Making sense of sub-lethal mixture effects

Tjalling Jager, Tine Vandenbrouck, Jan Baas, Wim De Coen, Bas Kooijman

Typical approaches for analyzing mixture ecotoxicity data only provide a 
description of the data; they cannot explain observed statistical 
interactions, nor explain why mixture effects can change in time and 
differ between endpoints. To improve our understanding of mixture 
toxicity, we need to explore the use of biology-based models. These 
models allow us to implement our knowledge on biological and 
toxicological mechanisms, and test whether this knowledge is sufficient 
to explain the observed response of the organisms. When experimental 
data deviate from the model predictions, the nature of the deviation 
provides excellent information for designing additional research. In 
this contribution, we present an extension of the biology-based method 
DEBtox to deal with sub-lethal effects of mixtures on growth and 
reproduction. DEBtox explicitly accounts for the toxicokinetics of all 
components in the mixture. The toxicodynamic component of the method is 
now formed by a non-simplified implementation of dynamic energy budget 
(DEB) theory, which provides a natural framework for the interactions 
between different metabolic processes in organisms (and toxic effects 
on these processes). Because this method is based on physiological 
processes, it explicitly predicts toxic effects on all endpoints in time 
over the life cycle. Furthermore, it provides a natural framework for 
the inclusion of non-toxicant stresses, such as food limitation. We will 
illustrate the potential of this approach with an analysis of 
experimental data for two PAHs in Daphnia magna.