ForthTox has an excellent track record for the successful submission of in silico reports to regulatory agencies. We provide in silico analysis coupled with expert knowledge to produce reports compliant with the requirements for ICH M7. ICH M7 requires the use of two complementary quantitative structural activity relationship ((Q)SAR) programs for the analysis of potential mutagenicity in actual and potential impurities.

At ForthTox we use well-validated in silico expert rule-based and statistical-based programs that have been accepted by major agencies such as the FDA and EMA for the assessment of genotoxicity and mutagenicity. These programs also have utility in assessing other toxicological endpoints and can be used in lead candidate selection or in comparative toxicity screens and to support read-across in situations such as REACH.

Using ICH M7 as a foundation, we have successfully extrapolated this philosophy to other areas, particularly agrochemical products.

Derek Nexus
Derek Nexus is an expert knowledge based SAR program which contains expert rules (derived from public and proprietary data) in toxicology and applies the rules to make predictions about the toxicity of chemicals. Derek Nexus is widely-respected and accepted for the assessment of bacterial mutagenicity and is an excellent tool for use in ICH M7 submissions.

Leadscope
The Leadscope Model applier software contains multiple suites for the prediction of toxicity. For the prediction of mutagenicity, Leadscope contains separate expert rule-based and statistical-based models – allowing full ICH M7 compliance within one software. The Leadscope statistical models analyses the structural similarity and structural fragments of the inputted structure to known structures with real experimental data then assigns a probability of occurrence value. The analysis takes account of both toxifying and de-toxifying groups within the structure, to give an accurate overall picture of toxicity. The Leadscope toxicity QSAR complements Derek Nexus as it uses different methodologies to assign a likelihood of toxicity. In addition, the Leadscope software contains a structural comparison browser for data-mining and read-across.

Meteor
Meteor is the metabolic counterpart of Derek Nexus and can be used in conjunction with Derek to assess potential metabolites of compounds and their potential toxicity. Meteor uses a similar expert knowledge base system similar to Derek but derived from metabolic data.

Leadscope Toxicity QSAR
The Leadscope Model applier software contains multiple suites for the prediction of toxicity. For the prediction of mutagenicity, Leadscope contains separate expert rule-based and statistical-based models – allowing full ICH M7 compliance within one software. The Leadscope statistical models analyses the structural similarity and structural fragments of the inputted structure to known structures with real experimental data then assigns a probability of occurrence value. The analysis takes account of both toxifying and de-toxifying groups within the structure, to give an accurate overall picture of toxicity. In addition, the Leadscope software contains a structural comparison browser for data-mining and read-across.

Leadscope Toxicity Database
The data mining software, gives access to a vast range of experimental data (ranging from mutagenicity to carcinogenicity bioassays, through to chronic toxicity and reproductive studies) to allow read-across for structural comparison. The databases come from a variety of sources and contain over 160 000 separate chemicals. These databases are curated by Leadscope and constantly updated from data sources including the FDA, NTP and RTECS.