Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms

Carlie A. LaLone, Jason P. Berninger, Daniel L. Villeneuve, Gerald T. Ankley

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations

Abstract

Medicinal innovation has led 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 as well as field monitoring. Current prioritization strategies typically emphasize likelihood for exposure (i.e. predicted/measured environmental concentrations), while incorporating only rather limited consideration of potential effects of the drug to non-target organisms. However, substantial mammalian pharmacokinetic and mechanism/mode of action (MOA) data are produced during drug development to understand drug target specificity and efficacy for intended consumers. An integrated prioritization strategy for assessing risks of human and veterinary drugs would leverage available pharmacokinetic and toxicokinetic data for evaluation of the potential for adverse effects to non-target organisms. In this reiview, we demonstrate the utility of read-across approaches to leverage mammalian absorption, distribution, metabolism and elimination data; analyse cross-species molecular target conservation and translate therapeutic MOA to an adverse outcome pathway(s) relevant to aquatic organisms as a means to inform prioritization of drugs for focused toxicity testing and environmental monitoring.

Original languageEnglish (US)
Article number20140022
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume369
Issue number1656
DOIs
StatePublished - Nov 19 2014

Keywords

  • Adverse outcome pathway
  • Molecular target conservation
  • Pharmacokinetics
  • Read-across
  • SeqAPASS

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