Please use this identifier to cite or link to this item:
|Title:||Mode of Action Classifications in the EnviroTox Database: development and implementation of a consensus MOA classification|
|Authors:||KIENZLER AUDE; CONNORS KRISTIN; BONNELL MARK; BARRON MACE; BEASLEY AMY; INGLIS CRISTINA; NORBERT-KING TERESA; MARTIN TODD; SANDERSON HANS; VALLOTTON NATHALIE; WILSON PETER; EMBRY MICHELLE|
|Citation:||ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY vol. 38 no. 10 p. 2294-2304|
|Type:||Articles in periodicals and books|
|Abstract:||Multiple modes of action (MOA) frameworks have been developed in aquatic ecotoxicology, mainly based on fish toxicity or associated with acute fish toxicity predictions. These frameworks have provided information on a key determinant of chemical toxicity, but the MOA categories and level of specificity remain unique to each of the classification schemes. The objective of this study was to develop a consensus MOA assignment within EnviroTox (https://envirotoxdatabase.org/), a curated in vivo aquatic toxicity database of 91,217 records representing 1,563 species, and 4,016 chemicals. Consensus rules were developed based on the degree of concordance among the four MOA classification schemes within EnviroTox: Verhaar (modifed) framework, ASTER 2.0, USEPA TEST 4.2, and LMC OASIS fish toxicity models. MOA classifications from each scheme were first collapsed into one of three categories: non-specifically acting (i.e., narcosis), specifically acting, or non-classifiable. A confidence rank was then assigned to the MOA classification of each of the 3900 non-ionized organic chemicals in EnviroTox based on the degree of consensus. Overall, 40% of the chemicals were classified as narcotics, 17% as specifically acting, and 43% could not be classified. Of the 2200 chemicals with MOA classifications, 60% had a medium to high consensus MOA assignment. EnviroTox is the first successful approach to establishing a high-level consensus across four computationally and structurally distinct MOA classification schemes. This consensus MOA classification provides both a transparent understanding of the variation between MOA classification schemes and an added certainty of the MOA assignment, when compared to a single framework approach. In terms of regulatory relevance, a reliable understanding of MOA, even at a simple binary level, can provide information that can infer chemical potency which can be a useful tool for the prioritization (ranking) and risk assessment of chemicals|
|JRC Directorate:||Health, Consumers and Reference Materials|
Files in This Item:
There are no files associated with this item.
Items in repository are protected by copyright, with all rights reserved, unless otherwise indicated.