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Journal of Applied Toxicology: JAT

Brittany F Karas, Leonor Côrte-Real, Cathleen L Doherty, Andreia Valente, Keith R Cooper, Brian T Buckley
As novel metallodrugs continue to emerge, they are evaluated using models, including zebrafish, that offer unique sublethal endpoints. Testing metal-based anticancer compounds with high-throughput zebrafish toxicological assays requires analytical methods with the sensitivity to detect these sublethal tissue doses in very small sample masses (e.g., egg mass 100 μg). A robust bioanalytical model, zebrafish embryos coupled with inductively coupled plasma-mass spectrometry (ICPMS) for measurement of delivered dose, creates a very effective means for screening metal-based chemotherapeutic agents...
April 8, 2019: Journal of Applied Toxicology: JAT
Sascha Pawlowski, Martina Dammann, Lennart Weltje, Samantha Champ, Michael Mathis, Douglas J Fort
The amphibian metamorphosis assay represents an OECD Level 3 and EDSP Tier 1 ecotoxicity test assessing thyroid activity of chemicals in African clawed frog (Xenopus laevis). To evaluate the effectiveness of snout-vent length (SVL) normalization of hindlimb length (HLL), correlation between the HLL and SVL or body weight was evaluated in the control groups of 10 individual studies from three laboratories. Two studies required separate analysis of the Nieuwkoop-Faber (NF) stage ≤60 and >60 animals creating a total of 12 data sets...
April 8, 2019: Journal of Applied Toxicology: JAT
Gregory D Rankin, Håkan Wingfors, Oskari Uski, Linnéa Hedman, Barbro Ekstrand-Hammarström, Jenny Bosson, Magnus Lundbäck
The use of electronic cigarettes (E-cigs) is rapidly increasing. The latest generation of E-cigs is highly customizable, allowing for high heating coil temperatures. The aim of this study was to assess the toxic potential of a fourth-generation E-cig. Aerosols generated from E-liquid with (24 mg/mL) and without nicotine, using a fourth-generation E-cig, were chemically analysed and compared with cigarette smoke (K3R4F). Human lung epithelial cell lines and distal lung tissue explants were exposed to E-cig vapour extract (EVE) and cigarette smoke extract for 24 hours and assessed for viability, inflammation, oxidative stress and genotoxicity...
April 8, 2019: Journal of Applied Toxicology: JAT
Lei Jiang, Tingwei Wang, Jing Xue, Pengfei Yu, Jinsong Zhang, Jun Wang
Carbon black in ambient air is believed to be the cause of many diseases; however, its potential neural toxicity and the underlying mechanisms remain poorly understood. The present study is to evaluate the toxic effects of carbon black nanoparticles, Printex 90, on the neural cell line PC-12. The study revealed that Printex 90 treatment significantly decreased cell viability, accompanied by an enormous increase in reactive oxygen species generation and a decrease in ATP. Additionally, NOX2 and NOX4, 4-hydroxynonenal, endoplasmic reticulum (ER) stress marker proteins (IRE-1α, ATF-6, GRP78, PERK and the downstream target protein CHOP) and antioxidative enzymes (glutathione and superoxide dismutase) were evaluated...
April 1, 2019: Journal of Applied Toxicology: JAT
Tamara J Martin, JaQuel Maise, Sahra Gabure, Margaret M Whalen
Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are organochlorine environmental contaminants found in human blood at very significant levels (as high as 5 μm for PCP and 260 nm for DDT). Cancers of the blood (lymphoma and myeloma) and kidney as well as others have been associated with exposure to these contaminants. Interleukin (IL)-1β is a proinflammatory cytokine and is involved in stimulating cell proliferation. High levels of IL-1β are associated with inflammatory diseases and tumor progression...
March 25, 2019: Journal of Applied Toxicology: JAT
Hui Gao, Jing Chen, Fan Ding, Xin Chou, Xiaoyan Zhang, Yi Wan, Jianying Hu, Qing Wu
Glyphosate-based herbicides have been used worldwide for decades and have been suggested to induce nephrotoxicity, but the underlying mechanism is not yet clear. In this study, we treated a human renal proximal tubule cell line (HK-2) with glyphosate for 24 hours at concentrations of 0, 20, 40 and 60 μm. Glyphosate was found to reduce cell viability and induce apoptosis and oxidative stress in a dose-dependent manner. Because the chemical structures of glyphosate and those of its metabolite AMPA are similar to glycine and glutamate, which are agonists of the N-methyl-d-aspartate receptor (NMDAR), we investigated the potential role of the NMDAR pathway in mediating the proapoptotic effect of glyphosate on proximal tubule cells...
March 25, 2019: Journal of Applied Toxicology: JAT
Sael Casas-Grajales, Karina Reyes-Gordillo, Carlos M Cerda-García-Rojas, Víctor Tsutsumi, M Raj Lakshman, Pablo Muriel
Rebaudioside A (Reb A) is a diterpenoid isolated from the leaves of Stevia rebaudiana (Bertoni) that has been shown to possess pharmacological activity, including anti-inflammatory and antioxidant properties. However, the ability of Reb A to prevent liver injury has not been evaluated. Therefore, we aimed to study the potential of Reb A (20 mg/kg; two times daily intraperitoneally) to prevent liver injury induced by thioacetamide (TAA) administration (200 mg/kg; three times per week intraperitoneally). In addition, cocultures were incubated with either lipopolysaccharide or ethanol...
March 18, 2019: Journal of Applied Toxicology: JAT
Keiko Ose, Fumihiro Yamada, Ayako Ohara, Noriyuki Suzuki, Takako Fukuda, Mitsugu Miyamoto, Kayo Sumida
Tadpoles during metamorphosis are sensitive to chemical exposure as shown in the amphibian metamorphosis assay, which is a method to detect effects of chemicals on the functions of hypothalamus-pituitary-thyroid axis. The present study reports existence of different modes of action between pyriproxyfen (PYR) and 6-propyl-2-thiouracil (PTU) under different feeding conditions based on gene expression profiles (transcriptomics) in the thyroid glands of tadpoles of the African clawed frog, Xenopus laevis. PTU and PYR were exposed to the tadpoles during metamorphosis under normal (fed groups, both of PTU and PRY) and restricted feeding (fasted groups, PTU only) conditions; and effects were compared to control groups...
March 18, 2019: Journal of Applied Toxicology: JAT
Cristina Monteiro, Conceição Santos, Verónica Bastos, Helena Oliveira
Occupational environments are major exposure routes to Cr(VI). However, Cr(VI) may also establish in bone tissues by ingestion or through Cr containing orthopaedic prostheses that, due to wear and corrosion, may release metal particles and ions potentially affecting bone tissue. The aim of this work was to evaluate the effects of clinically relevant concentrations of Cr(VI) in human osteoblasts, by integrating genotoxic effects, evaluated by the comet assay and cytokinesis-blocked micronucleus assay (scoring the presence of micronucleus, nucleoplasmic bridges and nuclear division index), with the effects on cell cycle and cell viability...
March 18, 2019: Journal of Applied Toxicology: JAT
Nicolas K Kambia, Isabelle Séverin, Amaury Farce, Emmanuel Moreau, Laurence Dahbi, Claire Duval, Thierry Dine, Valérie Sautou, Marie-Christine Chagnon
Plasticizers added to polyvinylchloride used in medical devices can be released into patients' biological fluids. The substitution of di-(2-ethylhexyl)phthalate (DEHP) by alternative plasticizers is essential but their safety must be demonstrated. DEHP, di-(2-ethylhexyl)terephthalate (DEHT) and their metabolites were investigated using level 2 Organization for Economic Co-operation and Development bioassays to screen for in vitro hormonal changes. Differences between the DEHP and DEHT metabolites were observed...
March 8, 2019: Journal of Applied Toxicology: JAT
Douglas J Fort, Michael B Mathis, Chelsea E Fort, Hayley M Fort, Troy D Fort, Patrick D Guiney, John A Weeks
The impact of the perfluoro-chemical, perfluorooctanesulfonate (PFOS), on gonadal steroidogenesis during sexual differentiation in Silurana tropicalis was examined because of its ubiquity in the environment, bioaccumulative nature and potential to disturb endocrine activity. A partial life cycle study exposing S. tropicalis to varying concentrations of PFOS 0.06, 0.13, 0.25, 0.50 and 1.0 mg PFOS/L [nominal]) was conducted. Gonad and plasma samples were collected from juvenile control specimens and organisms exposed to PFOS from early embryo through 150 days post-metamorphosis...
March 7, 2019: Journal of Applied Toxicology: JAT
Naresh Dumala, Bhanuramya Mangalampalli, Sarika Srinivas Kalyan Kamal, Paramjit Grover
Despite the increasing use of nickel oxide (NiO) nanoparticles (NPs), limited information is available on their toxicological effects. Health consequences of 28 days repeated oral exposure to NiO NPs have not been explored thoroughly. Hence, toxicity investigations were performed after 28-day daily exposure in albino Wistar rats with NiO NPs following Organization for Economic Co-operation and Development test guideline 407. Histopathology, biochemical indices including oxidative stress and biodistribution patterns were evaluated to decipher the toxicological impact of NiO NPs...
March 6, 2019: Journal of Applied Toxicology: JAT
Honesty Tohon, Mathieu Valcke, Sami Haddad
This study aimed to assess the impact of multi-route co-exposures to chemicals on interindividual variability in toxicokinetics. Probabilistic physiologically based pharmacokinetic multi-route interaction models were developed for adults and four younger subpopulations. Drinking water-mediated multi-route exposures were simulated for benzene alone or in co-exposure with toluene, ethylbenzene and m-xylene, for trichloroethylene or vinyl chloride (VC), alone and in mixture. These simulations were performed for "low" and "high" exposure scenarios, involving respectively the US EPA's short-term drinking water health advisories, and 10 times these advisory values...
March 5, 2019: Journal of Applied Toxicology: JAT
Liang Lu, Jia Chang, Yunliang Qiu, Yan Chang, Jing Ma
Fluorinated diiodine alkanes (FDIAs), important industrial intermediates in the synthesis of various perfluorinated compounds, which are distributed widely in wildlife and humans. Recent studies showed that FDIAs had in vitro estrogenic effects. However, to date, little information is available regarding the in vivo estrogenic effects of FDIAs and the mechanisms are unclear. In this study, a combination of in vitro and in vivo assays was used to investigate the estrogenic effects of FDIAs. We tested the in vitro estrogenic effects and estrogen receptor-related gene expression via MCF-7 cell assay...
March 4, 2019: Journal of Applied Toxicology: JAT
Diego García-Mendoza, Biyao Han, Hans J H J van den Berg, Nico W van den Brink
Toxic trace metals are widespread contaminants that are potentially immunotoxic even at environmentally low exposure levels. They can modulate the immunity to infections, e.g., in wildlife species living in contaminated areas. The diverse immune cell types can be differentially affected by the exposure leading to the modulation of specific protective mechanisms. Macrophages and mast cells, part of the innate immune system, trigger immune responses and perform particular effector functions. The present study compared toxicological and functional effects of cadmium in two models of murine macrophages (RAW264...
March 3, 2019: Journal of Applied Toxicology: JAT
Jnyandeep Hazarika, Mausumi Ganguly, Rita Mahanta
In recent years, there has been a widespread interest and awareness about health issues posed by endocrine-disrupting chemicals present in the environment. These chemicals, often present in food and many consumer products, can interfere with hormone biosynthesis and metabolism and may result in deviation from normal homeostatic control. Chlorpyrifos (CPF), a major endocrine-disrupting chemical is used worldwide as an agricultural insecticide against a broad spectrum of insect pests in rice cultivation and to control termites...
February 27, 2019: Journal of Applied Toxicology: JAT
Hector Rosas-Hernandez, Claudia Escudero-Lourdes, Manuel A Ramirez-Lee, Elvis Cuevas, Susan M Lantz, Syed Z Imam, Waqar Majeed, Shawn E Bourdo, Merle G Paule, Alexandru S Biris, Syed F Ali
Graphene-based nanomaterials hold the potential to be used in a wide variety of applications, including biomedical devices. Pristine graphene (PG) is an un-functionalized, defect-free type of graphene that could be used as a material for neural interfacing. However, the neurotoxic effects of PG, particularly to the blood-brain barrier (BBB), have not been fully studied. The BBB separates the brain tissue from the circulating substances in the blood and is essential to maintain the brain homeostasis. The principal components of the BBB are brain microvascular endothelial cells (BMVECs), which maintain a protectively low permeability due to the expression of tight junction proteins...
February 19, 2019: Journal of Applied Toxicology: JAT
Akiko Matsubara, Shingo Oda, Ru Jia, Tsuyoshi Yokoi
Glutathione (GSH) is one of the most extensively studied tripeptides. The roles for GSH in redox signaling, detoxification of xenobiotics and antioxidant defense have been investigated. A drug-induced rhabdomyolysis mouse model was recently established in L-buthionine-(S,R)-sulfoximine (BSO; a GSH synthesis inhibitor)-treated normal mice by co-administration of antibacterial drug and statin. In these models, mild kidney injury was observed in the BSO only-treated mice. Therefore, in this study, we studied kidney injury in the GSH-depleted mouse...
February 15, 2019: Journal of Applied Toxicology: JAT
Zimo Yin, Haixin Ai, Li Zhang, Guofei Ren, Yuming Wang, Qi Zhao, Hongsheng Liu
The prediction of compound cytotoxicity is an important part of the drug discovery process. However, it usually appears as poor predictive performance because the datasets are high-throughput and have a class-imbalance problem. In this study, several strategies of performing a structure-activity relationship study for a cytotoxic endpoint in the AID364 dataset were explored to solve the class-imbalance problem. Random forest adaboost was used as the base learners for 10 types of molecular fingerprints and an ensemble method and six data-balancing methods were applied to balance the classes...
February 14, 2019: Journal of Applied Toxicology: JAT
Naresh Dumala, Bhanuramya Mangalampalli, Paramjit Grover
The current study was intended to elucidate the cytotoxicity, genotoxicity ability of nickel oxide (NiO) nanoparticles (NPs) and assessment of preliminary mechanism of the toxicity. Characterization studies showed that NiO-NPs have a particle size of 17.94 (±3.48) nm. The particle size of the NPs obtained by dynamic light scattering method in Milli-Q and RPMI 1640 media was 189.9 (±17.1) and 285.9 (±19.6) nm, respectively. The IC50 concentration for NiO-NPs after 24 hours of treatment was estimated as 23...
February 14, 2019: Journal of Applied Toxicology: JAT
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