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PARC Sexual dimorphism associated to susceptibility to hepatotoxicity of environmental contaminants
Project
Project code: BfR-Bf3R-TOX-23-60-0103-01#00130, Grant Agreement 101057014
Contract period: 01.05.2025
- 30.04.2027
Purpose of research: Inventory & Assessment
Keywords: dimorphism, liver, sex, toxicity
The liver is one of the organs exhibiting the greatest sexual dimorphism, and the hepatic metabolic pathways subject to sexual dimorphism include the metabolism of xenobiotics, amino acids and lipids. Consequently, sex-specific biological and physiological differences influence individual susceptibility and the effects of chemical exposure on human health. For example, the likelihood of acute liver failure is higher in women than in men, and 70% of all cases of acute liver failure occur in women. Animal studies can account for sexual dimorphism by selecting the most sensitive sex for in vivo studies. However, the models and methods used to characterise the toxicity of pollutants in vitro do not yet allow for the prediction of individual susceptibility in the context of sexual dimorphism. It is therefore important to take hepatic sexual dimorphism into account when analysing the toxicological effects of environmental contaminants in in vitro studies and to integrate this knowledge, from a regulatory perspective, into the development of new alternative methods (NAMs). The aim of this project is to contribute to the improvement of current in vitro methods for assessing in vitro hepatotoxicity, taking sex differences into account, and to enhance our understanding through the use of various in vitro liver models in conjunction with predictive biomarkers. The project will be guided by the work carried out under the tasks of WP5, in particular 5.2.1 and 5.3, as well as WP6, and will take into account the ongoing work of the OECD Expert Group on Non-Genotoxic Carcinogens and Endocrine Disruptors.
Section overview
Subjects
- Toxicology
Framework programme
Funding programme
Excutive institution
BfR - Department: German Centre for the Protection of Laboratory Animals (BfR - Bf3R)
