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Molecular mechanisms of furan-mediated liver toxicity
Project
Project code: BfR-LMS-08-1322-414
Contract period: 01.04.2009
- 31.12.2009
Purpose of research: Applied research
The chemical furan is a conditional of manufacturing contaminant that was found in many foods. Animal studies demonstrated its mutagenic and cancerogenic potential. In these studies, liver was shown to be the primary target organ. Direct genotoxicity is presumably due to the oxidation of furan to the mutagenic substance cis-2-butene-1,4-dial mediated by the liver enzyme Cyp2E1. However, additional cytotoxic, Cyp2E1-independent effects of furan are discussed, the mechanisms of which are largely unknown so far. In an expert opin-ion on the occurrence of furan in foodstuffs by the BfR from June 6th 2004 as well as in a preliminary risk assessment by the EFSA from December 7th 2004 urgent need for research on the exposition of the consumer with furan and on the molecular mechanisms of the toxic-ity of furan was demanded. Recently, two research projects on the consumers exposition with furan were initiated by the EFSA (Call for proposals: CFP/EFSA/DATEX/2007/03: Small research projects on furan in food; and CFP/EFSA/ DATEX/2008/02: Research project on exposure to furan during food preparation). In addition, provision of data on furan exposure was requested (Call for scientific data on furan in food and beverages; deadline January 1st 2009). This underlines the actual priority of furan risk assessment in Europe.By using a proteomic approach, the project we here apply for will give insights into so far unidentified molecular mechanisms of furan toxicity. The study focuses on the identification of Cyp2E1-independent signalling and metabolic pathways addressed by furan. Based on the scientific data an assessment of Cyp2E1-dependent and ?independent modes of action in relation to furan toxicity will be conducted. In their expert opinions, both the BfR and the EFSA have also pointed out that studies on a possible developmental toxicity of furan are missing so far. Such studies on developmental toxicity are another focus of the project we here apply for.
Section overview
Subjects
- Toxicology