The structure-dependent effects of heptachlorodibenzofuran isomers in male C57BL/6 mice: immunotoxicity and monooxygenase enzyme induction.
The dose-response effects of the 1,2,3,4,6,7,8-, 1,2,3,4,7,8,9-, 1,2,3,4,6,8,9-, and 1,2,3,4,6,7,9-heptachlorodibenzofurans (HpCDFs) on the splenic plaque-forming cell (PFC) response to sheep erythrocytes and on the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (EROD) activities were determined in male C57BL/6 mice. The ED50 values for the decrease in the PFCs/spleen, the number of PFCs/10(6) viable cells, and the induction of AHH and EROD activities were 1,2,3,4,6,7,8-HpCDF, 0.011, 0.018, 0.11, and 0.315 mumol/kg, respectively; 1,2,3,4,7,8,9-HpCDF, 0.012, 0.054, 0.70, and 0.20 mumol/kg, respectively; 1,2,3,4,6,7,9-HpCDF, 1.2, 1.3, greater than 43, and greater than 43 mumol/kg, respectively; 1,2,3,4,6,8,9-HpCDF, 1.5, 3.4, 22, and 22 mumol/kg, respectively. It was apparent from these studies that the 2,3,7,8-substituted HpCDF isomers (1,2,3,4,6,7,8- and 1,2,3,4,7,8,9-) were significantly more potent than the compounds which contained only three lateral C1 groups. These results were obtained using a multiple dosing regimen in which 10 separate doses of the HpCDF isomers were administered to the mice by intraperitoneal injection over a period of 12 days. However, when the mice were treated with a single dose of an HpCDF congener, which was equivalent to the total dose used in the multiple dose study, the responses were comparable. A comparison of the relative immunotoxic potencies of the 2,3,7,8-substituted HpCDFs and 2,3,7,8-tetrachlorodibenzo-p-dioxin showed that the latter compound was approximately 10 times more active than the HpCDFs.
Dickerson
R
R
Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station 77843.
Howie
L
L
Davis
D
D
Safe
S
S
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001572:Benzofurans / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D007109:Immunity / Q000187:drug effects*; D007536:Isomerism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013329:Structure-Activity Relationship
D001572:Benzofurans; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases