Study On Toxicity Identification And Toxicity Mechanism Of Emerging Disinfection By-products

Disinfection by-products(DBPs)are formed when organic substances in raw water react with disinfectants that kill pathogens.Epidemiological studies have found that the occurrence of some cancers is directly related to by-products.However,little is known about the toxicity of many DBPs,and most of the existing methods for toxicity detection have the problems of high cost and long operation time.Therefore,it is necessary to adopt a new technical method to explore the toxic effects of DBPs,Toxicogenomics is a new field developed in the application of high-throughput technology.It has the characteristics of high throughput,cost-saving and short time-consuming.Therefore,toxicogenomics can provide more convenient and effective new technology support for the toxicity study of DBPs.In this paper,20 DBPs were studied,and the toxicity of DBPs was studied by real-time gene expression profiling based on gene toxicology.The mode of action and pathway of DBPs were analyzed from stress response and gene level.At the same time,quantitative structure-activity relationship(QSAR)method was used to analyze the physical and chemical structure of DBPs and the toxicity endpoints,and to determine the nature of DBPs that affect toxicity.The study draws the following conclusions:(1)12 out of 20 of the tested DBPs exhibited toxic MOA in toxicogenomic assays,which was consistent with the results reported in the literature.At the same time,stress reactions that had not been found in some existing studies were also found,suggesting that DBPs may have multiple potential toxic pathways.(2)The molecular toxicity of DBPs was characterized quantitatively,and the dose-effect relationship was established by four-parameter model.Among them,six DBPs showed flat dose-effect curves,seven DBPs showed typical"S" or partial "S" curves,and most of the other DBPs showed a relatively parallel trend.At the same time,quantitative molecular toxicity endpoints of DBPs,such as TELImax and EC-TELI1.5,can be calculated by dose-effect curve.(3)Gene expression induced by different DBPs is highly dynamic and complex.Among the three main stress mechanisms,oxidative stress,membrane stress and DNA damage,most DBPs induced oxidative stress and DNA damage.Most of the gene expression patterns induced by DBPs vary with the type and concentration of DBPs,suggesting that the type and exposure level of DBPs have a great influence on genomic activity.(4)Clustering analysis of the correlation between the expressed genes and DBPs with different concentrations showed that the toxicity mechanism of the same DBPs at different concentrations and the genotoxicity mechanism of DBPs with similar molecular structure might be different.It also indicated that toxicity similarity analysis of a given chemical could be carried out by using toxicological fingerprints provided by high-throughput toxicogenomics experiments.(5)QSAR study of 20 DBPs showed that quantum chemistry and topological structure parameters are strongly correlated with the toxicity endpoints of most DBPs,indicating that the main chemical structure parameters affecting the genotoxicity of DBPs are the quantum chemical parameters involving the whole compound molecule and the topological structure parameters reflecting the molecular skeleton and branching degree.