Public Deliverables

Computational modelling methods provide useful tools that support the development of novel materials (including nanomaterials) (Mikolajczyk, et al. 2016; Sikorska, et al. 2016) as well as assist in their risk assessment (Gajewicz, et al. 2012). Wide opportunities offered by these techniques attracted the interest of scientific communities and industry. Benefits from the application of modelling techniques in the risk assessment of nanomaterials and directions for further development were recently highlighted in publications summarizing discussions at the level of the EU NanoSafety Cluster (Puzyn et al., 2018) as well as in the “EU-US Nanoinformatics 2030 Roadmap” worked out within the joined EU-US initiative

The in vivo anchoring of in vitro assays depends on two major presumptions; first, that the adverse pathway can be mimicked in cell assays, and second, that the ENM can reach the target tissues and interact with the relevant cell types. Existing high quality in vivo toxicity data generated for the selected ENM after repeated exposures have been collected from PATROLS partners and the scientific literature. Data for crystalline silica (DQ12) have been included for comparison and benchmarking.

Materials with high regulatory and industrial relevance have been identified from the French inventory “R-nano”, which is based on mandatory industrial reporting of all materials produced or imported in nanoform (Ministère de l'Environnement 2015). Tier 1 PATROLS materials were selected from OECD ENM, were subsampled or newly synthesised material sub-samples were made accessible from JRC-Ispra and the Fraunhofer Institute via the PATROLS web-order system.

Task 2.2 was not supposed to perform new inhalation studies, (unless new data are really required) and rather to collect preserved tissues and redistribute those tissues to the project partners for generation of new data. BASF was responsible for coordinating the collection and distribution of available histological sections and paraffin embedded/frozen tissues among WP2 partners.

Increasing use of engineered nanomaterials (ENMs) in consumer goods have raised concern whether they can have detrimental effects on human and/or environmental health. Recent reviews have summarized the effects of ENMs on different organisms (e.g. Do Amaral et al. 2019; Lewis et al. 2019; Hou et al. 2018); however, it remains unclear which organisms are most sensitive and which parameters are most crucial to monitor during the tests.

Within WP2 of PATROLS, an overview of all internally available tissues was made. The tissues that were available for the inhalation route of exposure were listed in the Deliverable 2.2 report. Table 1 of the present report lists the available tissues from the oral exposure studies. It includes studies that used ENM application by oral gavage as well as studies in which ENM were provided ad libitum via introduction in feed pellets.

In response to WP1 specific objective: “Fit for purpose characterization of physicochemical properties to support test specific exposure, fate and dosimetry assessment”, the WP1 focused the characterization on two main issues that govern the dose, once NPs come in contact with the biological environment.

Report summarizing the interaction of the Tier 1 ENM with the lung, gut and liver models from WP3-5. This will include ENM uptake, intra-cellular fate and translocation across the cellular membrane within each test system.

Summary report detailing the fate and dosimetry of Tier 1 ENM in environmental matrices (water and sediment based systems including test organims) as defined in WP5.

Report on the KEs/pathways of developed AOPs based on established and putative AOPs, published toxicity data and meta-analyses with the aim of enabling WP3 and 4 to develop targeted in vitro bioassays with enhanced predictive value. The report will also provide data addressing knowledge gaps based on existing data and AOPs.

Report summarizing the exposure regimen for the selected ENM in each in vitro system based on several combined dosimetry models.

Report summerizing the comparison between toxicity endpoint data and/or AOPs data generated across species in WP5 (Task 5.3) with GIT and liver model data.

Electronic newsletters will be prepared every 6-months for dissemination of PATROLS achievements and updates through a wide contacts distribution list.

A report summarizing the management tools provided to facilitate the day-day project coordination.