TY  - JOUR
A1  - Duydu, Yalcin
A1  - Basaran, Nursen
A1  - Aydin, Sevtap
A1  - Ustundag, Aylin
A1  - Yalcin, Can Özgür
A1  - Anlar, Hatice Gul
A1  - Bacanli, Merve
A1  - Aydos, Kaan
A1  - Atabekoglu, Cem Somer
A1  - Golka, Klaus
A1  - Ickstadt, Katja
A1  - Schwerdtle, Tanja
A1  - Werner, Matthias
A1  - Meyer, Sören
A1  - Bolt, Hermann M.
T1  - Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions
JF  - Archives of toxicology : official journal of EUROTOX
N2  - Boric acid and sodium borates are currently classified in the EU-CLP regulation as "toxic to reproduction" under "Category 1B", with hazard statement of H360FD. However, so far field studies on male reproduction in China and in Turkey could not confirm such boron-associated toxic effects. As validation by another independent study is still required, the present study has investigated possible boron-associated effects on male reproduction in workers (n = 212) under different boron exposure conditions. The mean daily boron exposure (DBE) and blood boron concentration of workers in the extreme exposure group (n = 98) were 47.17 +/- 17.47 (7.95-106.8) mg B/day and 570.6 +/- 160.1 (402.6-1100) ng B/g blood, respectively. Nevertheless, boron-associated adverse effects on semen parameters, as well as on FSH, LH and total testosterone levels were not seen, even within the extreme exposure group. With this study, a total body of evidence has accumulated that allows to conclude that male reproductive effects are not relevant to humans, under any feasible and realistic conditions of exposure to inorganic boron compounds.
KW  - Boron exposure
KW  - Boric acid
KW  - Reproductive toxicity
KW  - FSH
KW  - LH
KW  - Testosterone
KW  - Semen parameters
Y1  - 2018
U6  - https://doi.org/10.1007/s00204-018-2296-7
SN  - 0340-5761
SN  - 1432-0738
VL  - 92
IS  - 10
SP  - 3051
EP  - 3059
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Witt, Barbara
A1  - Ebert, Franziska
A1  - Meyer, Sören
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons
JF  - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology
N2  - Scope: In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Methods and results: Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA(V)) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA(V) were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. Conclusion: These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment.
KW  - Arsenic-containing fatty acids
KW  - Arsenic-containing hydrocarbons
KW  - Arsenite
KW  - Arsenolipids
KW  - Neurodevelopmental toxicity
Y1  - 2017
U6  - https://doi.org/10.1002/mnfr.201700199
SN  - 1613-4125
SN  - 1613-4133
VL  - 61
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Witt, Barbara
A1  - Meyer, Sören
A1  - Ebert, Franziska
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons
JF  - Archives of toxicology : official journal of EUROTOX
N2  - Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly’s brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized.
KW  - Arsenolipids
KW  - Neurons
KW  - Cytotoxicity
KW  - Neurotoxicity
KW  - Arsenic-containing hydrocarbons
KW  - Arsenic-containing fatty acids
Y1  - 2017
U6  - https://doi.org/10.1007/s00204-017-1933-x
SN  - 0340-5761
SN  - 1432-0738
VL  - 91
SP  - 3121
EP  - 3134
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Müller, Sandra Marie
A1  - Ebert, Franziska
A1  - Raber, Georg
A1  - Meyer, Sören
A1  - Bornhorst, Julia
A1  - Hüwel, Stephan
A1  - Galla, Hans-Joachim
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Effects of arsenolipids on in vitro blood-brain barrier model
JF  - Archives of toxicology : official journal of EUROTOX
N2  - Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids (AsLs) occurring in fish and edible algae, possess a substantial neurotoxic potential in fully differentiated human brain cells. Previous in vivo studies indicating that AsHCs cross the blood–brain barrier of the fruit fly Drosophila melanogaster raised the question whether AsLs could also cross the vertebrate blood–brain barrier (BBB). In the present study, we investigated the impact of several representatives of AsLs (AsHC 332, AsHC 360, AsHC 444, and two arsenic-containing fatty acids, AsFA 362 and AsFA 388) as well as of their metabolites (thio/oxo-dimethylpropionic acid, dimethylarsinic acid) on porcine brain capillary endothelial cells (PBCECs, in vitro model for the blood–brain barrier). AsHCs exerted the strongest cytotoxic effects of all investigated arsenicals as they were up to fivefold more potent than the toxic reference species arsenite (iAsIII). In our in vitro BBB-model, we observed a slight transfer of AsHC 332 across the BBB after 6 h at concentrations that do not affect the barrier integrity. Furthermore, incubation with AsHCs for 72 h led to a disruption of the barrier at sub-cytotoxic concentrations. The subsequent immunocytochemical staining of three tight junction proteins revealed a significant impact on the cell membrane. Because AsHCs enhance the permeability of the in vitro blood–brain barrier, a similar behavior in an in vivo system cannot be excluded. Consequently, AsHCs might facilitate the transfer of accompanying foodborne toxicants into the brain.
KW  - Arsenolipids
KW  - Arsenic-containing hydrocarbons
KW  - Arsenic-containing fatty acids
KW  - In vitro blood-brain barrier model
Y1  - 2017
SN  - 0340-5761
SN  - 1432-0738
VL  - 92
IS  - 2
SP  - 823
EP  - 832
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Matissek, M.
A1  - Müller, Sandra Marie
A1  - Taleshi, M. S.
A1  - Ebert, Franziska
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - In vitro toxicological characterisation of three arsenic-containing hydrocarbons
JF  - Metallomics
N2  - Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.
KW  - cod-liver
KW  - human-cells
KW  - arsenolipids present
KW  - excision-repair
KW  - fatty-acids
KW  - marine oils
KW  - RP-HPLC
KW  - metabolites
KW  - identification
KW  - trivalent
Y1  - 2014
U6  - https://doi.org/10.1039/c4mt00061g
SN  - 1756-591X
SN  - 1756-5901
VL  - 2014
IS  - 6
SP  - 1023
EP  - 1033
ER  - 
TY  - GEN
A1  - Meyer, Sören
A1  - Matissek, M.
A1  - Müller, Sandra Marie
A1  - Taleshi, M. S.
A1  - Ebert, Franziska
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - In vitro toxicological characterisation of three arsenic-containing hydrocarbons
N2  - Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 170 
KW  - cod-liver
KW  - human-cells
KW  - arsenolipids present
KW  - excision-repair
KW  - fatty-acids
KW  - marine oils
KW  - RP-HPLC
KW  - metabolites
KW  - identification
KW  - trivalent
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-74201
SP  - 1023
EP  - 1033
ER  - 
TY  - JOUR
A1  - Duydu, Yalcin
A1  - Basaran, Nursen
A1  - Ustundag, Aylin
A1  - Aydin, Sevtap
A1  - Yalcin, Can Ozgur
A1  - Anlar, Hatice Gul
A1  - Bacanli, Merve
A1  - Aydos, Kaan
A1  - Atabekoglu, Cem Somer
A1  - Golka, Klaus
A1  - Ickstadt, Katja
A1  - Schwerdtle, Tanja
A1  - Werner, Matthias
A1  - Meyer, Sören
A1  - Bolt, Hermann M.
T1  - Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed females in Turkey
JF  - Archives of toxicology : official journal of EUROTOX
N2  - Boric acid and sodium borates are currently classified as being toxic to reproduction under "Category 1B" with the hazard statement of "H360 FD" in the European CLP regulation. This has prompted studies on boron-mediated reprotoxic effects in male workers in boron mining areas and boric acid production plants. By contrast, studies on boron-mediated developmental effects in females are scarce. The present study was designed to fill this gap. Hundred and ninety nine females residing in Bandirma and Bigadic participated in this study investigating pregnancy outcomes. The participants constituted a study group covering blood boron from low (< 100 ng B/g blood, n = 143) to high (> 150 ng B/g blood, n = 27) concentrations. The mean blood boron concentration and the mean estimated daily boron exposure of the high exposure group was 274.58 (151.81-975.66) ng B/g blood and 24.67 (10.47-57.86) mg B/day, respectively. In spite of the high level of daily boron exposure, boron-mediated adverse effects on induced abortion, spontaneous abortion (miscarriage), stillbirth, infant death, neonatal death, early neonatal death, preterm birth, congenital anomalies, sex ratio and birth weight of newborns were not observed.
KW  - Boric acid
KW  - Boron exposure
KW  - Biological monitoring
KW  - Developmental toxicity
KW  - Pregnancy outcomes
Y1  - 2018
U6  - https://doi.org/10.1007/s00204-018-2238-4
SN  - 0340-5761
SN  - 1432-0738
VL  - 92
IS  - 8
SP  - 2475
EP  - 2485
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Basaran, Nursen
A1  - Duydu, Yalcin
A1  - Ustundag, Aylin
A1  - Taner, Gokce
A1  - Aydin, Sevtap
A1  - Anlar, Hatice Gul
A1  - Yalcin, Can Özgür
A1  - Bacanli, Merve
A1  - Aydos, Kaan
A1  - Atabekoglu, Cem Somer
A1  - Golka, Klaus
A1  - Ickstadt, Katja
A1  - Schwerdtle, Tanja
A1  - Werner, Matthias
A1  - Meyer, Sören
A1  - Bolt, Hermann M.
T1  - Evaluation of the DNA damage in lymphocytes, sperm and buccal cells of workers under environmental and occupational boron exposure conditions
JF  - Mutation Research/Genetic Toxicology and Environmental Mutagenesis
N2  - Industrial production and use of boron compounds have increased during the last decades, especially for the manufacture of borosilicate glass, fiberglass, metal alloys and flame retardants. This study was conducted in two districts of Balikesir; Bandirma and Bigadic, which geographically belong to the Marmara Region of Turkey. Bandirma is the production and exportation zone for the produced boric acid and some borates and Bigadic has the largest B deposits in Turkey. 102 male workers who were occupationally exposed to boron from Bandirma and 110 workers who were occupationally and environmentally exposed to boron from Bigadic participated to our study. In this study the DNA damage in the sperm, blood and buccal cells of 212 males was evaluated by comet and micronucleus assays. No significant increase in the DNA damage in blood, sperm and buccal cells was observed in the residents exposed to boron both occupationally and environmentally (p = 0.861) for Comet test in the sperm samples, p = 0.116 for Comet test in the lymphocyte samples, p = 0.042 for micronucleus (MN) test, p = 0.955 for binucleated cells (BN), p = 1.486 for condensed chromatin (CC), p = 0.455 for karyorrhectic cells (KHC), p = 0.541 for karyolitic cells (KLY), p = 1.057 for pyknotic cells (PHC), p = 0.331 for nuclear bud (NBUD)). No correlations were seen between blood boron levels and tail intensity values of the sperm samples, lymphocyte samples, frequencies of MN, BN, KHC, KYL, PHC and NBUD. The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.
KW  - Boric acid
KW  - Boron exposure
KW  - DNA damage
KW  - Comet assay
Y1  - 2019
U6  - https://doi.org/10.1016/j.mrgentox.2018.12.013
SN  - 1383-5718
SN  - 1879-3592
VL  - 843
SP  - 33
EP  - 39
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Lopez-Serrano, Aniceto
A1  - Mitze, Hanna
A1  - Jakubowski, Norbert
A1  - Schwerdtle, Tanja
T1  - Single-cell analysis by ICP-MS/MS as a fast tool for cellular bioavailability studies of arsenite
JF  - Metallomics : integrated biometal science
N2  - Single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) has become a powerful and fast tool to evaluate the elemental composition at a single-cell level. In this study, the cellular bioavailability of arsenite (incubation of 25 and 50 mu M for 0-48 h) has been successfully assessed by SC-ICP-MS/MS for the first time directly after re-suspending the cells in water. This procedure avoids the normally arising cell membrane permeabilization caused by cell fixation methods (e.g. methanol fixation). The reliability and feasibility of this SC-ICP-MS/MS approach with a limit of detection of 0.35 fg per cell was validated by conventional bulk ICP-MS/MS analysis after cell digestion and parallel measurement of sulfur and phosphorus.
Y1  - 2017
U6  - https://doi.org/10.1039/c7mt00285h
SN  - 1756-5901
SN  - 1756-591X
VL  - 10
IS  - 1
SP  - 73
EP  - 76
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Markova, Mariya
A1  - Pohl, Gabriele
A1  - Marschall, Talke Anu
A1  - Pivovarova, Olga
A1  - Pfeiffer, Andreas F. H.
A1  - Schwerdtle, Tanja
T1  - Development, validation and application of an ICP-MS/MS method to quantify minerals and (ultra-)trace elements in human serum
JF  - Journal of trace elements in medicine and biology
N2  - Multi-element determination in human samples is very challenging. Especially in human intervention studies sample volumes are often limited to a few microliters and due to the high number of samples a high-throughput is indispensable. Here, we present a state-of-the-art ICP-MS/MS-based method for the analysis of essential (trace) elements, namely Mg, Ca, Fe, Cu, Zn, Mo, Se and I, as well as food-relevant toxic elements such as As and Cd. The developed method was validated regarding linearity of the calibration curves, method LODs and LOQs, selectivity and trueness as well as precision. The established reliable method was applied to quantify the element serum concentrations of participants of a human intervention study (LeguAN). The participants received isocaloric diets, either rich in plant protein or in animal protein. While the serum concentrations of Mg and Mo increased in participants receiving the plant protein-based diet (above all legumes), the Se concentration in serum decreased. In contrast, the animal protein-based diet, rich in meat and dairy products, resulted in an increased Se concentration in serum.
KW  - ICP-MS
KW  - Elemental blood serum concentration
KW  - Human nutritional intervention
Y1  - 2018
U6  - https://doi.org/10.1016/j.jtemb.2018.05.012
SN  - 0946-672X
VL  - 49
SP  - 157
EP  - 163
PB  - Elsevier GMBH
CY  - München
ER  -