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Genetic & in vitro Toxicology

Genetic and In Vitro Toxicology

The genetic and in vitro toxicology group performs both non-GLP and GLP assays (such as genotoxicity, in silico mutagenicity prediction, phototoxicity and in vitro electrophysiology) for regulatory filings as well as screening assays for safety lead optimization. Utilizing industry-leading instruments, technologies and expertise, our study directors are committed to presenting rapid, high-quality data that can inform of potential risk during subsequent stages of development.

Genetic Toxicology

When DNA is exposed to particular test articles, mutations and other damage can occur leading to cancer and/or teratogenic effects.  The severity of these effects then necessitates examining whether new or existing test articles intended for human use have any effect on DNA.  This genotoxic potential is an integral part of the basic toxicological information package used in the decision-making and risk assessment process of drug development.  Since no single test is capable of detecting all relevant genotoxic end-points, a battery of in vitro and in vivo tests for genotoxicity is recommended by regulatory agencies.

Genetic Toxicology Screening Assays
  • Micro-Ames assay
  • Mini-Ames assay
  • Microwell micronucleus assay


Genetic Toxicology GLP Assays
  • Ames assay
  • In vitro chromosomal aberration assay
  • In vitro micronucleus assay
  • Mouse lymphoma assay
  • In vivo micronucleus assay
  • In vivo alkaline comet assay
  • In vivo chromosomal aberration assay
  • In vivo Pig-a gene mutation assay


In Silico Mutagenicity Prediction

The International Conference on Harmonization (ICH) M7 guidelines for the assessment and control of DNA-reactive (mutagenic) impurities in pharmaceuticals allows for the consideration of in silico predictions in place of in vitro studies. This represents a significant advance in the acceptance of Quantitative Structure-active Relationship (Q)SAR models.

Two complementing (Q)SAR prediction methodologies should be applied for predicting the outcome of a bacterial mutagenicity assay: one expert rule-based and the other statistical-based.

(Q)SAR Prediction
  • Leadscope model applier (expert rule-based and statistical-based models)

Phototoxicity is defined as a toxic response elicited by topically or systemically administered photoreactive chemicals after the body’s exposure to environmental light.  Recommended by European Medical Agency (EMA) and ICH guidelines, the 3T3 Neutral Red Uptake (NRU) Phototoxicity (PT) assay is an established in vitro assay used extensively in the pharmaceutical industry.

GLP or Non-GLP In Vitro Phototoxicity Assay
  • MEC
  • 3T3 NRU phototoxicity assay
  • In vivo phototoxicity assay


In Vitro Electrophysiology

The ion channels usually play an important role in determining the repolarization of cardiac action potential.  Blocking the hERG channel may cause QT interval prolongation and may resulting in Torsade de Pointes (TdP).  In vitro evaluation of drug effects on hERG potassium channels is a valuable tool for identifying potential proarrhythmic side effects in drug safety testing and the implementation of the ICH S7B guideline has been successful in preventing the introduction of drugs with a potential risk of TdP to the market.  Sodium and calcium ion channel assays can be considered as follow-up studies because they can weaken the QT prolongation caused by hERG block.


GLP or Non-GLP in vitro Electrophysiology Assay
  • hERG assay
  • Peak hNav1.5 assay
  • Late hNav1.5 assay
  • hCav1.2 assay