1. 1 Dr. Richard Reiss Sciences International, Inc. October 20, 2005 Environmental Safety of Active Pharmaceutical Ingredients

2. 2 Introduction Talk will focus on triclosan (TCS) and triclocarban (TCC)Talk will focus on triclosan (TCS) and triclocarban (TCC) For each chemical, I will provide:For each chemical, I will provide: –General environmental fate characteristics –Representative environmental concentration data –Toxicity levels of most sensitive species –Comparison of concentrations and toxicity levels

3. 3 General Environmental Fate Properties Both compounds have similar fate properties:Both compounds have similar fate properties: –Very low vapor pressures –Soluble in water –Highly adsorbent to organic matter Both compounds will reach the environment through down-the-drain disposalBoth compounds will reach the environment through down-the-drain disposal –Both show significant degradation in water treatment plants (next slide) TCS shows rapid removal from water column in die-away studies (2-5 hour half-life)TCS shows rapid removal from water column in die-away studies (2-5 hour half-life) –Also, biodegrades in soil in 17-35 days TCC shows rapid degradation in biosolids (10 hour half-life)TCC shows rapid degradation in biosolids (10 hour half-life)

4. 4 Average Removal Rates in Wastewater Treatment Plants Actives Activated Sludge Trickling Filter TCC94%77% TCS95%83% Predominant pathway is biodegradation

5. 5 Freshwater Aquatic Environmental Concentrations in U.S. for TCC SourceResults TCC Consortium, 2002 Max=0.23 ppb, 90% less than 0.05 ppbMax=0.23 ppb, 90% less than 0.05 ppb Halden & Paull, 2005 Max=6.8 ppb in sites with significant raw sewageMax=6.8 ppb in sites with significant raw sewage EPA E-FAST model, TCC consortium, 2002 Model estimates, high-end at outfall = 0.017 ppb, median at outfall = 0.0013 ppbModel estimates, high-end at outfall = 0.017 ppb, median at outfall = 0.0013 ppb

6. 6 Freshwater Aquatic Environmental Concentrations in U.S. for TCS SourceStudy USGS, 2002 75 th Percentile = 0.2 ppb, median of measured conc =0.14 ppb. Sampling locations chosen as “susceptible to contamination.”75 th Percentile = 0.2 ppb, median of measured conc =0.14 ppb. Sampling locations chosen as “susceptible to contamination.” USGS, 2004 Non-detectable in typical flow conditions, Max=0.14 ppb in low flow conditions Non-detectable in typical flow conditions, Max=0.14 ppb in low flow conditions

7. 7 Most Sensitive Aquatic Species Actives Chronic Toxicity and No Observed Effect Concentrations (NOECs) TCC Waterflea, Ceriodaphnia dubia, NOEC = 1.5 ppb Algae, 6 ppb, minimum algistatic concentration TCS Blue-green algae, NOEC = 0.5 ppb (algistatic, not algicidal, recovery in 3-6 days) Waterflea, Ceriodaphnia dubia, NOEC=6 ppb

8. 8 Comparison of Environmental Concentrations to NOECs for TCC TCC Consortium Measurements

9. 9 Comparison of Environmental Concentrations to NOECs for TCS USGS Measurements

10. 10 Terrestrial Risk Both TCS and TCC can be present in sewage sludge in small concentrationsBoth TCS and TCC can be present in sewage sludge in small concentrations –Sludge may be used as soil amendments in agriculture –Low potential of exposure to ecological species Due to low mammalian toxicity, low sludge concentrations, and low potential for exposure, risks to ecological species are expected to be minimal (Federle et al., 2002)Due to low mammalian toxicity, low sludge concentrations, and low potential for exposure, risks to ecological species are expected to be minimal (Federle et al., 2002)

11. 11 Conclusions The large majority of the TCC and TCS mass will degrade in treatment plants, but some will be present in effluent and sludgeThe large majority of the TCC and TCS mass will degrade in treatment plants, but some will be present in effluent and sludge –Neither is expected to persist in the environment TCC shows low risk to aquatic species when high-end concentrations are compared to the no effect level for the most sensitive speciesTCC shows low risk to aquatic species when high-end concentrations are compared to the no effect level for the most sensitive species

12. 12 Conclusions (cont) TCS may have transitory algistatic effects on some algal species under worst case conditions and only in aquatic environments close to the effluent pipeTCS may have transitory algistatic effects on some algal species under worst case conditions and only in aquatic environments close to the effluent pipe –Downstream effects are not expected TCS is unlikely to have any significant effects on non-algal speciesTCS is unlikely to have any significant effects on non-algal species