title: How to confirm identified toxicants in effect-directed analysis.
abstract: 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). [figure: see text]
authors.affiliation: Department Effect-Directed Analysis, UFZ Helmholtz Centre for Environmental Research, Leipzig, Germany. werner.brack@ufz.de
authors.forename: Werner
authors.initials: W
authors.lastname: Brack
authors.forename: Mechthild
authors.initials: M
authors.lastname: Schmitt-Jansen
authors.forename: Miroslav
authors.initials: M
authors.lastname: Machala
authors.forename: Rikke
authors.initials: R
authors.lastname: Brix
authors.forename: Damià
authors.initials: D
authors.lastname: Barceló
authors.forename: Emma
authors.initials: E
authors.lastname: Schymanski
authors.forename: Georg
authors.initials: G
authors.lastname: Streck
authors.forename: Tobias
authors.initials: T
authors.lastname: Schulze
mesh_terms: D004784:Environmental Monitoring / Q000379:methods*; D015386:Hazardous Substances / Q000032:analysis*; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000592:standards
chemical_list: D015386:Hazardous Substances; D014874:Water Pollutants, Chemical