A toxic equivalency factor scale for polychlorinated dibenzofurans.
The ethoxyresorufin O-deethylase (EROD) induction of 20 polychlorinated 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.
Tysklind
M
M
Institute of Environmental Chemistry, University of Umeå, Sweden.
Tillitt
D
D
Eriksson
L
L
Lundgren
K
K
Rappe
C
C
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000633:toxicity*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D000072338:Dibenzofurans, Polychlorinated; D004790:Enzyme Induction / Q000187:drug effects; D005453:Fluorescence; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000503:physiopathology; D010088:Oxidoreductases / Q000096:biosynthesis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1