title: Plastic components affect the activation of the aryl hydrocarbon and the androgen receptor.
abstract: Phenols and plasticizers are widely used in the plastic industry, in food packaging and to impart softness and flexibility to normally rigid plastic medical devices and children's toys. The effects on the aryl hydrocarbon receptor (AhR) and the androgen receptor (AR) were assessed using luciferase reporter gene assays of the following compounds: bisphenol A (BPA), 4-n-nonylphenol (nNP), 4-tert-octylphenol (tOP), bis(2-ethylhexyl) phthalate (DEHP), di-isononyl phthalate (DINP), diisodecyl phthalate (DIDP), di-n-octyl phthalate (DNOP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), 4-chloro-3-methylphenol (CMP), 2-phenylphenol (2-PP), 2,4-dichlorophenol (DCP), resorcinol and bis(2-ethylhexyl) adipate (DEHA). Furthermore, a mixture of selected compounds was tested at the no-observed-effect concentration (NOEC), the low-observed-effect concentration (LOEC) and the half-maximum-effect/inhibitory concentration (EC50/IC50) of the single chemicals. Both receptors were affected by BPA, nNP, BBP, CMP, DCP and resorcinol whereas DEHP, DIDP and DBP affected only the AhR and tOP and 2-PP antagonised the AR activity. The mixture was composed of 6 compounds, of which one compound weakly induced the AhR but all compounds antagonized the AR activation. Using the concentration addition principle additive effects were observed at the NOEC, LOEC and EC50/IC50 for both receptors. Our in vitro data suggest that the effect of a mixture depends on the concentration, character, potency and composition of the single mixture compounds and that also the combined effects of the compounds should be taken into consideration for risk assessment of human health.
authors.affiliation: Unit of Cellular and Molecular Toxicology (CMT), Institute of Public Health, University of Aarhus, Denmark.
authors.forename: Tanja
authors.initials: T
authors.lastname: Krüger
authors.forename: Manhai
authors.initials: M
authors.lastname: Long
authors.forename: Eva C
authors.initials: EC
authors.lastname: Bonefeld-Jørgensen
mesh_terms: D000818:Animals; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015870:Gene Expression; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D010968:Plasticizers / Q000633:toxicity*; D010969:Plastics / Q000633:toxicity*; D011944:Receptors, Androgen / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D014162:Transfection
chemical_list: D004338:Drug Combinations; D010968:Plasticizers; D010969:Plastics; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D008156:Luciferases