A framework to facilitate consistent characterization of read across uncertainty

- Read across can potentially introduce additional uncertainty in risk assessment.
- A systematic framework is presented to characterize this potential uncertainty.
- A questionnaire to guide application of the framework was also developed.
- This should facilitate consistency and transparency in uncertainty characterization.
- This characterization can be used as a starting point for uncertainty refinement.

A process for evaluating analogues for use in structure activity relationship (SAR) assessments was previously published (Wu et al., 2010) and tested using a series of case studies (Blackburn et al., 2011). SAR-based “read across” approaches continue to be broadly used to address toxicological data gaps. The potential additional uncertainty introduced into risk assessments as a result of application of read across approaches to fill data gaps has been widely discussed (OECD, 2007; ECETOC, 2012; Patlewicz et al., 2013), but to date a systematic framework to guide the characterization of uncertainty in read across assessments has not been proposed. The current manuscript presents both a systematic framework to describe potential areas of additional uncertainty that may arise in read across (evaluated based on the number and suitability of analogues contributing data, severity of the critical effect, and effects and potency concordance), as well as a questionnaire for evaluating and documenting consideration of these potential additional sources of uncertainty by risk assessors. Application of this framework represents a next step in standardizing the read across process, both by providing a means to transparently assign a level of uncertainty to a SAR-based read across assessment and by facilitating consistency in read across conclusions drawn by different risk assessors.