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Journal of Applied Toxicology: JAT

Akiko Honda, Takahiro Sawahara, Tomohiro Hayashi, Kenshi Tsuji, Wataru Fukushima, Mizuki Oishi, Gaku Kitamura, Hitomi Kudo, Sho Ito, Seiichi Yoshida, Takamichi Ichinose, Kayo Ueda, Hirohisa Takano
Epidemiologic studies have revealed that Asian sand dust particles (ASDs) can affect respiratory and immune health represented by asthma. Factors responsible for the exacerbation of asthma remain unclear. The fungus Bjerkandera adusta ( and polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) have been identified in ASDs collected from the atmosphere when an ASD event occurred. We investigated the effects of and BaP related to ASDs on respiratory and immune systems. Bone marrow-derived antigen-presenting cells (APCs) and splenocytes from atopic prone NC/Nga mice and human airway epithelial cells were exposed to the B...
October 7, 2016: Journal of Applied Toxicology: JAT
Carmen Steinborn, Christoph Diegel, Manuel Garcia-Käufer, Carsten Gründemann, Roman Huber
Because different metals are used in complementary medicine for the treatment of diseases related to a dysfunction of the immune system, this study aimed at determining the immunomodulatory potential of Pb(NO3 )2 , AuCl3 , Cu(NO3 )2 , HgCl2 , AgNO3 , SnCl2 , AsCl3 and SbCl3 at sub-toxic concentrations and at assessing possible toxic side effects of low-concentrated metal preparations. The influence of the metal salts on primary human mononuclear cells was analyzed by measuring cell viability using the water-soluble tetrazolium salt assay, apoptosis and necrosis induction by annexin V/propidium iodide staining and proliferation by carboxyfluorescein diacetate succinimidyl ester staining and flow cytometry...
October 7, 2016: Journal of Applied Toxicology: JAT
Guihua Zhang, Naohide Shinohara, Yutaka Oshima, Toshio Kobayashi, Nobuya Imatanaka, Kenji Kawaguchi, Masashi Gamo
Intratracheal administration methods are used to conduct toxicological assessments of inhaled nanoparticles (NPs), and gavage needles or microsprayers are common intratracheal delivery devices. The NP suspension is delivered in a liquid state via gavage needle and as a liquid aerosol via microsprayer. The differences in local pulmonary NP distribution (called the microdistribution) arising from the different states of the NP suspension cause differential pulmonary responses; however, this has yet to be investigated...
October 6, 2016: Journal of Applied Toxicology: JAT
Timothy R Fennell, Ninell P Mortensen, Sherry R Black, Rodney W Snyder, Keith E Levine, Eric Poitras, James M Harrington, Christopher J Wingard, Nathan A Holland, Wimal Pathmasiri, Susan C J Sumner
Few investigations have been conducted on the disposition and fate of silver nanoparticles (AgNP) in pregnancy. The distribution of a single dose of polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate the role of AgNP diameter and particle dissolution in tissue distribution, internal dose and persistence. Dams were administered AgNP or AgAc intravenously (i.v.) (1 mg kg(-1) ) or by gavage (p...
October 3, 2016: Journal of Applied Toxicology: JAT
Sandesh Chibber, Rishi Shanker
Copper has been used from ancient time in various applications. Scientists have exploited its means of exposure and consequences to living organisms. The peculiar property of nanomaterials that is a high surface to volume ratio has increased the range of application in products. Copper oxide nanoparticles (CuO NPs) are widely used in industrial applications such as semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics, heat transfer fluids and consumer products. In contrast, acute toxicity of CuO NPs has also been reported...
September 30, 2016: Journal of Applied Toxicology: JAT
Dayton M Petibone, Waqar Majeed, Daniel A Casciano
Autophagy is a cellular process that facilitates nutrient turnover and removal of expended macromolecules and organelles to maintain homeostasis. The recycling of cytosolic macromolecules and damaged organelles by autophagosomes occurs through the lysosomal degradation pathway. Autophagy can also be upregulated as a prosurvival pathway in response to stress stimuli such as starvation, hypoxia or cell damage. Over the last two decades, there has been a surge in research revealing the basic molecular mechanisms of autophagy in mammalian cells...
September 29, 2016: Journal of Applied Toxicology: JAT
Jun-Kyoung Lee, Soyoung Lee, Moon-Chang Baek, Byung-Heon Lee, Hyun-Shik Lee, Taeg Kyu Kwon, Pil-Hoon Park, Tae-Yong Shin, Dongwoo Khang, Sang-Hyun Kim
Perfluorooctanoic acid (PFOA) has wide applications, including as a raw material for converted paper and packaging products. With the widespread use of PFOA, concerns regarding its potential environmental and health impacts have increased. In spite of the known hepatotoxicity and genotoxicity of PFOA, correlation with PFOA and allergic inflammation is not well known. In this study, the effect of PFOA on the degranulation of mast cells and mast cell-mediated allergic inflammation in the presence of FcεRI cross-linking was evaluated...
September 29, 2016: Journal of Applied Toxicology: JAT
Shingo Oda, Yuji Shirai, Sho Akai, Akira Nakajima, Koichi Tsuneyama, Tsuyoshi Yokoi
The acyl glucuronide (AG) metabolites of carboxylic acid-containing drugs are potentially chemically reactive and are suggested to be implicated in toxicity, including hepatotoxicity, nephrotoxicity and drug hypersensitivity reactions. However, it remains unknown whether AG formation is related to toxicity in vivo. In this study, we sought to determine whether AG is involved in the pathogenesis of liver injury using a mouse model of diclofenac (DIC)-induced liver injury. Mice that were administered DIC alone exhibited significantly increased plasma alanine aminotransferase levels, whereas mice that were pretreated with the UDP-glucuronosyltransferase inhibitor (-)-borneol (BOR) exhibited suppressed alanine aminotransferase levels at 3 and 6 h after DIC administration although not significant at 12 h...
September 27, 2016: Journal of Applied Toxicology: JAT
Jerine Peter Simon, Sabina Evan Prince
The liver is an important organ of the body, which has a vital role in metabolic functions. The non-steroidal anti-inflammatory drug (NSAID), diclofenac causes hepato-renal toxicity and gastric ulcers. NSAIDs are noted to be an agent for the toxicity of body organs. This review has elaborated various scientific perspectives of the toxicity caused by diclofenac and its mechanistic action in affecting the vital organ. This review suggests natural products are better remedies than current clinical drugs against the toxicity caused by NSAIDs...
September 22, 2016: Journal of Applied Toxicology: JAT
Isamu Suzuki, Young-Man Cho, Tadashi Hirata, Takeshi Toyoda, Jun-Ichi Akagi, Yasushi Nakamura, Azusa Sasaki, Takako Nakamura, Shigehisa Okamoto, Koji Shirota, Noboru Suetome, Akiyoshi Nishikawa, Kumiko Ogawa
We recently reported that 4-methylthio-3-butenyl isothiocyanate (MTBITC) exerts chemopreventive effects on the rat esophageal carcinogenesis model at a low dose of 80 ppm in a diet. In contrast, some isothiocyanates (ITCs) have been reported to cause toxic effects, promotion activity, and/or carcinogenic potential in the urinary bladder of rats. In the present study, we investigated whether MTBITC had toxic effects in the urinary bladder similar to other ITCs, such as phenethyl ITC (PEITC). First, to examine the early toxicity of MTBITC, rats were fed a diet supplemented with 100, 300 or 1000 ppm MTBITC for 14 days...
September 15, 2016: Journal of Applied Toxicology: JAT
Ilseob Shim, Kyunghee Choi, Seishiro Hirano
Silver is commonly used as a disinfectant, and chronic exposure to silver may cause argyria, resulting in a gray-blue discoloration of human skin. However, the mechanism for cellular toxicity of silver has not been well explained. We studied the mode of cell death, the ratio of glutathione disulfide/glutathione, induction of metallothionein and activation of mitogen-activated protein kinases in J774.1 cells together with activation of antioxidant responsive element and nuclear factor-κB in CHO cells following exposure to silver ion (Ag(+) ) to investigate the mechanism by which Ag(+) causes lethal effects...
September 14, 2016: Journal of Applied Toxicology: JAT
Dietrich E Lorke, Anka Stegmeier-Petroianu, Georg A Petroianu
The recognition in the early 1960s by Morifusa Eto that tri-o-cresyl phosphate (TOCP) is hydroxylated by the cytochrome P450 system to an intermediate that spontaneously cyclizes to a neurotoxic phosphate (saligenin phosphate ester) ignited the interest in this group of compounds. Only the ortho isomer can cyclize and clinically cause Organo Phosphate Induced Delayed Neurotoxicity (OPIDN); the meta and para isomers of tri-cresyl phosphate are not neuropathic because they are unable to form stable cyclic saligenin phosphate esters...
September 9, 2016: Journal of Applied Toxicology: JAT
Datis Kharrazian, Aristo Vojdani
Evidence continues to increase linking autoimmunity and other complex diseases to the chemicals commonly found in our environment. Bisphenol A (BPA) is a synthetic monomer used widely in many forms, from food containers to toys, medical products and many others. The potential for BPA to participate as a triggering agent for autoimmune diseases is likely due to its known immunological influences. The goal of this research was to determine if immune reactivity to BPA has any correlation with neurological antibodies...
September 9, 2016: Journal of Applied Toxicology: JAT
J Wang, B Che, L W Zhang, G Dong, Q Luo, L Xin
With the rapid expanding of human exposure to silver nanoparticles (AgNPs), genotoxicity screening of nanosilver is necessary to ensure consumer safety. Here, we assessed one key DNA damage responsive pathway activated by GADD45a gene after 24 h of AgNPs exposure in stable luciferase reporter cell systems based on two widely used in vitro cell models, human liver HepG2 and lung epithelial A549 cells. The comet assay and micronucleus test were also conducted to confirm the genetic damage induced by AgNPs. Our results showed that AgNPs produced a strong dose-dependent increase in transcriptional activation of GADD45a promoter indicated by luciferase activity accompanying by the significant decreases in cell viability...
September 7, 2016: Journal of Applied Toxicology: JAT
Abdullah Farasani, Philippa D Darbre
Dermal absorption of components of personal care products (PCPs) may contribute to breast cancer development. Cyclic volatile methylsiloxanes (cVMS) are used widely in the formulation of PCPs, and their presence has been recently detected in human blood. The objectives of this study were to investigate any genotoxic effects after short- (1 week) or longer-term (30 weeks) exposure to hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) or decamethylcyclopentasiloxane (D5) in MCF-10 A and MCF-10F immortalized non-transformed human breast epithelial cells...
September 7, 2016: Journal of Applied Toxicology: JAT
Lauren Schumacher, Louise C Abbott
Methyl mercury is an environmental contaminant of worldwide concern. Since the discovery of methyl mercury exposure due to eating contaminated fish as the underlying cause of the Minamata disaster, the scientific community has known about the sensitivity of the developing central nervous system to mercury toxicity. Warnings are given to pregnant women and young children to limit consumption of foods containing methyl mercury to protect the embryonic, fetal and postnatally developing central nervous system. However, evidence also suggests that exposure to methyl mercury or various forms of inorganic mercury may also affect development and function of other organs...
September 4, 2016: Journal of Applied Toxicology: JAT
Emma Nixon, James D Brooks, Patricia A Routh, Jason T Chittenden, Ronald E Baynes
Workers in the USA are exposed to industrial formulations, which may be toxic. These formulations often contain preservatives or biocides such as ortho-phenylphenol (OPP). There are limited data describing OPP following intravenous administration to assess truly the clearance of this chemical in humans and other species. In vivo experiments were conducted in pigs to determine related pharmacokinetic parameters. (14) C-OPP was administered as an intravenous bolus dose. Blood, feces, urine and tissue samples were collected for analysis by liquid scintillation...
September 4, 2016: Journal of Applied Toxicology: JAT
Waqar Majeed, Shawn Bourdo, Dayton M Petibone, Viney Saini, Kieng Bao Vang, Zeid A Nima, Karrer M Alghazali, Emilie Darrigues, Anindya Ghosh, Fumiya Watanabe, Daniel Casciano, Syed F Ali, Alexandru S Biris
Graphene and its derivative, because of their unique physical, electrical and chemical properties, are an important class of nanomaterials being proposed as foundational materials in nanomedicine as well as for a variety of industrial applications. A major limitation for graphene, when used in biomedical applications, is its poor solubility due to its rather hydrophobic nature. Therefore, chemical functionalities are commonly introduced to alter both its surface chemistry and biochemical activity. Here, we show that surface chemistry plays a major role in the toxicological profile of the graphene structures...
September 4, 2016: Journal of Applied Toxicology: JAT
Anna Karpeta, Ewa Łucja Gregoraszczuk
Data concerning possible carcinogenic action of polybrominated diphenyl ethers (PBDEs) in hormone-dependent tissues are limited. Our earlier studies showed that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) stimulated OVCAR-3 and MCF-7 cell proliferation, while its hydroxylated metabolites (5-OH-BDE-47 and 6-OH-BDE-47) increased estrogen receptors protein expression and extracellular signal-regulated kinase 1/2 and protein kinase Cα phosphorylation in these cell lines. In addition to cell proliferative disorder, a failure in the regulation of apoptosis can also lead to the formation and development of tumors...
September 2, 2016: Journal of Applied Toxicology: JAT
M Angeles Lillo, Cydney Nichols, Chanel Perry, Stephanie Runke, Raisa Krutilina, Tiffany N Seagroves, Gustavo A Miranda-Carboni, Susan A Krum
A body of epidemiological evidence implicates exposure to endocrine disrupting chemicals (EDCs) with increased susceptibility to breast cancer. To evaluate the physiological effects of a suspected EDC in vivo, we exposed MCF-7 breast cancer cells and a patient-derived xenograft (PDX, estrogen receptor positive) to physiological levels of methylparaben (mePB), which is commonly used in personal care products as a preservative. mePB pellets (4.4 μg per day) led to increased tumor size of MCF-7 xenografts and ER(+) PDX tumors...
September 1, 2016: Journal of Applied Toxicology: JAT
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