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Journal of Applied Toxicology: JAT

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https://www.readbyqxmd.com/read/28074598/prediction-of-skin-sensitization-potency-using-machine-learning-approaches
#1
Qingda Zang, Michael Paris, David M Lehmann, Shannon Bell, Nicole Kleinstreuer, David Allen, Joanna Matheson, Abigail Jacobs, Warren Casey, Judy Strickland
The replacement of animal use in testing for regulatory classification of skin sensitizers is a priority for US federal agencies that use data from such testing. Machine learning models that classify substances as sensitizers or non-sensitizers without using animal data have been developed and evaluated. Because some regulatory agencies require that sensitizers be further classified into potency categories, we developed statistical models to predict skin sensitization potency for murine local lymph node assay (LLNA) and human outcomes...
January 10, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27996102/current-sights-for-mechanisms-of-deoxynivalenol-induced-hepatotoxicity-and-prospective-views-for-future-scientific-research-a-mini-review
#2
REVIEW
Zhao Peng, Liangkai Chen, Andreas K Nüssler, Liegang Liu, Wei Yang
Deoxynivalenol (DON) belongs to the group B trichothecenes, which are the most common mycotoxins in cereal commodities. It is very stable within the temperature range 170-350 °C, showing no reduction in its concentration after 30 min at 170 °C. This chemical property is a very dangerous factor for human and animal health. Liver is also responsible for the detoxification and formation of DON-glucuronide in both human and animals. Some studies already demonstrated that DON could induce liver damage remarkably through DON altering expressions of p53, caspase-3, caspase-7, caspase-8 and Bax in different cell lines...
December 20, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27995640/genotoxic-risk-of-ethyl-paraben-could-be-related-to-telomere-shortening
#3
F Finot, A Kaddour, L Morat, I Mouche, N Zaguia, C Cuceu, D Souverville, S Négrault, O Cariou, A Essahli, N Prigent, J Saul, F Paillard, L Heidingsfelder, P Lafouge, M Al Jawhari, W M Hempel, M El May, B Colicchio, A Dieterlen, E Jeandidier, L Sabatier, J Clements, R M'Kacher
The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines...
December 20, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27995639/glucose-rich-diet-aggravates-monocrotophos-induced-dopaminergic-neuronal-dysfunction-in-caenorhabditis-elegans
#4
Chinnu Salim, P S Rajini
The present study aimed to obtain insights into the mechanism(s) by which glucose-rich diet aggravates monocrotophos (MCP)-induced dopaminergic neuronal dysfunction in Caenorhabditis elegans. In this study, we exposed three different strains of worms (wild-type N2, CB1112 (cat-2(e1112)II, tyrosine hydroxylase-deficient mutant, catecholamine absent) and the transgenic BZ555 (egls1-dat-1p::green fluorescent protein [GFP]) (in which bright GFP is tagged to the dopamine neuronal soma and processes) grown and maintained in normal nematode growth medium or 2% glucose enriched-nematode growth medium to MCP (0...
December 20, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27933654/in-vitro-detection-of-diesel-exhaust-particles-induced-human-lung-carcinoma-epithelial-cells-damage-and-the-effect-of-resveratrol
#5
Qifei Li, Mingjie Tang, Anhong Zhou
People are taking up antioxidants in their daily diet and being exposed to a potential diesel exhaust particles (DEP)-containing environment. Thus it is important to study in vitro cellular responses when cells are exposed to DEP with or without antioxidant treatment. The investigation of DEP and resveratrol (RES) on cellular biophysical and biochemical changes is needed to better understand the mechanisms of DEP and RES in mammalian cells. A combination of two non-invasive techniques (atomic force microscopy, AFM, and Raman spectroscopy, RM) and multimodal tools were applied to evaluate the biophysical, biochemical alterations and cytokine, membrane potential and cell cycle of cells with or without RES pretreatment to different times of DEP exposure...
December 9, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27933645/aflatoxin-biomarkers-in-hair-may-facilitate-long-term-exposure-studies
#6
Innocent Mupunga, Christo D Izaaks, Leshweni J Shai, David R Katerere
Aflatoxins are highly toxic fungal metabolites produced by some members of the Aspergillus species. They are low molecular weight lipophilic compounds that are easily absorbed from the gastrointestinal tract. They contaminate most staple foods, including maize, peanuts, peanut butter and sorghum mainly in the tropics where hot and humid conditions promote fungal growth. Absorbed aflatoxins are metabolized by the cytochrome P450 enzyme system in the liver into toxic metabolites. Aflatoxin B (AFB)1 is the most toxic, carcinogenic and mutagenic naturally occurring toxin...
December 9, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27917511/evidence-for-direct-effects-of-glyphosate-on-ovarian-function-glyphosate-influences-steroidogenesis-and-proliferation-of-bovine-granulosa-but-not-theca-cells-in-vitro
#7
Maria Chiara Perego, Luis F Schutz, Francesca Caloni, Cristina Cortinovis, Marco Albonico, Leon J Spicer
Glyphosate (GLY) is a common herbicide used worldwide but its effect on ovarian function in mammals is unknown. The aim of this study was to determine the potential endocrine disruptor effects of GLY on ovarian function evaluating cell proliferation, steroidogenesis and gene expression using bovine granulosa cells (GC) and theca cells as in vitro models. GC proliferation was impaired (P < 0.05) after exposure to GLY at 0.5, 1.7 and 5 μg ml(-1) . GC progesterone production was not affected (P ≥ 0...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27917510/activation-of-interleukin-6-and-8-expressions-by-methylmercury-in-human-u937-macrophages-involves-rela-and-p50
#8
Megumi Yamamoto, Noureen Khan, Muflihatul Muniroh, Eriko Motomura, Rie Yanagisawa, Takami Matsuyama, Christoph F A Vogel
The accumulation of macrophages has been observed around lesions of the brain in patients with Minamata disease. In this condition, mercury has been detected histochemically in macrophages throughout the brain. However, the role of macrophages in the neurotoxicity of methylmercury (MeHg) and the molecular mechanisms of their response to MeHg exposure remain to be elucidated. Here, we investigated how MeHg affects the expression of proinflammatory cytokines such as interleukin (IL)-6 and IL-8 in cultured human U937 macrophages...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27917506/comparative-in-vitro-toxicity-assessment-of-perfluorinated-carboxylic-acids
#9
Cecon T Mahapatra, Nur P Damayanti, Samuel C Guffey, Jennifer S Serafin, Joseph Irudayaraj, Maria S Sepúlveda
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic fluorinated compounds that are highly bioaccumulative and persistent organic pollutants. Perfluorooctanoic acid (PFOA), an eight-carbon chain perfluorinated carboxylic acid, was used heavily for the production of fluoropolymers, but concerns have led to its replacement by shorter carbon chain homologues such as perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA). However, limited toxicity data exist for these substitutes. We evaluated the toxicity of PFOA, PFHxA and PFBA on a zebrafish liver cell line and investigated the effects of exposure on cell metabolism...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27917503/responses-of-a549-human-lung-epithelial-cells-to-cristobalite-and-%C3%AE-quartz-exposures-assessed-by-toxicoproteomics-and-gene-expression-analysis
#10
Ngoc Q Vuong, Patrick Goegan, Francesco De Rose, Dalibor Breznan, Errol M Thomson, Julie S O'Brien, Subramanian Karthikeyan, Andrew Williams, Renaud Vincent, Premkumari Kumarathasan
In this study, we used cytotoxicity assays, proteomic and gene expression analyses to examine the difference in response of A549 cells to two silica particles that differ in physical properties, namely cristobalite (CR) and α-quartz (Min-U-Sil 5, MI). Cytotoxicity assays such as lactate dehydrogenase release, 5-bromo-2'-deoxyuridine incorporation and cellular ATP showed that both silica particles could cause cell death, decreased cell proliferation and metabolism in the A549 human lung epithelial cells. While cytotoxicity assays revealed little difference between CR and MI exposures, proteomic and gene expression analyses unveiled both similar and unique molecular changes in A549 cells...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27917502/relationship-between-increasing-concentrations-of-two-carcinogens-and-statistical-image-descriptors-of-foci-morphology-in-the-cell-transformation-assay
#11
Giulia Callegaro, Raffaella Corvi, Susan Salovaara, Chiara Urani, Federico M Stefanini
Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27896850/zebrafish-larva-as-a-reliable-model-for-in-vivo-assessment-of-membrane-remodeling-involvement-in-the-hepatotoxicity-of-chemical-agents
#12
Normand Podechard, Martine Chevanne, Morgane Fernier, Arnaud Tête, Aurore Collin, Doris Cassio, Olivier Kah, Dominique Lagadic-Gossmann, Odile Sergent
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury...
November 28, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27896817/lack-of-in-vivo-mutagenicity-of-1-2-dichloropropane-and-dichloromethane-in-the-livers-of-gpt-delta-rats-administered-singly-or-in-combination
#13
Tadashi Hirata, Young-Man Cho, Takeshi Toyoda, Jun-Ichi Akagi, Isamu Suzuki, Akiyoshi Nishikawa, Kumiko Ogawa
1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are possible causative agents associated with the development of cholangiocarcinoma in employees working in printing plant in Osaka, Japan. However, few reports have demonstrated an association between these agents and cholangiocarcinoma in rodent carcinogenicity studies. Moreover, the combined effects of these compounds have not been fully elucidated. In the present study, we evaluated the in vivo mutagenicity of 1,2-DCP and DCM, alone or combined, in the livers of gpt delta rats...
November 28, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27885692/physiologically-based-pharmacokinetic-model-for-ethyl-tertiary-butyl-ether-and-tertiary-butyl-alcohol-in-rats-contribution-of-binding-to-%C3%AE-2u-globulin-in-male-rats-and-high-exposure-nonlinear-kinetics-to-toxicity-and-cancer-outcomes
#14
Susan J Borghoff, Caroline Ring, Marcy I Banton, Teresa L Leavens
In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary-butyl ether (ETBE), caused liver tumors in male rats, while tertiary-butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary-butyl ether, a structurally similar chemical, and verified against the literature and study report data...
November 24, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27866382/immunotoxic-effects-of-in-vitro-exposure-of-dolphin-lymphocytes-to-louisiana-sweet-crude-oil-and-corexit%C3%A2
#15
Natasha D White, Celine Godard-Codding, Sarah J Webb, Gregory D Bossart, Patricia A Fair
The Deepwater Horizon oil spill was one of the worst environmental disasters on record in the United States. Response efforts to reduce the magnitude of the oil slick included the use of thousands of gallons of the chemical dispersant Corexit™ in surface and deep-water environments. The immunotoxicity of Louisiana sweet crude oil and the chemical dispersant Corexit was examined using lymphocyte proliferation (LP) and natural killer cell (NK) assays as measures of impact on the adaptive (LP) and innate (NK) immune response in bottlenose dolphins...
November 20, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27866379/effects-of-oral-exposure-to-the-phthalate-substitute-acetyl-tributyl-citrate-on-female-reproduction-in-mice
#16
Lindsay M Rasmussen, Nivedita Sen, Xiaosong Liu, Zelieann R Craig
Acetyl tributyl citrate (ATBC), is a phthalate substitute used in food and medical plastics, cosmetics and toys. Although systemically safe up to 1000 mg kg(-1)  day(-1) , its ability to cause reproductive toxicity in females at levels below 50 mg kg(-1)  day(-1) has not been examined. This study evaluated the effects of lower ATBC exposures on female reproduction using mice. Adult CD-1 females (n = 7-8 per treatment) were dosed orally with tocopherol-stripped corn oil (vehicle), 5 or 10 mg kg(-1)  day(-1) ATBC daily for 15 days, and then bred with a proven breeder male...
November 20, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27862064/cytotoxicity-oxidative-stress-and-inflammation-induced-by-zno-nanoparticles-in-endothelial-cells-interaction-with-palmitate-or-lipopolysaccharide
#17
Yu Gong, Yuejia Ji, Fang Liu, Juan Li, Yi Cao
Recent studies showed that ZnO nanoparticles (NPs) might induce the toxicity to human endothelial cells. However, little is known about the interaction between ZnO NPs and circulatory components, which is likely to occur when NPs enter the blood. In this study, we evaluated ZnO NP-induced cytotoxicity, oxidative stress and inflammation in human umbilical vein endothelial cells (HUVECs), with the emphasis on the interaction with palmitate (PA) or lipopolysaccharide (LPS), because PA and LPS are normal components in human blood that increase in metabolic diseases...
November 15, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27813112/developmental-toxicity-of-auranofin-in-zebrafish-embryos
#18
Xiao-Yan Gao, Kang Li, Ling-Ling Jiang, Ming-Fang He, Cun-Hai Pu, Dongzhou Kang, Jingjing Xie
Auranofin (AF) is used in clinic for the treatment of rheumatoid arthritis, repurposing of AF as an anticancer drug has just finished a phase I/II clinical trial, but the developmental toxicity of AF remains obscure. This study focused on its developmental toxicity by using zebrafish embryos. Zebrafish embryos were exposed to different concentrations (1, 2.5, 5, 10 μm) of AF from 2 h post-fertilization (hpf) to 72 hpf. At 72 hpf, two major developmental defects caused by AF were found, namely severe pericardial edema and hypopigmentation, when embryos were exposed to concentrations higher than 2...
November 4, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27813108/antagonistic-effect-of-n-ethylmaleimide-on-arsenic-mediated-oxidative-stress-induced-poly-adp-ribosyl-ation-and-cytotoxicity
#19
Alexander Sheng-Shin Wang, Yu-Ting Chou, Yeong-Shiau Pu
Long-term exposure to arsenic has been known to induce neoplastic initiation and progression in several organs; however, the role of arsenic (As2 O3 ) in oxidative stress-mediated DNA damage remains elusive. One of the immediate cellular responses to DNA damage is poly(ADP-ribosyl)ation (PARylation), which mediates DNA repair and enhances cell survival. In this study, we found that oxidative stress (H2 O2 )-induced PARylation was suppressed by As2 O3 exposure in different human cancer cells. Moreover, As2 O3 treatment promoted H2 O2 -induced DNA damage and apoptosis, leading to increased cell death...
November 4, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27785833/the-inadequacies-of-pre-market-chemical-risk-assessment-s-toxicity-studies-the-implications
#20
REVIEW
Anthony C Tweedale
Industry provides essentially all the data for most (pre-market) chemical risk assessments (RA); academics study a chemical once it is marketed. For two randomly-chosen high production chemicals, despite new European Union mandates to evaluate all data, just 13% of the herbicide bentazon and 15% of the flame-retardant hexabromocyclododecane's published toxicity studies were found in their pre-market RA, and a systematic review on bentazon concludes it has greater hazards than indicated in its RA. More important, for both, academia's toxicity studies were designated as lower quality than industries were, despite showing hazards at lower doses...
October 26, 2016: Journal of Applied Toxicology: JAT
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