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Toxicol In Vitro ; 70: 105042, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33129984

RESUMO

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 ß-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 ß-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.


Assuntos
Rim/citologia , Fígado/citologia , alfa-Cloridrina/toxicidade , Absorção Fisiológica , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Lactatos/metabolismo , Ratos , Espectrometria de Massas em Tandem
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