Nano-safety Research

The Next Global Frontier.

Nanotechnology, manipulation of extremely small things (at the level of atoms and molecules), is widely regarded as the next global frontier of science, bringing significant economic and societal benefits through major technological breakthroughs that improve quality of life. The field of nano-safety concerns the assessment of the unique health and safety implications that arise from this exciting industry.

The nano-safety sub-theme enjoys the €13million of funding, as part of the cross European H2020 PATROLS project, this major project aims to provide clearer regulatory framework for nanoparticles.

Our Nano-safety Areas Research Focus

Research conducted by Swansea University’s In Vitro Toxicology Group has been pivotal in developing standardised safety tests to facilitate nanomaterial human hazard identification, which is necessary to support risk assessment. Our research focuses on the development of in vitro techniques to determine the mechanisms associated with nanomaterial induced toxicity. We deduce the impact of industrially relevant nanoforms upon an array of different in vitro models of human tissues and relate these to their potential biological impact.

In vitro cell models

Monocultures of key cell types are widely used in safety assessment for human health, due to their regulatory acceptance. However, these standard systems fail to represent the complex biological processes that occur within the human body. As a result, animal models are relied upon to confirm the ‘whole-body’ hazard for risk assessment. At Swansea we are developing realistic and predictive 3D tissue models for nanomaterial safety assessment, reducing the need for animal testing. This has included the development of 3D liver spheroids, co-culture lung models, 3D skin models and systems that replicate the innate immune system.

Nano(geno)toxicology

An obstacle becoming increasingly evident is that traditional (geno)toxicological assays to detect induction of DNA damage, have been standardised and optimised for chemical compounds and it cannot be assumed that nanomaterials can be tested in the same way. Consequently, research at Swansea University has established the most suitable experimental protocols to assess the (geno)toxicity of nanomaterials and adapted traditional techniques to facilitate safety testing of these unique materials. These assays have since been implemented in evaluating the genotoxic potential of engineered nanomaterials as a function of their physico-chemical features.

Inhalation toxicology

Inhalation toxicology research at Swansea is concerned with the effects of foreign particulates into the lungs such as air pollutants or engineered nanomaterials. The in vitro toxicology laboratory at Swansea University is equipped with state-of-the-art exposure systems that allow for the characterisation of the aerosolised ENMs, exposed at the air-liquid interface to allow realistic exposure to the advanced, multicellular in vitro systems being developed.

Nanomaterial Physico-chemical Characterisation and NM:Cell Interaction

In order to fully understand a nanomaterial’s toxicological profile we need to understand its physico-chemical properties. At Swansea we have an array of different techniques that allow us to achieve this via interdisciplinary collaborations across the university including the Advanced Imaging of Materials (AIM) facility within the college of engineering. Understanding a nanomaterial’s physico-chemical properties is pivotal when interpreting nanomaterial-cell interactions. For example, how does the material interact at the cell surface, does it undergo cellular uptake and what effect will it have inside the cell.

Research Outcomes

Within the nano-safety theme, academics, researchers and post-graduate students work to ensure our research broadens our scientific understanding of the toxicological risks of nanomaterials. Our research has been pivotal in developing safety tests to identify nanomaterial hazards and in the development of new techniques to achieve this.

DNA Damage and the Safety of Nanomaterials

PATROLS

Prof Shareen Doak leads an international team of scientists including academics, industrial, government and risk assessment partners on the EU funded PATROLS project. PATROLS will provide an innovative and effective set of laboratory techniques and computational tools to more reliably predict potential human and environmental hazards resulting from engineered nanomaterial exposures. These tools will minimise the necessity of animal testing and will support future categorisation of ENMs in order to support safety frameworks.

Physiologically Anchored Tools for Realistic nanOmateriaL hazard aSsessment (PATROLS)

In vitro genotoxicity testing strategy for nanomaterials

For the first time this publication, specifically outlined which regulatory approved test systems were appropriate for nanomaterial DNA damage testing and where method adaptations were required. The recommendations and guidance have been widely adopted internationally. The paper underpins the changes to regulatory practice and consequently has been cited by regulatory bodies, and the World Health Organisation. The paper was a key output that led to the successful award of the Horizon 2020 PATROLS project.

Associated Collaborative and Industry Partners

Industrial Partners

AstraZeneca
Unilever
Glaxo Smith Klein (GSK)

University Partners

Adolphe Merkle Institute, University of Fribourg, CH.
Heriot-Watt University, Edinburgh, UK.
IUF-Leibniz Institute, Düsseldorf, Germany.
University of Edinburgh, UK.
University of Leeds, UK.

Other Collaborative Partners

BASF
Health Canada
MisVik Biology, Finland.
National Centre for 3Rs (UK)
Perpetuus Carbon technologies
Public Health England

Associated Research Projects

Celtic Advanced Life Science Innovation Network (CALIN)
HARMLESS
NanoInformaTIX
Physiologically Anchored Tools for Realistic nanOmateriaL hazard aSsessment (PATROLS)
RiskGONE
SUNSHINE

Associated Sub-Theme Publications

Clift, M., Jenkins, G., & Doak, S. (2020); An Alternatives Perspective Towards Deducing the Risk of Engineered Nanomaterials to Human Health. Small, 2002002.
Burgum, M., Clift, M., Evans, S., Hondow, N., Miller, M., Bustamante-Lopez, S., Williams, A., Tarat, A., Jenkins, G., & Doak, S. (n.d.) In Vitro Primary‐Indirect Genotoxicity in Bronchial Epithelial Cells Promoted by Industrially Relevant Few‐Layer Graphene. Small, 2002551
Llewellyn, S., Conway, G., Shah, U., Evans, S., Jenkins, G., Clift, M., & Doak, S. (n.d.) Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure. Journal of Visualized Experiments(160)
Conway, G., Shah, U., Llewellyn, S., Cervena, T., Evans, S., Al-Ali, A., Jenkins, G., Clift, M., & Doak, S. (2020). Adaptation of the in vitro micronucleus assay for genotoxicity testing using 3D liver models supporting longer-term exposure durations. Mutagenesis, 35(4), 319-329.
Conway, G., Shah, U., Llewellyn, S., Cervena, T., Evans, S., Al-Ali, A., Jenkins, G., Clift, M., & Doak, S. (2020). Adaptation of the in vitro micronucleus assay for genotoxicity testing using 3D liver models supporting longer-term exposure durations. Mutagenesis, 35(4), 319-330.
Cronin, J. G., Jones, N., Thornton, C. A., Jenkins, G. J. S., Doak, S. H., and Clift, M. J. D. (2020); Nanomaterials and innate immunity: A perspective of the current status in nanosafety. Chemical Research in Toxicology; 33, pp. 1061-1073.
Evans, S., Clift, M., Singh, N., Wills, J., Hondow, N., Wilkinson, T., Burgum, M., Brown, A., Jenkins, G., & Doak, S. (2019). In vitro detection of secondary mechanisms of genotoxicity induced by engineered nanomaterials. Particle and Fibre Toxicology, 16(1)
Burden, N., Aschberger, K., Chaudhry, Q., Clift, M. J. D., Fowler, P., Johnston, H., Landsiedel, R., Rowland, J., Stone, V. and Doak, S. (2017); Aligning nanotoxicology with the 3Rs: What is needed to realise the short, medium and long-term opportunities? Regulatory Toxicology and Pharmacology; 91; pp. 257-266.
Burden, N., Aschberger, K., Chaudhry, Q., Clift, M. J. D., Doak, S., Fowler, P., Johnston, H., Landsiedel, R., Rowland, J. and Stone, V. (2017); The 3Rs as a framework to support a 21st century approach for nanosafety assessment. Nano Today; 12, pp. 10-13.
Wills, J., Hondow, N., Thomas, A., Chapman, K., Fish, D., Maffeis, T., Penny, M., Brown, R., Jenkins, G., Brown, A., White, P., & Doak, S. (2016). Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™). Particle and Fibre Toxicology, 13(1)

Affiliated Researchers

Led by Prof. Shareen Doak, the Nanosafety Research Group predominantly focusses upon nanomaterial genotoxicity (Prof. Doak and Prof. Jenkins) and inhalation toxicology (Dr. Clift).