Environmental Burden of Pharmaceutical Pollution A Guide for Health Care Professionals Dr. Joel Kreisberg, DC, MA

1. Environmental Burden of Pharmaceutical PollutionA Guide for Health Care ProfessionalsDr. Joel Kreisberg, DC, MA

2. The Problem Drug consumption is increasing. From 1993-2003, the number of prescriptions rose 70%1 Drug expenditures have increased, but data shows that, from 1994-2000, 75% of this increase in price was caused by increasing consumption3 The increase in drug use coincides with an increase in the amount of medications that enter into and contaminate the environment U.S. EPA Office of Research and Development�s Strategy Plan 2000 has named pharmaceuticals and personal care products (PPCPs) as one of the top five �emerging� contaminants affecting human and ecological health4 

3. Emerging contaminants Synthetic or naturally occurring chemicals or microorganisms Not commonly monitored in the environment Potential to enter the environment and cause known or suspected adverse ecological and/or human health effects May be new chemicals OR Release may have occurred for a long time, but only recently recognized as a potential problem OR New use of existing chemicals

4. Examples of emerging contaminants Pesticides Flame retardants Pharmaceuticals Personal care products Antibacterial compounds Surfactants Plasticizers

5. Emerging Evidence 2002 report from the U.S. Geological Survey5 concludes that U.S. waterways contain: 17alpha Ethynyl Estradiol Synthetic estrogen present in 16% of rivers in USGS study Median concentration 73 ng/l Effects at as low as 1 ng/l Vitellogenin production (feminization) in male fish Acetaminophen (24%) Steroids and hormones (16%) Diltiazem (13%) Codeine (11%) Antibiotics and antimicrobials (10%) Ibuprofen (10%)

6. Impacts of pharmaceuticals Wild Geese resistant to ampicillin, tetracycline, penicillin, and erythromycin6 concentrations of clofibric acid in the North Sea (Northern Europe) to be up to 7.8 ng/L 7 Diclofenac has been proven to be toxic to vultures, decimating populations in the Indian subcontinent due to its ubiquitous use in cattle.8

7. More Evidence Prozac and Luvox induced spawning in bivalves at significantly low concentrations.19 Fluoxetine enhances the release of ovary-stimulating hormones in crayfish.10 SSRIs elicit aggressive behavior in lobsters, causing subordinates to engage in fighting against the dominant member, and reducing the propensity to retreat.11 Concentrations of six sunscreen agents have been found in fish on par with DDT and PCBs.12

8. Pathways to Nature Directly into the sewage system Excreted medicine Unmetabolized parent compounds Partially metabolized compounds Altered compounds Unused or unwanted medicines Manufacturing metabolites Aquatic environment Landfill leachate

10. How Can Pharmaceutical Waste Enter The Environment? 95% of antibiotics are excreted unaltered into the environment13 54% of people throw medicines into the trash14 35% of people flush medicines down the toilet14 Wastewater treatment do not treat medicinal compounds

11. Characteristics of Pharmaceutical Waste Persistence Drugs are considered �pseudo-persistent� due to continuous presence in the environment Significant concentrations of barbiturate drugs in a tributary near a landfill, even though barbiturates had been replaced 30 years ago14 Bioaccumluation Increase in the concentration of a chemical in a biological organism over time, compared to the chemical's concentration in the environment. Ecotoxicity A lethal concentration of chemical 96 hours after exposure.15

12. Health of Ecology v Ecology of Health How the environment effects us! Research found that a mixture of 13 common medications found in drinking water inhibits cell growth and causes negative changes in human embryonic cells16 More research is needed!

13. Potential Toxicological Significance Potential additive effects from multiple agents sharing common mechanisms of action (MOA). Individual concentrations combine to exceed an effects level. Possible interactive effects, especially synergism, where combined action exceeds the sum of individual effects. Hormesis- Effects below purported NOELs. Paradoxical �U-shaped� does response curves.

14. Potential Toxicological Significance as a Result of: Dynamic Dose-Response. Toxicant-induced Loss of Tolerance (TILT): initial exposure sensitizes, and subsequent exposure levels below those previously tolerated trigger symptoms Comparatively little research performed at extremely low concentrations. Non-target species receptor repertoires not well characterized.

15. Christian Daughton PhD Biological Systems and Stressors Complex system- 4Ts Toxicant Totality Tolerance Trajectory Beyond single toxicant/ single organism toxicology

16. Pharmaceutical Waste and Medical Practices Medications are discontinued by physicians 27% of the time because they are no longer needed or suitable for the patient. In 2007, the elderly population will waste more than 1 billion dollars of drugs Reducing a prescription to a 28 day supply could reduce the need for discarding by as much as 30%.

17. Cradle to Cradle Medicine In theory, waste occurs when the prescription isn�t effective If we get to the point where we have no leftover drugs, will that lead to improved therapeutic outcomes? Learning about what is unused will improve the quality of medical care

18. What Physicians Can Do Do not prescribe more medications than can be used Prescribe starter packs and refill packs Review and regularly reassess the patient�s total consumption of medication Consider environmental impact when prescribing medications Learn more about which drugs have large environmental impacts Educate consumers about the importance of proper disposal of pharmaceutical waste

19. Green Pharmacy Program A proactive, voluntary holistic stewardship program Cradle-to-Cradle Product Stewardship All sectors involved with the production, distribution, prescribing, marketing, and consuming of medicines should be involved with proper disposal.

20. Green Pharmacy Manufacturing Sector Green Chemistry Reduce ecological footprint Reduce packaging Health Care System Hospitals Primary Care Hospice Pharmacies

21. Green Pharmacy Government and Law Enforcement Waste Management Agencies NGO- Environmental Organizations Consumers Who pays Pharmaceutical Industry Waste management industry Advanced Recycling Fee Medical Professionals

22. What everyone can do! Dispose of unused or unwanted medications at take-back sites Do NOT dispose of any medication down the toilet or in the trash Purchase drugs in small amounts, limiting expired medications Ask for medications with low environmental impact Encourage your health provider to take back unused and expired drugs Commit to health and wellness strategies to reduce your reliance on medications Donate to Teleosis� Green Pharmacy Pollution Prevention Campaign

23. References 1 Henry J. Kaiser Family Foundation  2 Chapman A., Oliver D. Pharmaceutical Waste Survey. http://govlink.org/hazwaste/publications/pharmaceuticalwastesurvey.pdf Accessed March 15, 2007. 3 Berndt, E., "Pharmaceuticals in U.S. Health Care: Determinants of Quantity and Price," Journal of Economic Perspectives, Vol. 16, 4, Fall 2002, pp. 45-66. 4 Daughton C, Ternes T. Pharmaceuticals and personal care product in the environment: agents of subtle change? Environmental Health Perspectives. 1999;107(Suppl 6): 907-943. 5 Kolpin, Dana et al. Pharmaceuticals, hormones and other organic wastewater contaminants in US streams, 1999-2000: a national reconnaissance. Environmental Science and Technology. 2002; 26: 1202-1211. Available at http://pubs.acs.org/journals/esthag/36/i06/pdf/es011055j.pdf Accessed June 5, 2006

24. References 6 Ash RJ, Mauch B, Moulder W, Morgan M. Antibiotic-resistant bacteria in U.S. rivers. Abstract no Q-383. In Abstracts of the 99th General Meeting of the American Society for Microbiology (May 30-June 3):610. Chicago, IL. 7 Buser H-R, M�ller MD, Theobald N. Occurrence of the pharmaceutical drug clofibric acid and the herbicide mecoprop in various Swiss lakes and in the North Sea. Environmental Science and Technology. 1998;32:188-192. 8. Kreisberg, J. Ecological healing and the web of life. Explore: The Journal of Science and Healing. 2005; 1(2):133-135. 9. Fong PP. Zebra mussel spawning is induced in low concentrations of putative serotonin reuptake inhibitors. The Biological Bulletin. 1998;194:143-149.

25. References 11 Huber R, Smith K, Delago A, Isaksson K, Kravitz EA. Serotonin and aggressive motivation in 10 . Kulkarni GK, Nagabhushanam R, Amaldoss G, Jaiswal RG, Fingerman M. In vivo stimulation of ovarian development in the red swamp crayfish Procambarus clarkia (Girard) by 5-hydroxytryptamine. Invertebrate Reproduction and Development. 1992;21(3):231-240. crustaceans: altering the decision to retreat. Proceedings of the National Academy of Science; 1997; 94:5939-5942. 12 Nagtegaal M, Ternes TA, Baumann W, Nagel R. Nachweis von UV-Filtersubstanzen in Wasser und Fischen aus dem Meerfelder Maar in der Eifel. Detection of UV-sunscreen agents in water and fish of the Meerfelder maar the Eifel Germany. UWSF-Z f�r Umweltchem �kotox. 1997;9(2):79-86. 13 Boehringer S. What�s the Best Way to Dispose of Medications? Pharmacists�/Prescriber�s letter (2004).

26. References 14 Choi, C.O. Pollution in Solution, Drug-Resistance DNA as the Latest Freshwater Threat. Scientific American. Jan 2007: 22-23. 15 Wennmalm A, Gunnarson B.(2005) Public Health Care of Water Pollution with Pharmaceuticals: Environmental Classification and Analysis of Pharmaceutical Residues in Sewage Water. Drug Information Journal 16 Pomati F, Castiglioni S, Zuccato E, Fanelli R, Vigetti D, Rosseti C, Calamari D. Effects of a complex mixture of therapeutic drugs at environmental levels on human embryonic cells. Environmental Science & Technology. 2006; 40(7):2442-2447. 17. Donn, J, Mendoza, M & Pritchard, J. AP Probe Finds Drugs in Drinking Water, 2008 http://ap.google.com/article/ALeqM5hGsoyElv4ZL879LW6z2aZS0Pix7AD8VA14500 (accessed March 25,2008)