title: Multiple hormonal activities of UV filters and comparison of in vivo and in vitro estrogenic activity of ethyl-4-aminobenzoate in fish.
abstract: UV filters have been detected in surface water, wastewater and fish, and some of them are estrogenic in fish. At present, little is known about their additional hormonal activities in different hormonal receptor systems despite their increasing use and environmental persistence. Besides estrogenic activity, UV filters may have additional activities, both agonistic and antagonistic in aquatic organisms. In our study, we investigate a series of UV filters for multiple hormonal activities in vitro in human receptor systems and evaluate the predictive value of these findings for the activity in fish in vitro and in vivo. First we systematically analysed the estrogenic, antiestrogenic, androgenic, and antiandrogenic activity of 18 UV filters and one metabolite in vitro at non-cytotoxic concentrations with recombinant yeast systems carrying either a human estrogen (hERalpha) or androgen receptor (hAR). All 19 compounds elicited hormonal activities, surprisingly most of them multiple activities. We found 10 UV-filters having agonistic effects towards the hERalpha. Surprisingly, we identified for the first time six UV filters with androgenic activities and many of them having pronounced antiestrogenic and antiandrogenic activities. As much as 17 compounds inhibited 4,5-dihydrotestosterone activity in the hAR assay, while 14 compounds inhibited estradiol activity in the hERalpha assay, indicating antiandrogenic and antiestrogenic activity, respectively. In particular, the antiandrogenic activities of phenyl- and benzyl salicylate, benzophenone-1 and -2, and of 4-hydroxybenzophenone were higher than that of flutamide, a known hAR antagonist. In a second series of experiments, we investigated the predictive power of the hERalpha assay for aquatic organisms by further investigating the estrogenic UV filter ethyl 4-aminobenzoate (Et-PABA) in vitro and in vivo in fish. Et-PABA showed estrogenic activity in a recombinant yeast system carrying the rainbow trout estrogen receptor (rtERalpha) with higher activity than in the hERalpha assay. In addition, Et-PABA induced vitellogenin after 14 days of exposure in juvenile fathead minnows at 4394mug/L. Our study shows estrogenic activity of this UV filter in fish both in vitro and in vivo. In conjunction with in vitro human receptor-based systems our results give a more detailed picture about distinct hormonal activities of UV filters occurring in aquatic systems. We conclude that receptor-based assays are important for in vitro assessment of UV-filters prior to or concurrently with in vivo assays, which ultimately provide data for the environmental risk assessment of these important personal care products.
authors.affiliation: University of Applied Sciences Northwestern Switzerland, FHNW, School of Life Sciences, Institute of Ecopreneurship, St. Jakobs-Strasse 84, CH-4132 Muttenz, Switzerland. petra.kunz@fhnw.ch
authors.forename: Petra Y
authors.initials: PY
authors.lastname: Kunz
authors.forename: Karl
authors.initials: K
authors.lastname: Fent
mesh_terms: D000726:Androgen Antagonists / Q000032:analysis / Q000633:toxicity; D000728:Androgens / Q000032:analysis / Q000633:toxicity; D000818:Animals; D001566:Benzocaine / Q000633:toxicity*; D003530:Cyprinidae / Q000502:physiology*; D020847:Estrogen Receptor Modulators / Q000032:analysis / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000096:biosynthesis; D004967:Estrogens / Q000032:analysis / Q000633:toxicity; D017686:Oncorhynchus mykiss; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D013473:Sunscreening Agents / Q000633:toxicity*; D014819:Vitellogenins / Q000032:analysis; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D013473:Sunscreening Agents; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D001566:Benzocaine