Proceedings
Endocrine Disruptors Program
Progress Review Workshop
October 30, 2004
(Slew Orleans, LA
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Endocrine Disrupters Program Progress Review Workshop
Introduction
Despite considerable public interest and research activity, the scope and magnitude of the impact of
putative endocrine disrupting chemicals (EDCs) on human health are largely unknown. Human exposures to
these chemicals have been documented, and they are present in human tissues. Evidence is mounting from
laboratory animal studies that exposure to some environmental toxicants alters hormone signaling pathways
that can lead to toxic effects on reproduction and development, cancer, or other endocrine-related responses.
Adverse effects have been associated with hormonally active chemicals in wildlife, but few studies have
documented effects in humans exposed at levels encountered in the environment.
Research on endocrine disrupting chemicals is a high priority for the U.S. Environmental Protection
Agency's (EPA) Office of Research and Development (ORD). The U.S. EPA chairs an interagency working
group (IWG) under the Committee on the Environment and Natural Resources (CENR) of the Office of
Science and Technology Policy. The IWG, with representatives from as many as 14 agencies, coordinates
endocrine disrupters research on both the national and international level. Over the years, the CENR working
group has: (1) developed a framework for federal research related to the human health and ecological effects of
EDCs; (2) developed an inventory of ongoing federally funded research on EDCs; and (3) overlaid the frame-
work with the inventory to identify high-priority research gaps in the federal portfolio. To begin addressing
some of these gaps, the IWG has issued joint solicitations for research proposals.
ORD's National Center for Environmental Research (NCER) contributes to the endocrine disruption re-
search program through its Science To Achieve Results (STAR) grants program. Since 1995, NCER has par-
ticipated with the CENR IWG to support research to enhance our understanding about human and wildlife
exposure and health effects, toxicokinetics and toxicodynamics, and biologic pathways. In 2000, the EPA, the
National Institute for Occupational Safety and Health (NIOSH), the National Institute for Environmental
Health Sciences (NIEHS), and the National Cancer Institute (NCI) announced a joint program to support
research on exposure to endocrine disrupters and adverse health effects in humans, with a focus on epi-
demiologic approaches. Effects of interest included reduced fertility or altered reproductive function, preg-
nancy outcomes and developmental abnormalities of offspring of exposed women, hormonally mediated can-
cers among offspring exposed in utero, and endocrine-related malignancies. Study designs that clearly dif-
ferentiated exposure categories and used quantitative exposure assessment methodologies were of special
interest.
Twelve awards totaling almost $19 million were provided for studies to be conducted over a period of 3
years. The epidemiology studies are investigating effects on reproduction and development and other health
outcomes among exposed subjects or their offspring. Chemicals under study include dioxin compounds, poly-
chlorinated and polybrominated biphenyls, heptachlor, DDT/DDE, and other polyhalogenated persistent pol-
lutants, perfluorooctyl compounds, and phthalates. Investigative teams are using a variety of study designs and
methods to measure and quantify exposure and to identify susceptibility, including biomarkers and the evalua-
tion of gene-environment interaction. All of the studies will develop a quantitative estimate of risk of health
effects associated with exposure.
This Proceedings document describes a workshop held to discuss the progress of the 12 epidemiologic
studies funded as a result of the interagency collaboration. The workshop was held as a special symposium in
conjunction with the e.hormone2004 Conference organized by the Center for Bioenvironmental Research at
Tulane and Xavier Universities on October 30, 2004. The study investigators shared their research findings
regarding the association of reproductive, developmental, cancer, and other endocrine effects with exposure to
toxic hazards in the environment. The meeting culminated with a panel discussion on the "Translation of
Research Into Public Health Practice and Policy." The panel discussion provided the opportunity to present
and discuss different challenges in translating and applying the results of research to public health practice and
policy. Panelists offered brief perspectives related to state and local regulatory decisions/practices, economic
analyses, legal deliberations/actions, and public health promotions and interventions. This Proceedings in-
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Endocrine Disrupters Program Progress Review Workshop
eludes the agenda for the symposium, summaries of the progress of the 12 epidemiology studies, responses to
questions posed to the panelists before the workshop, a summary of the panel discussion, and biographical
sketches for all of the presenters and panelists.
This interagency research effort represents the largest portfolio of coordinated federal funding looking at
the impact of endocrine disrupters on humans. It is producing a body of work that will contribute significantly
to the state of scientific understanding about human exposure and health responses to potential EDCs found in
the environment. Policymakers and scientists will use the results of these studies to identify questions for
future research, inform risk assessments, and inform decisions designed to protect public health.
The research described in this report has not been subjected to the Agency's required peer review and
policy review, and does not necessarily reflect the views of the Agency. Therefore, no official endorsement
should be inferred. Any opinions, findings, conclusions, or recommendations expressed in this report are those
of the investigators who participated in the research or others participating in the Endocrine Disrupters
Program Progress Review Workshop, and not necessarily those of EPA or the other federal agencies sup-
porting the research.
For additional background information, go to the following Web site to read the Request for Applications
(RFAs) that resulted in the award of the grants described in this report:
http://es.epa.gov/ncer/rfa/archive/grants/01/endocrineOO.html
For more information on EPA's STAR program on endocrine disruption research, please contact Elaine
Francis at 202-343-9696 (francis.elaine@epa.gov). For more information on all research areas in EPA's STAR
program, please go to http://www.epa.gov/ncer.
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U.S. EPA National Center for Environmental Research
Endocrine Disrupters Program Progress Review Workshop
Endocrine Disrupters: Epidemiologic Approaches
Center for Bioenvironmental Research
Tulane and Xavier Universities
New Orleans, LA
October 30, 2004
Agenda
9:00 a.m. - 12:00 noon Part I
9:00 - 9:15 a.m. Welcome and Opening Remarks
Elaine Francis, Ph.D., U.S. Environmental Protection Agency, Office of
Research and Development; Kumiko Iwamoto, M.D., Dr.P.H.,
Epidemiology and Genetics Research Program, National Cancer Institute
9:15- 9:40 a.m. Phthalates in Pregnant Women and Children
Shanna H. Swan, Ph.D., University of Missouri—Columbia (Bio)
9:40 — 10:05 a.m. DDT, Endocrine Disruption, and Reproductive Outcomes
Xiaobin Wang, Sc.D., Children's Memorial Hospital, Chicago (Bio)
10:05 - 10:30 a.m. Exposure to EndocrineDisruptors andNeurodevelopmental Outcomes in
an Agricultural Community
Laura Fenster, Ph.D., California Department of Health Services (Bio)
10:30 — 10:55 a.m. Epidemiologic Evaluation of Perfluorooctyl Compounds as Endocrine
Disruptors in Men
James H. Raymer, Ph.D., RTI International (Bio)
10:55 — 11:20 a.m. Serum PCBs, CYPlal, GST Genetic Polymorphisms, and Breast Cancer
in Connecticut Women
Tongzhang Zheng, M.D., Sc.D., Yale University (Bio)
11:20 - 11:45 a.m. Persistent Organic Pollutants and Endometriosis Risk
Victoria Holt, Ph.D., Fred Hutchinson Cancer Research Center (Bio)
11:45 a.m. - 12:00 noon Questions and Discussions
12:00 noon-1:00 p.m. Lunch
1:00- 4:40 p.m. Part II
1:00-1:10 p.m. Reconvene
1:10— 1:30 p.m. Dioxins, Male PubertalDevelopment, and Testis Function
Russ Hauser, M.D., M.P.H., Sc.D., Harvard School of Public Health (Bio)
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1:30 —1:50 p.m. Latent Effects of Gestational Exposure to Heptachlor
Dean Baker, M.D., M.P.H., University of California (Bio)
1:50 — 2:10 p.m. Early Childhood Development and PCB Exposures in Slovakia
Irva Hertz-Picciotto, Ph.D., University of California (Bio)
2:10 — 2:30 p.m. Endocrine Disrupting Chemicals and Thyroid Outcome Study: The Great
Lakes Fish Consumption Study
Pamela Imm, M.S., Wisconsin Department of Health and Family
Services (Bio)
2:30 — 2:50 p.m. Persistent Organochlorine Compounds, Genetic Susceptibility, and
Testicular Cancer Risk
Stephen M. Schwartz, M.D., Fred Hutchinson Cancer Research Center (Bio)
2:50-3:10 p.m. Break
3:10- 4:40 p.m. Panel Discussion: Translation of Research Into Public Health Practice
and Policy
Confirmed Panelists:
Harold Zenick, National Health and Environmental Effects Research
Laboratory, U.S. EPA (moderator) (Bio)
R. DeLon Hull, Ph.D., National Institute for Occupational Safety and
Health, Centers for Disease Control and Prevention (Bio)
LuAnn White, Ph.D., DABT Center for Applied Environmental Public
Health, Tulane University (Bio)
Mark Dickie, Ph.D., University of Central Florida (Bio)
Dan Greenbaum, Health Effects Institute (Bio)
This 90-minute panel discussion will explore the interface between basic and applied health research and its
application to risk prevention and reduction and the promotion of health. The panel represents a broad
spectrum of perspectives in this area, including policymakers, regulators, researchers, medical practitioners,
economists, and environmental public health advocates.
4:45 p.m. Evaluations and Adjournment
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Meeting Abstracts
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Endocrine Disrupters Program Progress Review Workshop
Phthalates in Pregnant Women and Children
Shanna H. Swan
University of Missouri—Columbia, Columbia, MO
Scientific Question
In this study, we are examining current levels of phthalates in the environment in relation to human repro-
ductive health. We also are examining phthalate levels in relation to personal product use and other factors,
including geographic location.
Methods
We are following children born to subjects recruited in our Study for Future Families (SFF), a pregnancy
cohort study conducted in four U.S. cities. In addition to assaying urine samples from the babies and mothers
(both pre- and postnatally) for metabolite levels of nine phthalates, pediatric physicians are conducting stan-
dardized genital and anthropometric examinations on the babies, and the mothers are providing detailed infor-
mation on their use of personal care products. We expect that by December 2005, we will have complete data
on 500 families. We are examining mothers' self-reported use of phthalate-containing products (soaps, cosmet-
ics, teething rings, nipples, and other plastics) at the time of urine collection in relation to measured phthalate
metabolite levels. Levels of phthalate metabolites in the mothers' prenatal urine are being examined in relation
to infant growth and development. Data from maternal questionnaires are being modeled to identify factors
(including geographic location) that predict phthalate metabolite levels. Here we report on results from prena-
tal samples from 214 women in Columbia, MO (MO), Minneapolis, MN (MN) and Los Angeles, CA (CA).
Results
Of the nine phthalates assayed, all were found above the LOD in at least 50 percent of prenatal samples,
and five metabolites were found in almost all (over 90%) of the women (see Table 1). We saw a wide range for
most metabolites at levels consistent with prior reports. Surprisingly, we found considerable geographic vari-
ability, with higher levels for eight of nine metabolites in women living in mid-Missouri (MO) compared with
those in MN. Because we previously found poor semen quality in men living in MO compared with men living
in MN, we hypothesized that elevated phthalate levels in MO women reflected household exposure that was
shared by their partners and that adversely affected semen quality. In fact, in general linear models, we found
that metabolite levels in women's samples of three butyl phthalates, but not other phthalates, were significantly
and negatively associated with their partners' semen quality (see Table 2).
Conclusions
Our study is the first to obtain urinary phthalate metabolites in samples from mothers (pre- and postna-
tally) and infants. The finding of higher levels of eight of nine phthalates in pregnant women in mid-Missouri
compared with urban Minneapolis is unexpected but would be consistent with the use of phthalates as inert
compounds in pesticides commonly used in mid-Missouri. Our preliminary finding that mothers' levels of
three butyl phthalates are inversely related to fathers' semen quality is novel and surprising, suggesting that
mothers' levels may reflect a household exposure. We will measure phthalates in the men's urine and correlate
these with the mothers' and babies' levels to test this hypothesis. Two human and several animal studies have
found butyl phthalates to be related to decreased semen quality, consistent with our findings.
This work was supported by the Environmental Protection Agency STAR Grant No. R829436.
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Table 1. Phthalate metabolite levels by center.
Metabolite Statistics MO MN CA
N
mBP
mBZP
mCPP
mEHHP
mEHP
mEOHP
mEP
mMP
miBP
Mean
Median
% > LOD
Mean
Median
% > LOD
Mean
Median
% > LOD
Mean
Median
% > LOD
Mean
Median
% > LOD
Mean
Median
% > LOD
Mean
Median
% > LOD
Mean
Median
% > LOD
Mean
Median
% > LOD
63
19.1
26.6
95.2 %
29.2
15.6
95.2 %
3.1
2.5
77.8 %
61.7
14.6
96.8 %
15.7
5.9
85.7 %
52.3
13.9
95.2 %
876
100
96.8 %
2.0
2.0
46.0 %
4.0
3.0
82.5 %
87
14.8
19.1
95.4 %
13.2
8.2
93.1%
2.5
1.5
65.5 %
21.0.
9.7
98.9 %
7.7
4.1
83.9%
19.1
8.8
95.4 %
358
86
100 %
2.9
1.3
52.9 %
3.0
2.1
69.0 %
64
17.7
28.8
98.4 %
17.6
8.7
95.3 %
3.3
2.5
70.3 %
24.5
11.1
98.4 %
6.0
2.6
68.8 %
20.0
9.5
95.3 %
1489
265
100 %
2.4
1.3
51.6%
4.2
2.1
70.3 %
Table 2. Woman's prenatal levels of butyl phthalates and partner's semen parameters.
Semen Parameter Parameter mBP mBZP miBP
Concentration2
Total motile count2
Correlation
p-value
Beta coefficient1
p-value
Correlation
p-value
Beta coefficient1
p-value
-0.16
(0.028)
-0.0018
(0.025)
-0.21
(0.003)
-0.003
(0.0036)
-0.07
(0.32)
-0.006
(0.32)
-0.14
(0.048)
-0.0019
(0.045)
-0.17
(0.038)
-0.113
(0.05)
-0.22
(0.008)
-0.019
(0.024)
1 GLM models of log semen parameters in relationship to log phthalate metabolite level, controlling for absti
nence time, season, and fertility problems.
2 Using hemocytometer counts on first semen samples.
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DDE, Endocrine Disruption, and Reproductive Outcomes
Xiaobin Wang
Children's Memorial Hospital, Chicago, IL
Scientific Question/Hypothesis
Dichlorodiphenyl trichloroethane (DDT) is a broad-spectrum synthetic insecticide that was used widely in
agriculture and residential settings beginning in the 1940s. It was banned in the United States in 1972 and in China
in the 1980s. Because of their chemical stability, lipophilic nature, and propensity to bioaccumulate, DDT and its
primary metabolite, dichlorodiphenyl dichloroethene (DDE), remain ubiquitous contaminants of various en-
vironmental media, foods, and human adipose tissue despite bans on their use. DDE residues have been found
in detectable amounts in all human populations monitored to date. DDT and DDE are similar structurally to
various steroid hormones, including estrogens, and might interact with hormone functions, thereby raising
concerns about their potential toxicity via endocrine disruption. Both animal and in vitro studies support the
hypothesis that DDT, its metabolites, and related compounds are potentially important human reproductive toxins.
However, the epidemiologic data associating DDT with human reproductive health are limited. The overall goal
of this project, which is funded by the National Institute of Environmental Health Sciences, is to establish a
dose-response relationship between exposure to DDE, endocrine dysfunction, and adverse reproductive out-
comes in women.
Study Design
This prospective cohort study was conducted among women textile workers in China. The women were
enrolled before conception. The information collected at baseline and through followup questionnaire interviews
includes sociodemographic characteristics, medications, past medical and reproductive history, job history and
occupational exposures, job-related stress, social support, physical activities, active and passive smoking, indoor
air pollution, air conditioner use, consumption of tea, coffee, and alcohol, and dietary intake. The enrolled women
were followed prospectively for reproductive endpoints. Each woman kept a diary of menstrual bleeding, pre-
menstrual symptoms, use of medications, illness, sexual intercourse, contraceptive use, active and passive smok-
ing, alcohol use, physical activity, stress, and any unusual events or accidents and job activities. Daily urine sam-
ples were collected from each woman for up to 1 year or until she became pregnant. Urine samples were analyzed
for (3-hCG to detect early pregnancy loss. Furthermore, preconception serum DDT and DDE concentrations and
the urinary hormones pregnanediao-3-glucorinide (PdG) and estrogen conjugates (EiC) were measured.
Research Results/Conclusions
This presentation will summarize the major findings obtained to date, including: (1) distributions and
determinants of preconception serum DDT and its isomers; (2) DDT exposure, age at menarche, and length of
menstrual cycle; (3) DDT exposure and early pregnancy loss; (4) DDT exposure and birth outcomes; and (5)
DDT exposure and urinary hormone (PdG and EiC) concentrations. Our data provide consistent evidence that
DDT and DDE exposures affect reproductive hormones and a broad spectrum of reproductive outcomes in a
dose-response fashion.
Methodological Contributions/Innovations
The availability of prospectively collected epidemiologic and clinical data as well as urine and plasma samples
from a large homogeneous cohort of women, combined with a multidisciplinary approach and state-of-the-art
laboratory analyses of plasma DDT/DDE and urinary reproductive hormones, provides an opportunity to in-
vestigate dose-response relationships between DDE exposure, hormone dysfunction, and adverse reproductive
outcomes.
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Biological Mechanisms
Our data support the hypothesis that DDT/DDE is a reproductive toxin and might act at least in part via an
endocrine disruption mechanism.
Scientific Significance
The results from this study should improve our understanding of the scope, magnitude, and underlying
biological mechanisms of DDT/DDE related to human reproductive health.
This work was supported by the National Institute of Environmental Health Sciences Grant No. 7
R01ES011682-04.
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Exposure to Endocrine Disrupters and Neurodevelopmental
Outcomes in an Agricultural Community
Laura Fenster, California Department of Health Services, Emeryville, CA
(Brenda Eskenazi, Principal Investigator, University of California, Berkeley, CA)
Agricultural pesticide use may be a significant source of environmental endocrine disrupter (ED) exposure
in the United States. California, the leading agricultural state in the Nation, requires the reporting of all agricul-
tural pesticide use. The Pesticide Use Reporting (PUR) data indicate that over 600,000 pounds of potentially
ED pesticides are used annually in the Salinas Valley. Animal and human evidence suggests that prenatal ex-
posure to EDs might result in adverse neurodevelopmental effects on children. The objectives of this study are
to: (1) determine whether prenatal exposure to ED pesticides, including nonpersistent ED pesticides and or-
ganochlorine pesticides, is associated with adverse effects on fetal growth and neurobehavioral development of
children, and (2) identify population correlates of exposure (e.g., occupation, season, PUR data) so that appro-
priate interventions can be developed in the future to reduce exposure. We are investigating this relationship in
approximately 600 pregnant women and their children from low-income Latino families living in the Salinas
Valley of Monterey County, CA. These children, whose mothers were enrolled during pregnancy, are partici-
pants in the Center for Health Analysis of Mothers and Children of Salinas (CHAMACOS), a study conducted
by the Center for Children's Environmental Health Research at the University of California—Berkeley and
funded by the National Institute of Environmental Health Sciences and EPA. CHAMACOS is investigating the
relationship between environmental exposures and children's health.
We measured organochlorine pesticides and polychlorinated biphenyls (PCBs) in serum samples collected
from the pregnant women at 26 weeks gestation, and nonpersistent ED pesticides or their metabolites in mater-
nal urine samples collected at 13 and 26 weeks gestation. We are examining the association of these biomark-
ers with growth and neurodevelopment in newborns (Brazelton) and in 6-, 12-, and 24-month-old children.
Data were collected about family sociodemographic characteristics, habits, housing, exposure, work, and medi-
cal history. Geographic coordinates for each home have been linked to the PUR data.
We found that organochlorine and several other pesticide metabolite levels in our population were higher
than the U.S. averages reported by the Centers for Disease Control and Prevention (CDC) in the Second Na-
tional Report on Human Exposure to Environmental Chemicals (2003). For example, we observed that preg-
nant women in the CHAMACOS cohort had median DDE levels on average more than threefold higher than
Mexican-American women of reproductive age in the National Health and Nutrition Examination Survey
study during the same time period (1,053 versus 331 ng/g lipid, respectively). Factors related to increased
DDT/DDE levels included the mother's age and being born in Mexico versus the United States. Lower levels
of DDT/DDE were associated with more years lived in the United States, having more than one child, and
higher education. We have examined the relationship of these exposures to fetal growth and length of gestation
and found few adverse associations. Increased DDE levels were associated with somewhat shorter infant body
length (|3 = -0.43 centimeters, p = 0.07) and lower birthweight ((3 = -69 grams, p = 0.12) but were not related to
gestational age, head circumference, or ponderal index. However, the sum of PCBs reported to induce CYP1A
and CYP2B detoxifying enzymes was positively associated with neonatal thyroid-stimulating hormone (TSH)
levels. Neonatal TSH levels have been shown to be related to infant neurodevelopment. Finally, CDC has de-
veloped new laboratory methods to test for ethylene thiourea (ETU) in urine. ETU is an endocrine disrupter
and breakdown product of commonly used fungicides (maneb and mancozeb) in agriculture and forestry.
This study will provide key data on the exposure and health effects of persistent and nonpersistent ED
pesticides on pregnant women and their children living in an agricultural community. This information is
directly related to efforts by federal agencies, including the National Institute for Occupational Safety and
Health and EPA, to understand and reduce occupational and take-home exposures to these pesticides.
This work was supported by the National Institute of Occupational Health and Safety Grant No. 1
R010H007400-01.
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Potential Endocrine-Disrupting Pesticides
Use in 2000 by Public Lands Survey Section
(1 square mile)
GILROY
•• MCALLISTER
SALINAS
Legend
Urban Areas
~\ Salinas and Lower Pajara Valleys (Study Area)
Potential Endocrine-Disrupting Pesticides
>Zero to 76 pounds
76 to 543 pounds
B 543t° 2,006 pounds
H 2,006 to 6,815 pounds
Figure 1. Potential endocrine-disrupting pesticides.
Source: 2000 Pesticide Use Reports.
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Epidemiologic Evaluation of Perfluorooctyl Compounds
as Endocrine Disrupters in Men
James H. Raymer
RTI International, Research Triangle Park, NC
Products containing perfluorinated chemicals, including perfluorooctanesulfonate (PFOS) and perfluoro-
octanoate (PFOA), have been largely withdrawn from the market by a major manufacturer amid concerns of
persistence, toxicity, and widespread population exposures. Additional concerns have been raised recently
about PFOA from cookware. This study is focused on the possible relationships of PFOS/PFOA concentra-
tions in plasma and semen with semen quality and endocrine status of a potentially susceptible subpopulation
(i.e., men of couples who present at a fertility clinic). Study participants are expected to represent a range of
exposures to PFOA and PFOS (linear and branched), as well as a range of semen quality. Concentrations in
these biological media will reflect the multiroute exposures to these chemicals experienced by virtually all
people in our society. Semen quality is being assessed using both routine measures (sperm concentration, mo-
tility) and a test designed to more accurately and reproducibly assess normal, motile, and fertile sperm (swim-
up). Measurements of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and free and total
testosterone reflect the hormonal status of the males and will provide evidence of perturbed endocrine func-
tion. In 108 semen samples analyzed to date, the mean sperm concentration was 63 x 10 /mL (0-432 x
106/mL), the average motility was 53 percent (0-89%), and the average swim-up total motile was 1.4 x 106/mL
(0-4.5 x 106/mL). These results will be viewed in conjunction with concentrations of PFOS isomers/ PFOA in
plasma and semen, circulating hormones, and potential sources of exposure reported by participants.
This work was supported by the National Institute of Environmental Health Sciences Grant No. 1
R01ES011683-01.
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Serum PCBs, CYP1A1, GST Genetic Polymorphisms, and Breast
Cancer in Connecticut Women
Tongzhang Zheng, Y. Zhang, T.R. Holford, J.P. Wise, F. Ali-Osman, P. Boyle, and S.H. Zahm
Yale School of Public Health, New Haven, CT
This case-control study evaluated the potential gene-environment interaction between CYP1A1, glu-
tathione S-transferase (GST), and polychlorinated biphenyl (PCB) on the risk of breast cancer among Cauca-
sian women in Connecticut. A total of 374 histologically confirmed breast cancer cases and 406 noncancerous
controls were included in this study. Compared with those who had the homozygous wild-type CYP1A1 m2
genotype, a significantly increased risk of breast cancer was found for postmenopausal women who had the
CYP1A1 m2 variant genotype (OR = 2.4, 95% CI: 1.1,5.0). The risk was highest for postmenopausal women
with higher levels of serum PCBs (OR = 3.8, 95% CI: 1.2,12.1). CYP1A1 ml and m4 genotypes were not asso-
ciated with breast cancer risk independently or in combination with PCB exposures in this study. GSTM1 and
GSTP1 genotypes were not associated with breast cancer risk. Among postmenopausal women, GSTT1 null
genotype was associated with a 70 percent increased risk of breast cancer (OR = 1.7, 95% CI: 1.0,2.8), and a
nonsignificant twofold increased risk (OR = 2.2, 95% CI: 0.9,5.2) was observed for those who also had higher
serum levels of PCBs. In summary, the CYP1A1 m2 and GSTT1 genetic polymorphism was associated with an
increased risk of female breast cancer and may modify the relationship between PCB exposure and breast can-
cer risk.
This work was supported by the National Cancer Institute Grant No. 5 R01CA095788-02.
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Persistent Organic Pollutants and Endometriosis Risk
Victoria L. Holt1, Stephen M. Schwartz, and Dana B. Barr2
University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, WA;
Centers for Disease Control and Prevention, Atlanta, GA
Endometriosis, a chronic disease affecting approximately 5 percent of U.S. reproductive-aged women,
causes chronic pelvic pain, dysmenorrhea, and infertility. Endometriosis has been linked in epidemiologic
studies to exposures indicating high circulating estrogen levels. There has been recent public and scientific
concern that endocrine-disrupting chemicals in the environment may have estrogenic effects in the body and
therefore increase endometriosis risk, but results of the few epidemiologic studies of this issue have been
mixed. Thus, we undertook this study to examine the relationship between endometriosis and exposure to or-
ganochlorine compounds and polychlorinated biphenyls in a large health maintenance organization (HMO)
population. An additional question of interest was whether these associations are modified by polymorphisms
in genes involved in estrogen metabolism.
The current study is an ancillary investigation to a National Institute of Child Health and Human Devel-
opment-funded case-control study of risk factors for endometriosis that was conducted within a large Washing-
ton State HMO, providing extensive interview data on a variety of characteristics, including occupational and
nonoccupational chemical exposures. Results of laboratory analyses of two polymorphic genes (GSJM1 and
COMT) involved in detoxification and estrogen metabolism are available for 295 cases and 581 controls from
that study, and the current study determined genotypes of two polymorphic cytochrome p450 genes (1A1 and
1A2) in these subjects as well. Initial results from the interview data on pesticide exposures indicate no
association between self-reported exposure to all pesticides combined and endometriosis risk (OR 0.96, 95%
CI 0.70-1.33); however, exposure to herbicides and fungicides appeared to increase disease risk. Specifically,
any exposure (occupational and nonoccupational exposures combined) to herbicides was associated with a
significant increase in endometriosis risk (OR 1.65, 95% CI 1.03-2.64), and a stronger risk elevation was seen
when considering occupational herbicide exposure separately (OR 2.87, 95% CI 0.98-8.40). Similarly, any
self-reported exposure to fungicides was associated with more than a doubling of risk of endometriosis (OR
2.15, 95% CI 0.99-4.70), and there was a stronger risk elevation with occupational fungicide exposure (OR
2.80, 95% CI 0.95-8.23). There was little apparent modification of these risks by genetic polymorphisms.
We are currently in the process of determining serum levels of total polychlorinated biphenyls (PCBs),
PCB congeners, hexachlorobenzene, p-hexachlorocyclohexane ((3-HCH), X-HCH, aldrin, hepachlor epoxide,
oxychlordane, transnonachlor, p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE), o,p'-DDE, dieldrin, endrin,
o,p'-dichlorodiphenyl trichloroethane (o,p'-DDT), p,p'-DDT, and mirex residues for 283 cases and 581 con-
trols. In addition, 450 urine samples (150 cases and 300 controls) will be tested for levels of the methoxychlor
metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE).
This work was supported by the Environmental Protection Agency STAR Grant No. R829438.
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Dioxins, Male Pubertal Development, and Testis Function
Russ Hauser
Harvard School of Public Health, Boston, MA
Puberty is the transition from the prepubertal state to sexual maturity and the attainment of reproductive
capacity. There is currently scientific and public debate regarding the potential effects of environmental chemi-
cals on pubertal development. Specific concern centers on whether exposure to environmental toxins causes an
earlier onset of puberty and alters the progression of pubertal development and the attainment of sexual matu-
ration. Chemicals of concern include dioxins, a family of highly toxic environmental contaminants. Although
the general U.S. population has background exposure to dioxins through diet and air, there are special popula-
tions with high dioxin exposure. Studies within these special populations are more powerful than general popu-
lation studies with a narrower range of exposure. Therefore, in the proposed study, we targeted a population in
Chapaevsk, Russia, with documented high exposure to dioxins. The source of contamination is a large chemi-
cal-industrial complex built during World War II to manufacture chlorine-containing compounds, including
chemical warfare agents.
We are conducting a prospective cohort study designed to determine the association between dioxins and
physical growth and the timing of pubertal development in boys from Chapaevsk. Between May 2003 and
January 2005, we will recruit a cohort of 500 boys ages 8 and 9 years. At recruitment, baseline examinations
focus on physical and physiologic markers of growth and pubertal development. Physical markers include
careful measurement of anthropometric factors and determination of secondary sexual characteristics and go-
nadal maturation assessed by Tanner staging for genital and pubic hair development and measurement of tes-
ticular volume. Physiological markers consist of biochemical measures assessed by increased levels of repro-
ductive hormones, such as follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin, inhibin-
B, and mullerian-inhibiting substance. Blood samples will be collected and analyzed for dioxins.
The specific aims of the project are to: (1) investigate the relationship between exposure to dioxins and di-
oxin-like compounds with somatic growth, weight gain, and body mass index; (2) explore the relationship be-
tween serum levels of dioxins and dioxin-like compounds and the timing and tempo of pubertal development;
and (3) investigate the biological processes underlying the effects of dioxins and dioxin-like compounds on
growth and pubertal maturation.
This work was supported by the Environmental Protection Agency STAR Grant No. R829437.
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Latent Effects of Gestational Exposure to Heptachlor
Dean Baker1, Haiou Yang1, Ulrike Luderer1, Satry Gollapudi1, and James Kesner2
University of California—Irvine, Irvine, CA; 2National Institute for Occupational
Safety and Health, Washington, DC
Scientific Question
Does gestational exposure to the chlorinated cyclodiene pesticide heptachlor result in latent effects on
neurobehavioral, reproductive, or immunologic function?
Background
The study is based on a well-characterized episode in which the commercial milk supply on the Hawaiian
island of Oahu was contaminated with heptachlor epoxide (HE) during a 15-month period (1981-1982), result-
ing in gestational exposure to offspring of women who drank cow's milk during that period. The overall study
has had three phases. First, we conducted two statewide population-based surveys to measure HE concentra-
tions in human milk and sera. These surveys verified that HE concentrations in the biological specimens were
significantly higher in the Oahu population than on the unexposed neighbor islands. These surveys also dem-
onstrated a significant association between HE concentrations and reported cow's milk consumption during
1981 and 1982. Second, we conducted an islandwide survey of 20,408 high school students to identify 1,891
young adults who were born during 1981 and 1982 and lived on Oahu for at least 15 years. Using this sam-
pling frame, we selected 332 Oahu-born participants and 113 participants not born on Oahu to assess neurobe-
havioral function and academic achievement using standard test instruments and school records. Analyses con-
trolling for many confounding factors indicated that consumption of cow's milk by mothers during pregnancy
was associated with lower neurobehavioral performance and more reported behavioral problems. There were
no apparent associations for school-based performance measures.
Study Design
For the current study of reproductive and immune function, we are using the same sampling frame to re-
cruit 400 Oahu-born young adults and 200 comparison participants who were not born on Oahu, matched by
age and ethnicity. Indicators of reproductive function include serum testosterone in males; estradiol and pro-
gesterone in females; luteinizing hormone and follicle-stimulating hormone in both sexes; semen samples; and
daily first morning urine specimens in females for one menstrual cycle to measure luteinizing hormone, es-
trone-3-glucuronide, and pregnanediol 3-alpha-glucuronide. Indicators of immune function include skin tests
for standard recall antigens; antibody titer response to immunization with tetanus and pneumococcal vaccine;
Thl and Th2 type CD4+ cell subsets in peripheral blood; and susceptibility of peripheral blood T cells to acti-
vation-induced cell death using in vitro analysis of Fas (CD95) and its ligand (CD95L) expression.
Results
The study has initiated followup of one-half of the sampling frame and enrolled 250 participants, including
238 participants with substantially complete data collection. Of these participants, 209 were born on Oahu and
29 were born elsewhere. Initial analysis of the reproductive and immune function parameters has indicated no
clear associations with place of birth or, among Oahu-born participants, mothers' reported cow's milk con-
sumption during pregnancy.
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Discussion
The findings indicate that gestational exposure to HE may be associated with subtle latent effects on neu-
robehavioral performance. It is relevant to evaluate whether gestational HE exposure also is associated with
latent effects on reproductive and immune function. Further data collection will be needed to achieve sufficient
statistical power to address the hypotheses. This study is funded by the U.S. Environmental Protection Agency.
This work was supported by the Environmental Protection Agency STAR Grant No. R829439.
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Endocrine Disrupters Program Progress Review Workshop
PCB Exposures in Eastern Slovakia in a Birth Cohort
Irva Hertz-Picciotto1, A. Yu, H-YPark^A. Kocan2, J. Petrik2, T. Trnovec2
University of California—Davis, Davis, CA; 2Slovak Medical University,
Bratislava, Slovak Republic
Contamination from a polychlorinated biphenyl (PCB) manufacturing plant in eastern Slovakia is wide-
spread in the environment, and a cohort of births in two districts is being assembled to determine early life de-
velopmental effects from exposures. PCBs are being analyzed in maternal serum collected at delivery by gas
chromatography with an electron capture detector (GC-ECD) and will be related to a number of immunologic
and neurodevelopmental outcomes during the first few years of life. We report on exposure levels measured in
maternal serum as ug/dL on a wet weight basis, and on the individual-level predictors of these body burdens.
A measure of total PCBs was obtained by summing the following 15 PCB congeners: 28, 52, 101, 105, 114,
118, 123 and 149, 138, 153, 156 and 171, 157, 167, 170, 180, and 189. Preliminary data from several hundred
births indicate that the exposure levels are lower than those reported in the late 1990s, but are still high relative
to most other populations currently under investigation. From these data, we obtained a mean of 0.689 ug/dL,
with an interquartile range from 0.282 to 0.776 ug/dL and a median of 0.441 ug/dL. Descriptive data from the
first few hundred births show that more than one-half of the families grow their own fruits and vegetables,
about one-third raise their own chickens, and about one-third raise their own pigs. Total PCB concentration
was associated with increasing age of the mother, decreasing parity, increasing duration of pregnancy, having a
relative who worked at the Chemko manufacturing plant, district of residence, and consumption of eggs from
locally raised chickens. The association with age likely represents duration of exposure, whereas the inverse
relationship with parity reflects unloading during previous pregnancies and/or lactation. The gestation result
prob- ably is due to the rise in lipids during late pregnancy. The higher body burdens among those consuming
local eggs raises concerns about environmental cleanup.
This work was supported by the National Cancer Institute Grant No. 1 R01CA096525-01.
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Endocrine Disrupting Chemicals and Thyroid Outcome Study:
The Great Lakes Fish Consumption Study
Pamela Intnt, Wisconsin Department of Health and Family Services, Madison, WI
(Henry Anderson, Principal Investigator, Wisconsin Department of Health
and Family Services, Madison, WI)
The Wisconsin Department of Health and Family Services began survey data collection for the Endocrine
Disrupting Chemicals and Thyroid Outcome Study in the spring of 2004. The overall goal of the study is to
assess the impact offish consumption and other dietary and occupational exposure to polybrominated diphenyl
ether (PBDE), polychlorinated biphenyl (PCB), and other environmental contaminants on thyroid and repro-
ductive health status.
The study sample consists of charter boat captains, anglers, and infrequent fish consumers who partici-
pated in a 1993-94 reproductive outcome study. A screener questionnaire was mailed to over 3,600 respon-
dents and focused on fish consumption and medical history. Respondents who agreed to participate in the fol-
lowup study provided contact information.
The followup study will characterize serum thyroid parameters, reproductive hormone levels, and PCB
and PBDE levels of over 500 study participants. These participants also will complete another questionnaire
asking for a more detailed medical history, medication use, and occupational exposure to chemicals. Specimen
collection has just begun and will continue through 2005. Based on the preliminary analysis of 223 participants
in an Agency for Toxic Substances and Disease Registry repeat biomarker study in 2003, we anticipate di-
chlorodiphenyl dichloroethene and PCB levels to continue to decrease. (Biomarker data were compared with
1992 laboratory results.)
This work was supported by the Environmental Protection Agency STAR Grant No. R830254.
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Endocrine Disrupters Program Progress Review Workshop
Persistent Organochlorine Compounds, Genetic Susceptibility,
and Testicular Cancer Risk
Stephen M. Schwartz1, Mary L. Biggs1, Chu Chen1, Larry L. Needham2, and Dana B. Barr2
1Fred Hutchinson Cancer Research Center, Seattle, WA; 2National Center for Environmental Health,
Centers for Disease Control and Prevention, Atlanta, GA
Background
The incidence of testicular germ cell carcinoma (TGCC), the most common malignancy in young men, has
increased several-fold since the 1950s. Experimental and observational studies in animal systems have raised
concern that the increasing rates are due in part to populationwide, persistent exposure to endocrine-disrupting
compounds from industrial and agricultural applications. Many such compounds appear to impair the synthesis
or function of testosterone in vertebrates, and a reduced testosterone (e.g., as manifested by the testicular dys-
genesis syndrome) may be an important cause of TGCC in humans. Whether human exposure to such chemi-
cals is associated with TGCC risk has not been directly studied.
Objectives
We will determine whether the risk of TGCC is related to serum levels of persistent organochlorines, fo-
cusing on p,p'-DDE, polychlorinated biphenyls (PCBs), and other compounds (e.g., dieldrin, hexachlorocyclo-
hexane, hexachlorobenzene). We also will examine whether the risk of TGCC associated with these com-
pounds varies according to whether a person carries versions of genes that are likely to be involved in how
these compounds affect TGCC risk. Specifically, we will determine whether TGCC risk is related to interac-
tions between: (1) elevated serum p,p'-DDE and polyglutamine repeat tract polymorphisms in the androgen
receptor (AR) gene, and (2) elevated serum PCB levels and genetic polymorphisms in oxidative stress defense
enzyme genes (e.g., glutathione S-transferases and superoxide dismutases).
Approach
A population-based series of TGCC cases (-250) and controls (-750), all of whom resided in the Seattle
metropolitan area between 1999 and 2003, are being recruited into a protocol that includes: (1) a detailed in-
person interview; (2) a blood draw; (3) analyses of genetic variation in androgen synthesis, metabolism, and
signaling genes; and (4) analysis of serum levels of organochlorine compounds. Results relating to available
organochlorine compound data and genetic polymorphism data will be presented for approximately 560 and
775 participants, respectively. The results should add significant new information to our understanding of the
role, if any, of environmental contaminants in the pathogenesis of TGCC.
This work was supported by the National Cancer Institute Grant No. 1 R01CA095790-01.
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The Effects of Perinatal Endocrine Disruption in Children
Philippe Grandjean
Harvard School of Public Health, Boston, MA
Scientific Question/Hypothesis
The extended followup of this cohort, located in the Faroe Islands, will be used primarily to examine
whether biomarkers of exposure to endocrine disrupters are associated with development and neurobehavioral
function in boys and/or girls at prepuberty ages, and whether effects of organochlorine compounds, such as
polychlorinated biphenyls (PCBs), can be differentiated from those caused by exposures, such as methylmer-
cury.
Study Design
This study is based on consecutive singleton births at the National Hospital, Torshavn, Faroe Islands, dur-
ing a 12-month period in 1994-1995. In this community, excess exposures to persistent organic pollutants,
including PCBs and p,p'-DDE, occur because of the traditional habit of eating pilot whale, including the blub-
ber. The subjects also were exposed prenatally to elevated concentrations of methylmercury. The exposures
cover a range of up to 1,000-fold, and postnatal exposure data also have been obtained. Detailed clinical ex-
aminations were carried out at ages 7.5 and 10 years. Both examinations focus on neurobehavioral functions,
especially sex-dimorphic functions, and general development, and the tests included are comparable. Blood
samples are included for exposure assessment.
Research Results/Conclusions
At age 7 years, 165 of the 184 cohort members were examined. The attrition was due mainly to families
that had moved abroad. In the spring of 2004, the examinations at age 10 were initiated. All of the first 50
children invited for the 10-year examinations accepted, and all but two consented to have a blood sample
taken.
Preliminary analysis of the 7-year data suggests that the results are comparable to those of the first Faroese
cohort, also examined at age 7 years, and a neurotoxic effect of mercury exposure has been confirmed. How-
ever, detailed analysis of the data is awaiting the completion of advanced exposure measures (as well as the
examinations at age 10 years). We are using stored maternal pregnancy serum to determine the integrated es-
trogen activity (after removal of endogenous hormones), as well as the dioxin-like effect on the Ah receptor.
This work will be completed later this fall.
Methodological Contributions/Innovations in the Areas of Recruitment/Enrollment, Exposure Assess-
ment, Health Effects Assessment, FollowUp, or Analytic Models
The Faroe Islands constitute a highly useful setting for this type of research. Because some Faroese eat
substantial amounts of whale blubber and others eat little or none, a wide variety of exposures occur, and ex-
posures are independent of major confounders. The highest exposures greatly exceed those reported in Western
societies, whereas the lowest exposures overlap with U.S. levels and therefore comprise a built-in control
group.
Biological Mechanisms Suggested by Research Results
Research data have not yet been analyzed because we are still in the process of seeing subjects. We antici-
pate that the receptor-activation results will provide integrated measures of the exposure levels and that they
might affect sex-dimorphic functions.
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Scientific Significance
Environmental exposures to persistent pollutants include compounds that might cause disruption of endo-
crine functions. Prenatal exposures to endocrine disrupters (EDs) have been linked to developmental abnor-
malities and neurobehavioral deficits, but causal links to specific compounds as well as purported dose-
response relationships are unclear. This study includes advanced assessment of prenatal ED exposures and
objective assessment of important clinical outcomes assumed to be sensitive effects. The present study will
shed new light on these questions.
This work was supported by the National Institute of Environmental Health Sciences Grant No. 7
R01ES011681-03.
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U.S. EPA National Center for Environmental Research
Endocrine Disruptors Program Progress Review Workshop
Endocrine Disruptors: Epidemiologic Approaches
Center for Bioenvironmental Research
Tulane and Xavier Universities
New Orleans, LA
October 30, 2004
Panel Discussion Summary
Dr. Harold Zenick, Associate Director for Health, National Health and Environmental Effects Research Labo-
ratory (NHEERL), was the moderator of the panel discussion. He introduced each of the panel members. These
included: Mr. Dan Greenbaum from the Health Effects Institute, Boston, MA; Dr. R. DeLon Hull, National
Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention, Cincinnati,
OH; Dr. LuAnn White, Director of the Center for Applied Environmental Public Health (CAEPH), Tulane
University, New Orleans, LA; and Dr. Mark Dickie, Professor of Economics, University of Central Florida,
Orlando, FL.
Dr. Zenick noted that the seating arrangement was meant to encourage a dialog between the panel members
and the audience. Members of the panel were chosen for their wide variety of research throughout their ca-
reers. Prior to the panel discussion, each of the panel members was asked to respond to a set of five questions;
their written responses were included in the workshop's handout. Dr. Zenick posed each question. The panel
members provided verbal responses and then the audience was given an opportunity to comment.
Question 1: Do you have the opportunity to identify and use the most relevant research in carrying out your
professional obligations? If so, how can you document the value/impact of such research? Do
current systems/processes work to provide the needed information? What new approaches
should be considered?
Dr. Zenick posed Question One and commented that among the written responses from the panelists, one thing
that was consistently addressed was the issue of doing research for a specific purpose, as opposed to doing re-
search for the sake of it. He indicated that in his office, he works closely with the client. He asked the panelists
to describe how to create a dialog between researchers and end users.
Dr. White drew upon her experience with state health departments and practitioners in the field. She noted that
end users have some specific research needs, but that in her experience the research community has been rela-
tively unresponsive to end users of data. There is often a "disconnect" between the practitioners in the field and
the university researcher. Practitioners need information in a form that is readily available and understandable.
Dr. White posed the question—How do we create a system in which information cascades down from the basic
researcher to the community based researchers to the practitioners in the field?
Dr. Dickie responded that he brings two perspectives to this question. The first is that of the social scientist.
The social scientist tries to determine how environmental health affects peoples' lives and the quality of their
lives; what are the limitations on activities that they might experience, and what are the risks of illness that can
be determined. From the scientific perspective of the epidemiologist or toxicologist, interested in reliable and
precise measurements of subtle change in physiological function or indicator symptoms, there needs to be a
translation to peoples' understanding of how their lives are affected. Economists, as end users of health re-
search data, try to bridge the gap between those precise measurements of health researchers and the individ-
ual's perception and understanding of how these numbers will affect his life. Dr. Dickie elaborated that one
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can measure blood pressure and cholesterol levels, but that these are just numbers. Most people want to know
what is the link to long-term health risks and the activities that they can sustain. As an economist, he would
like to see a mapping between what epidemiologists can measure and what "ordinary" people experience and
understand as it pertains to them.
Mr. Greenbaum noted a difference between what the "policy world" needs and what the "science world" pro-
vides. He discussed the incentives and the system, currently in place, for the publishing of scientific informa-
tion. He noted that research findings such as hazards and effects are likely to be published, but that a more in-
tegrated approach would be beneficial for most policy analysts. He referred to air pollution studies that have
been underway for more than 35 years. A mechanism for integrating the various types of sciences has evolved.
He noted that endocrine disrupters (ED) studies have not been underway for nearly as long as the air pollution
studies, but that an integrated approach would be of value to policymakers.
Dr. Hull noted that researchers do a great job disseminating information to the research community, but that
they rarely take the next step that results in a stronger impact. Researchers need to know how their research is
to be used. Also, researchers need other pieces in their "research toolbox" to design relevant research.
A participant commented that ED studies have been ongoing for quite some time, although they appeared to be
in the early stages during the presentations. The audience member gave the example of Rachel Carson's animal
studies that were carried out quite some time ago, and noted that wildlife scientists are ahead of epidemiolo-
gists in studying ED-related questions. She noted that this opens up a number of questions about the relevance
of animal-human studies and extrapolations that have yet to be resolved.
It was agreed that scientists need to know more about the information policymakers require to make decisions.
Agencies are being held accountable for the kinds of impact their funded research will have in the long term.
Dr. White described a typical grant cycle as 3 or 5 years in duration. As such, the long-term impacts of the re-
search findings cannot be ascertained. At best, experiments may be completed. It is important to determine
what will be the short-term measures of impact to determine if research is beneficial. It is necessary to deter-
mine how information moves across fields, and whether somebody else will take up the research at the com-
pletion of a grant cycle.
Mr. Greenbaum described what he calls a tension between efforts that rely on the scientific community's crea-
tivity to address a range of problems, and the desire to have more closely overseen and managed research that
answers specific questions.
A participant commented that it is the scientist's job to define risk, and not to identify the acceptable risk. Dr.
Dickie agreed that there is a lot to be gained from a division of labor and that scientists are especially equipped
to do science, but perhaps there needs to be an intermediate step that translates science into what is amenable
to policy and social analysts. Mr. Greenbaum added that although differences need to be preserved, this trans-
lation moves us closer and closer to policy relevance. He described how studies pertaining to particulate matter
drove policy discussion with respect to air quality standards, which subsequently led to additional health ef-
fects studies. As research evolves, it becomes more usable to the policymaker. The scientific findings help to
form actions.
A participant took exception to the artificial separation between science and the rest of the world. He noted that
individuals are motivated by different things. Some scientists are more involved with social and political fac-
tors, others want to "solve the puzzle" or answer questions. He asked if perhaps there was a way to motivate
mechanistic researchers to areas of publicly relevant research. NIH's approach to research, which includes a
community outreach component, is clearly evolving. There are attempts to link research to outcomes, however,
there needs to be clarification in the evaluation of proposals as to what constitutes significance.
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Question 2: What roles have emerging information technologies (e.g., wide access to the Internet with its
massive volume of data and information) played to facilitate or complicate your ability to access
and use the research information ?
Dr. Zenick made the observation that from the written responses provided by the panel, Information Technol-
ogy is revolutionizing the ability to get information. He then moved on to the next question.
Question 3: What responsibilities should accompany publicly funded research? Is publication in peer-
reviewed journals enough"?
Dr. Zenick asked the audience if they were familiar with the recently published NIH proposal to ensure that
publicly funded research findings move quickly and readily to the public domain. The proposal is an attempt to
"change the playing field" and has generated intense dialog and discussion. He noted that a number of institu-
tional traditions are violated by going this route.
Dr. White was asked to respond. She noted that her organization acts somewhat in the role of translator, as data
are conveyed to the public. One of the challenges her office faces is to provide translation, to distill, and to
disseminate information to decisionmakers who often lack the necessary scientific knowledge. She stated that
it is important to distinguish between summaries of pertinent findings and collections of research, many of
which conflict with one another.
Mr. Greenbaum noted that in addition to the NIH proposal, there is a law that requires that data used in the
justification of a significant policy decision be made available to the public. He suggested that volumes of data
may be necessary for the scientific community, but that in the policy arena much of it is over the heads of pol-
icy analysts. He recognized the rights of the researchers to publish and get the benefits from their data, but held
that from the standpoint of the policy analyst, if a researcher was unwilling to share data, then there must be
something to hide. Dr. Dickie said that the flip side to this issue was that if data were shared, it increased the
credibility of the researcher. In his personal experience, there was no such thing as "bad publicity." He de-
scribed a controversial study in which his methods and results were criticized, but noted that because other
researchers were able to recreate identical results using his methods, his credibility was increased.
Dr. Hull noted that scientists can be very possessive of their data, but that sharing of data is the thing to do. It
saves a lot of time and effort. There may be some practical issues to be resolved in getting language into grants
to ensure that data are available.
A participant suggested that there is a need for infrastructure to support the translation of information. She
added that the process is expensive. Web sites are expensive and cannot be considered just a spin-off of re-
search. Additional funding should be included in proposals and grants to support the effort. Actually, raw data
may not be the right form for decisionmakers. Different target audiences may require different formats.
A participant stated that information was not passed along to the front line physicians. She stated that there
needs to be a forum to get the word out to medical schools and "into the trenches."
Question 4: What can academic researchers do to communicate and interpret the result of their re-
search to public health practitioners and policymakers at the local, state, and federal levels?
Dr. Zenick asked Mr. Greenbaum to discuss communicating scientific materials to audiences with different
levels of understanding. Mr. Greenbaum stated there is no gold standard, but that knowing your audience is of
paramount importance. He noted that his group makes a conscientious effort to communicate to different target
audiences through a system of tiered writings. Summaries approximately two pages in length are prepared for
decisionmakers, while multi-page documents with detailed information are prepared for the scientific commu-
nity. He noted that the degree to which information is cited in peer-reviewed literature is one measure of the
impact work is having in the policy process. He also commented that his group has begun to track citations in
regulatory documents.
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Dr. White acknowledged that knowing the target audience is imperative to getting the right message to the
right people. She noted that making data available and assessing how to make it accessible are challenging
issues. She stated that there needs to be an underlying infrastructure to aid the process. She recognized that
some public data lacks quality control.
Dr. Hull offered that research is needed on how to get the right message to the right people to effect behavioral
changes. He suggested that, not only should the target audience be correctly identified, but also that the audi-
ence needs to be part of the process to effect the greatest impact. He gave the example of lead studies in which
lead workers were bringing home contaminated clothing. Individuals were given a simple card with informa-
tion to slip into the pocket of their lead-contaminated clothing. These cards subsequently were removed at the
time the clothing was laundered, and the health information was passed on. He noted that the goal of research
is to have impact, and that the best way to ensure a change in the behavior of people is to bring them into the
process of change, rather than depend on regulations.
Question 5: How can institutions that support environmental health research facilitate the commu-
nication of research results to public health practitioners and policymakers? Are there in-
structive examples that you can provide?
The audience was asked to provide their input on investigative burden, the costs of doing business, and train-
ing concerns. From the audience, comments were made regarding involving other disciplines more formally in
one's research (e.g., risk communicators, social scientists, and other qualitative researchers). It was stated that
the peer review process generally does not merit or acknowledge the time that it takes to engage other groups.
Writing and translating science findings is a very time-consuming, ongoing process.
One participant commented that epidemiological research is in a "dire" condition. She noted that with telemar-
keting, one used to expect a 70-80 percent response rate. Today, it is more likely to be in the 25-30 percent
range. She stated that only well-educated and interested parties, those not likely to be Type A personalities,
provided any type of response. She also indicated that the response rate in control groups was even worse. She
feared enormous amounts of time were going to be spent on studies without representative samples. She also
expressed her frustration with trying to do research with respect to the Health Insurance Portability and Ac-
countability Act (HIPAA) Privacy Rule.
Another concern of researchers is that the public may not be aware of the quality of information posted on
various Web sites. The average person may view a very polished Web site and take it for granted that the data
are reputable, but another individual from the audience encouraged others not to underestimate the power of
the Web to inform individual decisionmakers. She noted that a number of individuals have requested citations
to pass along to their health care providers.
There was a consensus that the communication of scientific findings is time-consuming and costly, and that the
burden of these factors must be considered in the grant-giving process.
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Panelists' Responses to Questions
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Endocrine Disrupters Program Progress Review Workshop
R. DeLon Hull, Ph.D., National Institute for Occupational Safety and Health, Cen-
ters for Disease Control and Prevention, Cincinnati, OH
1. Do you have the opportunity to identify and use the most relevant research in carrying out your
professional obligations? If so, how can you subsequently document the value/impact of such
research? Do current systems/processes work to provide the needed information? What new
approaches should be considered?
Information on how to translate scientific research into public health practice would be very helpful.
It also would be helpful to have information available that would help researchers better understand
the needs of the potential users of their research results.
2. What roles have emerging information technologies (e.g., wide access to the Internet with its
massive volume of data and information) played to facilitate or complicate your ability to access
and use the research information?
The Internet makes a tremendous volume of information available, but sorting through it all to iden-
tify the most relevant information can be a burden. It does facilitate data collection with activities
such as Web-based surveys. It also allows researchers to more readily locate information about poten-
tial users of their research findings if the users are in an organization that has a Web site (e.g., trade
associations, worker unions, etc.).
3. What responsibilities should accompany publicly funded research? Is publication in peer-
reviewed journals enough?
Publication in peer-reviewed journals is an effective way of communicating research results to other
researchers, but is often not the best way to put the research results into practice that prevents injury
or illness. The needs of the audience the research is addressing must be understood to translate the re-
search findings into prevention practice.
4. What can academic researchers do to communicate and interpret the results of their research
to public health practitioners and policymakers at the local, state, and federal levels?
The key is in understanding the needs of the audience you are trying to address. Potential users, stake-
holders, and decisionmakers (policy implementers) should be involved during the early research plan-
ning phase so that their needs are well understood early in the research process. This group also
should be involved through the research process so that communication products and translation ac-
tivities address their needs.
5. How can institutions that support environmental health research facilitate the communication
of research results to public health practitioners and policymakers? Are there instructive ex-
amples that you can provide?
Research should be relevant, high quality, and lead to an illness or injury prevention impact. Translat-
ing research findings to products, interventions, or policies that have an impact is somewhat unique
for each research effort. We need to foster an environment in which researchers include appropriate
translation of research findings into their research plans. Some examples can be found on the National
Institute for Occupational Safety and Health (NIOSH) Web Site (www.cdc.gov/niosh) through the
Research to Practice (r2p) link or through NIOSH eNews, which includes an r2p example in each
newsletter. Subscribe to NIOSH eNews through the NIOSH Web Site.
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LuAnn White, Ph.D., Center for Applied Environmental Public Health, Tulane
University, New Orleans, LA
1. Do you have the opportunity to identify and use the most relevant research in carrying out your
professional obligations? If so, how can you subsequently document the value/impact of such
research? Do current systems /processes work to provide the needed information? What new
approaches should be considered?
Currently, scientific journals are the prime means of dissemination for most research. The reward sys-
tem for promotion and tenure in academia values only publication in scientific journals. Most re-
searchers target other scientists for communication and dissemination. The traditional system over-
looks major groups who could use and are in the position to act on the research findings.
Other modes of dissemination are more difficult to document in terms of impact. In journals, citations
are one monitor of impact. In public health practice, seldom is one research finding the basis for ac-
tion or policy; rather, the body of evidence is the driving factor, which is difficult to trace back to one
researcher or to one funded project. Furthermore, the impact might not be observed for years. Identi-
fying more proximate indicators of use of data is needed, but not easy.
2. What roles have emerging information technologies (e.g., wide access to the Internet with its
massive volume of data and information) played to facilitate or complicate your ability to access
and use the research information?
The Internet has opened access to information exponentially. Information that was once difficult to
find is now readily available from the desktop. Electronic journals have expanded access and reduced
the time needed to find information. Data and information can be disseminated widely, very quickly,
and less expensively than printed material. However, caution is necessary. Much of the historical lit-
erature is not in an electronic format. Just because something is posted on the Internet does not make
it true. This situation can cause problems with the lay audience, who might lack the knowledge to dis-
cern what is fact, what is opinion, and what is blatantly not true.
3. What responsibilities should accompany publicly funded research? Is publication in peer-
reviewed journals enough?
Receiving public funds brings the responsibility to disseminate the findings to multiple target audi-
ences, not just other scientists. Most of the time, scientists think of publication only in scientific jour-
nals. The scientific community is only one of many target audiences for dissemination; others include
the general public, policymakers, and professional organizations. Each audience receives information
through different media. There also is the responsibility to put the findings into language that the
various target audiences can understand and use. Many public health practitioners do not read scien-
tific journals because specific findings do not relate directly to their problems. Other modes of dis-
semination include white papers and summaries targeting specific users, training and education, tool-
kits for using the findings, and news media.
4. What can academic researchers do to communicate and interpret the results of their research
to public health practitioners and policymakers at the local, state, and federal levels?
The type and maturity of research determines how and to whom it might be communicated. Gener
ally, there needs to be a body of basic research that provides a basis for policy. Individual findings,
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unless a profound breakthrough, are not usually directly translatable to policy. Thinking of the path
that research takes to become useful might guide the communication of research to appropriate target
audiences.
Partnerships and interactions among those who conduct basic research, applied research, and commu-
nity-based research and practitioners can serve as a means for two-way communication—the dis-
semination of findings to those who use them and then communication back to researchers on re-
search questions needed to answer the problems faced in practice.
5. How can institutions that support environmental health research facilitate the communication
of research results to public health practitioners and policymakers? Are there instructive ex-
amples that you can provide?
Communication with practitioners depends on ongoing dialog, not sporadic pronouncement from the
Ivory Tower. In many of our projects at the Tulane Center for Applied Environmental Health, we
have advisory boards that include researchers, community members, governmental agency personnel,
and other policymakers. Regular meetings provide a means of communicating with public health
practitioners, policymakers, and the community. Regular exchanges of ideas and information set up a
two-way communication channel that helps to make research more relevant to practitioners.
Making data understandable to policymakers is essential in communication. In one project, we used
GIS mapping to show the prevalence of childhood lead poisoning in the city of New Orleans. The
graphic showed the areas of the city with the highest rates and identified the risk factors geographi-
cally. The graphic was used in the news media and in summary reports. This data served as the basis
of a city ordinance banning the dry sanding of leaded paint. The use of GIS provided an easy-to-see
graphic; the same policymakers would not have read a report with the same data in tables or charts.
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Mark Dickie, Ph.D., University of Central Florida, Orlando, FL
1. Do you have the opportunity to identify and use the most relevant research in carrying out your
professional obligations? If so, how can you document the value/impact of such research? Do
current systems/processes work to provide the needed information? What new approaches
should be considered?
Research in environmental epidemiology and environmental toxicology is an important input in con-
ducting economic analysis of environmental policies and regulations. The U.S. Environmental Protec-
tion Agency and other federal agencies are directed by executive orders, as well as some statutory re-
quirements, to conduct various types of economic analysis of regulations with significant economic
impact. These analyses range from assessments of impacts on specific groups, such as small busi-
nesses or minority populations, to estimates of benefits and costs throughout society. (Although use
of benefit-cost analysis in policy decisions is controversial, as a method of analysis rather than deci-
sionmaking, benefit-cost can be one useful way of highlighting the tradeoffs involved in any deci-
sion.) Economic analysis is rarely decisive in policy decisions, but it does provide information that
policymakers can use, along with other information, in examining options and setting priorities. Con-
sequently, economic analysis provides one avenue through which epidemiologic and toxicologic re-
search can enter the process of analyzing and setting environmental policies. For example, epidemi-
ologic research relating particulate air pollution to premature mortality has provided the basis for
establishing the enormous economic benefits of air quality improvements under the Clean Air Act.
However, epidemiologic and toxicologic research often does not provide the information necessary to
conduct economic analysis.
The ideal information to support an economic analysis is a best estimate of a dose-response or con-
centration-response function relating changes in a hazard to changes in the frequency, severity, or risk
of an adverse health effect that is meaningful to people, accounting for statistical uncertainty and for
any behavioral adjustments that people make to avoid exposure to the hazard. For three reasons, it can
be difficult or impossible in some cases to glean this information from epidemiologic or toxicologic
research.
Epidemiologists often measure somewhat subtle changes in physiologic or neurologic function, such
as decreased lung function associated with air pollution exposure. However, economic impacts arise
partly from avoiding, or from reducing the risk of, health effects that ordinary people recognize as
adverse. People may not recognize a decrease in lung function as adverse without additional informa-
tion about how lung function affects their daily activities, symptoms, or long-term health status. As a
result, economists have no way to estimate the economic impacts of avoiding reduced lung function
and thus might understate the beneficial effects of reducing air pollution. Similarly, increased finger-
tapping associated with manganese emissions, or heart rate variability, or changes in body chemistry
cannot be assessed economically without a mapping from these measures into effects that are mean-
ingful to people.
Research in the health sciences often does not account for behavioral adjustments people sometimes
make to avoid exposure to hazards. For example, some research indicates that symptomatic individu-
als restrict outdoor activities on days of elevated ozone concentrations. To the extent that behavioral
adjustments like this are effective in reducing adverse health effects, ignoring the responses could
lead to an underestimation of the true effect of a hazard, which in turn could lead to understatement of
the beneficial economic impacts of regulation. Of course, there are many situations in which behav-
ioral adjustments are unimportant, perhaps because people do not know they are exposed or have no
practical way of reducing exposure. However, the issue of behavioral adjustments may increase in
importance if warnings such as smog alerts or fish consumption advisories effectively encourage in-
dividuals to take the burden of protection on themselves.
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Epidemiologic and toxicologic research often does not provide enough information about the best
estimate of a dose-response or concentration-response function, information that would include esti-
mates of slope and curvature and an assessment of any thresholds, rather than simply the statistical
significance of an effect. This problem is particularly difficult to overcome when economists try to
use information from the risk assessments, more often based on toxicologic studies of animals than on
epidemiology, that summarize what is known about risks posed by hazardous substances. A key prob-
lem is the inherent conservatism in risk assessment, driven by an overall philosophy of avoiding un-
derstatement of risk. Although this philosophy is perfectly understandable from the standpoint of pro-
tecting public health, it is not conducive to economic analysis because it does not yield a best estimate
of the central tendency of the relationship between risk and exposure to a hazard. Furthermore, risk
assessments of noncancer health effects do not provide a measure of risk but only a threshold type of
measure, such as a reference dose or reference concentration. This situation makes it difficult or im-
possible for an economist to work out a dose-response function that would be needed to estimate the
economic impacts of controlling a hazard.
2. What roles have emerging information technologies (e.g., wide access to the Internet with its
massive volume of data and information) played to facilitate or complicate your ability to access
and use the research information?
Emerging information technologies, such as wide access to the Internet, have facilitated economists'
access to research in the health sciences.
3. What responsibilities should accompany publicly funded research? Is publication in peer-
reviewed journals enough?
One element of this question is whether publicly funded researchers have a responsibility to share
their data with others, and opinions differ on this point. I am not sure whether the government can re-
solve this issue to anyone's satisfaction. An often neglected point is that it can be in the self-interest
of researchers to make their data available, at least after they have had some time to make exclusive
use of the data themselves. For example, independent replication of a researcher's results enhances
the researcher's credibility.
4. What can academic researchers do to communicate and interpret the results of their research
to public health practitioners and policymakers at the local, state, and federal levels?
An important step in communicating research results to policymakers would be making clear the im-
plications of all key assumptions affecting the derivation of results or interpretation of conclusions. In
addition, the following steps would better communicate research results to economic analysts. First, if
effects measured in research studies represent changes in body chemistry or function, researchers
could provide a mapping of these effects to health effects meaningful to people, such as changes in
symptoms, ability to perform daily activities, or changes in risks of morbidity or premature mortality.
Second, researchers could characterize key features of the best estimate of central tendency of dose-
response or concentration-response functions, along with associated measures of statistical uncer-
tainty. Third, researchers could give more attention to the behavioral adjustments that people make to
protect themselves against environmental or other hazards, and how these adjustments may affect the
estimated association between ambient concentrations or emissions and health effects. Fourth, re-
searchers could provide some guidance as to what, if anything, relationships measured for a special
subpopulation, such as children aged 8 to 12 years, might imply for the broader population.
5. How can institutions that support environmental health research facilitate the communication
of research results to public health practitioners and policymakers? Are there instructive ex-
amples that you can provide?
If there were interest in incorporating behavioral adjustments into epidemiologic estimation of health
effects, funding agencies might encourage more communication and cooperation between environ-
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mental epidemiologists and researchers who specialize in studying human behavior, such as psy-
chologists, decision analysts, and possibly even the occasional economist. Interdisciplinary research
sometimes looks better on paper than in actual practice, but the strategy might be worth testing.
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Dan Greenbaum, Health Effects Institute, Boston, MA
1. Do you have the opportunity to identify and use the most relevant research in carrying out your
professional obligations? If so, how can you subsequently document the value/impact of such
research? Do current systems/processes work to provide the needed information? What new
approaches should be considered?
Both in my role as Commissioner of Environmental Protection in Massachusetts and at the Health
Effects Institute (HEI), I have had to frequently identify, from a wide range of sources and disci-
plines, the key findings for informing policy and public health decisions, ranging from the cleanup
standards for Superfund sites to the most relevant data for setting ambient air quality standards. To in-
form such decisions in often controversial settings, it is essential that the science be of the highest
quality, that is, drawn from studies relevant to the exposures and effects at issue, based on syntheses
of the full literature (rather than individual studies), and integrating results from a variety of disci-
plines (e.g., epidemiology, toxicology, exposure). Science can provide this information, but it is use-
fully incorporated into the decision process only if it is designed initially to answer key policy ques-
tions (e.g., by providing dose-response information rather than just hazard assessment at high doses)
and there is a transparent multidisciplinary expert process to ensure its thoughtful integration into de-
cisions. (One example has been, at times, EPA's Clean Air Scientific Advisory Committee.)
2. What roles have emerging information technologies (e.g., wide access to the Internet with its
massive volume of data and information) played to facilitate or complicate your ability to access
and use the research information?
There is no question that the Internet and enhanced computing power and data storage have provided
the possibility for much greater access to current scientific information and have, in some instances,
greatly enhanced the ability of decisionmakers to use the full range of information available (most
notably through the growing practice among journals of providing access to extensive backup data for
published articles). One particularly innovative approach to this practice has been the Internet Health
and Air Pollution Surveillance System Web Site (IHAPSS), developed by Johns Hopkins University
to place national health and air quality databases, along with the programs necessary to analyze them,
on the Web (www.ihapss.jhsph.edu).
The plethora of information now available, however, has greatly increased the need for the kind of
multidisciplinary synthesis and review processes mentioned above, as well as for new approaches to
data screening and quantitative synthesis to sift through the voluminous (and not always peer-
reviewed) information now available online.
3. What responsibilities should accompany publicly funded research? Is publication in peer-
reviewed journals enough?
I do not see a distinction between publicly and privately funded research. If research is being carried
out in areas affecting public health and policy decisions, both types of research should be carried out
in ways that maximize the utility for decisions, including being designed to answer policy-relevant
questions and having transparency in the funding, design, and reporting of results (i.e., all negative as
well as positive results). To meet these responsibilities, peer-reviewed publications—which often ab-
stract positive findings from a broader and more important and diverse context of data and find-
ings—are not sufficient, especially for studies that can be used for tasks such as quantitative risk as-
sessment. To further ensure the credibility of either kind of research, it is important that other investi-
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gators have access to data from important studies once the original investigators have had the oppor-
tunity to publish from their data.
4. What can academic researchers do to communicate and interpret the results of their research
to public health practitioners and policymakers at the local, state, and federal levels?
They can identify and work with professionals and professional associations that have expertise in
communicating complex scientific information in careful but understandable fashion to decisionmak-
ers. They also can learn how to communicate effectively in public settings, such as workshops, with
decisionmakers and how to testify before agency officials and legislators. These venues are challeng-
ing for many scientists, but scientists must increasingly realize that their communication work does
not end, but rather begins, with the publication of results.
5. How can institutions that support environmental health research facilitate the communication
of research results to public health practitioners and policymakers? Are there instructive ex-
amples that you can provide?
Institutions can facilitate the communication of research results in many ways, including the follow-
ing:
• Creating understandable summaries to accompany publication of studies. (HEI, for example, pub-
lishes both a two-page "Statement" and a longer "Commentary" with each research report.)
• Convening workshops and meetings with targeted sessions that bring together scientists, science
communicators, and public health and policy officials.
• Maintaining an accessible and easy-to-use Web site that quickly links users to different levels of
information depending on their interest and skills. One example is the site maintained by the
European group GreenFacts.org, which presents interlinked versions of complex reports (e.g.,
World Health Organization documents) at the executive summary, interpretive summary, and full
report levels.
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Biographical Sketches
Shanna H. Swan, Ph.D., University of Missouri—Columbia, Columbia, MO
Dr. Shanna H. Swan is Research Professor in the Department of Family and Community Medicine, School of
Medicine, and Adjunct Professor in Statistics at the University of Missouri—Columbia. She received an M.S.
in Biostatistics from Columbia University and a Ph.D. in Statistics from the University of California—Berke-
ley. From 1981 to 1998, she served as Chief of the Reproductive Epidemiology Section at the California De-
partment of Health Services. Dr. Swan is known for her work on the impact of environmental exposures on
male and female reproductive health and has served on the National Academy of Science's Committee on
Hormone-Related Toxicants. Since 1998 she has been Principal Investigator (PI) of the Study for Future Fami-
lies, a multicenter pregnancy cohort study examining environmental causes of geographic variation in repro-
ductive health endpoints in men, women, and children. Dr. Swan was elected Chair of the 2008 Gordon Re-
search Conference on Environmental Endocrine Disrupters.
Xiaobin Wang, Sc.D., Children's Memorial Hospital, Chicago, IL
Dr. Xiaobin Wang received her M.D. degree from Beijing Medical University in 1983, her M.P.H. degree from
Tulane University in 1987, and her Sc.D. degree from Johns Hopkins University in 1991. She received post-
doctoral training in Environmental Epidemiology at the Harvard School of Public Health from 1991 to 1994
and pediatric residency training at Boston Medical Center from 1994 to 1998.
In the past 15 years, Dr. Wang's research has focused on children's growth and development, respiratory
health, and molecular epidemiology of reproductive and birth outcomes. At present, Dr. Wang is the PI of
three epidemiology projects funded by the National Institutes of Health and one epidemiology project funded
by the March of Dimes Birth Defect Foundation. She leads a multidisciplinary research team that consists of
representative(s) from each of the following disciplines: clinical medicine, epidemiology, molecular biology/
genetics, biostatistics/bioinformatics, and environmental health sciences. The current research focus of her
team is to investigate environmental factors and gene-environmental interactions in determining the risk of
adverse reproductive outcomes and to integrate epidemiologic, clinical, and laboratory methods to better un-
derstand their pathogenic pathways and biological mechanisms.
Laura Fenster, Ph.D., California Department of Health Services, Emeryville, CA
Dr. Laura Fenster is a reproductive epidemiologist at the California Department of Health Services (CDHS),
where she has worked since completing her Ph.D. in Epidemiology at the University of California—Berkeley.
She has experience as a PI and co-investigator on a number of large collaborative multicenter studies of repro-
ductive outcomes associated with in utero toxicant exposures; these studies have examined risk factors for
spontaneous abortion and adverse fetal growth outcomes. She is currently the PI at the CDHS for the Endo-
crine Disrupters and Neurodevelopment Outcomes grant funded by the National Institute for Occupational
Safety and Health (NIOSH). In addition she is a co-investigator, with the Center for the Health Assessment of
Mothers and Children of Salinas, on a community-based participatory research project titled "A Longitudinal
Birth Cohort Study of the Effects of Pre- and Postnatal Pesticide Exposure on Growth, Neurodevelopment, and
Respiratory Health in Children Aged 3 to 7 Years in an Agricultural Community." She also has served as a co-
investigator on studies of other reproductive endpoints, such as menstrual function and semen quality. For ex-
ample, she was a co-investigator on the Women's Reproductive Health Study (WRHS) that involved daily col-
lection of urine samples to measure hormone metabolites. The focus in the WRHS study was on the steroid
hormones that were used to define several parameters of menstrual function, which were then examined in re-
lation to exogenous exposures. Dr. Fenster had primary responsibility for the analyses of the semen quality of
the male partners of women in the WRHS; semen quality was investigated in relation to a number of environ-
mental and lifestyle factors.
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James H. Raymer, Ph.D., RTI International, Research Triangle Park, NC
Dr. James H. Raymer of RTI International received a Ph.D. in Analytical Chemistry from Indiana Univer-
sity—Bloomington in 1984. His research interests have included the identification and quantitation of trace-
level organic compounds in biological and environmental media using chromatographic, spectroscopic, and
mass spectrometric methods. For the past 15 years, he has been heavily involved in human exposure analysis
research for both adults and children and currently holds the position of Senior Program Director for the
Health-Directed Exposure Research Program at RTI. Some of Dr. Raymer's current projects are focused on
linking adverse health outcomes with environmental exposures to various chemical classes, including pesti-
cides, water disinfection byproducts, endocrine disrupters, and persistent organic chemicals, including per-
fluorinated compounds.
Tongzhang Zheng, M.D., Sc.D., Yale University
Dr. Tongzhang Zheng is the Division Head for the Division of Environmental Health Sciences at Yale Univer-
sity School of Public Health. During the past 14 years, his research has been in the areas of environmental ex-
posures and cancer risk, including breast cancer, non-Hodgkin's lymphoma, and Hodgkin's disease. He is es-
pecially interested in the relationship between environmental endocrine disrupters and human cancer risk.
Victoria Holt, Ph.D., M.P.H., Fred Hutchinson Cancer Research Center, Seattle, VA
Dr. Victoria Holt is Professor of Epidemiology at the University of Washington School of Public Health and
Community Medicine and Member (Joint) at the Fred Hutchinson Cancer Research Center. She has more than
15 years of experience conducting epidemiologic studies of women's reproductive health issues, including
most recently a case-control study of the etiology of endometriosis conducted in a large health maintenance
organization in Washington State. Dr. Holt teaches a graduate-level course in Reproductive Epidemiology at
the University of Washington.
Russ Mauser, M.D., M.P.H., Sc.D., Harvard School of Public Health, Boston, MA
Dr. Russ Hauser is an Associate Professor in the Department of Environmental Health at the Harvard School
of Public Health. He obtained his M.D. from the Albert Einstein College of Medicine and his Sc.D. from the
Harvard School of Public Health. His research interests are in the areas of reproductive health and childhood
development. With funding provided by the U.S. EPA, he is conducting a large cohort study on the relation-
ship between dioxin exposure and growth and development in adolescent boys in Chapaevsk, Russia. He also
is conducting a study funded by the National Institute of Environmental Health Sciences on the relationship
between PCBs, phthalates, and male reproductive health.
Dean B. Baker, M.D., M.P.H., University of California—Irvine, Irvine, CA
Dr. Dean Baker is Professor and Chief of the Division of Occupational and Environmental Medicine, Depart-
ment of Medicine, and Director of the University of California—Irvine Center for Occupational and Environ-
mental Health (COEH). He is an expert in occupational and environmental health. Dr. Baker received his
medical degree from the University of California—San Diego and his M.P.H. degree in epidemiology from the
University of California—Berkeley. He completed residency training in Family Medicine and Occupational
Medicine prior to working as a medical officer for NIOSH. He was a faculty member of the UCLA School of
Public Health and the Mount Sinai School of Medicine in New York before coming to the University of Cali-
fornia—Irvine.
Dr. Baker's research emphasizes two areas. One area is the health effects of work environment and workplace
psychosocial stressors. Dr. Baker is the co-author of a seminal article that was the first publication in the
United States to demonstrate the association between high job strain (the combination of high work demands
and low control) and increased risk of cardiovascular disease. During the past 20 years, the Job Strain Model
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has become the predominate theoretical model of workplace stress, providing the foundation for a large body
of research conducted by investigators throughout the world. Over the years, Dr. Baker has made substantial
contributions to the medical literature in this area. Dr. Baker and colleagues at the University of Califor-
nia—Irvine will host an international conference on the Work Environment and Cardiovascular Disease next
March in Southern California.
Another area of research is children's environmental health. Dr. Baker conducted a series of epidemiologic
studies examining the health effects of gestational and early childhood exposure to heavy metals and or-
ganochlorine chemicals. For example, Dr. Baker completed a study of over 2,000 children in Tijuana, Mexico,
to determine their blood lead levels and sources of lead exposure. He also conducted studies of families poten-
tially exposed to DDT from a hazardous waste site in Southern California, and of high school students in Ha-
waii who had potential gestational exposure to the pesticide heptachlor. The research on the Hawaii cohort of
children, who are now 21 years of age, addressed biological indicators of exposure, latent neurobehavioral ef-
fects, and current reproductive and immunologic function effects due to the gestational pesticide exposure.
Because of this expertise, the UC Irvine COEH has been designated by the U.S. EPA as a regional Pediatric
Environmental Health Specialty Unit. In both of these areas, Dr. Baker made contributions to the epidemi-
ologic study design and methods. These contributions were recognized by the World Health Organization
(WHO), which asked Dr. Baker to serve as the lead editor for the WHO's textbook on Environmental Epide-
miology (1999). Dr. Baker also has been recognized by his peers, being elected twice as Secretary-Treasurer of
the International Society for Environmental Epidemiology, the leading international professional society in his
field of research. He also is strongly devoted to teaching occupational medicine and epidemiology. He was the
director of the preventive medicine residency program and professor of epidemiology at the UCLA School of
Public Health. He then directed an environmental epidemiology fellowship program at the Mount Sinai School
of Medicine in New York. Since 1993, he has directed the UC Irvine occupational medicine residency program
and taught in the graduate programs in epidemiology and toxicology at the university. His medical writings
include multiple chapters in reference and teaching textbooks.
Irva Hertz-Picciotto, Ph.D., University of California
Dr. Irva Hertz-Picciotto, Professor, received her B.A. in mathematics, M.A. in biostatistics, and Ph.D./M.P.H.
in epidemiology from the University of California (UC)—Berkeley. After 12 years on the faculty at the Uni-
versity of North Carolina (UNC)—Chapel Hill, she returned to California to join the UC Davis Department of
Public Health Sciences (formerly the Department of Epidemiology and Preventive Medicine). Her research
interests are in environmental exposures (metals, pesticides, polychlorinated biphenyls, air pollution), preg-
nancy outcomes (spontaneous abortion, fetal growth, early child development), and epidemiologic methods
(left truncation in survival analysis, the "healthy worker survivor bias," timing issues, and use of epidemi-
ologic data in quantitative risk assessment). Dr. Hertz-Picciotto authored the chapter "Environmental Epidemi-
ology" in the textbook Modern Epidemiology by Rothman and Greenland, and she currently serves on editorial
boards for the American Journal of Epidemiology, Environmental Health Perspectives, and Epidemiology, as
well as on scientific advisory boards for the State of California, EPA, the National Toxicology Program of the
National Institute of Environmental Health Sciences, and the National Institute for Occupational Safety and
Health. In 2000 and 2002, Dr. Hertz-Picciotto chaired the U.S. Institute of Medicine/National Academy of Sci-
ences Committee on the Health Effects in Vietnam Veterans of Exposure to Agent Orange and Other Herbi-
cides. She directed the program in Reproductive Epidemiology at UNC Chapel Hill and is the Deputy Director
of the Children's Center for Environmental Health at UC Davis, focused on autism and other neurodevelop-
mental disorders. Dr. Hertz-Picciotto has taught courses on 4 continents; was dissertation advisor for 17 doc-
toral students, 4 of whom won prizes for work conducted as doctoral students; and mentored 3 dozen other
Ph.D. students.
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Pamela Imm, M.S., Wisconsin Department of Health and Family Services,
Madison, Wl
Ms. Pamela Imm is currently the Research Program Manager/Epidemiologist for the Great Lakes Sport Fish
(GLSF) Consortium Program with the Wisconsin Department of Health and Family Services, Bureau of Envi-
ronmental Health. She joined the Bureau in January 2003 as an epidemiologist for the vermiculite/me-
sothelioma grant funded by the Agency for Toxic Substances and Disease Registry before becoming the man-
ager of the GLSF Consortium. Ms. Imm has worked for the Department for the past 10 years as a research and
policy analyst as well. She has managed two statewide health surveys, including the Behavioral Risk Factor
Survey, sponsored by the Centers for Disease Control and Prevention, and the Wisconsin Family Health Sur-
vey. She also has managed Medicaid programs as a policy analyst in the Wisconsin Division of Health Care
Financing.
Stephen M. Schwartz, M.D., Fred Hutchinson Cancer Research Center,
Seattle, WA
Dr. Stephen M. Schwartz currently is appointed as a Member in the Division of Public Health Sciences at the
Fred Hutchinson Cancer Research Center, where he directs molecular epidemiologic studies of testicular can-
cer, HPV-related anogenital cancers, and oral cancer. He also serves as co-Pi of the Cancer Surveillance Sys-
tem of western Washington and is a participant in the Surveillance, Epidemiology, and End Results (SEER)
program of population-based cancer registries funded by the National Cancer Institute. In addition, he is a Full
Professor in the Department of Epidemiology, School of Public Health and Community Medicine, University
of Washington, where he serves as Graduate Program Director and teaches courses on the integration of labo-
ratory methods in population studies.
Philippe Grandjean, M.D., Ph.D., Occupational Health Program, Harvard School
of Public Health, Boston, MA
Dr. Philippe Grandjean has been an Adjunct Professor of Environmental Health at the Harvard School of Pub-
lic Health since January 2003. Prior to this, he spent 8 years as an Adjunct Professor of Environmental Health
and Neurology at Boston University. Concurrently, Dr. Grandjean serves as Professor and Chair of Environ-
mental Medicine at the University of Southern Denmark, Odense, Denmark, and he has been appointed Con-
sultant at the National Board of Health, Denmark. He is editor-in-chief (with Dr. David Ozonoff) of the Web-
based journal Environmental Health and is a member of the editorial boards of 10 other scientific journals. He
has served on or chaired committees under the auspices of WHO, the International Agency for Research on
Cancer, the European Commission, the International Union of Pure and Applied Chemistry, and the U.S. EPA,
and he is a member of the newly founded Panel on Food Contaminants of the European Food Safety Authority.
The research on marine contaminants and their effects on child development in the Faroe Islands was initiated
in the mid-1980s, and the prospective birth cohort studies have led to an international collaborative project that
inspired downward revisions of methylmercury exposure limits worldwide. Dr. Grandjean was the founding
Director of the Department of Occupational Medicine at the Danish NIOSH and since then has never left oc-
cupational health research. His main research efforts relate to metal toxicology, biomarker development and
validation, endocrine disruption (especially estrogenicity caused by organochlorine exposures and their possi-
ble role as risk factors for breast cancer), and the carcinogenicity of fluoride, metals, and mineral fibers. In
addition, Dr. Grandjean is a leader in the effort to introduce the precautionary principle into standards-setting
in occupational and environmental health and research. Of his more than 300 scientific publications, half are in
international journals with peer review.
The Office of Research and Development's National Center for Environmental Research
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Endocrine Disrupters Program Progress Review Workshop
PANELISTS
Harold Zenick, Ph.D.
Dr. Harold Zenick is the Associate Director for Health, National Health and Environmental Effects Research
Laboratory (NHEERL) in the Office of Research and Development in the U.S. Environmental Protection
Agency (EPA). Dr. Zenick earned a Ph.D. in Physiological Psychology from the University of Missouri (Co-
lumbia). He also completed a Postdoctoral Fellowship in Toxicology at the University of Cincinnati. Prior to
joining NHEERL, he was a Branch Chief in EPA's Office of Health and Environmental Assessment, Office of
Research and Development. Before coming to EPA, Dr. Zenick spent 13 years in academia with the Depart-
ment of Environmental Health in the University of Cincinnati Medical School preceded by an appointment at
New Mexico Highlands University. Dr. Zenick serves as EPA's liaison to the National Institute of Environ-
mental Health Sciences (NIEHS), the National Toxicology Program (NTP), and the National Center for Envi-
ronmental Health/Centers for Disease Control and Prevention (NCEH/CDC) Advisory Councils/Boards.
Currently, Dr. Zenick serves as a U.S. Co-Chair of the Environmental Health Workgroup under the binational
U.S.-Mexico Border 2012 Program. Within the Agency, he is Chair of the Agency's Health Effects Institute
Advisory Board and is ORD's senior executive lead for environmental justice matters. He has received numer-
ous Agency awards, including the prestigious Presidential Meritorious Executive Rank Award and the ORD
Statesmanship award. Recently, he has had a leading role in several emerging programs at EPA, including ef-
forts to develop better indicators of public heath impact of environmental decisions. In this capacity, he has
participated on a number of prominent National and Federal projects. Dr. Zenick also has the lead for the Of-
fice of Research and Development for several cross-EPA/cross-Federal Agency initiatives, including the im-
pact of the environment on the rapidly growing, aging population and the Futures of Toxicity Testing.
Dr. Zenick has more than 100 publications. His current interests are in integrating human health and ecological
risk assessment, strengthening the linkages between environmental and public health agendas and agencies,
and the application of emerging computational and molecular sciences in improving risk assessment practices.
R. DeLon Hull, Ph.D., National Institute for Occupational Safety and Health,
Centers for Disease Control and Prevention, Cincinnati, OH
Dr. R. DeLon Hull is Director of NIOSH's Office of Research and Technology Transfer and leads the Re-
search to Practice (r2p) initiative. Research to Practice is an initiative directed at enhancing the relevance and
impact of NIOSH-funded research. Dr. Hull joined NIOSH in 1976 and has held a number of scientific and
managerial positions throughout the Institute. Prior to his current assignment, Dr. Hull served as the Acting
Deputy Director of NIOSH and Acting Director of NIOSH's field research division, which conducts health
hazard evaluations; epidemiologic and industrial hygiene evaluations and research; and hazard, illness, and
medical surveillance. He was involved in developing the National Occupational Research Agenda, was lead
author of the NIOSH Alert on Latex Allergy, and has authored numerous research publications and NIOSH
analytical methods.
LuAnn White, Ph.D., DABT, Center for Applied Environmental Public Health,
Tulane University, New Orleans, LA
Dr. LuAnn White, a toxicologist, serves as the Director of the Center for Applied Environmental Public Health
(CAEPH) at Tulane University School of Public Health and Tropical Medicine (SPHTM). She received a B.S.
degree in chemistry from St. Mary's Dominican College and a Ph.D. in Pharmacology and Toxicology from
Tulane University Medical Center. She is a Diplomate of the American Board of Toxicology.
Dr. White directs the Center of Excellence in Environmental Public Health Tracking and is co-director of the
Tulane Prevention Research Center. Both of these Centers are funded by the Centers for Disease Control and
Prevention and reside within CAEPH.
The Office of Research and Development's National Center for Environmental Research
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Endocrine Disrupters Program Progress Review Workshop
Dr. White's research focuses on the prevention of health effects in humans from environmental and occupa-
tional agents. She has developed methods to combine environmental health science with epidemiologic meth-
ods to identify and assess the effects of environmental and occupational agents on human health. Dr. White has
conducted community-based health studies that encompass both emergency response situations and long-term
exposures at hazardous waste sites. Her research also focuses on the prevention of childhood lead poisoning as
well as environmental and occupational exposures. Dr. White has developed methods for developing risk com-
munication messages for communities based on hazard, exposure, and health outcome data.
A leader in developing models for environmental health training and education programs, Dr. White has de-
veloped a skills-based approach for designing curricula for environmental health practice professionals. She
also established the master's programs in environmental toxicology and risk assessment and in occupational
health in the Department of Environmental Health Sciences at Tulane. Dr. White also has pioneered the devel-
opment of distance learning at SPHTM. She launched the distance learning programs leading to the M.P.H. in
Occupational Health and Safety Management, and Occupational Health, and the M.S.P.H. in Industrial Hy-
giene using interactive Internet technologies.
Mark Dickie, Ph.D., University of Central Florida, Orlando, FL
Dr. Mark Dickie is Professor of Economics at the University of Central Florida in Orlando, Florida. His re-
search involves estimating the economic benefits of reducing adverse environmental health effects, under-
standing the determinants of individuals' perceptions of health risks from environmental hazards, and examin-
ing individuals' behavioral reactions to environmental health hazards. His current research examines these is-
sues in the context of children's environmental health, focusing on asthma, acute symptoms of air pollution
exposure, and skin cancer. Dr. Dickie's work is funded by the U.S. Environmental Protection Agency. He also
serves on EPA's Children's Health Protection Advisory Committee.
Dan Greenbaum, Health Effects Institute, Boston, MA
Mr. Dan Greenbaum is the President and Chief Executive Officer of the Health Effects Institute (HEI), an in-
dependent nonprofit research institute supported jointly by the U.S. EPA and industry to provide public and
private decisionmakers with high-quality, impartial, relevant, and credible science about the health effects of
air pollution. Mr. Greenbaum has chaired a number of national panels on air pollution and health for EPA and
the National Research Council (NRC). Most recently, he served as vice chair of the NRC's Committee for Air
Quality Management in the United States. He regularly presents the results of HEI's scientific work to U.S.,
international, and state audiences; the U.S. Congress; the Asian Development Bank; and the European Parlia-
ment.
Mr. Greenbaum has three decades of government and nongovernment experience in environmental health.
Prior to coming to HEI, he served as Commissioner of the Massachusetts Department of Environmental Pro-
tection from 1988 to 1994.
The Office of Research and Development's National Center for Environmental Research
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Endocrine Disrupters Program Progress Review Workshop
U.S. EPA National Center for Environmental Research
Endocrine Disrupters Program Progress Review Workshop
Endocrine Disrupters: Epidemiologic Approaches
Center for Bioenvironmental Research
Tulane and Xavier Universities
New Orleans, LA
October 30, 2004
Participants List
Benson Akingbemi
Auburn University
Charles Allen
Tulane University
Dean Baker
University of California-Irvine
Lindsey Berkson
Tulane University
Nicholas Berry
Indiana University
Glen Boyd
Tulane University
Margaret Lee Braun
DES Stories
Deborah Burgin
U.S. Environmental Protection Agency
Tung-Chin Chiang
Tulane University
Adele Childress
Centers for Disease Control and Prevention
Cynthia Corbitt
University of Louisville
Mugunthu Dhananjeyan
University of Toledo
Paul Erhardt
University of Toledo
Laura Fenster
California Department of Health Services
Elaine Francis
U.S. Environmental Protection Agency
Neysa Garner
Tulane University
Barbara Glenn
U.S. Environmental Protection Agency
Norys Guerra
Centers for Disease Control and Prevention
Russ Hauser
Harvard University
Jerrold Heindel
National Institute of Environmental Health
Sciences
Rex Hess
University of Illinois
Janet Hess-Wilson
University of Cincinnati
Wendy Hessler
Center for Bioenvironmental Research
Victoria Holt
Fred Hutchinson Cancer Research Center
Toshihiro Horiguchi
National Institute of Environmental Studies
DeLon Hull
Centers for Disease Control and Prevention
The Office of Research and Development's National Center for Environmental Research
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Endocrine Disrupters Program Progress Review Workshop
Taisen Iguchi
National Institute of Natural Sciences
Pamela Imm
Wisconsin Department of Health and Family
Services
Scott Kerlin
DES Sons International Network
Niels Skakkebaek
University Department of Growth and
Reproduction
Rahul Khupse
University of Toledo
Wieslaw Klis
University of Toledo
Danielle Satre
University of Louisville
Deanna Scher
University of Minnesota
Stephen Schwartz
Fred Hutchinson Cancer Research Center
Mario Sellin
University of Nebraska-Omaha
Jimmy Spearow
University of California-Davis
Elizabeth Anne Stokes
Shanna Swan
University of Missouri-Columbia
Susan Laessig
U.S. Environmental Protection Agency
Enrique Luque
Universidad Nacional del Literal
Sonia Mallepell
Swiss Institute for Experimental Cancer Research
Melvenia Martin
Tulane University
John McLachlan
Tulane University
Monica Munoz-de-Toro
Universidad Nacional del Literal
Peter Nagy
University of Toledo
Kenneth Nephew
Indiana University
Pia Juul Nielsen
Danish Environmental Protection Agency
Yasuhiko Ohta
Tottori University
Janet Raloff
Science News
Julius Thigpen
National Institute of Environmental Health
Sciences
Vivian Turner
U.S. Environmental Protection Agency
Monica Unseld
University of Louisville
Alan Milan Vajda
University of Colorado
Scott Venners
Harvard University
Robert Wallace
Tulane University
Thomas Wiese
Tulane University
Harold Zenick
U.S. Environmental Protection Agency
Tongzhang Zheng
Yale University
Enmin Zou
Nicholls State University
The Office of Research and Development's National Center for Environmental Research
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