• Elena Fioravanzo

Toxicokinetics and read-across


This open-access paper (https://doi.org/10.1016/j.yrtph.2018.08.006) is a great overview on ongoing scientific activities in various sectors addressing the availability and the possible use of toxicolkinetics data to support read-across.


Abstract: The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum Toxicokinetics and Read-Acrossto provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. Currently, lacking toxicokinetic data often prevent the application of read-across. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance.....


Paragraphs:

Toxicokinetics strategy at the JRC and ongoing activities of the OECD

Ongoing sectorial activities:

- Pharmaceuticals and vaccines sector input

- Cosmetics sector input

- Fragrances sector input

- Agrochemicals sector input

- Chemicals sector input

Activities of the EC, EU agencies and multilateral research initiatives


Conclusions and recommendations

As an outcome of the EPAA Partners' Forum Finding synergies for 3Rs – toxicokinetics and read-across, the following conclusions were made:

  • Toxicokinetic data play an important role in risk assessment across all industry sectors and are subject to significant research effort by all relevant stakeholders.

  • Toxicokinetic data (in vivo data; ADME) strengthen the read-across WoE.

  • Toxicokinetic data should ideally be anchored towards human relevance and preferably be generated using in vitro methods and in silico tools.

  • Identification and characterisation of metabolism is a key component of toxicokinetics assessment in read-across.

The participants of the Forum expressed confidence that significantly more progress in toxicokinetics can be made if collaboration between sectors is enhanced and synergies are captured. In this context, the following actions were recommended:

  1. Promote the establishment of a Toxicokinetics Speciality Section within EUROTOX;

  2. Explore possibilities to create a database of modern toxicokinetic tools to assist hazard and risk assessment, building on existing information (e.g., EFSA, 2014a); collation of a contemporaneous list of open tools (open source, managed by the EPAA);

  3. Dissemination and training event on RVis with toxicokinetics stakeholders in early 2019.

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