Document e5bj7GBw0QxebOeOo5YJBeVky

Atete-tU7 (MO) %HCk-Ocl4-O 373 September 17, 2004 Via Federail Express Document Processing Center (Mail Code 7407M) Room 6428 Attention: 8(e) Coordinator Office of Pollution Prevention and Toxics i^J.S. Environmental Protection Agency, ICC Building (54)201 Constitution Ave., NW .Washington, DC 20460 -D ear 8(e) Coordinator: Ammonium Perfluorooctanoate 8EHQ-0381-0394 This letter is submitted "For Your Information" to supplement the letter of September 7, 2004 submitted by Mr. Edward E. Shea, representing MIC Specialty Chemicals, Inc. (Attachment I). Overall, the letter and accompanying trip report are an accurate reflection o f the proceedings of the meeting held at the Inn at Montchanin Village on August 20-21, 2004. Our conclusions from the meeting are summarized as follows: 1. No effects were observed on the general health of the workers at the Miteni plant. 2. No changes in clinical chemistry parameters were observed with the exception o f an apparent slight alteration of serum lipid levels that correlated with exposure. The cause and biological significance o f this observation is unclear and requires further analysis. 3. Although the observed changes appear to be correlated with exposure, it does not demonstrate a causal association with exposure to these substances. 4. Average serum levels of PFOA were higher in the Miteni workers than have been reported for occupational exposure, and significantly higher than levels reported in the general population. For the sake of completeness, we are submitting with this letter a copy o f the data slides that summarize DuPont's preliminary analysis o f the serum lipid data (Attachment 13). We note that 3M actually led the initial analysis of the Miteni data including the 37 blood parameters mentioned in Dr. Costa's trip report. After seeing the preliminary analysis of the serum lipid data, DuPont subsequently undertook an independent statistical analysis o f the serum lipid data only, and presented our preliminary analysis at the August 20-21 meeting. With respect to the data referenced in Mr. Shea's letter we note the following: 1. In Table 1 it should be noted that analyses of the sera of the "PFOA-exposed" group also revealed the presence of PFOS (perfluorooctanoic sulfonate). Dr. Costa confirmed that the plant worked with both perfluorinated compounds. The average serum PFOA concentration was - 1 6 ppm with a range o f 0.04-92 ppm and for serum PFOS the average was - 0.5 ppm with a range of 0.06-3.3 ppm. It should be noted that no analyses for these same perfluorinated compounds was undertaken for the sera of workers in the non-PFOA/non-PFOS area ("Non-PFOA" group). 8904000030 E.l. du Pont de Nemours and Company / 2. There are a number of caveats that are germane to the interpretation o f the data in addition to the fact that workers were exposed to both PFOA and PFOS; notably: a. The dataset consists of a small and arbitrary collection of subjects (--35 employees). b. There are no pre-employment/baseline lipid levels for historical reference in the study population. c. Concomitant exposure to other chemicals in the plant is an unknown variable. d. Serum lipids are well known to be affected by many different factors including family history, diet, and lifestyle; data on these factors were not available for inclusion for analysis. 3. There was a strong correlation observed between PFOA and PFOS levels. Therefore, we analyzed the relationship between the various serum lipids with respect to three dependent variables: total perfluorinated compound (the sum o f PFOA + PFOS), PFOA alone and PFOS alone. 4. The data have been analyzed in terms of a linear model; however, other models may fit the data better. In general, there is no a priori reason to expect a linear dose-response relationship in a biological system. As indicated in Mr. Shea's letter, DuPont has additional ongoing studies that may enable a broader interpretation of this small study in the Miteni workers. Notably, we are conducting a study, "Ammonium Perfluorooctanoate: Cross-Sectional Surveillance of Clinical Measures of General Health Status Related to a Serum Biomarker o f Exposure and Retrospective Cohort Mortality Analyses in a Polymer Production Plant" of over 1,000 employees at our Washington Works plant. Currently we are analyzing the data and expect to issue a final report by year's end. In addition, we are evaluating the effects of perfluorinated compounds on the activation of various nuclear receptors, e.g., PPARa, in an effort to better understand the biological activity of this class of chemicals. Finally, we are exploring the hypothesis that hyperlipidemia prolongs retention of PFOA in the serum, thus accounting for the observed correlations. A copy o f the final report(s)/manuscript(s) for the DuPont studies will be submitted to the Agency when available. Sincere.lv. A. Michael Kaplan, Ph.D. Director - Regulatory Affairs and Occupational Health AMK/RWR/PJG:clp (302) 366-5260 Attachments: (I) "Mr. Edward E. Shea's TSCA Letter, September 7, 2004" (II) "DuPont Statistical Analysis of Serum Lipid Data of Miteni Workers"