Genotoxicity testing plays a vital role in identifying the potential of a substance to be mutagenic. Pharmaceuticals, pesticides and chemical substances must be assessed for safety before being authorised for use.
Genotoxicity relates to the properties of chemical agents that can cause cell mutations and damage the cell’s genetic profile, potentially leading to cancer. Genotoxicity adverse outcomes, include inherited mutations and diseases as well as cancers, developmental toxicity and ageing.
Testing must investigate the ability of test substances to mutate DNA as part of the regulatory testing framework. Ames testing has been part of this process to understand the chemical properties and modes of action for many years. In particular, the most commonly required genotoxicity test is the OECD 471: Ames Test, which has been used for decades and remains equally relevant today.
To understand the results and the impacts of a positive or negative result from Ames testing, the expertise of specialist predictive toxicology experts is vital. Genotoxicity screening experts at companies such as Gentronix, a specialist CRO, have vast experience in delivering and assisting with a wide range of genetic toxicology and flow cytometry services to aid the industry with reaching optimal interpretation of endpoints. Therefore, you can be sure their services, knowledge and experience are working to deliver the innovative solutions to achieve chemical safety.
More on how the OECD 471: Ames test works
This Ames test is a bacterial reverse mutation assay, which investigates whether test substances cause mutations in Salmonella or E. coli strains so that they can grow on selective agar plates.
The test uses amino acid-deficient Salmonella typhimurium and Escherichia coli strains harbouring different genetic histidine and tryptophan operon mutations to identify those that cause substitution, deletion or addition to one or more DNA base pairs. When assessing the safety of a substance, a positive Ames test result is taken very seriously.
The Ames assay enables bacterial mutagenicity data collection that can be used as a part of the core data requirements required by regulatory bodies to accept safety and register products and chemicals, including drugs, food additives, pesticides, and biocides. Bacterial cells are exposed to the test chemical, and the bacterial growth is scored for indication of mutations. Metabolic activation is carried out typically using induced rat liver S9. However, other sources for activation are available to achieve a mutagenicity endpoint.
The Ames test provides valuable information to assist identification of mutagenic properties or modes of action to help determine testing changes and the viability of any progression.
The regulatory environment surrounding the development of new drugs, treatments, chemical-based products and food additives is immense, and many products fail during development, so early-stage genotoxicity studies can help identify the viability and suitability of the chemical for further development. Modes of action can be studied to determine changes or path changes that can better sustain continuous development or enable a risk/reward assessment that may identify a need to control exposure to reduce the identified risk.
As an in vitro short-term test, the Ames test offers excellent data for preliminary screening of chemical substance mutagenicity. Impurity genotoxicity can be assessed, and hazard identification information will form the basis of future decision-making.
A negative Ames test result will help with the regulatory process to support the evidence that the chemical is non-genotoxic at given levels. Considerable experience is required to conduct and interpret the results of the Ames test and to understand and contextualise the lowest effective dose effective in the Ames Test needed to provide accurate test results. Therefore, choosing professionals with a proven track record in performing and analysing such tests is vital.