title: Dynamic energy-based modeling of uranium and cadmium joint toxicity to Caenorhabditis elegans.
abstract: Toxicokinetic - toxicodynamic energy-based models offer new alternatives to the commonly used approaches for the analysis of mixture toxicity data. Based on the Dynamic Energy Budget theory, DEBtox models enable the description of several endpoints over time simultaneously under the same framework. However, such model still has to be faced with experimental data in a multi-contamination context. In this study, the predictive capacities of a DEBtox model to describe the uranium and cadmium joint toxicity over the entire growth and reproduction period of the soil nematode Caenorhabditis elegans was examined. The two reference additivity approaches, Concentration Addition and Response addition, implemented in the DEBtox model were tested. Assuming no interaction between the two toxicants through Response addition, the DEBtox model allowed a rather accurate fit of the U and Cd joint effects on the growth and reproduction of C. elegans: an interaction between the two metals at the toxicokinetic or toxicodynamic level seems thus unlikely or has only minor consequences. Interestingly, this study underlines that even if the compounds of a mixture share the same DEBtox physiological mode of action (in this case a decrease in assimilation), the Response addition approach may provide a better fit of joint toxicity data than the Concentration addition approach. Moreover, the present work highlighted limitations in the model predictions which are related to the simplifications of the DEBtox framework and its adaptations to the physiology of C. elegans and which lead to an overestimation of the U and Cd joint toxicity in some cases.
authors.affiliation: Biogeochemistry, Bioavailability and Radionuclide Transfer Laboratory (PRP-ENV/SERIS/L2BT), Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache, Building 183, BP3, 13115 St-Paul-lez-Durance Cedex, France. Electronic address: adrien.margerit@gmail.com.
authors.forename: Adrien
authors.initials: A
authors.lastname: Margerit
authors.affiliation: UMR Hydrosciences - Université Montpellier 1, DSESP - Faculté de Pharmacie, BP 14491, No 15 Av Charles Flahault, 34093 Montpellier Cedex 05, France.
authors.forename: Elena
authors.initials: E
authors.lastname: Gomez
authors.affiliation: Biogeochemistry, Bioavailability and Radionuclide Transfer Laboratory (PRP-ENV/SERIS/L2BT), Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache, Building 183, BP3, 13115 St-Paul-lez-Durance Cedex, France. Electronic address: rodolphe.gilbin@irsn.fr.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Gilbin
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D008962:Models, Theoretical; D012098:Reproduction / Q000187:drug effects; D014501:Uranium / Q000633:toxicity*
chemical_list: D002104:Cadmium; D014501:Uranium
keywords: Combined effects; Concentration addition; DEBtox; Independent action; Metal mixture; Sublethal toxicity