The Investigations Of Indoor Pollution Characteristics Of Organic UV Filters And Its Immune Toxicity Effects And Mechanisms On Macrophage

Organic ultraviolet(UV)filters are active ingredients in personal care products(PCPs)to absorb deleterious UV radiation and protect human skin.UV filters are listed as emerging contaminants due to their wide distribution in the environment,and the consequent potential risks to humans and wildlife.To date,studies of UV filters have focused mainly on the eco-toxicity and endocrine-disrupting effects on protozoan and aquatic organisms,but less is known about their chronic toxicity to humans.In this paper,we developed sensitive and reliable methods to measure the levels of UV filters in indoor dust and human urine matrices,then analyzed the pollution characteristics of UV filters in indoor dust and evaluated the health risks to humans.Furthermore,the immune toxicity effects and mechanism of UV filters to human macrophage were investigated with in vitro experiments and molecular simulations.The main results are as follows:(1)For indoor dust,the analytical method based on ASE-SPE-derivatization-GC-MS/MS were developed.For human urine,the method of SPE-derivatization-GC-MS/MS were optimized.The limit of detection(LOD)of the methods are in the magnitude of pg g^-1(except for 4-MBC),recoveries were in the range of70.5%?110.7%,relative standard deviation(RSD)was from 0.66%to 5.04%.(2)Analysis results of indoor dust(n=243)form eastern China showed that the detection rates of UV filters were from 82.3%to 99.0%,and the concentration of?_{UV filters}(BP-3,4-MBC,HMS,OC)was in the range of 66.6?56123.0 ng g^-1 with a median value of 1173.4 ng g^-1.OC was the most abundant in indoor dust(median:325.7 ng g^-1),approximately 2?4 times of others.The concentrations of UV filters were higher in indoor dust from the relatively wealthier and more urban households than in indoor dust from the relatively low income and more rural households(P<0.05).Significantly higher levels of UV filters were observed in indoor dusts from residences than from offices(P<0.05).Concentration of UV filters in indoor dust was positively correlated with family income and sunscreen use.Sources of UV filters in the indoor dust samples differed based on the geographical location.(3)Analysis results of human urine(n=98)form eastern China showed that the detection rates of UV filters were from 68.4%to 94.9%,and the concentration of?_{UV filters}(BP-3,4-MBC,HMS,OC)was in the range of 1.17?52.15?g g^-1 Cr with a median value of 3.73?g g^-1 Cr.BP-3 was the most abundant in human urine(median:1.89?g g^-1 Cr),approximately 3?10 times of others.BP-3 in human urine was significantly positive correlation with HMS(P<0.05).Significantly higher levels of UV filters were observed in human urine from adults than from children(P<0.05),higher in urine from females than from males(P<0.05).No significant correlations were found between UV filter concentrations in paired urine and dust samples.(4)The in vitro experiments indicated that after exposure to four UV filters(BP-3,4-MBC,EHMC,BDM)of environmental relevant concentrations(10^-6 mol L^-1?10^-5 mol L^-1),significant increases were found in the production of various inflammatory cytokines in macrophages,particular TNF-?and IL-6.UV filters significantly increased TNF-?and IL-6 m RNA expression(1.1?1.5 fold,P<0.05).In addition,both the p38 MAPK and the NF-?B signaling pathways were enhanced 2 to10 times in terms of phosphorylation after exposure to the UV filters,suggesting that these pathways are involved in the release of TNF-?and IL-6.The results provide new clue for the development of asthma or allergic diseases.Molecular docking indicated that the UV filter molecules bound TAK1 efficiently via?-?stacking,hydrogen bond,and hydrophobic force.Molecular dynamic simulation displayed the stable binding mode between UV filters and TAK1,and the binding did not affect the primary structure of protein.The above resluts predicted that all four UV filter molecules would efficiently bind TAK1,which is responsible for the activation of the p38 MAPK and NF-?B pathways.(5)Exposure risk assessment showed that the total daily intake of organic UV filters increased with age.Infants and toddlers malinly intake UV filters via dringking water(50.8%),indoor air(29.5%),and indoor air(17.3%);adults mainly intake UV filters via PCPs application(45.9%).Indoor environment is one of the main ways to intake UV filters for infants(46.8%).Health risk evaluation showed that the hazard index for children and adults of total UV filters>0.1,indicating a low hazard to humans.In this paper,we systematically analyzed the indoor pollution characteristics of organic UV filters,and explored the immune toxicity effects and mechanisms of organic UV filters on human macrophages.The results have important reference value for the health risk assessment of emerging contaminants,and provides new ideas for the further understanding of the toxicity of organic UV filters in human body.