Cradle-to-cradle stewardship of drugs for minimizing their environmental disposition while promoting human health. I. Rationale for and avenues toward a green pharmacy.

Since the 1980s, the occurrence of pharmaceuticals and personal care products (PPCPs) as trace environmental pollutants, originating primarily from consumer use and actions rather than manufacturer effluents, continues to become more firmly established. Although PPCPs typically have been identified in surface and ground waters, some are also undoubtedly associated with solid phases such as suspended particulates, sediments, and sewage sludges, despite their relatively high affinity for water. Often amenable to degradation, their continual introduction to waste-receiving waters results from their widespread, continuous, combined use by individuals and domestic animals, giving PPCPs a "pseudo-persistence" in the environment. Little is known about the environmental or human health hazards that might be posed by chronic, subtherapeutic levels of these bioactive substances or their transformation products. The continually growing, worldwide importance of freshwater resources, however, underscores the need for ensuring that any aggregate or cumulative impacts on (or from) water supplies are minimized. Despite the paucity of effects data from long-term, simultaneous exposure at low doses to multiple xenobiotics (particularly non-target-organism exposure to PPCPs), a wide range of proactive actions could be implemented to reduce or minimize the introduction of PPCPs to the environment. Most of these actions fall under what could be envisioned as a holistic stewardship program--overseen by the health care industry and consumers alike. Significantly, such a stewardship program would benefit not just the environment; additional, collateral benefits could automatically accrue, including reducing consumers' medication expenses and improving patient health and consumer safety. In this article, the first of a two-part mini-monograph describing the "green pharmacy," I focus initially on the background behind the imperative for an ecologically oriented stewardship program for PPCPs. I then present a broad spectrum of possible source control/reduction actions, controlled largely by the health care industry, that could minimize the disposition of PPCPs to the environment. This two-part mini-monograph attempts to capture cohesively for the first time the wide spectrum of actions available for minimizing the release of PPCPs to the environment. A major objective is to generate an active dialog or debate across the many disciplines that must become actively involved to design and implement a successful approach to life-cycle stewardship of PPCPs.

[1]  Robert L. Swain,et al.  National Association of Boards of Pharmacy , 1954 .

[2]  E. Lorenz Deterministic nonperiodic flow , 1963 .

[3]  W. Odum,et al.  Environmental Degradation and the Tyranny of Small Decisions , 1982 .

[4]  David Friedman,et al.  The Resource Conservation and Recovery Act , 1984 .

[5]  C. S. Holling Resilience of ecosystems: local surprise and global change. , 1985 .

[6]  Carl Rogers,et al.  AIDS Among Drug Users in Europe: Second Review. Copenhagen: WHO Regional Office For Europe. , 1994, British Journal of Psychiatry.

[7]  Gene Bazan Our Ecological Footprint: Reducing Human Impact on the Earth , 1997 .

[8]  P. Corey,et al.  Incidence of Adverse Drug Reactions in Hospitalized Patients , 2012 .

[9]  C. A. Smith RATIONALE FOR INCLUSION OF CRITERIA FOR PROPER DISPOSAL OF MONOGRAPH PHARMACEUTICAL PREPARATIONS BASED ON THE RESOURCE CONSERVATION AND RECOVERY ACT , 1999 .

[10]  J. Stoker,et al.  The Department of Health and Human Services. , 1999, Home healthcare nurse.

[11]  T. Ternes,et al.  Pharmaceuticals and personal care products in the environment: agents of subtle change? , 1999, Environmental health perspectives.

[12]  Tamar Terzian Direct-to-Consumer Prescription Drug Advertising , 1999, American Journal of Law & Medicine.

[13]  Organización Mundial de la Salud Guidelines for safe disposal of unwanted pharmaceuticals in and after emergencies , 1999 .

[14]  Canary Wharf,et al.  The European Agency for the Evaluation of Medicinal Products Evaluation of Medicines for Human Use , 2000 .

[15]  L. Greene Controversy swirls around toilet-to-tap project. , 2000, Environmental health perspectives.

[16]  J. Muñoz-Bellido,et al.  Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors. , 2000, International journal of antimicrobial agents.

[17]  U. Epa,et al.  Office of Pollution Prevention and Toxics , 2000 .

[18]  D. Handley,et al.  Dose-Response Evaluation of Levalbuterol Versus Racemic Albuterol in Patients with Asthma , 2000, The Journal of asthma : official journal of the Association for the Care of Asthma.

[19]  J. Thornton,et al.  Beyond Risk: An Ecological Paradigm to Prevent Global Chemical Pollution , 2000, International journal of occupational and environmental health.

[20]  Carola Hanisch,et al.  Is extended producer responsibility effective? , 2000, Environmental science & technology.

[21]  G. Cappiello,et al.  Hygienic aspects related to burial , 2000 .

[22]  L L Needham,et al.  Levels of seven urinary phthalate metabolites in a human reference population. , 2000, Environmental health perspectives.

[23]  R. Arole Community based health and development: the Jamkhed experience , 2001 .

[24]  Alastair Baker,et al.  Crossing the Quality Chasm: A New Health System for the 21st Century , 2001, BMJ : British Medical Journal.

[25]  Leon Mann,et al.  The Innovation Imperative , 2001 .

[26]  Christian G. Daughton,et al.  Pharmaceuticals and personal care products in the environment , 2001 .

[27]  J. Farman,et al.  Late lessons from early warnings: the precautionary principle 1896-2000 , 2002 .

[28]  G. Reid,et al.  Can bacterial interference prevent infection? , 2001, Trends in microbiology.

[29]  Christian G. Daughton,et al.  Illicit Drugs in Municipal Sewage: Proposed New Nonintrusive Tool to Heighten Public Awareness of Societal Use of Illicit-Abused Drugs and Their Potential for Ecological Consequences , 2001 .

[30]  P Slovic,et al.  The risk game. , 2001, Journal of hazardous materials.

[31]  E. Oren,et al.  Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. , 2001, JAMA.

[32]  K. Shen,et al.  Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low-dose naltrexone, unmasking potent opioid analgesia , 2001, Brain Research.

[33]  Christian G. Daughton Literature Forensics? Door to What Was Known but Now Forgotten☆☆☆ , 2001 .

[34]  L. Goldman,et al.  Technical report: mercury in the environment: implications for pediatricians. , 2001, Pediatrics.

[35]  J. Drewes,et al.  Concerns about Pharmaceuticals in Water Reuse, Groundwater Recharge, and Animal Waste , 2001 .

[36]  R. Velagaleti,et al.  Regulatory Oversight for the Environmental Assessment of Human and Animal Health Drugs: Environmental Assessment Regulations for Drugs , 2001 .

[37]  D. Epel,et al.  Multidrug-Multixenobiotic Transporters and Their Significance with Respect to Environmental Levels of Pharmaceuticals and Personal Care Products , 2001 .

[38]  Juan R. Granja,et al.  Antibacterial agents based on the cyclic d,l-α-peptide architecture , 2001, Nature.

[39]  P. Fong Antidepressants in Aquatic Organisms: A Wide Range of Effects , 2001 .

[40]  Christian G. Daughton,et al.  Pharmaceuticals and Care Products in the Environment: Scientific and Regulatory Issues , 2001 .

[41]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. , 2001, Advanced drug delivery reviews.

[42]  D. Christensen Medicinal mimicry: Sometimes, placebos work—but how? , 2001 .

[43]  M Maurer,et al.  Re-engineering the toilet for sustainable waste water management. , 2001, Environmental science & technology.

[44]  null null,et al.  2001 Report Card for America's Infrastructure , 2001 .

[45]  Michael Berry,et al.  Office of National Drug Control Policy , 2002 .

[46]  B. Levin,et al.  Antibiotics in agriculture: When is it time to close the barn door? , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[47]  A. Leuchter,et al.  Changes in brain function of depressed subjects during treatment with placebo. , 2002, The American journal of psychiatry.

[48]  Stu Borman In situ click chemistry , 2002 .

[49]  Paula Rochon,et al.  Improving the quality of medication use in elderly patients: a not-so-simple prescription. , 2002, Archives of internal medicine.

[50]  Hiroaki Suga,et al.  A tRNA aminoacylation system for non-natural amino acids based on a programmable ribozyme , 2002, Nature Biotechnology.

[51]  B. Shoichet,et al.  A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. , 2002, Journal of medicinal chemistry.

[52]  Frcp,et al.  Azithromycin for Acute Bronchitis , 2002 .

[53]  N. Kerse,et al.  Do delayed prescriptions reduce the use of antibiotics for the common cold? A single-blind controlled trial. , 2002, The Journal of family practice.

[54]  P. Maurette,et al.  [To err is human: building a safer health system]. , 2002, Annales francaises d'anesthesie et de reanimation.

[55]  Hans Söderlund,et al.  Antibody-Based Bio-Nanotube Membranes for Enantiomeric Drug Separations , 2002, Science.

[56]  R. Velagaleti,et al.  Impact of current good manufacturing practices and emission regulations and guidances on the discharge of pharmaceutical chemicals into the environment from manufacturing, use, and disposal. , 2002, Environmental health perspectives.

[57]  D. Rapport The Health of Ecology and the Ecology of Health , 2002 .

[58]  M. DiCarlo,et al.  How should a fever mercury thermometer be disposed of ? A survey of those likely to be asked. , 2002, Pediatrics.

[59]  Roman Frigg,et al.  Ubiquity. The Science of History ... Or Why The World is Simpler Than We Think , 2002 .

[60]  William McDonough,et al.  Cradle to Cradle: Remaking the Way We Make Things , 2002 .

[61]  R. Renner Do cattle growth hormones pose an environmental risk? , 2002, Environmental science & technology.

[62]  Disciplinary Committee,et al.  Royal Pharmaceutical Society of Great Britain , 2002 .

[63]  Stephen R. Johnson,et al.  Molecular properties that influence the oral bioavailability of drug candidates. , 2002, Journal of medicinal chemistry.

[64]  T. Heberer Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data. , 2002, Toxicology letters.

[65]  Joy Melnikow,et al.  Reporting number needed to treat and absolute risk reduction in randomized controlled trials. , 2002, JAMA.

[66]  E. Berndt,et al.  Promotion of prescription drugs to consumers. , 2002, The New England journal of medicine.

[67]  B. Beale Probiotics: Their tiny worlds are under scrutiny , 2002 .

[68]  D. Dietrich,et al.  Hot spot pollutants: pharmaceuticals in the environment. , 2004, Toxicology letters.

[69]  K. Chopra,et al.  Probiotics: potential pharmaceutical applications. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[70]  Stu Borman IN SITU CLICK CHEMISTRY: Templating strategy offers potential route to new drugs and other functional compounds , 2002 .

[71]  J. Straub Environmental risk assessment for new human pharmaceuticals in the European Union according to the draft guideline/discussion paper of January 2001. , 2002, Toxicology letters.

[72]  Terri Damstra,et al.  Global assessment of the state-of-the-science of endocrine disruptors , 2002 .

[73]  J. Alper Breaching the Membrane , 2002, Science.

[74]  M. I C H A E,et al.  Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999-2000: A National Reconnaissance , 2002 .

[75]  R Otterpohl,et al.  Options for alternative types of sewerage and treatment systems directed to improvement of the overall performance. , 2002, Water science and technology : a journal of the International Association on Water Pollution Research.

[76]  Jean Gayton Carroll,et al.  Crossing the Quality Chasm: A New Health System for the 21st Century , 2002 .

[77]  A. Evans,et al.  Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial , 2002, The Lancet.

[78]  B. Harder Germs that do a body good: Bacteria might someday keep the doctor away , 2002 .

[79]  J. Emanuel,et al.  Breaking down the barriers , 2002, Nature.

[80]  P. Kay,et al.  Review of Veterinary Medicines in the Environment , 2002 .

[81]  M. Magnani,et al.  Erythrocyte-mediated delivery of drugs, peptides and modified oligonucleotides , 2002, Gene Therapy.

[82]  N. Greenspan Not-so-intelligent design , 2002 .

[83]  C. Daughton Environmental stewardship and drugs as pollutants , 2002, The Lancet.

[84]  B. Sanders,et al.  Cross-shelf transport at Huntington Beach. Implications for the fate of sewage discharged through an offshore ocean outfall. , 2002, Environmental science & technology.

[85]  Wayne G. Landis,et al.  Uncertainty in the Extrapolation from Individual Effects to Impacts upon Landscapes , 2002 .

[86]  T. Strandberg,et al.  Inappropriate drug prescribing in home-dwelling, elderly patients: a population-based survey. , 2002, Archives of internal medicine.

[87]  Simon Webb,et al.  Exposure simulation for pharmaceuticals in European surface waters with GREAT-ER. , 2002, Toxicology letters.

[88]  David L. Smith,et al.  Animal antibiotic use has an early but important impact on the emergence of antibiotic resistance in human commensal bacteria , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[89]  C. Daughton Cradle-to-cradle stewardship of drugs for minimizing their environmental disposition while promoting human health. II. Drug disposal, waste reduction, and future directions. , 2002, Environmental health perspectives.

[90]  E. Dooley National Council for Science and the Environment. (Forum) , 2003 .

[91]  Effects Oil in the Sea III: Inputs, Fates, and Effects , 2003 .

[92]  H. Blutstein A forgotten pioneer of sustainability , 2003 .

[93]  Christine M. Coussens,et al.  Environmental health indicators : bridging the chasm of public health and the environment : workshop summary , 2004 .

[94]  Westone,et al.  Home Page , 2004, 2022 2nd International Conference on Intelligent Cybernetics Technology & Applications (ICICyTA).

[95]  David Gee,et al.  LATE LESSONS FROM EARLY WARNINGS , 2004 .

[96]  J. Weissman,et al.  Promoting Appropriate Antibiotic Use in the Community , 2005 .