Elucidating multilevel toxicity response differences between tris(1,3-dichloro-2-propyl) phosphate and its primary...

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and its primary metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) are frequently detected in aquatic environments. However, information regarding the biotoxicity of these compounds to bivalves is limited. We explored the multilevel physiological responses of Corbicula fluminea to TDCIPP and BDCIPP. The results indicated that TDCIPP/BDCIPP bioaccumulation in bivalves was positively correlated with their hydrophobicity. Furthermore, the higher body burden of TDCIPP in digestive glands led to significantly higher levels of ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), and P-glycoprotein (p < 0.05). Owing to different molecular structures of inducers, upregulations of cyp4, gstm1, and abcb1 mRNA exhibited different sensitivities to TDCIPP and BDCIPP. Although Phase-I and Phase-II biotransformation and the multixenobiotic resistance (MXR) system were activated to protect bivalves from TDCIPP or BDCIPP, digestive glands produced large amounts of reactive oxygen species (ROS). Moreover, oxidative stress, the percentage of apoptotic cells in digestive glands, and inhibition of siphoning behaviour in TDCIPP treatments were higher than those in BDCIPP treatments (p < 0.05), indicating that TDCIPP was more toxic to bivalves than BDCIPP. Lower bioaccumulation and rapid metabolism of BDCIPP in vivo may contribute to alleviating its toxicity. This research establishes a foundation for further understanding the differences between the toxic mechanisms of TDCIPP and its metabolites.