Investigation Of Toxic Mode Of Action Of Organic Pollutants To Different Sensitivity Species Based On Toxic Ratio

In aquatic toxicology,the ability to determine the toxic mode of action(MOA)for a diverse group of chemical is the basis of ecological risk assessment and plays an important role in the chemical regulation.Identification of the mode of toxic action can contribute to develop QSAR model and evaluate the toxic effects of organic pollutants,but also can contribute to discuss the toxic mechanisms of organic pollutants and provide a theoretical basis and scientific evidence for ecological risk assessment.One of the widely used methods of toxicity mechanism identification is the toxicity ratio(log TR> 1,also known as excess toxicity),and it has been well applied to investigate the toxic mechanism of organic compounds on fish.However,there is a large deviation when we apply this ratio to study the toxic effects of organic compounds for other sensitive species.In addition,the method of threshold of toxic ratio is only applicable to neutral organic pollutants.Because the toxic effects are closely related to p H,wrong classification of mode of action can be made from the apparent toxicities for ionizable organic pollutants.In this paper,the effect of species sensitivity on classifying different MOAs were investigated.The species-specific thresholds allowing for the better discrimination of acute modes of toxic action for different species were determined.The toxic modes of action of baseline,less inert and reactive compounds was discussed detailedly.Besides,the effect of p H on the toxicity in ionizable organic compounds were investigated.The effect of p H on bioconcentration factor(BCF)were discussed.The theoretical equation between the apparent toxicity and p H were developed.The effect of p H on the discrimination of toxic mode of action for ionizable organic compounds were discussed.At the same time,the toxicity data of 13 antibiotics to Daphnia magna,algae and Vibrio fisheri was determined.The toxic modes of action of antibiotic was investigated basing on the species-specific toxicity ratio.The research results can contribute to understand the toxic mode of action of antibiotics,on the growth and development of the environment,and lay a good theoretical foundation for the ecological risk assessment of antibiotics.The main conclusions are as follows:(1)The acute toxicity of class-based organic pollutants to fish,Daphnia magna,Tetrahymena pyriformis,and Vibrio fischeri was invesitgated.The results showed that the baseline compounds may share same modes of toxic action between species and the toxicity sensitivity of baseline compounds to Daphnia magna,fish and Vibrio fischeri is very similar.Therefore,the threshold log TR =1 which is based on the distribution of toxicity data to fish can also be used to discriminate reactive compounds from baseline narcotics for Daphnia magna and Vibrio fischeri.On the other hand,the toxicity sensitivity in Tetrahymena pyriformis is very different from the sensitivity in the other three species for baseline compounds.This suggests that the log TR = 1 obtained from fish toxicity is not an ideal threshold of excess toxicity for TP species.The threshold of toxicity ratio log TR = 0.8 was determined by investigating the relationship between the species sensitivity and the absolute averaged residuals(AAR)between the predicted baseline toxicity and experimental toxicity.(2)The interspecies correlation of toxicity to fish,algae,Daphnia magna and Vibrio fischeri was invesitgated basing on of the toxicity data of class-based organic compounds.The results indicate that the baseline compounds may share similar modes of toxic action between species and the toxicity sensitivity to the four species is very similar.Besides,similar relationship between log KOW and toxicities to the four species for baseline compounds suggest that they have similar critical body residues in the four species.Therefore,the threshold log TR =1 which is based on the distribution of toxicity data to fish can also be used to discriminate reactive compounds from baseline narcotics for algae.(3)The toxic mode of action of baseline,less inert and reactive compounds of fish,Daphnia magna,Tetrahymena pyriformis,and Vibrio fischeri were identified basing on the species-specific threshold of toxic ration(log TR=1 and log TR=0.8).The results indicate that less inert compounds exhibit higher toxicity to the Tetrahymena pyriformis and Vibrio fischeri than the high level species fish and Daphnia magna.More numbers of less inert compounds with log TR greater than the thresholds have been observed for Tetrahymena pyriformis and Vibrio fischeri.This may attributed to hydrophilic compounds may more easily pass through the cell membrane than the skin of organisms and have higher bioconcentration factors in Tetrahymena pyriformis and Vibrio fischeri,leading to higher toxic effects.Most of the classes with excess toxicity to one species also exhibit excess toxicity to other species.On the other hand,a few classes with excess toxicity to one species exhibit to other species.For examples,some β-halogenated alcohols show narcotic level toxicity to Vibrio fischeri species.Nitriates exhibit weak toxicity to Tetrahymena pyriformis.These compounds may share different MOAs among these species.Inspection of the log KOW values reveals that hydrophilic compounds are more toxic than the hydrophobic compounds and exhibit higher excess toxicity.There are two reasons leading to the excess toxicity for these compounds.Firstly,they are reactive or specifically-acting compounds with enhanced toxicity.Secondly,the bioconcentration potential is under-estimated from hydrophobic parameter(log KOW).Some ionisable compounds have strong toxicity with log TR greatly higher than one.For examples,a number of aliphatic diacids exhibit excess toxicity for the four speceis,respectively,and benzoic acids for Vibrio fischeri.Our investigation shows these compounds have lower log TR is because that the log KOW values are significantly over-estimated for the ionisable compounds.Besides,it is possible that some observed toxicities are less than that predicted from baseline models for different species because of experimental error,the size of molecular,the highly hydrophobic and the degree of ionizable.(4)In this paper,the toxicity data of 61 compounds to D.magna determined at three p H values were used to investigate the effect of p H on the discrimination of excess toxicity.The results show that the apparent toxicities are significantly less than the baseline level.Analysis on the effect of p H on bioconcentration factor(BCF)shows that the log BCF values are significantly over-estimated for the strongly ionizable compounds,leading to the apparent toxicities greatly less than the baseline toxicities and the toxic ratios greatly less than zero.A theoretical equation between the apparent toxicities and p H has been developed basing on the critical body residue(CBR).The apparent toxicities are non-linearly related to p H,but linearly to fraction of unionized form.The determined apparent toxicities are well fitted with the toxicities predicted by the equation.The toxicities in the unionized form calculated from the equation are close to,or greater than the baseline level for almost all the strongly ionizable compounds,which are very different from the apparent toxicities.The studied ionizable compounds can be either classified as baseline,less inert or reactive compounds in D.magna toxicity.Some ionizable compounds that do not exhibit excess toxicity at a certain p H are not due to their poor reactivity with target molecules,but because of the ionization in water.(5)The toxicity data of 13 different antibiotics to algae,Daphnia magna and Vibrio fischeri were used to discriminate excess toxicity from baseline level and MOAs.Comparison of toxicities shows that most of the antibiotics had a greater toxic effect to algae,and the toxic effects to Daphnia magna and Vibrio fischeri was relatively low.The main reasons for the difference in the toxicity of antibiotics to different species are the difference in species sensitivity,modes of actions and the bioavailability of the compounds.Investigation on the mode of action show that,except for rifampicin and azithromycin,almost all of the antibiotics exhibit excess toxicity to algae,Daphnia magna and Vibrio fischeri and their MOAs to these species were all identified as reactive mode of action.