You are here:
Applications of AOPs to ecotoxicology
Citation:
Ankley, G. Applications of AOPs to ecotoxicology. Belgium Society of Toxicology and Ecotoxicology, Antwerp, BELGIUM, December 09, 2016.
Impact/Purpose:
not applicable
Description:
Toxicologists conducting safety assessments for either human or ecological health are responsible for generating data for possible adverse effects of a rapidly increasing number of substances. For example, the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) program in Europe, and the recent reauthorization of the Toxic Substances Control Act (TSCA) in the United States (US) both explicitly mandate consideration of the potential toxicity of many thousands of chemicals that, in the past, would not have been assessed. There also is an increasing emphasis on understanding the effects of existing chemical mixtures on human health and the environment; for example in North America, the Great Lakes Restoration Initiative, sponsored by the Office of the President of the US, has identified complex mixtures of chemicals of emerging concern as one of the highest priority stressors in the lakes. These types of new regulatory programs and monitoring initiatives highlight the necessity of identifying and developing novel, rapid approaches for assessing the potential toxicity of substances, to augment (or, in some instances, replace) the more costly, long-term in vivo test methods that historically have supported chemical risk assessments. Fortunately, these chemical evaluation challenges are occurring against a backdrop of evolving data collection and analysis techniques that enable generation of biological information in manners previously considered unimaginable. For example, data from genomic technologies enable scientists to simultaneously probe chemical perturbations of hundreds of biological pathways in exposed organisms, and robotic high-throughput toxicology (HTT) technologies allow the rapid, cost-effective measurement of effects of chemicals using in vitro assays representing a diversity of biological systems. Moreover, rapidly-progressing bioinformatics approaches and advances in network and systems biology modeling enable an increasingly sophisticated understanding of the high-content data generated from genomic and/or HTT methodologies. A major challenge relative to use of these alternative data sources for regulatory purposes involves translation of the information into endpoints of direct applicability to risk assessment, that is, apical impacts of consequence (e.g., survival, development, reproduction) in individuals and/or populations of concern. The adverse outcome pathway (AOP) framework was developed to meet this translation question through the identification and depiction of causal linkages between mechanistic in vitro or in vivo data and biological endpoints meaningful to risk assessment. This presentation will focus on practical case studies demonstrating use of the AOP concept to apply mechanistic data to some of the challenges faced in ecotoxicology such as cross-species extrapolation of chemical effects and monitoring the occurrence and effects of complex mixtures