QSAR Analysis in Mixture Toxicity Assessment

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Abstract
It is known, more or less, how to create a QSAR model for predicting toxicological activities of one individual chemical not interfering with others. Combined chemical exposures are, however, rather the rule than an exception in workplaces and in the environment. Simultaneous or sequential exposures to two or more chemicals can change the toxicity of each chemical, both quantitatively and qualitatively. The resulting activities of mixtures may be additive, more often they are not. Numerous publications have already appeared describing a use of QSAR models as a criterium for a decision about the mode of joint actions of chemicals. Calculations of joint activities of mixtures of chemicals mostly deal with chemical safety limits not with the toxic indexes – activities – as EC50 or LD50. A proposal to express quantitatively a relationship between determined acute toxicity index and composition of two-component mixture is presented (quantitative composition-activity relationships QCAR). The isobolograms do not offer this possibility. For this purpose, a molar ratio of a mixture describing the mixture composition (composition descriptor) is suggested. The molar ratio can be determined experimentally. An example on the use of the molar ratio is shown with acute toxicity index EC50. It was determined as an inhibition of movement of worms Tubifex tubifex caused by mixtures of inorganic salts (zinc chloride with cadmium chloride and zinc nitrate with lead nitrate).