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

2. Introduction • Talk will focus on triclosan (TCS) and triclocarban (TCC) • 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. General Environmental 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 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) • Also, biodegrades in soil in 17-35 days • TCC shows rapid degradation in biosolids (10 hour half-life)

4. Average Removal Rates in Wastewater Treatment Plants Predominant pathway is biodegradation

5. Freshwater Aquatic Environmental Concentrations in U.S. for TCC

6. Freshwater Aquatic Environmental Concentrations in U.S. for TCS

7. Most Sensitive Aquatic Species

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

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

10. Terrestrial Risk • Both 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)

11. Conclusions • The 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 species

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 pipe • Downstream effects are not expected • TCS is unlikely to have any significant effects on non-algal species