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Journal of Applied Toxicology: JAT

Yoon Chan Rah, Eun Jung Han, Saemi Park, Jihye Rhee, Soonil Koun, Hae-Chul Park, June Choi
Recently, intratympanic injection of gadolinium-based contrast agent (GdC) is growing in use to visualize the endolymphatic hydrops. Although GdC has been quite safely used over 20 years through intravenous injection, the biological influence of GdC on sensory hair cells needs to be thoroughly assessed for wider clinical application of it through intratympanic injection. In this in vivo experimental study, the summated number of sensory hair cells (SO1, SO2, O1 and OC1 neuromasts) showed a steep decrease in the group exposed to 10% and 20% GdC (35...
June 29, 2018: Journal of Applied Toxicology: JAT
Robin Mesnage, Martina Biserni, Dilyana Genkova, Ludovic Wesolowski, Michael N Antoniou
Few studies have investigated non-target effects of neonicotinoid insecticides on mammalian physiology. This is largely due to the widespread perception that their weak affinity for nicotinic acetylcholine receptor subtypes in vertebrates makes mammalian exposures unlikely to pose health risks. To the best of our knowledge, we describe the first investigation evaluating the interaction of seven principal neonicotinoid insecticides (thiamethoxam, imidacloprid, clothianidin, flupyradifurone, dinotefuran, nitenpyram, thiacloprid) with oestrogen and thyroid hormone receptors, as well as their adipogenic effects, in mammalian cell culture assay systems...
June 27, 2018: Journal of Applied Toxicology: JAT
Lucía Z Flores-López, Heriberto Espinoza-Gómez, Ratnasamy Somanathan
The industry of nanotechnology has had a rapid development in the last decades. In particular, silver nanoparticles (AgNPs) have unique properties so they can be used in different industrial applications, mainly in areas such as electronics, environment, medicine, biosensors and biotechnology; as well as household and healthcare-related products, like cosmetics, due to their antimicrobial properties. These beneficial effects are also offset by the higher chemical reactivity of these NPs due to their surface area to volume ratio, leading to the increased formation of reactive oxygen species (ROS) within cells...
June 25, 2018: Journal of Applied Toxicology: JAT
Jinjun Shan, Tong Xie, Jianya Xu, Huifang Zhou, Xia Zhao
The use of Chinese medicines (CMs) during pregnancy has long been a major public health concern. Although CMs have been shown to be effective in treating infertility and preventing miscarriage, their use has been restricted, mainly because of limited knowledge of their potential toxicity. Accurate toxicology data are urgently required to assess whether these CMs are safe for maternal health and fetal development. Amniotic fluid (AF) contains carbohydrates, lipids and phospholipids, urea and proteins, all of which aid in the growth of the fetus and reflect the mother's health status as well...
June 21, 2018: Journal of Applied Toxicology: JAT
Sellamani Muthulakshmi, Pourmohammadi Fallah Hamideh, Hamid R Habibi, Kannan Maharajan, Krishna Kadirvelu, Venkataramana Mudili
In the present study, we aimed to assess the adverse effects of zearalenone (ZEA) at environmentally relevant concentrations (0.5, 1, 5 and 10 μg l-1 ) on hypothalamic-pituitary-gonadal axis associated reproductive function using zebrafish model. ZEA was exposed to female zebrafish for 21 days to assess growth indices such as condition factor, hepatosomatic index, gonadosomatic index and caspase 3 activity. Further, expression of estrogen receptor (ER) α and CYP19a1b genes in the brain, ERα and vitellogenin (Vtg) genes in the liver and follicle-stimulating hormone receptor, luteinizing hormone receptor, ERα, steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase (HSD), 17-βHSD and CYP19a1 genes in the ovary were also investigated...
June 19, 2018: Journal of Applied Toxicology: JAT
Yanglei Yi, Fan Zhao, Nan Wang, Huan Liu, Lijun Yu, Aihua Wang, Yaping Jin
T-2 toxin is one of the trichothecene mycotoxins commonly found in animal feed and agricultural products. Ingestion of T-2 toxin by animals results in acute and chronic diseases, as well as reproductive failure. This study aimed at investigating the role of endoplasmic reticulum (ER) stress in T-2 toxin-induced apoptosis in goat endometrium epithelial cells. Flow cytometry and cell viability assay showed that T-2 toxin significantly induced cell apoptosis, which was accompanied with increased expression of cleaved-caspase-3...
June 12, 2018: Journal of Applied Toxicology: JAT
Adedamola Olayanju, Lauren Jones, Karin Greco, Christopher E Goldring, Tahera Ansari
The gastrointestinal tract (GI) is a crucial part of the body for growth and development and its dysregulation can lead to several diseases with detrimental effects. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. Organoids are three-dimensional self-organizing and self-renewing structures that are composed of a cluster of different cells in vitro that resemble their organ of origin in architecture and function. Over recent years, organoids have been increasingly used to study developmental biology, disease progression, i...
June 11, 2018: Journal of Applied Toxicology: JAT
Xiao Chen, Guoying Zhu, Zhongqiu Wang, Yihuai Liang, Bo Chen, Ping He, Monica Nordberg, Gunnar F Nordberg, Xiaoqiang Ding, Taiyi Jin
The tolerable dietary intake of cadmium was recommended at provisional tolerable monthly intake of 25 μg kg-1 body weight. However, several studies indicated that this tolerable level should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using a benchmark dose (BMD) approach. A total of 790 subjects (302 men and 488 women) living in control and cadmium-polluted areas were included. The dietary cadmium intake was estimated by a food survey...
June 10, 2018: Journal of Applied Toxicology: JAT
Cristina Andreoli, Giorgio Leter, Barbara De Berardis, Paolo Degan, Isabella De Angelis, Francesca Pacchierotti, Riccardo Crebelli, Flavia Barone, Andrea Zijno
In the last years, a number of in vitro studies have been performed to assess the genotoxic activity of titanium dioxide (TiO2 ). To resolve the contradictory results, in this study, we investigated the genotoxic activity of commercial TiO2 nanoparticles (NPs) and microparticles of different forms (anatase, rutile and mix of both). We evaluated micronucleus formation in stimulated lymphocytes, as well as DNA strand breaks and 8-oxo-7,8-dihydro-2'-deoxyguanosine in peripheral blood mononuclear cells (PBMCs), a mixed population of lymphocytes and monocytes...
June 4, 2018: Journal of Applied Toxicology: JAT
Rhishikesh Thakare, Jawaher Abdullah Alamoudi, Nagsen Gautam, A David Rodrigues, Yazen Alnouti
One of the mechanisms of drug-induced liver injury (DILI) involves alterations in bile acid (BA) homeostasis and elimination, which encompass several metabolic pathways including hydroxylation, amidation, sulfation, glucuronidation and glutathione conjugation. Species differences in BA metabolism may play a major role in the failure of currently used in vitro and in vivo models to predict reliably the DILI during the early stages of drug discovery and development. We developed an in vitro cofactor-fortified liver S9 fraction model to compare the metabolic profiles of the four major BAs (cholic acid, chenodeoxycholic acid, lithocholic acid and ursodeoxycholic acid) between humans and several animal species...
May 29, 2018: Journal of Applied Toxicology: JAT
Marianne B Ariganello, Dharani D Das, Dalibor Breznan, Christine MacKinnon-Roy, Fred Elisma, Aziz Khanchi, Renaud Vincent, Prem Kumarathasan
Knowledge of biological reactivity and underlying toxicity mechanisms of airborne particulate matter (PM) is central to the characterization of the risk associated with these pollutants. An integrated screening platform consisting of protein profiling of cellular responses and cytotoxic analysis was developed in this study for the estimation of PM potencies. Mouse macrophage (J774A.1) and human lung epithelial cells (A549) were exposed in vitro to Ottawa urban particles (EHC6802) and two reference mineral particles (TiO2 and SiO2 )...
May 29, 2018: Journal of Applied Toxicology: JAT
Anna Beronius, Linda Molander, Johanna Zilliacus, Christina Rudén, Annika Hanberg
The Science in Risk Assessment and Policy (SciRAP) web-based platform was developed to promote and facilitate structure and transparency in the evaluation of ecotoxicity and toxicity studies for hazard and risk assessment of chemicals. The platform includes sets of criteria and a colour-coding tool for evaluating the reliability and relevance of individual studies. The SciRAP method for evaluating in vivo toxicity studies was first published in 2014 and the aim of the work presented here was to evaluate and develop that method further...
May 28, 2018: Journal of Applied Toxicology: JAT
Nicholas Buss, Patricia Ryan, Todd Baughman, Denis Roy, Claire Patterson, Carolyn Gordon, Rakesh Dixit
Exenatide, a glucagon-like peptide-1 receptor agonist was originally developed as either a twice daily or once weekly injectable therapeutic for patients with type 2 diabetes. Exenatide QW suspension was developed for use with an autoinjector device, in which the microspheres are suspended in Miglyol 812, a mixture of medium chain triglycerides (MCTs). MCTs are a class of lipids whose fatty acid chains contain from six to 12 carbon atoms (medium chain fatty acids or MCFAs). While MCTs are edible oils present in many foods, including foodstuffs containing coconut and palm kernel oils, limited information is available regarding the oral and subcutaneous bioavailability of MCTs as well as safety following subcutaneous injection...
May 28, 2018: Journal of Applied Toxicology: JAT
Yosuke Maeda, Haruka Hirosaki, Hidenori Yamanaka, Masahiro Takeyoshi
Photoallergic dermatitis, caused by pharmaceuticals and other consumer products, is a very important issue in human health. However, S10 guidelines of the International Conference on Harmonization do not recommend the existing prediction methods for photoallergy because of their low predictability in human cases. We applied local lymph node assay (LLNA), a reliable, quantitative skin sensitization prediction test, to develop a new photoallergy prediction method. This method involves a three-step approach: (1) ultraviolet (UV) absorption analysis; (2) determination of no observed adverse effect level for skin phototoxicity based on LLNA; and (3) photoallergy evaluation based on LLNA...
May 23, 2018: Journal of Applied Toxicology: JAT
Fang Ye, Xiaoyi Li, Yawen Liu, Wei Chang, Wenqi Liu, Jing Yuan, Jun Chen
The neurotoxicity of lead (Pb) is well established, and oxidative stress is strongly associated with Pb-induced neurotoxicity. Heme oxygenase 1 (HO-1) is an important antioxidative enzyme for protection against oxidative stress in many disease models. In this study, we applied hemin, the substrate and a well-known inducer of HO-1, to investigate the possible role of HO-1 in protecting against Pb neurotoxicity. Hemin can significantly attenuate Pb acetate-induced cell death and oxidative stress in the hippocampus and frontal cortex of developmental rats...
May 23, 2018: 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
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