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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 can be 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.

To harmonise best practices, the Organisation for Economic Development (OECD) has developed guidance on how to validate and document QSAR models for regulatory purposes.

In particular, QSAR models should be described  and documented according to the OECD standard (QSAR Model Reporting Format; QMRF). Examples are given  in the JRC QSAR Model Database.

Grouping and read-across

Chemical properties can also be predicted by grouping chemicals on the basis of structural and biological similarity, and by inferring (“reading across”) relevant properties of data-poor chemicals from those of  ”similar” data-rich chemicals. Read-across is typically carried out in addition to QSAR, to increase the overall confidence in the predicted properties.

The OECD has developed guidance on how to carry out read-across to inform a chemical safety assessment.

Chemical assessments based on 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 descriptions of how chemicals distribute in humans or other animal species.

PBK models are used, for example, to interpret in vitro toxicity data, and to simulate internal concentrations following exposure to the chemical via the diet, skin or inhalation.

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.

To support the design and interpretation of in vitro toxicity experiments, the JRC has developed the Virtual cell Based Assay (VCBA). This is a mathematical model that simulates the distribution (kinetics) and biological effects (dynamics) of chemicals in a range of in vitro systems.