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A 3R compliant testing strategy to predict chronic fish toxicity
Citation:
Vergauwen, L., Dan Villeneuve, S. Verstraelen, F. Dardenne, R. Blust, G. Ankley, H. Witters, AND D. Knapen. A 3R compliant testing strategy to predict chronic fish toxicity. Presented at SETAC Europe, Basel, SWITZERLAND, May 11 - 15, 2014.
Impact/Purpose:
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Description:
To ensure an ecologically relevant basis for environmental quality standards, whole-organism vertebrate tests are considered most suitable. Currently, the fish early life-stage (FELS) test (OECD 210), which involves an exposure up to one - two months, is used to estimate chronic toxicity of regulated chemicals. Several shortcomings to the FELS test can be identified, the most important being the use of high numbers of animals, low throughput and the lack of mechanistic information. We recently started the CEFIC LRI-ECO20-UA project to develop an alternative testing strategy for prediction of chronic fish toxicity. The goal of the project is to use in vivo alternative, in vitro and in silico tests to predict chronic toxicity in a 3R compliant way. Since the zebrafish is not considered a test animal according to EU regulation (2012/707/EU) up to the age of 120hpf (hours post fertilization), we put forward the 120 hpf ZFET (zebrafish embryo toxicity) test as an ideal in vivo alternative test system. We present a conceptual workflow combining in vivo alternative and in silico techniques to enable chronic toxicity prediction. It has become clear that chronic toxicity prediction cannot be generalized over a large range of different working mechanisms. We propose an alernative testing strategy based on the adverse outcome pathway (AOP) framework [1], delineating the sequence of key events at increasing levels of biological organization resulting in an ecologically relevant adverse outcome at a high level, in order to increase the mechanistic input in fish toxicity assessment and increase the biological relevance of applied testing strategies. This strategy relies on a classification of compounds according to their predominant AOP. The project presently focuses on four AOPs as case studies and will put forward AOP-specific methods for chronic toxicity prediction. The following three elements will be considered for each AOP.