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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. [ABSTRACT FROM AUTHOR]

The assessment of genotoxicity represents an essential component of the safety assessment of all types of substances. Several in vitro tests are available at different stages of development and acceptance, yet they are not considered at present sufficient to fully replace animal tests needed to evaluate the safety of substances. For an overall improvement of the traditional genotoxicity testing paradigm, several recent activities have taken place. These include the improvement of existing tests, the development of novel tests, as well as, the establishment and exploration of approaches to optimise in vitro testing accuracy. Furthermore, useful tools, such as databases or reference chemical lists have been developed to support advances in this field. [ABSTRACT FROM AUTHOR]

The detection of carcinogenic chemicals still remains a major challenge. The only carcinogenicity test accepted by regulatory authorities is the in vivo two-year bioassay. In the area of genotoxicity, although several in vitro assays are currently used, substantial in vivo testing is still required for confirmation of the genotoxic prediction. To face these challenges, the ECVAM key area on carcinogenicity and genotoxicity was established in January 2004 with the initiation of several activities related both to validation and applied research. [•] Ongoing validation Cell Transformation Assay in BALB/c 3T3 and SHE cells to detect genotoxic and non-genotoxic carcinogens (first international validation study involving Europe, USA and Japan). [•] Retrospective validation on in vitro Micronucleus Test based on the existing data and the ECVAM criteria for validation. ESAC statement on the validity of the MNT in vitro as an alternative to chromosome aberration test in vitro for genotoxicity testing was issued November 2006 (follow-up validation in vitro/in vivo MNT). [•] A submission of an in silico tool to predict rodent carcinogenicity is under evaluation. [•] Current data collection from industry to investigate reduction possibilities, e.g. omission of positive/negative controls in in vivo genotoxicity testing, reduction of the false positive in vitro results that lead to further in vivo testing (follow-up on ECVAM workshop recommendations in collaboration with COLIPA) [•] Inter-laboratory assessment of genotoxicity tests in target cells. [•] COMET assay in 3D skin model (in collaboration with COLIPA). [•] Toxicogenomics-based tests, e.g. exploratory project to search for biomarkers of exposure in BALB/c 3T3. ECVAM is involved also in support to OECD activities (DRP31 and TG development), REACH Implementation Project RIP 3.3.2, the validation of COMET assay coordinated by JaCVAM and the EU Competitive actions: CARCINOGENOMICS and COMICS. [Copyright &y& Elsevier]

Cancer is a key public health concern, being the second leading cause of worldwide morbidity and mortality after cardiovascular diseases. At the global level, cancer prevalence, incidence and mortality rates are increasing. These trends are not fully explained by a growing and ageing population: with marked regional and socioeconomic disparities, lifestyle factors, the resources dedicated to preventive medicine, and the occupational and environmental control of hazardous chemicals all playing a role. While it is difficult to establish the contribution of chemical exposure to the societal burden of cancer, a number of measures can be taken to better assess the carcinogenic properties of chemicals and manage their risks. This paper discusses how these measures can be informed not only by the traditional data streams of regulatory toxicology, but also by using new toxicological assessment methods, along with indicators of public health status based on biomonitoring. These diverse evidence streams have the potential to form the basis of an integrated and more effective approach to cancer prevention. Opportunities for carcinogenicity assessment to address the challenges of cancer disease and chemicals in the environment. The safety assessment of carcinogenicity needs to evolve to keep pace with changes in the chemical environment and cancer epidemiology. Future strategies for assessing carcinogenicity based on a more holistic approach, can take into account the prevalence of certain cancers, the contribution to the disease of different risk factors, the study of relationships between chemical exposures and risk factors, the disease aetiology and links with other disorders. In addition, changes in chemical exposure patterns and exposed populations are also critical considerations. Unlabelled Image • Cancer has become a key public health concern worldwide and at EU level. • Cancer disease is a central priority of EU public health policy. • Public health policy actions cannot be decoupled from environmental policy actions. • Carcinogenicity assessment must evolve to ensure adequate levels of human protection. • The regulatory assessment of chemical toxicity should consider human specific cancers. [ABSTRACT FROM AUTHOR]