Modern methods of computational toxicology and safety assessment are based on the idea that there is a relationship between the chemical structure of the compound and its properties, including biological activity. Computational methods are becoming an increasingly important tool offering both financial and business benefits. They allow for a significant reduction in cost, thanks to their greater efficiency – multiple substances can be analyzed in a shorter time frame.
In addition, these methods comply with REACH Regulation (EC 1907/2006) concerning the reduction of unnecessary animal testing.
QSAR Lab experts have many years of experience in computational toxicology, including the use of QSAR (Quantitative Structure-Activity Relationship) and read-across (RA) methods to predict the properties required for the registration of chemical substances.
The QSAR method expresses relationships between chemical structures and properties in a quantitative format, using number-encoded information about chemical structures to create a mathematical model capable of predicting selected properties of compounds that are yet to be experimentally tested.
Grouping and read-across methods make use of the similarities between compounds. According to REACH Regulation guidelines, substances with similar physicochemical, toxicological, ecotoxicological properties and chemical structure belong to one group/category. Based on these similarities, it is possible to use the above methods for predicting the properties of the target substance by using data available for source compounds. By that means, it is possible to gain knowledge about new, unexplored substances only on the basis of their properties and chemical structure.
QSAR Lab’s offer in the field of computational toxicology includes:
1) Performing an analysis using computational methods to assess the biological activity and/or properties of a chemical compound by:
- using the latest available specialized software (OECD QSAR Toolbox, VEGA HUB)
- chemoinformatic analysis from scratch, using the QSAR modeling/read-across approach in accordance with OECD guidelines
- preparation of analysis documentation that complies with the requirements for the registration of chemical substances
2) Support for R&D projects by providing information on the structural features of the test substance that determine their properties. Support for R&D projects includes, among others:
- Expert consultations to accurately identify the research problem and to propose hypotheses related to the use of computational methods in the presented project
- Subcontracting R&D works in the field of computational toxicology
3) Performing a “weight of evidence” process, which refers to the process of gathering, weighing and evaluating evidence in order to draw conclusions about the potential toxic effects of a substance.
In this process, selected tests are qualified in terms of qualitative acceptability criteria, their compliance with current OECD and other guidelines, GLP status, etc. A weight of evidence approach can be performed to assess virtually any in vitro and in vivo toxicity endpoint.
4) Support for the registration of substances under REACH by computer prediction of the properties described in Annexes VII-X.
Figure: OECD – ENV/JM/MONO(2019)31
Assessment of the developmental and reproductive toxicity is based on all relevant information on the test substance, including physicochemical properties; results of previous toxicity studies; absorption, distribution, metabolism, elimination (ADME) processes, and presence of the structural alerts. It will be the basis for further analysis with the use of structure-activity relationships (SARs) and read-across methods.