TY - JOUR
T1 - Systems toxicology approaches for understanding the joint effects of environmental chemical mixtures
AU - Spurgeon, David J.
AU - Jones, Oliver A. H.
AU - Dorne, Jean-Lou C. M.
AU - Svendsen, Claus
AU - Swain, Suresh
AU - Stuerzenbaum, Stephen R.
PY - 2010/8
Y1 - 2010/8
N2 - Environmental mixtures of chemicals constitute a prevalent issue in ecotoxicology and the development of new methods to reduce the uncertainties associated with their ecological risk assessment is a critical research need. Historically, a number of models have been explored to predict the potential combined effects of chemicals on species. These models, especially concentration addition and the independent action, have been applied to a number of mixtures. While often providing a good prediction of joint effect, there are cases where these models can have limitations: notably in cases where there are interactions for which they fail to adequately predict joint effects. To support the better mechanistic understanding of interactions in mixture toxicology a framework to support experimental studies to investigate the basis of observed interactions is proposed. The conceptual framework is derived from the extension of a three stage scheme which has previously been applied to understand chemical bioavailability. The framework considers that interactions in mixtures result from processes related to 1) the speciation, binding and transport of chemicals in the exposure medium (external exposure); 2) the adsorption, distribution, metabolism and excretion of chemicals within the organisms (toxicokinetics); 3) associations governing the binding and toxicity of the chemical(s) at the target site (toxicodynamics). The current state of the art in (eco)toxicology in relation to investigation of the mechanisms of interactions between chemicals is discussed with particular emphasis towards the multi-disciplinary tools and techniques within environmental chemistry; toxicology; biochemistry and systems biology that can be used to address such effects. (C) 2010 Elsevier B.V. All rights reserved.
AB - Environmental mixtures of chemicals constitute a prevalent issue in ecotoxicology and the development of new methods to reduce the uncertainties associated with their ecological risk assessment is a critical research need. Historically, a number of models have been explored to predict the potential combined effects of chemicals on species. These models, especially concentration addition and the independent action, have been applied to a number of mixtures. While often providing a good prediction of joint effect, there are cases where these models can have limitations: notably in cases where there are interactions for which they fail to adequately predict joint effects. To support the better mechanistic understanding of interactions in mixture toxicology a framework to support experimental studies to investigate the basis of observed interactions is proposed. The conceptual framework is derived from the extension of a three stage scheme which has previously been applied to understand chemical bioavailability. The framework considers that interactions in mixtures result from processes related to 1) the speciation, binding and transport of chemicals in the exposure medium (external exposure); 2) the adsorption, distribution, metabolism and excretion of chemicals within the organisms (toxicokinetics); 3) associations governing the binding and toxicity of the chemical(s) at the target site (toxicodynamics). The current state of the art in (eco)toxicology in relation to investigation of the mechanisms of interactions between chemicals is discussed with particular emphasis towards the multi-disciplinary tools and techniques within environmental chemistry; toxicology; biochemistry and systems biology that can be used to address such effects. (C) 2010 Elsevier B.V. All rights reserved.
U2 - 10.1016/j.scitotenv.2010.02.038
DO - 10.1016/j.scitotenv.2010.02.038
M3 - Article
VL - 408
SP - 3725
EP - 3734
JO - Science of the Total Environment
JF - Science of the Total Environment
IS - 18
ER -