Study On The Joint Toxicity Of Pollutants With Different Curve Types To Vibrio Fischeri

The evaluation of joint toxicity of mixtures is an important topic in toxicology.Previous studies have found that the characteristic parameter k·ECx of concentration response curves(CRCs)can be used to assess the applicability of concentration addition model(CA),and the CRCs of substances are related to the combined effect of the mixture.This study further assesses the predictability of k·ECx on the joint toxicity evaluation.The single and binary acute toxicity of 12 kinds of environmental pollutants from different sources to Vibrio fischeri was tested by using the microplate toxicity analysis.The joint toxicity evaluation of mixtures was conducted by CA and independent action model(IA).The relationship between the joint toxicity of binary mixture(measured by the relative model deviation ratio(rMDR))and the characteristic parameter k·ECx of each component was studied.However,the CA and IA models have certain shortcomings.The CA model has some prediction blind spots,and the IA model is a pure theoretical conception.Therefore,the theoretical non-linear combined toxicity assessment model(TNL)is introduced to supplement the evaluation of some mixtures,and the three models are optimally selected.First of all,in order to determine whether the characteristic parameter k·ECx of the substance can characterize the form of the substance CRCs and to verify the evaluation ability of two common additive models for the joint toxicity of binary mixtures,the acute toxicities of the single and binary mixtures of common pollutants in the environment to Vibrio fischeri were determined by using the microplate toxicity analysis.The CRC of a single substance was obtained by fitting,and the combined effect of the binary mixture was evaluated using CA and IA models.The result shows that the CRCs of 12 substances and their binary mixtures can be well fitted by Hill equation.The fitting parameter n value of CRCs is correlated with their morphology to some extent.The arrangement of the characteristic parameter k·ECx of 12 chemical substances and the n value of Hill function fitting parameter is basically,the same.Because k·ECx has its exact value in different concentrations,and the k·ECx could reflect the shape of CRCs in the whole concentration range.According to the prediction results CA and IA models,due to the large difference in k·ECx of the selected substances,65%of the mixtures with equal toxicity ratio produce strong antagonism or synergism.For the same combination,the combined action intensity of binary mixture with different concentration ratio is also different.The joint toxicity evaluation results of the mixture of CA and IA models are quite different.Combined with the experimental results and literature analysis,IA model is the best evaluation model.Secondly,in order to determine the functional relationship between the k·ECx of each component and the joint action of the mixture,the experimental data were processed by mathematical methods in this study.Through mathematical fitting,it is found that no matter how the mixture ratio changes,the relative difference of k·ECx of components and the rMDRx can be fitted by an exponential function.According to the change of ?(k·ECx)%and rMDRx,the exponential function is divided into four types of mixtures.For a1 type binary mixtures,all functions are non-monotonic functions.The intersection points of the dotted lines rMDRx=0 and ?(k·ECx)%=0 and the exponential function do not coincide.The concentration of the mixture corresponding to the intersection of the dotted line rMDRx=0 and the exponential function is lower.In other words,the change of the combined mode of action precedes the change of CRC shape.With the increase of |?(k·ECx)%|,the intensity of combined action first increases,then decreases and then increases,This law has nothing to do with the way of joint action.For a2 type binary mixtures,when the fitting exponential functions are non-monotonic and the joint action is antagonistic,with the increase of |?(k·ECx)%|,the intensity of the combined action first decreases and then increases.When the joint action is synergetic,the intensity of the combined effect changes in the opposite direction.For b1 type binary mixtures,when ?(k·ECx)%>0,with the increase of ?(k·ECx)%,the joint action strength first decreases and then increases.When ?(k·ECx)%<0,the intensity of the combined effect changes in the opposite direction.For b2 type binary mixtures,the fitting exponential functions are all monotone functions.Regardless of the mode of action,the probability of increasing or decreasing functions is similar.The combined action law of the four types of binary mixtures with different concentration ratios has the same toxicity study results,indicating that the law has universal applicability.This rule does provide a basis for predicting the combined toxicity of multiple mixtures.Finally,in order to select and optimize the joint toxicity evaluation model of the mixture,this study introduces the TNL model and uses three models to evaluate the mixture.This model is derived from the definition of mixture combined action,and its correctness has also been verified by biochemical tests.In this study,21 groups of binary mixtures with equal toxicity ratio and 5 sets of binary mixtures of 2 chemicals were selected for supplementary evaluation.The evaluation results of CA,IA and TNL models were quite different,the action mode of eight groups by the three models was different.When the difference of characteristic parameter k·ECx value was small,the CA model was used for evaluation.If the CA model has a prediction blind spot,the IA model was directly selected.When the difference of k·ECx was big,the TNL model should be used.In summary,the characteristic parameter k·ECx of CRC was determined,and the functional relationship between the parameter ?(k·ECx)%and the combined action of the mixture was explored.The parameter k·ECx is used to predict the joint toxicity of binary mixtures,which can quickly obtain very important data when planning experiments and the number of experiments can also be reduced.By studying the changing law of the combined action of the four types of mixtures,it can provide more detailed and specific theoretical support for the prediction of the joint toxicity of the binary mixture and the determination of the“effective combination".The joint toxicity evaluation model of the mixture was selected and optimized.As a supplementary model,the TNL model can be combined with CA and IA models to evaluate the combined effects of binary mixtures,and accurate results can be obtained.