PARENT SESSION
PM23 - Pharmaceuticals
Monday, 18 November 2002
8:00 AM to 6:30 PM
Exhibit Hall
(P416) Model for Utilizing Human Safety and Pharmacological Data to Prioritize Environmental Safety Initiatives Associated With Human Pharmaceuticals.
Huggett, Duane*,1, Cook, Jon1, Ericson, Jon1, Williams, Richard1, 1 Pfizer Global Research and Development, Groton, CT
ABSTRACT- Pharmaceuticals are extensively studied for the potential to cause human health effects. The Food and Drug Administration (FDA) is required to consider the potential for pharmaceuticals to have an environmental impact. The FDA environmental testing paradigm uses a traditional hazard assessment approach. Chronic environmental toxicity data is not required if the predicted environmental concentration (PEC) / predicted no effect concentration (PNEC) is < 1. This assessment generally requires an acute to chronic assessment factor of 100 to 1000. Because of the specific receptor-based mode of action of pharmaceuticals, suggestions have been made that the traditional hazard assessment process may not be appropriate. A model has been developed to utilize existing human safety data to identify potential environmental effects. The model is based on the conservation of receptors between separated classes of organisms. Human therapeutic plasma concentrations (TPC) for a pharmaceutical are compared to a predicted steady state plasma concentration (SSPC) in a fish species. The SSPC is derived by considering the PEC or measured environmental concentration (EC) and predicting a fish plasma concentration corrected for uptake based on Log Kow. A safety index (SI = TPC/SSPC) is computed where the lower the SI, the greater the toxicological risk. Twenty-eight compounds representing 15 therapeutic use areas were analyzed. Two compounds (17B-Estradiol and 17
Ethinyl Estradiol) were identified with an SI < 1 indicating that additional evaluation is appropriate. Estradiol and ethinyl estradiol have both been identified as requiring additional consideration through more traditional investigative approaches, thereby providing additional support that this is a valid approach for prioritizing resources and targeting initiatives.
Key words: Pharmaceuticals, Safety, Mammalian, Aquatic