HALOGENATED AROMATIC-HYDROCARBONS AND TOXICITY EQUIVALENCY FACTORS (TEFS) FROM THE PUBLIC-HEALTH ASSESSMENT PERSPECTIVE

The validity of the toxicity equivalency factors (TEFs) approach to pr edicting toxicity of mixtures was investigated on the basis of the pub lic health risk assessment that had been posted for different groups o f halogenated aromatic hydrocarbons. First, the minimal risk levels (M RLs) were derived based on the databases available for chlorinated dib enzo-p-dioxins (CDDs), chlorinated dibenzofurans (CDFs), and polychlor inated biphenyls (PCBs). The MRL values were then converted to 2,3,7,8 -tetrachlorinated dibenzo-p-dioxin (TCDD) toxicity equivalents (TEQs) and compared with each other. There was a good correlation between int ermediate duration oral MRLs for TCDD and 2,3,4,7,8-pentaCDF when expr essed in TEQs (7 pg/kg/day and 15 pg/kg/day). Although the studies tha t served for derivation of these MRLs used different species (guinea p igs and rats, respectively), the toxicity endpoints (immunological and hepatic for TCDD and hepatic for 2,3,4,7,8-pentaCDF) were comparable. The hepatic effects were measured by the same techniques (blood chemi stry and histopathology), ensuring similar sensitivity, However, there was a discrepancy between acute oral MRLs for TCDD and 2,3,4,7,8-pent aCDF when they were expressed in TEQs (20 pg/kg/day and 500 pg/kg/day, respectively). The studies used for MRL derivation involved not only different species (mice and guinea pigs, respectively), the immunotoxi city endpoints were measured by techniques with different sensitivity (serum complement activity versus histopathology), making comparison d ifficult. Further calculations showed that the TEFs approach may be fe asible for individual coplanar congeners of PCBs, but not for a mixtur e of Aroclors. Correlations presented here support the concept that th e TEFs are valid only if specific criteria for their derivation are me t (e.g., a broad database of information, consistency across endpoints , additivity for the effects, a common mechanism of action, etc.). In environmental exposure, the total toxicity of halogenated aromatic hyd rocarbons is not necessarily the sum of the total individual congener toxicities because individual congeners compete for the same receptor; therefore, nonadditive behavior may occur.