No single epidemiologic study is sufficient to determine whether C8 adversely affects health. The Science Panel has designed a series of different kinds of studies which are described briefly below. These studies began in late 2006 and are currently ongoing, with results already coming out of them (follow link at left to C8 study results). Results from these studies take from one year to five years from starting. Some of these studies are based on already collected information, while others require collection of new information, including interviews and blood samples. Any information gathered on individuals will be kept confidential by the Science Panel. In many cases a study requires a team of investigators, but in all studies a member of the Science Panel is overseeing the conduct of each specific study.

Choose from the list below to jump to a specific study:

Cholesterol, Diabetes, Uric Acid, and C8 Levels among Participants in the C8 Health Project
Cross Sectional Study of C8 and Immune Function, Hematopoietic Function, Liver, Kidney, and Endocrine Disorders and Cancer Prevalence - A Prevalence Study among Participants in the C8 Health Project.
Community Follow-up Study
Worker Follow-up Study
The Study of Birth Outcomes in the Mid-Ohio Valley
The Study of Birth Outcomes among the C8 Health Project Participants
The Geographic Patterns of Cancer Study
Short Term Follow-up Study of C8 and Immune, Liver, Kidney and Endocrine Function
Exposure Study
Half-life Study
Study of C8 and Neurobehavioral Development among Children from the C8 Health Project

1. Cholesterol, Diabetes, Uric Acid, and C8 Levels among Participants in the C8 Health Project (study completed)

Investigator: Kyle Steenland, Emory University

Outline of study

This study consists of an analysis of information from the C8 Health Project, which gathered information from 69,000 community residents in six water districts near the DuPont plant in Parkersburg, West Virginia. The C8 Health Project began in July 2005 and ended in August 2006. No new information will be gathered for this study.

Participants in the C8 Health Project filled out a questionnaire and usually also gave a blood sample. The blood was analyzed for C8 level and for a large number of other clinical markers, such as cholesterol and uric acid. There were also self reports of disease, including diabetes. The C8 Health Project contacted the relevant hospitals to ask for confirmation of the disease occurrence for many participants.

Study status

Several reports have been completed in this study – follow link at left to Study Results to see details. Our analyses of the 2005-2006 C8 Health Project data showed that those with more C8 in their blood also had more cholesterol in their blood. Higher cholesterol is known to be associated with heart disease. We found a similar pattern for uric acid and C8, a natural substance in the body which comes from the diet, and which has been linked to hypertension. Because cholesterol (and uric acid) were measured at the same time as the C8, we cannot tell which came first, the cholesterol (or the uric acid) or the C8. This prohibits us from drawing any firm conclusions linking higher levels of C8 to later higher levels of cholesterol (or uric acid). Our community and worker follow-up studies, described below, will be able to answer whether exposure to C8 is linked to later heart disease or hypertension.

We also studied diabetes in the C8 Health Project data of 2005-2006. We found no link between levels of C8 and diabetes in these data, whether the diabetes was self-reported or whether it was also validated by medical records. However, better data will be available in the community and worker cohort studies to answer more definitively whether C8 prior to disease onset is linked to diabetes.

Work in this study was completed in 2009.

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2. Cross Sectional Study of C8 and Immune Function, Hematopoietic Function, Liver, Kidney, and Endocrine Disorders and Cancer Prevalence - A Prevalence Study among Participants in the C8 Health Project.

Investigator: Tony Fletcher, LSHTM

Outline of study

This study addresses the cross sectional relationship of C8 and a number of disease and clinical disease markers in a population of 69,030 participants using data collected in the C8 Health Project. Participants resided or worked in the six water districts near the DuPont plant in Parkersburg, WV. The C8 Health Project collected data during August 2005 to August 2006 and participants completed a questionnaire and gave blood.

The blood was analyzed for C8 and a substantial set of clinical parameters. The questionnaire included self-reported medical history and information on education, smoking habits, age, and other characteristics which are taken into account in the analyses. Self-reported medical history included questions about whether the participant has ever been diagnosed with a number of diseases including cancers. Analyses will focus on the relationships between C8 blood levels and the prevalence of cancer and several clinical markers of diseases of liver, kidney and thyroid, along with immune and inflammatory markers, and endocrine effects such as pubertal development. C8 exposure classification will make use of measured C8 levels in blood and estimates of exposure to C8 in the past. Comparisons are adjusted for other variables of importance such as age, sex, smoking, weight and other clinical markers.

The first phase of analyses uses the C8 concentrations measured at the time of the C8 Health Project. A number of reports in this study are being completed in cooperation with scientists at West Virginia University. The second phase will use modelled estimates of past C8 exposure. Analysis and reporting will proceed in parallel with the other studies underway, and be completed in 2011.

Study status

This study has completed the following Status Reports: one on immune and inflammatory markers in adults, indicating that both immunoglobulin A (IgA) and C-reactive protein (CRP) levels fall with increasing levels of C8 (and also PFOS); one on patterns of age of puberty among children, indicating that age of puberty is delayed among girls with higher levels of C8 or PFOS, and delayed for boys with higher levels of PFOS but not C8; one on thyroid function in children showing some associations between reported thyroid disease and C8 and thyroid hormones and other types of perfluorinated compounds; and one on liver function in adults showing a small but clear linear association between PFOA and PFOS serum concentrations and ALT, a marker of liver injury. Work is ongoing in assessing sex hormones in children and, following the earlier Status Report on age of puberty and C8 measurements in the C8 Health Project, we are working on the potential role of earlier exposures in pubertal development, estimated at the time of the date of birth.

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3. Community Follow-up Study

Investigator: Kyle Steenland, Emory University

Outline of study

This study is a 4 year follow-up study exploring disease occurrence among adult participants in the C8 Health Project, a survey of about 70,000 community residents (of whom 55,000 were above age 20) residing in six water districts conducted from July 2005 – August 2006. Among these, about 40,000 have agreed to participate in the Community Follow-up Study. There are two rounds of interviews – one in 2009 and another in 2010.

Diseases of interest include cancer, heart disease, and any other important disease such as diabetes and neurologic disease. Interviews can be completed on the phone or on the Web. Forty dollars per person is paid for answering the questionnaire, which takes less than 30 minutes.

For those who answer positively to the occurrence of certain diseases we will ask permission to view medical records to confirm the new disease occurrence. We will also trace any deaths which occur during the 4 year follow-up and determine the cause of death. Finally, we will cross-link study participants with Ohio and WV cancer registries for another source of information on cancer occurrence.

Once all this information has been collected, we will compare the rate of disease occurrence in this population of adults to that expected based on comparable Americans who had minimal or no exposure to C8. If C8 is related to any health damage, then disease rates among the 40,000 living near the Washington Works plant will be higher than those in comparable Americans without exposure, after taking into account any other differences. Otherwise, they will not.

We will also make some comparisons of disease rates within the 40,000 adults with past exposure. Here we will draw on the C8 blood level measured during the C8 Health Project. We will compare the rate of new disease occurrence among those with higher levels in 2005-2006 to the rate among those with low levels in 2005-2006.

We will also estimate past levels of C8 exposure over time for all people in the study, based on their residential history and an estimate of C8 levels in the water over time (see Exposure Study). We can then analyze disease occurrence by total C8 in the body. If C8 is related to any health effects, long term exposure could be more important than recent exposure as measured in the blood in 2005-2006 in the C8 Health Project.

This study is anticipated to provide important evidence regarding whether there is a probable link between C8 and disease because, as a follow-up study, it will be clear that C8 exposure preceded disease.

Timeline: data collection to be finished in 2011, results in 2012.

Study status

Two rounds of interviews by telephone have been carried out. Approximately 80% of study subjects have completed interviews, and the response rate for those we were able to successfully contact was above 90%. In addition we are seeking medical records to confirm self-reports of disease. This process is long and ongoing, and requires that participants sign a medical release form. We have checked the Ohio and West Virginia cancer registries (for subjects who consented for us to do so) to check for cancer occurrence, and also checked the National Death Index to determine if people have died and what they died of.

In round 2 of interviews, we were also able to complete a good number of interviews for those we missed originally in round 1.

In the last quarter we obtained all medical records and began analyses. We issued a status report on thyroid disease in December. Our data showed a positive association between cumulative blood levels of PFOA and thyroid disease occurrence, using all cases or restricting to validated cases. Positive trends were statistically significant only for women. The risk of disease increased above the lowest exposure categories, but then did not increase after that.

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4. Worker Follow-up Study

Investigator: Kyle Steenland, Emory University

Outline of study

C8 has been used in the manufacturing of Teflon and other products by DuPont in its West Virginia Washington Works plant. Many workers in the plant have been exposed to C8 over time, at levels higher than the surrounding community. We will conduct a study of disease occurrence among workers at the plant.

DuPont has already assembled a group of approximately 6,000 workers who worked at the Washington Works plant at any time between Jan 1, 1952 and Dec 31, 2001. DuPont has studied the mortality of these workers to determine whether they died of certain diseases at a higher rate than expected. However, studies of death patterns may be less revealing than studies of disease occurrence (fatal and non-fatal disease). We are following these same workers to determine what diseases they have had, including non-fatal as well as fatal diseases. We are interested in major diseases such as cancer, heart disease, diabetes.

All workers will be free to participate or not. This study will be conducted independently of DuPont, and all information will be kept confidential. No information collected on any individual worker will be given to DuPont or anyone else. We estimate that about 2/3 of the 6,000 workers are no longer working.

DuPont has developed a way to estimate C8 exposure depending on where a worker has worked, based on C8 blood measurements for approximately 1,000 workers in 2004. DuPont has classified plant jobs into three groups of low, medium, and high exposure to C8. We plan to develop this work further, in order to take into account changes in exposure level over time. We may also create additional exposure categories beyond the low, medium, and high categories.

This study will have two rounds of interviews – one in 2009 and a second in 2010 – to determine disease occurrence over time. In addition we will seek medical records to confirm self-reports of disease.

Interviews are done either via a telephone interview or website interview, and take approximately 30 minutes in length. Interviews cover medical history and other descriptive information such as years of schooling, marital status, smoking history, alcohol history, height, and weight, and medications. Subjects are paid for their time as in the community study.

As part of our study we will determine whether workers have died and if so, cause of death. In addition, we will check the records of the West Virginia and Ohio cancer registries to see who has developed cancer. For those workers who report having had a disease, we will ask permission to review their medical records to confirm this information. For workers who have died we will interview their relatives to find out what diseases they had.

To estimate C8 levels among workers over time we will use both actual measured C8 data from an in-plant study in 2004, and measured levels among the approximately 2,000 workers who also participated in the C8 Health Project in 2005-2006. We also will use available data for workers over time dating from the 1980s. For workers without measured levels, we will estimate their levels based on where they worked in the plant, and when they worked there. Once all this information has been collected in 2009-2010, we will then compare the rate of new disease occurrence among the workers to that expected based on comparable Americans who had minimal or no exposure to C8. If C8 is related to any health damage, then disease rates among the workers will be higher than those in comparable Americans without exposure. Otherwise they will not.

We will also make some comparisons within the workers based on their level of exposure to C8. We will compare rate of new disease occurrence among those with higher levels of C8 over time to rate among workers with low levels of exposure.

This study is anticipated to provide important evidence regarding whether there is a probable link between C8 and disease because, as a follow-up study, it will be clear whether C8 exposure preceded disease. It is an important study because the workers had, in many cases, higher exposures than community residents who did not work at the plant. Taken together with all the other evidence, this study will provide the basis for a judgment about a probable link for chronic diseases such as cancer, heart disease and diabetes.

Timeline: data collection to be finished in 2011, results in 2012.

Study status

Two rounds of interviews by telephone have been carried out.

As of mid-2011, approximately 72% of study subjects have completed interviews, and the response rate for those we were able to successfully contact was above 90%. We are in the process of collecting medical records to validate self-reported disease. This process should be completed by the fall of 2011. We also expect to match workers who have consented to such matching with the WV cancer registry this fall. Data analysis should begin in late fall. Our work on estimating past exposures to workers in the plant is largely completed.

In the last quarter we obtained all medical records and data on workers from the WV cancer registry. We have begun analyses. We plan to combine the workers with the community cohort members for most analyses.

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5. The Study of Birth Outcomes in the Mid-Ohio Valley

Investigator: David Savitz, Brown University and MSSM

Outline of study

The Study of Birth Outcomes in the Mid-Ohio Valley will evaluate whether C8 exposure is related to birth outcomes, including stillbirth, preterm birth (early delivery), and birth weight. Birth outcome information was collected from state birth records for selected counties in Ohio and West Virginia. We are including areas that had C8 in the drinking water and areas that did not have C8 in the drinking water, all within the same general region. The State Health Departments' Vital Records offices maintain birth records and can provide a complete list of all births in the region. C8 exposure for the mother and child will be based on the estimated amount of C8 in the drinking water where the mother was living at the time the baby was born. We will get this estimate from another Science Panel study (see the Exposure Study). The Exposure Study is working to estimate exposure for different places at different times based on distance from the Washington Works plant and the amount of C8 released from the plant. The Study of Birth Outcomes in the Mid-Ohio Valley will help to determine whether mothers with higher estimated C8 exposure had a higher risk of having poor birth outcomes. If exposure to C8 increases the risk of a poor birth outcome, we expect to see worse birth outcomes in women with more C8 exposure. We will make adjustments for other influences on pregnancy health, including mother's age, race, education, marital status, number of previous births, and smoking habits. These characteristics about the mother are listed on the birth certificate. We will also take into account information from the U.S. Census about community characteristics, such as average income, proportion below the poverty level, and average housing value.

Study status

We worked with the Ohio and West Virginia health departments to identify the scope of the available birth and death certificate data. We applied for access to birth and death certificate data in Ohio and West Virginia. We received West Virginia vital registry birth data from 1957-2004 and fetal death data from 1967-2004. From Ohio we received vital registry birth data from 1960-2004. We cleaned and standardized all of the data and sent 11,779 addresses to Battelle for geocoding. Battelle conducted tracing and geocoding for the address data. With the geocoded data, the mother's residence at the time of birth was assigned to a location and then water source using either address or Zip Code. We also tabulated the U.S. Census data about the community characteristics.

We completed the analysis of birth outcomes based on vital records, which included an examination of stillbirth, preeclampsia, preterm birth (total, early preterm, and late preterm), term low birthweight, small-for-gestational-age births, and mean birthweight. We also linked a subset of birth records to C8 Health Project participants, and for that subset, we combined the higher quality exposure data based on residential history with the detailed birth outcome data based on vital records. These analyses and the resulting manuscript are under review for publication. A status report on this project was submitted on September 23, 2011. The results from this project were included in the reproductive health Probable Link reports submitted on December 5, 2011.

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6. The Study of Birth Outcomes among the C8 Health Project Participants

Investigator: David Savitz, Brown University and MSSM

Study Overview

The Study of Birth Outcomes among the C8 Health Project Participants will evaluate whether C8 exposure is related to birth outcomes, including miscarriage (pregnancy loss before 20 weeks), preterm birth (early delivery), low birth weight, average birth weight, preeclampsia (pregnancy complication with high blood pressure), and birth defects. The primary data source for this study is the C8 Health Project questionnaire. Women who enrolled in the C8 Health Project in 2005-2006 were asked questions about all of their pregnancies. Because women may not remember exactly how long the pregnancy lasted before the baby was born (important to define preterm birth) or exactly how much a baby weighed at birth (important to define low birth weight births), we will also use data from birth records kept by the Ohio and West Virginia Health Departments. The birth records are helpful because they have an exact measurement of gestational age and birth weight. However, we will only be able to use the extra information from the birth certificates for the 70% of women who consented to participate in Science Panel research linking data sources. For all women in the C8 Health Project reporting one or more pregnancies, we estimated their blood levels at the time of their pregnancies based on where she lived, her water consumption patterns, and her C8 blood level measured at the time of her enrollment. This estimate comes from another Science Panel study (see the Exposure Study). The Study of Birth Outcomes among the C8 Health Project Participants will help to determine whether mothers with higher estimated C8 exposure had a higher risk of having poor birth outcomes. If exposure to C8 increases the risk of a poor birth outcome, we expect to see worse birth outcomes in women with more C8 exposure. We will make adjustments for other influences on the health of pregnancy, such as mother's age, race, education, marital status, number of previous births, and smoking habits.

Study status

We cleaned and standardized the pregnancy and reproductive health data from the C8 Health Project. An initial analysis of C8 Health Project births was completed and submitted to the court in March 2009. For this initial analysis, we restricted to births in the 5 years before the Health Project and used the C8 blood measurement as the measure of exposure. This analysis used data only from the C8 Health Project questionnaire. A manuscript describing this initial analysis, entitled “Serum levels of PFOA and PFOS and pregnancy outcome”, was published in the American Journal of Epidemiology in October 2009.

For the 70% of the women who provided consent, we worked with statisticians at Mount Sinai to match C8 Health Project pregnancies to Ohio and West Virginia birth certificates. We also collaborated with the West Virginia Birth Score Registry Program to link additional births to consented C8 Health project women with the corresponding West Virginia birth certificate. In total, combining unique matches from the two processes, we linked 6,855 C8 Health Project births from 1984-2006 to Ohio and West Virginia birth certificate data. Separately, we analyzed the subset of births with linked Health Project-birth certificate data.

We have completed this analysis, filed a status report summarizing the results, and have a manuscript titled Perfluorooctanoic Acid Exposure and Pregnancy Outcome in a Highly Exposed Community to be published soon in the journal Epidemiology. The results from this project were included in the reproductive health Probable Link reports submitted on December 5, 2011.

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7. The Geographic Patterns of Cancer Study

Investigators: Tony Fletcher, LSHTM and Verónica Vieira, Boston University

Outline of study

This study addresses the relationship between past cancer incidence from 1993 to 2005 in regions of West Virginia and Ohio including the six contaminated water districts along with surrounding counties.

The goal is to determine if cancer rates by geographical area vary in relation to the C8 levels in those areas. The study is being carried out in collaboration with researchers at Boston University and Battelle and the state cancer registries in WV and OH. The population of approximately 500,000 people will be grouped by residence into geographic units of analysis according to similar average C8 exposure. The same exposure category will be assigned to all individuals in a geographic area (rather than to each individual as in the community cohort study). Information on cancer cases in the relevant counties is available from the West Virginia Cancer Registry and Ohio Cancer Surveillance Systems.

Estimated exposure to C8 in the water for these same geographical areas over time will be provided by the parallel exposure modeling project. Cancer cases will be assigned to these exposure groups by residence at time of diagnosis. Cancer incidence rates will then be computed to determine whether rates of cancer incidence differ in relation to levels of average exposure to C8. Results from this study will complement the community cohort study results. However, no Probable Link determination concerning cancer and C8 will be made until both studies are completed. Study to be completed in 2011.

Study status

The first major effort was to map the water district pipe networks for each of the six water districts so that exposure areas could be defined based on both geographic coverage and date of installation. Then for each of the two states, the incident cancers cases need to be assigned to the right exposure area, by geocoding the address of diagnosis. This assignment was completed for Ohio in 2009. Ohio Cancer data have been linked to US Census Bureau data based on address.

We have completed exposure assignment for the geographic units of analyses in Ohio and West Virginia. We have examined individual-level data for Ohio and area-level analyses for West Virginia. We are finalizing analyses of Ohio data, including examining a geographic subset of the cancer registry data for which we have additional risk factor information. This work is nearly completed.

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8. Short Term Follow-up Study of C8 and Immune, Liver, Kidney and Endocrine Function

Investigator: Tony Fletcher, LSHTM

Outline of study

This study will primarily assess changes of some clinical markers in relation to changes in C8, and detailed indicators of immune status, in a population of approximately 800 of the C8 Health Project participants who agreed to participate in Science Panel studies. We will also assess the risk of common infectious disease and urinary markers indicative of kidney disease.

These participants will be re-contacted and invited to participate in a second interview, provide a second blood sample and a urine sample. Statistical analyses will focus on the relationship between trends in C8 serum levels and trends in various clinical markers including immune, thyroid, endocrine, kidney and liver function tests; both C8 and the biomarkers will then have been measured on two occasions. An extended panel of tests for assessing immune function will be given and the association with C8 investigated. In a subset of 400 of these participants, the extent to which C8 modifies the immune response to routine influenza vaccination will be assessed. The incidence of infectious disease in relation to C8 will be assessed by both questionnaire data on self reported disease, including infectious diseases and serological tests of recent latent viral infections, specifically herpes simplex virus (HSV) infection.

The study will provide important new information because of its longitudinal nature; it will consider change in biomarkers over time in relation to changes in C8 levels in the blood. Results are expected in 2011.

Study status

A specially rented and prepared temporary office for collecting samples in Parkersburg was established, staff recruited and trained, and procedures put in place for shipping samples to the analytical laboratories. Then potential participants were written to and then telephoned to be invited to volunteer for this study. A final training day on site was set up and at that time, Tony Fletcher met with the local press to announce the new study, present the new facility and explain the study. That was March 12, 2010 and blood testing then started April 2. Over the next three months we got close to our target numbers of 800 participants; finally 755 completed the interview, visit and providing blood samples (94% of our target of 800. Preliminary analyses of data from this first phase have already yielded some important new results. Initial review of the first batch of repeated measurements of C8 show a drop in serum levels, relative to five years earlier. For the first 50 participants, the measurements in early 2010, indicated that C8/PFOA and PFOS levels fallen to between 40 and 50% of the levels for the same people in the C8 Health Project survey of 2005-2006.This study has also provided an opportunity to assess whether PFOA or PFOS interferes with measurements of free thyroxine in human population serum samples, a possibility suggested by some animal experiments. A research publication based on tests on rats had found that PFOS, though at much higher concentrations than in the mid Ohio population, can interfere with the measurement of thyroid hormones and give misleading results. Therefore we decided to investigate if interference between PFOA or PFOS and thyroid hormone measurements can happen for samples from exposed people in this study. We compared two different ways of measuring free thyroxine in the presence of PFOA and PFOS, and confirmed that there is no evidence of interference between these compounds. Therefore we can be confident that our findings will not be distorted by interference of the kind found between chemicals in the animal experiments. These results were presented in summary form at a conference on perfluorinated chemicals hosted by the EPA in North Carolina in June.

In Phase 2, we reached the target of 400 (we enrolled 403) participants who provided blood samples and received a flu shot. The purpose of this part of the C8 Science Panel Study is to understand the potential for exposure to C8 affect people's sensitivity to viral infection. All blood sample collection is now complete in this study, we are very pleased with the good co-operation of the community who donated blood samples and we are currently analyzing the results of laboratory analyses of the samples. We have confirmed that C8 blood concentrations are going down.

In a third phase we have been carrying out telephone interviews with mothers who were pregnant close to the date of the C8 Health Project survey to address whether or not infectious disease among children is related to exposure around birthtime. Interviews with 878 mothers were successfully completed and we are analyzing the results. In addition we are investigating possible biological mechanisms of action of C8, and specifically measures of gene expression are being assessed in the blood collected in the short term follow up study. The samples are currently at the lab for these gene expression assays. Finally, we are cooperating with a team in West Virginia University, whose CARDIAC project collects data over time on childhood cholesterol and blood pressure, to assess whether the trends in these cardiac risk factors correlate with trends in C8. These additional data will all contribute to the evidence for assessing probable links between C8 and disease.

The first results have been released in summary form as a Status Report, in which we report that there is an association between falling C8 and decreases in cholesterol levels. The main finding from modeling the relationship between C8 and LDL cholesterol was that a decrease in LDL cholesterol was associated with a decrease in C8, whereby a 50% drop in C8 predicted a 3.6% decrease in LDL cholesterol. Ongoing work is looking at infectious disease incidence, and immune and inflammatory markers, each in relation to C8.

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9. Exposure Study

Investigators: Kyle Steenland and Barry Ryan, Emory University; Scott Bartell, University of California, Irvine

Outline of study

This project will estimate past exposure levels to C8 in the water for community residents living near DuPont's Washington Works plant.

C8 from the plant was released in the air and also released into the Ohio River from the 1950s until recently, resulting in community exposure, largely via drinking water consumption. It is believed that most C8 in the body comes from the water supply rather than breathing air with C8 in it or eating food with C8 in it. C8 reached water supplies by entering the groundwater, which is the source of wells for both public and private drinking water. C8 entered the groundwater both by trickling down through the soil and via the Ohio River, which has some exchange with the groundwater. The peak of C8 use and of emissions occurred in the late 1990s. C8 emissions in the air have been largely eliminated in the last few years, as have any significant releases into the Ohio River. Historical exposure to C8 will be important for the other epidemiologic studies conducted by the Science Panel.

The proposed work will estimate exposure for all times back to the beginning of release of C8 from Washington Works. We will use information on how much C8 was released from the plant each year into air and water, known wind patterns, and whatever actual measurements exist of C8 in the water. This will let us estimate how much C8 was in the drinking water over time at different locations around the plant.

Taken together with residential histories available from the C8 Health Project, we will be able to estimate how much C8 participants in the C8 Health Project have taken into their bodies from drinking water over time. We will also consider what happens to C8 in the body in order to estimate what C8 levels have been in the blood over time for participants in the C8 Health Project.

Timeline: data collection and analysis began in 2007, final results were completed in 2011.

Study status

The overall purpose of this investigation is to estimate the exposure to C8 experienced by each member of the population under investigating commencing with the startup of C8 activities at the Washington Works Plant in 1951 and continuing through the present day. This work is complicated by the fact that exposures can occur through multiple pathways including inhalation of air containing particulate C8 and ingestion of water containing dissolved C8. Further, few historical data are available measuring this contaminant in the various environmental media. This requires the use of models to estimate what contaminant concentrations were historically as well as what intake and subsequent serum concentrations were. We used a series of models, accepted by the United States Environmental Protection Agency for regulatory purposes, coupled with newly developed approaches for joining these models together.

Ingestion of drinking water appears to be the main pathway for local exposure in more recent times, so much of our work has focused on detailed evaluation of past and present drinking water sources, and linking individual residential histories to those sources. Concentrations for the six public service districts (PSDs) involved in the settlement were predicted from our linked models, and calibrated using recent water samples from 1998-2006 (to improve the accuracy of the model). Calibration was conducted first by optimizing the organic carbon partition coefficient applied in the unsaturated soil zone model and groundwater transport model, then applying water-district specific correction factors. Detailed results for water concentration prediction and optimization can be found by following the link at the left to Study Results.

Since 1950, there has been a pattern of less use of small local wells and expansion of municipal water supplies. Since this movement was incremental, our models required both a detailed residential history for each individual and a detailed history of the areas served by municipal water supplies. We have produced estimates for C8 concentration in all water supplies and estimates of exposure to C8 experienced by individuals in the study. These estimates, along with occupational exposure estimates for DuPont workers in study #4, were combined with models of the elimination of C8 from the human body in order to develop historical estimates for C8 serum concentrations in each individual over time. The methods used to produce these estimates are described in a new publication also linked under the Study Results. This study has been completed and historical exposure estimates are now available for use in epidemiologic investigations.

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10. Half-life Study

Investigators: Kyle Steenland and Barry Ryan, Emory University; Scott Bartell, University of California, Irvine

Outline of study

This project will examine the blood C8 levels of about 70,000 people who live near the Washington Works plant in West Virginia and had their blood levels of C8 measured in the C8 Health Project. Although many of these people had been exposed to C8 for decades, their blood C8 levels were never measured before 2005. In order to better understand the relationship between past C8 exposures and current blood C8 levels, and to improve the quality of exposure estimates in ongoing health studies, we have invited 200 adults from the C8 Health Project to participate in a longer study designed to determine the rate of removal of C8 from the body. The rate of removal is often called the "half-life", the period of time necessary for the body to clear out half of its C8. Before this study there was an estimate that the average half-life of C8 for humans was 3-4 years, but this is based on only a few measurements among workers at 3M, another company which has used C8.

During 2007-8 carbon filters were installed to remove C8 from several contaminated water systems near the West Virginia chemical plant. People served by these water systems are expected to have lower exposures to C8 once filtration begins, which should cause a decline in blood C8 levels over time. This presents an opportunity to estimate the rate of decline through a half-life study based on repeated measurement of blood C8 levels before and after the carbon filters are installed.

Each participant in this half-life study has been asked to donate up to eight blood samples during a four year period. Levels of C8 will be measured in each blood sample. Participants will also be asked to complete a short questionnaire each time a blood sample is taken, and receive financial compensation for each blood sample. The results will help us estimate past C8 exposures for participants in the C8 Health Project, which will in turn help determine whether C8 has any health effects in the other studies being done by the Science Panel. As in all Science Panel studies, all individual data will be kept confidential.

Timeline: data collection 2007-2011, first results in 2010; final results by 2012.

Study status

This study began in 2007 when granular activated carbon filters were installed to remove C8 from public water supplies for Lubeck Public Service District and Little Hocking Water Association. We recruited 200 study participants served by these two water districts in 2007, and asked them to give up to 8 blood samples each over a period of 4 years. Participation has been excellent, with about 90% of our original participants remaining in the study throughout the entire 4 years. In the first year after filtration began, blood serum PFOA concentrations dropped by an average of 26%, corresponding to a half-life of about 2.3 years. Detailed results for the first year of the study can be found by following the link at the left to Study Results.

In the second year after filtration, serum PFOA did not decrease as quickly as it did during the first year, partly due to the increasing importance of background exposures from sources other than local drinking water. The mean background-adjusted decline in serum PFOA concentrations was 27% during year 1 and 11% percent during year 2. These rates of decline correspond to half-lives of 2.1 years during year 1, and 5.0 years during year 2. The final round of blood samples were collected in mid-2011 and have now been processed at the CDC laboratories. This final round also included optional genetic testing to determine if people with certain genes excrete PFOA at a faster rate. We expect to complete the analyses in early 2012.

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11. Study of C8 and Neurobehavioral Development among Children from the C8 Health Project

Investigator: David Savitz, Brown University and MSSM

Outline of study

The Study of C8 and Neurobehavioral Development among Children from the C8 Health Project will evaluate whether neurobehavioral development is related to C8 exposure among children who participated in the C8 Health Project. Neurobehavioral development refers to how children learn and behave compared to other children the same age. Some of the children who participated in the C8 Health Project and who were 6-12 years old during the data collection period were invited to participate in the Neurobehavioral Development Study. We used data from the C8 Health Project to identify eligible children and enrolled 320 children and their biological mothers. Only one child per family was allowed to participate. We enrolled children who were born and lived their entire lives in one of the affected water districts, and provided consent to participate in Science Panel research. By restricting the study to children who spent their entire lives in only one water district we will have a better idea of how much C8 a child was exposed to over his/her lifetime.

A mobile study van visited eligible families at their home. Children were weighed and measured, asked questions, and played reading, word, and number games with a specially trained research assistant to assess their skills. At the same time, the child's mother was interviewed. The mother was asked questions about the child's health, behavior, and home environment. Additionally, the mother took a short standardized test on vocabulary, similarities and block design. With the mother's permission, we are contacting the child's teacher for an evaluation of the child's performance at school relative to his/her classmates. At the end of the interview we cut a small piece of hair from the child's head for measuring environmental exposures.

The information we collect from the mother and child, together with the measure of C8 exposure we have from the C8 Health Project, will be used to help us understand whether there is a relation between C8 exposure and the way children learn and behave.

Study status

We have completed all data collection for the study and received the last data file from Battelle in December. This includes interviews with the parents and child, neurobehavioral testing of the child, and behavioral reports from the child’s teacher. The tests have been scored but there is extensive data preparation required before analyses can be completed. We are beginning data analysis and will complete the analyses and submit a status report and manuscripts in 2012.

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