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)) 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.
Heringa
Minne B
MB
Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584 CL Utrecht, The Netherlands. m.heringa@iras.uu.nl
Schreurs
Richard H M M
RH
Busser
Frans
F
van der Saag
Paul T
PT
van der Burg
Bart
B
Hermens
Joop L M
JL
D000818:Animals; D002417:Cattle; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004784:Environmental Monitoring / Q000295:instrumentation / Q000379:methods*; D004785:Environmental Pollutants / Q000032:analysis* / Q000633:toxicity; D004958:Estradiol / Q000097:blood; D005544:Forecasting; D008954:Models, Biological; D010636:Phenols / Q000097:blood; D011506:Proteins / Q000032:analysis; D018570:Risk Assessment; D018675:Toxicity Tests
D004785:Environmental Pollutants; D010636:Phenols; D011506:Proteins; C474055:octylphenol; D004958:Estradiol