Evaluation of Exposure to and Human Health Risks from Pcpps in Drinking Water from Lake Erie

Home , Atrazine

Evaluation of Exposure to and Human Health Risks from PCPPs in Drinking Water from Lake Erie

FINAL REPORT

By:

Michelle Homan, Ph.D. Hwidong Kim, Ph.D.

Department of Environmental Science and Engineering Gannon University

November 14, 2018

Project Period: February 1, 2016 - September 30, 2018

TABLE OF CONTENTS

List of Figures ...... iii

List of Tables ...... iv

Executive Summary ...... 1

Introduction ...... 3

Background ...... 3

Project Goals and Objectives ...... 4

Methodology ...... 5

OBJECTIVE 1: Determination of the concentrations of target PPCPs ...... 5

1. Sampling site ...... 6 2. Sampling methods ...... 8 3. Analytical methods ...... 13 4. Determination of PPCP concentration in water phase from POCIS analytical results .. 13 OBJECTIVE 2: Comparison of ELISA with Lab Analysis Results ...... 15

OBJECTIVE 3: Human Health Risk Assessment ...... 17

Results and Discussion ...... 19

OBJECTIVE 1: Determination of the concentrations of target PPCPs ...... 19

1. General water quality ...... 19 2. Sampling rates ...... 20 3. PPCPs in Grab samples ...... 23 4. POCIS sampler results ...... 25 Objective 2: ELISA versus Analytical Results ...... 30

Objective 3: Human Health Risk Assessment ...... 32

Conclusion ...... 35

Future Research ...... 35

Citations ...... 37

Appendix A: Metrics...... 40

Appendix B: Impact and/or Accomplishment Statement(s) ...... 41

Appendix C: Raw Data ...... 43

LIST OF FIGURES

Figure 1. (a) Location of the Wasielewski water treatment plant and (b) sampling points within the Wasielewski water treatment plant ...... 7 Figure 2. (a) an assembly of membrane discs and holder (b) and (c) sampling canister with POCIS membrane discs and holder ...... 9 Figure 3. A schematic of POCIS deployment setup (treated water) ...... 10 Figure 4. Sampling containers installed at (a) water treatment plant and (b) low duty pump station ...... 11 Figure 5. Sampling schedule for grab samples and POCIS sampler deployment ...... 12 Figure 6. Temperature and dissolved oxygen concentrations of water samples over time ...... 19 Figure 7. Frequency of detection of PPCPs in raw and treated samples (grab samples) ...... 24 Figure 8. Frequency of detection of PPCPs in POCIS sampler ...... 27 Figure 9. Comparison of atrazine, caffeine and simazine concentrations in raw and treated water samples (retrieved from POCIS sampler analytical results) ...... 29 Figure 10. Scatterplot and Bland-Altman plots from LC-MS/MS and ELISA test for Atrazine at various dilutions (3 replicates) ...... 30 Figure 11. Scatterplot and Bland-Altman plots from LC-MS/MS and ELISA test for Triclosan at various dilutions (3 replicates) ...... 31 Figure 12. Scatterplot of results from LC-MS/MS and ELISA test for caffeine at various dilutions (3 replicates)...... 31

iii

LIST OF TABLES

Table 1. Summary of PPCPs Included in this Study ...... 5 Table 2. A summary of experimental setup for determination of sampling rates...... 14 Table 3. Summary of Dilutions and Replicates for Validation Study ...... 15 Table 4. Summary of RfD values for Target PPCPs ...... 18 Table 5. Analytical results of raw- and treated water samples for basic water quality parameters (total number of samples = 45) ...... 20 Table 6. POCIS sampling rates results estimated from analytes remained in the solution ...... 21 Table 7. A summary of PPCPs in grab samples ...... 25 Table 8. A summary of concentrations of PPCPs estimated based on POCIS analytical results . 28 Table 9. Summary of Risk Calculations using Maximum PPCP Values in Treated Drinking Water ...... 33 Table 10 (Appendix). PPCP concentrations in grab samples ...... 43 Table 11 (Appendix). PPCP concentrations in POCIS samplers ...... 46 Table 12 (Appendix). Water quality data (raw water samples) ...... 52 Table 13 (Appendix). Water quality data (treated water samples) ...... 53

EXECUTIVE SUMMARY

The overall goal of this research project was to evaluate the exposure to and human health risks associated with pharmaceuticals and personal care products (PPCPs) in drinking water originating from Lake Erie. Three specific research objectives were identified and completed as part of this project including:

● to determine the concentrations of 8 target PPCPs (acetaminophen, ampicillin, caffeine, metformin, naproxen, sulfamethoxazole, triclosan, and trimethoprim) and an additional 10 analytes in raw and treated drinking water from Lake Erie;

● to evaluate whether the enzyme-linked immunosorbent assay (ELISA) is an effective method for screening and characterizing PPCPs in drinking water; and

● to quantify the human health risks from exposure to trace levels of PPCPs in drinking water from Lake Erie.

To achieve the first objective, raw and treated water samples were collected from the Wasielewski Water Treatment Plant in Erie, Pennsylvania between October 2016 and August 2017. Along with grab samples, long-term samples were collected using Polar Organic Chemical Integrative Samplers (POCIS). Samples were analyzed by liquid chromatography- mass spectroscopy (LC-MS-MS) by an accredited laboratory. For short-term samples, six of the 18 PPCPs were found at detectable levels in raw or treated drinking water including atrazine, bisphenol-A, caffeine, ibuprofen, metformin and simazine. In the majority of cases, analyte levels in treated water were lower compared to raw water samples. For long-term samples, an additional four PPCPs (ten total) were found at detectable levels including gemfibrozil, naproxen, sulfamethoxazole and trimethoprim. Aqueous phase concentrations of PPCPs were estimated using sampling rates, deployment periods and analytical results of POCIS samplers. Similar to the grab sample results, the concentration of all analytes in treated water were lower than those in raw water samples.

A method comparison study was conducted to assess the agreement between the ELISA test with that of LC-MS-MS for three analytes (atrazine, caffeine and triclosan). Spiked samples in

1 triplicate were prepared from certified standards to include concentrations of 0, 0.25, 0.5, 1.0 and 2.5 ng/mL. The spiked samples were split and analyzed separately using each method. Analyte concentrations from each method were compared using Pearson product moment correlations and the construction of Bland-Altman plots. Results across all three analytes showed a moderate to high level of agreement between the two analytical methods. The correlation coefficient ( r) ranged between 0.96 and 0.99. The highest level of agreement was observed with atrazine, followed by caffeine and triclosan, respectively.

The third objective was to calculate the human health risks from the PPCP concentrations found in treated water samples. A literature review was conducted to find sources of average daily intake (ADI) or reference dose (RfD) values needed to calculate a drinking water exposure level (DWEL) for each analyte. The value of the DWEL was then compared to the maximum measured value or the method detection limit for each of the 18 analytes to estimate the risk quotient (RQ). A cumulative RQ was estimated at 0.003 for the 18 PPCPs included in this study. This level is well below any level considered to pose a risk. A value approaching 1 would be considered significant.

The major public health finding was that the 18 PPCPs quantified in this study were found at trace or non-detect levels and estimated to pose an insignificant health risk to the community. Additional findings include that the long-term POCIS and ELISA methods were practical and appropriate for measuring trace levels of PPCPs in source and treated water.

2 INTRODUCTION

BACKGROUND

Public concern and scientific interest in the potential health risks associated with PPCPs in drinking water have recently increased as a result of studies documenting their presence in surface, ground and treated drinking water (Henderson et al., 1999; Alliance for the Great Lakes, 2010; Blair, et al., 2013). These compounds include a large variety of substances such as prescription and over-the-counter drugs, antibiotics, fragrances, preservatives, disinfectants, surfactants, among others. Drinking water that originates from a lake or river may contain PPCPs when these products enter sewage systems and survive treatment at wastewater treatment plants.

The presence and concentration of PPCPs in municipal drinking water from surface water sources is not routinely monitored in the U.S. due to the expense necessary for complex laboratory analysis and since most of these compounds are not currently regulated by the U.S. Environmental Protection Agency (USEPA). While limited research studies have measured PPCPs in trace levels (µg/L or ng/L) within raw or treated drinking water, few studies have evaluated the comprehensive human health risks from exposure to trace PPCP mixtures in this manner (Schwab, et al., 2005; Cunningham, et al. 2009; WHO, 2011; Leung, et al. 2013).

The City of Erie, Pennsylvania and several surrounding communities obtain their drinking water directly from Lake Erie. In the City of Erie, lake water is treated at either one of two treatment plants: the Wasielewski plant or the Chestnut Street plant. The Wasielewski plant is the main treatment facility and has recently been upgraded with an ultrafiltration membrane system replacing the previous sand filtration system. Although not required by law, Erie Water Works tests its raw and finished water for a subset of PPCPs on a periodic basis. Most of the PPCPs analyzed in the raw and treated water have been found in low or non-detect levels (Erie Water Works, 2014).

3 PROJECT GOALS AND OBJECTIVES

● to determine the concentrations of 8 target PPCPs (acetaminophen, ampicillin, caffeine, metformin, naproxen, sulfamethoxazole, triclosan, and trimethoprim) and an additional ten analytes in raw and treated drinking water from Lake Erie;

● to evaluate whether the enzyme-linked immunosorbent assay (ELISA) is an effective method for screening and characterizing PPCPs in drinking water; and

● to quantify the human health risks from exposure to trace levels of PPCPs in drinking water from Lake Erie.

4 METHODOLOGY

OBJECTIVE 1: DETERMINATION OF THE CONCENTRATIONS OF TARGET PPCPS

In this study short and long-term samples were collected between October 2016 and August 2017 from the Erie Water Works plant located in Erie, Pennsylvania (refer to Table 1). A total of eight target analytes and ten additional analytes were quantified in the raw and treated water samples. Analysis of the 18 target analytes was conducted by an outside accredited laboratory. Additional samples collected in high-density polyethylene (HDPE) bottles were analyzed for basic water quality parameters such as free chlorine, solids (TSS and TDS), and organic matter (BOD and COD).

Table 1. Summary of PPCPs Included in this Study ANALYTE USE

Acetaminophen Analgesic

Ampicillin Antibiotic

Atrazine Herbicide

Bisphenol-A Plasticizer

Caffeine Found in beverages and pharmaceuticals

Carbamazepine Anticonvulsant

Cimetidine Acid reducer

Ciprofloxacin Antibiotic

Digoxin Heart medication

Gemfibrozil Lipid regulator

Ibuprofen Nonsteroidal anti-inflammatory

Metformin Anti-diabetic

Naproxen Nonsteroidal anti-inflammatory

Simazine Herbicide

5 Sulfamethoxazole Antibiotic

Sulfathiazole Antibiotic

Triclosan Anti-microbial

Trimethoprim Antibiotic

1. Sampling site

The raw and treated water samples were collected from the Wasielewski water treatment plant. The Wasielewski water treatment plant was used to treat drinking water via conventional sand filtration system for 80 years, but has recently been retrofitted with an ultrafiltration membrane system with a capacity of treating over 45 million gallons of water per day. Lake water is being drawn from approximately 14.5 miles away from the treatment facility via an intake pipe that runs underneath the Presque Isle peninsula. To monitor water quality at the water intake point, Erie Water Works installed an additional pipeline from the water intake point to the water treatment plant. This pipeline is currently being used for collecting raw water samples. Since access to the water intake source by boat is not permitted due to security restrictions, for this research project, raw water samples were collected at the sampling point located within the low-duty pump station located on Sommerheim Drive. Treated water samples were collected directly from the main supply pipe. Sampling locations within the facility are illustrated in Figure 1.

(a)

(b)

Figure 1. (a) Location of the Wasielewski water treatment plant and (b) sampling points within the Wasielewski water treatment plant

7 2. Sampling methods

2.1. Grab sampling

Raw and treated water sampling were conducted using the grab water sampling technique. Samples were collected in two 1-liter-amber bottles (Fisher Scientific, USA). Since both raw- and treated water samples may contain 0.5 to 5.0 mg/L of chlorine for disinfection purposes, 50 mg/L of ascorbic acid was added to the sampling bottles prior to sampling to prevent PPCP degradation during shipping to the analytical lab (Urbansky and Schenck, 2000; USDA, 2005). The grab samples were shipped to the analytical laboratory by overnight delivery and maintained at temperatures below 4 oC. Researchers visited the sampling site on a weekly basis to monitor water flow, status of the sampler, temperature, dissolved oxygen, conductivity, and pH. Additional water samples were collected in 500-mL HDPE bottles (Fisher Scientific, USA). The samples collected in HDPE bottles were delivered to the water quality lab at Gannon University and stored in a refrigerator until analysis. The water samples were analyzed for basic water quality parameters such as residual chlorine, total suspended solids (TSS), total dissolved solids (TDS), BOD, and COD. All parameters were analyzed on the day of sample collection.

2.2. Polar Organic Chemical Integrative Sampler (POCIS)

In addition to grab sampling, PPCPs in raw and treated water were collected using the Polar Organic Chemical Integrative Sampler (POCIS). Unlike conventional sampling methods, such as grab or composite sampling, that are useful for measuring the presence of contaminants at a sampling moment, the POCIS was developed to collect lipophilic organic compounds over a long period of time (USGS, 2004; Alvarez, 2010; Kaserzon, et al., 2014). The sampler consists of a sorbent material that is sandwiched between two microporous membranes and a metal ring supporting membranes. Different types of sorbent materials can be utilized within the device to target specific types of compounds; in this research, OASIS TM HLB sorbent was used. Typical deployment time for the sampler is one month after which the sorbent material undergoes an extraction procedure to desorb contaminants followed by an appropriate analytical technique.

8 Techniques such as gas chromatography (GC) and mass spectroscopy (MS) or liquid chromatography followed by MS are employed. The assembly of the POCIS is presented in Figure 2.

(a)

(b)

(c) Figure 2. (a) an assembly of membrane discs and holder (b) and (c) sampling canister with POCIS membrane discs and holder

9 2.3. POCIS deployment

The schematic for the deployment of the POCIS sampler in the sampling container is presented in Figure 3. Two stainless-steel 10-gallon brew kettles were purchased from an online store (homebrewsupply.com ) and modified for POCIS sampling (Figure 4). The flow rates of water passing through the POCIS samplers were controlled by a valve at the bottom of the container. To prevent contamination from airborne organic compounds during sampling, the container was covered with lid during the period of deployment. After POCIS sampling was completed, the POCIS canister was retrieved and membrane discs were removed from the holders and wrapped in aluminum foil. The PPCP membranes were stored in a freezer (>-20 oC) prior to shipment to the analytical laboratory. For shipment, membrane discs were wrapped in aluminum foil, placed in labeled Ziploc TM bags and shipped to the analytical laboratory by overnight delivery while maintained at temperatures below 4 oC.

Figure 3. A schematic of POCIS deployment setup (treated water)

(a)

(b)

Figure 4. Sampling containers installed at (a) water treatment plant and (b) low duty pump station

11 2.4. Sampling schedule

The schedule for grab sampling and POCIS deployment period are presented in Figure 5. During the monitoring period, a total of 9 grab samples from each sampling site were collected, and 6 POCIS were deployed/retrieved. The grab samples were collected on a monthly basis, but the period of POCIS deployment varied; an average period of POCIS deployment for the first three POCIS (POCIS-1, 2, and 3) was 30 days, but extended to over 60 days for the rest of three POCIS (POCIS-4, 5 and 6). Water samples had not been collected since September in 2017 as the Wasielewski plant was closed for several months for maintenance purposes.

Figure 5. Sampling schedule for grab samples and POCIS sampler deployment

12 3. Analytical methods

Analysis of grab water samples and POCIS membranes for target PPCPs was conducted using EPA Method 1694 at Anatek Labs, Inc. (Moscow, ID). For QA/QC purpose, a duplicate of DI water spiked with 7 analytes (acetaminophen, caffeine, sulfamethoxazole, trimethoprim, ibuprofen, naproxen and triclosan) was analyzed and compared to a lab blank to estimate recovery %. As described in the sampling methods, researchers visited the sampling site on a weekly basis and monitored water samples for pH (Accumet AP110, Fisher Scientific, US), dissolved oxygen, temperature (Orion, Fisher Scientific, US) and conductivity (Corning 311, Corning, US). The analytical methods used for analyzing additional water samples collected on a weekly basis were Standard Method 2540D (TSS), Standard Method 2540C (TDS), Standard Method 5220 (COD), Standard Method 5210 (BOD) and HACH Method 8021 (Free Chlorine).

4. Determination of PPCP concentration in water phase from POCIS analytical results

Additional steps were required to determine the mass concentrations (mg/L) of PPCPs in the aqueous phase from POCIS analytical results (mg PPCP / mass adsorbent in POCIS) as follows (MacLeod et al., 2007):

Cw = C s * m s / (R s * t)

Where,

Cw = PPCP concentrations in water phase (mg/L) Cs = PPCP concentrations in solid phase (mg/g POCIS) ms = mass of sorbent (g) Rs = sampling rates t = time for testing sampling rates .

The sampling rates (R s) for each target compound were determined by a laboratory test and literature review. Prior to the test, all glassware was thoroughly rinsed with HPLC grade deionized water (Fisher Scientific, US). To determine the sampling rates, six 2-liter glass beakers (Fisher Scientific, US) were filled with 1 L of HPLC grade deionized water (Fisher Scientific, US), and four of them were fortified by 100 ug/L of 9 target PPCPs. A POCIS

13 sampler was placed in four of the six vessels (Test-1, 2, 3 and 6) and the other two vessels were used as negative controls to determine any potential contaminants within the water or POCIS. The water/analyte mixture was stirred at a slow speed to keep the analytes mixed, and at a consistent concentration within the vessel. Each vessel was wrapped with aluminum foil to prevent photo-degradation of PPCPs during the testing period. The tests were performed for 23 hours. After the testing period, the fortified water in each vessel was immediately transferred to clean amber HDPE bottles and shipped to the analytical laboratory for PPCP analysis. Based on

the PPCPs analyzed, the sampling rates (R s) of each 9 target PPCPs were estimated as follows (Morin et al., 2012):

Rs = (C i – Ct)/C t * V t / t

where C i and C t represent initial and final PPCP concentrations at time t (µg/L); C t is PPCP

concentration at time t (mg/L), and V t is total water volume. The experimental setup for determining sampling rates is summarized in Table 2.

Table 2. A summary of experimental setup for determination of sampling rates Test Solutions Conditions

1. Standards at 0.1 ppm in pure water + 1 ● Stirred for 23 hours POCIS disk (24 hours) ● Beaker covered with aluminum to protect from light 2. Standards at 0.1 ppm in pure water + 1 ● Room temperature POCIS disk (24 hours)

3. Standards at 0.1 ppm in pure water + 1 POCIS disk (24 hours)

4. Standards at 0.1 ppm in pure water Initial test solution . Immediately placed in sampling bottle and stored in refrigerator.

5. Pure water used for dilution. Blank. Immediately placed in sampling bottle and stored in refrigerator.

6. Pure water + POCIS disk (24 hours) Blank. ● Stirred for 23 hours ● Beaker covered with aluminum to protect from light

14 OBJECTIVE 2: COMPARISON OF ELISA WITH LC-MS-MS RESULTS

For the validation study, a set of dilutions were prepared in the lab according to Table 3 for atrazine, triclosan and caffeine. Each control and separate analyte dilution were prepared in triplicate in 1 liter of HPLC-grade water. All glassware and items used were cleaned with 10% hydrochloric acid followed by a triple rinse with deionized water and reagent grade acetone. The solvent was removed by heating glassware to 300 OF for 3 hours and then rinsing with purified water prior to use.

Table 3. Summary of Dilutions and Replicates for Validation Study Caffeine Atrazine Triclosan TOTAL (ng/L) (ng/L) (ng/L) VOLUME Replicate 1 Control 0.000 0.000 0.000 1 Liter Dilution 1 0.250 0.250 0.250 1 Liter Dilution 2 0.500 0.500 0.500 1 Liter Dilution 3 1.000 1.000 1.000 1 Liter Dilution 4 2.500 2.500 2.500 1 Liter Replicate 2 Control 0.000 0.000 0.000 1 Liter Dilution 1 0.250 0.250 0.250 1 Liter Dilution 2 0.500 0.500 0.500 1 Liter Dilution 3 1.000 1.000 1.000 1 Liter Dilution 4 2.500 2.500 2.500 1 Liter Replicate 3 Control 0.000 0.000 0.000 1 Liter Dilution 1 0.250 0.250 0.250 1 Liter Dilution 2 0.500 0.500 0.500 1 Liter Dilution 3 1.000 1.000 1.000 1 Liter Dilution 4 2.500 2.500 2.500 1 Liter

Analytes were purchased from Absolute Standards, Inc. (Hamden, CT) in 1 mL aliquots at a certified concentration of 1 mg/mL each. Dilutions were prepared using a Brand Handystep electronic autopipette with disposable 1 mL pipette tips. Samples were prepared by a serial dilution technique; 1:10 or 1:50 dilution was made by adding 1 part of stock solution to either 9 or 49 part of HPLC grade deionized water, and the same steps were repeated until target dilution ratio reached. At every step, a solution mixture was mixed by mechanical stirrer for at least 30 minutes.

15 Spiked one-liter samples for each dilution were split and analyzed separately for three PPCP concentrations (atrazine, triclosan and caffeine) using both the ELISA test and LC-MS-MS. A total of 100 mLs of each control and spiked sample were put into clean glass amber jars and shipped overnight on ice to Anatek Labs (Moscow, ID). Samples were analyzed using EPA method 1694 as previously described.

The ELISA test was performed according to the manufacturer’s instructions (Abraxis, 2008A, 2008B, 2010). The controls, samples and standards for atrazine, triclosan and caffeine were added to the microplate wells, then followed by the relevant antibody and enzyme. After the required incubation time, the microplate was rinsed with the washing buffer solution to remove unreacted constituents. The color indicator (substrate) was then added to the rinsed plate to estimate the total amount of target PPCP (analyte) bound to the conjugated enzyme by color change. As a result, the concentrations of PPCP were determined by measuring the light absorbance of individual wells using a Biotek Epoch microplate spectrophotometer. Standard curves were constructed for each analyte by plotting the B/B o for each standard on a vertical logit (Y) axis versus the corresponding analyte concentration on a horizontal logarithmic (X) axis. Data logging and analysis was performed using the Gen5 TM data analysis software, version 3.022. Minimum detection limits for each respective ELISA kit are 0.04 ng/L for atrazine, 0.02 ng/L for triclosan and 0.15 ng/L for caffeine (Abraxis, 2008A, 2008B, 2010).

Calibration linearity, bias, precision and method detection limits were determined using the protocols outlined in EPA method validation guidelines (USEPA, 1999, 2014). Calibration curve and linearity were assessed using the standards provided in each of the ELISA test kits for atrazine, triclosan and caffeine respectively.

Agreement between ELISA and LC-MS-MS results was assessed with NCSS software, version 12 (NCSS, 2018) by utilizing correlation analysis (Pearson product moment) and the construction of Bland-Altman plots.

16 OBJECTIVE 3: HUMAN HEALTH RISK ASSESSMENT

For those compounds that are found in detectable levels within drinking water, a cumulative risk assessment was performed to estimate the long term human health risks from exposure to these compounds. The process for determining the cumulative noncancer risk estimates from exposure to PPCPs in drinking water begins with a determination of the Acceptable Daily Intake (ADI) for each of the detected compounds. These values were obtained from a comprehensive review of the literature (Schwab, et al., 2005; USEPA, 2008; Cunningham, et al., 2009; Jeong, 2009; NACWA, 2010; Gaffney, et al., 2015; Minnesota DOH, 2017).

The most conservative ADI found for each PPCP was used to calculate a drinking water exposure level (DWEL) representing an estimate of the PPCP dose that a person drinking tap water with measured concentrations would be exposed to in µg/kg-day. DWELs are determined by utilizing default values for exposure parameters such as daily water intake, body weight, etc. per EPA guidance (USEPA, 2008; USEPA, 2011). The general formula is:

RSC represents the relative source contribution from tap water in which PPCPs were measured (generally assumed to be 100%). A unit conversion of 1,000 is applied to convert concentrations from micrograms to nanograms. BW represents body weight which is 70 Kg for an average adult (USEPA, 2011). IR is 2 L/day representing the 90 th percentile ingestion rate for drinking water for an average adult (USEPA, 2011).

Risk quotients (RQs) were calculated which represent the estimated noncancer risk for each PPCP. These were calculated by dividing the maximum PPCP concentration measured in treated water samples by the calculated DWEL. Compounds with risk quotients ≥1 are considered to potentially affect human health. The combined risk for the PPCP mixture was calculated by summing across the individual RQs for each PPCP.

An additional risk calculation included the use of the margin of exposure (MOE) approach to calculate the number of glasses of water that would need to be consumed to exceed the drinking water guideline value for each compound (Snyder, et al., 2003; NYC DEC, 2011).

17 Table 4. Summary of RfD values for Target PPCPs

18 RESULTS AND DISCUSSION

OBJECTIVE 1: DETERMINATION OF THE CONCENTRATIONS OF TARGET PPCPS

1. General water quality

Water quality data are presented in Table 5 and Table 13 in Appendix. Since dissolved oxygen (DO) concentrations are temperature dependent, DO results are presented separately in Figure 6. As shown in Figure 6, both raw and treated water samples were nearly saturated with oxygen at given temperatures across all sampling period. The pH, conductivity, TSS, TDS, BOD and COD were not significantly different between raw and treated water samples according to the analysis of variance (ANOVA) test results at the 0.05 level of significance. It is noted that a low level of chlorine (approximately 0.1 mg/L) is added to the raw water intake for the purpose of preventing the strainers from becoming clogged by mussels.

Figure 6. Temperature and dissolved oxygen concentrations of water samples over time

19 Table 5. Analytical results of raw- and treated water samples for basic water quality parameters (total number of samples = 45) Parameters Raw Treated

pH 8.12 +/- 0.22 8.08 +/- 0.14

Conductivity (µS/cm) 305.7 +/- 455.7 311.4 +/- 471.9

TSS (mg/L) 1.11E-04 +/- 1.65E-04 3.76E-05 +/- 7.97E-05

TDS (mg/L) 2.16E-04 +/- 5.54E-04 2.81E-04 +/-6.75E-04

Chlorine (mg/L) 0.14 +/- 0.18 1.32 +/- 0.22

BOD (mg/L) 1.50 +/- 1.14 1.51 +/- 1.12

COD (mg/L) 47.6 +/- 45.5 34.2 +/- 23.4

2. Sampling rates

The sampling rates obtained in the test are presented in Table 6. As outlined in the Method Section, sampling rates were estimated by analytes removal rates, reaction time and volume of water. The average values of sampling rates of triplicates (Std Mix #1, #2 and #3) were used

for estimating analytes concentrations in the water phase (C w). The sampling rates obtained in the test were compared to the values in literature for validation purpose; average sampling rates were similar to those reported in the literature. It is noted that the average values of sampling rates reported in Li et al (2010) (1.283 L/day) were adopted for triclosan because the concentrations of the residual triclosan in the standard mix after reaction were all below detection limits (< 10 ug/L).

20 Table 6. POCIS sampling rates results estimated from analytes remained in the solution Std Mix Sampling Std Mix Sampling Std Mix Sampling Sampling rates Sampling rates in literature #1 rates #2 rates #3 rates (ng/mL) (ng/mL) (ng/mL) Acetaminophen 87.2 0.123 86.2 0.132 96.9 0.030 0.095 +/- 0.057 0.145 (±0.033) Li et al 0.139 (±0.011) 2010 0.111 (±0.016)

Altrazine 34.3 0.630 45.7 0.520 43.9 0.538 0.563 +/- 0.059 Ampicillin 31 0.661 26.4 0.705 47.6 0.502 0.623 +/- 0.107 BPA 16.4 0.801 24.3 0.725 23.9 0.729 0.752 +/- 0.043 0.531±0.063 Li et al 0.740±0.036 0.835±0.058 0.482±0.066 Caffeine 76.9 0.221 83.4 0.159 81.6 0.176 0.186 +/- 0.032 0.127 (±0.021) Li et al 0.096 (±0.008) 2010 0.151 (±0.018)

0.2±0.097 Brown et al 0.27 Zenobio et al Carbamazepine 59.9 0.384 69.1 0.296 72.6 0.263 0.314 +/- 0.063 0.230±0.016 Li et al 0.397±0.018 0.561±0.024 0.235±0.046

0.112±0.023 Macleod 0.348±0.116 et al 0.227±0.045 Brown et al Cimetidine 19.9 0.768 20.6 0.761 24.4 0.725 0.751 +/- 0.023 Ciprofloxacin 22.3 0.745 37.4 0.600 32.8 0.644 0.663 +/- 0.074 Digoxin 79.7 0.195 79.5 0.196 90.6 0.090 0.16 +/- 0.061 Gemfimbrozil 33.7 0.635 47 0.508 42.5 0.551 0.565 +/- 0.065 0.257±0.005 Li et al 0.306±0.031 0.350±0.012 0.222±0.014 Ibuprofen 59.4 0.389 69.3 0.294 68 0.307 0.33 +/- 0.052 0.204±0.004 Li et al

21 0.254±0.019 0.348±0.052 0.197±0.013 Metformin 92.6 0.071 88.9 0.106 91.7 0.080 0.086 +/- 0.018 Naproxen 53.1 0.449 66 0.326 62.9 0.356 0.377 +/- 0.065 0.392 (±0.024) Li et al 0.298 (0.016) 0.239 (±0.009) 0.200 (±±0.037) Simazine 37.6 0.598 52.4 0.456 48.9 0.490 0.515 +/- 0.074 0.223 Harman 0.119 et al 0.21 0.081 Sulfathiazole 64 0.345 79.7 0.195 73.2 0.257 0.265 +/- 0.076 0.22 Harman 0.187 et al Sulfamethoxazole 67.1 0.315 81.1 0.181 72.7 0.262 0.253 +/- 0.068 0.339 (±0.057) Li et al 0.348 (±0.049) 0.291 (±0.004) 0.202 (±0.019) Triclosan < 10 - < 10 - < 10 - - 1.929 (±0.232) Li et al 1.442 (±0.105) 1.006 (±0.037) 0.753 (±0.081) Trimethoprim 40.1 0.574 58.2 0.401 46.7 0.511 0.495 +/- 0.088 0.436 (±0.006) Li et al 0.411 (±0.073) 0.213 (±0.035) 0.215 (±0.003)

22 3. PPCPs in Grab samples

The concentrations of the analytes found in individual grab samples are presented in Table 10 in the Appendix, and average concentrations and standard deviation of analytes found in grab samples are summarized in Table 7. With the exception of a few analytes, concentrations of most observed analytes were below detection limits. The frequencies of detection of individual PPCPs in grab samples are illustrated in Figure 7. Among the18 analytes, atrazine was found in all raw water samples and caffeine was found in all raw and treated water samples. Metformin was detected in 6 raw water samples (67%), and simazine was detected in 5 raw water samples (56%). On comparing PPCPs in raw and treated water samples, no detectable levels of BPA, ibuprofen or metformin were detected in treated water samples although they were detected in at least one raw sample. This suggests that these analytes were removed or reduced in concentrations below detection limits by the water treatment system (ultrafiltration membrane system). On the contrary, detectable concentrations of atrazine, caffeine and simazine still remained in treated water samples. Comparing concentrations of atrazine, caffeine and simazine in raw and treated water, approximately 31% and 36% of atrazine and caffeine were removed by the water treatment system, respectively.

23 Acetaminophen

Ampicillin

Atrazine

Bisphenol-A

Caffeine

Carbamazepine

Cimetidine

Ciprofloxacin

Digoxin

Gemfibrozil

Ibuprofen

Metformin

Naproxen

Simazine

Sulfamethoxazole

Sulfathiazole

Triclosan

Trimethoprim

0 20 40 60 80 100 Frequency, % (total number of samples = 9)

Treated Water Raw Water

Figure 7. Frequency of detection of PPCPs in raw and treated samples (grab samples)

24 Table 7. A summary of PPCPs in grab samples Raw Water Treated Water Analyte (ng/L) (ng/L) Avg St dev Avg St dev

Acetaminophen

Ampicillin

Atrazine 50.34 31.99 41.26 34.52

Bisphenol-A 91.44 88.20

Caffeine 124.97 207.90 39.88 59.68

Carbamazepine

Cimetidine

Ciprofloxacin

Digoxin

Gemfibrozil

Ibuprofen 1.13

Metformin 58.15 62.75

Naproxen

Simazine 4.01 2.07 3.74 2.61

Sulfamethoxazole

Sulfathiazole

Triclosan

Trimethoprim

4. POCIS sampler results

Figure 8 shows the frequencies of PPCP detection in the POCIS samplers. As described in the Method Section, the POCIS samplers were deployed at the sampling sites for 1 to 2 months. In addition to 6 PPCPs found in grab samples, a total of 10 analytes were found at detectable level in the POCIS samplers. Unlike grab samples, however, metformin was not detected in any

25 POCIS samplers. Among 16 PPCPs of interest, metformin is the only aliphatic compound that contains no benzene-ring; therefore, metformin would potentially be more susceptible to biological and/or chemical decomposition. Analyte decomposition or modification cannot be ruled out since deployment of the sampler was conducted within chlorinated water for 1 to 2 months. On comparing types of analytes at detectable levels found in grab samples and in POCIS samplers, detectable levels of gemfibrozil, naproxen, sulfamethoxazole and trimethoprim were found only in POCIS samplers. It is noted that these four PPCPs were found only once when the deployment period was extended to 60 days. For 30-day deployment, only atrazine, caffeine and simazine were found in detectable levels within the POCIS samplers.

The average and standard deviation of concentrations of analytes estimated using analytical results, sampling rates and deployment periods are summarized in Table 8. Analytical results of individual POCIS samplers and analyte concentrations in the water phase are presented in Table 11in Appendix. The analyte levels represent the average concentrations during the period of deployment. Among 10 analytes found in the POCIS samplers, atrazine, caffeine and simazine were found in all POCIS samplers. On comparing the concentrations of those analytes in raw and treated waters (Figure 9), approximately 22%, 36% and 27% of atrazine, caffeine and simazine, respectively, were potentially removed by the water treatment system.

26 Acetaminophen

Ampicillin

Atrazine

Bisphenol-A

Caffeine

Carbamazepine

Cimetidine

Ciprofloxacin

Digoxin

Gemfibrozil

Ibuprofen

Metformin

Naproxen

Simazine

Sulfamethoxazole

Sulfathiazole

Triclosan

Trimethoprim

0 20 40 60 80 100 Frequency, % (total number of samples = 6)

Treated Water Raw Water

Figure 8. Frequency of detection of PPCPs in POCIS samplers

27 Table 8. A summary of concentrations of PPCPs estimated based on POCIS analytical results Analytes Raw water (ng/L) Treated water (ng/L)

average std average std

Acetaminophen

Ampicillin

Atrazine 12.97 6.34 10.41 5.51

Bisphenol-A 0.31

Caffeine 2.21 2.39 0.98 0.49

Carbamazepine 1.41 0.32 0.34 0.10

Cimetidine

Ciprofloxacin

Digoxin

Gemfibrozil 0.69 1.00 0.22

Ibuprofen 0.63

Metformin

Naproxen 0.36

Simazine 1.18 0.46 0.82 0.26

Sulfamethoxazole 0.38

Sulfathiazole

Triclosan

Trimethoprim 0.19 1E

Figure 9. Comparison of atrazine, caffeine and simazine concentrations in raw and treated water samples (retrieved from POCIS sampler analytical results)

29 OBJECTIVE 2: ELISA VERSUS ANALYTICAL RESULTS

The agreement between ELISA and LC-MS-MS results show comparable results for the three analytes. Figures 10 through 12 show the scatter and Bland-Altman plots to compare the results obtained between the two methods. The analyte showing the most consistent and accurate results between the ELISA test and analytical results is atrazine, with a correlation coefficient of 0.99 (p<0.001) and a bias of 0.23. This value indicates that the ELISA test was biased in the positive direction as concentrations were consistently higher than that from LC- MS-MS. The correlation between the two methods for triclosan resulted in a correlation coefficient of 0.96 (p<0.001) and a bias of 0.21. The results of the method comparison for caffeine showed a relatively high correlation coefficient ( r) with values of 0.984 and a bias of - 0.59. This latter result indicates that ELISA concentrations were consistently lower (negatively biased) by 0.59 compared to LC-MS-MS.

Figure 10. Scatterplot and Bland-Altman plots from LC-MS/MS and ELISA test for atrazine at various dilutions (3 replicates)

Figure 11. Scatterplot and Bland-Altman plots from LC-MS/MS and ELISA test for triclosan at various dilutions (3 replicates)

Figure 12. Scatterplot of results from LC-MS/MS and ELISA test for caffeine at various dilutions (3 replicates)

31 OBJECTIVE 3: HUMAN HEALTH RISK ASSESSMENT

Table 9 summarizes the results of the health risk assessment. The maximum measured value of each PPCP from grab sampling was compared with that of the DWEL and the more conservative screening values. Only three (atrazine, caffeine and simazine) of the 18 PPCPs measured in the grab samples had values above the method detection limit (MDL). All measured PPCP concentrations were below both the DWELs and screening values. The cumulative non-cancer risk calculation (risk quotient = measured concentration divided by the DWEL) was found to be negligible and less than 0.003. This risk estimate includes the MDL in the calculation for all 15 PPCPs that were found in concentrations below its respective MDL. A risk quotient approaching 1 and greater would be of concern.

32 Table 9. Summary of Risk Calculations using Maximum PPCP Values in Treated Drinking Water Analyte ADI/RfD DWEL SCREENING MAX Risk Quotient Source of ADI/RfD (µg/kg-dy) (µg/L) VALUE or VALUE (RQ) HEALTH RISK treated water LEVEL sample (µg/L) (µg/L)

Acetaminophen 250 8750 200 2 <.0025 2.9E-07 Minnesota Dept. of Health, 2015a

Ampicillin 1.6 56 10 1 <.0025 4.5E-05 WHO, 2017

Atrazine 3.5 123 32 0.118 9.6E-04 EPA, 1993a

Bisphenol-A 50 1750 20 1 <.0025 1.4E-06 EPA, 1988

Caffeine 150 5250 .197 3.8E-05 Gaffney, et al, 2015

Carbamazepine 0.34 11.9 40 2 <.0025 2.1E-04 NACWA, 2010

Cimetidine 28.6 1001 30 1 <.0025 2.5E-06 Cunningham et al, 2009

Ciprofloxacin 0.15 5.25 61 <.0025 4.8E-04 Jeong et al, 2009

Digoxin 0.071 2.485 0.0004 1 <.0025 1.0E-03 Cunningham et al, 2009

Gemfibrozil 1.3 45.5 10 1 <.0025 5.5E-05 NACWA, 2010

Ibuprofen 6.7 234.5 51 <.001 4.3E-06 Minnesota Dept. of Health, 2017

Metformin 79.4 2779 41 <.0025 9.0E-07 Cunningham et al, 2009

Naproxen 46 1610 20 1 <.001 6.2E-07 Gaffney, et al 2015

Simazine 5 175 42 .0071 4.1E-05 EPA, 1993b

33 Sulfamethoxazole 510 17850 100 2 <.0025 1.4E-07 NACWA, 2010

Sulfathiazole 130 4550 11 <.0025 5.5E-07 Gaffney, et al, 2015

Triclosan 67 2345 50 2 <.0025 1.1E-06 Minnesota Dept. of Health, 2015b

Trimethoprim 190 6650 41 <.0025 3.8E-07 NACWA, 2010

Cumulative RQ 2.8E-03 1 Minnesota Department of Health (2018), Pharmaceutical Water Screening Values Report. 2 Minnesota Department of Health Human Health-based Water Guidance Table, Accessed on 9/18/18 at http://www.health.state.mn.us/divs/eh/risk/guidance/gw/table.html

34 CONCLUSION

The results of this project have benefits to a broad audience that includes the general public, water quality officials and the scientific community. The monitoring component provided meaningful results about the quality of the drinking water as it relates to the analytes assessed in this study. The 18 analytes were all found at very low or non-detect levels. In a majority of cases, analyte concentrations were lower in treated water compared to raw water from Lake Erie showing the effectiveness of the ultrafiltration membrane system. The results of the human health risk assessment component confirm that the level of the 18 PPCPs measured within the treated water pose an insignificant risk to the community.

The method evaluation component yielded practical information about the comparability between ELISA testing and laboratory analysis using LC-MS-MS for PPCP quantification. The two methods show moderate to high comparability for atrazine, triclosan and caffeine as shown in the results section. ELISA testing is a much faster and cheaper test allowing for rapid testing of water samples and may be useful for screening specific target analytes.

The development of a methodology for evaluating the human health risks of these compounds in drinking water will offer a model for water quality officials to assess the human health risks of multiple compounds. It is anticipated that the risk assessment spreadsheet could be used to help guide risk management decisions. Additionally, this project offers benefits to the scientific community by adding additional sampling rate values for the POCIS sampler; a method evaluation study of ELISA results to that of analytical lab techniques (i.e., GC-MS); and methods for determining the human health risks from PPCPs in drinking water.

FUTURE RESEARCH

The major conclusion from this study is that the water used for drinking water for the City of Erie has low or below detectable levels of certain PPCPs that pose insignificant known human health risks. As a result of this conclusion, several additional lines of inquiry in future studies include:

35 ● To quantify the levels of other PPCPs that were not included in this study (i.e., opioids, pesticides, personal care products and other emerging contaminants of concern) ● To evaluate the levels of PPCPs within both the influent and effluent of the waste water treatment plant. ● To evaluate the levels of PPCPs in tributaries to and in Presque Isle Bay and Lake Erie.

36 CITATIONS

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Jeong SH, Song YK, Cho JH (2009). Risk assessment of ciprofloxacin, flavomycin, olaquindox and colistin sulfate based on microbiological impact on human gut biota. Regul Toxicol Pharmacol . Apr;53(3) Kaserzon, S.L.; Hawker, D.W.; Kennedy, K.; Bartkow, M.; Carter, S.; Booij, K.; Mueller, J.F. (2014). Characterization and comparison of the uptake of ionizable and polar pesticides, pharmaceuticals and personal care products by POCIS and Chemcatchers. Environ Sci-Proc Imp. 16: 2517-2526. Leung H.W., Ling J., Wei, S., et al. (2013). Pharmaceuticals in Tap Water: Human Health Risk Assessment and Proposed Monitoring Framework in China. Environ Health Perspectives 121(7): 839-846.

37 Li, H.X., Helm, P.A., Metcalfe, C.D. (2010). Sampling in the Great Lakes for Pharmaceuticals, Personal Care Products, and Endocrine-Disrupting Substances Using the Passive Polar Organic Chemical Integrative Sampler. Environ Toxicol Chem . 29:751-762. Macleod, S.L.; McClure, E.L.; Wong, C.S. (2007) Laboratory calibration and field deployment of the polar organic chemical integrative sampler for pharmaceuticals and personal care products in wastewater and surface water. Environ Toxicol Chem. 26:2517-2529. Minnesota Department of Health (2015a). Toxicological Summary for Acetaminophen. Accessed 9/1/18 at: http://www.health.state.mn.us/divs/eh/risk/guidance/dwec/sumacetamin.pdf .

Minnesota Department of Health (2015b). Toxicological Summary for Triclosan. Accessed 9/1/18 at: http://www.health.state.mn.us/divs/eh/risk/guidance/gw/triclosan.pdf .

Minnesota Department of Health (2017). Pharmaceutical Water Screening Values Report Methods and Results of Rapid Assessments for Pharmaceuticals. Accessed on 9/8/18 at: http://www.health.state.mn.us/divs/eh/risk/guidance/dwec/pharmwaterrept.pdf

Morin, N.; Miege, C.; Randon, J.; Coquery, M. (2012) Chemical calibration, performance, validation and applications of the polar organic chemical integrative sampler (POCIS) in aquatic environments. Trac-Trend Anal Chem . 36:144-175. National Association of Clean Water Agencies (NACWA), 2015. Pharmaceuticals in the Water Environment. Accessed on September 15, 2018 at: https://www.acs.org/content/dam/acsorg/policy/acsonthehill/briefings/pharmaceuticalsinwater/nacwa-paper.pdf Schwab B., Hayes E.P., Fiori J.M., Frank J. Mastrocco F.J.,Roden N.M., Cragin D., Meyerhoff R.D., D’Aco V.J. and Anderson P. (2005). Human pharmaceuticals in US surface waters: A human health risk assessment. Regulatory Toxicology and Pharmacology 42, 296–312. Schwab B., Hayes E.P., Fiori J.M., Frank J. Mastrocco F.J.,Roden N.M., Cragin D., Meyerhoff R.D., D’Aco V.J. and Anderson P. (2005). Human pharmaceuticals in US surface waters: A human health risk assessment. Regulatory Toxicology and Pharmacology 42: 296–312. U.S. Department of Agriculture Forest Service (2005), Using Vitamin C To Neutralize Chlorine in Water Systems, 1301-SDTDC, Office of Civil Rights, Washington, D.C. U.S. Environmental Protection Agency (1988). Bisphenol-A CASRN 80-05-7. Integrated Risk Information System (IRIS) Chemical Assessment Summary. U.S. Environmental Protection Agency (1993a). Simazine CASRN 122-34-9. Integrated Risk Information System (IRIS) Chemical Assessment Summary. U.S. Environmental Protection Agency (1993b). Atrazine CASRN 1912-24-9. Integrated Risk Information System (IRIS) Chemical Assessment Summary. U.S. Environmental Protection Agency (1999). Protocol for EPA Approval of New Methods for Organic and Inorganic Analytes in Wastewater and Drinking Water. EPA 821-B-98-003.

38 U.S. Environmental Protection Agency (2007), Method 1694: Pharmaceuticals and Personal Care Products in Water, Soil, Sediment, and Biosolids by HPLC/MS/MS, EPA 821-R-08-002, Office of Water, Washington DC. U.S. Environmental Protection Agency (2014). Project Quality Assurance and Quality Control, U.S. Environmental Protection Agency, Washington, DC, SW-846 Chapter 1. U.S. Geological Survey (2004). Polar Organic Compound Integrated Sampler. Columbia Environmental Research Center. Accessed 9/12/15 at: http://www.cerc.usgs.gov/pubs/center/pdfDocs/POCIS.pdf Urbansky, E. T., & Schenck, K. M. (2000). Ascorbic acid reduction of active chlorine prior to determining Ames mutagenicity of chlorinated natural organic matter (NOM). Journal of Environmental Monitoring, 2 (2): 161- 163. World Health Organization (2011). Pharmaceuticals in Drinking Water. WHO Press, Geneva Switzerland World Health Organization (2017). Evaluations of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Zenobio, J. E., Sanchez, B. C., Leet, J. K., Archuleta, L. C., & Sepulveda, M. S. (2015). Presence and effects of pharmaceutical and personal care products on the Baca National Wildlife Refuge, Colorado. Chemosphere, 120 : 750-755

39 APPENDIX A: METRICS

UNDERGRADUATE AND GRADUATE STUDENT SUPPORT : Student Degree Job upon graduation Emily Hesch MS in Environmental Health & Chemist, Erie Wastewater Engineering, December 2017 Treatment Plant Colleen Lawrence MS in Environmental Health & not currently employed Engineering, May 2018 Matthew Loughner MS in Environmental Health & currently employed at Engineering, in progress (May Gannon university as a 2019 graduation date) Graduate Research Assistant and at Lord Corporation in Environmental Health & Safety Internship.

FACULTY AND STAFF SUPPORT : Faculty Title FTE Michelle Homan, Ph.D. Professor and Chair 0.79 Hwidong Kim, Ph.D. Associate Professor 0.94

PUBLICATIONS: Hesch, Emily (2017). “Pharmaceuticals and Personal Care Products (PPCPs) within Wastewater Effluent and Lake Erie in the Erie, Pennsylvania Area.” Research project report submitted in fulfillment of the requirements for the M.S. degree in Environmental Health & Engineering, Gannon University, December 2017.

PUBLIC AND PROFESSIONAL PRESENTATIONS, AND ATTENDEES: No presentations to-date. Two presentations are planned for 2018 to present the ELISA validation study and the results of the PPCP concentrations in raw and treated water.

PROJECT COLLABORATORS : o Erie Water Works o Erie Wastewater Treatment Plant

40 APPENDIX B: IMPACT AND/OR ACCOMPLISHMENT STATEMENT(S)

IMPACT STATEMENTS o The sampling results for this study demonstrate the effectiveness of the current drinking water system in Erie, PA in reducing the amount of PPCPs in City’s drinking water. o The results of the method comparison evaluation show good agreement between the ELISA test and laboratory analysis. These results suggest that the ELISA could be a practical, relatively low-cost screening test to determine the presence of selected PPCPs in drinking water. o The levels of the 18 PPCPs measured in the City of Erie’s drinking water pose minimal risks to the community. All measured concentrations were orders of magnitude below minimum risk values.

ACCOMPLISHMENT STATEMENTS

This study used procedures to evaluate the human health risks from trace levels of PPCPs in drinking water. These same procedures can be used by water quality managers to evaluate risks by entering future PPCP monitoring results into the risk spreadsheet. This spreadsheet may need to be updated to include emerging PPCPs and changes in toxicity values used to calculate risks.

STATEMENT FORMAT o Title : Evaluation of Exposure to and Human Health Risks from PCPPs in Drinking Water from Lake Erie. o Collaborators: Gannon University and Erie Water Works o Recap : This research project evaluated the levels of 18 pharmaceuticals and personal care products (PPCPs) in raw and drinking water from Lake Erie as well as estimating human health risks.

41 o Relevance : Public concern of the potential health risks associated with PPCPs in drinking water have recently increased as a result of studies documenting their presence in surface, ground and treated drinking water. This study looks at whether there are human health risks from exposure to PPCPs from drinking water from Lake Erie for residents of the City of Erie, PA. o Response : Researchers from Gannon University collected raw and treated water samples from the Wasielewski Treatment Facility which supplies drinking water for the City of Erie, PA. Both grab and long-term samples were analyzed for the presence of 20 PPCPs. PPCP concentrations were then used to estimate human health risks from exposure to these chemicals within the drinking water. o Results : The results comparing raw and treated water samples show a decline in almost all analytes upon treatment demonstrating the effectiveness of the ultrafiltration membrane system. The levels of PPCPs found were low in source waters and were reduced to lower levels upon water treatment. This study suggests that there are low human health risks from exposure to the 18 PPCPs included in this study.

42 APPENDIX C: RAW DATA

Table 10 (Appendix). PPCP concentrations in grab samples Sampling date 10/31/2016 11/30/2016 1/17/2017 Treated Raw Water Treated Raw Water Treated Raw Water Water (ng/L) Water (ng/L) Water (ng/L) Analytes (ng/L) (ng/L) (ng/L) Acetaminophen < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ampicillin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Atrazine 50.7 50.4 < 1.0 52.4 37.7 53 Bisphenol-A < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Caffeine 18.1 16.7 4.48 20.2 9.64 30.6 Carbamazepine < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Cimetidine < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ciprofloxacin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Digoxin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Gemfibrozil < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ibuprofen < 1.0 < 1.0 < 1.0 1.13 < 1.0 < 1.0 Metformin < 2.5 < 2.5 < 2.5 19.8 < 2.5 < 2.5 Naproxen < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 Simazine < 1.0 < 1.0 < 1.0 <1.0 2.08 1.48 Sulfamethoxazole < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Sulfathiazole < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Triclosan < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Trimethoprim < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5

43 Table 10 (Appendix). PPCP concentrations in grab samples (continued) 2/27/2017 3/28/2017 5/3/2017 Sampling date Treated Raw Water Treated Raw Water Treated Raw Water Water (ng/L) Water (ng/L) Water (ng/L) Analytes (ng/L) (ng/L) (ng/L) Acetaminophen < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ampicillin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Atrazine 19.3 25.6 19.9 23.7 8.01 35.2 Bisphenol-A < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Caffeine 22.2 16.9 27.3 26.7 29.3 30.6 Carbamazepine < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Cimetidine < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ciprofloxacin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Digoxin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Gemfibrozil < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ibuprofen < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 Metformin < 2.5 0.0585 < 2.5 < 2.5 < 2.5 0.0585 Naproxen < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 Simazine < 1.0 < 1.0 4.48 3.4 < 1.0 6.31 Sulfamethoxazole < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Sulfathiazole < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Triclosan < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Trimethoprim < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5

44 Table 10 (Appendix). PPCP concentrations in grab samples (continued) 6/8/2017 7/13/2017 8/23/2017 Sampling date Treated Raw Water Treated Raw Water Treated Raw Water Water (ng/L) Water (ng/L) Water (ng/L) Analytes (ng/L) (ng/L) (ng/L) Acetaminophen < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ampicillin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Atrazine 26.2 33.7 118 130 50.3 49.1 Bisphenol-A < 2.5 0.0055 < 2.5 98.3 < 2.5 176 Caffeine 197 196 34.5 134 16.4 653 Carbamazepine < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Cimetidine < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ciprofloxacin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Digoxin < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Gemfibrozil < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Ibuprofen < 1.0 < 1.0 < 1.0 < 2.5 < 1.0 < 2.5 Metformin < 2.5 116 < 2.5 148 < 2.5 65 Naproxen < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 Simazine < 1.0 <1.0 7.09 5.96 1.32 2.89 Sulfamethoxazole < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Sulfathiazole < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Triclosan < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 Trimethoprim < 2.5 < 2.5 < 2.5 < 2.5 < 2.5 < 2.5

45 Table 11 (Appendix). PPCP concentrations in POCIS samplers Sampling Date 11/30/2016 Treated Raw Analytes Cw (ng/L) Cw (ng/L) (ug/pocis) (ug/pocis) Acetaminophen < 0.005

46 Table 11 (Appendix). PPCP concentrations in POCIS samplers Sampling Date 1/17/2017 Cw Raw Cw Analytes Treated (ug/pocis) (ng/L) (ug/pocis) (ng/L) Acetaminophen < 0.005

47 Table 11 (Appendix). PPCP concentrations in POCIS samplers Sampling Date 2/27/2017

Treated Cw Raw Analytes Cw (ng/L) (ug/pocis) (ng/L) (ug/pocis)

Acetaminophen < 0.005

48 Table 11 (Appendix). PPCP concentrations in POCIS samplers Sampling Date 5/3/2017

Treated Raw Analytes Cw (ng/L) Cw (ng/L) (ug/pocis) (ug/pocis)

Acetaminophen < 0.005

49 Table 11 (Appendix). PPCP concentrations in POCIS samplers Sampling Date 6/8/2017 Treated Raw Analytes Cw (ng/L) Cw (ng/L) (ug/pocis) (ug/pocis) Acetaminophen < 0.005

50 Table 11 (Appendix). PPCP concentrations in POCIS samplers Sampling Date 8/23/2017

Treated Raw Analytes Cw (ng/L) Cw (ng/L) (ug/pocis) (ug/pocis) Acetaminophen < 0.005

51 Table 12 (Appendix). Water quality data (raw water samples) temp DO pH Conductivity TSS Chlorine BOD TDS COD DATE o ( C) (mg/L) uS/m (mg/L) (mg/L) (mg/L) (mg/L) (mg/L) 7/29/16 7.85 3250 1.80E-06 1.81E-05

9/13/16 23.9 10.57 8.36 278 6.25E-07 1.85E-04 22.5

9/20/16 23.5 6.63 8.33 254 bdl bdl 5

9/27/16 21.2 6.59 8.25 258 2.94E-05 1.75E-04 40

10/4/16 20 7.15 8.29 256 6.25E-07 1.50E-04 32.5

10/18/16 18.8 8.38 8.37 238 bdl 2.04E-04 16.25

10/25/16 15.9 9.1 8.04 249 1.25E-06 1.1 1.43E-04 26.67

11/1/16 16.6 10.34 8.38 245 1.00E-04 0.225 1.22 9.31E-05 34.17 11/8/16 21.7 9.14 8.27 261 bdl 0.025 1.58 1.63E-04 22.22 11/15/16 14.5 10.09 8.32 235 2.00E-04 0.045 1.17 1.19E-04 24.17 11/29/16 10 10.89 8.29 222 4.00E-04 0.235 0.14 1.38E-04 52.5 12/6/16 9.1 10.94 8.25 238 1.13E-05 0.32 0.52 1.78E-04 14.03 12/14/16 5.6 12.19 8.14 228 4.18E-04 0.04 3.88 1.36E-04 30.83 12/21/16 2.9 11.03 8.03 212 1.36E-04 0.09 0.83 1.85E-04 16.67 12/28/16 6.1 9.8 8.17 214 1.29E-04 0.12 2.13 5.10E-05 24.7 1/4/17 4.9 11.03 8.1 236 1.02E-04 0.14 2.87 9.13E-05 23.33 1/17/17 3.5 12.19 8.06 229 1.35E-04 0.3 1.55 bdl 14.44 1/24/17 4.7 12.11 8.04 252 bdl 0.22 3.09 1.26E-04 6.66 1/31/17 3.3 12.75 8.06 162 3.38E-05 0.34 2.41 8.13E-06 10 2/8/17 2.6 12.5 8.01 241 1.38E-04 0.42 4.03 1.10E-04 74.08 2/14/17 2.7 12.8 8.06 222 2.81E-05 0.26 3.42 4.13E-05 55.83 2/21/17 4.3 13.17 8.03 144 8.13E-06 0.4 1.36 8.13E-06

2/27/17 4 9.87 7.08 134 1.89E-04 0.4 0.98 1.74E-04 27.42 3/7/17 10.2 11.86 7.97 213 5.17E-04 0.47 1 2.77E-04 56.65 3/14/17 2.7 11.26 8.04 188 1.00E-05 0.49 1.37 9.61E-05 26.65 3/21/17 3.1 13.65 8.17 147 bdl 0.52 3.65 1.34E-04 33.34 3/28/17 4.6 13.83 8.24 7.50E-06 0.43 0.55 1.53E-04 11.66

4/4/17 6.7 13.21 8.11 248 1.38E-05 1.3 2.38E-04 111.67

4/11/17 8.7 12.47 8.04 346 7.26E-04 1.14E-04 2.5

4/25/17 9.1 13.34 8.13 251 1.45E-04 2.58 1.68E-04 30

5/5/17 11.7 10.99 8.05 247 4.70E-05 1.11 8.63E-05 39.17

5/10/17 11.1 10.51 7.99 248 bdl 0.07 1.66E-04 150.83

5/18/17 14.4 8.3 252 8.50E-05 1.08 3.66E-03 46.67

5/25/17 14.2 8.54 8.16 253 bdl 1.11 bdl 62.5

6/1/17 16.5 9.54 8.19 255 bdl 0.57 1.04E-04 39.17

6/8/17 16.5 9.61 8.12 225 bdl 1.38 bdl 23.33

6/15/17 19.1 9.66 8.23 250 8.75E-06 0.12 1.81E-04 100

6/22/17 22.1 8.73 8.17 243 3.75E-06 0.02 1.05E-04

6/29/17 24.9 8.66 8.19 268 1.50E-05 1.89E-04 81.67

7/6/17 24.9 7.94 8.18 257 bdl 0.2175 1.98E-04 50.83

7/13/17 26.2 7.29 8.09 277 5.06E-05 2.87 9.44E-05 81.67

7/20/17 26.2 8.2 8.22 260 2.62E-05 1.11 7.69E-05 126.67

7/27/17 24.9 7.59 7.57 257 1.31E-04 bdl 1.36E-04 245

8/10/17 24.8 10.01 8.29 261 1.94E-05 1.53 7.50E-05 41.67

8/17/17 25.3 7.7 8.35 248 1.06E-05 0.13 1.14E-04 63.33

52 Table 13 (Appendix). Water quality data (treated water samples) temp DO pH Conductivity TSS Chlorine BOD TDS COD DATE o ( C) (mg/L) S/m (mg/L) (mg/L) (mg/L) (mg/L) (mg/L) 7/29/16 8.09 3330 6.90E-06 4.69E-05

9/13/16 24 12.01 8.39 260 bdl 1.87E-04 5.83

9/20/16 23.3 8.06 8.35 256 bdl n/a 15.83

9/27/16 21.5 8.54 8.36 252 bdl 3.34E-04 22.49

10/4/16 19.9 9.05 8.37 247 1.25E-06 1.56E-04 19.37

10/18/16 18.2 9.47 7.99 254 bdl 1.88E-04 10.62

10/25/16 15.8 9.94 8.1 244 bdl 1.44 1.55E-04 16.67

11/1/16 14.3 10.08 8.15 237 bdl 1.375 1.07 3.63E-05 30 11/8/16 14.4 9.96 8.21 239 6.25E-05 1.5 0.655 1.66E-04 28.33 11/15/16 12.6 10.35 8.2 246 3.00E-04 1.52 0.948 2.50E-03 43.33 11/29/16 9.5 11.08 8.14 232 bdl 1.52 0.583 1.53E-04 36.42 12/6/16 8.4 11.52 8.12 232 bdl 1.64 0.21 1.85E-04 16.66 12/14/16 5.7 11.35 8.01 243 bdl 1.48 2.97 1.36E-04 12.5 12/21/16 3.2 11.01 8.06 1.26E-05 1.35 0.53 1.74E-04 13.33

12/28/16 3.7 11.96 8.02 216 1.28E-06 1.21 2.23 4.88E-05 15 1/4/17 3.3 12.25 7.91 203 4.83E-06 1.31 1.49 1.74E-04 26.66 1/17/17 2.8 12.62 7.94 229 1.25E-05 1.37 1.76 bdl 21.11 1/24/17 3 12.4 7.94 244 bdl 1.56 3.72 9.75E-05 bdl 1/31/17 2.3 12.77 7.99 208 bdl 2.25 8.13E-06 13.33

2/8/17 2.2 12.8 7.89 239 bdl 1.35 4.26 5.19E-05 84.17 2/14/17 1.6 12.52 7.91 224 3.75E-06 1.5 3.6 1.15E-04 50.83 2/21/17 2.6 13.63 7.86 175 2.50E-06 1.56 1.85 9.13E-05

2/27/17 3.7 13.12 8.07 173 2.50E-04 0.97 2.50E-04 25

3/7/17 4.4 11.51 8.07 213 bdl 1.41 1.55 2.63E-04 80.83 3/14/17 2.7 11.26 8.04 188 1.13E-05 1.5 1.61 9.74E-05 26.6 3/21/17 2.5 12.7 8.02 204 5.63E-06 1.45 2.85 1.50E-04 10 3/28/17 4.6 13.83 8.24 bdl 1.48 1.49 2.22E-04 86.6

4/4/17 5.5 12.46 7.88 235 bdl 1.47 1.09 2.34E-04 89.17 4/11/17 7.2 11.7 8.01 244 2.97E-05 1.48 1.14E-05 17.5

4/25/17 10.6 12.4 8.05 253 bdl 1.51 3 1.82E-04 60 5/5/17 12.1 10.2 8.04 243 bdl 1.14 0.01 6.06E-05 11.67 5/10/17 11.6 11.4 7.95 247 3.75E-06 1.08 0.67 bdl 44.17 5/18/17 14.4 8.07 260 8.06E-05 1.24 0.74 3.65E-03 35.83

5/25/17 14.9 8.79 8.05 260 bdl 1.13 1.53 bdl 56.67 6/1/17 16.7 9.61 7.98 254 bdl 1.52 0.58 9.31E-05 50 6/8/17 16.9 10.55 8.01 255 bdl 1.42 0.83 bdl 21.67 6/15/17 19.1 10.4 8.02 262 bdl 1.25 bdl 1.48E-04 67.5 6/22/17 22.4 8.08 7.93 260 bdl 1.26 bdl 9.69E-05

6/29/17 24.9 8.66 8.03 270 1.25E-06 1.11 2.33E-05 47.5

7/6/17 24.9 8.44 8.07 261 1.56E-05 1.09 0.1 1.48E-04 24.17 7/13/17 24.3 9.03 8.23 260 2.50E-06 1.01 bdl bdl 36.67 7/20/17 25.7 8.52 8.12 267 6.25E-06 1.03 0.24 2.75E-05 33.33 7/27/17 24.9 8.28 8.21 263 1.06E-05 0.93 bdl 1.36E-04 65.83 8/10/17 24.8 8.94 8.29 261 2.50E-06 0.88 bdl 6.44E-05 12.5 8/17/17 25.5 8.13 8.35 248 bdl 0.83 bdl 1.11E-04 16.67