Challenges for Early, Predictive Genotoxicity Testing

Major Challenges for Early, Predictive Genotoxicity Testing 

The assessment of metabolites often requires complex preclinical studies and there are currently no cell-based assays that fully reproduce the in vivo metabolism of the human liver, or other tissues. The rodent S9 liver extracts used as an exogenous source of metabolism are incomplete metabolic surrogates, and perhaps more relevantly here, their properties are inappropriate for handling on an automated HTS platform. 

Ames and repeat 5 mg/plate Ames one complete assay tested to first precipitating dose Ames one complete assay, tested to first precipitating dose 

In vitro mammalian cell assay chromosome aberrations or tk mutations in mouse lymphoma cells 10 mM In vitro mammalian cell assay chromosome aberrations or tk mutations in mouse lymphoma cells or in vitro micronucleus assay 1 mM or 0.5 mg/ml top concentration No in vitro mammalian assay 

In vivo cytogenetic assay In vivo cytogenetic assay integrated into 28 d rodent toxicity study, provided it is adequate to support dinical trials and sampling within a day of last day of dosing In vivo cytogenetic assay and a 2nd in vivo endpoint, integrated wilh 28 d rodent assay and 1st in vivo endpoint if possible 

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