Association of urinary concentrations of phthalate metabolites with quinolinic acid among women: A potential link to neurological disorders,Environment International

当前位置： X-MOL 学术 › Environ. Int. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Association of urinary concentrations of phthalate metabolites with quinolinic acid among women: A potential link to neurological disorders
Environment International ( IF 10.3 ) Pub Date : 2020-03-14 , DOI: 10.1016/j.envint.2020.105643
Feiby L Nassan ₁ , Joshua A Gunn ₂ , Melissa M Hill ₂ , Paige L Williams ₃ , Russ Hauser ₄

Affiliation

Background

Quinolinic acid (QA), a neuroactive metabolite produced during tryptophan degradation, is implicated in the pathogenesis of several neurological disorders. Phthalates are structurally similar to QA, and exposure to phthalates has demonstrated increased QA production and excretion in rodent studies. We recently showed that very high exposure to dibutyl phthalate was associated with higher concentrations of urinary QA in men. However, no human studies examined the associations between background (low) phthalate exposures and QA.

Objectives

To examine the associations of urinary concentrations of phthalate metabolites with QA.

Methods

Female participants (N = 126) who participated in a prospective cohort study at the Massachusetts General Hospital Fertility Center provided 758 urine samples (273 during pregnancy and 485 during non-pregnancy). Concentrations of 11 phthalate metabolites and QA in urine were measured. We used multivariable linear mixed effect models to estimate the percent change in urinary QA concentrations associated with a doubling (100%) of urinary phthalate metabolite concentration, and evaluated whether there was effect modification by pregnancy status.

Results

Women’s mean (standard deviation) age was 34.2 (4.0) years with a body mass index of 23.5 (3.7) kg/m². The women were primarily Caucasian (92%), had at least a college degree (98%), and none were current smokers. Pairwise Spearman correlations between concentrations for phthalate metabolites and QA measured in the same urine samples ranged from 0.36 for MEHP to 0.68 for dibutyl phthalate (DBP) metabolites. In multivariable-adjusted models, the percent change in urinary QA concentrations was significantly higher for each doubling of several urinary phthalate metabolite concentrations. For example, each doubling of DBP metabolites was associated with a 13.7% (95%CI: 10.6, 16.9)% higher QA. Associations between the low molecular weight phthalate metabolites and QA were stronger among samples collected during pregnancy as compared to non-pregnancy samples from the same women.

Conclusions

Urinary concentrations of several phthalate metabolites were positively associated with QA among women. These findings, along with the known neurotoxicity of QA, warrant the need to examine whether QA concentrations may serve as a pathway for the adverse neurodevelopment outcomes found in children’s health studies.

中文翻译：

女性尿液中邻苯二甲酸酯代谢物浓度与喹啉酸的关联：与神经系统疾病的潜在联系

背景

喹啉酸 (QA) 是色氨酸降解过程中产生的一种神经活性代谢物，与多种神经系统疾病的发病机制有关。邻苯二甲酸盐在结构上与 QA 相似，啮齿动物研究表明，接触邻苯二甲酸盐会增加 QA 的产生和排泄。我们最近发现，男性大量接触邻苯二甲酸二丁酯与尿液中 QA 浓度较高有关。然而，没有人类研究检验背景（低）邻苯二甲酸盐暴露与质量保证之间的关联。

目标

检查尿液中邻苯二甲酸酯代谢物浓度与 QA 的关系。

方法

参与马萨诸塞州总医院生育中心前瞻性队列研究的女性参与者 (N = 126) 提供了 758 份尿液样本（273 份怀孕期间的尿液样本，485 份非怀孕期间的尿液样本）。测量了尿液中 11 种邻苯二甲酸酯代谢物和 QA 的浓度。我们使用多变量线性混合效应模型来估计与尿邻苯二甲酸酯代谢物浓度加倍 (100%) 相关的尿 QA 浓度的百分比变化，并评估妊娠状态是否会影响效果。

结果

女性的平均（标准差）年龄为 34.2 (4.0) 岁，体重指数为 23.5 (3.7) kg/m ² 。这些女性主要是白人（92%），至少拥有大学学位（98%），并且目前没有吸烟者。同一尿液样本中邻苯二甲酸酯代谢物浓度与 QA 之间的成对 Spearman 相关性范围为 MEHP 的 0.36 到邻苯二甲酸二丁酯 (DBP) 代谢物的 0.68。在多变量调整模型中，尿中邻苯二甲酸酯代谢物浓度每次加倍时，尿中 QA 浓度的百分比变化显着更高。例如，DBP 代谢物每增加一倍，QA 就会提高 13.7% (95%CI: 10.6, 16.9)%。与同一女性的非怀孕样本相比，怀孕期间收集的样本中低分子量邻苯二甲酸酯代谢物与 QA 之间的关联更强。