ToxSci Advance Access originally published online on January 10, 2006
Toxicological Sciences 2006 90(2):349-361; doi:10.1093/toxsci/kfj082
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Comparison of In Vitro and In Vivo Estrogenic Activity of UV Filters in Fish
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* University of Applied Sciences Basel, Institute of Environmental Technology, St. Jakobs-Strasse 84, CH-4132 Muttenz, Switzerland; University of Zürich, Institute of Plant Biology, Limnology, Seestrasse 987, CH-8802 Kilchberg, Switzerland; Springborn Smithers Laboratories (Europe) AG, Seestrasse 21, CH-9326 Horn, Switzerland; and Swiss Federal Institute of Technology (ETH), Department of Environmental Sciences, CH-8092 Zürich, Switzerland
Received July 28, 2005; accepted December 8, 2005
In this work, we evaluate whether in vitro systems are good predictors for in vivo estrogenic activity in fish. We focus on UV filters being used in sunscreens and in UV stabilization of materials. First, we determined the estrogenic activity of 23 UV filters and one UV filter metabolite employing a recombinant yeast carrying the estrogen receptor of rainbow trout (rtER
) and made comparisons with yeast carrying the human hER for receptor specificity. Benzophenone-1 (BP1), benzophenone-2 (BP2), 4,4-dihydroxybenzophenone, 4-hydroxybenzophenone, 2,4,4-trihydroxy-benzophenone, and phenylsalicylate showed full dose–response curves with maximal responses of 81–115%, whereas 3-benzylidene camphor (3BC), octylsalicylate, benzylsalicylate, benzophenone-3, and benzophenone-4 displayed lower maximal responses of 15–74%. Whereas the activity of 17ß-estradiol was lower in the rtER than the hER assay, the activities of UV filters were similar or relatively higher in rtER, indicating different relative binding activities of both ER. Subsequently, we analyzed whether the in vitro estrogenicity of eight UV filters is also displayed in vivo in fathead minnows by the induction potential of vitellogenin after 14 days of aqueous exposure. Of the three active compounds in vivo, 3BC induced vitellogenin at lower concentrations (435 µg/l) than BP1 (4919 µg/l) and BP2 (8783 µg/l). The study shows, for the first time, estrogenic activities of UV filters in fish both in vitro and in vivo. Thus we propose that receptor-based assays should be used for in vitro screening prior to in vivo testing, leading to environmental risk assessments based on combined, complementary, and appropriate species-related assays for hormonal activity.
Key Words: UV filters; Pimephales promelas; vitellogenin; in vitro-in vivo comparison; fish estrogen receptor ; human estrogen receptor .
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  P. Y. Kunz, T. Gries, and K. Fent The Ultraviolet Filter 3-Benzylidene Camphor Adversely Affects Reproduction in Fathead Minnow (Pimephales promelas) Toxicol. Sci., October 1, 2006; 93(2): 311 - 321. [Abstract] [Full Text] [PDF]
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