Impact of solvents on the in vitro genotoxicity of TMPTA in human HepG2 cells. (December 2020)

• Record Type: Journal Article
• Authors: Le Hegarat, Ludovic; Huet, Sylvie; Pasquier, Elodie; Charles, Sandrine
• Is Part Of: Toxicology in vitro. Volume 69(2020)
• Publication Date: 2020-12
• Subjects: PEG-400 -- DMSO -- TMPTA -- Genotoxicity -- HepG2 -- γH2AX; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.105003
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Small hydrophobic chemical compounds require solvents to produce suitable solutions for toxicological studies. However, some solvents can modify the biological properties of substances and therefore their toxicity. This specific issue has been raised for PEG-400 as an anti-inflammatory and anti-oxidative compound. Recently, in the context of the REACH Regulation, PEG-400 was used to test the in vivo genotoxicity of trimethylolpropane triacrylate (TMPTA) in the comet assay. TMPTA failed to increase DNA damage whereas it induces genotoxicity in vitro in DMSO. Therefore, we questioned whether PEG-400 could modify the genotoxicity of TMPTA. The aim of this study was to determine the potential impact of PEG-400 on the in vitro genotoxicity of TMPTA, compared to DMSO. TMPTA was dissolved in either PEG-400 or DMSO, and the induction of γH2AX and Caspase-3 was analyzed in HepG2 cells. TMPTA induced γH2AX and Caspase-3 with both PEG-400 and DMSO. However, TMPTA induced effects at 4-fold lower concentrations when PEG-400 is used as the solvent compared to DMSO. While genotoxic effects are observed at much lower concentrations with PEG-400, it does not modify the in vitro genotoxicity of TMPTA. However, further in vitro studies with small hydrophobic compounds should be done to clarify the effect of PEG-400. Moreover, in vivo studies should be performed to confirm that PEG-400 remains suitable for in vivo genotoxicity tests. Highlights: TMPTA induces γH2AX and Caspase-3 in HepG2 cells. PEG-400 does not prevent in vitro genotoxicity effect of TMPTA. The genotoxic effect of TMPTA is more pronounced when it is diluted in PEG400 than in DMSO.