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Computational Methods

Computational methods can also be used as alternatives to animal testing.

In particular, mathematical approaches such as Quantitative Structure-Activity Relationship (QSAR) modelling and Physiologically Based Kinetic and Dynamic (PBK/D) modelling have been applied to replace and reduce the use of animals in safety and efficacy testing.

Quantitative Structure-Activity Relationship (QSAR) models

QSAR models predict biological or toxicological properties on the basis of the physicochemical and structural properties of chemicals.

Guidance on the validation of QSAR models for regulatory purposes has been developed by the OECD.

Examples of QSAR models that have been characterised and documented according to the OECD standard (QSAR Model Reporting Format; QMRF) are published in the JRC QSAR Model Database.

Grouping and read-across

In addition to QSARs, chemical properties can be predicted by grouping chemicals on the basis of structural and biological similarity, and by “reading across” relevant properties between the analogues.

Guidance on the application of grouping and read-across has been developed by the OECD. Read-across is typically carried out alongside QSAR, to increase the weight of evidence in prediction.

Chemical assessments based on grouping and read-across can be supported by using computational tools such as Toxmatch and Toxtree, and by consulting sources of toxicological data via on-line resources such as ChemAgora and CheLIST.

Physiologically based kinetic (PBK) models

Physiologically based kinetic (PBK) models are mathematical representations of the absorption, distribution, metabolism and elimination (ADME) of chemicals in humans or other animal species.

They are used for multiple purposes, including the interpretation of in vitro toxicity data by in vitro to in vivo extrapolation (IVIVE) and the simulation of internal concentrations in the organism of interest.

When coupled with mathematical models of biological response in the target organ/tissue, they are referred to as physiologically based kinetic and dynamic (PBKD) models.

For the better design and interpretation of in vitro toxicity experiments, the JRC has developed the Virtual cell Based Assay (VCBA).

The VCBA is a mathematical model that simulates the in vitro kinetics and dynamics of chemicals in a a range of in vitro systems.

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