Document bGZqoKQLV8z7j4Z08DjpgnL6

Taft/ Taft Stettinius & Hollister LLP 425 Walnut Street, Suite 1800 /Cincinnati, OH 45202-3957 /Tel : 513 .381 .2838 / Fax : 513 .381 .0205 /www .taftlaw .com Cincinnati / Clevelancl /Columbus / Dayton / Indianapolis / Nortnern Kentucky / Phoenix / Beijing RoBeRT A. BiLorT 513 .357 .9638 bilott@taftlaw.com -`~73 ~~"~s ~3$g~' February 2, 2009 TSCA Confidential Business Information Center (7407M) EPA East - Room 6428, Attn: Section 8(e) & FYI U .S . Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, DC 20460-0001 Re: Submission To TSCA 8(e FYI Database Re: PFOA/PFOS To TSCA 8(e)/FYI Database : We are hereby providing the following information for inclusion in the TSCA 8(e)/ FYI databases with respect to PFOA/PFOS : 1 . C-8 Science Panel Status Report, "Association of Perfluorooctanic Acid (PFOA) and Perfluorooctanesulfonate (PFOS) with Uric Acid Among Adults with Elevated Community Exposure to PFOA" (Jan . 23, 2009); 2 . Fei, C., et al, "Maternal Levels of Perfluorinated Chemicals and Subfecundity," 1 Hum . Reprod . 1-6 (Jan . 28, 2009) ; 3 . West Virginia University, "C-8 Health Project Results: C-8 and Other Clinical Conditions and Diagnoses" (Jan . 2009); and 4. West Virginia University, "C-8 Health Project Results: C-8 and Other Laboratory Values" (Tabular Format) (Jan . 2009). Illl~~i~~~~~ RAB :mdm Enclosures 11322984 .1 COWAM No Co E... .- . . .. ~,~ V` : p. 2 StRtus report : Association of perfluorooctanic acid (PFOA) and pertluoroctanesulfonate (PFOS) with uric acid among adults with elevated community exposure to PFOA The C8 Science Panel (Kyle Steenland, Tony Fletcher, David Savitz) January 23, 2009 This report summarizes the findings relating PFOA (C8) and PFOS (C8S) to levels of uric acid in the serum of the participants in the C8 Health Project, which was carried out in 2005-2006 in the Mid-Ohio Valley . A full report ofthese findings will be submitted to a peer-reviewed scientific journal. p. 4 Background : Perfluorooctanoic acid (PFOA, also known at C8) and perfluoroctanesulfonte (PFOS, also known at C8S) are compounds which do not occur in nature but have been widely used in chemical production since WWII, and persist indefinitely in the environment . They are present in the serum of most Americans at median (50`h percentile) levels of 4 ng/ml (nanogram/milliter) and 21 ng/ml, respectively, and also present in the serum of residents of many other countries. PFOA has been associated with elevated uric acid in one study of exposed workers, but not previously studied in a general population . Uric acid is a risk factor for hypertension and possibly for other cardiovascular disease. Methods : We conducted a cross sectional study to examine the association between PFOA and PFOS and uric acid in the serum among 55,388 community residents age 18 and older in Ohio and West Virginia, who lived or worked in six water districts contaminated with PFOA from a chemical plant. All these residents participated in the C8 Health Project in 2005-2006. At that time they gave blood, which was used to measure both PFOA and uric acid in the serum (the liquid clear part ofthe blood after blood cells have been taken out). We compared their levels of uric acid in relation to levels of C8 via multiple regression techniques, while adjusting for other variables which could influence uric acid. Results: The median (50`l' percentile) of uric acid level in the population was 5 .5 mg/dl (milligram/deciliter). The median level of PFOA was 30 ng/ml, while the median level of PFOS was 20 ng/ml. Both PFOA and PFOS were significantly associated with increases in uric acid levels, with an increase of0.2-0 .3 mg/dl in uric acid associated with an increase from the lowest to highest decile (each decile represents 10% ofthe population) of either PFOA or PFOS . The risk ofexcessive uric acid (defined as >6 mg/dl in women, >6.8mg1dl in men) increased modestly with increasing quartile of each of the two chemicals; the ratios of risk for each quartile versus the first quartile were 1 .00, 1 .24 (95% confidence interval 1 .16-1 .32), 1 .34 (95% confidence interval 1 .26-1 .43), and 1 .38 (95% confidence interval 1 .30-1 .47) for PFOA and 1 .00, 1 .06 (95% confidence interval 0.99-1 .12), 1 .17 (95% confidence interval 1 .10-1 .24), and 1 .25 (95% confidence interval 1 .17-1 .33) for PFOS. Conclusion : Higher serum levels of both PFOA and PFOS were associated with a higher risk of excessive uric acid in the blood. However, because of the fact that uric acid and PFOA/PFOS were measured at the same time, we cannot know if an increase in either PFOA or PFOS would lead to an increase in uric acid. Other possibilities include that both uric acid and these two chemicals increase in relation to some other unknown chemical in the blood, or even that an increase in uric acid in fact causes an increase in PFOA or PFOS for unknown reasons. Therefore no firm conclusions about a causal relationship between PFOA or PFOS and uric acid can be drawn from these findings . p. 6 Hum . Reprod. Advance Access published January 28, 2009 Human Reproduction, Vol. l, No. l pp. 1-6, 2009 doi :10.1093/humrep/den490 Maternal levels of perfluorinated chemicals and subfecundity Chunyuan Fei 1~5, Joseph K. McLaughlin2,3, Loren Lipworth2,3, and Jorn Olsen 11,4 'Department of Epidemiology, School of Public Health, University of California - Los Angeles, PO Box 951772, 71-254 CHS, 650 Charles E. Young Drive South, Los Angeles, CA 90095-1772, USA Zlntemational Epidemiology Institute, 1455 Research Boulevard, Rockville, MD 20850, USA 3Vanderbih University Medical Center, Vanderbitt-Ingram Cancer Center, Nashville, TN 37232, USA 4Institute of Public Health, University of Aarhus, VenneFyst Boulevard 6, DK 8000 Aarfius C. Denmark SCorrespondence address. Tel: + I-310-825-5373 ; Fax: + I-310-206-6039 ; E-mail: cfeiQa ucla.edu BACIFCPROtiND: PerFfuorooctanoate (PFOA) and perfiuorooctane sull'onate (PFOS) are ubiquitous man-made compounds that are possible hormonal disruptors . We examined whether exposure to these compotu3lds may decrease fecundity in: humans . METHODS: Plasma levels of PFOS and PFOA were measured at weeks 4-14 ofpregnancy among 1240 women from the Danish National Birth Cohort recruited from 1996 to 2002. For this pregnancy, women reported time to pregnancy (TTP) in five categories (< I , 1-2, 3-5, 6-12 and > 12 months) . Infertility was defined as having a TTP of > 12 months or received infertility treatment to establish this pregnancy. REStCIL.TS : Longer TTP was associated with higher matemal levels of PFOA and PFOS (P < 0 .001) . Compared with women in the lowest exposure quarble, the acQusted odds of infertility increased by. 20-134- and 60-1'54% among women in the ihigher ttr+ee quartiles of PFOS and PFOA: respectively. Fecundity odds ratios (FORs)ivere also estimated usmgCox discrete-time models . The adjuste4FORs were virtually identicai -#yr women irlt#re three- highest exposure .groups of PF{flS-(FOR ; 0.70l. 0.67 and 0.74, respectivi!ly) compared with the lowest quartile. A 'Fmear-lik&-.tsend was observed for PF4A (fOR= 0:33, C~:73 and 060 for three- highest quartiles versus lowest quartile). When: aN-quartitIes were included in a likelihood -ratio test, the trends were, sqpIficant for PFOS and PFLSA (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: These findings suggest that PFOA and PFOS exposure at plasma levels seen in the general population may reduce fecundity; such exposure levels are common in developed countries . Key words: matemal blood / time to pregnancy / fecundity / perfluorooctanoate / perfluorooctane sulfonate Introduction Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) belong to a class of perfluorinated chemicals (PFCs) that are widely used in many consumer products (paper wraps, fire-fighting foams, pesticides, textiles including clothing, upholstery, carpets and personal care products) and in manufacturing processes (industrial surfactants and emulsifiers) . They are persistent in the environment and have been detected in wildlife and humans around the world (Giesy and Kannan, 2001 ; Kannan et al., 2004 ; Apelberg et al ., 2007 ; Calafat et al ., 2007; Fei et al., 2007) . They were considered biologically inactive when first commercially introduced in the 1950's, but animal studies of PFOA and PFOS have since indicated toxic effects on the liver, immune system and developmental and reproductive organs (Kennedy et al ., 2004 ; Lau et al., 2004, 2007). PFOA and PFOS may affect sex hormone homeostasis, and have been associated with increased incidence of fetal resorptions and pregnancy loss in animals (Case et al., 2001 ; Butenhoff et al., 2004 ; Lau et al ., 2006 ; Wolf et al., 2007) . In recent decades, a remarkable decline in fertility rates has been observed in developed countries, which can largely be explained by social changes in desired family sizes and better contraceptive methods, but may also in part be attributed to reduced fecundity, the biological capacity to reproduce (Olsen and Rachootin, 2003). In the USA, 2% of women of reproductive age had an infertility-related medical appointment within the previous year, and 8% had an infertility-related medical visit at some point in the past (Centers for Disease Control and Prevention (CDC), 2008). Infertility is associated with psychological stress and anxiety for women and couples, and with adverse birth outcomes or diseases (Zhu et al., 2007 ; Jensen et al., 2008), and treatment carries financial burdens for individuals and for society. Environmental pollutants, such as polychlorinated biphenyls, pesticides and other chemicals (Taskinen et al ., 1999; Law et al., 2005), The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please emaid: joumals.permissionsQoxfordloumals.org. Fei et al. have been linked to subfecundity. In a previous paper (Fei et at., 2007), we reported that maternal PFOS and PFOA levels were inversely related to parity, perhaps due to fetal uptake during pregnancy or excretion by breast milk, but this association could also be explained by a link between exposure to PFOS or PFOA and subfecundity . We used data from the Danish National Birth Cohort (DNBC) to assess whether maternal plasma PFOS and PFOA levels, measured in early pregnancy, were associated with a longer time to pregnancy (TTP), a measure that has been used to estimate fecundity in epidemiologic studies for more than 25 years (Rachootin and Olsen, 1982) . Materials and Methods The women were enrolled into the DNBC, a nationwide follow-up study of almost 100 000 children and their mothers. More details about the cohort have been presented elsewhere (Olsen et al., 2001). Briefly, pregnant women were recruited through their general practitioners around weeks 6-12 of gestation . Approximately 50% of all general practitioners in Denmark participated in the study, and approximately 60% of invited women accepted the invitation to participate. Self-reported data were collected by computer-assisted telephone interviews twice during pregnancy and twice after birth. A study biobank was set up, consisting of two maternal blood samples taken during pregnancy, and one umbilical cord blood sample obtained shortly after birth. We measured plasma PFOA and PFOS levels in a subset of DNBC participants. Among all participants (n = 43 045) who provided the first maternal blood sample, gave birth to a single live born child without congenital malformation, and completed all four telephone interviews, we randomly selected 1400 women. Detailed information about sampling has been described elsewhere (Fei et al ., 2007). We excluded 160 with unplanned pregnancies or unknown TTP. Altogether, 1240 women were included in our main analyses . Written informed consent was obtained from all participants at recruitment . The UCLA Office for Protection of Research Subjects (Reference No . 06-08-023-01) and the Danish Data Protection Agency (Reference No. J.Nr 2006-41-6324) approved the study protocol . Time to pregnancy In the first interview (at approximately 12 weeks of gestation), women were asked if their pregnancy was planned, partly planned or not planned. All except those responding 'not planned' were further asked, 'For how long did you try to get pregnant before you succeeded?' followed by five fixed answering categories of TTP: got pregnant immediately (i.e. < I months), 1-2, 3-5, 6-12 and > 12months . Infertility was defined as having a TTP of > 12 months or infertility treatment to establish the current pregnancy. PFOA and PFOS exposure We used the maternal blood samples taken at the first antenatal visit (weeks 4-14 of pregnancy) for this study. Concentrations of PFOS and PFOA in plasma were measured by high performance liquid chromatography/tandem mass spectrometry at the 3M Toxicology Laboratory (Ehresman et al., 2007). Stable labeled analogs of PFOS (1802 PFOS) and PFOA (13C2 PFOA) were used in extraction procedures, and the extractions were perforrned using solid phase extraction techniques and based on 100 W of plasma. All values were above LLOQ (the lower limit of quantification : I ng/ml), except one PFOA value that was assigned a value of half the LLOQ . Further details about the analysis methods were given in our eariier report (Fei et al., 2007). The laboratory was blinded to any information on the pregnant women. Statistical analysis PFOA and PFOS levels were analyzed as continuous variables and were also categorized a priori into quartiles using the lowest quartile as the reference group. We first used logistic regression to estimate the odds ratios (ORs) of infertility for women who were exposed to higher levels of PFOA or PFOS compared with the reference level. Fecundity odds ratios (FORs) were then estimated using the Cox model modified for discrete time data (Allison 1995). Approximate median numbers of months (i .e . 1, 2, 4 and 9) were assigned to the first four reported categories of TTP. TTP was censored at the 13th month if women had a TTP > 12 months or received infertility treatment for this pregnancy (n = 201) . In our study, FORs measure the odds of a successful conception for women who had higher levels of PFOA or PFOS compared with the reference levels within a given calendar month, given that the women did not become pregnant in the previous month. FORs < I therefore indicate decreased fecundity and a longer TTP. Avalue of P < 0.05 was considered statistically significant. Potential confounders included maternal age at delivery, parity, prepregnancy body mass index (BMI), maternal socio-occupational status, paternal education, paternal age and alcohol consumption before pregnancy. Age at menarche, irregular menstrual periods, history of spontaneous miscarriages, abdominal diseases (e.g. endometriosis, pain), paternal occupation and gestational weeks at blood drawing were also considered, but were not included in the final models as they had little effect on the estimated associations. Information on smoking and coffee consumption were only reported after pregnancy and women with TTP > 12 months were more likely to have stopped smoking; furthermore, adjustment for these variables did not change the associations between PFOA or PFOS and the outcome, and were therefore not included in the models . Results Half of the women became pregnant within the first 2 months of trying, while 379 (30%) had a TTP of >_6 months, 188 of whom had a TTP of > 12 months. The average age of the women was 30.6 years and 15% were above 35 years of age at delivery. About half of the women were expecting their first child (Table I), and one-third were overweight or obese . Eighteen per cent had a history of spontaneous miscarriages and 14% reported experiencing irregular menstrual cycles prior to this pregnancy. The median plasma PFOA and PFOS levels among the planned or partly planned pregnancies were 5.3 ng/ml [interquartile (IQR) : 4 .0, 7 .0] and 33.7 ng/ml (IQR : 26 .6, 43 .5), respectively. As previously reported (Fei et al., 2007), PFOS and PFOA levels decreased with increasing age or parity and with decreasing pre-pregnancy BMI. PFOA levels were associated with irregular menstrual periods (9 .0% in the lowest quartile versus 15 .0% in the upper three quartiles), as well as PFOS (11 .6% in the lowest quartile versus 14.2% in the upper three quartiles) . Compared with women who got pregnant in the first 6 months of waiting time, women who had a longer TTP had higher PFOA and PFOS levels (P < 0.001 for both), and they were more likely to be older, of middle socio-occupational status, and to have a history of spontaneous miscarriages or irregular menstrual cycles (Table I) . Those with younger partners or partners with higher education levels had a shorter TTP. The proportion of women with TTP > 12 months (infertility) was higher in the higher three quartiles of PFOA and PFOS versus the lowest quartile (Table 11). We estimated that the odds of infertility p. 8 . Perfluorinated chemicals and time to pregnancy Table I Characteristics (if" subjects and TTP among women with planned pregnancy* Women with planned Pregnancy (n = 1240)% . . .. .. . .. . . .. . . . .. . .. .. .. .. .. .. .. .. .. ... . . . . . . . . . . . . . . . . PFOS, ng/mh 35 .5+ 12.8 PFOA, ng/mlb 5 .6+2.6 Matemal age at delivery <6 months (n = 861)% .. .. .. . . . .. .. . . .. . 34.6+ 12 .7 5.4+2 .2 6-12 months > 12 months PFOA (n = 191)% (n = 188)% (nglml)" . .. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . .. . . . 36 .6+ 12 .5 38.3 + 13.0 - 6.0+3 .4 6.3 2.7 PFOS (nglml)e . . . .... - <25 years 7.8 25-29 years 40.0 30-34 years 37.0 >_35 years 15 .2 Parity 8 .8 8.4 2 .1 6.1 1 .9 38.0+ 10.9 42 .1 39.3 31 .4 6.1 +2 .8 37.1 12.6 37 .0 35 .1 39 .4 5.2+2 .3 34 .2+ 13 .3 12 .1 17.3 27.1 5.2 2.4 33 .2 12.5 0 44 .7 1 36 .3 >2 19 .0 Pre-pregnancy BMI 41 .9 49 .2 54.8 6 .7+2.7 37 .8+ 12 .7 39.4 32 .5 33 .0 4 .8+2.0 33 .7 12 .7 18.7 18 .3 12.2 4.62.2 33.5 12 .3 < 18 .5 kg/m2 4.2 18 .5-24.9 kg/m2 66.3 25 .0-29.9 kg/m2 22.3 >30.0 kg/m2 7.2 Matemal SES 3 .8 5.9 4.3 5.2+2 .1 32.9+ 13 .8 67 .9 61 .0 64 .2 5.6+2 .7 35 .0 12.8 21 .9 24.6 21 .4 5.7+2 .3 36 .7 11 .8 6 .3 8.6 10 .2 6.1 +2 .6 38 .8+ 13 .8 Higher 51 .9 54 .2 45 .3 47.6 5 .6+2.4 34 .2+ 12 .5 Middle 40.2 37 .4 47 .4 46.0 5 .7+2.8 37.1 12 .8 Lower 7.9 8.4 7 .4 6 .4 5.6+2 .2 36.9 13.8 Alcohol consumption before pregnancy (drinks/week) 0 to < 1 22 .0 1-1 .5 24 .0 2-3 22 .0 >3 32.0 Smoking in early pregnancy 20.8 23.7 25 .7 5.3+2 .2 35 .4+ 12.4 227 22.6 31 .6 5.8+2 .4 37.0+ 12.8 23 .3 20.5 17 .6 5.5+2 .2 35 .7+ 13.1 33 .3 33 .2 25.1 5.9 3.1 34 .4 12.8 Yes 22.7 No 77.3 History of spontaneous miscarriages 22 .5 27 .2 19.0 5 .6+2.3 34.4+ 11 .7 77.5 72 .8 81 .0 5.6 2.6 35.8 13 .1 No 82 .0 Yes 18 .0 Irregular menstrual periods 85.2 74.9 74 .3 5.7+2 .6 35 .6_+ 12.7 14 .8 25.1 25 .7 5.3+2 .2 35 .1 13 .4 No 86.4 Yes 13 .6 Paternal age 88 .2 87.9 77.1 5 .6+2.6 35 .4+ 13 .0 11 .8 12 .1 22.9 5 .8+2.0 36.0 11 .6 <30 years 29 .4 30-34 years 39.3 35-39 years 23 .1 >40 years 8 .2 Paternal education 32.3 28 .4 17 .1 6.2+2 .4 38.0_+ 12.3 41 .0 35.8 35 .3 5.5+2 .8 35 .0+ 12.9 20.1 24.7 35 .3 5.3 +2.2 34 .3 + 13 .4 6 .7 11 .0 1 2.3 5 .2+2.5 33 .3 1 1 .3 Lower 20 .2 Middle 33 .9 Higher 41 .6 Other or unknown 4.3 19 .2 24 .6 20.7 5.7 2.1 38.2+ 12 .4 3 1 .7 36 . 1 41 .5 5.9+3 .0 37.5 +_ 12.8 45.1 34.6 33 .0 5.4+2 .4 32-8+ 12.5 4.1 4.7 4.8 5 .7+2.6 33 .4 + 12.9 W-ft daq:, niaternrd a$e at delivery (r,= i). pre-Kegnancy. ghM (h- n).materru} .aocio-occulratianalst~ta;l~' (^ '2fj:'~`d spontaneous cons-pt3~n before pregnancy (n = 3). patemal age (n= t f); bd~'ye mean f SD.PFOA. perlluoroocu~ PFpS;_~~e. m`s~'ages (~ = 1), alcohol Fei et af. Table 11 Estimated OR for infertility (TTP > 12 months) and FOR according to plasma concentrations of PFOS or PFOA (ng/ml) in early pregnancy' Exposure PF05 (ng/ml) 6 .4-26 .0 26 .1-33.3 33 .4-43.2 >_43 .3 P-value for trend PFOA (ng/ml) <LLOQ-3 .9 1 3 .91-5 .20 5 .21-6.96 >_ 6.97 P-value for trend No . of planned pregnancy 293 305 317 317 293 308 315 316 Infertility Per cent ' 10 .6 15.4 19.5 18.6 8,9 18 .2 15 .5 21 .5 .. . .. .. . . .. .. . . . .. . FOR (95% CI)` OR (95% CI)b .. . .. . . . .. .. . . . .. . . . . . . . . . . . . . . . .. . . . . . . . .. . 1 .00 1 .70 (1 .01, 2.86) 2.34 (1 .40, 3.89) 1 .77 (1 .06, 2.95) 0.025 1 .00 0.70 (0.56, 0.87) 0.67 (0.53, 0.84) 0.74 (0.58, 0.93) 0.002 1 .00 2.06 (1 .22, 3.51) 1 .60 (0 .93, 2.78) 2.54 (1 .47, 4.39) 0.006 1 .00 0.72 (0 .57, 0.90) 0.73 (0 .58, 0.92) 0.60 (0 .47, 0.76) <0.001 'Tlie-estknates were ad1~ted for maternat age atdetrv~r. ~y. prapr~rancq BMI,-rnat~srat5E5, alcoholconsuinpEion before ~u+i~i~rst. ?al,Se, and paternaled,Ka,;c,F; seva, women (trom a total d 12413):were'exduded berause ofmiasing data on covariates, Logistic regression; `Coxdiscrete-tiaiemodek'ythe ;P-~es for uend tests of FOP. were given for thefourvquaiYNe compatTsan of'BFpA and PFQS learelk using z IikeFhood ratio tes[ GI, confidence interval, FpR fec~ od~fs ralic~; CEC1Q~ lower limit of quantification. increased by 70-134% for women in each of the higher exposure categories of PFOS, and 60-154% for women in each of the higher exposure categories of PFOA, compared with the lowest quartile. Women who were exposed to higher levels of PFOA or PFOS had a longer TTP; the adjusted FORs were 0.70, 0 .67 and 0 .74 for the top three quartiles of PFOS and 0.72, 0 .73 and 0.60 for the top three quartiles of PFOA (versus the lowest quartile) (Table II) . When all quartiles were included in a likelihood ratio test, the trends were significant for PFOS and PFOA (P=0 .002 and <0.001, respectively) . Women who were carrying unplanned pregnancies had lower PFC levels . The median level was 4 .8 ng/ml (IQR: 3 .5, 6 .6) for PFOA and 30.0 ng/ml (IQR: 26 .6, 43 .5) for PFOS . They were of younger age (<25 years) or much older (>35 years), more often parous and of lower socio-occupational status . They were less likely to take contraceptive pills and to drink alcohol before pregnancy, but more likely to smoke in early pregnancy . Including these women as having a TTP of ' < I month' strengthened the observed associations (data not shown) . Only including women with regular menstrual periods slightly lessened the association (data not shown). Discussion To our knowledge, this is the first study to assess the associations between PFOA and PFOS plasma levels and TTP in humans . Higher maternal PFOA and PFOS levels measured in early pregnancy were found to be associated with longer TTP . The odds of a conception leading to a recognized pregnancy were reduced for women who were exposed to PFOS and PFOA above the lowest quartile, and the magnitude of the reduction in fecundity was similar for the three higher quartiles . The exposure time window of interest is at the start of pregnancy planning, but our exposure data were taken at 4-14 weeks gestation . PFOA and PFOS levels were, however, rather stable over pregnancy (Fei et al., 2007) . We assume that our exposure assessment reflects the exposure level during the entire pregnancy planning time period . Information on TTP was obtained during the first trimester when women should be able to recall this with reasonable accuracy aoffe et al ., 2005) . We further provided five response categories in order to facilitate valid recall, at the expense of precision . Differential recall by women according to PFC levels is unlikely to be a problem in our study since the exposure levels were unknown to them. Maternal age, paternal age and paternal education substantially changed the associations between PFOS and TTP, while parity and paternal education were the most influential confounders in the analysis of PFOA . We did not have information on some important determinants of TTP, including frequency and timing of intercourse, and sperm quality . Sperm quality could potentially contribute to the associations between maternal PFC levels and TTP, if these compounds impact sperm quality and if PFC levels in male and female partners are similar, which is likely to some extent since the couples may share some aspects of lifestyle and around 99% subjects in this subcohort had a spouse or partner . Adjustment for paternal occupation did not change the estimates . There are several potential limitations of our study. First, we studied TTP of pregnancies which led to the birth of a child, limiting conclusions that can be drawn regarding women who were unable to get pregnant, even after infertility treatment . Only couples who planned or partly planned their pregnancy can report a TTP. Ninety per cent of the women planned or partly planned their pregnancy in our study . Selection bias resulting from exclusion of fertile women who did not plan their pregnancy is possible, and our data showed that the associations between PFC levels and longer TTP . ' Perfluorinated chemicals and time to pregnancy p. 10 5 were stronger after inclusion of unplanned pregnancies in the analyses . The biological mechanism by which exposure to PFOS and PFOA may reduce fecundity is unknown. PFCs may interfere with hypothalamic-pituitary-ovarian regulation, possibly causing irregular menstrual cycles, delayed ovulation or early abortions not recognized by the mother . In this study, we found similarly higher proportions of women reporting irregular menstrual periods in the upper three quartiles of PFCs compared with the lowest. Similarly, exposure to PFOS can reduce the number of regular estrous cycles in rats (Austin et al ., 2003) . Although the doses administered to rats were higher than the levels found in our study, but close to those found in occupationally exposed human populations (Olsen et al., 1999), the findings of Austin et al. (2003) may not apply to man, since the rodent estrous cycle is not an ideal model for the human cycle and the half-lives of these chemicals in humans greatly differ from those in animals . Increased levels of estrogen and/or decreased levels of testosterone have also been found in male rats given oral doses of PFOA at 2 mg/kg/day or higher (Cook et al., 1992; Biegel et al., 1995; Liu et al ., 1996; Martin et af., 2007) . A dose of 3 mg/kg/day is approximately equivalent to 4000 ng/ml in rat serum, which is slightly higher than levels observed in occupationally exposed populations (Butenhoff et al., 2004), but female rats were not studied as often as male rats in the studies of PFOA . Abnormal hormone levels may have an impact on infertility, and results from several animal studies, although not all, showed that exposure to PFOA or PFOS increased the incidence of spontaneous miscarriages (Case et al., 2001 ; Butenhoff et al., 2004 ; Lau et al ., 2006 ; Wolf et al., 2007). In conclusion, our data suggest that exposure to PFOA and PFOS at levels found in the general population may increase TTP. Whether our results will add PFCs to the list of risk factors for subfecundity remains to be seen, but PFCs may explain some of the fertility differences seen among different populations in developed countries . Authors' contributions C .F. designed the study, analyzed and interpreted the data, drafted the paper. J.O. monitored each step of the study, designed the study, guided analysis and interpretation of the data, and revised the paper.J .K.M . designed the study, interpreted the data and revised the paper. L.L. interpreted the data and revised the paper. Acknowledgements Thanks are extended to the 3M Toxicology Laboratory led by David J . Ehresman . They performed all laboratory analyses . Funding The original study was supported by the International Epidemiology Institute (IEI), which received a funding grant from the 3M Company . The 3M Company has no control over the design, data analysis and interpretation or writing of this study . J .K .M . and L .L. were employed by IEI . J .O. and C.F. independently work at the University of California, Los Angeles and have no competing financial interest. References AIIison PD . Survival Analysis using SAS: A Practical Guide. Cary, NC: SAS Institute Press, 1995, 134- 136 . Apelberg BJ, Witter FR, Herbstman JB, Calafat AM, Halden RU, Needham LL, Goldman LR. Cord serum concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in relation to weight and size at birth. Environ Health Perspect 2007 ; 115 :1670-1 676 . Austin ME, Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SM . Neuroendocrine effects of perfluorooctane sulfonate in rats . Environ Health Perspect 2003 ;1 1 1 : 1485-1489 . Biegel LB, Liu RC, Hurtt ME, Cook JC. Effects of ammonium perfluorooctanoate on Leydig cell function: in vitro, in vivo and ex vivo studies . Toxicol Appl Pharmacol 1995 ;134:1 8-25. Butenhoff JL, Kennedy GL Jr, Frame SR, O'Connor JC, York RG. The reproductive toxicology of ammonium perfluorooctanoate (APFO) in the rat . Toxicology 2004 ;196 :95- 116 . Calafat AM, Wong LY, Kuklenyik Z, Reidy JA, Needham LL. Polyfluoroalkyl chemicals in the U .S . population: data from the National Health and Nutrition Examination Survey (NHANES) 20032004 and comparisons to NHANES 1999-2000. Environ Health Perspect 2007; 1 I S : 1 596- 1 602 . Case MT, York RG, Christian MS . Rat and rabbit oral developmental toxicology studies with two perfluorinated compounds. Int J Toxicol 2001 ;20:101- 109, Centers for Disease Control and Prevention (CDC) . Assisted Reproductive Technology . 2008 ; http ://www .cdc .gov/ART/2008(date last accessed, 6 May 2008) . Cook JC, Murray SM, Frame SR Hurtt ME. Induction of Leydig cell adenomas by ammonium perfluorooctanoate : a possible endocrinerelated mechanism. Toxicol Appl Pharmacol 1992; 1 13 :209-217. Ehresman DJ, Froehlich JW, Olsen GW, Chang SC, ButenhoffjL. Comparison of human whole blood, plasma, and serum matrices for the determination of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other fluorochemicals. Environ Res 2007 ;103 :176-184 . Fei CY, McLaughlin JK, Tarone RE, Olsen J. Perfluorinated chemicals and fetal growth : a study within the Danish National Birth Cohort . Environ Health Perspect 2007 ;115 : 1677 -1682. Giesy JP, Kannan K. Global distribution of perfluorooctane sulfonate in wildlife. Environ Su Technol 2001 ;35:1339-1342 . Jensen A, Sharif H, Olsen JH, Kjaer SK. Risk of breast cancer and gynecologic cancers in a large population of nearly 50,000 infertile Danish women. Am J Epidemiol 2008 ;168 :49-57 . Joffe M, Key), Best N, Keiding N, Scheike T, Jensen TK. Studying time to pregnancy by use of a retrospective design . Am f EpidemioL 2005 ; 162:1 15-124 . Kannan K, Corsolini S, Falandysz J, Fillmann G, Kumar KS, Loganathan BG, Mohd MA, Olivero J, Van Wouwe N, Yang JH et al. Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries. Environ Sci Technol 2004 ;38:4489-4495. Kennedy GL Jr, Butenhoff JL, Olsen GW, O'Connor JC, Seacat AM, Pericins RG, Biegel LB, Murphy SR, Farrar DG . The toxicology of perfluorooctanoate . Grit Rev Toxicol 2004 ;34:351 -384 . Lau C, Butenhoff JL, Rogers JM. The developmental toxicity of perfluoroalkyl acids and their derivatives . Toxicol Appl Pharrnacol 2004 ; 198:231-241 . Lau C, Thibodeaux JR, Hanson RG, Narotsky MG, Rogers JM, Lindstrom AB, Strynar MJ . Effects of perfluorooctanoic acid exposure during pregnancy in the mouse. Toxicol Sci 2006;90:510-518 . p. 11 Fei et al. Lau C, Anitole K, Hodes C, Lai D, Pfahles-Hutchens A, Seed J . Perfluoroalkyl acids : a review of monitoring and toxicological findings . Toxicol Sci 2007 ;99 :366-394. Law DC, Klebanoff MA, Brock JW, Dunson DB, Longnecker MP. Maternal serum levels of polychlorinated biphenyls and 1,1-dichloro-2,2-bis (p-chtorophenyl)ethylene (DDE) and time to pregnancy. Am j Epidemiol 2005 ;162:523-532. Liu RC, Hurtt ME, Cook JC, Biegel LB . Effect of the peroxisome proliferators, ammonium perfluorooctanoate (C8), on hepatic aromatase activity in adult male Cri: CD BR (CD) rats . Fundarn Appl Toxicol 1996;30:220-228 . Martin MT, Brennan R), Hu W, Ayanoglu E, Lau C, Ren H, Wood CR Corton JC, Kavlock RJ, Dix DJ . Toxicogenomic study of triazole fungicides and perfluoroalkyl acids in rat livers predicts toxicity and categorizes chemicals based on mechanisms of toxicity. Toxicof Sci 2007;97 :595-613 . Olsen J, Rachootin P. Invited commentary: Monitoring fecundity over time if we do it, then let's do it right. Am J Epidemiol 2003 ;157:94-97. Olsen GW, Burris JM, Mandel JH, Zobel LR . Serum perfluorooctane sulfonate and hepatic and lipid clinical chemistry tests in fluorochemical production employees .] Occup Environ Med 1999; 41 :799-806. Olsen J, Melbye M, Olsen SF, Serensen TI, Aaby P, Andersen AM, Taxb01 D, Hansen KID. Juhl M, Schow TB et al. The Danish National Birth Cohort-its background, structure and aim. Scand f Public Health 2001 ;29 :300-307. Rachootin P, Olsen J . Prevalence and socioeconomic correlates of subfecundity and spontaneous abortion in Denmark. Int J Epidemio! 1982; 1 1 :245-249 . Taskinen HK, Kyyronen P, Sallmen M, Virtanen SV, Liukkonen TA, Huida O, Lindbohm ML, Anttila A. Reduced fertility among female wood workers exposed to formaldehyde . Am J Ind Med. 1999 ; 36 :206-212 . Wolf CJ, Fenton SE, Schmid JE, Calafat AM, Kuklenyik Z, Bryant XA, Thibodeaux J, Das KR White SS, Lau CS et al. Developmental toxicity of perfluorooctanoic acid in the CD- I mouse after cross-foster and restricted gestational exposures . Toxicol Sci 2007 ; 95:462-473 . Zhu JL, Obel C, Hammer Bech B, Olsen J, Basso 0 . Infertility, infertility treatment. and fetal growth restriction . Obstet Gynecol 2007 ; 110 :1 326-1334 . Submitted on September 12, 2008; resubmitted on November 7, 2008; accepted on December 18, 1008 W-W : : School of Medicine : : Community Medicine : : C8 P 44 of 2 ~. Z Site In~_lcti " C~r,ip :~s P~' rp " ~';'.I; dire~tnr~t ~ Corttar,t Site Map C8 Home What is C8 What's New? C8 Health Project ; Settlement Details Brookmar Project Team Science Panel WVU Project Team C8 Health Project Results .~ Contact Us Other Links Department Home SoM Home Search : 0 Department Q Health Sciences Center G WVU [ C8 Home > C8 Results > Other Clinical Cond . and Diagnoses Prinl C8 Health Project Results C8 and Other Clinical Conditions and Diagnoses The WVU website is a communication vehicle to depict associations or their public use. These tables and graphs show many comparisons between diag reported and / or validated) and corresponding population serum PFOA (C8) lev appears that there is a clear relationship between serum C8 and a clinical di ; meaning of that relationship still requires thought and discussion . Some of the r, while real, are weak and not likely to be important. Several are strong, intE potentially important, and none of them can be taken to show an etiologic (caus( relationship or its absence without more work . When it comes to causes, scienti these preliminary data with deference to additional work that needs to be done . These data concerning associations are for public use. They will receivi collaborative work in peer review format. We hope they prompt public cl suggestions of interested scientists . Download Abobe Reader Congenital Malformations, Deformations and Chromosomal Abnormal : Defects) Diseases of the Blood and Blood-Forming Organs and Certain Disorders In Immune Mechanism Diseases of the Circulatory System Self-Reported Raynaud's Syndrome (44 KB) Diseases of the Digestive System Diseases of the Genitourinary System " Self-Reported Endometriosis (40 KB) " Self-Reported Kidney Disease (59 KB) " Self-Repoded Uterin e Fibroids (40 KB) Diseases of the Musculoskeletal System and Connective Tissue " Self-Reported Osteoarthritis (58 KB) Diseases of the Respiratory System http ://www.hsc .wvu .edulsom/cmed/c8/results/otherConditionsAndDiagnoses/index .asp 2/2/2009 . 'VV : : School of Medicine : : Community Medicine : : C8 . Diseases of the Skin and Subcutaneous Tissue . Diseases of the Nervous System " Self-Reported Parkinson's Disease (35 KB) Endocrine, Nutritional and Metabolic Diseases " Self-Reported Thyroid Disease (74 KB) Infectious Diseases 41 Mental and Behavioral Disorders Neoplasms (Cancer) School of Medicine I Robert C. Byrd Health Sciences Center I P.O . Box 9100 I Morgantown, WV 26506-9100 Webmaster I Site Design by WVU Web Services PRgI3'Z of 2 Last Modified : Ja O 2009 West Vir http://www.hsc.wvu.edu/som/cmed/c8/results/otherConditionsAndDiagnoses/index .asp 2/2/2009 p. 14 Self-Reported Raynaud's Syndrome and C8lPFOA Adults (>=18Y0) Only NOTE: All results reported here are based on information as reported by participants and were not independently verified . The association between self-reported Raynaud's Syndrome and C8/PFOA is unadjusted for any potential confounders or covariates. Caution in interpretation is warranted . Female Male Quartile Group -- C8 Quartile Group -- C8 1 2 3 4 Total 1 2 3 4 Total Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count 9'o within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Count % within Quartile Group - C8 % within Self-Reported Raynaud's Syndrome Self-Reported Raynaud's Syndrome No/No Response Yes Total 9119 53 9172 99.4% .6% 100.0% 31 .1% 27.9% 31 .1% 7289 33 7322 99 .5% .5% 100.0% 24 .9% 17 .4% 24 .8% 6680 52 6732 99 .2% .8% 100.0% 22 .8% 27 .4% 22 .8% 6190 99.2% 52 6242 .8% 100.0% _ 21 .1% 27 .4% 21 .2% 29278 190 29468 99 .4% .6% 100.0% 100.0% 100.0% 100.0% 4839 3 4842 99 .9% 18.1% .1% 100.0% 10.0% 18.1% 6853 8 6861 99 .9% .1% 100.0% 25 .7% 26.7% 25 .7% 7121 7 7128 99 .9% .1% 100.0% 26 .7% 23 .3k 26 .7% 7864 12 7876 99 .8% 29 .5% .2% 100.0k 40 .0% 29.5% 26677 30 26707 99 .9% .1 % 100.0% 100.0% 100.0% 100.O ~o 0 2009 West Virginia University School of Medicine Participants with Self-Reported Raynaud's Syndrome within C8iPF0A Population Quartile Group Gender 0 Female M Male p. 15 Population Quartile Group -- C8 C8IPFOA for Participants Stratified by Self-Reported Raynaud's Syndrome 3W .OO-1 Self-Reported Raynaud's Syndrome I No I Yes V 250 .00" aP of + r- 2W .04'I J 1= ' 15o.on-I 0 a a Cc>O >oo.oo- W.W- 1 Female Gender I -Male 2009 West Virginia University School of Medicine p. 16 Self-Reported Endometriosis and C8/PFOA Adult (>=18Y0) Women Only NOTE : All results reported here are based on information as reported by participants and were not independently verified . The association between self-reported endometriosis and C8/PFOA is unadjusted for any potential confounders or covariates . Caution in interpretation is warranted. Female Quartile Group -- C8 1 2 3 4 Total Count % within Quartile Group - C8 % within Self-Reported Endometdosis Count % within Quartile Group - C8 % within Self-Reported Endometriosis Count % within Quartile Group - C8 % within Seff-Reported Endometriosis Count % within Quartile Group - C8 % within Self-Reported Endometriosis Count % within Quartile Group- C8 % within Self-Reported Endometriosis Self-Reported Endometriosis No/No Response Yes Total 8113 88 .5% 31 .4% 6415 87 .6% 24 .8% 5900 87 .6% 22 .8% 5431 87 .0% 21 .0% 25859 87 .8% 100.0% 1059 11 .5% 29 .3% 907 12.49~0 25.1% 832 12 .4% 23.1% 811 13 .0% 22 .5% 3609 12.2% 100.0% 9172 100.0% 31 .1% 7322 100.0% 24.8% 6732 100.0% 22.8% 6242 100.0% 21 .2% 29468 100.0% 100.0% 0 2009 West Virginia University School of Medicine p. 17 Number of Participants with Self-Reported Endometriosis within C8tPF0A Population Quartile Group . 0 10,000- +d. E 'Oa W 8 11 Self-Reported Endometriosis "Wo /Yes d 0 Q d ' 41 6,0-O i Vf i 431 a+ 4,000-' R a u a 0 2,000- E 3 0 11 2 3 Population Quartile Group -- C8 CBIPFOA for Participants Stratified by Self-Reported Endometriosis Self-Reported Endometriosis 0 2009 West Virginia University School of Medicine p. 18 Self-Reported Kidney Disease and C8IPFOA Adults (>=18Y0) Only NOTE All results reported here are based on information as reported by participants and were not independently verified. The association between self-reported kidney disease and C8/PFOA is unadjusted for any potential confounders or covariates. Caution in interpretation is warranted . Female Quartile Group - C8 Male Quarti le Group - C8 1 Count % within Quartile Group - C8 % within Self-Reported IGdney Disease 2 Count % within Quartile Group - C8 % within Self-Reported Kidney Disease 3 Count % within Quartile Group - C8 % within Self-Reported FGdney Disease 4 Count Total % within Quartile Group - C8 % within Self-Reported Kidney Disease Count % within Quartile Group - C8 % within Self-Reported IGdney Disease 1 Count % within Quartile Group - C8 % within Self-Reported IGdney Disease 2 Count % within Quartile Group - C8 % within Self-Reported IGdney Disease 3 Count % within Quartile Group - C8 % within Self-Reported IGdney Disease 4 Count % within Quartile Group - C8 % within Self-Reported IGdney Disease _ Total Count % within Quartile Group - C8 % within Self-Reported IGdney Disease Self-Reported IGdney Disease No/No Response Yes Total 8131 1041 9172 88 .7% 11 .3% 100.0% _ 30 .9% 6534 33 .0% 788 31 .1% 7322 89 .2% 10.8% 100.0% 24 .8% 25 .0% 24 .8% 6079 90.3% 653 6732 9.7% 100.0% 23 .1% 20 .7% 22 .8% 5567 675 6242 89 .2% 21 .2% 10.8% 100.0% 21 .4% 21 .2% 26311 89 .3% 3157 29468 10.7% 100.0% 100.0% 100.0% 100.0% 4348 89.8% 494 4842 10 .2% 100.0% 17.9k 19 .9% 18 .1% 6240 621 6861 90 .9% 9.1% 100.0% 25 .8% 25 .0% 25.7% 6465 663 7128 90 .7% 26.7% 9.3% 100.0% 26.7% 26 .7% 7172 91 .1% 704 7876 8.9% 100.0% 29 .6% 28 .4% 29.5% 24225 90 .7% 2482 26707 9.3% 100.0% 100.0% 100.0% 100.0% 2009 West Virginia University School of Medicine p. 19 Participants with Self-Reported Kidney Disease within C81PFOA Population Quartile Group Gender / Female / Male Population Quartile Group -- C8 C8IPFOA for Participants Stratified by Self-Reported Kidney Disease Self-Reported Kidney Disease I No I Yes Gender 0 2009 West Virginia University School of Medicine p. 20 Self-Reported Uterine Fibroids and C8/PFOA Adult (>=?8Y0) Women Only NOTE: All results reported here are based on information as reported by participants and were not independently verified . The association between self-reported uterine fibroids and C8/PFOA is unadjusted for anv potential confounders or covariates. Caution in interpretation is warranted . Female Quartile Group -- C8 1 2 3 4 Total Count % within Quartile Group - C8 % within Self-Reported Uterine Fibriods Count % within Quartile Group - C8 % within Self-Reported Uterine Fibriods Count % within Quartile Group - C8 % within Self-Reported Uterine Fibriods Count % within Quartile Group - C8 % within Self-Reported Uterine Fibriods Count % within Quartile Group - CS % within Self-Reported Uterine Fibriods Self-Reported Uterine Fibriods No/No Response 7959 86 .8% 31 .6% 6257 85.5% 24.8% 5757 85 .5% _ 22 .8% 5226 83 .7% 20 .7% 25199 85.5% 100.0% Yes 1213 13 .2% 28 .4% 1065 14 .5% 24 .9% 975 14.5% 22 .8% 1016 16 .3% 23 .8% 4269 14 .5% 100.0% Total 9172 100.0% 31 .1% 7322 100.0% 24 .8% 6732 100.0% 22 .8% 6242 100.0% 21 .2% 29468 100.0% 100.0% , 0 2009 West Virginia University School of Medicine Number of Participants with Self-Reported Uterine Fibroids within C8lPFOA Population Quartile Group SetMeported Uterine Fibroids " No M Yes Population Quartile Group - C8 C8IPFOA for Participants with Self-Reported Uterine Fibroids 0 2009 West Virginia University School of Medicine p. 22 Self-Reported Osteoarthritis and C8/PFOA Adults (>=18Y0) Only NOTE: All results reported here are based on information as reported by participants and were not independently verified . The association between self-reported osteoarthritis and C8/PFOA is unadjusted for any potential confounders or covariates . Caution in interpretation is warranted. Female Quarti le Group - C8 Male Quar6le Group - C8 1 2 3 4 Total 1 2 3 4 Total Count % within Quartile Group - C8 % within Self-Reported Osteoarthritis Count % within Quartile Group - C8 % within Self-Reported Osteoarthritis Count % within Quartile Group - C8 % within Self-Reported Osteoarthritis Count % within Quartile Group - C8 % within Self-Reported Osteoarthritis Count % within Quartile Group - C8 % within Self-Reported Osteoarthritis Count % within Quartile Group - C8 % within Self-Reported Osteoarthritis Count % within Quartile Group - C8 % within Self-Reported Osteoarihritis Count % within Quartile Group - C8 % within Self-Reported Osteoarihritis Count %within Quartile Group - C8 % within Self-Reported Osteoarthritis Count % within Quartile Group - C8 % within Self-Reported Osteoarthri6s Self-Reported Osteoarthritis No/No Response Yes Total 8502 670 9172 92 .7% 7.3% 100.0% 32.2% 6625 21 .8% 697 31 .1% 7322 90.5% 9.5% 100.0% 25.1% 22 .7% 24 .8% 5978 88 .8% 22 .6% 754 11 .2% 24 .5% 6732 100.0% 22 .8% 5289 953 6242 84 .7% 20 .0% 15 .3% 100.0% 31 .0% 21 .2% 26394 3074 29468 89 .6% 10.4% 100.0% 100.0% 100.0% 100.0% 4618 224 4842 95.4% 4.6% 100.0% 18.2% 16 .8% 18 .1% 6580 95 .9% 25 .9% 281 4.1% 21 .1% 6861 100.0% 25 .7% 6766 362 7128 94 .9% 26 .7% 5.1% 100.0% 272% 26 .7% 7413 94 .1% 29.2% 463 5.9% 34 .8% 7876 100.0% 29.5% 25377 1330 26707 95 .0% 5.0% 100.0% 100.0% 100.0% 100.0% 0 2009 West Virginia University School of Medicine p. 23 Participants with Self-Reported Osteoarthritis within C8IPFOA Population Quartile Group Gender /Fernale /Male Population Quartile Group - CS C8lPFOA for Participants Stratified by Self-Reported Osteoarthritis Self-Reported Osteoarthritis I No I Yes Gender 0 2009 West Virginia University School of Medicine p. 24 Self-Reported Parkinson's and C8IPFOA Adults l>=18Y0) Only NOTE: All results reported here are based on information as reported by participants and were not independently verified . The association between self-reported Parkinson's and C8/PFOA is unadjusted for any potential confounders or covariates. Caution in interpretation is warranted . Female Quartile Group -- C8 Male Quartile Group -- C8 1 2 3 4 Total 1 2 3 4 Total Count % within Quartile Group - C8 % within Self-Reported Parkinson's Disease Count % within Quartile Group - C8 % within Self-Reported Parkinson's Disease Count % within Quartile Group - C8 % within Self-Reported Parkinson's Disease Count % within Quartile Group - C8 % within Self-Reported Parkinson's Disease Count % within Quartile Group - C8 % within Self-Reported Parkinson's Disease Count % within Quartile Group - C8 % within Self-Reported Parkinson's Disease Count % within Quartile Group - C8 % within Self-Reported Parkinson's Disease Count % within Quartile Group - C8 % within SeK-Reported Parkinson's Disease Count % within Quartile Group - C8 % within SeIF-Reported Parkinson's Disease Count % within Quartile Group - C8 % within Self-Reported Parkinson's Disease Self-Reported Pa rkinson's Disease No/No Response Yes Total 9164 99.9% 31 .1% 8 9172 .1% 100.0% 17 .8% 31 .1% 7313 9 7322 99 .9% .1% 100.0% 24 .9% 20 .0% 24 .8% 6716 16 6732 99 .8% 22.8l0 .2% 100.0% 35 .6l0 22 .8% 6230 99.8% 21 .2% 12 6242 .2% 100.0% 26.7% 21 .2% 29423 45 29468 99 .8% 100.0% 4836 .2% 100.0% 6 100.0% 100.0% 4842 99 .9% 18 .1% 6849 .1% 1_1 .8% 12 100.0% 18 .1% 6861 99 .8% .2% 100.0% 25 .7% 7113 23.5% 15 25 .7% 7128 99 .8% 26 . 7% .2% 100.0% 29 .4% 26.7% 7858 18 7876 99.8% .2% 100.0% _ 29 .5% 35 .3% 29 .5% 26656 51 26707 99 .8% .2% 100.0% 100.O% 100.0% 100.0% 2009 West Virginia University School of Medicine . p. 25 Participants with Self-Reported Parkinson's Disease within C81PFOA Population Quartile Group Gender / Female E Male Population Quartile Group -- C8 C81PFOA for Participants Stratified by Self-Reported Parkinson's Disease Self-Reported Parkinson's Disease I No I Yes Gender 2009 West Virginia University School of Medicine p. 26 Self-Reported Thyroid Disease and C8/PFOA Adults (>=18YO Only NOTE : All results reported here are based on information as reported by participants and were not independently verified. The association between self-reported thyroid disease and C8/PFOA is unadjusted for anv potential confounders or covariates. Caution in interpretation is warranted . Female Quartile Group -- C8 Male Quartile Group -- C8 1 2 3 4 Total 1 2 3 4 Total Count % within Quartile Group - C8 % within Self-Reported Thyroid Disease Count % within Quartile Group - C8 % within Self-Reported Thyroid Disease Count % within Quartile Group - C8 % within Self-Reported Thyroid Disease Count % within Quartile Group - C8 % within Self-Reported Thyroid Disease Count % within Quartile Group - CS % within Self-Reported Thyroid Disease Count !o within Quartile Group - CS % within Self-Reported Thyroid Disease Count % within Quartile Group - C8 % within Self-Reported Thyroid Disease Count % within Quartile Group - C8 % within Self-Reported Thyroid Disease Count % within Quartile Group - C8 % within Self-Reported Thyroid Disease Count % within Quartile Group - C8 % within Self-Reported Thyroid Disease beff- Repor ted Th yroid Disease o No esponse Yes o a 8211 961 9172 89 .5% 31 .7% 6510 88 .9% 25 .1% 5877 10 .5% 26 .9% 812 11 .1% 22 .7% 855 100.0% 31 .1% 7322 100.0% 24 .8% 6732 87 .3% 22 .7% 12 .7% 100 .0% 23 .9% 22 .8% 5298 944 6242 84 .9% 15 .1% 100.0% 20 .5% 26 .4% 21 .2% 25896 87 .9% 100.0% 4694 96 .9% 18 .1 % 6675 97 .3% 25 .7% 3572 12 .1% 100.0% 148 3 .1 % 18 .9% 186 2 .7% 23 .8% 29468 100.0% 100.0% 4842 100.0% 18 .1% 6861 100.0% 25 .7% 6942 97 .4% 26 .8% 7614 96 .7% 29 .4% 25925 97 .1% 186 2.6% 23 .8% 262 3.3% 33 .5% 782 2 .9% 7128 100.0% 26 .7% 7876 100.0% 29 .5% 26707 100.0% 100 .0% 100.0% 100.0% Female Male Quartile Group -- CS Quartile Group-- C8 1 Count % within Quartile Group - C8 2 3 4 Total 1 % within T Count Of Self-Re ported Th yroid Condition % within Quartile Group - CS % within Type OF Self-Reported Thyroid Condition Count %within Quartile Group - CS %within T Of Self-RReeppoorrtteed Thyroid Condifion Count % within Quartile Group - C8 % within T Count Of Self-Re ported Th yroid Condition % within Quartile Group - C8 %within Type Of SelF-Reported Thyroid Condition Count %wdhinQuartileGroup- CS % within T Of SeM-Re rted Thyroid Condition Count %withinQuartileGroup - C8 % within Type Of SeK-Reported Thyroid Condition 3 Count % within Quartile Group - C8 4 Total % within Type Of Seff-Reported Thyroid Condition Count % within Quartile Group - C8 % within T Of Seif-Re rted Thyroid Condition Count % within Quartile Group - C8 % wiUiin Type Of Self-Reported Thyroid Condition Goiter 135 14 .0% 23 .9% 136 16.7% 24.0% 144 16.8% 25.4% 151 16 .0% 26 .7% 566 15 .8% 100.0% 11 7.4% 20.4% 17 9 .1% 31 .5% 13 7 .0% 24.1h 13 5.0% 24 .1% 54 6 .9% 100.0h Type Of Self-Reported Thyroid Condition Grave's disease ashimoto's Otier Total 59 6 .1% 27.4% 45 5.5% 20.9'/ 48 5 .6% 22 .3% 63 6 .7% 29.3% 215 6.0/ 100.0% 53 5.5% 29.1% 51 6 .3% 2&01/6 1 30 3.5% 16.5% 48 5.1% 26 .4% 182 5 .1% 100 .0% 714 743% 27.4% 580 71 .4% 222% 633 74.0% 24.3% 682 722% 26.1% 2609 73.0% 100.0% 961 100.0% 26.9% 812 100 .0% 22 .7% 85 100.0% 23.9% 944 100.0% 26 .4k 3572 100.0% 100 .0% 8 3 126 148 5 .4% 21 .6% 5 2 .7% 13.5% 8 4.3% 21 .6/ 16 6 .1% 43 .2% 37 4 .7% 100.0% 2.0% 12.0% 10 5 .4% 40 .0% 4 2 .2% 16.0% 8 3.1 % 32 .0% 25 3 .2% 100 .0% 85.1% 18.9% 154 828 23.I % 161 86.6% 24.2% 225 85.9% 33.8/ 666 85.2% 100.0h 100 .0% 18.9*/.l 186 100.0% 23 .8% 186 100 .0/ 23 .8% 262 100.0% 33 .5% 782 100 .0% 100 .0% 0 2009 West Virginia University School of Medicine p. 27 Participants with Self-Reported Thyriod Disease within C8lPFOA Population Quartile Group Gender /Female EMale Population Quartile Group -- C8 C81PFOA for Participants Stratified Self-Reported Thyroid Disease Self" Reported Thyroid Disease I No I Yes Gender 0 2009 West Virginia University School of Medicine p. 28 C8tPFOA for Participants Stratified by Type of Seif-Reported Thyroid Disease Type Of SelfReported Thyroid Condition I GoDer I Grave's disease Hastwnoto's I Other Gender 2009 West Virginia University School of Medicine School of Medicine : : Community Medicine : : C8 Page~9of 12 Site .M_ap C8 Home What is C8 What's New? C8 Health Project Settlement Details Brookmar Project Team Science Panel WVU Project Team C8 Health Project Results 40 Contact Us Other Links Department Home SoM Home Search : 0 Department * Health Sciences Center 0 WVU C8 Home > C8_ Results > Other Clinical Lab Values Print C8 Health Project Results C8 and Other Laboratory Values The WVU website is a communication vehicle to depict associations or their public use. These tables and graphs show many comparisons between lal corresponding population serum PFOA (C8) levels . When it appears that ther relationship between serum C8 and a clinical laboratory value, the mear relationship still requires thought and discussion . Some of the relationships, wt weak and not likely to be important. Several are strong, interesting and potential and none of them can be taken to show an etiologic (cause and effect) relati( absence without more work . When it comes to causes, scientists interpret these data with deference to additional work that needs to be done . These data concerning associations are for public use. They will receivi collaborative work in peer review format. We hope they prompt public ci suggestions of interested scientists. The results summarized on this page include differences in C8 values based on abnormal clinical laboratory results (normal / abnormal laboratory cutoff values : referenced on each graph), and for differences on clinical laboratory values b deciles. The files below present the summaries for C8 deciles in a graphical foi results in tabular format, please click here . For a summary of C8 decile cutoffs, here). Download Abobe Reader Other Laboratory Values AB_CDEFG_HIJKL_MNOPORST_UVWXYZ Alpha-Fetoprotein Tumor Marker (Serum) Description of AFP (39 KB) " Serum C8 By AFP for Participants 1-2 Years of Age (24 KB) " Serum C8 By AFP for Participants >= 3 Years of Age (24 KB) " C8 Population Deciles & Alpha-Fetoprotein Tumor Marker (35 KB) Albumin (Serum) Description of Albumin (37 KB) " Serum C8 By Albumin (Serum) Levels In Participants <18 Years Of Age (2 " " Serum C8 By Albumin (Serum) Levels In Participants >=18 Years OfAge (: " C8 Population Deciles & Albumin (37 KB) Alkaline Phosphatase (Serum) " Description of Alkaline Phosphatase (40 KB) " Serum C8 By Alkaline Phosphatase Levels in ParticiDants 1-3 Years of Ac~E " Serum C8 By Alkaline Phosphatase Levels in Participants 4-6 Years of Ag"E " Serum C8 By Alkaline Phosphatase Levels in Participants 7-9 Years of AgE http ://www.hsc .wvu .edu/som/cmed/c8/results/otherLaboratoryValues/index .asp 2/2/2009 L C / v, R J " J , inou> o>oao cM. O O. 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S m N O N ~S O 1q e~ Y S N c0 O m AS O 1p M d d S V cA9 ~ a~0 S a CIS t S O W 1~ A ~ ~ O d N N W GO CO d a0 a0 d 0 a.D- d 01 Q) d OI O d Ol c~0 R Ol Q.-I d Ol W d ~ W d Of O7 d O7 Ol d U F u E ~g ~ o S v "S M oS ~ oS v ~o v 2oo ~ nS v ~S v ~S v ~S v i 0] P1 fV JO O 0) !7 O O N (O C7 O O N l'7 f0 O O N l0 cD O O N lV lD O O N N f7 N O O N (O N O O N C6 N O O .- N Ol O O (Ni N v7 O O N o E O L z E Po ~- U J A (O o Cl? a (D cn o 1A Ci d N h o CV d N o ~ o t? Pdr aOi O N WN) N a0 o N r1fn1 cA) o C7 cq f7 c.) o M~ N N1A mo N 10 l'7 C~ v> o 1A l7 co rr O I~ (? CD Cp E c.i .- cy cS - - .- .- - - .- o O N w C a W > U w l7 O d O t0 d O O cO O c0 O N h O ~ aD O ^ O O G1 d O 07 N O if) CO O O . E f7 t0 t0 d fA t0 (O IA A aD A N N O 1n O t0 W ~ A O Ol C'f f0 O~ e- pf O t0 O c0 N W fn O N N O a0 N O w C6 O ~ f7 ~ N P7 O ~ CO O N t0 O 1"1 N O O N ~ c0 P1 O N .- O U U v n m v m m ~ OAR S ~ coo aoo ~ m ~ ~ ~ ~ m rn coo a`Oo ~ ~ 'a$ $~ ~ coo ~ a0n aAO ~ cDo oi oi c ci om o oi oi o m oi o ci CD o NoOiR oi o oi oi o oi 'm o a oi o CD CD o oi (D o J E E U A U e~ O N O m m aD O af A S m d S ~ O S ~ ~ O W r S ~ N S q N O O A O 00f. n S O ~ O O ~ V^ C C V V V d at ~ d d ~ d tt ~ l~) O ~ d VO P7 d ~ d ~! ^ c7 O ~ d Y d d FL > O s~ m m 0 c c ~ O c_a a LL a~ v ~ ~ io c m c w0 ~m~ ` L fp o m c .m c .30 ov ~ ~ U) 0 io c 0 c m_ U ro~$ ~ M en o io W cm c RO a~~o ~ 2 V! c2 m c m cm m_~ m o~ M 2 tq co_ io c 0 c_m 0 cmc y q f 2 0 i c .m c a~ 'oa a f n . 9 ~ico c o cco '109 ~ m-o ~ m c .m c Mm~ s O o fp ~d i c ~m cM 'm 0 0 m o$ ~ ~ v1 U i n n n O m m 0 m sW` m d ~ N an d v> to A m rn o w 4 y ,h a W 0 m M A p. 52 C7 - (O O n 'O O O co O a0 O O t0 <O O W) O ~ O O~ WO W tpo O c0 fD O v 'n O h p O Of O O < ~O ~O O e~ W O n O OO O t0 O n ~O n aW0 O tU n tp N O cp O O Ci E (no ~ ~ N cO~ O O C9 n O c~l O O l'9 ~ O N ~ O N N O N~ O O^ N Ol V Go c7 p(~y .!~- O O 2 j _ N N N N ~ NN N N N N N N N N N N N N ~ NN ~ N N ~ ~~ E E EQ 'W O O C7 O O O C ~O ~O a O V N ~ OO 10 t0 C7 O 1~ 10 O O ~ ~O n O O ~O t0 < .0 0 O ~O h n O O t0 O N h O t0 < i0 O U~ V ~O a .-, _Op J O E 0 x o CD f? v O mO n o n (i t1oA o op cto7 O e uv~ R h N v o P) h o w) e th n o Ol N t0 W o n W ~p c7 co ~O o cq ~ ~p aIon o Ol ~Po) ~ n o 1D v N o~ o N t0 t0 N t0 o n oN, .t-p o cp lc+ol tb 1I) Pf o e tf) If) !n a e 1f) h v v P) W v wv1 f7 u1 w v v en 1n 1n PI v v tf) v7 O) v v 1f) U) Oi v v W E m x ~ o 8 ~ o 2 n g cn~, m o tn(P cWO g ~ ~ g ~ ~ g ~co. ~ g c~! m'~~. g ~ w, oo a~o. ~ V) N J ~J R < ~ f0 N V O '- tb N V O .- P') N V V ~ l7 N V V ~ O) N O< ~ cq N < V .- M N O O ~ v l7 < ~ ~ y (h (n N VV ~ KV ~ =o E L V E cR o Lo. O o O mo m I~ O n ao o fy O ao Of 0 o ao n o .- O N N O v oo ~- ~ O ~O ao o fD O iWo W o W O v n r) o cp ~n cn o m 0 0 'n n o W : ~ v o m ~n+~ o m ~o ~ O W CMD CO O Ol c7 ~ ce O W cOc) ~c ~ O T ~ m O Cc OD O Of N r~ t7 t7 O ~o ~ W vi cq O r~ co t0 oi O OW v) O Cf t~ i E $ v _ ecno oco N v mco oao w ci 0co oco mco mco oco m m Lcoo oco '~o w co o co cco~ Lcoo oco c~o (coo oao w ~ Lcoo oco ur)~ vco Oao ~coo vao oao n co ( ~ cm " O fV fV C (V cq O N lV O (V cV O fN cV O fV fV O fV fV O lV fV O IlI fN O cV cV O s~ J C C u a 0 O i `_o (m0 g J OWf O 9 O N 1 O N awD O l0 ~ O ~ O O Gn0 O O V, iD O n 1~ O ~ V O O Q Oi In O O 1~ N t0 (0 Y) ("O t0 In n 1~ u _ Ol N U1 v N co l7 N V N V V) N V O) t0 fn N O GO f~ tD P) N Ol V I~: (0 O CO N v) Y) !~ fD !7 N f7 n aD (T1 N to l") n 1~ 07 N lh 10 _r. H 0 s > c ~ n O c~ cn In v N o O e co a ~ O 1U vc v N O v e a0 v O v v ~O v O v O o O~W v O v a0 N O a vo Y v N o 'Q oe v o o O e W v o In c 7 .Q ~ j N N O N N O N fV O N N O N N O NN O N N C NN O N N O NN O vv o NN O V_. P F w C ; U_ W O __ a0 O N J ID O aD O O 01 c0 ~ ~ t0 O tO h NO ~O p cp o cp O 0! O1 O y~ ^ Y ~~ ~ v O O m Oi 'D n o N ~ tOD. O N On V b c E oi ai v oi m v o ai o 0 oi v o ai v o oi v o oi o 0 oi v o oi v o aW v o oi 0 a w 8m - U " N O tD ~ O ^ N O tD O O aD f0 tD n tp op (p W V1 aD wO W ~ t0 CD 10 Go N O N~ O NV t0 10 O fD (V N f0 O O O .- N N o O f0 N O N a E f, v v ,7 J ~ O fA t9 ~ ~- O fC 17 O! ~ tC ~ Oi !~ O .- Oi h~ C .- 1~ ~ Oi f~ ~ O cC N O aD 1n C n O ! jp~^ C 75 Q O cW0 O N (O O ~O O ' ~O O V In O 1f N O oU O a0 O O 1A N O n ~ O ~ 07 O N O C N O t0 $ ~ 00 ~ mO W t0 ~O 'Q N N ~ O V O~ N N OO W N N N O N N Of YI O N N O) 1A V W O7 'C M R O O7 ~U O W LO to W O W N -4 (p N N NN N NN N N N N N N f0 vm E mo to w o i>o C m C W Q a S C CI C ya Q O O$ o m > C m C ~ -p Q m m 9 o _ io C " W Q m ~ ~ o ii C Ol m ~ 'O C O C ~ ~ Si c o C m C m m O 0 %o C m C 9Q 0 m C Ol C AQ 0 i C .m C WQ c 0 i a C m C !g Q O a 11 0 ^ Q O U Q _ O C 7 C m O L N ~ O L n 1 0 n t 0 W O p. 53 oc)o o0 c0o> amo oo O~q Aco oco Iun> Gco ow n m ca) oa ; c~oo na oo C~cn o OO Nv~ oo oO ~~n -o- oo om) no oo Ln u~ no~ oo cuo~ o ~ ~ o ~ ~ o o ~ o o ~ o o -= o ~ ~ ~ .- " 2 r~ c~ co cn vo co cn m en o~ i+) co cn ~n c co m In m m m U N o J O O m ~ vO) o O m ~- m O o O m ~ o O o O v~ ~ a O o O m '7 v O o O Lc) - v O o O in - E ~ (V N O N N O N N O N N O (V N O fV [V O N N O y7 E m -E 5A , ~ Uro v no oo en Lon oo C~oo a0 oo cmo CoO oo Nn io. oo Aco o oa~ ~ ooD OO ceo N (V O N N O N N O N N O N N o N ~ o N N N n~ m in o Ln OO NN O g oo~ co o! NI o Ln o Ln O -7 -7 NN O Lon oorn m CS! un o v~ O -7 -7 NN O o oo~ M Co N~ O v o Ln O O -7 NN O L0n o0 cn NN ~ Q x no> 0 9 ai ~ GO r~ y NN L G E J 00 ac 0 o N v cti oi n N N crno 0o ocn aNc aNc ~ _ N O O ~ 9 M ~O W J g ~ O O t~~7 O ~ l+~l O O M O _j u UU No 0o nc~ CD oi A N N V O pp A ~O ~ m'. o0 0o cNo cNc ~ (P S p~ M ~ O 0f~1 Cmn 0o i cNu cNu n O S ~ N O O c O1m 0o 0o 0tc vm 0o ve o n 0o oo oi oi r~ CD uo 1 w oi r~ N N N N N N ' t0 O O p~ N V ~O V S ol ~ p c+l m O h ~O ~ O M ~ O ~ c~1 N ~ m ~ oo o? au oi n N N m O N S I~ ~ ~ ~ 1 ~1 on oo ma ao ao ~ N N n mS N O O 0 1+1 J N S ~ O O aloo eNo S V .~- O b n S Of O S ~ tDm. O V, O S ~ i~0f, S c0 V O V N S < ~ m fn 'mR N n 1m~ O v Cml tmO N ~n i~ m m 'cOo O n 1m~ i~~ i~ h m O v i: 1m~ n co ~ h m Cc7o n OmD O 11 N n Om) O m ~ fm~ 'coO S J n O V O O N O o N Hl O 1'O O Vl co O 01 m `-' E v1 O A A o O) aG O V h O ~ "- O N fn O O S S t~0 S n S O N S f~0 ~ S O ai vi v oi oi e cNi ai oi oi vi wi p vi oi ~i " i+i v o oi m vi o e~ v o y 2 J co co f1 Wm m Of co M ~ aD t7 W W l+! Ol aD ~ 01 T lh O) (D t7 Ol S m O) C1 tn W m l+l m N C O O C V - m ~o $ ~ m h ~ ~n A g ~n m mS S c"o g ~ n S v ~ g ~ n S ` u? S o cv o v oS n a f 01 J O v~ m ts V O N m A N (7 tD CO 'Q v~ v W m ~ 10 a v W O m O~n N v m ID O m C~Dn . - N ID 1A o cL~n o m Po7 0 cn lvol ~ m m ImD O o O) ~n a ~l c ti O r ~ c -c o CD nO N O m A O N V m V n O Y lq O < O O A A O a_0 n O O (7 O a0 V O N m W (O n O ~ O ~ m m n (O Of O f0 lh m N m n m Ol A a0 m P9 ~ C7 t+f a~ fn tG fn CO C c m f9 - J N ~ O v t~l O N~ O (O l+) O) Pl N ~ 17 V) N t0 fY N ~ fq N ~ m N (V N N~ aC (4 N N N~ N NN l+) N ~ v) e0 fV N ~ O M O ~ N ~ h N N fV N ~ CO 7 E c > W q C O ; g w S t~D ~ O ~ N O ~ O S a00 ( S O n S S am0_ S :1 O S c')~ W S q O~ N mS W E Ol m N t7 OD f0 1U N GD N O f0 R c0 P m CD ~q O n ~f) M `R O) N N n a0 M O) aD O c' ao A o w A O o) m O m m o m n o m n o m w o ~ m o co m o w m o ao A O m J 0c E E a Eg C ~ O O " - v7 A m .y O a0 c7 O O O <O O 1D 1t O O G7 O M OO IA O O Y m c0 O ~ O c9 N O cC O V Ol O ~ Ol O - (0 O O NO n c0 o O O N O V O I~ Ow1'NCW- pOl tm0 n OPl) Cpf7 Ot01~ E O go LA 1q N N N n " O_ O! N N Gf ~p O 1~ O U) N 7 at 1~ Of m n O 2J O S N OO N OO N O O N N v O O P7 V N N OO N p) O O (~1 N OO N (7 O O O O N N O O O A N O O y N ~ .- C 3a E E Vm N E(5 CJ N O M f'') S ~ AO ~ N S f09 CmD S W (+) S S O S O m CD O ED O cO N O Ol t0 O N O c~ N O O lV O N c0 O j E D :5 Z:i l") m NO !n N lq ~p m ~ips W N co GW a0 ON O ON O tp m C7 cV O! ON N ON f%: m 1~ m P'1 1G co ifi a0 V Cb N O~ N f7 O N O l7 l0 t~ N (7 N t0 N c0 N M Ol- C E ~E w g .m c W Q ~ 10 0 mm v ~n Q m C m ~ 10 ~ m $ a f~co _ o `m c m C W0 m a o io C m c -0 ~ m ~E q m c N C W0 m ~ a _co io c m ~ l0 ~ m ~v _co m c .m ~ W0 m oo c o m C ~N C l0 ~ m o v c o m c m C l0 0 ` m v c o m c m N ~ m ~ c o m C N m m~yB 0 U n r 3 O ^ m U d C R 0 O C W 7 m G N ~ ~ o v m A m ~ m F p. 54 _ OO W JNN V N O M M N t0 O a MM N tD O O MO V W O M O N rO Y MO M O m O C? < N V c0 O N CO O MV V MV et r O M ? 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