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. 

MONO4ERA project

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


Draft of an EU register for health-based limit values

As part of its “one substance, one assessment” approach, the European Commission is planning a centralized, structured database for health-based limit values (HBLVs). This database will make it easy to access all relevant HBLVs in one place.


In-vitro inhalation methods help with safe product development of cosmetic sprays

Fraunhofer researchers have been investigating a spray product for room conditioning in hairdressing salons.


Assessment of emissions from e-liquids

EVape helps to improve safety for e-cigarette consumers.

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 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.


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.


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 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 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.


Assessing microplastic inhalation toxicity

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

Preclinical studies for repurposing of Aloxistatin

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


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.

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).


Project Cell Painting

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


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.

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.

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. 

Project archive

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


  • Blümlein, K., Nowak, N., Ellinghusen, B., Gerling, S., Badorrek, P., Hansen, T., Hohlfeld, J. M., Paul, R., Schuchardt, S. (2023). Occupational exposure to veterinary antibiotics: Pharmacokinetics of enrofloxacin in humans after dermal, inhalation and oral uptake - A clinical study. Environmental Toxicology and Pharmacology 100: 104139. doi: 10.1016/j.etap.2023.104139
  • Bowden, A., Escher, S., Rose, J., Sadekar, N., Patlewicz, G., O'Keeffe, L., Bury, D., Hewitt, N. J., Giusti, A., Rothe, H. (2023). Workshop report: Challenges faced in developing inhalation thresholds of Toxicological Concern (TTC) - State of the science and next steps. Regulatory Toxicology and Pharmacology 142: 105434. doi: 10.1016/j.yrtph.2023.105434  - Open Access
  • Dekant, W., Antoniou, E. E., Bosch, A., Bruer, G. G., Colnot, T., Creutzenberg, O., Drexel, C. P., Duffin, R., Krueger, N., Nolde, J., Poland, C., Schaudien, D., Schuster, T. B., Stintz, M., Weber, K., Wessely, B., Zeegers, M. P. (2023). Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS). Toxicology Letters [Epub ahead of print]. doi: 10.1016/j.toxlet.2023.02.002
  • Drake, C., Wehr, M. M., Zobl, W., Koschmann, J., De Lucca, D., Kühne, B. A., Hansen, T., Knebel, J., Ritter, D., Boei, J., Vrieling, H., Bitsch, A., Escher, S. E. (2023). Substantiate a read-across hypothesis by using transcriptome data—A case study on volatile diketones. Frontiers in Toxicology 5: 14p. doi: 10.3389/ftox.2023.1155645  - Open Access
  • Escher, S. E., Felter, S. P., Hollnagel, H., Boobis, A. R., Yang, C., Rathman, J., Cronin, M. T. D., Batke, M. (2023). Workshop report on the evaluation of the updated and expanded carcinogen database to support derivation of threshold of toxicological concern values for DNA-reactive carcinogens. Altex 40(2): 341-349. doi: 10.14573/altex.2210111  - Open Access
  • Lange, F., Koch, W. (2023). Application of Resuspension Data of Respirable Particles for Early Phase Inhalation Following Deposition Contamination in Radiological Emergencies. Health Physics 124(3): 155-165. doi: 10.1097/HP.0000000000001648 - Open Access
  • Reamon-Buettner, S. M., Rittinghausen, S., Klauke, A., Hiemisch, A., Ziemann, C. (2024). Malignant peritoneal mesotheliomas of rats induced by multiwalled carbon nanotubes and amosite asbestos: transcriptome and epigenetic profiles Particle and Fibre Toxicology 21(1). doi: 10.1186/s12989-024-00565-x - Open Access
  • Rodríguez, J. M. M., Frisk, A.-L., Kreutzer, R., Lemarchand, T., Lezmi, S., Saravanan, C., Stierstorfer, B., Thuilliez, C., Vezzali, E., Wieczorek, G., Yun, S.-W., Schaudien, D. (2023). European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development. Toxicologic Pathology [Epub ahead of print]. doi: 10.1177/019262332311782  - Open Access
  • Sanz, F., Pognan, F., Steger-Hartmann, T., Díaz, C., Asakura, S., Amberg, A., Bécourt-Lhote, N., Blomberg, N., Bosc, N., Briggs, K., Bringezu, F., Brulle-Wohlhueter, C., Brunak, S., Bueters, R., Callegaro, G., Capella-Gutierrez, S., Centeno, E., Corvi, J., Cronin, M. T. D., Drew, P., Duchateau-Nguyen, G., Ecker, G. F., Escher, S., Felix, E., Ferreiro, M., Frericks, M., Furlong, L. I., Geiger, R., George, C., Grandits, M., Ivanov-Draganov, D., Kilgour-Christie, J., Kiziloren, T., Kors, J. A., Koyama, N., Kreuchwig, A., Leach, A. R., Mayer, M.-A., Monecke, P., Muster, W., Nakazawa, C. M., Nicholson, G., Parry, R., Pastor, M., Piñero, J., Oberhauser, N., Ramírez-Anguita, J. M., Rodrigo, A., Smajic, A., Schaefer, M., Schieferdecker, S., Soininen, I., Terricabras, E., Trairatphisan, P., Turner, S. C., Valencia, A., van de Water, B., van der Lei, J. L., van Mulligen, E. M., Vock, E., Wilkinson, D. (2023). eTRANSAFE: data science to empower translational safety assessment. Nature Reviews Drug Discovery 22(8): 605-606. doi: 10.1038/d41573-023-00099-5
  • 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 67(7): 858-875. doi: 10.1093/annweh/wxad037 - Open Access
  • Schwarz, K., Blumlein, K., Goen, T., Hahn, S., Hebisch, R., Koch, W., Poppek, U., Schaferhenrich, 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
  • Warner, L., Bach-Hagemann, A., Schmidt, T. P., Pinkernell, S., Schubert, G. A., Clusmann, H., Albanna, W., Lindauer, U., Conzen-Dilger, C. (2023). Opening a window to the acutely injured brain: Simultaneous retinal and cerebral vascular monitoring in rats. Frontiers in Molecular Neuroscience 16: 1116841. doi: 10.3389/fnmol.2023.1116841 - Open Access