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Sherif A. Kafafi,¹ Hussein Y. Afeefy,² Ali H. Ali,¹ Hakim K. Said,¹ and Abdel G. Kafafi³

¹Department of Environmental Health, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205 USA; ²National Institute of Standards and Technology, Chemical Kinetics and Thermodynamics Division, Gaithersburg, MD 20899 USA; ³Dynex International Inc., Oakville, Ontario L6M 2M7 Canada

Abstract
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. Key words: aryl hydrocarbon receptor, binding affinity, polychlorinated biphenyls, structure-activity relationships, toxic equivalency factors. Environ Health Perspect 101:422-428(1993)

Address correspondence to S. A. Kafafi, Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205 USA.

This research was supported by the U.S. Environmental Protection Agency (R-817056-010) . We thank the Johns Hopkins University School of Public Health Computer Center for the allocated computer time and the staff of Dynex International Inc. for their assistance in performing the computations. Certain commercial equipment, instruments, or computer programs are identified in this paper to adequately specify the research work. Such identification does not imply recognition or endorsement by the National Institute of Standards and Technology, nor does it imply that the programs or equipment identified are the best available for the purpose.

Received 20 April 1993 ; accepted 22 June 1993.

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