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Archives of Toxicology

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https://www.readbyqxmd.com/read/29453549/the-german-reach-congress-2016-a-workshop-report
#1
Antonia Reihlen, Dirk Jepsen, Lutz Broschinski, Andreas Luch, Agnes Schulte
In October 2016, the German REACH Congress was held at the German Federal Institute for Risk Assessment (BfR) in Berlin. Here, the associated improvement made in the fields of consumer protection and the progress in and experiences gained from the implementation of the authorisation procedure were discussed. Several speakers from EU institutions, German authorities, industry, and civil society organisations were invited to present their views. There was a shared consensus that REACH contributes to the advancement of consumer protection against chemical risks, mainly because more and higher quality information on substance-related hazards and potential exposures becomes available...
February 17, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29450565/tissue-distribution-of-gold-and-silver-after-subacute-intravenous-injection-of-co-administered-gold-and-silver-nanoparticles-of-similar-sizes
#2
Ji Hyun Lee, Jae Hyuck Sung, Hyun Ryol Ryu, Kyung Seuk Song, Nam Woong Song, Hyun Min Park, Beom Soo Shin, Kangho Ahn, Mary Gulumian, Elaine M Faustman, Il Je Yu
Gold (AuNPs, 12.8 nm) and silver nanoparticles (AgNPs, 10 nm), mixed or separate, were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The rats were allowed to recover for further 4 weeks to examine the differences in AuNP/AgNP tissue distribution and clearance. The size distribution of injected AuNPs and AgNPs were not statistically different. The dose groups (five males per group for the administration and three males for the recovery) consisted of seven divisions, i.e., control, AgNPs (with a low dose of 10 µg/kg/day, and, a high dose of 100 µg/kg/day), AuNPs (with a low dose of 10 µg/kg/day, and, a high dose of 100 µg/kg/day), as well as mixed AgNPs/AuNPs (with a low dose of 10/10 µg/kg/day, and a high dose of 100/100 µg/kg/day)...
February 15, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29445839/vocalization-as-a-novel-endpoint-of-atypical-attachment-behavior-in-2-3-7-8-tetrachlorodibenzo-p-dioxin-exposed-infant-mice
#3
Eiki Kimura, Chiharu Tohyama
Mammalian attachment behaviors, such as crying, are essential for infant survival by receiving food, protection, and warmth from caregivers. Ultrasonic vocalization (USV) of infant rodents functions to promote maternal proximity. Impaired USV emission has been reported in mouse models of autism spectrum disorder, suggesting that USV is associated with higher brain function. In utero and lactational dioxin exposure is known to induce higher brain function abnormalities in adulthood; however, whether perinatal dioxin exposure affects behavior during infancy is unclear...
February 14, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29435600/the-role-of-unfolded-protein-response-and-er-phagy-in-quantum-dots-induced-nephrotoxicity-an-in-vitro-and-in-vivo-study
#4
Shengwei Jiang, Yuchun Lin, Huan Yao, Chuanli Yang, Liyin Zhang, Bing Luo, Zhao Lei, Liwei Cao, Naibo Lin, Xiangyang Liu, Zhongning Lin, Chengyong He
Unfolded protein response (UPR) and endoplasmic reticulum (ER)-phagy are essential for cell homeostasis. Quantum dots (QDs), which have been widely used for biomedical applications, can accumulate in the kidney tissues and may cause renal dysfunction. However, the molecular mechanism of QDs-induced nephrotoxicity is still obscure. The present study was aimed to elucidate the role and mechanism of UPR and ER-phagy in QDs-induced nephrotoxicity. Herein, human embyronic kidney (HEK) cells were exposed to 15, 30, 45, and 60 nM cadmium telluride (CdTe)-QDs for 12 and 24 h...
February 12, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29417167/maternal-no2-exposure-induces-cardiac-hypertrophy-in-male-offspring-via-ros-hif-1%C3%AE-transcriptional-regulation-and-aberrant-dna-methylation-modification-of-csx-nkx2-5
#5
Yingying Zhang, Wei Yan, Xiaotong Ji, Huifeng Yue, Guangke Li, Nan Sang
Maternal exposure to nitrogen dioxide (NO2) poses a risk for morbidity and mortality in infantile congenital heart diseases and even adult cardiovascular diseases. However, the experimental evidence supporting these effects is insufficient, and the related regulatory mechanisms are unknown. In the present study, we aimed to determine whether maternal NO2 exposure causes cardiac hypertrophy-related consequences in offspring, and if so, how these adverse effects occur in the postnatal heart. The results indicate that in mice, maternal NO2 exposure causes cardiac hypertrophy in male offspring...
February 7, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29411057/biomarker-monitoring-for-food-contaminants
#6
EDITORIAL
Hermann M Bolt
No abstract text is available yet for this article.
February 6, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29411056/a-novel-genotoxin-specific-qpcr-array-based-on-the-metabolically-competent-human-heparg%C3%A2-cell-line-as-a-rapid-and-reliable-tool-for-improved-in-vitro-hazard-assessment
#7
Gamze Ates, Birgit Mertens, Anja Heymans, Luc Verschaeve, Dimiter Milushev, Philippe Vanparys, Nancy H C Roosens, Sigrid C J De Keersmaecker, Vera Rogiers, Tatyana Y Doktorova
Although the value of the regulatory accepted batteries for in vitro genotoxicity testing is recognized, they result in a high number of false positives. This has a major impact on society and industries developing novel compounds for pharmaceutical, chemical, and consumer products, as afflicted compounds have to be (prematurely) abandoned or further tested on animals. Using the metabolically competent human HepaRG™ cell line and toxicogenomics approaches, we have developed an upgraded, innovative, and proprietary gene classifier...
February 6, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29404631/new-mechanistic-insights-on-the-metabolic-disruptor-role-of-chlorpyrifos-in-apoe-mice-a-focus-on-insulin-and-leptin-signalling-pathways
#8
Fiona Peris-Sampedro, Jordi Blanco, Maria Cabré, Pia Basaure, Laia Guardia-Escote, Jose L Domingo, Domènec J Sánchez, Maria Teresa Colomina
Recently, we have provided evidence, suggesting that mice expressing the human apolipoprotein E3 (apoE3) are more prone to develop an obesity-like phenotype and a diabetic profile when subchronically fed a chlorpyrifos (CPF)-supplemented diet. The aim of the current study was to examine the underlying mechanisms through which CPF alters both insulin- and leptin-signalling pathways in an APOE-dependent manner. Both adult apoE3- and E4-targeted replacement and C57BL/6 mice were exposed to CPF at 0 or 2 mg/kg body weight/day through the diet for 8 consecutive weeks...
February 5, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29397400/cell-death-mechanisms-of-the-anti-cancer-drug-etoposide-on-human-cardiomyocytes-isolated-from-pluripotent-stem-cells
#9
Harshal Nemade, Umesh Chaudhari, Aviseka Acharya, Jürgen Hescheler, Jan Georg Hengstler, Symeon Papadopoulos, Agapios Sachinidis
Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue and the underlying cardiotoxic mechanisms are not well understood. This study is aiming to unravel the cardiotoxicity profile of ETP in comparison to anthracyclines using physiologically relevant human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). Using xCELLigence real-time cell analyser (RTCA), we found that single high dose of ETP induces irreversible increase in hPSC-CMs beating rate and decrease in beating amplitude...
February 3, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29383422/proteomic-alterations-of-brain-subcellular-organelles-caused-by-low-dose-copper-exposure-implication-for-alzheimer-s-disease
#10
Haitao Yu, Dian Wang, Liangyu Zou, Zaijun Zhang, Hua Xu, Feiqi Zhu, Xiaohu Ren, Benhong Xu, Jianhui Yuan, Jianjun Liu, Peter S Spencer, Xifei Yang
Excessive copper intake can lead to neurotoxicity, but there is a lack of comprehensive understanding on the potential impact of copper exposure especially at a low-dose on brain. We used 3xTg-AD mice to explore the potential neurotoxicity of chronic, low-dose copper treatment (0.13 ppm copper chloride in drinking water) on behavior and the brain hippocampal mitochondrial and nuclear proteome. Low-dose copper increased the spatial memory impairment of these animals, increased accumulation of intracellular amyloid 1-42 (Aβ1-42), decreased ATP content, increased the positive staining of 8-hydroxyguanosine (8-OHdG), a marker of DNA oxidative damage, and caused apoptosis and a decrease in synaptic proteins...
January 30, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29380012/lymphocyte-surface-markers-and-cytokines-are-suitable-for-detection-and-potency-assessment-of-skin-sensitizing-chemicals-in-an-in-vitro-model-of-allergic-contact-dermatitis-the-lcsa-ly
#11
Janna Frombach, Anna Sonnenburg, Björn-Dirk Krapohl, Torsten Zuberbier, Matthias Peiser, Ralf Stahlmann, Maximilian Schreiner
Allergic contact dermatitis is a widespread health disorder and occupational skin disease. Hence, screening for contact-sensitizing chemicals is highly relevant to toxicology, dermatology, and occupational medicine. The use of animal tests for this purpose is constrained by ethical considerations, need for high-throughput screening, and legislation (e.g., for cosmetics in the European Union). T cell activation is the final and most specific key event of the "adverse outcome pathway" for skin sensitization and therefore a promising target for the development of in vitro sensitization assays...
January 30, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29380011/effects-of-bisphenol-a-on-ovarian-follicular-development-and-female-germline-stem-cells
#12
Xiaoqin Zhu, Geng G Tian, Baoli Yu, Yanzhou Yang, Ji Wu
Bisphenol A (BPA), one of the most frequently detected emerging pollutants in the environment, has been implicated in adverse effects in male and female reproduction at extremely low concentrations. This study aimed to investigate the effects and potential mechanism of BPA on mouse ovarian follicular development and female germline stem cells (FGSCs). Female CD-1 adult mice were administered gradient concentrations of BPA (12.5, 25, and 50 mg/kg/day) by intraperitoneal injection. We found that the number of atretic ovarian follicles was significantly increased at high BPA concentrations...
January 29, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29368147/cytochrome-b-5-impacts-on-cytochrome-p450-mediated-metabolism-of-benzo-a-pyrene-and-its-dna-adduct-formation-studies-in-hepatic-cytochrome-b-5-p450-reductase-null-hbrn-mice
#13
Lindsay Reed, Iveta Mrizova, Frantisek Barta, Radek Indra, Michaela Moserova, Klaus Kopka, Heinz H Schmeiser, C Roland Wolf, Colin J Henderson, Marie Stiborova, David H Phillips, Volker M Arlt
Benzo[a]pyrene (BaP) is an environmental pollutant that, based on evidence largely from in vitro studies, exerts its genotoxic effects after metabolic activation by cytochrome P450s. In the present study, Hepatic Reductase Null (HRN) and Hepatic Cytochrome b 5 /P450 Reductase Null (HBRN) mice have been used to study the role of P450s in the metabolic activation of BaP in vivo. In HRN mice, cytochrome P450 oxidoreductase (POR), the electron donor to P450, is deleted specifically in hepatocytes. In HBRN mice the microsomal haemoprotein cytochrome b 5 , which can also act as an electron donor from cytochrome b 5 reductase to P450s, is also deleted in the liver...
January 24, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29368146/irritant-induced-asthma-to-hypochlorite-in-mice-due-to-impairment-of-the-airway-barrier
#14
Sofie Van Den Broucke, Lore Pollaris, Greetje Vande Velde, Erik Verbeken, Benoit Nemery, Jeroen Vanoirbeek, Peter Hoet
Inhalation of commonly present irritants, such as chlorine and chlorine derivatives, can cause adverse respiratory effects, including irritant-induced asthma (IIA). We hypothesize that due to airway barrier impairment, exposure to hypochlorite (ClO-) can result in airway hypersensitivity. C57Bl/6 mice received an intra-peritoneal (i.p.) injection of the airway damaging agent naphthalene (NA, 200 mg/kg body weight) or vehicle (mineral oil, MO). In vivo micro-computed tomography (CT) images of the lungs were acquired before and at regular time points after the i...
January 24, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29362864/tacrolimus-induced-nephrotoxicity-in-mice-is-associated-with-microrna-deregulation
#15
Cyrille Vandenbussche, Cynthia Van der Hauwaert, Edmone Dewaeles, Jessica Franczak, Marie-Flore Hennino, Viviane Gnemmi, Grégoire Savary, Quentin Tavernier, Nicolas Nottet, Agnès Paquet, Michaël Perrais, David Blum, Bernard Mari, Nicolas Pottier, François Glowacki, Christelle Cauffiez
Although Tacrolimus is an immunosuppressive drug widely used in renal transplantation, its chronic use paradoxically induces nephrotoxic effects, in particular renal fibrosis, which is responsible for chronic allograft dysfunction and represents a major prognostic factor of allograft survival. As molecular pathways and mechanisms involved in Tacrolimus-induced fibrogenic response are poorly elucidated, we assessed whether miRNAs are involved in the nephrotoxic effects mediated by Tacrolimus. Treatment of CD-1 mice with Tacrolimus (1 mg/kg/d for 28 days) resulted in kidney injury and was associated with alteration of a gene expression signature associated with cellular stress, fibrosis and inflammation...
January 23, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29362863/innovative-organotypic-in-vitro-models-for-safety-assessment-aligning-with-regulatory-requirements-and-understanding-models-of-the-heart-skin-and-liver-as-paradigms
#16
REVIEW
Chris S Pridgeon, Constanze Schlott, Min Wei Wong, Minne B Heringa, Tobias Heckel, Joe Leedale, Laurence Launay, Vitalina Gryshkova, Stefan Przyborski, Rachel N Bearon, Emma L Wilkinson, Tahera Ansari, John Greenman, Delilah F G Hendriks, Sue Gibbs, James Sidaway, Rowena L Sison-Young, Paul Walker, Mike J Cross, B Kevin Park, Chris E P Goldring
The development of improved, innovative models for the detection of toxicity of drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new products safely to market in a cost-effective and timely manner. In addition, improvement in models to detect toxicity may reduce the incidence of unexpected post-marketing toxicity and reduce or eliminate the need for animal testing. The safety of novel products of the pharmaceutical, chemical, or cosmetics industry must be assured; therefore, toxicological properties need to be assessed...
January 23, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29362862/the-development-of-an-in-vitro-pig-a-assay-in-l5178y-cells
#17
Rhiannon David, Emily Talbot, Bethany Allen, Amy Wilson, Usman Arshad, Ann Doherty
A recent flow cytometry-based in vivo mutagenicity assay involves the hemizygous phosphatidylinositol class A (Pig-a) gene. Pig-a forms the catalytic subunit of N-acetylglucosaminyltransferase required for glycophosphatidylinositol (GPI) anchor biosynthesis. Mutations in Pig-a prevent GPI-anchor synthesis resulting in loss of cell-surface GPI-linked proteins. The aim of the current study was to develop and validate an in vitro Pig-a assay in L5178Y mouse lymphoma cells. Ethyl methanesulfonate (EMS)-treated cells (186...
January 23, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29362861/ethanol-potentiates-the-genotoxicity-of-the-food-derived-mammary-carcinogen-phip-in-human-estrogen-receptor-positive-mammary-cells-mechanistic-support-for-lifestyle-factors-cooked-red-meat-and-ethanol-associated-with-mammary-cancer
#18
Durr-E-Shahwar Malik, Rhiannon M David, Nigel J Gooderham
Consumption of cooked/processed meat and ethanol are lifestyle risk factors in the aetiology of breast cancer. Cooking meat generates heterocyclic amines such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Epidemiology, mechanistic and animal studies indicate that PhIP is a mammary carcinogen that could be causally linked to breast cancer incidence; PhIP is DNA damaging, mutagenic and oestrogenic. PhIP toxicity involves cytochrome P450 (CYP1 family)-mediated metabolic activation to DNA-damaging species, and transcriptional responses through Aryl hydrocarbon receptor (AhR) and estrogen-receptor-α (ER-α)...
January 23, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29356862/flame-retardants-hexabromocyclododecane-hcbd-and-tetrabromobisphenol-a-tbbpa-alter-secretion-of-tumor-necrosis-factor-alpha-tnf%C3%AE-from-human-immune-cells
#19
Sharia Yasmin, Margaret Whalen
Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are flame retardants, used in a variety of applications, which contaminate the environment and are found in human blood. HBCD and TBBPA have been shown to alter the tumor killing function of natural killer (NK) lymphocytes and the secretion of the inflammatory cytokines interferon gamma (IFNγ) and interleukin 1 beta (IL-1β). The current study examined the effects of HBCD and TBBPA on secretion of the critical pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells...
January 22, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29356861/identification-of-approved-drugs-as-potent-inhibitors-of-pregnane-x-receptor-activation-with-differential-receptor-interaction-profiles
#20
Oliver Burk, Maria Kuzikov, Thales Kronenberger, Judith Jeske, Oliver Keminer, Wolfgang E Thasler, Matthias Schwab, Carsten Wrenger, Björn Windshügel
Activation of pregnane X receptor (PXR) results in the induction of first-pass metabolism and drug efflux. Hereby, PXR may cause adverse drug reactions or therapeutic failure of drugs. PXR inhibition is thus an attractive option to minimise adverse effects or to improve therapeutic efficiencies; however, only a limited number of antagonists have been identified so far. We performed a cell-based high-throughput screen to identify PXR antagonists, using a library of approved and investigational drugs. Two approved drugs, pimecrolimus and pazopanib, emerged as novel potent antagonists of PXR activation, with IC50 values of 1...
January 22, 2018: Archives of Toxicology
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