title: Molecular modelling of phthalates - PPARs interactions.
abstract: Di(2-ethylhexyl) phthalate (DEHP) is the most widely plasticizer for polyvinyl chloride (PVC) that is used in plastic tubes, in medical and paramedical devices as well as in food storage packaging. The toxicological profile of DEHP has been evaluated in a number of experimental animal models and has been extensively documented. Its toxicity is in part linked to the activation of the peroxisome proliferator-activated receptor alpha (PPAR(alpha)). As a response, an intensive research for a new, biologically inert plasticizer has been initiated. Among the alternative studied, tri(2-ethylhexyl) trimellitate (TEHTM) or trioctyl trimellitate (TOTM) has attracted increasing interest. However, very little information is available on their biological effects. We proceeded to dock TOTM, DEHP and its metabolites in order to identify compounds that are likely to interact with PPAR(alpha) and PPAR(gamma) binding sites. The results obtained hint that TOTM is not able to bind to PPARs and should therefore be safer than DEHP.
authors.affiliation: Laboratoire de Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Lille Cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kambia
authors.forename: Nicolas
authors.initials: N
authors.lastname: Renault
authors.forename: Sebastien
authors.initials: S
authors.lastname: Dilly
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Thierry
authors.initials: T
authors.lastname: Dine
authors.forename: Bernard
authors.initials: B
authors.lastname: Gressier
authors.forename: Michel
authors.initials: M
authors.lastname: Luyckx
authors.forename: Claude
authors.initials: C
authors.lastname: Brunet
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavatte
mesh_terms: D001565:Benzoates / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008958:Models, Molecular; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010795:Phthalic Acids / Q000737:chemistry* / Q000633:toxicity; D010968:Plasticizers / Q000737:chemistry / Q000633:toxicity; D011485:Protein Binding
chemical_list: D001565:Benzoates; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D010795:Phthalic Acids; D010968:Plasticizers; C036101:tri-(2-ethylhexyl)trimellitate; C034367:trioctyl trimellitate