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:
- 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;
- Calculate effective chemical activities (e.g., Ea50 or La50) corresponding to concentration-based testing data (e.g. EC50 or LC50);
- 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;
- 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;
- 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 [1-3]; 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;
- 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).
April, 2015 – June, 2017
Thomas, P.; Mackay, D.; Mayer, P.; Arnot, J.; Burgos, M. G. 2016. Response to Comment on “Application of the activity framework for assessing aquatic ecotoxicology data for organic chemicals”. Environ. Sci. Technol. 50, (7), 4141-4142.
Klüver, N.; Vogs, C.; Altenburger, R.; Escher, B. I.; Scholz, S., 2016. Development of a general baseline toxicity QSAR model for the fish embryo acute toxicity test. Chemosphere, 164, 164-173.
Stibany, F.; Schmidt, S. N.; Schäffer, A.; Mayer, P. 2017. Aquatic toxicity testing of liquid hydrophobic chemicals – Passive dosing exactly at the saturation limit. Chemosphere, 167, 551-558.
Posters and Platform Presentations:
Schmidt SN, Armitage JM, Arnot JA, Kusk KO, Mayer P. 2016. Linking algal growth inhibition to chemical activity: A tool for identifying excess toxicity. SETAC Conference, May 22-26, Nantes, France.
Schmidt SN, Armitage JM, Arnot JA, Kusk KO, Mayer P. 2015. Linking algal growth inhibition to chemical activity. SETAC Conference, November 1-5, Salt Lake City, UT.
Armitage JM, Arnot JA. Mackay D. 2015. Why is chemical activity successful as a metric of aquatic toxicity? A gedanken experiment explains why. SETAC Conference, November 1-5, Salt Lake City, UT.
Brown TN, Armitage JM, Arnot JA. 2015. Addressing uncertainty in sub-cooled liquid property estimation: Applications for chemical activity calculations. SETAC Conference, November 1-5, Salt Lake City, UT.