Integrated Toxicology as a Basis for Species Extrapolation in Assessing the Ecological Risk of Pharmaceuticals in the Environment
Possible effects of pharmaceutical chemicals in surface water on aquatic species are an emerging issue of concern. For example, drugs emanating from wastewater treatment plants and concentrated animal feeding operations have been demonstrated to elicit responses indicative of endocrine disruption. In addition to the endocrine system, pharmaceuticals may interact with a diversity of physiological targets that are critical to normal development, survival, and reproduction. As opposed to most other types of environmental contaminants, pharmaceuticals are unique in that there often is extensive information concerning their persistence, biological activity, and potency in target species (e.g., humans, livestock). However, the extent to which these chemicals are active in non-target species, via the same or different physiological pathways, is largely unknown. The issue of pharmaceuticals in the environment is an appropriate research area for applying an integrated, comparative toxicology approach to the challenge of species extrapolation. Research is aimed at testing the hypothesis that conservation of nucleotide and/or amino acid sequence (i.e., primary structure) of a particular drug target, as well as those factors known to modulate the response to a particular drug (e.g., xenobiotic metabolism), can be used to predict species sensitivity. Existing information is being used to select a series of drugs whose targets are conserved to varying degrees among vertebrate and invertebrate taxa. Then, the relative sensitivity of the various species will be predicted on the basis of sequence conservation. These predictions will be evaluated empirically using a combination of targeted in vitro and in vivo studies. The resultant data will serve as a basis for developing and evaluating a quantitative approach to species extrapolation. At the same time, these data shall serve to inform the description and modeling of additional (non-endocrine) pathways relevant to population maintenance, such as those associated with growth, survival, reproduction, and development. This will further "populate" the library of well-described adverse outcome pathways and provide a basis for developing predictive toxicological models and prioritizing empirical testing.
Reports/journal articles describing approaches for use of existing data for characterizing ecological risk of drugs.
Research project update date
April 13 , 2010