Energy-based modelling to assess effects of chemicals on Caenorhabditis elegans: a case study on uranium

Abstract

The ubiquitous free-living nematode Caenorhabditis elegans is a powerful animal model for measuring the evolutionary effects of pollutants which is increasingly used in (eco) toxicological studies. Indeed, toxicity tests with this nematode can provide in a few days data on the whole life cycle. These data can be analysed with mathematical tools such as toxicokinetic-toxicodynamic modelling approaches. In this study, we assessed how a chronic exposure to a radioactive heavy metal (uranium) affects the life-cycle of C. elegans using a mechanistic model. In order to achieve this, we exposed individuals to a range of seven concentrations of uranium. Growth and reproduction were followed daily. These data were analysed with a model for nematodes based on the Dynamic Energy Budget theory, able to handle a wide range of plausible biological parameters values. Parameter estimations were performed using a Bayesian framework. Our results showed that uranium affects the assimilation of energy from food with a no-effect concentration (NEC) of 0.42 mM U which would be the threshold for effects on both growth and reproduction. The sensitivity analysis showed that the main contributors to the model output were parameters linked to the feeding processes and the actual exposure concentration. This confirms that the real exposure concentration should be measured accurately and that the feeding parameters should not be fixed, but need to be reestimated during the parameter estimation process.

Keywords: Bayesian; Caenorhabditis elegans; Dynamic Energy Budget; Numerical behaviour; Uranium.