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Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms
Citation:
LaLone, C., J. Berninger, Dan Villeneuve, AND G. Ankley. Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms. Philosophical Transactions of the Royal Society B: Biological Sciences. Royal Society Publishing, London, Uk, 369(1656):1-10, (2014).
Impact/Purpose:
The manuscript describes a strategy for prioritization of human and veterinary drugs as a means to focus toxicity testing and environmental monitoring on those chemicals most likely to cause adverse effects to wildlife. Current prioritization strategies typically emphasize likelihood for exposure (i.e., predicted/measured environmental concentrations), while incorporating only rather interspersed considerations of potential effects of the drug to non-target organisms. However, ample mammalian pharmacokinetic and mechanism/mode of action data are produced during drug development to understand drug target specificity and efficacy for intended consumers. In this paper we demonstrate the utility of read-across approaches to leverage mammalian absorption, distribution, metabolism, and elimination data, analyze cross-species molecular target conservation (using our SeqAPASS tool), and translate therapeutic mode of action to an adverse outcome pathway relevant to risk assessment, as a means to inform prioritization of drugs.
Description:
Medicinal innovation has lead to the discovery and use of thousands of human and veterinary drugs. With this comes the potential for unintended effects on non-target organisms exposed to pharmaceuticals inevitably entering the environment. The impracticality of generating whole-organism chronic toxicity data representative of all species in the environment has necessitated prioritization of drugs for focused empirical testing and field monitoring. Current prioritization strategies typically emphasize likelihood for exposure (i.e., predicted/measured environmental concentrations), while incorporating only rather interspersed considerations of potential effects of the drug to non-target organisms. However, ample mammalian pharmacokinetic and mechanism/mode of action data are produced during drug development to understand drug target specificity and efficacy for intended consumers. A comprehensive and integrated prioritization strategy for human and veterinary drugs would leverage all available pharmacokinetic and toxicokinetic data for thorough evaluation of the potential for adverse effects to non-target organisms. In this paper, we demonstrate the utility of read-across approaches to leverage mammalian absorption, distribution, metabolism, and elimination data, analyze cross-species molecular target conservation, and translate therapeutic mode of action to an adverse outcome pathway relevant to risk assessment as a means to inform prioritization of drugs for focused toxicity testing and environmental monitoring.
