Regulatory research

Our approach

With self-initiated research projects, we contribute to the development of novel assessment strategies to help improve and refine existing risk assessment methods and ultimately to minimize the need for experimental studies, in particular animal studies. Examples of such projects are elucidation of structure-activity relationships ((Q)SAR), category approaches such as read across, the setting up of databases, and further development of the TTC concept.

Our services

Data gap analysis and literature search: What data are available? Which additional studies are necessary? Is there information publicly available about the substance in question? We are particularly experienced in working with substance categories and read-across.

Your benefits

  • We analyze the available data for data gaps and close existing gaps by using structure-activity relationships ((Q)SAR models), read across, or waiving; whenever necessary, we develop an optimized testing strategy.
  • Besides access to other public databases, we have proprietary toxicological databases (RepDose, FeDTex, PaFTox) which we can customize to your specific requirements.

Concepts and scientific basic principles of risk assessment

Further development of the TTC concept, derivation of a TTC for inhalation exposure, derivation of extrapolation factors, concepts for categorization of (nano-)particles

Our services and expertise

 

  • Improvement of risk assessment methods:
    Development of integrated testing strategies (e.g. for the endpoint repeated-dose toxicity within the EU projekt OSIRIS); verification of predictiveness of in-vitro/in-silico screening methods (e.g. within the EU project ChemScreen)
  • Scientific basic principles of risk assessment:
    Enhancement and improvement of TTC concepts including inhalation, extrapolation factors, and concepts for (nano-)particles
  • Exposure:
    Development and validation of models and scenarios (e.g. SprayExpo, ESDs); evaluation of risk mitigation measures; development of analytical methods
  • Toxicological databases:
    We develop databases and perform database analyses, for example, with regard to repeated-dose toxicity (RepDose), reproductive and developmental toxicity (FeDTex), and inhalation studies with nanoparticles (PaFTox); we furthermore develop ontologies for databases to enable uniform description of effects
  • (Q)SAR and investigation of structurally related substances:
    Models of qualitative or quantitative structure-activity relationship; investigation of structurally related substances (definition of groups or analogy); development and assessment of substance categories by using our own or third-party databases (e.g. OECD toolbox)
  • Expert reports:
    In the form of expert reports, we document the (eco-)toxicological properties of substances and assess their risks to human health and the environment, for example, in the event of contamination or chemical residues in foods and products.

 

Toxicology databases

Database development and queries, e.g. with regard to repeated-dose toxicity (RepDose) and reproductive and developmental toxicity (FeDTex)

To support the process of international standardization of nomenclature and diagnostic criteria a team of scientists at the Fraunhofer ITEM are engaged in establishing different toxicology databases. This multidisciplinary team has many years of experience in designing, developing, and operating databases and electronic information systems for current issues in toxicology and toxicologic pathology.

To provide the required technical support for the databases goReni and DevTox, the team cooperates with the Fraunhofer ITEM Department of Pathology and the Working Group on Reproductive Toxicology as well as with numerous national and international societies and organizations.

The databases for Repeated Dose Toxicity (RepDose) and Reprotoxicity (FeDTex) are used to develop risk assessment strategies and to identify (quantitative) structure-activity relationships ((Q)SAR).

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Methods and expertise/etc/designs/default/0.gif

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  • Database design and development
  • Technical support for standardization and international harmonization issues in toxicological pathology
  • Software development
  • Statistical analysis
  • Development and implementation of information systems for stand-alone usage or for the Internet
  • Image analysis: e.g. procedures for the quantitative evaluation of cell proliferation measurements

Our databases

RITA (Registry of Industrial Toxicology Animal-data)

RITA is a database for the collection of peer-reviewed histopathological diagnoses on tumors and other proliferative lesions as well as study-associated information from control rats and mice. Since 1988, this database has been operated for major European chemical and / or pharmaceutical companies in collaboration with the Department of Pathology.

See the RITA website for more information

This RITA-associated project focuses on the development of a database and standardized procedures for applying cell proliferation techniques (e.g. BrdU and PCNA labeling) to toxicity testing.

Please see the RITA CEPA website for more details.

RENI is an information system for toxicologic pathology on the Web including a standardized nomenclature and diagnostic criteria for proliferative lesions in rats and mice together with images of histopathological slides and literature references. For further information, please visit the RENI website.

The development of a database system for the evaluation of results from reproductive toxicology studies has been started in 1999. The project is carried out in cooperation with the working groups on General Toxicology and Reproductive Toxicology. For more details please see the related website.

FeDTex is a reproductive toxicology database with a focus on multi-generation studies. Affected parameters and effects are documented in relation to the developmental stage, gender, and generation. This database allows e.g. structureactivity relationships to be developed.

RepDose (repeated-dose toxicity) is a relational database on subacute to chronic toxicity and currently contains 655 chemicals. The toxicity of these chemicals has been documented in about 2280 studies, carried out in rats, mice or dogs with oral or inhalation exposure. The content and structure of the database RepDose provide a sound basis to perform analyses on repeated-dose toxicity. RepDose is used by the Department of Chemical Risk Assessment at the Fraunhofer ITEM to analyze and improve risk assessment strategies. Further information

Testing strategies and structure-activity relationships

Models of qualitative or quantitative structure-activity relationships, investigation of structurally related substances, development and assessment of substance categories

Alternative methods to animal testing are required to reduce animal tests, e.g. under REACH. Our working group QSAR/New Methodologies for Risk Assessment is involved in several projects developing strategies for human risk assessment within the European Framework Programs 6 and 7 and in projects sponsored by the chemical industry. In this context, two databases – RepDose and FeDTex – have been developed to address repeated-dose and reproductive toxicity.

RepDose – Repeated-Dose Toxicity:
RepDose, a database funded by Cefic LRI, contains peer-reviewed and confidential repeated-dose toxicity studies in rodents with subacute to chronic exposure durations. It is a continuously growing database and currently contains about 650 chemicals and 2500 studies. The database is available at: www.fraunhofer-repdose.de.

FeDTex – Reproductive and Developmental Toxicity:
FeDTex is a database on reproductive toxicity with a focus on one- and two-generation studies. Parameters and effects describing maternal toxicity, reproductive performance, and developmental toxicity are documented according to affected generation, developmental stage, and sex. The database can be used both for risk assessment and for structure-activity analyses.

 

Our services and expertise

  • Development and assessment of chemical categories
  • Assessment of chemicals using read across and/or structure-activity relationships
  • Development of risk assessment methodologies, e.g. TTC and extrapolation factors
  • Analysis of modes of action
  • Development of databases for toxicological endpoints

All services can be performed with customized datasets (existing databases, literature search, confidential data).

Project insights

ExITox – Explain Inhalation Toxicity

Development of an integrated testing strategy for the prediction of toxicity after repeated dose inhalation exposure: a proof of concept

EU-ToxRisk

Toxicological risk assessment - an integrated European "flagship" program driving mechanism-based, animal-free toxicity testing and risk assessment for the 21st century

ChemScreen

Chemical substance and in-vitro/in-silico screening system to predict human- and ecotoxicological effects (EU FP7)

Cooperation US EPA & TNO

Cooperation with US EPA (ToxRef database) and TNO, The Netherlands Organization for Applied Scientific Research (Toxbase database)

TTC-Konzept

Evaluation of the threshold of toxicological concern (TTC) concept using RepDose; refinement of oral thresholds and the Cramer decision tree and derivation of TTC for inhalation exposure

Industry Consortium ERASM

Analysis of extrapolation factors for route-to-route, interspecies, and time extrapolation for the industry consortium ERASM with special focus on surfactants

Category approach

Category approach funded by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety: development of a strategy to derive new categories for risk assessment based on the toxicological profile and/or the structural features of the substances

Your contact for regulatory research of chemical substances

Sylvia Escher

Contact Press / Media

Dr. Sylvia Escher

Head of Department of In-silico Toxicology

Phone +49 511 5350-330