M11 PM Internal Exposure
Monday, 14 November 2005: 1:50 PM - 5:30 PM in 343-344

(MOE-1117-823281) Pharmaceutical Plasma Concentrations As A Hazard Identification Tool For Fish.

Moen, M¹, Glieco, J¹, Verman, N¹, Huggett, D¹, ¹ Pfizer, Inc., Groton, CT, USA

ABSTRACT- Pharmaceuticals typically have specific receptor / enzyme based mechanisms of action. Pharmacologically active and toxicological effective pharmaceutical concentrations in mammals are typically denoted by circulating plasma levels. These effective mammalian plasma concentrations have been hypothesized as being predictors of pharmacological or toxicological responses in fish. A modified hazard identification model was developed whereby known effective mammalian plasma levels are compared to predict fish steady state plasma levels. The estrogen receptor is highly conserved between mammals and fish, and represents a viable target for determining the applicability of using mammalian plasma concentrations as predictors of the pharmacological response in fish. Juvenile rainbow trout, Oncorhynchus mykiss, were exposed via water exposure for 14 days to the synthetic estrogen 17-ethinylestradiol, EE2, (0.5, 1, 10, 100 ng/L, nominal). In EE2 exposed fish, a dose dependent increase in Hepatic Somatic Index (HSI) and vitellogenin (VTG) were observed with statistically significant differences at the highest levels of exposure (10 and 100 ng/L). Measured plasma levels of EE2 in fish were within the mammalian therapeutic effective range. These data indicate that mammalian plasma concentrations can be useful for predicting pharmacological / toxicological responses in fish and can be used as part of a tiered environmental risk assessment process for determining testing needs in fish.

Key words: fish, mammalian, plasma, pharmaceutical