© 1994 Oxford University Press
research-article |
A Toxic Equivalency Factor Scale for Polychlorinated Dibenzofurans
*Institute of Environmental Chemistry, University of Umeå S-901 87 Umeå, Sweden
U.S. Fish and Wildlife Service, National Fisheries Contaminant Research Center 4200 New Haven Road, Columbia, Missouri 65201
Research Group for Chemometrics, University of Umeå S-901 87 Umeå, Sweden
Received May 4, 1993; accepted September 27, 1993
The ethoxyresorufin O-deethylase (EROD) induction of 20 polychiorinated dibenzofurans (PCDFs) was examined in the H4IIE rat hepatoma cell bioassay. The selection of the compounds tested was based on a multivariate chemical characterization laying the groundwork for covering the whole chemical series of PCDFs. The EROD induction potency was found to vary in ED50 values from 25 to 100,000,000 pg/mg, i.e., nearly seven orders of magnitude. The response of the bioassay was calibrated against the 2,3,7,8-tetrachlorodibenzo-p-dioxin, enabling the corresponding toxic equivalency factors (TEFs) to be calculated. In order to establish a quantitative structure-activity relationship (QSAR) for the TEF values, 37 physicochemical descriptor variables were used to chemically characterize the 87 tetra- to octachlorinated PCDFs. Using partial least-squares modeling on a training set of 10 congeners, a QSAR model with sound predictive power was obtained. The QSAR model was validated with a validation set of additional 10 congeners. The predicted TEFs indicate that a large number of congeners are potent EROD inducers.