| Factors influencing nominal effective concentrations of chemical compounds in vitro: cell concentration. | |
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MedLine Citation:
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PMID: 11377096 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In vitro potency data (e.g. EC(50) values), used to characterise the biological activity of chemicals, are generally based on nominal effective concentrations and thus depend on any factor influencing the availability of a compound. In this study the significance of cell binding for the availability of chemicals in vitro is (i) theoretically investigated by means of a simple equilibrium distribution model and (ii) experimentally examined using a bull sperm assay to measure the cytotoxic potency of selected compounds at different cell concentrations. Compounds were selected either to cover a wide range of hydrophobicity (log K(ow)=2.52-5.69) or to represent modes of cell binding other than partitioning into cellular lipids. With the exception of xylene, the EC(50) values increased with increasing cell concentration. The ratios of EC(50) values determined at about 120 x 10(6) and 15 x 10(6) cells/ml were: pentachlorophenol. 1.2, 1-nitronaphthalene: 1.9, thioridazine: 2.7, dieldrin: 4.1, hexachlorophene: 4.1, digitonin: 5.1, methylmercury chloride: 7.9, antimycin A: 10.1 and p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE): >19.1. The influence of partitioning into cell lipids was rather well predicted by the equilibrium distribution model, except for p,p'-DDE. The results show that cell binding can significantly affect the availability of compounds in vitro and thus toxic potencies and toxic equivalency factors. |
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Authors:
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M Gülden; S Mörchel; H Seibert |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: 15 ISSN: 0887-2333 ISO Abbreviation: Toxicol In Vitro Publication Date: 2001 Jun |
Date Detail:
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Created Date: 2001-05-29 Completed Date: 2001-08-23 Revised Date: 2009-04-10 |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: England |
Other Details:
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Languages: eng Pagination: 233-43 Citation Subset: IM |
Affiliation:
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Institut für Toxikologie, Universitätsklinikum Kiel, Weimarer Str. 8, Haus 3, D-24106, Kiel, Germany. guelden@toxi.uni-kiel.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Assay / methods* Cattle Cell Compartmentation Cell Count Cell Survival / drug effects Hydrogen-Ion Concentration Lipid Metabolism Male Mathematics Models, Biological Pharmacokinetics Predictive Value of Tests Protein Binding Solubility Spermatozoa / drug effects, metabolism* Time Factors Toxicity Tests / methods* Water / metabolism Xenobiotics / toxicity |
| Chemical | |
Reg. No./Substance:
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0/Xenobiotics; 7732-18-5/Water |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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