Development of an In Vitro Test Battery for the Estimation of Acute Human Systemic Toxicity: An Outline of the EDIT Project

The aim of the Evaluation-guided Development of New In Vitro Test Batteries (EDIT) multicentre programme is to establish and validate in vitro tests relevant to toxicokinetics and for organ-specific toxicity, to be incorporated into optimal test batteries for the estimation of human acute systemic toxicity. The scientific basis of EDIT is the good prediction of human acute toxicity obtained with three human cell line tests (R2 = 0.77), in the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme. However, the results from the MEIC study indicated that at least two other types of in vitro test ought to be added to the existing test battery to improve the prediction of human acute systemic toxicity — to determine key kinetic events (such as biotransformation and passage through biological barriers), and to predict crucial organ-specific mechanisms not covered by the tests in the MEIC battery. The EDIT programme will be a case-by-case project, but the establishment and validation of new tests will be carried through by a common, step-wise procedure. The Scientific Committee of the EDIT programme defines the need for a specific set of toxicity or toxicokinetic data. Laboratories are then invited to perform the defined tests in order to provide the “missing” data for the EDIT reference chemicals. The results obtained will be evaluated against the MEMO (the MEIC Monograph programme) database, i.e. against human acute systemic lethal and toxicity data. The aim of the round-table discussions at the 19th Scandinavian Society for Cell Toxicology (SSCT) workshop, held in Ringsted, Denmark on 6–9 September 2001, was to identify which tests are the most important for inclusion in the MEIC battery, i.e. which types of tests the EDIT programme should focus on. It was proposed that it is important to include in vitro methods for various kinetic events, such as biotransformation, absorption in the gut, passage across the blood–brain barrier, distribution volumes, protein binding, and renal clearance/accumulation. Models for target organ toxicity were also discussed. Because several of the outlier chemicals (paracetamol, digoxin, malathion, nicotine, paraquat, atropine and potassium cyanide) in the MEIC in vivo–in vitro evaluation have a neurotoxic potential, it was proposed that the development within the EDIT target organ programme should initially be focused on the nervous system.

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The Prediction of Human Acute Systemic Toxicity by the EDIT/MEIC In Vitro Test Battery: The Importance of Protein Binding and of Partitioning into Lipids

Alternatives to Laboratory Animals ◽

10.1177/026119290303100306 ◽

2003 ◽

Vol 31 (3) ◽

pp. 245-256 ◽

Cited By ~ 1

Author(s):

Cecilia Clemedson ◽

Paul J. Dierickx ◽

Michael Sjöström

Keyword(s):

Protein Binding ◽

Mercuric Chloride ◽

Culture Medium ◽

Systemic Toxicity ◽

Test Battery ◽

In Vitro Test ◽

Blood Concentrations ◽

Uptake Inhibition ◽

Vitro Test

The aim of the two studies presented in this paper was to further improve the predictability of the original Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) in vitro test battery for acute systemic toxicity. In the first study, whether a protein-free cytotoxicity assay could improve the prediction of human acute systemic toxicity was investigated. The cytotoxicity of 39 MEIC reference chemicals was measured by the neutral red uptake inhibition test after 30 minutes in phosphate-buffered saline (PBS), with hepatoma-derived Fa32 cells. The results were compared with the corresponding values obtained in complete culture medium, including 10% fetal calf serum. Mercuric chloride and hexachlorophene were much more cytotoxic in PBS, as was the case, to a lesser extent, for seven other chemicals. Potassium cyanide and eight other chemicals were less cytotoxic in PBS than in complete culture medium, probably because of poor physiological conditions. The correlation between the cytotoxicity measured in PBS and human acute toxicity was rather low, but became of the same order as for other assays, when mercuric chloride and hexachlorophene were withdrawn from the comparison. In the second study, modelling of human lethal blood concentrations by using the results of the three cell line tests of the original MEIC test battery were complemented by logP (octanol–water partition coefficient) values. The introduction of logP into the modelling did not improve the correlations, but some improvement of both R2 and Q2 was obtained by expanding the logP values with logP2 values. The highest R2 (0.84) and Q2 (0.80) values were obtained for a model in which both experimental and calculated (ambiguous) logP values were used. When only experimental logP values were used, the corresponding values were 0.80 and 0.78. These two studies showed that including protein binding and the partition of chemicals in the MEIC in vitro test battery is important, in order to improve the predictability of the results obtained.

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Recombinant in vitro test T-SPOT.TB as a screening method for early diagnosis of tuberculosis infection

Tuberculosis and lung diseases ◽

10.21292/2075-1230-2020-98-4-48-52 ◽

2020 ◽

Vol 98 (4) ◽

pp. 48-52

Author(s):

E. P. Eremenko ◽

E. A. Borodulina ◽

I. A. Sergeeva ◽

D. A. Kudlay ◽

B. E. Borodulin

Keyword(s):

Screening Method ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

Mantoux Test ◽

Skin Tests ◽

In Vitro Tests ◽

In Vitro Test ◽

Healthy Children ◽

Vitro Test

In addition to standard skin tests (Mantoux test with 2 TU PPD-L and diaskintest) for the diagnosis of tuberculosis infection, in vitro tests are used. One of these tests is T-SPOT.TB being more widely used in recent years.The objective: to evaluate the effectiveness of T-SPOT.TB test for early detection of tuberculosis infection in children and adolescents in Samara Region.Subjects and methods. From 2016 to 2019, results of T-SPOT.TB tests performed in 596 children aged 2 to 17 years inclusive were analyzed; those children had no immunodiagnosis of tuberculosis infection using skin tests since their parents refused to have it.Results. It was found out that the major reason for refusing skin tests was the “fear” of visiting a TB dispensary if the result had been positive — 38.43% (n = 229). The latent tuberculosis infection according to the results of T-SPOT.TB among children with concomitant pathology made 2.6%, among healthy children – 0.7%.Conclusion. T-SPOT.TB test may be used as an alternative method for diagnosis of tuberculosis infection, should the parent refuse to have skin tests. In children with concomitant pathology, T-SPOT.TB test can serve as a leading method for immunodiagnosis of tuberculosis.The authors state that they have no conflict of interests.

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UJI DAYAHAMBAT EUGENOL DARI DAUN CENGKEH HASIL FRAKSINASI TERHADAP PERTUMBUHAN JAMUR PATOGEN Fusarium oxysporum f.sp. Cubense Eugenol Inhibitory Test From Clove Leaf Fractionation Of Fungal Patogen Growth Fusarium oxysporum f.sp. cubense

AgriPeat ◽

10.36873/agp.v20i02.146 ◽

2019 ◽

Vol 20 (02) ◽

pp. 107-113

Author(s):

Admin Journal

Keyword(s):

Fusarium Oxysporum ◽

Vacuum Distillation ◽

Pathogenic Fungus ◽

Lethal Concentration ◽

In Vitro Tests ◽

In Vitro Test ◽

Microsoft Excel ◽

Vitro Test

ABSTRACTThis study aims to determine the inhibition of eugenol derived from fractionation clove leaf essentialoils (CLEO) on the growth of pathogenic fungus Fusarium oxysporum f. sp. cubense (Foc) and LC50(Lethal Concentration 50). This research was in vitro, started with purification of clove leaf essentialoil, fractionation by vacuum distillation and bioassay. In vitro tests include exploration of minimuminhibition and preventability tests. Data were analyzed with Microsoft Excel 2010 program. Theresults of minimum inhibition showed at 218,75 ppm concentration of each level was able to inhibitthe growth of Foc fungi. The minimum inhibition exploration was carried out at 218,75 ppm, 109,38ppm, 54,69 ppm and 27,34 ppm. Exploration results showed that fractionated CLEO has been able toinhibit the growth of Foc fungi at 27,34 ppm in the amount of 15,60%. This concentration is used asthe lowest concentration in the inhibitory test. Furthermore, the inhibitory test was carried out startingat the highest concentration of 218,75 ppm, 109,38 ppm, 54,69 ppm and 27,34 ppm. Observationswere made for 7 days after inoculation (DAI). The results showed the best inhibition was at aconcentration of 218,75 ppm at 90,70% and LC50 at 11.17 µL.Keywords: CLEO, fractionation, Foc, in vitro test and LC50

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Target Organ Cells as in Vitro Test Systems for Toxicity, Mutagenicity, DNA-Repair and Transformation by Environmental Pollutants

Environmental Hygiene ◽

10.1007/978-3-642-73766-4_12 ◽

1988 ◽

pp. 49-53

Author(s):

M. Riebe ◽

M. Emura ◽

M. Aufderheide ◽

U. Mohr

Keyword(s):

Dna Repair ◽

Environmental Pollutants ◽

Target Organ ◽

In Vitro Test ◽

Test Systems ◽

Vitro Test

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Comparison of methods for measurement of the pressure exerted by knitted fabrics

Textile Research Journal ◽

10.1177/0040517516665255 ◽

2016 ◽

Vol 87 (17) ◽

pp. 2117-2126 ◽

Cited By ~ 7

Author(s):

Małgorzata Cieślak ◽

Agnieszka Karaszewska ◽

Ewa Gromadzińska ◽

Izabela Jasińska ◽

Irena Kamińska

Keyword(s):

In Vitro Tests ◽

Knitted Fabric ◽

In Vitro Test ◽

Knitted Fabrics ◽

Weft Knitted Fabric ◽

In Vivo Tests ◽

Vitro Test ◽

Warp Knitted Fabric

The article presents the results of measurements of pressure exerted by two model knitted products – bands with different structure (WI jersey weft-knitted fabric and WII openwork warp-knitted fabric). The tests were carried out with using the I-Scan system (in vivo and in vitro tests) and the STM 579 device (in vitro test). A comparative analysis of the in vivo and in vitro results for the I-Scan method and in vitro results for the I-Scan and STM 579 method was performed. It was found that the pressure values are lower for openwork warp-knitted fabric than for jersey weft-knitted fabric both in the case of the in vitro and in vivo tests, and the values of pressure for the same band are higher in the case of the in vitro tests.

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The Prediction of Systemic Toxicity by Integrating the Results of Biokinetic Models and Biologically Based In Vitro Test Methods

The Practical Applicability of Toxicokinetic Models in the Risk Assessment of Chemicals ◽

10.1007/978-94-017-3437-0_9 ◽

2002 ◽

pp. 155-194

Author(s):

Bas J. Blaauboer ◽

Joost DeJongh ◽

Anna Forsby ◽

J. Brian Houston ◽

André Guillouzo ◽

...

Keyword(s):

Test Methods ◽

Systemic Toxicity ◽

In Vitro Test ◽

Vitro Test

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In Vitro Toxicology and the Test Guidelines

Alternatives to Laboratory Animals ◽

10.1177/026119299602400320 ◽

1996 ◽

Vol 24 (3) ◽

pp. 435-438

Author(s):

Kimmo Louekari

Keyword(s):

Cost Effective ◽

Test Methods ◽

In Vitro Tests ◽

In Vitro Test ◽

In Vitro Methods ◽

Effective Manner ◽

Genotoxic Carcinogens ◽

Vitro Test

Ethical, economical and scientific considerations should encourage the development of alternative and in vitro test methods. Before their adoption, in vitro methods need to be validated and scientifically justified. Demand for rigorous validation schemes for in vitro tests must be emphasised, even more than in the case of in vivo tests. The OECD has adopted in vitro guidelines for testing genotoxicity; several endpoints and mechanisms can be studied in a cost-effective manner in vitro. Similar advantages could be afforded if acute irritation and corrosion, as well as the non-genotoxic carcinogenic effects of chemicals, could be studied in vitro. Evaluation of the validation status of various methods used to study non-genotoxic carcinogens was begun by the Nordic Working Group on In Vitro Methods for Non-genotoxic Mechanisms in 1996. In some established OECD test guidelines (for example, the dermal irritation/corrosion test), there is already room for the application of in vitro methods which have not been formally validated. In January 1996, the OECD Workshop on Harmonisation of Validation and Acceptance Criteria for Alternative Toxicological Test Methods set the basis for internationally acceptable principles to be followed in the validation of in vitro test methods.

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