title: Estrogenic activity of UV filters determined by an in vitro reporter gene assay and an in vivo transgenic zebrafish assay.
abstract: In the past decade the list of chemicals in the environment that are able to mimic the natural hormone estrogen, thereby disrupting endocrine function, has grown rapidly. These chemicals are able to bind to estrogen receptors (ERs) and influence estrogen signalling pathways, although several of them have structures that differ substantially from the endogenous hormone 17beta-estradiol. In this study, six extensively used ultraviolet (UV) filters were assessed for transcriptional activation of estrogen receptors. Because of their high lipophilicity, these UV filters tend to bioaccumulate in the environment. They have been found in surface waters, fish, and in human milk fat. Using a sensitive in vitro reporter gene assay, we found that all six compounds induce estrogenic activity towards ERalpha, while four out of six compounds induced transcriptional activity of ERbeta. Zebrafish, in which an estrogen responsive luciferase reporter gene has been stably introduced, were used for in vivo testing. In this transgenic zebrafish assay none of the compounds showed estrogenic activity. Our findings suggest that one should be aware of over-interpretation when predicting in vivo effects from weak in vitro data. However, it can not be ruled out that these UV filters have long-term effects in the environment.
authors.affiliation: Institute for Risk Assessment Sciences, PO Box 80.176, 3508 TD Utrecht, The Netherlands. r.schreurs@iras.uu.nl
authors.forename: Richard
authors.initials: R
authors.lastname: Schreurs
authors.forename: Peter
authors.initials: P
authors.lastname: Lanser
authors.forename: Willem
authors.initials: W
authors.lastname: Seinen
authors.forename: Bart
authors.initials: B
authors.lastname: van der Burg
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001681:Biological Assay; D002460:Cell Line; D004958:Estradiol / Q000633:toxicity; D045166:Estradiol Congeners / Q000633:toxicity*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects*; D013473:Sunscreening Agents / Q000633:toxicity*; D015533:Transcriptional Activation; D014466:Ultraviolet Rays; D015027:Zebrafish
chemical_list: D045166:Estradiol Congeners; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D013473:Sunscreening Agents; D004958:Estradiol; D008156:Luciferases