Generic Solving of One-compartment Toxicokinetic Models

Sandrine Charles (1) , Aude Ratier (1) , Christelle Lopes (1)

1 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558

This paper gives the full analytical solution of the generic set of ordinary differential equations that define onecompartment toxicokinetic models. These models describe the uptake and elimination processes that occur within living organisms when exposed to chemical substances. The models solved in this paper consider living organisms as a unique compartment, into which a parent compound enters via several possible exposure routes and from which it is eliminated as well as its potential metabolites. Benefiting from generic solutions of onecompartment toxicokinetic models is particularly useful when fitting them to experimental data, facilitating the writing of the inference algorithms leading to parameter estimates. Additionally, these models are of crucial interest in environmental risk assessment for the calculation of bioaccumulation metrics as required by regulators in support of decision-making when they evaluate dossiers for marketing authorisation of active substances.

Mots clés: Ordinary differential equations; Environmental risk assessment; Living organisms; Active substances; Toxicokinetic models; Bioaccumulation metrics. Abbreviations: ADME; absorption; distribution; metabolism and excretion; EFSA; European food safety authority; ERA; environmental risk assessment; ODE; ordinary differential equation; PBPK; physiologically based pharmacokinetic; PBTK; physiologically based toxicokinetic; TK; toxicokinetic

Domaines: Méthodologie [stat.ME]; Applications [stat.AP]; Mathématiques générales [math.GM]; Statistiques [math.ST]; Modélisation et simulation; Ecotoxicologie; Interactions entre organismes; Ecosystèmes; Bio-Informatique, Biologie Systémique [q-bio.QM]; Environnement et Société; Biodiversité et Ecologie

Sandrine Charles, Aude Ratier, Christelle Lopes. Generic Solving of One-compartment Toxicokinetic Models. Journal of Exploratory Research in Pharmacology, 2021, ⟨10.14218/JERP.2021.00024⟩. ⟨hal-03362341⟩