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. W hile 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 per ceptible degradation was found, even for the 2,3,7,8-TFDD. Stepwise ch lorination 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 inductio n 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. Com parison of the metabolic rates of different TCDD with those of the ana logous TFDD demonstrates that the order of enzymatic degradation of di fferent TCDD and the analogous TFDD is identical. The TFDD are degrade d slightly faster than the corresponding TCDD. Surprisingly 1,4,6,9-TX DD showed the second slowest metabolic rate of the fluorinated and chl orinated TXDD after 2,3,7,8-TXDD although none of the 2,3,7,8-position s were substituted. Judging from 2,3,7,8-TFDD and 1,7-dichloro-2,8-dif luorodibenzofuran the metabolic pathway of fluorinated and chlorinated -fluorinated congeners seem to be comparable to the chlorinated congen ers. Copyright (C) 1996 Elsevier Science Ltd