The Experts below are selected from a list of 112068 Experts worldwide ranked by ideXlab platform
Tzankov Borislav - One of the best experts on this subject based on the ideXlab platform.
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In Vitro Toxicity evaluation of lomefloxacIn-loaded MCM-41 mesoporous silica nanoparticles
'Informa UK Limited', 2019Co-Authors: Tzankova Virginia, Aluani Denitsa, Yordanov Yordan, Valoti Massimo, Frosini Maria, Spassova Ivanka, Kovacheva Daniela, Tzankov BorislavAbstract:LomefloxacIn (LF) is InterestIng as a model molecule from a safety poInt of view because of its high potential for serious adverse drug effects (i.e. phototoxic reactions). In this study, MCM-41 mesoporous silica nanoparticles (MCM-41) were loaded with lomefloxacIn, aimIng to overcome the drug's IntrInsic cytoToxicity. The good biocompatibility of the empty drug carrier (0.1-1.0 mg/ml) was established by the absence of red blood cell lysis (hemolysis assay). The cytoToxicity of empty MCM-41 and lomefloxacIn-loaded MCM-41 (LF-MCM-41) was evaluated by usIng a battery of In Vitro cytoToxicity assays: Alamar blue, lactate dehydrogenase release and reactive oxygen species formation by dichlorofluoresceIn assay. Three cell cultures models: hepatoma HepG2, fibroblasts L929 and endothelial EA.hy926 cells were used to compare the cytoToxicity and reactive oxygen species formation by free drug, empty MCM-41, and LF-MCM-41. The fIndIngs from the study Indicated that empty MCM-41 (0.1-1.0 mg/ml) showed a low cytotoxic potential In HepG2, followed by L929 and EA.hy926 cells. LomefloxacIn loadIng In MCM-41 mesoporous silica nanocarrier reduced the cytoToxicity of the free lomefloxacIn, especially In the high concentration (1.0 mg/ml MCM-41, contaInIng 120 µg/ml LF). L929 and EA.hy926 cells were more sensitive to the protective effects of LF-MCM-41, compared to HepG2 cells. The results Indicate that an improvement In lomefloxacIn safety might be expected after Incorporation In an appropriate drug delivery system
Daniel M Rotroff - One of the best experts on this subject based on the ideXlab platform.
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IncorporatIng human dosimetry and exposure Into high throughput In Vitro Toxicity screenIng
Toxicological Sciences, 2010Co-Authors: Daniel M Rotroff, Barbara A Wetmore, David J Dix, Stephen S Ferguson, Harvey J Clewell, Keith A Houck, Edward L Lecluyse, Melvin E Andersen, Richard S JudsonAbstract:Many chemicals In commerce today have undergone limited or no safety testIng. To reduce the number of untested chemicals and prioritize limited testIng resources, several governmental programs are usIng high-throughput In Vitro screens for assessIng chemical effects across multiple cellular pathways. In this study, metabolic clearance and plasma proteIn bIndIng were experimentally measured for 35 ToxCast phase I chemicals. The experimental data were used to parameterize a population-based In Vitro-to-In vivo extrapolation model for estimatIng the human oral equivalent dose necessary to produce a steady-state In vivo concentration equivalent to In Vitro AC50 (concentration at 50% of maximum activity) and LEC (lowest effective concentration) values from the ToxCast data. For 23 of the 35 chemicals, the range of oral equivalent doses for up to 398 ToxCast assays was compared with chronic aggregate human oral exposure estimates In order to assess whether significant In Vitro bioactivity occurred withIn the range of maximum expected human oral exposure. Only 2 of the 35 chemicals, triclosan and pyrithiobac-sodium, had overlappIng oral equivalent doses and estimated human oral exposures. RankIng by the potencies of the AC50 and LEC values, these two chemicals would not have been at the top of a prioritization list. IntegratIng both dosimetry and human exposure Information with the high-throughput Toxicity screenIng efforts provides a better basis for makIng Informed decisions on chemical testIng priorities and regulatory attention. Importantly, these tools are necessary to move beyond hazard rankIngs to estimates of possible In vivo responses based on In Vitro screens.
Ivonne M C M Rietjens - One of the best experts on this subject based on the ideXlab platform.
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use of physiologically based kInetic modelIng based reverse dosimetry to predict In vivo Toxicity from In Vitro data
Chemical Research in Toxicology, 2017Co-Authors: Jochem Louisse, Karsten Beekmann, Ivonne M C M RietjensAbstract:The development of reliable nonanimal based testIng strategies, such as In Vitro bioassays, is the holy grail In current human safety testIng of chemicals. However, the use of In Vitro Toxicity data In risk assessment is not straightforward. One of the maIn issues is that concentration–response curves from In Vitro models need to be converted to In vivo dose–response curves. These dose–response curves are needed In toxicological risk assessment to obtaIn a poInt of departure to determIne safe exposure levels for humans. Recent scientific developments enable this translation of In Vitro concentration–response curves to In vivo dose–response curves usIng physiologically based kInetic (PBK) modelIng-based reverse dosimetry. The present review provides an overview of the examples available In the literature on the prediction of In vivo Toxicity usIng PBK modelIng-based reverse dosimetry of In Vitro Toxicity data, showIng that proofs-of-prInciple are available for Toxicity end poInts rangIng from developmental...
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the use of In Vitro Toxicity data and physiologically based kInetic modelIng to predict dose response curves for In vivo developmental Toxicity of glycol ethers In rat and man
Toxicological Sciences, 2010Co-Authors: Jochem Louisse, Esther De Jong, Johannes J M Van De Sandt, Bas J Blaauboer, Ruud Woutersen, Aldert H Piersma, Ivonne M C M Rietjens, Miriam VerweiAbstract:At present, regulatory assessment of systemic Toxicity is almost solely carried out usIng animal models. The European Commission's REACH legislation stimulates the use of animal-free approaches to obtaIn Information on the Toxicity of chemicals. In Vitro Toxicity tests provide In Vitro concentration-response curves for specific target cells, whereas In vivo dose-response curves are regularly used for human risk assessment. The present study shows an approach to predict In vivo dose-response curves for developmental Toxicity by combInIng In Vitro Toxicity data and In silico kInetic modelIng. A physiologically based kInetic (PBK) model was developed, describIng the kInetics of four glycol ethers and their embryotoxic alkoxyacetic acid metabolites In rat and man. In Vitro Toxicity data of these metabolites derived In the embryonic stem cell test were used as Input In the PBK model to extrapolate In Vitro concentration-response curves to predicted In vivo dose-response curves for developmental Toxicity of the parent glycol ethers In rat and man. The predicted dose-response curves for rat were found to be In concordance with the embryotoxic dose levels measured In reported In vivo rat studies. Therefore, predicted dose-response curves for rat could be used to set a poInt of departure for derivIng safe exposure limits In human risk assessment. CombInIng the In Vitro Toxicity data with a human PBK model allows the prediction of dose-response curves for human developmental Toxicity. This approach could therefore provide a means to reduce the need for animal testIng In human risk assessment practices. © The Author 2010. All rights reserved.
Kimberlee Moran - One of the best experts on this subject based on the ideXlab platform.
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big data In chemical Toxicity research the use of high throughput screenIng assays to identify potential toxicants
Chemical Research in Toxicology, 2014Co-Authors: Jun Zhang, Abena Boison, Alexander Sedykh, Kimberlee MoranAbstract:High-throughput screenIng (HTS) assays that measure the In Vitro Toxicity of environmental compounds have been widely applied as an alternative to In vivo animal tests of chemical Toxicity. Current HTS studies provide the community with rich toxicology Information that has the potential to be Integrated Into Toxicity research. The available In Vitro Toxicity data is updated daily In structured formats (e.g., deposited Into PubChem and other data-sharIng web portals) or In an unstructured way (papers, laboratory reports, Toxicity Web site updates, etc.). The Information derived from the current Toxicity data is so large and complex that it becomes difficult to process usIng available database management tools or traditional data processIng applications. For this reason, it is necessary to develop a big data approach when conductIng modern chemical Toxicity research. In Vitro data for a compound, obtaIned from meanIngful bioassays, can be viewed as a response profile that gives detailed Information about th...
Martin Wagner - One of the best experts on this subject based on the ideXlab platform.
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are bioplastics and plant based materials safer than conventional plastics In Vitro Toxicity and chemical composition
Environment International, 2020Co-Authors: Lisa Zimmermann, Andrea Dombrowski, Carolin Volker, Martin WagnerAbstract:Plastics contaIn a complex mixture of known and unknown chemicals; some of which can be toxic. Bioplastics and plant-based materials are marketed as sustaInable alternative to conventional plastics. However, little is known with regard to the chemicals they contaIn and the safety of these compounds. Thus, we extracted 43 everyday bio-based and/or biodegradable products as well as their precursors, coverIng mostly food contact materials made of nIne material types, and characterized these extracts usIng In Vitro bioassays and non-target high-resolution mass spectrometry. Two-third (67%) of the samples Induced baselIne Toxicity, 42% oxidative stress, 23% antiandrogenicity and one sample estrogenicity. In total, we detected 41,395 chemical features with 186-20,965 features present In the Individual samples. 80% of the extracts contaIned >1000 features, most of them unique to one sample. We tentatively identified 343 priority compounds IncludIng monomers, oligomers, plastic additives, lubricants and non-Intentionally added substances. Extracts from cellulose- and starch-based materials generally triggered a strong In Vitro Toxicity and contaIned most chemical features. The toxicological and chemical signatures of polyethylene (Bio-PE), polyethylene terephthalate (Bio-PET), polybutylene adipate terephthalate (PBAT), polybutylene succInate (PBS), polylactic acid (PLA), polyhydroxyalkanoates (PHA) and bamboo-based materials varied with the respective product rather than the material. Toxicity was less prevalent and potent In raw materials than In fInal products. A comparison with conventional plastics Indicates that bioplastics and plant-based materials are similarly toxic. This highlights the need to focus more on aspects of chemical safety when designIng truly "better" plastic alternatives.
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benchmarkIng the In Vitro Toxicity and chemical composition of plastic consumer products
Environmental Science & Technology, 2019Co-Authors: Lisa Zimmermann, Carolin Volker, Martin Wagner, Georg Dierkes, Thomas A TernesAbstract:Plastics are known sources of chemical exposure and few, promInent plastic-associated chemicals, such as bisphenol A and phthalates, have been thoroughly studied. However, a comprehensive characterization of the complex chemical mixtures present In plastics is missIng. In this study, we benchmark plastic consumer products, coverIng eight major polymer types, accordIng to their toxicological and chemical signatures usIng In Vitro bioassays and nontarget high-resolution mass spectrometry. Most (74%) of the 34 plastic extracts contaIned chemicals triggerIng at least one end poInt, IncludIng baselIne Toxicity (62%), oxidative stress (41%), cytoToxicity (32%), estrogenicity (12%), and antiandrogenicity (27%). In total, we detected 1411 features, tentatively identified 260, IncludIng monomers, additives, and nonIntentionally added substances, and prioritized 27 chemicals. Extracts of polyvInyl chloride (PVC) and polyurethane (PUR) Induced the highest Toxicity, whereas polyethylene terephthalate (PET) and high-density polyethylene (HDPE) caused no or low Toxicity. High baselIne Toxicity was detected In all "bioplastics" made of polylactic acid (PLA). The toxicities of low-density polyethylene (LDPE), polystyrene (PS), and polypropylene (PP) varied. Our study demonstrates that consumer plastics contaIn compounds that are toxic In Vitro but remaIn largely unidentified. SInce the risk of unknown compounds cannot be assessed, this poses a challenge to manufacturers, public health authorities, and researchers alike. However, we also demonstrate that products not InducIng Toxicity are already on the market.
