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Journal of Applied Toxicology: JAT

Rhishikesh Thakare, Jawaher Abdullah Alamoudi, Nagsen Gautam, A David Rodrigues, Yazen Alnouti
Maintenance of bile acid (BA) homeostasis is essential to achieve their physiologic functions and avoid their toxic effects. The marked differences in BA composition between preclinical safety models and humans may play a major role in the poor prediction of drug-induced liver injury using preclinical models. We compared the composition of plasma and urinary BAs and their metabolites between humans and several animal species. Total BA pools and their composition varied widely among different species. Highest sulfation of BAs was observed in human and chimpanzee...
May 21, 2018: Journal of Applied Toxicology: JAT
Tim Erkens, Ruud Bueters, Marjolein van Heerden, Filip Cuyckens, Rob Vreeken, Nick Goeminne, Lieve Lammens
The intestinal barrier controls intestinal permeability, and its disruption has been associated with multiple diseases. Therefore, preclinical safety biomarkers monitoring barrier integrity are essential during the development of drugs targeting the intestines, particularly if starting treatment early after onset of disease. Classical toxicology endpoints are not sensitive enough and therefore our objective was to identify non-invasive markers enabling early in vivo detection of colonic barrier perturbation...
May 20, 2018: Journal of Applied Toxicology: JAT
Yuan Li, Weiwei Qian, Dengdian Wang, Yu Meng, Xiaoqian Wang, Yue Chen, Xiaoting Li, Chunfeng Xie, Caiyun Zhong, Suming Fu
Oxidative stress and inflammation are critically implicated in ambient fine particulate matter (mean diameter < 2.5 μm; PM2.5 )-induced lung injury. Autophagy, playing a crucial role in various physiopathological conditions, modulates cellular homeostasis and stress adaptation. Resveratrol is a phytoalexin that exerts potent antioxidant effects on cardiopulmonary diseases. To date, the mechanisms by which resveratrol protects against PM2.5 remain to be elucidated. In the present study, we investigated the effect of resveratrol on PM2...
May 20, 2018: Journal of Applied Toxicology: JAT
Renata K Carvalho, Monaliza L Santos, Maingredy R Souza, Thiago L Rocha, Francisco S Guimarães, Janete A Anselmo-Franci, Renata Mazaro-Costa
Children and adults with frequent and severe episodes of epilepsy that do not respond to standard treatments (such as carbamazepine, phenytoin and valproate) have long been prescribed cannabidiol (CBD) as an anticonvulsant drug. However, the safety of its chronic use in relation to reproduction has not been fully examined. This study aimed to assess the effects of chronic CBD exposure on the male reproductive system. CBD was orally administered to 21-day-old male Swiss mice at doses of 15 and 30 mg kg-1 daily (CBD 15 and 30 groups, respectively), with a control group receiving sunflower oil, for 34 consecutive days...
May 16, 2018: Journal of Applied Toxicology: JAT
Christian Imholt, Tariq Abdulla, Alexander Stevens, Peter Edwards, Jens Jacob, David Woods, Elaine Rogers, Leon Aarons, Daniel Segelcke
Compounds and products in the biocide and plant protection sector can only be registered after formal risk assessment to ensure safety for users and the environment. In bird and mammal risk assessment, this is routinely done using generic focal species as models, which are of particular exposure risk. Such a species is the common vole (Microtus arvalis) due to its high food intake relative to the low body weight. For wild species, biological samples, data and hence realistic exposure estimations are particularly difficult to obtain...
May 16, 2018: Journal of Applied Toxicology: JAT
M P Navarrete-Meneses, A I Pedraza-Meléndez, C Salas-Labadía, D Moreno-Lorenzana, P Pérez-Vera
Pesticides are commonly used worldwide and almost every human is potentially exposed to these chemicals. Exposure to pesticides such as permethrin and malathion has been associated with hematological malignancies in epidemiological studies. However, biological evidence showing if these chemicals induce genetic aberrations involved in the etiology of leukemia and lymphoma is missing. In our previous work, we have shown that a single high exposure (200 μm, 24 hours) of permethrin and malathion induce damage in genes associated with hematological malignancies in peripheral blood mononuclear cells analyzed by interphase fluorescence in situ hybridization (FISH)...
May 9, 2018: Journal of Applied Toxicology: JAT
Laura Vila, Alba García-Rodríguez, Ricard Marcos, Alba Hernández
The widespread use of titanium dioxide nanoparticles (TiO2 NPs) in commercial food products makes intestinal cells a suitable target. Accordingly, we have used the human colon adenocarcinoma Caco-2 cells to detect their potential harmful effects. Caco-2 cells can differentiate in to enterocytic-like cells, forming consistent cell monolayers and are used as a model of the intestinal barrier. Using both undifferentiated and differentiated Caco-2 cells, we have explored a set of biomarkers, aiming to evaluate undesirable effects associated to TiO2 NP exposure...
May 3, 2018: Journal of Applied Toxicology: JAT
Tatsushi Toyooka, Yukie Yanagiba, Yuko Ibuki, Rui-Sheng Wang
Trichloroethylene (TCE), a chlorinated hydrocarbon, was recently reclassified as a human carcinogen by the International Agency for Research on Cancer. Genotoxic events are known to be crucial steps in the initiation of cancer. The genotoxic properties of TCE have been examined in many studies using a standard battery of genotoxicity tests both in vitro and in vivo. However, consistent results have not been obtained, and studies investigating the mechanism behind the genotoxicity of this compound are lacking...
May 3, 2018: Journal of Applied Toxicology: JAT
Hideyuki Mizumachi, Megumi Sakuma, Mayu Ikezumi, Kazutoshi Saito, Midori Takeyoshi, Noriyasu Imai, Hiroko Okutomi, Asami Umetsu, Hiroko Motohashi, Mika Watanabe, Masaaki Miyazawa
The epidermal sensitization assay (EpiSensA) is an in vitro skin sensitization test method based on gene expression of four markers related to the induction of skin sensitization; the assay uses commercially available reconstructed human epidermis. EpiSensA has exhibited an accuracy of 90% for 72 chemicals, including lipophilic chemicals and pre-/pro-haptens, when compared with the results of the murine local lymph node assay. In this work, a ring study was performed by one lead and two naive laboratories to evaluate the transferability, as well as within- and between-laboratory reproducibilities, of EpiSensA...
May 3, 2018: Journal of Applied Toxicology: JAT
Vasiliki Karzi, Manolis N Tzatzarakis, Elena Vakonaki, Thanasis Alegakis, Ioanna Katsikantami, Stavros Sifakis, Apostolos Rizos, Aristidis M Tsatsakis
Bisphenol A (BPA), triclosan (TCS) and perfluorooctanoic acid (PFOA) are endocrine disruptors linked with negative health effects such as developmental, reproductive and cardiovascular toxicity. The aim of this study was to determine simultaneously the concentration of BPA, TCS and PFOA in hair from children and adults and examine possible associations between biomonitoring data and age, gender, dietary habits and body mass index. Methanolic extraction was applied and the compounds were determined by liquid chromatography-mass spectrometry...
May 3, 2018: Journal of Applied Toxicology: JAT
Tianshu Wu, Xue Liang, Keyu He, Tingting Wei, Yan Wang, Lingyue Zou, Jie Lu, Ying Yao, Na Liu, Ting Zhang, Yuying Xue, Meng Tang
Recently, the increasing number of bio-safety assessments on cadmium-containing quantum dots (QDs) suggested that they could lead to detrimental effects on the central nervous system (CNS) of living organisms, but the underlying action mechanisms are still rarely reported. In this study, whole-transcriptome sequencing was performed to analyze the changes in genome-wide gene expression pattern of rat hippocampus after treatments of cadmium telluride (CdTe) QDs with two sizes to understand better the mechanisms of CdTe QDs causing toxic effects in the CNS...
May 3, 2018: Journal of Applied Toxicology: JAT
Yunfeng Luo, Chaohua Wu, Liangliang Liu, Yu Gong, Shengming Peng, Yixi Xie, Yi Cao
It is recently shown that flavonoids might reduce the toxicity of nanoparticles (NPs) due to their antioxidative properties. In this study, the influence of 3-hydroxyflavone (H3) on the toxicity of ZnO NPs was investigated. H3 increased hydrodynamic size, polydispersity index and absolute value of the zeta potential of ZnO NPs, which indicated that H3 could influence the colloidal aspects of NPs. Surprisingly, H3 markedly decreased the initial concentration of ZnO NPs required to induce cytotoxicity to Caco-2, HepG2, THP-1 and human umbilical vein endothelial cells, which suggested that H3 could promote the toxicity of ZnO NPs to both cancerous and normal cells...
April 25, 2018: Journal of Applied Toxicology: JAT
Michał Otręba, Leon Kośmider, Jakub Knysak, Jared D Warncke, Andrzej Sobczak
E-cigarettes are used by millions of people despite the fact that the harmful effect of aerosol emitted from these products to the human organism is still not clear. In this paper, toxicity of vapor generated using different solutions and battery output voltage on A549 cells viability is presented. The obtained EC50 values for commercially available propylene glycol/glycerol solution 1:1 e-liquids based on 3.2 V (0.127%), 4.0 V (0.112%) and 4.8 V (0.038%) were about 1.5-4.5 times higher than in tobacco smoke (0...
April 17, 2018: Journal of Applied Toxicology: JAT
Rachid Jellali, Françoise Gilard, Vittoria Pandolfi, Audrey Legendre, Marie-José Fleury, Patrick Paullier, Cécile Legallais, Eric Leclerc
Despite the diversity of studies on pesticide toxicities, there is a serious lack of information concerning the toxic effect of pesticides mixtures. Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are among the most prevalent pesticides in the environment and have been the subject of several toxicological studies. However, there are no data on the toxicity of their mixtures. In this study, we used an approach combining cell culture in microfluidic biochips with gas chromatography-mass spectrometry metabolomics profiling to investigate the biomarkers of toxicity of DDT, PMT and their mixtures...
April 16, 2018: Journal of Applied Toxicology: JAT
Tianyi Li, Hongqun Qiao, Peng Yue, Ming Cai, Xuejun He
Vonoprazan is a new potassium-competitive acid blocker to treat acid-related diseases. However, its safety during pregnancy is unclear. The aim of the study was to investigate the potential reproductive toxicity on the embryo-fetal development of vonoprazan. Vonoprazan acetate was administered by intravenous injection to pregnant rats (0, 2, 6 and 20 mg kg-1 day-1 ) and rabbits (0, 1.2, 3.6 and 12 mg kg-1 day-1 ) during the organogenetic period (gestation day 6-15 [rats] and 6-18 [rabbits]). Maternal reproductive endpoints were evaluated, together with effects on fetal growth and morphological development...
April 16, 2018: Journal of Applied Toxicology: JAT
L Barr, M Alamer, P D Darbre
The human population is widely exposed to benzophenone-3 (BP-3), octylmethoxycinnamate (OMC), 4-methylbenzilidenecamphor (4-MBC) and homosalate from their use in consumer goods to absorb ultraviolet (UV) light. Their oestrogenic activity and presence in human milk suggest a potential to influence breast cancer development. In this study, high-performance liquid chromatography-tandem mass spectrometry was used to measure concentrations of these UV filters in human breast tissue from three serial locations across the breast from 40 women undergoing mastectomy for primary breast cancer...
April 16, 2018: Journal of Applied Toxicology: JAT
Srinath Patibandla, Yinan Zhang, Ali Mohammad Tohari, Peng Gu, James Reilly, Yu Chen, Xinhua Shu
The use of nanoparticles - particles that range in size from 1 to 100 nm - has become increasingly prevalent in recent years, bringing with it a variety of potential toxic effects. Zebrafish embryos were exposed during the 3 day postfertilization period to gold nanospheres (GNSs), gold nanorods (GNRs), GNRs coated with polystyrene sulphate (PSS-GNRs) and GNRs coated with both PSS and polyallamine hydrochloride (PAH-PSS-GNRs). All nanorods were stabilized with cetyltrimethylammonium bromide. GNSs were the least toxic of the nanoparticles studied, with exposure resulting in no significant changes in mortality, hatching or heart rate...
April 15, 2018: Journal of Applied Toxicology: JAT
Danica Sabolová, Pavol Kristian, Mária Kožurková
This review describes the synthesis of a wide range of novel tetrahydroacridine derivatives (tiocyanates, selenocyanates, ureas, selenoureas, thioureas, isothioureas, disulfides, diselenides and several tacrine homo- and hetro-hybrids). These tacrine congeners exhibit significant anticholinesterase and cytotoxic properties and may therefore be of considerable potential for the development of new drugs for the treatment of Alzheimer's disease.
April 6, 2018: Journal of Applied Toxicology: JAT
Kinga Anna Urbanek, Dominika Ewa Habrowska-Górczyńska, Karolina Kowalska, Anna Stańczyk, Kamila Domińska, Agnieszka Wanda Piastowska-Ciesielska
Deoxynivalenol (DON) is a type B trichothecene, produced by the Fusarium species. Exposure to DON might cause disruptive effects such as reduced weight gain, neuroendocrine changes and immune modulation in animals (rats, dogs, pigs). There is huge concern that similar effects can be observed in humans. DON is a potential regulator of intracellular steroidogenesis. It is also possible that DON will be involved in the regulation of miRNAs connected with steroidogenesis. This review summarizes the latest knowledge about the influence of DON on steroidogenesis and human hormonal balance...
April 3, 2018: Journal of Applied Toxicology: JAT
Andrew Croaker, Graham J King, John H Pyne, Shailendra Anoopkumar-Dukie, Lei Liu
Epidemic dropsy is a potentially life-threatening condition resulting from the ingestion of argemone oil derived from the seeds of Argemone mexicana Linn. Exposure to argemone oil is usually inadvertent, arising from mustard cooking oil adulteration. Sanguinarine, an alkaloid present in argemone oil, has been postulated as a causative agent with the severity of epidemic dropsy correlating with plasma sanguinarine levels. Cases of epidemic dropsy have also been reported following the topical application of argemone containing massage oil...
March 30, 2018: Journal of Applied Toxicology: JAT
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