Integrated assessment and Advanced Characterisation of Neuro-Nanotoxicity

Project Information

iCare

Grant agreement ID: 101092971

DOI

10.3030/101092971

EC signature date 24 November 2022

Start date 1 January 2023

End date 31 December 2026

Funded under

• Digital, Industry and Space

Total cost

€ 2 744 655,00

EU contribution

€ 2 744 654,75

Coordinated by

INTERNATIONAL IBERIAN NANOTECHNOLOGY LABORATORY
Portugal

Periodic Reporting for period 2 - iCare (Integrated assessment and Advanced Characterisation of Neuro-Nanotoxicity)

Reporting period: 2024-07-01 to 2025-12-31

Summary of the context and overall objectives of the project

The iCare project addresses a critical gap in the European regulatory and scientific landscape: the lack of harmonised methods and regulatory frameworks to assess the neurotoxicity of advanced nanomaterials and nanocomposites (ANMC), particularly their interactions with the blood–brain barrier and potential long-term effects on the central nervous system. Currently, no OECD or ISO test guidelines exist for in vitro neuro-nanotoxicity assessment, creating uncertainty for regulators, industry and innovators and limiting safe and sustainable innovation. iCare aims to establish an integrated framework for comprehensive neuro-nanotoxicity assessment by combining advanced imaging and characterisation technologies, high-throughput biological testing, human-relevant in vitro models, alternative biological systems, and structured data integration. The project evaluates nanomaterial transformations during manufacturing, use and environmental release, generating standardised data that support grouping and read-across approaches for regulatory risk assessment under REACH. Through this integrated approach, iCare supports safer material design, more reliable safety assessment, reduced reliance on animal testing, and responsible market uptake of innovative nanomaterials, in line with EU sustainability and health protection objectives.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

iCare has implemented an integrated scientific framework combining advanced laboratory methods, biologically relevant models and structured data infrastructures to support regulatory-relevant neuro-nanotoxicity assessment. The project developed and validated advanced imaging and physicochemical characterisation methods for nanomaterials in complex matrices, enabling detailed analysis of material transformations, aggregation behaviour and reactivity under realistic conditions. New human-relevant in vitro models, including advanced blood–brain barrier systems, neurotoxicity co-cultures and high-content phenotypic assays, were established to enable sensitive, multiparametric assessment of neuro-nanotoxicity. In parallel, alternative biological models such as C. elegans and planarians were developed as bridging systems between in vitro and in vivo assessment, supporting predictive toxicology while reducing reliance on vertebrate animal testing. All methods and datasets were integrated through a structured computational pipeline and data infrastructure, enabling standardised reporting, multiparametric analysis and regulatory-relevant data exploitation. Together, these achievements provide a coherent scientific basis for reliable, reproducible and evidence-based neuro-nanotoxicity assessment.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

iCare has delivered results that significantly advance the state of the art in nanosafety assessment. These include super-resolution and multimodal imaging workflows for nanomaterials in complex biological and environmental matrices, high-throughput biochemical screening assays for nanomaterial reactivity, and high-content phenotypic imaging platforms adapted for nanotoxicology. The project established advanced human-relevant neurotoxicity models and alternative biological systems that enable mechanistic, multiparametric and predictive assessment of nanomaterial effects beyond conventional viability-based testing. Industry-relevant sampling and exposure assessment protocols were also developed, enabling testing under realistic use and end-of-life scenarios rather than pristine laboratory conditions. Together, these results form a new integrated scientific framework for neuro-nanotoxicity assessment that goes beyond fragmented, endpoint-based approaches. Further uptake and impact will be supported through continued validation, large-scale data generation, integration into regulatory guidance, development of standard operating procedures, alignment with standardisation processes, and pathways for regulatory acceptance and industrial adoption.