Phthalate

邻苯二甲酸酯
  • 文章类型: Systematic Review
    邻苯二甲酸盐在不同的环境中无处不在,并与无数有害的健康结果有关。然而,邻苯二甲酸盐暴露与过敏性鼻炎(AR)之间的关联尚不清楚.为了解决这个知识差距,我们进行了系统评价和荟萃分析,以全面评估邻苯二甲酸盐暴露与儿童AR风险之间的关系.我们搜索了护理和相关健康文献的累积指数,摘录医学数据库,和PubMed收集相关研究,并估计合并比值比(OR)和95%置信区间(CI)进行风险估计。最终,18条,包括七个横截面,七个病例控制,和四项前瞻性队列研究,被选中进行我们的系统评价和荟萃分析。我们的汇总数据显示,儿童尿液中邻苯二甲酸二-2-乙基己酯(DEHP)暴露与AR风险之间存在显着关联(OR=1.188;95%CI=1.016-1.389)。此外,产前暴露于孕妇尿液中的邻苯二甲酸盐及其代谢产物与儿童AR的风险显着相关(OR=1.041;95%CI=1.003-1.081),尽管邻苯二甲酸酯及其代谢物的特定类型并不显著。此外,我们检查了家庭粉尘中的环境邻苯二甲酸盐暴露,发现与AR风险无显著关联(OR=1.021;95%CI=0.980-1.065).我们的发现强调了邻苯二甲酸酯对儿童AR的潜在危险影响,并为其发病机理和预防提供了有价值的见解。
    Phthalates are ubiquitous in diverse environments and have been linked to a myriad of detrimental health outcomes. However, the association between phthalate exposure and allergic rhinitis (AR) remains unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to comprehensively evaluate the relationship between phthalate exposure and childhood AR risk. We searched the Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, and PubMed to collect relevant studies and estimated pooled odds ratios (OR) and 95% confidence intervals (CI) for risk estimation. Ultimately, 18 articles, including seven cross-sectional, seven case-control, and four prospective cohort studies, were selected for our systematic review and meta-analysis. Our pooled data revealed a significant association between di-2-ethylhexyl phthalate (DEHP) exposure in children\'s urine and AR risk (OR = 1.188; 95% CI = 1.016-1.389). Additionally, prenatal exposure to combined phthalates and their metabolites in maternal urine was significantly associated with the risk of childhood AR (OR = 1.041; 95% CI = 1.003-1.081), although specific types of phthalates and their metabolites were not significant. Furthermore, we examined environmental phthalate exposure in household dust and found no significant association with AR risk (OR = 1.021; 95% CI = 0.980-1.065). Our findings underscore the potential hazardous effects of phthalates on childhood AR and offer valuable insights into its pathogenesis and prevention.
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  • 文章类型: Journal Article
    背景:邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种常用于多种产品的增塑剂,包括医疗设备。它通过口服吸收后在肝脏中迅速代谢成各种代谢物,皮肤吸收,和吸入。DEHP在啮齿动物中被归类为非遗传毒性肝癌,因为它的长期暴露与这些动物肝癌的发展有关,但大多数遗传毒性研究都是阴性的.人类流行病学研究表明,长期高摄入DEHP可能是肝功能障碍的危险因素。重复剂量肝微核(RDLMN)测定法是一种公认的方法,用于评估由肝基因毒素和/或致癌物引起的染色体变化。它对于检测经历代谢活化的物质特别有价值,特别是当代谢物半衰期短或不能有效到达骨髓时。因此,我们调查了RDLMN试验是否能检测到DEHP诱导的肝脏微核形成,治疗14或28天后.
    结果:我们报道RDLMN分析显示暴露于DEHP14或28天的大鼠肝脏微核频率增加。微核的增加与肝肿大相关,对肝脏中邻苯二甲酸盐的既定反应。相反,在使用这些大鼠骨髓的微核试验中未观察到这种增加。
    结论:通过RDLMN测定法检测DEHP诱导的微核表明该测定法可以检测DEHP的潜在遗传毒性和肝癌性。它还证明了RDLMN测定在鉴定代谢激活的肝致癌物中的实用性。
    BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in a wide variety of products, including medical devices. It is rapidly metabolized in the liver into various metabolites upon absorption through oral ingestion, dermal absorption, and inhalation. DEHP is classified as a non-genotoxic hepatocarcinogen in rodents, as its chronic exposure has been associated with the development of liver cancer in these animals, but most genotoxicity studies have been negative. Epidemiologic studies in humans suggest that long-term high intakes of DEHP may be a risk factor for liver dysfunction. The repeated-dose liver micronucleus (RDLMN) assay is a well-established method for assessing chromosomal changes caused by hepatic genotoxins and/or carcinogens. It is particularly valuable for detecting substances that undergo metabolic activation, especially when the metabolite has a short half-life or does not reach the bone marrow effectively. Therefore, we investigated whether the RDLMN assay could detect DEHP-induced micronucleus formation in the liver following a 14 or 28-day treatment.
    RESULTS: We report that the RDLMN assay demonstrated an increased frequency of hepatic micronuclei in rats exposed to DEHP for 14 or 28 days. The increases in micronuclei correlated with hepatomegaly, an established response to phthalates in the liver. Conversely, no such increases were observed in the micronucleus assay using bone marrow from these rats.
    CONCLUSIONS: The detection of DEHP-induced micronuclei by the RDLMN assay suggests that this assay could detect the potential genotoxicity and hepatocarcinogenicity of DEHP. It also demonstrated the utility of the RDLMN assay in identifying metabolically activated hepatic carcinogens.
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  • 文章类型: Journal Article
    微塑料和纳米塑料(MNPs)存在于城市灰尘和工业化城市的水生环境中。人体内的MNPs积聚在淋巴滤泡中,Peyer的胃肠道斑块,和肺血管内皮细胞,缓慢地导致毒性。由于以前的研究引入了姜黄素作为天然保护剂对抗环境毒素,我们回顾了使用姜黄素保护器官或细胞免受暴露于MNPs后的毒性的临床前研究.发现暴露于MNPs会导致骨质溶解,免疫毒性,甲状腺功能紊乱,肾毒性,神经毒性,肝毒性,肺毒性,胃肠道毒性,心血管毒性,尤其是内分泌,和生殖毒性。然而,除了一项审查的研究,由于姜黄素固有的抗氧化剂,姜黄素恢复了MNPs诱导的所有氧化和组织病理学损伤,抗凋亡,抗炎,和抗增殖特性。
    Microplastics and nanoplastics (MNPs) are present in urban dust and the aquatic environments of industrialized cities. MNPs in the human body accumulate in the lymphoid follicles, Peyer\'s patches of the gastrointestinal tract, and pulmonary vascular endothelial cells, which slowly result in toxicity. Since previous studies introduced curcumin as a natural protective agent against environmental toxins, we reviewed preclinical studies that had used curcumin to protect organs or cells from toxicity secondary to exposure to MNPs. It was found that exposure to MNPs resulted in osteolysis, immunotoxicity, thyroid disturbances, nephrotoxicity, neurotoxicity, hepatotoxicity, pulmonary toxicity, gastrointestinal toxicity, cardiovascular toxicity, and especially endocrine, and reproductive toxicity. Nevertheless, except for one study reviewed, curcumin restored all oxidative and histopathological damages induced by MNPs to normal due to curcumin\'s inherent antioxidant, antiapoptotic, anti-inflammatory, and anti-proliferative properties.
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  • 文章类型: Journal Article
    邻苯二甲酸二(2-乙基己基)酯(DEHP)是通常用于血袋的增塑剂。尽管它对红细胞(RBC)储存有保护作用,存在对其生殖毒性的担忧。这项研究调查了使用二(异壬基)环己烷-1,2-二羧酸酯(DINCH)作为替代增塑剂存储在袋中的RBC浓缩物的体外质量。
    使用池和拆分研究设计,我们在两个DINCH袋和三个DEHP袋中使用柠檬酸盐磷酸盐葡萄糖腺嘌呤(CPDA-1)抗凝剂生产了20个匹配的均匀五元红细胞浓缩物。每周评估RBC储存质量,持续35天。
    在第35天,DINCH袋中的中值溶血水平(0.297-0.342%)略高于(p<0.05)DEHP袋(0.204-0.240%)。所有DINCH袋显示<0.8%溶血。与DEHP袋相比,DINCH袋中的红细胞显示出平均红细胞体积增加和伊红5'马来酰亚胺结合减少。DINCH袋中较高的pO2和较低的pCO2水平表明比DEHP袋中更好的气体渗透性。其他代谢参数在两个袋中相当。与DEHP相比,DINCH表现出相当低的增塑剂浸出到血袋中的水平。
    在带有CDPA-1的DINCH增塑血袋中储存35天的RBC浓缩物的质量通常与DEHP袋中的质量相当。因此,DINCH可以是血液袋中DEHP的可行替代品,用于非白细胞减少的RBC储存,即使不使用下一代添加剂解决方案来提高RBC保存质量。
    增塑剂是添加到塑料中以增加其柔韧性的化学物质。DEHP是一种增塑剂,已广泛用于许多产品,包括塑料管和医疗设备袋。然而,对DEHP相关毒性的担忧已经争论了很多年。在许多产品中,DEHP已被其他增塑剂取代,但由于它对红细胞保存的保护作用,它仍被用于血袋。DINCH是一种具有低毒理学特征的替代增塑剂。这项研究调查了使用DINCH储存在血袋中的RBC浓缩物的质量。使用两个DINCH袋和三个带有CPDA-1抗凝剂的DEHP袋生产了20套五种RBC浓缩物,每周评估储存质量,持续35天。在第35天,DINCH袋中的中值溶血水平(0.297-0.342%)比DEHP袋(0.204-0.240%)略微增加。然而,所有DINCH袋均显示溶血低于0.8%的监管限值.DINCH袋表现出比DEHP袋更好的气体渗透性。与DEHP相比,DINCH表现出相当低的增塑剂浸出到血袋中的水平。大多数其他代谢参数在两个袋中都是可比的。在含有CDPA-1的DINCH增塑血袋中储存35天的非白细胞减少的RBC浓缩物的质量通常与DEHP袋中的质量相当。因此,DINCH可以在血袋中替代DEHP用于RBC存储,即使不使用下一代添加剂解决方案,以提高红细胞保存质量。
    UNASSIGNED: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in blood bags. Despite its protective effects on red blood cell (RBC) storage, concerns about its reproductive toxicity exist. This study investigated the in vitro quality of RBC concentrates stored in bags using di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) as an alternative plasticizer.
    UNASSIGNED: Using a pool-and-split study design, we produced 20 matched homogenous quintets of RBC concentrates in two DINCH bags and three DEHP bags with citrate phosphate dextrose adenine (CPDA-1) anticoagulant. RBC storage quality was assessed weekly for 35 days.
    UNASSIGNED: On day 35, the median hemolysis levels in the DINCH bags (0.297-0.342%) were marginally higher (p < 0.05) than the DEHP bags (0.204-0.240%). All DINCH bags showed <0.8% hemolysis. RBCs in the DINCH bags showed increased mean corpuscular volume and decreased eosin 5\' maleimide binding than in the DEHP bags. Higher pO2 and lower pCO2 levels in the DINCH bags indicated better gas permeability than in DEHP bags. Other metabolic parameters were comparable in both bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags.
    UNASSIGNED: The quality of RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for nonleukoreduced RBC storage even without the use of next-generation additive solutions to improve RBC preservation quality.
    A plasticizer is a chemical substance added to plastic to increase its flexibility. DEHP is a plasticizer that has been widely used in many products including plastic tubing and bags of medical devices. However, concerns about DEHP-related toxicity have been debated for many years. DEHP has been replaced with other plasticizers in many products, but it is still being used in blood bags due to its protective effect on RBC preservation. DINCH is an alternative plasticizer with a low toxicology profile. This study investigated the quality of RBC concentrates stored in blood bags using DINCH. Twenty sets of five RBC concentrates were produced using two DINCH bags and three DEHP bags with CPDA-1 anticoagulant, and the storage quality was assessed weekly for 35 days. On day 35, the median hemolysis levels in the DINCH bags (0.297–0.342%) were slightly increased than the DEHP bags (0.204–0.240%). However, all DINCH bags showed hemolysis lower than the regulatory limit of 0.8%. DINCH bags exhibited better gas permeability than DEHP bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Most of the other metabolic parameters were comparable in both bags. The quality of nonleukocyte-reduced RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for RBC storage, even without the use of next-generation additive solutions to improve RBC preservation quality.
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  • 文章类型: Journal Article
    食物垃圾(FW)及其沼气残留物被认为是陆地微塑料(MPs)和邻苯二甲酸酯(PAEs)污染的来源。然而,对FW干式厌氧消化(DADP)过程中的MPs和PAEs污染问题缺乏研究和了解。确定了中国单体处置规模最大的DADP三个阶段的MPs和PAEs。在沼渣挤压阶段,MPs丰度和PAEs浓度达到最高值,分别为3.63±0.45×103N·kg-1和3.62±0.72mg·kg-1。此外,在整个过程中,MPs与PAEs呈显著正相关(p<0.05)。尽管在所有阶段都存在具有塑料降解潜力的细菌和真菌,通过DADP不能完全解决MP和PAEs的污染问题。本研究为预防和控制MPs和PAEs污染提供了科学依据。
    Food waste (FW) and its biogas residue were considered as sources of terrestrial microplastics (MPs) and phthalic acid esters (PAEs) contamination. However, there was a lack of research and understanding of the MPs and PAEs pollution problem in FW dry anaerobic digestion process (DADP). The MPs and PAEs in three stages of the DADP with the largest monomer disposal scale in China were identified. At the biogas residue extrusion stage, MPs abundance and PAEs concentration reached the highest values, which were 3.63 ± 0.45 × 103 N·kg-1 and 3.62 ± 0.72 mg·kg-1, respectively. Furthermore, there was a significant positive correlation between MPs and PAEs throughout the process (p < 0.05). Although bacteria and fungi with plastic degradation potential were present in all stages, the contamination problem of MPs and PAEs cannot be completely solved through DADP. This study provides a scientific basis for preventing and controlling the pollution of MPs and PAEs.
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  • 文章类型: Journal Article
    这项研究的目的是研究邻苯二甲酸酯在食管鳞状细胞癌(ESCC)患者中的作用。
    共纳入116例ESCC患者和58例没有任何已知恶性肿瘤病史的对照。测量所有八种尿邻苯二甲酸酯代谢物以评估邻苯二甲酸酯水平。临床和尿邻苯二甲酸酯代谢物谱比较亚组之间,以确定差异,我们还研究了邻苯二甲酸酯对ESCC临床结局的影响.
    ESCC组某些尿邻苯二甲酸酯代谢物的浓度高于对照组,包括邻苯二甲酸单(3-羧基丙基)酯(MCPP),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),和邻苯二甲酸单正丁酯(MnBP)。较高浓度的尿邻苯二甲酸酯代谢物与临床T3-T4状态相关。邻苯二甲酸单(2-乙基-5-羧基戊基)(MECPP)浓度较高的患者,邻苯二甲酸单-2-乙基己酯(MEHP),在我们的单因素分析中,MEOHP的1年和2年总生存率(OS)低于这些代谢物浓度较低的患者.多因素分析显示尿MEHP≥3μg/L和临床分期IVB是OS恶化的独立预后因素。
    我们的研究结果表明,在ESCC患者中,尿邻苯二甲酸盐代谢产物升高,并与晚期肿瘤分期有关,尿MEHP浓度高是OS恶化的独立预后因素。
    UNASSIGNED: The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC).
    UNASSIGNED: A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined.
    UNASSIGNED: The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3-T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥3 μg/L and clinical stage IVB were independent prognostic factors for worse OS.
    UNASSIGNED: The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.
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  • 文章类型: Journal Article
    塑料已成为现代社会的重要组成部分。它们的性质可以很容易地通过掺入添加剂来赋予所需的属性来控制,比如颜色,灵活性,或稳定。然而,许多添加剂被归类为有害物质。为了更好地了解海洋生态系统中塑料污染的风险,需要确定塑料碎片中添加剂的类型和浓度。我们报告了三十一种常见塑料添加剂(包括增塑剂,抗氧化剂,和紫外线稳定剂)在新西兰Aotearoa收集的搁浅塑料碎片中。通过溶剂萃取从塑料碎片中分离出添加剂,并使用高分辨率液相色谱-质谱法进行定量。在200项碎片中检测到25种目标添加剂,增塑剂检测频率最高(99%检测频率)。在所有样品中检测到添加剂,每个碎片项目的中位数为四种添加剂。与聚乙烯或聚丙烯(中位数=4)相比,聚氯乙烯(中位数=7)的每个碎片项目检测到的添加剂数量明显更高。添加剂邻苯二甲酸二(2-乙基己基)酯,邻苯二甲酸二异壬酯,邻苯二甲酸二异癸酯,和抗氧化剂702在最高浓度(高达196,930μg/g)下检测到。与其他塑料类型相比,聚氯乙烯塑料中每个碎片项目的添加剂总浓度(高达320,325μg/g)明显更高(中位数94,716μg/g),主要是由于邻苯二甲酸酯增塑剂的存在。非目标分析与目标分析一致,表明与所有其他聚合物类型相比,聚氯乙烯碎片项目中添加剂的数量和浓度更高。特征识别表明存在比以前在目标分析中检测到的更多的添加剂,包括增塑剂(邻苯二甲酸酯和非邻苯二甲酸酯),加工助剂,和成核剂。这项研究强调了邻苯二甲酸酯和聚氯乙烯作为生态毒理学和风险评估中考虑的关键目标。以及制定减少塑料污染影响的政策。
    Plastics have become an essential part of modern society. Their properties can be easily manipulated by incorporating additives to impart desirable attributes, such as colour, flexibility, or stability. However, many additives are classified as hazardous substances. To better understand the risk of plastic pollution within marine ecosystems, the type and concentration of additives in plastic debris needs to be established. We report the quantification of thirty-one common plastic additives (including plasticisers, antioxidants, and UV stabilisers) in beached plastic debris collected across Aotearoa New Zealand. Additives were isolated from the plastic debris by solvent extraction and quantified using high-resolution liquid chromatography-mass spectrometry. Twenty-five of the target additives were detected across 200 items of debris, with plasticisers detected at the highest frequency (99 % detection frequency). Additives were detected in all samples, with a median of four additives per debris item. A significantly higher number of additives were detected per debris item for polyvinyl chloride (median = 7) than polyethylene or polypropylene (median = 4). The additives bis(2-ethylhexyl) phthalate, diisononyl phthalate, diisodecyl phthalate, and antioxidant 702 were detected at the highest concentrations (up to 196,930 μg/g). The sum concentration of additives per debris item (up to 320,325 μg/g) was significantly higher in polyvinyl chloride plastics (median 94,716 μg/g) compared to other plastic types, primarily due to the presence of phthalate plasticisers. Non-target analysis was consistent with the targeted analysis, indicating a higher number and concentration of additives in polyvinyl chloride debris items compared to all other polymer types. Feature identification indicated the presence of more additives than previously detected in the targeted analysis, including plasticisers (phthalate and non-phthalate), processing aids, and nucleating agents. This study highlights phthalates and polyvinyl chloride as key targets for consideration in ecotoxicology and risk assessments, and the development of policies to reduce the impacts of plastic pollution.
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  • 文章类型: Journal Article
    背景:内分泌干扰化学物质(EDCs)在日常环境中普遍存在。这些化学物质的影响,以及与EDC相关的生活方式和饮食习惯对神经认知功能的影响,不是很了解。
    方法:长贡社区医学研究中心进行了一项涉及887名参与者的横断面研究。从最初的队列中,根据他们的EDC暴露分数选择120个个体进行详细分析。其中,使用AscertainDementia-8(AD-8)问卷进一步选择67名55岁或以上的参与者进行认知障碍评估。
    结果:这67名年龄较大的参与者在年龄上没有显著差异,白蛋白尿,或估计的肾小球滤过率与受损评分较低的肾小球滤过率相比。这项研究表明,邻苯二甲酸单(2-乙基己基)酯(MEHP)水平(8.511vs.6.432微克/克肌酐,p=0.038)与更高的认知障碍风险(AD-8≥2)相关。根据年龄调整的统计模型,性别,和糖尿病表明MEHP水平与AD-8评分呈正相关,在更全面的模型中达到统计学意义(β±SE:0.160±0.076,p=0.042)。Logistic回归分析强调了高MEHP水平和较高AD-8评分之间的显著正相关(比值比:1.217,p=0.006)。受试者工作特征曲线突出了高MEHP水平和EDC暴露评分与显著认知障碍的相关性,曲线下面积分别为66.3%和66.6%,分别。
    结论:暴露于EDCs,特别是邻苯二甲酸二(2-乙基己基)酯,MEHP的前身,可能与中老年人的神经认知障碍有关。
    BACKGROUND: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood.
    METHODS: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire.
    RESULTS: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (β ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively.
    CONCLUSIONS: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.
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  • 文章类型: Journal Article
    背景:内分泌干扰化学物质(EDC)是广泛使用的化合物,具有影响儿童神经发育结果的潜力,包括自闭症谱系障碍(ASD)。我们的目的是检查尿液中EDC生物标志物的浓度,包括邻苯二甲酸酯,酚类物质,和对羟基苯甲酸酯,并调查婴儿期早期暴露是否与后期ASD或其他非典型发育(Non-TD)或不良认知发育的风险增加相关。
    方法:这项分析包括来自婴儿学习早期体征(MARBLES)研究中自闭症风险标志物的婴儿,高危ASD队列(n=148;对应于188个尿液样本)。对3个月和/或6个月大的婴儿的尿中的32个EDC生物标志物进行定量。使用最小二乘几何平均值计算EDC生物标志物浓度的趋势。36个月大的时候,儿童被临床分类为患有ASD(n=36),非典型发展(非TD;n=18),或通过临床评估的典型发展(TD;n=81)。三项逻辑回归分析用于测试生物标志物与ASD之间的关联,或非TD,与TD儿童相比。在单一分析物分析中,在4个评估时间点(6,12,24和36月龄),使用Mullen早期学习量表(MSEL),使用广义估计方程研究了每种EDC生物标志物与认知发展纵向变化之间的关联.此外,分位数g计算用于测试混合效应。
    结果:EDC生物标志物浓度在研究期间普遍下降,除了对苯二甲酸单-2-乙基-5-羧基戊基酯。总的来说,3和/或6月龄EDC生物标志物与ASD或非TD风险增加无关。一些显示出显著的逆关联。然而,在评估四个评估时间点的MSEL分数的纵向变化时,邻苯二甲酸单乙酯(MEP)升高与复合评分(β=-0.16,95%CI:0.31,-0.02)和精细运动技能分量表(β=-0.09,95CI:0.17,0.00)的评分降低显着相关,和视觉接收(β=-0.11,95%CI:0.23,0.01)。此外,对苯二甲酸二(2-乙基己基)酯(DEHTP)的代谢物总和与较差的视觉接收有关(β=-0.09,95%CI:0.16,-0.02),综合评分降低(β=-0.11,95%CI:0.21,-0.01)。使用分位数g计算分析的混合物分析未显示EDC生物标志物的混合物与MSEL子量表或复合评分之间的显著关联。
    结论:这些发现强调了婴儿暴露对认知发育的潜在重要性。未来的研究可以帮助进一步调查早期婴儿暴露是否与长期缺陷有关,并特别注意随时间趋势增加的EDC,以及它们是否可能对神经发育产生不利影响。
    BACKGROUND: Endocrine disrupting chemicals (EDCs) are widely used compounds with the potential to affect child neurodevelopmental outcomes including autism spectrum disorders (ASD). We aimed to examine the urinary concentrations of biomarkers of EDCs, including phthalates, phenols, and parabens, and investigate whether exposure during early infancy was associated with increased risk of later ASD or other non-typical development (Non-TD) or adverse cognitive development.
    METHODS: This analysis included infants from the Markers of Autism Risks in Babies-Learning Early Signs (MARBLES) study, a high-risk ASD cohort (n = 148; corresponding to 188 urine samples). Thirty-two EDC biomarkers were quantified in urine among infants 3 and/or 6 months of age. Trends in EDC biomarker concentrations were calculated using least square geometric means. At 36 months of age, children were clinically classified as having ASD (n = 36), nontypical development (Non-TD; n = 18), or typical development (TD; n = 81) through a clinical evaluation. Trinomial logistic regression analysis was used to test the associations between biomarkers with ASD, or Non-TD, as compared to children with TD. In single analyte analysis, generalized estimating equations were used to investigate the association between each EDC biomarkers and longitudinal changes in cognitive development using the Mullen Scales of Early Learning (MSEL) over the four assessment time points (6, 12, 24, and 36 months of age). Additionally, quantile g-computation was used to test for a mixture effect.
    RESULTS: EDC biomarker concentrations generally decreased over the study period, except for mono-2-ethyl-5-carboxypentyl terephthalate. Overall, EDC biomarkers at 3 and/or 6 months of age were not associated with an increased risk of ASD or Non-TD, and a few showed significant inverse associations. However, when assessing longitudinal changes in MSEL scores over the four assessment time points, elevated monoethyl phthalate (MEP) was significantly associated with reduced scores in the composite score (β = -0.16, 95% CI: 0.31, -0.02) and subscales of fine motor skills (β = -0.09, 95%CI: 0.17, 0.00), and visual reception (β = -0.11, 95% CI: 0.23, 0.01). Additionally, the sum of metabolites of di (2-ethylhexyl) terephthalate (ƩDEHTP) was associated with poorer visual reception (β = -0.09, 95% CI: 0.16, -0.02), and decreased composite scores (β = -0.11, 95% CI: 0.21, -0.01). Mixtures analyses using quantile g-computation analysis did not show a significant association between mixtures of EDC biomarkers and MSEL subscales or composite scores.
    CONCLUSIONS: These findings highlight the potential importance of infant exposures on cognitive development. Future research can help further investigate whether early infant exposures are associated with longer-term deficits and place special attention on EDCs with increasing temporal trends and whether they may adversely affect neurodevelopment.
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  • 文章类型: Journal Article
    孕前健康与母婴健康结局之间有着密切的关系,后果可能会代代相传。2018年,《柳叶刀》连续发表了三篇文章,强调了孕前时期的重要性。在此期间,邻苯二甲酸酯(PAE)暴露可能会影响配子体的配子发生和表观遗传信息,从而影响胚胎发育和后代健康。因此,本文回顾了父母孕前PAE暴露对生殖/出生结局和后代健康的影响,在这个问题上提供新的证据。我们搜索了WebofScience,MEDLINE(通过PubMed),中国国家知识基础设施(CNKI),ScienceDirect,和贵宾期刊图书馆从数据库建立之日起至2024年7月3日。最后,包括12篇文章。三项研究调查了健康危害(对出生体重的影响,流产,等。)女性的孕前PAE暴露。九项研究涉及父母双方。九项研究考虑了PAE孕前暴露对生殖/出生结局的影响,关注出生体重,怀孕失败,早产,胚胎质量,胎盘重量。三项研究考虑了孕前PAE暴露对后代行为的影响。本综述的结果表明,父母孕前PAE暴露可能对生殖/出生结果和后代行为产生影响,包括出生体重,儿童行为,和饮食行为。然而,关于孕前PAE暴露对健康危害的研究相对较少,当前研究的结果各不相同。有必要使用系统评价来验证准确的研究问题,为公共卫生政策制定提供建议。
    There is a close relationship between preconception health and maternal and child health outcomes, and the consequences may be passed down from generation to generation. In 2018, Lancet published three consecutive articles emphasizing the importance of the preconception period. Phthalic acid ester (PAE) exposure during this period may affect gametogenesis and epigenetic information in gametophytes, thereby affecting embryonic development and offspring health. Therefore, this article reviews the effects of parental preconception PAE exposure on reproductive/birth outcomes and offspring health, to provide new evidence on this topic. We searched Web of Science, MEDLINE (through PubMed), the China National Knowledge Infrastructure (CNKI), ScienceDirect, and the VIP Journal Library from the date of database establishment to July 3, 2024. Finally, 12 articles were included. Three studies investigated the health hazards (effects on birth weight, abortion, etc.) of women\'s preconception PAE exposure. Nine studies involved both parents. Nine studies considered the impacts of PAE preconception exposure on reproductive/birth outcomes, focusing on birth weight, pregnancy loss, preterm birth, embryo quality, and placental weight. Three studies considered the impacts of preconception PAE exposure on offspring behavior. The results of this review suggested that parental preconception PAE exposure may have an impact on reproductive/birth outcomes and offspring behavior, including birth weight, child behavior, and dietary behavior. However, studies on the health hazards of preconception PAE exposure are relatively scarce, and the outcomes of current studies are varied. It is necessary to use systematic reviews to verify an accurate research question to provide recommendations for public health policy making.
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