Toxicological interactions evaluation

Component-Based Methods. Component-based approaches (Figure 5.5) are generally used to evaluate human health risks from exposure to a limited number of chemicals as a mixture. Key issues for component-based assessments include similarity in dose-response curves and similar vs. independent toxic modes of action (MOAs) among mixture components. A distinction can be made between 1) assessments using relatively simple additivity methods without the consideration of potential interaction effects, and 2) assessments that include data on toxicological interactions. Both types of assessments are discussed in more detail below. 

A Weight-of-Evidence (WOE) Method To provide further guidance on the evaluation of chemical interactions and their impact on risk values calculated from data not reflective of the mixture, a weight-of-evidence (WOE) method was developed [25,26], The assessment of WOE for interactions enables assessors to judge if the interactions influence the overall toxicity of the mixture and if the anticipated joint toxicity will be greater than or less than expected based on the principle of additivity. The WOE method yields a composite representation of all the evidence on toxicologic interactions from human studies to animal bioassay data relevance of route, duration, and sequence and the significance of interactions. The method consists of a classification... 

Bucher, J., S. Masten, B. Moudgil, et al., 2004. Developing Experimental Approaches for the Evaluation of Toxicological Interactions of Nanoscale Materials. Einal Workshop Report 3-4 November 2004, University of Florida, Gainesville, FL. Available at www.nanotoxicology.ufl.edu/workshop/images/ NanoToxWorkshop.pdf... 

Many compounds may interact and cause unexpected toxic effects which could not be expected from the known toxicity of the individual components. Often one of three principles applies for assessment of the interactions between compounds in a mixed exposure. These are (i) independent action or no interaction between the components (ii) interaction between the compounds (which in some cases may be dealt with by adding the expected effects of the individual compounds using a weight factor expressing the relative potency of the compounds) and (iii) no assessment is possible because the interaction mechanisms are too complex for normal toxicological evaluation. It should be noted that different types of health effects may require different types of assessments of the interactions and that these assessments have different accuracy. These interactions are the main causes of the slow process of establishing official guidelines of IAQ. Further information is found in Cochet et al., (2006). 

Herbrandson, C., Bradbury, S.P. and Swackhamer, D.L. (2003b) Influence of suspended solids on acute toxicity of carbofuran to Daphnia magna II. An evaluation of potential interactive mechanisms, Aquatic Toxicology 63(4), 343-355. 

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