Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults

Lin, Chien‐Yu; Hsieh, Chia‐Jung; Lo, Su Shun; Chen, Pau‐Chung; Torng, Pao-Ling; Hu, Anren; Sung, Fung‐Chang; Su, Ta‐Chen

doi:10.1016/j.envint.2016.04.006

Cited by 41 publications

(15 citation statements)

References 47 publications

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“…Human exposure to PAEs mainly occurs through food due to the use of PVC in wrapping materials and food processing [1,8]. Once ingested through food contamination, di-(2-ethylhexyl) phthalate (DEHP), one of the most widely used and studied phthalates esters, is quickly metabolized to its monoester equivalent mono-(2-ethylhexyl) phthalate] (MEHP), which is preferentially absorbed [9,10]. The biological effects of MEHP are hence of major concern; however, gaining an understanding of the underlying mechanistic events has posed several challenges.…”

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confidence: 99%

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

et al. 2018

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Abstract. Di-(2-ethylhexyl) phthalate (DEHP) is extensively used in many personal care and consumer products, which has resulted in widespread human exposure. Limited studies have suggested that exposure to DEHP may affect thyroid function, but little is known about the effect and mechanisms of DEHP exposure on the hypothalamic-pituitary-thyroid axis (HPTA). The present study was conducted to elucidate the potential mechanisms in which DEHP disrupts the function of the HPTA. Wistar rats were administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/day for 28 days and then sacrificed within 24 h following the last dose. Hormones of HPTA was quantified with radioimmunoassay and enzyme-linked immunosorbent assay, protein levels of thyrotropin-releasing hormone receptor (TRHR) and thyroid-stimulating hormone receptor (TSHR) were analyzed by Western blot and immunohistochemistry, expression levels of TRHR and TSHR mRNA were measured by quantitative real-time PCR. Rats treated with DEHP resulted in increased bodyweight, on the HPTA, down-regulated the protein levels of TRH in the hypothalamus, up-regulated the protein and mRNA levels of TRHR in the pituitary, downregulated mRNA expression of TSHR in the thyroid, while the difference of TSH in various dose groups was not statistically significant and T3, T4, FT3, FT4 levels in serum were decreased compared with control. DEHP could interfere with the balance of HPTA of adolescent rats, and increase the body weight, down-regulate the homeostasis of thyroid related hormones and receptors expression levels. Correspondence to: Lin Ye, Department of Occupational and Environmental Health, School of Public Health, Jilin University, 1163 Xin Min Street, Changchun, 130021, China. E-mail: jlyelin@163.com *These authors equally contributed to this work. Abbreviations: DEHP, Di-(2-ethylhexyl) phthalate; EEDs, environmental endocrine disruptors; HPTA, hypothalamic-pituitary-thyroid axis; MEHP, mono-(2-ethylhexyl) phthalate; PAEs, Phthalic acid esters; PVC, polyvinyl chloride; QPCR, quantitative real-time PCR; THs, thyroid hormones; TRH, thyrotropin-releasing hormone; TRHR, thyrotropin-releasing hormone receptor; TSH, thyroidstimulating hormone; TSHR, thyroid-stimulating hormone receptor ambient air, water sources, and sediments [5][6][7]. Human exposure to PAEs mainly occurs through food due to the use of PVC in wrapping materials and food processing [1,8]. Once ingested through food contamination, di-(2-ethylhexyl) phthalate (DEHP), one of the most widely used and studied phthalates esters, is quickly metabolized to its monoester equivalent mono-(2-ethylhexyl) phthalate] (MEHP), which is preferentially absorbed [9,10]. The biological effects of MEHP are hence of major concern; however, gaining an understanding of the underlying mechanistic events has posed several challenges. In the past, researches about DEHP mainly focused on reproductive defects [11][12][13]. More recently, greater attention has been paid on the thyroid toxic of DEHP.The thyroid is the largest endocrine organ in h...

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confidence: 99%

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

et al. 2018

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“…In May 2011, the Taiwan Food and Drug Administration reported that the plasticizer DEHP and di-iso-nonyl phthalate were illegally added to clouding agents used in foods and beverages 7 9 . Higher DEHP exposure in our study population may have been a r‘12esult of this scandal because the samples were collected from 2006 to 2008 28 . However, it is recognized that MiNP, secondary metabolites of di-iso-nonyl phthalate, is not found often in urine samples in this study.…”

Section: Discussionmentioning

confidence: 94%

“…The urine samples were stored at −80 °C before analysis. Detailed information on the measurement has been published before 28 . Briefly, nine standard phthalate metabolites, including DEHP metabolites (mono(2-ethylhexyl) phthalate (MEHP), mono(ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethly-5-oxoheyl) phthalate (MEOHP)), di-methyl phthalate (DMP) metabolite (mono-methyl phthalate (MMP)), di-iso-butyl phthalate metabolite (mono-isobutyl phthalate (MiBP)), di-ethyl phthalate metabolite (mono-ethyl phthalate (MEP)), di-butyl phthalate metabolite (mono-n-butyl phthalate (MnBP)), butyl-benzyl phthalate metabolite (mono-benzyl phthalate (MBzP)), di-iso-nonyl phthalate metabolite (mono-iso-nonyl phthalate (MiNP)) and their corresponding isotopic 13 C 4 -labeled compounds, were purchased from Cambridge Isotope Laboratories (Andover, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Positive Association between Urinary Concentration of Phthalate Metabolites and Oxidation of DNA and Lipid in Adolescents and Young Adults

Lin

Chen

Hsieh

et al. 2017

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Phthalate has been used worldwide in various products for years. Little is known about the association between phthalate exposure and biomarkers of oxidative stress in adolescents and young adults. Among 886 subjects recruited from a population-based cohort during 2006 to 2008, 751 subjects (12–30 years) with complete phthalate metabolites and oxidation stress measurement were enrolled in this study. Nine urine phthalate metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso prostaglandin F2α (8-isoPGF2α) were measured in urine to assess exposure and oxidative stress to DNA and lipid, respectively. Multiple linear regression analysis revealed that an ln-unit increase in mono-methyl phthalate (MMP) concentration in urine was positively associated with an increase in urine biomarkers of oxidative stress (in μg/g; creatinine of 0.098 ± 0.028 in 8-OHdG; and 0.253 ± 0.051 in 8-isoPGF2α). There was no association between other eight phthalate metabolite concentrations and oxidative stress. In conclusion, a higher MMP concentration in urine was associated with an increase in markers of oxidative stress to DNA and lipid in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to phthalate and oxidative stress.

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“…Endothelial and platelet microparticles (EMPs, CD31+/CD42a−; PMPs, CD31+/CD42a+) have been used as surrogate markers of endothelial dysfunction and cardiovascular diseases [15][16][17][18][19][20]. Previous literature identified that clinically, EMPs, which can be shed from impaired and/or apoptotic endothelial cells, are indicative of cardiovascular damage [15,21].…”

Section: Introductionmentioning

confidence: 99%

“…We noted few articles that explored the association between phthalate exposure and microparticle formation as an indicator of cardiotoxicity; Kataria and colleagues reported a negative association between the metabolites of high-molecular weight phthalate and EMPs [22]. Our previous study in adolescents and young adults found a positive association between mono-2-ethylhexyl phthalate (MEHP), a metabolite of DEHP, and endothelial and platelet microparticles [19]. However, the association between exposure to commonly used phthalates, such as ΣDEHP and DnBP, and microparticles is yet to be investigated, especially in adolescents and young adults.…”

Section: Introductionmentioning

confidence: 99%

Association between Urinary Phthalate Metabolites and Markers of Endothelial Dysfunction in Adolescents and Young Adults

Chu

2021

Toxics

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Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; β = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs.

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Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults

Cited by 41 publications

References 47 publications

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

Positive Association between Urinary Concentration of Phthalate Metabolites and Oxidation of DNA and Lipid in Adolescents and Young Adults

Association between Urinary Phthalate Metabolites and Markers of Endothelial Dysfunction in Adolescents and Young Adults

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