Implications for Water Sustainability

Pharmaceuticals and Endocrine Disruptors: Implications for Water Sustainability

Shane Snyder, Ph.D. Applied R&D Center Southern Nevada Water Authority

Garrison, Pope, and Allen - 1975

August, 2004, Estrone

-10 30 -30 INTAKE 1 x INTAKE 2 x 25 -50 20 h ( m ) -70 p t e -90 15 D -110 10 -130 -150 5 0 2 4 6 8 10 12 14 16 0 LV Wash>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>Hoover Dam August 9, 2004, DEET

-10 30 -30 INTAKE 1 x

) INTAKE 2 x 25 -50 20 h ( m -70 p t e -90 15 D -110 10 -130 -150 5 0 2 4 6 8 10 12 14 16 0 LV Wash>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>Hoover Dam August 9, 2004, Meprobamate (ng/L) -10 50 -30 ) 40 m -50 ( h -70 t NH2 O 30 p O e -90

D O O -110 20 H2N -130 10 -150 0 2 4 6 8 10 12 14 16 LV Wash Hoover Dam 0

August, 9, 2004, Sulfamethoxazole (ng/L)

-10 30

-30 O

) 25

m -50 N O ( HN S O 20 h -70 t p e -90 15 D -110 10 -130 NH2 -150 5 0 2 4 6 8 10 12 14 16 LV Wash Hoover Dam 0 Drought Effect on Pharmaceutical and EDC Concentrations

100 18 source water concentration Lake Mead Volume

17 Lake Mead volume (10 80

16 60

40 6 14 acre-ft)

20 13

0 12 sum of pharmaceutical and EDC concentrations (ng/L) concentrations EDC and ofsum pharmaceutical

01/2003 07/2003 01/2004 07/2004 01/2005 07/2005 01/2006 07/2006 01/2007 07/2007 01/2008

UV 40 mJ Chlorine 3.5 mg/L Ozone 2.5 mg/L

Caffeine

Fluoxetine

Meprobamate

Diazepam

Dilantin

Carbamazepine

0 20 40 60 80 100 % Removal

Antoine-Laurent de Lavoisier (26 August 1743 – 8 May 1794) •Called the father of modern chemistry •Conservation of mass: “although matter can change its state in a chemical reaction, the quantity of matter is the same at the end as at the beginning of every chemical change”

http://en.wikipedia.org/wiki/Antoine_Lavoisier Recent History Senate Hearing & call to Action

350

300 Pharmaceuticals in Water

250 Estrogen and Water

Endocrine Disrupting 200 Compounds

150

100 Total PublishedTotal Articles

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

QA/QC

http://toxics.usgs.gov/regional/est_errata.html

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, public, •In vivo drinking water kinetics scientific treatment •Relevant species •Availability of interest •Availability of •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)

Pharmaceuticals Potential EDCs Steroid Hormones Phytoestrogens

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 * In at least 20% of samples US Source Water Raw Intake for 19 Drinking Water Facilities (>50% Freq.) Compound Max (ng/L) Median (ng/L) Frequency (%) Sulfamethoxazole 110 12 89 Meprobamate 73 8.2 84 Atrazine 870 32 79 Carbamazepine 51 4.1 79 Estrone 0.94 0.33 79 Dilantin 29 5.0 74 Atenolol 36 2.2 63 Gemfibrozil 24 2.2 58 Naproxen 32 0.93 58 Trimethoprim 11 0.75 58 TCEP 530 120 53 Detected in Drinking Water* (11/62)

Pharmaceuticals Potential EDCs Steroid Hormones Phytoestrogens

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 * 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 (151st – 2007) 19 6.2 56 Atenolol (99th- 2007) 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 Carisoprodol – The Source of Meprobamate in the Environment?

Carisoprodol Mosby’s Drug Consult lists carisoprodol as the 75th most prescribed drug in 2003.

Meprobamate was not listed in the top 200. Metabolism via CYP2C19 enzyme

Meprobamate Olsen, H. et al. Therapeutic Drug Monitoring 1994, 16, 337-340. 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 Potential EDC Evaluation

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

Atrazine Herbicide 3 0.870 15 8

Linuron Herbicide 70 0.0062 2 23,000 p-Nonylphenol Industrial chemical 1,800 0.10 2 35,000

Bisphenol A Industrial chemical 1,800 0.025 1 140,000

Triclosan Antibacterial 2,600 0.0012 1 4,400,000

17b-Estradiol Hormone 1.8 <0.00050 0 >7,000 Bis(2- ethylhexyl) phthalate Industrial chemical 420 <0.10 0 >8,400

Butylbenzyl phthalate Industrial chemical 3,500 <0.050 0 >140,000 http://jecfa.ilsi.org

= 50 ng/Kg = 3500 ng/70 Kg person Estrogenicity Comparison

≈

1 Liter Secondary Teaspoon of Soy Sauce Wastewater (300 ng/L, 15 mL) (4.6 ng/L) March 25th, 2009

• 28.4 grams per serving • 142 grams per serving

 88 ng Carbamazepine  440 ng Carbamazepine  142 ng Norfluoxetine  710 ng Norfluoxetine  540 ng Sertraline  2,700 ng Sertraline  ~ 60,000 ng Galaxolide  ~300,000 ng Galaxolide

Summary • All water has been, or will be, reused – Global sustainability depends on recycling water – Analytical instruments can detect nearly any substance in water – Population & urban density exacerbate water challenges • Treatment can remove or transform contaminants – No system can provide complete removal (zero does not exist) – Most efficacious processes are energy intensive – Are we trading water quality for air quality? • Meaningful water quality goals must be health-based – Monitoring alone will not establish safety – Detection does not = safe, just as non-detection does not = risk – Protection of public health must be based on sound science Shane Snyder, Ph.D. [email protected]