Neurotoxicity and related mechanisms of flame retardant TCEP exposure in mice

Abstract

<b>Objective:</b> To explore the neurotoxicity and mechanism of tris(2-chloroethyl) phosphate (TCEP) exposure in mice.<b>Methods:</b> Total 30 adult Kunming mice were randomly divided into normal control group (0 mg/kg·d), low-dose TCEP group (10 mg/kg·d), and high-dose TCEP group (100 mg/kg·d), and administered continuously by gavage for 30 days.<b>Results:</b> Compared with the control group, the water intake of high-dose TCEP group was declined significantly (<i>p</i> < 0.05), and the organ index of liver and spleen were increased significantly (<i>p</i> < 0.05). In addition, the escape latency of TCEP exposed mice were longer than that in the control group in water maze test (<i>p</i> < 0.05), while the total swimming course of high-dose TCEP group was elevated and the swimming time in target quadrant was obviously shortened compared with the control group (<i>p</i> < 0.05). The serum levels of total-triiodothyronine (TT3) and free triiodothyronine (FT3) were significantly higher in the high-dose TCEP group than in the control group (<i>p</i>＜0.05). Compared with the control group, the activities of glutathione transferase (GST) and super oxide dismutase (SOD) in the high-dose TCEP group were increased, and GST in the low-dose TCEP group were decreased, while the content of malonaldehyde (MDA) in both groups was increased (<i>p</i>＜0.05). In the CCK8 assay, the viability of PC12 cells decreased with an increase of TCEP concentration, indicating a concentration dependent neurotoxicity.<b>Conclusion:</b> TCEP exposure can cause neurotoxicity by increasing thyroid hormones and inducing oxidative damage in mice.