TOXIC EQUIVALENCY FACTORS DO NOT PREDICT THE ACUTE TOXICITIES OF DIOXINS IN RATS

Risk evaluation of complex environmental mixtures of polychlorinated d ibenzo-p-dioxins and related halogenated aromatic hydrocarbons (polych lorinated dibenzofurans, azo- and azoxybenzenes, naphthalenes and some of the biphenyls) is currently carried out by measuring the concentra tion of each congener in the mixture and then multiplying every figure by its specific constant, toxic equivalency factor (TEF). All congene rs are thought to produce highly similar effects albeit at different d oses, and the TEFs are believed to represent the potencies of the cong eners relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), consider ed the most toxic derivative of this class of environmental contaminan ts. Here we compared the acute toxicities of TCDD, 1,2,3,7,8-penta-, 1 ,2,3,4,7,8-hexa- and 1,2,3,4,6,7,8-heptachloro-dibenzo-p-dioxin in the most TCDD-susceptible (Long-Evans Turku AB; L-E) and the most TCDD-re sistant (Han/Wistar Kuopio; H/W) rat strain. While L-E rats exhibited the expected rank order of sensitivities to the four dioxins, the high er chlorinated dioxins were more toxic than TCDD (in terms of acute le thality) to H/W rats, with the hexachlorodioxin showing the greatest p otency. Even if the doses were adjusted according to the LD(50) values , both biochemical and morphological effects elicited by the dioxins t urned out to depend, often critically, on strain, congener or the inte raction of these two determinants. These findings demonstrate that the dioxins have distinct profiles of acute toxicities and underscore the importance of response and test organism in defining the TEFs.