Hokkaido University, Center for Environmental and Health Sciences, Kita 12, Nishi 7, Kita-ku, Sapporo, 060-0812, Japan.
Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
Environ Res. 2020 Apr;183:109212. doi: 10.1016/j.envres.2020.109212. Epub 2020 Feb 3.
Phthalate esters and phosphate flame retardants and plasticizers (PFRs) are both used as plasticizers and are commonly detected in indoor environments. Although both phthalates and PFRs are known to be associated with children's wheeze and allergic symptoms, there have been no previous studies examining the effects of mixtures of these exposures.
To investigate the association between exposure to mixtures of phthalate esters and PFRs, and wheeze and allergic symptoms among school-aged children.
A total of 128 elementary school-aged children were enrolled. Metabolites of 3 phthalate esters and 7 PFRs were measured in urine samples. Parent-reported symptoms of wheeze, rhinoconjunctivitis, and eczema were evaluated using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. In the primary model, we created a phthalate ester and PFR mixture exposure index, and estimated odds ratios (ORs) using weighted quantile sum (WQS) regression and quantile g (qg)-computation. The two highest chemicals according to qg-computation weight %s were combined to create a combination high × high exposure estimate, with ORs calculated using the "low × low" exposure group as the reference category. Concentrations of each metabolite were corrected by multiplying this value by the sex- and body size-Standardised creatinine concentration and dividing by the observed creatinine value. All models were adjusted for sex, grade, dampness index and annual house income.
The odds ratio of rhinoconjunctivitis for the association between exposure to chemical mixtures according to the WQS index positive models was; OR = 2.60 (95% confidence interval [CI]: 1.38-5.14). However, wheeze and eczema of the WQS index positive model, none of the WQS index negative models or qg-computation result yielded statistically significant results. Combined exposure to the two highest WQS weight %s of "high-high" ΣTCIPP and ΣTPHP was associated with an increased prevalence of rhino-conjunctivitis, OR = 5.78 (1.81-18.43) to the "low × low" group.
Significant associations of mixed exposures to phthalates and PFRs and increased prevalence of rhinoconjunctivitis was found among elementary school-aged children in the WQS positive model. Mixed exposures were not associated with any of allergic symptoms in the WQS negative model or qg-computation approach. However, the combined effects of exposure to two PFRs suggested an additive and/or multiplicative interaction, potentially increasing the prevalence of rhinoconjunctivitis. A further study with a larger sample size is needed to confirm these results.
邻苯二甲酸酯和磷酸盐阻燃剂和增塑剂（PFRs）都被用作增塑剂，并且通常在室内环境中被检测到。尽管邻苯二甲酸酯和 PFRs 都已知与儿童喘息和过敏症状有关，但以前没有研究过这些暴露的混合物的影响。
研究邻苯二甲酸酯和 PFRs 混合物暴露与学龄儿童喘息和过敏症状之间的关系。
共纳入 128 名小学生。在尿液样本中测量了 3 种邻苯二甲酸酯和 7 种 PFR 代谢物。使用国际儿童哮喘和过敏研究（ISAAC）问卷评估父母报告的喘息、鼻结膜炎和湿疹症状。在主要模型中，我们创建了邻苯二甲酸酯和 PFR 混合物暴露指数，并使用加权分位数总和（WQS）回归和分位数 g（qg）计算估计比值比（OR）。根据 qg 计算权重 %，将两种最高的化学物质组合在一起，创建一个组合高×高暴露估计值，使用“低×低”暴露组作为参考类别计算 OR。每个代谢物的浓度通过将该值乘以性别和身体大小标准化的肌酐浓度并除以观察到的肌酐值进行校正。所有模型均调整了性别、年级、湿度指数和年收入。
根据 WQS 指数阳性模型，化学混合物暴露与鼻结膜炎之间的关联的比值比为；OR=2.60（95%置信区间[CI]：1.38-5.14）。然而，WQS 指数阳性模型的喘息和湿疹，WQS 指数阴性模型或 qg 计算结果均未得出统计学意义的结果。暴露于两个最高 WQS 权重 %的“高-高”ΣTCIPP 和 ΣTPHP 的组合与“低×低”组相比，与鼻结膜炎的患病率增加相关，OR=5.78（1.81-18.43）。
在 WQS 阳性模型中，邻苯二甲酸酯和 PFRs 的混合暴露与学龄儿童鼻结膜炎的患病率增加之间存在显著关联。在 WQS 阴性模型或 qg 计算方法中，混合暴露与任何过敏症状均无关联。然而，两种 PFR 暴露的组合效应表明存在相加和/或相乘相互作用，可能会增加鼻结膜炎的患病率。需要进一步的研究来确认这些结果。
