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Many toxicological test methods, including assays of cell viability and function, require an evaluation of concentration-response data. This often involves curve fitting, and the resulting mathematical functions are then used to determine the concentration at which a certain deviation from the control value occurs (e.g. a decrease of cell viability by 15%). Such a threshold is called the benchmark response (BMR). For a toxicological test, it is often of interest to determine the concentration of test compound at which a pre-defined BMR of e.g. 10, 25 or 50% is reached. The concentration at which the modelled curve crosses the BMR is called the benchmark concentration (BMC). We present a user-friendly, web-based tool (BMCeasy), designed for operators without programming skills and profound statistical background, to determine BMCs and their confidence intervals. BMCeasy allows simultaneous analysis of viability plus a functional test endpoint, and it yields absolute BMCs with confidence intervals for any BMR. Besides an explanation of the algorithm underlying BMCeasy, this article also gives multiple examples of data outputs. BMCeasy was used within the EU-ToxRisk project for preparing data packages that were submitted to regulatory authorities, demonstrating the real-life applicability of the tool. This work was supported by the BMBF, EFSA, the DK-EPA, and the DFG (Konstanz Research School of Chemical Biology; KoRS-CB). It has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements No. 681002 (EU-ToxRisk) and No. 825759 (ENDpoiNTs). We are grateful to collaborators R. von Hellfeld and T. Braunbeck (University of Heidelberg), and H. Vrieling and J. Boei (Leiden University Medical Center) of the EU-ToxRisk con-sortium for providing the experimental data. We are indebted to S. Förster for triggering this work and to other colleagues for in-sightful discussions.

WOS: 000378646700040, PubMed ID: 27513427, Background/aim: This study investigates whether 1-(2-trifluoromethylphenyl)-imidazole (TRIM), originally proposed as a nitric oxide synthase inhibitor and also suggested to be an inhibitor of store-operated calcium entry in mouse anococcygeal muscle, inhibits receptor-independent and -dependent responses in rat thoracic aorta. Materials and methods: Cyclopiazonic acid-and serotonin-induced vascular responses were investigated in aortic segments isolated from male Sprague Dawley rats using isolated tissue experiments. Changes in intracellular calcium levels were also monitored via front surface fluorescence measurements in fura-2-loaded embryonic rat vascular smooth muscle cell line A7r5. Results: TRIM inhibited serotonin-mediated vascular contractions without affecting cyclopiazonic acid-induced responses. In addition, TRIM caused a nonlinear rightward shift in the serotonin concentration-response curve, possibly via serotonin receptor modulation. Conclusion: TRIM may have an impact on investigation of tissue-specific receptor-independent and -dependent vascular responses. It may also be used as a lead compound in the development of selective serotonin receptor modulators., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [104S568]; Ege UniversityEge University [BAP-02ECZ006], This work was supported in part by the Scientific and Technological Research Council of Turkey (TUBITAK, 104S568, to MT) and Ege University (BAP-02ECZ006, to MT).