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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

Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells.
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. We also identified 58 deregulated genes consisting of 33 upregulated and 25 downregulated genes in hPSC-CMs after ETP treatment. Gene ontology (GO) and pathway analysis showed that most upregulated genes are enriched in GO categories like positive regulation o...
Source: Archives of Toxicology - February 3, 2018 Category: Toxicology Authors: Nemade H, Chaudhari U, Acharya A, Hescheler J, Hengstler JG, Papadopoulos S, Sachinidis A Tags: Arch Toxicol Source Type: research

Proteomic alterations of brain subcellular organelles caused by low-dose copper exposure: implication for Alzheimer's disease.
Abstract 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-hydroxyg...
Source: Archives of Toxicology - January 30, 2018 Category: Toxicology Authors: Yu H, Wang D, Zou L, Zhang Z, Xu H, Zhu F, Ren X, Xu B, Yuan J, Liu J, Spencer PS, Yang X Tags: Arch Toxicol Source Type: research

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.
This study is the first to prove the suitability of lymphocyte surface markers for sensitization testing and potency assessment. PMID: 29380012 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 30, 2018 Category: Toxicology Authors: Frombach J, Sonnenburg A, Krapohl BD, Zuberbier T, Peiser M, Stahlmann R, Schreiner M Tags: Arch Toxicol Source Type: research

Effects of bisphenol A on ovarian follicular development and female germline stem cells.
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. Additionally, the numbers of primordial follicles, primary follicles, and corpus luteum (CL) were significantly reduced at high BPA concentrations. Interestingly, the number of FGSCs was remarkably reduced in BPA-treated ovaries....
Source: Archives of Toxicology - January 29, 2018 Category: Toxicology Authors: Zhu X, Tian GG, Yu B, Yang Y, Wu J Tags: Arch Toxicol Source Type: research

Irritant-induced asthma to hypochlorite in mice due to impairment of the airway barrier.
Abstract 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.p. TREATMENT: After a recovery peri...
Source: Archives of Toxicology - January 24, 2018 Category: Toxicology Authors: Van Den Broucke S, Pollaris L, Vande Velde G, Verbeken E, Nemery B, Vanoirbeek J, Hoet P Tags: Arch Toxicol Source Type: research

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.
Abstract 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...
Source: Archives of Toxicology - January 24, 2018 Category: Toxicology Authors: Reed L, Mrizova I, Barta F, Indra R, Moserova M, Kopka K, Schmeiser HH, Wolf CR, Henderson CJ, Stiborova M, Phillips DH, Arlt VM Tags: Arch Toxicol Source Type: research

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.
Abstract 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...
Source: Archives of Toxicology - January 23, 2018 Category: Toxicology Authors: Malik DE, David RM, Gooderham NJ Tags: Arch Toxicol Source Type: research

The development of an in vitro Pig-a assay in L5178Y cells.
In conclusion, this in vitro Pig-a assay could complement the in vivo version, and follow up weak Ames positives and late-stage human metabolites or impurities. PMID: 29362862 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 23, 2018 Category: Toxicology Authors: David R, Talbot E, Allen B, Wilson A, Arshad U, Doherty A Tags: Arch Toxicol Source Type: research

Innovative organotypic in vitro models for safety assessment: aligning with regulatory requirements and understanding models of the heart, skin, and liver as paradigms.
Abstract 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. Accepted methods for gathering the information required by ...
Source: Archives of Toxicology - January 23, 2018 Category: Toxicology Authors: Pridgeon CS, Schlott C, Wong MW, Heringa MB, Heckel T, Leedale J, Launay L, Gryshkova V, Przyborski S, Bearon RN, Wilkinson EL, Ansari T, Greenman J, Hendriks DFG, Gibbs S, Sidaway J, Sison-Young RL, Walker P, Cross MJ, Park BK, Goldring CEP Tags: Arch Toxicol Source Type: research

Tacrolimus-induced nephrotoxicity in mice is associated with microRNA deregulation.
In conclusion, this study suggests for the first time that miRNAs, especially fibromiRs, participate to Tacrolimus-induced nephrotoxic effects. Therefore, targeting miRNAs may be a new therapeutic option to counteract Tacrolimus deleterious effects on kidney. PMID: 29362864 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 23, 2018 Category: Toxicology Authors: Vandenbussche C, Van der Hauwaert C, Dewaeles E, Franczak J, Hennino MF, Gnemmi V, Savary G, Tavernier Q, Nottet N, Paquet A, Perrais M, Blum D, Mari B, Pottier N, Glowacki F, Cauffiez C Tags: Arch Toxicol Source Type: research

Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through disruption of co-activator recruitment: experimental and computational studies.
Abstract As a potential endocrine disruptor, tris(2,3-dibromopropyl) isocyanurate (TBC) has previously been demonstrated to reduce expression of estrogen-dependent vitellogenin (vtg) mRNA in adult zebrafish. However, the underlying toxicity pathways and molecular mechanisms involved in TBC-induced endocrine disruption remain elusive. In the current study, E-Screen and MVLN assays were employed to explore the potential anti-estrogenic effects of TBC via the estrogen receptor α (ERα)-mediated signaling pathway. Within a dose range between 1 × 10- 9 and 1 × 1...
Source: Archives of Toxicology - January 22, 2018 Category: Toxicology Authors: Cao H, Li X, Zhang W, Wang L, Pan Y, Zhou Z, Chen M, Zhang A, Liang Y, Song M Tags: Arch Toxicol Source Type: research

Identification of approved drugs as potent inhibitors of pregnane X receptor activation with differential receptor interaction profiles.
In conclusion, we here have identified two approved drugs as novel potent PXR inhibitors with differential receptor interaction profiles and gene selectivity in primary human hepatocytes. PMID: 29356861 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 22, 2018 Category: Toxicology Authors: Burk O, Kuzikov M, Kronenberger T, Jeske J, Keminer O, Thasler WE, Schwab M, Wrenger C, Windshügel B Tags: Arch Toxicol Source Type: research

Flame retardants, hexabromocyclododecane (HCBD) and tetrabromobisphenol a (TBBPA), alter secretion of tumor necrosis factor alpha (TNF α) from human immune cells.
Flame retardants, hexabromocyclododecane (HCBD) and tetrabromobisphenol a (TBBPA), alter secretion of tumor necrosis factor alpha (TNFα) from human immune cells. Arch Toxicol. 2018 Jan 22;: Authors: Yasmin S, Whalen M Abstract 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 interl...
Source: Archives of Toxicology - January 22, 2018 Category: Toxicology Authors: Yasmin S, Whalen M Tags: Arch Toxicol Source Type: research

Highlight report: 'Big data in the 3R's: outlook and recommendations', a roundtable summary.
PMID: 29340744 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 16, 2018 Category: Toxicology Authors: Mahony C, Currie R, Daston G, Kleinstreuer N, van de Water B Tags: Arch Toxicol Source Type: research

Reply to Zamani and Hassanian-Moghaddam, 2017: being specific and targeting disease-causing pathology matter in therapeutics.
PMID: 29332132 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 13, 2018 Category: Toxicology Authors: Asghari MH, Moloudizargari M, Abdollahi M Tags: Arch Toxicol Source Type: research

Correction to: Selective determination of mandelic acid in urine using molecularly imprinted polymer in microextraction by packed sorbent.
Abstract In the original publication of the article, there is an error in Fig. 2c. The authors would like to correct this error and the corrected version of Fig. 2c is as follow. PMID: 29308533 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 8, 2018 Category: Toxicology Authors: Soleimani E, Bahrami A, Afkhami A, Shahna FG Tags: Arch Toxicol Source Type: research

Exposure assessment of process-related contaminants in food by biomarker monitoring.
d G Abstract Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitate...
Source: Archives of Toxicology - January 4, 2018 Category: Toxicology Authors: Rietjens IMCM, Dussort P, Günther H, Hanlon P, Honda H, Mally A, O'Hagan S, Scholz G, Seidel A, Swenberg J, Teeguarden J, Eisenbrand G Tags: Arch Toxicol Source Type: research

The formation of estrogen-like tamoxifen metabolites and their influence on enzyme activity and gene expression of ADME genes.
Mürdter TE Abstract Tamoxifen, a standard therapy for breast cancer, is metabolized to compounds with anti-estrogenic as well as estrogen-like action at the estrogen receptor. Little is known about the formation of estrogen-like metabolites and their biological impact. Thus, we characterized the estrogen-like metabolites tamoxifen bisphenol and metabolite E for their metabolic pathway and their influence on cytochrome P450 activity and ADME gene expression. The formation of tamoxifen bisphenol and metabolite E was studied in human liver microsomes and Supersomes™. Cellular metabolism and impact on CYP e...
Source: Archives of Toxicology - December 28, 2017 Category: Toxicology Authors: Johänning J, Kröner P, Thomas M, Zanger UM, Nörenberg A, Eichelbaum M, Schwab M, Brauch H, Schroth W, Mürdter TE Tags: Arch Toxicol Source Type: research

Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts.
Abstract Experimental and/or epidemiological studies suggest that prenatal exposure to bisphenol A (BPA) may delay fetal lung development and maturation and increase the susceptibility to childhood respiratory disease. However, the underlying mechanisms remain to be elucidated. In our previous study with cultured human fetal lung fibroblasts (HFLF), we demonstrated that 24-h exposure to 1 and 100 µM BPA increased GPR30 protein in the nuclear fraction. Exposure to 100 μM BPA had no effects on cell viability, but increased cytoplasmic expression of ERβ and release of GDF-15, as well as decrea...
Source: Archives of Toxicology - December 23, 2017 Category: Toxicology Authors: Mahemuti L, Chen Q, Coughlan MC, Qiao C, Chepelev NL, Florian M, Dong D, Woodworth RG, Yan J, Cao XL, Scoggan KA, Jin X, Willmore WG Tags: Arch Toxicol Source Type: research

Nanomaterials: certain aspects of application, risk assessment and risk communication.
Luch A Abstract Development and market introduction of new nanomaterials trigger the need for an adequate risk assessment of such products alongside suitable risk communication measures. Current application of classical and new nanomaterials is analyzed in context of regulatory requirements and standardization for chemicals, food and consumer products. The challenges of nanomaterial characterization as the main bottleneck of risk assessment and regulation are presented. In some areas, e.g., quantification of nanomaterials within complex matrices, the establishment and adaptation of analytical techniques such as l...
Source: Archives of Toxicology - December 22, 2017 Category: Toxicology Authors: Laux P, Tentschert J, Riebeling C, Braeuning A, Creutzenberg O, Epp A, Fessard V, Haas KH, Haase A, Hund-Rinke K, Jakubowski N, Kearns P, Lampen A, Rauscher H, Schoonjans R, Störmer A, Thielmann A, Mühle U, Luch A Tags: Arch Toxicol Source Type: research

Combination of etoposide and fisetin results in anti-cancer efficiency against osteosarcoma cell models.
In conclusion, these results show that the combination of fisetin with etoposide has higher anti-proliferative effects in osteosarcoma associated with cell cycle arrest, allowing the use of lower doses of the chemotherapeutic agent, which has important implications for osteosarcoma treatment. PMID: 29270805 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - December 21, 2017 Category: Toxicology Authors: Ferreira de Oliveira JMP, Pacheco AR, Coutinho L, Oliveira H, Pinho S, Almeida L, Fernandes E, Santos C Tags: Arch Toxicol Source Type: research

Mesenchyme-derived factors enhance preneoplastic growth by non-genotoxic carcinogens in rat liver.
In conclusion, our findings reveal profound effects of two prototypical NGC on the hepatic mesenchyme. The resulting release of factors, which suppress apoptosis and/or enhance cell replication preferentially in cancer prestages, appears to be crucial for tumor promotion by NGC in the liver. PMID: 29270806 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - December 21, 2017 Category: Toxicology Authors: Nejabat M, Riegler T, Reitinger T, Subosits S, Römer M, Eichner J, Bilban M, Zell A, Huber WW, Schulte-Hermann R, Grasl-Kraupp B Tags: Arch Toxicol Source Type: research

A methodology for the assessment of inhalation exposure to aluminium from antiperspirant sprays.
Abstract Inhalative exposure can occur accidentally when using cosmetic spray products. Usually, a tiered approach is applied for exposure assessment, starting with rather conservative, simplistic calculation models that may be improved with measured data and more refined modelling. Here we report on an advanced methodology to mimic in-use conditions for antiperspirant spray products to provide a more accurate estimate of the amount of aluminium possibly inhaled and taken up systemically, thus contributing to the overall body burden. Four typical products were sprayed onto a skin surrogate in defined rooms. For al...
Source: Archives of Toxicology - December 21, 2017 Category: Toxicology Authors: Schwarz K, Pappa G, Miertsch H, Scheel J, Koch W Tags: Arch Toxicol Source Type: research

Lanthanum chloride reduces lactate production in primary culture rat cortical astrocytes and suppresses primary co-culture rat cortical astrocyte-neuron lactate transport.
This study provides some novel clues for clarifying the mechanism underlying the neurotoxicity of La. PMID: 29264619 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - December 20, 2017 Category: Toxicology Authors: Sun Y, Yang J, Hu X, Gao X, Li Y, Yu M, Liu S, Lu X, Jin C, Wu S, Cai Y Tags: Arch Toxicol Source Type: research

Resveratrol protects primary cilia integrity of human mesenchymal stem cells from cigarette smoke to improve osteogenic differentiation in vitro.
Abstract Several studies have explored the negative effects of cigarette smoke on bone healing; however, the complex pathogenesis still remains unclear. One crucial and primary factor determining effective fracture repair is the recruitment and differentiation of mesenchymal stem cells (MSCs) into bone-forming cells. Recently, primary cilia, microtubule-based sensory organelles, have been shown to be critical in lineage commitment and differentiation of MSCs. Our present study indicates that exposure to cigarette smoke extract (CSE 0.1-10%) impaired osteogenic differentiation of human mesenchymal stem cell line (S...
Source: Archives of Toxicology - December 20, 2017 Category: Toxicology Authors: Sreekumar V, Aspera-Werz R, Ehnert S, Strobel J, Tendulkar G, Heid D, Schreiner A, Arnscheidt C, Nussler AK Tags: Arch Toxicol Source Type: research

RE: Comment on Asghari et al. 2017: On the mechanisms of melatonin in protection of aluminum phosphide cardiotoxicity.
PMID: 29255933 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - December 18, 2017 Category: Toxicology Authors: Zamani N, Hassanian-Moghaddam H Tags: Arch Toxicol Source Type: research

Towards a generic physiologically based kinetic model to predict in vivo uterotrophic responses in rats by reverse dosimetry of in vitro estrogenicity data.
Abstract Physiologically based kinetic (PBK) modelling-based reverse dosimetry is a promising tool for the prediction of in vivo developmental toxicity using in vitro concentration-response data. In the present study, the potential of this approach to predict the dose-dependent increase of uterus weight in rats upon exposure to estrogenic chemicals was assessed. In vitro concentration-response data of 17β-estradiol (E2) and bisphenol A (BPA) obtained in the MCF-7/BOS proliferation assay, the U2OS ER-CALUX assay and the yeast estrogen screen (YES) assay, were translated into in vivo dose-response data in rat, ...
Source: Archives of Toxicology - December 12, 2017 Category: Toxicology Authors: Zhang M, van Ravenzwaay B, Fabian E, Rietjens IMCM, Louisse J Tags: Arch Toxicol Source Type: research

Update to 'Re: Tarazona et al. (2017): glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC. doi: 10.1007/s00204-017-1962-5'.
PMID: 29230486 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - December 11, 2017 Category: Toxicology Authors: Portier CJ, Clausing P Tags: Arch Toxicol Source Type: research

Activation of intestinal GR-FXR and PPAR α-UGT signaling exacerbates ibuprofen-induced enteropathy in mice.
Activation of intestinal GR-FXR and PPARα-UGT signaling exacerbates ibuprofen-induced enteropathy in mice. Arch Toxicol. 2017 Dec 08;: Authors: Lu Z, Lu Y, Wang X, Wang F, Zhang Y Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury (enteropathy) occurs in about two-thirds of regular NSAID users. To date, there is no proven-effective treatment for NSAID enteropathy, and its underlying mechanism remains obscure. The present study showed that glucocorticoids are an important determinant of NSAID enteropathy. High dose dexamethasone (DEX, 75 mg/kg) markedly ex...
Source: Archives of Toxicology - December 8, 2017 Category: Toxicology Authors: Lu Z, Lu Y, Wang X, Wang F, Zhang Y Tags: Arch Toxicol Source Type: research

MiR-26a functions as a tumor suppressor in ambient particulate matter-bound metal-triggered lung cancer cell metastasis by targeting LIN28B-IL6-STAT3 axis.
In this study, human lung adenocarcinoma A549 cells were treated with serial concentrations of water-extracted PM10 (WE-PM10) collected from Beijing, China. Our results showed that exposure to 25 and 50 μg/ml of WE-PM10 for 48 h significantly suppressed miR-26a to upregulate lin-28 homolog B (LIN28B), and in turn activated interleukin 6 (IL6) and signal transducer and activator of transcription 3 (STAT3) in A549 cells, subsequently contributing to enhanced epithelial-mesenchymal transition and accelerated migration and invasion. In vivo pulmonary colonization assay further indicated that WE-PM10 enhanced the m...
Source: Archives of Toxicology - December 8, 2017 Category: Toxicology Authors: Lu YY, Lin Y, Ding DX, Su S, Chi QQ, Zhang YC, Sun J, Zhang X, Zhu HM, Huang QS, Chi YL, Ye GZ, Tao S, Dong SJ Tags: Arch Toxicol Source Type: research

Cadmium favors F-actin depolymerization in rat renal mesangial cells by site-specific, disulfide-based dimerization of the CAP1 protein.
Abstract Cadmium is a toxic metal that produces oxidative stress and has been shown to disrupt the actin cytoskeleton in rat renal mesangial cells (RMC). In a survey of proteins that might undergo Cd2+-dependent disulfide crosslinking, we identified the adenylyl cyclase-associated protein, CAP1, as undergoing a dimerization in response to Cd2+ (5-40 µM) that was sensitive to disulfide reducing agents, was reproduced by the disulfide crosslinking agent diamide, and was shown by site-directed mutagenesis to involve the Cys29 residue of the protein. Reactive oxygen species are not involved in the thiol oxi...
Source: Archives of Toxicology - December 8, 2017 Category: Toxicology Authors: Liu Y, Xiao W, Shinde M, Field J, Templeton DM Tags: Arch Toxicol Source Type: research

Use of HuH6 and other human-derived hepatoma lines for the detection of genotoxins: a new hope for laboratory animals?
asmüller S Abstract Cell lines which are currently used in genotoxicity tests lack enzymes which activate/detoxify mutagens. Therefore, rodent-derived liver preparations are used which reflect their metabolism in humans only partly; as a consequence misleading results are often obtained. Previous findings suggest that certain liver cell lines express phase I/II enzymes and detect promutagens without activation; however, their use is hampered by different shortcomings. The aim of this study was the identification of a suitable cell line. The sensitivity of twelve hepatic cell lines was investigated in single c...
Source: Archives of Toxicology - December 7, 2017 Category: Toxicology Authors: Waldherr M, Mišík M, Ferk F, Tomc J, Žegura B, Filipič M, Mikulits W, Mai S, Haas O, Huber WW, Haslinger E, Knasmüller S Tags: Arch Toxicol Source Type: research

Protective effect of cadmium-induced autophagy in rat renal mesangial cells.
Abstract Cadmium damages renal cells, and in particular may cause mesangial cell death by necrosis or apoptosis, depending on exposure conditions in cultured cells. However, there is an uncertainty as to whether Cd2+-induced autophagy can protect mesangial cells against these other mechanisms of cell death. We have used autophagy-incompetent mouse embryonic fibroblast (MEF) cells lacking the Atg16 gene, as well as cultured rat mesangial cells (RMC) in which Atg16 has been silenced, to examine this issue. Measuring the processing of LC3-I to LC3-II and expression of sequestosome-1 (p62), we define conditions under ...
Source: Archives of Toxicology - December 7, 2017 Category: Toxicology Authors: Fujishiro H, Liu Y, Ahmadi B, Templeton DM Tags: Arch Toxicol Source Type: research

An adverse outcome pathway for parkinsonian motor deficits associated with mitochondrial complex I inhibition.
Abstract Epidemiological studies have observed an association between pesticide exposure and the development of Parkinson's disease, but have not established causality. The concept of an adverse outcome pathway (AOP) has been developed as a framework for the organization of available information linking the modulation of a molecular target [molecular initiating event (MIE)], via a sequence of essential biological key events (KEs), with an adverse outcome (AO). Here, we present an AOP covering the toxicological pathways that link the binding of an inhibitor to mitochondrial complex I (i.e., the MIE) with the onset ...
Source: Archives of Toxicology - December 5, 2017 Category: Toxicology Authors: Terron A, Bal-Price A, Paini A, Monnet-Tschudi F, Bennekou SH, EFSA WG EPI1 Members, Leist M, Schildknecht S Tags: Arch Toxicol Source Type: research

Monitoring cytochrome P450 activity in living hepatocytes by chromogenic substrates in response to drug treatment or during cell maturation.
l S Abstract The metabolic activity of hepatocytes is a central prerequisite for drug activity and a key element in drug-drug interaction. This central role in metabolism largely depends on the activity of the cytochrome P450 (CYP450) enzyme family, which is not only dependent on liver cell maturation but is also controlled in response to drug and chemical exposure. Here, we report the use of VividDye fluorogenic CYP450 substrates to directly measure and continuously monitor metabolic activity in living hepatocytes. We observed time- and dose-dependent correlation in response to established and putative CYP450 ind...
Source: Archives of Toxicology - December 5, 2017 Category: Toxicology Authors: Theobald J, Cheng X, Ghanem A, Gaitantzi H, Song G, Klipp E, Wodke J, Becker H, Mrowka R, Breitkopf-Heinlein K, Dooley S, Wölfl S Tags: Arch Toxicol Source Type: research

Gestational exposure to inorganic arsenic (iAs3+) alters glutamate disposition in the mouse hippocampus and ionotropic glutamate receptor expression leading to memory impairment.
Mercado K, Gonsebatt ME Abstract Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking wat...
Source: Archives of Toxicology - December 4, 2017 Category: Toxicology Authors: Nelson-Mora J, Escobar ML, Rodríguez-Durán L, Massieu L, Montiel T, Rodríguez VM, Hernández-Mercado K, Gonsebatt ME Tags: Arch Toxicol Source Type: research

Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity.
Abstract Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (...
Source: Archives of Toxicology - December 4, 2017 Category: Toxicology Authors: Nourozi MA, Neghab M, Bazzaz JT, Nejat S, Mansoori Y, Shahtaheri SJ Tags: Arch Toxicol Source Type: research

The PPAR α-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions.
The PPARα-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions. Arch Toxicol. 2017 Dec 02;: Authors: Corton JC, Peters JM, Klaunig JE Abstract A number of industrial chemicals and therapeutic agents cause liver tumors in rats and mice by activating the nuclear receptor peroxisome proliferator-activated receptor α (PPARα). The molecular and cellular events by which PPARα activators induce rodent hepatocarcinogenesis have been extensively studied elucidating a number of consistent mechanistic changes linked to the increased incidence of liver...
Source: Archives of Toxicology - December 2, 2017 Category: Toxicology Authors: Corton JC, Peters JM, Klaunig JE Tags: Arch Toxicol Source Type: research

PARP1 protects from benzo[a]pyrene diol epoxide-induced replication stress and mutagenicity.
In conclusion, this study demonstrates a profound role of PARylation in BPDE-induced genotoxic stress response with significant functional consequences and potential relevance with regard to B[a]P-induced cancer risks. PMID: 29196784 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - December 1, 2017 Category: Toxicology Authors: Fischer JMF, Zubel T, Jander K, Fix J, Trussina IREA, Gebhard D, Bergemann J, Bürkle A, Mangerich A Tags: Arch Toxicol Source Type: research

Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate fluoride toxicity in ameloblasts responsible for enamel formation.
Abstract Low-dose fluoride is an effective caries prophylactic, but high-dose fluoride is an environmental health hazard that causes skeletal and dental fluorosis. Treatments to prevent fluorosis and the molecular pathways responsive to fluoride exposure remain to be elucidated. Previously we showed that fluoride activates SIRT1 as an adaptive response to protect cells. Here, we demonstrate that fluoride induced p53 acetylation (Ac-p53) [Lys379], which is a SIRT1 deacetylation target, in ameloblast-derived LS8 cells in vitro and in enamel organ in vivo. Here we assessed SIRT1 function on fluoride-induced Ac-p53 fo...
Source: Archives of Toxicology - November 28, 2017 Category: Toxicology Authors: Suzuki M, Ikeda A, Bartlett JD Tags: Arch Toxicol Source Type: research

Highlight report: gene dose response in N-acetylation capacity.
PMID: 29185025 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - November 28, 2017 Category: Toxicology Authors: Selinski S Tags: Arch Toxicol Source Type: research

Highlight report: prediction of drug induced liver injury (DILI) with human hepatocytes in vitro.
PMID: 29181616 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - November 27, 2017 Category: Toxicology Authors: Albrecht W Tags: Arch Toxicol Source Type: research