Strategy on how to avoid and reduce animal use for assessing chemicals for genotoxicity
In December 2013, the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) of the European Commission's Joint Research Centre released its Strategy on how to avoid and reduce animal use for assessing chemicals for genotoxicity.
The assessment of genotoxicity represents an important component of the safety assessment of all types of substances. Although several in vitro tests are available at different stages of development and acceptance, they cannot at present be considered to fully replace animal tests needed to evaluate the safety of substances.
Based on an analysis of regulatory requirements for this endpoint within different pieces of EU legislation, EURL ECVAM proposes a pragmatic approach to improve the traditional genotoxicity testing paradigm that offers solutions in both the short- and medium-term and that draws on the considerable experience of 40 years of regulatory toxicology testing in this area.
EURL ECVAM considers that efforts should be directed towards the overall improvement of the current testing strategy for better hazard and risk assessment approaches, which either avoids or minimises the use of animals, whilst satisfying regulatory information requirements, irrespective of regulatory context. Several opportunities for the improvement of the testing strategy have been identified which aim to enhance the performance of the in vitro testing battery so that fewer in vivo follow-up tests are necessary, and guide more intelligent in vivo follow-up testing to reduce unnecessary use of animals.
The strategy went through consultation with its advisory and stakeholder bodies (*) and aims to satisfy regulatory requirements within various pieces of EU legislation.
The implementation of this strategic plan will rely on the cooperation of EURL ECVAM with other existing initiatives and the coordinated contribution from various stakeholders.
Genotoxicity testing includes both the measurement of direct, irreversible damage to the DNA ("mutagenicity"), that is transmissible to the next cell generation, as well as the measurements of early, potentially reversible effects on the DNA or on mechanisms involved in the preservation of the integrity of the genome ("genotoxicity"). For an adequate evaluation of the genotoxic potential of a chemical substance, different endpoints (i.e. induction of gene mutation, structural and numerical chromosome alterations) have to be assessed, as each of these events has been implicated in carcinogenesis and heritable diseases.
(*) Advisory and Consultation Bodies: the Preliminary Assessment of Regulatory Relevance (PARERE) Network), the EURL ECVAM Stakeholder Forum (ESTAF) and the EURL ECVAM Scientific Advisory Committee (ESAC); Commission Services and Partner Organizations of the International Cooperation on Alternative Test Methods (ICATM).