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Project ID: EVK1-CT-2001-00100
Finanziato nell'ambito di: FP5-EESD
Paese: Germany

Development of a set of criteria for mixture studies with fish

Existing evidence from mixture studies in other bioassays (especially from the PREDICT and BEAM EU-projects) as well as conceptual/mathematical arguments have been analysed in order to identify the major issues, that facilitate or hamper the successful completion of the mixture studies with the fathead minnow and the sea bass in ACE.

The following topics have been identified as being of major importance:
(a) If the single substance concentration-response relationships are of low accuracy, the assessment of the predictive power of both concepts (Concentration Addition and Independent Action) is severely limited. A low accuracy can either have experimental reasons (a low overall reproducibility of the concentration-effect data) or biometrical reasons (biased, inadequate modelling of the concentration-effect curve).
(b) Predictions according to the concept of Concentration Addition are restricted to the range of effects, which can be described for all mixture components. Hence, if clear differing maximum and/or minimum effects are observed, the applicability of the concept is limited.
(c) Independent Action assumes, that all concentration-effect curves can be reasonably scaled to a common minimum and maximum effect.
(d) The precise estimation of low-effect levels (whose determinations have a high demand in terms of experimental capacity and necessary test animals) is of paramount importance for the application of the concept of Independent Action to multi-component mixtures.
(e) Non-monotonic concentration-effect relationships (as they might be observed for chemicals that show endocrine effects and a high toxicity simultaneously) would clearly violate the conceptual basis of the prediction concepts.
(f) Long time intervals between the first single substance experiments and the final mixture experiments may introduce additional uncertainties.
(g) The number of possible mixture components is only restricted by the available experimental capacity. A high number of mixture components doesn't per se diminish the predictive power.

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Thomas BACKHAUS, (Scientist)
Tel.: +49-042-12184208
Fax: +49-042-12184920