Safe-by-design and sustainable by design approach to avoid potential risks associated with exposure to nanomaterials

Principal investigator: Anna Luisa Costa
Involved personnel: Magda Blosi, Carlo Baldisserri, Andrea Brigliadori, Antonio Crimaldi, Lara Faccani, Davide Gardini, Simona Ortelli, Marina Serantoni, Felice Carlo Simeone, Ilaria Zanoni

The unique properties of nanomaterials are related to their dimensions, 1-100 nm, just above molecular level. These materials have a remarkably high surface reactivity and some anomalous behaviours, seen from the classical physics point of view. These characteristics, which make them extremely attractive to chemical designers, are also related to their potential risk once they meet biological systems.

Safe-by-Design (SbD) Strategies
Applied to materials and processes, they make it possible to obtain intrinsically safe nanotechnological products. They are promising solutions for the preventive management of risk in the production and use of nanoparticles and derivative products. SbD solutions must be validated throughout the life cycle of the products and attention need to be paid in preserving and optimizing:
• performance attributes linked to their specific functionality
• production techniques
• safety
• environmental sustainability
• cost/benefit ratio
• regulatory requirements and standardization.

Sustainable by Design
In the last ten years ISTEC has strongly contributed, in the European scenario, to the promotion of a sustainable approach in the development of nanomaterials and nano-products and to the management of the risk associated with nanotechnologies (Safe-by-design, Sustainable by design) (SANOWORK, SUN, PROTECT, BIORIMA, PATROLS, NANOINFORMATIX). As part of two recent European projects: ASINA (coordinated by ISTEC) and SABYNA (coordinated by LEITAT) entirely dedicated to the implementation of Safe-by Design strategies, the following topics are under study:
• the development of design alternatives on materials, products, and processes
• the development of easy-to-use measurement strategies and models for data analysis and preventive risk estimation.

Control banding (risk for workers in the sector)
The growing development of nanomaterial production processes leads to face and manage the increased potential risks for workers, that are considered the most exposed subjects. In order to evaluate the risks deriving from occupational exposure to nanomaterials, we have entered into a collaboration with CNR-ISAC (Dr. F. Belosi and Dr. F. Ravegnani) to carry out monitoring campaigns for the emission of nanoparticles in indoor occupational scenarios, starting from monitoring pilot lines dedicated to the deposition of antibacterial nano-structural coatings on flexible surfaces, such as fabrics and membranes (PROTECT EU project).

Identification of physico-chemical descriptors
An obligatory step towards the development and validation of SbD strategies in the design of nanomaterials is the identification and measurement of the main physico-chemical descriptors, the so-called drivers for the toxicity, transport, and fate of nanomaterials in biological and environmental matrices.
As part of European projects, ISTEC studies the chemical-physical-identity of materials, in their exposure conditions and along their life cycle, also contributing to the definition of the real dose administered to the biological target.
Several experimental set-ups have been optimized to characterize the colloidal properties of nanoparticles dispersed in media relevant for exposure, use / measurement / or biological media matrices simulations:

DLS / ELS for measuring the hydrodynamic diameter and the zeta potential
ICP-OES for elemental analysis in various ex vivo / in vitro compartments
Electrochemical analysis of the pro-oxidative potential.

Standardizations and regulations for use of nanoparticles
The title of the call to which the ASINA and SABYNA projects responded, i.e., “Safe for design: from science to regulation”, stresses the central role of technical standardization. The Italian National Unification body (UNI) collaborates with ISTEC, in order to establish a strategic and integrated action plan, which offers input data for future technical standardization activities, in the nano-SbD area.

Safe by Design solutions

Main collaborations
Dr. Matteo Zanotti Russo, Angel Consulting (regulatory issues)
Prof. Paride Mantecca, Università Milano Bicocca (toxicological tests)
Prof. Lang Tran, IOM (Institute of Occupational Medicine) (toxicology of inhaled nanoparticles and fibers, dosimetry models)
Prof. Bengt Fadeel, Karolinska Institute (study of the in vitro toxicity mechanisms of nanomaterials)
Prof. Barbara Rothen, Adolphe Merkle Institute (interaction of nanoparticles with lung cells)
Dr. Wendel Wohlleben, BASF SE (physics of materials and experimental toxicology)


Pubblications and patents

  • A.L. Costa, “Applying Safety by Molecular Design Concepts to Nanomaterials Risk Management”, Managing Risk in Nanotechnology – Topics in Governance, Assurance and Transfer, Springer Publishing, 2016, Editor (s) Finbarr Murphy, Eamonn M. McAlea, Martin Mullins
  • A. L. Costa, “A Rational Approach for the Safe Design of Nanomaterial”, Nanotoxicology: Progress toward Nanomedicine, Second Edition, March 3, 2014 by CRC Press Content, Editor(s): Nancy A. Monteiro-Riviere; C. Lang Tran (2014)
  • R. Bengalli, S. Ortelli, M. Blosi, A. Costa, P. Mantecca, L. Fiandra,. In Vitro Toxicity of TiO2: SiO2 Nanocomposites with Different Photocatalytic Properties. Nanomaterials 9, 1041 (2019)
  • M.Bianchi, L. Campagnolo, M. Allegri, S. Ortelli, M. Blosi, M. Chiu, G. Taurino, V. Lacconi, A. Pietroiusti, A. L. Costa, C. A. Poland, D. Baird, R. Duffin, O. Bussolati, E. Bergamaschi, Length-dependent toxicity of TiO2 nanofibers: mitigation via shortening. Nanotoxicology 15, 1-20 (2019)
  • A.L. Costa, M. Blosi, Process for the preparation of nanoparticles of noble metals in hydrogel and nanoparticles thus obtained; US Patent 10,525,432 (2020)