Metabolic profiling reveals structure-based common metabolites for liquid crystal monomers

The liquid crystal monomers (LCMs) widely used in electronic displays are increasingly detected in environmental and human matrices. However, their metabolism in humans and the toxicity of them and their metabolites is poorly understood. In this study, in vitro phase I metabolism of six representative LCMs (three cyano LCMs (CN-LCMs), three fluorinated LCMs (F-LCMs)), were investigated using human liver microsomes (HLMs). A total of 26 metabolites were tentatively identified and structurally elucidated by ultrahigh performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Two metabolites were identified as 4-cyano-4'-hydroxybiphenyl (CN-195) and 2-fluoro-4-hydroxybenzonitrile (2F4OHBN). Notably, structurally related LCMs were found to converge to common metabolites, CN-195 for alkoxy-substituted cyanobiphenyl-LCMs (OCB-LCMs) and 2F4OHBN for monofluorinated phenylbenzoate LCMs, indicating that structurally related LCMs will generate structure-based common metabolites. Targeted analysis confirmed the presence of CN-195 and 2F4OHBN in meconium from newborns, with detection frequencies of 30% and 55%, respectively. In silico toxicity predictions indicated that, while parent LCMs were generally more bioaccumulative, several metabolites strongly suggested mutagenicity, developmental toxicity, skin sensitization, and endocrine disruption properties. Together, these findings demonstrate that the potential toxicity of LCM biotransformation should not be underestimated, and that using common metabolites from structurally related LCMs warrants exploration for future human biomonitoring and risk assessment of LCMs.