Unit Fibre and Nanotoxicology

The unit is in charge of health risk assessments for (nano-) particles and fibres in consumer products. The tasks also include the assessments of fibres and substances in nanoform within the framework of the overarching European chemicals legislation, REACH. All assessments are conducted in close collaboration with other units of the Chemical and Product Safety Department and often involve collaborations with units of other departments. Important endpoints in the toxicological assessment are carcinogenic, mutagenic, reproductive, and sensitizing properties. The inhalation of fibres and (nano-)particles is of particular concern.

In addition, the unit leads the BfR's internal working group on nanomaterials (AG Nano) which co-ordinates the communication between different departments with regard to the health risks of nanomaterials, fibres and other advanced materials. Furthermore, the unit leads a German interagency working group Advanced Materials aiming to exchange on material developments, to identify potentially critical materials early on and to address the need for actions in a timely manner.

At the European level, the unit contributes to the development and amendment of legal procedures, in addition to relevant technical guidance for chemicals in nanoform. Internationally, the unit participates in the adaptation of OECD test guidelines and guidance documents for the toxicological testing of nanomaterials. For this purpose, it is actively engaged in round-robin studies and represents the BfR in relevant expert committees such as the ECHA Nanomaterial Expert Group (NMEG), the EFSA cross-cutting Working Group on Nanotechnologies and the OECD Working Party on Manufactured Nanomaterials (WPMN) at the European and International level.

The unit is active in applied safety research for nano- and other advanced materials. Research needs are continuously identified, new projects are initiated accordingly. Hence, the unit participates in numerous national and international third-party funded projects. The overarching research focus of the unit is the development of new approach methodologies (NAMs) for the toxicological assessment of nano- and other advanced materials and their application in tiered testing strategies and/or integrated approaches to testing and assessment (IATAs) for risk assessment and for Safe-and-Sustainable-by-Design. This includes the establishment of grouping approaches, the development of screening procedures for instance based on (surface) reactivity, and the development of alternative and, in particular, data-driven (in-silico) methods to improve the predictability of the toxicological potential of nanomaterials. Additional research activities focus on nano-specific modes of action, inter alia, by means of sophisticated cell biology (e.g. flow cytometry, confocal microscopy) and ‘omics techniques (e.g. proteomics, metabolomics).

Main fields of activity

• Assessment of health risks of fibres and nanomaterials according to the European chemicals legislation (REACH regulation, 1907/2006 / EC)
• Classification and labelling of fibres and nanomaterials according to the European CLP regulation (1272/2008 / EC)
• Contribution to Member State activities, supporting the German representatives in the Member State Committee (MSC) as well as in the committees for Risk Assessment (RAC) and Socio-Economic Analysis (SEAC) at ECHA
• Expertise to and support of the Federal Government and Federal Authorities on aspects related to fibre and nanotoxicology
• Participation in BfR commissions on questions regarding fibre and nanotoxicology
• Chairing the BfR’s internal working group on nanomaterials (AG Nano)
• Chairing the German Interagency Working Group Advanced Materials
• Participation in national and international bodies (BMUV, BMAS / AGS, MAK, EU, ECHA, EFSA, WHO, OECD)
• Further development of EU chemicals legislation and supporting activities, including technical guidance with regard to fibres and nanomaterials
• Identification of new research needs, as well as initiation of and participation in national and international research projects in the field of fibre and nanotoxicology (including third-party funded research)

Current research projects

• EFSA NAMS4NANO (04/2023- 03/2027)
• Lot 1: Review of Tools and Qualification System
• Lot 2: Risk Assessment Case Studies
• Lot 3: Methodologies Case Studies
• EU POLYRISK (04/2021- 03/2025), https://polyrisk.science/
• EU HARMLESS (01/2021- 01/2025), https://www.harmless-project.eu/
• EU NanoHarmony (04/2020- 09/2023), https://nanoharmony.eu/

Completed research projects

• EU NanoInformaTIX (01/2019- 02/2023)
• EU Gov4Nano (01/2019- 02/2023)
• BMBF InnoMat.Life (04/2019- 06/2022)
• EU nanoCommons (01/2018- 06/2022)
• EU GRACIOUS (01/2018- 09/2021)
• ERANET SIINN NanoToxClass (12/2015- 02/2019)
• EU NanoReg2 (09/2005- 02/2019)
• BMBF nanoGRAVUR (05/2015- 06/2018)   

Selected Recent Publications

2023
Murphy F.A., Johnston H.J., Dekkers S., Bleeker E.A.J., Oomen A.G., Fernandes T.F., Rasmussen K., Jantunen P., Rauscher H., Hunt N., di Cristo L., Braakhuis H.M., Haase A., Hristozov D., Wohlleben W., Sabella S., and Stone V.
How to formulate hypotheses and IATAs to support grouping and read-across of nanoforms. ALTEX - Alternatives to animal experimentation 40 (1), 125-140.
https://doi.org/10.14573/altex.2203241

Bahl, A., Ibrahim C., Plate C., Haase A., Dengjel J., Nymark P., Dumit V.I.
PROTEOMAS: A workflow enabling harmonized proteomic meta-analysis and proteomic signature mapping. Journal of Cheminformatics 15 (1), 34.
https://doi.org/10.1186/s13321-023-00710-2

2022
Emecheta E.E., Borda D.B., Pfohl P.M., Wohlleben W., Hutzler C., Haase A., and Roloff A.
A comparative investigation of the sorption of polycyclic aromatic hydrocarbons to various polydisperse micro- and nanoplastics using a novel third-phase partition method. Microplastics and Nanoplastics 2 (1), 29.
https://doi.org/10.1186/s43591-022-00049-9

Boyles M., Murphy F., Mueller W., Wohlleben W., Jacobsen N.R., Braakhuis H., Giusti A., and Stone V.
Development of a standard operating procedure for the DCFH2-DA acellular assessment of reactive oxygen species produced by nanomaterials. Toxicology Mechanisms and Methods 32 (6), 439-452.
https://doi.org/10.1080/15376516.2022.2029656

Di Cristo L., Janer G., Dekkers S., Boyles M., Giusti A., Keller J.G., Wohlleben W., Braakhuis H., Ma-Hock L., Oomen A.G., Haase A., Stone V., Murphy F., Johnston H.J., and Sabella S.
Integrated approaches to testing and assessment for grouping nanomaterials following dermal exposure. Nanotoxicology 16 (3), 310-332.
https://doi.org/10.1080/17435390.2022.2085207

Verdon R., Stone V., Murphy F., Christopher E., Johnston H. J., Doak S. H., Vogel U., Haase A., and Kermanizadeh A.
The application of existing genotoxicity methodologies for grouping of nanomaterials: towards an integrated approach to testing and assessment. Particle and Fibre Toxicology 19 (1), 32.
https://doi.org/10.1186/s12989-022-00476-9

Ag Seleci D., Tsiliki G., Werle K., Elam D.A., Okpowe O., Seidel K., Bi X., Westerhoff P., Innes E., Boyles M., Miller M., Giusti A., Murphy F., Haase A., Stone V., and Wohlleben W.
Determining nanoform similarity via assessment of surface reactivity by abiotic and in vitro assays. NanoImpact 26, 100390.
https://doi.org/10.1016/j.impact.2022.100390

Jeliazkova N., Bleeker E., Cross R., Haase A., Janer G., Peijnenburg W., Pink M., Rauscher H., Svendsen C., Tsiliki G., Zabeo A., Hristozov D., Stone V., and Wohlleben W. How can we justify grouping of nanoforms for hazard assessment? Concepts and tools to quantify similarity. NanoImpact 25, 100366. https://doi.org/10.1016/j.impact.2021.100366

2021
Melanie Kah, Linda J. Johnston, Rai Kookana, Wendy Bruce, Andrea Haase, Vera Ritz, Jordan Dinglasan, Shareen Doak, Hemda Garelick, Vladimir Gubala
Comprehensive Framework for Human Health Risk Assessment of Nanopesticides
Nature Nanotechnology 16, 955
https://www.nature.com/articles/s41565-021-00964-7

Jeliazkova N., Apostolova M.D., Andreoli C., Barone F., Barrick A., Battistelli C., Bossa C., Botea-Petcu A., Châtel A., De Angelis I., Dusinska M., El Yamani N., Gheorghe D., Giusti A., Gómez-Fernández P., Grafström R., Gromelski M., Jacobsen N.R., Jeliazkov V., Jensen K.A., Kochev N., Kohonen P., Manier N., Mariussen E., Mech A., Navas J.M., Paskaleva V., Precupas A., Puzyn T., Rasmussen K., Ritchie P., Llopis I.R., Rundén-Pran E., Sandu R., Shandilya N., Tanasescu S., Haase A., and Nymark P. Towards
FAIR nanosafety data.
Nature Nanotechnology 16, 644
https://doi.org/10.1038/s41565-021-00911-6

Höper T., Siewert K., Dumit V.I., von Bergen M., Schubert K., and Haase A.
The Contact Allergen NiSO4 Triggers a Distinct Molecular Response in Primary Human Dendritic Cells Compared to Bacterial LPS. Frontiers in Immunology 12 (656).
https://doi.org/10.3389/fimmu.2021.644700

2020
Stone V., Gottardo S., Bleeker E.A.J., Braakhuis H., Dekkers S., Fernandes T., Haase A., Hunt N., Hristozov D., Jantunen P., Jeliazkova N., Johnston H., Lamon L., Murphy F., Rasmussen K., Rauscher H., Jiménez A.S., Svendsen C., Spurgeon D., Vázquez-Campos S., Wohlleben W., and Oomen A.G.
A framework for grouping and read-across of nanomaterials- supporting innovation and risk assessment. Nano Today 35, 100941.
https://doi.org/10.1016/j.nantod.2020.100941

Bahl A., Hellack B., Wiemann M., Giusti A., Werle K., Haase A., and Wohlleben W. Nanomaterial categorization by surface reactivity: A case study comparing 35 materials with four different test methods. NanoImpact, 100234.
https://doi.org/10.1016/j.impact.2020.100234

Bannuscher A., Hellack B., Bahl A., Laloy J., Herman H., Stan M., Dinischiotu A., Giusti A., Krause B.-C., Tentschert J., Rosu M., Balta C., Hermenean A., Wiemann M., Luch A., and Haase A. Metabolomics profiling to investigate nanomaterial toxicity in vitro and in vivo. Nanotoxicology, 1-20.
https://doi.org/10.1080/17435390.2020.1764123

Bannuscher A., Karkossa I., Buhs S., Nollau P., Kettler K., Radu M., Dinischiotu A., Hellack B., Wiemann M., Luch A., Von Bergen M., Haase A., and Schubert K.
A multi-omics approach reveals mechanisms of nanomaterial toxicity and structure–activity relationships in alveolar macrophages. Nanotoxicology 14, 1-15.
https://doi.org/10.1080/17435390.2019.1684592

Bewersdorff T., Glitscher E., Bergueiro J., Eravci M., Miceli E., Haase A., and Calderon M. (2020): The influence of shape and charge on protein corona composition in common gold nanostructures. Materials Science and Engineering: C, 111270.
https://doi.org/10.1016/j.msec.2020.111270

2019
Bahl A., Hellack B., Radu M., Dinischiotu A., Wiemann M., Brinkmann, J., Luch A., Renard B., and Haase A. Recursive feature elimination in random forest classification supports nanomaterial grouping. NanoImpact 15, 100179.
https://doi.org/10.1016/j.impact.2019.100179

Bewersdorff T., Gruber A., Eravci M., Dumbani M., Klinger D., and Haase A. Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake. International Journal of Nanomedicine Volume 14, 7861-7878
https://doi.org/10.2147/IJN.S215935

Karkossa I., Bannuscher A., Hellack B., Bahl A., Buhs S., Nollau P., Luch A., Schubert K., Von Bergen M., and Haase A. An in-depth multi-omics analysis in RLE-6TN rat alveolar epithelial cells allows for nanomaterial categorization. Particle and Fibre Toxicology 16.
https://doi.org/10.1186/s12989-019-0321-5

Wohlleben W., Hellack B., Nickel C., Herrchen M., Kerstin H.-R., Kettler K., Riebeling C., Haase A., Funk B., Kühnel D., Göhler D., Stintz M., Schumacher C., Wiemann M., Keller J., Landsiedel R., Broßell D., Pitzko S., and Kuhlbusch T.A.J. The nanoGRAVUR grouping framework for nanomaterials concerning occupational, consumer, environmental risk: Conception, property harmonization strategy and proof of concept/suitability. Nanoscale 11.
https://doi.org/10.1039/c9nr03306h

2018
Riebeling C, Piret J-P, Trouiller B, Nelissen I, Saout C, Toussaint O, Haase A. A guide to nanosafety testing: Considerations on cytotoxicity testing in different cell models. NanoImpact, 10:1-10,
DOI: https://doi.org/10.1016/j.impact.2017.11.004

2017
Haase A, Dommershausen N, Schulz M, Landsiedel R, Reichardt P, Krause BC, Tentschert J, Luch A. Genotoxicity testing of different surface-functionalized SiO2, ZrO2 and silver nanomaterials in 3D human bronchial models. Arch Tox, 91:3991-4007
https://doi.org/10.1007/s00204-017-2015-9

2016
Wohlleben W*, Driessen MD*, Raesch S, Schaefer UF, Schulze C, Vacano Bv, Vennemann A, Wiemann M, Ruge CA, Platsch H, Mues S, Ossig R, Tomm JM, Schnekenburger J, Kuhlbusch TA, Luch A, Lehr CM*, Haase A.* Influence of agglomeration and specific lung lining lipid/protein interaction on short-term inhalation toxicity. Nanotox 10: 970-980
https://doi.org/10.3109/17435390.2016.115567

2015
Driessen MD, Mues S, Vennemann A, Hellack B. Bannuscher A, Vimalakanthan V, Riebeling C, Ossig R, Wiemann M, Schnekenburger J, Kuhlbusch TA, Renard B, Luch A, Haase A. Proteomic analysis of protein carbonylation: a useful tool to unravel nanoparticle toxicity Mechanisms. Part Fibre Tox 12: 36
https://doi.org/10.1186/s12989-015-0108-2