Document Detail


Factors influencing nominal effective concentrations of chemical compounds in vitro: cell concentration.
MedLine Citation:
PMID:  11377096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M Gülden; S Mörchel; H Seibert
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
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:
Created Date:  2001-05-29     Completed Date:  2001-08-23     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  233-43     Citation Subset:  IM    
Affiliation:
Institut für Toxikologie, Universitätsklinikum Kiel, Weimarer Str. 8, Haus 3, D-24106, Kiel, Germany. guelden@toxi.uni-kiel.de
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MeSH Terms
Descriptor/Qualifier:
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:
0/Xenobiotics; 7732-18-5/Water

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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