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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.

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) 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. Current research focuses on the establishment of grouping approaches for the toxicological assessment of nanomaterials, the development of screening procedures for nanomaterials 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
  • Co-ordination of the BfR’s internal working group on nanomaterials (AG Nano)
  • Participation in national and international bodies (BMU, BMAS / AGS, MAK, EU, ECHA, 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

Completed research projects

  • ERANET SIINN NanoToxClass (12/2015- 02/2019)
  • EU NanoReg2 (09/2015- 02/2019)
  • BMBF nanoGRAVUR (05/2015- 06/2018)

Selected Recent Publications

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. (2020): 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. (2020): 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., Ro?u M., Balta C., Hermenean A., Wiemann M., Luch A., and Haase A. (2020): 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. (2019): 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. (2019): 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. (2019): 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. (2019): 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. (2019): 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
Gajewicz A, Puzyn T, Odziomek K, Urbaszek P, Haase A, Riebeling C, Luch A, Irfan MA, Landsiedel R, van der Zande M, Bouwmeester H. Decision tree models to classify nanomaterials according to the DF4nanoGrouping scheme. Nanotoxicology, 12:1-17
https://doi.org/10.1080/17435390.2017.1415388

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

Salvati A, Nelissen I, Haase A, Åberg C, Moya S, Jacobs A, Alnasser F, Bewersdorff T, Deville S, Luch A, Dawson KA. Quantitative measurement of nanoparticle uptake by flow cytometry illustrated by an interlaboratory comparison of the uptake of labelled polystyrene nanoparticles. NanoImpact 9: 42-50
https://doi.org/10.1016/j.impact.2017.10.004

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

Guehrs E, Schneider M, Gu?nther CM, Hessing P, Heitz K, Wittke D, López-Serrano Oliver A, Jakubowski N, Plendl J, Eisebitt S*, Haase A.* Quantification of silver nanoparticle uptake and distribution within individual human macrophages by FIB/SEM slice and view. J Nanobiotechn 15:21,
https://doi.org/10.1186/s12951-017-0255-8

Bewersdorff T, Vonnemann J, Kanik A, Haag R, Haase A. The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles. Int J Nanomedicine 12:2001-2019
https://doi.org/10.2147/IJN.S124295

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
DOI: https://doi.org/10.1186/s12989-015-0108-2

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