Comparative Cell Toxicology: The Basis for In Vitro Toxicity Testing

1994 ◽  
Vol 22 (3) ◽  
pp. 168-174
Author(s):  
Hasso Seibert ◽  
Michael Gulden ◽  
Jens-Uwe Voss
Keyword(s):  
Toxicity Testing ◽  
Cell Types ◽  
Scientific Basis ◽  
In Vitro Models ◽  
In Vitro Toxicity ◽  
Full Potential ◽  
Type B ◽  
Cell Type ◽  
In Vitro Systems

If “cell toxicology” is defined as the discipline aimed at studying the general principles of chemical interference with cellular structures and/or functions, then “comparative cell toxicology” may be defined as the study of the variety of responses to xenobiotics using: (a) different endpoints within one cell type; (b) cell types from different tissues from one species; and (c) homologous cell types from different species. If the full potential of in vitro models for toxicity testing is to be realised and the scientific basis for hazard assessment improved, then comparative cell toxicological approaches have to be developed further. In the present paper, an approach using different in vitro systems is described. The approach is aimed at the assessment of the basic toxicological characteristics of chemicals.

scholarly journals Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

2022 ◽  
Vol 23 (2) ◽  
pp. 855
Author(s):  
Dinko Mitrečić ◽  
Valentina Hribljan ◽  
Denis Jagečić ◽  
Jasmina Isaković ◽  
Federica Lamberto ◽  
...  
Keyword(s):  
Biomedical Research ◽  
Cell Types ◽  
In Vitro Models ◽  
Medical Systems ◽  
Heart Infarction ◽  
Affected Tissue ◽  
In Vitro Systems ◽  
Different Cell Types ◽  
The Brain

From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the human body. Moreover, obtaining sufficient number of standardized cells allows for cell transplantation approach with the goal of improving the regeneration of injured/disease affected tissue. However, different cell types bring different needs and place various types of hurdles on the path of regenerative neurology and regenerative cardiology. In this review, written by European experts gathered in Cost European action dedicated to neurology and cardiology-Bioneca, we present the experience acquired by working on two rather different organs: the brain and the heart. When taken into account that diseases of these two organs, mostly ischemic in their nature (stroke and heart infarction), bring by far the largest burden of the medical systems around Europe, it is not surprising that in vitro models of nervous and heart muscle tissue were in the focus of biomedical research in the last decades. In this review we describe and discuss hurdles which still impair further progress of regenerative neurology and cardiology and we detect those ones which are common to both fields and some, which are field-specific. With the goal to elucidate strategies which might be shared between regenerative neurology and cardiology we discuss methodological solutions which can help each of the fields to accelerate their development.

scholarly journals Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing

2020 ◽  
Vol 3 (4) ◽  
pp. 74
Author(s):  
Valentina Citi ◽  
Eugenia Piragine ◽  
Simone Brogi ◽  
Sara Ottino ◽  
Vincenzo Calderone
Keyword(s):  
Three Dimensional ◽  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Rapid Expansion ◽  
Anatomy And Physiology ◽  
Complex Anatomy ◽  
Computational Procedures ◽  
Scientific Challenge

The human eye is a specialized organ with a complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years, many in vitro models have been developed in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review, the ocular cell types and functionality are described, providing an overview about the scientific challenge for the development of three-dimensional (3D) in vitro models.

scholarly journals Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing and Legislative Aspects

2020 ◽  
Author(s):  
Valentina Citi ◽  
Eugenia Piragine ◽  
Simone Brogi ◽  
Sara Ottino ◽  
Marco Sansò ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Rapid Expansion ◽  
Anatomy And Physiology ◽  
Complex Anatomy ◽  
Computational Procedures ◽  
Scientific Challenge

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing which is necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria and are clearly labelled. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

scholarly journals Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing

2020 ◽  
Author(s):  
Valentina Citi ◽  
Eugenia Piragine ◽  
Simone Brogi ◽  
Sara Ottino ◽  
Vincenzo Calderone
Keyword(s):  
Three Dimensional ◽  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Rapid Expansion ◽  
Anatomy And Physiology ◽  
Complex Anatomy ◽  
Computational Procedures ◽  
Scientific Challenge

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

scholarly journals Validation of In Vitro Models

1990 ◽  
Vol 9 (3) ◽  
pp. 355-359 ◽  
Author(s):  
John M. Frazier
Keyword(s):  
Safety Evaluation ◽  
Toxicity Testing ◽  
Evaluation Process ◽  
Scientific Basis ◽  
Difficult Problem ◽  
In Vitro Models ◽  
New Methodologies ◽  
Criteria For Evaluation ◽  
Alternative Toxicity Testing

The 1980s have seen major research efforts focused on the development of alternative toxicity testing methodologies for the safety evaluation of chemicals. A difficult problem which has slowed the implementation of these methodologies has been validation. Validation means different things to different toxicologists; however, successful validation can take place only within the context of how the methodology is to be used: as a screen, an adjunct, or a replacement. The strategy for performing a validation study as well as the criteria for evaluation of the test methodologies will vary for each of these use categories. Correlative tests are adequate for screening purposes but mechanistic tests are required for adjuncts and replacements. The time has come to define the scientific basis of validation so that new methodologies can be efficiently processed through validation programs and incorporated into the safety evaluation process.

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 Testing Strategies of the In Vitro Micronucleus Assay for the Genotoxicity Assessment of Nanomaterials in BEAS-2B Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1929
Author(s):  
Tereza Cervena ◽  
Andrea Rossnerova ◽  
Tana Zavodna ◽  
Jitka Sikorova ◽  
Kristyna Vrbova ◽  
...  
Keyword(s):  
Cytochalasin B ◽  
Culture Media ◽  
Methodological Approach ◽  
Micronucleus Assay ◽  
Toxicity Testing ◽  
In Vitro Toxicity ◽  
Testing Strategies ◽  
Transmission Electron ◽  
The Impact

The evaluation of the frequency of micronuclei (MN) is a broadly utilised approach in in vitro toxicity testing. Nevertheless, the specific properties of nanomaterials (NMs) give rise to concerns regarding the optimal methodological variants of the MN assay. In bronchial epithelial cells (BEAS-2B), we tested the genotoxicity of five types of NMs (TiO2: NM101, NM103; SiO2: NM200; Ag: NM300K, NM302) using four variants of MN protocols, differing in the time of exposure and the application of cytochalasin-B combined with the simultaneous and delayed co-treatment with NMs. Using transmission electron microscopy, we evaluated the impact of cytochalasin-B on the transport of NMs into the cells. To assess the behaviour of NMs in a culture media for individual testing conditions, we used dynamic light scattering measurement. The presence of NMs in the cells, their intracellular aggregation and dispersion properties were comparable when tests with or without cytochalasin-B were performed. The genotoxic potential of various TiO2 and Ag particles differed (NM101 < NM103 and NM302 < NM300K, respectively). The application of cytochalasin-B tended to increase the percentage of aberrant cells. In conclusion, the comparison of the testing strategies revealed that the level of DNA damage induced by NMs is affected by the selected methodological approach. This fact should be considered in the interpretation of the results of genotoxicity tests.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

scholarly journals A survey of aerosol exposure systems relative to the analysis of cytotoxicity: A Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) perspective

2021 ◽  
Vol 5 ◽  
pp. 239784732110222
Author(s):  
David Thorne ◽  
Roman Wieczorek ◽  
Toshiro Fukushima ◽  
Han-Jae Shin ◽  
Robert Leverette ◽  
...  
Keyword(s):  
Scientific Research ◽  
Toxicity Testing ◽  
User Preferences ◽  
In Vitro Toxicity ◽  
Aerosol Generation ◽  
Aerosol Exposure ◽  
Comprehensive Survey ◽  
Survey Results ◽  
System Data

During a Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) meeting, the in vitro toxicity testing Sub-Group (IVT SG) met to discuss the evolving field of aerosol exposure research. Given the diversity of exposure parameters and biological endpoints being used, it was considered a high priority to investigate and contextualise the responses obtained. This is particularly driven by the inability to compare between studies on different exposure systems due to user preferences and protocol differences. Twelve global tobacco and contract research companies met to discuss this topic and formulate an aligned approach on how this diverging field of research could be appropriately compared. Something that is becoming increasingly important, especially in the light of more focused regulatory scrutiny. A detailed and comprehensive survey was conducted on over 40 parameters ranging from aerosol generation, dilution and data analysis across eight geographically independent laboratories. The survey results emphasise the diversity of in vitro exposure parameters and methodologies employed across the IVT SG and highlighted pockets of harmonisation. For example, many of the biological protocol parameters are consistent across the Sub-Group. However, variables such as cell type and exposure time remain largely inconsistent. The next steps for this work will be to map parameters and system data against biological findings and investigate whether the observed inconsistencies translate into increased biological variability. The results from the survey provide improved awareness of parameters and nuances, that may be of substantial benefit to scientists in intersecting fields and in the development of harmonised approaches.

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