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

(OWE-1117-622554) Cardiac and Growth Performance of Rainbow Trout (Oncorhynchus mykiss) Exposed to Propranolol: Non-invasive Fish ECG.

Owen, S¹, Huggett, D², Hutchinson, T³, Kinter, L⁴, Ericson, J², Hetheridge, M³, Sumpter, J¹, ¹ Brunel University, London, UK² Pfizer, Global R&D, Groton, CT, USA³ AstraZeneca, Global Saftey Health and Environment, Brixham, UK⁴ AstraZeneca Pharmaceuticals, Wilmington, PE, USA

ABSTRACT- Propranolol, a non-specific beta1/beta2 adrenergic antagonist has been detected in sewage treatment effluents and receiving waters in Europe and USA. Rainbow trout have beta-adrenergic signalling systems analogous to human cardiovascular receptors that respond to pharmacological doses of agonists and antagonists. Additional beta-receptor sub-types associated with functions that are physiologically different to the known mammalian functions suggest propranolol may interact with non-cardiovascular systems such as those for homeostasis, reproduction and immunocompetence. Little information is available on the physiological effects of water-borne propranolol or plasma concentrations in exposed fish. We report that trout took propranolol up from water such that after 40 days of exposure/acclimation, the linear relationship between water and plasma concentrations was described by [plasma] = 0.59[water], (n=31, r=0.96). Thus, uptake may potentially be modelled in fish by accounting for lipophillicity and processes such as protein binding and metabolism of the pharmaceutical. Physiological and biometric effects were also examined. Growth-rate was affected only at very high propranolol concentrations (LOEC 10mg/l). However, additional endpoints suggested morphological responses on the liver and heart size at 100ng/l (close to environmental measured range), the consequences of which are unknown at present. Interestingly, the 'mammalian-fish leverage model' (Huggett et al., 2004) predicts plasma concentrations at these exposures that would fall within the range of active mammalian plasma concentrations. Additional endpoints were examined including ECGs from unrestrained fish. In this presentation we report a preliminary study using waterborne cardio-modulators (ethanol and propranolol) and using spectral analysis of the ECG to examine heart rate variability, changes in QRS complex and QT-period in comparison with other measures of overall performance and homeostasis such as growth and condition.

Key words: pharmaceutical, environment, mammalian-fish-leverage-model, plasma