C8 Science Panel Newsletter
C8 Science Panel Quarterly Newsletter #5
1. Science Panel attends hearing with Judge Beane
1. Science Panel attends hearing with Judge Beane
The three members of the C8 Science Panel attended Wood County Court on May 18, for a Status Hearing with Judge JD Beane, who is overseeing the implementation of the C8 Settlement Agreement. Judge Beane had requested that the Science Panel members brief him on research progress, and work toward delivering probable link findings. We reported on our schedule for completion of the detailed research work and then our complete syntheses of the evidence, to allow Probable Link assessments, as agreed under the Settlement.
Panelists testified that the detailed research work is proceeding on schedule and as the research is completed they will complete syntheses of the evidence, to allow Probable Link assessments, as agreed under the Settlement. The priority is to address outcomes which past research has raised as particular concerns, including heart disease, cancer, diabetes, thyroid disease, liver disease, kidney disease, and reproductive outcomes. For each of these, the group will determine whether or not there is evidence of a probable link between PFOA/C8 and disease. These findings are on schedule to be completed by July 2012 at the latest, although the Panel told Judge Beane that any probable link judgments that can be completed earlier will be done. The first is on pregnancy outcomes and will be completed this year.
2. Science Panel to hold public forum
The Judge requested specifically that a public forum be organized so that the public can meet with the Science Panel and ask questions. Following discussion between the Settling Parties and the Science Panel, we have agreed to work together to plan a public meeting for early this fall. This will occur before our first Probable Link findings and will be an opportunity to discuss and take questions on the process and on the way we have been working towards the Probable Link assessment. The meeting will be publicized locally as well as on the Science Panel website. To provide opportunities for as many people as possible to attend, the plan is to hold two evening meetings on consecutive days in late September, in different towns.
3. Science Panel submits three Status Reports to the Court
The Science Panel is accumulating evidence to enable us to deliver conclusions to the Court on whether or not there is a probable link between C8 and any disease. As these results come out, we endeavor to make them available to the public as quickly as we can. However, we are obliged to provide any new results first to the Court. Once we have received confirmation that the Court has the report, we then either send out a press release to interested press contacts and then put them on our website, or we simply put them on the website, so the public can see them within only a few hours of being filed at the Court. At the end of each quarter, this newsletter summarizes recent status reports. On July 19, three Status Reports were filed.
The first report, investigating liver function markers, related PFOA (C8) levels in the 47,092 adults from the C8 Health Project in 2005-2006 to three clinical markers of liver function. Previously published research findings have reported an association with relatively high concentrations of PFOA in the liver to effects of exposure such as liver enlargement and liver cancer in animals. The three markers measured include bilirubin, ALT (alanine aminotransferase), and GGT (gamma glutamyltransferase). With all three markers, increased levels indicate lowered liver function. In the case of ALT, 11.2% of the study population have values above the normal range.
While there was no direct association between increase of PFOA and bilirubin or GGT, there was an increase in levels of ALT, related to increasing PFOA. This association is highly statistically significant and is not explained by other factors, such as age, physical activity, body mass index (BMI), average household income, educational level, race, alcohol consumption and cigarette smoking. Having higher levels of ALT does not necessarily imply liver disease, although many liver conditions manifest themselves with increases in these markers before clinical signs are evident.
However, the Science Panel advises caution in interpreting this link found between PFOA and a marker of liver injury, because of the cross-sectional design of the C8 Health Project. Both PFOA and the liver markers were measured at the same time and therefore we cannot be sure whether the PFOA exposure came before any changes in markers of liver function. Ongoing work is addressing whether liver disease may be affected by raised exposure to PFOA.
The second report submitted to the court detailed the mortality (death) rate of workers employed at the DuPont chemical plant in Parkersburg, West Virginia. The group included 5,793 workers employed there between 1948 and 2002. The mortality of these workers was tracked through 2008.
During the follow-up period, 18% of the workers died (1085/5793). The DuPont workers had 30% lower mortality compared to the national average, due to the 'healthy worker effect'. This is because the general US population includes many people who are sick, while worker populations, when they are working, do not. In this comparison the Science Panel took into account the age, sex, and racial distribution of the workers. Similarly, worker deaths from cancer were 26% less than expected based on the US population.
The Science Panel looked at 92 causes of death, and the only one significantly higher than the US population was mesothelioma, a rare cancer caused only by exposure to asbestos and unlikely to be related to PFOA. Significant trends of increased kidney cancer and nonmalignant kidney disease were seen with higher PFOA exposure, based on small numbers. There was no overall excess of kidney disease compared to the US population.
The Panel noted that mortality studies are not the best way to study many diseases which may not be fatal. Additional ongoing C8 Science Panel studies, based on disease occurrence rather than deaths, will provide better evidence about a probable link between PFOA and specific diseases. To accomplish this, the Science Panel has conducted interviews regarding past diseases with about 4,500 workers and about 30,000 community residents, and matched them with cancer registries and other sources of medical records. These study results will be available in the first half of 2012.
In the third report, the Science Panel analyzed 11,737 pregnancies of women in the C8 Health Project occurring between 1990 and 2005. They studied the relationship between PFOA exposure around the time of pregnancy and the risk of miscarriage (loss of pregnancy before 20 weeks), stillbirth (loss of pregnancy after 20 weeks), preeclampsia (a condition involving high blood pressure and leakage of protein into the urine during pregnancy), preterm birth (early delivery), term low birth weight (an indication of reduced growth), and birth defects (abnormalities in the infant). Factors such as calendar year when the births occurred, the mother’s age at the time of the birth, the mother’s education, parity (whether the woman had previous births), and tobacco smoking history were taken into account in this analysis.
No association was found between PFOA levels and miscarriage (based on 1,443 cases), stillbirth (106 cases), preterm birth (1,843 cases), low birth weight (133 cases) or birth defects (149 cases). There was a small but clear connection between preeclampsia (based on 730 cases) and higher levels of PFOA. There are no other studies to support or challenge this finding.
These conclusions need to take into account limitations in estimating serum PFOA levels at the time of pregnancy, the potential for errors in the self-reported pregnancy outcome information, and incomplete information on other factors that might affect the outcome of pregnancy, such as other health problems the mother may have had. The group will be obtaining additional information on preterm birth and birth weight from ongoing analyses of health department birth records for the study area. These new records will be combined with the current records and other new data before a final assessment about pregnancy outcomes is made.
4. New publications
In the last quarter the following journal article of work in progress, summarized below, from the C8 Science Panel team has gone online. It is now freely available at the journal website.
Retrospective exposure estimation and predicted versus observed serum perfluorooctanoic acid concentrations for participants in the C8 Health Project
Shin HM, Vieira VM, Ryan PB, Steenland K, Bartell SM.
This scientific paper details the methods used to estimate the historical amounts of exposure to PFOA levels in the blood of the 45,276 participants in the C8 Health Project who had not worked at DuPont and who consented to be in Science Panel studies. We estimated the amount of exposure separately for each individual, based on residential histories and predicted amounts of C8 in local water and air for each year since 1952. Our water and air predictions were published earlier this year, and summarized in the C8 Science Panel Quarterly Newsletter #4 (May, 2011).
These predicted serum PFOA concentrations were compared to levels measured in the C8 Health Project in 2005-2006, and they correlated well. Our predictions were similar but slightly lower on average than the actual blood sample measurements, but we were able to distinguish those who had lower exposures from those who had higher exposures. These comparisons are presented in detail in the paper. These modelled PFOA levels are being used for Science Panel studies based on past PFOA exposure, such as the pregnancy outcome study with results described above.
5. C8 Panel study news
Children's exposure and health
From Tony Fletcher:
We have some news on our work looking at children's exposures to C8. By looking at matched pairs of mothers and their children, we can compare the average levels of C8 in the blood and it appears that children have higher C8 in their blood than their mothers. Also, we are pleased to announce the addition of two more studies to our work programme. One is a collaboration with West Virginia University to look at trends in cardiovascular disease in children, the other involves additional interviews to check on patterns of infectious disease in children in the study area. This additional work has been agreed with the Settling Parties and will be completed during this year; it does not change our timetable to complete the Science Panel program of work. These are described here.
Children's levels of C8 are higher than their mother's
By matching children's data to the data from their mothers, we have looked at the relationship between a child's and the mother's PFOA serum concentrations. We matched children under the age of 20 at the time of the C8 Health Project survey to their mothers using identifiers and, for the successfully matched pairs, the child to mother PFOA ratios were calculated and analyzed. Quality of data was very good, and we succeeded in matching 71% of the children to their mothers. We looked at the ratio of the child's to the mother's concentrations of PFOA in serum and investigated how it varies with the age of the child, drinking water PFOA concentration and reported bottled water consumption, or mother's breast-feeding intention classified as exclusive breast-feeding versus breast- and/or infant formula.
The main finding is that, up to age 12, children on average have higher PFOA concentrations than their mothers. Among young children up to the age of 5 years, on average, children had PFOA serum concentrations 44% higher than their mothers. This is likely due to a combination of exposure to the developing child during pregnancy, via breast milk and directly from drinking water in the home. While it is a concern that children seem to accumulate PFOA from drinking water more rapidly than adults, this all relates to exposures prior to 2005/6 and since emissions of PFOA have fallen and the water supplies are filtered, this should no longer be a problem.
Study on trends in heart disease risk factors in children
There is some evidence that PFOA is linked to increased cholesterol levels and there is no data on whether it affects blood pressure. We are collaborating with investigators at the West Virginia University Pediatrics Department in their Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) surveillance study. They have been carrying out annual screening for blood pressure and cholesterol in the blood of school children across West Virginia since 1998. This overlaps with the period when PFOA contamination was discovered and stopped, in areas covered by Mason County and Lubeck water supply, in Mason and Wood Counties.
By bringing together data we have assembled on trends in serum levels of PFOA, with data the CARDIAC project has collected on trends in cholesterol and blood pressure, we plan to investigate if we can find an association between falling C8 and falling cardiac risk factors in these children. For some children who are in both studies and so have had their blood tested at different points in time, their individual trends in cholesterol can be investigated. We will not need to contact the children again, as we have all the information we need. The study will start this month and the results will be available by the end of the year.
Childhood infections in children of parents exposed to C8
It is possible that PFOA affects the immune system, which could result in people exposed to higher PFOA levels in their blood having more infections compared to those with lower levels. Development of the immune system takes place before birth, i.e. in the womb, and the developing fetus will be exposed to similar levels of PFOA circulating in the blood as the mother.
We are investigating whether exposure to PFOA is related to the number of childhood infections, for which we need to gather some more information by a short telephone interview. Mothers in the C8 Science Panel Community Study who gave birth around the time of the 2005/2006 survey will receive an invitation letter and phone call inviting them to take part. In the telephone interview, the mothers will only be asked questions about their child’s health. These interviews will take place between August and October this year, and the results will be available by the end of the year.