title: Association of current phthalate exposure with neurobehavioral development in a national sample.
abstract: Previous studies have indicated that phthalate exposure may influence the development of children, but the current data are limited, and controversy remains regarding the sex-specific and age-specific effects of phthalate exposure.
  
  
  
  We investigated the sex- and age-specific associations of current phthalate exposure with neurobehavioral development scores in a nationally representative sample of 6-18-year-olds participating in the Korean Environmental Health Survey in Children and Adolescents (KorEHS-C). Neurobehavioral development was assessed using the Korean Child Behavior Checklist (CBCL, N=1723) and the Korean Attention Deficit Hyperactivity Disorder Rating Scale (ARS, N=867). We measured the concentrations of phthalate metabolites in urine samples using high-performance liquid chromatography tandem mass spectrometry. The associations between urine phthalate metabolite concentrations and neurobehavioral development were examined by survey regression analysis for complex sampling and penalized regression splines using a generalized additive model.
  
  
  
  Survey regression analysis revealed that a higher mono-n-butyl phthalate (MnBP) level was associated with social (β=0.60; 95% confidence interval=0.15-1.05), thought (0.55; 0.08-1.03), and attention (0.68; 0.21-1.14) problems on the CBCL. A significant association was found between the MnBP level and the ARS hyperactivity subscale score (0.42; 0.05-0.58). Higher levels of MnBP (0.87; 0.20-1.54), mono-2-ethyl-5-oxohexyl phthalate (MEOHP, 0.61; 0.11-1.11) and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP, 0.51; 0.04-0.97) were associated with an increase in thought problems among the girls. Among the younger children aged 6-11 years, significant positive associations between the MnBP (0.71; 0.09-1.33), MECPP (0.74, 0.14-1.34), MEOHP (0.65; 0.10-1.20), and MEHHP (0.71; 0.21-1.21) levels and social problems and between the MnBP (1.11; 0.37-1.84), MEOHP (0.64; 0.13-1.15), and MEHHP (0.66; 0.18-1.14) levels and attention problems were observed. The penalized regression splines for the age-specific relationships between the urinary MnBP, MEOHP, and MEHHP levels and social and attention problems exhibited positive supralinear relationships with downward curvature in the 6-11 year age group. In contrast, the score for social problems exhibited nearly linear relationships with these levels in the 12-18 year age group.
  
  
  
  In this national sample, increased phthalate exposure exhibited supralinear associations with social, thought and attention problems in children aged 6-11 years, who showed greater vulnerability to phthalate exposure. The results highlight the need for the environmental regulation of phthalate exposure in younger children, even at low dosages.
authors.affiliation: Department of Child Psychiatry, National Center for Child and Adolescent Psychiatry, Seoul National Hospital, Seoul, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Won
authors.affiliation: Department of Child Psychiatry, National Center for Child and Adolescent Psychiatry, Seoul National Hospital, Seoul, Republic of Korea. Electronic address: yeni1004@gmail.com.
authors.forename: Yeni
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea. Electronic address: minaha@dku.edu.
authors.forename: Mina
authors.initials: M
authors.lastname: Ha
authors.affiliation: Department of Nursing, Munkyung College, Munkyung, Republic of Korea.
authors.forename: Eunae
authors.initials: E
authors.lastname: Burm
authors.affiliation: Department of Dental Hygiene, Yeongdong University, Yeongdong, Republic of Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Hyungryul
authors.initials: H
authors.lastname: Lim
authors.affiliation: Department of Child Psychiatry, National Center for Child and Adolescent Psychiatry, Seoul National Hospital, Seoul, Republic of Korea.
authors.forename: Da-Eun
authors.initials: DE
authors.lastname: Jung
authors.affiliation: Department of Occupational and Environmental Medicine, College of Medicine, Kyunghee University, Seoul, Republic of Korea.
authors.forename: Sinye
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Preventive Medicine, School of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine, School of Medicine, Dong-A University, Busan, Republic of Korea.
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Occupational and Environmental Medicine, School of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Hwan-Cheol
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Information Statistics, College of Natural Science, Korean National Open University, Seoul, Republic of Korea.
authors.forename: Kee Jae
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Social and Preventive Medicine, School of Medicine, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Hae-Kwan
authors.initials: HK
authors.lastname: Cheong
authors.affiliation: Department of Occupational and Environmental Medicine, Wonju Severance Christian Hospital, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.
authors.forename: Hee-Tae
authors.initials: HT
authors.lastname: Kang
authors.affiliation: Department of Preventive Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Mia
authors.initials: M
authors.lastname: Son
authors.affiliation: Department of Preventive Medicine and Public Health, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Sakong
authors.affiliation: Department of Preventive Medicine, School of Medicine, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Gyung-Jae
authors.initials: GJ
authors.lastname: Oh
authors.affiliation: Department of Occupational and Environmental Medicine, School of Medicine, Chosun University, Gwangju, Republic of Korea.
authors.forename: Chul-Gab
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Department of Preventive Medicine, School of Medicine, Jeju National University, Jeju, Republic of Korea.
authors.forename: Su Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Environmental Epidemiology, Division of Environmental Health, National Institute of Environment, Incheon, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ryu
authors.affiliation: Department of Environmental Epidemiology, Division of Environmental Health, National Institute of Environment, Incheon, Republic of Korea.
authors.forename: Sue Jin
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000453:epidemiology / Q000652:urine; D002648:Child; D002652:Child Behavior; D004781:Environmental Exposure / Q000032:analysis*; D004785:Environmental Pollutants / Q000097:blood / Q000652:urine*; D005260:Female; D006801:Humans; D007854:Lead / Q000097:blood; D008297:Male; D010795:Phthalic Acids / Q000652:urine*; D056910:Republic of Korea; D012919:Social Behavior
chemical_list: D004785:Environmental Pollutants; D010795:Phthalic Acids; D007854:Lead
keywords: Adolescents; Behavior; Children; Development; Environment; Phthalate