title: Mixture Effects of Estrogenic Pesticides at the Human Estrogen Receptor α and β.
abstract: Consumers of fruits and vegetables are frequently exposed to small amounts of hormonally active pesticides, some of them sharing a common mode of action such as the activation of the human estrogen receptor α (hERα) or β (hERβ). Therefore, it is of particular importance to evaluate risks emanating from chemical mixtures, in which the individual pesticides are present at human-relevant concentrations, below their corresponding maximum residue levels. Binary and ternary iso-effective mixtures of estrogenic pesticides at effect concentrations eliciting a 1 or 10% effect in the presence or absence of 17β-estradiol were tested experimentally at the hERα in the yeast-based estrogen screen (YES) assay as well as in the human U2-OS cell-based ERα chemical-activated luciferase gene expression (ERα CALUX) assay and at the hERβ in the ERβ CALUX assay. The outcome was then compared to predictions calculated by means of concentration addition. In most cases, additive effects were observed with the tested combinations in all three test systems, an observation that supports the need to expand the risk assessment of pesticides and consider cumulative risk assessment. An additional testing of mixture effects at the hERβ showed that most test substances being active at the hERα could also elicit additive effects at the hERβ, but the hERβ was less sensitive. In conclusion, effects of the same ligands at the hERα and the hERβ could influence the estrogenic outcome under physiological conditions.
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany.
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, Salzdahlumerstr. 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, Salzdahlumerstr. 46/48, 38302, Wolfenbüttel, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Nguema 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: D001681:Biological Assay; D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D010575:Pesticides / Q000633:toxicity*; D012044:Regression Analysis; D018570:Risk Assessment; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010575:Pesticides
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