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International Journal of Toxicology

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https://www.readbyqxmd.com/read/30453808/percutaneous-hepatic-perfusion-with-filtered-melphalan-for-localized-treatment-of-metastatic-hepatic-disease-a-risk-assessment
#1
Pauline E McEwan, Lynn Bailey, David Trost, Christopher Scull, John H Keating, Misty Williams, Robert J Guttendorf
Regional therapies for metastatic liver disease have garnered interest in recent years due to technological advances in drug delivery. A percutaneous hepatic perfusion (PHP) using a newly developed generation 2 (GEN2) filtration system was designed to mitigate systemic toxicity and cardiovascular risk associated with hepatic blood filtration during hepatic artery infusion of the chemotherapy drug melphalan. The GEN2 system was evaluated in healthy swine, and plasma samples were assessed for clinical chemistry, melphalan toxicokinetics (TK), inflammatory cytokines, catecholamines, hematological, and cardiac biomarkers...
November 19, 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30380967/toxicity-and-mutagenicity-evaluation-following-risug-contraception-reversal-in-rats
#2
Abdul S Ansari, Mubarik Hussain, Sadi Rehan Khan, Ayesha Badar, N K Lohiya
Reestablishment of fertility, after a male contraceptive method, is of great concern. In this context, RISUG (Reversible Inhibition of Sperm Under Guidance) has been evaluated for its mutagenicity following reversibility with dimethyl sulfoxide (DMSO)/sodium bicarbonate (NaHCO3 ) in Wistar albino rats. Animals were divided into 7 groups, namely, sham-operated control, vas occlusion with RISUG for 90 and 360 days, reversal with DMSO and NaHCO3 after 90 and 360 days, respectively. The testis, cauda epididymis, cauda epididymal spermatozoa, and serum were evaluated for apoptosis and hormonal status through various assays...
November 1, 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30373422/long-term-systemic-treatment-with-methamphetamine-causes-retinal-damage-in-cd1-mice
#3
Haojiang Yang, Liming Tao, Lin Li
As a powerful psychostimulant with high potential for abuse, methamphetamine (Meth) could cause long-lasting abnormalities in retinas. The purpose of this study was to investigate the effects of systemic administration of Meth at low dose on retinal damage and understand the underlying mechanisms of pathology. CD1 mice were treated with 0.5 mg/kg or 1 mg/kg Meth by intraperitoneal injection daily for 2 months, mice treated with saline were used as negative control. Electroretinography (ERG) reflects the mass response of photoreceptor cells and was used to test the outer retinal function after Meth treatment...
October 29, 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30282506/embracing-transparency-through-data-sharing
#4
Stéphanie Boué, Michael Byrne, A Wallace Hayes, Julia Hoeng, Manuel C Peitsch
Low rates of reproducibility and translatability of data from nonclinical research have been reported. Major causes of irreproducibility include oversights in study design, failure to characterize reagents and protocols, a lack of access to detailed methods and data, and an absence of universally accepted and applied standards and guidelines. Specific areas of concern include uncharacterized antibodies and cell lines, the use of inappropriate sampling and testing protocols, a lack of transparency and access to raw data, and deficiencies in the translatability of findings to the clinic from studies using animal models of disease...
October 3, 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30244632/-not-everything-that-shakes-is-a-seizure-making-the-determination-of-test-article-induced-convulsions-in-toxicology-studies
#5
David V Gauvin, Zachary J Zimmermann, Joshua Yoder, Theodore J Baird
Spontaneous unexpected events occasionally develop during the course of rodent preclinical toxicology studies. The presentation of serious adverse events on animal studies may require notification of these events to the Food and Drug Administration if the events are most likely the direct result of test article administration. Classical conditioning of emotional responses may occur over the course of a repeat-dose study and clinical observation calls of "convulsions" are reported to the study director and/or staff veterinarians...
September 24, 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30526174/ernest-hodgson-1932-2018
#6
(no author information available yet)
No abstract text is available yet for this article.
November 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30236031/editor-s-note
#7
Mary Beth Genter
No abstract text is available yet for this article.
September 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30235961/safety-assessment-of-pegs-cocamine-and-related-ingredients-as-used-in-cosmetics
#8
Ivan Boyer, Christina L Burnett, 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, Lillian J Gill, Bart Heldreth
The Cosmetic Ingredient Review Expert Panel assessed the safety of 47 polyethylene glycols (PEGs) cocamine and related ingredients, which are reported to function mostly as surfactants and antistatic agents. The Panel reviewed the relevant data and developed a framework to satisfy previously identified data deficiencies for this group of materials as well as extend the scope of related materials covered by the analysis. The irritation potential of these ingredients is consistent with the surface active properties that are characteristic of surfactants...
September 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30235960/safety-assessment-of-peg-150-pentaerythrityl-tetrastearate-as-used-in-cosmetics
#9
Wilbur Johnson, 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, Bart Heldreth
The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of polyethylene glycol (PEG)-150 pentaerythrityl tetrastearate, which functions as a viscosity-increasing agent-aqueous in cosmetic products and is being used at concentrations up to 5%. Given the chemical structure (large molecule), skin penetration is not likely. The available toxicity data and the low ingredient use concentrations suggest that systemic toxicity would not be likely even if percutaneous absorption were to occur. Additionally, the negative human repeated insult patch test data on the undiluted ingredient were deemed sufficient for evaluating skin irritation and sensitization potential...
September 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30235959/safety-assessment-of-tocopherols-and-tocotrienols-as-used-in-cosmetics
#10
Monice M Fiume, 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, Bart Heldreth
The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 14 tocopherols and tocotrienols and concluded these ingredients are safe as used in cosmetics. The tocopherols are reported to function in cosmetics as antioxidants or skin-conditioning agents; in contrast, tocotrienols are not reported to function as an antioxidants in cosmetics but as a light stabilizer, oral care agent, or skin-conditioning agent. The Panel reviewed the new and existing animal and clinical data to determine the safety of these ingredients and found it appropriate to extrapolate the existing information to conclude on the safety of all the tocopherols and tocotrienols...
September 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30134762/paradoxical-protective-effect-of-perfluorooctanesulfonic-acid-against-high-fat-diet-induced-hepatic-steatosis-in-mice
#11
Ian Huck, Kevin Beggs, Udayan Apte
Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant with worldwide bioaccumulation due to a very long half-life. Perfluorooctanesulfonic acid exposure results in significant hepatic effects including steatosis, proliferation, hepatomegaly, and in rodents, carcinogenesis. The objective of this study was to determine whether PFOS exposure exacerbates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis pathogenesis. Eight-week-old male C57BL/6 J mice (n = 5 per group) were fed ad libitum normal chow diet (ND) alone, 60% high-fat diet (HFD) alone, ND + PFOS, and HFD + PFOS (0...
September 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30134751/characterization-of-the-testicular-toxicity-of-3-nitro-1-2-4-triazol-5-one-and-2-4-dinitroanisole-in-rats-rattus-norvegicus
#12
Emily May Lent, Anna B Mullins, Anthony D May, Cary L Honnold, Kenneth E Despain
Nitrotriazolone (3-nitro-1,2,4-triazol-5-one; NTO) and dinitroanisole (2,4-dinitroanisole; DNAN), insensitive energetic materials used in explosive formulations, have induced testicular toxicity and oligospermia in repeated-dose oral toxicity tests. To identify the target site of testicular toxicity of NTO and DNAN, Sprague Dawley rats were orally dosed with NTO (500 mg/kg/d) or DNAN (50 or 100 mg/kg/d) in corn oil for 1, 3, 7, or 14 days. Degeneration of germinal epithelium occurred in multiple tubule stages on days 7 and 14 in treated rats...
September 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/29879849/behavioral-pharmacokinetic-and-cardiovascular-evaluation-of-candidate-oximes-in-african-green-monkeys
#13
Mark C Moffett, John H McDonough, Joseph D McMonagle, Todd M Myers
Oxime reactivators are critical antidotes after organophosphate pesticide or nerve agent poisoning, directly restoring the function of inhibited acetylcholinesterase. In the continuing search for more broad-spectrum acetylcholinesterase reactivators, this study evaluated one of the leading next-generation oxime reactivators: methoxime, (1,1'-trimethylene bis[4-(hydroxyimino)methyl]pyridinium dichloride (MMB-4). The pharmacokinetics of both salts of MMB-4 (dichloride [2Cl] and dimethanesulphonate [DMS]) were characterized across a range of relevant doses (19, 58, and 116 µmol/kg, intramuscular) in a nonhuman primate model (male African green monkeys), and only subtle differences were observed between the salts...
September 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30016916/how-did-i-ever-get-here-the-2018-mildred-s-christian-award-winner
#14
Linda S Birnbaum
No abstract text is available yet for this article.
July 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/30016915/editor-s-note
#15
Mary Beth Genter
No abstract text is available yet for this article.
July 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/29916280/similar-and-differential-canonical-pathways-and-biological-processes-associated-with-multiwalled-carbon-nanotube-and-asbestos-induced-pulmonary-fibrosis-a-1-year-postexposure-study
#16
Julian M Dymacek, Brandi N Snyder-Talkington, Rebecca Raese, Chunlin Dong, Salvi Singh, Dale W Porter, Barbara Ducatman, Michael G Wolfarth, Michal E Andrew, Lori Battelli, Vincent Castranova, Yong Qian, Nancy L Guo
Respiratory exposure to multiwalled carbon nanotubes (MWCNT) or asbestos results in fibrosis; however, the mechanisms to reach this end point may be different. A previous study by our group identified pulmonary effects and significantly altered messenger RNA (mRNA) signaling pathways following exposure to 1, 10, 40, and 80 µg MWCNT and 120 µg crocidolite asbestos on mouse lungs over time at 1-month, 6-month, and 1-year postexposure following pulmonary aspiration. As a continuation to the above study, this current study took an in-depth look at the signaling pathways involved in fibrosis development at a single time point, 1 year, and exposure, 40 µg MWCNT, the lowest exposure at which fibrosis was pathologically evident...
July 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/29898631/development-of-a-phototoxicity-testing-strategy-for-accurate-photosafety-evaluation-of-pharmaceuticals-based-on-the-assessment-of-possible-melanin-binding-effects
#17
Jelle Reinen, Pieter van Sas, Ton van Huygevoort, Leticia Rubio, Kevin Scase, Mira Wenker
Drug-induced phototoxicity occurs when drugs absorb natural sunlight, leading to chemical reactions causing cellular damage. Distribution to light-exposed tissues is critical and is enhanced by binding to melanin. The International Council on Harmonization S10 guidance document on photosafety evaluation of pharmaceuticals states that although nonpigmented skin tends to be more sensitive than pigmented skin, pigmented skin models should be considered for drugs that bind significantly to melanin. In this study, an in vitro melanin-binding assay was evaluated as prescreening tool for animal model selection...
July 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/29890881/comparative-assessment-on-mechanism-underlying-renal-toxicity-of-commercial-formulation-of-roundup-herbicide-and-glyphosate-alone-in-male-albino-rat
#18
Gabriel A Dedeke, Folarin O Owagboriaye, Kehinde O Ademolu, Olanrewaju O Olujimi, Adeyinka A Aladesida
There have been major concerns that the nephrotoxicity of commercial formulations of Roundup herbicide is due to the active ingredient glyphosate. We therefore investigated and compared the mechanisms underlining the nephrotoxicity of Roundup herbicide and glyphosate alone in rat. Fifty-six adult male rats randomized into 7 groups of 8 rats per group were exposed to Roundup formulation and glyphosate alone daily by gavage at 3.6, 50.4, and 248.4 mg/kg body weight (bw) of glyphosate concentrations for 12 weeks with distilled water administered to the control group...
July 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/29862868/inhibition-of-mast-cell-degranulation-with-cromolyn-sodium-exhibits-organ-specific-effects-in-polycystic-kidney-pck-rats
#19
Lu Jiang, Pingping Fang, Seth Septer, Udayan Apte, Michele T Pritchard
Autosomal recessive polycystic kidney disease (ARPKD) is a monogenic disease characterized by development of hepatorenal cysts, pericystic fibrosis, and inflammation. Previous studies show that mast cell (MC) mediators such as histamine induce proliferation of cholangiocytes. We observed robust MC accumulation around liver cysts, but not kidney cysts, in polycystic kidney (PCK) rats (an animal model of ARPKD). Therefore, we hypothesized that MCs contribute to hepatic cyst growth in ARPKD. To test this hypothesis, we treated PCK rats with 1 of 2 different MC stabilizers, cromolyn sodium (CS) or ketotifen, or saline...
July 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/29862856/toxicological-assessment-of-venlafaxine-acute-and-subchronic-toxicity-study-in-rats
#20
Melad G Paulis, Essam M Hafez, Nashwa F El-Tahawy, Mohmed K M Aly
Antidepressants are the most commonly prescribed drugs for psychiatric treatment, and venlafaxine (VEN) is one of the most popular options. Venlafaxine is a nontricyclic dual-acting serotonin-norepinephrine reuptake inhibitor. Although an increased incidence of acute toxicity and addiction has been reported, controlled studies examining its toxic effects on different organs are still lacking. This study investigated the possible toxic effects of VEN on the liver, kidney, and gastric tissues. Three groups of rats were administered saline, a single LD50 dose (350 mg/kg), or 100 mg/kg VEN daily, followed by increases in the dose of 50 mg/kg every 10 days for 30 days (about 10 times the therapeutic doses)...
July 2018: International Journal of Toxicology
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