Mixture exposure to plastic-related short half-life chemicals and associations with childhood asthma and allergies: The Hokkaido Study

In recent years, exposure to environmental chemicals is thought to be one of the factors contributing to allergies. However, studies examining the effects of mixture chemical exposures on allergies are limited. The aim of this study is to examine the associations between exposure to mixtures of phthalates, phosphorous flame retardants (PFRs), bisphenols (BPs) and childhood allergies. This study is a part of an on-going birth cohort, the Hokkaido Study. Wheeze, rhino-conjunctivitis, and eczema were defined by the ISAAC questionnaire at age 7. Morning void urine of children was also collected at age 7 for exposure measurements. We included 346 children who were selected based on a case-cohort design (n=400) and we completed exposure measurements of all three classes of chemicals. We measured 10 and 13 urinary metabolites of phthalates and PFRs respectively using LC-MS/MS, and 7 BPs using GC-MS/MS. Associations between the chemical mixtures and allergies were examined by Weighted Quantile Sum (WQS) analyses adjusted for sex, BMI, and environmental tobacco smoke. The exposure levels were corrected by individual urinary creatinine and ln-transformed. The most dominant urinary markers of phthalates, PFRs and BPs were 5cx-MEPP (median 38.5 ng/mL), BCIPHIPP (0.38 ng/mL), and BPA (0.89 ng/mL), respectively. In WQS analyses, exposure to mixtures of chemicals was associated with increasing risks of wheeze (OR, 95%CI: 2.0, 1.3-3.1), rhino-conjunctivitis (1.8, 1.1-3.1), and eczema (1.8, 1.2-2.8). The contributions of each chemical were BDCIPP (33%) and cx-MiNP (13%) for wheeze, BPF (13%) and BPA (10%) for rhino-conjunctivitis, and BBOEHEP (23%) and 5oxo-MEHP (18%) for eczema, respectively. Compounds showing high contributions to rhino-conjunctivitis and eczema were consistent with previous reports examining single exposures. However, the interpretation should be considered with caution, as urinary concentrations were measured only once, and the study was cross-sectional with a modest sample size. Keywords: Mixture exposure, childhood allergies, cross-sectional study