Description
Repeated dose toxicity studies in animals form the basis of chemical safety evaluations. Many parameters can be measured and analysed to assess the potential of the test chemical to cause adverse effects in the test animals and predict potential adverse effects in humans. However, these parameters can be quite general in nature and are not necessarily always helpful in understanding the mechanism(s) of the toxicities observed. In this study we analysed the parameters measured in animal studies and attempted to map these to more mechanistically informative endpoints. The study was conducted by collecting relevant mechanistic data from literature, public and private databases. The scope was limited to the liver, cardiovascular system, kidney and lung, and the oral route of exposure. The ultimate goal was to better understand the nature of chronic toxicity to facilitate and expedite the development of human-centric non-animal prediction models.
Contact
Contributors
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- Federica Madia
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- Pilar PRIETO PERAITA
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- Tatyana Doktorova
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- Barry Hardy
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- Ellen Langemeijer
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- Vidya Chandrasekaran
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- Paul Jennings
How to cite
Madia, Federica; Pilar Prieto; Doktorova, Tatyana; Hardy, Barry; Langemeijer, Ellen; Chandrasekaran, Vidya; Jennings, Paul (2023): EURL ECVAM In Vivo Repeated Dose Toxicity Database. European Commission, Joint Research Centre (JRC) [Dataset] PID: http://data.europa.eu/89h/4824023e-ad0f-4126-a6a4-f0e7b0bc330a
Keywords
cardiovascular system key characteristics kidney liver lung NAMs repeated dose toxicity
Data access
Repeated dose toxicity data should, in principle, be available through many sources. However, access to the raw data as well as richness of information was not easy to obtain. We had performed a series of interviews with different industries (e.g., pharmaceutical, agrochemical, cosmetics etc) in order to ask for access to such data. Additionally, we have tried to connect with projects that focused on gathering repeated dose toxicity data. The challenges identified were that: 1) organisations are reluctant to share information 2) the databases for which access was given contained either insufficient data or very generic information that could not be used for the purpose of this project. The first database to which we have gained access was the eTOX database. It had a very rich source on repeated dose toxicity data, but a main drawback was that it was only focused on drugs. In order to include information also from other chemical sectors such as industrial chemicals, consumer products, cosmetic ingredients, agrochemicals etc., we searched for other data sources. Two other databases were included, namely HESS (Hazard Evaluation Support System Integrated Platform) DB and CEBS (Chemical Effects in Biological Systems).
The "HIST_merged_all_data" file contains the joint histopathological information from the eTOX and HESS databases. The histopathological changes
graded
as "mild, moderate, severe, 3 (corresponds to moderate), and 4 (corresponds to severe)" were further explored in the analysis presented in the JRC Technical Report.
Similar effects were grouped and a new term created to refer to them.
The "HIST_function of time" file contains processed information on the time trends per target organ of the identified histopathological findings from eTOX and HESS databases. Common observations (e.g., necrosis, pneumonia etc.), a description of the effect, the severity of the effects at each time point (i.e. 28, 90, 180, and 365 days) and the name of the chemicals are reported in each of the columns of the target organ sheets (i.e. liver, kidney, heart and lung).
Publications
- Publications Office of the European Union, Luxembourg, Luxembourg
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Abstract
Repeated dose toxicity studies in animals form the basis of chemical safety evaluations. Many parameters can be measured and analysed to assess the potential of the test chemical to cause adverse effects in the test animals and predict potential adverse effects in humans. However, these parameters can be quite general in nature and are not necessarily always helpful in understanding the mechanisms of the toxicities observed. Here we analysed the parameters measured in animal studies and attempted to map these to more mechanistically informative endpoints. The study was conducted by collecting relevant mechanistic data from literature, public and private databases. The scope was limited to the liver, cardiovascular system, kidney and lung, and the oral route of exposure. The ultimate goal was to better understand the nature of chronic toxicity to facilitate and expedite the development of human-centric non-animal prediction models. An extended list of chemical Key Characteristics causing liver, lung, cardiovascular and kidney toxicities in repeat dose exposures were drawn up using both literature and data driven approaches. Case study chemicals, known to cause chronic toxicity helped to generate a shortened list of KCs per organ, giving a rationalisation of the target organ specificity of these chemicals. The approach and the data elaborated should prove helpful in developing methodologies for mechanistic understanding of toxicological data and for designing/optimising new experimental methods.
Additional information
- Published by
- European Commission, Joint Research Centre
- Created date
- 2023-02-16
- Modified date
- 2023-05-30
- Issued date
- 2023-03-31
- Landing page
- https://joint-research-centre.ec.europa.eu/eu-reference-laboratory-alternatives-animal-testing-eurl-ecvam_en
- Language(s)
- English
- Data theme(s)
- Health, Science and technology
- Update frequency
- unknown
- Identifier
- http://data.europa.eu/89h/4824023e-ad0f-4126-a6a4-f0e7b0bc330a
- Popularity
- 16 Apr 2024: 1 visits