Urinary Concentrations of Major Phthalate and Alternative Plasticizer Metabolites in Children of Thailand, Indonesia, and Saudi Arabia, and Associated Risks

Abstract

Phthalates are widely used in consumer products and are well-known for adverse endocrine outcomes. Di-(2-ethylhexyl) phthalate (DEHP), one of the most extensively used phthalates, has been rapidly substituted with alternative plasticizers in many consumer products. The aim of this study was to assess urinary phthalate and alternative plasticizer exposure and associated risks in children of three Asian countries with different geographical, climate, and cultural characteristics. Children were recruited from elementary schools of Saudi Arabia (n = 109), Thailand (n = 104), and Indonesia (n = 89) in 2017–2018, and their urine samples were collected. Metabolites of major phthalates and alternative plasticizers were measured in the urine samples by HPLC-MS/MS. Urinary metabolite levels differed substantially between the three countries. Metabolite levels of diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di­(2-ethylhexyl) terephthalate (DEHTP), and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were the highest in Saudi children: Median urinary concentrations of oxo-MiNP, OH-MiDP, 5cx-MEPTP, and OH-MINCH were 8.3, 8.4, 128.0, and 2.9 ng/mL, respectively. Urinary DEHP metabolite concentrations were the highest in the Indonesian children. The hazard index (HI) derived for the plasticizers with antiandrogenicity based reference doses (RfDAA) was >1 in 86%, 80%, and 49% of the Saudi, Indonesian, and Thai children, respectively. DEHP was identified as a common major risk driver for the children of all three countries, followed by DnBP and DiBP depending on the country. Among alternative plasticizers, urinary DEHTP metabolites were detected at levels comparable to those of DEHP metabolites or higher among the Saudi children, and about 4% of the Saudi children exceeded the health based human biomonitoring (HBM)-I value. Priority plasticizers that were identified among the children of three countries warrant refined exposure assessment for source identification and relevant exposure reduction measures.

Insights into the Endocrine Disrupting Activity of Emerging Non-Phthalate Alternate Plasticizers against Thyroid Hormone Receptor: A Structural Perspective

“…A recent study reported 56% of human serum samples from a US population had detectable levels of DINCH metabolites [ 27 ]. In another study, alternate plasticizers have been detected in urinary samples of school kids from many countries, including Saudi Arabia [ 28 ].…”

Biomarker-Determined Nonylphenol Exposure and Associated Risks in Children of Thailand, Indonesia, and Saudi Arabia

“…Moreover, associations with the low-molecular weight phthalates DMP and DEP were positive but very weak to non-existent (ρ ≤ 0.2) in all countries (Figure S1). Overall, the associations observed between NP and the plasticizers were much weaker than within the group of plasticizers in the very same population (Lee et al 2021) . There, correlations among high-molecular weight plasticizers were generally higher than or equal to ρ = 0.7 for DINP, DiDP, DINCH, and DEHTP with a similar cluster of higher associations for the low-molecular weight plasticizers.…”

“…This study has been approved by the Research Ethics Committees of King Saud University (CAMS 053-37/38), Mahidol University (MUTM2017-209-01), and Halu Oleo University (007/ECHR-IPHA/XII/2017). For details of sample collection and treatment, see Lee et al (2021) …”

“…This study population is identical to that of Lee et al. (2021) where exposures to plasticizers (phthalates and substitutes) have been investigated. Countries had been selected to represent the Middle East and Southeast Asia, regions with sparse knowledge of exposures to endocrine disruptive, environmental contaminants, especially in children.…”

“…In the present study, we apply this novel approach to determine the NP exposure in children of the three Asian countries of Thailand, Indonesia, and Saudi Arabia. This study population is identical to that of Lee et al (2021) 66 where exposures to plasticizers (phthalates and substitutes) have been investigated. Countries had been selected to represent the Middle East and Southeast Asia, regions with sparse knowledge of exposures to endocrine disruptive, environmental contaminants, especially in children.…”