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3071020 
Journal Article 
Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin 
Ma, P; Liu, X; Wu, J; Yan, B; Zhang, Y; Lu, Y; Wu, Y; Liu, C; Guo, J; Nanberg, E; Bornehag, CG; Yang, X 
2015 
1 
Scientific Reports
EISSN: 2045-2322 
NATURE PUBLISHING GROUP 
LONDON 
5 
1 
14676 
English 
26424168 
WOS:000362087500001 
Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products. In vivo studies on the neurotoxicity of DINP are however, limited. This work aims to investigate whether DINP causes neurobehavioral changes in mice and to provide useful advice on preventing the occurrence of these adverse effects. Behavioral analysis showed that oral administration of 20 or 200 mg/kg/day DINP led to mouse cognitive deficits and anxiety. Brain histopathological observations, immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8-hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and assessment of inflammation (tumor necrosis factor alpha [TNF-а] and interleukin-1 beta [IL-1β]) of mouse brains showed that there were histopathological alterations in the brain and increased levels of oxidative stress, and inflammation for these same groups. However, some of these effects were blocked by administration of melatonin (50 mg/kg/day). Down-regulation of oxidative stress was proposed to explain the neuroprotective effects of melatonin. The data suggests that DINP could cause cognitive deficits and anxiety in mice, and that melatonin could be used to avoid these adverse effects. 
Glial Fibrillary Acidic Protein; Neuroprotective Agents; Phthalic Acids; glial fibrillary astrocytic protein, mouse; diisononyl phthalate; 4010KIX4CK; Casp3 protein, mouse 
IRIS
• Dibutyl Phthalate (DBP)
     Excluded: No Primary Data on Health Effects
          Not chemical specific
          Use in sample prep or assay
     Litsearch June 2015 - Jan 2016
          Pubmed
• Diisononyl Phthalate (DINP)
     Literature Search
          LitSearch June 2015 - Jan 2016 Update
               Pubmed
               Toxline
               Web of Science