Evaluation of the EYTEX™ System as a Screening Method for Ocular Tolerance: Application to Raw Materials and Finished Products

In vitro evaluation of ocular irritation requires the use of a battery of tests, for example cell culture assays and the HET-CAM test. In order to check the field applications of the different methods and their complementation, we have studied the EYTEX™ physicochemical model in an internal validation study. In this study, we compared the EYTEX™ results with the in vitro ocular irritation potencies of 52 formulations and 49 chemicals. The in vivo/in vitro correlation was highly significant, p < 0.01%, K = 0.8 (Kappa method). On the other hand, the concordance, sensitivity and specificity of this method were, 85%, 89% and 83% respectively. The compatability of 98% obtained showed the kit to be applicable to cosmetic formulations. The EYTEX™ system has also been evaluated during a comparative study of EYTEX™ human clinical tests, performed on 12 finished products; we have observed a concordance equal to 92%, indicating an excellent correlation between the two methodologies. These results suggest that the EYTEX™ test could be a reliable in vitro prescreening system for determining the eye irritation potential of cosmetic formulations, and that it should be accepted as a component of our battery of alternative methods.

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HET-CAM test for determining the possible eye irritancy of pesticides

Acta Veterinaria Hungarica ◽

10.1556/avet.58.2010.3.9 ◽

2010 ◽

Vol 58 (3) ◽

pp. 369-377 ◽

Cited By ~ 8

Author(s):

Péter Budai ◽

József Lehel ◽

Judit Tavaszi ◽

Éva Kormos

Keyword(s):

Screening Method ◽

Chorioallantoic Membrane ◽

Alternative Methods ◽

Eye Irritation ◽

Parallel Data ◽

Hen’S Egg ◽

Irritation Test ◽

Veterinary Products

Agrochemicals and veterinary products must undergo numerous toxicological tests before registration. The use of animals in these studies is a controversial issue. The Draize eye irritation test is one of the most criticised methods because of the injuries inflicted on the test animals. Several in vitro methods have been used to investigate the toxicity of potential eye irritants with a view to replacing in vivo eye irritation testing. One of these alternative methods is the Hen’s Egg Test — Chorioallantoic Membrane (HET-CAM) test. In the present studies comparative screening was performed with a set of agrochemicals to establish parallel data on in vitro (HET-CAM) and in vivo (Draize) results. The examined materials were: Totril (ioxynil), Omite 57 E (propargit), Actellic 50 EC (pyrimiphos-methyl), Stomp 330 EC (pendimethalin), Mospilan 3 EC (acetamiprid), Alirox 80 EC (EPTC), Match 050 EC (lufenuron), Nonit (dioctyl sulphosuccinate sodium), Perenal (haloxyfop-R methyl ester), Pyrinex 48 EC (chlorpyrifos). These experiments showed good correlation between results obtained by the HET-CAM test and those of the Draize rabbit eye test in most cases. The present form of the HET-CAM test can be proposed as a pre-screening method for the determination of eye irritative potential, therefore the number of test animals can be reduced and/or experimental animals can be replaced.

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A Study on UV Filter Chemicals from Annex VII of European Union Directive 76/768/EEC, in the In Vitro 3T3 NRU Phototoxicity Test

Alternatives to Laboratory Animals ◽

10.1177/026119299802600511 ◽

1998 ◽

Vol 26 (5) ◽

pp. 679-708 ◽

Cited By ~ 5

Author(s):

Horst Spielmann ◽

Michael Balls ◽

Jack Dupuis ◽

Wolfgang J. W. Pape ◽

Odile de Silva ◽

...

Keyword(s):

Neutral Red ◽

Optimum Concentration ◽

Alternative Methods ◽

Uv Filter ◽

Eu Directive ◽

Optimum Concentration Range ◽

The Impact ◽

Positive Results

In 1996, the Scientific Committee on Cosmetology of DGXXIV of the European Commission asked the European Centre for the Validation of Alternative Methods to test eight UV filter chemicals from the 1995 edition of Annex VII of Directive 76/768/EEC in a blind trial in the in vitro 3T3 cell neutral red uptake phototoxicity (3T3 NRU PT) test, which had been scientifically validated between 1992 and 1996. Since all the UV filter chemicals on the positive list of EU Directive 76/768/EEC have been shown not to be phototoxic in vivo in humans under use conditions, only negative effects would be expected in the 3T3 NRU PT test. To balance the number of positive and negative chemicals, ten phototoxic and ten non-phototoxic chemicals were tested under blind conditions in four laboratories. Moreover, to assess the optimum concentration range for testing, information was provided on appropriate solvents and on the solubility of the coded chemicals. In this study, the phototoxic potential of test chemicals was evaluated in a prediction model in which either the Photoirritation Factor (PIF) or the Mean Photo Effect (MPE) were determined. The results obtained with both PIF and MPE were highly reproducible in the four laboratories, and the correlation between in vitro and in vivo data was almost perfect. All the phototoxic test chemicals provided a positive result at concentrations of 1μg/ml, while nine of the ten non-phototoxic chemicals gave clear negative results, even at the highest test concentrations. One of the UV filter chemicals gave positive results in three of the four laboratories only at concentrations greater than 100μg/ml; the other laboratory correctly identified all 20 of the test chemicals. An analysis of the impact that exposure concentrations had on the performance of the test revealed that the optimum concentration range in the 3T3 NRU PT test for determining the phototoxic potential of chemicals is between 0.1μg/ml and 10μg/ml, and that false positive results can be obtained at concentrations greater than 100μg/ml. Therefore, the positive results obtained with some of the UV filter chemicals only at concentrations greater than 100μg/ml do not indicate a phototoxic potential in vivo. When this information was taken into account during calculation of the overall predictivity of the 3T3 NRU PT test in the present study, an almost perfect correlation of in vitro versus in vivo results was obtained (between 95% and 100%), when either PIF or MPE were used to predict the phototoxic potential. The management team and participants therefore conclude that the 3T3 NRU PT test is a valid test for correctly assessing the phototoxic potential of UV filter chemicals, if the defined concentration limits are taken into account.

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Application of the EYTEX™ System to the Evaluation of Cosmetic Products and their Ingredients

Alternatives to Laboratory Animals ◽

10.1177/026119299202000120 ◽

1992 ◽

Vol 20 (1) ◽

pp. 146-163

Author(s):

Francis H. Kruszewski ◽

Laura H. Hearn ◽

Kyle T. Smith ◽

Janice J. Teal ◽

Virginia C. Gordon ◽

...

Keyword(s):

Double Blind ◽

Eye Irritation ◽

Ocular Irritation ◽

Rabbit Eye ◽

Wide Range ◽

High Concentrations ◽

Alkaline Membrane ◽

Positive Agreement

465 cosmetic product formulations and raw ingredients were evaluated with the EYTEX™ system to determine the potential of this in vitro alternative for identifying eye irritation potential. The EYTEX™ system is a non-animal, biochemical procedure developed by Ropak Laboratories, Irvine, CA, that was designed to approximate the Draize rabbit eye irritation assay for the evaluation of ocular irritation. Avon Products Inc. provided all the test samples, which included over 30 different product types and represented a wide range of eye irritancy. All the EYTEX™ protocols available at the time of this study were used. Samples were evaluated double-blind with both the membrane partition assay (MPA) and the rapid membrane assay (RMA). When appropriate, the standard assay (STD) and the alkaline membrane assay (AMA) were used, as well as specific, documented protocol modifications. EYTEX™ results were correlated with rabbit eye irritation data which was obtained from the historical records of Avon Products Inc. A positive agreement of EYTEX™ results with the in vivo assay was demonstrated by an overall concordance of 80%. The assay error was 20%, of which 18% was due to an overestimation of sample irritancy (false positives) and 2% was attributed to underestimation (false negatives). Overestimation error in this study was due in part to the inability of the protocols to accurately classify test samples with very low irritation potential. Underestimation of sample irritancy was generally associated with ethoxylated materials and high concentrations of specific types of surfactants. 100% sensitivity and 85% predictability were described by the data, indicating the efficiency of EYTEX™ in identifying known irritants. A specificity rate of 39% showed the EYTEX™ assay to be weak in discerning non-irritants. However, the EYTEX™ protocols used in this study were not designed to identify non-irritants. A compatibility rate of 99% proved the effectiveness of the EYTEX™ assay in accommodating a diversity of product types. The EYTEX™ system protocols, when used appropriately, can provide a conservative means of assessing the irritant potential of most cosmetic formulations and their ingredients.

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Therapeutic Potential of CUDC-907 (Fimepinostat) for Hepatocarcinoma Treatment Revealed by Tumor Spheroids-based Drug Screening

10.21203/rs.3.rs-125324/v1 ◽

2020 ◽

Author(s):

Wei Liao ◽

Wanren Yang ◽

Yue Zhang ◽

Fanhong Zeng ◽

Jiecheng Xu ◽

...

Keyword(s):

Cell Lines ◽

Drug Screening ◽

Screening Method ◽

Screening Methods ◽

Spheroid Culture ◽

3D Print ◽

Culture Plate ◽

Hcc Cells

Abstract Background: Cancer is the second leading cause of death globally. However, most of the new anti-cancer agents screened by traditional drug screening methods fail in the clinic because of lack of efficacy. One of the reasons for this dilemma is that the two-dimensional (2D) culture cancer cell lines could not represent the in vivo cancer cells well. Fortunately, the development of a three-dimensional (3D) culture technique helps in this problem. Methods: The high-throughput spheroid culture plate was fabricated by using 3D print technique and agarose. 4 hepatocarcinoma (HCC) cell lines were 3D cultured to screen 19 small molecular agents based on the spheroid culture plate. 3D cultured primary HCC cells and tumor-bearing mice model were established to verify the candidate anti-hepatocarcinoma agent. Cell function experiments and western blotting were conducted to explore the anti-hepatocarcinoma mechanism of the candidate agent. Results: Based on the previous study, we established an in vitro 3D drug screening method by using our invented spheroid culture device and found that CUDC-907 can serve as a potent anti-hepatocarcinoma agent. The study data show that CUDC-907 (fimepinostat), a novel dual acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC), has potent inhibitory effects on HCC cell lines and primary HCC cells in vitro, Animal studies have shown that CUDC-907 can also suppress HCC cells in vivo. Furthermore, we investigated the antitumor mechanism of CUDC-907 in HCC cells. We found that it inhibits the PI3K/AKT/mTOR pathway and downregulates the expression of c-Myc, leading to the suppression of HCC cells. Conclusion: Our results suggest that CUDC-907 can be a candidate anti-HCC drug, and the 3D in vitro drug screening method based on our novel spheroid culture device is promising for drug screening.

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Imbir i czosnek – surowce roślinne obniżające poziom cholesterolu i glukozy

Postępy Fitoterapii ◽

10.25121/pf.2020.21.3.169 ◽

2020 ◽

Vol 21 (3) ◽

Author(s):

Małgorzata Kania-Dobrowolska ◽

Justyna Baraniak ◽

Aleksandra Górska ◽

Marlena Wolek ◽

Anna Bogacz

Keyword(s):

Type Ii Diabetes ◽

Processed Food ◽

Clinical Tests ◽

Cholesterol Levels ◽

Elevated Glucose ◽

Unbalanced Diet ◽

Lifestyle Diseases

Atherosclerosis and type II diabetes can be classified as lifestyle diseases. Unbalanced diet (highly processed food, excess salt food), a sedentary lifestyle and the use of stimulants (cigarettes, alcohol) can contribute to the emergence of both diseases. Both these diseases can coexist simultaneously. The development of type 2 diabetes may accelerate the development of atherosclerotic plaque, which in turn leads to many organ complications as well as death. People with slightly elevated glucose and cholesterol levels can be advised to take natural plant ingredients such as garlic and ginger along with changing their diet and increasing physical activity. garlic and ginger can be consumed alone as well as an addition to many dishes. In vitro and in vivo and clinical tests indicate the possibility of supporting the regulation of blood glucose and cholesterol levels by adding garlic and ginger to the diet.

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Assessment of the dermal and ocular irritation potential of multi-walled carbon nanotubes by using in vitro and in vivo methods

Toxicology Letters ◽

10.1016/j.toxlet.2009.09.007 ◽

2009 ◽

Vol 191 (2-3) ◽

pp. 268-274 ◽

Cited By ~ 50

Author(s):

A. Sairam Kishore ◽

P. Surekha ◽

P. Balakrishna Murthy

Keyword(s):

Carbon Nanotubes ◽

Ocular Irritation ◽

Multi Walled Carbon Nanotubes ◽

Walled Carbon Nanotubes

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Bioaccessibility of Anthocyanins on in vitro Digestion Mmodels: Factors Implicated and Role in Functional Foods Development

Current Medicinal Chemistry ◽

10.2174/0929867328666211123102536 ◽

2021 ◽

Vol 28 ◽

Author(s):

Gabriel Prado ◽

Isidora Pierattini ◽

Guiselle Villarroel ◽

Fernanda Fuentes ◽

Alejandra Silva ◽

...

Keyword(s):

Functional Foods ◽

Raw Materials ◽

Food Product ◽

In Vitro Digestion ◽

Raw Material ◽

Simulated Digestion ◽

Prevalence Of Obesity ◽

Food Matrices

Background: Worldwide, the prevalence of obesity and related non-communicable chronic diseases is high and continues to grow. In that sense, anthocyanins (ANC) have shown beneficial health effects in preventing obesity and metabolic risk factors. Moreover, the demand for functional foods incorporating these compounds has risen significantly in the past years. Thus, there is a need for validations of the functional properties of these formulations; nevertheless, in vivo assays are complex and require a lot of resources. One approach for estimating bioactive compounds' functionality and health benefits is to evaluate their bioaccessibility on a specific food matrix, determined by various factors. This article aims to review different factors influencing the bioaccessibility of ANC evaluated on in vitro digestion models as a functionality parameter, elucidating the effect of chemical composition, raw materials, food matrices, and vehicles for the delivery of ANC. Methods: Study searches were performed using PubMed, Web of Science, Scopus, and Science Direct databases. Results: Different factors influenced bioaccessibility and stability of ANC studied by in vitro digestion which are: i) the raw material used for ANC obtention; ii) food processing; iii) other food components; iv) the extraction method and solvents used; v) the structure of ANC; vi) delivery system (e.g., microencapsulation); vii) pH of the medium; viii) the digestion stage. Conclusion: Simulated digestion systems allow to determine free or encapsulated ANC bioaccessibility in different food matrices, which offers advantages in determining the potential functionality of a food product.

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Fruit Seeds as Sources of Bioactive Compounds: Sustainable Production of High Value-Added Ingredients from By-Products within Circular Economy

Molecules ◽

10.3390/molecules24213854 ◽

2019 ◽

Vol 24 (21) ◽

pp. 3854 ◽

Cited By ~ 14

Author(s):

Fidelis ◽

Moura ◽

Kabbas Junior ◽

Pap ◽

Mattila ◽

...

Keyword(s):

Chemical Composition ◽

Circular Economy ◽

Raw Materials ◽

Scale Up ◽

Sustainable Use ◽

Value Added ◽

Water Soluble ◽

Lipophilic Compounds

The circular economy is an umbrella concept that applies different mechanisms aiming to minimize waste generation, thus decoupling economic growth from natural resources. Each year, an estimated one-third of all food produced is wasted; this is equivalent to 1.3 billion tons of food, which is worth around US$1 trillion or even $2.6 trillion when social and economic costs are included. In the fruit and vegetable sector, 45% of the total produced amount is lost in the production (post-harvest, processing, and distribution) and consumption chains. Therefore, it is necessary to find new technological and environmentally friendly solutions to utilize fruit wastes as new raw materials to develop and scale up the production of high value-added products and ingredients. Considering that the production and consumption of fruits has increased in the last years and following the need to find the sustainable use of different fruit side streams, this work aimed to describe the chemical composition and bioactivity of different fruit seeds consumed worldwide. A comprehensive focus is given on the extraction techniques of water-soluble and lipophilic compounds and in vitro/in vivo functionalities, and the link between chemical composition and observed activity is holistically explained.

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HEMATOPOETIC STEM CELL RESPONSE TO STIMULATION OF EXTRACTS FROM ANIMAL MATERIALS

Jurnal Teknologi ◽

10.11113/jt.v78.8642 ◽

2016 ◽

Vol 78 (5-6) ◽

Author(s):

Ivan Smirnov ◽

Victor Keino ◽

Ksenia Goryacheva ◽

Alexander Shunk ◽

Alexander Bondarev ◽

...

Keyword(s):

Raw Materials ◽

Raw Material ◽

Animal Origin ◽

Aqueous Extracts ◽

Second Stage ◽

Hematopoetic Stem Cell ◽

Two Stages ◽

Stimulation Of

The article presents the results of the research hemostimulating activity of aqueous extracts of antler young Siberean stag and drone larvae homogenate. These substrates were obtained from raw materials of animal origin. Altai Krai andAltaiRepublicare subjects of theRussian Federationwhich is the place of production of the raw material. Experiments were conducted in two stages. The first stage - in vitro, which included a research of experimental substrates on the culture of mouse marrow cells. During the experiments were obtained different results. We counted the number of colonies grown in cell culture for this. The second stage of experimenters - in vivo. It included an assessment of the myeloprotector on model of cytostatic myelosuppression of mice and analysis of bone marrow and peripheral blood.

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