Absorption and metabolism of 3-MCPD in hepatic and renal cell lines. (February 2021)

• Record Type: Journal Article
• Authors: Schultrich, Katharina; Oez, Fulya; Bergau, Nick; Buhrke, Thorsten; Braeuning, Albert
• Is Part Of: Toxicology in vitro. Volume 70(2021)
• Publication Date: 2021-02
• Subjects: 3-MCPD -- β-Chlorolactic acid -- in vitro cytotoxicity -- Absorption -- Metabolism; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.105042
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: 3-Monochloropropane-1, 2-diol (3-MCPD) fatty acid esters are process contaminants mainly formed during the refinement of vegetable oils. Gastrointestinal hydrolysis yields free 3-MCPD, which is resorbed into the body. In long-term rat studies, 3-MCPD caused renal and testicular neoplasms. 3-MCPD metabolism via β-chlorolactic acid has been postulated to underlie the toxic effects of 3-MCPD. Various efforts are ongoing to characterize the toxicological mode of action of 3-MCPD using in vitro systems. Published results suggest a very low sensitivity of cell cultures in vitro, as compared to 3-MCPD levels causing toxic effects in vivo . The insensitivity of in vitro systems raises the question to which extent 3-MCPD is absorbed and metabolized in vitro . We therefore analyzed cytotoxicity, absorption and metabolism of 3-MCPD and its metabolite β-chlorolactic acid in renal and hepatic cells. Cytotoxicity tests using up to 100 mM 3-MCPD confirmed the low sensitivity of human and rat cell lines towards 3-MCPD toxicity. Furthermore, absorption and metabolism of 3-MCPD examined via GC–MS and LC-MS/MS were only observed to a minor degree, and 3-MCPD was also not converted by a metabolizing system (S9 fraction). In conclusion, our data indicate that current in vitro models are not well suited for studying 3-MCPD metabolism and toxicity. Highlights: Lack of in vitro cytotoxicity of 3-MCPD using in vivo -relevant doses. Low 3-MCPD amounts detected in hepatic and renal cell lines after 24 h. Limited 3-MCPD metabolism in HepaRG cells. Current in vitro models are not sufficiently suited for studying 3-MCPD metabolism.