Phthalates: Toxicogenomics and health effects

Phthalates are a group of similar phthalic acid esters and are widely used as plasticizers to soften and increase the flexibility in polyvinyl chloride plastics. Since phthalates are not covalently bound to the plastic matrix, they can easily leach into the surrounding environment. There is sufficient evidence in rodents that phthalate exposure causes developmental and reproductive toxicities. We have recently analyzed the interactions between 16 phthalates and genes/proteins in the Comparative Toxicogenomic Database (CTD; http://ctd.mdibl.org), and a total of 445 interactions between the five most frequently curated phthalates (DEHP/MEHP and DBP/BBP/MBP) and 249 unique genes/proteins were found. The GeneOntology, pathways and networks of these 249 unique genes/proteins were fully analyzed using the computer software programs from MetaCore analytical Suite, Ingenuity Pathways Analysis and Pathway Studio. The pathways and networks of the top 34 genes/proteins were found to be very similar to those of the 249 unique genes/proteins. Thus, the top 34 genes/proteins may serve as molecular biomarkers to assay toxicities of phthalate exposure. The top three phthalate toxicity categories were found to be cardiotoxicity, hepatotoxicity and nephrotoxicity, and the top 20 diseases included cardiovascular, liver, urologic, endocrine and genital diseases. Recently, rat neonatal cardiomyocytes treated with clinically relevant DEHP concentrations were independently shown to exhibit global changes in expression of genes associated with cell electrical activity, calcium handling, adhesion and microtubular transport, and these changes may explain the arrythmogenic effects of phthalates on these cardiomyocytes.