Mixture Toxicity Effects Of Organic Pollutants

Mixtures of organic pollutants frequently expose in the realistic environment. Ecological toxicologists historically have assessed the risks associated with exposure to single chemicals in laboratory, including acute and chronic toxicity test. However, based on the experiment for single chemicals, it is difficult to reflect the ecological behavior and environmental harmfulness. Increasing awareness of the extent of mixture contamination, therefore, has brought into sharp focus on developing computational models for quantificationally predicting the toxicity of chemical mixtures.This thesis studied whether the observed toxicity of mixture composed of components with different dose-level or toxicity degree deviate the conception of concentration addition (CA) and independent action (IA). The single toxicity of Chlorpyrifos, Diazinon and Malathion and joint toxicity of ternary mixtures of organophosphate insecticides to photobacterium phosphoreum were determined. The result showed that CA and IA models produced the deviations while synergistic/antagonistic, dose level-dependent and dose ratio-dependent effects occurred in this mixture with the result of significance testing. When all the mixtures mixed the chemicals in their EC₁ and EC₅₀, the overall effects of the mixture mainly performed synergistic. However, since the dose level of mixture varied and the single toxicity of mixture components was different, antagonistic also occured. Based on the analysis, the relationship of mixture components was quantified, and the transformation between antagonistic and synergistic was demonstrated.Because it is difficult to predict these complex modes of action for mixtures using CA and IA model, this study verified an effective toxicity prediction approach for complex mixtures under the condition of unknown MOA. Mixture toxicities were determined for 12 industrial organic chemicals bearing four different modes of toxic actions (MOAs) to Photobacterium phosphoreum in order to compare the predictability of the integrated fuzzy concentration addition-independent action model (INFCIM) with two-stage prediction (TSP) model. Three mixtures were designed, with the first and second mixtures based on the ratios at the 1% and 50% effect concentration (EC₁ and EC₅₀) of each component, respectively, and the third mixture equimolar ratio of individual components. For the EC₁, EC₅₀ and equimolar ratio, prediction errors from the INFCIM at the 50% combination effects in all the validation sets were 0.3%, 6% and 0.6%, respectively. While for the TSP model, the corresponding errors were 2.8%, 19% and 24% respectively. Thus the INFCIM performed better than the TSP model. INFCIM calculated two weight coefficients from molecular structural descriptors, which weigh the relationship between concentration addition (CA) and independent action (IA) through fuzzy membership functions. Thus MOAs are not pre-requisitions for mixture toxicity prediction by the INFCIM approach, implying the practicability of this method in risk assessment of mixtures.