Dr. James Armitage, AES Armitage Environmental Sciences, Inc., Toronto, ON, CA, email@example.com
Prof. Beate I. Escher, Helmholtz Centre for Environmental Research, Leipzig, DE, firstname.lastname@example.org
Prof. Philipp Mayer, Stine N. Schmidt Technical University of Denmark, Department of Environmental Engineering, Denmark, email@example.com
Dr. Barbara A. Wetmore, The Hamner Institutes for Health Sciences, Durham, NC, USA
Don Mackay, Don Mackay Environmental Research, Toronto, ON, CA, firstname.lastname@example.org
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; 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).
Read the Executive Summary here.
Thomas P, Dawick J, Lampi M, Lemaire P, Presow S, van Egmond R, Arnot JA, Mackay D, Mayer P, Galay Burgos M. Application of the Activity Framework for Assessing Aquatic Ecotoxicology Data for Organic Chemicals. Environ Sci Technol. 2015 Oct 20;49(20):12289-96.
Thomas P, Mackay D, Mayer P, Arnot J, Burgos MG. Response to Comment on “Application of the Activity Framework for Assessing Aquatic Ecotoxicology Data for Organic Chemicals”. Environ Sci Technol. 2016 Apr 5;50(7):4141-2.
Klüver N, Vogs C, Altenburger R, Escher BI, Scholz S. Development of a general baseline toxicity QSAR model for the fish embryo acute toxicity test. Chemosphere. 2016 Dec;164:164-173.
Stibany F, Schmidt SN, Schäffer A, Mayer P. Aquatic toxicity testing of liquid hydrophobic chemicals – Passive dosing exactly at the saturation limit. Chemosphere. 2017 Jan;167:551-558.
Fischer FC, Henneberger L, König M, Bittermann K, Linden L, Goss KU, Escher BI. Modeling Exposure in the Tox21 in Vitro Bioassays. Chem Res Toxicol. 2017 May 15;30(5):1197-1208.
Scholz S, Schreiber R, Armitage J, Mayer P, Escher BI, Lidzba A, Léonard M, Altenburger R. Meta-analysis of fish early life stage tests-Association of toxic ratios and acute-to-chronic ratios with modes of action. Environ Toxicol Chem. 2018 Apr;37(4):955-969.
Schmidt SN, Armitage JM, Arnot JA, Mackay D, Mayer P. Linking algal growth inhibition to chemical activity: Excess toxicity below 0.1% of saturation. Chemosphere. 2018 Oct;208:880-886.
Gobas FAPC, Mayer P, Parkerton TF, Burgess RM, van de Meent D, Gouin T. A chemical activity approach to exposure and risk assessment of chemicals. Environ Toxicol Chem. 2018 May;37(5):1235-1251.
Philipp Mayer. ECO30: Mining toxicity data to expand the domain of applicability of chemical activity. Cefic-LRI 19th Annual Workshop, November 2017, Brussels, Belgium.
Armitage JM, Arnot JA, Orazietti A, Brown TN, Celsie A, McCarty LS, Mackay D. Expanding the evaluation of the chemical activity hypothesis for toxicity assessment. SETAC Europe 27th Annual Meeting, May 2017, Brussels, Belgium.
Schmidt SN, Armitage JM, Arnot JA, Kusk KO, Mayer P. Linking algal growth inhibition to chemical activity: A tool for identifying excess toxicity. SETAC Europe 26th Annual Meeting, May 2016, Nantes, France.
Schmidt SN, Armitage JM, Arnot JA, Kusk KO, Mayer P. Linking algal growth inhibition to chemical activity. SETAC North America 36th Annual Meeting, November 2015, Salt Lake City, Utah, USA.
Armitage JM, Arnot JA. Mackay D. Why is chemical activity successful as a metric of aquatic toxicity? A gedanken experiment explains why. SETAC North America 36th Annual Meeting, November 2015, Salt Lake City, Utah, USA.
Brown TN, Armitage JM, Arnot JA. Addressing uncertainty in sub-cooled liquid property estimation: Applications for chemical activity calculations. SETAC North America 36th Annual Meeting, November 2015, Salt Lake City, Utah, USA.