Calcium, magnesium and aluminium ions as decontaminating agents against dermal fluoride absorption following hydrofluoric acid exposure.
o S Abstract The fluoride ions of the industrially largely irreplaceable, locally corrosive hydrofluoric acid (HF) can scavenge cations in biological tissues, which explains their high toxic potential, and also leads to local acidification through proton release. The influence of three complexing agents, calcium (Ca2+) gluconate (as 2.5% Ca2+gel and individually (2.84%) or commercially (10%) formulated Ca2+solution), magnesium (Mg2+) gluconate (2.84%) solution and aluminium (Al3+) solution (Hexafluorine®, pure and diluted) on the absorption of fluoride following HF exposure (1-3 min, 100 μl, 30%/0.64 ...
Source: Toxicology in Vitro - November 20, 2020 Category: Toxicology Authors: Vijayan SM, Göen T, Dennerlein K, Horch RE, Ludolph I, Drexler H, Kilo S Tags: Toxicol In Vitro Source Type: research

Corrigendum to partition coefficient and diffusion coefficient determinations of 50 compounds in human intact skin, isolated skin layers and isolated stratum corneum lipids.
laki A, Schepky A PMID: 33223358 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - November 19, 2020 Category: Toxicology Authors: Ellison CA, Tankersley KO, Obringer CM, Carr GJ, Manwaring J, Rothe H, Duplan H, Géniès C, Grégoire S, Hewitt NJ, Jamin CJ, Klaric M, Lange D, Rolaki A, Schepky A Tags: Toxicol In Vitro Source Type: research

Integration of transcriptomic, proteomic and metabolomic data to reveal the biological mechanisms of AAI injury in renal epithelial cells.
This study provides large-scale omics data that can be used to formulate new strategies for the prevention, rapid diagnosis, and treatment of AAI injury. PMID: 33212167 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - November 16, 2020 Category: Toxicology Authors: Li Y, Xu H, Cai D, Zhu S, Liu X, Zhao Y, Zhang Z, Bian Y, Xue M, Zhang L Tags: Toxicol In Vitro Source Type: research

Are atranols the only skin sensitizers in oakmoss? A systematic investigation using non-animal methods.
Abstract Oakmoss and treemoss absolutes are the major natural extracts of concern as potential sources of skin sensitizers in cosmetics and personal care products (PCP). Two single constituents, atranol and chloroatranol, have been identified as primary culprits in both lichens, and industrial self-regulation has been proposed to limit their contents to less than 100 ppm. Nonetheless, evidence points to the presence of additional candidate skin sensitizers in these multicomponent extracts. These observations, along with a lack of data from non-animal alternative methods and the chemical variability of commercial...
Source: Toxicology in Vitro - November 16, 2020 Category: Toxicology Authors: Avonto C, Chittiboyina AG, Khan S, Dale OR, Parcher JF, Wang M, Khan IA Tags: Toxicol In Vitro Source Type: research

Calycosin induces mitochondrial-dependent apoptosis and cell cycle arrest, and inhibits cell migration through a ROS-mediated signaling pathway in HepG2 hepatocellular carcinoma cells.
Abstract Calycosin is one of the main ingredients extracted from the Chinese medical herb, Radix astragali (RA). It has been shown to inhibit cell proliferation and induce apoptosis in several cancer cell lines, but the underlying mechanism remains unclear. The effects of calycosin on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells, as well as its mechanism, were investigated in this study. Cell Counting Kit-8 assay results suggested that calycosin had anti-proliferation effects on HCC in dose- and time-dependent manners, and had less cytotoxicity in normal cells. Hoechst/PI double staining...
Source: Toxicology in Vitro - November 11, 2020 Category: Toxicology Authors: Liu Y, Piao XJ, Xu WT, Zhang Y, Zhang T, Xue H, Li YN, Zuo WB, Sun G, Fu ZR, Luo YH, Jin CH Tags: Toxicol In Vitro Source Type: research

Metabolism and plasma protein binding of 16 straight- and branched-chain parabens in in vitro liver and skin models.
In conclusion, the major and common paraben metabolite in PHH, liver S9 and EpiSkin™ S9 was 4-HBA. The rate of metabolism, type of metabolite and contribution of hydrolysis was tissue-specific (liver, skin) and was influenced by the chain length (and hence LogP), structural isomeric form (straight vs branched), and/or the identity of the alkyl group. SHORT ABSTRACT: We investigated how the chain structure of parabens affects their metabolism by liver and EpiSkin™ S9. The major and common metabolite in primary human hepatocytes, liver S9 and EpiSkin™ S9 was 4-HBA plus the corresponding alcohols. The rate o...
Source: Toxicology in Vitro - November 11, 2020 Category: Toxicology Authors: Lester C, Hewitt NJ, Müller-Vieira U, Mayer M, Ellison C, Duplan H, Genies C, Jacques-Jamin C, Fabian E, Sorrell I, Lange D, Schepky A, Grégoire S Tags: Toxicol In Vitro Source Type: research

Hazard assessment using an in-silico toxicity assessment of the transformation products of boscalid, pyraclostrobin, fenbuconazole and glyphosate generated by exposure to an advanced oxidative process.
In this study, previously published transformation products of boscalid, pyraclostrobin, fenbuconazole and glyphosate were identified after exposure to 3% hydrogen peroxide, UV-C irradiation or their combination in an advanced oxidative process on glass, their oral toxicity, carcinogenicity and developmental toxicity were identified in-silico and an initial tier hazard assessment was conducted. Of the 87 total structures that were searched for, 53 were detected by UPLC-QTOF-MS and identified by mass spectra: 15, 13, 22 and 3 structures for boscalid, pyraclostrobin, fenbuconazole and glyphosate respectively, including the p...
Source: Toxicology in Vitro - November 7, 2020 Category: Toxicology Authors: Skanes B, Warriner K, Prosser RS Tags: Toxicol In Vitro Source Type: research

Corrigendum to 'Comparison of In Vivo Derived and Scaled In Vitro Metabolic Rate Constants for Several Volatile Organic Compounds (VOCs)' [toxicology in vitro 68 (2020) start page-end page].
PMID: 33160764 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - November 5, 2020 Category: Toxicology Authors: Kenyon EM, Eklund C, Pegram RA, Lipscomb JC Tags: Toxicol In Vitro Source Type: research

Inorganic nitrite alters mitochondrial dynamics without overt changes in cell death and mitochondrial respiration in cardiomyoblasts under hyperglycemia.
Abstract Inorganic nitrate or nitrite supplementation has been reported to demonstrate positive outcomes in rodent models of obesity and diabetes as well as in type 2 diabetic humans and even included in clinical trials pertaining to cardiovascular diseases in the recent decade. However, there are contrasting data regarding the useful and toxic effects of the anions. The primary scope of this study was to analyze the beneficial/detrimental alterations in redox status, mitochondrial dynamics and function, and cellular fitness in cardiomyoblasts inflicted by nitrite under hyperglycemic conditions compared with normo...
Source: Toxicology in Vitro - November 5, 2020 Category: Toxicology Authors: Anand CR, Bhavya B, Jayakumar K, Harikrishnan VS, Gopala S Tags: Toxicol In Vitro Source Type: research

Cellular uptake and toxicity on two distinct hepatic cell models.
Abstract Gold nanoparticles (AuNPs) have huge potential for various biomedical applications, but their successful use depends on their uptake and possible toxicity in the liver, their main site for accumulation. Therefore, in this work we compared the cytotoxic effects induced by AuNPs with different size (~15 nm and 60 nm), shape (nanospheres and nanostars) and capping [citrate- or 11-mercaptoundecanoic acid (MUA)], in human HepaRG cells or primary rat hepatocytes (PRH) cultivated with serum-free or Foetal Bovine Serum (FBS)-supplemented media. The safety assessment of the AuNPs demonstrated that overall they...
Source: Toxicology in Vitro - November 1, 2020 Category: Toxicology Authors: Enea M, Pereira E, Costa J, Soares ME, da Silva DD, de Lourdes Bastos M, Carmo HF Tags: Toxicol In Vitro Source Type: research

Highly accurate predictor of eye irritation utilizing potential parameters of a reconstructed human cornea epithelium model calculated based on Hansen solubility parameters.
In this study, we evaluated whether Hansen solubility parameter (HSP) values can be used to predict RhCE using the LabCyte CORNEA-MODEL results for 65 test substances. We found that HSP values can predict the RhCE method with high correlation (accuracy 84.6% (55/65), false-negative rate of 16.2% (7/43), and false-positive rate of 13.6% (3/22). These results indicate that HSP values can be used to predict RhCE using LabCyte CORNEA-MODEL results with high reproducibility, and thus are useful for evaluating the safety of substances. To our knowledge, this is the first study to report the application of HSPs to determine the s...
Source: Toxicology in Vitro - October 30, 2020 Category: Toxicology Authors: Ito L, Fujii T, Watanabe S, Yamamoto H Tags: Toxicol In Vitro Source Type: research

Effect of silibinin on ethanol- or acetaldehyde-induced damge of mouse primary hepatocytes in vitro.
This study investigates the underlying mechanism of silibinin in the protection against ethanol- or acetaldehyde-induced damage of neonatal mouse primary hepatocytes in vitro. The results show that ethanol inhibited proliferation of hepatocytes in a time (12, 24, 36 h) and dose-dependent (0-800 mM) manner. However, silibinin did not show protective effect on ethanol (500 mM)-induced suppression of hepatocyte proliferation. Acetaldehyde, the toxic metabolite of ethanol, appearing immediately in individuals after drink also inhibited the proliferation of hepatocytes in a dose-dependent (0-12 mM) manner. Surprisingly,...
Source: Toxicology in Vitro - October 30, 2020 Category: Toxicology Authors: Song XY, Li RH, Liu WW, Hayashi T, Mizuno K, Hattori S, Fujisaki H, Ikejima T Tags: Toxicol In Vitro Source Type: research

Correction to: YAN, a novel microtubule inhibitor, inhibits P-gp and MRP1 function and induces mitotic slippage followed by apoptosis in multidrug-resistant A549/Taxol cells.
PMID: 33131967 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - October 29, 2020 Category: Toxicology Authors: Gao M, Liu T, Li J, Guan Q, Wang H, Yan S, Li Z, Zuo D, Zhang W, Wu Y Tags: Toxicol In Vitro Source Type: research

Toluene diisocyanate-induced inflammation and airway remodeling involves autophagy in human bronchial epithelial cells.
Abstract Toluene-diisocyanate (TDI) is one of the main causes of occupational asthma. To study the role of autophagy in TDI-induced airway inflammation and airway remodeling in bronchial airway epithelial (16HBE) cells. We treated 16HBE cells with TDI-human serum albumin (TDI-HSA) conjugate to observe reactive oxygen species (ROS) release, autophagy activation, airway inflammation and airway remodeling. 3-Methyladenine (3-MA) and Rapamycin (Rapa) intervention were used to explore the effects of autophagy on inflammatory response and protein expression related to airway remodeling in 16HBE cells treated with TDI-HS...
Source: Toxicology in Vitro - October 27, 2020 Category: Toxicology Authors: Jiao B, Chen Y, Yang Y, Sai L, Yu G, Bo C, Zhang Y, Peng C, Jia Q, Shao H Tags: Toxicol In Vitro Source Type: research

TGF- β1 decreases CHOP expression and prevents cardiac fibroblast apoptosis induced by endoplasmic reticulum stress.
In conclusion, TGF-β1 partially protects CF apoptosis induced by sI/R or Tn, through a mechanism that would involve ER stress. PMID: 33127435 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - October 27, 2020 Category: Toxicology Authors: Olivares-Silva F, Espitia-Corredor J, Letelier A, Vivar R, Parra-Flores P, Olmedo I, Montenegro J, Pardo-Jiménez V, Díaz-Araya G Tags: Toxicol In Vitro Source Type: research

In vitro cytotoxicity of zinc oxide nanoparticles in mouse ovarian germ cells.
Abstract Recently, metal oxide nanoparticles such as zinc oxide nanoparticles (ZnO-NPs) have received considerable attention and humans are exposed to them in everyday life. The increasing use of ZnO-NPs may lead to human health issues. However, little is known about their effects on female reproductive systems, particularly on female germ cells. Germ cells differentiation is a complex biological process that is sensitive to environmental insults and any negative effect on germ cells development may inhibit fertility. Therefore, this study aimed to determine the impact of ZnO-NPs on mouse ovarian germ cells in an ...
Source: Toxicology in Vitro - October 21, 2020 Category: Toxicology Authors: Saber M, Hayaei-Tehrani RS, Mokhtari S, Hoorzad P, Esfandiari F Tags: Toxicol In Vitro Source Type: research

In vitro toxicity assessment of crosslinking agents used in hyaluronic acid dermal filler.
Abstract Hyaluronic acid (HA) dermal fillers are produced by crosslinking HA with agents, such as 1,4-butanediol diglycidyl ether (BDDE) and poly (ethylene glycol) diglycidyl ether (PEGDE) to acquire desired properties. Thus, the safety evaluation of these crosslinkers is needed at the cellular level. In the present study, cell viability, cytotoxicity, membrane integrity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory responses were evaluated in the human keratinocyte cell line, HaCaT and human dermal fibroblast cell line, HDF in response to treatment with the crosslinkers....
Source: Toxicology in Vitro - October 20, 2020 Category: Toxicology Authors: Jeong CH, Kim DH, Yune JH, Kwon HC, Shin DM, Sohn H, Lee KH, Choi B, Kim ES, Kang JH, Kim EK, Han SG Tags: Toxicol In Vitro Source Type: research

Mechanical cues protect against silica nanoparticle exposure in SH-SY5Y neuroblastoma.
Abstract The increasing appearance of engineered nanomaterials in broad biomedical and industrial sectors poses an escalating health concern from unintended exposure with unknown consequences. Routine in vitro assessments of nanomaterial toxicity are a vital component to addressing these mounting health concerns; however, despite the known role of cell-cell and cell-matrix contacts in governing cell survival, these physical interactions are generally ignored. Herein, we demonstrate that exposure to amorphous silica particles destabilizes mitochondrial membrane potential, stimulates reactive oxygen species (ROS) pr...
Source: Toxicology in Vitro - October 16, 2020 Category: Toxicology Authors: Bell KJ, Lansakara TI, Crawford R, Monroe TB, Tivanski AV, Salem AK, Stevens LL Tags: Toxicol In Vitro Source Type: research

Assessment of an ex vivo irritation test performed on human skin explants and comparison of its results with those of a 24-/48-h human patch test for the evaluation of cosmetics.
te; K Abstract When developing new cosmetics, it is extremely important to consider the safety of consumers. Absence of potential irritancy is generally assessed using an OECD TG439 compliant Reconstructed Human Epidermis (RHE) systems and MTT assays, resulting in an irritant/not irritant classification. To gain insight into the irritancy of molecules/finished cosmetic products and to predict the outcome of irritation tests performed on subjects whatever their nature, we developed a test that uses skin explants and histological analysis. Results showed that this irritation test is sensitive enough to accurately an...
Source: Toxicology in Vitro - October 12, 2020 Category: Toxicology Authors: Matarrese P, Beauchef G, Peno-Mazzarino L, Lati E, Fitoussi R, Vié K Tags: Toxicol In Vitro Source Type: research

Cellular evaluation of the metal-organic framework PCN-224 associated with inflammation and autophagy.
In this study, the general cytotoxicity of PCN-224 were examined in both human hepatocytes L-02 cells and mouse macrophages RAW264.7. Furthermore, the effect of inflammation and autophagy were measured in L-02 cells. The results indicated that PCN-224 was engulfed in L-02 cells and subsequently resulted in morphological changes, cell membrane destruction, and oxidative stress in L-02 cells. PCN-224 might trigger inflammation by promoting the secretion of inflammatory factors such as Tumor necrosis factors (TNF-α) and Interleukin (IL-6). PCN-224 might induce autophagosome accumulation and subsequently autophagic dysfu...
Source: Toxicology in Vitro - October 12, 2020 Category: Toxicology Authors: Li X, Qin H, Zhou Z, Li Y, Wang J, Lin M, Dong X, Yang M, Li L Tags: Toxicol In Vitro Source Type: research

The quantitative analysis of the mechanism involved in pertussis toxin-mediated cell clustering and its implications in the in vitro quality control of diphtheria tetanus and whole cell pertussis vaccines.
Abstract Some of the adverse side-effects such as leukocytosis, hyperinsulinemia, hypoglycemia and sensitization to histamine, caused by diphtheria, tetanus and whole cell pertussis (DTwP) vaccines are related to the presence of non-inactivated pertussis toxin residues (NiPTxR). The Chinese hamster ovary (CHO) cell clustering assay is an in vitro assay to measure NiPTxR in DTwP vaccines based on the ability of active pertussis toxin (PTx) to cause cellular clustering. To study the biochemical mechanism involved in the clustering effect in CHO cells by PTx and by different dilutions of two DTwP vaccines, the levels...
Source: Toxicology in Vitro - October 12, 2020 Category: Toxicology Authors: da Silva Zamith HP, Godinho RO, da Costa Junior VL, Corrado AP Tags: Toxicol In Vitro Source Type: research

Evaluation of a multiplexed, multispecies nuclear receptor assay for chemical hazard assessment.
Abstract Sensitivity to potential endocrine disrupting chemicals in the environment varies across species and is influenced by sequence conservation of their nuclear receptor targets. Here, we evaluated a multiplexed, in vitro assay testing receptors relevant to endocrine and metabolic disruption from five species. The TRANS-FACTORIAL™ system of human nuclear receptors was modified to include additional species: mouse (Mus musculus), frog (Xenopus laevis), zebrafish (Danio rerio), chicken (Gallus gallus), and turtle (Chrysemys picta). Receptors regulating endocrine function and xenobiotic recognition were in...
Source: Toxicology in Vitro - October 10, 2020 Category: Toxicology Authors: Houck KA, Simha A, Bone A, Doering JA, Vliet SMF, LaLone C, Medvedev A, Makarov S Tags: Toxicol In Vitro Source Type: research

The secretome of non-tumorigenic mammary cells MCF-10A elicits DNA damage in MCF-7 and MDA-MB-231 breast cancer cells.
iacute;n GA Abstract Radiotherapy is used in breast cancer to destroy tumor cells lingering after surgery. It is accepted that lethal effects of ionizing radiation occur as a result of damage to DNA in irradiated (IR) cells. However, response mechanisms may promote cell survival with efficient DNA repair or genomic alterations. Chromosomal aberrations are frequent in surviving cells and may enhance chromosomal instability (CIN) which is associated with increased risk of recurrence and metastasis. Intercellular communication can affect the response in IR cells and cause damage in non-irradiated (N-IR) cells. We eva...
Source: Toxicology in Vitro - October 10, 2020 Category: Toxicology Authors: Vedoya GM, López Nigro MM, Martín GA Tags: Toxicol In Vitro Source Type: research

Uptake and cellular effects of PE, PP, PET and PVC microplastic particles.
Sieg H Abstract Humans are exposed to small plastic particles through contaminated food. Such contaminations usually comprise different particulate plastic materials differing in size, shape and surface. Up to now, data on intestinal uptake and adverse effects resulting from plastic particles other than polystyrene are scarce. In order to fill these knowledge gaps, this study aims to elucidate the gastrointestinal uptake and effects of microplastic particles of the materials polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET) and polyvinyl chloride (PVC) using human in vitro systems. The human...
Source: Toxicology in Vitro - October 10, 2020 Category: Toxicology Authors: Stock V, Laurisch C, Franke J, Dönmez MH, Voss L, Böhmert L, Braeuning A, Sieg H Tags: Toxicol In Vitro Source Type: research

An in vitro alveolar epithelial cell model recapitulates LRRK2 inhibitor-induced increases in lamellar body size observed in preclinical models.
Abstract Alveolar type II (ATII) epithelial cells contain lamellar bodies (LBs) which synthesize and store lung surfactants. In animals, the inhibition or knockout of leucine-rich repeat kinase 2 (LRRK2) causes abnormal enlargement of LBs in ATII cells. This effect of LRRK2 inhibition in lung is largely accepted as being mediated directly through blocking of the kinase function; however, downstream consequences in the lung remain unknown. In this work we established an in vitro alveolar epithelial cell (AEC) model that recapitulates the in vivo phenotype of ATII cells and developed an assay to quantify changes in ...
Source: Toxicology in Vitro - October 10, 2020 Category: Toxicology Authors: Harney J, Bajaj P, Finley JE, Kopec AK, Koza-Taylor PH, Boucher GG, Lanz TA, Doshna CM, Somps CJ, Adkins K, Houle C Tags: Toxicol In Vitro Source Type: research

In vitro evaluation of immunobiological activity of simple mannolipids.
M, Pánik M, Jantová S Abstract Immunomodulation, cytotoxicity and anti-cancer activity of selected amphiphilic non-ionic (thio)alkyl α-D-mannosides (with aglycone of C6-C12) were investigated in vitro in human cervix epitheloid carcinoma cell line HeLa, murine melanoma cancer cells B16, murine lymphocytic leukemia cell line L1210, murine fibroblast cell line NIH 3 T3 and murine macrophage cell line RAW 264.7. Toxicological studies revealed structure-dependent immunobiological effectivity based on a tight interaction with relevant cells. The results demonstrated diverse immunomodulation of mac...
Source: Toxicology in Vitro - October 10, 2020 Category: Toxicology Authors: Paulovičová E, Paulovičová L, Poláková M, Pánik M, Jantová S Tags: Toxicol In Vitro Source Type: research

Comparison of the predictive nature of the genomic allergen rapid detection (GARD) assay with mammalian assays in determining the skin sensitisation potential of agrochemical active ingredients.
Abstract Alternatives to mammalian testing are highly desirable to predict the skin sensitisation potential of agrochemical active ingredients (AI). The GARD assay, a stimulated, dendritic cell-like, cell line measuring genomic signatures, was evaluated using twelve AIs (seven sensitisers and five non-sensitisers) and the results compared with historical results from guinea pig or local lymph node assay (LLNA) studies. Initial GARD results suggested 11/12 AIs were sensitisers and six concurred with mammalian data. Conformal predictions changed one AI to a non-sensitiser. An AI identified as non-sensitising in the ...
Source: Toxicology in Vitro - October 7, 2020 Category: Toxicology Authors: Masinja W, Elliott C, Modi S, Enoch SJ, Cronin MTD, McInnes EF, Currie RA Tags: Toxicol In Vitro Source Type: research

Structural component changes of erythrocytes caused by oxidative stress generated by indoxyl sulfate.
We examined thiols, carbonyl groups, peroxides, and TBARS levels in erythrocyte incubated with IS. The treatment of erythrocytes with IS led to increase in lipid membrane fluidity, decrease in the internal viscosity of the cells and the motion of the spin labels attached to hemolysate proteins. We did not observe conformational changes in plasma membrane proteins; however, in the plasma membranes of erythrocytes incubated with IS, a decrease in the content of thiol groups and increase in the carbonyls levels and peroxides and TBARS in comparison with the control was observed. The obtained results indicate that IS induces t...
Source: Toxicology in Vitro - October 7, 2020 Category: Toxicology Authors: Pieniazek A, Szczepocki A Tags: Toxicol In Vitro Source Type: research

Effect of perfluorohexane sulfonate on pig oocyte maturation, gap-junctional intercellular communication, mitochondrial membrane potential and DNA damage in cumulus cells in vitro.
e;lvarez L, Mateos RA, Altamirano MA, Bonilla E Abstract Perfluorohexane sulfonate (PFHxS) is one of the most abundant perfluorinated compounds in the environment. Exposure to this compound has been correlated to a decrease in human fertility, although the molecular and cellular mechanisms underlying this correlation have not been described. The adverse reproductive effects of PFHxS could be based on alterations in oocyte maturation, the process rendering oocytes competent for fertilization. The aim of this study was to evaluate the effect of PFHxS on porcine oocyte viability and maturation in vitro, as well as on...
Source: Toxicology in Vitro - October 7, 2020 Category: Toxicology Authors: Martínez-Quezada R, González-Castañeda G, Bahena I, Domínguez A, Domínguez-López P, Casas E, Betancourt M, Casillas F, Rodríguez JJ, Álvarez L, Mateos RA, Altamirano MA, Bonilla E Tags: Toxicol In Vitro Source Type: research

Effects of environmental metals on mitochondrial bioenergetics of the CD-1 mice pancreatic beta-cells.
In conclusion, the tested metals significantly affected the bioenergetics of the pancreatic ꞵ-cells with significant effect on GSIS. Cd showed the most significant functional and structural effects on their mitochondria followed by Pb, then Hg, while Mo was almost safe up to 10 μM concentration. Hence, bioenergetic mitochondrial disruption can be considered as an underlying mechanism of the diabetogenic effects of the tested metals. PMID: 33038468 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - October 7, 2020 Category: Toxicology Authors: Elmorsy E, Al-Ghafari A, Doghaither, Ghulam J Tags: Toxicol In Vitro Source Type: research

Characterization of primary mouse hepatocyte spheroids as a model system to support investigations of drug-induced liver injury.
Abstract Primary mouse hepatocytes isolated from genetically defined and/or diverse lines and disease models are a valuable resource for studying the impact of genetic and environmental factors on drug response and disease. However, standard monolayer cultures result in a rapid decline in mouse hepatocyte viability and functionality. Therefore, we evaluated 3D spheroid methodology for long-term culture of primary mouse hepatocytes, initially to support investigations of drug-induced liver injury (DILI). Primary hepatocytes isolated from male and female C57BL/6 J mice were used to generate spheroids by spontaneou...
Source: Toxicology in Vitro - October 2, 2020 Category: Toxicology Authors: Nautiyal M, Qasem RJ, Fallon JK, Wolf KK, Liu J, Dixon D, Smith PC, Mosedale M Tags: Toxicol In Vitro Source Type: research

Differential inhibition of naringenin on human and rat cytochrome P450 2E1 activity.
Abstract Cytochrome P450 2E1 (CYP2E1) has been proposed as a molecular target in oxidative stress-associated metabolic diseases. Rats are chosen as model organisms in most experiments studying CYP2E1-related toxicity; however, the human relevance of these results remains unclear. To describe differences in catalysis and inhibition between human and rat CYP2E1, recombinant human and rat CYP2E1 enzymes were treated with different concentrations of naringenin (NAR, 10 nM - 1 mM), and inhibition parameters were calculated. Interspecies differences in the catalytic efficiency for O-demethylation of 7-methoxy-4-(tri...
Source: Toxicology in Vitro - September 28, 2020 Category: Toxicology Authors: Rebeca SP, Sitlali OR, Luz HS, Rafael CC, Javier EJ Tags: Toxicol In Vitro Source Type: research

Oral anti-diabetic drugs as endocrine disruptors in vitro - No evidence for additive effects in binary mixtures.
In conclusion, more dynamic models are needed to predict mixture effects in complex systems. PMID: 33002602 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - September 27, 2020 Category: Toxicology Authors: Munkboel CH, Hansen HS, Jessen JB, Johannsen ML, Styrishave B Tags: Toxicol In Vitro Source Type: research

Differences in apoptosis levels in the different skin origin cells: Fibroblasts and keratinocytes after in vitro exposure to preservatives used in cosmetic products and present in the working environment.
PMID: 32987124 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - September 24, 2020 Category: Toxicology Authors: Miranowicz-Dzierzawska K, Zapor L, Skowron J Tags: Toxicol In Vitro Source Type: research

Mutagenicity evaluation of pesticide analogs using standard and 6-well miniaturized bacterial reverse mutation tests.
Abstract The Ames test is widely used in the mutagenicity evaluation of new and existing chemicals as a part of a compound selection strategy, regulatory control, the equivalence assessment, carcinogenic potential measurement etc. Intensification of the chemical industry and synthesis of plenty of new molecules has led to the necessity of tests with a higher throughput capacity. The 6-well miniaturized bacterial reverse mutation test and the standard Ames test were compared using 14 technical grade active ingredients (TGAIs) of pesticides. With some exceptions, the responses obtained in the miniscreen Ames are sim...
Source: Toxicology in Vitro - September 21, 2020 Category: Toxicology Authors: Egorova OV, Ilyushina NA, Rakitskii VN Tags: Toxicol In Vitro Source Type: research

Comparative analysis of the impact of e-cigarette vapor and cigarette smoke on human gingival fibroblasts.
In conclusion, when compared to conventional CS, a less harmful effect of eCV on HGF can be assumed. PMID: 32956835 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - September 17, 2020 Category: Toxicology Authors: Vermehren MF, Wiesmann N, Deschner J, Brieger J, Al-Nawas B, Kämmerer PW Tags: Toxicol In Vitro Source Type: research

Impact of solvents on the in vitro genotoxicity of TMPTA in human HepG2 cells.
Abstract Small hydrophobic chemical compounds require solvents to produce suitable solutions for toxicological studies. However, some solvents can modify the biological properties of substances and therefore their toxicity. This specific issue has been raised for PEG-400 as an anti-inflammatory and anti-oxidative compound. Recently, in the context of the REACH Regulation, PEG-400 was used to test the in vivo genotoxicity of trimethylolpropane triacrylate (TMPTA) in the comet assay. TMPTA failed to increase DNA damage whereas it induces genotoxicity in vitro in DMSO. Therefore, we questioned whether PEG-400 could m...
Source: Toxicology in Vitro - September 15, 2020 Category: Toxicology Authors: Hegarat LLE, Huet S, Pasquier E, Charles S Tags: Toxicol In Vitro Source Type: research

Cytotoxicity comparison of 35 developmental neurotoxicants in human induced pluripotent stem cells (iPSC), iPSC-derived neural progenitor cells, and transformed cell lines.
This study demonstrates an alternative protocol that is simple, quick, less expensive, and standardized to evaluate DNT of many chemicals using human induced pluripotent stem cells (iPSC) and their differentiation to neural progenitor cells (NPC). Initially, concentration-dependent cytotoxicity of 35 DNT chemicals, including industrial materials, insecticides, and clinical drugs, were compared among iPSC, NPC, and two transformed cells, Cos-7 and HepG2, using tetrazolium dye (MTS)-reducing colorimetric and ATP luciferase assays, and IC50 values were calculated. Next, inhibitory effects of the 14 representative chemicals (m...
Source: Toxicology in Vitro - September 15, 2020 Category: Toxicology Authors: Kamata S, Hashiyama R, Hana-Ika H, Ohkubo I, Saito R, Honda A, Anan Y, Akahoshi N, Noguchi K, Kanda Y, Ishii I Tags: Toxicol In Vitro Source Type: research

Comparison of in vivo derived and scaled in vitro metabolic rate constants for several volatile organic compounds (VOCs).
Abstract Metabolic rate parameters estimation using in vitro data is necessary due to numbers of chemicals for which data are needed, trend towards minimizing laboratory animal use, and limited opportunity to collect data in human subjects. We evaluated how well metabolic rate parameters derived from in vitro data predict overall in vivo metabolism for a set of environmental chemicals for which well validated and established methods exist. We compared values of VmaxC derived from in vivo vapor uptake studies with estimates of VmaxC scaled up from in vitro hepatic microsomal metabolism studies for VOCs for which da...
Source: Toxicology in Vitro - September 14, 2020 Category: Toxicology Authors: Kenyon EM, Eklund C, Pegram RA, Lipscomb JC Tags: Toxicol In Vitro Source Type: research

Novel diphenyl urea derivative serves as an inhibitor on human lung cancer cell migration by disrupting EMT via Wnt/ β-catenin and PI3K/Akt signaling.
In this study, we explored the anti-metastatic potential of DUD for NSCLC in vitro. DUD significantly suppressed A549 cell migration by reversing EMT. The inhibition was reflected on upregulation of E-cadherin and downregulation of N-cadherin, vimentin, Snail and HIF-1α. Meanwhile, DUD inhibited the β-catenin nuclear translocation by upregulating Axin and downregulating the expression of APC, CK1 and phosphorylation of GSK3β, and simultaneously decreasing MMP9 and MMP13 expression. Moreover, it was associated with the downregulation of the PI3K/Akt/mTOR signaling. Furthermore, we used XAV939, an β-cate...
Source: Toxicology in Vitro - September 13, 2020 Category: Toxicology Authors: Dai B, Fan M, Yu R, Su Q, Wang B, Yang T, Liu F, Zhang Y Tags: Toxicol In Vitro Source Type: research

Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: in vitro testing in human liver cells.
Abstract It has been hypothesized that high glucose concentrations might contribute to the overall intracellular oxidative stress either by the direct generation of reactive oxygen species (ROS) or by altering the redox balance. Moreover, it has also been suggested that high glucose concentration can increase the susceptibility of DNA to genotoxic effects of xenobiotics. The aim of this approach was to test high glucose concentrations for pro-genotoxicity in human liver cells by setting up an in vitro model for hyperglycaemia. Increased cell susceptibility to genotoxic xenobiotics was tested by challenging cell cu...
Source: Toxicology in Vitro - September 13, 2020 Category: Toxicology Authors: Acito M, Bartolini D, Ceccarini MR, Russo C, Vannini S, Dominici L, Codini M, Villarini M, Galli F, Beccari T, Moretti M Tags: Toxicol In Vitro Source Type: research

Molecular fingerprints of conazoles via functional genomic profiling of Saccharomyces cerevisiae.
Abstract Conazoles were designed to inhibit ergosterol biosynthesis. Conazoles have been widely used as agricultural fungicides and are frequently detected in the environment. Although conazoles have been reported to have adverse effects, such as potential carcinogenic effects, the underlying molecular mechanisms of toxicity remain unclear. Here, the molecular fingerprints of five conazoles (propiconazole (Pro), penconazole (Pen), tebuconazole (Teb), flusilazole (Flu) and epoxiconazole (Epo)) were assessed in Saccharomyces cerevisiae (yeast) via functional genome-wide knockout mutant profiling. A total of 169 (4.4...
Source: Toxicology in Vitro - September 8, 2020 Category: Toxicology Authors: Guan M, Xia P, Tian M, Chen D, Zhang X Tags: Toxicol In Vitro Source Type: research

Differential influences of the BPA, BPS and BPF on in vitro IL-17 secretion by mouse and human T cells.
This study reports the ability of these bisphenols, at low and environmentally relevant concentration, i.e, 0.05 nM, to increase significantly IL-17 production in mouse T cells but not in human T lymphocytes. The use of an aryl hydrocarbon receptor (AhR) specific inhibitor demonstrated its involvement in this bisphenol-induced IL-17 production. We also observed an increased IL-17 secretion by BPS and BPF, and not by BPA, in mouse naive T cells undergoing in vitro Th17 differentiation. In total, this study emphasizes the link between bisphenol exposures and the susceptibility to develop immune diseases, questioning thus t...
Source: Toxicology in Vitro - September 6, 2020 Category: Toxicology Authors: Malaisé Y, Le Mentec H, Sparfel L, Guzylack-Piriou L Tags: Toxicol In Vitro Source Type: research

Development of a 96-well based assay for kinetic determination of catalase enzymatic-activity in biological samples.
Abstract Oxidative stress biomarkers are powerful endpoints in toxicological research. Cellular reductive/oxidative balance affects numerous signaling pathways involving H2O2. Detoxification and control of H2O2 levels results mainly from catalase-activity. The aim of this work is to develop a precise, simple, cost-effective microassay to measure catalase-activity in small tissue samples and cell extracts. We developed a protocol that quantifies H2O2 decomposition by intrinsic catalase in biological samples. Catalase-activity is calculated based on rate of decomposition of H2O2, following absorbance at 240 nm. We...
Source: Toxicology in Vitro - September 4, 2020 Category: Toxicology Authors: Grilo LF, Martins JD, Cavallaro CH, Nathanielsz PW, Oliveira PJ, Pereira SP Tags: Toxicol In Vitro Source Type: research

Toxicological analysis of aerosols derived from three electronic nicotine delivery systems using Normal human bronchial epithelial cells.
In this study, we evaluated aerosols collected from three ENDS - Juul Fruit Medley (5% nicotine), Logic Power (2.4% nicotine), and Mistic (1.8% nicotine). ENDS aerosols were generated using standard machine puffing regimen and collected with a novel fluoropolymer condensation trap. Triple quadrupole-inductively coupled plasma-mass determined the presence of heavy metals in collected aerosols. The toxicological effects of ENDS aerosols on normal human bronchial epithelial cells (NHBE) were investigated using cellular viability, reactive oxygen species, oxidative stress assays, along with DNA damage assessments using the Com...
Source: Toxicology in Vitro - September 3, 2020 Category: Toxicology Authors: Pearce K, Gray N, Gaur P, Jeon J, Suarez A, Shannahan J, Pappas RS, Wright C Tags: Toxicol In Vitro Source Type: research

The suitability of reconstructed human epidermis models for medical device irritation assessment: A comparison of In Vitro and In Vivo testing results.
Abstract The ISO 10993 standards on biocompatibility assessment of medical devices discourage the use of animal tests when reliable and validated in vitro methods are available. A round robin validation study of in vitro reconstructed human epidermis (RhE) assays was performed as potential replacements for rabbit skin irritation testing. The RhE assays were able to accurately identify strong irritants in dilute medical device extracts. However, there was some uncertainty about whether RhE tissues accurately predicted the results of the rabbit skin patch or intracutaneous irritation test. To address that question, ...
Source: Toxicology in Vitro - September 2, 2020 Category: Toxicology Authors: De Jong WH, Carraway JW, Liu C, Fan C, Liu J, Turley AP, Rollins TS, Coleman KP Tags: Toxicol In Vitro Source Type: research

Toxicogenomic study to identify potential signaling alterations related to nasal inflammatory damages induced by diesel exhaust particles in primary human nasal epithelial cells.
In this study, we aimed to identify signaling alteration caused by exposure to diesel exhaust particles (DEPs) \using primary human nasal epithelial cells (PHNECs). Global gene expression profiles in PHNECs following 50 and 200 μg/ml of DEP exposure were identified using microarray analysis. To cover the limitation of array-based mRNA expression analysis, text-mining-based software was used to analyze the integrative biological networks and relevant disease-focused functions among identified DEP-responsive genes. The confidence was valued based on the connectivity between the analyzed pathway and marker candidates. Thro...
Source: Toxicology in Vitro - September 2, 2020 Category: Toxicology Authors: Kim HS, Kim HJ, Kim N, Song JJ, Son BS, Yang JH, Lee CM, Park MK, Seo YR Tags: Toxicol In Vitro Source Type: research

Classifying polycyclic aromatic hydrocarbons by carcinogenic potency using in vitro biosignatures.
Abstract One of the most difficult challenges for risk assessment is evaluation of chemicals that predominately co-occur in mixtures like polycyclic aromatic hydrocarbons (PAHs). We previously developed a classification model in which systems biology data collected from mice short-term after chemical exposure accurately predict tumor outcome. The present study demonstrates translation of this approach into a human in vitro model in which chemical-specific bioactivity profiles from 3D human bronchial epithelial cells (HBEC) classify PAHs by carcinogenic potency. Gene expression profiles were analyzed from HBEC expo...
Source: Toxicology in Vitro - September 1, 2020 Category: Toxicology Authors: Chang Y, Huynh CTT, Bastin KM, Rivera BN, Siddens LK, Tilton SC Tags: Toxicol In Vitro Source Type: research

Epigenetic priming by EHMT1/EHMT2 in acute lymphoblastic leukemia induces TP53 and TP73 overexpression and promotes cell death.
ujo F Abstract Euchromatic histone-lysine N-methyltransferase 1 (EHMT1) and EHMT2 are upregulated in various human cancers, and their deregulation is associated with tumor development and progression. In this paper, we investigated the expression level of EHMT1/EHMT2 in acute lymphoblastic leukemia (ALL) and whether the modulation of these enzymes could have any cellular or molecular impact on ALL cells. For this, we used UNC0646 as a priming strategy to target EHMT1/EHMT2 and investigated its effect on proliferation and cell viability of Jurkat cells by MTT assay. Then, considering the IC50 and IC75, cellular dea...
Source: Toxicology in Vitro - August 31, 2020 Category: Toxicology Authors: Silva-Carvalho AÉ, Alencar APD, Resende MR, da Costa DF, Nonino A, Neves FAR, Saldanha-Araujo F Tags: Toxicol In Vitro Source Type: research

Partition coefficient and diffusion coefficient determinations of 50 compounds in human intact skin, isolated skin layers and isolated stratum corneum lipids.
laki A, Schepky A Abstract A standard protocol was used to determine partition (K) and diffusion (D) coefficients in dermatomed human skin and isolated human skin layers for 50 compounds relevant to cosmetics ingredients. K values were measured in dermatomed skin, isolated dermis, whole epidermis, intact stratum corneum (SC), delipidized SC and SC lipids by direct measurements of the radioactivity in the tissue layers/lipid component vs. buffer samples. D determinations were made in dermatomed skin, isolated dermis, whole epidermis and intact SC using a non-linear regression of the cumulative receptor fluid conten...
Source: Toxicology in Vitro - August 30, 2020 Category: Toxicology Authors: Ellison CA, Tankersley KO, Obringer CM, Carr GJ, Manwaring J, Rothe H, Duplan H, Géniès C, Grégoire S, Hewitt NJ, Jamin CJ, Klaric M, Lange D, Rolaki A, Schepky A Tags: Toxicol In Vitro Source Type: research