Drug Disposal & Stewardship:
Ramifications for the Environment and Human Health
Overview of research conducted at the U.S. EPA, Office of Research and Development (ORD),
National Exposure Research Laboratory (NERL), Environmental Sciences Division (ESD),
Las Vegas, Nevada
The entry to the environment of the active pharmaceutical ingredients (APIs) used in pharmaceutical products is a complex issue. A sufficient understanding of APIs as contaminants with respect to possible impacts on environmental and human health requires assessment of the many facets of the risk paradigm - - ranging from sources, fate and transport, exposure, biological effects, and mitigation. A major aspect of the risk paradigm that has received comparatively little attention in the scientific literature is that of environmental stewardship and pollution prevention strategies for reducing entry of APIs to the environment, with the ultimate intent to minimize exposures (both chronic and acute) for humans and wildlife alike.
A long-standing assumption has been that APIs enter the environment as trace contaminants primarily as a result of their excretion via urine and feces. Disposal of unwanted, leftover medications by flushing into sewers has been considered a minor secondary route - - one that does not contribute substantially to overall environmental loadings.
This project had multiple goals, the major ones being: (i) Define the scope of the scientific issues surrounding the disposal or accidental entry of pharmaceuticals to the environment; (ii) Identify the numerous sources and routes where drugs are used and accumulate in society - - eventually requiring disposal or leading to diversion and accidental poisonings; (iii) Develop a new methodology for accurately identifying and quantifying all APIs accumulated by a particular sub-population in a defined locale; (iv) Develop an approach for predicting which drugs hold the greatest potential for disposal and entry to the environment, and which drugs pose the greatest risks with respect to poisonings; (v) Define the processes that control and drive the consumption, accumulation, and disposal of human pharmaceuticals; and (vi) Identify those aspects of the health care industry and the practice of medicine that could lessen the accumulation of drugs leading to disposal - - stewardship opportunities for pollution prevention and source reduction.
A major long-term objective was to determine whether the accumulation of drugs awaiting disposal is a significant factor in two key, unanswered questions. First, do drugs awaiting disposal contribute significantly to diversion, abuse, or poisonings? Second, do these drugs, once disposed of, make a significant contribution to the overall loadings of drug residues present in the environment?
A major question not yet answered is the overall significance of drug disposal to sewers as a contributing factor for environmental residues of APIs. The project developed the first evidence-based approach for addressing questions surrounding drug disposal. The new methodology involves collecting the drug inventory and disposal data maintained by many coroner offices as a result of decedent investigations. This approach could lead to an eventual assessment of the relative significance or impact of drug disposal versus excretion, bathing, and other routes of API entry to the environment.
This project has led to the first conceptualization of an environmental stewardship framework for optimizing the use of pharmaceuticals throughout the healthcare system. Implementing some well-targeted actions in the delivery of health care could have profound, far-reaching benefits for human and ecological health, both of which are intimately linked. By integrating ecological concerns with conventional pharmacovigilance programs (which are designed for detection, assessment, and prevention of adverse effects from the use of medications), a more holistic system for care of both human health and the environment could be created - - one termed pharmEcovigilance. Its implementation could reduce the cost of health care, improve therapeutic outcomes, and lessen unintentional acute and chronic exposures of humans and wildlife.
A pharmEcovigilance program would focus on the numerous points along the network spanning from manufacturers to patients - - where medications are designed, packaged, prescribed, dispensed, and consumed - - and where numerous processes and procedures could be redesigned to ensure optimal therapeutic outcomes by optimizing drug usage. The ultimate objective and measure of success would be the degree to which medications are fully consumed (reducing leftovers) while maintaining or improving therapeutic outcomes. Such a program could lead to a more efficient, optimized, sustainable healthcare system, resulting in a cleaner environment and improved, less-costly treatment outcomes. An ultimate goal would be to change the human and healthcare processes that lead to excess drug accumulation in the first place - - to eliminate accumulation (and the consequent need for disposal) altogether. If new approaches to medical care were developed that eliminated leftover drugs, it is possible that the consequent environmental residues could be reduced, therapeutic endpoints or outcomes could improve, healthcare expenses could be lessened, and human morbidity and mortality (due to abusive and addictive usage, and poisonings from diverted, leftover drugs) could decline. Reducing, minimizing, or eliminating leftover drugs represents a very significant opportunity to improve both ecological and human health.
The project also examined the role of previously under-appreciated secondary routes by which APIs are released to the environment - - two of these being sweating and bathing. This included an aspect of drug exposure that has been largely ignored - - unintentional human exposure by direct and indirect dermal transfer. Understanding these secondary routes is especially important from the perspective of pollution prevention, as actions can be more easily targeted for reducing the environmental impact of APIs than with the route of direct excretion, as well as for reducing the incidence of unintentional and purposeful poisonings of humans and pets and for improving the quality and cost-effectiveness of healthcare. Overall unintentional exposure to APIs for humans via these previously unrecognized secondary routes is possibly more important than exposure to all trace residues of APIs recycled from the environment via drinking water or foods.
The data revealed some under-appreciated hazards associated with the handling of medications as recommended in the initial federal guidance for preparing unwanted leftovers for disposal. The findings have relevance for the refinement of guidelines regarding the disposal of certain drugs.
This project was the focus and outgrowth of a doctoral dissertation by an EPA Student Volunteer (Ilene Ruhoy, MD) engaged in research toward a doctorate in Environmental Studies at the University of Nevada, Las Vegas, working under the technical guidance of Dr. Christian Daughton (EPA, Las Vegas). As an MD, Dr. Ruhoy brought valuable knowledge and perspective from the medical community. Dr. Ruhoy is currently a Pediatric Neurology Resident at Seattle Children’s Hospital, University of Washington, Seattle, WA (email@example.com).
The project has directly resulted in over 8 articles in peer-reviewed journals, 8 invited book chapters, a doctoral dissertation, a major EPA report, and over a dozen invited presentations at scientific conferences. These publications and several other miscellaneous outputs are listed below. As an historical aside, the project originated from prior work that first set forth the idea of the Green Pharmacy, previously published in a 2-part monograph in 2003 (see references below).
Drug disposal and its attendant pollution of the environment occupies the interface between the practice of medicine and our environment. As such, its study is truly transdisciplinary - - involving an understanding of the many aspects of healthcare and environmental science. The ultimate outcome being sought by this project is to catalyze a dialog and collaborations among the medical and healthcare communities with those involved in environmental science - - in altering how medications are prescribed and used, thereby reducing the need for drug disposal and minimize other routes of API entry to the environment.
The following EPA products regarding pharmaceutical stewardship, pollution prevention, and disposal have been completed as of January 2013:
EPA PUBLICATIONS (reverse chronological order)
Daughton CG and Ruhoy IS. "Lower-Dose Prescribing: Minimizing 'Side Effects' of Pharmaceuticals on Society and the Environment" Science of the Total Environment 2013, 443:324-337; doi:10.1016/j.scitotenv.2012.10.092; available (OpenAccess; including supplementary data):
Daughton CG "Comment on "Life cycle comparison of environmental emissions from three disposal options for unused pharmaceuticals"," Environmental Science & Technology, 2012, 46(14):8519-8520; doi: 10.1021/es301975v; available:http://pubs.acs.org/doi/pdfplus/10.1021/es301975v
[note: this paper is a Correspondence/Comment in critique of the ES&T paper: Cook SM, VanDuinen BJ, Love NG, and Skerlos SJ. "Life Cycle Comparison of Environmental Emissions from Three Disposal Options for Unused Pharmaceutical." Environ. Sci. Technol. 2012, 46(10):5535-5541; doi:10.1021/es203987b.]
Daughton CG and Ruhoy IS. "Green Pharmacy & PharmEcovigilance: Prescribing and the Planet," Expert Review of Clinical Pharmacology, 2011, 4(2):211-232; doi: 10.1586/ecp.11.6; available:
Daughton CG "Drugs and the Environment: Stewardship & Sustainability," (PDF, 196 pp., 4.75MB, about PDF) National Exposure Research Laboratory, Environmental Sciences Division, US EPA, Las Vegas, NV; NERL-LV-ESD 10/081, EPA/600/R-10/106; 12 September, 2010, 196 pp; available:
Daughton CG and Ruhoy IS. "Reducing the Ecological Footprint of Pharmaceutical Usage: Linkages between Healthcare Practices and the Environment," In: Green and Sustainable Pharmacy, Klaus Kümmerer and Maximilian Hempel (Eds.), Springer, Chapter 6, VIII, 2010, pages 77-102; ISBN: 978-3-642-05198-2; available:
Daughton CG and Ruhoy IS. "Pharmaceuticals in the Environment - Why Should We Care?" In: Pharmaceuticals in the Environment: Current Knowledge and Need Assessment to Reduce Presence and Impact, B. Roig (Ed.), IWA Publishing, London, UK, 2010, Foreword pages xiii-xvii; ISBN: 9781843393146; pre-print: http://www.epa.gov/esd/bios/daughton/IWA-2010.pdf;
Daughton CG "Chemicals from the Practice of Healthcare: Challenges and Unknowns Posed by Residues in the Environment," Environmental Toxicology & Chemistry, 2009, 28(12):2490-2494; doi:10.1897/09-138.1; available:
Daughton CG and Ruhoy IS. "Environmental Footprint of Pharmaceuticals: The Significance of Factors Beyond Direct Excretion to Sewers," Environmental Toxicology & Chemistry, 2009, 28(12):2495-2521; doi:10.1897/08-382.1; available:
Daughton CG and Ruhoy IS. "Pharmaceuticals and Sustainability: Concerns and Opportunities Regarding Human Health and the Environment," In: A Healthy Future - Pharmaceuticals in a Sustainable Society, collaborative publication of Apoteket AB, MistraPharma, and Stockholm County Council, Sweden; Chapter 1, pp 14-39, 2009; ISBN: 2184-01; available:
Glassmeyer ST, Hinchey EK, Boehme SE, Daughton CG, Ruhoy IS, Conerly O, Daniels RL, Lauer L, McCarthy M, Nettesheim TG, Sykes K, and Thompson VG. "Disposal Practices for Unwanted Residential Medications in the United States," Environ. Internat., 2009, 35(3): 566-572; doi:10.1016/j.envint.2008.10.007.
Daughton CG and Ruhoy IS "PharmEcovigilance: Aligning Pharmacovigilance with Environmental Protection" In: An Introduction to Environmental Pharmacology, SZ Rahman, M Shahid, and V Gupta (Eds.), Ibn Sina Academy, Aligarh, India; 2008, Chapter 1 (Introductory Overview), pp 21-34; ISBN # 978-81-906070-5-6; available:
Daughton CG and Ruhoy IS "Accumulation and disposal of leftover medications: A key aspect of pharmEcovigilance" In: An Introduction to Environmental Pharmacology, SZ Rahman, M Shahid, and V Gupta (Eds.), Ibn Sina Academy, Aligarh, India; 2008, Chapter 5, pp 101-107; ISBN # 978-81-906070-5-6; available:
Daughton CG and Ruhoy IS "The Afterlife of Drugs and the Role of PharmEcovigilance," Drug Safety, 2008, 31(12):1069-1082; doi: 10.2165/0002018-200831120-00004; reprint available on request.
Ruhoy IS and Daughton CG "Beyond the Medicine Cabinet: An Analysis of Where and Why Medications Accumulate," Environ. Internat., 2008, 34(8):1157-1169; doi:10.1016/j.envint.2008.05.002; available:
Daughton CG "Pharmaceuticals as Environmental Pollutants: the Ramifications for Human Exposure," In: International Encyclopedia of Public Health, Kris Heggenhougen and Stella Quah (Eds.), Vol. 5, Oxford: Academic Press; 2008, pp. 66-102; DOI: 10.1016/B978-012373960-5.00403-2; reprint available on request; pre-galley version:
Daughton, C.G. "Drug Usage and Disposal: Overview of Environmental Stewardship and Pollution Prevention (with an emphasis on activities in the Federal Government)," US EPA, Office of Research and Development, Environmental Sciences Division, Las Vegas, Nevada, 23 pp, 15 October 2008; prepared for: Research Triangle Environmental Health Collaborative - an Environmental Health Summit, "Pharmaceuticals in Water: What We Know, Don't Know, and Should Do," 10-11 November 2008, North Carolina Biotechnology Center, Research Triangle Park, North Carolina; available:
Ruhoy, Ilene Sue "Examining Unused Pharmaceuticals in the Environment," Ph.D. Dissertation, University of Nevada, Las Vegas, Dept. Environmental Studies; August 2008, publication number 3352183; ISBN 9781109091083; 153 pp; accessible:
Ruhoy IS and Daughton CG "Types and Quantities of Leftover Drugs Entering the Environment via Disposal to Sewage - Revealed by Coroner Records," Sci. Total Environ., 2007, 388(1-3):137-148; doi 10.1016/j.scitotenv.2007.08.013; available:
Daughton CG "Pharmaceuticals in the Environment: Sources and Their Management," Chapter 1, 1-58, In: Analysis, Fate and Removal of Pharmaceuticals in the Water Cycle (M. Petrovic and D. Barcelo, Eds.), Wilson & Wilson's Comprehensive Analytical Chemistry series (D. Barcelo, Ed.), Volume 50, Elsevier Science; 2007, 564pp; doi:10.1016/S0166-526X(07)50001-2; available:
Daughton, C.G. "Cradle-to-Cradle Stewardship of Drugs for Minimizing Their Environmental Disposition while Promoting Human Health. I. Rationale for and Avenues toward a Green Pharmacy," Environ. Health Perspect. 2003, 111(5):757-774; doi: 10.1289/ehp.5947; available:
Daughton, C.G. "Cradle-to-Cradle Stewardship of Drugs for Minimizing Their Environmental Disposition while Promoting Human Health. II. Drug Disposal, Waste Reduction, and Future Direction," Environ. Health Perspect. 2003, 111(5):775-785; doi: 10.1289/ehp.5948; available:
Daughton CG and Ruhoy IS "PharmEcovigilance & Stewardship: Reducing Human and Ecological Exposure from Pharmaceutical Residues," illustrated poster prepared for the "Environmental Sciences Division Peer Review," 14 May 2009, National Exposure Research Laboratory, Office of Research and Development, US EPA, Las Vegas, NV, Session 5: Water Quality – Stressor/Receptor Characterization, poster #SRC-3; available:
Ruhoy IS and Daughton CG "Pharmaceutical Disposal and the Environment," U.S. EPA, Las Vegas, NV; illustrated poster, December 2007, NERL-LV-ESD-07-132; available:
Ruhoy IS and Daughton CG "Disposal as a Source of Pharmaceuticals in the Environment," U.S. EPA, Las Vegas, NV; illustrated poster, December 2007; NERL-LV-ESD-07-129; available:
Daughton CG "The Environmental Life Cycle of Pharmaceuticals," illustration, US EPA, NERL, Las Vegas, NV, 2 December 2006; available:
[note - published in: Daughton CG "Pharmaceuticals as Environmental Pollutants: the Ramifications for Human Exposure," In: International Encyclopedia of Public Health, Kris Heggenhougen and Stella Quah (Eds.), Vol. 5, San Diego: Academic Press; 2008, pp. 66-102].
Contact (and requests for reprints):
Christian Daughton at firstname.lastname@example.org