Yang An-Ming, Lai Tai-Shuan, Lin Yu-Ling, Wang ChiKang, Lin Chien-Yu
Department of Internal Medicine, En Chu Kong Hospital, No. 399, Fuxing Rd., Sanxia Dist., New Taipei City, 237, Taiwan.
Department of Healthcare Management, Yuanpei University of Medical Technology, Hsinchu, 300, Taiwan.
Environ Sci Pollut Res Int. 2023 May;30(24):66417-66425. doi: 10.1007/s11356-023-26943-0. Epub 2023 Apr 25.
Di (2-ethylhexyl) phthalate (DEHP) is a chemical commonly used in the manufacturing of plastics and can pose human health risks, including endocrine disruption, reproductive toxicity, and potential carcinogenic effects. Children may be particularly vulnerable to the harmful effects of DEHP. Early exposure to DEHP has been linked to potential behavioral and learning problems. However, there are no reports to date on whether DEHP exposure in adulthood has neurotoxic effects. Serum neurofilament light chain (NfL), a protein released into the blood after neuroaxonal damage, has been shown to be a reliable biomarker for many neurological diseases. To date, no study has examined the relationship between DEHP exposure and NfL. For the present study, we selected 619 adults (aged ≥ 20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to examine the association between urinary DEHP metabolites and serum NfL. We reported higher urinary levels of ln-mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), ln-mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and ln-mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and ln-ΣDEHP levels were associated with higher serum levels of ln-NfL (ΣDEHP: β-coefficient = 0. 075; S.E. = 0.026; P = 0.011). When we divided ΣDEHP into quartiles, mean NfL concentrations increased with quartiles of MEHHP (P for trend = 0.023). The association was more pronounced in males, non-Hispanic white race, higher income, and BMI < 25. In conclusion, higher DEHP exposure was positively associated with higher serum NfL in adults from NHANES 2013-2014. If this finding is causal, it is possible that DEHP exposure in adulthood may also induce neurological damage. Although the causality of this observation and the clinical significance are uncertain, our findings suggest that additional research is needed on DEHP exposure, serum NfL, and neurological disease in adults.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种常用于塑料制造的化学物质，会对人体健康构成风险，包括内分泌干扰、生殖毒性和潜在致癌作用。儿童可能尤其容易受到DEHP有害影响。早期接触DEHP与潜在的行为和学习问题有关。然而，迄今为止，尚无关于成年期接触DEHP是否具有神经毒性作用的报道。血清神经丝轻链（NfL）是神经轴突损伤后释放到血液中的一种蛋白质，已被证明是许多神经系统疾病的可靠生物标志物。迄今为止，尚无研究探讨DEHP暴露与NfL之间的关系。在本研究中，我们从2013 - 2014年国家健康与营养检查调查（NHANES）中选取了619名成年人（年龄≥20岁），以研究尿中DEHP代谢物与血清NfL之间的关联。我们报告尿中邻苯二甲酸单（2-乙基-5-羟基己基）酯（MEHHP）、邻苯二甲酸单（2-乙基-5-氧代己基）酯（MEOHP）和邻苯二甲酸单（2-乙基-5-羧基戊基）酯（MECPP）以及总DEHP（ln-ΣDEHP）水平较高，且与较高的血清ln-NfL水平相关（ΣDEHP：β系数 = 0.075；标准误 = 0.026；P = 0.011）。当我们将ΣDEHP分为四分位数时，平均NfL浓度随MEHHP四分位数的增加而升高（趋势P = 0.023）。这种关联在男性、非西班牙裔白人、高收入和BMI<25的人群中更为明显。总之，在2013 - 2014年NHANES的成年人中，较高的DEHP暴露与较高的血清NfL呈正相关。如果这一发现具有因果关系，那么成年期接触DEHP也可能诱发神经损伤。尽管这一观察结果的因果关系和临床意义尚不确定，但我们的研究结果表明，需要对成年人DEHP暴露、血清NfL和神经系统疾病进行更多研究。
