Document 99eqEjmxK7DOO7NwoQVJ7aze3

Taft/ T" Taft Stettiriius S Hollister LLP 4 25 W alnut Street, Suite 1 8 0 0 /Cincinnati, O H 4 5 2 0 2-3 9 57 / Tel: 5 1 3 . 3 8 1 . ; $ g i( ) j 4 > V ^ B 3 81.0205 /w w w .taftlaw.com Cincinnati / Cleveland / Colum bus / Dayton / Indianapolis'/ Npfth^rji Kentucky / Phoenix / Beijing 09JUH16 ftHIQ: 36 Robert A. Bilott 513.357.9638 bilo tt@ taftlaw .com June 5, 2009 FYI-00-001378 FY 00 T S C A Confidential Business Information Center (7407M) E P A East - Room 6428, Attn: Section 8(e) & FYI U.S. Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, D C 20460-0001 Re: Submission To T S C A 8(e)/FYI Database Re: PFO A/PFO S To T S C A 8(e)/FYI Database: W e are hereby providing the following information for inclusion in the T S C A 8(e)/ FYI databases with respect to PFO A/PFO S: 1. Post, G.B., et al., "Occurrence and Potential Significance of Perfluorooctanoic Acid (PFOA) Detected in New Jersey Public Drinking Water Systems." Environ. Sci. Technol., Article A S A P (May 8, 2009). RAB:mdm Enclosure 11423033.1 85090000009 0 90Q Contains No CM -> CONTAINS NO CM 09 P-2 Environ. Sci. TechnoL XXXX. xxx, 000-000 Occurrence and Potential Significance of Perfluorooctanoic Acid (PF0A) Detected in New Jersey Public Drinking Water Systems GL OR I A B. P O S T . *-' J U D I T H B. L O U I S . 1 K E I T H R. C O O P E R , 1 BETTY JANE BOR O S - RU SS O , * AND R. LEE L I P P I N C O T T 1 Division of Science, Research and Technology, New Jersey Department o f Environmental Protection, P.O. Box 409, Trenton, New Jersey 08625, Department o f Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, Room 218, New Brunswick, New Jersey 08901, and Bureau o f Safe Drinking Water, New Jersey Department o f Environmental Protection, P.O. Box 426, Trenton, New Jersey 08625 Received January 28, 2009. Revised manuscript received April 16, 2009. Accepted April 28, 2009. After detection of perfluorooctanoic acid (PF0A) in two New Jersey (NJ) public water system s (P W S) at concentrations up to 0.19 p gH , a study of PFOA in 23 other N J P W S w as conducted in 2006. PFOA w a s detected in 15 (65%) of the system s at concentrations ranging from 0005 to 0.039//g/L To a sse ss the significance of these data, the contribution of drinking water to human exposure to PFOA w as evaluated, and a health-based drinking w ater concentration protective for lifetime exposure of 0.04 ig/L w a s developed through a risk assessm ent approach. Both the exposure assessm ent and the health-based drinking w ater concentrations are based on the previously reported 100:1 ratio between the concentration of PFOA in serum and drinking water in a community with highly contaminated drinking water. The applicability of this ratio to lower drinking water concentrations w a s confirmed using data on serum levels and w ater concentrations from other communities. The health-based concentration is based on toxicological end points identified by U.S. Environmental Protection Agency (U SEPA) in its 2005 draft risk assessm ent Recent information on PFQA's toxicity not considered in the U SEPA risk assessm ent further supports the health-based concentration of 0.04 p g /L In additional sam pling of 18 P W S in 2007-2008, PFOA in most system s w as below the health-based concentration. However, PFOA w as detected above the health-based concentration in five system s, including one not previously sam pled. Introduction Perfluorooctanoic acid (PFOA) is found in blood of people worldwide (7), including 99.7% of a representative sample of * Corresponding author phone: (609) 292-8497; gloria.post@dep.state.nj.us. 1Division of Science, Research and Technology. *Rutgers University. * Bureau of Safe Drinking Water. e-mail: 10.1021 /B S 9 0 0 3 0 1 S CCC: V S 0.7 5 XXXX A m e ric a n C hem ical Sociaty the U.S. population (2). In studies of U.S. populations, the geometric m ean serum levels were 3.9 pg/L in 2003--2004 and 3.4/tg/L in 2006 (2,3). This widespread hum an exposure is of concern due to PFOA's persistence and toxicity. PFOA has a half-life o f several years in humans (4), and caused adverse effects on development, lipid metabolism, liver, and the immune system, and tumors in several organs in animals (5). In some studies, maternal exposures in the general population were associated with decreased birth weight and other measures offetal growth 16-8), while other studies did not find these effects 19,10). Some studies ofexposed workers found associationswith adverse outcomes including diabetes mellitus and increased cholesterol, whereas other studies were negative (5). Preliminary results of a study of almost 70 000 people exposed through drinking water suggest an association with several clinical parameters measured in blood, Including increased cholesterol (.11, 12). Sources of exposure to PFOA include consumer products (13), house dust (14), diet (15), and drinking water (16). Exposure also occurs through metabolism and environmental transformation of the related chemical, 8:2 fluorotelomer alcohol, which is widely used in food packaging and other products (17). PFOA and other perfluorinated chemicals were detected in surface waters (18--23) and drinking water (20,24,25) in several countries, and in groundwater contaminated by fire fighting foams (26). Drinking water has been contaminated by sources such as industrial facilities and landfills (16,27), and by use ofa contaminated soil conditioner on agricultural land (20). Blood levels of PFOA are elevated in communities with contaminated drinking water (76,20), with the median serum concentration approximately 100-fold higher than in drinking water in those exposed for at least two years (16). The first goal ofthis study was to evaluate the occurrence of PFOA in NJ public water systems (PWS), following its detection in groundwater of two PWS at concentrations from 0.007 to 0.19//g/L (28). An occurrence study was conducted by NJDEP in 2006, and additional sampling was performed by NJ PWS in 2007--2008. The additional goals were to evaluate the significance ofPFOAin drinkiiigwater for human exposure and potential human health risk. The contribution of drinking water concentrations such as those found in NJ to total exposure to PFOA was evaluated. A health-based drinkingwater conceuUaiiun was developed using end points for toxicity identified by U.S. Environmental Protection Agency (USEPA) (29). Both the exposure assessment and health-based water concentration were based on the ob served relationship between the concentration of PFOA in drinking water and serum in humans (16). Experimental Section Sample Site Selection. For the 2006 occurrence study, 36 samples collected by the New Jersey Department of Envi ronmental Protection (NJDEP), including 29 from 23 PWS, one duplicate sample, six field blanks, and one trip blank, were analyzed for PFOA The study included systems supplied by groundwater and surface water. The systems chosen included seven with surface water intakes within 10 miles, or with public wells within 1 mile, of five facilities where PFOA or related chemi.cais may have been present. Four additional systems with a history of organic contamination were included, since these systems Eire thought to be impacted by releases from industrial and commercial activities, increasing the likelihood of PFOA detection (30). One groundwater and one surface water system with no history of organic contamination were VOL. xxx, NO. XX. XXXX / ENVIRONMENTAL SCIENCE i t TECHNOLOGY A P-3 TABLE t. PFOA in NJ PWS Sample* by 8IJDEP, 2016* public water system site no. ID number source water raw/ finished PFOA frrg/l) 1 NJ2119001 GW, unconfined Raw N D * 2-W1 NJ0217001, GW, unconfined raw 0.026 Well 1 2-W2 NJ0217001, GW, unconfined raw 0.033 Well 2 3 NJ0221001 GW, unconfined raw 0.033 4 NJ1604001 GW, unconfined raw 0.029 5 NJ1107002 GW, unconfined raw 0.007 6 NJ0424001 GW, unconfined raw NO 7 NJ0119002 GW, unconfined raw NQC 8 NJ0717001 GW, unconfined raw 0.021 9 NJ1434001 GW, unconfined raw 0.008 10 NJ0614003 GW, unconfined raw ND 11R NJ1435002 GW, unconfined raw 0-006 11F NJ1435002 GW, unconfined finished 0.006 1 2 ' NJ1007002 GW, unconfined finished 0.005 13GW* NJ1712001 GW, semiconfined raw 0.027/0.025' 14 NJ1316001 GW, confined raw NO 15 NJ0514Q01 GW, confined finished ND 16 NJ1613001 SW raw 0.008 1 3 SW ' NJ1712001 SW raw 0.010 17 NJ1219001 SW raw 0.014 18 NJ1915001 SW finished NQ 19R NJ0327001 SW raw NQ 19F NJ0327001 SW finished NQ 20R NJ1605002 SW raw 0.026 20F NJ1605002 SW finished 0.027 21R NJ2013001 SW raw 0.035 21F NJ2013001 SW finished 0.039 22 NJ1352005 SW, reservoir raw 0.011 23 NJD238001 SW, reservoir raw 0.021 * GW, ground water; SW, surface water. * NO, not detected. c NQ, detected below Rl_ "'There is no history of organic contamination at these PWS. 'T h is PWS has both a groundwater and a surface water source. 'Laboratory duplicate. selected for comparison (.30). Other sites were chosen to expand the geographic extent of the sampling. Both raw and finished water samples were collected at three surface water and one groundwater system. In 2007-2008, additional sampling was conducted by NI PWS. Samples (201) were collected from points of entry (POEs) into the distribution system, individual wells, and surface water intakes at 18 systems, including 12 with detectable levels of PFOA in 2006, and six not sampled in 2006. Sampling Procedure. Sample collection was performed by NJDEP personnel, following the standard operating procedure for the analytical method (31). A single unfiltered 250 mLgrab sample was collected from designated sampling locations used for other monitoring purposes. Six field blanks were prepared by pouring distilled water into collection bottles at sites where the greatest and least possibility of contamination was expected. The trip blank containing distilled water was prepared by the analytical laboratory, shipped to NJDEP personnel, and returned to the laboratory unopened with that day's other samples. A duplicate sample was collected at one site (Table 1). Procedures for sampling conducted by NJ systems in 2007--2008 conformed to relevant NJDEP and USEPA regu lations, with analysis performed by several NJDEP certified laboratories. Analytical Method. The 2006 samples were analyzed for PFOA by Test America, Denver, CO using liquid chroma tography and tandem mass spectrometry (LC/MS/MS) (Micromass Ultima MS/MS or Waters Micromass Quattro Premier tandem mass spectrometer) (31). An isotope dilution techniqueusing a 13C labeled PFOA analogis used to quantify FIGURE 1. Locations of N J P W S sam pled in 200S PFOA occuirence study. PFOA. The PFOA parent ion (m lz = 413 arau) and two daughter ions (m lz = 369 and 219 amu) are used for qualitative identification. This approach provides low detec tion limits and a high level of qualitative certainty. The laboratory's reporting limt (RL) for this study was 0.004 /rg/L Detections below the RL are reported as not quantifiable (NQ). The 2007--2008 samples were analyzed by several labo ratories certified by NJDEP using the LC/MS/MS technique. Samples were generally collected and analyzed quarterly. Reporting values differ among laboratories and ranged from 0.01 to 0.015 /<g/L. Resnhs and Discnssion 2006 Study o f O ccurrence o f PFOA In NJ PWS. PFOA was detected at or above the RL in 20 (69%) of the 29 samples, and in four additional samples below the RL (Table 1, Figure 1). Of the 23 PWS in this study, 15 (65%) had detections at or above the RL, and three additional systems had detections below the RL. PFOA was detected in 9 of 12 (75%) raw groundwater samples from unconfined or semiconfined aquifers, but was not detected in the two raw (e.g., untreated) groundwater samples from confined aquifers. AH three samples of finished (e.g., treated) groundwater from un confined aquifers had detectable levels of PFOA. Seven of B ENVIRONMENTAL SCIENCE & TECHNOLOGY / VO L xxx. NO. XX, XXXX P-4 TABLE 2. NJ PWS witb PFOA Detections >8.04 /<g/L w Data Submitted to NJDEP. 2087-2088* site no. PWSID source water 8A NJ0717001 GW, unconfined 8B NJ0717001 GW, unconfined 24 NJ0809002 GW, unconfined 25A NJ1707001 GW,unconfined 25B NJ1707001 GW, unconfined 25C NJ177001 GW, unconfined 21 NJ2013001 SW 3 NJ0221001 GW, unconfined *GW, ground water; SW, surface water. type POE POE POE Well 1 Well 2 POE POE POE number of samples 4 4 3 5 6 6 1 4 average (/g/L) 0.068 0.069 0.050 0.083 0.078 0.079 0.040 0.034 range (/g/L) 0.058-0.084 0.063-0.072 0.018-0.069 0.062-0.1 0.055-0.14 0.053-0.10 0.040 0.029-0.048 the eight raw surface water samples and two of the four finished surface water samples had detectable levels ofPFOA. There was no apparent difference between raw and finished water collected at the sam e system. PFOA was not detected above the health-based concentration (see below) of 0.04 /g/L in this study. PFOA was not detected in the six field blanks or the one trip blank. Additional details are provided in an NJDEP report (28). Additional PFOA Data from NJ PWS. In 2006, PFOA data were submitted to NJDEP from two PWS with wells located near a facility that used PFOA in manufacturing processes and processed waste containing PFOA. These samples were analyzed by Axys Analytical Services, Sidney, Canada, and Exygen Research, State College, PA. At one of these systems (NJ1707001, site no. 25), PFOA was detected at up to 0.123 and 0.19/g/Lin shallow, unconfined wellsfrom two different wellfields, but was not detected in deep unconfined wells from these wellfields. At the other system (NJ1708001, site no. 26), PFOA was detected in one of eight raw groundwater samples at 0.0176 and 0.0179/g/L, and in finished water up to 0.0081 n g/L (23). In 2007-2008,201 samples collected by 18PWS, including 12 sampled in the 2006 study, were analyzed for PFOA. Samples were collected from one or more POE at each system, with one to sue samples for each POE, as well as from individual wells and surface water intakes. PFOA concentra tions ranged from nondetectable (<0.01 /g/L) to 0.14 /g/L. PFOA was detected at or above the health-based concentra tion (see below) of 0.04 /g/L in at least one sample from five systems (Table 2), including one not sampled in 2006. Yearly average concentrations (average results from four consecutive quarters) exceeded the health-based concentration for four POE from three different systems. P otential Contribution o f PFOA at Concentrations Found in NJ Drinking W ater to PFOA in Serum. A median ratio of approximately 1:100 was observed between the concentration of PFOA in drinking water and serum in Little Hocking, Ohio (J6). In this community, drinking water had been contaminated by a nearby industrial facility, with an average concentration of3.55,ug/Lin 2002-2005. The median PFOA serum concentration in 282 individuals tested in 2004--2006 was 371 /g/L, with occupationally exposed individuals excluded. This ratio is based on those six years and older, while a higher ratio was observed for younger children (16). The ratio was based on data from individuals who had resided in Little Hocking for at least two years and was n o t related to years ofresidence. If a similar relationship is valid atlower drinking water concentrations, such as those detected in NJ (Tables 1 and 2), then such concentrations may contribute substantially to total exposure to PFOA. Data are available on both the range of historic drinking water concentrations (32) and the serum levels of PFOA in samples taken in 2005-2006 (33) in five Ohio and West Virginia water districts with lower PFOAconcentrations than Little Hocking. The median serum level in each of these districts (Table 3) is higher than the U.S. median of 4 /g/L TABLE 3. PfOA Levels ia Drinking Water and Senna in Conunnnities a Okie and West Virginia water district PFOA levels median serum reported by PFOA level water district (/g/L) (32) (/g/L) (33) Little Hocking, OH Lubeck, WV Tuppers Plains, OH City of Belpre, OH Mason County, WV Village of Pomeroy, OH 1.7-4.3 0.4-3.9 0.25-0.37 0.08-0.13 0.06-0.1 0.06-0.07 224 70 35 37 12 12 (2). The range of PFOA levels in these districts may include results from multiple POEs, and the num ber ofpeople served by each POE, as well as the variation of concentration over time, are not known. Therefore, the m ean or median drinking water concentrations in these districts cannot be accurately estimated from the range of concentrations. For this reason, the median ratio of drinking water to serum concentrations for these districts cannot be reliably determined, as was done for Little Hocking (16). However, it can be seen that the m edian PFOAserum concentration increases with increasing PFOA concentration in the drinking water. Village o f Pomeroy had the lowest PFOA concentration (0.06--0.07/g/L), about 50-fold lower than in Little Hocking. Since this range is narrow, the average can be reliably estimated as 0.065/g/L. Based on this estimate, the average ratio o f PFOA in serum to drinking water in this district is 185:1. For lower drinking water concentrations, nonwater sources are likely to contribute a greater proportion of the PFOA in the blood than in those using highly contaminated water. To find a lower bound on the ratio of serum to water PFOA concentrations, it can be assumed that none of the U.S. background serum concentration ofabout 4/g/Lresults from drinking water. If this serum concentration of 4 /g/L is subtracted from the median serum concentration forVillage of Pomeroy (12 /g/L), the ratio of the remaining serum concentration (8 /g/L) to the drinking water concentration (0.065/g/L) is 123:1.Therefore, PFOA appears to concentrate in serum of people exposed to lower drinking water con centrations in a similar ratio to that reported in a highly exposed community (16). It should be noted that serum levels for individuals with occupational exposure (2% current, 3% fomer) (33) were not excluded from the data shown in Table 3. However, since the num ber of subjects in each district is large, and the serum concentrations are medians, rather than means, it is unlikely that the overall trend would change ifoccupationally exposed individuals were excluded. This observed serum/drinking water ratio of approxi mately 100:1 is in agreement with a one-compartment model (34) which predicts that ingestion of0.0017/g/kg/day would result in serum levels of 13 /g/L in males and 8 /g/L in VOL. xxx. NO. xx. XXXX / ENVIRONMENTAL SCIENCE Si TECHNOLOGY C P-5 females, or a m ean of 10.5 /g/L. Assuming a drinking water intake of 0.017 L/kg/day (35), a dose of 0.0017 pg/kg/day would result from a water concentration of 0.1 ig/L. The ratio between a serum concentration of 10.5 ^g/L and this water concentration of 0.1 /cg/L is 105:1, identical to the m edian ratio reported in Little Hocking (16). These results suggest that PFOA in drinking water at concentrations such as those found in NJ PWS can sub stantially contribute to total exposure to PFOA. For example, PFOA was found at >0.01 /<g/L in 13 of 29 samples in the 2006 study (Table 1). Based on the 100:1 ratio, a drinking water concentration of 0.01 ig/L is estimated to contribute about 1 /<g/L to PFOA in serum, or about 25% of the 4/<g/L m edian serum level in the general population. Development of a Health-Based Drinking Water Con centration for PFOA. The draft risk assessment for PFOA developed by USEPA (29). which identified toxicological end points in experimental animals,was used as the starting point for development of a health-based drinking water concen tration protective forlifetime exposure. The goal ofthe USEPA risk assessment (29) was to evaluate the significance of exposure in the general population. Because the half-life of PFOA is much longer in hum ans (several years) than in the animals studied (2--4 h to 30 days) (5 ,29), a given external dose (e.g., administered dose in units of mg/kg/day) results in a m uch greater internal dose (as indicated by serum level) in hum ans than in animals. Therefore, comparisons between effect levels in animal studies and hum an exposures were m ade on the basis of serum levels rather than external dose (29). USEPA (29) compared serum levels of PFOA at the No Observed Adverse EffectLevels (NOAELs) or Lowest Observed Adverse Effect Levels (LOAELs) from animal studies to serum levels of PFOA in the general hum an population to develop margins ofexposure for noncancer end points. Additionally, USEPA (29) classified PFOA as having "suggestive evidence of carcinogenic potential', whereas the USEPA Science Advisory Board (36) disagreed and recommended a clas sification of "likelyto be carcinogenic to hum ans". The blood concentrations at the NOAELs and LOAELs for noncancer end points (29), as well as for the data used for cancer risk assessment (37), are shown in Table 4. USEPA (29) did not develop a Reference Dose (RfD) or cancer slope factor for PFOA, nor did they address the relationship between the external dose and the human serum level. Information on this relationship is valuable for development ofa health-based drinking water concentration. To develop a health-based drinking water concentration for PFOA, we derived target hum an serum levels by applying standard uncertainty factors (UFs) for RfD development (36) to the measured or modeled serum levels identified (29,39) as NOAELs or LOAELs for noncancer end points (Table 4). The UF of 10 for interspecies extrapolation typically includes two factors of 3 each for toxicokinetic and toxico- dynamic differences between humans and animals (36). Since the health-based drinking water concentrations are based on comparison of serum levels in animals and humans, the question arose as to whether comparison on this basis hilly addresses interspecies toxicokinetic differences, and whether an interspecies UF of 3 rather than 10 is thus appropriate. TheUSEPAScience Advisory Board (36) believed that overall uncertainty about the interspedes differences in PFOA toxicity was not suffidently reduced by comparison on the basis of serum levels to justify modifying the default interspecies UF. Therefore, the standard interspecies UF of 10 was used. For the cancer end point, the serum level resulting in a 10~6risk level was estimated by linear extrapolation from the serum level in animals at a dose resulting in an approximate 10% tum or incidence (Table 4 (37)). Linear extrapolation is recommended by USEPA (40) as a default approach when the mode of action for carcinogenicity is unknown. In developing health-based drinking water values for noncancer end points, a relative source contribution (RSC) is applied to account for nondrinking water exposures to the contaminant (41,42). The default value for this factor is 20% (e.g., nondrinking water sources are assumed to provide 80% ofexposure) when the relative contributions ofdrinkingwater versus nondrinkingwater sources are not fully characterized, as is the case for PFOA. Therefore, an RSCof20% was applied to the target human serum levels for noncancer end points to derive the serum concentrations that are the target contribution to the hum an serum levels from drinking water (Table 4). No RSC is used for the cancer end point, as the target hum an serum concentration is based on the 10"risk level from drinking water exposure only. As discussed above, the relationship between external dose and serum level was used for development of a healthbased drinking water concentration for PFOA. The ratio of 100:1 between the concentration of PFOA in serum and in drinking water which was reported for a high drinking water concentration (16) also appears to be valid at lower con centrations relevant to this analysis (Table 3). I h e healthbased drinking water concentration for each end point was derived using the 100:1 ratio from the target hum an serum concentration contributed by drinking water for that end point (Table 4). As this approach is based on the observed relationship between serum and drinking water concentra tions, assumptions for body weight and volume of water ingested daily are not required. The range ofhealth-based drinking water concentrations for the seven end points assessed is 0.04--0.26 /ig /t, and several ofthe concentrations are very sim ilar 0.04,0.05,0.06, 0.07, and 0.08^g/L (Table 4). The most sensitive end points, resulting in the lowest drinking water concentration of 0.04 MglU were decreased body weight and hematological effects in the aduh female rat. Cancer was not the most sensitive end point, as the drinking water concentration based on the 10' cancer risk level is 0.06 /tg/L. Therefore, the recom mended health-based drinkingwater concentration for PFOA is 0.04 /tg/L. Both the USEPA Site Specific Action Level for PFOA in drinking water in West Virginia and Ohio (43), and the Minnesota Department of Health's (MNDOH) Health Based Value (44) for PFOA in groundwater are 0.5 /tg/L. These assessments are based on a 6 m onth (subchronic) study in male cynomolgus monkeys (Table 4), and use the ratio of half-lives for PFOA to extrapolate between animals and humans, rather than the 100:1 ratio between serum and drinking water used in Table 4. Based on pharmacokinetic principles, both approaches should give the same result if the parameters and assumptions used are correct The drinking water concentration derived in Table 4 for the same study and end point used by USEPA (43) and MNDOH (44) is 0.0S ftg/L. The 10-fold difference arises only because the drinking water concentrations developed in Table 4 include an UF for extrapolation from subchronic to chronic exposure, while the USEPA and MNDOH risk assessments do not. Aside from the 10-fold difference, which is explained by the use of the UF for duration of exposure, the approach used in Table 4 and the approaches used by USEPA and MNDOH give identical results, providing further strength for the use ofthe 100:1 ratio in developing a health-based drinking water concentration for PFOA. Recent Human and Animal Data Not Considered in Development of a Health-Based Drinking Water Concen tration. The health-based drinking water concentration of 0.04^g/L considered only toxicological end points identified D ENVIRONMENTAL SCIENCE & TECHNOLOGY I VOL. xx x , NO. X X . XXXX VOL. XXX. NO. XX. X X X X / ENVIRONMENTAL SCIENCE & TECHNOLOGY E TABLE 4. Derivation of Health-Based Drinking Water Concentrations for PFOA from End Points in Animal Studies (29) species adult female rat key study (29) chronic diet end point (29) 1 body weight, hematology NOAEL or LOAEL (29) NOAEL 1.6 mg/kg/day (30 ppm) animal serum level (/rg/L) at LOAEL or NOAEL (29) 1800 (based on modeled AUC) uncertainty factor 100(10 intraspecies, 10 interspecies) target human serum level* (/rg/L) 18 target contribution to human serum from drinking water* (/rg/L) 4 health-based drinking water concentration' <A9/U 0.04 adult male rat two-generation 1 body weight, 1 LOAEL 1 mg/kg/day 42 000 (USEPA 1000(10 42 8 0.08 reproductive, liver and kidney model) intraspecies, 10 gavage weight In FI Interspecies, 10 generation LOAEL to NOAEL) nonhuman primate subchronic male eynomolgus monkey, capsule Increased liver weight and possible mortality LOAEL 3 mg/kg/day pregnant female rat two-generation reproductive, gavage 1 body weight in mala F1 pups during postweaning NOAEL 3 mg/kg/day 77 000 (measured) 3S00 (based on modeled AUC) 3000(10 intraspecies, 3 Interapecies, 10 subchronic to chronic, 10 LOAEL to NOAEL) 100(10 Intraspecies, 10 Interspecies) 26 35 5 7 0.05 0.07 male rat pups, postwean ing two-generation reproductive, gavage l body weight in male F1 pups during postweaning NOAEL 3 mg/kg/day 8400(based on modeled AUC at week 4) 100(10 intraspecies, 10 interspecies) 84 17 0.17 female rat pups, two-generation 1 body weight In NOAEL 10 mg/kg/day 13 000 (based on 100 (10 130 26 0.26 postweaning reproductive, female FI pups modeled AUC at intraspecies, 10 gavage during week 7) Interspecies) postweaning male rats (tumor) (67) chronic diet Leydig cell, pancreatic, and liver tumors 13.6 mg/kg/day (300 ppm) (~10% tumor Incidence) (LOAEL or NOAEL not applicable) 572 OOOug/L (USEPA model) not applicable, target human serum level is baaed on linear extrapolation from 10"1 tumor incidence to 10"* incidence 5.7 5.7 0.06' 'T a rge t human serum level is derived by application of uncertainty factors to animal serum level at N O AEL or LOAEL. ''Target contribution to human serum from drinking water is derived by applying a relative source contribution factor of 20% (to account for nondrinking water sources of exposure) to target human serum level. 'Health-based drinking water concentration assum es a 100:1 ratio between PFOA concentrations In serum and drinking water (76). 'N o te : 2 0 % relative source contribution factor w as not used for cancer endpoint., -p <T> P-7 by USEPA (29). Additional data from hum an and animal studies not considered by USEPA (29) have since become available. ThedevelopmentaJ studies considered by USEPA (29) were conducted in rats. The rat is not an appropriate model for evaluating potential hum an developmental effects of PFOA because its half-life in the female rat is very short (2--4 h) (5). In the two-generation rat study considered by USEPA (29) in which PFOAwas administered as a bolus dose, blood levels did not reach steady state and exposure to the developing fetuses was not continuous. The mouse is more appropriate for developmental studies of PFOA, since the half-life in female mice is longer (17 days) (5), and PFOA levels reach steady state, with continuous exposure to the fetuses. Recent mouse developmental studies (5, 45--43) show significant effects not seen in the rat, including full litter resorptions, postnatal mortality, decreased birth weight, delayed growth and development, effects on mammary gland development, increased pup liver weight, structural changes in the uterus, and metabolic effects in adulthood after prenatal exposures. USEPA (49) has recently Qanuary 2009) developed a Provisional Short-term Health Advisory for PFOAin drinking water of 0.4 /tg/L, based on increased maternal liver weight after administration of PFOA for 17 days (45). Applying a standard UF of 10 for subchronic to chronic exposure to this value would result in a drinking water concentration of 0.04 Hg/L, identical to the lifetime health-based guidance devel oped here. However, exposure for 17 days is insufficient to be considered subchronic (50). and therefore may not be appropriate for extrapolation to a chronic risk assessment based on a systemic effect such as increased liver weight. Additionally, other studies of similar or shorter duration not considered by USEPA (49) show effects in mice at doses below those used in the study selected by USEPA (45). These effects include increased liver weight in dosed adults (51), and increased pup liverweight (46), metabolic effects in adulthood (47), and structural changes in the uterus (48) foDowing prenatal exposure. Evaluation of these studies could result in a short-term health-based concentration below 0.4 /(g/L. Preliminary data are available from the C8 Health Study, a study of approximately 70 000 people in Ohio and West Virginia exposed to PFOA in drinking water at 0.05 /tg/L or above U l, 33). This study is unique because serum levels were measured, so that effects may be correlated with internal dose rather than with a surrogate such as drinking water concentration for this very large study group. The median serum levels in the first and second deciles, 6 and 9.8 /g/L (11) are within the range prevalent in the U.S. general population, where, for 2003--2004, the 75th and 95th percentile levels were 5.8 and 9.8 /tg/L (2). Increased cholesterol and other lipids were associated with serum PFOA levels, alter adjustment for age, gender, body mass index, and other factors (12). In the cholesterol study (12), the median PFOA serum level was 27 /(g/L, and the risk of high cholesterol increased in each quartile of exposure with a 40-50% increase in the top quartile compared to the lowest quartile. Similarly, serum PFOA was significantly associated with increased uric acid levels (52) and changes in several indicators of inflammatory and imm une response (53) in this population. Additionally, preliminary data suggest an association between PFOA serum levels and several other clinical parameters measured in blood, including liver enzymes (11). It should be noted that these studies are ongoing and the results are currently undergoing peer review. The health-based drinking water concentrations devel oped in this paper (Table 4) are intended to protect against adverse effects from a lifetime of exposure. They are based on target human serum levels developed from animal data through a conservative approach using standard UFs for RfD development However, recent data suggest that biological effects may occur in hum ans in the range ofthe target serum levels presented in Table 4. The lowest target serum level derived from animal studies (18/tg/L) fallswithin the second quartile of the C8 Health Study (12), where associations with elevated cholesterol and uric acid, and changes in imm une system function, were seen (12, 33, 52, 53). Additionally, associations with effects on growth ofinfants (6--6), increased time to pregnancy (54), and decreased normal sperm count (55) were reported in humans at serum levels below the target hum an serum levels in Table 4, although other studies (9,10) did n o t show effects on infant growth. In conclusion, PFOA was commonly detected in raw and finished water from NI PWS using both surface and groundwater sources. Based on the relationship between the PFOA concentrations in drinking water and serum in humans, drinking water concentrations such as those detected in NJ (e.g, 0.01/tg/L) may contribute substantially to total exposure to PFOA. A health-based drinking water concentration of 0.04 /tg/L was developed based on effects in animal studies. Recent animal and human studies provide additional in formation on exposure to and effects of PFOA. While PFOA in most NI PWS was below the health-based concentration, several New Jersey PWS exceeded this concentration. Acknowledgm ents Theoccurrence studywas conducted through the cooperative efforts of the staff of the N] Department of Environmental Protection Bureau of Safe Drinking Water, Office of Quality Assurance, and Division ofScience, Research and Technology (DSRT), including Edward Apalinski, John Berchtold, Linda Bonnette, Alan Dillon, Marc Ferko, Karen Fell, Barker Hamill, Dr. Eileen Murphy, Michele Putnam, and Dr. Bemie Wilk. We thank Gail Carter of DSRT for creating the map, Dr. Thomas Atherhoh of DSRT for helpful comments, and Dr. Alan Stem ofDSRTand Dr. Perry Cohn ofthe N) Department of Health and Senior Services for their earlier review of the basis for the health-based drinking water concentration. Finally, we especially thank Dr. Eileen Murphy, Director, DSRT, for her enthusiastic support of this work. The views expressed are those of the authors and do not necessarily represent those of the New Jersey Department of Environ mental Protection. 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