A review of DEB theory in assessing toxic effects of mixtures.

In this manuscript we review the use of mechanistic models to interpret effects of mixtures of compounds within the framework of the Dynamic Energy Budget (DEB) theory. Within this approach the effect of a mixture is built up from the effects of the individual components making up the mixture. Understanding effects of mixtures is essential as it is impossible to assess effects of all possible mixtures experimentally. In contrast to the more classical way of interpreting effects of mixtures with concentration addition or effect addition models, DEB theory offers a single consistent framework to understand effects of mixtures on growth, reproduction and survival in an integrated, way. It systematically incorporates exposure time and biology of the organisms, including the natural links between the processes of feeding, maintenance, growth, development and reproduction. We also give directions for an experimental setup to interpret the results within the DEB framework. The DEB framework was successfully applied to assess effects of complex mixtures on survival and binary mixtures on sub-lethal endpoints. It gives the possibility to explain observed interactions by the underlying biological mechanisms or pinpoint interactions. We expect this approach to help in identifying key mechanisms and enable to focus further research in cooperation with modelers and experimentalists to improve our understanding of the mechanisms underlying mixture toxicity.

Chemical contamination and the ecological quality of surface water.

In the assessment of the quality of surface waters, the typical procedure is that the concentration of contaminants in the surface water is monitored and subsequently compared with their respective Maximum Permissible Concentrations (MPCs). If the MPCs are not exceeded the water quality is considered to be safe. But can we be certain that this is true? We compared MPCs to observed and calculated effects of measured contaminants in Dutch surface waters and showed that effects of mixtures can cause a daphnid population to go extinct within 30h of exposure even when MPCs are not exceeded. We conclude that there are shortcomings underlying the concepts of the MPCs. And that the MPCs aim to protect 95% of all species is not met.

Understanding toxicity as processes in time.

Studies in ecotoxicology usually focus on a single end point (typically mortality, growth, or reproduction) at a standardized exposure time. The exposure time is chosen irrespective of the properties of the chemical under scrutiny, but should depend on the organism of choice in combination with the compound(s) of interest. This paper discusses the typical patterns for toxic effects in time that can be observed for the most encountered endpoints growth reproduction and survival. Ignoring the fact that toxicity is a process in time can lead to severe bias in environmental risk assessment. We show that especially EC(x) values for sublethal endpoints can show very distinct patterns in time. We recommend that the test duration for survival as an endpoint should be extended till the incipient LC(50) is observed. Given the fact that toxicity data for single compounds show clear patterns in time, it is to be expected that effects of mixtures will also be strongly dependent on time. The few examples that have been published support this statement.

MODELKEY. Models for assessing and forecasting the impact of environmental key pollutants on freshwater and marine ecosystems and biodiversity.

BACKGROUND: Triggered by the requirement of Water Framework Directive for a good ecological status for European river systems till 2015 and by still existing lacks in tools for cause identification of insufficient ecological status MODELKEY (http:// www.modelkey.org), an Integrated Project with 26 partners from 14 European countries, was started in 2005. MODELKEY is the acronym for 'Models for assessing and forecasting the impact of environmental key pollutants on freshwater and marine ecosystems and biodiversity'. The project is funded by the European Commission within the Sixth Framework Programme. OBJECTIVES: MODELKEY comprises a multidisciplinary approach aiming at developing interlinked tools for an enhanced understanding of cause-effect-relationships between insufficient ecological status and environmental pollution as causative factor and for the assessment and forecasting of the risks of key pollutants on fresh water and marine ecosystems at a river basin and adjacent marine environment scale. New modelling tools for risk assessment including generic exposure assessment models, mechanistic models of toxic effects in simplified food chains, integrated diagnostic effect models based on community patterns, predictive component effect models applying artificial neural networks and GIS-based analysis of integrated risk indexes will be developed and linked to a user-friendly decision support system for the prioritisation of risks, contamination sources and contaminated sites. APPROACH: Modelling will be closely interlinked with extensive laboratory and field investigations. Early warning strategies on the basis of sub-lethal effects in vitro and in vivo are provided and combined with fractionation and analytical tools for effect-directed analysis of key toxicants. Integrated assessment of exposure and effects on biofilms, invertebrate and fish communities linking chemical analysis in water, sediment and biota with in vitro, in vivo and community level effect analysis is designed to provide data and conceptual understanding for risk arising from key toxicants in aquatic ecosystems and will be used for verification of various modelling approaches. CONCLUSION AND PERSPECTIVE: The developed tools will be verified in case studies representing European key areas including Mediterranean, Western and Central European river basins. An end-user-directed decision support system will be provided for cost-effective tool selection and appropriate risk and site prioritisation.