TP20 Ecological Risk Assessment
Tuesday, 15 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall

(ERI-1117-829901) Exemestane (Aromasin) Environmental Fate and Ecotoxicity Overview.

Ericson, J¹, Huggett, D¹, Constantine, L¹, ¹ Pfizer Inc, Pfizer Global R&D, Chemical R &D, Environmental Sciences, Groton, CT, USA

ABSTRACT- Environmental fate, physical-chemical and ecotoxicology studies were conducted in support of an environmental risk assessment for the new chemical entity exemestane, a selective aromatase inhibitor used for the treatment of advanced breast cancer in postmenopausal women. A full summary of the environmental fate and effects data associated with exemestane will be presented. Exemestane is extensively metabolized with less than 1% excreted into wastewater treatment plants as unchanged drug. Subsequent wastewater treatment of these residues shows considerable biotransformation (k 1.8 hr-1) and mineralization (k 0.7 hr-1) during a typical hydraulic residence time and further biotransformation and loss once in the aquatic environment (k 0.06 hr-1). Such depletion indicates that exemestane will not persist once in the environment. Minimal sludge sorption (sludge Koc 2285) and soil sorption (Koc 1594-6533) indicate that these residues will mainly reside in the aquatic environment, but will not bioconcentrate (log P 2.5). Acute and/or chronic ecotoxicology studies with wastewater treatment organisms (EC50 > 1000 mg/L) and various environmental species (NOEC 48 hr. daphnia, 96 hr. rainbow trout, 72 hr green algae and 7-day ceriodaphnia 4.1, 1.9, 2.3 and 1.2 mg a.i./L, respectively) indicate aquatic effects are unlikely at relevant environmental levels.

Key words: exemestane, environmental, fate, ecotoxicity