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RECORD NUMBER: 119 OF 265

OLS Field Name OLS Field Data
Main Title Polychlorinated Dibenzo-p-Dioxins and Dibenzofurans: Correlation between In vivo Structure-Activity Relationships (SARs).
Author Safe, S. ; Mason, G. ; Keys, B. ; Farrell, K. ; Zmudzka, B. ;
CORP Author Texas A and M Univ., College Station.;Environmental Research Lab.-Duluth, MN.
Publisher c1986
Year Published 1986
Report Number EPA-810995; EPA/600/J-86/535;
Stock Number PB90-265117
Additional Subjects In vitro analysis ; In vivo analysis ; Biochemistry ; Public health ; Laboratory animals ; Toxicity ; Enzymes ; Pesticides ; Bioassay ; Proteins ; Molecular structure ; Reprints ; Polychlorinated dibenzodioxins ; Polychlorinated dibenzofurans ; Risk assessment ; Biological effects ; Dose-response relationships ; Toxic substances
Holdings
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Status
NTIS  PB90-265117 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. NTIS 12/03/1990
Collation 8p
Abstract
Polychlorinated dibenzofurans (PCDFs) and dibenzo-p-dioxins (PCDDs) elicit a number of common biologic and toxic responses which are triggered by their initial binding to a cytosolic receptor protein. These effects include the induction of several cytochrome P-448 dependent monoxygenases (eg, aryl hydrocarbon hydroxylase, AHH), body weight loss and thymic atrophy. The dose-response effects of selected PCDFs on AHH induction in rat hepatoma H-4-II E cells and cytosolic receptor binding affinities have been determined. The results of these in vivo and in vitro studies demonstrate the remarkable effects of structure on the activity of PCDFs. A systematic study of each of the four different position for chlorine substitution in the dibenzofuran ring system showed that the toxic and biologic potencies of these compounds varied with respect to differential chlorine substitution at all four position, i.e. C-3(7) > C-2(8) >C-4(6) > C-1(9). In vitro SARs for PCDDs confirmed the importance of the lateral CI substituents and also showed that 1,2(or 6,7-) substituted PCDDs were more active than the corresponding 1,3-dichloro analogs. In addition, there were significant decreases in activity with increasing non-lateral CI substitution. The SARs for PCDFs were different from the PCDDs and this was directly related to the asymmetric structure of the former group of compounds.