title: Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms.
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.
authors.affiliation: Water Resources Center, College of Food, Agricultural and Natural Resource Sciences, University of Minnesota, 1985 Buford Avenue, St Paul, MN 55108, USA Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, US Environmental Protection Agency, 6201 Congdon Boulevard, Duluth, MN 55804, USA lalone.carlie@epa.gov.
authors.forename: Carlie A
authors.initials: CA
authors.lastname: LaLone
authors.affiliation: National Research Council, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Berninger
authors.affiliation: Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, US Environmental Protection Agency, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
authors.affiliation: Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, US Environmental Protection Agency, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
mesh_terms: D000818:Animals; D059001:Aquatic Organisms / Q000187:drug effects*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012307:Risk Factors; D013045:Species Specificity; D014874:Water Pollutants, Chemical / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D004364:Pharmaceutical Preparations; D014874:Water Pollutants, Chemical
keywords: SeqAPASS; adverse outcome pathway; molecular target conservation; pharmacokinetics; read-across