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 (-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, -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, -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, -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.

中文翻译：

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HBM4EU 一致性研究中欧洲儿童和青少年的尿邻苯二甲酸盐/DINCH 代谢物浓度和体重指数：一项横断面多国研究


邻苯二甲酸盐在环境中普遍存在。尽管半衰期很短，但长期接触可能会导致内分泌紊乱。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盐/DINCH 代谢物浓度与体重指数 (BMI) z 分数之间的关联。我们使用了欧洲联合研究人类生物监测数据，该数据来自 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），其中含有多达 14 种邻苯二甲酸盐/DINCH 尿液代谢物。我们使用多级线性回归来评估邻苯二甲酸盐/DINCH 浓度与 BMI z 分数之间的关联，并测试性别影响的影响。在一个子集中，贝叶斯核机器回归 (BKMR) 和基于分位数的 g 计算评估了重要的预测变量和混合效应。在儿童中，我们发现单一污染物模型中几乎没有关联，并且没有性别间的相互作用（-相互作用> 0.1）。 BKMR 未检测到相关暴露（后包含概率，PIP < 0.25），也未检测到联合混合效应。在青少年单一污染物分析中，邻苯二甲酸单乙酯 (MEP) 浓度与男性较高的 BMI z 分数相关（β = 0.08，95% CI：0.001,0.15，ln 转换浓度每四分位数增加，-相互作用 = 0.06）。相反，邻苯二甲酸单异丁酯 (MiBP) 与两性的较低 BMI z 分数相关（β = -0.13，95 % CI：-0.19，-0.07，-交互作用 = 0.74），di(2 的总和)邻苯二甲酸-乙基己酯 (ΣDEHP) 仅在女性中代谢（β = -0.08，95 % CI：-0.14，-0.02，-相互作用 = 0.01）。在 BKMR 中，MEP (PIP=0.90) 和 MBzP (PIP=0.84) 预测男性的 BMI z 分数较高。 MiBP (PIP=0.999)、OH-MIDP (PIP=0.999) 预测较低的 BMI z 分数。88) 和 OH-MINCH (PIP=0.72) 在两性中均存在，而 DEHP (PIP=0.61) 在女性中的稳健性较差。在分位数 g 计算中，男性的总体混合效应为零，女性​​的趋势为负（β = -0.11，95% CI：-0.25，0.03，每个联合暴露分位数）。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和 BMI z 分数之间的年龄/性别差异在青少年中更为明显。需要进行重复邻苯二甲酸盐测量的纵向研究。