Abstract

Background:

Research on the health effects of chemical mixtures has focused mainly on early life rather than adolescence, a potentially important developmental life stage.

Objectives:

We examined associations of a metal mixture with general cognition in a cross-sectional study of adolescents residing near ferromanganese industry, a source of airborne metals emissions.

Methods:

We measured manganese (Mn), lead (Pb), copper (Cu), and chromium (Cr) in hair, blood, urine, nails, and saliva from 635 Italian adolescents 10–14 years of age. Full-scale, verbal, and performance intelligence quotient (FSIQ, VIQ, PIQ) scores were assessed using the Wechsler Intelligence Scale for Children-III. Multivariable linear regression and Bayesian kernel machine regression (BKMR) were used to estimate associations of the metal mixture with IQ. In secondary analyses, we used BKMR’s hierarchical variable selection option to inform biomarker selection for Mn, Cu, and Cr.

Results:

Median metal concentrations were as follows: hair Mn, $0.08\mathrm{\mu }\mathrm{g}/\mathrm{g}$; hair Cu, $9.6\mathrm{\mu }\mathrm{g}/\mathrm{g}$; hair Cr, $0.05\mathrm{\mu }\mathrm{g}/\mathrm{g}$; and blood Pb, $1.3\mathrm{\mu }\mathrm{g}/\text{dL}$. Adjusted models revealed an inverted U-shaped association between hair Cu and VIQ, consistent with Cu as an essential nutrient that is neurotoxic in excess. At low levels of hair Cu (10th percentile, $5.4\mathrm{\mu }\mathrm{g}/\mathrm{g}$), higher concentrations (90th percentiles) of the mixture of Mn, Pb, and Cr ($0.3\mathrm{\mu }\mathrm{g}/\mathrm{g}$, $2.6\mathrm{\mu }\mathrm{g}/\text{dL}$, and $0.1\mathrm{\mu }\mathrm{g}/\mathrm{g}$, respectively) were associated with a 2.9 (95% CI: $-5.2$, $-0.5$)–point decrease in VIQ score, compared with median concentrations of the mixture. There was suggestive evidence of interaction between Mn and Cu. In secondary analyses, saliva Mn, hair Cu, and saliva Cr were selected as the biomarkers most strongly associated with VIQ score.

Discussion:

Higher adolescent levels of Mn, Pb, and Cr were associated with lower IQ scores, especially at low Cu levels. Findings also support further investigation into Cu as both beneficial and toxic for neurobehavioral outcomes. https://doi.org/10.1289/EHP6803

中文翻译：

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多种生物标记物中测量的金属混合物与 IQ 的关联：来自居住在铁合金工业附近的意大利青少年的证据。

摘要

背景：

关于化学混合物对健康影响的研究主要集中在生命早期而不是青春期，青春期是一个潜在的重要发展阶段。

目标：

我们在一项针对居住在铁锰工业附近的青少年的横断面研究中检查了金属混合物与一般认知的关联，铁锰工业是空气中金属排放的来源。

方法：

我们测量了 635 名 10-14 岁意大利青少年的头发、血液、尿液、指甲和唾液中的锰 (Mn)、铅 (Pb)、铜 (Cu) 和铬 (Cr)。使用 Wechsler Children-III 智力量表评估全面、语言和表现智商（FSIQ、VIQ、PIQ）分数。多变量线性回归和贝叶斯核机器回归 (BKMR) 用于估计金属混合物与智商的关联。在二次分析中，我们使用 BKMR 的分层变量选择选项来告知 Mn、Cu 和 Cr 的生物标志物选择。

结果：

中值金属浓度如下：头发Mn，$0.08\mathrm{\mu }\mathrm{G}/\mathrm{G}$; 头发铜，$9.6\mathrm{\mu }\mathrm{G}/\mathrm{G}$; 头发Cr，$0.05\mathrm{\mu }\mathrm{G}/\mathrm{G}$; 和血铅，$1.3\mathrm{\mu }\mathrm{G}/\text{分升}$. 调整后的模型显示头发铜和 VIQ 之间存在倒 U 形关联，这与铜是一种过量的神经毒性必需营养素一致。在低水平的头发铜（第 10 个百分位数，$5.4\mathrm{\mu }\mathrm{G}/\mathrm{G}$), Mn、Pb 和 Cr ($0.3\mathrm{\mu }\mathrm{G}/\mathrm{G}$,$2.6\mathrm{\mu }\mathrm{G}/\text{分升}$， 和$0.1\mathrm{\mu }\mathrm{G}/\mathrm{G}$, 分别) 与 2.9 (95% CI:$-5.2$,$-0.5$)– 与混合物的中值浓度相比，VIQ 分数降低了一点。有迹象表明 Mn 和 Cu 之间存在相互作用。在二次分析中，唾液 Mn、头发 Cu 和唾液 Cr 被选为与 VIQ 评分最相关的生物标志物。

讨论：

较高的青少年 Mn、Pb 和 Cr 水平与较低的 IQ 分数相关，尤其是在低 Cu 水平时。研究结果还支持进一步研究铜对神经行为结果的有益和毒性。https://doi.org/10.1289/EHP6803