SPECIES EXTRAPOLATION FOR THE 21ST CENTURY

Safety factors are used in ecological risk assessments to extrapolate from the toxic responses of laboratory test species to all species representing that group in the environment More accurate extrapolation of species responses is important Advances in understanding the mechanistic basis for toxicological responses and identifying molecular response pathways can provide a basis for extrapolation across species and in part an explanation for the variability in whole organism responses to toxicants We highlight potential short and medium term development goals to meet our long term aspiration of truly predictive in silica extrapolation across wildlife species response to toxicants A conceptual approach for considering cross species extrapolation is presented Critical information is required to establish evidence-based species extrapolation including identification of critical molecular pathways and regulatory networks that are linked to the biological mode of action and species homologies A case study is presented that examines steroidogenesis inhibition in fish after exposure to fadrozole or prochloraz Similar effects for each compound among fathead minnow medaka and zebrafish were attributed to similar inhibitor pharmacokinetic/pharmacodynamic distributions and sequences of cytochrome P45019A1/2 (CYP19A1/2) Rapid advances in homology modeling allow the prediction of interactions of chemicals with enzymes for example CYP19 aromatase which would eventually allow a prediction of potential aromatase toxicity of new compounds across a range of species Eventually predictive models will be developed to extrapolate across species although substantial research is still required Knowledge gaps requiring research include defining differences in life histories (e g reproductive strategies) understanding tissue specific gene expression and defining the role of metabolism on toxic responses and how these collectively affect the power of interspecies extrapolation methods Environ Toxicol Chem 2011 30 52-63 (C) 2010 SETAC