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Genotoxicity Testing – Screening vs OECD

Genotoxicity testing is a key testing requirement in a range of different industries, and is used to assess potential risk of pharmaceuticals, chemicals, pesticides, and cosmetics and personal care products. There are a vast number of different methods for determining DNA damage or genetic mutations so how do you choose an appropriate method?

The choice of method is typically dependent on a number of factors;

Timing and Budget – Early in a project it is common for larger numbers of test article to be tested. Often the purpose of the testing is to identify the best candidate or product to take forward. Due to the larger numbers of test articles, the cost of testing through OECD compliant protocols under GLP may be prohibitive, therefore often screening assays are used at this stage. Although in silico approaches may be a valuable first step, in vitro methods used in a screening format are useful in confirming these predictions, and have the advantage that they cost less and require less compound than the OECD compliant protocols. Commonly used in vitro screening methods include the 2 strain mini-Ames test, in vitro MNT, GreenScreen HC and H2AX assay.

Later on as the project progresses and one or two substances are selected for further development, it is common for the screening data to be confirmed in a number of in vitro OECD compliant protocols which are usually performed under GLP. These data are suitable for regulatory submission and depending on the industry and the results from the in vitro tests, further testing may be required in animal based models.

Industry – In the pharmaceutical industry, screening methods are commonly used within discovery stage projects, and then GLP OECD compliant in vitro and in vivo test methods are incorporated during preclinical development.

Within the cosmetics industry in the EU, animal testing is no longer is permitted. Therefore, genotoxicity testing is solely based on in silico methods, read across or in vitro based testing methods. Within the US, US law does not require specific tests to be performed to demonstrate safety of cosmetics. Despite this, the companies who manufacture or market these products have a legal responsibility to ensure their safety. Therefore, for cosmetics distributed in the US, non-GLP in vitro tests may be considered sufficient to demonstrate this in many cases. It is also well recognised that existing in vitro test methods may not be appropriate for assessing skin genotoxins and a high rate of false positives is observed. This is due to the fact that the substance has to be absorbed into the skin and reach the basal cell layer to cause any genotoxic effects. To address this, 3D reconstructed human skin models are currently being developed and evaluated to see if they have improved predictive capability.

Mechanistic Information – The choice of test method used for assessing genotoxic potential is often dependent on the mechanism of genotoxicity anticipated from structurally related compounds or from previous in vitro data. For example, the micronucleus test is more appropriate for detecting aneugens and the chromosomal aberration test tends to be used for detecting clastogens.

Find out more about genotoxicity testing in our Mechanisms of Drug-Induced Toxicity guide and our Chemical and Cosmetics Testing guide or through our website http://www.cyprotex.com/toxicology/genotoxicity.

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