Ensuring the Safety of Ingredients through Genotoxicity Testing

By: Scott Hickman, Head of Toxicology Marketing, BioReliance®

White Paper

genotoxicity of ingredientsIt is the mission of every product manufacturer to provide value in the materials they sell to their customers. This is no different in the F&F industry. Raw Material suppliers want to provide materials they can ensure are safe and will assist, not disable product development. Ingredients suppliers want to focus on safety and risk assessments while also ensuring quality products (“Help Reduce Risk”). Large Personal Care companies want to focus on the overall product not the ingredients, to comply with regulations and public perception (“Maintain Brand Value”). Contract Service Organizations (CSO) provide the testing that creates the value for these customers.

CSOs provide specific results that facilitate faster, more efficient development and ensure more reliable and safer products. One primary form of testing is Genotoxicity assessment that is not only required from many regulatory bodies, but also provides valuable mechanistic information to make decisions throughout the product development process.

Genotoxicity testing, which provides information on potential DNA damage resulting from human exposure to F&F ingredients and products, is a primary component in much worldwide legislation. The FDA, CPSC, EPA, EFSA, SCCS all have requirements for Genotoxicity assessment. The specifics vary slightly among jurisdictions, but all call for a common battery of assays that is tested on any component that will be sold for or involved in human consumption. In addition, various screening, non-GLP versions of these assays can be employed early on in the product development process to provide valuable characterization of materials before expensive development and expensive regulatory testing.

Genotoxicity assessment is provided in the form of a variety of testing options that have all been submitted to worldwide regulatory bodies and are approved by expert groups within the F&F industry. To begin with, high-throughput screening is used to screen potential product candidates. While not regulatory-approved these tests provide the same mechanistic and Mode of Action information as GLP, regulatory-approved assays, while much less expensive, require far less material, and can provide results in much less time. Examples in this area are the GreenScreen® HC and BlueScreen™ HC, Ames II™ assays and the new and novel CAN MultiFlow™ Assay. Whereas the Ames II™, GreenScreen® HC and BlueScreen™ HC assays either provide specific predictivity for one assay or are general predictors, the CAN MultiFlow™ can provide information on which Mode of Action (MOA) is present therefore providing definitive information on whether or not a substance is genotoxic and whether or not it should be continued and/or marketed.

Testing can also be performed with predictive, non-GLP screening assays. These assays can provide prediction for how a chemical compound will perform in a GLP assay. However, do to the value of compounds for the F&F industry, this step is mostly skipped, relying on the high-throughput screening assays to weed out potential hazardous compounds.

Most guidelines and regulatory agencies do require assays be performed in GLP conditions before a product is marketed to ensure that humans are not exposed to chemicals that could cause cancer or other harmful effects. The traditional battery performed in this stage includes a test for bacterial mutations (Ames assay), an in vitro cytogenetics assay (most commonly the Micronucleus Assay), and a follow up assay to rule out any Genotoxicity. Historically, an in vivo test on animals has been used as a follow up assay, but many current regulatory requirements employ a 3Rs strategy (Reduction, Refinement, Replacement) that precludes the use of animals. To remedy this, in vitro alternative assays have been introduced. The most common in this category is the 3D Skin Micronucleus Assay which employs a 3D reconstructed skin model that mimics an in vivo animal model. Recently a 3D skin model of the Comet assay has also been used, but is mostly still in validation.

How do we know the products we use are safe? Through companies like our services arm, BioReliance®, testing is performed to reduce risk and ensure safety. BioReliance focuses on Genetic Toxicology and is the one-stop-shop for complete, effective assessment of F&F ingredients. In fact, BioReliance’s assays and testing designs are approved by expert panels and used by suppliers, associations, and organizations throughout the F&F industry.