Mixture extrapolation approaches

In our opinion, the data are sufficiently clear to suggest that when it is not feasible to test the mixture in question, mixture extrapolation is the preferred option compared to no extrapolation. Indeed, all literature observations suggest that applying mixture extrapolation is to be preferred over not applying mixture extrapolation. Technical options for extrapolation are concentration addition, response addition, and the mixed-model approach, of which concentration addition is most often applied. Exceptions may apply in cases that are more specific. For example, when it is clear that 2 compounds precipitate (a situation of no exposure due to chemical interactions in the environment), one should acknowledge this prior to assessing mixture risks by mixture extrapolation approaches. When the data of a study allow, refined conclusions are possible. For example, when the study design is appropriate and the mathematical models are appropriate, researchers are able to discriminate between concentration addition and response addition, and (with sufficient experiment efforts) between these models and the mixed-model approach. 

Overview of mixture extrapolation approaches used in practice... 

Higher tier mixture extrapolation approaches such as this are used in practice, by calculating site-specific msPAF values, across a broad range of assessment questions. A practical example is provided by De Zwart (2005), who studied the impacts of pesticide use in The Netherlands. In this study, the specific mode of action of the pesticide was taken into account, as shown in Box 5.2. This analysis resulted in spatiotemporal indicators of relative toxic pressure across The Netherlands (Figure 5.3). 

Posthuma L, Richards S, De Zwart D, Dyer SD, Sibley P, Hickey C, Altenburger R. 2008. Mixture extrapolation approaches. In Solomon KR, Brock TCM, De Zwart D, Dyer SD, Posthuma L, Richards S, Sanderson H, Sibley R, Van den Brink PJ, editors, Extrapolation practice for ecotoxicological effect characterization of chemicals. Results of the EXPECT workshop, February 2005, St. Petersburg, FL, USA. Pensacola (FL) SETAC Press. 

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