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 …

N-nitrosamine SAR Working group

Leadscope, Inc. (an Instem company), in collaboration with Lhasa Limited are leading a working group of pharmaceutical toxicologists and consultants investigating the carcinogenic potency and structure-activity relationships of N-nitrosamines. This is in response to the recent discovery of N-nitrosamines in marketed pharmaceuticals and the regulatory changes that have resulted. The working group is run by …

New acute toxicity (Q)SAR manuscript

Late last year we reviewed a collaboration to assess whether acute (Q)SAR models are fit-for-purpose1 to support classification and labeling, since the use of an alternative approach would support the 3Rs. As part of this exercise, a series of primarily proprietary chemicals with acute toxicity data were run through the different acute (Q)SAR methodologies and …

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 customer support question do we hear the most?

One of the most common questions we are asked is how an overall toxicity assessment for a given chemical is arrived at, especially when there are conflicting study results available. To answer this question, it is often helpful to review the process of producing the content in Leadscope’s databases, which is overseen by Leadscope’s Manager …

Are (Q)SAR models fit-for-purpose for classification and labelling?

We were recently involved in a cross-industry project to determine whether (Q)SAR models were fit-for-purpose for classification and labelling. To test this hypothesis, a series of companies across different industrial sectors each compiled a data set of chemicals with experimental acute rat oral data. These chemicals were run against the first version of the Leadscope …

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 …

Understanding false negatives

For toxicological tests, a false negative (i.e., predicting a chemical is negative when it is in fact positive) is one type of error. It is often desirable to minimize the number of false negatives to decrease the risk of missing a toxic chemical. Computational toxicology is a rapid high-throughput test of multiple chemicals, and like …

Why is it important to define confidence?

As Candice described in her recent blog “So many pieces of information!” – making actionable decisions is extremely complicated, especially when integrating the results from in silico models alongside historical in vivo studies and in vitro experiments. When is there sufficient information to make a decision? Well, it depends the type of decision and the …

Establishing potency categories for Nitrosamine impurities

Nitrosamine impurities currently belong to a “cohort of concern” because of their potential to be potent mutagenic carcinogens, as described in the ICH M7 guideline1. They are also coming under increasing regulatory scrutiny with the US Food and Drug Administration and European Medicines Agency recently issuing new guidelines2,3 for examination of this class. These guidelines …