RELATIVE POTENCY OF POLYCHLORINATED DIBENZO-P-DIOXINS AND DIBENZOFURANS FOR INDUCING MIXED-FUNCTION OXYGENASE ACTIVITY IN RAINBOW-TROUT

Toxic equivalent factors (TEFs) were generated for various polychlorin ated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDF s) to compare the relative potencies as inducers of liver mixed-functi on oxygenase (MFO) activity in rainbow trout (Oncorhynchus mykiss). Tr out, dosed orally with one of five PCDD congeners, either [H-3]-2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8-pentachlorodibenzo-p-d ioxin (PnCDD), 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (1,2,3,6,7,8-HxC DD), [C-14]-1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (1,2,3,4,7,8-HxCDD) , or [C-14]-1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) or one o f four PCDF congeners, either 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1,2,3,7,8-PnCDF), 2,3,4,7,8-pentach lorodibenzofuran (2,3,4,7,8-PnCDF), or 1,2,3,4,7,8-hexachlorodibenzofu ran (HxCDF), showed increases in liver ethoxyresorufin O-deethylase (E ROD) activity up to 250-fold. Liver concentrations of congeners were b etter predictors of EROD activity than oral dose. TEFs, ratios of the potency of each congener to that of TCDD, were calculated comparing '' threshold'' PCDD concentrations that induced EROD significantly above control levels. In cases of nonparallel dose-response curves between c ongeners, these comparisons are more relevant to environmental situati ons as PCDDs are compared at concentrations closer to those in the env ironment, instead of at higher pharmaceutical levels. Threshold-based TEFs were: PnCDD, 1.8; 1,2,3,6,7,8-HxCDD and 1,2,3,4,7,8-HxCDD, 0.4; H pCDD, 0.05; 2,3,4,7,8-PnCDE 2; TCDF, 0.5; 1,2,3,7,8-PnCDF and HxCDF, 0 .4. The ranking of potencies of the PCDFs was the same in fish as in m ammalian tests, with the exception of PnCDD and 2,3,4,7,8-PnCDF, which were more potent to fish than was TCDD. Fish TEFs calculated at the t hreshold of EROD induction were about four to five times larger than i nternational TEFs (I-TEFs), which are based on mammalian tests. At low concentrations typical of environmental exposures, TEFs may be differ ent from mammalian-based TEFs.