This document reviews current research on pharmaceutical residues found in water sampling studies. It discusses the various sources of pharmaceuticals entering the environment from improper storage, disposal, and prescribing of leftover drugs. The document examines the potential ecological and human health impacts of long-term exposure to low levels of multiple active pharmaceutical ingredients found in the environment.

1. Pharmaceutical In the Environment: An Evidence-based Review Ilene S. Ruhoy, M.D., PhD Director, Institute for Environmental Medicine Touro University Nevada Henderson, Nevada 89014 Ilene.ruhoy@tun.touro.edu Source: US Environmental Protection Agency. Paul Horn, Union Tribute. Retrieved from: http://www.flickr.com/photos/cooljerk/219637528/#/

2. Course Objectives 1 Review current research on pharmaceutical residues found in water sampling studies. 2 Understand the various sources of pharmaceuticals in the environment. 3 4 Discuss the ecological impact of pharmaceuticals in the environment. Examine the potential for human health impact from exposure to pharmaceutical residues.

3. Sections Pharmaceuticals as Chemicals Significance of long-term exposure to multiple APIs Evidence for ecotoxity Environmental Impact of Disposal PharmEcovigilance Reducing Unused Pharmaceuticals Conclusion

4. Pharmaceuticals as Chemicals

5. Stockpiling & improper storage Leftover Drugs Imprudent prescribing & patient use Imprudent disposal Residues recycled from environment Wasted healthcare resources Poisonings

6. The Chemical Universe We live in a chemical sea of continually changing composition – comprising both anthropogenic and naturally occurring chemical stressors. Unlike biota, chemical pollutants have no boundaries in their global distribution – “everything is everywhere,” only the concentrations vary.

8. ¼ million inventoried or regulated by numerous government bodies worldwide

9. Representing:0.7% of commercially available0.5% of the known chemicals.

10. 12,000new substances are added each day.* Indexed by the American Chemical Society's Chemical Abstracts Service in their CAS Registry; excluding bio-sequences such as proteins and nucleotides: http://www.cas.org/expertise/cascontent/registry/regsys.html

11. The Chemical Universe The largest virtual chemical database yet reported comprises small drug-like molecules – a total of over 977,000,000 structures (Blum and Reymond, 2009). Restricted to organic molecules containing fewer than 14 atoms of C, N, O, and S (and limited types of Cl-substituted molecules). Excluded likely substituents such as F, Br, I, P, Si, metals, and most Cl. Database represents the enormously large numbers of chemicals that could possibly be synthesized just from a very limited spectrum of types of elements and numbers of atoms. Source: Blum, L. C., and J.-L. Reymond. 2009. 970 Million Druglike Small Molecules for Virtual Screening in the Chemical Universe Database GDB-13. J. Am. Chem. Soc. 131 (25):8732-8733.

13. Over 1,460 FDA-approved small-molecule APIs(oral >80, parenteral >420, topical >270)

16. The combinedactions, behaviors, and activities of individuals.

17. The extensive interconnections and feedback loops between humans and the environment.

19. Diagnostic agents(e.g., X-ray contrast media)

20. “Nutraceuticals” (bioactive food supplements such as huperzine A)

21. And other consumer chemicals, such as fragrances (e.g., musks) and sun-screen agents (e.g., 4-methylbenzylidene camphor; octocrylene)

23. Available: http://www.epa.gov/nerlesd1/chemistry/pharma/image/drawing.pdf