Toxicity of Organophosphorus Flame Retardants (OPFRs) and Their Mixtures in Aliivibrio fischeri and Human Hepatocyte HepG2

Background: Organophosphorus flame retardants (OPFRs) are a group of chemical substances used in building materials and plastic products to suppress or mitigate the combustion of materials.Although OPFRs are generally used in mixed form, information on their mixture toxicity is quite scarce.Objectives: This study aims to elucidate the toxicity and determine the types of interaction (e.g., synergistic, additive, and antagonistic effect) of OPFRs mixtures.Methods: Nine organophosphorus flame retardants, including TEHP (tris(2-ethylhexyl) phosphate) and TDCPP (tris(1,3-dichloro-2-propyl) phosphate), were selected based on indoor dust measurement data in South Korea.Nine OPFRs were exposed to the luminescent bacteria Aliivibrio fischeri for 30 minutes and the human hepatocyte cell line HepG2 for 48 hours.Chemicals with significant toxicity were only used for mixture toxicity tests in HepG2.In addition, the observed EC x values were compared with the predicted toxicity values in the CA (concentration addition) prediction model, and the MDR (model deviation ratio) was calculated to determine the type of interaction.Results: Only four chemicals showed significant toxicity in the luminescent bacteria assays.However, EC 50 values were derived for seven out of nine OPFRs in the HepG2 assays.In the HepG2 assays, the highest to lowest EC 50 were in the order of the molecular weight of the target chemicals.In the further mixture tests, most binary mixtures show additive interactions except for the two combinations that have TPhP (triphenyl phosphate), i.e., TPhP and TDCPP, and TPhP and TBOEP (tris(2-butoxyethyl) phosphate). Conclusions:Our data shows OPFR mixtures usually have additivity; however, more research is needed to find out the reason for the synergistic effect of TPhP.Also, the mixture experimental dataset can be used as a training and validation set for developing the mixture toxicity prediction model as a further step.