Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification

Abstract

Multiple mode of action (MOA) frameworks have been developed in aquatic ecotoxicology, mainly based on fish toxicity. These frameworks provide 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 present study aimed to develop a consensus MOA assignment within EnviroTox, a curated in vivo aquatic toxicity database, based on the following MOA classification schemes: Verhaar (modified) framework, Assessment Tool for Evaluating Risk, Toxicity Estimation Software Tool, and OASIS. The MOA classifications from each scheme were first collapsed into one of 3 categories: non–specifically acting (i.e., narcosis), specifically acting, or nonclassifiable. Consensus rules were developed based on the degree of concordance among the 4 individual MOA classifications to attribute a consensus MOA to each chemical. A confidence rank was also assigned to the consensus MOA classification based on the degree of consensus. Overall, 40% of the chemicals were classified as narcotics, 17% as specifically acting, and 43% as unclassified. Sixty percent of chemicals had a medium to high consensus MOA assignment. When compared to empirical acute toxicity data, the general trend of specifically acting chemicals being more toxic is clearly observed for both fish and invertebrates but not for algae. EnviroTox is the first approach to establishing a high‐level consensus across 4 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. In terms of regulatory relevance, a reliable understanding of MOA can provide information that can be useful for the prioritization (ranking) and risk assessment of chemicals. Environ Toxicol Chem 2019;38:2294–2304. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Assessment of ecological hazards and environmental fate of disinfectant quaternary ammonium compounds

“…Further evidence of the MOA of cationic surfactants can be gathered through the HESI EnviroTox database ( Connors et al, 2019 ; http://www.envirotoxdatabase.org/ ). The database permits a Consensus MOA assessment for compounds for which it has data available ( Kienzler et al, 2019 ). For ADBAC (CASRN 68424-85-1), the EnviroTox database produces a Consensus MOA as narcotic with a confidence score of 1 (lowest).…”

Ecological Thresholds of Toxicological Concern: A Review

“…Since its formation and publication of the paper outlining the concept (Belanger et al, 2015), this multi-stakeholder group has advanced the ecoTTC approach. Actions have included developing an open-access EnviroTox database and analysis tools (Connors et al, 2019), determining and exploring MOA schemes and assignments applicable to aquatic toxicity (Kienzler et al, 2017(Kienzler et al, , 2019, assessing acute to chronic relationships in algal species, and applying the concept to a case study on chemical mixtures (Kienzler et al, 2020). The objectives of this article are to briefly describe the ecoTTC concept and potential applications in ERA, provide an overview of the ecoTTC workflow and how the values can be derived, and highlight recent developments and ongoing research.…”

Use of the Species Sensitivity Distribution Approach to Derive Ecological Threshold of Toxicological Concern (eco-TTC) for Pesticides

“…The classification scheme proposed by Verhaar et al [20] was based on acute toxicity data for a single species (the guppy (Poecilia reticulata)). Other MoA classification schemes were successively proposed by Kienzler et al [22,23]. However, more recently, a study [24] proposed to expand the approach proposed by Verhaar et al [20] at the hierarchical scale of aquatic communities.…”