When testing novel active pharmaceutical ingredients (API) for their genotoxic properties in early phases of drug development, it is not always possible to avoid residual solvent in the formulation. These solvent residues can lead to misleading genotoxicity results that are unrelated to the API. To evaluate solvent‑related genotoxicity and define acceptable solvent concentrations, we tested 19 commonly used solvents in the ToxTracker genotoxicity assay in collaboration with Eli Lilly.

Key Findings:

• Many commonly used solvents, including DMSO, THF, isopropanol and methanol are suitable vehicles in ToxTracker at concentrations up to 1% v/v, producing ≤20% cytotoxicity and no genotoxicity reporter activation.
• Isopropyl amine was the only solvent that triggered a positive ToxTracker response below 10 mM; however, the absence of in vivo genotoxicity data limits interpretation of its biological relevance.
• The OECD‑recommended limit concentration of 10 mM was confirmed as an effective threshold to minimize false‑positive ToxTracker outcomes when benchmarked against available in vivo genotoxicity data.

A full overview of the solvents evaluated is available in our poster.  In the upcoming ToxTracker OECD Test Guideline, we have also defined a panel of eight solvents compatible with ToxTracker for dissolving test substances.

Contact us if you would like to verify whether your solvent system is appropriate.