A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that the majority of PCBs are likely to interact with AhR in their nonplanar conformations. In addition, we demonstrate that the affinities of PCBs for AhR relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding toxic equivalency factors in animals. The reported methodology is likely to be applicable to other polyhalogenated and mixed polyhalogenated bi- and terphenyls and related xenobiotics; thus, it could minimize the number of in vivo studies in laboratory animals and facilitate the identification of potentially hazardous aromatic xenobiotics.Imagesp422-aFigure 2.

Polychlorinated biphenyls (PCBs) are nonplanar aromatic xenobiotics that are not structurally related to polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), yet, some PCBs are potent ligands for the aryl hydrocarbon receptor (AhR), active inducers of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (EROD), and elicit toxicological responses in animals similar to PCDDs and PCDFs. We report new methodologies for quantifying the affinities of PCBs for AhR and corresponding potencies as AHH and EROD inducers. The models show that lipophilicities, electron affinities, entropies and electronic energy gaps of PCBs are key physicochemical properties controlling their AhR, AHH and EROD activities. Using 3,3',4,4'-tetrachlorobiphenyl (TCB) as the reference compound, it is shown that PCBs having higher electron affinities, lower lipophilicities and entropies than TCB are potent ligands for rat hepatic AhR. In addition, the congeners having higher binding affinities to AhR and smaller energy gaps than TCB are potent AHH and EROD inducers in rat hepatoma cells in culture. The reported models qualitatively explain and quantify AhR, AHH and EROD activities of all 209-PCBs and related xenobiotics, e.g. PCDDs and PCDFs. Furthermore, we demonstrated that AhR and AHH activities of PCBs relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding in vivo relative toxicities in animals as well as assigned toxic equivalency factors. The reported methodologies are likely to be useful for identifying potentially toxic aromatic xenobiotics in mammals, and minimizing the need for animal testing.

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Heavy weight high performance concrete (HPC) can be used when particular properties, such as high strength and good radiation shielding are required. Such concrete, using ilmenite and hematite coarse aggregates can significantly have higher specific gravities than those of concrete made with dolomite and air-cooled slag aggregates. Four different concrete mixes with the same cement content and different w/c ratios were designed using normal dolomite aggregate, air-cooled slag by-product and two different types of iron ore aggregates. High performance concrete (grade-M60) can be achieved using superplasticizer to reduce the water/cement ratio; the effect of SF on the performance of concrete was studied by addition of 10% silica fume to the total cement content. The physico-mechanical properties of coarse aggregates and hardened concrete were studied. The results show that, Ilmenite coarse aggregate gives higher physical and mechanical properties than the other aggregates. Also, addition of 10% silica fume developed a stronger and a denser interfacial transition zone (ITZ) between concrete particles and the cement matrix. Crushed air-cooled slag can be used to produce a high-strength concrete with better mechanical properties than corresponding concrete made with crushed hematite and ilmenite. Heavy density concrete made with fine aggregates of ilmenite and air-cooled slag are expected to be suitable as shielding materials to attenuate gamma rays.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives. the empirical structural descriptors of xenobiotics to biological activities have limited applicabilities. For example, the regression equation derived for estimating the binding affinities of PCDDs to AhR in rat liver cannot be applied to PCDFs interacting with the same cytosol (4,7,9). The latter difficulty is known as the cross-class comparison problem. Therefore, classical approaches to AhR binding and AhRmediated biological and toxicological responses will remain incomplete without an understanding of the electronic and thermodynamic aspects of these processes.Using a different approach, Kafafi et al. (1S15) developed a new methodology for AhR binding based on electron affinities, entropies, and lipophilicities of the ligands. w S . . . . nese quantltles are lmportant p nyslcochemical properties that control the interaction between aromatic xenobiotics and AhR, as quantified by the AhR-ligand complex dissociation constant. Unlike traditional studies, Kafafi et al.'s methodology eliminated the majority of empirical structural parameters and multiple regression analysis in its formulation, reliably quantified the affinities of PCDDs and PCDFs for AhR, explained the results of in vitro binding studies in a physically consistent way, and eliminated the cross-class comparison problem inherent to classical studies. Furthermore, Kafafi et al. (15) were able to establish quantitative relationships between receptor binding avidities of PCDDs and PCDFs and corresponding AHH and EROD enzyme induction potencies.PCBs are nonplanar, aromatic xenobiotics that are not structurally related to PCDDs and PCDFs, yet some of these compounds bind to AhR effectively and produce biologic and toxicologic responses A new thermodynamie modeX for vlciating the dissociaiion conts of comieses formed between the aryl hydrocarbon receptor (AhR) and polychlorxnated biphenyis (PCBs) is reportedo The iee energies of binding of PCBs to AhR ae controlled by their lipophilicities, electron aSaities, and entropies. Ihe corresponding physicochemiS properties d pQlyiOrinated dibenzotdiosxns and dibenzefiXrans also control t}e;r interactions with AhR We present evidence supponing the hypothesis the the majority of PCBs are likely to interact with AhR xn their nonplanar conformatsons. In addition, we demonstrate that the affinities of PCBs for AhR relative to 2,3,7,8-tetrachiorodibenzo-t dioun correlate with corresponding toxic equiYalenFy ictors in animals. Environmental Health Perspectives