Multi-Strategy Assessment of Different Uses of QSAR under REACH Analysis of Alternatives to Advance Information Transparency.

Abstract

Under the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) analysis of alternatives (AoA) process, quantitative structure–activity relationship (QSAR) models play an important role in expanding information gathering and organizing frameworks. Increasingly recognized as an alternative to testing under registration. QSARs have become a relevant tool in bridging data gaps and supporting weight of evidence (WoE) when assessing alternative substances. Additionally, QSARs are growing in importance in integrated testing strategies (ITS). For example, the REACH ITS framework for specific endpoints directs registrants to consider non-testing results, including QSAR predictions, when deciding if further animal testing is needed. Despite the raised profile of QSARs in these frameworks, a gap exists in the evaluation of QSAR use and QSAR documentation under authorization. An assessment of the different uses (e.g., WoE and ITS) in which QSAR predictions play a role in evidence gathering and organizing remains unaddressed for AoA. This study approached the disparity in information for QSAR predictions by conducting a substantive review of 24 AoA through May 2017, which contained higher-tier endpoints under REACH. Understanding the manner in which applicants manage QSAR prediction information in AoA and assessing their potential within ITS will be valuable in promoting regulatory use of QSARs and building out future platforms in the face of rapidly evolving technology while advancing information transparency.