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Similarity, independence, or interaction for binary mixture effects of nerve toxicants for the nematode Caenorhabditis elegans.

Svendsen, Claus; Siang, Pia; Lister, Lindsay J.; Rice, Annabel; Spurgeon, David J.. 2010 Similarity, independence, or interaction for binary mixture effects of nerve toxicants for the nematode Caenorhabditis elegans. Environmental Toxicology and Chemistry, 5. 1182-1191. 10.1002/etc.140

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Abstract/Summary

Intensive agriculture can require the simultaneous use of more than one pesticide, resulting in the presence of mixtures in soils and waters. To assess mixture effects, concentration addition (CA) for similar acting chemicals and independent action (IA) for dissimilar acting chemicals are the most frequently used models. While the mechanistic basis for the selection of CA and IA for a given mixture appears appealing (similar vs dissimilar action), it has not yet been established how similar chemicals need to be in their effect before CA should be viewed as the most appropriate model. Here this is investigated in studies of the toxicity of binary mixtures of five different pesticides from three classes that have the same putative mode of action (neuroexcitation) but different molecular mechanisms in binary mixture tests with the nematode Caenorhabditis elegans. Effects of exposure on nematode survival were limited at the concentrations tested. Data analysis, therefore, focused on reproductive toxicity. Both CA and IA were found to be valid models for prediction of the toxicity of the 10 mixtures, although for seven CA provided a mathematically better fit. Both models could describe the toxicity for four mixtures; however, evidence for interaction was found in the remaining six cases. Where interactions occurred, these could be explained by information on the potential mechanisms of compound toxicokinetics—particularly when mixtures comprised a metabolically activated and a metabolically deactivated chemical and/or cases where the relative potencies of the two tested chemicals differed greatly. It is concluded, therefore, that detailed analysis of toxicokinetics and toxicodynamics can aid further understanding of interactions in mixtures

Item Type: Publication - Article
Digital Object Identifier (DOI): 10.1002/etc.140
Programmes: CEH Topics & Objectives 2009 onwards > Biodiversity > BD Topic 1 - Observations, Patterns, and Predictions for Biodiversity
CEH Sections: Hails
ISSN: 0730-7268
Additional Information. Not used in RCUK Gateway to Research.: Open access paper. Follow Official URL for access to full-text.
Additional Keywords: mixture toxicity, independent action, concentration addition, toxicokinetics, Cytochrome P450
NORA Subject Terms: Biology and Microbiology
Ecology and Environment
Date made live: 07 Sep 2010 08:20
URI: http://nora.nerc.ac.uk/id/eprint/10906

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