Toward Good Read-Across Practice (GRAP) guidance

Abstract

SummaryGrouping of substances and utilizing read-across of data within those groups represents an important data gap filling technique for chemical safety assessments. Categories/analogue groups are typically developed based on structural similarity and, increasingly often, also on mechanistic (biological) similarity. While read-across can play a key role in complying with legislation such as the European REACH regulation, the lack of consensus regarding the extent and type of evidence necessary to support it often hampers its successful application and acceptance by regulatory authorities. Despite a potentially broad user community, expertise is still concentrated across a handful of organizations and individuals. In order to facilitate the effective use of read-across, this document presents the state of the art, summarizes insights learned from reviewing ECHA published decisions regarding the relative successes/pitfalls surrounding read-across under REACH, and compiles the relevant activities and guidance documents. Special emphasis is given to the available existing tools and approaches, an analysis of ECHA's published final decisions associated with all levels of compliance checks and testing proposals, the consideration and expression of uncertainty, the use of biological support data, and the impact of the ECHA Read-Across Assessment Framework (RAAF) published in 2015.

The need for strategic development of safety sciences

“…-The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) aims, outside of the pressures of regulating or being regulated, to be an engine of change in the safety sciences and other areas of animal use, overcoming the limitations of animal-based approaches and accelerating the uptake of new technologies by collaboration with all stakeholder groups. CAAT has started a number of collaborative programs to advance safety sciences, which include the Human Toxome Collaboration (see above), the Evidence-based Toxicology Collaboration (see below), the Good Cell Culture Practice Collaboration (Pamies et al, 2017) building on earlier work steered by ECVAM (Coecke et al, 2005), the Good ReadAcross Practice Collaboration (Patlewicz et al, 2014, Ball et al, 2016Zhu et al, 2016), the Refinement Collaboration (Zurlo and Hutchinson, 2014) and others. CAAT's transatlantic think tank for toxicology (t 4 ) has organized more than 30 workshops to advance concepts of toxicology such as integrated testing strategies (Hartung et al, 2013b;Rovida et al, 2015b), epithelial barrier models (Gordon et al, 2015), 3D cell cultures (Alépée et al, 2014), microphysiological systems (Marx et al, 2016), high-content imaging (van Vliet et al, 2014), and has commissioned a number of white papers.…”

Rebooting the generally recognized as safe (GRAS) approach for food additive safety in the US

“…This process using structural similarity to known toxicants is often referred to as read-across. Lately, initiatives to establish a Good Read-Across Practice (GRAP) have resulted in initial guidance (Ball et al, 2016); GRAP should be used in order to comply with the standard to be developed and any deviation should be justified.…”

Evolution of toxicological science: the need for change

“…Most recently, there is a lot of advance of read-across approaches (Patlewicz et al, 2014), which are ideally suited for this purpose. The recent move to Good Read-Across Practice guidance (Ball et al, 2016) and availability of large datasets on in vivo toxicology , will boost this field. Helping to choose substances with a better likelihood of being non-hazardous is sufficiently attractive to foster dialogue between synthetic chemists and toxicologists.…”