title: The ability of the YAS and AR CALUX assays to detect the additive effects of anti-androgenic fungicide mixtures.
abstract: Actual risk assessment only takes single pesticides into account, although about one third of the analyzed food samples in the European Union was contaminated with pesticide mixtures in 2013. A cumulative approach would group pesticides that share the same mechanism of toxicity. We evaluated the combination effects of low effect concentrations of binary and ternary mixtures of six anti-androgenic fungicides (procymidone, vinclozolin, tebuconazole, propiconazole, fenarimol and prochloraz) antagonizing the human androgen receptor (hAR) in the Yeast-based Androgen Screen assay (YAS) as well as in the AR Chemical-Activated LUciferase gene eXpression (AR CALUX) assay by means of concentration addition and nonlinear regression. The mixture effects were essentially additive when the fungicides were applied as iso-effective low inhibitory concentration combinations, independently from the used assay and as shown by the excellent agreement between experimental and predicted data. Both assays were successfully applied to evaluate the additive effects of fungicide mixtures at low concentrations. Since pesticide residues occur in/on foodstuffs in the EU at rather low concentrations and hormonally active environmental contaminants may concomitantly be present, more complex mixtures of anti-androgenic chemicals, not only pesticides, should be tested in the future when wanting to apply a target organ-based risk assessment approach.
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173 Hannover, Germany. Electronic address: bettina.seeger@tiho-hannover.de.
authors.forename: Bettina
authors.initials: B
authors.lastname: Seeger
authors.affiliation: Biostatistics Group, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany; Department of Computer Science, Ostfalia University of Applied Sciences, Salzdahlumer Str. 46/48, 38302 Wolfenbüttel, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Klawonn
authors.affiliation: Department of Computer Science, Ostfalia University of Applied Sciences, Salzdahlumer Str. 46/48, 38302 Wolfenbüttel, Germany.
authors.forename: Boris Nguema
authors.initials: BN
authors.lastname: Bekale
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173 Hannover, Germany.
authors.forename: Pablo
authors.initials: P
authors.lastname: Steinberg
mesh_terms: D000465:Algorithms; D000726:Androgen Antagonists / Q000633:toxicity*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D052244:Endocrine Disruptors / Q000633:toxicity*; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics*; D011944:Receptors, Androgen / Q000187:drug effects; D018570:Risk Assessment; D015003:Yeasts / Q000235:genetics*
chemical_list: D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D005659:Fungicides, Industrial; D011944:Receptors, Androgen; D008156:Luciferases
keywords: AR CALUX; Anti-androgen; Concentration addition; Fungicides; Sumulative risk assessment; YAS