In Vitro Toxicity Testing: Purpose, Validation and Strategy

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 11-18 ◽  
Author(s):  
Oliver P. Flint
Keyword(s):  
Cell Function ◽  
Toxicity Testing ◽  
In Vitro Toxicity ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Vitro Test ◽  
Basal Cytotoxicity ◽  
Biological Endpoint

The fullest potential for in vitro evaluation of toxicity will be realised in the context of the process of assessing the risk of human toxicity. This article is an attempt to clarify what contributions can be made by in vitro tests and what types of in vitro test can best be used. In vitro tests are clarified according to the type of biological endpoint evaluated, first into tests for general (‘basal’) cytotoxicity and, secondly, into tests for differentiated cell function. The role of each type of test is analysed and it is suggested that tests for general cytotoxicity, as opposed to differentiated function, are difficult to interpret in terms of in vivo toxicity. A general approach to evaluating in vitro tests is described, and a strategy for using these tests is proposed.

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

2016 ◽  
Vol 87 (17) ◽  
pp. 2117-2126 ◽  
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.

In Vitro Toxicology and the Test Guidelines

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.

MEIC Evaluation of Acute Systemic Toxicity

1998 ◽  
Vol 26 (1_suppl) ◽  
pp. 93-129 ◽  
Author(s):  
Cecilia Clemedson ◽  
Frank A. Barile ◽  
Barbro Ekwall ◽  
Maria José Gómez-Lechón ◽  
Tony Hall ◽  
...  
Keyword(s):  
Cell Lines ◽  
Primary Cultures ◽  
Toxicity Testing ◽  
Preceding Paper ◽  
In Vitro Toxicity ◽  
Toxicity Data ◽  
Animal Cells ◽  
Basal Cytotoxicity

Results from tests on the first 30 MEIC reference chemicals in 16 different systems are presented as a prerequisite to the subsequent in vitro/in vivo comparisons of acute toxicity data, i.e. the final MEIC evaluation of all test results of the study. The study is a supplement to the previously published results from 68 methods (including methods 45B and 46B [old numbers]) used to test the same set of chemicals. The strategies and methods of the preceding paper were employed to enable a comparative cytotoxicity analysis of the results from these 68 methods and from the 16 new methods to be made. Principal components analysis (PCA) of 82 assays demonstrated a dominating first component which described as much as 83% of the variance in the toxicity data. This remarkable similarity of all toxicity data was the main finding of the present study, and confirmed the results of the previous study with a less-extensive database. Also, the influence on the general variability of results of several key methodological factors was evaluated by analysis of selected sets of data, including linear regression of the results of pairs of methods, which were similar in all respects except for the factor under analysis. This analysis of the same 82 assays as before also confirmed previous results from the 68 assay database: a) the toxicities of a third of the chemicals increased considerably with exposure time; b) in general, cytotoxicity for human cells was well predicted by cytotoxicity tests with animal cells; c) this prediction was poor for two chemicals, i.e. digoxin and malathion; d) prediction of human cytotoxicity by ecotoxicological tests was only fairly good; e) 25 comparisons of similar assays employing different cell lines showed strikingly similar toxicities (mean R2 = 0.86); f) 22 comparisons of similar pairs of assays employing different primary cultures and cell lines also revealed similar toxicities (mean R2 = 0.79); and g) 15 comparisons of similar assays with different growth/viability endpoint measurements demonstrated strikingly similar toxicities (mean R2 = 0.89). Results b, e, f and g must be the main causes of the general similarity of results, while results a, c and d, together with other factors, could explain the 20% dissimilarity. These findings support the basal cytotoxicity concept and may assist in guiding and refining in vitro toxicity testing in the future.

MEIC Evaluation of Acute Systemic Toxicity

1996 ◽  
Vol 24 (1_part_1) ◽  
pp. 273-311 ◽  
Author(s):  
Cecilia Clemedson ◽  
Elisabeth McFarlane-Abdulla ◽  
Marianne Andersson ◽  
Frank A. Barile ◽  
Mabel C. Calleja ◽  
...  
Keyword(s):  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Toxicity ◽  
Test Systems ◽  
Differentiated Cells ◽  
Basal Cytotoxicity ◽  
Linear Contrast ◽  
Different Cell Types

Results from tests of the first 30 MEIC reference chemicals in 68 different toxicity assays are presented as a prerequisite to subsequent in vitro/in vivo comparisons of acute toxicity data. A comparative cytotoxicity study was also carried out. Firstly, the variability of all of the results was analysed by using principal components analysis (PCA), analyses of variance (ANOVAs) and pairwise comparisons of means according to Tukey's method. The first PCA component described 80% of the variance of all of the cytotoxicity data. Tukey's ANOVA indicated a similar sensitivity for the assays, of approximately 80%. Secondly, the influence of five major methodological components on the general variability of the results was evaluated by linear regression and ANOVA linear contrast analyses. The findings were that: a) the toxicity of many chemicals increased with exposure time; b) in general, human cytotoxicity was predicted well by animal cytotoxicity tests; c) this prediction was poor for two chemicals; d) the prediction of human cytotoxicity by the ecotoxicological tests was only fairly good; e) one organotypic endpoint used, i.e. contractility of muscle cells, gave different results to those obtained according to viability/growth toxicity criteria; f) twelve comparisons of similar test systems involving different cell types (including highly differentiated cells) showed similar toxicities regardless of cell type; and g) nine out often comparisons of test systems with identical cell types and exposure times revealed similar toxicities, regardless of the viability or growth endpoint measurement used. Factors b, f and g must be the main causes of the remarkable similarity between the total results, while factors a, c, d and e, together with other minor factors that were not analysed, contributed to the 20% dissimilarity. The findings strongly support the basal cytotoxicity concept, and will facilitate future in vitro toxicity testing.

scholarly journals Assessment of Three In Vitro Tests and an In Vivo Test for Chloroquine Resistance in Plasmodium falciparumClinical Isolates

1998 ◽  
Vol 36 (1) ◽  
pp. 243-247 ◽  
Author(s):  
Jean Bickii ◽  
Leonardo K. Basco ◽  
Pascal Ringwald
Keyword(s):  
Host Factors ◽  
Chloroquine Resistance ◽  
In Vitro Assays ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
In Vivo Evaluation ◽  
In Vivo Test ◽  
Vitro Test

Three in vitro assays (the isotopic semimicrotest [700 μl per well; 24-well plates], the isotopic microtest [200 μl per well; 96-well plates], and the rapid in vitro test) and the standard in vivo test for chloroquine resistance were compared for 99 clinical isolates of Plasmodium falciparum obtained from symptomatic African patients. The 50% inhibitory concentrations determined by the two isotopic tests were similar and were highly correlated (r = 0.965; P < 0.05), showing a high concordance between the semimicrotest and the microtest. There was a moderate agreement between these two isotopic tests and the in vivo test. Most of the discordant results were probably due to host factors, including reinfections, pharmacokinetic variations, and immunologic response, which are eliminated in in vitro assays. The rapid in vitro test based on the inhibition of chloroquine efflux in the presence of verapamil was poorly concordant with the other tests. Despite some discordant results, isotopic in vitro assays are useful to characterize the phenotypes of individual isolates without the interference of host factors and are complementary to in vivo evaluation of drug efficacy. However, in vitro assays need to be standardized to allow direct comparison of results between different laboratories.

In Vitro Toxicology Methods in Risk Assessment

1996 ◽  
Vol 24 (3) ◽  
pp. 325-331
Author(s):  
Iain F. H. Purchase
Keyword(s):  
Risk Assessment ◽  
Hazard Assessment ◽  
Human Health Risk ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
New Concepts ◽  
Vitro Test

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined, and risk can then be assessed. In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames Salmonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification. The future development of in vitro methods is likely to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed in vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, will be more difficult to replace.

Animal Models and Alternatives in the Quality Control of Vaccines: Are In Vitro Methods or In Vivo Methods the Scientific Equivalent of the Emperor's New Clothes?

1995 ◽  
Vol 23 (1) ◽  
pp. 61-73
Author(s):  
Coenraad Hendriksen ◽  
Johan van der Gun
Keyword(s):  
Quality Control ◽  
Test Methods ◽  
In Vitro Test ◽  
Large Numbers ◽  
Alternative Approach ◽  
Inactivated Vaccines ◽  
Vitro Test

In the quality control of vaccine batches, the potency testing of inactivated vaccines is one of the areas requiring very large numbers of animals, which usually suffer significant distress as a result of the experimental procedures employed. This article deals with the potency testing of diphtheria and tetanus toxoids, two vaccines which are used extensively throughout the world. The relevance of the potency test prescribed by the European Pharmacopoeia monographs is questioned. The validity of the potency test as a model for the human response, the ability of the test to be standardised, and the relevance of the test in relation to the quality of the product are discussed. It is concluded that the potency test has only limited predictive value for the antitoxin responses to be expected in recipients of these toxoids. An alternative approach for estimating the potency of toxoid batches is discussed, in which a distinction is made between estimation of the immunogenic potency of the first few batches obtained from a seed lot and monitoring the consistency of the quality of subsequent batches. The use of animals is limited to the first few batches. Monitoring the consistency of the quality of subsequent batches is based on in vitro test methods. Factors which hamper the introduction and acceptance of the alternative approach are considered. Finally, proposals are made for replacement, reduction and/or refinement (the Three Rs) in the use of animals in the routine potency testing of toxoids.

Analogy Models for Prediction of Human Toxicity

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 103-116
Author(s):  
Sven Hellberg ◽  
Lennart Eriksson ◽  
Jörgen Jonsson ◽  
Fredrik Lindgren ◽  
Michael Sjöström ◽  
...  
Keyword(s):  
Human Subjects ◽  
Toxicity Testing ◽  
In Vitro Cytotoxicity ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
In Vitro Tests ◽  
Human Toxicity ◽  
Efficient Data ◽  
Basal Cytotoxicity

Estimating the toxicity to humans of chemicals by testing on human subjects is not considered to be ethically acceptable, and toxicity testing on laboratory animals is also questionable. Therefore, there is a need for alternative methods that will give estimates of various aspects of human toxicity. Batteries of in vitro tests, together with physicochemical and toxicokinetic data, analysed by efficient data analytical methods, may enable analogy models to be constructed that can predict human toxicity. It may be possible to model non-specific toxicity relating to lipophilicity, or basal cytotoxicity, for a series of diverse compounds with large variation in chemical structure and physicochemical properties. However, local models for a series of similar compounds are generally expected to be more accurate, as well as being capable of modelling more-specific interactions. Analogy models for the prediction of human toxicity are discussed and exemplified with physicochemical and cytotoxicity data from the first ten chemicals in the multicenter evaluation of in vitro cytotoxicity (MEIC) project.

In Vitro Methods as a Tool in Neurotoxicity Studies

1995 ◽  
Vol 23 (4) ◽  
pp. 491-496
Author(s):  
Hanna Tähti ◽  
Leila Vaalavirta ◽  
Tarja Toimela
Keyword(s):  
Risk Evaluation ◽  
Toxicity Testing ◽  
In Vitro Models ◽  
In Vitro Tests ◽  
Industrial Chemicals ◽  
Mercury Compounds ◽  
Toxicological Data ◽  
In Vivo Tests

— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tasks concerning the use of in vitro models in the evaluation of neurotoxic risks. It is based on our previous studies with various in vitro models and on recent literature. The induction of glial fibrillary acidic protein in astrocyte cultures after treatment with known neurotoxicants (mercury compounds and aluminium) is discussed in more detail as an important response which can be detected in vitro. When used appropriately with in vivo tests and with previous toxicological data, in vitro neurotoxicity testing considerably improves risk assessment. The incorporation of in vitro tests into the early stages of risk evaluation can reduce the number of animals used in routine toxicity testing, by identifying chemicals with high neurotoxic potential.

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

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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