TY - JOUR
T1 - Polybrominated dibenzo-p-dioxins and related compounds
T2 - Quantitative in vivo and in vitro structure-activity relationships
AU - Mason, G.
AU - Zacharewski, T.
AU - Denomme, M. A.
AU - Safe, L.
AU - Safe, S.
N1 - Funding Information:
This research was supported by the U.S. Environmental Protection Agency, the Texas Agricultural Experiment Station and Natural Sciences and Engineering Research Council of Canada.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1987/6
Y1 - 1987/6
N2 - The effects of structure on the in vitro receptor binding affinities, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction potencies in rat hepatoma cells were determined for the following compounds: 2-bromo-, 2,7/2,8-dibromo-, 2,3,7-tribromo-, 2,4,6,8/1,3,7,9-tetrabromo-, 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,3,7,8-pentabromo-, 1,2,4,7,8-pentabromo-, 2,3,-dibromo-7,8-dichloro-, 2,8-dibromo-3,7-dichloro- and 2-bromo-3,7,8-trichlorodibenzo-p-dioxin. The structure-activity relationships (SARs) for the polybrominated dibenzo-p-dioxins (PBDDs) were comparable for both in vitro responses: the most active compounds were substituted only in the lateral 2,3,7 and 8 position and the addition of non-lateral or removal of lateral halogen substituents reduced the activity of the resultant compound. The biologic and toxic effects of 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,4,7,8-pentabromo-1,2,3,7,8-pentabromo-, 2-bromo-3,7,8-trichloro- and 2,3-dibromo-7,8-dichlorodibenzo-p-dioxin on several receptor-mediated responses (thymic atrophy, body weight loss, hepatic microsomal AHH and EROD induction) were determined in a dose-response fashion in immature male Wistar rats. A comparison of the ED50 values for the in vivo responses demonstrated that the SARs for the PBDDs and brominated polychlorinated dibenzo-p-dioxins were comparable to those observed for in vitro receptor binding and AHH induction. Moreover, there was an excellent linear correlation between the -log EC50 (in vitro AHH induction) vs. the in vivo -log ED50 (thymic atrophy) and -log ED50 (body wt loss) correlation coefficient, r = 0.97 for all 2 correlations).
AB - The effects of structure on the in vitro receptor binding affinities, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction potencies in rat hepatoma cells were determined for the following compounds: 2-bromo-, 2,7/2,8-dibromo-, 2,3,7-tribromo-, 2,4,6,8/1,3,7,9-tetrabromo-, 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,3,7,8-pentabromo-, 1,2,4,7,8-pentabromo-, 2,3,-dibromo-7,8-dichloro-, 2,8-dibromo-3,7-dichloro- and 2-bromo-3,7,8-trichlorodibenzo-p-dioxin. The structure-activity relationships (SARs) for the polybrominated dibenzo-p-dioxins (PBDDs) were comparable for both in vitro responses: the most active compounds were substituted only in the lateral 2,3,7 and 8 position and the addition of non-lateral or removal of lateral halogen substituents reduced the activity of the resultant compound. The biologic and toxic effects of 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,4,7,8-pentabromo-1,2,3,7,8-pentabromo-, 2-bromo-3,7,8-trichloro- and 2,3-dibromo-7,8-dichlorodibenzo-p-dioxin on several receptor-mediated responses (thymic atrophy, body weight loss, hepatic microsomal AHH and EROD induction) were determined in a dose-response fashion in immature male Wistar rats. A comparison of the ED50 values for the in vivo responses demonstrated that the SARs for the PBDDs and brominated polychlorinated dibenzo-p-dioxins were comparable to those observed for in vitro receptor binding and AHH induction. Moreover, there was an excellent linear correlation between the -log EC50 (in vitro AHH induction) vs. the in vivo -log ED50 (thymic atrophy) and -log ED50 (body wt loss) correlation coefficient, r = 0.97 for all 2 correlations).
KW - Enzyme induction
KW - Polybrominated dibenzo-p-dioxins
KW - Quantitative structure-activity relationships
KW - Toxicity
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U2 - 10.1016/0300-483X(87)90027-8
DO - 10.1016/0300-483X(87)90027-8
M3 - Article
C2 - 3033849
AN - SCOPUS:0023258062
SN - 0300-483X
VL - 44
SP - 245
EP - 255
JO - Toxicology
JF - Toxicology
IS - 3
ER -