Information on how a chemical enters, moves and behaves throughout its journey inside the human body is crucial in the assessment of its safety. Such data is traditionally obtained through animal-based test procedures. The JRC-run EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) has just published its strategy to promote ways of integrating data obtained through non-animal tests with computer models of the human body.
The strategy aims at reducing animal testing while at the same time improving the protection of human health from exposure to chemicals. It identifies the four main areas where further development work is needed to integrate knowledge on the four important processes that drive the fate of a chemical within the body: absorption (following exposure through air, water, food or via skin), distribution (mainly via blood transport), metabolism (biochemical transformation) and excretion; the ADME processes.
In the next five years, more in vitro methods for testing chemicals' ADME processes in humans should be further developed and standardised. Secondly, the establishment of comprehensive 'one-stop' web-based portals for kinetic modelling (in silico) is needed to provide a collaborative environment which would facilitate the development and use of kinetic models. Such portals should contain or link to freely available kinetic modelling tools and databases for in silico, in vitro and in vivo data. Thirdly, the strategy calls for a coordinated action to stimulate generation and collection of these data to fill these public databases so they can be used in the kinetic models. In the long run, there is a need for a stronger regulatory anchoring of these human in silico and in vitro ADME data and of human physiologically-based toxicokinetic modelling tools to support decision-making and decrease uncertainties involved in human risk assessment of chemicals.
EURL ECVAM strategy - provisional timelines
© EU, 2015
The strategy fully supports the actions set out in the recent Commission communication in reply to the European Citizen's Initiative "Stop Vivisection" and the goal to eventually phase out animal testing as described in Directive 2010/63 on the protection of animals used for scientific purposes.
Despite the usefulness of toxicokinetic information in safety assessment there are currently few, if any, explicit requirements to conduct tests to establish human ADME and toxicokinetics in the EU regulatory frameworks on chemicals such as REACH, Cosmetics, Biocidal Products and Plant Protection Products Regulations. The EU test methods and OECD test guidelines that can be used to meet these data requirements are mostly based on animal procedures. However, by exploiting recent scientific and technological developments, there are increasing opportunities to foster replacement, reduction and refinement of animal testing, the so called 3R's. Whole-body toxicokinetics can be simulated by computer models.