TY - JOUR A1 - Guth, Sabine A1 - Hüser, Stephanie A1 - Roth, Angelika A1 - Degen, Gisela A1 - Diel, Patrick A1 - Edlund, Karolina A1 - Eisenbrand, Gerhard A1 - Engel, Karl-Heinz A1 - Epe, Bernd A1 - Grune, Tilman A1 - Heinz, Volker A1 - Henle, Thomas A1 - Humpf, Hans-Ulrich A1 - Jäger, Henry A1 - Joost, Hans-Georg A1 - Kulling, Sabine E. A1 - Lampen, Alfonso A1 - Mally, Angela A1 - Marchan, Rosemarie A1 - Marko, Doris A1 - Mühle, Eva A1 - Nitsche, Michael A. A1 - Röhrdanz, Elke A1 - Stadler, Richard A1 - van Thriel, Christoph A1 - Vieths, Stefan A1 - Vogel, Rudi F. A1 - Wascher, Edmund A1 - Watzl, Carsten A1 - Nöthlings, Ute A1 - Hengstler, Jan G. T1 - Contribution to the ongoing discussion on fluoride toxicity JF - Archives of Toxicology N2 - Since the addition of fluoride to drinking water in the 1940s, there have been frequent and sometimes heated discussions regarding its benefits and risks. In a recently published review, we addressed the question if current exposure levels in Europe represent a risk to human health. This review was discussed in an editorial asking why we did not calculate benchmark doses (BMD) of fluoride neurotoxicity for humans. Here, we address the question, why it is problematic to calculate BMDs based on the currently available data. Briefly, the conclusions of the available studies are not homogeneous, reporting negative as well as positive results; moreover, the positive studies lack control of confounding factors such as the influence of well-known neurotoxicants. We also discuss the limitations of several further epidemiological studies that did not meet the inclusion criteria of our review. Finally, it is important to not only focus on epidemiological studies. Rather, risk analysis should consider all available data, including epidemiological, animal, as well as in vitro studies. Despite remaining uncertainties, the totality of evidence does not support the notion that fluoride should be considered a human developmental neurotoxicant at current exposure levels in European countries. KW - pharmacology/toxicology KW - occupational medicine/industrial medicine KW - environmental health KW - biomedicine, general Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307161 SN - 0340-5761 SN - 1432-0738 VL - 95 IS - 7 ER - TY - JOUR A1 - Dekant, Raphael A1 - Langer, Michael A1 - Lupp, Maria A1 - Adaku Chilaka, Cynthia A1 - Mally, Angela T1 - In vitro and in vivo analysis of ochratoxin A-derived glucuronides and mercapturic acids as biomarkers of exposure JF - Toxins N2 - Ochratoxin A (OTA) is a widespread food contaminant, with exposure estimated to range from 0.64 to 17.79 ng/kg body weight (bw) for average consumers and from 2.40 to 51.69 ng/kg bw per day for high consumers. Current exposure estimates are, however, associated with considerable uncertainty. While biomarker-based approaches may contribute to improved exposure assessment, there is yet insufficient data on urinary metabolites of OTA and their relation to external dose to allow reliable estimates of daily intake. This study was designed to assess potential species differences in phase II biotransformation in vitro and to establish a correlation between urinary OTA-derived glucuronides and mercapturic acids and external exposure in rats in vivo. In vitro analyses of OTA metabolism using the liver S9 of rats, humans, rabbits and minipigs confirmed formation of an OTA glucuronide but provided no evidence for the formation of OTA-derived mercapturic acids to support their use as biomarkers. Similarly, OTA-derived mercapturic acids were not detected in urine of rats repeatedly dosed with OTA, while indirect analysis using enzymatic hydrolysis of the urine samples prior to LC–MS/MS established a linear relationship between urinary glucuronide excretion and OTA exposure. These results support OTA-derived glucuronides but not mercapturic acids as metabolites suitable for biomonitoring. KW - ochratoxin A KW - biomarker of exposure KW - glucuronide KW - mercapturic acid KW - mycotoxin Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245146 SN - 2072-6651 VL - 13 IS - 8 ER - TY - JOUR A1 - Bauer, Benedikt A1 - Mally, Angela A1 - Liedtke, Daniel T1 - Zebrafish embryos and larvae as alternative animal models for toxicity testing JF - International Journal of Molecular Sciences N2 - Prerequisite to any biological laboratory assay employing living animals is consideration about its necessity, feasibility, ethics and the potential harm caused during an experiment. The imperative of these thoughts has led to the formulation of the 3R-principle, which today is a pivotal scientific standard of animal experimentation worldwide. The rising amount of laboratory investigations utilizing living animals throughout the last decades, either for regulatory concerns or for basic science, demands the development of alternative methods in accordance with 3R to help reduce experiments in mammals. This demand has resulted in investigation of additional vertebrate species displaying favourable biological properties. One prominent species among these is the zebrafish (Danio rerio), as these small laboratory ray-finned fish are well established in science today and feature outstanding biological characteristics. In this review, we highlight the advantages and general prerequisites of zebrafish embryos and larvae before free-feeding stages for toxicological testing, with a particular focus on cardio-, neuro, hepato- and nephrotoxicity. Furthermore, we discuss toxicokinetics, current advances in utilizing zebrafish for organ toxicity testing and highlight how advanced laboratory methods (such as automation, advanced imaging and genetic techniques) can refine future toxicological studies in this species. KW - danio rerio KW - alternative methods KW - organ toxicity KW - 3R KW - transgenic animals Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284225 SN - 1422-0067 VL - 22 IS - 24 ER - TY - JOUR A1 - Barile, Frank A. A1 - Berry, Colin A1 - Blaauboer, Bas A1 - Boobis, Alan A1 - Bolt, Herrmann M. A1 - Borgert, Christopher A1 - Dekant, Wolfgang A1 - Dietrich, Daniel A1 - Domingo, Jose L. A1 - Galli, Corrado L. A1 - Gori, Gio Batta A1 - Greim, Helmut A1 - Hengstler, Jan G. A1 - Heslop-Harrison, Pat A1 - Kacew, Sam A1 - Marquardt, Hans A1 - Mally, Angela A1 - Pelkonen, Olavi A1 - Savolainen, Kai A1 - Testai, Emanuela A1 - Tsatsakis, Aristides A1 - Vermeulen, Nico P. T1 - The EU chemicals strategy for sustainability: in support of the BfR position JF - Archives of Toxicology N2 - The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved. A continuous process of improvement in consumer protection is clearly desirable but any initiative directed towards this objective must be based on scientific knowledge. It must not confound risk with other factors in determining policy. This conclusion is fully supported in the present Commentary including the request to improve both, data collection and the time-consuming and bureaucratic procedures that delay the publication of regulations. KW - pharmacology/toxicology KW - occupational medicine/industrial medicine KW - environmental health KW - biomedicine, general Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307154 SN - 0340-5761 SN - 1432-0738 VL - 95 IS - 9 ER -