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OBJECTIVE 1-Bromopropane (1-BP) has been introduced as an alternative toozonedepleting solvents and exhibits neurotoxicity both in experimental animals and human.To obtain further information on the underlying mechanisms of 1-BP-induced neurotoxicity in the central nerve system (CNS), a proteomic analysis was conducted to identify and characterize 1-BP-induced modification of phosphoprotein expression in the hippocampus of rats.METHODS Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8 h·d-1 for 1 week and 4 weeks by inhalation (n =9 rats of each group).Hippocampal protein extracts (n =3 rats of each group) from control and 1000 ppm in 4-week exposure were resolved by two-dimensional electrophoresis (2DE), Pro-Q Diamond Phosphoprotein Gel Staining and SYPRO gel staining for qualitation of phosphoproteins.Two-dimensional difference in gel electrophoresis (2D-DIGE) was conducted to quantitatively analysis of phosphoprotein (n =6 rats in each group) and matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) was used for protein identification.Selected protein was further confirmed by Phos-tag SDSPAGE.RESULTS 2D-DIGE revealed 28 protein spots in 1000 ppm group of 4-week 1-BP exposure with statistically significant difference (P <0.05) compared with the controls, including 21 up-regulated spots and 7 down-regulated spots, which were detected as phosphoproteins by Pro-Q Diamond gel staining combined with SYPRO staining.MALDI-TOF-TOF/MS successfully identified 19 up-regulated spots and 7 down-regulated spots.These identified proteins participate in the biological processes of metabolic, immune, response to stimulus, transport and cellular communication, and involved in pathways including Parkinsons disease, apoptosis signaling, FGF and EGF receptor signaling pathway, etc.Expression of phosphorylated 14-3-3 theta protein was further confirmed by Phos-tag SDS-PAGE.CONCLUSION These results help us understand the pro-apoptosis mechanism of 1-BP-induced hippocampal response and establish potential biomarkers for neurotoxicity induced by 1-BP in the CNS.