Advancing Prediction of Nitrosamine Carcinogenicity Potency

This week, Dr. Kevin Cross from Instem is presenting at the 2022 Genetic Toxicology Association meeting on recent progress in predicting N-nitrosamine carcinogenicity potency. The presentation outlines progress over the last year and provides an update on different collaborative working groups, including a recently announced EMA-MutAmind project funded by the European Medicine’s Agency and led …

Predicting toxicity using read-across

Read-across is an example of a flexible in silico toxicology methodology whereby a toxicity prediction for a chemical (often referred to as the target compound) is made using experimental data on one or more similar analogs (often referred to as source compound(s)). This is a lengthy process highly reliant on an expert review of the …

Neurotoxicity hazard assessment framework that integrates in silico approaches

This week we are pleased to welcome Dr. Kevin Crofton and Dr. Arianna Bassan as guest contributors to the blog. Within the in silico toxicology project, a position paper on neurotoxicity is appearing in a special issue of the journal of Computational Toxicology1. This paper discusses the need for the development of more informative new …

A protocol to support the weight-of-evidence for human carcinogenicity assessment of pharmaceuticals

This week we are pleased to welcome Dr. Arianna Bassan as a guest contributor to the blog. The recently published draft addendum of the ICH S1B guideline1 introduces a weight-of-evidence (WoE) approach to assess human carcinogenic potential of small molecule pharmaceuticals and determine whether a 2-year rat carcinogenicity study would add value. Application of this …

New book on mutagenic impurities

We were delighted to contribute to a new book on Mutagenic Impurities, edited by Andrew Teasdale – “Mutagenic Impurities: Strategies for Identification and Control”.1 The book incorporates a discussion on the ICH M7 guideline and covers the in silico assessment of mutagenicity, including the use of structure-activity relationship methodologies, to support the evaluation of impurities. …

Predicting the 6-pack

The 6-pack provides information on health hazards from short-term exposure to a test substance. It is a battery of in vivo tests that evaluate 1) acute systemic toxicity by different routes of exposure (i.e., oral, inhalation and dermal); 2) skin and eye irritation/corrosion; 3) dermal sensitization. It is used in the assessment of many products …

Improving the prediction of bioactivation in relation to drug-drug interactions using proprietary data

The bioactivation of drugs may result in the generation of reactive metabolites that irreversibly inactivate cytochrome P450 (requiring synthesis of new enzyme for recovery of activity). This process is referred to as mechanism-based inhibition (MBI) or time-dependent inhibition and is often involved in damaging drug-drug interactions (DDIs). Within the FDA guidance “In Vitro Drug Interaction …

In silico toxicology project 2021 review

The in silico toxicology project objective is to support the acceptance and implementation of in silico toxicology through working groups and publications covering: (1) protocols, (2) position papers, (3) case studies, (4) fit-for-purpose evaluations, and (5) structure-activity relationships. As we look back at 2021, it’s been another great year of progress. So far this year, …

New posters and papers

We recently published a blog describing four new publications.1 Since this post, we have received news that 2 more papers, submitted earlier this year to the Journal of Computational Toxicology, have been published: Evaluating Confidence in Toxicity Assessments Based on Experimental Data and In Silico Predictions2 Reliability, relevance, and confidence are defined within the context …

Availability of Original CPDB Data in Original Website Format

The Carcinogenicity Potency Data Bank or CPDB has long been an authoritative and trusted source of in vivo carcinogenicity data used in toxicological assessments worldwide. Unfortunately, for over 10 years the database has not been updated and all the original formatted and unaltered content is no longer publicly available. For many years, Leadscope has included …