Document yVEp9zOYvjGm1LmJyKLza23X

P-1 "McCrea, Deborah" <mccrea@taftlaw.com> 06/05/2009 12:20 PM To NCIC OPPT@EPA cc "Bilott, Robert A." <bilott@taftlaw.com> bcc Subject 06/05/2009 Letter To EPA Docket Center Taft/ Deborah McCrea / Legal Assistant Taft Stettinius & Hollister LLP 425 W alnut Street, Suite 1800 Cincinnati, Ohio 45202-3957 Tel: 513.381.2838 Fax: 513.381.0205 www.taftlaw.com / mccrea@taftlaw.com o uo c_ cr r~ ro o -o 3C no jr CO .T 'O r .-c O^ Internal Revenue Service Circular 230 Disclosure: A s provided for in Treasury regulations, advice (if any) relating to federal taxes that is contained in this communication (including attachments) is not intended or written to be used, and cannot be used, for the purpose of (1) avoiding penalties under the Internal Revenue C ode or (2) promoting, marketing or recommending to another party any transaction or matter addressed herein. This m essage may contain information that is attorney-client privileged, attorney work product or otherwise confidential. If you are not an intended recipient, use and disclosure of this m essage are prohibited. If you received this transm ission in error, please notify the sender by reply e-mail and delete the m essage and any attachments. From: canoncopy20a@ taftlaw.com [mailto:canoncopy20a@ taftlaw.com] Sent: Friday, June 05, 2009 12:29 PM To: McCrea, Deborah Subject: 06/05/2009 Letter To EPA Docket Center 276G_001.pdf c o n ta in s n o c p P-2 Taft/ Taft Stettinius & Hollister LLP 425 W alnut Street, Suite 1 8 0 0 / Cincinnati, OH 4 5 2 0 2 -3 9 5 7 /Tei: 5 1 3 .3 8 1 .2 8 3 8 /Fax: 5 13 .3 8 1 .0 2 0 5 / w w w .taftlaw.com Cincinnati / Cleveland / Columbus / Dayton / Indianapolis / Northern Kentucky / Phoenix / Beijing ROBERT A . BlLOTT 513-357-9638 bHott@tafHaw.com June 5, 2009 FEDERAL EXPRESS E P A Docket Center, M C 2822T U.S. Environmental Protection Agency E P A West, Room 3334 1301 Constitution Avenue, NW Washington, D.C. 20004 Re: Submission to IRIS and AR-226 Database For PFO A/PFO S: EPA-H Q ORD-2003-0016 To IRIS Database for PFO A/PFOS: In response to the Notice issued by U S E P A on February 23, 2006, regarding U S E P A 's efforts to consider perfluorooctanoic acid ("P F O A ") and perfluorooctane sulfonate ("P F O S ") within the Integrated Risk Information System ("IRIS"), 71 Fed. Reg. 9333-9336 (Feb. 23, 2006), we are submitting the following additional information to U S E P A for inclusion in that review, and for inclusion in the AR-226 database: 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). Robert A. Bilott RAB:mdm Enclosure cc: Gloria Post (NJDEP)(w/ end.) (via U.S. Mail) Helen Goeden (MDH)(w/ end.) (via U .S. Mail) Lora Werner (ATSDR)(w/ end.) (via U.S. Mail) 11423035.1 P-3 Environ. Sci. Techno!. XXXX, soar. 000-000 Occurrence and Potential Significance of Perfloorooctaitoic Acid (PF0A) Detected in New Jersey Public Drinking Water Systems G L O R I A B. P O S T , *-' J U D I T H B. L O U I S , * K E I T H R. C O O P E R . * BETTY JANE B OROS- RUSSO, * AND R. L E E L I P P I N C O T T * Division o f Science, Research and Technology, New Jersey Department o f Environmental Protection, P.O. Sox 409, Trenton, New Jersey 00625, Department o f Biochemistry and Microbiology, Rutgers University, 76 Upman Drive, Room 216, 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 perftuorooctanoic acid (PF0A) in two New Jersey (NJ) public water systems (PWS) at concentrations up to 0.19 ftg/L, a study of PFDA in 23 other NJ PWS was conducted in 2006. PFOA was detected in IS (65%) of the systems at concentrations ranging from 0005 to (UBSpg/L To assess the significance of these data, the contrSwtion of drinking water to human exposure to PFOA was evaluated, and a health-based drinking water concentration protective for lifetime exposure of 0.04pg/L was developed through a risk assessment approach. Both the exposure assessment and the health-based drinking water concentrations are based on tiie previously reported 100:1 ratio between the concentration of PFOA in serum and drinking water in a community with highly contaminated drinking water. The appficabiKty ofthis rat to tower drinking water concentrations was confirmed using data on serum levels and water concentrations from other communities. The health-based concentration is based on toxicological end points identified by U.S. Environmental Protection Agency (USEPA) in its 2005 draft risk assessment Recentinformation on PFOA'stoxicitynotconsideredinthe USEPA riskassessment furthersupports the health-based concentration of 0.04pg!L hi additional sampling of 18 PWS in 2007-2008, PFOA in mostsystemswasbelowthe health-basedconcentration. However, PFOA was detected above the health-based concentration in five systems, including one not previously sampled. InUMhrction Perfluorooctanoic a d d (PFOA) is found in blood of people worldwide (I), including 99.7% o f a representative sample of * Corresponding author phone: (609) 292-8497: gloria.post@dep.state.nj.us. ' Division of Science, Research and Technology. *Rutgers University. * Bureau of Safe Drinking Water. e-roaiL 10.1021/900301s C C C S40.7E XXXX A m u fc s n C hem ical S ociety the U.S. population (2). In studies of U.S. populations, the geometric m ean serum levels were 3.9 pglL in 2003-2004 and 3.4pg/L in 2006(2.31, This widespread hum an exposure is of concern due to PFOA's persistence and taxidty. PFOA has a half-life o f several years in hum ans 14), and caused adverse effects o n development, lipid metabolism, liver, and the im mune system, and tumors in several organs in animals (5). In some studies, m aternal exposures in the general population were associated with decreased birth weight and other measures offetal growth {6-8), while other studies did not find these effects (9,10). Some studies of exposedworkers found associations with adverseoutcomes including diabetes mellitus and increased cholesterol, whereas other studies were negative (5). Preliminary results of a study o f almost 70 000 people exposed through drinking water suggest an association with several clinical parameters measured in blood, including increased cholesterol (11.12). Sources o fexposure to PFOA include consum er products (13), house dust (14), diet (15), and drinking w ater (i6). Exposure also occurs throughmetabolism and environmental transformation of the related chemical, 8:2 fhiorotelomer alcohol, which is widely used in food packaging and other products (17). PFOAand 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 contam inated 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 contam inated drinking water (16,20), 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 oftwo PWS at concentrations from 0.007 to 0.19^g/L (28). An occurrence study was conducted by NTDEP in 2006, and additional sampling was performed by NJ PWS in 2007-2008. The additional goals were to evaluate the significance ofPFOAin drinkingwater for human exposure and potential hum an health risk. The contribution o f drinking w ater concentrations such as those found in NJ to total exposure to PFOA was evaluated. A health-based drinklngwaterconcentration was developed using end points for toxicity identified by U.S. Environmental Protection Agency (USEPA) (23). Both the exposure assessm ent and health-based water concentration were based on the ob served relationship betw een the concentration o f PFOA in drinking water and serum in hum ans (16). Experimental Sectian Sam ple Site Selection. For the 2006 occurrence study, 36 samples collected by the New Jersey D epartm ent of Envi ronm ental 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, o r with public wells within 1 mile, of five facilities where PFOA or related chemicals may have been present. Four additional systems with a history of organic contamination were included, since these systems are 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 V O L X , NO. ex. XXXX / ENVIRONMENTAL SCIENCE & TECHNOLOGY A P-4 IABLE !. PFOA in !U PWS Sample by ilJOEP, 2016" public water system site no. ID number source water raw/ fnistied PFOA i/rg/U 1 NJ2119001 GW, unconfined Raw NO* 2-W1 NJ0217001, GW, unconfined raw Wall 1 0.026 2-W2 NJ0217001, GW, unconfined raw Welt 2 0.033 3 NJQ221001 GW, unconfined raw 0.033 4 NJ1804001 GW, unconfined raw 0.029 S NJ1107002 GW, unconfined raw 0.007 6 NJ0424001 GW, unconfined raw ND 7 NJ0119002 GW, unconfined raw NQ' 8 NJ0717001 GW, unconfined raw 0.021 9 NJ1434001 GW, unconfined raw 0.008 10 NJ0614003 GW, unconfined raw ND 11R NJ14360Q2 GW, unconfined raw 0.006 11F NJ14350Q2 GW, unconfined finished 0.006 12* NJ1007002 GW, unconffned finished 0.008 13GW* NJ1712001 GW, semiconfined raw 0.027/0.026' 14 NJ1316001 GW, confined raw ND IS NJ0614001 GW, confined finished ND 16 NJ1613001 SW raw 0.008 13SW* 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 NJ1005002 SW raw 0.026 20F NJ1605002 SW finished 0.027 21R NJ2013Q01 SW raw 0.035 21F NJ2013001 SW finished 0.039 22 NJ13620Q6 SW, reservoir raw 0.011 23 NJ0238001 SW, reservoir raw 0.021 *GW , ground w ater; SW, surface w ater. * ND, not detected. NQ, detected below RL a There is no history of organic contamination at these PWS. 'T h is PWS has both a groundwater and a surface w ater source. 'Laboratory duplicate. selected for comparison (3Q). 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 o n e groundwater system. In 2007 -2008, additional sampling was conducted by NJ 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 n o t sampled in 2006. Sam pling Procedure. Sample collection was performed by NJDEP personnel, following th e standard operating procedure for the analytical m ethod (31). A single unfiltered 2SOm L grab sam ple 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 die greatest and least possibility of contamination was expected. The trip blank containing distilled water was prepared by the analytical laboratory, shipped to NJDEP perso n n el 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 M ethod. The 2006 samples were analyzed for PFOA by Test America, Denver, CO using liquid chrom a tography and tandem mass spectrometry (LC/MS/MS) (Micromass Ultima MS/MS or Waters Micromass Quattro Prem ier tandem mass spectrometer) (31).An isotope dilution technique usinga 13C labeled PFOAanalog is used to quantify FIGURE 1. Locations of NJ PWS sampled in 2066 PFOA nccurrcnce study. PFOA. The PFOA parent ion (m /z -- 413 amu) and two daughter ions (m /z = 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 /ig/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 am ong laboratories and ranged from 0.01 to 0.015 /rg/L. Results and Discussion 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, an d three additional systems bad detections below the RL. PFOA was detected in 9 of 12 (75%) raw groundwater samples from unconfined or semiconfined aquifers, but was n o t detected in the two raw (e.g.. untreated) groundwater samples from confined aquifers. All three samples of finished (e.g., treated) groundwater from un confined aquifers had detectable levels of PFOA. Seven of B ENVIRONM ENTAL SCIENCE Si TECHNOLOGY / V O L XXX. NO. x x . XXXX P-5 TARI 2. NJ PWS with PfOA Detectiois >B.M/rg/l Data Sabaritttd to KJDEP. 2017-2088* site ns. PWS source water 8A NJ0717001 GW, unconfined 8B NJ0717001 GW, unconfined 24 NJ08090Q2 GW, unconfined 25A NJ1707001 G W .unconfined 258 NJ1707001 GW, unconfined 2SC NJ177001 GW, unconfined 21 N J2013001 SW 3 NJ0221001 GW, unconfined ' GW. ground w ater; SW, surface water. TP POE POE POE Weil 1 Well 2 POE POE POE number of nples 4 4 3 5 6 6 1 4 average (prg/L) 0.068 0.069 0.050 0.083 0.078 0.079 0.040 0.034 raege(/ig/U 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 watersam ples had detectable levels ofPFOA. There was no apparent difference between raw and finished w ater collected at th e sam e system. PFOA was not detected above th e health-based concentration (see below) of 0.04 /tg/L in this study. PFOA w as not detected in the six field blanks or th e one trip blank. Additional details are provided in a n NJDEP report (2 0 . A dditional PFOA D a ta from NI PWS. In 2006, PFOA data were subm itted 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 (NJ1707Q01, site no. 25), PFOA was detected a t u p to 0.123 andO. 19/(g/L in shallow, unconfm ed wells from two different wellfields, b u t was n o t detected in deep unconfined wells from these wellfields. At d ie other system (NJ1708001, site no. 26), PFOA was detected in one ofeight raw groundwater sam ples at 0.0176 an d 0.0179/tg/L, an d In finished water up to 0.0081 n g/L (20. I n 2007-2006,201 sam ples collected by 18PWS, including 12 sam pled in th e 2006 study, were analyzed for PFOA. Samples were collected from one or more POE at each system, with one to six sam ples for each FOB, as well as from individual wells and surface water intakes. PFOA concentra tions ranged from nondetectable (<0.01 ttglli to 0-14 tg/L. PFOA was detected at o r above the health-based concentra tion (see below) of 0.04 tg/L in a t least one sam ple from five system s (Table 2), including one n o t sam pled i n 2006. Yearly average concentrations (average results from fourconsecutive quarters) exceeded the health-based concentration for four POE from three different systems. P o ten tial C ontribution o f PFOA a t C oncentrations Found in NJ Drinking W ater to PFOA in Serum . A median ratio o f approximately 1:100 was observed between the concentration ofPFOA in drinking w ater an d serum in little H ocking Ohio U6). In this community, drinking water had been contam inated by a nearby industrial facility, with an average concentration of3.55/tg/Lin2iX)2-2005. The median PFOA serum concentration in 282 individuals tested in 2004--2006 was 371 /tg/L, with occupationally exposed individuals excluded. This ratio is based o n those six years and older, while a higher ratio was observed for younger children (1 0 . 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 o f residence. Ifa similar relationship is valid at lower drinkingwater concentrations, such as those detected in NJ (Tables 1 a n d 2), then such concentrations may contribute substantially to total exposure to PFOA. D ata are available on both the range o f historic drinking w ater concentrations (32) and the serum levels ofPFOA in sam ples taken in 2005-2006 (30 in five Ohio and West Virginia water districts w ith lower PFOAconcentrations than Little Hocking. The m edian serum level in each o f these districts (Table 3) is higher than the U.S. m edian of 4 /tg/L TABU 3. PFOA Levels a Ditafa'ag Water a*d Sema io Csmmmties ia Okie aod West Vbghris water district PFOA levels median seism reported by PFOA level water district (rg/L) (38 (pg/U (38 Little Hocking, OH Lubesk, WV T ap p ers Plains, OH Crty of Before, OH M ason County, WV Village of Pom eroy, 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 o fpeople served by each POE, as well as th e variation o f concentration over time, are notknown. Therefore, the mean or median drinking water concentrations in these districts cannot b e accurately estimated from the range ofconcentrations. For this reason, the m edian ratio of drinking water to serum concentrations for these districts cannot b e reliably determined, as was done for little Hocking (10. 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 die lowest PFOA concentration (0.06-0.07/tg/L), about 50-fold lower than in little Hocking. Since this range is narrow, the average can be reliably estim ated as 0.065/tg/L. Based on this estimate, die 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 th e blood than in those usinghighly contam inated water. To find a lower bound o n th e ratio o f serum to water PFOA concentrations, it can be assumed th at none o f the U.S. backgroundserum concentration ofabout4/ig/Lresuhsfroro drinking water. If this serum concentration of 4 /tg/L is subtracted from th e m edian serum concentration for Village of Pomeroy (12 /tg/L), the ratio o f the rem aining serum concentration (8 /tg/L) to the drinking water concentration (0.065/tg/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 (f0 . It should be noted that serum levels for individuals with occupational exposure (2% current, 3% fomer) (3 0 were not excluded from the data shown in Table 3. However, since the num ber of subjects in each district is huge, and the serum concentrations are medians, rather th an means, it is unlikely that the overalltrend wouldchange ifoccupationally exposed individuals were excluded. This observed serum/drinking water ratio of approxi mately 100:1 is in agreement with a one-com partm ent model (34) which predicts that ingestion of 0.0017 /tg/kg/day would result in serum levels of 13 /tg/L in males and 8 /(g/L in V O I. x x x . N O . XX. XXXX ! ENVIRONMENTAL SCIENCE & TECHNOLOGY C P-6 females, or a m ean of 10.5 ftg/L. Assuming a drinking water intake of 0.017 U kg/day (35). a dose of 0.0017 pg/kg/day w ould result from a water concentration of 0.1 ftg/L. The ratio between a serum concentration of 10.5 ftg/L and this w ater concentration of 0.1 ftg/L is 105:1, identical to the m edian ratio reported in little Hocking (15). These results suggest th a t 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 ftg/L in 13 of 29 samples in the 2006 study (Table 1). Based o n the 100:1 ratio, a drinking w ater concentration of 0.01 ^g/L is estim ated to contribute about 1 ftg/L to PFOA in serum, o r about 25% of the 4 ftg/L m edian serum level in the general population. Development of a Health-Based Drinking W ater Con c e n tratio n fo r PFOA. The draft risk assessm ent for PFOA developed by USEPA (29), which identified toxicological end points in experimental animals, was used as the starting point for developm ent of a health-based drinking water concen tration protective forlifetime exposure. Thegoal ofthe USEPA risk assessm ent (29) was to evaluate the significance of exposure in th e general population. Because the half-life of PFOA is m uch longer in hum ans (several years) th an in the anim als 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 o n the basis of serum levels rather th a n external dose (2 . 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 m argins of exposure 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 recom m ended a clas sification of'likely to 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 assessm ent (37), are shown in Table 4. USEPA [23l did not develop a Reference Dose (RfD) or cancer slope factor for PFOA nor did they address the relationship between the externaldose and the human serum level. Information on this relationship is valuable for developmentofa health-based drinkingwaterconcentration. 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 th e measured or modeled serum levels identified (29,395 as NOAELs o r LOAELs for noncancer end points (Table 4). T he UF o f 10 for interspecies extrapolation typically Includes two factors of 3 each for toxicokinetic and toxicodynamic differences between hum ans and animals (36). Since the health-based drinking water concentrations are based on com parison of serum levels in animals and humans, the question arose as to whether comparison on this basis folly addresses interspecies toxicokinetic differences, and whether an interspecies UF of 3 rather than 10 is thus appropriate. The USEPA ScienceAdvisoryBoard (361 believed that overall uncertainty about die interspecies differences in PFOA toxicity was not sufficiently reduced by comparison on the basis o f serum levels to justify modifying the default interspecies UF. Therefore, the standard interspecies UF of 10 w as used. For the cancer end point, the serum level resulting in a 10~* risk 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 die contam inant (41,42). The default value for this factor is 20% (e.g., nondrinkingw ater sources are assumed to provide 80% ofexposure) whenthe relative contributions ofdrinkingwater versus nondrinking water sources are not folly 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 nicer end point, as the target hum an serum concentration is based on the I0~* 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). The healthbased drinking water concentration for each end point was derived using tire 100:1 ratio from th e 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 waterconcentrations for the seven end points assessed is 0.04-0.26 ftg/L, and several of the concentrations are very similar. 0.04,0.05,0.06, 0.07, and 0.08^g/L (Table 4). The m ost sensitive end points, resulting in the lowest drinking w ater concentration of 0.04 fig/L, were decreased body weight and hematological effects in the adult female rat. Cancer was n o t the most sensitive end point, as the drinkingwater concentration based on the 10~s cancer risk level is 0.06 ftg /L Therefore, the recom mended health-based drinldngwater concentration forPFOA is 0.04 ftg/L. Both tile USEPA Site Specific Action Level for PFOA in drinking water in West Virginia and Ohio (43), and the Minnesota D epartm ent o f H ealth's (MNDOH) Health Based Value (44) for PFOA in groundwater are 0.5 ftg/L. These assessments are based on a 6 month (subchionic) study in male cynomolgus monkeys (Table 4), and use the ratio of half-lives for PFOA to extrapolate between animals and humans, rather than th e 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 0.05 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 chronicexposure, while the USEPAand MNDOH risk assessments do n o t 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 0.04fig/ Lconsidered only toxicological end points identified D ENVIRONM ENTAL SCIENCE & TECHNOLOGY / V O L x x x . N O . XX, XXXX TABLE 4. Derivation of Health-Based Drinking Water Concentratigns for PFOA from End Points in Animal Studios (2D) species adult female rat key study (29) chronic diet end paint (29) I 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) uncartsinty factor 100(10 Intrsspacies, 10 interspecies) target human aarum laval' (Pfl/L) 18 target cootrihutioi to human aarum from drinking water* (pg/ll 4 health-based drinking water concentration* (A9/L) 0.04 adult mala rat two-generation J body weight, I LOAEL 1 mg/kg/day 42 000 (USEPA 1000 (10 42 8 0.08 reproductive, liver and kidney model) Intrsspacies, 10 gavage weight In F1 Interspecias, 10 generation LOAEL to NOAEL) nonhuman primate subchronic mala Increased liver LOAEL 3 mg/kg/day 77 000 (measured) 3000 (10 26 S 0.05 cynomolgus weight and Intraspsclea, 3 monkey, capsule possible mortality Interspades, 10 subchronic to chronic, 10 LOAEL to NOAEL) pregnant female rat two-generation reproductive, gavage 1 body weight in male FI pups during postweaning NOAEL 3 mg/kg/day 3500 (based on modeled AUC) 100 (10 Intrsspacies. 10 interspecias) 35 7 0.07 male rat pups, postweaning two-generation reproductive, gavage 1 body weight in mala FI pups during postweaning NOAEL 3 mg/kg/day 8400 (based on modeled AUC at weak 4| 100(10 intrsepecles, 10 Interspecias) 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 Ft pups modeled AUC at intraspacies, 10 gavage during weak 7) Interspades) postweaning male rats (tumor) (37) chronic diet Leydig cell, pancreatic, and fiver tumore 13.6 mg/kg/day (300 ppm) (~10% tumor incidence) (LOAEL or NOAEL not applicable) 572 000 pg/L (USEPA model) not applicable, target human serum level is baaed on linear extrapolation from 10-1 tumor incidence to 10~* Incidence 6.7 5.7 0.06rf ` Target hum an serum level is derived by application of uncertainty factors to anim al serum level at NOAEL or LOAEL. ''T argetcontribution to hum an serum from drinking w ater is derived by applying a relative source contribution factor of 20% (to account for nondrinking w ater sources of exposure) to target hum an serum level. ` Health-based drinking water concentration assu m e s a 100:1 ratio betw een PFOA concentrations in serum and drinking w ater ( J8). rfNote: 20% relative source contribution factor w as not used for cancer e n dpoint p -4 p.8 by USEPA 129). Additional data from hum an and animal studies not considered by USEPA (29) have since become available. The developmental studies considered by USEPA 129)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 die female rat is very short (2 -4 h) (5). In th e 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 o f PFOA, since the half-life in fem ale mice is longer (17 days) (5). and PFOA levels reach steady state, with continuous exposure to the fetuses. Recent m ouse developmental studies (5, 45-48) show significant effects not seen in the rat, including full liner 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 (January 2009) developed a Provisional Short-term HealthAdvisory forPFOA in drinking w ater of 0.4 /rg/L, based o n increased maternal liver weight after administration of PFOA for 17 days (49). Applying a standard UF of 10 for subchronic to chronic exposure to this value would result in a drinking water concentration of0.04 figfL. 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 ofsimilar or shorter duration not considered by USEPA (49) show effectsin mice a t doses below those used in tire study selected by USEPA (45). These effects include increased liver weight in dosed adults (51), and increased pup Overweight(45), metabolic effects in adulthood (47), and structural changes in th e uterus (48) following prenatal exposure. Evaluation of these studies could result in a short-term health-based concentration below 0.4/rg/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 ftg/L or above ( l i, 33). This study Is unique because serum levels were measured, so that effects m aybe 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 /rg/L (II) a re 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 otherlipids were associated with serum PFOA levels, alter adjustm ent for age, gender, body mass index, and other factors (12). In the cholesterol study (12), the m edian PFOA serum level was 27 /rg/L, and the risk of high cholesterol increased in each quartiie of exposure with a 40-50% increase in the top quartiie compared to the lowest quartiie. Similarly, serum PFOA was significantly associated with increased uric acid levels (52) and changes in several indicators of inflammatory an d im m une response (53) in this population. Additionally, preliminary data suggest an association between PFOA serum levels and several other clinical param eters m easured in blood, including liver enzymes (II). It shouid 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 hum an serum levels developed from animal data through a conservative approach usingstandard UFs for RfD developm ent However, recent data suggest that biological effects may occur in humans in the range ofthe target serum levels presented in Table 4. The lowest target serum level derived from anim al studies (18/rg/L) foilswithin the second quartiie of the C8 Health Study (12), where associations with elevated cholesterol and uric acid, and changes in immune system function, were seen (12, 33, 52, 53). Additionally, associationswith effects on growth ofinfants (6-5), increased time to pregnancy (54), and decreased normal sperm count (55) were repotted in humans at serum levels below the target hum an serum levels in Table 4, although other studies (9 ,10) did not show effects on infant growth. In conclusion, PFOA was commonly detected in raw and finished w ater from NJ PWS using both surface and ground- water 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/rg/L) may contribute substantially to total exposure to PFOA. A health-based drinking water concentration of 0.04/tg/L was developed based o n effects in animal studies. Recent animal and hum an studies provide additional in formation o n exposure to and effects of PFOA. While PFOA in m ost NJ PWS was below the health-based concentration, several New Jersey PWS exceeded this concentration. Acknowledfmeats The occurrence study was conducted through the cooperative efforts of the staff o f th e NJ D epartm ent 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 HamOl, Dr. Eileen Murphy, Michele Putnam, and Dr. Bemie Wilk. We thank Gail Carter of DSRT for creating the map, Dr. Thomas Atherhoit o f DSRT for helpful comments, and Dr. Alan Stern ofDSRT and Dr. Perry Cohn o fthe N)D epartm ent 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 h er 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. Note Added after ASAP Publication There was an error in tire range column of Table 2 in the version of this paper th a t published ASAP May 8. 2009; the corrected version published ASAP May 12, 2009. Literature Cited (1) Kannan. K.; Corsoiitu. S.; Faiandysz, I.; Fillmann, G.: Kumar. K. S.; Loganathan, B. G.; Mohd, M. A; Oliroro, J.; Van Wouwe, N.; Yang J. H.; Aldous, K. M. 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