Toward More Useful In Vitro Toxicity Data with Measured Free Concentrations

In vitro assays and computer models are promising alternatives for in vivo animal testing, but the power of these alternative methods to predict in vivo risk is still very limited. One step forward is to make the outcome of in vitro assays (such as median effect concentrations (EC50 values)) indepen...

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Veröffentlicht in:Environmental science & technology 2004-12, Vol.38 (23), p.6263-6270
Hauptverfasser: Heringa, Minne B, Schreurs, Richard H. M. M, Busser, Frans, Van Der Saag, Paul T, Van Der Burg, Bart, Hermens, Joop L. M
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container_end_page 6270
container_issue 23
container_start_page 6263
container_title Environmental science & technology
container_volume 38
creator Heringa, Minne B
Schreurs, Richard H. M. M
Busser, Frans
Van Der Saag, Paul T
Van Der Burg, Bart
Hermens, Joop L. M
description In vitro assays and computer models are promising alternatives for in vivo animal testing, but the power of these alternative methods to predict in vivo risk is still very limited. One step forward is to make the outcome of in vitro assays (such as median effect concentrations (EC50 values)) independent of assay conditions such as protein content. Here we show that measured free concentrations of chemicals in the in vitro assay medium result in system-independent EC50 values. We introduce a very simple method to measure free concentrations in miniature test systems using negligible depletion solid-phase microextraction. The generated data are much more suitable for extrapolation to in vivo, provide unbiased input for computational methods (for example, quantitative structure−activity relationships), and can shed an entirely different light on the activity of environmental contaminants.
doi_str_mv 10.1021/es049285w
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source MEDLINE; ACS Publications
subjects Animal, plant and microbial ecology
Animals
Applied ecology
Biological and medical sciences
Cattle
Cell Survival
Chemicals
Contamination
Dose-Response Relationship, Drug
Drug-Related Side Effects and Adverse Reactions
Ecotoxicology, biological effects of pollution
Environmental Monitoring - instrumentation
Environmental Monitoring - methods
Environmental Pollutants - analysis
Environmental Pollutants - toxicity
Estradiol - blood
Forecasting
Fundamental and applied biological sciences. Psychology
General aspects
Models, Biological
Phenols - blood
Proteins - analysis
Risk Assessment
Toxicity
Toxicity Tests
title Toward More Useful In Vitro Toxicity Data with Measured Free Concentrations
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