WP5

What they do: Human and environmental toxicology

Objectives

To develop the “What they do: human and environmental toxicity” ITS tailored to address specific hypotheses for grouping (e.g. an ITS for HARN, and for soluble NMs). The ITS will be in the form of decision trees consisting of human and environmental toxicity criteria/descriptors combined with testing (e.g. in vitro, in vivo) (where needed) and non-testing (e.g. in silico) methods to support grouping and read-across approaches.
To identify criteria and guiding principles for grouping and read-across for the ITS based upon established toxicity endpoints and endpoints from published MoA and AOPs.
To organise the tools needed for the ITS into tiers according to Fig. 1.2 and 1.4: i.e. (i) intrinsic material properties, (ii) extrinsic properties derived from in vitro data, environmentally relevant organisms and modelling tools to identify nano-bio interactions and toxicity, plus (iii) rodent/mammalian in vivo data.
To test and verify the ITS using the project case studies.
To contribute to the Framework Guidance Document, providing detailed guidance on when to apply (a combination of) the different types of testing and non-testing information for justification of grouping and read-across hypotheses.
To provide a detailed description of the Framework components, tools and read-across options accompanied by user level guidance and assess their applicability for regulation and SbD.

Tasks

Contribute to the overall GRACIOUS Framework design and its iterative refinement.
Derive initial grouping hypothesis and development of in silico approaches.
Test reactivity of NMs/NFs in physiological or environmental media (NMs/NFs transform medium).
Assess nano-bio interactions that transform the surface identity of the NMs/NFs (medium transforms NMs/NFs).
Develop in vitro test systems to support grouping based upon human toxicity.
Develop test systems to support grouping based upon environmental toxicity.
Develop a tiered hazard ITS.

WP leader: Andrea Haase, BfR