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Potential Upstream Strategies for the Mitigation of Pharmaceuticals in the Aquatic Environment: a Brief Review

Current Environmental Health Reports volume 3, pages 153–160 (2016)Cite this article

Abstract

Active pharmaceutical ingredients represent a class of pollutants of emerging concern, and there is growing evidence that these pollutants can cause damage to the aquatic environment. As regulations to address these concerns are expected in developed nations, decision-makers are looking to the scientific community for potential solutions. To inform these regulatory efforts, further information on the potential strategies to reduce the levels of pharmaceuticals entering the aquatic environment is needed. End-of-pipe (i.e., wastewater treatment) technologies that can remove pharmaceuticals exist; however, they are costly to install and operate. Thus, the goal of this brief review is to look beyond end-of-pipe solutions and present various upstream mitigation strategies discussed within the scientific literature. Programs such as pharmaceutical take-back programs currently exist to attempt to reduce pharmaceutical concentrations in the environment, although access and coverage are often limited for many programs. Other potential strategies include redesigning pharmaceuticals to minimize aquatic toxicity, increasing the percent of the pharmaceuticals metabolized in the body, selecting less harmful pharmaceuticals for use, starting new prescriptions at lower dosages, selecting pharmaceuticals with lower excretion rates, and implementing source treatment such as urine separating toilets. Overall, this brief review presents a summary of the upstream preventative recommendations to mitigate pharmaceuticals from entering the aquatic environment with an emphasis on regulatory efforts in the USA and concludes with priorities for further research.

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References

Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance

  1. Zhong W, Maradit-Kremers H, St. Sauver JL, Yawn BP, Ebbert JO, Roger VL, et al. Age and sex patterns of drug prescribing in a defined American population. Mayo Clin Proc. 2013;88:697–707. doi:10.1016/j.mayocp.2013.04.021.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Phillips PJ, Smith SG, Kolpin DW, Zaugg SD, Buxton HT, Furlong ET, et al. Pharmaceutical formulation facilities as sources of opioids and other pharmaceuticals to wastewater treatment plant effluents. Environ Sci Technol. 2010;44:4910–6. doi:10.1021/es100356f.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Daughton CG. Cradle-to-cradle stewardship of drugs for minimizing their environmental disposition while promoting human health. I. Rational for and avenues toward a green pharmacy. Environ Health Perspect. 2003;111:757–74. doi:10.1289/ehp.5948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Verlicchi P, Al Aukidy M, Zambello E. Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load and environmental risk after a secondary treatment—a review. Sci Total Environ. 2012;429:123–55. doi:10.1016/j.scitotenv.2012.04.028.

    Article  CAS  PubMed  Google Scholar 

  5. Masoner JR, Kolpin DW, Furlong ET, Cozzarelli IM, Gray JL. Landfill leachate as a mirror of today’s disposable society: pharmaceuticals and other contaminants of emerging concern in final leachate from landfills in the conterminous United States. Environ Toxicol Chem. 2015. doi:10.1002/etc.3219.

    PubMed  Google Scholar 

  6. Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, et al. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: a national reconnaissance. Environ Sci Technol. 2002;36:1202–11. doi:10.1021/es011055j.

    Article  CAS  PubMed  Google Scholar 

  7. Christensen AM, Markussen B, Baun A, Halling-Sørensen B. Probabilistic environmental risk characterization of pharmaceuticals in sewage treatment plant discharges. Chemosphere. 2009;77:351–8. doi:10.1016/j.chemosphere.2009.07.018.

    Article  CAS  PubMed  Google Scholar 

  8. Blair BD, Crago JP, Hedman CJ, Klaper RD. Pharmaceuticals and personal care products found in the Great Lakes above concentrations of environmental concern. Chemosphere. 2013;93:2116–23. doi:10.1016/j.chemosphere.2013.07.057.

    Article  CAS  PubMed  Google Scholar 

  9. Deo RP. Pharmaceuticals in the surface water of the USA: a review. Curr Environ Heal Reports. 2014;1:113–22. doi:10.1007/s40572-014-0015-y. The report reviewed the levels and risk quotients for 93 pharmaceuticals that have been reported in US surface waters.

    Article  Google Scholar 

  10. Niemuth NJ, Klaper RD. Emerging wastewater contaminant metformin causes intersex and reduced fecundity in fish. Chemosphere. 2015;135:38–45. doi:10.1016/j.chemosphere.2015.03.060. This study reported environmentally relevant concentrations of the antidiabetic metformin causes the development of intersex gonads of male and reduced fecundity of pairs of fathead minnows.

    Article  CAS  PubMed  Google Scholar 

  11. Kidd KA, Blanchfield PJ, Mills KH, Palace VP, Evans RE, Lazorchak JM, et al. Collapse of a fish population after exposure to a synthetic estrogen. Proc Natl Acad Sci U S A. 2007;104:8897–901. doi:10.1073/pnas.0609568104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tahrani L, Soufi L, Mehri I, Najjari A, Hassan A, Van Loco J, et al. Isolation and characterization of antibiotic-resistant bacteria from pharmaceutical industrial wastewaters. Microb Pathog. 2015;89:54–61. doi:10.1016/j.micpath.2015.09.001.

    Article  CAS  PubMed  Google Scholar 

  13. Meena VD, Dotaniya ML, Saha JK, Patra AK. Antibiotics and antibiotic resistant bacteria in wastewater : impact on environment, soil microbial activity and human health. African J Microbiol Res. 2015;9.

  14. Brodin T, Fick J, Jonsson M, Klaminder J. Dilute concentrations of a psychiatric drug alter behavior of fish from natural populations. Science. 2013;339:814–5. doi:10.1126/science.1226850.

    Article  CAS  PubMed  Google Scholar 

  15. Sumpter J. Pharmaceuticals in the environment: moving from a problem to a solution. In: Green Sustain. Pharmcacy. Klaus Kümmerer, Maximilian Hempel, 2010. pp. 11–22.

  16. 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;60:1–19. doi:10.1016/j.yrtph.2009.12.010.

    Article  CAS  PubMed  Google Scholar 

  17. Oulton RL, Kohn T, Cwiertny DM. Pharmaceuticals and personal care products in effluent matrices: a survey of transformation and removal during wastewater treatment and implications for wastewater management. J Environ Monit. 2010;12:1956–78. doi:10.1039/c0em00068j.

    Article  CAS  PubMed  Google Scholar 

  18. Blair BD, Crago JP, Hedman CJ, Treguer RJF, Magruder C, Royer LS, et al. Science of the total environment evaluation of a model for the removal of pharmaceuticals, personal care products, and hormones from wastewater. Sci Total Environ. 2013;444:515–21. doi:10.1016/j.scitotenv.2012.11.103.

    Article  CAS  PubMed  Google Scholar 

  19. Blair BD, Kehl J, Klaper R. Assessing emerging wastewater regulations to minimize the risk from pharmaceuticals and personal care products. Manag Environ Qual An Int J. 2015;26:966–83. doi:10.1108/MEQ-12-2014-0171.

    Article  Google Scholar 

  20. Molinos-Senante M, Hernández-Sancho F, Sala-Garrido R. Economic feasibility study for wastewater treatment: a cost-benefit analysis. Sci Total Environ. 2010;408:4396–402. doi:10.1016/j.scitotenv.2010.07.014.

    Article  CAS  PubMed  Google Scholar 

  21. Daughton CG, Ruhoy IS. Green pharmacy and pharmEcovigilance: prescribing and the planet. Expert Rev Clin Pharmacol. 2011;4:211–32. doi:10.1586/ecp.11.6. Introduces eco-directed sustainable prescribing, which could reduce pharmaceutical entry to the environment by minimizing the need for disposal and reducing the excretion of unmetabolized pharmaceutical.

    Article  PubMed  Google Scholar 

  22. Sorell TL. Approaches to the development of human health toxicity values for active pharmaceutical ingredients in the environment. AAPS J. 2016;18:92–101. doi:10.1208/s12248-015-9818-5.

    Article  CAS  PubMed  Google Scholar 

  23. Molinos-Senante M, Hernández-Sancho F, Sala-Garrido R. Economic feasibility study for new technological alternatives in wastewater treatment processes: a review. Water Sci Technol. 2012;65:898. doi:10.2166/wst.2012.936.

    Article  PubMed  Google Scholar 

  24. Rudd MA, Ankley GT, Boxall ABA, Brooks BW. International scientists’ priorities for research on pharmaceutical and personal care products in the environment. Integr Environ Assess Manag. 2014;10:576–87. doi:10.1002/ieam.1551.

    Article  PubMed  Google Scholar 

  25. Eckstein G. Emerging EPA regulation of pharmaceuticals in the environment. Environ Law Rep. 2012;42:11105–8.

    Google Scholar 

  26. Boxall ABA, Rudd MA, Brooks BW, Caldwell DJ, Choi K, Hickmann S, et al. Pharmaceuticals and personal care products in the environment: what are the big questions? Environ Health Perspect. 2012;120:1221–9. doi:10.1016/j.envint.2013.06.012.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kümmerer K, Dionysiou DD, Fatta-Kassinos D. Long-term strategies for tackling micropollutants. 2015; 1–9. doi:10.1007/698_2015_447.

  28. U.S. Food and Drug Administration, Safe disposal of medicines—disposal of unused medicines: what you should know, (2015). http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/SafeDisposalofMedicines/ucm186187.htm (accessed January 9, 2016).

  29. Teske J, Weller J-P, Larsch K, Tröger HD, Karst M. Fatal outcome in a child after ingestion of a transdermal fentanyl patch. Int J Legal Med. 2007;121:147–51. doi:10.1007/s00414-006-0137-3.

    Article  PubMed  Google Scholar 

  30. Bound JP, Voulvoulis N. Household disposal of pharmaceuticals as a pathway for aquatic contamination in the United Kingdom. Environ Health Perspect. 2005;113:1705–11. doi:10.1289/ehp.8315.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cook SM, Vanduinen BJ, Love NG, Skerlos SJ. Life cycle comparison of environmental emissions from three disposal options for unused pharmaceuticals. Environ Sci Technol. 2012;46:5535–41. doi:10.1021/es203987b.

    Article  CAS  PubMed  Google Scholar 

  32. Becker JA, Ortner PM, Tullai-McGuinness S. Don’t rush to flush: safer pharmaceutical practices for hospice home care and home health nurses. Home Health Care Manag Pract. 2010;22:202–6. doi:10.1177/1084822309348696.

    Article  Google Scholar 

  33. U.S. Center for Disease Control, Understanding the epidemic, prescription drug overdose, (2015). http://www.cdc.gov/drugoverdose/epidemic/index.html (accessed November 24, 2015).

  34. Daughton CG. Eco-directed sustainable prescribing: feasibility for reducing water contamination by drugs. Sci Total Environ. 2014;493:392–404. doi:10.1016/j.scitotenv.2014.06.013.

    Article  CAS  PubMed  Google Scholar 

  35. Carballa M, Omil F, Lema JM. Comparison of predicted and measured concentrations of selected pharmaceuticals, fragrances and hormones in Spanish sewage. Chemosphere. 2008;72:1118–23. doi:10.1016/j.chemosphere.2008.04.034.

    Article  CAS  PubMed  Google Scholar 

  36. Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, et al. Clin Pharmacokinetics Metf ormin. 2011;50:81–98.

    Article  CAS  Google Scholar 

  37. Wisconsin Department of Natural Resource, Pharmaceuticals and personal care products in the environment, (2016). http://dnr.wi.gov/topic/healthwaste/pharm.html (accessed January 17, 2016).

  38. Corominas L, Foley J, Guest JS, Hospido A, Larsen HF, Morera S, et al. Life cycle assessment applied to wastewater treatment: state of the art. Water Res. 2013;47:5480–92. doi:10.1016/j.watres.2013.06.049.

    Article  CAS  PubMed  Google Scholar 

  39. U.S. Drug Enforcement Administration, 21 CFR Parts 1300, 1301, 1304, et al. Disposal of controlled substances, 2014.

  40. Supreme Court of the United States, Pharmaceutical Research and Manufacturers of America, et al., Petitioners v. County of Alameda, California, et al., (2014). http://www.supremecourt.gov/search.aspx?filename=/docketfiles/14-751.htm (accessed December 7, 2015).

  41. Glassmeyer ST, Hinchey EK, Boehme SE, Daughton CG, Ruhoy IS, Conerly O, et al. Disposal practices for unwanted residential medications in the United States. Environ Int. 2009;35:566–72. doi:10.1016/j.envint.2008.10.007.

    Article  CAS  PubMed  Google Scholar 

  42. Barlas S. Take-back programs opportunities for congress, liabilities for pharmacies. Pharmacol Ther. 2009;34:404.

    Google Scholar 

  43. Doerr-MacEwen NA, Haight ME. Expert stakeholders’ views on the management of human pharmaceuticals in the environment. Environ Manag. 2006;38:853–66. doi:10.1007/s00267-005-0306-z.

    Article  Google Scholar 

  44. Kotchen M, Kallaos J, Wheeler K, Wong C, Zahller M. Pharmaceuticals in wastewater: behavior, preferences, and willingness to pay for a disposal program. J Environ Manag. 2009;90:1476–82. doi:10.1016/j.jenvman.2008.10.002.

    Article  Google Scholar 

  45. State Prescription Drug Return, Reuse and Recycling Laws -NCSL, (2015). http://www.ncsl.org/research/health/state-prescription-drug-return-reuse-and-recycling.aspx (accessed November 29, 2015).

  46. Gibson K. Pharmaceuticals and personal care products (PPCPs): disposal, scientific, and regulatory challenges. Environ Qual Manag. 2010;20:39–48. doi:10.1002/tqem.20270.

    Article  Google Scholar 

  47. D.B. Stoddard, K. I., & Huggett, No Title, in: D.B.H. Bryan W. Brooks (Ed.), Hum Pharm Environ. Springer, New York, 2012: pp. 257–285.

  48. U.S. Food and Drug Administration. How to dispose of unused medicines. 2009; 1–2.

  49. Khetan SK, Collins TJ. Human pharmaceuticals in the aquatic environment: a challenge to green chemistry. Chem Rev. 2007;107:2319–64. doi:10.1021/cr020441w.

    Article  CAS  PubMed  Google Scholar 

  50. Lubick N. Opening the “green pharmacy”. Environ Sci Technol. 2008;42:8620–1. doi:10.1021/es802555w.

    Article  CAS  PubMed  Google Scholar 

  51. Rastogi T, Leder C, Kümmerer K. Re-designing of existing pharmaceuticals for environmental biodegradability: a tiered approach with β-blocker propranolol as an example. Environ Sci Technol. 2015; 150908080052000. doi:10.1021/acs.est.5b03051. This study is a recent example of developing a green pharmaceutical by redesigning propranolol to have increased biodegradability.

  52. Blair B, Nikolaus A, Hedman C, Klaper R, Grundl T. Evaluating the degradation, sorption, and negative mass balances of pharmaceuticals and personal care products during wastewater treatment. Chemosphere. 2015;134:395–401. doi:10.1016/j.chemosphere.2015.04.078.

    Article  CAS  PubMed  Google Scholar 

  53. Kawabata K, Sugihara K, Sanoh S, Kitamura S, Ohta S. Photodegradation of pharmaceuticals in the aquatic environment by sunlight and UV-A, -B and -C irradiation. J Toxicol Sci. 2013;38:215–23. doi:10.2131/jts.38.215.

    Article  CAS  PubMed  Google Scholar 

  54. Adams C, Brantner V. Estimating the cost of new drug development: is it really $802 million? Health Aff. 2006;25:420–8. doi:10.1377/hlthaff.25.2.420.

    Article  Google Scholar 

  55. Daughton CG, Ruhoy IS. Lower-dose prescribing: minimizing “side effects” of pharmaceuticals on society and the environment. Sci Total Environ. 2013;443:324–37. doi:10.1016/j.scitotenv.2012.10.092.

    Article  CAS  PubMed  Google Scholar 

  56. Dohle S, Campbell VEA, Arvai JL. Consumer-perceived risks and choices about pharmaceuticals in the environment: a cross-sectional study. Environ Health. 2013;12:45. doi:10.1186/1476-069X-12-45.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Lamichhane K, Babcock R. An economic appraisal of using source separation of human urine to contain and treat endocrine disrupters in the USA. J Environ Monit. 2012;14:2557. doi:10.1039/c2em30254c.

    Article  CAS  PubMed  Google Scholar 

  58. Borsuk ME, Maurer M, Lienert J, Larsen TA. Charting a path for innovative toilet technology using multicriteria decision analysis. Environ Sci Technol. 2008;42:1855–62. doi:10.1021/es702184p.

    Article  CAS  PubMed  Google Scholar 

  59. Larsen TA, Alder AC, Eggen RIL, Maurer M, Lienert J. Source separation: will we see a paradigm shift in wastewater handling? Environ Sci Technol. 2009;43:6121–5. doi:10.1021/es803001r.

    Article  CAS  PubMed  Google Scholar 

  60. Escher BI, Pronk W, Suter MJF, Maurer M. Monitoring the removal efficiency of pharmaceuticals and hormones in different treatment processes of source-separated urine with bioassays. Environ Sci Technol. 2006;40:5095–101. doi:10.1021/es060598w.

    Article  CAS  PubMed  Google Scholar 

  61. Lienert J, Güdel K, Escher BI. Screening method for ecotoxicological hazard assessment of 42 pharmaceuticals considering human metabolism and excretory routes. Environ Sci Technol. 2007;41:4471–8. doi:10.1021/es0627693.

    Article  CAS  PubMed  Google Scholar 

  62. Brack W, Altenburger R, Schüürmann G, Krauss M, López Herráez D, van Gils J, et al. The SOLUTIONS project: challenges and responses for present and future emerging pollutants in land and water resources management. Sci Total Environ. 2015;503–504:22–31. doi:10.1016/j.scitotenv.2014.05.143.

    Article  PubMed  Google Scholar 

  63. Leung HW, Jin L, Wei S, Tsui MMP, Zhou B, Jiao L, et al. Pharmaceuticals in tap water: human health risk assessment and proposed monitoring framework in China. Environ Health Perspect. 2013;121:839–46. doi:10.1289/ehp.1206244.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Verlicchi P, Galletti A, Petrovic M, Barceló D. Hospital effluents as a source of emerging pollutants: an overview of micropollutants and sustainable treatment options. J Hydrol. 2010;389:416–28. doi:10.1016/j.jhydrol.2010.06.005.

    Article  CAS  Google Scholar 

  65. Herrmann M, Olsson O, Fiehn R, Herrel M, Kümmerer K. The significance of different health institutions and their respective contributions of active pharmaceutical ingredients to wastewater. Environ Int. 2015;85:61–76. doi:10.1016/j.envint.2015.07.020.

    Article  CAS  PubMed  Google Scholar 

  66. Verlicchi P, Al Aukidy M, Zambello E. What have we learned from worldwide experiences on the management and treatment of hospital effluent?—an overview and a discussion on perspectives. Sci Total Environ. 2015;514:467–91. doi:10.1016/j.scitotenv.2015.02.020.

    Article  CAS  PubMed  Google Scholar 

  67. Metz F, Ingold K. Sustainable wastewater management: is it possible to regulate micropollution in the future by learning from the past? A policy analysis. Sustain. 2014;6:1992–2012. doi:10.3390/su6041992.

    Article  Google Scholar 

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  1. Colorado School of Public Health, Department of Environmental and Occupational Health, University of Colorado Denver, Aurora, CO, USA

    Benjamin D. Blair

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Blair, B.D. Potential Upstream Strategies for the Mitigation of Pharmaceuticals in the Aquatic Environment: a Brief Review. Curr Envir Health Rpt 3, 153–160 (2016). https://doi.org/10.1007/s40572-016-0088-x

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Keywords

  • Pharmaceuticals
  • Take-back
  • Green pharmaceuticals
  • Management
  • Regulation