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Impact of the carbon chain length of perfluor carbonic acids toxicity and molecular charac-terisation of the hepatotoxic effects of PFOA on the proteomic level
Project
Project code: BfR-LMS-08-1322-327
Contract period: 01.04.2008
- 31.12.2010
Purpose of research: Basic research
Perfluoroalkyl acids (PFAAs) are needed for the fabrication of various industrial products. These substances are chemically and biologically inert; they are global contaminants of wa-ter and soil. Contaminated foodstuff such as drinking water, fish, eggs and game are the main sources for oral uptake of PFAAs by the consumer (expert's report by the BfR on PFOS and PFOA in food; Sept. 11th 2008).
Perfluorooctanoate (PFOA) is the leading substance of the class of PFAAs. PFOA is toxico-logically well characterised and was recently assessed by the EFSA Scientific Panel on Contaminants in the Food chain (Febr. 21st 2008). In this report recommendations were given for further research activities, i. e. on the elucidation of the mode of action of PFOA on the molecular level. It is known that PFOA exerts its hepatotoxic effects via activation of the nuclear receptor PPARalpha, however, other, PPARalpha-independent mechanisms are also dis-cussed. These alternative mechanisms are poorly examined so far.
The project will focus exactly on those open questions addressed by EFSA and BfR. Aim of this study is to generate additional experimental data on activating mechanisms of PFOA that will substantially contribute to the further risk assessment of PFOA.
Result: Analysis of the effect of perflourooctanoic acid on the proteome of the human hepatocellular cell line HepG2 show an influence on different proteins involved in stress response, protein metabolism, and cellular organisation. Ingenuity Pathway analysis indicated PPARalpa-independent mechanisms relating to identified proteins within the project. An essential regula-tor is the hepatocyte nuclear factor 4alpha (HNF4alpha) whose activity is affected by PFOA.
Section overview
Subjects
- Toxicology
