R4 PM Effects and Risk Assessment of Pharmaceutical and Other Emerging Wastewater Contaminants in Aquatic Systems
Thursday, 17 November 2005: 1:50 PM - 5:30 PM in Ballroom 4

(SIM-1117-827609) Polycyclic Musks are estrogen receptor modulators: confirmation in vitro and in vivo.

Simmons, D, Sherry, J, Trudeau, V, Balch, G¹, Metcalfe, C¹, ¹ Trent University

ABSTRACT- Polycyclic synthetic musks are ubiquitous, and have been found in numerous river, sewage, lake and other water samples. Due to their lipophilicity (logKows = 5.7-5.9), HHCB and AHTN tend to accumulate in biological tissues. Gatermann et al., 1999, determined tissue levels of these polycyclic musks in North American biota, where Canadian freshwater fish ranged from 25 to 100 ng/g lipid, or 3 to 9 mg/kg wet.w. (Chemosphere, 38(14):3431-3441.). There is additional evidence that polycyclic musks may be weak environmental estrogens. Schreurs et al. (2002) demonstrated that both HHCB and AHTN were selective estrogen receptor modulators (SERMs) in vitro, meaning that they can induce estrogenic and antiestrogenic activity. Our Data indicate that concentrations of polycyclic synthetic musks in the tissues of fish from the lower Great Lakes may exceed 1mg/kg; depending upon sampling location and fish species. A three-tiered decision tree-design was used for this study. The yeast estrogen screen assay was used to first chose the most stronges estrogen modulator and a dual luciferase reporter gene assay was employed in rainbow trout gonadal cells with the rtER to assess interactions with fish estrogen receptors. The results of these assays indicated that both musks were inhibitors at the ER, however, HHCB had stronger effects at the hER and was therefore chosen for tests at the rainbow trout estrogen receptor. As an evaluation of the in vivo sublethal responses of fish to synthetic musks, rainbow trout were injected intraperitoneally with the polycyclic musk compound HHCB alone and HHCB plus E2. Vitellogen concentrations were reduced when HHCB was injected with E2.

Key words: polycyclic musks, estrogen receptor, rainbow trout