Metabolic degradation, inducing potency, and metabolites of fluorinated and chlorinated-fluorinated dibenzodioxins and dibenzofurans.
The metabolic degradation of fluorinated, chlorinated-fluorinated and chlorinated congeners was measured in liver homogenate of NMRI mice. While in the time period between 0 and 240 min no degradation of the 2,3,7,8-TCDD/TCDF could be detected, for all fluorinated congeners a perceptible degradation was found, even for the 2,3,7,8-TFDD. Stepwise chlorination of the 2,3,7,8-fluorinated congeners leads to a decrease of the degradation rate. In the EROD test, the exchange of chloro- with fluorosubstituents in the 2,3,7,8-TCDF leads to a decrease of induction potency. 3,7-Dichloro-2,8-difluorodibenzofuran was about 1/1000th as potent as 2,3,7,8-TCDF, while 2,3,7,8-TFDF was complete inactive. Comparison of the metabolic rates of different TCDD with those of the analogous TFDD demonstrates that the order of enzymatic degradation of different TCDD and the analogous TFDD is identical. The TFDD are degraded slightly faster than the corresponding TCDD. Surprisingly 1,4,6,9-TXDD showed the second slowest metabolic rate of the fluorinated and chlorinated TXDD after 2,3,7,8-TXDD although none of the 2,3,7,8-positions were substituted. Judging from 2,3,7,8-TFDD and 1,7-dichloro-2,8-difluorodibenzofuran the metabolic pathway of fluorinated and chlorinated-fluorinated congeners seem to be comparable to the chlorinated congeners.
Weber
R
R
Institute of Organic Chemistry, University of Tübingen.
Schmitz
H J
HJ
Schrenk
D
D
Hagenmaier
H
H
D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D001711:Biotransformation; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D004147:Dioxins / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000633:toxicity*; D012989:Soil Pollutants / Q000378:metabolism / Q000633:toxicity*; D013329:Structure-Activity Relationship
C092566:2,3,7,8-tetrafluorodibenzodioxin; D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D012989:Soil Pollutants; D019363:Cytochrome P-450 CYP1A1; C014211:2,3,7,8-tetrachlorodibenzofuran