7,142 results match your criteria Archives of Toxicology[Journal]


Pulmonary and pleural toxicity of potassium octatitanate fibers, rutile titanium dioxide nanoparticles, and MWCNT-7 in male Fischer 344 rats.

Arch Toxicol 2019 Feb 13. Epub 2019 Feb 13.

Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Potassium octatitanate (KO·8TiO, POT) fibers are used as an alternative to asbestos. Their shape and biopersistence suggest that they are possibly carcinogenic. However, inhalation studies have shown that respired POT fibers have little carcinogenic potential. Read More

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http://dx.doi.org/10.1007/s00204-019-02410-zDOI Listing
February 2019

Lack of adverse effects in subchronic and chronic toxicity/carcinogenicity studies on the glyphosate-resistant genetically modified maize NK603 in Wistar Han RCC rats.

Arch Toxicol 2019 Feb 12. Epub 2019 Feb 12.

Institute for Biosafety in Plant Biotechnology, Julius Kühn-Institut (JKI), Federal Research Centre for Cultivated Plants, Erwin-Baur-Str. 27, 06484, Quedlinburg, Germany.

In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Read More

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http://dx.doi.org/10.1007/s00204-019-02400-1DOI Listing
February 2019

Urinary metabolites of the UV filter octocrylene in humans as biomarkers of exposure.

Arch Toxicol 2019 Feb 9. Epub 2019 Feb 9.

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.

Octocrylene (OC) is a UV filter used in sun screens and other personal care products, but also in polymers and food contact materials for stabilization. In this study, we investigate human OC metabolism and urinary excretion after oral dosage of approx. 5 mg OC [≙ 61. Read More

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http://dx.doi.org/10.1007/s00204-019-02408-7DOI Listing
February 2019
1 Read
5.980 Impact Factor

Silica-coated magnetic nanoparticles induce glucose metabolic dysfunction in vitro via the generation of reactive oxygen species.

Arch Toxicol 2019 Feb 8. Epub 2019 Feb 8.

Department of Physiology, Department of Biomedical Sciences, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, 16499, Suwon, Republic of Korea.

Nanoparticles are a useful material in biomedicine given their unique properties and biocompatibility; however, there is increasing concern regarding the potential toxicity of nanoparticles with respect to cell metabolism. Some evidence suggests that nanoparticles can disrupt glucose and energy homeostasis. In this study, we investigated the metabolomic, transcriptomic, and integrated effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO(RITC)] on glucose metabolism in human embryonic kidney 293 (HEK293) cells. Read More

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http://dx.doi.org/10.1007/s00204-019-02402-zDOI Listing
February 2019
2 Reads

Repetitive antidotal treatment is crucial in eliminating eye pathology, respiratory toxicity and death following whole-body VX vapor exposure in freely moving rats.

Arch Toxicol 2019 Feb 7. Epub 2019 Feb 7.

Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, 74100, Ness Ziona, Israel.

Exposure to the chemical warfare nerve agent VX is extremely toxic, causing severe cholinergic symptoms. If not appropriately treated, death ultimately ensues. Based on our previously described whole-body vapor exposure system, we characterized in detail the clinical outcome, including respiratory dynamics, typical of whole-body exposure to lethal doses of VX vapor in freely moving rats. Read More

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http://dx.doi.org/10.1007/s00204-019-02401-0DOI Listing
February 2019
1 Read

Toxicokinetics of N-ethyl-2-pyrrolidone and its metabolites in blood, urine and amniotic fluid of rats after oral administration.

Arch Toxicol 2019 Feb 7. Epub 2019 Feb 7.

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.

The toxicokinetics of N-ethyl-2-pyrrolidone (NEP), an embryotoxic organic solvent, has been studied in Sprague-Dawley rats after oral exposure. NEP and its metabolites 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI) were measured in plasma of pregnant and non-pregnant rats, and fetuses after NEP administration by gavage for 14 consecutive days at 50 mg/kg/day, and in plasma of non-pregnant rats after a single NEP administration. Additionally, amniotic fluid and 24-h urine samples of the pregnant rats were analyzed for NEP metabolites. Read More

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http://dx.doi.org/10.1007/s00204-019-02404-xDOI Listing
February 2019
5.980 Impact Factor

ABC transporters Mdr1a/1b, Bcrp1, Mrp2 and Mrp3 determine the sensitivity to PhIP/DSS-induced colon carcinogenesis and inflammation.

Arch Toxicol 2019 Jan 30. Epub 2019 Jan 30.

Division of Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is an abundant dietary carcinogen, formed during high-temperature cooking of meat. In this study, we investigated whether clinically relevant ATP-binding cassette (ABC) efflux transporters can modulate PhIP-induced colorectal carcinogenesis in vivo using wild-type (WT), Bcrp1; Mrp2; Mrp3 and Bcrp1; Mdr1a/b; Mrp2 mice. We used a physiological mouse model of colorectal cancer; a combination of a single high-dose oral PhIP administration (200 mg/kg), followed by administering a colonic inflammatory agent, dextran sodium sulfate (DSS), in drinking water for 7 days. Read More

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http://dx.doi.org/10.1007/s00204-019-02394-wDOI Listing
January 2019

Evaluation of inhaled low-dose formaldehyde-induced DNA adducts and DNA-protein cross-links by liquid chromatography-tandem mass spectrometry.

Arch Toxicol 2019 Jan 30. Epub 2019 Jan 30.

Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

As a widespread industrial chemical, formaldehyde carcinogenicity has been highly controversial. Meanwhile, formaldehyde is an essential metabolite in all living cells. Previously, we have demonstrated exogenous formaldehyde causes DNA adducts in a nonlinear manner between 0. Read More

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http://dx.doi.org/10.1007/s00204-019-02393-xDOI Listing
January 2019

Identification of interactions of binary variables associated with survival time using survivalFS.

Arch Toxicol 2019 Jan 29. Epub 2019 Jan 29.

Mathematical Institute, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.

Many medical studies aim to identify factors associated with a time to an event such as survival time or time to relapse. Often, in particular, when binary variables are considered in such studies, interactions of these variables might be the actual relevant factors for predicting, e.g. Read More

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http://dx.doi.org/10.1007/s00204-019-02398-6DOI Listing
January 2019

N-(2-Hydroxyethyl)-L-valyl-L-leucine in rat urine as a hydrolytic cleavage product of ethylene oxide adduct with globin.

Arch Toxicol 2019 Jan 21. Epub 2019 Jan 21.

Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Technická 1905, 166 28, Prague, Czech Republic.

Ethylene oxide (EO), a genotoxic industrial chemical and sterilant, forms covalent adducts with DNA and also with nucleophilic amino acids in proteins. The adduct with N-terminal valine in globin [N-(2-hydroxyethyl)valine (HEV)] has been used in biomonitoring of cumulative exposures to EO. Here we studied in rats the fate of EO-adducted N-termini of globin after life termination of the erythrocytes. Read More

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http://link.springer.com/10.1007/s00204-019-02388-8
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http://dx.doi.org/10.1007/s00204-019-02388-8DOI Listing
January 2019
4 Reads

Use of an in vitro-in silico testing strategy to predict inter-species and inter-ethnic human differences in liver toxicity of the pyrrolizidine alkaloids lasiocarpine and riddelliine.

Arch Toxicol 2019 Jan 19. Epub 2019 Jan 19.

Division of Toxicology, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, The Netherlands.

Lasiocarpine and riddelliine are pyrrolizidine alkaloids (PAs) known to cause liver toxicity. The aim of this study was to predict the inter-species and inter-ethnic human differences in acute liver toxicity of lasiocarpine and riddelliine using physiologically based kinetic (PBK) modelling based reverse dosimetry of in vitro toxicity data. The concentration-response curves of in vitro cytotoxicity of lasiocarpine and riddelliine defined in pooled human hepatocytes were translated to in vivo dose-response curves by PBK models developed using kinetic data obtained from incubations with pooled tissue fractions from Chinese and Caucasian individuals, providing PBK models for the average Chinese and average Caucasian, respectively. Read More

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http://dx.doi.org/10.1007/s00204-019-02397-7DOI Listing
January 2019
1 Read

Roles of mitochondrial fission inhibition in developmental fluoride neurotoxicity: mechanisms of action in vitro and associations with cognition in rats and children.

Arch Toxicol 2019 Jan 18. Epub 2019 Jan 18.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

Fluoride neurotoxicity is associated with mitochondrial disruption. Mitochondrial fission/fusion dynamics is crucial to maintain functional mitochondria, yet little is known about how fluoride perturbs this dynamics and whether such perturbation contributes to impaired neurodevelopment. Here in human neuroblastoma SH-SY5Y cells treated with sodium fluoride (NaF, 20, 40 and 60 mg/L), mitochondrial fission suppression exerted a central role in NaF-induced mitochondrial abnormalities and the resulting autophagy deficiency, apoptosis augmentation, and compromised neuronal survival. Read More

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http://dx.doi.org/10.1007/s00204-019-02390-0DOI Listing
January 2019
2 Reads
5.980 Impact Factor

Boron-exposed male workers in Turkey: no change in sperm Y:X chromosome ratio and in offspring's sex ratio.

Arch Toxicol 2019 Jan 18. Epub 2019 Jan 18.

Leibniz Research Center for Working Environment and Human Factors (IfADo), Ardey Str. 67, 44139, Dortmund, Germany.

Boron-associated shifts in sex ratios at birth were suggested earlier and attributed to a decrease in Y- vs. X-bearing sperm cells. As the matter is pivotal in the discussion of reproductive toxicity of boron/borates, re-investigation in a highly borate-exposed population was required. Read More

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http://dx.doi.org/10.1007/s00204-019-02391-zDOI Listing
January 2019
2 Reads

Chemosensitization of hepatocellular carcinoma cells to sorafenib by β-caryophyllene oxide-induced inhibition of ABC export pumps.

Arch Toxicol 2019 Jan 18. Epub 2019 Jan 18.

Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain.

Several ATP-binding cassette (ABC) proteins reduce intracellular concentrations of antitumor drugs and hence weaken the response of cancer cells to chemotherapy. Accordingly, the inhibition of these export pumps constitutes a promising strategy to chemosensitize highly chemoresistant tumors, such as hepatocellular carcinoma (HCC). Here, we have investigated the ability of β-caryophyllene oxide (CRYO), a naturally occurring sesquiterpene component of many essential oils, to inhibit, at non-toxic doses, ABC pumps and improve the response of HCC cells to sorafenib. Read More

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http://link.springer.com/10.1007/s00204-019-02395-9
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http://dx.doi.org/10.1007/s00204-019-02395-9DOI Listing
January 2019
5 Reads

Effects of cannabis tetrahydrocannabinol on endocannabinoid homeostasis in human placenta.

Arch Toxicol 2019 Jan 18. Epub 2019 Jan 18.

UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313, Porto, Portugal.

Cannabis use has become a hot topic in several countries due to the debate about its legalization for medical purposes. However, data are limited regarding adverse events, safety and potential impact on reproductive health. Cannabis consumption during pregnancy has been associated with gestational disorders such as preterm birth, intrauterine growth restriction, low birth weight and increased risk of miscarriage, though the underlying biochemical mechanisms are still unknown. Read More

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http://dx.doi.org/10.1007/s00204-019-02389-7DOI Listing
January 2019
1 Read

Learning, memory and the expression of cholinergic components in mice are modulated by the pesticide chlorpyrifos depending upon age at exposure and apolipoprotein E (APOE) genotype.

Arch Toxicol 2019 Jan 18. Epub 2019 Jan 18.

Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain.

Polymorphisms of the apolipoprotein E (APOE) gene differentially affect neurobiological functions and cognitive performance and confer different vulnerabilities to subclinical exposures to chlorpyrifos (CPF), a pesticide used worldwide. The data reported on this topic suggest a complex interaction between cholinergic signaling and the APOE genotype. To gain greater functional insight into this interaction, we evaluated spatial learning and memory and hippocampal cholinergic expression in young apoE3 and apoE4 transgenic mice exposed to CPF. Read More

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http://dx.doi.org/10.1007/s00204-019-02387-9DOI Listing
January 2019
1 Read

Distinct differences in the mechanisms of mucosal damage and γ-H2AX formation in the rat urinary bladder treated with o-toluidine and o-anisidine.

Arch Toxicol 2019 Jan 17. Epub 2019 Jan 17.

Division of Pathology, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, 210-9501, Japan.

Although aromatic amines are widely used as raw materials for dyes, some of them have been concerned about carcinogenicity in the urinary bladder. We examined early changes in histopathology and the formation of γ-H2AX, a biomarker of DNA damage, in the urinary bladder of rats to investigate the mechanisms of mucosal damage induced by monocyclic aromatic amines. 6-week-old male F344 rats were administered 0. Read More

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http://dx.doi.org/10.1007/s00204-019-02396-8DOI Listing
January 2019
2 Reads

Bituminous coal combustion and Xuan Wei Lung cancer: a review of the epidemiology, intervention, carcinogens, and carcinogenesis.

Arch Toxicol 2019 Jan 16. Epub 2019 Jan 16.

Li Ka Shing Faculty of Medicine, School of Public Health, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong SAR, China.

Indoor air pollution from bituminous coal combustion has been linked to the extremely high lung cancer rates of nonsmoking women in Xuan Wei County, Yunnan Province, China. Venting the smoke outdoors by installing chimneys was found to be effective at reducing the lung cancer risk in a cohort study of 21,232 farmers in central Xuan Wei. However, the lung cancer mortality rates in all 1. Read More

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http://dx.doi.org/10.1007/s00204-019-02392-yDOI Listing
January 2019
1 Read

Differential expression of cyclin-dependent kinases in the adult human retina in relation to CDK inhibitor retinotoxicity.

Arch Toxicol 2019 Jan 8. Epub 2019 Jan 8.

School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, UK.

Cyclin-dependent kinases (CDKs) are a family of kinases associated predominantly with cell cycle control, making CDK inhibitors interesting candidates for anti-cancer therapeutics. However, retinal toxicity (loss of photoreceptors) has been associated with CDK inhibitors, including the pan-CDK inhibitor AG-012896. The purpose of this research was to use a novel planar sectioning technique to determine CDK expression profiles in the ex vivo human retina with the aim of identifying isoforms responsible for CDK retinotoxicity. Read More

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http://dx.doi.org/10.1007/s00204-018-2376-8DOI Listing
January 2019
1 Read

Plausibility of microplastic uptake in a paper by Deng et al., Scientific reports 7:46687, 2017.

Arch Toxicol 2019 Jan 2;93(1):217-218. Epub 2019 Jan 2.

Department of Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.

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http://dx.doi.org/10.1007/s00204-018-2383-9DOI Listing
January 2019
2 Reads

Response to Uptake of microplastics and related health effects: a critical discussion of Deng et al., Scientific reports 7: 46687, 2017.

Arch Toxicol 2019 Jan 2;93(1):213-215. Epub 2019 Jan 2.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, Jiangsu, China.

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http://dx.doi.org/10.1007/s00204-018-2384-8DOI Listing
January 2019
1 Read

Importance of in vitro conditions for modeling the in vivo dose in humans by in vitro-in vivo extrapolation (IVIVE).

Arch Toxicol 2019 Jan 2. Epub 2019 Jan 2.

Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

In vitro studies are increasingly proposed to replace in vivo toxicity testing of substances. We set out to apply physiologically based pharmacokinetic (PBPK) modeling to predict the in vivo dose of amiodarone that leads to the same concentration-time profile in the supernatant and the cell lysate of cultured primary human hepatic cells (PHH). A PBPK human model was constructed based on the structure and tissue distribution of amiodarone in a rat model and using physiological human parameters. Read More

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http://dx.doi.org/10.1007/s00204-018-2382-xDOI Listing
January 2019
6 Reads

Sex-dependent effects of bisphenol A on type 1 diabetes development in non-obese diabetic (NOD) mice.

Arch Toxicol 2019 Jan 2. Epub 2019 Jan 2.

Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.

Type 1 diabetes (T1D) is an autoimmune disease caused by immune-mediated pancreatic β-cell destruction. The endocrine disrupting chemical bisphenol A (BPA) has widespread human exposure and can modulate immune function and the gut microbiome (GMB), which may contribute to the increasing T1D incidence worldwide. It was hypothesized that BPA had sex-dependent effects on T1D by modulating immune homeostasis and GMB. Read More

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http://dx.doi.org/10.1007/s00204-018-2379-5DOI Listing
January 2019
2 Reads

Effects of diisononyl phthalate (DiNP) on the endocannabinoid and reproductive systems of male gilthead sea bream (Sparus aurata) during the spawning season.

Arch Toxicol 2019 Jan 2. Epub 2019 Jan 2.

Dipartimento Scienze Della Vita e dell'Ambiente, Università Politecnica Delle Marche, Via Brecce Bianche, 60131, Ancona, Italy.

Diisononyl phthalate (DiNP) is a plasticizer used to improve plastic performance in a large variety of items which has been reported as an endocrine-disrupting chemical (EDC) in several organisms. The endocannabinoid system (ECS) is a cellular signaling system, whose functionality is tightly involved with reproductive function. The aim of the present study was the assessment of the effects of DiNP on the gonadal ECS and on the reproductive function of male gilthead sea bream Sparus aurata, an important marine aquacultured species in Europe, during the reproductive season. Read More

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http://link.springer.com/10.1007/s00204-018-2378-6
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http://dx.doi.org/10.1007/s00204-018-2378-6DOI Listing
January 2019
5 Reads

Ultrasensitivity dynamics of diverse aryl hydrocarbon receptor modulators in a hepatoma cell line.

Arch Toxicol 2018 Dec 19. Epub 2018 Dec 19.

Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.

The aryl hydrocarbon receptor (AhR) is a nuclear receptor that facilitates a wide transcriptional response and causes a variety of adaptive and maladaptive physiological functions. Such functions are entirely dependent on the type of ligand activating it, and therefore, the nuances in the activation of this receptor at the single-cell level have become a research interest for different pharmacological and toxicological applications. Here, we investigate the activation of the AhR by diverse classes of compounds in a Hepa1c1c7-based murine hepatoma cell line. Read More

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http://dx.doi.org/10.1007/s00204-018-2380-zDOI Listing
December 2018
1 Read

Oxime K203: a drug candidate for the treatment of tabun intoxication.

Arch Toxicol 2018 Dec 18. Epub 2018 Dec 18.

Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01, Hradec Králové, Czech Republic.

For over 60 years, researchers across the world have sought to deal with poisoning by nerve agents, the most toxic and lethal chemical weapons. To date, there is no efficient causal antidote with sufficient effect. Every trialed compound fails to fulfil one or more criteria (e. Read More

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http://link.springer.com/10.1007/s00204-018-2377-7
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http://dx.doi.org/10.1007/s00204-018-2377-7DOI Listing
December 2018
3 Reads

A simple approach for restoration of differentiation and function in cryopreserved human hepatocytes.

Arch Toxicol 2018 Dec 17. Epub 2018 Dec 17.

Department of Pharmacy and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Primary human hepatocytes are used in all facets of liver research, from in vitro studies of xenobiotic disposition and toxicity to the clinical management of liver failure. Unfortunately, cellular stress during isolation and cryopreservation causes a highly unpredictable loss of the ability to attach and form cell-matrix and cell-cell interactions. Reasoning that this problem could be mitigated at the post-thawing stage, we applied label-free quantitative global proteomics to analyze differences between attached and non-attached fractions of cryopreserved human hepatocyte batches. Read More

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http://dx.doi.org/10.1007/s00204-018-2375-9DOI Listing
December 2018
1 Read

In vitro-to-in vivo extrapolation (IVIVE) by PBTK modeling for animal-free risk assessment approaches of potential endocrine-disrupting compounds.

Arch Toxicol 2019 Feb 14;93(2):401-416. Epub 2018 Dec 14.

BASF SE, Experimental Toxicology and Ecology, Carl Bosch Straße 38, 67056, Ludwigshafen, Germany.

While in vitro testing is used to identify hazards of chemicals, nominal in vitro assay concentrations may misrepresent potential in vivo effects and do not provide dose-response data which can be used for a risk assessment. We used reverse dosimetry to compare in vitro effect concentrations-to-in vivo doses causing toxic effects related to endocrine disruption. Ten compounds (acetaminophen, bisphenol A, caffeine, 17α-ethinylestradiol, fenarimol, flutamide, genistein, ketoconazole, methyltestosterone, and trenbolone) have been tested in the yeast estrogen screening (YES) or yeast androgen-screening (YAS) assays for estrogen and androgen receptor binding, as well as the H295R assay (OECD test guideline no. Read More

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http://dx.doi.org/10.1007/s00204-018-2372-zDOI Listing
February 2019
2 Reads
5.980 Impact Factor

Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism.

Arch Toxicol 2019 Feb 14;93(2):341-353. Epub 2018 Dec 14.

Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.

Acetaminophen (APAP) is one of the most commonly used analgesics worldwide, and overdoses are associated with lactic acidosis, hepatocyte toxicity, and acute liver failure due to oxidative stress and mitochondrial dysfunction. Hepatoma cell lines typically lack the CYP450 activity to generate the reactive metabolite of APAP observed in vivo, but are still subject to APAP cytotoxicity. In this study, we employed metabolic profiling and isotope labelling approaches to investigate the metabolic impact of acute exposure to cytotoxic doses of APAP on the widely used HepG2 cell model. Read More

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http://dx.doi.org/10.1007/s00204-018-2371-0DOI Listing
February 2019
5 Reads

Sex-specific differences in genotoxic and epigenetic effects of 1,3-butadiene among mouse tissues.

Arch Toxicol 2018 Dec 14. Epub 2018 Dec 14.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.

Exposure to environmental chemicals has been shown to have an impact on the epigenome. One example is a known human carcinogen 1,3-butadiene which acts primarily by a genotoxic mechanism, but also disrupts the chromatin structure by altering patterns of cytosine DNA methylation and histone modifications. Sex-specific differences in 1,3-butadiene-induced genotoxicity and carcinogenicity are well established; however, it remains unknown whether 1,3-butadiene-associated epigenetic alterations are also sex dependent. Read More

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http://dx.doi.org/10.1007/s00204-018-2374-xDOI Listing
December 2018
14 Reads

Re: Gi et al. 2018, In vivo positive mutagenicity of 1,4-dioxane and quantitative analysis of its mutagenicity and carcinogenicity in rats, Archives of Toxicology 92:3207-3221.

Arch Toxicol 2019 Jan 11;93(1):211-212. Epub 2018 Dec 11.

Swansea University Medical School, Swansea University, Swansea, Wales, UK.

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http://dx.doi.org/10.1007/s00204-018-2370-1DOI Listing
January 2019
3 Reads
5.980 Impact Factor

Compound selection and annotation to validate the predictivity of in vitro toxicity assays for use in drug discovery, in response to Commentary by Dr. Zink (Zink, D. Arch Toxicol (2018)).

Arch Toxicol 2019 Jan 11;93(1):225-226. Epub 2018 Dec 11.

RIA Safety, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

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http://dx.doi.org/10.1007/s00204-018-2359-9DOI Listing
January 2019
2 Reads

The hemoglobin adduct N-(2,3-dihydroxypropyl)-valine as biomarker of dietary exposure to glycidyl esters: a controlled exposure study in humans.

Arch Toxicol 2019 Feb 10;93(2):331-340. Epub 2018 Dec 10.

Department of Food Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.

Fatty acid esters of glycidol (glycidyl esters) are heat-induced food contaminants predominantly formed during industrial deodorization of vegetable oils and fats. After consumption, the esters are digested in the gastrointestinal tract, leading to a systemic exposure to the reactive epoxide glycidol. The compound is carcinogenic, genotoxic and teratogenic in rodents, and rated as probably carcinogenic to humans (IARC group 2A). Read More

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http://link.springer.com/10.1007/s00204-018-2373-y
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http://dx.doi.org/10.1007/s00204-018-2373-yDOI Listing
February 2019
8 Reads

The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves: from field observations to toxicokinetics.

Arch Toxicol 2019 Feb 10;93(2):293-310. Epub 2018 Dec 10.

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

A clinical case in Belgium demonstrated that feeding a feed concentrate containing considerable levels of deoxynivalenol (DON, 1.13 mg/kg feed) induced severe liver failure in 2- to 3-month-old beef calves. Symptoms disappeared by replacing the highly contaminated corn and by stimulating ruminal development via roughage administration. Read More

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http://dx.doi.org/10.1007/s00204-018-2368-8DOI Listing
February 2019
3 Reads

Toxicogenomics directory of rat hepatotoxicants in vivo and in cultivated hepatocytes.

Arch Toxicol 2018 Dec 3;92(12):3517-3533. Epub 2018 Dec 3.

Leibniz Research Centre for Working Environment and Human Factors, Technical University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.

Transcriptomics is developing into an invaluable tool in toxicology. The aim of this study was, using a transcriptomics approach, to identify genes that respond similar to many different chemicals (including drugs and industrial compounds) in both rat liver in vivo and in cultivated hepatocytes. For this purpose, we analyzed Affymetrix microarray expression data from 162 compounds that were previously tested in a concentration-dependent manner in rat livers in vivo and in rat hepatocytes cultivated in sandwich culture. Read More

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http://dx.doi.org/10.1007/s00204-018-2352-3DOI Listing
December 2018
3 Reads

PGC-1β modulates statin-associated myotoxicity in mice.

Arch Toxicol 2019 Feb 3;93(2):487-504. Epub 2018 Dec 3.

Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital, Hebelstrasse 20, 4031, Basel, Switzerland.

Statins inhibit cholesterol biosynthesis and lower serum LDL-cholesterol levels. Statins are generally well tolerated, but can be associated with potentially life-threatening myopathy of unknown mechanism. We have shown previously that statins impair PGC-1β expression in human and rat skeletal muscle, suggesting that PGC-1β may play a role in statin-induced myopathy. Read More

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http://dx.doi.org/10.1007/s00204-018-2369-7DOI Listing
February 2019
2 Reads

Medicines associated with folate-homocysteine-methionine pathway disruption.

Arch Toxicol 2019 Feb 29;93(2):227-251. Epub 2018 Nov 29.

University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, Ljubljana, Slovenia.

Folate is vital for cell development and growth. It is involved in one-carbon transfer reactions essential for the synthesis of purines and pyrimidines. It also acts in conjunction with cobalamin (vitamin B) as a fundamental cofactor in the remethylation cycle that converts homocysteine to methionine. Read More

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http://link.springer.com/10.1007/s00204-018-2364-z
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http://dx.doi.org/10.1007/s00204-018-2364-zDOI Listing
February 2019
2 Reads

Targeted deletion of the aryl hydrocarbon receptor in dendritic cells prevents thymic atrophy in response to dioxin.

Arch Toxicol 2019 Feb 29;93(2):355-368. Epub 2018 Nov 29.

Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Drive, Skaggs Building Room 284, Missoula, MT, 59812, USA.

In nearly every species examined, administration of the persistent environmental pollutant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin, TCDD) causes profound immune suppression and thymic atrophy in an aryl hydrocarbon receptor (AhR) dependent manner. Moreover, TCDD alters the development and differentiation of thymocytes, resulting in decreases in the relative proportion and absolute number of double positive (DP, CD4CD8) thymocytes, as well as a relative enrichment in the relative proportion and absolute number of double negative (DN, CD4CD8) and single-positive (SP) CD4CD8 and CD4CD8 thymocytes. Previous studies suggested that the target for TCDD-induced thymic atrophy resides within the hemopoietic compartment and implicated apoptosis, proliferation arrest of thymic progenitors, and emigration of DN thymocytes to the periphery as potential contributors to TCDD-induced thymic atrophy. Read More

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http://dx.doi.org/10.1007/s00204-018-2366-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367717PMC
February 2019
2 Reads

Exploring sex differences in human health risk assessment for PFNA and PFDA using a PBPK model.

Arch Toxicol 2019 Feb 27;93(2):311-330. Epub 2018 Nov 27.

College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea.

Perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), which are classified as perfluoroalkyl and polyfluoroalkyl substances (PFASs), have been widely used in industrial applications as a surface protectant. PFASs have been detected in wildlife and in humans around the globe. The purposes of this study are to develop and validate a physiologically based pharmacokinetic (PBPK) model for detecting PFNA and PFDA in male and female rats, and to apply the model to a human health risk assessment regarding the sex difference. Read More

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http://dx.doi.org/10.1007/s00204-018-2365-yDOI Listing
February 2019
1 Read

Highlight report: Stem cell-based developmental toxicity tests.

Authors:
Florian Seidel

Arch Toxicol 2018 Dec 26;92(12):3609-3610. Epub 2018 Nov 26.

IfADo, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Ardeystr. 67, 44139, Dortmund, Germany.

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http://dx.doi.org/10.1007/s00204-018-2357-yDOI Listing
December 2018
2 Reads

Uptake of microplastics and related health effects: a critical discussion of Deng et al., Scientific reports 7:46687, 2017.

Authors:
Albert Braeuning

Arch Toxicol 2019 Jan 23;93(1):219-220. Epub 2018 Nov 23.

Department of Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.

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http://link.springer.com/10.1007/s00204-018-2367-9
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http://dx.doi.org/10.1007/s00204-018-2367-9DOI Listing
January 2019
9 Reads

Highlight report the food additive dammar resin is a rat hepatocarcinogen.

Arch Toxicol 2018 Dec 23;92(12):3611-3612. Epub 2018 Nov 23.

Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.

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http://dx.doi.org/10.1007/s00204-018-2362-1DOI Listing
December 2018
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Highlight report: New applications of chimeric mice with humanized livers.

Authors:
Wiebke Albrecht

Arch Toxicol 2018 Dec 23;92(12):3607-3608. Epub 2018 Nov 23.

IfADo-Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Ardeystr. 67, 44139, Dortmund, Germany.

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http://dx.doi.org/10.1007/s00204-018-2358-xDOI Listing
December 2018
1 Read

In vitro proteomic analysis of methapyrilene toxicity in rat hepatocytes reveals effects on intermediary metabolism.

Arch Toxicol 2019 Feb 22;93(2):369-383. Epub 2018 Nov 22.

Dept. Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.

The antihistaminic drug methapyrilene was withdrawn from the market in 1979 because of hepatocarcinogenicity in rats. Since then, the drug has been used as a model hepatotoxin especially for transcriptomic analyses using material from in vivo studies. Much less transcriptomics data are available from in vitro studies, and no studies have investigated proteomic effects of methapyrilene in vitro. Read More

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http://dx.doi.org/10.1007/s00204-018-2360-3DOI Listing
February 2019
15 Reads

The dangers of preemptive obedience to political pressure and media campaigns in science.

Authors:
Colin Berry

Arch Toxicol 2019 Jan 22;93(1):209. Epub 2018 Nov 22.

Queen Mary University of London, London, EN1 4NS, UK.

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http://link.springer.com/10.1007/s00204-018-2363-0
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http://dx.doi.org/10.1007/s00204-018-2363-0DOI Listing
January 2019
9 Reads

Highlight Report: humanized mice reveal interspecies differences in triclosan hepatotoxicity.

Arch Toxicol 2018 Dec 21;92(12):3613-3614. Epub 2018 Nov 21.

Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt.

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http://dx.doi.org/10.1007/s00204-018-2361-2DOI Listing
December 2018
1 Read

3D visualization of the biliary tree by X-ray phase-contrast computed tomography.

Arch Toxicol 2018 Dec 20;92(12):3601-3602. Epub 2018 Nov 20.

IfADo, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Ardeystr. 67, 44139, Dortmund, Germany.

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http://dx.doi.org/10.1007/s00204-018-2346-1DOI Listing
December 2018
15 Reads

MicroRNAs in the diagnosis and prevention of drug-induced cardiotoxicity.

Arch Toxicol 2019 Jan 20;93(1):1-9. Epub 2018 Nov 20.

Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, Hradec Králové, Czech Republic.

Drug-induced cardiotoxicity is a serious problem associated with the administration of many drugs. MicroRNAs (miRNAs) have been reported to be affected by drugs and other xenobiotics, and the potential of miRNAs as biomarkers and diagnostic tools has been considered. In recent years, an association of certain miRNAs with the cardiotoxicity of some drugs, namely anthracyclines, bevacizumab, cyclosporine A and isoprenaline, has already been found. Read More

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http://dx.doi.org/10.1007/s00204-018-2356-zDOI Listing
January 2019
16 Reads

A systematic analysis of Nrf2 pathway activation dynamics during repeated xenobiotic exposure.

Arch Toxicol 2019 Feb 20;93(2):435-451. Epub 2018 Nov 20.

Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.

Oxidative stress leads to the activation of the Nuclear factor-erythroid-2-related factor 2 (Nrf2) pathway. While most studies have focused on the activation of the Nrf2 pathway after single chemical treatment, little is known about the dynamic regulation of the Nrf2 pathway in the context of repeated exposure scenarios. Here we employed single cell live imaging to quantitatively monitor the dynamics of the Nrf2 pathway during repeated exposure, making advantage of two HepG2 fluorescent protein reporter cell lines, expressing GFP tagged Nrf2 or sulfiredoxin 1 (Srxn1), a direct downstream target of Nrf2. Read More

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http://dx.doi.org/10.1007/s00204-018-2353-2DOI Listing
February 2019
2 Reads