Urinary phthalate metabolites over the first 15 months of life and risk assessment – CHECK cohort study
Graphical abstract
Introduction
Phthalates have been used in various consumer products such as vinyl floors, food processing materials, plastic bags, toys, and personal care products. In addition, diets, water, and dust are also reported as major exposure sources of phthalates to human (Fromme et al., 2013, Guo and Kannan, 2011, Koch et al., 2013). As a consequence, phthalates and their metabolites have been frequently detected in human urines and breast milks around the world (Katsikantami et al., 2016).
Phthalate exposure has been associated with various adverse health effects such as endocrine disruption and neurodevelopmental disorders (Engel et al., 2009). Especially, fetuses and young children are thought to be vulnerable to the phthalate exposure. Prenatal exposure to di-ethyl hexyl phthalate (DEHP) or di-n-butyl phthalate (DnBP) has been associated with adverse mental and motor development (Kim et al., 2011, Whyatt et al., 2012) and neurobehavioral disorders (Kobrosly et al., 2014) in children. Exposure to DEHP metabolites during gestation is associated with increased risk of genital anomalies in male infants (Sathyanarayana et al., 2016). Negative health effects due to the postnatal exposure to phthalates were also reported among children. In Main et al. (2006), breast milk mono-n-butyl phthalate (MnBP), mono-iso-nonyl phthalate (MiNP), and monoethyl phthalate (MEP) levels showed strong inverse association with free serum testosterone levels, and positive associations with serum luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels, suggesting anti-androgenic effects of these compounds. Urinary levels of several phthalate metabolites were significantly associated with anti-androgenic effects, delays of growth and timing of pubertal onset, and serum testosterone levels in boys (Xie et al., 2015, Zhang et al., 2015). In Canada and Korea, urinary concentrations of DEHP metabolites, and MnBP or mono-benzyl phthalate (MBzP) showed significant associations with learning and behavioral problems in children (Arbuckle et al., 2016, Park et al., 2014).
As both behavior and diet would change rapidly during infancy and early childhood, not to mention physiological changes such as body weight or metabolic activities, exposure profile of phthalates are expected to vary significantly during these early stages of life. Therefore, understanding exposure levels of phthalates during these stages is important, but very limited information is available (Arbuckle et al., 2016, Carlstedt et al., 2013, Frederiksen et al., 2014, Sathyanarayana et al., 2008, Volkel et al., 2014). Among Korean children, urinary levels of phthalate metabolites of infants up to 72 weeks of age have been reported, but the age of the infants was not specified (Kim et al., 2011, Song et al., 2013).
The present study was conducted to determine the temporal pattern of major phthalates exposure among young children (< 15 months of age). For this purpose, we collected urine samples from young children of 3–15 months of age who participated in ‘Children's Health and Environmental Chemicals in Korea (CHECK)’ cohort. Health risks associated with phthalate exposure were assessed as well. The results of this study will help identify important phthalates of concern during infancy and early childhood, and develop necessary mitigation measures.
Section snippets
Study population, questionnaire and sample collection
The CHECK cohort is composed of healthy pregnant women and their full term babies recruited from areas representing metropolitan, industrial, residential, and pristine areas of Korea, and is expected to represent general population in Korea (Lee et al., 2013, Kim et al., 2016). Young infants of CHECK cohort were followed up for collecting urine samples between 2012 and 2013. From 171 participating infants or children, a total of 286 urine samples were collected, i.e., 81, 83, 35, and 17 urine
Use of cloth diaper to collect urine samples from young children
Trace levels of MEHP were detected from blank cloth diapers. In the cloth diapers (n = 5) that were used for the urine sampling, on average 1.09 μg/L (SD of 0.37) of MEHP was detected. The other DEHP metabolites such as MEHHP and MEOHP, as well as MEP, MiBP, and MnBP were not detected in the blank diapers. Since MEHP is a hydrolytic metabolite of DEHP, that can be formed during sample collection, transportation, or sample preparation by external DEHP contamination (Koch et al., 2003b), our
Conclusions
Infants during the first 15 months of age were widely exposed to phthalates, and their exposure levels increased by time. Depending on the age, between 4 and 26% of the infants showed HI > 1, implying possible endocrine disrupting consequences. The estimated risks were mostly due to the exposure to DEHP and DnBP. The within-subject variation was lessor for DEHP and DnBP metabolites, indicating consistent exposure sources present in the nurturing environment. Further researches on exposure sources
Contributors' statement
SMK and JIP conducted questionnaire survey, analyzed data, and prepared manuscript. HJK, JJL, GYC, SRC, SJK, SYK, GJC, YDK, ESS, SKK, SHE, SYE, SHK, and GHK recruited subjects, collected biological specimens, and contributed the interpretation of the clinical data. JWL, HBM and SKK analyzed the compounds, and KHC designed the study and prepared the manuscript.
Acknowledgements
We would like to thank participating mothers and their young children in Children's Health and Environmental Chemicals in Korea (CHECK) cohort. This study was funded by the Korea Ministry of Environment (MOE) in “Environmental Health Action Program (1485014467)”. This study employed the samples collected by support from Ministry of the Food and Drug Safety (12162MFDS731).
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