Next generation risk assessment to set the stage for the future

© Fraunhofer ITEM, Ralf Mohr

Fraunhofer ITEM stands for toxicology testing and risk assessment of chemicals, active substances and drugs – with a focus on inhalation toxicology. Continued development of the corresponding exposure methods enables very small amounts of test substances to be used with high efficiency in toxicological studies.

Next Generation Risk Assessment

While conventional toxicology testing is still the required regulatory standard, our researchers are contributing to new assessment strategies through their own research projects based on the next generation risk assessment concept, aiming to provide predictive models for assessing the safety of compounds.

Based on the precision-cut lung slices (PCLS) technology that is well established at the institute, more human or humanized ex-vivo organ models, for example of the heart and liver, are in the process of further development. These models can also be used to test biopharmaceuticals and advanced therapy medicinal products (ATMPs). To analyze the results, the researchers combine the traditional endpoints among others with omics technologies, in particular metabolomics and functional genomics, and complex advanced bioinformatics analyses.

Assessment methods based on databases, such as the TTC (threshold of toxicological concern) concept, are being further developed, for example to identify non-genotoxic tumorigenic substances or to allow these methods to be used for the development of medical devices as well.

Toxicology: recent projects and highlights


RISK-HUNT3R project

For next generation risk assessment of toxic effects, human-based testing strategies are being developed to reduce, refine and, wherever possible, replace animal testing. 


Inhalation and dermal exposure from foam spray applications

Using a methodology recently developed at Fraunhofer ITEM, the scientists determined the aerosol release for common foaming technologies applied according to their intended use.

Mutagenicity of N-nitrosamines

In the MutaMind project, funded by the European Medicines Agency (EMA) and led by Fraunhofer ITEM, the carcinogenic potency of different nitrosamines are investigated.

Inhalation toxicity of niobium

Researchers of the Fraunhofer ITEM investigated the toxicity of niobium likewise the influence of the respiratory tract.

MONO4ERA project

Feasibility study of an active-substance-based system and other potential alternatives for environmental risk assessment of veterinary medicinal products.


Assessing microplastic inhalation toxicity

Development of a tiered testing and assessment approach for human risk assessment of microplastic.


New-approach methodologies (NAMs)

The EFSA project "Development of roadmaps for action on NAMs in risk assessment" is aimed at prioritizing the incorporation of NAMs into chemical risk assessment.

Project SEAWave

In the Europe-wide SEAWave project, we are conducting an exposure and risk assessment of radio frequency and mm-wave (5G) systems with several partner organisations.


Understanding Cabin Air Quality

The recently launched research project ”Cabin air quality III“ is aimed at assessing long-term effects of contaminants that aircraft passengers and crew members are exposed to on board.


Toxicokinetics of carbon black

The toxicokinetic behavior of nanoscale particles after pulmonary deposition is of great scientific interest because they might have a potential for systemic exposure.

Project ZET-O-MAP

Scientists of Fraunhofer ITEM have developed an analysis pipeline in the CEFIC-LRI project ZET-O-MAP to identify biomarkers for developmental toxicity.

Project ZeroPM: Zero pollution from persistent, mobile substances

Aimed at reducing the risk of our drinking water resources getting contaminated with persistent, mobile substances (PM).

Focus on the food chain

In the EFSA project "Emerging Risk III" we investigate and assess potential risks from industrial chemicals that could possibly be present in the food chain.


Toxicological risk assessment for PFAS

At Fraunhofer ITEM, we are investigating how PFAS impact people’s health. Our main objective here is to separate the PFAS family into subclasses according to their structures and physical and chemical properties, and use this as a basis for determining limits for safe amounts of ingestion for each subclass. 


Project Cell Painting

Scientists from Faunhofer establish a promising tool for next generation risk assessment.


PREMIER project

Setup of a database that is to deliver relevant data for the development of models for prediction of environmental data to enable better assessment and characterization of the environmental risks of pharmaceuticals. 

Preclinical studies for repurposing of Aloxistatin

Fraunhofer ITEM performed inhalation toxicology studies under GLP conditions to prepare for regulatory approval of Aloxistatin. 

Project archive

Here you can find more projects sorted by our research and development competences. 


  • Batke, M., Damm, G., Foth, H., Freyberger, A., Gebel, T., Gundert-Remy, U., Hengstler, J., Mangerich, A., Partosch, F., Rohl, C., Schupp, T., Wollin, K. M. (2022). The EU chemicals strategy for sustainability: critical reflections on proposed regulatory changes for endocrine disruptors and mixture toxicity. Archives of Toxicology [Epub ahead of print]. doi: 10.1007/s00204-022-03227-z  -
  • Burzlaff, A., Creutzenberg, O., Schaudien, D., Viegas, V., Danzeisen, R., Warheit, D. (2022). A tiered approach to investigate the inhalation toxicity of cobalt substances. Tier 4: Effects from a 28-day inhalation toxicity study with tricobalt tetraoxide in rats. Regulatory Toxicology and Pharmacology 130: 105129. doi: 10.1016/j.yrtph.2022.105129  - Open Access
  • Creutzenberg, O., Oliveira, H., Farcal, L., Schaudien, D., Mendes, A., Menezes, A. C., Tischler, T., Burla, S., Ziemann, C. (2022). PLATOX: Integrated In Vitro/In Vivo Approach for Screening of Adverse Lung Effects of Graphene-Related 2D Nanomaterials. Nanomaterials (Basel) 12(8). doi: 10.3390/nano12081254  - Open Access
  • Escher, S. E., Aguayo-Orozco, A., Benfenati, E., Bitsch, A., Braunbeck, T., Brotzmann, K., Bois, F., van der Burg, B., Castel, J., Exner, T., Gadaleta, D., Gardner, I., Goldmann, D., Hatley, O., Golbamaki, N., Graepel, R., Jennings, P., Limonciel, A., Long, A., Maclennan, R., Mombelli, E., Norinder, U., Jain, S., Capinha, L. S., Taboureau, O. T., Tolosa, L., Vrijenhoek, N. G., van Vugt-Lussenburg, B. M. A., Walker, P., van de Water, B., Wehr, M., White, A., Zdrazil, B., Fisher, C. (2022). Integrate mechanistic evidence from new approach methodologies (NAMs) into a read-across assessment to characterise trends in shared mode of action. Toxicology in Vitro 79: 105269. doi: 10.1016/j.tiv.2021.105269  -
  • Funk, J., Ruehl-Fehlert, C., Leonard, C., Kellner, R., Rittinghausen, S. (2022). Immunohistochemical Characterization of Proliferative Lesions in the Thymus of Aging CD-1 Mice From Two Studies on the RITA Database, With Special Reference to the Perivascular Space. Toxicologic Pathology [Epub ahead of print]: 1926233221082972. doi: 10.1177/01926233221082972  - Open Access
  • Hahn S, Meyer J, Roitzsch M, Delmaar C, Koch W, Schwarz J, et al. Modelling Exposure by Spraying Activities—Status and Future Needs. International journal of environmental research and public health (2021) 18(15):7737. 
  • Hahn S, Hennecke D. What Can We Learn from Biodegradation of Natural Polymers for Regulation? Environmental Sciences Europe (2023) 35(1). doi: 10.1186/s12302-023-00755-y.
  • Henschenmacher, B., Bitsch, A., de Las Heras Gala, T., Forman, H. J., Fragoulis, A., Ghezzi, P., Kellner, R., Koch, W., Kuhne, J., Sachno, D., Schmid, G., Tsaioun, K., Verbeek, J., Wright, R. (2022). The effect of radiofrequency electromagnetic fields (RF-EMF) on biomarkers of oxidative stress in vivo and in vitro: A protocol for a systematic review. Environ Int 158: 106932. doi: 10.1016/j.envint.2021.106932  - Open Access
  • Janssen, P., Barton, G., Kietzmann, M., Meissner, J. (2022). Treatment of pigs with enrofloxacin via different oral dosage forms - environmental contaminations and resistance development of Escherichia coli. Journal of Veterinary Science [Epub ahead of print]. doi: 10.4142/jvs.21216  - Open Access
  • Lu, D., Chatterjee, S., Xiao, K., Riedel, S., Huang, C., Costa, A., Cushman, S., Neufeldt, D., Rode, L., Schmidt, A., Juchem, M., Leonardy, J., Büchler, G., Blume, J., Gern, O., Kalinke, U., Tan, W., Foo, R., Vink, A., van Laake L., van der Meer, P., Bär, C., Thum, T. (2022). A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. European Heart Journal. doi: 10.1093/ehac337
  • Nendza M, Hahn S, Klein M, Klaschka U, Gabbert S. Scoring Scheme for Comparative Ranking of Impact Potential of Chemical Alternatives (Scora). Environmental Sciences Europe (2023) 35(1):11. doi: 10.1186/s12302-023-00718-3.
  • Rohl, C., Batke, M., Damm, G., Freyberger, A., Gebel, T., Gundert-Remy, U., Hengstler, J. G., Mangerich, A., Matthiessen, A., Partosch, F., Schupp, T., Wollin, K. M., Foth, H. (2022). New aspects in deriving health-based guidance values for bromate in swimming pool water. Archives of Toxicology [Epub ahead of print]. doi: 10.1007/s00204-022-03255-9  - Open Access
  • Schäferhenrich, A., Blümlein, K., Koch, W., Hahn, S., Schwarz, K., Poppek, U., Hebisch, R., Schlüter, U., Krug, M., Göen, T. (2023). "Inhalation and dermal exposure to biocidal products during foam and spray applications." Ann Work Expo Health [Epub ahead of print]. doi: 10.1093/annweh/wxad037 - Open Access
  • Schwarz, K., Blümlein, K., Göen, T., Hahn, S., Hebisch, R., Koch, W., Poppek, U., Schäferhenrich, A., Schluter, U., Krug, M. (2023). "Aerosol formation during foam application of non-volatile biocidal substances." Ann Work Expo Health 67(6): 731-743. doi: 10.1093/annweh/wxad031 - Open Access
  • Teigeler, M., Schaudien, D., Bohmer, W., Lange, R., Schafers, C. (2022). Effects of the Gestagen Levonorgestrel in a Life Cycle Test with Zebrafish (Danio rerio). Environmental Toxicology and Chemistry 41(3): 580-591. doi: 10.1002/etc.5008  - Open Access
  • Vrijenhoek, N. G., Wehr, M. M., Kunnen, S. J., Wijaya, L. S., Callegaro, G., Mone, M. J., Escher, S. E., Van de Water, B. (2022). Application of high-throughput transcriptomics for mechanism-based biological read-across of short-chain carboxylic acid analogues of valproic acid. Altex [Epub ahead of print]. doi: 10.14573/altex.2107261  - Open Access
  • Wall, J., Seleci, D. A., Schworm, F., Neuberger, R., Link, M., Hufnagel, M., Schumacher, P., Schulz, F., Heinrich, U., Wohlleben, W., Hartwig, A. (2022). Comparison of Metal-Based Nanoparticles and Nanowires: Solubility, Reactivity, Bioavailability and Cellular Toxicity. Nanomaterials (Basel) 12(1): 147. doi: 10.3390/nano12010147  - Open Access
  • Wehr, M. M., Sarang, S. S., Rooseboom, M., Boogaard, P. J., Karwath, A., Escher, S. E. (2022). RespiraTox - Development of a QSAR model to predict human respiratory irritants. Regulatory Toxicology and Pharmacology 128: 105089. doi: 10.1016/j.yrtph.2021.105089