Chemical Safety Assessment Using Read-Across: Assessing the Use of Novel Testing Methods to Strengthen the Evidence Base for Decision Making

Abstract

BackgroundSafety assessment for repeated dose toxicity is one of the largest challenges in the process to replace animal testing. This is also one of the proof of concept ambitions of SEURAT-1, the largest ever European Union research initiative on alternative testing, co-funded by the European Commission and Cosmetics Europe. This review is based on the discussion and outcome of a workshop organized on initiative of the SEURAT-1 consortium joined by a group of international experts with complementary knowledge to further develop traditional read-across and include new approach data.ObjectivesThe aim of the suggested strategy for chemical read-across is to show how a traditional read-across based on structural similarities between source and target substance can be strengthened with additional evidence from new approach data—for example, information from in vitro molecular screening, “-omics” assays and computational models—to reach regulatory acceptance.MethodsWe identified four read-across scenarios that cover typical human health assessment situations. For each such decision context, we suggested several chemical groups as examples to prove when read-across between group members is possible, considering both chemical and biological similarities.ConclusionsWe agreed to carry out the complete read-across exercise for at least one chemical category per read-across scenario in the context of SEURAT-1, and the results of this exercise will be completed and presented by the end of the research initiative in December 2015.CitationBerggren E, Amcoff P, Benigni R, Blackburn K, Carney E, Cronin M, Deluyker H, Gautier F, Judson RS, Kass GE, Keller D, Knight D, Lilienblum W, Mahony C, Rusyn I, Schultz T, Schwarz M, Schüürmann G, White A, Burton J, Lostia AM, Munn S, Worth A. 2015. Chemical safety assessment using read-across: assessing the use of novel testing methods to strengthen the evidence base for decision making. Environ Health Perspect 123:1232–1240; http://dx.doi.org/10.1289/ehp.1409342

A chemical–biological similarity-based grouping of complex substances as a prototype approach for evaluating chemical alternatives

“…While the requirements for the information needed for approval of pharmaceuticals and pesticides are very proscriptive and largely harmonized across the globe, the regulatory regimes for most chemicals in commerce not only vary from country to country, but are also evolving rapidly. 23,24 Identification of “safer alternatives” to products already on the market is yet another challenge whereby no uniform process or standard exists to establish what “safer” means. 1 Human health considerations are frequently behind a desire for an alternative, and weigh heavily into the overall safety considerations for the choice among the alternatives.…”

Grouping of Petroleum Substances as Example UVCBs by Ion Mobility-Mass Spectrometry to Enable Chemical Composition-Based Read-Across

“…Grouping and read-across are encouraged in regulatory submissions for both mono-constituents and UVCBs. 31–33 However, the inherent compositional complexity and variability of many UVCBs creates unique challenges for their grouping and read-across. Regulatory guidelines allow for inclusion of multidimensional data to support read-across submissions; these can include data on biological activity (toxicological and mechanistic) and bioavailability (including metabolite profiling).…”

Adverse Outcome Pathways--Organizing Toxicological Information to Improve Decision Making

“…The use of AOPs in a read-across context was considered at a workshop held as part of the SEURAT-1 project (Berggren et al, 2015). The goal of the workshop was to increase confidence in read-across using results from alternative methods.…”