Human Health Relevance of Pharmaceutically Active Compounds in Drinking Water

AAPS Journal

Volumn 17, Issue 3, 2015, Pages 558-585

  Khan, Usman ^a   Nicell, Jim ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

drinking water; hospitals; human health; pharmaceuticals; risk assessment

Indexed keywords

DRINKING WATER; DRUG; WATER POLLUTANT;

ANALYSIS; CANADA; CHEMISTRY; ENVIRONMENTAL MONITORING; HUMAN; PROCEDURES; RISK ASSESSMENT; STANDARDS; WATER POLLUTANT; WATER SUPPLY;

CANADA; DRINKING WATER; ENVIRONMENTAL MONITORING; HUMANS; PHARMACEUTICAL PREPARATIONS; RISK ASSESSMENT; WATER POLLUTANTS, CHEMICAL; WATER SUPPLY;

EID: 84939952797     PISSN: None     EISSN: 15507416     Source Type: Journal    
DOI: 10.1208/s12248-015-9729-5     Document Type: Article

References (106)

1. Daughton CG. Pharmaceutical ingredients in drinking water: overview of occurrence and significance of human exposure. In: Halden RU, editor. Contaminants of emerging concern in the environment: ecological and human health considerations. Washington, DC: American Chemical Society; 2010.
2. MDH. Human health-based water guidance table. St. Paul: Minnesota Department of Health; 2013.
3. WHO. Pharmaceuticals in drinking-water: public health and environment water, sanitation, hygiene and health. Geneva: World Health Organization; 2011.
4. Cunningham VL, Binks SP, Olson MJ. Human health risk assessment from the presence of human pharmaceuticals in the aquatic environment. Regul Toxicol Pharmacol. 2009;53(1):39–45.
5. Zhang QQ, Zhao JL, Ying GG, Liu YS, Pan CG. Emission estimation and multimedia fate modelling of seven steroids at the river basin scale in China. Environ Sci Technol. In press doi:10.1021/es501226h.
6. Khan U, Nicell J. Assessment of the aquatic release and relevance of selected endogenous chemicals: androgens, thyroids and their in vivo metabolites. In: Halden RU, editor. Contaminants of emerging concern in the environment: ecological and human health considerations. Washington, DC: American Chemical Society; 2010.
7. Cardoso O, Porcher J-M, Sanchez W. Factory-discharged pharmaceuticals could be a relevant source of aquatic environment contamination: review of evidence and need for knowledge. Chemosphere. 2014;115:20–30.
8. Khan U, Nicell J. Assessing the risk of exogenously consumed pharmaceuticals in land-applied human urine. Water Sci Technol. 2010;62(6):1335–45.
9. Venkatesan A, Halden RU. Wastewater treatment plants as chemical observatories to forecast ecological and human health risks of manmade chemicals. Sci Rep. 2014;4:3731. doi:10.1038/srep03731.
10. Langford KH, Thomas KV. Determination of pharmaceutical compounds in hospital effluents and their contribution to wastewater treatment works. Environ Int. 2009;35(5):766–70.
11. Cook SM, VanDuinen B, Love NG, Skerlos SJ. Life cycle comparison of environmental emissions from three disposal options for unused pharmaceuticals. Environ Sci Technol. 2012;46(10):5535–41.
12. Khan U, Nicell J. Refined sewer epidemiology mass balances and their application to heroin, cocaine and ecstasy. Environ Int. 2011;37(7):1236–52.
13. Khan U, Nicell J. Sewer epidemiology mass balances for assessing the illicit use of methamphetamine, amphetamine and tetrahydrocannabinol. Sci Total Environ. 2012;421–422:144–62.
14. Besse J-P, Kausch-Barreto C, Garric J. Exposure assessment of pharmaceuticals and their metabolites in the aquatic environment: application to the French situation and preliminary prioritization. Hum Ecol Risk Assess. 2008;14(4):665–95.
15. Bull RJ, Crook J, Whittaker M, Cotruvo JA. Therapeutic dose as the point of departure in assessing potential health hazards from drugs in drinking water and recycled municipal wastewater. Regul Toxicol Pharmacol. 2011;60(1):1–19.
16. Caldwell DJ, Mastrocco F, Nowak E, Johnston J, Yekel H, Pfeiffer D, et al. An assessment of potential exposure and risk from estrogens in drinking water. Environ Health Perspect. 2010;118(3):338–44.
17. Cunningham VL, Perino C, D’Aco VJ, Hartmann A, Bechter R. Human health risk assessment of carbamazepine in surface waters of North America and Europe. Regul Toxicol Pharmacol. 2010;56(3):343–51.
18. Schwab BW, Hayes EP, Fiori JM, Mastrocco FJ, Roden NM, Cragin D, et al. Human pharmaceuticals in US surface waters: a human health risk assessment. Regul Toxicol Pharmacol. 2005;42(3):296–312.
19. Bruce GM, Pleus RC, Snyder SA. Toxicological relevance of pharmaceuticals in drinking water. Environ Sci Technol. 2010;44(14):5619–26.
20. Kostich MS, Lazorchak JM. Risks to aquatic organisms posed by human pharmaceutical use. Sci Total Environ. 2008;389(2–3):329–39.
21. Sedlak DL, Pinkston K, Huang C-H. Occurrence survey of pharmaceutically active compounds. Alexandria: AWWA Research Foundation; 2005.
22. Kumar A, Xagoraraki I. Pharmaceuticals, personal care products and endocrine-disrupting chemicals in US surface and finished drinking waters: a proposed ranking system. Sci Total Environ. 2010;408(23):5972–89.
23. Watts C, Maycock D, Crane M, Fawell J, Goslan E. Desk based review of current knowledge on pharmaceuticals in drinking water and estimation of potential levels. London: Watts and Crane Associates; 2007.
24. de Jongh CM, Kooij PJF, de Voogt P, ter Laak TL. Screening and human health risk assessment of pharmaceuticals and their transformation products in Dutch surface waters and drinking water. Sci Total Environ. 2012;427–428:70–7.
25. OECD. OECD health data. Paris: Organisation for Economic Co-operation and Development; 2013.
26. Roos V, Gunnarsson L, Fick J, Larsson DGJ, Rudén C. Prioritising pharmaceuticals for environmental risk assessment: towards adequate and feasible first-tier selection. Sci Total Environ. 2012;421:102–10.
27. Brogan IMS. Canadian compuscript audit database. Montreal: IMS Brogan; 2007.
28. Brogan IMS. Canadian drug store and hospital purchases audit database. Montreal: IMS Brogan; 2007.
29. Benotti MJ, Trenholm RA, Vanderford BJ, Holady JC, Stanford BD, Snyder SA. Pharmaceuticals and endocrine disrupting compounds in U.S. drinking water. Environ Sci Technol. 2009;43(3):597–603.
30. INCB. Psychotropic substances—2013 report. Vienna: International Narcotics Control Board; 2013.
31. Health Canada. Drug product database (DPD). Ottawa: Health Canada; 2013.
32. Lamshöft M, Grobe N, Spiteller M. Picomolar concentrations of morphine in human urine determined by dansyl derivatization and liquid chromatography–mass spectrometry. J Chromatogr B. 2011;879(13):933–7.
33. Helwig K, Hunter C, MacLachlan J, McNaughtan M, Roberts J, et al. Micropollutant point sources in the built environment: identification and monitoring of priority pharmaceutical substances in hospital effluents. J Environ Anal Toxicol. 2014;3:177.
34. Riaz ul Haq M, Metcalfe C, Li H, Parker W. Discharge of pharmaceuticals into municipal sewers from hospitals and long-term care facilities. Water Qual Res J Can. 2012;47(2):140–52.
35. STOWA. Inventarisatie van emissie van geneesmiddelen uit zorginstellingen. ZORG, Deel C. Amersfoor: Stichting Toegepast Onderzoek Waterbeheer (STOWA); 2011.
36. Miljøstyrelsen. Begrænsning af humane lægemiddelrester og antibiotikaresistens i spildevand med fokus på reduktion ved kilden. DHI og B. Halling-Sørensen; 2007.
37. Le Corre KS, Ort C, Kateley D, Allen B, Escher BI, Keller J. Consumption-based approach for assessing the contribution of hospitals towards the load of pharmaceutical residues in municipal wastewater. Environ Int. 2012;45:99–111.
38. Straub JO, Flückiger A. Proposal for an environmental quality standard according to the EU Water Framework Directive for the Anti-Hyperlipidaemic Pharmaceutical Bezafibrate. Poster presented at 20th SETAC Europe Annual Meeting: Seville; 2010.
39. Boyd GR, Reemtsma H, Grimm DA, Mitra S. Pharmaceuticals and personal care products (PPCPs) in surface and treated waters of Louisiana, USA and Ontario, Canada. Sci Total Environ. 2003;311(1–3):135–49.
40. Chen M, Ohman K, Metcalfe C, Ikonomou MG, Amatya PL, Wilson J. Pharmaceuticals and endocrine disruptors in wastewater treatment effluents and in the water supply system of Calgary, Alberta, Canada. Water Qual Res J Can. 2006;41(4):351–64.
41. Garcia-Ac A, Segura PA, Gagnon C, Sauvé S. Determination of bezafibrate, methotrexate, cyclophosphamide, orlistat and enalapril in waste and surface waters using on-line solid-phase extraction liquid chromatography coupled to polarity-switching electrospray tandem mass spectrometry. J Environ Monit. 2009;11(4):830–8.
42. Kleywegt S, Pileggi V, Yang P, Hao C, Zhao X, Rocks C, et al. Pharmaceuticals, hormones and bisphenol A in untreated source and finished drinking water in Ontario, Canada—occurrence and treatment efficiency. Sci Total Environ. 2011;409(8):1481–8.
43. MDDEP. Résultats du suivi des produits pharmaceutiques et de soins personnels ainsi que des hormones dans des eaux usées, de l’eau de surface et de l’eau potable au Québec (in French). Quebec City: MDDEP; 2011. Available at: http://www.mddelcc.gouv.qc.ca/eau/potable/prod-pharma-eau2003-2009.pdf.
44. Metcalfe CD, Chu S, Judt C, Li H, Oakes KD, Servos MR, et al. Antidepressants and their metabolites in municipal wastewater, and downstream exposure in an urban watershed. Environ Toxicol Chem. 2010;29(1):79–89.
45. Tabe S, Yang P, Zhao X, Hao C, Seth R, Schweitzer L, et al. Occurrence and removal of PPCPs and EDCs in the Detroit river watershed. Water Pract Technol. 2010. doi:10.2166/wpt.2010.015.
46. Bouchard M, Morselli C, Gallupe O, Easton S, Descormiers K, Turcotte M, et al. Estimating the size of the Canadian illicit METH and MDMA markets: a multi-method approach. Ottawa: Public Safety Canada; 2012.
47. WHO. ATC classification system. Oslo: WHO Collaborating Centre for Drug Statistics Methodology; 2013.
48. Fu W, Franco A, Trapp S. Methods for estimating the bioconcentration factor of ionizable organic chemicals. Environ Toxicol Chem. 2009;28(7):1372–9.
49. Travis CC, Arms AD. Bioconcentration of organics in beef, milk, and vegetation. Environ Sci Technol. 1988;22:271–4.
50. Statistics Canada. CANSIM database. Ottawa: Statistic Canada; 2013.
51. CCSA. Misuse of opioids in Canadian communities—April Bulletin. Ottawa: Canadian Centre on Substance Abuse; 2013.
52. RCMP. Report on the illicit drug situation in Canada—2009. Ottawa: Royal Canadian Mounted Police; 2010.
53. Environment Canada. The municipal water and wastewater survey. Ottawa: Environment Canada; 2011.
54. Lehner B, Nicell J, Grill G, Khan U, Ariwi J. Down-the-drain geospatial fate model for substances in consumer products. Report Submitted by McGill University to Health Canada; 2013.
55. Environment Canada. Data sources and methods: municipal wastewater treatment indicator. Ottawa: Environment Canada; 2012.
56. RIVM. Evaluation of the model simple treat. Bilthoven: National Institute for Public Health and the Environment (RIVM); 2013.
57. Franco A, Fu W, Trapp S. The effect of pH on the sorption of ionizable chemicals: effects and modeling advances. Environ Toxicol Chem. 2008;28:458–64.
58. ECETOC. Environmental risk assessment of ionisable compounds. Brussels: European Centre for Ecotoxicology and Toxicology of Chemicals; 2013.
59. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug information handbook. 20th ed. Hudson: Lexi-Comp, Inc.; 2011.
60. www.UptoDate.com. UpToDate, Waltham, MA; 2013.
61. NIOSH. List of antineoplastic and other hazardous drugs in healthcare settings. Cincinnati: National Institute for Occupational Safety and Health; 2012.
62. Binks SP. Occupational toxicology and the control of exposure to pharmaceutical agents at work. Occup Med. 2003;53:363–70.
63. Christensen FM. Pharmaceuticals in the environment—a human risk. Regul Toxicol Pharmacol. 1998;28(3):212–21.
64. California EPA. Proposition 65 safe harbor levels: no significant risk levels for carcinogens and maximum allowable dose levels for chemicals causing reproductive toxicity. Sacramento: California EPA; 2012.
65. Gold L. The Carcinogenic Potency Project (CPDB). Berkley: United States; 2011.
66. Health Canada. Federal contaminated site risk assessment in Canada. Part 1: guidance on human health preliminary quantitative risk assessment. Ottawa: Health Canada; 2013.
67. Weissbrodt D, Kovalova L, Ort C, Pazhepurackel V, Moser R, Hollender J, et al. Mass flows of X-ray contrast media and cytostatics in hospital wastewater. Environ Sci Technol. 2009;43(13):4810–7.
68. FDA. Drugs@FDA. Silve Spring, Maryland: 2013.
69. Laurenson JP, Bloom RA, Page S, Sadrieh N. Ethinyl estradiol and other human pharmaceutical estrogens in the aquatic environment: a review of recent risk assessment data. AAPS J. 2014;16(2):299–310.
70. Khan U, Nicell JA. Contraceptive options and their associated estrogenic environmental loads: relationships and trade-offs. PLoS ONE. 2014;9(3):e92630. doi:10.1371/journal.pone.009263.0.
71. Khan U, van Nuijs ALN, Li J, Maho W, Du P, Li K, et al. Application of a sewage-based approach to assess the use of ten illicit drugs in four Chinese megacities. Sci Total Environ. 2014;487:710–21.
72. Oosterhuis M, Sacher F, ter Laak TL. Prediction of concentration levels of metformin and other high consumption pharmaceuticals in wastewater and regional surface water based on sales data. Sci Total Environ. 2013;442:380–8.
73. Straub J. An environmental risk assessment for human-use trimethoprim in European surface waters. Antibiotics. 2013;2(1):115–62. doi:10.3390/antibiotics2010115.
74. Shutt DA, Cox RI. Steroid and phyto-oestrogen binding to sheep uterine receptors in vitro. J Endocrinol. 1972;52:299–310.
75. Trudeau VL, Heyne B, Blais JM, Temussi F, Atkinson SK, Pakdel F, et al. Lumiestrone is photochemically derived from estrone and may be released to the environment without detection. FMICB. 2011;2(Article 83):1–13.
76. Svanfelt J, Eriksson J, Kronberg L. Analysis of thyroid hormones in raw and treated waste water. J Chromatogr A. 2010;1217(43):6469–74.
77. Howard PH, Muir DCG. Identifying new persistent and bioaccumulative organics among chemicals in commerce II: pharmaceuticals. Environ Sci Techol. 2011;45(16):6938–46.
78. ANSES. Campagne nationale d’occurrence des résidus de médicaments dans les eaux destinées à la consommation humaine. Maisons-Alfort: Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail; 2011.
79. Ericson JF, Smith RM, Roberts G, Hannah B, Hoeger B, Ryan J. Experiences with the OECD 308 transformation test: a human pharmaceutical perspective. Integra Environ Assess Manag. 2014;10(1):114–24.
80. Bayer A, Asner R, Schüssler W, Kopf W, Weiß K, Sengl M, et al. Behavior of sartans (antihypertensive drugs) in wastewater treatment plants, their occurrence and risk for the aquatic environment. Environ Sci Pollut Res. In press. doi:10.1007/s11356-014-3060-z.
81. Kostich MS, Batt AL, Lazorchak JM. Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the USA and implications for risk estimation. Environ Pollut. 2014;184:354–9.
82. Health Canada. Uses of antimicrobials in food animals in Canada: impact on resistance and human health. Ottawa: Health Canada; 2002.
83. Gros M, Rodriguez-Mozaz S, Barceló D. Fast and comprehensive multi-residue analysis of a broad range of human and veterinary pharmaceuticals and some of their metabolites in surface and treated waters by ultra-high performance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry. J Chromatogr A. 2013;1248:104–21.
84. Vulliet E, Cren-Olive C, Grenier-Loustalot M-F. Occurrence of pharmaceuticals and hormones in drinking water treated from surface waters. Environ Chem Lett. 2011;9:103–14.
85. Rodayan A, Majewsky M, Yargeau V. Impact of approach used to determine removal levels of drugs of abuse during wastewater treatment. Sci Total Environ. 2014;487:731–9.
86. Huerta-Fontela M, Galceran MT, Ventura F. Stimulatory drugs of abuse in surface waters and their removal in a conventional drinking water treatment plant. Environ Sci Technol. 2008;42(18):6809–16.
87. van der Aa M, Bijlsma L, Emke E, Dijkman E, van Nuijs ALN, van de Ven B, et al. Risk assessment for drugs of abuse in the Dutch watercycle. Water Res. 2013;47(5):1848–57.
88. Loos R, Carvalho R, António DC, Comero S, Locoro G, Tavazzi S, et al. EU-wide monitoring survey on emerging polar organic contaminants in wastewater treatment plant effluents. Water Res. 2013;47(17):6475–87.
89. Fischer B, Jones W, Rehm J. Trends and changes in prescription opioid analgesic dispensing in Canada 2005–2012: an update with a focus on recent interventions. BMC Health Serv Res. 2014;14(1):90. http://www.biomedcentral.com/1472-6963/14/90.
90. Boxall ABA, Monteiro SC, Fussell R, Williams RJ, Bruemer J, Greenwood R, et al. Targeted monitoring for human pharmaceuticals in vulnerable source and final waters. London: Drinking Water Inspectorate; 2012.
91. Kim M, Guerra P, Shah A, Parsa M, Alaee M, Smyth SA. Removal of pharmaceuticals and personal care products in a membrane bioreactor wastewater treatment plant. Water Sci Technol. 2014;69(11):2221–9.
92. Lowe CJ. Pharmaceuticals, personal care products, illicit drugs and their metabolites in screened municipal wastewaters. Master’s Thesis. Victoria: University of Victoria; 2011.
93. Derksen A, ter Laak T. Human pharmaceuticals in the water cycle. Netherlands: Joint STOWA and KWR Report; 2013.
94. Yargeau V, Taylor B, Li H, Rodayan A, Metcalfe CD. Analysis of drugs of abuse in wastewater from two Canadian cities. Sci Total Environ. 2014;487:722–30.
95. Hummel D, Löffler D, Fink G, Ternes TA. Simultaneous determination of psychoactive drugs and their metabolites in aqueous matrices by liquid chromatography mass spectrometry. Environ Sci Technol. 2006;40(23):7321–8.
96. Huerta-Fontela M, Galceran MT, Ventura F. Occurrence and removal of pharmaceuticals and hormones through drinking water treatment. Water Res. 2011;45:1432–42.
97. EMA. Questions and answers on 'Guideline on the environmental risk assessment of medicinal products for human use'. London: European Medicine Agency; 2011.
98. NHTSA. Cocaine: drug profile. Washington, DC: National Highway Traffic Safety Administration; 2013.
99. Chari BP, Halden RU. Predicting the concentration range of unmonitored chemicals in wastewater-dominated streams and in run-off from biosolids-amended soils. Sci Total Environ. 2012;440:314–20.
100. Boleda MR, Huerta-Fontela M, Ventura F, Galceran MT. Evaluation of the presence of drugs of abuse in tap waters. Chemosphere. 2011;84(11):1601–7.
101. Block JH, BealeWilson JM. Gisvold’s textbook of organic medicinal and pharmaceutical chemistry. Philadelphia: Lippincott Williams & Wilkins; 2004.
102. Verho M, Luck C, Shelter WJ, Rangoonwala B, Bender N. Pharmacokinetics, metabolism and biliary and urinary excretion of oral ramipril in man. Curr Med Res Opin. 1995;13:264–73.
103. Anderson P. Perspectives on estrogen sources and effects in us surface waters. Presentation given at CropLife America & RISE 2013 Spring Conference. Crystal City: Virginia; 2013.
104. Government of Canada. Canadian integrated program for antimicrobial resistance surveillance (CIPARS) 2009 Annual Report. Guelph: Public Health Agency of Canada; 2013.
105. Handa A, Webster P. Industry-led committee urges delay in closing loophole allowing import of unapproved antibiotics for animals. CMAJ. 2009;180:914–6.
106. Daughton CG. The Matthew effect and widely prescribed pharmaceuticals lacking environmental monitoring: case study of exposure-assessment vulnerability. Sci Total Environ. 2014;466:315–25.