title: Estrogenic activity of UV filter mixtures.
abstract: UV-absorbing chemicals (UV filters) are widely used for protection against UV radiation in sunscreens and in a variety of cosmetic products and materials. Depending on the breadth and factor of UV protection, they are added as single compounds or as a combination thereof. Some UV filters have estrogenic activity, but their activity and interactions in mixtures are largely unknown. In this work, we analyzed 8 commonly used UV filters, which are pure or partial hERalpha agonists, for their estrogenic activity in equieffective mixtures in a recombinant yeast assay carrying the human estrogen receptor alpha (hERalpha). Mixtures of two, four and eight UV filters alone, or in combination with 17 beta estradiol (E2), were assessed at different effect levels and no-observed-effect-concentrations (NOEC). Predictions of the joint effects of these mixtures were calculated by employing the concentration addition (CA) and independent action (IA) model. Most binary mixtures comprising of pure hERalpha agonists showed a synergistic activity at all mixture combinations. Only in combination with benzophenone-1, antagonistic activity was observed at some effect levels. All mixtures of four or eight, pure or pure and partial hERalpha agonists, alone or including E2, showed synergistic activity at concentrations giving an increase of 10% of basal activity (BC10). This occurred even at concentrations that were at the NOEC level of each single compound. Hence, there were substantial mixture effects even though each UV filter was present at its NOEC level. These results show that significant interactions occur in UV filter mixtures, which is important for the hazard and risk assessments of these personal care products.
authors.affiliation: University of Applied Sciences Northwestern Switzerland FHNW, School of Life Sciences, Institute of Ecopreneurship, Gründenstrasse 40, CH-4132 Muttenz, Switzerland. petra.kunz@fhnw.ch <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: D001566:Benzocaine / Q000633:toxicity; D001577:Benzophenones / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000737:chemistry / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D018570:Risk Assessment; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012459:Salicylates / Q000633:toxicity; D013473:Sunscreening Agents / Q000737:chemistry / Q000633:toxicity*
chemical_list: D001577:Benzophenones; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011994:Recombinant Proteins; D012459:Salicylates; D013473:Sunscreening Agents; C035476:2,2',4,4'-tetrahydroxybenzophenone; D001566:Benzocaine; C039672:benzyl salicylate