NHRI researchers conduct a benchmark dose study of prenatal exposure to DEHP and behavioral problems in children

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) of 50 μg/kg_bw/day and reference dose (RfD) of 20 μg/kg_bw/day. Given the ubiquitous existence of DEHP in the environment and its impacts on public health, Dr. Chu-Chih Chen from the Institute of Population Sciences collaborated with Dr. Shu-Li Julie Wang from the National Institute of Environmental Health Sciences to derive the prenatal DEHP exposure level that is acceptable without adverse effects on children’s neurobehavioral development using a benchmark dose approach.

The team analyzed a total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study 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. A multivariate regression model was employed to assess the statistical associations between the estimated maternal average daily intake of DEHP and child’s individual child behavior checklist (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. The team 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, the team went further to derive the benchmark dose (BMD) and the lower limit (BMDL).

The team reported associations of maternal DEHP exposure (median 4.54 μg/kg_bw/day) with the CBCL scores were all significant, except for somatic complaints, adjusting for child’s age, gender, IQ, and family income. The lower bound benchmark dose (BMDL), given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 μg/kg_bw/day (2.16 μg/kg_bw/day) for an integrated CBCL score. These findings suggested that the current TDI and RfD for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. The above findings have been published in International Journal of Hygiene and Environmental Health (2019 Jun 17;Article in Press).

Citation: Chen, CC; Wang, YH; Chen, WJ; Hsiung, CA; Leon Guo, YL; Julie Wang, SL. A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children. International Journal of Hygiene and Environmental Health. 2019 Jun 17;Article in Press.

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