| Polybrominated Biphenyls(PBBs)are brominated flame retardants that were introduced in the 1950 s and contain 209 homologues.In 1973,Michigan,USA,PBBs were accidentally added to cattle feed as magnesium oxide,causing varying degrees of adverse effects on organisms,so its harmfulness is taken seriously.In 1976,the United States stopped producing PBBs,followed by other countries.Although PBBs have been discontinued and banned,they have environmental persistence,bioenrichment,longdistance transport and toxicity.They can be released slowly from products,enriched in environmental media and organisms,and can be transmitted through breast milk,which still has certain environmental hazards.Besides,there is a high concentration of PBBs in the e-waste dismantlement area.In view of the high flame retardant function and poor environmental friendliness of PBBs,it is necessary to conduct molecular structureactivity relationship analysis to explore the mechanism and control scheme from the source.Moreover,there are few studies on the environmental migration and transformation process of PBBs and the risk evaluation of transformation products.In addition,PBBs has a series of toxicity,such as: carcinogenicity,developmental toxicity,epigenetic toxicity,and the mechanism and regulation of toxicity remain to be understood and studied.Therefore,this paper studied PBBs from three perspectives:environmental comprehensive effect structure-activity relationship analysis,environmental transformation mechanism and toxic risk control strategy.First of all,this paper combined the efficacy coefficient method to synthesize the two spectral effects of PBBs infrared vibration and ultraviolet absorption,and constructed a 3D-QSAR model with dual spectral effects.The contribution rates of electrostatic and steric field were 55.2% and 44.8%,respectively.In the threedimensional contour maps,The influence region of electrostatic field is distributed in the 3,3',6',4 and 5 substituents of PBB-153 molecule,and the influence region of steric field is distributed in the 4,5 and 3' substituents.According to the information of threedimensional contour maps,groups with strong negative point and large volume were selected to replace No.4 and 5 sites of PBB-153 molecule,which enhanced the bispectral detection characteristics of PBBs molecule.Infrared spectral effects with significant changes were selected to construct a 3D-QSAR model modified by standard deviation standardization method with the three effects of PBBs molecular infrared vibration intensity,bioenrichment and toxicity.Considering biohazard and spectral detection comprehensively,the contribution rates of electrostatic field and steric field to the three effects of PBBs were 59.9% and 40.1%,respectively.In the threedimensional contour maps,the influence region of electrostatic field is distributed in the 2,4,3',6',3 substituents and benzene ring skeleton of PBB-153 molecule,and the influence region of steric field is distributed in the 3,4' and 5' substituents.Substituting positive and large groups at site 4 can improve the infrared vibration intensity,bioenrichment and toxicity of the molecule.Then,a 3D-QSAR model for the comprehensive effects of bioenrichment,long-distance transport and infrared vibration intensity of PBBs was constructed based on the threshold method.Considering biohazard,environmental transport and spectral detection,the contribution rates of electrostatic and steric field to the comprehensive effects of PBBs were 53.4% and46.6%,respectively.the influence region of electrostatic field is distributed in the 2,2',3,3',4,5 and 6 substituents,and the influence region of steric field is distributed in the3,3',5,5',6,6' and 4 substituents.The introduction of electronegative and small groups at the 2,5 and 5' sites can improve the bioenrichment,long-distance transport and infrared vibration intensity of the molecule.All the constructed models have good prediction ability,fitting ability and external prediction ability,and 3D-QSAR models with multiple effects have passed the reliability verification.The main molecular points and functional groups that affect the environmental effects of PBBs in different scenarios were identified,and the comprehensive environmental effects of PBBs were improved by changing the group properties.Then,the transformation pathways of PBBs in environmental media,such as photodegradation,microbial degradation,combustion oxidation,and in vivo metabolism,were deduced and sorted out,and various transformation products of PBBs and designed substitute molecules were summarized.A variety of 3D-QSAR models were constructed for the human toxicity(carcinogenicity,developmental toxicity,hepatotoxicity,epigenetic toxicity,neurotoxicity and immunotoxicity)of PBBs,and the potential toxicity risk(rodent carcinogenicity,rodent toxicity,mutagenicity,potential developmental toxicity,skin and eye irritation,skin sensitization and aquatic toxicity)of the transformation products was evaluated in combination with the toxicity kinetics model.According to the detection of PBBs in waste disposal sites.It can be inferred that photodegradation is the main environmental degradation path of PBBs.The transformation products of PBBs and their substitutes have high toxicity risks to organisms,including potential carcinogenicity,mutagenicity and developmental toxicity.They also have high potential environmental risks to aquatic organisms,such as fish and daphnia magna.In general,PBBs combustion oxidation products have higher potential environmental and ecological risks.Among the potential toxicity risks to human body,the developmental toxicity of PBBs and its substitutes transformation products theoretically has a high impact,and the human toxicity risk of combustion transformation products is increased in general.Besides,the mechanism of the effect of PBBs on thyroid cancer was studied.Molecular docking and molecular dynamics methods were adopted.The process of PBBs being metabolized by CYP1A1 enzyme into single and dihydroxylated metabolites mediated by AHR was taken as the molecular initiation event(MIE).The interaction between PBBs and its metabolites and TBG was taken as the key event(KE)to construct the harmful outcome pathway(AOP)of human thyroid cancer induced by PBBs exposure.Based on 2D-QSAR models,amino acid residues and binding energy contribution analysis,the mechanism of carcinogenicity(adverse effect,AE)pathway of PBBs was speculated.Hydrogen bonding force,van der Waals interaction and critical pressure are the internal key factors affecting the carcinogenicity pathway of PBBs molecules.Based on the analysis of non-bonding forces,PBBs and its hydroxylated products were mainly bonded to TBG by hydrophobic interaction and hydrogen bond interaction,and the key hydrophobic amino acids were identified as alanine Ala330,arginine Arg381 and Lys270,respectively.It provides a basis for the study of human health risk mechanism under PBBs exposure.Finally,by means of molecular docking,molecular dynamics,Taguchi experimental design and fractional factorial experimental design,we tried to identify the compound developmental toxicity characteristics of human body under exposure to10 kinds of developmental toxic pollutants such as PBBs,and carried out correlation analysis and sensitivity analysis between molecular developmental toxicity and structural parameters.The molecular key structural parameters of pollutants affecting human developmental toxicity were screened,and the complementary food factors that could alleviate the developmental toxicity of pollutants such as PBBs were screened accordingly,so as to develop complementary food programs to prevent or alleviate the developmental toxicity of human for the specially exposed population(pregnant women,infants).The results showed that the developmental toxicity of human body was controlled by the main effects of PBBs and other 10 pollutants,and the significant factor was PBB-153 molecule,accounting for 37.06% of the significant effect statistics.The most significant cofactor that could reduce the developmental toxicity of PBBs was the combination of carotene and DHA.The improvement degree of human developmental toxicity under PBB-153 exposure was 17.28%,and most of human developmental toxicity under the combination of carotene and DHA exposure of other pollutants was significantly improved,indicating that the selected complementary diet has certain universal applicability.The purpose of this paper is to study PBBs comprehensive environmental effect mechanism of structure-activity,analysis the environmental transformation process and biological health risks,in-depth analysis and explore PBBs toxicity mechanism of risk and control scheme,to further improve the pollution prevention and control of PBBs and risk evaluation system,and also provide theoretical feasible ideas and methods for the assessment of environmental risk of other environmental organic pollutants. |
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