T3 PM Aquatic Ecotoxicology (Part 2)
Tuesday, 15 November 2005: 1:50 PM - 5:30 PM in Ballroom 3

(WAT-1117-839036) Physiologically Based Pharmacokinetic Model of Ethinylestradiol Exposed Fathead Minnows (Pimephales promelas).

Watanabe, K¹, Kroll, K², Orlando, E³, Sepulveda, M⁴, Nichols, J⁴, Knoebl, I⁶, Lazorchak, J⁶, Collette, T^{2, 7}, Szabo, N², Denslow, N², ¹ Oregon Health & Science University, Beaverton, OR, USA² University of Florida, Gainesville, FL³ Florida Atlantic University, Boca Raton, FL, USA⁴ Purdue University, West Lafayette, IN, USA⁶ U.S. EPA, ORD, NERL, EERD, Cincinnati, OH, USA⁷ U.S. EPA, ORD, NERL, ERD, Athens, GA, USA

ABSTRACT- Endocrine disrupting chemicals are known to cause adverse reproductive effects in animals, including humans. 17-ethinylestradiol (EE₂) is a potent estrogenic endocrine disruptor that is used in pharmaceutical formulations, and is discharged to the aquatic environment. To further our understanding of the impact of EE₂ on reproduction in fathead minnows (FHM, Pimephales promelas) we are developing an integrated, systems model of the hypothalamic- pituitary-gonadal axis in this fish species. One hundred five adult male FHM were exposed for 48 hours under static aqueous conditions to 0, 10 and 50 ng/L EE₂. Following exposure, fish were anesthetized, sacrificed, and tissue (blood, brain, liver, testes, and carcass) were snap-frozen and stored at -800°C until analyzed. Concentrations of EE₂, 17-estradiol (E₂), testosterone (T), and 11-ketotestosterone (11-KT) were measured using GC/MS. As a first step, we have developed a physiologically based pharmacokinetic (PBPK) model to describe the disposition of EE₂ within FHM. The model also simulates steroid hormone concentrations (i.e., E₂, T, 11-KT) because of their importance in regulating the reproductive system. Markov Chain Monte Carlo simulations were used to estimate unknown model parameters including kinetic rate constants for steroid hormone reactions and the elimination of EE₂. In this presentation, results from the PBPK model will be presented along with the uncertainty and variability in the model outputs.

Key words: Pimephales promelas, ethinylestradiol, pharmacokinetic, model