Temporal dynamics of effect concentrations.

In effect assessment the comparability and applicability of LCx and ECx values, which are calculated at single points in time during exposure, relies on the ability to perform a valid extrapolation to other time points of interest. The behavior of LCx in time has been extensively studied, and the behavior of ECx in time is expected to follow similar dynamics, as it is considered that the LCx is just a specific case of ECxs. However, most models have focused on validating the dynamics of LCx, and hardly anything is known about the time dependence of ECx for other endpoints or whether it is comparable to that of LCxs. We have created four scenarios where we study the dynamics of the ECx for different endpoints and how it is affected by the characteristics of two different compounds (carbendazim and pentachlorobenzene) and of two different life history strategies (hermaphroditic and sexually reproducing strains of Caenorhabditis elegans). The observed patterns of behavior in time of the ECx for body size and for reproduction showed unexpected dynamics that deviate considerably from that of the LCx. It was demonstrated that the temporal dynamics of ECx were very different for each particular endpoint. The shape of the ECx-time curves depends on the intrinsic characteristics of the endpoint of study, as well as on the characteristics of the compound and life history strategy of the organism. This makes extrapolation in time or between endpoints difficult and hampers the comparability of results based on this summary statistic. The interpretation of the results from toxicity tests can be improved through process-based modeling, as demonstrated on the current data set.

Mapping determinants of gene expression plasticity by genetical genomics in C. elegans.

Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 degrees C and 24 degrees C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 degrees C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity.

Physiological modes of action of toxic chemicals in the nematode Acrobeloides nanus.

To gain a better understanding of the mechanisms through which a chemical exerts toxicity, a deeper insight is needed regarding the physiological processes that take place during a toxic stress. This issue can have important benefits for risk assessment, because it can contribute to a better interpretation of toxicity data. Here, we study the physiological mode of action of three different compounds (cadmium, carbendazim, and pentachlorobenzene) with an experimental data-based approach using whole life-cycle toxicity data from the nematode Acrobeloides nanus. We use a process-based model, based on the dynamic energy budget theory, to study the fluxes of energy related to physiological processes and their variation throughout the life cycle. With this approach, we unravel the physiological modes of action based on resource allocation, and we model the effects of the different modes of action at the population level. The mode of action of carbendazim was through a decrease in assimilation, with an additional effect on the production of reactive oxygen species (ROS). Cadmium increased the costs of growth, with an extra effect on ROS production, and pentachlorobenzene decreased assimilation. We compared the present results with those of previous studies using the nematode Caenorhabditis elegans, and we found that the modes of action for the three compounds differed from those found in A. nanus, showing that the life-history characteristics of each organism have a clear influence on the resulting modes of action. This highlights the importance of the interactions between a chemical and the biological characteristics of the organism in determination of the resulting physiological modes of action.