Abstract
Uranium (U) is a natural ubiquitous radioelement whose occurrence may be magnified in the vicinity of some nuclear fuel cycle facilities orintensive farming areas. As mixtures are common in environment, U may be found associated with other contaminants such as cadmium (Cd).The exposure of organisms to these mixtures may result in unexpected synergism or antagonism that may be explained by interactions occurringat the exposure, toxicokinetics and/or toxicodynamic levels. The identification of these interactions and their underlying mechanisms may be ofinterest for a better risk characterization of multi-metallic polluted sites. In the present study, toxicity of binary mixture of U and Cd was assessedover time on physiological parameters, maximal length and brood size, in a partial lifespan experiment with the soil nematode Caenorhabditiselegans. A 49-condition fractional factorial design (extended design) was used with U and Cd concentrations, representative of some highlypolluted soils, ranging from 0.95 to 1.30 mM and 0.006 to 0.040 mM, respectively. Combined effects were analyzed using MixTox tool (Jonkeret al., 2005) to identify possible synergistic or antagonistic interactions.The best description of the toxic effects was met with the response addition concept and considering a dose-level dependent interaction model.An early significant antagonism was found at 1.2 d. Then, a continuous antagonism was identified for mixture levels upper than the EC36 or atlow U concentrations. As diet is suspected to be the main route of exposure of C. elegans to contaminants, an investigation of the diffusion of Uand Cd from agar to bacteria and their bioaccumulation by nematodes was achieved in a reduced design (8 conditions). A significant reductionof Cd internalization by C. elegans was observed in case of co-exposure with U and these results were correlated with the concentration of contaminants in bacteria. The observed antagonism of toxicity may thus be the resultant of an interaction at the exposure level where the diffusion oradsorption of Cd to bacteria is decreased by U. These findings underline the importance of studying chemical mixtures at various levels to fullyunderstand the underlying mechanisms and thus, avoid misinterpretations in the prediction of combined toxicity. Measurements of U and Cdconcentrations in bacteria are currently performed with the extended design in order to reinterpret the combined toxic effects on the basis ofthese concentrations.