Enhancing global and local decision making for chemical safety assessments through increasing the availability of data.

Toxicity safety assessments are a fundamental part of the lifecycle of products and aim to protect human health and the environment from harmful exposures to chemical substances. To make decisions regarding the suitability of testing strategies, the applicability of individual tests or concluding an assessment for an individual chemical requires data. This review outlines how different forms of data sharing, from enhancing publicly-available data to extracting knowledge from commercially-sensitive data, leads to increased quantity and quality of evidence being available for safety assessors to review. This can result in more confident decisions for different use cases in the context of chemical safety assessments. Although a number of challenges remain with progressing the evolution of toxicity safety assessments, data sharing should be considered as a key approach to accelerating the development and uptake of new best practices.

The importance of expert review to clarify ambiguous situations for (Q)SAR predictions under ICH M7.

The use of in silico predictions for the assessment of bacterial mutagenicity under the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 guideline is recommended when two complementary (quantitative) structure-activity relationship (Q)SAR models are used. Using two systems may increase the sensitivity and accuracy of predictions but also increases the need to review predictions, particularly in situations where results disagree. During the 4th ICH M7/QSAR Workshop held during the Joint Meeting of the 6th Asian Congress on Environmental Mutagens (ACEM) and the 48th Annual Meeting of the Japanese Environmental Mutagen Society (JEMS) 2019, speakers demonstrated their approaches to expert review using 20 compounds provided ahead of the workshop that were expected to yield ambiguous (Q)SAR results. Dr. Chris Barber presented a selection of the reviews carried out using Derek Nexus and Sarah Nexus provided by Lhasa Limited. On review of these compounds, common situations were recognised and are discussed in this paper along with standardised arguments that may be used for such scenarios in future.

Investigating a Relationship between the Mutagenicity of Arylboronic Acids and (11)B NMR Chemical Shifts.

The mutagenicity of arylboronic acids has recently become an important area of research because of their potential to be genotoxic impurities in active pharmaceutical ingredients. There is no known mechanism, so currently all structure-activity relationships have been derived using Ames test data. We present preliminary data supporting a hypothesis that the mutagenicity of arylboronic acids is related to the (11)B NMR chemical shift. This could indicate that the mutagenic activity of the arylboronic acids is related to the reactivity of the boron center.