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Computational identification of structural factors affecting the mutagenic potential of aromatic amines: study design and experimental validation.
BJ Abstract A grid-based, alignment-independent 3D-SDAR (three-dimensional spectral data-activity relationship) approach based on simulated 13C and 15N NMR chemical shifts augmented with through-space interatomic distances was used to model the mutagenicity of 554 primary and 419 secondary aromatic amines. A robust modeling strategy supported by extensive validation including randomized training/hold-out test set pairs, validation sets, "blind" external test sets as well as experimental validation was applied to avoid over-parameterization and build Organization for Economic Cooperation and Development ...
Source: Archives of Toxicology - May 19, 2018 Category: Toxicology Authors: Slavov SH, Stoyanova-Slavova I, Mattes W, Beger RD, Brüschweiler BJ Tags: Arch Toxicol Source Type: research

Prediction of deoxynivalenol toxicokinetics in humans by in vitro-to-in vivo extrapolation and allometric scaling of in vivo animal data.
ig S Abstract Deoxynivalenol (DON) is the most prevalent mycotoxin in cereals worldwide. It can cause adverse health effects in humans and animals, and maximum levels in food and feed have been implemented by food authorities based on risk assessments derived from estimated intake levels. The lack of human toxicokinetic data such as absorption, distribution, and elimination characteristics hinders the direct calculation of DON plasma levels and exposure. In the present study, we have, therefore, used in vitro-to-in vivo extrapolation of depletion constants in hepatic microsomes from different species and allometri...
Source: Archives of Toxicology - May 17, 2018 Category: Toxicology Authors: Fæste CK, Ivanova L, Sayyari A, Hansen U, Sivertsen T, Uhlig S Tags: Arch Toxicol Source Type: research

Association study of genetic variants in estrogen metabolic pathway genes and colorectal cancer risk and survival.
Abstract Although studies have investigated the association of genetic variants and the abnormal expression of estrogen-related genes with colorectal cancer risk, the evidence remains inconsistent. We clarified the relationship of genetic variants in estrogen metabolic pathway genes with colorectal cancer risk and survival. A case-control study was performed to assess the association of single-nucleotide polymorphisms (SNPs) in ten candidate genes with colorectal cancer risk in a Chinese population. A logistic regression model and Cox regression model were used to calculate SNP effects on colorectal cancer suscept...
Source: Archives of Toxicology - May 16, 2018 Category: Toxicology Authors: Li S, Xie L, Du M, Xu K, Zhu L, Chu H, Chen J, Wang M, Zhang Z, Gu D Tags: Arch Toxicol Source Type: research

Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures.
Abstract Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event. Transcriptom...
Source: Archives of Toxicology - May 14, 2018 Category: Toxicology Authors: Rodrigues RM, Kollipara L, Chaudhari U, Sachinidis A, Zahedi RP, Sickmann A, Kopp-Schneider A, Jiang X, Keun H, Hengstler J, Oorts M, Annaert P, Hoeben E, Gijbels E, De Kock J, Vanhaecke T, Rogiers V, Vinken M Tags: Arch Toxicol Source Type: research

Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation.
Abstract Wear particles from automotive friction brake pads of various sizes, morphology, and chemical composition are significant contributors towards particulate matter. Knowledge concerning the potential adverse effects following inhalation exposure to brake wear debris is limited. Our aim was, therefore, to generate brake wear particles released from commercial low-metallic and non-asbestos organic automotive brake pads used in mid-size passenger cars by a full-scale brake dynamometer with an environmental chamber simulating urban driving and to deduce their potential hazard in vitro. The collected fractions w...
Source: Archives of Toxicology - May 10, 2018 Category: Toxicology Authors: Barosova H, Chortarea S, Peikertova P, Clift MJD, Petri-Fink A, Kukutschova J, Rothen-Rutishauser B Tags: Arch Toxicol Source Type: research

The polymorphism rs2480258 within CYP2E1 is associated with different rates of acrylamide metabolism in vivo in humans.
, Landi S Abstract In a recent study, we demonstrated that the variant allele of rs2480258 within intron VIII of CYP2E1 is associated with reduced levels of mRNA, protein, and enzyme activity. CYP2E1 is the most important enzyme in the metabolism of acrylamide (AA) by operating its oxidation into glycidamide (GA). AA occurs in food, is neurotoxic and classified as a probable human carcinogen. The goal of the present study was to further assess the role of rs2480258 by measuring the rate of AA > GA biotransformation in vivo. In blood samples from a cohort of 120 volunteers, the internal doses of AA...
Source: Archives of Toxicology - May 10, 2018 Category: Toxicology Authors: Pellè L, Carlsson H, Cipollini M, Bonotti A, Foddis R, Cristaudo A, Romei C, Elisei R, Gemignani F, Törnqvist M, Landi S Tags: Arch Toxicol Source Type: research

Validity of different biomonitoring parameters for the assessment of occupational exposure to N,N-dimethylformamide (DMF).
This study was performed to assess the relation between occupational exposure to N,N-dimethylformamide after an 8 h work shift in the acrylic fibre industry and its three biological markers N-methylformamide (NMFtotal), N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC), and N-methylcarbamoyl adduct at haemoglobin (MCVal). External DMF exposure of 220 workers was determined during the whole shift. A standardised questionnaire was used to obtain information about the worker's general health status, medical treatment, smoking habits, protective measures, and possible symptoms caused by DMF exposure. NMF and AMCC were analyse...
Source: Archives of Toxicology - May 10, 2018 Category: Toxicology Authors: Seitz M, Kilo S, Eckert E, Müller J, Drexler H, Göen T Tags: Arch Toxicol Source Type: research

Levels of selected analytes in the emissions of "heat not burn" tobacco products that are relevant to assess human health risks.
Levels of selected analytes in the emissions of "heat not burn" tobacco products that are relevant to assess human health risks. Arch Toxicol. 2018 May 05;: Authors: Mallock N, Böss L, Burk R, Danziger M, Welsch T, Hahn H, Trieu HL, Hahn J, Pieper E, Henkler-Stephani F, Hutzler C, Luch A Abstract Consumers of combustible cigarettes are exposed to many different toxicologically relevant substances associated with negative health effects. Newly developed "heat not burn" (HNB) devices are able to contain lower levels of Harmful and Potentially Harmful Constituents (HPHCs) in thei...
Source: Archives of Toxicology - May 5, 2018 Category: Toxicology Authors: Mallock N, Böss L, Burk R, Danziger M, Welsch T, Hahn H, Trieu HL, Hahn J, Pieper E, Henkler-Stephani F, Hutzler C, Luch A Tags: Arch Toxicol Source Type: research

Using the lentiviral vector system to stably express chicken P-gp and BCRP in MDCK cells for screening the substrates and studying the interplay of both transporters.
In this study, BCRP single and BCRP/P-gp double-transfected MDCK cell lines (named MDCK-chAbcg2 and MDCK-chAbcg2/Abcb1, respectively) were generated using lentiviral vector system to develop reliable systems for screening the substrates for these two transporters and study the interplay between them. The constructed cell lines significantly expressed functional exogenous proteins and expression persisted for at least 50 generations with no decrease. Enrofloxacin, ciprofloxacin, tilmicosin, sulfadiazine, ampicillin and clindamycin were classified as the substrates of chicken P-gp according to the rules suggested by FDA, as ...
Source: Archives of Toxicology - May 3, 2018 Category: Toxicology Authors: Zhang Y, Huang J, Liu Y, Guo T, Wang L Tags: Arch Toxicol Source Type: research

Activation of autophagic flux and the Nrf2/ARE signaling pathway by hydrogen sulfide protects against acrylonitrile-induced neurotoxicity in primary rat astrocytes.
In conclusion, we identified a crucial role of  autophagy and the Nrf2/ARE signaling pathway in H2S-mediated neuroprotection against AN-induced toxicity in primary rat astrocytes. Our findings provide novel insights into the mechanisms of H2S-mediated neuroprotection, and suggest that H2S-based donors may serve as potential new candidate drugs to treat AN-induced neurotoxicity. PMID: 29725710 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 3, 2018 Category: Toxicology Authors: Yang B, Bai Y, Yin C, Qian H, Xing G, Wang S, Li F, Bian J, Aschner M, Lu R Tags: Arch Toxicol Source Type: research

Lon in maintaining mitochondrial and endoplasmic reticulum homeostasis.
Abstract As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine-lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc. Furthermore, the up-regulated LONP increased mitochondrial ROS generation ...
Source: Archives of Toxicology - May 2, 2018 Category: Toxicology Authors: Yang J, Chen W, Zhang B, Tian F, Zhou Z, Liao X, Li C, Zhang Y, Han Y, Wang Y, Li Y, Wang GQ, Shen XL Tags: Arch Toxicol Source Type: research

Corticosteroid-binding globulin, induced in testicular Leydig cells by perfluorooctanoic acid, promotes steroid hormone synthesis.
Abstract Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. It is a ubiquitous environmental pollutant and suspected endocrine disruptor. Corticosteroid-binding globulin (CBG) is a monomeric glycoprotein that can bind specifically to anti-inflammatory steroids, such as glucocorticoids and progesterone, in circulation. Our previous proteomic profile analysis revealed that CBG levels increased in testes after PFOA treatment. In the present study, we verified its increase in mouse testes following oral exposure to PFOA (0, 1.25 and 5 mg/kg/da...
Source: Archives of Toxicology - May 2, 2018 Category: Toxicology Authors: Sun S, Wang J, Lu Y, Dai J Tags: Arch Toxicol Source Type: research

Prenatal arsenic exposure and dietary folate and methylcobalamin supplementation alter the metabolic phenotype of C57BL/6J mice in a sex-specific manner.
blo M Abstract Inorganic arsenic (iAs) is an established environmental diabetogen. The link between iAs exposure and diabetes is supported by evidence from adult human cohorts and adult laboratory animals. The contribution of prenatal iAs exposure to the development of diabetes and underlying mechanisms are understudied. The role of factors that modulate iAs metabolism and toxicity in adults and their potential to influence diabetogenic effects of prenatal iAs exposure are also unclear. The goal of this study was to determine if prenatal exposure to iAs impairs glucose metabolism in mice and if maternal supplement...
Source: Archives of Toxicology - May 2, 2018 Category: Toxicology Authors: Huang MC, Douillet C, Dover EN, Stýblo M Tags: Arch Toxicol Source Type: research

The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice.
Abstract The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86&...
Source: Archives of Toxicology - May 2, 2018 Category: Toxicology Authors: Wilson CE, Dickie AP, Schreiter K, Wehr R, Wilson EM, Bial J, Scheer N, Wilson ID, Riley RJ Tags: Arch Toxicol Source Type: research

Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence.
Abstract Human lungs are susceptible to the toxicity induced by soluble xenobiotics. However, the direct cellular effects of many pulmonotoxic chemicals are not always clear, and thus, a general in vitro assay for testing pulmonotoxicity applicable to a wide variety of chemicals is not currently available. Here, we report a study that uses high-throughput imaging and artificial intelligence to build an in vitro pulmonotoxicity assay by automatically comparing and selecting human lung-cell lines and their associated quantitative phenotypic features most predictive of in vivo pulmonotoxicity. This approach is called...
Source: Archives of Toxicology - April 28, 2018 Category: Toxicology Authors: Lee JJ, Miller JA, Basu S, Kee TV, Loo LH Tags: Arch Toxicol Source Type: research

From basic research to applied veterinary sciences: current status, challenges and perspectives.
PMID: 29700555 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 26, 2018 Category: Toxicology Authors: Hammad S, Othman A, Abdel-Wareth AAA, Ahmed H, Abdel-Daim MM, Gherbawy YA Tags: Arch Toxicol Source Type: research

Highlight report: Mycotoxins as food contaminants in Africa-challenges and perspectives.
PMID: 29654336 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 13, 2018 Category: Toxicology Authors: Abdallah MF, De Boevre M, Audenaert K, Haesaert G, De Saeger S Tags: Arch Toxicol Source Type: research

Human-relevant potency threshold (HRPT) for ER α agonism.
Human-relevant potency threshold (HRPT) for ERα agonism. Arch Toxicol. 2018 Apr 09;: Authors: Borgert CJ, Matthews JC, Baker SP Abstract The European Commission has recently proposed draft criteria for the identification of endocrine disrupting chemicals (EDCs) that pose a significant hazard to humans or the environment. Identifying and characterizing toxic hazards based on the manner by which adverse effects are produced rather than on the nature of those adverse effects departs from traditional practice and requires a proper interpretation of the evidence regarding the chemical's ability to pr...
Source: Archives of Toxicology - April 9, 2018 Category: Toxicology Authors: Borgert CJ, Matthews JC, Baker SP Tags: Arch Toxicol Source Type: research

Membrane microdomains regulate NLRP10- and NLRP12-dependent signalling in A549 cells challenged with cigarette smoke extract.
Abstract Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death and disability worldwide by 2030; with cigarette smoking (active or passive) being one of the chief cause of its occurrence. Cigarette smoke exposure has been found to result in excessive inflammation and tissue injury, which might lead to COPD, although the exact pathophysiology of the disease remains elusive. While previous studies have demonstrated the role of membrane-bound Toll-like receptors (TLRs) in cigarette smoke (CS)-induced inflammation, scant information is available about the role of cytosoli...
Source: Archives of Toxicology - April 6, 2018 Category: Toxicology Authors: Singh DP, Kaur G, Bagam P, Pinkston R, Batra S Tags: Arch Toxicol Source Type: research

The role of hepatic cytochrome P450s in the cytotoxicity of dronedarone.
In this study, we examined further the underlying mechanisms and found that after a 24-h treatment of HepG2 cells, dronedarone caused cytotoxicity, G1-phase cell cycle arrest, suppression of topoisomerase II, and DNA damage in a concentration-dependent manner. We also investigated the role of cytochrome P450s (CYPs)-mediated metabolism in the dronedarone-induced toxicity using our previously established HepG2 cell lines expressing individually 14 human CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). We demonstrated that CYP3A4, 3A5, and 2D6 were the major enzymes that metabolize dronedaro...
Source: Archives of Toxicology - April 3, 2018 Category: Toxicology Authors: Chen S, Wu Q, Ning B, Bryant M, Guo L Tags: Arch Toxicol Source Type: research

EPHX1 rs1051740 T > C (Tyr113His) is strongly associated with acute myeloid leukemia and KMT2A rearrangements in early age.
In conclusion, EPHX1 rs1051740 plays an important role in i-AML's genetic susceptibility by modulating the carcinogenic effects of epoxide exposures in the bone marrow. PMID: 29605894 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 31, 2018 Category: Toxicology Authors: Brisson GD, de Almeida Lopes B, Andrade FG, Dos Santos Bueno FV, Sardou-Cezar I, de Aguiar Gonçalves BA, Terra-Granado E, Paraguassú-Braga FH, S Pombo-de-Oliveira M Tags: Arch Toxicol Source Type: research

Arsenic-containing hydrocarbons: effects on gene expression, epigenetics, and biotransformation in HepG2 cells.
e T Abstract Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-...
Source: Archives of Toxicology - March 30, 2018 Category: Toxicology Authors: Müller SM, Finke H, Ebert F, Kopp JF, Schumacher F, Kleuser B, Francesconi KA, Raber G, Schwerdtle T Tags: Arch Toxicol Source Type: research

Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay.
In this study, we combined MITA with the IL-8 Luc assay to detect skin sensitization chemicals (OECD 442E) (modified MITA: mMITA) and established a data set of 60 chemicals examined by mMITA. Using the mMITA results, chemicals can be classified based on the lowest observed effect level (LOEL) of chemicals in suppressing or augmenting the promoter activities of the four cytokines. Moreover, we demonstrated that K-means clustering and hierarchical clustering of the 60 chemicals based on the LOEL for their effects on IL-2 and IL-8 promoter activities and the judgment by the IL-8 Luc assay resulted in the same 6-cluster soluti...
Source: Archives of Toxicology - March 29, 2018 Category: Toxicology Authors: Kimura Y, Fujimura C, Ito Y, Takahashi T, Terui H, Aiba S Tags: Arch Toxicol Source Type: research

Dysregulation of autophagy in rat liver with mitochondrial DNA depletion induced by the nucleoside analogue zidovudine.
In conclusion, rat liver with AZT-induced mtDNA depletion presented dysregulations in autophagosome formation and degradation balance, which results in accumulation of these structures in parenchymal liver cells, favouring hepatocarcinogenesis. PMID: 29594326 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 28, 2018 Category: Toxicology Authors: Santos-Llamas A, Monte MJ, Marin JJG, Perez MJ Tags: Arch Toxicol Source Type: research

Coffee consumption, metabolic syndrome and clinical severity of psoriasis: good or bad stuff?
Abstract Despite the wide consumption of coffee, its anti-inflammatory effect on clinical severity of psoriasis is still debatable. The aim of this study was to evaluate the association between the coffee consumption and clinical severity of psoriasis in a sample of patients stratified according to the presence of the metabolic syndrome (MetS) and smoking. This cross-sectional case-control observational study was conducted on 221 treatment-naïve psoriatic patients. Lifestyle habits, anthropometric measures, clinical and biochemical evaluations were obtained. Clinical severity of psoriasis was assessed by Psor...
Source: Archives of Toxicology - March 28, 2018 Category: Toxicology Authors: Barrea L, Muscogiuri G, Di Somma C, Annunziata G, Megna M, Falco A, Balato A, Colao A, Savastano S Tags: Arch Toxicol Source Type: research

Loss of Wilms tumor 1 protein is a marker for apoptosis in response to replicative stress in leukemic cells.
h N Abstract A remaining expression of the transcription factor Wilms tumor 1 (WT1) after cytotoxic chemotherapy indicates remaining leukemic clones in patients. We determined the regulation and relevance of WT1 in leukemic cells exposed to replicative stress and DNA damage. To induce these conditions, we used the clinically relevant chemotherapeutics hydroxyurea and doxorubicin. We additionally treated cells with the pro-apoptotic kinase inhibitor staurosporine. Our data show that these agents promote apoptosis to a variable extent in a panel of 12 leukemic cell lines and that caspases cleave WT1 during apoptosis...
Source: Archives of Toxicology - March 27, 2018 Category: Toxicology Authors: Pons M, Reichardt CM, Hennig D, Nathan A, Kiweler N, Stocking C, Wichmann C, Christmann M, Butter F, Reichardt S, Schneider G, Heinzel T, Englert C, Hartkamp J, Krämer OH, Mahendrarajah N Tags: Arch Toxicol Source Type: research

Particulate matter 2.5 damages skin cells by inducing oxidative stress, subcellular organelle dysfunction, and apoptosis.
Abstract The skin is the largest organ of the human body and the one mostly exposed to outdoor contaminants. To evaluate the biological mechanisms underlying skin damage caused by fine particulate matter (PM2.5), we analyzed the effects of PM2.5 on cultured human keratinocytes and the skin of experimental animals. PM2.5 was applied to human HaCaT keratinocytes at 50 µg/mL for 24 h and to mouse skin at 100 µg/mL for 7 days. The results indicate that PM2.5 induced oxidative stress by generating reactive oxygen species both in vitro and in vivo, which led to DNA damage, lipid peroxidat...
Source: Archives of Toxicology - March 26, 2018 Category: Toxicology Authors: Piao MJ, Ahn MJ, Kang KA, Ryu YS, Hyun YJ, Shilnikova K, Zhen AX, Jeong JW, Choi YH, Kang HK, Koh YS, Hyun JW Tags: Arch Toxicol Source Type: research

In vitro prediction of drug-induced cholestatic liver injury: a challenge for the toxicologist.
PMID: 29574564 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 24, 2018 Category: Toxicology Authors: Vinken M Tags: Arch Toxicol Source Type: research

Atorvastatin decreases steroid production in H295R cells and in major endocrine tissues of male rats.
Abstract Obesity is increasing worldwide, and since obesity is associated with dyslipidemia, the consumption of cholesterol-lowering pharmaceuticals has increased. The aim of this study was therefore to study potential endocrine disrupting effects of one of the world's most frequently prescribed drugs, the cholesterol-lowering drug, atorvastatin (ATO) in vitro using the H295R steroidogenesis assay and in vivo using male Sprague-Dawley rats. We analyzed all major steroids in the mammalian steroidogenesis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In vitro, ATO significantly decreased all stero...
Source: Archives of Toxicology - March 24, 2018 Category: Toxicology Authors: Munkboel CH, Baake MLK, Styrishave B Tags: Arch Toxicol Source Type: research

Polymyxin B causes DNA damage in HK-2 cells and mice.
Abstract Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events...
Source: Archives of Toxicology - March 20, 2018 Category: Toxicology Authors: Yun B, Zhang T, Azad MAK, Wang J, Nowell CJ, Kalitsis P, Velkov T, Hudson DF, Li J Tags: Arch Toxicol Source Type: research

Induction of hemangiosarcoma in mice after chronic treatment with S1P-modulator siponimod and its lack of relevance to rat and human.
In conclusion, the molecular mechanisms leading to siponimod-induced HSA in mice are considered species specific and likely irrelevant to humans. PMID: 29556671 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 19, 2018 Category: Toxicology Authors: Pognan F, Mahl JA, Papoutsi M, Ledieu D, Raccuglia M, Theil D, Voytek SB, Devine PJ, Kubek-Luck K, Claudio N, Cordier A, Heier A, Kolly C, Hartmann A, Chibout SD, Bouchard P, Trendelenburg C Tags: Arch Toxicol Source Type: research

Gestational bisphenol S impairs placental endocrine function and the fusogenic trophoblast signaling pathway.
Abstract Exposure to bisphenolic chemicals during pregnancy occurs in> 90% of pregnancies. Bisphenolic compounds can cross the placental barrier reaching fetal circulation. However, the effects of emerging bisphenolic compounds, such as bisphenol S (BPS), on placental function remain untested. The aim was to determine if bisphenol A (BPA) or BPS, at an environmentally relevant dose, impairs placental function. Pregnant sheep were randomly distributed into three treatment groups (n = 7-8/group): control, BPA, and BPS. All animals received daily injections of corn oil (control), BPA, or BPS (...
Source: Archives of Toxicology - March 17, 2018 Category: Toxicology Authors: Gingrich J, Pu Y, Roberts J, Karthikraj R, Kannan K, Ehrhardt R, Veiga-Lopez A Tags: Arch Toxicol Source Type: research

Respiratory hazard of Li-ion battery components: elective toxicity of lithium cobalt oxide (LiCoO2) particles in a mouse bioassay.
This study identified, for the first time, the respiratory hazard of LIB particles. LCO was at least as potent as crystalline silica to induce lung inflammation and fibrosis. Iron and cobalt, but not lithium, ions appear to contribute to LFP and LCO toxicity, respectively. PMID: 29550861 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 17, 2018 Category: Toxicology Authors: Sironval V, Reylandt L, Chaurand P, Ibouraadaten S, Palmai-Pallag M, Yakoub Y, Ucakar B, Rose J, Poleunis C, Vanbever R, Marbaix E, Lison D, van den Brule S Tags: Arch Toxicol Source Type: research

The future trajectory of adverse outcome pathways: a commentary.
Abstract The advent of adverse outcome pathways (AOPs) has provided a new lexicon for description of mechanistic toxicology, and a renewed enthusiasm for exploring modes of action resulting in adverse health and environmental effects. In addition, AOPs have been used successfully as a framework for the design and development of non-animal approaches to toxicity testing. Although the value of AOPs is widely recognised, there remain challenges and opportunities associated with their use in practise. The purpose of this article is to consider specifically how the future trajectory of AOPs may provide a basis for addr...
Source: Archives of Toxicology - March 16, 2018 Category: Toxicology Authors: Sewell F, Gellatly N, Beaumont M, Burden N, Currie R, de Haan L, Hutchinson TH, Jacobs M, Mahony C, Malcomber I, Mehta J, Whale G, Kimber I Tags: Arch Toxicol Source Type: research

Adipose tissue stem cell-derived hepatic progenies as an in vitro model for genotoxicity testing.
ek TL, Filipič M Abstract The problem of the currently used routine genotoxicity tests is relatively low predictivity of in vitro tests for in vivo genotoxicity and carcinogenicity. An important reason is considered to be inadequate expression of xenobiotic-metabolizing enzymes in indicator cell lines. The aim of our study was to generate metabolically active differentiated hepatic progenies (hDHP) from human adipose tissue-derived mesenchymal stem cells (hASC) for genotoxicity testing. hDHP, generated using a three-step hepatic differentiation procedure, expressed hepatic properties such as glycogen storage and ...
Source: Archives of Toxicology - March 16, 2018 Category: Toxicology Authors: Tomc J, Kološa K, Žegura B, Kamenšek U, Breznik B, Turnšek TL, Filipič M Tags: Arch Toxicol Source Type: research

CMR substances in consumer products: from food contact materials to toys.
PMID: 29546521 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 16, 2018 Category: Toxicology Authors: Lenzner A, Vieth B, Luch A Tags: Arch Toxicol Source Type: research

Acute exposure to diesel exhaust impairs adult neurogenesis in mice: prominence in males and protective effect of pioglitazone.
Abstract Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit a...
Source: Archives of Toxicology - March 10, 2018 Category: Toxicology Authors: Coburn JL, Cole TB, Dao KT, Costa LG Tags: Arch Toxicol Source Type: research

DNA methylation profiling of asbestos-treated MeT5A cell line reveals novel pathways implicated in asbestos response.
Abstract Occupational and environmental asbestos exposure is the main determinant of malignant pleural mesothelioma (MPM), however, the mechanisms by which its fibres contribute to cell toxicity and transformation are not completely clear. Aberrant DNA methylation is a common event in cancer but epigenetic modifications involved specifically in MPM carcinogenesis need to be better clarified. To investigate asbestos-induced DNA methylation and gene expression changes, we treated Met5A mesothelial cells with different concentrations of crocidolite and chrysotile asbestos (0.5 ÷ 5.0 µg...
Source: Archives of Toxicology - March 9, 2018 Category: Toxicology Authors: Casalone E, Allione A, Viberti C, Pardini B, Guarrera S, Betti M, Dianzani I, Aldieri E, Matullo G Tags: Arch Toxicol Source Type: research

In utero and lactational exposure to BDE-47 promotes obesity development in mouse offspring fed a high-fat diet: impaired lipid metabolism and intestinal dysbiosis.
In this study, we investigated the effects of in utero and lactational exposure to BDE-47 on the progression of obesity and metabolic dysfunction in a diet-induced obesity model. Pregnant ICR mice were treated via oral gavage with low doses of BDE-47 (0, 0.002, and 0.2 mg/kg body weight) from gestational day 6 to postnatal day 21. After weaning, male offspring were fed an AIN93-based normal diet (ND) or high-fat diet (HFD: 60% calories from fat) for 14 weeks. We examined body weight, liver weight, histopathology, blood biochemistry, gene expression, and serum metabolic changes. A combination of 16S rRNA gene sequ...
Source: Archives of Toxicology - March 9, 2018 Category: Toxicology Authors: Wang D, Yan J, Teng M, Yan S, Zhou Z, Zhu W Tags: Arch Toxicol Source Type: research

Dynamic imaging of adaptive stress response pathway activation for prediction of drug induced liver injury.
Abstract Drug-induced liver injury remains a concern during drug treatment and development. There is an urgent need for improved mechanistic understanding and prediction of DILI liabilities using in vitro approaches. We have established and characterized a panel of liver cell models containing mechanism-based fluorescent protein toxicity pathway reporters to quantitatively assess the dynamics of cellular stress response pathway activation at the single cell level using automated live cell imaging. We have systematically evaluated the application of four key adaptive stress pathway reporters for the prediction of D...
Source: Archives of Toxicology - March 3, 2018 Category: Toxicology Authors: Wink S, Hiemstra SW, Huppelschoten S, Klip JE, van de Water B Tags: Arch Toxicol Source Type: research

Perfluorooctanoic acid (PFOA) exposure promotes proliferation, migration and invasion potential in human breast epithelial cells.
Abstract Despite significant advances in early detection and treatment, breast cancer remains a major cause of morbidity and mortality. Perfluorooctanoic acid (PFOA) is a suspected endocrine disruptor and a common environmental pollutant associated with various diseases including cancer. However, the effects of PFOA and its mechanisms of action on hormone-responsive cells remain unclear. Here, we explored the potential tumorigenic activity of PFOA (100 nM-1 mM) in human breast epithelial cells (MCF-10A). MCF-10A cells exposed to 50 and 100 µM PFOA demonstrated a higher growth rate compared to ...
Source: Archives of Toxicology - March 3, 2018 Category: Toxicology Authors: Pierozan P, Jerneren F, Karlsson O Tags: Arch Toxicol Source Type: research

New interplay between interstitial and alveolar macrophages explains pulmonary alveolar proteinosis (PAP) induced by indium tin oxide particles.
Abstract Occupational exposure to indium tin oxide (ITO) particles has been associated with the development of severe lung diseases, including pulmonary alveolar proteinosis (PAP). The mechanisms of this lung toxicity remain unknown. Here, we reveal the respective roles of resident alveolar (Siglec-Fhigh AM) and recruited interstitial (Siglec-Flow IM) macrophages contributing in concert to the development of PAP. In mice treated with ITO particles, PAP is specifically associated with IL-1α (not GM-CSF) deficiency and Siglec-Fhigh AM (not Siglec-Flow IM) depletion. Mechanistically, ITO particles are preferent...
Source: Archives of Toxicology - February 26, 2018 Category: Toxicology Authors: Huaux F, De Gussem V, Lebrun A, Yakoub Y, Palmai-Pallag M, Ibouraadaten S, Uwambayinema F, Lison D Tags: Arch Toxicol Source Type: research

The German REACH Congress 2016: a workshop report.
Abstract 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 informa...
Source: Archives of Toxicology - February 17, 2018 Category: Toxicology Authors: Reihlen A, Jepsen D, Broschinski L, Luch A, Schulte A Tags: Arch Toxicol Source Type: research

Tissue distribution of gold and silver after subacute intravenous injection of co-administered gold and silver nanoparticles of similar sizes.
In conclusion, AgNPs and AuNPs showed different toxicokinetic properties and the mixed administration of AgNPs with AuNPs resulted in mutual reduction of their tissue distribution which appeared to be due to competitive inhibition. Furthermore, this subacute intravenous injection study has suggested that these nanoparticles were distributed to the organs in particulate instead of ionic forms. PMID: 29450565 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - February 15, 2018 Category: Toxicology Authors: Lee JH, Sung JH, Ryu HR, Song KS, Song NW, Park HM, Shin BS, Ahn K, Gulumian M, Faustman EM, Yu IJ Tags: Arch Toxicol Source Type: research

Vocalization as a novel endpoint of atypical attachment behavior in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed infant mice.
Abstract 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. Therefore, we studied the impact of di...
Source: Archives of Toxicology - February 14, 2018 Category: Toxicology Authors: Kimura E, Tohyama C Tags: Arch Toxicol Source Type: research

The role of unfolded protein response and ER-phagy in quantum dots-induced nephrotoxicity: an in vitro and in vivo study.
Abstract 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. And CdTe-QDs (30-60 nM...
Source: Archives of Toxicology - February 12, 2018 Category: Toxicology Authors: Jiang S, Lin Y, Yao H, Yang C, Zhang L, Luo B, Lei Z, Cao L, Lin N, Liu X, Lin Z, He C Tags: Arch Toxicol Source Type: research

Maternal NO2 exposure induces cardiac hypertrophy in male offspring via ROS-HIF-1 α transcriptional regulation and aberrant DNA methylation modification of Csx/Nkx2.5.
Maternal NO2 exposure induces cardiac hypertrophy in male offspring via ROS-HIF-1α transcriptional regulation and aberrant DNA methylation modification of Csx/Nkx2.5. Arch Toxicol. 2018 Feb 07;: Authors: Zhang Y, Yan W, Ji X, Yue H, Li G, Sang N Abstract 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 mat...
Source: Archives of Toxicology - February 7, 2018 Category: Toxicology Authors: Zhang Y, Yan W, Ji X, Yue H, Li G, Sang N Tags: Arch Toxicol Source Type: research

A novel genotoxin-specific qPCR array based on the metabolically competent human HepaRG ™ cell line as a rapid and reliable tool for improved in vitro hazard assessment.
A novel genotoxin-specific qPCR array based on the metabolically competent human HepaRG™ cell line as a rapid and reliable tool for improved in vitro hazard assessment. Arch Toxicol. 2018 Feb 06;: Authors: Ates G, Mertens B, Heymans A, Verschaeve L, Milushev D, Vanparys P, Roosens NHC, De Keersmaecker SCJ, Rogiers V, Doktorova TY Abstract 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, ...
Source: Archives of Toxicology - February 6, 2018 Category: Toxicology Authors: Ates G, Mertens B, Heymans A, Verschaeve L, Milushev D, Vanparys P, Roosens NHC, De Keersmaecker SCJ, Rogiers V, Doktorova TY Tags: Arch Toxicol Source Type: research

Biomarker monitoring for food contaminants.
PMID: 29411057 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - February 6, 2018 Category: Toxicology Authors: Bolt HM Tags: Arch Toxicol Source Type: research

New mechanistic insights on the metabolic-disruptor role of chlorpyrifos in apoE mice: a focus on insulin- and leptin-signalling pathways.
Colomina MT Abstract 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. We determined the express...
Source: Archives of Toxicology - February 5, 2018 Category: Toxicology Authors: Peris-Sampedro F, Blanco J, Cabré M, Basaure P, Guardia-Escote L, Domingo JL, Sánchez DJ, Colomina MT Tags: Arch Toxicol Source Type: research