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A Critical Review of Mode of Action (MOA) Assignment Classifications for Ecotoxicology
Citation:
Embry, M., M. Barron, M. Beasley, S. Belanger, R. Bjorkland, J. Brill, D. De Zwart, B. Farr, M. Halder, R. Hummel, A. Kienzler, T. Norberg-King, H. Sanderson, R. Sternberg, J. Suski, AND P. Wilson. A Critical Review of Mode of Action (MOA) Assignment Classifications for Ecotoxicology. SETAC Europe 26th Annual Meeting, Nantes, FRANCE, May 22 - 26, 2016.
Impact/Purpose:
Reporting a database of mode of action approaches and tools
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 health toxicology. With increasing calls to assess thousands 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. 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 class specified for those chemicals that are not classified in the other 4. ASTER/Russom includes 8 classifications: narcotics (3 groups), oxidative phosphorylation uncouplers, respiratory inhibitors, electrophiles/proelectrophiles, AChE inhibitors, or CNS seizure agents. Other methodologies include TEST (Toxicity Estimation Software Tool), a computational chemistry-based application that allows prediction to one of 5 broad MOAs (AChE inhibition, narcosis, reactivity, uncoupling, and neurotoxicity), with specific MOAs developed as subcategories. MOAtox is a dataset of MOA assignments for over 1200 chemicals that draws from various schemes and assigns 6 broad and 31 specific acute aquatic toxicity MOAs. Cramer Classification is a widely used approach for classifying and ranking chemicals based on oral systemic toxicity, and is based on short-term or chronic mammalian dietary studies. This scheme is used as the basis for the human health TTC, though its structure-based approach may be useful for ecological applications. Other classification systems that provide insight on a chemicals’ MOA include the Wood Pesticide Compendium, WHO Classification of Pesticides, and other information included in risk assessment tools, such as the USEPA’s EPISuite and the OECD QSAR Toolbox. This presentation will summarize the available MOA assignment schemes, providing a critical evaluation of their limitations and utility.