Behavioral toxicity of TDCPP in marine zooplankton: Evidence from feeding and swimming responses, molecular dynamics and metabolomics of rotifers

Abstract

As new organic flame retardants, chlorinated organophosphate esters (Cl-OPEs) have high water solubility and structural similarity to organophosphate pesticides, posing risks to aquatic organisms. The potential neurotoxicity of Cl-OPEs has attracted attention, especially in marine invertebrates with a relatively simple nervous system. In this study, a marine rotifer with a cerebral ganglion, Brachionus plicatilis, was exposed to tris (1,3-dichloro-2-propyl) phosphate (TDCPP) (two environmental concentrations and one extreme level), and the changes in feeding and swimming behaviors and internal mechanism were explored. Exposure to 1.05 nM TDCPP did not change the filtration and ingestion rates of rotifers and average linear velocity. But 0.42 and 4.20 μM TDCPP inhibited these three parameters and reduced unsaturated fatty acid content, reproduction and population growth. All TDCPP test concentrations suppressed AChE activity, causing excessive accumulation of acetylcholine within rotifers, thereby disturbing the neural innervation of corona cilia. Molecular docking and molecular dynamics revealed that this inhibition was because TDCPP can bind to the catalytic active site of rotifer AChE through van der Waals forces and electrostatic interactions. TRP420 was the leading amino residue in the binding, and GLY207 contributed to a hydrogen bond. Nontargeted metabolomics using LC-MS and GC-MS identified differentially expressed metabolites in TDCPP treatments, mainly from lipid and lipid-like molecules, especially sphingolipids. TDCPP decreased ganglioside content but stimulated ceramide generation and the expression levels of 3 genes related to ceramide de novo synthesis. The mitochondrial membrane potential (MMP) and ATP content decreased, and the electron respiratory chain complex and TCA cycle were deactivated. An inhibitor of ceramide synthase, fumonisin, alleviated MMP and ATP, implying a critical role of ceramide in mitochondrial dysfunction. Thus, TDCPP exposure caused an energy supply deficit affecting ciliary movement and ultimately inhibiting rotifer behaviors. Overall, this study promotes the understanding of the neurotoxicity of Cl-OPEs in marine invertebrates.