Funded Institutions

State University of New York at Buffalo
Matthew R. Bonner, Ph.D.

Project Period
9/30/2007 – 9/29/2010

Project Title:
New York State Angler Cohort Follow-up Study

Project Description:
The goal is to evaluate the risk of disease occurrence and associations with long-term fish consumption of contaminated Great Lakes fish. A mailed follow-up health survey is being conducted in a large established and well-characterized cohort of adults enrolled in the New York State Angler Cohort Study (NYSACS). Study participants are 18,963 middle-aged women and men who are New York State fishing license holders and who reside in 16 New York counties that border Lakes Ontario and Erie. An important feature of the NYSACS is the detailed and precise assessment of Great Lakes fishing habits and fish consumption at baseline in 1991 and again during a follow-up survey conducted in 1997. Questionnaire items focus on information pertaining to the frequency (in years) of harvesting and eating fish from waters in the Great Lakes Basin, the specific species and size of fish harvested and consumed, and how the fish was prepared and cooked, both in the 12 months preceding completion of the questionnaire and historically across the period 1955-1991. Research activities to date have focused on developmental and reproductive health consequences associated with Great Lakes fish consumption. The current study will expand on existing follow-up to ascertain the occurrence of select fatal and nonfatal health outcomes and to relate these outcomes with reported Great Lakes fish consumption, recent and long-term. Findings from this study could inform and improve existing public health recommendations on contaminated Great Lakes fish consumption.

Michigan State University
Janet R. Osuch, M.D.

Project Period
9/30/2008 – 9/29/2012

Project Title:
Organochlorine and Gene Expression of Sex Steroids in a Multigenerational Cohort

Project Background:
A widely accepted theory is that human growth, development and disease occurrence depends upon a complicated interaction between inherited genes and interactions with the environment. In addition, theories linking exposure to substances in the womb (through the mother's blood) with diseases found in adulthood has also been accepted by a number of scientists from different fields. The explanation for this has to do with chemical changes in inherited genes that occur because of the substances to which we are exposed in the womb. These chemical changes can sometimes change the way that our genes function.

Organochlorines, many of which are toxic chemicals that were banned by the government decades ago because of health concerns, are present in the blood of most human beings alive today. Examples of some organochlorine compounds include polychlorinated biphenyls (PCBs) and the well know pesticide DDT. These chemicals do not break down in the body quickly, and they are stored in fatty tissue of animals and humans. They are present in much of the food that we eat, especially fish, meat, and dairy products. They can change the way that hormones function (called endocrine disruption) in both animals and humans. Even more worrisome, these chemicals can cause changes that can be passed from one generation to another in laboratory animals. We want to know if this can happen in humans.

Project Description:
The overall goal is to explore whether the genes that control the function of sex hormones are changed by exposure to two chemicals in the womb, PCB and DDT. We will study a group of people who have participated in a previous research project, the Michigan Fisheaters' Group, and their children and grandchildren, The study group will be recruited from a pool of female parents (n=90), daughters (n=195), granddaughters (n=219); and, male parents (n=80), sons (n=103) and grandsons (n=220). Telephone interviews will be conducted to collect a medical history, an exposure history, and when applicable a reproductive history. Blood will be collected to study the function of the genes that control sex hormone levels in each person.

The current study aims to more firmly establish the link between organochlorine exposure and endocrine disruption. It will also allow us to find out if genes affecting the function of sex hormones are altered and if so, whether this is related to exposure to PCBs or DDT. These theories may help guide future studies to explore whether inheritance of epigenetic modifications due to endocrine disruption exposure is possible in humans.

State University of New York College at Oswego
Paul Stewart, Ph.D.

Project Period
9/30/2007 – 9/29/2011

Project Title:
Prenatal PCB Exposure and Cognitive Development

Project Description:
The goal of the current project is to examine the important putative effects of polychlorinated biphenyls (PCBs), with methylmercury (MeHg), and lead (Pb) on response inhibition in a longitudinal cohort of children. The project tracks three cohorts of children born in 1991-92, 1992-93, and 1993-94. Participants were selected along with a larger group of non-longitudinal subjects when the study began in 1990. Currently, the longitudinal sample includes 199 subjects; 101 Lake Ontario fisheaters and 98 controls who reported not eating fish. Over the past 17 years, project investigators have developed an extensive database of exposure, outcome and potentially confounding/mediating variables which permit rigorous assessment of the impact of prenatal PCB exposure into the late teen years. The project has demonstrated that PCB exposure is related to an impaired ability to inhibit behavior, or impaired response inhibition. This deficit is characterized by an inability to inhibit prepotent response tendencies, rather than just excessive motor activity, perseveration, or an attention deficit. While these findings have advanced the field in important ways, it is the data that relate to the putative effects of PCBs, in combination with MeHg, and even Pb, that is most compelling. Current research involves fMRI neuroimaging in an effort to examine the neurological underpinnings of impaired impulse control.

University of Illinois, Urbana-Champaign
Susan L. Schantz , Ph.D.

Project Period
9/30/2007 – 9/29/2011

Project Title:
Health Effects of PCB Exposure from Contaminated Fish

Project Description:
The overall goal is to evaluate neuropsychological outcomes in adolescents exposed to polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), methyl mercury (MeHg) and other contaminants via consumption of fish from highly polluted waters in northeast Wisconsin. The research builds on the investigator’s previous study of neuropsychological function in Southeast Asian (Hmong) immigrants from this region using similar evaluations in adolescent children in the general population of sports anglers. The study is expanding to include all risk groups that are consuming fish from local waters.

The current study will include 14-18 year-old children from households with a currently valid Wisconsin fishing license in the Green Bay, Wisconsin area. A sampling strategy will identify participants using the Wisconsin Department of Natural Resources (WDNR) license angler database. The database contains 857,353 residents who purchased a fishing license during 2006-2007 and approved the release of their information; approximately 61% of the 1.4 million licensed anglers in the state.

State University of New York at Buffalo
John Vena, Ph.D.

Project Title:
The New York Angler Cohort Study--Exposure Characterization and Reproductive Developmental Health

Project Description:
The New York State Angler Cohort Study (NYSACS) is a population-based study the research program established to assess the association between past and current consumption of contaminated sport fish, from the Great Lakes, and short-and long-term human health effects. The NYS angler cohort is a representative sample of New York State fishing license holders between 18 and 40 years of age in 1991 who resided in 16 upstate New York counties in close geographic proximity to Lake Ontario. The research program's current objectives include:

• Establish a cohort of African-American and Hispanic anglers from the Buffalo River and Niagara River; these are geographical areas of concern identified by the International Joint Commission (IJC).
• Conduct a pilot study of 5th-8th graders at Buffalo's Science Magnet School and begin development of Great Lake Environmental Education and Community Action Initiative.
• Continue the study of the prospective pregnancy cohort study (to include other at-risk women) analyzing the relationship between consumption of contaminated fish from Lake Ontario and two sensitive reproductive outcomes: time to pregnancy and early pregnancy loss.
• Assess biomarkers of exposure and/or susceptibility to dioxin-like compounds and biomarkers of immune status.
• Continue the tracing of the entire cohort and conduct passive follow-up through vital records.
• Continue to implement dissemination and communications efforts in concert with the New York State Health Department.

New York State Department of Health
Edward Fitzgerald, Ph.D.

Project Title:
PCB, DDE, mirex, and HCB Exposure Among Native American Men and Women from Contaminated Great Lakes and St. Lawrence River Basin Fish and Wildlife and Neurological Effects of Environmental Exposure to PCBs

Project Description:

Project 1
An epidemiologic study in an established cohort of Native Americans, the Mohawk Indian tribe, which investigates the association between the consumption of locally caught fish and wildlife and body burdens of PCBs , 68 PCB congeners, DDE, mirex, and HCB in men and women who live along the St. Lawrence River and its tributaries. The investigators will also examine residential, occupational, and recreational exposure to these contaminants.

Project 2
In order to investigate the hypothesis that exposure to PCBs via fish consumption, close proximity to a hazardous waste site, and other sources has resulted in elevated body burdens of PCBs and has caused PCB congener-specific and age-specific neurological effects, the investigators propose to recruit 75 men and 75 women, 55-74 years of age from an area with historically high PCB contamination. They will recruit a comparison group of equal number, matched to the study population regarding age and gender. Their objectives are to estimate cumulative and peak dietary and residential exposure of PCBs among the study population using current and estimated air concentrations. Investigators will use a questionnaire regarding fish consumption to estimate PCB exposure via fish, and will analyze blood samples from these individuals for 109 PCB congeners levels and correlated the environmental levels using "fingerprinting" methods. Additionally, investigators will perform a neuropsychological test battery on the subjects and attempt to correlate with the exposure estimates and serum PCB levels, as well as compare serum PCB levels and neuropsychological function to a matched control group.

University of Illinois at Chicago
Donald P. Waller, Ph.D.

Project Title:
Great Lakes Fish as a Source of Maternal and Fetal Exposure to Chlorinated Hydrocarbons

Project Description:
The purpose of this study is to determine the effects of consumption from possibly contaminated fish (PCB's, DDT/DDE and dieldrin) on pregnant woman of African-American descent and their newborns. The subject population will consist of a control and a fish consuming group who will be identified at the U.Chicago Lying-in Hospital, U. Ill Hospital, Miles Square Clinic and Altgeld Gardens Clinic (and possible other area clinics). The investigators will interview subjects followed throughout pregnancy to term. Biological specimen collections consists of maternal and fetal cord blood, placenta, breast milk, adipose tissue and meconium. The investigators will evaluate meconium as a biologic specimen to predict infant in utero exposure to toxic chemicals.

University of Wisconsin-Milwaukee
John Dellinger, Ph.D.

Project Title:
Ojibwa Health Study II - Epidemiology, Laboratory Toxicology, and Outreach

Project Description:
This proposal continues the study of the original Ojibwa Health Study on dietary fish contaminated with methylmercury and organochlorines (polychlorinated biphenyls and pesticides) and their correlation with adverse health outcomes. The first three years (Phase I) of the project focused on setting up the participating tribes and conducting laboratory toxicological studies. The second three years (Phase II) continued those studies with the emphasis on completing sample collections. Additionally, the investigators will conduct neurobehavioral assessment of individuals who provide biologic samples because of the known relationship between the fish contaminants and neurologic dysfunction. The next three years (Phase III) the investigators will complete all chemical analyses on biologic samples and report the results back to the tribes. Health promotion and risk communication strategies will be implemented with the input from the tribes. The research program will also support the ongoing tribal research aimed at monitoring contaminant levels in the local fisheries run by the different tribes. The specific aims of the research falls in two categories human epidemiology studies and outreach activities.

University of Illinois at Urbana-Champaign
Susan L. Schantz, Ph.D.

Project Title:
Longitudinal Assessment of Neuropsychological and Thyroid Function in Aging Great Lakes Fisheaters and a Prospective Study of Health Outcomes in Asian Americans

Project Description:

The objectives of the proposal are to:

• Complete follow-up neuropsychological assessments of aging Lake Michigan fisheaters, statistically analyze the data and prepare manuscripts for publication.
• Establish a cohort of Asian American (Hmong people from Laos and Cambodia) men and women of childbearing age who have a high probability of consuming contaminated fish from the Fox River and/or other local polluted water.
• Describe the reproductive experiences of this population.
• Determine fish consumption practices of this population.
• Determine the distribution of serum PCB levels in a subset of the cohort.
• Examine changes in serum PCB and serum thyroid hormone levels during pregnancy.
• Evaluate health outcomes in infants born to the women in this cohort.

In the first study, the researchers will evaluate cognitive and motor function in aging (50 to 70 plus years old) fisheaters and in their age- and sex-matched non-fisheating controls. Investigators will test the two groups using a neuropsychological assessment battery designed to detect subtle deficits in cognitive and motor functioning.

In the second study of this research project, some of the activities will include determining the levels of PCBs in mothers' blood during pregnancy and at delivery; samples will also be collected from the umbilical cord. Investigators will also perform the following activities:

• examine mothers’ blood to assess thyroid status in relation to PCB exposure.
• assess the cochlear function in the newborns within 24-48 hours of postnatal age.
• assess physical measurements (height, weight, head circumference) at birth, and then at 6, 9, and 12 months.
• conduct a behavioral assessment in the newborns (Brazelton Neonatal Behavioral Assessment Scale) at 6 and 12 months of age (Bayley Scales of Infant Development).
• Perform cognitive testing at 6 months of age (Fagan Test of Visual Recognition Memory). Further cognitive testing will be done at 9 and 12 months of age.

State University of New York at Oswego
Thomas Darvill, Ph.D.

Project Title:
Behavioral Effects of Consumption of Lake Ontario Fish: Two Methodological Approaches - Continuation of A Longitudinal Study Testing 4 and 6 Year Olds

Project Description:
Dr. Thomas Darvill of SUNY College at Oswego conducted research entitled, "Behavioral effects of consumption of Lake Ontario fish: Two methodological approaches (Continuation of a longitudinal study testing children ages 4-8 years). The proposal is the continuation of a project which has been supported by ATSDR since 1992. The proposal consists of two parts, i.e., a human and an animal study.

Human study: This is a longitudinal-sequential study involving behavioral testing of three cohorts of children born to women from Oswego County, New York, who consumed large amounts of Lake Ontario sportfish over their lifetime. Initial data from the Oswego study of newborns (supported by ATSDR) show that newborns from mothers who consumed ~ 40 equivalent pounds of Lake Ontario fish scored more poorly on reflex, automatic, and habituation clusters of the Neonatal Behavioral Assessment Scale than those from mothers who consumed 40 PCB equivalent pounds of Lake Ontario fish or no fish. These data represent the first replication and extension of the neonatal results of the Lake Michigan Maternal Infant Cohort study by Jacobson et al. (1984). More recent data from the Oswego project indicate that prenatal exposure to PCBs impairs cognitive functioning in children as early as 1 and 3 years of age. To date, the investigators have obtained behavioral data at 3, 6, 12, 24, 36, 51, and 54 months of age. Researchers requested funds to continue the assessment of behavioral and cognitive development of the children in the study as they enter elementary education years (grade K-2).

Animal study: The investigators have previously demonstrated that a diet of Lake Ontario salmon causes a significant behavioral change in laboratory rats, i.e., rats fed Lake Ontario salmon are hyper-reactive to adverse events, but react normally when "life is pleasant." The purpose of the current proposal is to examine putative learning and memory deficits in rats pre- and postnatally exposed to environmentally relevant levels of PCBs.

Michigan State University
Lawrence J. Fischer, Ph.D.

Project Title:
Health Risks from Consumption of Great Lakes Fish

Project Description:
This research grant seeks to continue and expand mercury exposure research supported by the ATSDR Great Lakes Human Health Effects Research Program. This research effort will provide additional information needed regarding mercury exposure and possible health risks to women of childbearing age living in the Great Lakes Basin. This is important because the developing human fetus is known to be particularly susceptible to the neurotoxic effects of methylmercury, the primary form of mercury present in sport-caught and purchased fish.

The proposed research has been divided into 3 subprojects, each with a specific focus. The subprojects are as follows:

Subproject 1. Determination Using Segmental Hair Analysis of the Time Course of Exposure to Methylmercury in Pregnant and Non-Pregnant Women: The goal of this proposed research is to determine the time course of mercury exposure in pregnant women throughout the entire period of gestation. Further, non-pregnant women have been recruited for studies using the same sampling and analytical methodology so that a comparison between the two groups can be made. This comparison will provide information on mercury exposure and toxicokinetic differences that may be related to pregnancy itself.

Subproject 2. Mercury Hair Levels at Mid-Pregnancy and Risk for Preterm Delivery in a Cohort of Michigan Women: The goal of this proposed research is to examine the relationship between methylmercury and early pregnancy loss in particularly susceptible populations. This study will also provide mercury body burden data for a population that has traditionally been understudied, African-Americans.

Subproject 3. Develop and Implement a Pilot Project for Monitoring the Michigan Population for Mercury Exposure: A pilot project will be undertaken to investigate the feasibility of state-wide random sampling of Michigan women to determine baseline mercury levels. Additionally, historical data regarding mercury levels in various species of freshwater fish obtained through the State of Michigan yearly fish monitoring effort will be analyzed to evaluate possible regional differences in fish contamination and to evaluate in a systemic way, the chronology and regionality of mercury-related fish contamination in the state. Results from these studies will permit a much better understanding of fish contamination and consumption as they relate to methylmercury exposure in women.

Wisconsin Department of Health and Family Services
Henry A. Anderson, M.D.

Project Title:
Consortium for the Health Assessment of Great Lakes Sport Fish Consumption

Project Description:
This renewal grant continues to examine the association between sport caught fish consumption in the diet of Great Lakes area residents and serum levels of 1) PCBs, 2) DDE, 3) dioxins, and 4) furans which have been detected in Great Lakes contaminated fish. The area residents consist of a cohort of frequent consumers of Great Lakes fish (charter boat captains and their spouses with n = 1868 households, and Wisconsin anglers with n = 129 households) and infrequent consumers (n = 1,300 households from the same community as the captains). In addition, serum PCB and DDE levels are being evaluated in the group to determine if an association exists between the serum levels and 1) birth outcomes, 2) serum thyroid and steroid hormone levels, and 3) reproductive outcomes (e.g., semen quality). Risk communication has also been a component of the study.

The cohort had blood serum samples drawn for contaminants and received a phone interview dealing with 1) fish consumption, 2) reproductive history, 3) health advisory awareness, 4) risk factors (e.g., smoking), and 5) demographic information. Of the frequent consumers, 1868 households completed the phone interview with more than 500 individuals participating in the blood drawing. Of the infrequent consumers, 1,300 households completed the phone survey and 99 of these individuals had blood drawn.

Results have shown the PCB and DDE levels were higher in frequent consumers of Great Lakes fish when compared to the infrequent consumers. A pilot study also revealed that frequent consumers had higher serum dioxin, furan, and coplanar PCB levels than a comparison group.

State University of New York at Albany
Anthony DeCaprio, Ph.D.

Project Title:
PCB Congener and Metabolite Patterns in Adult Mohawks: Biomarkers of Exposure and Individual Toxicokinetics

Project Description:
To conduct statistical analyses of congeners-specific serum PCB data for ~750 adult Mohawk Indians using multivariate techniques and to compare the results with those for other published relevant databases to identify unique populations and environmental variables in the Mohawk cohort.

Michigan State University
Wilfried Karmaus, M.D., MPH

Project Title:
Assessing Effects of Human Reproductive Health of PCB Exposure via Consumption of Great Lakes Fish

Project Description:
The proposed project is a renewal research grant entitled "Assessing effects on human reproductive health of PCB exposure via consumption of Great Lakes fish." The study design is a cross-sectional and longitudinal observational assessment of the effects of PCB exposure, both current and in utero, on reproductive health. The main goal of this project is to assess fecundability and reproductive success in two cohort studies of individuals selected from two source populations at elevated risk of exposure to PCBs via consumption of Great Lakes sport-caught fish. A secondary goal is to pilot a case control study of low sperm count in relation to the same exposures. In the two cohort studies, investigators aim to examine specific hypotheses about the relationship of PCB exposure to reproductive health occurring directly through consumption of sport-caught Great Lakes fish, and occurring indirectly through in utero exposure. PCB exposure, in both the cohort and case-control studies will be assessed by a detailed questionnaire on fishing practices and through serum analysis for PCBs. To assess reproductive health in the cohort studies, investigators will examine time to pregnancy, sex ratio and selected correlates of fertility, including serum levels of testosterone, LH and FSH in men, and cyclic levels of urinary progesterone, estradiol, LH, and FSH in women. The first population (Cohort A), which is already assembled and will be expanded in the next fiscal year, is a sample of couples, one or both of whom is a licensed angler, and individuals resident in one of ten Michigan counties abutting on three of the Great Lakes. Cohort A consists of couples and individuals who completed a questionnaire on sports fish eating practices and who indicated plans to have a child within the next five years. The second population (Cohort B), to be assembled, consists of adult offspring of an existing cohort of Michigan anglers interviewed and assessed by the Michigan Department of Health, starting in the 1970's. In Cohort A, the exposures of interest will be assessed in the couples themselves; in Cohort B, the exposures of interest are in the female member of the couple, with emphasis on exposures that are likely to have occurred while the woman was in utero or exposed to breast milk. Couples from both cohorts who are planning pregnancies will be followed prospectively. Specific reproductive outcomes will be assessed in relation to both serum PCB levels and to self-reported Great Lakes fish consumption.

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