Zeitschriftenartikel: „Toxicity testing In vitro“

1

Ciabattoni, G., P. Montuschi, D. Curró und P. Preziosi. „In vitro testing for lung toxicity“. Toxicology in Vitro 7, Nr. 5 (September 1993): 581–85. http://dx.doi.org/10.1016/0887-2333(93)90091-i.

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2

Flint, Oliver. „In Vitro Toxicity Testing: Redefining our Objectives“. Alternatives to Laboratory Animals 20, Nr. 4 (Oktober 1992): 571–74. http://dx.doi.org/10.1177/026119299202000411.

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3

Soldatow, Valerie Y., Edward L. LeCluyse, Linda G. Griffith und Ivan Rusyn. „In vitro models for liver toxicity testing“. Toxicol. Res. 2, Nr. 1 (2013): 23–39. http://dx.doi.org/10.1039/c2tx20051a.

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4

Lipman, Jack, Oliver Flint, June Bradlaw, John Frazier, Charlene McQueen, Carol Green, Daniel Acosta et al. „Cell culture systems andin vitro toxicity testing“. Cytotechnology 8, Nr. 2 (Juni 1992): 129–76. http://dx.doi.org/10.1007/bf02525495.

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5

DelRaso, N. J. „In vitro methodologies for enhanced toxicity testing“. Toxicology Letters 68, Nr. 1-2 (Mai 1993): 91–99. http://dx.doi.org/10.1016/0378-4274(93)90122-e.

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6

Prieto, Pilar. „Barriers, Nephrotoxicology and Chronic Testing In Vitro“. Alternatives to Laboratory Animals 30, Nr. 2_suppl (Dezember 2002): 101–5. http://dx.doi.org/10.1177/026119290203002s15.

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In many organs of the human body, there are effective physiological barriers which contribute to regulation of the uptake, transport and secretion of endogenous and exogenous materials. ECVAM is involved in the development of several in vitro models for detecting damage to various barriers, including, the renal epithelium, the intestinal barrier, and the blood–brain barrier, after acute and chronic exposure to chemicals and products of various kinds. Long-term toxicity testing is an important issue in toxicology. At present, there are no generally accepted in vitro models available for replacing chronic testing in animals. Under chronic exposure conditions, the cellular response is greater than that which can be predicted in the standard cytotoxicity models. Therefore, the approach to predicting chronic toxicity will need to involve more-complex in vitro models. Several currently available in vitro long-term toxicity systems are under evaluation.

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7

Flint, Oliver P. „In Vitro Toxicity Testing: Purpose, Validation and Strategy“. Alternatives to Laboratory Animals 18, Nr. 1_part_1 (November 1990): 11–18. http://dx.doi.org/10.1177/026119299001800103.1.

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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.

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8

Vinken, M. „Liver-based in vitro models for toxicity testing“. Toxicology Letters 295 (Oktober 2018): S7. http://dx.doi.org/10.1016/j.toxlet.2018.06.029.

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9

Jennings, P. „Kidney-based in vitro models for toxicity testing“. Toxicology Letters 295 (Oktober 2018): S7—S8. http://dx.doi.org/10.1016/j.toxlet.2018.06.030.

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10

Constant, S. „Lung-based in vitro models for toxicity testing“. Toxicology Letters 295 (Oktober 2018): S8. http://dx.doi.org/10.1016/j.toxlet.2018.06.031.

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11

Gutleb, A. C. „Three-dimensional models for in vitro toxicity testing“. Toxicology Letters 295 (Oktober 2018): S8. http://dx.doi.org/10.1016/j.toxlet.2018.06.033.

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12

Dover, R., W. R. Otto, J. Nanchahal und D. J. Riches. „Toxicity testing of wound dressing materials in vitro“. British Journal of Plastic Surgery 48, Nr. 4 (1995): 230–35. http://dx.doi.org/10.1016/0007-1226(95)90007-1.

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13

Rodriguez, Rosita J. „In vitro toxicity testing. Applications to safety evaluation“. Toxicology Letters 63, Nr. 2 (November 1992): 221–23. http://dx.doi.org/10.1016/0378-4274(92)90014-b.

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14

Ackerman, Steven B., Gordon L. Stokes, R. James Swanson, Sherry P. Taylor und Lori Fenwick. „Toxicity testing for human in vitro fertilization programs“. Journal of In Vitro Fertilization and Embryo Transfer 2, Nr. 3 (September 1985): 132–37. http://dx.doi.org/10.1007/bf01131499.

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15

May, J. E., J. Xu, H. R. Morse, N. D. Avent und C. Donaldson. „Toxicity testing: the search for an in vitro alternative to animal testing“. British Journal of Biomedical Science 66, Nr. 3 (Januar 2009): 160–65. http://dx.doi.org/10.1080/09674845.2009.11730265.

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16

Watanabe, Masami. „Safety Evaluation and Toxicity Testing Using In Vitro Methods“. Journal of Toxicological Sciences 16, SupplementII (1991): 91–95. http://dx.doi.org/10.2131/jts.16.supplementii_91.

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17

Vippola, M., GCM Falck, HK Lindberg, S. Suhonen, E. Vanhala, H. Norppa, K. Savolainen, A. Tossavainen und T. Tuomi. „Preparation of nanoparticle dispersions for in-vitro toxicity testing“. Human & Experimental Toxicology 28, Nr. 6-7 (Juni 2009): 377–85. http://dx.doi.org/10.1177/0960327109105158.

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Studies on potential toxicity of engineered nanoparticle (ENP) in biological systems require a proper and accurate particle characterization to ensure the reproducibility of the results and to understand biological effects of ENP. A full characterization of ENP should include various measurements such as particle size and size distribution, shape and morphology, crystallinity, composition, surface chemistry, and surface area of ENP. It is also important to characterize the state of ENP dispersions. In this study, four different ENPs, rutile and anatase titanium dioxides and short single- and multi-walled carbon nanotubes, were characterized in two dispersion media: bronchial epithelial growth medium, used for bronchial epithelial BEAS cells, and RPMI-1640 culture media with 10% of fetal calf serum (FCS) for human mesothelial (MeT-5A) cells. The purpose of this study was to determine the characteristics of ENPs and their dispersions as well as to compare dispersion additives suitable for toxicity tests and thus establish an appropriate way to prepare dispersions that performs well with the selected ENP. Dispersion additives studied in the media were bovine serum albumin (BSA) as a protein resource, dipalmitoyl phosphatidylcholine (DPPC) as a model lung surfactant, and combination of BSA and DPPC. Dispersions were characterized using optical microscopy and transmission electron microscopy. Our results showed that protein addition, BSA or FCS, in cell culture media generated small agglomerates of primary particles with narrow size variations and improved the stability of the dispersions and thus also the relevance of the in-vitro genotoxicity tests to be done.

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Smoot, E. Clyde, John O. Kucan, Allan Roth, Nat Mody und Natalio Debs. „In Vitro Toxicity Testing for Antibacterials Against Human Keratinocytes“. Plastic and Reconstructive Surgery 87, Nr. 5 (Mai 1991): 917–24. http://dx.doi.org/10.1097/00006534-199105000-00017.

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19

Simms, L., L. Czekala, M. Stevenson, G. Phillips, R. Tilley, K. Rudd und T. Walele. „An in vitro approach to e-cigarette toxicity testing“. Toxicology Letters 295 (Oktober 2018): S118. http://dx.doi.org/10.1016/j.toxlet.2018.06.658.

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20

Orbach, Sophia M., Rebekah R. Less, Anjaney Kothari und Padmavathy Rajagopalan. „In Vitro Intestinal and Liver Models for Toxicity Testing“. ACS Biomaterials Science & Engineering 3, Nr. 9 (23.01.2017): 1898–910. http://dx.doi.org/10.1021/acsbiomaterials.6b00699.

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21

Jarrell, John F., Margaret L. Sevcik, David C. Villeneuve und Per O. Janson. „Toxicity testing using the isolated in vitro perfused ovary“. Reproductive Toxicology 7 (Januar 1993): 63–68. http://dx.doi.org/10.1016/0890-6238(93)90070-n.

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22

Catroux, P., A. Rougier, K. G. Dossou und M. Cottin. „The silicon microphysiometer for testing ocular toxicity in vitro“. Toxicology in Vitro 7, Nr. 4 (Juli 1993): 465–69. http://dx.doi.org/10.1016/0887-2333(93)90048-a.

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23

Phalen, Robert F. „Commentary on ‘‘Toxicity Testing in the 21st Century: A vision and a Strategy’’“. Human & Experimental Toxicology 29, Nr. 1 (Januar 2010): 11–14. http://dx.doi.org/10.1177/0960327109354660.

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Toxicity Testing in the 21st Century: A Vision and a Strategy (NRC, 2007) presents a bold plan for chemical toxicity testing that replaces whole-animal tests with cell-culture, genetic, other in-vitro techniques, computational methods, and human monitoring. Although the proposed vision is eloquently described, and recent advances in in-vitro and in-silico methods are impressive, it is difficult believe that replacing in-vitro testing is either practical or wise. It is not clear that the toxicity-related events that occur in whole animals can be adequately replicated using the proposed methods. Protecting public health is a serious endeavor that should not be limited by denying animal testing. Toxicologists and regulators are encouraged to read the report, carefully consider its implications, and share their thoughts. The vision is for too important to ignore.

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Bhanushali, M., V. Bagale, A. Shirode, Y. Joshi und V. Kadam. „An in-vitro toxicity testing - a reliable alternative to toxicity testing by reduction, replacement and refinement of animals.“ International Journal of Advances in Pharmaceutical Sciences 1, Nr. 1 (12.03.2010): 15–31. http://dx.doi.org/10.5138/ijaps.2010.0976.1055.01002.

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25

Tabernilla, Andrés, Bruna dos Santos Rodrigues, Alanah Pieters, Anne Caufriez, Kaat Leroy, Raf Van Campenhout, Axelle Cooreman et al. „In Vitro Liver Toxicity Testing of Chemicals: A Pragmatic Approach“. International Journal of Molecular Sciences 22, Nr. 9 (10.05.2021): 5038. http://dx.doi.org/10.3390/ijms22095038.

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The liver is among the most frequently targeted organs by noxious chemicals of diverse nature. Liver toxicity testing using laboratory animals not only raises serious ethical questions, but is also rather poorly predictive of human safety towards chemicals. Increasing attention is, therefore, being paid to the development of non-animal and human-based testing schemes, which rely to a great extent on in vitro methodology. The present paper proposes a rationalized tiered in vitro testing strategy to detect liver toxicity triggered by chemicals, in which the first tier is focused on assessing general cytotoxicity, while the second tier is aimed at identifying liver-specific toxicity as such. A state-of-the-art overview is provided of the most commonly used in vitro assays that can be used in both tiers. Advantages and disadvantages of each assay as well as overall practical considerations are discussed.

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Northup, Sharon J. „Perspectives on In Vitro Toxicity for Medical Devices“. Journal of the American College of Toxicology 7, Nr. 4 (Juli 1988): 481–89. http://dx.doi.org/10.3109/10915818809019521.

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In vitro toxicity testing has found widespread application in its use for screening materials for medical devices. Cytotoxicity tests, which have been in use for nearly 20 years, have been validated for intralaboratory repeatability, interlaboratory reproducibility, and correlation with acute animal toxicity assays. The three primary cytotoxicity assays, i.e., direct contact, agar diffusion, and elution tests, allow a selection between assay and material characteristics. Mutagenicity assays have had limited application to materials testing because of the insoluble nature of the materials and the low level of extractable chemicals, which are generally below the sensitivity limit of these assays. In vitro blood compatibility tests for hemolysis and complement activation are used primarily for blood contacting materials in applications where there is a large surface area of material for ex vivo applications.

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Flatt, L., S. Hartvelt, M. Feliksik, T. Zwetsloot, G. Hendriks, T. Osterlund und A. Jamalpoor. „P06-12 ReproTracker: Next generation in vitro developmental toxicity testing“. Toxicology Letters 368 (September 2022): S117. http://dx.doi.org/10.1016/j.toxlet.2022.07.330.

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28

Herrala, M., M. Huovinen, E. Järvelä, M. Lahtela-Kakkonen, R. Räisänen, J. Yli-Öyrä und J. Rysä. „P07-18 In vitro toxicity testing of environmental water contaminants“. Toxicology Letters 368 (September 2022): S127. http://dx.doi.org/10.1016/j.toxlet.2022.07.361.

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29

Fentem, Julia H. „Book Review: In Vitro Toxicity Testing: Applications to Safety Evaluation“. Alternatives to Laboratory Animals 20, Nr. 4 (Oktober 1992): 581. http://dx.doi.org/10.1177/026119299202000417.

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30

Seibert, Hasso, Michael Gulden und Jens-Uwe Voss. „Comparative Cell Toxicology: The Basis for In Vitro Toxicity Testing“. Alternatives to Laboratory Animals 22, Nr. 3 (Mai 1994): 168–74. http://dx.doi.org/10.1177/026119299402200306.

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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.

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31

Watanabe, Masami. „Toxicity and Effectiveness Testing of Drugs Using In Vitro Methods“. Japanese Journal of Pharmacology 71 (1996): 44. http://dx.doi.org/10.1016/s0021-5198(19)36430-3.

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32

Bakand, Shahnaz, und Amanda Hayes. „Troubleshooting methods for toxicity testing of airborne chemicals in vitro“. Journal of Pharmacological and Toxicological Methods 61, Nr. 2 (März 2010): 76–85. http://dx.doi.org/10.1016/j.vascn.2010.01.010.

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Ehnert, S., L. Schyschka, A. Noss, D. Knobeloch, J. Kleeff, P. Büchler, S. Gillen et al. „Further characterization of autologous NeoHepatocytes for in vitro toxicity testing“. Toxicology in Vitro 25, Nr. 6 (September 2011): 1203–8. http://dx.doi.org/10.1016/j.tiv.2011.05.013.

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34

Faria, João, Sabbir Ahmed, Karin G. F. Gerritsen, Silvia M. Mihaila und Rosalinde Masereeuw. „Kidney-based in vitro models for drug-induced toxicity testing“. Archives of Toxicology 93, Nr. 12 (29.10.2019): 3397–418. http://dx.doi.org/10.1007/s00204-019-02598-0.

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Abstract The kidney is frequently involved in adverse effects caused by exposure to foreign compounds, including drugs. An early prediction of those effects is crucial for allowing novel, safe drugs entering the market. Yet, in current pharmacotherapy, drug-induced nephrotoxicity accounts for up to 25% of the reported serious adverse effects, of which one-third is attributed to antimicrobials use. Adverse drug effects can be due to direct toxicity, for instance as a result of kidney-specific determinants, or indirectly by, e.g., vascular effects or crystals deposition. Currently used in vitro assays do not adequately predict in vivo observed effects, predominantly due to an inadequate preservation of the organs’ microenvironment in the models applied. The kidney is highly complex, composed of a filter unit and a tubular segment, together containing over 20 different cell types. The tubular epithelium is highly polarized, and the maintenance of this polarity is critical for optimal functioning and response to environmental signals. Cell polarity is dependent on communication between cells, which includes paracrine and autocrine signals, as well as biomechanic and chemotactic processes. These processes all influence kidney cell proliferation, migration, and differentiation. For drug disposition studies, this microenvironment is essential for prediction of toxic responses. This review provides an overview of drug-induced injuries to the kidney, details on relevant and translational biomarkers, and advances in 3D cultures of human renal cells, including organoids and kidney-on-a-chip platforms.

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Barile, F. A., P. J. Dierickx und U. Kristen. „In vitro cytotoxicity testing for prediction of acute human toxicity“. Cell Biology and Toxicology 10, Nr. 3 (Juni 1994): 155–62. http://dx.doi.org/10.1007/bf00757558.

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36

Kolárová, H., J. Mosinger, R. Lenobel, K. Kejlová, D. Jı́rová und M. Strnad. „In vitro toxicity testing of supramolecular sensitizers for photodynamic therapy“. Toxicology in Vitro 17, Nr. 5-6 (Oktober 2003): 775–78. http://dx.doi.org/10.1016/s0887-2333(03)00094-8.

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37

Botham, P. A. „Book Reviews: In Vitro Toxicity Testing. Applications to Safety Evaluation“. Human & Experimental Toxicology 13, Nr. 2 (Februar 1994): 142. http://dx.doi.org/10.1177/096032719401300217.

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Kimmel, Gary L. „Invited perspective: In vitro testing in developmental toxicity risk assessment“. Teratology 58, Nr. 2 (August 1998): 25–26. http://dx.doi.org/10.1002/(sici)1096-9926(199808)58:2<25::aid-tera1>3.0.co;2-#.

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39

Combes, Robert, Christina Grindon, Mark T. D. Cronin, David W. Roberts und John F. Garrod. „Integrated Decision-tree Testing Strategies for Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH Legislation“. Alternatives to Laboratory Animals 36, Nr. 1 (Februar 2008): 45–63. http://dx.doi.org/10.1177/026119290803600107.

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Liverpool John Moores University and FRAME conducted a joint research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for acute systemic toxicity and toxicokinetic testing. The paper reviews in vitro tests based on basal cytotoxicity and target organ toxicity, along with QSAR models and expert systems available for this endpoint. The use of PBPK modelling for the prediction of ADME properties is also discussed. These tests are then incorporated into a decision-tree style, integrated testing strategy, which also includes the use of refined in vivo acute toxicity tests, as a last resort. The implementation of the strategy is intended to minimise the use of animals in the testing of acute systemic toxicity and toxicokinetics, whilst satisfying the scientific and logistical demands of the EU REACH legislation.

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Combes, Robert, Christina Grindon, Mark T. D. Cronin, David W. Roberts und John F. Garrod. „Integrated Decision-tree Testing Strategies for Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH Legislation“. Alternatives to Laboratory Animals 36, Nr. 1_suppl (Oktober 2008): 91–109. http://dx.doi.org/10.1177/026119290803601s08.

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Liverpool John Moores University and FRAME conducted a joint research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for acute systemic toxicity and toxicokinetic testing. The paper reviews in vitro tests based on basal cytotoxicity and target organ toxicity, along with QSAR models and expert systems available for this endpoint. The use of PBPK modelling for the prediction of ADME properties is also discussed. These tests are then incorporated into a decision-tree style, integrated testing strategy, which also includes the use of refined in vivo acute toxicity tests, as a last resort. The implementation of the strategy is intended to minimise the use of animals in the testing of acute systemic toxicity and toxicokinetics, whilst satisfying the scientific and logistical demands of the EU REACH legislation.

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Zavala, Jose, Anastasia N. Freedman, John T. Szilagyi, Ilona Jaspers, John F. Wambaugh, Mark Higuchi und Julia E. Rager. „New Approach Methods to Evaluate Health Risks of Air Pollutants: Critical Design Considerations for In Vitro Exposure Testing“. International Journal of Environmental Research and Public Health 17, Nr. 6 (23.03.2020): 2124. http://dx.doi.org/10.3390/ijerph17062124.

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Air pollution consists of highly variable and complex mixtures recognized as major contributors to morbidity and mortality worldwide. The vast number of chemicals, coupled with limitations surrounding epidemiological and animal studies, has necessitated the development of new approach methods (NAMs) to evaluate air pollution toxicity. These alternative approaches include in vitro (cell-based) models, wherein toxicity of test atmospheres can be evaluated with increased efficiency compared to in vivo studies. In vitro exposure systems have recently been developed with the goal of evaluating air pollutant-induced toxicity; though the specific design parameters implemented in these NAMs-based studies remain in flux. This review aims to outline important design parameters to consider when using in vitro methods to evaluate air pollutant toxicity, with the goal of providing increased accuracy, reproducibility, and effectiveness when incorporating in vitro data into human health evaluations. This review is unique in that experimental considerations and lessons learned are provided, as gathered from first-hand experience developing and testing in vitro models coupled to exposure systems. Reviewed design aspects include cell models, cell exposure conditions, exposure chambers, and toxicity endpoints. Strategies are also discussed to incorporate in vitro findings into the context of in vivo toxicity and overall risk assessment.

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Neagu, Monica, Fabia Grisi, Alfio Pulvirenti, Rosana Simón-Vázquez, Carlos A. García-González und Antonella Caterina Boccia. „Updated Aspects of Safety Regulations for Biomedical Applications of Aerogel Compounds—Compendia-Like Evaluation“. Safety 9, Nr. 4 (20.11.2023): 80. http://dx.doi.org/10.3390/safety9040080.

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Aerogels have recently started to be considered as “advanced materials”; therefore, as a general consideration, aerogels’ toxicity testing should focus on their functionality which resides in their nanoscale open internal porosity. To assess the hazards of organic aerogels, testing at three levels may characterize their biophysical, in vitro and in vivo toxicity, defining distinct categories of aerogels. At the first level of testing, their abiotic characteristics are investigated, and the best aerogel(s) is forwarded to be tested at level 2, wherein in vitro methodologies may mainly evaluate the aerogels’ cellular behavior. Within level 2 of testing, the main characteristics of toxicity are investigated and the selected aerogels are introduced to in vivo animal models at level 3. In the animal model testing, target organs are investigated along with systemic parameters of toxicity. Some study cases are presented for organic or anorganic aerogels. Within this tiered workflow, aerogels-based materials can be tested in terms of human health hazard.

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Lamb, J. C. „Reproductive Toxicity Testing: Evaluating and Developing New Testing Systems“. Journal of the American College of Toxicology 4, Nr. 2 (März 1985): 163–71. http://dx.doi.org/10.3109/10915818509014511.

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Reproductive toxicity testing systems are used by national and international regulatory agencies. Protocols have not been standardized between agencies or even within certain agencies. Although there have been efforts at standardization, a certain amount of the differences between testing protocols is a reflection of the needs of the particular agency. New developments in in vitro techniques might lead to new test systems, but reproductive function is dependent upon the interaction of various cells and organs that cannot presently be copied in the test tube; this makes whole-animal testing systems a necessity. The present whole-animal models used by the Food and Drug Administration include the 3 segment reproduction studies used for testing drug safety and the multigeneration studies used for food additives. The Environmental Protection Agency has adopted 2 similar versions of a 2-generation study for the Office of Pesticide Programs and the Office of Toxic Substances. The National Toxicology Program, although not a regulatory agency, has taken a prominent role in reproductive toxicity testing, test system development, and test system evaluation. A new testing system, Fertility Assessment by Continuous Breeding (FACB), is currently being studied as a cost-effective and reliable alternative test system. The FACB protocol houses male and female mice as breeding pairs and removes offspring as soon as they are born during the first 14 weeks to allow continuous mating. Each breeding pair normally has up to 5 litters, and the last litter is saved to evaluate the second generation. The efficiency, reliability, and expense of the protocol are being compared to the existing testing systems.

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Citi, Valentina, Eugenia Piragine, Simone Brogi, Sara Ottino und Vincenzo Calderone. „Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing“. Methods and Protocols 3, Nr. 4 (02.11.2020): 74. http://dx.doi.org/10.3390/mps3040074.

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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.

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Bouwmeester, Manon C., Yu Tao, Susana Proença, Frank G. van Steenbeek, Roos-Anne Samsom, Sandra M. Nijmeijer, Theo Sinnige et al. „Drug Metabolism of Hepatocyte-like Organoids and Their Applicability in In Vitro Toxicity Testing“. Molecules 28, Nr. 2 (07.01.2023): 621. http://dx.doi.org/10.3390/molecules28020621.

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Emerging advances in the field of in vitro toxicity testing attempt to meet the need for reliable human-based safety assessment in drug development. Intrahepatic cholangiocyte organoids (ICOs) are described as a donor-derived in vitro model for disease modelling and regenerative medicine. Here, we explored the potential of hepatocyte-like ICOs (HL-ICOs) in in vitro toxicity testing by exploring the expression and activity of genes involved in drug metabolism, a key determinant in drug-induced toxicity, and the exposure of HL-ICOs to well-known hepatotoxicants. The current state of drug metabolism in HL-ICOs showed levels comparable to those of PHHs and HepaRGs for CYP3A4; however, other enzymes, such as CYP2B6 and CYP2D6, were expressed at lower levels. Additionally, EC50 values were determined in HL-ICOs for acetaminophen (24.0–26.8 mM), diclofenac (475.5–>500 µM), perhexiline (9.7–>31.5 µM), troglitazone (23.1–90.8 µM), and valproic acid (>10 mM). Exposure to the hepatotoxicants showed EC50s in HL-ICOs comparable to those in PHHs and HepaRGs; however, for acetaminophen exposure, HL-ICOs were less sensitive. Further elucidation of enzyme and transporter activity in drug metabolism in HL-ICOs and exposure to a more extensive compound set are needed to accurately define the potential of HL-ICOs in in vitro toxicity testing.

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Kolossa, Marike, und Hasso Seibert. „Toxicity Testing by Means of Cryopreserved Bovine Spermatozoa“. Alternatives to Laboratory Animals 19, Nr. 2 (April 1991): 204–8. http://dx.doi.org/10.1177/026119299101900210.

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The aim of the present study was to investigate the suitability of bovine spermatozoa cryopreserved in a “defined” medium as an in vitro model for the assessment of the cytotoxic potential of chemicals. The endpoints used for this purpose were motion activity and cellular ATP content. The evaluation of properties of cryopreserved sperm shortly after thawing and at the end of a one-hour incubation period, shows that the cryoprotective medium developed is able to provide suitable cellular material for cytotoxicity tests. Results from experiments employing substances with known modes of action are presented, and suggest that cryopreserved sperm can be used as successfully as native sperm in cytotoxicity tests.

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Yan, Zhen-guang, Xin Zheng, Fu Gao, Jun-tao Fan, Shu-ping Wang und Li-xin Yang. „A Framework for Ecotoxicity Testing in the 21st Century: Ecotox21“. Applied Sciences 9, Nr. 3 (28.01.2019): 428. http://dx.doi.org/10.3390/app9030428.

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To reduce the considerable investments of toxicity testing and protecting animal welfare, a new toxicity testing strategy based on response pathways of human cell lines has been proposed in the United States to evaluate the chemical exposure risks to human health. However, the in vitro high-throughput assays have not yet been fully applied in ecotoxicity testing. This paper proposes a framework for high-efficiency ecotoxicity testing strategies to evaluate the ecological risk of chemicals. It consists of pathway-based toxicity testing, embryo-based toxicity testing, and predictive toxicology and data extrapolation, etc., according to different situations. The results of ecotoxicity testing or data mining are analyzed together with physicochemical properties, environmental fate, and exposure data of chemicals to conduct a comprehensive risk assessment of chemicals. The framework provides valuable points to establish high-efficiency ecotoxicity testing strategies in the 21st century.

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Li, Meng, Rui Han, Juan Li, Wenhui Wu und Jianqi Gu. „Research Progress in Acute Oral Toxicity Testing Methods“. International Journal of Biology and Life Sciences 6, Nr. 1 (29.05.2024): 19–22. http://dx.doi.org/10.54097/nv9van65.

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Acute oral toxicity is the first phase of safety toxicological evaluation, with the median lethal dose (LD50) being the most commonly used assessment parameter. This paper aims to summarize and compare conventional methods for determining LD50 and alternative approaches, along with their respective advantages and disadvantages, to provide options for further toxicological studies. Alternative tests, which do not require the precise determination of LD50 values, minimize animal mortality to the greatest extent and reduce the waste of human and material resources, making them worthy of promotion. Additionally, the development of Quantitative Structure-Activity Relationship (QSAR) models for predicting in vivo acute toxicity and in vitro cell culture toxicity assays are also in progress.

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Bakand, Shahnaz, Amanda Hayes und Chris Winder. „An Integrated in Vitro Approach for Toxicity Testing of Airborne Contaminants“. Journal of Toxicology and Environmental Health, Part A 70, Nr. 19 (31.08.2007): 1604–12. http://dx.doi.org/10.1080/15287390701434604.

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Vinken, Mathieu, und Jan G. Hengstler. „Characterization of hepatocyte-based in vitro systems for reliable toxicity testing“. Archives of Toxicology 92, Nr. 10 (23.08.2018): 2981–86. http://dx.doi.org/10.1007/s00204-018-2297-6.

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