Leadscope database update process and statistics

The development of databases is fundamentally important to in silico toxicology. As part of our yearly release, we update Leadscope’s databases to capture either new or existing information in the public domain or data received from our collaborative partners. The process involves careful curation of chemical structures by normalization, registering the structures and resolving any …

In silico toxicology vis-à-vis new therapeutics

In silico toxicology has its established place in the assessment of therapeutics and is used routinely to assess toxicity endpoints with application in research, discovery, and regulatory submissions. During the pandemic we have gotten a glimpse of innovative therapeutics and the public now has an appreciation for how important these are in advancing patient care. …

How an expert-review could be used to resolve out-of-domains

One of the more challenging outcomes from a (Q)SAR model is the out-of-domain (OOD) result. This result is possible since (Q)SAR models are, in many situations (such as the ICH M7 guideline), required to perform an applicability domain analysis to satisfy OECD validation principles1.  Although a (Q)SAR model may still generate a prediction, the OOD …

The use of chemical analogs in expert reviews

Computational tools offer a rapid, cost-saving advantage to toxicologists assessing the hazard of chemicals. The predictivity of a model for a group of structures is one aspect to be considered in a computational assessment. However, given the universe of chemicals, there are structural classes which a model will predict with a higher level of reliability …

Endocrine activity in silico protocol

The in silico toxicology protocol consortium has been working on developing in silico protocols across various endpoints. While there are existing frameworks for identifying endocrine disrupting chemicals, there remains a lack of guidance on the usefulness and limitations of predicting relevant effects and mechanisms using in silico methodologies and how to combine relevant information inclusive …

In silico toxicology consortia: impact and future direction

In a previous blog entry, Dr. Glenn Myatt discussed the impetus for developing a consortium to define best in silico practices around toxicological endpoints, such as, genetic toxicity, skin sensitization, carcinogenicity, neurotoxicity and acute toxicity, to name a few. The aim of these protocols is to reduce the burden on industry and regulators to justify …

What does the harmonization of in silico safety assessments mean for extractables and leachables?

The ICH M7 guideline1 presents the types of methodologies that are relevant to assess mutagenic impurities. The guideline goes further than simply mentioning that QSAR methods and analogs should be considered prior to conducting an experimental study, and it details two complementary methodologies (statistical and expert rule-based), and how the results should be considered to …

So many pieces of information!

The movement of toxicology away from an observational-based paradigm and towards a mechanism-based one is ongoing. One pertinent question is how to combine data across mechanistic pathways to derive an overall assessment of hazard and what level of confidence should be placed in such a result. Further, where data gaps exist, how could in silico …