Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway; PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, University of Oslo, Oslo, Norway.
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Sweden.
Environ Int. 2024 Aug;190:108931. doi: 10.1016/j.envint.2024.108931. Epub 2024 Aug 3.
Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear.
To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents.
We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6-12 years, 2014-2021) and 2499 adolescents (10 studies, 12-18 years, 2014-2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects.
In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (β = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (β = -0.13, 95 % CI: -0.19, -0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (β = -0.08, 95 % CI: -0.14, -0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (β = -0.11, 95 % CI: -0.25, 0.03, per joint exposure quantile).
In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.
邻苯二甲酸酯在环境中无处不在。尽管半衰期较短，但长期接触仍可能导致内分泌紊乱。邻苯二甲酸酯替代品 DINCH 的安全性尚不清楚。
评估儿童和青少年尿液中邻苯二甲酸酯/DINCH 代谢物浓度与体重指数（BMI）z 评分之间的关联。
我们使用了来自 2876 名儿童（12 项研究，6-12 岁，2014-2021 年）和 2499 名青少年（10 项研究，12-18 岁，2014-2021 年）的欧洲人体生物监测研究数据，这些儿童和青少年的尿液中最多含有 14 种邻苯二甲酸酯/DINCH 代谢物。我们使用多水平线性回归来评估邻苯二甲酸酯/DINCH 浓度与 BMI z 评分之间的关联，检验性别对这些关联的调节作用。在一个亚组中，贝叶斯核机器回归（BKMR）和基于分位数的 g 计算法评估了重要的预测因素和混合效应。
在儿童中，我们在单污染物模型中发现了一些关联，且性别之间没有交互作用（p 交互作用>0.1）。BKMR 未检测到相关暴露（后验纳入概率，PIP<0.25），也未检测到联合混合效应。在青少年的单污染物分析中，单乙基邻苯二甲酸酯（MEP）浓度与男性的 BMI z 评分呈正相关（β=0.08，95%CI：0.001，0.15，ln 转化浓度的每四分位距增加，p 交互作用=0.06）。相反，单异丁基邻苯二甲酸酯（MiBP）与两性的 BMI z 评分呈负相关（β=-0.13，95%CI：-0.19，-0.07，p 交互作用=0.74），女性中二（2-乙基己基）邻苯二甲酸酯（∑DEHP）代谢物的总和也是如此（β=-0.08，95%CI：-0.14，-0.02，p 交互作用=0.01）。在 BKMR 中，男性的 BMI z 评分与 MEP（PIP=0.90）和 MBzP（PIP=0.84）呈正相关，而 MiBP（PIP=0.999）、OH-MIDP（PIP=0.88）和 OH-MINCH（PIP=0.72）在两性中呈负相关，在女性中 DEHP（PIP=0.61）的相关性稍弱。在分位数 g 计算法中，男性的整体混合效应为零，女性的混合效应为负（β=-0.11，95%CI：-0.25，0.03，每联合暴露分位数增加）。
在这项欧洲范围内的大型研究中，我们发现邻苯二甲酸酯代谢物与 BMI z 评分之间存在年龄/性别特异性差异，在青少年中更为明显。需要进行具有重复邻苯二甲酸酯测量的纵向研究。
