ECO30-ARC: Expanding the applicability domain of the chemical activity approach for hazard and risk assessment

Description

The general objectives of this proposed research are (a) to link the toxicity of chemicals to their chemical activity, (b) to expand and critically evaluate the applicability domain of chemical activity for interpreting toxicity data, and (c) to facilitate the application of chemical activity within chemical hazard and risk assessments. To satisfy these objectives we will:

1. Develop and critically evaluate a large database of in vivo, in vitro and bioactivity testing data for a range of organic chemicals, a range of species and a range of endpoints (e.g., lethality, sub-lethal, acute, chronic, mode-of-action specific) and develop an evaluated database of physical-chemical properties for these chemicals;
2. Calculate effective chemical activities (e.g., Ea₅₀ or La₅₀) corresponding to concentration-based testing data (e.g. EC₅₀ or LC₅₀);
3. Where appropriate, parameterize and apply toxicokinetic mass balance models to calculate internal effect concentrations (IECs) and internal effect chemical activities (IEa) from exposure-based toxicity testing data;
4. Parameterize and apply mass balance models for in vitro testing to calculate dissolved concentrations and chemical activities corresponding with test endpoints (e.g. EC₅₀ and Ea₅₀) and nominal or measured concentrations;
5. Develop a tiered strategy for using toxicity/bioassay data and physical-chemical property data for overall chemical activity estimate reliability for different classes of organic chemicals: a) Acceptable quality data will be used to examine relationships between chemicals expected to exert only a baseline narcosis mode of action (MoA) and those expected to exert specific or reactive MoA; b) Acceptable quality data will be used to examine acute-chronic ratios for baseline toxicants and those expected to exert specific or reactive MoA; c) Less reliable data may be used in a supportive role to examine differences in chemical activities and MoA and acute vs. chronic values;
6. Show how these data could lead towards new criteria for hazard assessment and new thresholds for acceptable levels of environmental exposures for screening-level risk prioritization (lethal and sub-lethal endpoints, acute and chronic exposures).

Read the Executive Summary here.