Risk assessment of mixtures: possibility of prediction of interaction between chemicals

Objectives: Potentiation, inhibition, antagonism, synergism or other interactions of chemicals in an organism may significantly affect the toxicity of chemical mixtures. Therefore, a suitable physicochemical parameter is sought as a predictor of these effects. Methods: Acute toxicity EC50 (mol/l) was used as an index of toxic hazard. The EC50 was defined here as the concentration inhibiting movement of 50% of Tubifex tubifex worms in a standardised short-term test. The EC50 for the mixture benzene/ethanol was measured over the whole range of molar fractions between 0 and 1. The determined EC50 values were compared with those calculated by the effect-addition and concentration-addition models. The distribution of benzene and ethanol between the aqueous and gaseous phases was determined by gas chromatography. Results: The determined EC50 of the benzene/ethanol mixtures exhibited deviations from the values predicted using the EC50 of the single compounds. The magnitude of this deviation depended on the composition of the mixture, and could be as high as 80% if the effect-addition model is used or 20% if the concentration-addition model is applied. The air/water distribution coefficients of benzene and ethanol measured in aqueous solutions of their mixtures exhibit unobservable to slight deviations from those obtained by simple summation. Conclusion: The determined values of the EC50 of benzene/ethanol mixtures calculated by either the concentration-addition or effect-addition model differ from the true values due to interactions among chemicals. The deviations depend on a quantitative composition of a mixture. The air/water distribution coefficient of chemicals in a mixture is not the most suitable predictor of the interactions.