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Mode of Action (MOA) Assignment Classifications for Ecotoxicology: Evaluation of Available Methods
Citation:
Embry, M., M. Barron, A. Beasley, S. Belanger, J. Brill, D. De Zwart, B. Farr, M. Halder, A. Kienzler, T. Norberg-King, H. Sanderson, R. Sternberg, AND P. Wilson. Mode of Action (MOA) Assignment Classifications for Ecotoxicology: Evaluation of Available Methods. SETAC North America 37th Annual Meeting, Orlando, FL, November 06 - 10, 2016.
Impact/Purpose:
This abstract presentation will provide an overview of available aquatic toxicity mode of action (MOA) assignment tools, including summarizing their technical basis, comparing consistency in MOA classifications, and assess utility for grouping compounds in large structurally diverse datasets. It is important because it is the first comprehensive assessment of MOA tools, which have application in AOP and compound classification in general.
Description:
There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human toxicology. With increasing calls to assess 1000s of chemicals, some of which have little available information other than structure, clear understanding how each of these MOA schemes was devised, what information they are based on, and the limitations of each approach is critical. Several groups are developing low-tier methods to more easily classify or assess chemicals, using approaches such as the ecological threshold of concern (eco-TTC) and chemical-activity. Evaluation of these approaches and determination of their domain of applicability is partly dependent on the MOA classification that is used to group chemicals. The objectives of this study were to critically evaluate available MOA classification methodologies using a set of unique chemicals from a large aquatic toxicity dataset, compare the various approaches, and evaluate their utility and limitations in low-tier assessment approaches. The most commonly used MOA classification schemes for ecotoxicology include Verhaar and Russom (included in ASTER), both of which are used to predict acute aquatic toxicity MOA. Verhaar is a QSAR-based system that classifies chemicals into one of 4 classes, with a 5th “other” class, whereas ASTER/Russom includes 8 classifications. Other methodologies include Toxicity Estimation Software Tool (TEST), an application that allows prediction into 5 broad MOAs, with specific MOAs developed as subcategories. MOAtox is a dataset of MOA assignments for >1200 chemicals that draws from various schemes and assigns 6 broad and 31 specific acute aquatic toxicity MOAs. Other classification systems that can provide insight on a chemicals’ MOA include ECOSAR, EPISuite, and the OECD QSAR Toolbox. In this study, >5600 unique CAS numbers were evaluated using the classification and MOA schemes described above. In all of the approaches used, a large percentage (>40%) were classified as narcotics, with very few classified into categories describing more specific mechanisms. However, a large percentage of chemicals were not classified, either because the chemical was not within the domain of applicability for the classification system, or due to issues with CAS number recognition. This presentation will provide an overview of available MOA assignment tools, including summarizing their technical basis, comparing consistency in MOA classifications, and assess utility for grouping compounds in large structurally diverse datasets.