Halogenated aromatic hydrocarbons and toxicity equivalency factors (TEFs) from the public health assessment perspective.
The validity of the toxicity equivalency factors (TEFs) approach to predicting toxicity of mixtures was investigated on the basis of the public health risk assessment that had been posted for different groups of halogenated aromatic hydrocarbons. First, the minimal risk levels (MRLs) were derived based on the databases available for chlorinated dibenzo-p-dioxins (CDDs), chlorinated dibenzofurans (CDFs), and polychlorinated 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 intermediate duration oral MRLs for TCDD and 2,3,4,7,8-pentaCDF when expressed in TEQs (7 pg/kg/day and 15 pg/kg/day). Although the studies that served for derivation of these MRLs used different species (guinea pigs 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 chemistry and histopathology), ensuring similar sensitivity. However, there was a discrepancy between acute oral MRLs for TCDD and 2,3,4,7,8-pentaCDF 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 immunotoxicity endpoints were measured by techniques with different sensitivity (serum complement activity versus histopathology), making comparison difficult. Further calculations showed that the TEFs approach may be feasible for individual coplanar congeners of PCBs, but not for a mixture of Aroclors. Correlations presented here support the concept that the TEFs are valid only if specific criteria for their derivation are met (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 hydrocarbons is not necessarily the sum of the total individual congener toxicities because individual congeners compete for the same receptor; therefore, nonadditive behavior may occur.
Pohl
H
H
Division of Toxicology, U.S. Department of Health and Human Services, Atlanta, Georgia 30333, USA.
Holler
J
J
D000818:Animals; D001572:Benzofurans / Q000009:adverse effects*; D000072338:Dibenzofurans, Polychlorinated; D004781:Environmental Exposure; D006168:Guinea Pigs; D006801:Humans; D007256:Information Systems; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects*; D011634:Public Health / Q000592:standards*; D018570:Risk Assessment; D013329:Structure-Activity Relationship
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D000072317:Polychlorinated Dibenzodioxins; D011078:Polychlorinated Biphenyls