport, binding, action, or elimination
of natural hormones. Some scientists prefer the m o r e neutral but just as incl usive
term “endocrine modulators” over t he better known t erm “endocrine disruptors.”
Ex posure t o h igh l evels o f m anufactured endocri n e d i s ruptors i n t he
envi ronm ent h as been shown t o h arm i nsect s, som e vert ebrat e wi l d l i fe, and aquat i c
life b y i nte r f e ring with the action o f rep roductive and other hormones. Selected,
peer-reviewed studies are d escrib ed and references are cited b elow. 2 There also i s
scientific evidence that relatively l ow e nvironmental l evels o f endocrine disruptors
m ay b e h arm ful , p art i cul arl y when t h ey bi oaccum u l at e, ex posi n g ani m al s hi gh er on
t h e food chai n t o great er chem i cal concent rat i ons. S om e s ci ent i s t s hypot hesi z e t h at

1 T he endocrine system includes t he gl ands (e.g., thyr oid, pituitary gl and, pancreas, ovaries,
o r t e s t e s ) and their s ecretions (i.e., hormones), t hat are released directly into the body’s
circulatory s ys tem (rather than through duc ts). T he endocrine system controls blood sugar
levels, blood pressure, metabolic rates, gr owth, development, aging, and r eproduction.
2 T he pesticide i ndustry has studied and exploited chemi cals t hat can disrupt the endocrine
systems of i nsects. For example, s yn t h e t i c j uvenile hormone analogs control i nsect pests
b y i nterfering with the natural j uvenile hor mone, which suppresses metamorphic c hange
during molting and induces production of egg yolk protein during ovarian development. T he
pesticides can act to enhance or obstruct t hese endocrine effects. Examples include
phenoxyphenoxy carbama te and methoprene. Howeve r , r e s e a r ch on insecticides is not
described below, because it appears t o be l ess r elevant t han r esearch on vertebrates t o t he
question of human health effects from environmental exposures.

ex isting env i r o n m e n t al l evels o f endocrine disruptors also m ay be harming human
Congressional a nd Administrative Attention. The U.S. C ongress began
investigating t he effect s of endo crine disruptors i n t he environment at a hearing i n

1993. 3 Am ong t hose t est i fyi ng at t h at heari n g were s e v e r a l r esearchers who l at er4

published t heir findings i n t he book, Our Stolen Future. It summariz ed s tudies by
wildlife biologi sts, epidemiologi s t s , and other scientists, and hypothesized t hat
endocrine disru p t i o n b y environmental pollutants might have caused observed
increases in deformities and population d eclines of amphibians, evidence of declining
human fertility, and alleged i ncreas es in human rates of breast, testicular, and prostate
cancers, as well as endometriosis.
In t h e n ex t few years, research produced evi d ence bot h for and agai n st t h e
hypothesis t hat environmental l evels o f endocrine disruptors are harming human and
ecol o gi c al h eal t h . 5 Congress continued t o s tudy the i ssue, and i n 1996 concluded
that there was a need to screen pestici d es and drinking water contaminants for
potential t o d isrupt endocrine systems. A screening p rogram was established i n t he
Food Quality Protection Act (Public Law 104-170) and t he 1996 Amendments to the
Safe Drinking W ater Act (Public Law 104-182).
The Food Quality Protection Act (FQPA) Section 408(p) 6 directs EPA, not later
than 3 years after Augu st 3, 1996, to require validated tests t o d etermine t he potential
of pesticides to produce effects i n hum ans s imilar t o t h o s e p r oduced by naturally
occurring estrogens o r, at the d iscretion o f t he Administrator, o ther endocrine effects
in humans. The m andate covers al l registered pes ticide i ngredients (both active and
inert), as wel l as other substances identified by t he Administrat or which might have

3 U.S. Hous e o f R e presentatives, Committee on Energy and Commerce, Subcommittee on
Health and t he Envi ronment. Health Effects of Estrogenic Pesticides. 103rd Cong., 1st Sess.,
Oct. 21, 1993. Washington, DC: U.S. Govt. Print. Off. (1994) 185 p.
4 Colburn, T heo, Dianne Duma noski , a nd J ohn Peterson Myers. Our Stolen Future : Are We
Threatening Our Fertility, I ntelligence, and Survival? A Scientific Detective Story .New
York: Penguin. ( 1996) 316 p.
5 Initially, one of the most i nfluential studies (“Synergistic activation of estrogen r eceptor
with combinat i o n s of envi ronmental chemi cals.” Arnold, S.F., D.M. K lotz, B.M. Collins,
et a l . ( 1996) Science, v. 272, p. 1489-1492.) was l ater retr acted, when t he authors were
unable t o r eplicate t heir results (McLachlan, J .A. (1997) “S yn e r gi s t ic effect of
envi ronmental e stroge ns: r eport withdrawn.” Science, v. 277, p. 459-463.) T he o r i ginal
report i ndicated that effects of combined expos ure t o t wo different pesticides could be
gr eater than effects from an equivalent exposure t o either of the i ndivi dual pesticides alone.
However, synergy ( a s we l l as antagonism, i n which effects are less than expected from
exposure t o a combination of chemi cals) has been demonstrated for other health effects of
exposure t o PCBs and s everal pesticide f ormu lations (Hook, G.E., and G.W. Lucier. (1997)
“Editorial: Synergy, antagonism, and scientific processes. ” E n vironmental Health
Perspectives , v. 105, p. 784.)
6 See §405 of P.L. 104-170, amending §408 of the Federal Food, Drug, a nd Cosmetic Act ( 21

a cumulative effect together with pes t i c ides and t o which a s ubstantial population
may b e ex posed. 7
The 1996 Safe Drinking W ater Act Amendments (P.L. 104-182) authoriz e
screening for endocrine disruption potentia l o f contaminants found in sources of
d r inking water. 8 Actual screening o f chemicals f or tox i c effects will be conducted
by m anufacturers o f s uspect chemicals. Fo r s ubstances found to have endocrine
effect s i n hum ans, t h e l aws aut hori z e E P A to take appropriate action t o protect public
health under ex i sting s tatutory authority.9
To help im p l e m e n t t h e n e w p r o v i s i o n s , E P A o r ga n i z e d t he Endocrine Disruptors
Screening and Testing Advisory Committee (EDSTAC ). This co mmittee of
scientists (some i ndependent and o thers representing various chemi cal m a nufact urers
and d i s t ri but ors, chem i cal users, publ i c heal t h advocat es, e n v i ronm ent al i s t s , and
other s t a k eholder groups), assisted EPA i n d esigning the chemical screening and
testing p rogram. The committee’s recommendations, released October 5 , 1998, were
revi ewed by a s peci al peer revi ew panel consi s t i n g o f m em bers of t h e Federal
In sect i ci d e, Fungi ci d e, and R odent i ci d e A ct (FIFR A ) S ci ence Advisory Panel and t h e
independent Science Advisory Board. EPA relied h eavily on EDSTAC
recommendations in devel o p i n g the Endocrine Disruptor Screening P rogram.10
Although t he program was design ed and “es tablished” in 1998, it is not yet operating.
EPA i s s till developing the m ethods that w ill be used to prioritize c h e micals for
scre e n i n g a n d is attempting t o v alidate t he methods that will be used to test high -
priority chemicals. In a d d ition, a n ew Endocrine Disruptor Method Validation
Subcommittee h as been established t o advise EPA o n how i t should evaluate t he
screens and tests d eveloped. The S ubcommittee m et for t he first time in December

2001. The p rogram is not yet operational.

Current Research Initiatives. The h ypothesis t hat ex i sting environmental
levels of endocrine disruptors m ay be harming human healt h i s h o t l y debated. At
present, there i s n o conclusiv e evidence to support t his h ypothesis, but research
interest is growing. Scientists are working t o better define t he range of potential
heal t h effect s a n d t o i d ent i fy vul nerabl e ani m al s peci es and chem i cal s w i t h
endocrine-disrupting poten tial. Attention h as focused o n certain chemicals t hat are
ubiquitous at low l evels i n t he air, surface water, and food, and at h i g h e r l evels i n
many consumer products, i ncluding medi cal devices and b aby t oys . Chemicals o f
potential concern i nclude a number o f pesticides (e.g., DDT, lindane, and
vincloz o lin), medicinal d rugs (especially synthetic hormones), and certain industrial

7 T he EPA Office of Science Coor d i n a t i o n a nd Policy website describes t he statutory
authority for t he Endocrine Di sruptor Screening Progr am.
[ ht t p: / / www.epa.gov/ sci pol y/ oscpendo/ ]
8 See §136 of P.L. 104-182, adding a new §1457 to the Safe Drinking Water Act ( 42 U.S.C.


9 Federal Food, Drug, a nd Cosmetic Act, as amended; 21 U.S.C. 346a(p)(6).
10U.S. Envi ronmental Protection Age ncy. “Environmental Protection A ge ncy Endocrine
Disruptor Screening Progr am, Report t o Congress.” August 2000. p. 5.

compounds (e.g., phthalates, bisphenol A, pol ychlorinated biphenyls (PCBs), s ome
dibenz odiox ins, lead, m ethyl m ercury, arsenic, and organotins).
Many U.S. and o ther governmental and i ntergovernme n t a l organiz ations are
sponsoring and coor d i nating research effo rts t o clarify the s cope and s everity of
potential endocrine disruptor effects. In the United S tates, work w ithin federal public
health and environmental agencies i s b ei ng coordinated b y t he Endocrine Disruptor
W o rking Group, which was established b y t he Nation a l S cience and Technology
Council’s C ommittee on t he Environment and Natural R esources.11 Internationally,
t h e O r g a n i z a t i o n f o r E c o n o m i c Cooperation and Developme n t ( O E C D ) i s d e v e l o p i n g
harmoniz ed i nternational t est guidelines to detect endocrine disruptors.
Scientific Evidence
Human Health Trends. Proponents o f t he hypothesi s t hat environmental
ex posure t o endocrine di s r u p t o rs m ay be affecting human health have pointed to
apparent increases in U.S. rates o f certain cancers, reported d eclines in sperm counts
in v a rious nations, and some scientific evidence of increasing rat es of some birth
defect s, thyroid disorders, attention deficit disorder, p remature births, and premature
puberty. In fact, t here appears t o b e a w o r ldwide increase i n t he incidence o f
t est i cul ar cancer, for whi ch t here i s no cl ear cause. 12 Reported rates of other human
cancers al s o h ave i nc reased, but t h ese i ncreases m ay refl ect i m p rovem ent s i n
di agnost i c t ool s o r report i n g rat es rat h er t h an i n creased rat es o f d i s ease.
R esearch in some nations has found a d ecline i n s emen quality13 over t he last
f ew d ecades and i ncreasing rates of defor mities o f m ale reproductive o rgans (i.e.,
undescended t estes and misplaced urethra opening) b efore 198 5 , a fter which rates14
stabilized. S o m e researche r s al s o h ave report ed i ncreased rat es o f t hyroi d
dysfunction, attention deficit disorder, and prem at ure births, as well as a t rend toward
onset of puberty at an earlier age. Any of these effects could b e linked t o hormone
di srupt i o n b ecause t h ey ar e h o rm one m edi at ed, but such l i nks have not been
Human E vi dence of P otential Chemical Toxicity to E ndocrine
Systems. The h ypothesiz ed link b etween human health problems and the
d i s ruption o f hormone activity as a result o f ex posure t o chemicals i n t h e
envi ronm ent i s b i o l o gi cal l y pl ausi bl e; som e chem i cal s h av e b een shown t o affect

11For more i nforma tion a bout this gr oup, see EPA’s website on the Endocrine D i sruptors
Research Initiative.
[ h t t p : / / www.epa.go v/ endocr i ne/ ]
12Safe, S.H. ( 2000) Endocrine disr uptors a nd human health: Is t here a problem? An update.
Environmental Health Perspectives, v. 108, n. 6, p. 487-493.
13Seme n q u a l i t y i s based on ej aculate volume, s perm concentration, sperm motility, and
sperm morphology.
14Safe, i bid.

hormonal p rocesses i n p eople and wildlife, 15 especi ally if the chemical is directly
adm i n i s t ered o r o t h erwi se recei ved i n a concent rat ed dose duri n g fet al or i n fant
development. Fo r ex ample, i t i s well known t hat d augh ters born t o women who t ook
the drug diethyl stilbes trol (DES), a s ynthetic es trogen, early in thei r pregnanci es
between the mid 1940s and 1971, now have a greatly increased ri s k o f v a gi nal
cancer. 16 In addition, studies have documented a h i gh er t h an norm al i nci d ence of
genital t ract abnormalities i n n ewborns following in utero ex posure t o DES. 17 The
rol e of m al e and fem al e s ex horm ones i n t he growt h of prost at e and b reast cancer i s
well es tablished s ci entifically. 18
Although t he production and use of P CBs has been strictly regu lated s ince 1976,
P C Bs are ubiquitous in the air, wat er, soil, and m any animal tissues due to t h ei r
envi ronm ent al p ersi st ence and p revi ousl y wi despread use i n el ect ri cal t ransform ers,
plastics, and o ther industrial applicati ons. S ome P CBs are known t o b e estrogenic;
others may affect thyroid function. 19 There i s evidence t hat fetal ex posure t o P CBs
may affect cogn itive d evelopment, although i t i s not known whether this tox i city is
related t o hormone disruption. 20 In addition, some studies have found an association

15Generally, scientists have studied effects i n vertebrates, especially amphibians, freshwater
f i s h , a n d ma mma l s .
16He r b s t , A., H. Ul f e l d e r , a nd D. Pos ka n ze r . “Adenocarcinoma of t he va gi na: Association
of maternal stilbestrol therapy with tumor appearance in young women,” New England
Journal of Medicine , v. 284, (1971) p. 878-881.
17Mittendorf, R. T eratogen update: Carcinogen e s i s a n d t eratogenesis associated with
exposure t o diethyl stilbestrol (DES) i n utero. Te ratology , v. 51, n. 6, (1995) p. 435-445.
18See t he National Cancer Institute website at [http://www.nci.nih.gov]
19Longnecker, M .P., W.J . Roga n, and G. Lucier. T he human health e f f ects of DDT
(dichlorodiphenyltrichloroethane) and PCBs ( polychlorinated biphenyls) and an overvi ew
of organochlorines in public health. Annual Review of Public Health, v. 18, p. 211-244.
Brouwer, A., U.G. Ahlborg, F.X . va n Leeu we n, and M .M. Feeley. Report o f t h e WHO
working group on the a ssessment of health risks f or human infants from e xposure t o PCDDs,
PCDFs a nd PCBs. Chemosphere, v. 37, n. 9-12, p. 1627-1643. (1998)
20Stewart, P., J . Reihman, E. Lonky, T . Da rvill, and J . Pagano. (2000) Pre n a t a l PCB
exposure a nd neonatal behavioral a ssessment s cale ( NBAS) performance. Neurotoxicology
and Teratology , v.22, n. 1, p. 21-29.
J acobson, J .L., S.W. J acobson, and H.E. Humphrey. ( 1990) Effects of e xposure t o PCBs
and r elated compounds on gr owth and activity in children. Neurotoxicology and Teratol o gy,
v. 12, n. 4, p. 319-26.
Patandin, S., C.I. Lan t i n g, P.G. Mulder, E.R. Boersma , P.J . Sauer, a nd N. Weisglas-
K uperus. ( 1999) Effects of e nvironmental e xposure t o polychlorinated biphenyls and
dioxins on cognitive abilities i n Dutch children at 42 months of age [ see comments]. Journal
of Pediatrics , v. 134, n. 1, p.33-41.
J acobson, J .L., a nd S.W. J acobson. (1996) Intellectual i mpairment i n c hildren e xposed
to polychlorinated biphenyls in utero [see comments]. New England Journal of Medicine ,
v. 335, n. 11, p. 783-789.
J acobson, J .L., a nd S.W. J acobson. (1996) D o s e -r e s ponse in perinatal exposure t o
polychlorinated biphenyls (PCBs): the M ichigan and North Carolina c o h ort studies.

b e tween human PCB ex posure and low s perm counts, undescended t estes, a l t e r e d
semen quality, l ower age o f onset of pube rty, and s horter h eigh t at m aturity.
Such developmental, reproductive, and car cinogenic effects for which increased
incidences hav e b een reported i n human s are similar t o effects o n reproductive
structure and function t hat h ave b een observed i n w i l d life and fish ex posed to
endocrine disruptors.21
On the o ther hand, some chemicals wit h e f f e c t s o n endocrine systems h ave
therapeutic value. For ex ample, s ex hormones are used to treat s o me forms of
cancer. T here also is evidence that some plant-derived endocrine disruptors 22 (e.g.,
phytoest rogens p reval ent i n soy b eans) m ay p rot ect agai nst d i s ease. 23 Some scientists
argu e t hat s uch evidence undermines the h ypothesis t hat endocrine disruptors i n t he
environment are a t hreat to human health. O ther scientists believe the evidence for
therapeutic effects only underscores t he potency of hormonally active chemicals.
Animal Evidence. The m ost compelling evidence for endocrine disruption
due to environmental ex posure t o contaminants has b een obtained i n aquatic systems,24
with most of the published literature based on s tudies of fish. In particular,
feminization of m ales due to endocrine disrupting chemicals i s an i ncreasing concern.
Fem i n i z at i o n h as al so been report ed i n o t h er vert ebr a t e speci es i n cl udi ng bi rds
(especi al l y fi sh-eat i n g s peci es, s uch as gul l s , t erns, o spreys , eagl es, and p el i cans) and25
Florida p ant h ers. In addition, there i s evidence o f h armful effects o f endocrine
disrupting chemical s on alligat ors26 and mink27 as well as circumstantial evidence

Toxicology and Industrial Health, v. 12, n. 3-4, p. 435-445.
21U.S. Envi ronmental Protection Age nc y ( 1997). Special Re port on Environmental
Endocrine Disruption: An E ffects Assessment and Analys is, EPA/630/R-96/012. p. 5.
22Perhaps i n t his case, the t erm endocrine modulator is more appropriate.
23V i ncent, A. and L.A. Fitzpatrick. (2000) Soy i soflavones: are t hey useful i n menopause?
Mayo Clinic Proceedings, v. 75, n. 11, p. 1174-1184.
Stephens, F.O. ( 19 9 7) Breast cancer: aetiologi cal factors and associations (a possible
protective r ole of phytoestrogens). The Australian and New Zealand Journal of Surgery ,v.

67, n. 11, p. 755-760.

24J obling, Susan, et al. ( 1998) “Widespread sexual disruption i n wild fish,” Environmental
Science and Technology , v. 32, p. 2498-2506.
25Facemire, Charles F., T i mothy S. Gross, and Louis J . Guillette, J r., ( 1995) “Reproductive
impairment in the Florida panther: nature or nurture?” Environmental Health Perspectives,
v. 103, Supp. 4, p. 79-86.
26Guillette, Louis J ., et al. ( 1995) “Gonadal s teroidogenesis in vitro from j uvenile alligators
obtained from contaminated or control l akes,” Environmental Health Perspectives, v. 103,
27Golub, Mari S., J ames M. Donald, and Joe A. Reyes. ( 1991) “Reproductive t oxicity of
c o mme r c i a l P C B mi x t u r e s : L O A E L s and NOAELs from a nima l s tudies,” Environmental
Health Perspectives, v. 94, p. 245-253.

for m arine m ammals.28 For ex am p l e , t he accum u l at i o n o f p ersi st ent chl ori n at ed
organi c chem i cal s, such as P C Bs, i n s eal s and dolphins has b een well documented.29
In addition, laboratory s tudies of a b el uga w hale protein t hat i s k ey in many
endocrine disrupting effects (the aryl h yd rocarbon receptor) reveal t h a t it binds
strongly to diox ins and PCBs . This m ay increase t he likelihood that tox i c responses
can be turned on at physiologically relevant co n c e n trations of contaminants.30
H o w e v e r, as is the case with humans, direct tox i city testing i n m arine m ammals is
precl uded b y l ogi s t i cal , l egal , and et hi cal const rai nt s, whi ch m ake cause-and-effect
relationships difficult (or impossible) to show ex perimentally.
Feminization of m al e fish collect ed from British rivers alerted t h e sci entific
community to the potential haz ard of chemical s (in those cas es , x enoestrogens) i n t he
environment.31 Feminization of m al es was confirmed by t he pres ence of eggs in the
testes and t he female-specific yolk p ro tein vitellogenin (a c o m ponent of yolk for
eggs , u sual l y m ade onl y b y fem al es) i n t he blood of male fish. W hile manufacture
of vitellogenin b y m ales is clearly abnormal, it is not clear whether t hese males are
impaired in their normal male rep roductive function. More recent l y, m ari n e f i s h
populations in the English C hannel and in Tokyo Bay have also shown evidence o f
feminization. Less information i s available for the United S tates. However, there i s
a report o f complete s ex revers a l o f male salmon i n W ashington. 32 Androgenic
substances (i.e., substances with an effect similar t o t hat of m al e s ex hormones) have
al so been detect ed in environmental s am ples , especi ally in pulp mill effluents.
Bony fish33 appear to be useful as sentinels for the p resence and possible h az ard
of endocrine disrupting chemicals i n t he aquatic environment, s i n c e t h ese fish are
current l y t h e onl y v ert ebrat es for w hi ch t h e connect i o n b et ween envi ronm ent al

28Cooper, Ralph L., and Robert J . K a vl ock. (1997) “Comme ntary: endoc rine disruptors and
reproductive development: a weight-of-evi dence overview,” Journal of. Endocrinology ,v.

152, n. 2, p. 159-166.

Ross, Peter S. ( 2000) “Marine mammals as sentinels i n ecologi cal risk assessment,”
Human and Ecological Risk Assessment ,v.6,p.29-46.
29Watanabe, M., K . K annan, A. T a ka hashi, et al. ( 2000) “Pol yc h l orinated biphenyls,
organochlorine pesticides, t ris(4-chlorophenyl)methane, and t ris(4-chlorophenyl)methanol
in livers of s mall cetaceans s t r a n d e d along Florida coastal waters, USA,” Environmental
Toxicology and Chemistry , v. 19, n. 6, p. 1566-1574.
Re ddy, M .L., J .S. Re if, A. Bachand, et al. ( 2001) “Opportunities f or using Navy marine
mammals to e x p l ore associations between organochlorine contaminants and unfavorable
effects on r eproduction,” Science of t he Total Environment , v. 274, n. 1-3, p. 171-182.
30J e nsen, Brenda A., a nd Mark E. Hahn. (200 1 ) “ c DNA cloning and characterization of a
high affinity aryl hydrocarbon receptor i n a cetacean, t he beluga, Delphinapterus leucas ,”
Toxicological Sciences , v. 64, p. 41-56.
31J obling, Susan, et al. ( 1998) “Widespread sexual disruption i n wild fish,” Environmental
Science and Technology , v. 32, p. 2498-2506.
32J ames J . Nagler, J ames J ., et al. ( 2001) “High i ncidence of a male-specific genetic marker
in phenotypic female Chinook salmon from t he Columbia River,” Environmental H e a lth
Perspectives , v. 109, n. 1, p. 67-69.
33As opposed to cartilagi nous fish, s uch as s harks and rays .

contamination and adverse effects o n o rganism health has been established i n both
field 34 and l aboratory35 studies. The aquatic environmen t i s especi ally well suited for
these s tudies as it is the u ltimate sink for m any n atural and anthropogenic compounds
rel eased i n t o t h e envi ronm ent . Fi sh, i n t urn, are wel l s ui t ed for such research as our
understanding of their endocrinology i s far s uperior to that of aquatic invertebrates.
Bo th androgenic36 and estrogenic37 effects h ave b een observed and published, with

34Folmar, Leroy C., et al. (2001) “V itellogenin-induced pathology i n male s umme r f lounder
( Paralichthys dentatus ),” Aquatic Toxicology, v. 51, p. 431-441.
Folmar, Leroy C., et al. (1996) “V itellogenin i ntroduction and reduced serum t estosterone
concentrations in feral male carp ( Cyprinus carpio) captured near a maj or metropolitan
sewage treatment plant,” Environmental Health Perspectives, v. 104, p. 1096-1100.
Harries, J .E., et al. ( 1997) “Estroge nic activity in five United K ingdom rivers detected by
measurement of vite llogensis in caged male trout,” Environmental Toxicology and
Chemistry, v. 16, p. 534-542.
J obling, Susan, et al. ( 1998) “Widespread sexual disruption i n wild fish,” Environmental
Science and Technology , v. 32, p. 2498-2506.
35Panter, Grace H., R. S. T hompson, and J ohn P. Sumpter. (1998) “Adverse reprod u c t i ve
effects i n male f athead mi nnows ( Pimephales promelas ) exposed to e n vi r o nmentally
relevant concentrations of the natural oestrogens, oestradiol and oestron e , ” A quatic
Toxicology , v. 42, n. 4, p. 243-253.
36Galloway, Brendan, et al. ( 2000) “Exami nation of t he cumulative r esponses of s l i my
sculpin ( Cottus c ognatus ) and white sucker ( Catostomus commersoni ) collected on the Saint
J ohn Ri ver downstream of a pulp mill, paper mill, and s ewage discharges,” Society of
Environmental Toxicology and Chemistry (SETAC), p. 255, SET AC: Na shville, T N.
J oakim Larsson, D.G., et al. (1999) “More male embryos near a pulp mill,” In 6th
International Symposium on t he Reproductive Physiology of Fish , ( ed. B. Norberg, et al .).
Munkittrick, Kelly R. et a l . ( 1999) “Secondary sex characteristics and gonadal s ize i n
white sucker ( Catostomus commersoni ) during modernization at a pulp mill,” In 6th
International Symposium on t he Reproductive Physiology of Fish , ( ed. B. Norberg, et al .),
37Bayl ey, M ark, J acob R. Nielsen, a nd Erik Baatrup. (1999) “Guppy sexual behavior a s a n
effect biomarker of estrogen mimics,” Ecotoxicology and Envi ronmental Safety , v. 43, p.


B j e r s e lius, Rickard, et al. ( 1999) “Estroge n i n f ood or water s everely e ffect the ma l e
go l d f i s h ( Carassius auratus ) s exual behavior,” In 6th I nternational Sympos i u m o n t he
Reproductive Physiology of Fish ,(ed.B.Norberg,et al .), Berge n, Norway.
Haek, R.A., e t a l . ( 1997) “During development, 17a-estradiol is a potent estrogen and
carcinogen,” Environmental Health Perspectives, v. 105, p. 577-581.
J obling, Susan, et al. ( 1996) “Inhibiti on of testicular gr owth in rainbow trout
( Oncorhynchus mykiss ) exposed to estrogenic alkyl phenolic chemicals,” En v i r onmental
Toxicology and Chemistry , v. 15, p. 194-202.
K i me , David E., a nd J on P. Nash,(2000) “Estroge nic e ndo c r i n e disruptors act on ma ny
components of r eproduction, over multiple generations to cause reproductive f ailure in
ze b r a f i s h ( Dania r erio),” In 4th I nternational Sympos ium on Fish Endocrinology ,p.Poster,
K r amer, V .J ., et al. ( 1998) “Reproductive i mpairment a n d i nduction of alkaline-labile
phosphate, a biomarke r of e stroge n e xposure, in fathead mi nnows ( Pimephales promelas )
exposed to waterborne 17b-estradiol,” Aquatic Toxicology, v. 40, p. 335-360.

est rogeni c act i v i t y appeari n g t o b e m ore ubi qui t ous and h ence bet t er s t udi ed. It h as
become almost routine i n l aboratories around the world to isolate x enoestrogens from
the aquatic environment, ex pose fish t o t he isolated compounds in the l aboratory, and
achieve similar endocrine modulation (i.e., v itellogenin i nduction) as was observed
at the corresponding field s ite. Other endoc rine modu l a t i n g effects (e.g. , hormone
levels, b ehavior, reproductive s uccess, intersex ) are much less successfully
reproduced in the l aboratory. Currently laborat ories i n t he United S tates, Europe, and
J apan are working t o devel op a biomarker38 t o assess adverse h eal t h effect s due t o
ex posure t o endocrine disrupting chemical s o r x enoestrogens, i n p articular.
The endocrinology o f m ost i nvertebrates i s l ess well understood. Reproductive
impairment h as been noted in some species of snails ex posed to v ery low amounts
of tributyltin (TBT), a constituent i n anti-fouling pai nts used on boats. This chemical
causes female s nails to grow male reproductive o rgans i n addition t o normal female
ones, a condition called “imposex .” When th is condition b ecomes s evere, affected
fem a l e s cannot function as females or as males; the resulting reproductive failure
caused s evere population d eclines in some species. W hile the u se of TBT i n a n t i -
fouling p aints h as been seve rely rest ricted in the United S tates (P.L. 100-333,
Organotin Antifouling P aint Control Act of 1988) and European countries, i t remains
in use i n o ther parts o f t he world. In addition, ambiguous genitalia have been found
by the EPA in Maine bival ves, allegedly due to herbicides.39
In l aborat ory ex p eri m ent s wi t h rodent s, t h ere i s cl ear evi d ence t h at ex posure t o
some endocrine disruptors affects the developmen t o f reproductive o rgans and causes
tumor d evelopment. Fo r ex ample, one study found that ex posure o f n ewborn mice
t o geni st ei n (a n at ural l y occurri ng pl ant e s t rogen) at a l evel “wi t h i n t h e range t o
which humans m a y be ex posed in soy-based i nfant formulas” caused growths on
oviducts that would impai r fertility, and lack of certain cel l m asses i n d i cating
impaired abil ity to ovulate i n every ex posed mouse and in no mouse t hat was

Matthiessen, P. (1998) “Effect s o n f ish of estrogenic s ubstances in English r ivers,” In
Principles and Processes f or Evaluating Endocrine Di sruption i n Wildlife ,(ed.R.Kendall,
et al .), p. 239-247, Pensacola, FL: SET AC Press.
Panter, Grace, R. S. T hompson, and J ohn P. Sumpter. (19 98) “Adverse reproductive
effects i n male f athead mi nnows ( Pimephale s p r o melas ) exposed to envi ronmentally
relevant concentrations of t h e n a t ural oestrogens, oestradiol and oestrone,” Aquatic
Toxicology , v. 42, n. 4, p. 243-253.
38A biomarker is a biochemical, morphological , or f unctional c hange t hat i ndicates exposure,
response, or potential s usceptibility to an envi ronmental s ubstance or agent. Biomarkers are
generally used to increase sensitivity, specificity, or r esponse capacity, t he obj ective being
to establish a causal r elationship between a chemi cal agent and its effect on an organism.
39V an Beneden, R.J ., et al. ( 1993) “Implication f o r t h e p resence of t ransforming genes in
gonadal t umors i n t wo biva lve mollusk species,” Cancer Research, v. 53, p. 2976-2979.
V a n Beneden, R.J . ( 1996) “Comparative s tudies of molecular mechanisms of tumorige nesis
in herbicide-exposed bivalves,” In Interconnections between Human and Ecosystem Health
(eds. R. DiGiulio and E. M onosson), Chapman and Hall Ecotoxicology S e r i e s , London,
Engl and, p. 29-43.

unex posed, and uterine cancer in about one-third of the ex posed mice and none of the
unex posed mice. 40
E n vironmental E xposure to P otential Endocrine Disrup t o r s . C oncern
about possible human hormone disruption h as been fueled by the limited i nformation
available about levels of potential hormone disrupto r s i n t h e environment. It is
known t hat s ome potential endocrine disrupt ors are heavily used and, in some cases,
rel eased t o t h e envi ronm ent . For ex am p l e, w ast ewat er effl uent from s ewage
treatment plants contains many potent i a l endocrine disruptors, including synthetic
(pharmaceutical) h o r mones. Other potential endocrine disruptors are prevalent i n
certain foods, s uch as s oy-based milk substitutes, becau s e s o y b eans contain
phytoestrogens (i.e., i soflavonoids) at relatively h igh l evels.41 Some argu e t hat t he
high phytoestrogen concentrations in food far ex ceed concentratio n s of endocrine
disruptors i n t he environ m ent, implying t hat environmental ex posures are likely t o
be relativel y i nsignificant. However, this conclusion is not nece s s arily justified,
beca use i t i s b ased on a comparison o f apples with oranges, or rather a mix ture of
isoflavonoids and o ther phytohormones w ith a m i x t u r e o f synthetic industrial
compounds, i ncluding pharmaceuticals a n d o t h e r c h e m i cal s , each o f w h i ch m ay ex er t
a d ifferent biological effect and b e m ore o r l ess potent at v arious concentrations.
Of course, rel ease o f a chem i cal does not necessari l y i m p l y t h at envi ronm ent al
levels of ex posure are t o x i c , even to vul nerable populations of animals or people.
Available d ata are somewhat reassuri ng, b ecause known potential d i s r uptors o f
endocrine function generally are p resent in the environment at v ery l ow levels.42 On
the other hand, little is known about possible hea lth effects for children o f ex posure
t o l o w l evel s o f cont am i n at i on, and t here are n o m easurem ent s a t al l o f am b i ent
c o n centrations for m ost chemicals i n t he environment, some of which m ay be
affecting hormones. Many known hormone disruptors are ubiquitous at low l evels,
raising t he question of l ong-term effect s and possible additive or s ynergi stic effect s
with continual ex posure. 43 Foods and s urface water o ft en contain t race amounts o f
pesticides, and many consumer products c ontain l ow levels of endocrine modulators
such as phthalates or bis p h e n o l A. For ex ample, P CBs and some diox ins are very
persistent in the environment and are known t o b ioconcentrate i n t he food c h ain.
Children are ex posed to PCBs through breas t milk, and by eating fish and other fatty

40Newbold, R.R., E.P. Banks , B. Bullock, e t al. (2001) “Uterine adenocarcinoma i n mice
treated neonatally with genistein,” Cancer Research, v. 61, n. 11, p. 4325-4328.
41T he i soflavonoids appear to exert both estrogenic and anti-estrogenic effects which are not
completely understood.
42T oxicologi sts generally assume that toxicity increases with increasing l evels of exposure.
B u t concentrations of some chemicals measured in the environment are similar t o t ho s e
measured in the bodies of some healthy animals. M oreover, some scientists argue t hat l ow
levels of exposure t o hormones may exert a d i s p roportionately large effect compared to
43National Academy of Scienc e s ( 1 999). Hormonally Active Agents i n t he Environment,
National Academy Press, Washington, DC.
U.S. Envi ron me n t a l Protection Age ncy. (1997) Special Report on Environmental
Endocrine Disruption: An Effects Assessment a nd An alys is, EPA/630/R-96/012.

foods that contain relatively h igh co n centrations of PCBs . 44 C h i l d ren can al so be
ex posed i n t h e wom b, as P C Bs m ove across t he pl acent a.
One reason for concern about potential human healt h effects from hormone
disruptors i s t he high level of biologi cal availability and potency of some
pharm aceut i cal and agri cul t u ral chem i cal s t hat m ay be rel eased t o t h e envi ronm ent .
Synt h e tic hormones are an obvious ex ample. Bi rth control compounds, s yn thetic
estroge n f o r postmenopausal women, and s yn thetic thyroid hormone are t hree
com m o n cont am i n ant s of wast ewat er.
Potential t ox icity (i.e., ability to adversel y affect hormone function) and
pot ent i al e x p o s u r e are not necessari l y suffi ci ent t o d em onst rat e s i gni fi cant publ i c
health or ecologi cal risks. Knowledge about the range of potential h ealth effects i n
immature, as wel l as m at ure wildlife and humans, and act ual ex posure m eas urem ents
are needed to accu r at el y assess risks. Existing data s ometimes s upport conflicting
vi ews, leading t o controversies about the ex t ent t o which people generally are
ex posed to endocrine modulators, w h e t h e r v ery l ow levels of ex posure potentially
could affect human health, and whether ex posure t o v ery l ow levels of chemicals i n
the environment cu r r e ntly is affecting reproduction, fetal d evelopment, or other
h o r m o n e - d e p e n d e n t f u n c t i o n s i n a n i m a l o r human populations. N e v e r t h e l e s s , a p a n e l
convened b y t he National Academy o f S ciences concluded –
Envi ronmental [ hormonally active agents] probably have contributed to declines
in some wildlife populations, i ncluding fish an d b irds of the Great Lakes and
j uvenile alligators of Lake Apopka, and possibly t o diseases and deformities i n
mi nk in the United Stat e s , r i ve r otters in Europe, and marine mammals in
European waters. Such contaminants, alo n g wi t h inbreeding, mi ght have
contributed to the poor reproductive s uccess of t he endangered Florida panther45
and t he increased embryonic mortality of the s napping turtle in the Great Lakes.
Those s keptical of the d isruptor hypothesis argue that mammal s h a ve
homeostatic mechanisms to moderate smal l fluct uations in hormone levels, s o t hey
are unlikely t o b e overwhelmed b y l ow levels of environmental ex p o s u re. To the
argument that low concentrations of several chemical s m ay additivel y ex ert influence
on t h o s e e x p o s ed, s keptics counter that multiple disruptors are just as likely t o
compet e, resulting i n combined effect s t hat are less than additive.
Some on-going s tudies of developmental effects i n rats h a v e f ound effects o n
the reproductive o rgans from v ery l ow levels of ex posure t o DES and b isphenol-A,
an ingredient in some plastic. S imilarly, preliminary res ults indicat e l ow-dose effect s
on the b rain an d i m m u n e system from genistein and nonylphenol (a chemical in
detergents). An ex pert workshop to evaluate the d a t a o n l ow-dose effects o f
endocrine disruptors recently concluded t hat b iologi cal effects h ave b een shown t o46
occur following ex posure t o s ome est rogenic compounds at very low l evels. The

44Longnecker et al., ibid.
45National Academy of Sciences, p. 7.
46National T oxicology Program’ s Report of t he Endocrine Disruptors Low D o s e P e e r

question rema i ns whether t hose effect s would adversely affect human health,
however. 47
Pace of FQPA Implementation. Environmental, consu m e r , and public
health advocacy groups accuse EP A o f “draggi ng its fee t ” i n i m p lementing m any
provisions of the Food Quality Protection Act (FQPA), i nclud i n g t h e m andate to
establish an endocrine disruptor screening p rogram. T he Natural R esources Defense
Council (NRDC) and s ix California-based public interest groups alleged i n a lawsuit
filed August 3, 1999, in the U.S. District C ourt for the Northern District o f C alifornia
that delays had caused EPA to miss F Q P A deadlines (Natural Resources Defense
Council v. U.S. Environmental Protection Agency, No. C993701CAL). On J anuary
19, 2001, EPA and NRDC agreed to s e ttle the lawsuit. The settlement agreement
states that endocrine disruptor screening w ill begi n n o l ater than spring 2004 (Natural
Resources Defense C ouncil v. EPA, No. C 993701CAL, J an. 19, 2001).
Although grower groups and t he pesticide i ndustry h ave echoed c omplaints
about delays in overall FQPA implementation, they also have complained that EPA
is proceeding t oo fast, j eo p ardiz ing t he scientific basis for decisions about the
screeni n g p rogram . C urrent l y, few t est protocols h ave b een developed and validated
for s creening chemicals for endocrine di sruption. Since c h emical producers will
conduc t t h e a c t ual s creening o f chemicals, they want to ensure that screening
requirements established by EPA will be cost-effective i n i dentifyi ng po t e n tially
haz ardous pesticides rather than wasteful of company resources. T hus, they generally
woul d p refer rel at i v el y qui ck and i nex p ensi ve screens t o qui ckl y rul e out (or at l east
delay) the need to pursue t es ting of chemical s t hat are less likel y t o pose health risks.
This approach would allow time for additional, and p erhaps improved, test methods
t o be val i d at ed. P ubl i c heal t h advocat es would p refer m ore t horough t e s t i n g o f a
l arger num ber o f chem i cal s, t o ensure t h at al l pot ent i al l y haz ardo u s s ubst ances 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 t h e f i e l d of study is so
n e w a n d developing rapidly. Almost certainly, better t ests 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 di s r u p t e d . A key
question t hen i s how flex ible the adopted program s hould b e: W ill it be allowed t o
evolve quickly in response t o n ew knowledge? On t h e o ther hand, most scientists
appear optimistic about the v alue of screening chemicals with the m ethods that are

Revi ew. ( 200 1 ) N a t i onal T oxicology Program, U.S. Departme nt of Health and Human
[http://ntp-s erver.niehs.nih.gov/htdocs/liason/LowDoseWebPage.html ]
47T hat is, t he effects observed are not known t o be adverse. For example, at certain very low
doses fetal exposure t o bisphenol-A produces enlarged prostates i n male r ats, but it is not
clear that an enlarged prostate is an adverse health impact.

being d eveloped, as long as they are v alid ated prior t o b eing employed on hundreds,
if not thousands, of chemicals.
Welfar e of Test Animals. Traditional m ethods of tox i city testing o ften
involve administration o f m easured doses o f chemicals t o groups of laboratory
animals (usually rodents), which are t hen observed for heal t h effect s. Test ani m al s
may be affect ed in a positive way (if t he chemical at the administered dose improves
health), unaffect ed , mildly adversel y affect ed , s ev erel y adversel y affect ed or ev en
killed by t he administered dose. If they survive (which generally is the s ci entifically
preferable result), t hey m ay be sacrificed (i.e., killed) at some future date to permit
intern al i n s p ection of tissues, or t hey m ay be allowed t o live a normal lifespan. In
som e cases, t est ani m al s are al l o wed t o rep roduce, so t h at any adverse h eal t h effect s
on the reproductive p rocess o r o n o f f s p ring m ay be observed. St andard scientific
protocols generally require the u se of groups of animals for s uch t ests, s o as t o p ermit
statistical anal ysis of the results. For ex ample, many tests require the u se of 25 or 50
rat s of each gender at each dose l evel .
As mentioned above, few test protocols h ave b een developed and validated for
screening chemicals for endocrine disruption. At the end of Augu st 2001, only one
(the uterotrophic assay for estrogenic effects) of t h e 1 3 t ests proposed for t he
endocrine disruptor screening p rogram was validated, although work was proceeding
on most of the other tests as w ell. According t o t he NRDC-EPA settlement
agreement, all eight “tier 1 " s creening t ests must be validated by December 2003, so
that testing can begi n i n s pring 2004. The s econd tier o f five t ests must be validated
Ani m al w el fare advocat es are concerne d t hat a large number of animals might
be sacrificed for t he Endocrine Disrup tor S creening P rogram, and they have
questioned t he value o f s uch t ests for assessing human health risks. They argu e t hat
alternatives to animal t ests ex ist, an d t hat o thers s houl d b e d eveloped, both t o
improve the predictive val ue of the t es ts for human health and t o protect the animals
that otherwise might suffer or die.
Fo r s everal years, federal agencies h av e b een evaluating alternative m ethods for
s c r eening chemicals for tox i city, which would require the u se of fewer l abo r a t o r y
rodents or other animals than are required using traditional t ox icity tests. Alternative
tox i city testing m ethods ex ist, but their resu lts are m ore d ifficult to interpret, in terms
of what t h ey m i ght m ean for hum an heal t h , and few are used rout i n el y b y federalrd
agenci es. T he 103 Congress established t he Applied T ox i col ogi cal R esearch and
Testing P rogram within the National Institute of Env i ronmental Health Sciences
(NIEHS), in part, “to develop and validat e assays and protocols, i ncluding alternative
methods that can reduce o r eliminate t he use o f animals in acu t e or chronic s afety
t e s t i n g, ” “t o est abl i s h cri t eri a for t h e v al i d at i o n and regu l at o ry accept ance o f
alternative t esting[ ,] and t o r eco m m e nd a process t hrough which scientifically
validated alternative m ethods can be accepted for regu latory use” (P ublic Law 103-
43, Section 1301(a)). To implement the p rogram, NIEHS established an ad hoc
In teragency C oo r d inating C ommittee on t he Validation o f Alternative M ethods
(IC C VAM). The 106 th Congress made ICCVAM a p e r m a nent interagency
coordinating committee (Public Law 106-545). EPA is a m ember of t his committee.

To date, ICCVAM has endorsed one alternative m ethod, the s o-called Up-and-Down
P roce d ure, whi ch reduces t h e num ber o f rodent s n eeded t o eval uat e acut e t o x i ci t y.
Agencies reportedly are spending approx imately $13 to $15 million t o s upport
research and d evelopment o f endocrine disruptor methods in FY2002 and FY2003.48
Legislation i n t he 107 th Congr ess
The 107 th Congress may consider proposals t o i ncrease o r d ecrease funding for
the endocrine disruption s creening p rogram , o r t o ex p and its requirements t o i nclude
additi o n a l c h e micals o r endocrine effects. Fo r ex ample, S . 1712 in the 106th
Congress would h ave required s creening o f substances discharged into the n ation’s
water. Congress appropriated $20.6 million for EPA’s endocrine disruptor screening
program and research in FY2000; $22.9 million i n FY2001; and $20.3 million, the
full amount requested in the P resident’s budget, i n FY2002. The House C ommittee
on Appropriations urged EPA “to d evelop validation p rocesses t hat i ncorporate t he
advice of the EDMVS” (Endocrine Disruptor Methods Validation S ubcommittee),
“and t o provide a report t o t he Committee on t he stat us of the EDMVS by March 15,

2002" (H. R ept. 107-159, p. 59).

Other l egislative p roposals i n t he 107 th Congress (H.R. 1990, S. 855, and S . 940)
would ex p and t he re p o rting o r regulatory r equirements o f o ther environmental
statutes to cover chemicals with possible estrogenic o r o ther hormonal effects. Such
proposals m ay garner gr eater support i f s ci entific evidence accumulates i ndicating
sign ificant adverse environmental o r hum an heal t h effect s. On t h e o t h er hand, on-
going s tudies may not substantiate cl aims of widespread adverse health or ecologi cal
effect s o f ex posure t o endocrine disruptors at environmental l evels, leading t o l ess
support from appropriators and fewer proposal s for additional research or regu lation.
Addi ti onal Resour ces
Addition a l i nformation about endocrine disruptor science, the human health
effect hypothesis, and t he views o f v arious stakeholders may b e found on the W orld
W i de W eb. The v iews of the authors o f Our Stolen Future and o t h er envi ronm ent al
protection advocat es may be ex plored at [ http://ww w . pmac.net/theos.htm]. A
skeptical view of the h ypothesis t hat pollu tants are disrupting t he endocrine systems
of humans and wildlife m ay be found at
[ h ttp://www.acsh.org/ press/releases/endmod062999.html] . EPA programs, policies
and activities are summariz ed at [ http://www.epa.gov/scipoly/oscpendo/] . A s ite that
provides links to many other websites with information about endocrine disruptors
is the Endocrine/Estrogen Letter at [ http://www.eeletter.com/links.htm] .

48“Research on Endocrine Disrupt or Exposure Focus of Grants from EPA, Other Agencies,”
Daily Environment Report, Nov. 1 , 2001, p. A-7-8.