Tox - Transcriptomic Point of Departure

The investigation of chronic toxicity in fish for the authorisation-relevant environmental risk assessment of substances, for example within the framework of REACH, is time-, cost- and animal-intensive. For this reason, international efforts are being made to develop so-called New Approach Methods (NAMs) and to test their regulatory applicability in order to identify hazards and risks with regard to chronic toxic effects in a time- and cost-saving and 3R-compliant manner. In this context, the transcriptomic point of departure (tPOD) is increasingly being discussed in ecotoxicology in order to derive quantitative endpoints of chronic toxicity from RNA sequencing studies. The use of transcriptomic data in the zebrafish embryo model as a NAM is particularly attractive for this purpose, as it is recognised as an alternative to animal testing in accordance with EU Directive 2010/63/EU (see Figure 1). The limited literature available to date suggests that the tPOD values from fish embryo toxicity tests (FET) are protective, i.e. they are of a comparable order of magnitude but tend to be below the No Observed Effect Concentration (NOEC) derived from long-term chronic fish toxicity tests. We offer our customers the identification of tPODs for substances in the fish embryo model. We have already identified sublethal transcriptomic and proteomic profiles for a variety of mechanisms of action (MoA) in this model (see Ecotoxicogenomic Screening), which can be used as a basis for the identification of MoA-specific tPODs. While a larger database on tPODs and chronic data will support the assessment of the regulatory utility of tPODs for the identification of chronic toxicity, tPOD values can be used to determine the concentration range of the NOEC for chronic toxicity studies in fish and thus save time-, cost- and animal-intensive pre-tests.