Introduction and Historical Context: Endocrine Disrupting Compounds (EDCs) and Pharmaceuticals / Personal Care Products (PPCPs)

Trace/Acute Exposure

Introduction and Historical Context 3 Definitions • Microconsitutents (formerly known as Emerging contaminants, or ECs) • Pharmaceuticals and personal care products (PPCPS) • Pharmaceutically Active Compounds (PhACs) • Trace Organic Contaminants (TOrCs) • Endocrine Disrupting Compounds (EDCs) – Chemicals that interfere with the function of the endocrine system

Introduction and Historical Context 4 Emerging Contaminant Definition

• A chemical or material that is characterized by a perceived, potential, or real threat to human health of the environment or a lack of published health standards… • A new source or a new pathway to humans has been discovered or a new detection method or treatment technology has been developed

USEPA, Fact Sheet referencing DOD, 2009

Introduction and Historical Context 5 Historic Background

Introduction and Historical Context 6 Historic Background

Introduction and Historical Context 7 Historic Background

Developments in Industrial Microbiology - 1970

Introduction and Historical Context 8 Historic Background

Introduction and Historical Context 9 Historic Background

Introduction and Historical Context 10 Historic Background

Introduction and Historical Context 11 Historic Background

Introduction and Historical Context 12 Historic Background One of Discover Magazine’s Top 100 Stories of 2007:

Entire fathead minnow population nearly extinct in lake after 5 ng/L exposure to EE2

Introduction and Historical Context 13 Other Ecological Impacts Documented

• and abnormalities of fish – Dioxins from paper mill effluent – (2 ng/L) in municipal wastewater – from decomposition of organic matter • Deformed sex organs in gulls from DDT – Decline in shellfish population – Tributvltins (PVS pipes and paints) • Changes in microbial communities after nonylphenol exposure

Introduction and Historical Context 14 Human Impacts

• Nelson and Bunge, 1974; – Missouri men have lower sperm counts than men in LA, NY, and Minneapolis – No reason found • Swan et al., 2003; – Confirmed earlier study – Missouri low-sperm count men had higher levels of , Alachlor, and Diazinon – Link between and reproductive effect – No occupational exposure – Source identified drinking water contamination

Introduction and Historical Context 15 More Human Cases of Endocrine Effects

• Diethyl (DES) daughters – Synthesized from 1940 to 1970 – Drug to reduce risk of complications and loss • Hypospadias doubled from 1970-1991 (Paulozzi, et al., 1997) • Dioxins and endometriosis in monkeys (Rier and Foster, 2002) • Link between increases in breast, testicular and prostrate cancers over the past 40 years? (Krishnan and Safe, 1993; Carlsen et al., 1995; EPA, 1997, more) • All linked to mimicking or disrupting compounds • But is water the culprit??

Introduction and Historical Context 16 Common Factors for Endocrine Disruption

• Disruption of hormone processes • Hormone release • Hormone transport • Hormone receptors • Signaling pathways • Parent compound or metabolite may be cause • Synergistic and antagonistic pathway unclear

Introduction and Historical Context 17 Historic Background

Introduction and Historical Context 18 Two General Categories of Trace Organics

• Groundwater Concerns – Typically substances released from now-banned industrial disposal practices or as additives to another released material – Released historically at a finite number of discrete locations – 1,4-dioxane, perchlorate, PCE/TCE, etc. • Surface Water Concerns – Substances that enter the aquatic environment through normal everyday use – Currently released at a large number of widespread locations (e.g., wastewater treatment plants)

In many locales, these distinctions may be blurred

Introduction and Historical Context 19 Categories and Pathways

Veterinary and Human Tetracycline Antibiotics Prescription Drugs Codeine, Antacids, Anti-depressants

Non-Prescription Drugs Ibuprofen, Acetaminophen, Caffeine

Steroids and Estrogenic Compounds, Hormones

Anti-Microbial Disinfectants

Plasticizers A

Industrial Nonylphenol and Octylphenol

Other Fragrances,

Introduction and Historical Context 20 Pharmaceuticals and Personal Care Products

• Lipitor #1 by $$$ sales in 2009 • Hydrocodone #1 by prescription in 2009 • Thousands of drugs and personal care products on the market • Largely excreted by the body • Parent compounds or metabolites • Some disposal issues are contamination sources • Bathing

Introduction and Historical Context 21 Partial List of Potential EDCs By Category

• • • Perchlorate • Atrazine • Ethinyl • Trenbolone • Thiocyanate Estradiol • p,p’-DDE • PCBs •

• Linuron Thyroid • Genestein • Vinclozolin Estrogenic • Androgenic • Procymidone • Co-planar PCBs Neuroendocrine

Introduction and Historical Context 22 Pesticides, Dioxins Medical Waste

http://palwv.org/wren/pubs/primer.html

Introduction and Historical Context 23 De Facto Water Reuse (www.waterreuseguidelines.org)

Introduction and Historical Context 24 Rice et al., 2013

Introduction and Historical Context 25 Categories and Pathways Direct contact Respiration Ingestion of Ingestion of water

What is the Consider aggregate Significance of magnitude, exposure (from multiple exposure to multiple frequency, and sources) and cumulative chemicals at trace duration of exposure (to multiple concentrations over exposure? chemicals) long durations is unknown Introduction and Historical Context 26 Introduction and Historical Context 27 Samples collected per time zone

195 43 88

17 Participating Utilities

Introduction and Historical Context 28 Occurrence: Analyte List Pharmaceuticals (20) Potential EDCs (26) Hormones (5) Phytoestrogens (11)

Atenolol Atrazine Estradiol Atorvastatin Benzophenone Estrone o-Hydroxy atorvastatin BHA Chrysin p-Hydroxy atorvastatin BHT Progesterone Carbamazepine a-BHC Testosterone Diazepam b-BHC Diclofenac g-BHC Dilantin d-BHC Enalapril Fluoxetine Butylbenzyl Matairesinol Norfluoxetine DEET Gemfibrozil Diazinon Meprobamate Dioctyl phthalate Naproxen Galaxolide Risperidone Linuron Simvastatin Methoxychlor Simvastatin hydroxy acid Metolachlor Sulfamethoxazole Musk ketone Triclosan Nonylphenol Trimethoprim Octachlorostyrene Octylphenol TCEP Target Compounds in Raw Water TCPP Results from Benotti et al., 2009 Tonalide Traseolide Vinclozolin Occurrence: Raw Water 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 a-BHC Testosterone Daidzein Diazepam b-BHC Equol Diclofenac g-BHC Formononetin Dilantin d-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 Detected in Raw Water (24 / 62) Octylphenol In at least 20% of samples TCEP Results from Benotti et al., 2009 TCPP Tonalide Traseolide Vinclozolin Occurrence: Finished Water 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 a-BHC Testosterone Daidzein Diazepam b-BHC Equol Diclofenac g-BHC Formononetin Dilantin d-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 Detected in Drinking Water (11 / 62) Trimethoprim Octachlorostyrene In at least 20% of samples Octylphenol Results from Benotti et al., 2009 TCEP TCPP Tonalide Traseolide Vinclozolin Occurrence Raw Intake for Drinking Water Facilities (n = 19)

Compound Max (ng/L) Median (ng/L) Frequency Sulfamethoxazole 110 12 89 Meprobamate 73 8.2 84 Carbamazepine 51 4.1 79 Atrazine 870 32 79 Estrone 0.90 0.33 79 Dilantin 29 5.0 74 Atenolol 36 2.2 63 Trimethoprim 11 0.75 58 Gemfibrozil 24 2.2 58 Naproxen 32 0.93 58 Diethylhexyl Phthalatephthalate 170 90 58 Nonylphenol 130 88 58 TCEP 530 120 53 Results from Benotti et al. – different data analysis Introduction and Historical Context 32 Occurrence

Finished Water for Drinking Water Facilities (n = 15)

Median Frequency Compound Max (ng/L) (ng/L) ( > 50%) Atrazine * 870 8.4 80 Meprobamate 42 6.2 73 Dilantin 19 5.8 60 Diethylhexyl 120 66 53 phthalate

* Atrazine is the only regulated compound Results from Benotti et al. – different data analysis

Introduction and Historical Context 33 Journal of Environmental Quality, July 2010

Introduction and Historical Context 34 slope 1 = 0.02 p < 0.0001 slope = -0.00007 slope = 0.0002 p < 0.0001 p < 0.0001 slope 2 = 0.008 p = 0.004

Journal of Environmental Quality, July 2010

Introduction and Historical Context 35 Summary • Pathways to the environment well understood • Ecological effects well documented • “Emerging Contaminants” documented and studied for 50 years • Wastewater and drinking water are linked • Drought impacts concentration in water supplies • EDCs/PPCPs are ubiquitous in water supplies

Introduction and Historical Context 36 Introduction and Historical Context 37