A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children

Chu-Chih Chen; Yin-Han Wang; Wei J Chen; Chao A Hsiung; Yue-Liang Leon Guo; Shu-Li Julie Wang

doi:10.1016/j.ijheh.2019.06.002

A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children

Int J Hyg Environ Health. 2019 Jul;222(6):971-980. doi: 10.1016/j.ijheh.2019.06.002. Epub 2019 Jun 17.

Authors

Chu-Chih Chen¹, Yin-Han Wang², Wei J Chen³, Chao A Hsiung², Yue-Liang Leon Guo⁴, Shu-Li Julie Wang⁵

Affiliations

¹ Institute of Population Health Sciences, National Health Research Institutes, Taiwan. Electronic address: ccchen@nhri.edu.tw.
² Institute of Population Health Sciences, National Health Research Institutes, Taiwan.
³ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan.
⁴ Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taiwan; Institute of Environmental Health Sciences, National Health Research Institutes, Taiwan.
⁵ Institute of Environmental Health Sciences, National Health Research Institutes, Taiwan. Electronic address: slwang@nhri.edu.tw.

PMID: 31221485
DOI: 10.1016/j.ijheh.2019.06.002

Abstract

Introduction: Prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).

Objectives: Our aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.

Methods: A total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).

Results: Associations of maternal DEHP exposure (median 4.54μg/kg_bw/day) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) μg/kg_bw/dayfor an integrated CBCL score.

Conclusions: The current TDI (RfD) of 50 (20) μg/kg_bw/day for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.

Keywords: Child behavior checklist; Reference dose; Structural equation models; Taiwan maternal and infant cohort study; Tolerable daily intake.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Environmental Pollutants / urine*
Female
Humans
Male
Maternal Exposure*
Maternal-Fetal Exchange
Phthalic Acids / urine*
Pregnancy
Prenatal Exposure Delayed Effects*
Problem Behavior*

Substances

Environmental Pollutants
Phthalic Acids