Toxicokinetic-toxicodynamic modeling of quantal and graded sublethal endpoints: a brief discussion of concepts

Roman Ashauer (1) , Annika Agatz (2) , Carlo Albert (1) , Virginie Ducrot (3) , Nika Galic (4) , Jan Hendriks (5) , Tjalling Jager (6) , Andreas Kretschmann (1) , Isabel O'Connor (1, 5) , Mascha Nadine Rubach (4, 7) , Anna-Maija Nyman (1, 8) , Walter Schmitt (9) , Julita Stadnicka (1, 8) , Paul J van den Brink (4) , Thomas G Preuss (10)

1 EAWAG - Swiss Federal Insitute of Aquatic Science and Technology [Dübendorf]
2 University of York [York, UK]
3 ESE - Écologie et santé des écosystèmes
4 WUR - Wageningen University and Research [Wageningen]
5 Radboud University [Nijmegen]
6 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
7 Syngenta Crop Protection
8 ETH Zürich - Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich]
9 CropScience
10 RWTH - Rheinisch-Westfälische Technische Hochschule Aachen University

We report on the advantages and problems of using toxicokinetic-toxicodynamic (TKTD) models for the analysis, understanding, and simulation of sublethal effects. Only a few toxicodynamic approaches for sublethal effects are available. These differ in their effect mechanism and emphasis on linkages between endpoints. We discuss how the distinction between quantal and graded endpoints and the type of linkage between endpoints can guide model design and selection. Strengths and limitations of two main approaches and possible ways forward are outlined.

Mots clés: Dynamic energy budget; Dose–response; Adverse outcome pathway; Mechanistic effect model; toxicity; toxicokinetics

Mots clés: toxicité; toxicocinétique

Domaines: Santé publique et épidémiologie

Roman Ashauer, Annika Agatz, Carlo Albert, Virginie Ducrot, Nika Galic, et al.. Toxicokinetic-toxicodynamic modeling of quantal and graded sublethal endpoints: a brief discussion of concepts. Environmental Toxicology and Chemistry, 2011, 30 (11), pp.2519-2524. ⟨10.1002/etc.639⟩. ⟨hal-01453851⟩