Analytical and Bioanalytical Chemistry

, Volume 390, Issue 8, pp 1959–1973 | Cite as

How to confirm identified toxicants in effect-directed analysis

  • Werner Brack
  • Mechthild Schmitt-Jansen
  • Miroslav Machala
  • Rikke Brix
  • Damià Barceló
  • Emma Schymanski
  • Georg Streck
  • Tobias Schulze


Due to the production and use of a multitude of chemicals in modern society, waters, sediments, soils and biota may be contaminated with numerous known and unknown chemicals that may cause adverse effects on ecosystems and human health. Effect-directed analysis (EDA), combining biotesting, fractionation and chemical analysis, helps to identify hazardous compounds in complex environmental mixtures. Confirmation of tentatively identified toxicants will help to avoid artefacts and to establish reliable cause–effect relationships. A tiered approach to confirmation is suggested in the present paper. The first tier focuses on the analytical confirmation of tentatively identified structures. If straightforward confirmation with neat standards for GC–MS or LC–MS is not available, it is suggested that a lines-of-evidence approach is used that combines spectral library information with computer-based structure generation and prediction of retention behaviour in different chromatographic systems using quantitative structure–retention relationships (QSRR). In the second tier, the identified toxicants need to be confirmed as being the cause of the measured effects. Candidate components of toxic fractions may be selected based, for example, on structural alerts. Quantitative effect confirmation is based on joint effect models. Joint effect prediction on the basis of full concentration–response plots and careful selection of the appropriate model are suggested as a means to improve confirmation quality. Confirmation according to the Toxicity Identification Evaluation (TIE) concept of the US EPA and novel tools of hazard identification help to confirm the relevance of identified compounds to populations and communities under realistic exposure conditions. Promising tools include bioavailability-directed extraction and dosing techniques, biomarker approaches and the concept of pollution-induced community tolerance (PICT).


Toxicity confirmation in EDA as a tiered approach


Effect-directed analysis Toxicity identification evaluation Toxicity confirmation Structural analysis Mixture toxicity Hazard 



arylhydrocarbon receptor


Automated Mass Spectral Deconvolution and Identification System


benzo[a]pyrene equivalent quantity


boiling point


concentration addition


chemical-activated luciferase expression


effect concentration required to achieve X% effect


effect-directed analysis




deoxyribonucleic acid


gas chromatography with mass-selective detection


independent action


index of confirmation quality


induction equivalent quantities


identification points


liquid chromatography with a hybrid quadrupole–time-of-flight mass spectrometer


linear solvation free-energy relationships


National Institute of Standards and Technology


nuclear magnetic resonance


polycyclic aromatic hydrocarbon


polychlorinated biphenyl


polychlorinated dibenzo-p-dioxin and furan




pollution-induced community tolerance


quantitative structure–activity relationship


quantitative structure–retention relationship


relative potency


retention index


rainbow trout liver cell line W1


semipermeable membrane device


toxicity equivalent quantity


toxicity identification evaluation


toxic units


United States Environmental Protection Agency



This study was funded by the European Union in the framework of the Integrated Project MODELKEY (Contract 511237-GOCE).


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Werner Brack
    • 1
  • Mechthild Schmitt-Jansen
    • 2
  • Miroslav Machala
    • 3
  • Rikke Brix
    • 4
  • Damià Barceló
    • 4
  • Emma Schymanski
    • 1
  • Georg Streck
    • 1
  • Tobias Schulze
    • 1
  1. 1.Department Effect-Directed AnalysisUFZ Helmholtz Centre for Environmental ResearchLeipzigGermany
  2. 2.Department Bioanalytical EcotoxicologyUFZ Helmholtz Centre for Environmental ResearchLeipzigGermany
  3. 3.Veterinary Research InstituteBrnoCzech Republic
  4. 4.Department of Environmental ChemistryIIQAB-CSICBarcelonaSpain

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