[SAR and QSAR methods in the study of dioxin action]

Thousand chemicals are present within our environment, and for many of them, there is a little reliable information detailing their relative hazard. Added to that increasing concern over the use of animals in toxicity testing, high costs of these tests has made the search for and validation of alternative methods to predict the hazard and the relative risk of xenobiotics. QSAR (quantitative structure activity relationship) attempt to relate statistically the biological activity of compound with its physicochemical and structural properties. QSAR methods are often seen as the first step for valid toxicological prediction. Halogenated aromatic hydrocarbons typified by polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF) and biphenyls (PCBs) have been identified as residues in almost every component of the ecosystem. Some chemicals in this class cause adverse biological effects after binding to an intracellular cytosolic protein called the Ah receptor (AhR). Because of importance of the Ah receptor in determining toxicity, there have been a number of attempts to model the relationship between receptor binding and structure of xenobiotics. QSAR have found wide use in correlating the bioactivity of dioxins and related compounds with many kinds of biological entities. This paper will briefly summarise some SAR and QSAR study for halogenated aromatics as ligand for Ah receptor and the characteristic biological and toxic responses elicit by this class of chemicals. These study strongly support the role of AhR in dioxin toxicity.