Most genetic toxicology Test Guidelines include three equal considerations when assessing whether a response is positive or negative, i.e. (i) a statistically significant increase from the concurrent negative control, (ii) a concentration/dose related response and (iii) the comparison to the historical negative control distributions, for assessing biological relevance. The three considerations are said to hold “equal” weight. However, recent analyses suggest historical controls can only be used to assess normal biological variation when they are of sufficient quality.
First commenting round on the draft updated Test Guidelines 488 and 470 on in vivo gene mutation assays
- Submission period
- 5 Dec 2024 - 23 Jan 2025
Background public consultation
Project description
A project led by the US and Canada was included in the Test Guideline Programme workplan in 2024 for the Revision of in vivo genotoxicity Test Guidelines’ “Evaluation and Interpretation of Results” and “Test Report” language. Beginning first with TGs 470 and 488, the purpose of the current revisions is to (i) provide more guidance for assessing the quality of historical negative control data (HDC) and databases; ii) update the study reports to include important information showing how the HCD and associated distribution and limit values were generated; and iii) giving more flexibility to the interpretation criteria associated with the comparisons with historical control intervals, including consideration of the quality of the underlying HCD.
How to contribute
The draft updated TG 470 and 488 are currently under a commenting round by the Working Party of the National Coordinators of the Test Guidelines Programmes and open for comments from the public at the same time. Interested parties are invited to contact their National Coordinators at least a week before 23 January 2025.
