Recommendations for safety testing with the in vivo comet assay

► We present in vivo comet assay data from blind GLP testing of pharmaceuticals. ► Pre-lethal events before necrosis is evident are most likely to confound comet. ► Due to its sensitivity, comet is more appropriate as an acute study. ► Tissues other than just the liver and site of contact should be evaluated. ► Using our criteria, comet can detect biologically relevant low dose responses.