Metrika

  • citati u SCIndeksu: 0
  • citati u CrossRef-u:0
  • citati u Google Scholaru:[]
  • posete u poslednjih 30 dana:9
  • preuzimanja u poslednjih 30 dana:1

Sadržaj

članak: 9 od 1871  
Back povratak na rezultate
2022, vol. 79, br. 3, str. 249-255
Da li postoji razlika u izloženosti ftalatima između odraslih osoba sa metaboličkim poremećajima i zdravih osoba?
aUniverzitet u Novom Sadu, Medicinski fakultet, Srbija + Klinički centar Vojvodine, Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Novi Sad, Srbija
bUniverzitet u Novom Sadu, Medicinski fakultet, Srbija
cHealth Center Ruma, Ruma
dUniverzitet u Novom Sadu, Medicinski fakultet, Srbija + Univerzitet u Novom Sadu, Medicinski fakultet, Institut za zdravstvenu zaštitu dece i omladine, Srbija
eVojnomedicinska akademija, Institut za higijenu, Beograd, Srbija

e-adresamilica.medic-stojanoska@mf.uns.ac.rs
Projekat:
This research has been financially supported by the Provincial Secretariat for Science and Technological Development, AP of Vojvodina, Republic of Serbia, Grant No 114-451-2216/2016.

Ključne reči: endokrini sistem, bolesti; ftalna kiselina; monoetil ftalat; rizik, procena; Srbija
Sažetak
Uvod/Cilj. Ftalati predstavljaju grupu jedinjenja za koje je poznato da imaju štetan uticaj na endokrini system, a nalaze se u različitim potrošačkim proizvodima. Hronična ekspozicija ftalatima dovodi se u vezu sa nastankom mnogobrojnih oboljenja. Cilj rada bio je da se utvrdi zastupljenost ftalatnih metabolita u uzorcima urina odraslih osoba u Vojvodini, Srbija, kao i da se utvrdi prevalenca ftalatnih metabolita kod zdravih ispitanika i onih sa metaboličkim poremećajima kao što su gojaznost i novootkriveni dijabetes melitus tip 2 (T2DM). Metode. Za ispitivanje je korišćen prvi jutarnji uzorak urina 308 ispitanika koji je analiziran na prisustvo 10 ftalatnih metabolita: mono-etil ftalata (MEP), mono-2-etilheksil ftalata (MEHP), mono-n-butil ftalata (MBP), mono-izo-amil-ftalata (MiAP), mono-n-amil ftalata (MnAP), mono-cikloheksil ftalata (MCHP), mono-benzil ftalata (MBzP), mono-n-oktil ftalata (MOP), mono-n-propil ftalata (MPP) i mono-metil ftalata (MMP). Rezultati. Kod 50,32% ispitivane populacije u uzorku urina detektovan je najmanje jedan ftalatni metabolit. Najzastupljeniji ftalatni metaboliti bili su MEP i MEHP. Među ispitanicima pozitivnim na prisustvo ftalatnih metabolita, 38,3% ispitanika imalo je detektovan jedan, 10,7% imalo je dva, a 1,3% ispitanika imalo je prisutna 3 ftalatna metabolita u uzorku jutarnjeg urina. Utvrđeno je postojanje značajne razlike (p < 0,05) između grupa u prisustvu MEP i MMP ftalatnih metabolita, kao i granične značajnosti (p < 0,1) između grupa u prisustvu MEHP i MHCP ftalatnih metabolita. Zaključak. U populaciji Vojvodine, i zdrave osobe i one sa metaboličkim poremećajima, kao što su gojaznost i novootkriveni T2DM, dominatno su izložene di-etil ftalatu i di-2-etilheksil ftalatu, s obzirom na to da su najzastupljeniji ftalatni metaboliti bili MEP i MEHP. Neophodna su dalja istraživanja koja će omogućiti bolji uvid u štetan uticaj ftalata na zdravlje.

Introduction

Phthalates represent a large group of omnipresent industrial chemicals, ordinarily used as plasticizers, and can make up to 40%-50% of the polyvinyl chloride plastic product's weight. They are known to act as endocrinedisrupting chemicals (EDCs) [1]. Phthalates can be found in food packaging, furniture, toys, and many other household products, but also in medical devices, such as tubing and intravenous bags. Phthalates are also popular in the cosmetic industry. Since they are not covalently bound to the plastic, phthalates can leach and transfer to the air, food, and water, and thus become inhaled, ingested, or absorbed through the skin [2]. After being absorbed in the circulation, phthalates are metabolized in two phases: hydrolysis (monoester phthalates are produced) and conjugation. Phthalates are mainly excreted through urine, but they can also be detected in various fluids like blood (serum and plasma), breast milk, saliva, feces, etc. [3].

Monoester phthalates have a fairly short half-life in humans. Despite this fact, numerous scientific evidence implies that phthalate diesters and monoesters can lead to health disorders such as mental retardation, body composition problems, as well as endocrine, pulmonary, and cardiovascular diseases [4].

Phthalates can activate different pathways, but nuclear receptors (NR) are recognized as a primary target [5]. Acting as a partial or complete agonist or antagonist, phthalates can alter NR signaling involved in the regulation of the metabolism and energy homeostasis. The main NRs targeted by phthalates are peroxisome proliferator-activated receptors (PPARα, γ), androgen receptors, thyroid hormone receptors (TRα, β), pregnane X receptor (PXR), estrogen receptors (ERα, β), and estrogen-related receptors [6][7].

By binding to the different components of the PPARs involved in the regulation of adipose tissue and lipid homeostasis, phthalates affect the fat distribution and alter the lipid status [8][9]. Moreover, through the PPAR-γ receptor component, phthalates could induce insulin resistance and impair glucose homeostasis. Besides genetic inheritance and lifestyle, chronic exposure to environmental pollutants, including chronic phthalate exposure, may attribute to the global epidemics of obesity and type 2 diabetes mellitus (T2DM) [10].

The aim of the study was to examine the presence of phthalate metabolites among adults in the Autonomous Province (AP) of Vojvodina (both healthy ones and those with metabolic disorders) in order to find the most abundant metabolites. An additional aim was to determine the prevalence of phthalate metabolites in the control group, obese and a group of participants with newly diagnosed T2DM.

Methods

A total of 308 participants aged 18-50 years from the Vojvodina region, Serbia, were enrolled in a cross-sectional study. The participants were divided into 3 groups: 103 in the control [healthy persons with normal body mass index (BMI)], 104 in the obese (BMI > 30 kg/m2), and 101 in the group of patients with newly diagnosed T2DM (fasting plasma glucose value > 7.0 mmol/L), without medical treatment.

Participants with a history of chronic diseases such as dyslipidaemia, autoimmune disease, chronic infections, malignant disease, or those with possible or proven pregnancy or lactation were not involved in the study. Participants treated with any kind of medication that could affect the lipid status or the body composition (such as hypolipidemics, glucocorticoids, oral contraceptives, or immunosuppressive drugs) were not included in the study.

The study participants provided written informed consent, and the study protocol was approved by the Ethics Board of the Faculty of Medicine, University of Novi Sad, Serbia. All subjects who decided to withdraw their informed consent were excluded from the study.

Firstly, all participants were surveyed and asked specific questions about their medical and personal history. Afterward, anthropometric values such as weight, height, waist circumference were taken, and BMI was calculated using the following formula - weight/height2 (kg/m2). Waist circumference was measured in the middle of the line joining the anterior superior iliac spine and rib arc.

The first morning urine sample of the volunteers who participated in this study was screened for the presence of 10 phthalate metabolites: mono-ethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), mono-n-butyl phthalate (MBP), mono-iso-allyl phthalate (MiAP), mono-n-allyl phthalate (MnAP), mono-cyclohexyl phthalate (MCHP), mono-benzyl phthalate (MBzP), mono-n-octyl phthalate (MOP), mono-n-propyl phthalate (MPP), and mono-methyl phthalate (MMP).

After enzymatical treatment of collected urine samples, methyl-tert-butyl-ether was used as a solvent for the extraction of phthalate metabolites. The samples were prepared and analyzed by the previously developed method accurately described by Milošević et al. [11]. Gas chromatography coupled to mass spectrometric detection (Agilent GC 7890A, 5975C VLMSD) equipped with a fused silica capillary column (30 m, 0.25 mm id. and 0.25 μm film thickness; J&WScientific, Folsom, CA, USA) was used for the determination of phthalates residues in urine. The limit of detection (LOD) for 10 phthalate metabolites was 0.25 ng/mL.

Separate groups were designed for each phthalate metabolite dividing them between phthalate-free and phthalate positive samples (binary distribution), as the span of positive values was too wide so that standard deviations would exclude valuable patients.

Statistical analysis

The data were analyzed using the Pearson's χ2 test (in cases of a low number of positive phthalate values coefficient of contingence was used) with the significant results being recorded at p < 0.05 and p < 0.1. The statistical analyses and graphical representation were done using SPSS 23.0 (SPSS Inc., Chicago, Illinois, USA) and MS Excel Package.

Results

General characteristics of the analyzed population such as male to female ratio, gender, height, age, body weight, waist circumference, and BMI values are shown in Table 1.

Table 1. General characteristics of the entire cluster

Participants n Gender (n) Age (years) Height (cm) Weight (kg) Waist circumference (cm) BMI (kg/m2)
male female
Control 103 51 52 35.91 ± 8.00b 173.37 ± 8.44 69 ± 10.71a, b 78.38 ± 7.99a, b 22.60 ± 2.07a, b
Obese 104 51 53 38.61 ± 8.69c 174.10 ± 9.94 106.36 ± 20.37a,c 110.29 ± 14.79a,c 35.23 ± 6.74a, c
T2DM 101 57 44 44.94 ± 7.38b, c 171.56 ± 10.83 91.79 ± 23.21b, c 103.01 ± 16.81b, c 31.18 ± 7.25b, c
Total/
Average
308 108 96 39.75 ± 8.87 173.03 ± 9.82 89.08 ± 24.33 97.21 ± 19.36 29.91 ± 7.88

n – number of volunteers; T2DM – type 2 diabetes mellitus; BMI – body mass index; Statistically significant difference (p < 0.01): a – between control and obese, b – between control and T2DM; c – between obese and T2DM.
All values are expressed as mean ± standard deviation or number (n).

Statistically significant differences in age, body weight, waist circumference, and BMI were observed among the studied groups.

Phthalate metabolite abundance is shown in Table 2.

Table 2. Phthalate metabolites abundance in the examined population

Participants MEP MEHP MBP MiAP MnAP MCHP MBzP MOP MPP MMP
Control
(n = 103)
26 (25.3) 17 (16.5) 4 (3.9) 2 (1.9) 1 (1) 0 (0) 1 (1) 4 (3.9) 2 (1.9) 0 (0)
Obese
(n = 104)
30 (28.8) 27 (26) 4 (3.8) 1 (1) 1 (1) 0 (0) 3 (2.9) 1 (1) 2 (1.9) 6 (5.7)
T2DM
(n = 101)
13 (12.8) 29 (28.7) 5 (4.9) 1 (1) 0 (0) 3 (2.9) 3 (2.9) 1 (1) 0 (0) 9 (8.9)
Total
(n = 308)
69 (22.4) 73 (23.7) 13 (4.2) 4 (1.2) 2 (0.6) 3 (0.97) 7 (2.2) 6 (1.9) 4 (1.2) 15 (4.8)

T2DM – type 2 diabetes mellitus; MEP – mono-ethyl phthalate; MEHP – mono-(2-ethylhexyl) phthalate;
MBP – mono-n-butyl phthalate; MiAP – mono-iso-allyl phthalate; MnAP – mono-n-allyl phthalate;
MCHP – mono-cyclohexyl phthalate; MBzP – mono-benzyl phthalate; MOP – mono-n-octyl phthalate;
MPP – mono-n-propyl phthalate; MMP – mono-methyl phthalate. All results are presented as number (percentage).

The most frequently detected phthalate metabolites were MEP and MEHP, while MnAP was the least represented.

Out of 308 participants, 155 (50.32%) had at least one phthalate metabolite detected in the first morning urine sample.

The abundance of phthalate metabolites in each group is shown in Figure 1.

Figure 1 Abundance of phthalate metabolites in each individual group

In the control group, the most abundant phthalate metabolites were MEP and MEHP, while MCHP and MMP were not detected. Analyzing the frequency of all metabolites separately, 26 (25.3%) out of 103 participants in the control group had MEP in their urine, 17 (16.5%) had MEHP, and 4 (3.9%) participants were MBP or MOP exposed. Additionally, MiAP and MPP were detected in two samples in the control group (1.7%), while MnAP and MBzP were above the limit of detection in only one sample (0.9%).

In the group of obese participants, MEP and MEHP were also the most abundant phthalate metabolites, while the presence of MCHP again was not determined. In terms of frequency of detection, MEP was determined in the urine of 30 (28.8%) participants, MEHP was found in 27 (25.9%) obese participants, while 4 (3.9%) of them had MBP in their urine sample. Moreover, only one participant was MiAP or MnAP exposed. Three (2.9%) participants were positive with MBzP presence, and 2 (1.9%) of them had MPP in their urine sample. Only 1 (0.9%) participant was positive with MOP presence, while 6 (5.7%) participants had MMP in the urine sample.

In the group of participants with T2DM, MEP and MEHP were again the most frequently detected metabolites in the urine, while the presence of MPP and MnAP was not determined. Out of 101 participants with T2DM, 13 (12.8%) had MEP, while 29 (28.7%) of them had MEHP in their urine sample. MBP was detected in the urine of 5 (4.9%) participants, while only one participant was positive with MiAP or MOP presence. Both MCHP and MBzP were detected in the urine of 3 participants, and 9 participants had MMP phthalate metabolite in their urine sample.

The distribution of analyzed metabolites in the phthalate-positive participants is presented in Figure 2.

Figure 2 Number of phthalate metabolites detected in the urine samples

MEP – mono-ethyl phthalate; MEHP – mono-(2-ethylhexyl) phthalate;
MBP – mono-n-butyl phthalate; MiAP –mono-iso-allyl phthalate;
MnAP – mono-n-allyl phthalate; MCHP – mono-cyclohexyl phthalate;
MBzP – mono-benzyl phthalate; MOP – mono-n-octyl phthalate;
MPP – mono-n-propyl phthalate; MMP – mono-methyl phthalate.

Out of 308 participants, 118 (38.3%) had one phthalate metabolite, 33 (10.7%) of them had two, while 4 (1.3%) participants had three phthalate metabolites in their urine sample. There were no participants with four or more phthalate metabolites detected in their urine samples.

All phthalates were tested for significant differences between the control and obese/T2DM groups of participants. MEP and MMP had p values less than 0.05, while MEHP and MCHP had p values less than 0.1 and, therefore, were considered significant and will be further discussed.

In the examined population of 308 participants, a significant difference was seen in MEP frequency between the control group and T2DM group (χ² = 5.058, df = 1, p = 0.025). Precisely, 26 (25.2%) out of 103 participants in the control group were MEP positive, exactly double in comparison with the number of exposed T2DM patients (13 out of 101; 12.9%).

Considering the MMP occurrence in urine samples, a significant difference in frequencies was observed between the control group and T2DM group (χ² = 8.491, df = 1, p = 0.004), and the obese group and control group (χ² = 6.120, df = 1, p = 0.013), but one must stress the relative significance of this finding as T2DM group had 9 positive values (9/101, 8.9%), the obese group had 6 (6/104, 5.8%), and the control group had none (0/103, 0%).

MEHP was present in 29 (28.9%) of 101 T2DM participants, in 27 (26%) of 104 in the obese group, and in 17 (16.5%) of 103 in the control group, where a borderline significant difference was observed between the control and T2DM group (χ² = 3.435, df = 1, p = 0.064), and between the obese group and control group (χ² = 2.765, df = 1, p = 0.096).

This metabolite was detected in 3 (3%) of 101 T2DM patients and in none of 103 (0%) participants in the control group with moderate significant difference observed (χ² = 3.105, df = 1, p = 0.078).

Again, among the groups, no statistically significant differences were observed between the characteristics of the MBP, MiAP, MnAP, MBzP, MOP, MPP subgroups.

Discussion

Many chemicals whose presence in nature has been increased after the industrial revolution can act as endocrine disruptors by interfering with endogenous hormonal pathways. Epidemiological studies [12][13][14] have shown the link between exposure to these chemicals and the development of common disorders and diseases such as obesity and T2DM. Taking into consideration that the pathogenesis of these disorders depends on the combination of lifestyle habits and genetics, it is lately hypothesized that exposure to endocrine disruptors during or after pregnancy can play a significant role in the onset of some diseases [15]. Phthalates are usually found in large quantities in daily products. The number of publications that investigate the positive linkage between phthalates exposure and adipogenesis and T2DM, some of the largest epidemics of the modern world, increases continuously. Although chemical industry representatives assert that levels of phthalates found in the human body are well below the “safe” concentrations by some regulatory agencies, endocrinologists consider that phthalates exposure, even at low doses, during vulnerable periods, can lead to adverse health effects [16]. Although it is estimated that the average level of human exposure to DEHP is around 0.0024 mg/kg/day, much below the current DEHP "No Observed Adverse Effect Level" (NOAEL) by the European Food Safety Authority, the chronic exposure even at low doses could be more harmful than single acute exposure to high dose [17]. Natural hormones are active at the pico- to nanomolar range. Hence, phthalates as EDCs might ameliorate hormone homeostasis and cause biological impact at low doses [18]. According to literature data [12][19], fetuses, newborns, and adolescents are vulnerable groups and particularly susceptible to phthalate exposure, which is explained by the high levels of cell activity in those age groups.

The obtained results showed that the urine sample of 50.32% of participants was positive for the presence of at least one phthalate metabolite.

The ubiquitous presence of phthalates in human urine samples is documented in the study published by Zota et al. [20]. Eleven phthalate metabolites were analyzed in the urine sample of more than 11,000 adults and children, and data from five cycles of NHANES (National Health and Nutrition Examination Survey) study from 2001-2010 were used. MEP, MBzP, and MnBP were detected in 98% of participants, while MiBP was detected in 72% of participants in the period 2001-2002 and in 96% participants in the period 2009-2010.

Earlier, Stahlhut et al. [21] concluded that the urine of more than 95% of participants was positive with the following phthalate metabolites: MEP, MBP, and MBzP, while 80% of participants had MEHP in urine. In the same study, MEP metabolite had noticeably the highest level, followed by MBP and MBzP, while MEHP had the lowest level. In this research, MEHP (detected in 23.7% of cases) and MEP (in 22.4%) were the most represented in the urine sample. The high frequency of the detection of MEHP could be due to the wide use of products that contain di-(2-ethylhexyl)phthalate (DEHP), such as plastic food packaging, toys, and many other household products, while MEP presence is probably the consequence of the increased use of different cosmetic and beauty products, as well as medications, containing diethyl phthalate (DEP) [22].

Similar to the findings of previous studies, Hoppin et al. [23] found the highest levels of MEP, MBzP, MBP, and MEHP in the two consecutive morning urine samples of 46 Afro-American women. There was no significant difference in the level of phthalate metabolites between the two urine samples, which indicates that urine is a suitable medium for the measurement of phthalates with a short half-life. Additionally, high urinary levels of MEP, MnBP, and MBzP were found in a study conducted on 289 adult persons by Blount et al. [24], while MEHP was measured in much lower concentrations.

Similar to this research, detectable levels of MEP, MBP, MBzP, MEHP, MiNP, MOP, and MCHP were found in the urine sample of 2,540 volunteers, but with a higher frequency of detection (75%) [25]. A possible reason for the difference in the distribution is the much smaller sample size in our research (308 vs 2,540 volunteers).

When exposure to six urinary phthalate metabolites was examined in 370 healthy Czech preschool and school children, MEHP, mono (2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono (2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), MBzP, MiBP, and mono-n-butyl phthalate (MnBP) were analyzed. Among all samples, the two latter monobutyl phthalate isoforms dominated [26].

Comparable to similar studies were the results obtained by Frederiksen et al. [27], who conducted research on 60 young men to examine the correlation between 13 phthalates metabolites levels in different mediums, such as urine, semen, and serum. DEHP phthalate metabolites, accompanied by MEP, MiBP, MBzP, and MnBP, were detected in the urine samples in the highest amount.

In this research, MEP and MEHP were the most frequently detected metabolites in the control, obese, and T2DM groups. Significant differences were observed for MEP frequency between healthy and T2DM participants (p = 0.025). Regarding MEHP, a borderline significant difference was observed between the control and T2DM group (p = 0.064), and between the obese and control group (p = 0.096).

It is known that activation of PPAR receptors plays an important role in different steps of glucose homeostasis, including insulin secretion and insulin resistance. It can also affect circulating levels of lipids thereby modulating the quantity of subcutaneous and visceral fat. Phthalate metabolites are well-known ligands to PPAR receptors and, therefore, could influence both homeostases of glucose and lipid metabolism. Through the PPAR-signaling pathways deterioration, phthalate metabolites could contribute to the development of obesity and diabetes [28]. The precise mechanism by which phthalates influence these PPARmediated actions is expected to be explained with further experiments.

Limitations and advantages of the study

This study focused only on a middle-aged cluster of white (Caucasian) persons, hence, the results can not be extrapolated to other ethnic and other age groups. Being conducted as a cross-sectional study, this research has a risk of selection bias. Thereby, further studies are needed to confirm the present data. Further studies are also needed for clustering the geographical, age, ethnic, sexual, and other characteristics.

In the current study, urine was used as a matrix for measurements of phthalate metabolites. The advantage of urinary measurements is that apart from low cost and noninvasive methods of obtaining samples, usually higher levels are found compared with serum and, thereby, more phthalate metabolites could be measured above the lower detection limit.

Conclusion

Approximately half of the examined participants (50.32%) had at least one phthalate metabolite in their urine sample. Our study showed that the most abundant phthalate metabolite present in the group of obese participants was MEP, while MEHP was the most common phthalate metabolite in the T2DM group. A group of healthy individuals had the highest percentage of presence of MEP amongst examined phthalate metabolites. The obtained results indicate that in the Vojvodina region, both healthy adults and those with metabolic disorders such as obesity and newly diagnosed T2DM are predominantly exposed to widespread DEHP and DEP phthalates.

Further research that will provide more detailed insight into phthalate interference with glucose and lipid metabolism and their influence on the endocrinological balance is needed.

Dodatak

Acknowledgement

This research has been financially supported by the Provincial Secretariat for Science and Technological Development, AP of Vojvodina, Republic of Serbia, Grant No 114-451-2216/2016.

References

1.Halden RU. Plastics and Health Risks. Annu Rev Public Health. 2010;31(1):179-194. [Crossref]
2.Heudorf U, Mersch-Sundermann V, Angerer J. Phthalates: Toxicology and exposure. Int J Hyg Environ Health. 2007;210(5):623-634. [Crossref]
3.Wittassek M, Angerer J. Phthalates: Metabolism and exposure. Int J Androl. 2008;31(2):131-138. [Crossref]
4.Katsikantami I, Sifakis S, Tzatzarakis MN, Vakonaki E, Kalantzi OI, Tsatsakis AM, et al. A global assessment of phthalates burden and related links to health effects. Environ Int. 2016;97:212-236. [Crossref]
5.Hatch EE, Nelson JW, Stahlhut RW, Webster TF. Association of endocrine disruptors and obesity: Perspectives from epidemiological studies. Int J Androl. 2010;33(2):324-332. [Crossref] [PubMed] [PMC]
6.Grimaldi M, Boulahtouf A, Delfosse V, Thouennon E, Bourguet W, Balaguer P. Reporter Cell Lines for the Characterization of the Interactions between Human Nuclear Receptors and Endocrine Disruptors. Frontiers in Endocrinology (Lausanne). 2015;6. [Crossref] [PubMed] [PMC]
7.Milošević N, Milanović M, Suđi J, Bosić-Živanović D, Stojanoski S, Vuković B, et al. Could phthalates exposure contribute to the development of metabolic syndrome and liver disease in humans? Environ Sci Pollut Res Int. 2020;27(1):772-784. [Crossref]
8.Shoshtari-Yeganeh B, Zarean M, Mansourian M, Riahi R, Poursafa P, Teiri H, et al. Systematic review and meta-analysis on the association between phthalates exposure and insulin resistance. Environ Sci Pollut Res Int. 2019;26(10):9435-9442. [Crossref]
9.Martínez-Ibarra A, Martínez-Razo LD, Vázquez-Martínez ER, Martínez-Cruz N, Flores-Ramírez R, García-Gómez E, et al. Unhealthy Levels of Phthalates and Bisphenol A in Mexican Pregnant Women with Gestational Diabetes and Its Association to Altered Expression of miRNAs Involved with Metabolic Disease. Int J Mol Med. 2019;20(13). [Crossref] [PubMed] [PMC]
10.James-Todd TM, Huang T, Seely EW, Saxena AR. The association between phthalates and metabolic syndrome: The National Health and Nutrition Examination Survey 2001-2010. Environ Health Global Access Sci Sour. 2016;15(1). [Crossref] [PubMed] [PMC]
11.Milošević N, Milić N, Živanović-Bosić D, Bajkin I, Perčić I, Abenavoli L, et al. Potential influence of the phthalates on normal liver function and cardiometabolic risk in males. Environ Monit Assess. 2017;190(1). [Crossref]
12.Stojanoska-Medić M, Milošević N, Milić N, Abenavoli L. The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders. Endocrine. 2017;55(3):666-681. [Crossref]
13.Radke EG, Galizia A, Thayer KA, Cooper GS. Phthalate exposure and metabolic effects: A systematic review of the human epidemiological evidence. Environ Int. 2019;132. [Crossref]
14.Benjamin S, Masai E, Kamimura N, Takahashi K, Anderson RC, Faisal PA. Phthalates impact human health: Epidemiological evidences and plausible mechanism of action. J Hazard Mater. 2017;340:360-383. [Crossref]
15.Baillie-Hamilton PF. Chemical toxins: A hypothesis to explain the global obesity epidemic. J Altern Complement Med. 2002;8(2):185-192. [Crossref]
16.Wittassek M, Wiesmüller GA, Koch HM, Eckard R, Dobler L, Helm D. Internal phthalate exposure over the last two decades: A retrospective human biomonitoring study. Int J Hyg Environ Health. 2007;210(3-4):319-333. [Crossref]
17.Genuis SJ, Beesoon S, Lobo RA, Birkholz D. Human elimination of phthalate compounds: Blood, urine, and sweat (BUS) study. ScientificWorldJournal. 2012;2012. [Crossref] [PubMed] [PMC]
18.Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, et al. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses. Endocr Rev. 2012;33(3):378-455. [Crossref] [PubMed] [PMC]
19.Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, et al. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocr Rev. 2009;30(4):293-342. [Crossref] [PubMed] [PMC]
20.Zota AR, Calafat AM, Woodruff TJ. Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001-2010. Environ Health Perspect. 2014;122(3):235-241. [Crossref] [PubMed] [PMC]
21.Stahlhut RW, Wijngaarden E, Dye TD, Cook S, Swan SH. Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males. Environ Health Perspect. 2007;115(6):876-882. [Crossref] [PubMed] [PMC]
22.Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals [Internet]. 2011 [cited 2019 November 11]. Available from: http://www.cdc.gov/exposurereport/.
23.Hoppin JA, Brock JW, Davis BJ, Baird DD. Reproducibility of urinary phthalate metabolites in first morning urine samples. Environ Health Perspect. 2002;110(5):515-518. [Crossref] [PubMed] [PMC]
24.Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, Sampson EJ, et al. Levels of seven urinary phthalate metabolites in a human reference population. Environ Health Perspect. 2000;108(10):979-982. [Crossref] [PubMed] [PMC]
25.Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, et al. Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Environ Health Perspect. 2004;112(3):331-338. [Crossref] [PubMed] [PMC]
26.Puklová V, Janoš T, Sochorová L, Vavrouš A, Vrbík K, Fialová A, et al. Exposure to Mixed Phthalates in Czech Preschool and School Children. Arch Environ Contam Toxicol. 2019;77(4):471-479. [Crossref]
27.Frederiksen H, Jorgensen N, Andersson AM. Correlations between phthalate metabolites in urine, serum, and seminal plasma from young Danish men determined by isotope dilution liquid chromatography tandem mass spectrometry. J Anal Toxicol. 2010;34(7):400-410. [Crossref]
28.Ding Y, Liu Y, Fei F, Yang L, Mao G, Zhao T, et al. Study on the metabolism toxicity, susceptibility and mechanism of di-(2-ethylhexyl) phthalate on rat liver BRL cells with insulin resistance in vitro. Toxicology. 2019;422:102-120. [Crossref]
Reference
Baillie-Hamilton, P.F. (2002) Chemical toxins: A hypothesis to explain the global obesity epidemic. J Altern Complement Med, 8(2): 185-192
Benjamin, S., Masai, E., Kamimura, N., Takahashi, K., Anderson, R.C., Faisal, P.A. (2017) Phthalates impact human health: Epidemiological evidences and plausible mechanism of action. J Hazard Mater, 340: 360-383
Blount, B.C., Silva, M.J., Caudill, S.P., Needham, L.L., Pirkle, J.L., Sampson, E.J., Lucier, G.W., Jackson, R.J., Brock, J.W. (2000) Levels of seven urinary phthalate metabolites in a human reference population. Environ Health Perspect, 108(10): 979-982
Centers for Disease Control and Prevention (CDC) (2011) Fourth National Report on Human Exposure to Environmental Chemicals. Updates Tables, Available from: http://www.cdc.gov/exposurereport/ [accessed 2019 November 11]
Diamanti-Kandarakis, E., Bourguignon, J.P., Giudice, L.C., Hauser, R., Prins, G.S., Soto, A.M., Zoeller, T.R., Gore, A.C. (2009) Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocr Rev, 30(4): 293-342
Ding, Y., Liu, Y., Fei, F., Yang, L., Mao, G., Zhao, T., Zhang, Z., Yan, M., Feng, W., Wu, X. (2019) Study on the metabolism toxicity, susceptibility and mechanism of di-(2ethylhexyl) phthalate on rat liver BRL cells with insulin resistance in vitro. Toxicology, 422: 102-120
Frederiksen, H., Jorgensen, N., Andersson, A.M. (2010) Correlations between phthalate metabolites in urine, serum, and seminal plasma from young Danish men determined by isotope dilution liquid chromatography tandem mass spectrometry. J Anal Toxicol, 34(7): 400-410
Genuis, S.J., Beesoon, S., Lobo, R.A., Birkholz, D. (2012) Human elimination of phthalate compounds: Blood, urine, and sweat (BUS) study. ScientificWorldJournal, 2012: 615068
Grimaldi, M., Boulahtouf, A., Delfosse, V., Thouennon, E., Bourguet, W., Balaguer, P. (2015) Reporter Cell Lines for the Characterization of the Interactions between Human Nuclear Receptors and Endocrine Disruptors. Frontiers in Endocrinology (Lausanne), 6: 62
Halden, R.U. (2010) Plastics and Health Risks. Annu Rev Public Health, 31(1): 179-194
Hatch, E.E., Nelson, J.W., Stahlhut, R.W., Webster, T.F. (2010) Association of endocrine disruptors and obesity: Perspectives from epidemiological studies. Int J Androl, 33(2): 324-332
Heudorf, U., Mersch-Sundermann, V., Angerer, J. (2007) Phthalates: Toxicology and exposure. Int J Hyg Environ Health, 210(5): 623-634
Hoppin, J.A., Brock, J.W., Davis, B.J., Baird, D.D. (2002) Reproducibility of urinary phthalate metabolites in first morning urine samples. Environ Health Perspect, 110(5): 515-518
James-Todd, T.M., Huang, T., Seely, E.W., Saxena, A.R. (2016) The association between phthalates and metabolic syndrome: The National Health and Nutrition Examination Survey 2001-2010. Environ Health Global Access Sci Sour, 15(1): 52
Katsikantami, I., Sifakis, S., Tzatzarakis, M.N., Vakonaki, E., Kalantzi, O.I., Tsatsakis, A.M., Rizos, A.K. (2016) A global assessment of phthalates burden and related links to health effects. Environ Int, 97: 212-236
Martínez-Ibarra, A., Martínez-Razo, L.D., Vázquez-Martínez, E.R., Martínez-Cruz, N., Flores-Ramírez, R., García-Gómez, E., López-López, M., Ortega-González, C., Camacho-Arroyo, I., Cerbón, M. (2019) Unhealthy Levels of Phthalates and Bisphenol A in Mexican Pregnant Women with Gestational Diabetes and Its Association to Altered Expression of miRNAs Involved with Metabolic Disease. Int J Mol Med, 20(13): 3343
Milošević, N., Milanović, M., Suđi, J., Bosić-Živanović, D., Stojanoski, S., Vuković, B., Milić, N., Medić, S.M. (2020) Could phthalates exposure contribute to the development of metabolic syndrome and liver disease in humans?. Environ Sci Pollut Res Int, 27(1): 772-784
Milošević, N., Milić, N., Živanović-Bosić, D., Bajkin, I., Perčić, I., Abenavoli, L., Medić-Stojanoska, M. (2017) Potential influence of the phthalates on normal liver function and cardiometabolic risk in males. Environ Monit Assess, 190(1): 17
Puklová, V., Janoš, T., Sochorová, L., Vavrouš, A., Vrbík, K., Fialová, A., Hanzlíková, L., Černá, M. (2019) Exposure to Mixed Phthalates in Czech Preschool and School Children. Arch Environ Contam Toxicol, 77(4): 471-479
Radke, E.G., Galizia, A., Thayer, K.A., Cooper, G.S. (2019) Phthalate exposure and metabolic effects: A systematic review of the human epidemiological evidence. Environ Int, 132: 104768
Shoshtari-Yeganeh, B., Zarean, M., Mansourian, M., Riahi, R., Poursafa, P., Teiri, H., Rafiei, N., Dehdashti, B., Kelishadi, R. (2019) Systematic review and meta-analysis on the association between phthalates exposure and insulin resistance. Environ Sci Pollut Res Int, 26(10): 9435-9442
Silva, M.J., Barr, D.B., Reidy, J.A., Malek, N.A., Hodge, C.C., Caudill, S.P., Brock, J.W., Needham, L.L., Calafat, A.M. (2004) Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Environ Health Perspect, 112(3): 331-338
Stahlhut, R.W., Wijngaarden, E., Dye, T.D., Cook, S., Swan, S.H. (2007) Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males. Environ Health Perspect, 115(6): 876-882
Stojanoska-Medić, M., Milošević, N., Milić, N., Abenavoli, L. (2017) The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders. Endocrine, 55(3): 666-681
Vandenberg, L.N., Colborn, T., Hayes, T.B., Heindel, J.J., Jacobs, D.R., Lee, D.H., Shioda, T., Soto, A.M., Frederick, V.S.S., Welshons, W.V., Zoeller, T.R., Myers, J.P. (2012) Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses. Endocr Rev, 33(3): 378-455
Wittassek, M., Wiesmüller, G.A., Koch, H.M., Eckard, R., Dobler, L., Helm, D., et al. (2007) Internal phthalate exposure over the last two decades: A retrospective human biomonitoring study. Int J Hyg Environ Health, 210(3-4): 319-333
Wittassek, M., Angerer, J. (2008) Phthalates: Metabolism and exposure. Int J Androl, 31(2): 131-138
Zota, A.R., Calafat, A.M., Woodruff, T.J. (2014) Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001-2010. Environ Health Perspect, 122(3): 235-241
 

O članku

jezik rada: engleski
vrsta rada: originalan članak
DOI: 10.2298/VSP200220093S
primljen: 20.02.2020.
revidiran: 21.05.2020.
prihvaćen: 25.09.2020.
objavljen onlajn: 26.09.2020.
objavljen u SCIndeksu: 02.04.2022.
metod recenzije: dvostruko anoniman
Creative Commons License 4.0

Povezani članci

Nema povezanih članaka