Exposure Trends to the Non-phthalate Plasticizers DEHTP, DINCH, and DEHA in Children from 2012 to 2017: The Hokkaido Study

Abstract

Phthalates owing to their endocrine-disrupting effects are regulated in certain products, leading to their replacement with substitutions such as di-2-ethylhexyl terephthalate (DEHTP), 1,2-cyclohexane dicarboxylic acid di(isononyl) ester (DINCH), and di(2-ethylhexyl) adipate (DEHA). However, information on human exposure to these substitutes, especially in susceptible subpopulations such as children, is limited. Thus, we examined the levels and exposure trends of DEHTP, DINCH, and DEHA metabolites in 7 year-old Japanese school children. In total, 180 urine samples collected from 2012 to 2017 were used to quantify 10 DEHTP, DINCH, and DEHA metabolites via isotope dilution liquid chromatography with tandem mass spectrometry. DEHTP and DINCH metabolites were detected in 95.6 and 92.2% of the children, respectively, and DEHA was not detected. This study, annually conducted between 2012 and 2017, revealed a significant (p < 0.05) 5-fold increase in DEHTP metabolites and a 2-fold increase in DINCH metabolites. However, the maximum estimated internal exposures were still below the health-based guidance and toxicological reference values. Exposure levels to DEHTP and DINCH have increased considerably in Japanese school children. DEHA is less relevant. Future studies are warranted to closely monitor the increasing trend in different aged and larger populations and identify the potential health effects and sources contributing to increasing exposure and intervene if necessary.

Global environmental and toxicological data of emerging plasticizers: current knowledge, regrettable substitution dilemma, green solution and future perspectives

“…100 The concentration of DINCH is rising in populations; especially, reports are emerging for mothers 100 and children 124 as indicated above (due to high exposure levels and lower tolerance levels), which need serious consideration and intervention if necessary. 123 Despite this evidence, some researchers, companies, and agencies consider DINCH to be the least or non-toxic, safe, and non-bioaccumulative, 67,[124][125][126] which is indeed alarming and should be challenged to avoid global contamination and regrettable substitution at early stages.…”

“…The concentration of DINCH is rising in populations; especially, reports are emerging for mothers 100 and children 124 as indicated above (due to high exposure levels and lower tolerance levels), which need serious consideration and intervention if necessary. 123…”

Association of Di(2-ethylhexyl) Terephthalate and Its Metabolites with Nonalcoholic Fatty Liver Disease: An Epidemiology and Toxicology Study

“…The extensive use of DEHTP reported in recent years implies an increasing exposure risk for people. Human biomonitoring studies in several countries, such as the U.S., Belgium, Germany, Mexico, Japan, and Denmark, have shown that representative urinary metabolites of DEHTP, such as mono­(2-ethyl-5-hydroxyhexyl) terephthalate (MEHHTP or 5 OH-MEHTP) and mono­(2-ethyl-5-carboxypentyl) terephthalate (MECPTP or 5 cx-MEPTP), were detectable in almost all populations and at increasing concentrations over time. − Saudi children and U.S. pregnant women had similar or higher concentrations of urinary DEHTP metabolites than DEHP metabolites. − Craig et al evaluated the exposure of nail salon workers to 19 semivolatile organic compounds and found that urinary DEHTP metabolite (i.e., MECPTP) was the one that changed the most pre- and postshifts . Despite limited knowledge regarding DEHTP’s health consequences in humans, such observations have raised public health concerns.…”