An expert review of potentially reactive features

In several recent posts1,2 we highlighted the usefulness of an expert review of potentially reactive features. This is particularly important when an out-of-domain result is returned or when an area of the test chemical is not being considered by the computational model. The US Food and Drug Administration (FDA) recently published a paper showing that …

Expanding the use of in silico toxicology

The application of in silico toxicology is constantly increasing as we better understand how such methods can support different applications (such as the assessment of genotoxic impurity, extractables and leachables, chemicals requiring classification and labelling, and so on). Position papers are critical to support this expansion. We have reported in some recent blog posts progress …

Predicting organ toxicity

The ability to predict organ toxicity directly from a chemical structure would support many applications throughout the product life cycle, from screening candidates to formulating testing strategies and assessing non-genotoxic impurities. A recent cross-industry working group, as part of the in silico toxicology protocol project1, was initiated to understand the needs and challenges for in …

Cross-industry development of structural alerts to support the FDA Guidance on in vitro drug interaction studies

A recent FDA guidance for industry, titled “In Vitro Drug Interaction Studies – Cytochrome P450 Enzyme- and Transporter- Mediated Drug Interactions”1 includes the following statement:  “A lower cut-off value for the metabolite-to-parent AUC ratio may also be considered for metabolites with structural alerts for potential mechanism-based inhibition (Orr, 2012; Yu, 2013; Yu, 2015)” Today, a …

New book on Mutagenic Impurities

We have been really happy to contribute to a number of chapters in an important new book edited by Dr. Andrew Teasdale: “Mutagenic Impurities: Strategies for Identification and Control”1 This will be an essential read for students and professionals in the field of genotoxic impurities (GTIs) assessment covering topics including a history of the regulatory …

Instem’s Computational Toxicology and Genetic Toxicology Groups at GTA 2021

We are pleased to be attending this year’s virtual GTA meeting1 and will be presenting on several topics throughout the course of the event. On Thursday May 6th, Dr. Kevin Cross will be presenting “Predicting N-Nitrosamine Activity from Structure-Activity Relationships” as part of a Symposium on “The 3Rs and in Silico Modeling”. This presentation addresses …

Computational toxicology at the SOT 2021 Meeting

We are happy to be presenting at this year’s virtual SOT meeting1 on a number of topics throughout the course of the event. On Monday 15th March at 3pm (EST), we are covering some new areas at the session “Hot Topics in Computational Toxicology: New Developments that Support Regulatory Submissions.” This includes a discussion on …

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 …

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 …