Contaminants of Emerging Concern and Arid West Water Resources

Shane Snyder, Ph.D. Professor & Co-Director Chem. & Environ. Engineering University of Arizona

Three Key Points

I. Trace contaminants are ubiquitous in water II. Ecological impacts demonstrated, human unlikely III. Public perception and trust are critical for water reuse “We know the value of water when the well runs dry.”

Benjamin Franklin

Poor Richard’s Almanac - 1732 “I am convinced that, under present conditions and with the way water is being managed, we will run out of water long before we run out of fuel.” Peter Brabeck-Letmathe

Chairman of Nestlé The Economist – November 2008 FishingFishing DockDock atat LakeLake MeadMead LakeLake LanierLanier -- GeorgiaGeorgia LakeLake WivenhoeWivenhoe –– AustraliaAustralia U.S.U.S. PopulationPopulation CouldCould ExceedExceed 400,000,000400,000,000 byby 20502050

=Approximately 2.5M people/year for the next 40 years =Approximately the population of Houston TX each year

Low Growth in Water Storage

Adapted from Graf, 1999

DeDe FactoFacto oror UnplannedUnplanned ReuseReuse TrinityTrinity River,River, TexasTexas ManyMany USUS CitiesCities AlreadyAlready ReuseReuse WaterWater forfor PotablePotable SuppliesSupplies Source: http://www.hcn.org/issues/354/17227 “Analytical Arms Race” FTMS Sensitivity: ppb-ppt LC-MS/MS Selectivity: Ret Time Sensitivity: ppt accurate mass, MRM GC MSD Selectivity: Ret Time Sensitivity: ppb unit resolution, MRM Selectivity: Ret Time GC-FID unit resolution, SIM Sensitivity: ppm Selectivity: Ret Time

Snyder et al., 1999. Environmental Science & Technology, pgs. 2814-2829

Interlaboratory Comparison (WaterRF 4167) 22 compounds & 24 labs

Number of Number of Target Compounds Laboratories Target Compounds Laboratories Carbamazepine 24 Diclofenac 16 Ibuprofen 23 17β-Estradiol 16

Caffeine 22 Estrone 16

Sulfamethoxazole 21 Fluoxetine 15

Gemfibrozil 20 Ciprofloxacin 13

Triclosan 20 Progesterone 12

17α-Ethynylestradiol 18 Testosterone 12

Trimethoprim 18 Erythromycin 11 Naproxen 17 4-nonylphenol 11

Acetaminophen 16 Primidone 11

Bisphenol A 16 4-tert-octylphenol 10 Interlaboratory comparison (DI water)

Sulfamethoxazole

90%

80% s 70%

60% Good 50% 40%

30%

20% Average Absolute Bia

10%

0% 5A 16A 10B 23D 1C 4 11 26 27 7 22A 12B 24 20B 9B 25 8C 18C 10A 3 14A 9A 20A 17A Laboratory

80% 1210% 70% Erythromycin

60%

50% 40% Bad 30%

20% Average AbsoluteBias 10%

0% 10B 3 27 26 23 4 12B 20B 24 20A 16A 1C 9B 17A 8C Laboratory Interlaboratory comparison (DI water)

Ciprofloxacin

140%

120%

100%

80% Ugly 60% 40%

Average Absolute Bias Absolute Average 20%

0% 10B 10A 1C 22A 27 24 4 20B 20A 3 12B 23 17A 8C Laboratory

All compounds

0 All Average Absolute Bias (%) Bias Absolute Average Median Absolute Bias (%) Bias Absolute Median l e e il c n l e n e e en io n z e i on in d en o x no n c r p prim fei h r e ti azol e rof o p ro mycin h e henol stradiol x Estrone p h o lofena p o x p oxa ste u t Caf a r o l fl e E Ib Triclosan tylp y o stosteronetho maz emfib Dic isphenolN A th Primidonec Flu rog e e a G B O ipr P T rb Ery Non C a Trime lfam C Ethynylestra Acetamin Su Three Key Points

I. Trace contaminants are ubiquitous in water II. Ecological impacts demonstrated, human unlikely III. Public perception and trust are critical for water reuse Hudson River Anglers in the 1940s

Noticed that fish caught below a pharmaceutical plant were far larger than other parts of the river.

Fish had been exposed to significant concentrations of tetracycline.

Later experiments determine the effect was also reproducible in chickens and cows. Estradiol

Nonylphenol

10.2 10.2

3.5 3.5 7.8

ThreeThree AdvancedAdvanced WWTPs:WWTPs: ≈≈300300 mgdmgd

X X X

Estrone (ng/L) -10 30 -30 25 ) -50 20 -70 th (m p -90 15 De -110 10 -130 5 -150 02468101214160 DEET (ng/L) -10 30 -30 25 -50 20 -70 -90 15 Depth (m) -110 10 -130 5 -150 02468101214160 Kilometers from WWTP effluent confluence to Hoover Dam Meprobamate (ng/L) -10 50 -30

) 40 NH2 O -50 O

-70 O O 30

H2N

epth (m -90

D 20 -110 -130 10 -150 0 2 4 6 8 101214160 LV Wash kilometers Hoover Dam

Sulfamethoxazole (ng/L) 30 -10 O N O -30 25 HNS O ) -50 20 -70 15

epth (m -90 NH2 D -110 10 -130 5 -150 0 2 4 6 8 101214160 LV Wash kilometers Hoover Dam Lake Mead volume (106 acre-ft)

18 17 16 15 14 13 12

01/2008

07/200

2007

01/ 07/2006

source water concentration water source Lake Mead Volume

2006

01/

7/2005

005

01/2

2004 07/

Effect on Pharmaceuticals and EDCs

2004

01/

07/2003 003 0

80 60 40 20 01/2 100

Drought: Drought: EDC concentrations (ng/L) concentrations EDC and pharmaceutical of sum Las Vegas Wash monitoring – 5 years Lake Mead monitoring – 6+ years Finished drinking water monitoring – 6+ years

Pharmaceuticals

Prescription Potential drugs Most used for Final 1 toxicity candidates 2 3 3,000+ 300 39 16 4 Detection; Public interest

5 Drug groups Suspected EDCs 1 Status as an 2 EDC 3 Occurrence Potential & exposure •Hundreds of for toxicity Final purported EDCs •Occurrence in candidates •Selected data •Severity of drinking water, 13 compilations especially U.S. effects screened EDCs •Resistance to •Potency Criteria: conventional •Pharmaco- 4 PAC, •In vivo drinking water kinetics public, treatment •Relevant species •Availability of scientific •Availability of interest •Endocrine studies suitable method for mediated effect for risk 5 analysis assessment Endocrine •Adverse effect Mode of Action Samples collected per time zone

195 43 88

17 Participating Utilities Target Compounds

Pharmaceuticals (20) Potential EDCs (26) Steroid Hormones (5) Phytoestrogens (11)

Atenolol Atrazine Estradiol Apigenin Atorvastatin Benzophenone Estrone Biochanin A o-Hydroxy atorvastatin BHA Ethinylestradiol Chrysin p-Hydroxy atorvastatin BHT Progesterone Coumestrol Carbamazepine α-BHC Testosterone Daidzein Diazepam β-BHC Equol Diclofenac γ-BHC Formononetin Dilantin δ-BHC Genistein Enalapril Bisphenol A Glycitein Fluoxetine Butylbenzyl phthalate Matairesinol Norfluoxetine DEET Naringenin Gemfibrozil Diazinon Meprobamate Dioctyl phthalate Naproxen Galaxolide Risperidone Linuron Simvastatin Methoxychlor Simvastatin hydroxy acid Metolachlor Sulfamethoxazole Musk ketone Triclosan Nonylphenol Trimethoprim Octachlorostyrene Octylphenol TCEP TCPP Tonalide Traseolide Vinclozolin Detected in Raw Water* (24/62)

Pharmaceuticals Potential EDCs Steroid Hormones Phytoestrogens

Atenolol AtrazineEstradiol Apigenin Atorvastatin Benzophenone Estrone Biochanin A o-Hydroxy atorvastatin BHA Ethinylestradiol Chrysin p-Hydroxy atorvastatin BHT Progesterone Coumestrol Carbamazepine α-BHC Testosterone Daidzein Diazepam β-BHC Equol Diclofenac γ-BHC Formononetin Dilantin δ-BHC Genistein Enalapril Bisphenol A Glycitein Fluoxetine Butylbenzyl phthalate Matairesinol Norfluoxetine DEET Naringenin GemfibrozilDiazinon Meprobamate Dioctyl phthalate Naproxen Galaxolide Risperidone Linuron Simvastatin Methoxychlor Simvastatin hydroxy acid Metolachlor SulfamethoxazoleMusk ketone Triclosan Nonylphenol TrimethoprimOctachlorostyrene Octylphenol TCEP TCPP Tonalide Traseolide Vinclozolin * In at least 20% of samples Detected in Drinking Water* (11/62)

Pharmaceuticals Potential EDCs Steroid Hormones Phytoestrogens

Atenolol AtrazineEstradiol Apigenin Atorvastatin Benzophenone Estrone Biochanin A o-Hydroxy atorvastatin BHA Ethinylestradiol Chrysin p-Hydroxy atorvastatin BHT Progesterone Coumestrol Carbamazepine α-BHC Testosterone Daidzein Diazepam β-BHC Equol Diclofenac γ-BHC Formononetin Dilantin δ-BHC Genistein Enalapril Bisphenol A Glycitein Fluoxetine Butylbenzyl phthalate Matairesinol Norfluoxetine DEET Naringenin GemfibrozilDiazinon MeprobamateDioctyl phthalate Naproxen Galaxolide Risperidone Linuron Simvastatin Methoxychlor Simvastatin hydroxy acid Metolachlor SulfamethoxazoleMusk ketone Triclosan Nonylphenol Trimethoprim Octachlorostyrene Octylphenol TCEP TCPP Tonalide Traseolide Vinclozolin * In at least 20% of samples US Drinking Water

Finished Water for 18 Drinking Water Treatment Facilities

Compound Max (ng/L) Median (ng/L) Frequency (%) Atrazine 870 49 83 Meprobamate 42 5.7 78 Dilantin 19 6.2 56 Atenolol 18 1.2 44 Carbamazepine 18 6.0 44 Gemfibrozil 2.1 0.48 39 TCEP 470 120 39 DEET 93 63 33 Metolachlor 27 16 33 TCPP (Fyrol PCF) 510 210 28 Sulfamethoxazole 3.0 0.39 22

Detected in systems with chloramination or UV DWELDWEL ≈≈ MCLGMCLG

Drinking Water Equivalent Level (DWEL) = ADI * 70 kg 2 L Pharmaceutical Evaluation

ADI- Max. Sites with DWEL conc. Detection Liters per Day to Drug Class (µg/L) (µg/L) (n=18) Exceed DWEL

Risperidone Antipsychotic 0.49 0.0029 1 340

Phenytoin Anticonvulsant 6.8 0.019 10 700

Carbamazepine Anticonvulsant 12 0.018 8 1,300

Atenolol Beta-blocker 70 0.018 8 7,800

Meprobamate Antianxiety agent 260 0.042 14 13,000

Gemfibrozil Antilipidemic 45 0.0021 7 43,000 SSRI Fluoxetine antidepressant 34 0.00082 2 82,000

Norfluoxetine Metabolite 34 0.00077 1 88,000 Benzodiazepine Diazepam tranquilizer 35 0.00033 1 210,000

Sulfamethoxazole Anti-infective 18,000 0.003 4 12,000,000 Bruce, Pleus, & Snyder, 2010 Environ. Sci. Technol. 44:5619-5626 E-screen Assay

• MCF-7 breast cancer cell line proliferates in response to estrogenic compounds • Developed by oncologists Ana Soto & Carlos Sonnenschein at Tufts University EEq Comparison (“Worst” WWTP)

≈ +

Mug of Beer 1.4 L Wastewater (6 ng/L, 500 mL) (4.6 ng/L) EEq Comparison (“Worst” WWTP)

≈

1 cup coffee 890 mL Secondary (17 ng/L, 240 mL) Wastewater (4.6 ng/L) EEq Comparison “Worst” WWTP ≈

1 Liter Secondary Teaspoon of Soy Sauce Wastewater (300 ng/L, 15 mL) (4.6 ng/L) Three Key Points

I. Trace contaminants are ubiquitous in water II. Ecological impacts demonstrated, human unlikely III. Public perception and trust are critical for water reuse US Regulatory History • 1962: 28 discrete “chemical” contaminants regulated US Regulatory History • 1962: 28 discrete “chemical” contaminants regulated Universe CCL Process - Chemicals Screening

PCCL Classification Algorithm, training set, criteria PCCL Expert (Attribute scoring Review protocol) Nomination Surveillance Preliminary CCL

CCL Expert Review

Defend how and why these CCL Contaminant Validation contaminants made it to the list

CCL CCL3 – Key Highlights

• Draft CCL3 – essentially no pharmaceuticals or steroids – Did include PFOA and PFOS – Did include nitroglycerine (but not for pharmaceutical reasons) • Final CCL3 – addition of 9 estrogens, 1 progestin, & 1 antibiotic – Estrogens (17a-estradiol, 17b-estradiol, equilenin, equilin, estriol, estrone, ethynylestradiol, estriol, estrone, mestranol) – Progestin (norethindrone) – Antibiotic (erthythromycin) • Steroid hormones on CCL3 largely due to: – Kolpin 2002 (USGS) – hormones at hundreds of ng/L – California E2 Cancer Risk – DWEL = 0.9 ng/L Contaminant: Estradiol (17-beta estradiol) Attribute Scores Potency Severity Prevalence Magnitude 88105 3-model Categorical Prediction

HRL Ratio(s) NC HRL/Kolpin MAX: 1.75 CAR HRL/Kolpin MAX: 0.0045

Health Reference Level (HRL)2 cancer 0.0009 ug/L

Maximum Median % 90% of Units for Water Data value of value of Detects Detects Mag data Detects Detects Snyder, et al., 2007 FINISHED 0.0 Not detected Not detected Not detected ug/L Snyder, et al., 2007 RAW 0.0064 ug/L Kolpin, et al., 2002 10.6 0.2 0.16 ug/L http://jecfa.ilsi.org

= 50 ng/Kg = 3500 ng/70 Kg person BUT What about the MIXTURES?

WHO – Drinking Water Quality Guidelines

• Dosed entire lake with ≈6 ng/L of ethynylestradiol (EE2) – Compared to two reference Lakes (pristine) – Seven years of monitoring, three years of dosing EE2 • Fathead minnow population dwindled to near extinction – Male fish had VTG levels 1000x higher than controls – Histological impacts, including intersex, observed – Reproductive failure persisted 2-year after exposure ceased • Only study showing pop. impact of a pharm. in water 1969, Transactions of the American Fisheries Society; Zn 50% Spawning Reduction = 88 μg/L Drinking Water Zn > 150 μg/L Wastewater Zn < 50 μg/L 2.5 120 Spawning Events, Trial 1

Spawning Events, Trial 2 100 2 Percent Wastewater Influence

80 1.5

1 40

Number of Spawning Events 0.5

20 Composition Wastewater Percent

0 0 Drinking 6.25% 12.5% 25% WW 50% WW 100% EE2 + EE2 + Water WW WW WW DW WW Three Key Points • All water has been, or will be, reused – Global sustainability depends on recycling water – Analytical instruments can detect nearly any substance • Pharmaceuticals can be measured ubiquitously – But, analytical methods are not yet standardized – Lists if pharmaceuticals are largely arbitrary • Public perception and trust are critical – Human and fish exposure is dramatically different – Help fish through reuse of surface discharge for potable reuse – We have challenges, but should focus on those that matter – Regulations MAY help with public perception, but move slowly The Path Forward Increased reuse of water -Especially in coastal cities -More efficient technologies -Direct reuse -Not just in African anymore -Cloudcroft, NM -Amarillo, TX -Your town? -What does the environmental buffer contribute to safety? -Right quality of water for use -Toilet flushing vs. drinking -Lawn irrigation vs. bathing Life Cycle of Water http://icosse11.org/ Shane Snyder University of Arizona [email protected]

AZ Laboratory for Emerging Contaminants www.alec.arizona.edu