研究実績の概要 |
Urine was collected from 7-year-old children participating in the Hokkaido birth cohort, and 10 metabolites of 4 phthalate compounds were measured by UPLC-MS/MS. Levels of 3 oxidative stress markers (8-OHdG, HEL, HNE)) were measured by ELISA kits. ISAAC questionnaire completed by parents of the child used to define wheeze, rhino conjunctivitis, and eczema. All metabolites were detected in > 96% of samples. Highest detection was in MECPP, MnBP, and MEHHP with median 37.4 ng/mL, 36.8 ng/mL, and 25.8 ng/mL, respectively. No exposure change was observed in these phthalate metabolites from 2012 to 2017. The Japan phthalate ester regulation revised in 2010 in toys and food containers related to children could not alter the phthalates exposure change. Individual phthalate metabolites, MECPP (OR = 1.41) and cx-MINP (OR = 1.40) increased the risk of wheeze. In a mixed exposure analysis, the Weighted Quantile Sum index showed significant association (OR = 1.46) with wheeze and (OR = 1.40) eczema. The Bayesian Kernel Machine Regression model, DINP metabolites showed the highest group posterior inclusion probability (PIP). Among DINP metabolites, MINP in wheeze, cx-MINP in rhino-conjunctivitis and OH-MINP in eczema showed the highest conditional PIPs. The overall metabolites mixture effect was associated with eczema. On the contrary, no mediation of oxidative stress was observed in the association between phthalates and symptoms, which may be due to low oxidative stress. Participants in this study were only 7 years old, demonstrating the importance of continuing the study in the future.
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