Association of phthalate replacement DINCH metabolite concentrations with adiposity in a multi-site, multi-racial cohort of children

Abstract

BACKGROUND AND AIM: 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) is a recent plasticizer replacing high molecular weight phthalate diesters in items such as toys, medical devices, and food packaging. Little is known regarding the association of DINCH exposure and adiposity in children. METHODS: Analyses included 629 racial/ethnically diverse children ages 4-8 in the Environmental Influences on Child Health Outcomes (ECHO) study, a follow-up of the NICHD Fetal Growth Studies at 10 US sites. Urinary oxidative metabolites of DINCH (cyclohexane-1,2-dicarboxylic acid mono carboxyisooctyl [MCOCH] and cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl [MHNCH] esters) were determined using liquid chromatography tandem-mass spectrometry (UPLC-ESI-MS/MS). Values were divided by molecular weight and summed to obtain a composite DINCH value (nmol/ml). Outcomes were child’s body mass index (BMI) z-score, waist circumference z-score, percent body fat, and categorized BMI percentiles (85, 85 to 95, ≥95). Multivariable linear and logistic regression models adjusted for urine specific gravity, gender, age, race/ethnicity, birth weight, prolonged exclusive breastfeeding, reported physical activity level, frequency of fast-food consumption, cigarette smoke exposure, neighborhood traffic, mother’s education and pre-pregnancy BMI were used to analyze the association between natural log transformed DINCH levels and outcomes. RESULTS:88% of children had DINCH levels at or above the limit of detection. For each unit increase in natural log transformed DINCH there was a significant decrease in BMI z-score (β [95% CI]: -0.103 [-0.180, -0.026]), waist circumference z-score (β [95% CI]: -0.126 [-0.198, -0.054]) and percent body fat (β [95% CI]: -0.022 [-0.035, -0.009]). DINCH levels were not associated with overweight [OR=0.82 (95% CI: 0.66, 1.02)] or obese [OR=0.88 (95% CI: 0.69, 1.12)] versus normal BMI percentile categories. CONCLUSIONS:In this cross-sectional analysis there were significant inverse associations between children’s DINCH exposure levels and adiposity measures. Additional research is needed to confirm this association and identify possible interactions between DINCH and joint exposure to other related chemicals. KEYWORDS: Phthalates, Obesity and metabolic disorders, Children's environmental health