Moving forward in carcinogenicity assessment: Report of an EURL ECVAM/ESTIV workshop

Abstract

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. 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.

EURL ECVAM Genotoxicity and Carcinogenicity Database of Substances Eliciting Negative Results in the Ames Test: Construction of the Database

“…The construction of a consolidated database of genotoxicity and carcinogenicity results for >700 Ames-positive chemicals, which was developed [ 7 , 8 ] as a follow-up activity of an EURL ECVAM workshop (2013), led to the public release of a powerful data resource intended to aid in the interpretation of in vitro genotoxicity results in general, likewise implementing the EURL ECVAM strategy on genotoxicity testing [ 3 ]. As such, the EURL ECVAM Consolidated Genotoxicity and Carcinogenicity Database of Ames-positives has, over recent years, become a reference for a number of regulatory activities in the area of genotoxicity testing across different product-type sectors [ 30 ].…”

“…The assessment is performed in a step-wise fashion whereby a battery of in vitro tests in both bacterial and mammalian cells are employed to detect a variety of effects (e.g., mutations, structural and numerical chromosomal aberrations); in certain cases in vitro testing is followed by in vivo studies. The exact combination of in vitro and in vivo studies may vary depending on the outcomes of initial testing, and/or the type of substance under investigation, and/or the requirements of the relevant legislation; the strategies employed generally depend on jurisdictions [ 3 , 4 ].…”

3S - Systematic, systemic, and systems biology and toxicology

“…Promise for all systemic toxicities comes from the starting development of integrated testing strategies driven by mechanistic relevance: By mapping the human reproductive cycle and its disturbance or the array of pathways of carcinogenesis with a number of assays, the hope is to design more human-relevant test strategies. These and other approaches form part of the emerging roadmap for replacement (Basketter et al, 2012; Leist et al, 2014; Corvi et al, 2017; ICCVAM, 2018) and will contribute to the momentum for implementing alternative approaches, which is also aided by the increasing recognition of the shortcomings of current testing methods.…”

Hazard identification, classification, and risk assessment of carcinogens: too much or too little? – Report of an ECETOC workshop

“…For example, the JRC is coleading the European Partnership for Alternative Approaches to Animal Testing (EPAA) activity on Mechanism-based approach to cancer risk assessment of agrochemicals incorporating 3Rs principles (https://ec.europa.eu/docsroom/documents/36296 [accessed ) and is contributing to the OECD working group on the development of an integrated approach for testing and assessment (IATA) for non-genotoxic carcinogens (Jacobs et al 2016). Moreover, the JRC is taking a broader look into an approach to carcinogenicity assessment which keeps pace with cancer burden and evolving chemical environment and considers more human data, related to etiology and links with other diseases, most common types of cancer and biomarkers of exposure (Corvi et al 2017;Madia et al 2019). The reduction or abandonment of the 2-year bioassay requires in the short-term new approaches to be implemented within the current regulatory frameworks and long-term initiatives to redesign the hazard and risk assessment paradigm as such.…”