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Human Health Risk Assessment for Pharmaceuticals in the Environment: Existing Practice, Uncertainty, and Future Directions

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Human Pharmaceuticals in the Environment

Part of the book series: Emerging Topics in Ecotoxicology ((ETEP,volume 4))

Abstract

Globally, several thousand substances are produced for pharmaceutical and biomedical applications in humans. The production tonnage of these compounds is astronomical, ranging to hundreds of tons annually. Based on data collected by the National Center for Health Statistics, individuals who visited their physician recorded an average of almost seven medications taken per person. As expected, this number increases dramatically in older persons to almost 20 medications per person after age 65. As the global population ages, the use of pharmaceuticals to alleviate age-related conditions can reasonably be expected to increase. Further, the ongoing development of large markets such as China and India will further increase the magnitude of pharmaceutical consumption. In general, it has been believed that the environmental concentrations of APIs are too low to constitute a risk to human health in developed countries, and several studies have been conducted to assess this perspective. However, a recent poll among expert stakeholders reported that 62% of those interviewed believed that pharmaceuticals in the environment (PIE) represent a risk to human health. In recent years, higher potential exposure levels in developing countries, potable water reuse and public health concerns regarding antibiotic resistance are receiving increased attention. Here we provide a critical examination of the state of human health risk assessment for human pharmaceuticals in the environment. We further identify important uncertainties and future research needs.

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Abbreviations

5-FU:

5-Fluorouracil

ADI:

Acceptable daily intake

API:

Active pharmaceutical ingredient

BCF:

Bioconcentration factor

CBZ:

Carbemazepine

COPC:

Contaminant of potential concern

CPA:

Cyclophosphamide

E2:

Estradiol

EDC:

Endocrine-disrupting compound

EE2:

Ethinylestradiol

ERA:

Ecological or environmental risk assessment

GAC:

Granular activated carbon

GREAT-ER:

Geography-referenced regional exposure assessment tool for European rivers

HHRA:

Human health risk assessment

HQ:

Hazard quotient

LOAEL:

Lowest observed adverse effects level

LOEL:

Lowest observed effects level

MEC:

Measured or monitored environmental concentration

MOA:

Mode of action

MOS:

Margin of safety

NOAEL:

No observed adverse effects level

NOEL:

No observed effects level

OTC:

Over the counter

PEC:

Predicted environmental concentration

PhATE:

Pharmaceutical Assessment and Transport Evaluation

PIE:

Pharmaceuticals in the environment

PNEC:

Predicted no-effect concentration

POD:

Point of departure

RfD:

Reference dose

TTC:

Threshold of toxicologic concern

UF:

Uncertainty factor

WWTP:

Wastewater treatment plant

References

  1. NCHS (2008) Health, united states, 2008 with special feature on the health of young adults. NCHS, Hyattsville

    Google Scholar 

  2. Zuccato E, Castiglioni S, Fanelli R, Reitano G, Bagnati R, Chiabrando C, Pomati F, Rossetti C, Calamari D (2006) Pharmaceuticals in the environment in Italy: causes, occurrence, effects and control. Environ Sci Pollut Res Int 13:15–21

    Article  CAS  Google Scholar 

  3. Kumar A, Chang B, Xagoraraki I (2010) Human health risk assessment of pharmaceuticals in water: issues and challenges ahead. Int J Environ Res Public Health 7:3929–3953

    Article  CAS  Google Scholar 

  4. Fent K, Weston AA, Caminada D (2006) Ecotoxicology of human pharmaceuticals. Aquat Toxicol 76:122–159

    Article  CAS  Google Scholar 

  5. Carlsson C, Johansson AK, Alvan G, Bergman K, Kuhler T (2006) Are pharmaceuticals potent environmental pollutants? Part I: environmental risk assessments of selected active pharmaceutical ingredients. Sci Total Environ 364:67–87

    Article  CAS  Google Scholar 

  6. Stuer-Lauridsen F, Birkved M, Hansen LP, Lutzhoft HCH, Halling-Sorensen B (2000) Environmental risk assessment of human pharmaceuticals in Denmark after normal therapeutic use. Chemosphere 40:783–793

    Article  CAS  Google Scholar 

  7. Doerr-MacEwen NA, Haight ME (2006) Expert stakeholders’ views on the management of human pharmaceuticals in the environment. Environ Manage 38:853–866

    Article  Google Scholar 

  8. Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. Streams, 1999–2000: a national reconnaissance. Environ Sci Technol 36:1202–1211

    Article  CAS  Google Scholar 

  9. Colborn T, vom Saal FS FS, Soto AM (1993) Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect 101:378–384

    Article  CAS  Google Scholar 

  10. Safe S (2004) Endocrine disruptors and human health: is there a problem. Toxicology 205:3–10

    Article  CAS  Google Scholar 

  11. Kime DE, Nash JP (1999) Gamete viability as an indicator of reproductive endocrine disruption in fish. Sci Total Environ 233:123–129

    Article  CAS  Google Scholar 

  12. Jobling S, Beresford N, Nolan M, Rodgers-Gray T, Brighty GC, Sumpter JP, Tyler CR (2002) Altered sexual maturation and gamete production in wild roach (Rutilus rutilus) living in rivers that receive treated sewage effluents. Biol Reprod 66:272–281

    Article  CAS  Google Scholar 

  13. Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, Shivaprasad HL, Ahmed S, Chaudhry MJ, Arshad M, Mahmood S, Ali A, Khan AA (2004) Diclofenac residues as the cause of vulture population decline in pakistan. Nature 427:630–633

    Article  CAS  Google Scholar 

  14. Jones OAH, Voulvoulis N, Lester JN (2002) Aquatic environmental assessment of the top 25 English prescription pharmaceuticals. Water Res 36:5013–5022

    Article  CAS  Google Scholar 

  15. Ferrari B, Mons R, Vollat B, Fraysse B, Paxeus N, Lo Giudice R, Pollio A, Garric J (2004) Environmental risk assessment of six human pharmaceuticals: Are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environ Toxicol Chem 23:1344–1354

    Article  CAS  Google Scholar 

  16. Workgroup OOEC (2008) White paper: aquatic life criteria for contaminants of emerging concern, Part I: general challenges and recommendations. United States Environmental Protection Agency, Washington, DC

    Google Scholar 

  17. Bercu JP, Parke NJ, Fiori JM, Meyerhoff RD (2008) Human health risk assessments for three neuropharmaceutical compounds in surface waters. Regul Toxicol Pharm 50:420–427

    Article  CAS  Google Scholar 

  18. Kummerer K, Al-Ahmad A (2010) Estimation of the cancer risk to humans resulting from the presence of cyclophosphamide and ifosfamide in surface water. Environ Sci Pollut Res Int 17:486–496

    Article  CAS  Google Scholar 

  19. Emmanuel E, Pierre MG, Perrodin Y (2009) Groundwater contamination by microbiological and chemical substances released from hospital wastewater: health risk assessment for drinking water consumers. Environ Int 35:718–726

    Article  CAS  Google Scholar 

  20. Schulman LJ, Sargent EV, Naumann BD, Faria EC, Dolan DG, Wargo JP (2002) A human health risk assessment of pharmaceuticals in the aquatic environment. Hum Ecol Risk Assess 8:657–680

    Article  CAS  Google Scholar 

  21. Cunningham VL, Binks SP, Olson MJ (2009) Human health risk assessment from the presence of human pharmaceuticals in the aquatic environment. Regul Toxicol Pharmacol 53:39–45

    Article  CAS  Google Scholar 

  22. Cunningham VL, Perino C, D’Aco VJ, Hartmann A, Bechter R (2010) Human health risk assessment of carbamazepine in surface waters of north America and Europe. Regul Toxicol Pharmacol 56:343–351

    Article  CAS  Google Scholar 

  23. Schwab BW, Hayes EP, Fiori JM, Mastrocco FJ, Roden NM, Cragin D, Meyerhoff RD, D’Aco VJ, Anderson PD (2005) Human pharmaceuticals in US surface waters: a human health risk assessment. Regul Toxicol Pharmacol 42:296–312

    Article  CAS  Google Scholar 

  24. Johnson AC, Jurgens MD, Williams RJ, Kummerer K, Kortenkamp A, Sumpter JP (2008) Do cytotoxic chemotherapy drugs discharged into rivers pose a risk to the environment and human health? An overview and UK case study. J Hydrol 348:167–175

    Article  CAS  Google Scholar 

  25. Christensen FM (1998) Pharmaceuticals in the environment—a human risk? Regul Toxicol Pharmacol 28:212–221

    Article  CAS  Google Scholar 

  26. Kumar A, Xagoraraki I (2010) Human health risk assessment of pharmaceuticals in water: an uncertainty analysis for meprobamate, carbamazepine, and phenytoin. Regul Toxicol Pharmacol 57:146–156

    Article  CAS  Google Scholar 

  27. Rowney NC, Johnson AC, Williams RJ (2009) Cytotoxic drugs in drinking water: a prediction and risk assessment exercise for the Thames catchment in the United Kingdom. Environ Toxicol Chem 28:2733–2743

    Article  CAS  Google Scholar 

  28. Schriks M, Heringa MB, van der Kooi MM, de Voogt P, van Wezel AP (2010) Toxicological relevance of emerging contaminants for drinking water quality. Water Res 44:461–476

    Article  CAS  Google Scholar 

  29. Snyder SA (2008) Occurrence, treatment, and toxicological relevance of EDCS and pharmaceuticals in water. Ozone Sci Eng 30:65–69

    Article  CAS  Google Scholar 

  30. Crane C, Maycock D, Crane D, Fawell J, Goslan E (2007) Desk based review of current knowledge on pharmaceuticals in drinking water and estimation of potential levels. Drinking Water Inspectorate http://dwi.defra.gov.uk/research/completed-research/reports/dwi70-2-213.pdf

  31. Webb S, Ternes T, Gibert M, Olejniczak K (2003) Indirect human exposure to pharmaceuticals via drinking water. Toxicol Lett 142:157–167

    Article  CAS  Google Scholar 

  32. Boxall AB, Kolpin DW, Halling-Sorensen B, Tolls J (2003) Are veterinary medicines causing environmental risks? Environ Sci Technol 37:286A–294A

    Article  CAS  Google Scholar 

  33. Daughton CG, Ternes TA (1999) Pharmaceuticals and personal care products in the environment: agents of subtle change? Environ Health Perspect 107(suppl 6):907–938

    Article  CAS  Google Scholar 

  34. Kummerer K (2009) The presence of pharmaceuticals in the environment due to human use—present knowledge and future challenges. J Environ Manage 90:2354–2366

    Article  CAS  Google Scholar 

  35. Hursthouse A, Kowalczyk G (2009) Transport and dynamics of toxic pollutants in the natural environment and their effect on human health: research gaps and challenge. Environ Geochem Health 31:165–187

    Article  CAS  Google Scholar 

  36. Focazio MJ, Kolpin DW, Barnes KK, Furlong ET, Meyer MT, Zaugg SD, Barber LB, Thurman ME (2008) A national reconnaissance for pharmaceuticals and other organic wastewater contaminants in the united states—II untreated drinking water sources. Sci Total Environ 402:201–216

    Article  CAS  Google Scholar 

  37. Erickson BE (2002) Analyzing the ignored environmental contaminants. Environ Sci Technol 36:140A–145A

    Article  CAS  Google Scholar 

  38. Loraine GA, Pettigrove ME (2006) Seasonal variations in concentrations of pharmaceuticals and personal care products in drinking water and reclaimed wastewater in Southern California. Environ Sci Technol 40:687–695

    Article  CAS  Google Scholar 

  39. Zuccato E, Castiglioni S (2009) Illicit drugs in the environment. Philos Transact A Math Phys Eng Sci 367:3965–3978

    Article  CAS  Google Scholar 

  40. Bartelt-Hunt SL, Snow DD, Damon T, Shockley J, Hoagland K (2009) The occurrence of illicit and therapeutic pharmaceuticals in wastewater effluent and surface waters in Nebraska. Environ Pollut 157:786–791

    Article  CAS  Google Scholar 

  41. Petrovic M, de Alda MJ, Diaz-Cruz S, Postigo C, Radjenovic J, Gros M, Barcelo D (2009) Fate and removal of pharmaceuticals and illicit drugs in conventional and membrane bioreactor wastewater treatment plants and by riverbank filtration. Philos Transact A Math Phys Eng Sci 367:3979–4003

    Article  CAS  Google Scholar 

  42. Zuccato E, Castiglioni S, Fanelli R (2005) Identification of the pharmaceuticals for human use contaminating the Italian aquatic environment. J Hazard Mater 122:205–209

    Article  CAS  Google Scholar 

  43. Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2009) Illicit drugs and pharmaceuticals in the environment—forensic applications of environmental data. Part 1: estimation of the usage of drugs in local communities. Environ Pollut 157:1773–1777

    Article  CAS  Google Scholar 

  44. Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2009) Illicit drugs and pharmaceuticals in the environment—forensic applications of environmental data, Part 2: pharmaceuticals as chemical markers of faecal water contamination. Environ Pollut 157:1778–1786

    Article  CAS  Google Scholar 

  45. Nikolaou A, Meric S, Fatta D (2007) Occurrence patterns of pharmaceuticals in water and wastewater environments. Anal Bioanal Chem 387:1225–1234

    Article  CAS  Google Scholar 

  46. Zuccato E, Calamari D, Natangelo M, Fanelli R (2000) Presence of therapeutic drugs in the environment. Lancet 355:1789–1790

    Article  CAS  Google Scholar 

  47. Ternes TA (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32:3245–3260

    Article  CAS  Google Scholar 

  48. Hirsch R, Ternes T, Haberer K, Kratz KL (1999) Occurrence of antibiotics in the aquatic environment. Sci Total Environ 225:109–118

    Article  CAS  Google Scholar 

  49. Coetsier CM, Spinelli S, Lin L, Roig B, Touraud E (2009) Discharge of pharmaceutical products (PPS) through a conventional biological sewage treatment plant: MECS vs PECS? Environ Int 35:787–792

    Article  CAS  Google Scholar 

  50. Comoretto L, Chiron S (2005) Comparing pharmaceutical and pesticide loads into a small Mediterranean river. Sci Total Environ 349:201–210

    Article  CAS  Google Scholar 

  51. Andreozzi R, Raffaele M, Nicklas P (2003) Pharmaceuticals in STP effluents and their solar photodegradation in aquatic environment. Chemosphere 50:1319–1330

    Article  CAS  Google Scholar 

  52. Ferrari B, Paxeus N, Lo Giudice R, Pollio A, Garric J (2003) Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac. Ecotoxicol Environ Saf 55:359–370

    Article  CAS  Google Scholar 

  53. Holm JV, Rugge K, Bjerg PL, Christensen TH (1995) Occurrence and distribution of pharmaceutical organic compounds in the groundwater downgradient of a landfill (Grindsted, Denmark). Environ Sci Technol 29:1415–1420

    Article  CAS  Google Scholar 

  54. Braga O, Smythe GA, Schafer AI, Feitz AJ (2005) Fate of steroid estrogens in Australian inland and coastal wastewater treatment plants. Environ Sci Technol 39:3351–3358

    Article  CAS  Google Scholar 

  55. Falconer IR, Chapman HF, Moore MR, Ranmuthugala G (2006) Endocrine-disrupting compounds: a review of their challenge to sustainable and safe water supply and water reuse. Environ Toxicol 21:181–191

    Article  CAS  Google Scholar 

  56. Ort C, Lawrence MG, Reungoat J, Eaglesham G, Carter S, Keller J (2010) Determining the fraction of pharmaceutical residues in wastewater originating from a hospital. Water Res 44:605–615

    Article  CAS  Google Scholar 

  57. Fick J, Soderstrom H, Lindberg RH, Phan C, Tysklind M, Larsson DG (2009) Contamination of surface, ground, and drinking water from pharmaceutical production. Environ Toxicol Chem 28:2522–2527

    Article  CAS  Google Scholar 

  58. Larsson DG, de Pedro C, Paxeus N (2007) Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J Hazard Mater 148:751–755

    Article  CAS  Google Scholar 

  59. Stumpf M, Ternes TA, Wilken RD, Rodrigues SV, Baumann W (1999) Polar drug residues in sewage and natural waters in the state of Rio de Janeiro, Brazil. Sci Total Environ 225:135–141

    Article  Google Scholar 

  60. Han GH, Hur HG, Kim SD (2006) Ecotoxicological risk of pharmaceuticals from wastewater treatment plants in Korea: occurrence and toxicity to daphnia magna. Environ Toxicol Chem 25:265–271

    Article  CAS  Google Scholar 

  61. Takahashi A, Higashitani T, Yakou Y, Saitou M, Tamamoto H, Tanaka H (2003) Evaluating bioaccumulation of suspected endocrine disruptors into periphytons and benthos in the Tama river. Water Sci Technol 47:71–76

    CAS  Google Scholar 

  62. Nakada N, Tanishima T, Shinohara H, Kiri K, Takada H (2006) Pharmaceutical chemicals and endocrine disrupters in municipal wastewater in Tokyo and their removal during activated sludge treatment. Water Res 40:3297–3303

    Article  CAS  Google Scholar 

  63. Nakada N, Kiri K, Shinohara H, Harada A, Kuroda K, Takizawa S, Takada H (2008) Evaluation of pharmaceuticals and personal care products as water-soluble molecular markers of sewage. Environ Sci Technol 42:6347–6353

    Article  CAS  Google Scholar 

  64. Cui CW, Ji SL, Ren HY (2006) Determination of steroid estrogens in wastewater treatment plant of a controceptives producing factory. Environ Monit Assess 121:409–419

    Article  CAS  Google Scholar 

  65. Richardson BJ, Lam PK, Martin M (2005) Emerging chemicals of concern: pharmaceuticals and personal care products (PPCPs) in Asia, with particular reference to Southern China. Mar Pollut Bull 50:913–920

    Article  CAS  Google Scholar 

  66. Managaki S, Murata A, Takada H, Tuyen BC, Chiem NH (2007) Distribution of macrolides, sulfonamides, and trimethoprim in tropical waters: ubiquitous occurrence of veterinary antibiotics in the Mekong delta. Environ Sci Technol 41:8004–8010

    Article  CAS  Google Scholar 

  67. Lin AY, Tsai YT (2009) Occurrence of pharmaceuticals in Taiwan’s surface waters: impact of waste streams from hospitals and pharmaceutical production facilities. Sci Total Environ 407:3793–3802

    Article  CAS  Google Scholar 

  68. Bound JP, Voulvoulis N (2005) Household disposal of pharmaceuticals as a pathway for aquatic contamination in the United Kingdom. Environ Health Perspect 113:1705–1711

    Article  Google Scholar 

  69. Joss A, Keller E, Alder AC, Gobel A, McArdell CS, Ternes T, Siegrist H (2005) Removal of pharmaceuticals and fragrances in biological wastewater treatment. Water Res 39:3 139–3152

    Article  CAS  Google Scholar 

  70. Winker M, Faika D, Gulyas H, Otterpohl R (2008) A comparison of human pharmaceutical concentrations in raw municipal wastewater and yellowwater. Sci Total Environ 399:96–104

    Article  CAS  Google Scholar 

  71. Bendz D, Paxeus NA, Ginn TR, Loge FJ (2005) Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Hoje river in Sweden. J Hazard Mater 122:195–204

    Article  CAS  Google Scholar 

  72. Jjemba PK (2006) Excretion and ecotoxicity of pharmaceutical and personal care products in the environment. Ecotoxicol Environ Saf 63:113–130

    Article  CAS  Google Scholar 

  73. Mompelat S, Le Bot B, Thomas O (2009) Occurrence and fate of pharmaceutical products and by-products, from resource to drinking water. Environ Int 35:803–814

    Article  CAS  Google Scholar 

  74. Claudel JP, Touboul P (1995) Sotalol: From “just another beta blocker” to “the prototype of Class III antidysrhythmic compound”. Pacing Clin Electrophysiol 18:451–467

    Article  CAS  Google Scholar 

  75. Lienert J, Gudel K, Escher BI (2007) Screening method for ecotoxicological hazard assessment of 42 pharmaceuticals considering human metabolism and excretory routes. Environ Sci Technol 41:4471–4478

    Article  CAS  Google Scholar 

  76. Alder AC, Schaffner C, Majewsky M, Klasmeier J, Fenner K (2010) Fate of beta-blocker human pharmaceuticals in surface water: comparison of measured and simulated concentrations in the Glatt Valley watershed, Switzerland. Water Res 44:936–948

    Article  CAS  Google Scholar 

  77. Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2008) The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK. Water Res 42:3498–3518

    Article  CAS  Google Scholar 

  78. Heberer T (2002) Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data. Toxicol Lett 131:5–17

    Article  CAS  Google Scholar 

  79. Park GR (2001) Drug metabolism. Br J Anaesth CEPD Rev 1:185–188

    Google Scholar 

  80. Daughton CG (2003) Cradle-to-cradle stewardship of drugs for minimizing their environmental disposition while promoting human health. II. Drug disposal, waste reduction, and future directions. Environ Health Perspect 111:775–785

    Article  CAS  Google Scholar 

  81. Daughton CG (2009) Chemicals from the practice of healthcare: challenges and unknowns posed by residues in the environment. Environ Toxicol Chem 28:2490–2494

    Article  CAS  Google Scholar 

  82. Rouen D, Dolan K, Kimber J (2001) A review of drug detection testing and an examination of urine, hair, saliva, and sweat. Vol Technical Report No. 120. National Drug and Alcohol Research Centre, Sydney, Australia

    Google Scholar 

  83. Daughton CG, Ruhoy IS (2009) Environmental footprint of pharmaceuticals: the significance of factors beyond direct excretion to sewers. Environ Toxicol Chem 28:2495–2521

    Article  CAS  Google Scholar 

  84. Bound JP, Voulvoulis N (2006) Predicted and measured concentrations for selected pharmaceuticals in UK rivers: implications for risk assessment. Water Res 40:2885–2892

    Article  CAS  Google Scholar 

  85. Glassmeyer ST, Hinchey EK, Boehme SE, Daughton CG, Ruhoy IS, Conerly O, Daniels RL, Lauer L, McCarthy M, Nettesheim TG, Sykes K, Thompson VG (2009) Disposal practices for unwanted residential medications in the United States. Environ Int 35:566–572

    Article  CAS  Google Scholar 

  86. Kuspis DA, Krenzelok EP (1996) What happens to expired medications? A survey of community medication disposal. Vet Hum Toxicol 38:48–49

    CAS  Google Scholar 

  87. Adler NE, Koschorreck J, Rechenberg B (2008) Environmental impact assessment and control of pharmaceuticals: the role of environmental agencies. Water Sci Technol 57:91–97

    Article  CAS  Google Scholar 

  88. Jones OA, Voulvoulis N, Lester JN (2003) Potential impact of pharmaceuticals on environmental health. Bull World Health Organ 81:768–769

    Google Scholar 

  89. Joakim Larsson DG, Fick J (2009) Transparency throughout the production chain—a way to reduce pollution from the manufacturing of pharmaceuticals? Regul Toxicol Pharmacol 53:161–163

    Article  CAS  Google Scholar 

  90. Li D, Yang M, Hu J, Ren L, Zhang Y, Li K (2008) Determination and fate of oxytetracycline and related compounds in oxytetracycline production wastewater and the receiving river. Environ Toxicol Chem 27:80–86

    Article  CAS  Google Scholar 

  91. Langford KH, Thomas KV (2009) Determination of pharmaceutical compounds in hospital effluents and their contribution to wastewater treatment works. Environ Int 35:766–770

    Article  CAS  Google Scholar 

  92. Castiglioni S, Bagnati R, Fanelli R, Pomati F, Calamari D, Zuccato E (2006) Removal of pharmaceuticals in sewage treatment plants in Italy. Environ Sci Technol 40:357–363

    Article  CAS  Google Scholar 

  93. Choi K, Kim Y, Park J, Park CK, Kim M, Kim HS, Kim P (2008) Seasonal variations of several pharmaceutical residues in surface water and sewage treatment plants of Han River, Korea. Sci Total Environ 405:120–128

    Article  CAS  Google Scholar 

  94. Brun GL, Bernier M, Losier R, Doe K, Jackman P, Lee HB (2006) Pharmaceutically active compounds in Atlantic Canadian sewage treatment plant effluents and receiving waters, and potential for environmental effects as measured by acute and chronic aquatic toxicity. Environ Toxicol Chem 25:2163–2176

    Article  CAS  Google Scholar 

  95. Conley JM, Symes SJ, Schorr MS, Richards SM (2008) Spatial and temporal analysis of pharmaceutical concentrations in the upper Tennessee River Basin. Chemosphere 73:1178–1187

    Article  CAS  Google Scholar 

  96. Vieno NM, Tuhkanen T, Kronberg L (2005) Seasonal variation in the occurrence of pharmaceuticals in effluents from a sewage treatment plant and in the recipient water. Environ Sci Technol 39:8220–8226

    Article  CAS  Google Scholar 

  97. Gros M, Petrovic M, Barcelo D (2007) Wastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the Ebro river basin (Northeast Spain). Environ Toxicol Chem 26:1553–1562

    Article  CAS  Google Scholar 

  98. Standley LJ, Rudel RA, Swartz CH, Attfield KR, Christian J, Erickson M, Brody JG (2008) Wastewater-contaminated groundwater as a source of endogenous hormones and pharmaceuticals to surface water ecosystems. Environ Toxicol Chem 27:2457–2468

    Article  CAS  Google Scholar 

  99. Lapen DR, Topp E, Metcalfe CD, Li H, Edwards M, Gottschall N, Bolton P, Curnoe W, Payne M, Beck A (2008) Pharmaceutical and personal care products in tile drainage following land application of municipal biosolids. Sci Total Environ 399:50–65

    Article  CAS  Google Scholar 

  100. Topp E, Monteiro SC, Beck A, Coelho BB, Boxall AB, Duenk PW, Kleywegt S, Lapen DR, Payne M, Sabourin L, Li H, Metcalfe CD (2008) Runoff of pharmaceuticals and personal care products following application of biosolids to an agricultural field. Sci Total Environ 396:52–59

    Article  CAS  Google Scholar 

  101. Boxall AB, Blackwell P, Cavallo R, Kay P, Tolls J (2002) The sorption and transport of a sulphonamide antibiotic in soil systems. Toxicol Lett 131:19–28

    Article  CAS  Google Scholar 

  102. Radjenovic J, Petrovic M, Barcelo D (2009) Fate and distribution of pharmaceuticals in wastewater and sewage sludge of the conventional activated sludge (CAS) and advanced membrane bioreactor (MBR) treatment. Water Res 43:831–841

    Article  CAS  Google Scholar 

  103. Spongberg AL, Witter JD (2008) Pharmaceutical compounds in the wastewater process stream in Northwest Ohio. Sci Total Environ 397:148–157

    Article  CAS  Google Scholar 

  104. Xia K, Bhandari A, Das K, Pillar G (2005) Occurrence and fate of pharmaceuticals and personal care products (PPCPs) in biosolids. J Environ Qual 34:91–104

    Article  CAS  Google Scholar 

  105. Monteiro SC, Boxall AB (2009) Factors affecting the degradation of pharmaceuticals in agricultural soils. Environ Toxicol Chem 28:2546–2554

    Article  CAS  Google Scholar 

  106. Slack RJ, Gronow JR, Voulvoulis N (2005) Household hazardous waste in municipal landfills: contaminants in leachate. Sci Total Environ 337:119–137

    Article  CAS  Google Scholar 

  107. Barnes KK, Christenson SC, Kolpin DW, Focazio M, Furlong ET, Zaugg SD, Meyer MT, Barber LB (2004) Pharmaceuticals and other organic waste water contaminants within a leachate plume downgradient of a municipal landfill. Ground Water Monit Remed 24:119–126

    CAS  Google Scholar 

  108. Schwarzbauer J, Heim S, Brinker S, Littke R (2002) Occurrence and alteration of organic contaminants in seepage and leakage water from a waste deposit landfill. Water Res 36:2275–2287

    Article  CAS  Google Scholar 

  109. Breton R, Boxall A (2003) Pharmaceuticals and personal care products in the environment: regulatory drivers and research needs. QSAR Comb Sci 22:399–409

    Article  CAS  Google Scholar 

  110. Hamscher G, Sczesny S, Hoper H, Nau H (2002) Determination of persistent tetracycline residues in soil fertilized with liquid manure by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. Anal Chem 74:1509–1518

    Article  CAS  Google Scholar 

  111. Boxall AB, Fogg LA, Blackwell PA, Kay P, Pemberton EJ, Croxford A (2004) Veterinary medicines in the environment. Rev Environ Contam Toxicol 180:1–91

    Article  CAS  Google Scholar 

  112. Khetan SK, Collins TJ (2007) Human pharmaceuticals in the aquatic environment: a challenge to green chemistry. Chem Rev 107:2319–2364

    Article  CAS  Google Scholar 

  113. Loffler D, Rombke J, Meller M, Ternes TA (2005) Environmental fate of pharmaceuticals in water/sediment systems. Environ Sci Technol 39:5209–5218

    Article  CAS  Google Scholar 

  114. Latch DE, Stender BL, Packer JL, Arnold WA, McNeill K (2003) Photochemical fate of pharmaceuticals in the environment: cimetidine and ranitidine. Environ Sci Technol 37:3342–3350

    Article  CAS  Google Scholar 

  115. Lin AY, Reinhard M (2005) Photodegradation of common environmental pharmaceuticals and estrogens in river water. Environ Toxicol Chem 24:1303–1309

    Article  CAS  Google Scholar 

  116. Canonica S, Meunier L, von Gunten U (2008) Phototransformation of selected pharmaceuticals during UV treatment of drinking water. Water Res 42:121–128

    Article  CAS  Google Scholar 

  117. Kim I, Tanaka H (2009) Photodegradation characteristics of PPCPs in water with UV treatment. Environ Int 35:793–802

    Article  CAS  Google Scholar 

  118. Packer JL, Werner JJ, Latch DE, McNeill K, Arnold WA (2003) Photochemical fate of pharmaceuticals in the environment: naproxen, diclofenac, clofibric acid, and ibuprofen. Aquat Sci 65:342–351

    Article  CAS  Google Scholar 

  119. Benotti MJ, Brownawell BJ (2007) Distributions of pharmaceuticals in an urban estuary during both dry- and wet-weather conditions. Environ Sci Technol 41:5795–5802

    Article  CAS  Google Scholar 

  120. Zorita S, Martensson L, Mathiasson L (2009) Occurrence and removal of pharmaceuticals in a municipal sewage treatment system in the south of Sweden. Sci Total Environ 407:2760–2770

    Article  CAS  Google Scholar 

  121. Baumgarten S, Schroder HF, Charwath C, Lange M, Beier S, Pinnekamp J (2007) Evaluation of advanced treatment technologies for the elimination of pharmaceutical compounds. Water Sci Technol 56:1–8

    CAS  Google Scholar 

  122. Stackelberg PE, Gibs J, Furlong ET, Meyer MT, Zaugg SD, Lippincott RL (2007) Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds. Sci Total Environ 377:255–272

    Article  CAS  Google Scholar 

  123. Vieno NM, Harkki H, Tuhkanen T, Kronberg L (2007) Occurrence of pharmaceuticals in river water and their elimination in a pilot-scale drinking water treatment plant. Environ Sci Technol 41:5077–5084

    Article  CAS  Google Scholar 

  124. Huber MM, Gobel A, Joss A, Hermann N, Loffler D, McArdell CS, Ried A, Siegrist H, Ternes TA, von Gunten U (2005) Oxidation of pharmaceuticals during ozonation of municipal wastewater effluents: a pilot study. Environ Sci Technol 39:4290–4299

    Article  CAS  Google Scholar 

  125. Ternes TA, Stuber J, Herrmann N, McDowell D, Ried A, Kampmann M, Teiser B (2003) Ozonation: a tool for removal of pharmaceuticals, contrast media and musk fragrances from wastewater? Water Res 37:1976–1982

    Article  CAS  Google Scholar 

  126. Paraskeva P, Graham NJ (2002) Ozonation of municipal wastewater effluents. Water Environ Res 74:569–581

    Article  CAS  Google Scholar 

  127. Ternes TA (2001) Pharmaceuticals and metabolites as contaminants of the aquatic environment. In: Daughton CG, Jones-Lepp TL (eds) Pharmaceuticals and personal care products in the environment - scientific and regulatory issues, ACS Symposium series 791. American Chemical Society, Washington, DC, pp 39–54

    Chapter  Google Scholar 

  128. Ternes TA (2001) Analytical methods for the determination of pharmaceuticals in aqueous environmental samples. Trac Trend Anal Chem 20:419–434

    Article  CAS  Google Scholar 

  129. Jones OA, Lester JN, Voulvoulis N (2005) Pharmaceuticals: a threat to drinking water? Trends Biotechnol 23:163–167

    Article  CAS  Google Scholar 

  130. Benotti MJ, Trenholm RA, Vanderford BJ, Holady JC, Stanford BD, Snyder SA (2009) Pharmaceuticals and endocrine disrupting compounds in U.S. Drinking water. Environ Sci Technol 43:597–603

    Article  CAS  Google Scholar 

  131. Rabiet M, Togola A, Brissaud F, Seidel JL, Budzinski H, Elbaz-Poulichet F (2006) Consequences of treated water recycling as regards pharmaceuticals and drugs in surface and ground waters of a medium-sized Mediterranean catchment. Environ Sci Technol 40:5282–5288

    Article  CAS  Google Scholar 

  132. Anderson PD, D’Aco VJ, Shanahan P, Chapra SC, Buzby ME, Cunningham VL, Duplessie BM, Hayes EP, Mastrocco FJ, Parke NJ, Rader JC, Samuelian JH, Schwab BW (2004) Screening analysis of human pharmaceutical compounds in U.S. Surface waters. Environ Sci Technol 38:838–849

    Article  CAS  Google Scholar 

  133. Feijtel T, Boeije G, Matthies M, Young A, Morris G, Gandolfi C, Hansen B, Fox K, Holt M, Koch V, Schroder R, Cassani G, Schowanek D, Rosenblom J, Niessen H (1997) Development of a geography-referenced regional exposure assessment tool for European rivers—GREAT-ER contribution to GREAT-ER #1. Chemosphere 34:2351–2373

    Article  CAS  Google Scholar 

  134. Brooks BW, Chambliss CK, Stanley JK, Ramirez A, Banks KE, Johnson RD, Lewis RJ (2005) Determination of select antidepressants in fish from an effluent-dominated stream. Environ Toxicol Chem 24:464–469

    Article  CAS  Google Scholar 

  135. Brown JN, Paxeus N, Forlin L, Larsson DGJ (2007) Variations in bioconcentration of human pharmaceuticals from sewage effluents into fish blood plasma. Environ Toxicol Pharmacol 24:267–274

    Article  CAS  Google Scholar 

  136. Chu S, Metcalfe CD (2007) Analysis of paroxetine, fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction, mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry. J Chromatogr A 1163:112–118

    Article  CAS  Google Scholar 

  137. Nakamura Y, Yamamoto H, Sekizawa J, Kondo T, Hirai N, Tatarazako N (2008) The effects of ph on fluoxetine in Japanese Medaka (Oryzias latipes): acute toxicity in fish larvae and bioaccumulation in juvenile fish. Chemosphere 70:865–873

    Article  CAS  Google Scholar 

  138. Ramirez AJ, Mottaleb MA, Brooks BW, Chambliss CK (2007) Analysis of pharmaceuticals in fish using liquid chromatography-tandem mass spectrometry. Anal Chem 79:3155–3163

    Article  CAS  Google Scholar 

  139. Boxall AB, Johnson P, Smith EJ, Sinclair CJ, Stutt E, Levy LS (2006) Uptake of veterinary medicines from soils into plants. J Agric Food Chem 54:2288–2297

    Article  CAS  Google Scholar 

  140. Jones OA, Voulvoulis N, Lester JN (2004) Potential ecological and human health risks associated with the presence of pharmaceutically active compounds in the aquatic environment. Crit Rev Toxicol 34:335–350

    Article  CAS  Google Scholar 

  141. Herrman JL, Younes M (1999) Background to the adi/tdi/ptwi. Regul Toxicol Pharmacol 30:S109–S113

    Article  CAS  Google Scholar 

  142. Galli CL, Marinovich M, Lotti M (2008) Is the acceptable daily intake as presently used an axiom or a dogma? Toxicol Lett 180:93–99

    Article  CAS  Google Scholar 

  143. Kroes R, Galli C, Munro I, Schilter B, Tran L, Walker R, Wurtzen G (2000) Threshold of toxicological concern for chemical substances present in the diet: a practical tool for assessing the need for toxicity testing. Food Chem Toxicol 38:255–312

    Article  CAS  Google Scholar 

  144. Kim S, Aga DS (2007) Potential ecological and human health impacts of antibiotics and antibiotic-resistant bacteria from wastewater treatment plants. J Toxicol Environ Health B Crit Rev 10:559–573

    Article  CAS  Google Scholar 

  145. Jorgensen SE, Halling-Sorensen B (2000) Drugs in the environment. Chemosphere 40:691–699

    Article  CAS  Google Scholar 

  146. Schwartz T, Kohnen W, Jansen B, Obst U (2003) Detection of antibiotic-resistant bacteria and their resistance genes in wastewater, surface water, and drinking water biofilms. FEMS Microbiol Ecol 43:325–335

    Article  CAS  Google Scholar 

  147. Guardabassi L, Petersen A, Olsen JE, Dalsgaard A (1998) Antibiotic resistance in Acinetobacter spp. isolated from sewers receiving waste effluent from a hospital and a pharmaceutical plant. Appl Environ Microbiol 64:3499–3502

    CAS  Google Scholar 

  148. Reinthaler FF, Posch J, Feierl G, Wust G, Haas D, Ruckenbauer G, Mascher F, Marth E (2003) Antibiotic resistance of E. coli in sewage and sludge. Water Res 37:1685–1690

    Article  CAS  Google Scholar 

  149. Goni-Urriza M, Capdepuy M, Arpin C, Raymond N, Caumette P, Quentin C (2000) Impact of an urban effluent on antibiotic resistance of riverine Enterobacteriaceae and Aeromonas spp. Appl Environ Microbiol 66:125–132

    Article  CAS  Google Scholar 

  150. Kummerer K (2009) Antibiotics in the aquatic environment—a review—part II. Chemosphere 75:435–441

    Article  CAS  Google Scholar 

  151. Dorne JL, Skinner L, Frampton GK, Spurgeon DJ, Ragas AM (2007) Human and environmental risk assessment of pharmaceuticals: differences, similarities, lessons from toxicology. Anal Bioanal Chem 387:1259–1268

    Article  CAS  Google Scholar 

  152. Zhang Z, Feng Y, Gao P, Wang C, Ren N (2011) Occurrence and removal efficiencies of eight EDCS and estrogenicity in a STP. J Environ Monit 13:1333–1373

    Google Scholar 

  153. Kusk KO, Kruger T, Long M, Taxvig C, Lykkesfeldt AE, Frederiksen H, Andersson AM, Andersen HR, Hansen KM, Nellemann C, Bonefeld-Jorgensen EC (2011) Endocrine potency of wastewater: contents of endocrine disrupting chemicals and effects measured by in vivo and in vitro assays. Environ Toxicol Chem 30:413–426

    Article  CAS  Google Scholar 

  154. Swart JC, Pool EJ, van Wyk JH (2011) The implementation of a battery of in vivo and in vitro bioassays to assess river water for estrogenic endocrine disrupting chemicals. Ecotoxicol Environ Saf 74:138–143

    Article  CAS  Google Scholar 

  155. Lissemore L, Hao C, Yang P, Sibley PK, Mabury S, Solomon KR (2006) An exposure assessment for selected pharmaceuticals within a watershed in Southern Ontario. Chemosphere 64:717–729

    Article  CAS  Google Scholar 

  156. Cleuvers M (2003) Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol Lett 142:185–194

    Article  CAS  Google Scholar 

  157. Richards SM, Wilson CJ, Johnson DJ, Castle DM, Lam M, Mabury SA, Sibley PK, Solomon KR (2004) Effects of pharmaceutical mixtures in aquatic microcosms. Environ Toxicol Chem 23:1035–1042

    Article  CAS  Google Scholar 

  158. Pomati F (2007) Pharmaceuticals in drinking water: is the cure worse than the disease? Environ Sci Technol 41:8204

    Article  CAS  Google Scholar 

  159. Gurr CJ, Reinhard M (2006) Harnessing natural attenuation of pharmaceuticals and hormones in rivers. Environ Sci Technol 40:2872–2876

    Article  CAS  Google Scholar 

  160. Ashton D, Hilton M, Thomas KV (2004) Investigating the environmental transport of human pharmaceuticals to streams in the united kingdom. Sci Total Environ 333:167–184

    Article  CAS  Google Scholar 

  161. Henschel KP, Wenzel A, Diedrich M, Fliedner A (1997) Environmental hazard assessment of pharmaceuticals. Regul Toxicol Pharmacol 25:220–225

    Article  CAS  Google Scholar 

  162. Halling-Sorensen B, Nors Nielsen S, Lanzky PF, Ingerslev F, Holten Lutzhoft HC, Jorgensen SE (1998) Occurrence, fate and effects of pharmaceutical substances in the environment—a review. Chemosphere 36:357–393

    Article  CAS  Google Scholar 

  163. Bound JP, Voulvoulis N (2004) Pharmaceuticals in the aquatic environment—a comparison of risk assessment strategies. Chemosphere 56:1143–1155

    Article  CAS  Google Scholar 

  164. Schowanek D, Webb S (2002) Exposure simulation for pharmaceuticals in European surface waters with greater. Toxicol Lett 131:39–50

    Article  CAS  Google Scholar 

  165. Boeije GM, Wagner JO, Koormann F, Vanrolleghem PA, Schowanek DR, Feijtel TC (2000) New PEC definitions for river basins applicable to GIS-based environmental exposure assessment. Chemosphere 40:255–265

    Article  CAS  Google Scholar 

  166. Sanderson H, Johnson DJ, Reitsma T, Brain RA, Wilson CJ, Solomon KR (2004) Ranking and prioritization of environmental risks of pharmaceuticals in surface waters. Regul Toxicol Pharmacol 39:158–183

    Article  CAS  Google Scholar 

  167. Ruhoy IS, Daughton CG (2008) Beyond the medicine cabinet: an analysis of where and why medications accumulate. Environ Int 34:1157–1169

    Article  CAS  Google Scholar 

  168. Brain RA, Sanderson H, Sibley PK, Solomon KR (2006) Probabilistic ecological hazard assessment: evaluating pharmaceutical effects on aquatic higher plants as an example. Ecotoxicol Environ Saf 64:128–135

    Article  CAS  Google Scholar 

  169. Sanderson H, Johnson DJ, Wilson CJ, Brain RA, Solomon KR (2003) Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish, daphnids and algae by ecosar screening. Toxicol Lett 144:383–395

    Article  CAS  Google Scholar 

  170. Cunningham VL, Buzby M, Hutchinson T, Mastrocco F, Parke N, Roden N (2006) Effects of human pharmaceuticals on aquatic life: next steps. Environ Sci Technol 40:3456–3462

    Article  CAS  Google Scholar 

  171. Philips PJ, Smith SG, Kolpin DW, Zaugg SD, Buxton HT, Furlong ET, Esposito K, Stinson B (2010) Pharmaceutical formulation facilities as sources of opioids and other pharmaceuticals to wastewater treatment plant effluents. Environ Sci Technol 44(13):4910–16

    Article  CAS  Google Scholar 

  172. Brooks BW, Riley TM, Taylor RD (2006) Water quality of effluent-dominated ecosystems: ecotoxicological, hydrological, and management considerations. Hydrobiologica 556:365–79

    Article  CAS  Google Scholar 

  173. Brooks BW, Huggett DB, Boxall AB (2009) Pharmaceuticals and personal care products: Research needs for the next decade. Environ Toxicol Chem 28(12):2469–72

    Article  CAS  Google Scholar 

  174. Monteiro SC, Boxall AB (2010) Occurrence and fate of human pharmaceuticals in the environment. Rev Environ Contam Toxicol 202:53–154

    Article  CAS  Google Scholar 

  175. Daughton CG, Brooks BW (2011) Active pharmaceutical ingredients and aquatic organisms. In: Environmental Contaminants in Wildlife: Interpreting Tissue Concentrations, 2nd ed. Eds: Meador J, Beyer N. Taylor and Francis. p. 281–341

    Article  CAS  Google Scholar 

  176. Valenti TV, Gould GG, Berninger JP, Connors KA, Keele NB, ProsserKN, Brooks BW (2012) Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter seeking behavior in adult male fathead minnows. Environ Sci Technol 46:2427–35

    Article  CAS  Google Scholar 

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  1. Department of Environmental Science, Institute of Biomedical Studies, Center for Reservoir and Aquatic Systems Research, Baylor University, One Bear Place, #97266, Waco, TX, 76798-7266, USA

    E. Spencer Williams & Bryan W. Brooks

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  1. E. Spencer Williams
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  2. Bryan W. Brooks
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  1. Baylor University, 1 Bear Place, Waco, 76798, Texas, USA

    Bryan W. Brooks

  2. University of North Texas, N/A, Denton, 76203, Texas, USA

    Duane B. Huggett

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Williams, E.S., Brooks, B.W. (2012). Human Health Risk Assessment for Pharmaceuticals in the Environment: Existing Practice, Uncertainty, and Future Directions. In: Brooks, B., Huggett, D. (eds) Human Pharmaceuticals in the Environment. Emerging Topics in Ecotoxicology, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3473-3_8

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