Pharmaceuticals In The Environment (PIE): Assessing Risk to Human Health

1. Pharmaceuticals In The Environment (PIE): Assessing Risk to Human Health Frank Mastrocco, DABT Director, Hazard Communication & Environmental Toxicology Pfizer Inc 14 June 2005

2. Overview • PIE Issue Primer • USGS National Survey • Pharmaceutical Research & Manufacturers of America(PhRMA) PhATETM model • Human Health Risk Assessment • Conclusions • Future Direction

3. Issue Primer • Recent advancements in analytical techniques have made detection of trace quantities of contaminants possible • To date, more than 190 pharmaceuticals have been detected in surface and/or drinking water at ppb-ppt levels • The source is widely agreed to be patient excretion and incomplete removal in treatment plants • The media have reported on the issue, focusing on uncertainty around both human health and ecological impacts • Industry has taken action toward improved understanding of the issue

5. USGS Data Summary • Koplin, et al. (2002) Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999-2000: A National Reconnaissance Envir. Sci Tech.36:1202-1211 • Sampling Locations • 142 streams across 30 states • 70 to 200 samples per target compound • Targeted towards streams susceptible to contamination • High population centers and livestock production • Of the 56 pharmaceutical compounds analyzed for: • 13 were not detected at all • 24 with <10% detection rate • 19 with 10% to 70% detection rate • Overall detection rate: 11%

6. Principles of Risk Assessment • Risk = ƒ(hazard, exposure) • hazard: The potential to cause harm • exposure: Opportunity for harm to occur A hazard does not pose a risk unless there is potential for exposure

7. The PhATETM Model (Pharmaceutical Assessment and Transport Evaluation) INPUTS OUTPUTS • MODEL • For 11 U.S. watersheds: • Population Distribution • Sewage Treatment Plant Flows • Stream/River Flows • Drinking Water Treatment Plant Flows • Human Health Risk Assessment Module Annual US Sales (IMS) • Percent Removal • at Each Step • Metabolism • Wastewater Treatment • In-Stream Loss • Drinking Water Treatment • Predicted Concentrations • In Sewage Treatment Plant • Effluent • In Streams/Rivers • In Drinking Water Acceptable Daily Intake (ADI) or toxicity data Predicted No Effect Concentration for Human Health

8. PhATE GIS* Output *Geographic Information System overlays predicted concentrations over maps of river reaches.

9. Summary of PhATE Screening Study • Anderson, P. D., et al. (2004) Screening Analysis of Human Pharmaceutical Compounds in U.S. Surface Waters, Envir. Sci. Tech., 38:838-849 • PhATE PECs (Predicted) vs. USGS MECs (Measured) for 11 compounds: • PEC/MEC in agreement for 2; • PEC<LOD (Limits of Detection) for 3; evaluate potential effects below LOD; • PEC>MEC for 3; Depletion unaccounted for by model, evaluate impact of POTW and in-stream removal; • PEC<<MECs for 3; Comparing the PECs to the measured data identified some questionable analytical findings.

10. Human Health Risk Assessment • Analysis include 26 USGS human health pharmaceuticals • Non-steroidal analgesic, non-steroidal anti-inflammatory • Bronchodilator • H2 receptor antagonist • Antimicrobial, antibiotic, antibacterial • Calcium blocker, ACE inhibitor, anti-hypertensive • Serotonin uptake inhibitor, anti-depressive • Hypoglycemic • Glycoside • Compounds studied excluded hormones which are being evaluated separately due to the complexity of that evaluation

11. Human Health Risk Assessment(cont.) • Identified concentrations for compounds reported in published articles (MEC) • Used PhATE in screening mode to estimate concentration in environment (PEC) • Developed predicted no effect concentrations (PNEC) • Considered drinking water and fish consumption exposure pathways • Evaluated MEC/PNEC and PEC/PNEC ratios

12. Human Health Risk Assessment(cont.) • Results of this human health assessment indicate that no appreciable human health risk exists from the presence of these trace residues in surface water and drinking water. • Manuscript accepted for publication in Reg. Tox. Pharmacol.

13. Other Human Health Publications • Christensen, F.M. (1998) Pharmaceuticals in the environment – A Human Risk?, Reg. Toxicol. & Pharmacol., 28, 212-221. • Schulman, et al., (2002) A Human Health Risk Assessment of Pharmaceuticals in the Aquatic Environment, Human & Ecological Risk Assessment, 8(4), pp. 657-680. • Mons, M.N., (2003) Pharmaceuticals and drinking water supply in the Netherlands, Kiwa N.V. Water Research. • Webb, et al., (2003) Indirect Human Exposure to Pharmaceuticals via Drinking Water, Toxicology Letters, 142, 157-167. • All concluded that exposure to human pharmaceuticals poses negligible human health risk.

14. Conclusions • Patient use is widely accepted as the primary source • Disposal of unused medicines considered insignificant • Critical opinion leaders consider Human impact a ‘non-issue’; possible exception - hormones

15. Current/Future Activity • Environmental species are primary concern • Current regulatory focus: • More rigorous pre-approval risk assessment • Waste water treatment improvements (municipal, possibly private) • Industry initiatives: • Proactively engaging US and Int. regulatory agencies • Collaborating with academic researchers • Presenting/publishing research