Dietary diisononylphthalate contamination induces hepatic stress: a multidisciplinary investigation in gilthead seabream (Sparus aurata) liver.
In this study, adult gilthead seabream (Sparus aurata) were exposed for 21 days to Di-iso-nonylphthalte (DiNP at 15 and 1500 μg kg-1 bw day-1) via the diet. This plastic additive has been recently introduced to replace the di-(2-ethylhexyl)phthalate, the toxicity of which has been demonstrated conclusively both in vivo and in vitro trials. An analysis of a set of biomarkers involved in stress and immune response provides evidence of hepatic toxicity by DiNP in the present study. Both hsp70 and gr mRNA levels were upregulated significantly by DiNP, while plasma cortisol increased only in fish fed...
Source: Archives of Toxicology - June 22, 2019 Category: Toxicology Authors: Carnevali O, Santobuono M, Forner-Piquer I, Randazzo B, Mylonas CC, Ancillai D, Giorgini E, Maradonna F Tags: Arch Toxicol Source Type: research

Quantification of freely dissolved effect concentrations in in vitro cell-based bioassays.
In this study, we quantified freely dissolved concentrations in medium sampled from in vitro cell-based bioassays (Cfree,medium) for nine chemicals with different hydrophobicity and speciation at the time point of dosing and after an incubation period of 24 h using solid-phase microextraction. The chemicals were tested in two reporter gene assays, the AREc32 assay indicative of the oxidative stress response and the PPARγ-GeneBLAzer assay that responds to chemicals which bind to the peroxisome proliferator-activated receptor gamma. For seven of the nine chemicals, Cfree,medium did not change significantly ov...
Source: Archives of Toxicology - June 22, 2019 Category: Toxicology Authors: Henneberger L, Mühlenbrink M, König M, Schlichting R, Fischer FC, Escher BI Tags: Arch Toxicol Source Type: research

Distribution of the (synthetic) cannabinoids JWH-210, RCS-4, as well as ∆9-tetrahydrocannabinol following pulmonary administration to pigs.
midt PH Abstract New psychoactive substances, especially synthetic cannabinoids (SC), are gaining increasing relevance in postmortem forensic toxicology. Particularly, the interpretation of analytical results is challenging, as usually, no toxicokinetic (TK) data concerning distribution in organs and tissues are available. Thus, a controlled pig TK study allowing for examination of organ and tissue distribution of SC was performed. For this purpose, 12 pigs received a single pulmonary dose of 200 µg/kg body weight each of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphen...
Source: Archives of Toxicology - June 21, 2019 Category: Toxicology Authors: Schaefer N, Kröll AK, Körbel C, Laschke MW, Menger MD, Maurer HH, Meyer MR, Schmidt PH Tags: Arch Toxicol Source Type: research

Intestinal and hepatic biotransformation of pyrrolizidine alkaloid N-oxides to toxic pyrrolizidine alkaloids.
Abstract Pyrrolizidine alkaloids (PAs) are among the most significant groups of phytotoxins present in more than 6000 plants in the world. Hepatotoxic retronecine-type PAs and their corresponding N-oxides usually co-exist in plants. Although PA-induced hepatotoxicity is known for a long time and has been extensively studied, the toxicity of PA N-oxide is rarely investigated. Recently, we reported PA N-oxide-induced hepatotoxicity in humans and rodents and also suggested the association of such toxicity with metabolic conversion of PA N-oxides to the corresponding toxic PAs. However, the detailed biochemical mechan...
Source: Archives of Toxicology - June 20, 2019 Category: Toxicology Authors: Yang M, Ma J, Ruan J, Ye Y, Fu PP, Lin G Tags: Arch Toxicol Source Type: research

Validity of different biomonitoring parameters in human urine for the assessment of occupational exposure to naphthalene.
This study was performed to reveal the relation between occupational exposure to naphthalene and biological exposure markers. Therefore, ten lowly and highly exposed workers from the abrasives industry were selected to characterise a broad exposure range. Naphthalene in air was determined by personal air monitoring during one shift. For biological monitoring, pre- and post-shift urine samples collected on 2 days of a working week were analysed for 1,2-dihydroxynaphthalene (1,2-DHN), 1- and 2-naphthol, 1- and 2-naphthylmercapturic acid (NMA). The naphthalene concentration in air was in the range of 0.5 to 11.6 mg/...
Source: Archives of Toxicology - June 20, 2019 Category: Toxicology Authors: Klotz K, Weiß T, Zobel M, Bury D, Breuer D, Werner S, Sucker K, Zschiesche W, Göen T, Brüning T, Drexler H Tags: Arch Toxicol Source Type: research

Deciphering the uranium target proteins in human dopaminergic SH-SY5Y cells.
Abstract Uranium (U) is the heaviest naturally occurring element ubiquitously present in the Earth's crust. Human exposure to low levels of U is, therefore, unavoidable. Recently, several studies have clearly pointed out that the brain is a sensitive target for U, but the mechanisms leading to the observed neurological alterations are not fully known. To deepen our knowledge of the biochemical disturbances resulting from U(VI) toxicity in neuronal cells, two complementary strategies were set up to identify the proteins that selectively bind U(VI) in human dopaminergic SH-SY5Y cells. The first strategy relies on th...
Source: Archives of Toxicology - June 20, 2019 Category: Toxicology Authors: Vidaud C, Robert M, Paredes E, Ortega R, Avazeri E, Jing L, Guigonis JM, Bresson C, Malard V Tags: Arch Toxicol Source Type: research

PON1 increases cellular DNA damage by lactone substrates.
Abstract Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that by hydrolysing exogenous and endogenous substrates can provide protection against substrate induced toxicity. To investigate the extent to which PON1 provides protection against lactone induced DNA damage, DNA damage was measured in HepG2 cells using the neutral Comet assay following lactone treatment in the presence and absence of exogenous recombinant PON1 (rPON1). Low dose lactones (10 mM) caused little or no damage while high doses (100 mM) induced DNA damage in the following order of potency: α-angeli...
Source: Archives of Toxicology - June 17, 2019 Category: Toxicology Authors: Shangula S, Noori M, Ahmad I, Margison GP, Liu Y, Siahmansur T, Soran H, Povey AC Tags: Arch Toxicol Source Type: research

Bioactivation of the tobacco carcinogens 4-aminobiphenyl (4-ABP) and 2-amino-9H-pyrido[2,3-b]indole (A αC) in human bladder RT4 cells.
In this study, we have examined the capacity of RT4 cells, an epithelial human bladder cell line, to bioactivate AAs and HAAs to DNA damaging agents, which may contribute to BC. 4-ABP and AαC formed DNA adducts, but DNA adducts of 2-NA, PhIP, and MeIQx were not detected. 4-ABP DNA adducts were formed at tenfold higher levels than AαC adducts. Pretreatment of RT4 cells with α-naphthoflavone (1-10 µM), a specific cytochrome P450 1 (CYP1) inhibitor, decreased AαC adduct formation by 50% but did not affect the level of 4-ABP adducts. However, cell pretreatment with 8-methoxypsoralen (0.1-1&nb...
Source: Archives of Toxicology - June 15, 2019 Category: Toxicology Authors: Bellamri M, Yao L, Bonala R, Johnson F, Von Weymarn LB, Turesky RJ Tags: Arch Toxicol Source Type: research

Combined transcriptomic and proteomic analysis reveals a diversity of venom-related and toxin-like peptides expressed in the mat anemone Zoanthus natalensis (Cnidaria, Hexacorallia).
ee SM Abstract Venoms from marine animals have been recognized as a new emerging source of peptide-based therapeutics. Several peptide toxins from sea anemone have been investigated as therapeutic leads or pharmacological tools. Venom complexity should be further highlighted using combined strategies of large-scale sequencing and data analysis which integrated transcriptomics and proteomics to elucidate new proteins or peptides to be compared among species. In this work, transcriptomic and proteomic analyses were combined to identify six groups of expressed peptide toxins in Zoanthus natalensis. These include neur...
Source: Archives of Toxicology - June 15, 2019 Category: Toxicology Authors: Liao Q, Gong G, Poon TCW, Ang IL, Lei KMK, Siu SWI, Wong CTT, Rádis-Baptista G, Lee SM Tags: Arch Toxicol Source Type: research

Development of a neurotoxicity assay that is tuned to detect mitochondrial toxicants.
Abstract Many neurotoxicants affect energy metabolism in man, but currently available test methods may still fail to predict mito- and neurotoxicity. We addressed this issue using LUHMES cells, i.e., human neuronal precursors that easily differentiate into mature neurons. Within the NeuriTox assay, they have been used to screen for neurotoxicants. Our new approach is based on culturing the cells in either glucose or galactose (Glc-Gal-NeuriTox) as the main carbohydrate source during toxicity testing. Using this Glc-Gal-NeuriTox assay, 52 mitochondrial and non-mitochondrial toxicants were tested. The panel of chemi...
Source: Archives of Toxicology - June 12, 2019 Category: Toxicology Authors: Delp J, Funke M, Rudolf F, Cediel A, Bennekou SH, van der Stel W, Carta G, Jennings P, Toma C, Gardner I, van de Water B, Forsby A, Leist M Tags: Arch Toxicol Source Type: research

Correction to: A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice.
Abstract In the original publication of the article. PMID: 31177290 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 8, 2019 Category: Toxicology Authors: Wang X, Tanaka N, Hu X, Kimura T, Lu Y, Jia F, Sato Y, Nakayama J, Moriya K, Koike K, Aoyama T Tags: Arch Toxicol Source Type: research

Verification of soman-related nerve agents via detection of phosphonylated adducts from rabbit albumin in vitro and in vivo.
Abstract A major challenge in organophosphate compound (OP) and OP nerve agent (OPNA) research has been in the identification and utilization of reliable biomarkers for rapid, sensitive, and efficient detection of OP exposure. Albumin has been widely studied as a biomarker for retrospective verification of exposure to OPNAs, including soman (GD), by detecting the phosphonylation of specific amino acid residues. The aim of the present study was to identify binding sites between GD and rabbit serum albumin in vitro and in vivo. A nano-liquid chromatography coupled with a quadrupole-orbitrap mass ...
Source: Archives of Toxicology - June 3, 2019 Category: Toxicology Authors: Fu F, Gao R, Zhang R, Zhao P, Lu X, Li L, Wang H, Pei C Tags: Arch Toxicol Source Type: research

Uptake and effects of orally ingested polystyrene microplastic particles in vitro and in vivo.
n A Abstract Evidence exists that humans are exposed to plastic microparticles via diet. Data on intestinal particle uptake and health-related effects resulting from microplastic exposure are scarce. Aim of the study was to analyze the uptake and effects of microplastic particles in human in vitro systems and in rodents in vivo. The gastrointestinal uptake of microplastics was studied in vitro using the human intestinal epithelial cell line Caco-2 and thereof-derived co-cultures mimicking intestinal M-cells and goblet cells. Different sizes of spherical fluorescent polystyrene (PS) particles (1, 4 and 10 &mic...
Source: Archives of Toxicology - May 28, 2019 Category: Toxicology Authors: Stock V, Böhmert L, Lisicki E, Block R, Cara-Carmona J, Pack LK, Selb R, Lichtenstein D, Voss L, Henderson CJ, Zabinsky E, Sieg H, Braeuning A, Lampen A Tags: Arch Toxicol Source Type: research

Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans.
rr MK Abstract Recent studies suggest that the anabolic effect of ecdysterone, a naturally occurring steroid hormone claimed to enhance physical performance, is mediated by estrogen receptor (ER) binding. In comparison with the prohibited anabolic agents (e.g., metandienone and others), ecdysterone revealed to be even more effective in a recent study performed in rats. However, scientific studies in humans are very rarely accessible. Thus, our project aimed at investigating the effects of ecdysterone-containing products on human sport exercise. A 10-week intervention study of strength training of young men (n&thin...
Source: Archives of Toxicology - May 23, 2019 Category: Toxicology Authors: Isenmann E, Ambrosio G, Joseph JF, Mazzarino M, de la Torre X, Zimmer P, Kazlauskas R, Goebel C, Botrè F, Diel P, Parr MK Tags: Arch Toxicol Source Type: research

Neurotoxicity of Micrurus lemniscatus lemniscatus (South American coralsnake) venom in vertebrate neuromuscular preparations in vitro and neutralization by antivenom.
Abstract We investigated the effect of South American coralsnake (Micrurus lemniscatus lemniscatus) venom on neurotransmission in vertebrate nerve-muscle preparations in vitro. The venom (0.1-30 µg/ml) showed calcium-dependent PLA2 activity and caused irreversible neuromuscular blockade in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. In BC preparations, contractures to exogenous acetylcholine and carbachol (CCh), but not KCl, were abolished by venom concentrations ≥ 0.3 µg/ml; in PND preparations, the amplitude of the tetanic response was...
Source: Archives of Toxicology - May 23, 2019 Category: Toxicology Authors: Floriano RS, Schezaro-Ramos R, Silva NJ, Bucaretchi F, Rowan EG, Hyslop S Tags: Arch Toxicol Source Type: research

Proteomic analysis of hippocampal proteins in acrylamide-exposed Wistar rats.
Abstract Acrylamide has been used industrially and also found in certain foods cooked at high temperatures. Previous reports described acrylamide-related human intoxication who presented with ataxia, memory impairment, and/or illusion. The aim of this study was to characterize the molecular mechanisms of neurotoxicity of acrylamide by analyzing the expression levels of various proteins in the hippocampus of rats exposed to acrylamide. Male Wistar rats were administered acrylamide by gavage at 0, 2, and 20 mg/kg for 1 week or 0, 0.2, 2, and 20 mg/kg for 5 weeks. At the end of the experiment, the...
Source: Archives of Toxicology - May 23, 2019 Category: Toxicology Authors: Nagashima D, Zhang L, Kitamura Y, Ichihara S, Watanabe E, Zong C, Yamano Y, Sakurai T, Oikawa S, Ichihara G Tags: Arch Toxicol Source Type: research

Novel insight in estrogen homeostasis and bioactivity in the ACI rat model of estrogen-induced mammary gland carcinogenesis.
n L Abstract Despite being widely used to investigate 17β-estradiol (E2)-induced mammary gland (MG) carcinogenesis and prevention thereof, estrogen homeostasis and its significance in the female August Copenhagen Irish (ACI) rat model is unknown. Thus, levels of 12 estrogens including metabolites and conjugates were determined mass spectrometrically in 38 plasmas and 52 tissues exhibiting phenotypes ranging from normal to palpable tumor derived from a representative ACI study using two different diets. In tissues, 40 transcripts encoding proteins involved in estrogen (biotrans)formation, ESR1-mediated signali...
Source: Archives of Toxicology - May 22, 2019 Category: Toxicology Authors: Pemp D, Esch HL, Hauptstein R, Möller FJ, Zierau O, Bosland MC, Geppert LN, Kleider C, Schlereth K, Vollmer G, Lehmann L Tags: Arch Toxicol Source Type: research

The in vivo developmental toxicity of diethylstilbestrol (DES) in rat evaluated by an alternative testing strategy.
Abstract In the present study, we evaluated an alternative testing strategy to quantitatively predict the in vivo developmental toxicity of the synthetic hormone diethylstilbestrol (DES). To this end, a physiologically based kinetic (PBK) model was defined that was subsequently used to translate concentration-response data for the in vitro developmental toxicity of DES, obtained in the ES-D3 cell differentiation assay, into predicted in vivo dose-response data for developmental toxicity. The previous studies showed that the PBK model-facilitated reverse dosimetry approach is a useful approach to quantitatively pre...
Source: Archives of Toxicology - May 22, 2019 Category: Toxicology Authors: Adam AHB, Zhang M, de Haan LHJ, van Ravenzwaay B, Louisse J, Rietjens IMCM Tags: Arch Toxicol Source Type: research

Okadaic acid activates Wnt/ β-catenin-signaling in human HepaRG cells.
In conclusion, our results show a significant induction of the canonical Wnt/β-catenin-signaling pathway by OA in human liver cells. Our data contribute to a better understanding of the molecular mechanisms underlying OA-induced carcinogenesis. PMID: 31115591 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 21, 2019 Category: Toxicology Authors: Dietrich J, Sommersdorf C, Gohlke S, Poetz O, Traenkle B, Rothbauer U, Hessel-Pras S, Lampen A, Braeuning A Tags: Arch Toxicol Source Type: research

Case study: Is bisphenol S safer than bisphenol A in thermal papers?
ova E Abstract The Risk Assessment Committee of the European Chemical Agency released a scientific opinion alerting that the risk associated with dermal occupational exposure to bisphenol A (BPA) via thermal paper might not be adequately controlled because the estimated exposure was around twice the Derived No Effect Level (DNEL) and the European Commission will effectively restrict BPA in thermal paper as soon as 2020. Bisphenol S (BPS) is currently being used as a BPA surrogate and is already widespread in thermal paper receipts. Based on publically available information in the scientific literature, we assessed...
Source: Archives of Toxicology - May 20, 2019 Category: Toxicology Authors: Sogorb MA, Estévez J, Vilanova E Tags: Arch Toxicol Source Type: research

The Toll-like receptor agonist imiquimod is metabolized by aryl hydrocarbon receptor-regulated cytochrome P450 enzymes in human keratinocytes and mouse liver.
Abstract The Toll-like receptor 7 agonist imiquimod (IMQ) is an approved drug for the topical treatment of various skin diseases that, in addition, is currently tested in multiple clinical trials for the immunotherapy of various types of cancers. As all of these trials include application of IMQ to the skin and evidence exists that exposure to environmental pollutants, i.e., tobacco smoke, affects its therapeutic efficacy, the current study aims to elucidate the cutaneous metabolism of the drug. Treatment of human keratinocytes with 2.5 µM benzo[a]pyrene (BaP), a tobacco smoke constituent and aryl hydro...
Source: Archives of Toxicology - May 20, 2019 Category: Toxicology Authors: Mescher M, Tigges J, Rolfes KM, Shen AL, Yee JS, Vogeley C, Krutmann J, Bradfield CA, Lang D, Haarmann-Stemmann T Tags: Arch Toxicol Source Type: research

Quantitative in vitro-to-in vivo extrapolation (QIVIVE) of estrogenic and anti-androgenic potencies of BPA and BADGE analogues.
Abstract The goal of the present study was to obtain an in vivo relevant prioritization method for the endocrine potencies of different polycarbonate monomers, by combining in vitro bioassay data with physiologically based kinetic (PBK) modelling. PBK models were developed for a selection of monomers, including bisphenol A (BPA), two bisphenol F (BPF) isomers and four different bisphenol A diglycidyl ethers (BADGEs), using in vitro input data. With these models, the plasma concentrations of the compounds were simulated, providing means to estimate the dose levels at which the in vitro endocrine effect concentratio...
Source: Archives of Toxicology - May 20, 2019 Category: Toxicology Authors: Punt A, Aartse A, Bovee TFH, Gerssen A, van Leeuwen SPJ, Hoogenboom RLAP, Peijnenburg AACM Tags: Arch Toxicol Source Type: research

Correction to: 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.
Abstract The publisher would like to apologize for the failed cross-linking to the following Letter to the Editor by Paul A. PMID: 31098698 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 17, 2019 Category: Toxicology Authors: White PA, Zeller A, Pfuhler S, Johnson GE Tags: Arch Toxicol Source Type: research

Angiotensin II-induced hypertension increases the mutant frequency in rat kidney.
Abstract Epidemiological studies revealed an increased risk for kidney cancer in hypertensive patients. In many of these patients, the blood pressure regulating renin-angiotensin-aldosterone system (RAAS) is activated. A stimulated RAAS leads to oxidative stress and increases markers of DNA damage, both in vitro and in animal models of hypertension. However, the mutagenic potential of RAAS activation has not been investigated yet. To quantify hypertension-induced mutations, BigBlue®+/- rats, which carry a transgenic lacI gene for mutation analysis, were treated for 20 weeks with a mean dose of 400 &m...
Source: Archives of Toxicology - May 16, 2019 Category: Toxicology Authors: Hartmann C, Schulz I, Epe B, Schupp N Tags: Arch Toxicol Source Type: research

Letter to the editor.
PMID: 31087121 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 13, 2019 Category: Toxicology Authors: Pallocca G Tags: Arch Toxicol Source Type: research

Letter to the Editor : Comment on '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' by Ning et al., Arch Toxicol doi: https://doi.org/10.1007/s00204-019-02397-7.
PMID: 31076803 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 10, 2019 Category: Toxicology Authors: Mielke H, Partosch F, Gundert-Remy U Tags: Arch Toxicol Source Type: research

Functional transepithelial transport measurements to detect nephrotoxicity in vitro using the RPTEC/TERT1 cell line.
In conclusion, these data demonstrate that functional parameters are important, highly sensitive and meaningful additional readouts for nephrotoxicity assessment in human renal proximal tubule epithelial cells. PMID: 31076804 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 10, 2019 Category: Toxicology Authors: Secker PF, Schlichenmaier N, Beilmann M, Deschl U, Dietrich DR Tags: Arch Toxicol Source Type: research

Role of microglial activation and neuroinflammation in neurotoxicity of acrylamide in vivo and in vitro.
Abstract Acrylamide, a soft electrophile, is widely used in the industry and laboratories, and also contaminates certain foods. Neurotoxicity and neurodegenerative effects of acrylamide have been reported in humans and experimental animals, although the underlying mechanism remains obscure. Activation of microglia and neuroinflammation has been demonstrated in various neurodegenerative diseases as well as other pathologies of the brain. The present study aimed to investigate the role of microglial activation and neuroinflammation in acrylamide neurotoxicity. Male 10-week-old Wistar rats were exposed to acrylamide ...
Source: Archives of Toxicology - May 9, 2019 Category: Toxicology Authors: Zong C, Hasegawa R, Urushitani M, Zhang L, Nagashima D, Sakurai T, Ichihara S, Ohsako S, Ichihara G Tags: Arch Toxicol Source Type: research

Forensic evidence of sulfur mustard exposure in real cases of human poisoning by detection of diverse albumin-derived protein adducts.
We present the forensic analyses of plasma samples of human victims exposed to sulfur mustard (SM) in a crisis region in the Middle East in 2015. A few hours after exposure, poisoned persons showed typical signs and symptoms of percutaneous SM exposure including erythema and later on blisters and hardly healing skin wounds. Blood samples were collected 15 days after poisoning to be analyzed for the presence of long-lived protein-adduct biomarkers to verify SM poisoning. We applied a novel bioanalytical toolbox targeting four human serum albumin-derived biomarkers that were made accessible after plasma proteolysis. The...
Source: Archives of Toxicology - May 8, 2019 Category: Toxicology Authors: John H, Koller M, Worek F, Thiermann H, Siegert M Tags: Arch Toxicol Source Type: research

Behavioural and metabolomic changes from chronic dietary exposure to low-level deoxynivalenol reveal impact on mouse well-being.
Abstract The mycotoxin deoxynivalenol (DON) has a high global prevalence in grain-based products. Biomarkers of exposure are detectable in most humans and farm animals. Considering the acute emetic and chronic anorexigenic toxicity of DON, maximum levels for food and feed have been implemented by food authorities. The tolerable daily intake (TDI) is 1 µg/kg body weight (bw)/day for the sum of DON and its main derivatives, which was based on the no-observed adverse-effect level (NOAEL) of 100 µg DON/kg bw/day for anorexic effects in rodents. Chronic exposure to a low-DON dose can, however, als...
Source: Archives of Toxicology - May 7, 2019 Category: Toxicology Authors: Faeste CK, Pierre F, Ivanova L, Sayyari A, Massotte D Tags: Arch Toxicol Source Type: research

Selecting the dose metric in reverse dosimetry based QIVIVE : Reply to 'Comment on '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' by Ning et al., Arch Toxicol doi: https://doi.org/10.1007/s00204-019-02397-7', Arch Toxicol doi: https://doi.org/10.1007/s0020 4-019-02421-w.
PMID: 31062055 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 7, 2019 Category: Toxicology Authors: Rietjens IMCM, Ning J, Chen L, Wesseling S, Strikwold M, Louisse J Tags: Arch Toxicol Source Type: research

Naturally occurring bisphenol F in plants used in traditional medicine.
n C Abstract Bisphenol F (BPF, 4-[(4-hydroxyphenyl)methyl]phenol) is a bisphenol that is structurally similar to bisphenol A (BPA). In response to consumer concern towards BPA, industry has started to substitute BPA for BPF and other bisphenol analogues in the production of epoxy resins and coatings for various applications. In 2016, it was reported that commercially sold mustard contained naturally occurring BPF. Here, the existing literature was reviewed to investigate whether other natural sources of BPF among edible plants exist, including their impact on human exposure to BPF. Coeloglossum viride var. bractea...
Source: Archives of Toxicology - May 5, 2019 Category: Toxicology Authors: Huang T, Danaher LA, Brüschweiler BJ, Kass GEN, Merten C Tags: Arch Toxicol Source Type: research

Minor structural modifications of bisphenol A strongly affect physiological responses of HepG2 cells.
In conclusion, the read-across approach revealed non-applicable in the case of the various structurally and physicochemically comparable bisphenols tested in this study, as the presence of one or two additional methyl group(s) attached at the phenol ring profoundly affected cellular physiology. PMID: 31055635 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 4, 2019 Category: Toxicology Authors: Padberg F, Tarnow P, Luch A, Zellmer S Tags: Arch Toxicol Source Type: research

Integration of epidemiological findings with mechanistic evidence in regulatory pesticide risk assessment: EFSA experiences.
Abstract Toxicological risk assessment of plant protection products (PPP) is currently carried out with the principal input from regulatory toxicology studies following OECD test guidelines, with little input from epidemiological data. An EFSA-commissioned systematic review of pesticide epidemiological studies (Ntzani et al. in Literature review on epidemiological studies linking exposure to pesticides and health effects. EFSA supporting publication 2013:EN-497, 2013) revealed statistically significant associations, among others, between pesticide exposures, and Parkinson's disease and childhood leukemia. Thereaft...
Source: Archives of Toxicology - May 3, 2019 Category: Toxicology Authors: Pelkonen O, Bennekou SH, Crivellente F, Terron A, Hernandez AF Tags: Arch Toxicol Source Type: research

Key performance indicators of the contemporary European academic toxicologist.
PMID: 31049612 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 2, 2019 Category: Toxicology Authors: Vinken M, Wallace HM Tags: Arch Toxicol Source Type: research

The Fusarium metabolite culmorin suppresses the in vitro glucuronidation of deoxynivalenol.
rko D Abstract Glucuronidation is a major phase II conjugation pathway in mammals, playing an important role in the detoxification and biotransformation of xenobiotics including mycotoxins such as deoxynivalenol (DON). Culmorin (CUL), a potentially co-occurring Fusarium metabolite, was recently found to inhibit the corresponding detoxification reaction in plants, namely DON-glucoside formation, raising the question whether CUL might affect also the mammalian counterpart. Using cell-free conditions, CUL when present equimolar (67 µM) or in fivefold excess, suppressed DON glucuronidation by human liver mi...
Source: Archives of Toxicology - May 2, 2019 Category: Toxicology Authors: Woelflingseder L, Warth B, Vierheilig I, Schwartz-Zimmermann H, Hametner C, Nagl V, Novak B, Šarkanj B, Berthiller F, Adam G, Marko D Tags: Arch Toxicol Source Type: research

Technological advancements for the development of stem cell-based models for hepatotoxicity testing.
Abstract Stem cells are characterized by their self-renewal capacity and their ability to differentiate into multiple cell types of the human body. Using directed differentiation strategies, stem cells can now be converted into hepatocyte-like cells (HLCs) and therefore, represent a unique cell source for toxicological applications in vitro. However, the acquired hepatic functionality of stem cell-derived HLCs is still significantly inferior to primary human hepatocytes. One of the main reasons for this is that most in vitro models use traditional two-dimensional (2D) setups where the flat substrata cannot properl...
Source: Archives of Toxicology - April 29, 2019 Category: Toxicology Authors: Natale A, Vanmol K, Arslan A, Van Vlierberghe S, Dubruel P, Van Erps J, Thienpont H, Buzgo M, Boeckmans J, De Kock J, Vanhaecke T, Rogiers V, Rodrigues RM Tags: Arch Toxicol Source Type: research

Feeding of deoxynivalenol increases the intestinal paracellular permeability of broiler chickens.
Abstract In recent years, the deleterious effects attributed to mycotoxins, in particular on the intestine, faced increased attention and it was shown that deoxynivalenol (DON) causes adverse effects on gut health. In this context, it has been repeatedly reported that DON can alter the intestinal morphology, disrupt the intestinal barrier and reduce nutrient absorption. The underlying mechanism of a compromised intestinal barrier caused by DON in chickens has yet to be illustrated. Although, DON is rapidly absorbed from the upper parts of the small intestine, the effects on the large intestine cannot be excluded. ...
Source: Archives of Toxicology - April 27, 2019 Category: Toxicology Authors: Awad WA, Ruhnau D, Hess C, Doupovec B, Schatzmayr D, Hess M Tags: Arch Toxicol Source Type: research

Upregulation of phosphoinositide 3-kinase prevents sunitinib-induced cardiotoxicity in vitro and in vivo.
In this study, we investigated whether SNT-induced cardiotoxicity could be prevented by blocking SNT-induced alteration in the corresponding signaling pathways. In human induced pluripotent stem cell-derived cardiomyocytes, SNT (0.5-20 µmol/L) inhibited contractility of cardiomyocytes in a concentration-dependent manner, and the inhibitory effect was prevented either by PIP3 (1 µmol/L) application or PI3K overexpression. On the contrary, the CaMKII inhibitor KN-93 (50 nmol/L), PKA inhibitor H89 (1 µmol/L), and AMPK activators metformin (2 mmol/L) and 5-aminoimidazole-4-carboxamide...
Source: Archives of Toxicology - April 25, 2019 Category: Toxicology Authors: Li C, Zou R, Zhang H, Wang Y, Qiu B, Qiu S, Wang W, Xu Y Tags: Arch Toxicol Source Type: research

Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration.
The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in...
Source: Archives of Toxicology - April 25, 2019 Category: Toxicology Authors: Li M, Cheng YH, Chittenden JT, Baynes RE, Tell LA, Davis JL, Vickroy TW, Riviere JE, Lin Z Tags: Arch Toxicol Source Type: research

Involvement of Nrf2/HO-1 antioxidant signaling and NF- κB inflammatory response in the potential protective effects of vincamine against methotrexate-induced nephrotoxicity in rats: cross talk between nephrotoxicity and neurotoxicity.
Involvement of Nrf2/HO-1 antioxidant signaling and NF-κB inflammatory response in the potential protective effects of vincamine against methotrexate-induced nephrotoxicity in rats: cross talk between nephrotoxicity and neurotoxicity. Arch Toxicol. 2019 Apr 24;: Authors: Shalaby YM, Menze ET, Azab SS, Awad AS Abstract Methotrexate (MTX) is a cytotoxic chemotherapeutic agent widely used in the treatment of cancer and autoimmune diseases like rheumatoid arthritis. However, its use has been limited by its nephrotoxicity. MTX-induced renal injury results in uremia which may influence both the periphe...
Source: Archives of Toxicology - April 24, 2019 Category: Toxicology Authors: Shalaby YM, Menze ET, Azab SS, Awad AS Tags: Arch Toxicol Source Type: research

Exposure to acetaminophen impairs vasodilation, increases oxidative stress and changes arterial morphology of rats.
Abstract Acetaminophen (APAP) is one of the most widely consumed drugs in the world. Studies have shown renal and hepatic damage as the direct result of high oxidative stress induced by APAP. Since the cardiovascular system is sensitive to oxidative stress and literature describes increased cardiovascular dysfunction in APAP consumers, this work aimed to evaluate harmful effects of APAP on the vascular system. Rats were exposed to APAP (400 mg/kg/day in drinking water) for 14 days. Plasma and aortas were collected and stored in - 80 °C and a selection of arteries was prepared for isometri...
Source: Archives of Toxicology - April 24, 2019 Category: Toxicology Authors: Porto HKP, Grando MD, Ramalho LNZ, Valadares MC, Bendhack LM, Batista AC, Rocha ML Tags: Arch Toxicol Source Type: research

2,3',4,4',5-Pentachlorobiphenyl induced autophagy of the thyrocytes via DAPK2/PKD/VPS34 pathway.
This study aimed to elucidate the mechanism by which PCB118 induces the abnormalities of the thyrocytes. Wistar rats were injected intraperitoneally with PCB118 (0, 10, 100 and 1000 μg/kg/d) for 13 weeks, and FRTL-5 cells were treated with PCB118 (0, 0.25, 2.5 and 25 nM). Transmission electron microscopy showed typical autophagosomes in the thyroid of PCB118-treated rats. Immunofluorescence staining showed dose-dependent increase of autophagy in FRTL-5 cells exposed to PCB118. In vivo and vitro studies found that Tubulin beta 3 class III (Tubb3) mRNA and protein levels decreased significantly, while Death...
Source: Archives of Toxicology - April 24, 2019 Category: Toxicology Authors: Zhou Q, Wang L, Chen H, Xu B, Xu W, Sheng Y, Duan Y Tags: Arch Toxicol Source Type: research

A long-wave UVA filter avobenzone induces obesogenic phenotypes in normal human epidermal keratinocytes and mesenchymal stem cells.
This study suggests that avobenzone functions as a metabolic disrupting obesogen. PMID: 31016361 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 23, 2019 Category: Toxicology Authors: Ahn S, An S, Lee M, Lee E, Pyo JJ, Kim JH, Ki MW, Jin SH, Ha J, Noh M Tags: Arch Toxicol Source Type: research

Ablation of aryl hydrocarbon receptor promotes angiotensin II-induced cardiac fibrosis through enhanced c-Jun/HIF-1 α signaling.
Ablation of aryl hydrocarbon receptor promotes angiotensin II-induced cardiac fibrosis through enhanced c-Jun/HIF-1α signaling. Arch Toxicol. 2019 Apr 23;: Authors: Ichihara S, Li P, Mise N, Suzuki Y, Izuoka K, Nakajima T, Gonzalez F, Ichihara G Abstract Aryl hydrocarbon receptor (AHR) is a transcription factor that binds to DNA as a heterodimer with the AHR nuclear translocator (ARNT) after interaction with ligands, such as polycyclic and halogenated aromatic hydrocarbons and other xenobiotics. The endogenous ligands and functions of AHR have been the subject of many investigations. In the pres...
Source: Archives of Toxicology - April 23, 2019 Category: Toxicology Authors: Ichihara S, Li P, Mise N, Suzuki Y, Izuoka K, Nakajima T, Gonzalez F, Ichihara G Tags: Arch Toxicol Source Type: research

Multispecies study: low-dose tributyltin impairs ovarian theca cell cholesterol homeostasis through the RXR pathway in five mammalian species including humans.
Abstract Tributyltin (TBT), an organotin chemical used as a catalyst and biocide, can stimulate cholesterol efflux in non-steroidogenic cells. Since cholesterol is the first limiting step for sex hormone production, we hypothesized that TBT disrupts intracellular cholesterol transport and impairs steroidogenesis in ovarian theca cells. We investigated TBT's effect on cholesterol trafficking, luteinization, and steroidogenesis in theca cells of five species (human, sheep, cow, pig, and mice). Primary theca cells were exposed to an environmentally relevant dose of TBT (1 or 10 ng/ml) and/or retinoid X receptor ...
Source: Archives of Toxicology - April 21, 2019 Category: Toxicology Authors: Pu Y, Pearl S, Gingrich J, Jing J, Martin D, Murga-Zamalloa CA, Veiga-Lopez A Tags: Arch Toxicol Source Type: research

The role of fuel type and combustion phase on the toxicity of biomass smoke following inhalation exposure in mice.
In this study, we developed a computer-controlled inhalation system which can precisely control complex biomass smoke emissions from different combustion conditions. This system was used to examine the toxicity of inhaled biomass smoke from peat, eucalyptus, and oak fuels generated under smoldering and flaming phases with emissions set to the same approximate concentration of carbon monoxide (CO) for each exposure (60-110 ppm), resulting in PM levels of ~ 4 mg/m3 for flaming and ~ 40 mg/m3 for smoldering conditions. Mice were exposed by inhalation 1 h/day for 2 days, and...
Source: Archives of Toxicology - April 20, 2019 Category: Toxicology Authors: Kim YH, King C, Krantz T, Hargrove MM, George IJ, McGee J, Copeland L, Hays MD, Landis MS, Higuchi M, Gavett SH, Gilmour MI Tags: Arch Toxicol Source Type: research

A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice.
Abstract Previous epidemiological studies have suggested a link between high-cholesterol intake and liver disease progression, including hepatocellular carcinoma (HCC). However, the precise mechanism of hepatotoxicity and hepatocarcinogenesis caused by excessive cholesterol consumption remains unclear. We aimed to investigate the impact of dietary cholesterol using hepatitis C virus core gene transgenic (HCVcpTg) mice, which spontaneously developed HCC with age. Male HCVcpTg mice were treated for 15 months with either a control diet or an isocaloric diet containing 1.5% cholesterol, and liver phenotypes and t...
Source: Archives of Toxicology - April 19, 2019 Category: Toxicology Authors: Wang X, Tanaka N, Hu X, Kimura T, Lu Y, Jia F, Sato Y, Nakayama J, Moriya K, Koike K, Aoyama T Tags: Arch Toxicol Source Type: research

Understanding the skin sensitization capacity of ascaridole: a combined study of chemical reactivity and activation of the innate immune system (dendritic cells) in the epidermal environment.
z-Arnau E Abstract To improve the prediction of the possible allergenicity of chemicals in contact with the skin, investigations of upstream events are required to better understand the molecular mechanisms involved in the initiation of allergic reactions. Ascaridole, one of the compounds responsible for skin sensitization to aged tea tree oil, degrades into intermediates that evolve via different mechanisms involving radical species. We aimed at broadening the knowledge about the contribution of radical intermediates derived from ascaridole to the skin sensitization process by assessing the reactivity profile tow...
Source: Archives of Toxicology - April 16, 2019 Category: Toxicology Authors: Sahli F, Sousa MSE, Vileno B, Lichter J, Lepoittevin JP, Blömeke B, Giménez-Arnau E Tags: Arch Toxicol Source Type: research

Will worker DNELs derived under the European REACH regulation extend the landscape of occupational exposure guidance values?
In conclusion, with extensive substance coverage, wDNELs extend the landscape beyond the OELs. That said, important limitations are (1) that many air pollutants relevant for workers' health are not covered by REACH, and (2) concerns for inconsistencies in the derivation of wDNELs and in their level of protection. In particular, that route-to-route extrapolation is a common practice that may be grossly misleading when the effect of concern is local, e.g. sensitisation. PMID: 30993379 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 16, 2019 Category: Toxicology Authors: Schenk L, Johanson G Tags: Arch Toxicol Source Type: research