EURL ECVAM-ESTIV workshop on the way forward
As resulted from Madia et al., 2016, there is an increased need to develop novel alternative approaches to the two-year rodent bioassay for the carcinogenicity assessment of substances where the rodent bioassay is still a basic requirement, as well as for those substances where animal use is banned or limited or where information gaps are identified within legislation. The current progress in this area was addressed in a EURL ECVAM- ESTIV workshop held in October 2016, in Juan les Pins (Corvi et al., 2017).
A number of initiatives were presented and discussed, including data-driven, technology-driven and pathway-driven approaches. Despite a seemingly diverse range of strategic developments, commonalities are emerging. For example, providing insight into carcinogenicity mechanisms is becoming an increasingly appreciated aspect of hazard assessment and is suggested to be the best strategy to drive new developments.
Thus, now more than ever, there is a need to combine and focus efforts towards the integration of available information between sectors. Such cross-sectorial harmonisation will aid in building confidence in new approach methods leading to increased implementation and thus a decreased necessity for the two-year rodent bioassay.
Non-genotoxic carcinogens contribute to an increased cancer risk by a variety of mechanisms that are not yet included in international regulatory approaches. To address this need, an integrated approach to testing and assessment (IATA) of non-genotoxic carcinogens is beginning to be developed internationally under the auspices of the OECD.
An expert working group has in fact been set up to examine the current international regulatory requirements and their limitations in respect to non-genotoxic carcinogenicity, and how an IATA could be developed to assist regulators in their assessment of non-genotoxic carcinogenicity.
Moreover, the working group is tasked to review, describe and assess relevant in vitro assays with the aim of tentatively organising them into levels of testing, following the adverse outcome pathway format, such as that possible structure(s) of the future IATA(s) can be created.
Some preliminary work to this activity has already been described in a publication of Jacobs and colleagues (Jacobs et al., 2016). EURL ECVAM is an active player of the group.
CarcinoGENOMICS FP6 project
EURL ECVAM has been involved in the CARCINOGENOMICS FP6 project, which aimed at developing toxicogenomics- and metabolomics-based in vitro tests to detect potential genotoxicants and carcinogens.
Two tests have been selected for further optimization: a toxicogenomics-based test in HepaRG cells for the liver and a toxicogenomics-based test in RPTEC/TERT1 cells for the kidney. The optimisation/prevalidation work package was coordinated by EURL ECVAM and aimed at
- further developing the two test models by testing 15 additional chemicals;
- assessing test models transferability and reproducibility using the same agreed SOPs and
- develop dedicated bioinformatics tools to serve as basis for future validations of omics-based tests.
The results of this workpackage are published in Doktorova et al., 2014 and Herwig et al., 2016.
See also Vinken et al., 2008 for chemical selection.