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</o:shapelayout></xml><![endif]--></head><body lang=EN-US link=blue vlink=purple><div class=WordSection1><p class=MsoNormal>Before the “humorous” exchanges took over last week, Fred Miller asked how consuming dilute levels of substances can cause ills while consuming higher concentrations is considered therapeutic. This gets to the real heart of matter. Should we spend lots of time worrying about ALL pharmaceutical contamination in the environment or should we be working to require Pharmaceutical companies to provide information about the environmental impact of their drugs and not just their therapeutic impact on the patient. With correct information about negative tox for low concentration drugs on non-target species, we could better concentrate our resources on the drugs that will cause the greatest trouble at low doses for species most likely to be injured. We also need to know not only which drugs leave a patient’s body in significant quantities but also which ones 1) are not destroyed by activated sludge in WWT, 2) are removed from the water stream because they are absorbed into the activated sludge (and thus carry through with disposal of the sludge) and 3) are not removed by other downstream practices. <o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>The bottom line is something could be of extreme benefit to one species with little or no negative tox even at very high levels and could be a disaster for another species due to specific negative organ effects. If you want a humorous example, I love dark chocolate. As a human I could eat pounds of it and it would have beneficial therapeutic effects on my brain. The only negative tox would be my waist line. However, a small “dose” could kill a dog because it cannot properly metabolize theobromine in the chocolate and its extreme stimulant effects could cause cardiac arrest. Depending on the breed of dog, the lethal mg/kg dose varies. If fact, the lethal mg/Kg dose for a cat is much lower but cats rarely have a sweet tooth so are rarely attracted to chocolate. In these species, there is no beneficial therapeutic dose and extremely low doses are toxic. <o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>The issue with doses can also vary dramatically with age and in some examples, a small recurring dose could have a much greater negative effect than a very large one. An example of this would be a female toddler eating birth control pills. Unfortunately children think they look like candy and have been known to eat months of supply in one go. Although the protocol is to get as much of the undigested pills out of the child as quickly as possible, in many cases a child could eat many months’ worth of birth control pills with little to no long-term negative effect. On the other hand, if a 2 year old child was fed a quarter or less of a birth control pill every day for a year, there would be profound negative effects on that child. Birth control pills have no beneficial therapeutic dose in children and low doses have negative tox.<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>As some of you may know, Pharma-Cycle is very concerned about 24 cytotoxic chemotherapy drugs because 1) they exit patients intact at high levels, 2) they cause damage to ALL non-patients at ultra-low levels (OSHA allow exposure for adult employee is 0) with greatest damage to fetus, baby and child due to their high concentration of fast growing cells (target of problem cytotoxic drugs) and 3) many cannot be cleared by wastewater treatment or drinking water purification (>95% of cyclophosphamide passes through all treatment intact). These issues have been known for decades but ignored because there is a disconnect between the benefit to the patient taking therapeutic doses and the extreme negative effects of non-therapeutic doses on non-patient populations and the environment.<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>When drug companies develop drugs they conduct a wide range of tox studies on multiple species. They also must determine the distribution and excretion of the drug and its metabolites. Another test is to determine the drugs’ reproductive effects in multiple species but all of this is used to only determine the effects on the patient. Maybe the time has come to require drug companies to also determine environmental effects. At a minimum, they should be required to determine how the drugs transit through wastewater treatment and both short and long-term effects on aquatic species (maybe in zebrafish assays). Finally, the information must be made freely available in easy to understand language. Only with this will we be able to target our efforts at the drugs that will have the worst effect on our water and environment.<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>Theresa O’Keefe, Ph.D.<o:p></o:p></p><p class=MsoNormal>Chief Scientific Officer<o:p></o:p></p><p class=MsoNormal>Pharma-Cycle Inc.<o:p></o:p></p><p class=MsoNormal><a href="http://www.pharma-cycle.org">www.pharma-cycle.org</a><o:p></o:p></p><p class=MsoNormal> <o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal><o:p> </o:p></p></div></body></html>