Enhanced toxicity of 2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] (V6) by nanopolystyrene particles towards HeLa cells.

2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] (V6) has been widely used as an additive in a variety of plastics due to its extremely low toxicity. However, we showed in the study that once mixed with nanopolystyrene particles (NPs), the nontoxic V6 could exhibit significant toxicity to HeLa cells. The enhanced toxicity was much higher than the toxicity of NPs alone and was related to the size of NPs. The mixture of V6 and small polystyrene NPs (10 nm and 15 nm in radius) showed obvious toxicity to HeLa cells. The toxicity increased with the concentrations of both V6 and NPs. On the contrary, the mixture of V6 and larger NPs (25 nm, 50 nm, 100 nm, and 500 nm in radius) showed almost no toxicity even at extremely high concentrations (NPs: 100 mg/L; V6: 50 mg/L). The small NPs could enter the cells and accumulated in cytoplasm. However, the larger NPs did not distribute inside the cells. NPs efficiently adsorbed V6 on the surface. The mechanism of the enhanced toxicity was attributed to the increased intracellular reactive oxygen species (ROS) production and the regulation of gene expression concerning apoptosis and ROS scavenging. Our study not only showed that a safe chemical V6 could be turned to be toxic by NPs, but also pointed out a potential risk caused by the joint toxicity of 'safe' chemicals and plastic particles with small size.