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International Journal of Toxicology

Tennille K Marx, Róbert Glávits, John R Endres, Philip A Palmer, Amy E Clewell, Timothy S Murbach, Gábor Hirka, Ilona Pasics
Morus alba L. (white mulberry) leaves are one of the oldest recognized traditional Chinese medicines. More recently, M alba leaves and their constituents, particularly iminosugars (or azasugars), have garnered attention for their ability to maintain normal blood glucose concentrations, an effect identified in both animal studies and human clinical trials. Reducose (Phynova Group Limited) is a commercial water-soluble extract of M alba leaves standardized to 5% 1-deoxynojirimycin (DNJ), an iminosugar with α-glucosidase inhibition properties...
October 12, 2016: International Journal of Toxicology
Alexander Batista-Duharte, Gisela Jorge Murillo, Ulpiano Marqués Pérez, Enieyis Naranjo Tur, Deivys Fuentes Portuondo, Bruno Téllez Martínez, Damiana Téllez-Martínez, Juan E Betancourt, Oliver Pérez
Local reactions are the most frequent adverse event associated with vaccines. Adjuvants are major constituents of many vaccines and they are frequently involved in these reactions, associated with their irritating effect and the stimulation of local inflammation. The hen's egg test on chorioallantoic membrane (HET-CAM) is an alternative toxicological method widely used to determine ocular irritation potential, but very few studies have demonstrated the utility of this method for assessing the irritant properties of vaccine adjuvants...
October 12, 2016: International Journal of Toxicology
Emily May Lent, Lee C B Crouse, Shannon M Wallace
Subacute and subchronic studies were conducted to assess the toxicity of 2,4-dinitroanisole (DNAN) and to provide information important for protecting the health of military and civilian personnel. In the subchronic study, male and female Sprague-Dawley rats were dosed with DNAN via oral gavage at 0, 1.25, 5, 20, and 80 mg/kg/d. Likely owing to its conversion to 2,4-dinitrophenol, an inhibitor of energy homeostasis, DNAN caused an apparent increase in metabolism, leading to reduced feed efficiency ratios and body mass gains in males...
October 7, 2016: International Journal of Toxicology
Ling-Ling Jiang, Mei-Hui Liu, Jian-Ying Li, Zhi-Heng He, Huan Li, Ning Shen, Ping Wei, Ming-Fang He
With the increasing use of mycophenolic acid (MPA) in solid organ transplantation, some clinical studies indicate that it is also a human teratogen. However, it is unknown by which mechanism MPA acts as a teratogen. Mycophenolic acid was a selective blocker of de novo purine synthesis, and its immunosuppressive effect is mediated by the inhibition of inosine monophosphate dehydrogenase, which could be a target for MPA-induced toxicity as well. The aim of our study was to examine the direct influence of MPA exposure on zebrafish (Danio rerio) embryos...
September 30, 2016: International Journal of Toxicology
Chengbin Xue, Xiaonan Li, Guozhen Liu, Wei Liu
Nanosized titanium dioxide (nano-TiO2) is widely used in the chemical, electrical, and electronic industries. Nanosized TiO2 has been reported to be an efficient photocatalyst, which is able to produce reactive oxygen species (ROS) under UVA irradiation. In the present work, we evaluate the effect of mitochondrial respiratory chain on the generation of ROS and cytotoxicity in keratinocyte (HaCaT) cells induced by nano-TiO2 under UVA irradiation. HaCaT cells were pretreated with different inhibitors of mitochondrial respiratory chain and followed by treatment with 200 µg/mL nano-TiO2, then exposed to UVA (365 nm) for 1 hour and cultured for 24 hours...
August 8, 2016: International Journal of Toxicology
Lillian C Becker, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, F Alan Andersen
The Cosmetic Ingredient Review Expert Panel (CIR Panel) reviewed the safety of hydroxypropyl bis(N-Hydroxyethyl-p-Phenylenediamine) HCl, which functions as an oxidative hair dye ingredient. The Panel considered relevant animal and human data provided in this safety assessment and concluded that hydroxypropyl bis(N-hydroxyethyl-p-phenylenediamine) HCl is safe for use in oxidative hair dye formulations as described in this safety assessment.
August 3, 2016: International Journal of Toxicology
John A Budny
No abstract text is available yet for this article.
August 1, 2016: International Journal of Toxicology
Adriana Campos, Débora Barbosa Vendramini-Costa, Giovanna Barbarini Longato, Tailyn Zermiani, Ana Lúcia Tasca Gois Ruiz, João Ernesto de Carvalho, Atanasio Pandiella, Valdir Cechinel Filho
Synadenium grantii is frequently used for the treatment of various diseases such as allergies, gastric disorders, and especially cancer. The aim of this study was to evaluate the possible antiproliferative potential of the methanol extract, fractions, and pure compounds from the stems of S grantii Phytochemical analysis was carried out by conventional chromatographic techniques, and the antiproliferative activity was analyzed using the sulforhodamine B assay and an MTT-based assay. Nonpolar fraction and its subfractions from the stems of S grantii exhibited promising cytostatic effect against several human tumor cell lines (glioma, breast, kidney, and lung), with total grown inhibition values ranging from 0...
July 27, 2016: International Journal of Toxicology
Qudes Al-Anbaky, Zeiyad Al-Karakooly, Surya P Kilaparty, Megha Agrawal, Yahya M Albkuri, Ambar B RanguMagar, Anindya Ghosh, Nawab Ali
Manganese (Mn) complexes are widely studied because of their important catalytic properties in synthetic and biochemical reactions. A Mn (III) complex of an amidoamine ligand was synthesized using a tetradentate amidoamine ligand. In this study, the Mn (III) complex was evaluated for its biological activity by measuring its cytotoxicity in human breast adenocarcinoma cell line (MCF-7). Cytotoxic effects of the Mn (III) complex were determined using established biomarkers in an attempt to delineate the mechanism of action and the utility of the complex as a potential anticancer drug...
July 26, 2016: International Journal of Toxicology
(no author information available yet)
No abstract text is available yet for this article.
September 2016: International Journal of Toxicology
David W Hobson, JoAnn C L Schuh, Daniel V Zurawski, Jianyong Wang, Sam Arbabi, Maralee McVean, Kathleen A Funk
As the skin is the primary barrier to infection, the importance of wound healing has been understood since ancient times. This article provides a synopsis on the symposium presentations focusing on how wounds were traditionally treated, what models and pathology endpoints exist to study wound healing, special considerations for wound healing studies, an overview of regulatory aspects of new pharmaceutical and medical device development, and the clinical relevance of such models. The clinical treatment of small and large wounds is also considered...
September 2016: International Journal of Toxicology
Judith W Henck, Ikram Elayan, Charles Vorhees, J Edward Fisher, LaRonda L Morford
The study of developmental neurotoxicity (DNT) continues to be an important component of safety evaluation of candidate therapeutic agents and of industrial and environmental chemicals. Developmental neurotoxicity is considered to be an adverse change in the central and/or peripheral nervous system during development of an organism and has been primarily evaluated by studying functional outcomes, such as changes in behavior, neuropathology, neurochemistry, and/or neurophysiology. Neurobehavioral evaluations are a component of a wide range of toxicology studies in laboratory animal models, whereas neurochemistry and neurophysiology are less commonly employed...
September 2016: International Journal of Toxicology
D Schmitt, R Levy, B Carroll
In a subchronic toxicity study, administration of β-caryophyllene (BCP) oil by oral gavage to Wistar rats at dosages of 0, 150, 450, or 700 mg/kg/d for 90 days, including a 21-day recovery period, did not produce any significant toxicologic manifestations. The study design also included a 28-day interim sacrifice in the control and high-dose groups. The BCP oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral end points, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, and necropsy findings...
September 2016: International Journal of Toxicology
Palma Ann Marone, Jan Trampota, Steven Weisman
l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1...
September 2016: International Journal of Toxicology
Philippe Bissel, Katie Boes, Jonathan Hinckley, Bernard S Jortner, Geraldine Magnin-Bissel, Stephen R Werre, Marion Ehrich, Adria Carbo, Casandra Philipson, Raquel Hontecillas, Noah Philipson, Richard D Gandour, Josep Bassaganya-Riera
Lanthionine synthetase cyclase-like receptor 2 (LANCL2) is a novel therapeutic target for Crohn's disease (CD). BT-11 is a small molecule that binds LANCL2, is orally active, and has demonstrated therapeutic efficacy in 3 validated mouse models of colitis at doses as low as 8 mg/kg/d. Exploratory experiments evaluated BT-11 in male Harlan Sprague Dawley rats with a single oral dose of 500 mg/kg and 80 mg/kg/d for 14 days (n = 10 rats dosed/group). Treated and control rats were observed for behavioral detriments, and blood and tissues were collected for clinical pathology and histopathological examination...
September 2016: International Journal of Toxicology
Patrick J Sabourin, Christina L Kobs, Seth T Gibbs, Peter Hong, Claire M Matthews, Kristen M Patton, Carol L Sabourin, Edgar J Wakayama
Potassium cyanide (KCN) is an inhibitor of cytochrome C oxidase causing rapid death due to hypoxia. A well-characterized model of oral KCN intoxication is needed to test new therapeutics under the Food and Drug Administration Animal Rule. Clinical signs, plasma pH and lactate concentrations, biomarkers, histopathology, and cyanide and thiocyanate toxicokinetics were used to characterize the pathology of KCN intoxication in adult and juvenile mice. The acute oral LD50s were determined to be 11.8, 11.0, 10.9, and 9...
September 2016: International Journal of Toxicology
Michael A Hawk, Glenn D Ritchie, Kim A Henderson, Katherine A B Knostman, Brian M Roche, Zhenxu J Ma, Claire M Matthews, Carol L Sabourin, Edward J Wakayama, Patrick J Sabourin
The Food and Drug Administration Animal Rule requires evaluation of cardiovascular and central nervous system (CNS) effects of new therapeutics. To characterize an adult and juvenile mouse model, neurobehavioral and cardiovascular effects and pathology of a single sublethal but toxic, 8 mg/kg, oral dose of potassium cyanide (KCN) for up to 41 days postdosing were investigated. This study describes the short- and long-term sensory, motor, cognitive, and behavioral changes associated with oral dosing of a sublethal but toxic dose of KCN utilizing functional observation battery and Tier II CNS testing in adult and juvenile mice of both sexes...
September 2016: International Journal of Toxicology
Vic Ciaravino, Dina Coronado, Cheryl Lanphear, Alan Hoberman, Sanjay Chanda
Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. The effects of tavaborole on gestation, parturition (delivery, labor), offspring development, and survival during the perinatal and postnatal periods were assessed in mated female rats. Females (F0 generation) were administered single daily oral (gavage) doses of 15, 60, or 100 mg/kg/d from gestation day 6 through lactation day 20. The females were allowed to deliver naturally and rear their offspring until lactation day 21, at which time the F0 females were euthanized...
September 2016: International Journal of Toxicology
Vic Ciaravino, Dina Coronado, Cheryl Lanphear, Alan Hoberman, Sanjay Chanda
Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. As part of the nonclinical development program, reproductive and developmental toxicity studies were conducted (rat oral fertility and early embryonic development, rat (oral) and rabbit (dermal) embryo-fetal development). There were no effects on fertility or reproductive performance at doses up to 300 mg/kg/d (107 times the maximum recommended human dose [MRHD] based on mean area under the plasma concentration-time curve comparisons)...
September 2016: International Journal of Toxicology
Vivekkumar P Dadhania, Levan Muskhelishvili, John R Latendresse, Harihara M Mehendale
Compensatory tissue repair (CTR) in thioacetamide (TA)-primed rats protects them against acetaminophen (APAP)-induced lethality. This study was aimed at investigating the mechanisms of CTR-mediated heteroprotection in mice. Male Swiss Webster mice received a priming dose of TA (40 mg/kg body weight [BW] in 10 mL distilled water [DW]/kg BW, intraperitoneally [IP]). Thioacetamide-induced liver injury, CTR, and expression of annexin A1 and A2 (ANX1 and ANX2), the endogenous inhibitors of the death protein secretory phospholipase A2 (sPLA2), were measured over a time course of 84 hours after TA priming...
July 22, 2016: International Journal of Toxicology
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