EURL ECVAM strategy for achieving 3Rs impact in the assessment of toxicokinetics and systemic toxicity

Abstract

Robust genomic approaches are now available to realize improvements in efficiencies and translational relevance of cancer risk assessments for drugs and chemicals. Mechanistic and pathway data generated via genomics provide opportunities to advance beyond historical reliance on apical endpoints of uncertain human relevance. Published research and regulatory evaluations include many examples for which genomic data have been applied to address cancer risk assessment as a health protection endpoint. The alignment of mature, robust, reproducible, and affordable technologies with increasing demands for reduced animal testing sets the stage for this important transition. We present our shared vision for change from leading scientists from academic, government, nonprofit, and industrial sectors and chemical and pharmaceutical safety applications. This call to action builds upon a 2017 workshop on “Advances and Roadblocks for Use of Genomics in Cancer Risk Assessment.” The authors propose a path for implementation of innovative cancer risk assessment including incorporating genomic signatures to assess mechanistic relevance of carcinogenicity and enhanced use of genomics in benchmark dose and point of departure evaluations. Novel opportunities for the chemical and pharmaceutical sectors to combine expertise, resources, and objectives to achieve a common goal of improved human health protection are identified.