Mediating Effect Of Oxidative Stress On The Association Between Bisphenol A,Phthalate,and Emotional And Behavioral Problems Among Adolescents

ObjectiveEmotional and behavioral problems of adolescents is a worldwide public health problem.It is still unclear that the relationship and mechanism between Bisphenol A(BPA),Phthalates(PAEs)exposure,and emotional and behavioral problems(EBPs)of adolescents.This study aimed to understand the prevalence of EBPs among Chinese adolescents,evaluate the association between BPA,PAEs exposure and EBPs,and explore the mediating effects of oxidative stress on the association of BPA,PAEs exposure and EBPs.The results could provide theoretical basis for the prevention of adolescent emotional symptoms and behavioral problems.MethodsThis study was conducted in November 2015.We collected questionnaires data and urine samples of 1047 students from one primary school and one junior high school of Shenyang by purposive sampling.A total of 1001 valid questionnaires and 907 urine samples were collected.Finally 865 adolescents were included in the data statistics.The Strengths and Difficulties Questionnaire was used to assess adolescent emotional and behavioral problems.Urinary concentrations of BPA and PAE metabolites were assessed using high-performance liquid chromatography tandem mass spectrometry,while 8-isoprostaglandin levels were determined by enzyme-linked immunosorbent assay to evaluate oxidative stress levels.SPSS 23.0(Statistical Product and Service Solution)and R 4.2.0 were used to analyze the data.Chi-square test was used to compare the prevalence of EBPs among adolescents with different social demographic characteristics.Spearman correlation analysis was used to evaluate the correlation between BPA,PAEs exposure and oxidative stress markers among adolescents.The association between BPA,PAEs metabolites,and EBPs were analyzed by logistic regression model.PROCESS software was used to analyze the mediating effect.ResultsThe average age of 865 adolescents in this study was 11.13±2.45 years old,of which 411 were boys(47.5%)and 454 were girls(52.5%).The prevalence of emotional symptoms,conduct problems,hyperactivity problems,peer problems,prosocial behaviors and total difficulties were 10.4%,9.0%,7.4%,9.1%,11.7% and 14.9%,respectively.The detection rates of bisphenol A(BPA)and phthalic acid(2-ethylhexyl)ester(MEHP),phthalic acid-mono-(2-ethyl-5-hydroxyethyl)ester(MEHHP),phthalic acid-mono-(2-ethyl-5-oxo-hexyl)ester(MEOHP),mono-methyl phthalate(MMP),mono-ethyl phthalate(MEP),mono-n-butyl phthalate(MBP)and mono-benzyl phthalate(MBZP)were from 94.6% to 99.7%,and the median of creatinine adjusted concentrations were from 0.76 to 259.87 μg/g Cr.The detection rate of 8-iso-PGF2αwas 99.4%,and the median of creatinine corrected concentration was 2.00μg/g Cr.There were positive association between BPA,PAEs metabolites and EBPs,after adjusting for confounders(age,gender,family economic level,parental education level,self-assessment pubertal status,parental smoking status and screen time).Concentration of BPA in the second,the third and the fourth quartiles were found to be positively correlated with emotional symptoms.At the same time,concentration of MEHP,MEHHP,MEOHP,MBP and MBZP were found to be positively correlated with total difficulties.Increased concentrations of MEHP and MMP in urine were correlated with higher odds of conduct problems.MEHP,MEHHP,MEOHP,MEP and MBZP were positively associated with increased risk of hyperactivity among adolescents.Concentration of MEHHP,MEOHP,MBP were found to be positively correlated with peer problems.MEHHP and MEOHP were associated with increased risk of abnormal prosocial behavior among adolescents.BPA,MEHP,MEHHP,MEOHP and MMP were associated with increased risk of total difficulties among adolescents.Mediating effect analysis showed that 8-iso-PGF2α played a partial mediating role in the association of emotional symptoms and BPA,MEHP,MEOHP,MBP before adjusting for confounding factors,and the mediating proportion was 7.1%,11.6%,5.7%and 5.7%,respectively.8-iso-PGF2α also played a partial mediating role in the association between peer problems and BPA,MEOHP,MBP,with the mediating proportion of 7.6%,4.0% and 3.9%,respectively.At the same time,8-iso-PGF2α also partially mediated the association between BPA,MBP and total difficulties,with the mediation ratio of 4.7% and 6.6%.ConclusionAdolescents are commonly exposed to BPA and PAEs in our study.BPA and PAEs exposure are associated with emotional symptoms and behavioral problems among adolescents,and oxidative stress may partially mediate the association between BPA,and PAEs exposure,and emotional symptoms and behavioral problems among adolescents.