Title: Determination of the endocrine disrupting potency of hydroxylated PCBs and Flame Retardents with in vitro bioassays

Auteur(s): Legler J ; Cenijn P ; Malmberg T ; Bergman A ; Brouwer A ;  ; 

Year: 2002

Journal: Organohalogen Compounds

Subject(s): bioassay ; PCB ; PCBs ; blood plasma ; food ; environment ; brominated flame retardant ; metabolite ; PBDE ; endocrine ; Reporter gene ; Reporter gene assay ; estrogen ; Luciferase ;  ; 

Summary: Organohalogenated compounds (OHS) are one of the most prominent and persistent classes of environmental pollutants that has been associated with adverse health effects in humans and wildlife. Recent evidence has shown that PCB levels in human blood plasma have not changed between the beginning of the 1990s and 1999, suggesting that the decline in PCBs in food and the environment may have leveled off. There are also several new classes of OHS that are still in use as high production volume chemicals in Europe and the rest of the world, such as the brominated flame retardants, polybrominated bisphenols and -diphenylethers (BDEs). These compounds have recently been shown to incline in the environment. Moreover, they show a striking resemblance in structure, environmental fate and toxicological effects with 'old' OHS classes. Recent studies have identified a large number of hydroxylated metabolites of these classes of organohalogens in human blood, which apparently are formed in considerable amounts in vivo. Within the E.U. project 'Comparison of Exposure-Effect Pathways to Improve the Assessment of Human Health Risks of Complex Environmental Mixtures of Organohalogens' (COMPARE), comparative pathways for early life-stage exposure and long-term effects of hydroxylated PCBs and PBDEs are under investigation. The in vitro endocrine disrupting potency of a number of hydroxylated ORS was studied using CALUX® reporter gene assays based on cell lines stably transfected with dioxin-receptor (DR) and estrogen receptor (ER)-mediated luciferase gene constructs. In addition, the potency ofthe compounds to interfere with thyroid hormone (T4) transport via binding to the transport protein transthyretin (TTR) was measured with an in vitro T4-TTR competitive binding assay.