Concentrations of urinary parabens and reproductive hormones in Iranian women: Exposure and risk assessment.

Parabens are antimicrobial preservatives in a variety of processed foods and beverages, cosmetics, pharmaceuticals, and personal care products. Parabens may be associated with reproductive and endocrine disorders among women of reproductive age. The first objective of this study was to examine the association between urinary parabens concentrations and follicle-stimulating hormone(FSH), luteinizing hormone (LH), and prolactin disorders. The second objective of this study was to calculate the Hazard Quotient (HQ) and Margin of Exposure (MOE) to assess the potential risk for endocrine disrupts for each woman based on urinary paraben concentrations. To address these two objectives, a cross-sectional study was designed in the Imam Reza Hospital in Kermanshah. The association between early morning urinary paraben concentrations and the serum of fasting blood specimens was analyzed using multivariable linear regressions adjusted for confounding variables (i.e., creatinine, age, body mass index, and time spent on physical activity). Among the 96 women who participated in the study, those with BMI> 25 and aged 18-40 years showed higher levels of total urinary parabens. The highest sum of urinary parabens (54,955.16 µg/L) was observed among the women who were using toothpaste several times per day. Almost all the parabens such as methyl paraben(MeP), ethyl paraben(EtP), propyl paraben(PrP), butyl paraben(BuP) had a positive and negative significant association with serum concentrations of FSH and LH (p-value < 0.05). However, no significant association was found between any of the four parabens and serum prolactin hormone (p-value > 0.05). The Margin of Exposure (MOE) approach calculated for all parabens (<10000) showed a potential risk in the studied population. The results suggested that parabens could adversely affect reproductive and endocrine systems in women. Further studies relying on long-term exposure to parabens are necessary to better understand the potential risk of the association between urinary parabens concentrations with reproductive hormones.

Investigating the pollution of bottled water by the microplastics (MPs): the effects of mechanical stress, sunlight exposure, and freezing on MPs release.

Bottled water is becoming more popular worldwide and possible contamination's need to be analyzed. Microplastics (MPs) are ubiquitous environmental pollutants and have recently been regarded as an important contaminant in bottled water due to oral intake and possible threats to human health. In the present study, MP amounts in 23 popular Iranian brands of bottled water were determined by filtration and counting under scanning electron microscopy (SEM). The effects of mechanical stress, environmental factors, and freezing on MP release also were investigated. The average amounts of MPs in water samples were 1496.7 ± 1452.2 particles/L (199.8 to 6626.7 particles/L). The amounts of MPs in different brands was significantly different (p < 0.05). As much as 91.3% of detected particles had the size between 1 and 10 µm. The most likely polymers determined by FTIR spectroscopy was polyethylene terephthalate (PET). The freezing of water in the bottles did not show any significant effect on the MPs release, but mechanical stress to the bottles increased MP amounts in the water significantly. Environmental factors including sunlight exposure and the age of bottles showed the most degradative effects on the structure of polymers in the body of PET bottles and release of MPs. Regardless of their type, source and commercial brands, bottled water is contaminated with hundreds to thousands MPs/L. The main portion (above 90%) of these MPs are < 5 µm particles with considerable effects on human health.

Effect of Maternal Triclosan Exposure on Neonatal Thyroid-Stimulating Hormone Levels: A Cross-Sectional Study.

Objective: This study is aimed at assessing the relationship between maternal urinary triclosan (uTCS) exposure and the thyroid-stimulating hormone (TSH) level of infant cord blood. Methods: This cross-sectional study was carried out in 2019-2020 in Isfahan, Iran, and 99 pregnant women participated in the study. Urine samples were collected after the 28th week of pregnancy, and the concentration of TCS was measured using GC/MS. The cord blood levels of TSH (CBL-TSH) were measured. The association between uTCS and CBL-TSH was examined based on the general linear model. Results: TCS was detected (≥0.01 ng/mL) in 100% of the urine samples, with the interquartile range (25%-75%) of uTCS levels 0.6-6.23 µg/g Cr. uTCS was not associated with CBL-TSH after adjustment for covariates. A significant relationship was observed between CBL-TSH of neonates born to mothers who had given birth only once compared to mothers who had given birth twice or more times. Conclusions: Maternal exposure to TCS did not affect the infant CBL-TSH. However, the high concentrations of TCS in maternal urinary samples indicate the necessity of more precise regulations to decrease the use of this chemical in the industry and increase public awareness about using TCS-free compounds.

The Association Between Heavy Metals Exposure and Sex Hormones: a Systematic Review on Current Evidence.

The general population is voluntarily or unintentionally exposed to heavy metals through ingestion of food, polluted water, or contact with soil, dust, or polluted air. A number of metals are considered as endocrine disruptors and can alter the level of reproductive hormones. This study aims to systematically review the epidemiological studies on the association between heavy metals exposure and sex hormones level. We conducted a systematic search from available databases, including PubMed, Clarivate Web of Science, Scopus, Google Scholar, and Cochrane Collaboration, until April 2021. The relevant studies were selected, and two reviewers conducted the quality assessment. Then, data were extracted based on the inclusion criteria. We identified nine articles related to the association between heavy metals exposure and sex hormones level. We summarized the relevant information. Due to the diversity of metals and the variety of sex hormones, the effect of exposure on hormones level was not clear; however in most studies, at least for one metal, a significant association (inverse or positive) was observed between metals exposure and hormones level. Heavy metals exposure may potentially alter sex hormone levels; however, further research is needed to evaluate the impact of this association.

Systematic review and meta-analysis on the association between seasonal variation and gestational diabetes mellitus.

Recently, there is growing evidence that ambient temperature and seasonal changes are related to the incidence of gestational diabetes mellitus (GDM). Thereby, this study was conducted to evaluate the association between seasonal changes and ambient temperature and GDM. We conducted a systematic search in PubMed, ISI Web of Science, Scopus, Google Scholar, and Cochrane Collaboration for human studies available until the end of 2020. We used the following keywords to identify relevant articles: "Diabetes, Gestational" (MeSH), "Glucose Tolerance Test" (MeSH), "Glucose intolerance" (MeSH), "Pregnancy outcome" (MeSH), "Birth outcome", "Seasons" (MeSH), "Weather" (MeSH), "Ambient Temperature," "Climate Change" (MeSH). Meta-analyses by using STATA software were conducted for analyzing data. Due to the high heterogeneity between included studies, a random-effects model was used. Subgroup analysis, meta-regression, and sensitivity analysis were used to define a source of heterogeneity. We found 13 studies related to the association between ambient temperature and season changes and GDM, which 11 of them were included in meta-analyses. Despite inconsistencies in outcome assessment across studies, we found a significant positive association between seasons of GDM screening and risk of GDM (pooled OR=1.12; 95% CI (1.03, 1.21)). The funnel plot and Egger's test showed that there was no significant publication bias among these studies (p=0.51). In general, season changes showed a significant positive relationship with prevalence of GDM. However, due to the unknown exact mechanism on this association, further studies should be conducted.

The association between maternal exposure to organophosphate pesticides and neonatal anthropometric measures: A systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate the epidemiological studies on the relationship between organophosphate (OP) pesticide exposure during pregnancy and neonatal anthropometric measures. MATERIALS AND METHODS: In this systematic review and meta analyses, a comprehensive search of the literature for the association of maternal exposure to OP pesticides and birth outcome including birth weight, birth length, and head circumference was conducted from scientific databases of MEDLINE, Scopus, Web of Science, and Cochrane library until the end of April 2019. We used the following keyword to identify the relevant studies: "birth weight," "birth length," "pregnancy outcome,""birth outcome," "organophosphate pesticides," and "organophosphate metabolites." Only English language studies investigating the relationship between pregnant mothers' exposure to OP metabolites and birth outcomes were examined. RESULTS: Of the 10 articles reviewed, eight studies used to assess the association with birth weight, as well as five, and six studies were used in meta analysis to determine the association between OP exposure and birth length and head circumference. Pooled estimates were performed using a fixed effects model or random effects model. No significant association was observed between maternal exposure to OPs and birth weight (ß = 1.520;95% confidence interval [CI] [-10.781, 13.820]), birth length (ß = -0.011; [-0.132, 0.109]), and head circumference (ß =0.022; 95%CI [-0.06, 0.103]). CONCLUSION: Although the effect of maternal exposure to OP on the birth outcome is not completely clear, strategies should be adopted to control the use of these substances.

Urinary paraben concentrations and their implications for human exposure in Iranian pregnant women.

Parabens are widely used as preservatives in cosmetics, medicines, and foods due to its antimicrobial properties. Concerns have been raised regarding the estrogenic activity and potential endocrine disruption effects of parabens. Studies on monitoring of paraben exposure in the Iranian population are very scarce. This study was carried out to measure urinary concentrations of parabens, to estimate their daily intake, and to identify some of the sociodemographic factors affecting exposure to these compounds. The concentrations of methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP) were measured in urine samples collected from 95 Iranian pregnant women by gas chromatography mass spectrometry. The highest median concentration was 87.0 µg/L for MP, followed by PP, EP, and BP with median concentrations of 15.6, 9.64, and 8.57 µg/L, respectively. Except BP, the urinary concentrations of other parabens were comparable to those in other countries. Also, the highest daily intake was related to MP (median = 16.5 µg/kg-BW/day), which is less than the acceptable daily intake (ADI). A significant positive correlation was observed between the measured parabens. Significant negative associations were observed between age and BP, BMI and EP as well as parity and PP. On the other hand, income and smoking were significantly positively associated with MP, BP and EP, BP, respectively. The urinary MP and BP concentrations were higher among the subjects with diploma education (P = 0.003 and P = 0.006, respectively), and during the spring, urinary MP concentration was higher than other seasons. The results showed that Iranian pregnant women are more prone to parabens and their urinary paraben concentrations are associated with sociodemographic factors. This result could serve as a basis for evaluating the rate of exposure of the Iranian population to parabens in future studies.

Maternal Exposure to Cadmium and Fetal Growth: a Systematic Review and Meta-Analysis.

This study aims to review the epidemiological studies on the association between cadmium (Cd) exposure during pregnancy and neonatal anthropometric measures. Electronic search of PubMed, Scopus, Web of Science, and Cochrane Collaboration was conducted till end of 2018. Pooled estimates were performed using a fixed-effects model or random-effects model. A total of 22 studies included in the meta-analyses. Subgroup analyses on sample type (maternal urine, maternal blood, cord blood, and placenta), meta-regression, and sensitivity analysis were performed to seek the sources of heterogeneity. In the random-effects meta-analysis of included studies, the pooled correlation coefficient between maternal exposure to Cd with birth weight was - 0.04 [95% CI (- 0.07, - 0.01), with birth length and head circumference as - 0.01 [95% CI (- 0.04, 0.02)] and - 0.02 [95% CI (- 0.06, 0.02)]. Our findings showed significant relationship between Cd exposure of pregnant women with low birth weight, but not with birth length and head circumference.

Exposure to phthalates and bisphenol A is associated with higher risk of cardiometabolic impairment in normal weight children.

Some obese individuals have normal metabolic profile, and some normal-weight persons have impaired metabolic status. Our hypothesis was that one of the potential underlying factors for such differences in cardiometabolic profiles might be the exposure to some environmental chemicals. This study aimed to investigate the association of serum bisphenol A (BPA) and phthalate metabolites with cardiometabolic risk factors in children and adolescents independent of their weight status. This case-control study was conducted on a subsample of 320 participants of a national school-based surveillance program in Iran. We measured serum BPA and phthalate metabolites by gas chromatography mass spectrophotometry. We compared them in children and adolescents with and without excess weight and those with and without cardiometabolic risk factors (80 in each group). We categorized the concentrations of chemicals to tertiles and then we applied logistic regression models after adjustment for potential confounding factors. The concentrations of BPA and some metabolites of phthalates were significantly different in the four groups studied. MEHP concentration was associated with higher odds ratio of cardiometabolic risk factors in participants with normal weight (OR, 95% CI 2.82, 1.001-7.91) and those with excess weight (OR, 95% CI 3.15, 1.27-7.83). MBP concentration increased the odds ratio of cardiometabolic risk factors only in normal weight children and adolescents (OR, 95% CI 6.59, 2.33-18.59, P < 0.001). In participants without cardiometabolic risk factor, MMP and MEHHP were significantly associated with increased risk of excess weight (OR, 95% CI 5.90, 1.21-28.75 and 7.82, 1.5-41.8, respectively). This study showed that the association of BPA and phthalate with cardiometabolic risk factors is independent of the weight status. Our findings suggest that the metabolic impairment in some normal weight children and normal metabolic profile of some obese children can be, in part, related to exposure to these environmental chemicals. Graphical abstract.

Systematic review and meta-analysis on the association between phthalates exposure and insulin resistance.

This study aims to provide an overview of human studies on the association of exposure to phthalates and insulin resistance. We systematically searched human studies available until 15 January 2018.We conducted a literature search in Scopus, ISI Web of Science, PubMed, Google Scholar, and Cochrane Collaboration. We used the following keywords to identify relevant articles: "phthalate", "phthalate ester", "metabolic syndrome", "insulin resistance", "glucose intolerance", and "diabetes". For analyzing data, we conducted meta-analysis using the Stata software. We appraised each study to examine the sources of heterogeneity, including difference in clinical outcomes and exposure measurements. To determine the robustness and whether some of the factors have the highest impact on the results of the present meta-analysis, several sensitivity analyses were conducted. Sensitivity analysis showed that by removing studies with the highest weight and age groups, no change was observed in heterogeneity. Moreover, with excluding the study conducted in Europe, the results remained unchanged and constant. In addition, the funnel plot and Egger's tests were executed to access publication bias. Both the funnel plots and Egger's test did not show any evidence of publication bias (P = 0.31). In the random effects meta-analysis of all studies (n = 8), the pooled correlation coefficient between phthalate exposure and HOMA-IR was 0.10 (95% CI; 0.07-0.12, P < 0.001), with significant heterogeneity (P < 0.001, I2 = 85.5%). Our findings revealed positive association between exposure to phthalate metabolites and increased HOMA-IR; this association remained significant even after adjusting the analysis for multiple confounding variables.

Simultaneous removal of Pb(II), Cd(II) and bacteria from aqueous solution using amino-functionalized Fe3O4/NaP zeolite nanocomposite.

Fe3O4/NaP nanocomposite was synthesized and modified using 3-aminopropyltrimethoxysilane (3-APTS)-functionalization. Fe3O4/NaP/NH2 was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, elemental analysis, energy-dispersive X-ray analysis, vibrating sample magnetometer, Brunauer-Emmett-Teller and thermogravimetric analysis techniques. Batch adsorption studies of Pb(II) and Cd(II) on Fe3O4/NaP/NH2 were investigated. The effect of experimental parameters (including pH, adsorbent dose, heavy metals' concentration, adsorption time and temperature) was studied. The results indicated that Fe3O4/NaP/NH2 have a high removal percent for Pb(II) and Cd(II) (more than 95%). The metal-loaded Fe3O4/NaP/NH2 nanocomposite could be recovered from the aqueous solution by magnetic separation and regenerated easily by acid treatment. The experimental data were fitted to Langmuir, Freundlich and Dubinin-Kaganer-Radushkevich (DKR) isotherm models. The Langmuir equation showed a better correlation with the experimental data than the other two models. The adsorption kinetics data were found to follow the pseudo-second-order kinetic model for Pb(II) and pseudo-first-order for Cd(II). The thermodynamic parameters (ΔG, ΔH and ΔS) were measured and the negative value of Gibbs energy indicated that the adsorption process was spontaneous in nature. The in vitro antibacterial activity of Fe3O4/NaP/NH2 composites before and after removal of metals show good inhibition on bacterial growth against Bacillus subtilis (as Gram-positive bacteria) and Pseudomonas aeruginosa (as Gram-negative bacteria), and the antibacterial activity of it comparison with standard drugs.

Association of exposure to Bisphenol A with obesity and cardiometabolic risk factors in children and adolescents.

In this study, the association of exposure to Bisphenol A (BPA) with obesity and cardiometabolic risk factors was investigated on 132 children and adolescents aged 6-18 years living in Isfahan, Iran. Potential contributors to BPA exposure were assessed by a questionnaire. Total BPA was detected in urine samples of all participants without significant difference in boys and girls. The mean body mass index (BMI) and waist circumference (WC) increased significantly across the BPA tertiles (p for trend = < 0.001). Similar trend was documented for systolic blood pressure (SBP) and diastolic blood pressure (DBP) as well as fasting blood sugar. The risk of obesity was 12.48 times higher in participants in the third tertile of BPA than in others (95% CI: 3.36-46.39, p < 0.001). The current study showed significant association between BPA exposure with obesity and some cardiometabolic risk factors in children and adolescents, however, further longitudinal studies are necessary to evaluate the clinical effects of this finding. Abbreviations: BMI: Body Mass Index; BPA: Bisphenol A; BSTFA: N, O-Bistrifluoroacetamide; CDC: Centers for Disease Control and Prevention; CI: Circumference Interval; DBP: Diastolic Blood Pressure; DLLME: Dispersive liquid-liquid microextraction method; FBS: Fasting Blood Glucose; HDL: high-density lipoprotein cholesterol were; LDL: low-density lipoprotein cholesterol; OR: Odd Ratio; PA: Physical Activity; SBP: Systolic Blood Pressure; TC: total cholesterol; TG: triglycerides; WC: Waist Circumference.

Association of benzene exposure with insulin resistance, SOD, and MDA as markers of oxidative stress in children and adolescents.

Benzene is a ubiquitous environmental pollutant with various health effects. It is reported that benzene exposure might be associated with insulin resistance in elderly adults. The aim of this study is to investigate the association between urinary benzene metabolite, trans, trans-muconic acid (t,t-ma) and markers of oxidative stress and insulin resistance in children and adolescents. This cross-sectional study was conducted in 2017 among 86 children and adolescents, aged 6-18 years, living in Isfahan, Iran. t,t-ma was measured as urinary benzene metabolite and homeostasis model assessment (HOMA-IR) was determined as an index of insulin resistance. Moreover, malondialdehyde (MDA) and superoxide dismutase (SOD) were assessed as oxidative stress markers. We found significant association between insulin resistance, fasting blood glucose, and fasting blood insulin with t,t-ma (p values = 0.002, 0.03, and 0.001, respectively). Results of this study indicate that benzene metabolite in higher concentrations in comparison with lower concentrations is associated with increased risk of insulin resistance. Moreover, after adjustment for age, sex, and household passive smoking, statistically significant increase were documented in SOD and MDA (4.49- and 3.54-fold, respectively) in intermediate levels of t,t-ma vs. low levels of t,t-ma (p values = 0.01 and 0.034, respectively). To the best of our knowledge, this is the first study in its kind in the pediatric age group. It showed that benzene exposures, even in environmental levels, might be associated with insulin resistance and oxidative stress in children and adolescents. Further longitudinal studies are necessary to assess the clinical impacts of this finding.

Association of urinary concentrations of phthalate metabolites with cardiometabolic risk factors and obesity in children and adolescents.

This study aimed to investigate the association of urinary concentration of phthalate metabolites with obesity and cardiometabolic risk factors in a pediatric population. This study was conducted in 2016 on 242 children and adolescents, aged 6-18 years, living in Isfahan, Iran. Urinary concentration of mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), Mono-2-ethylhexyl phthalate (MEHP), Mono-methyl phthalate (MMP), Mono (2-ethyl-5-exohexyl) phthalate (MEOHP), and mono (2-ethyl-5hydroxyhexyl) phthalate (MEHHP) metabolites were determined. The association of these metabolites with obesity and cardiometabolic risk factors was examined using student t-test, linear and logistics regression tests. Of the 242 participants studied, 140 (57.9%) were girls and 102 (42.1%) were boys. The mean (SD) age of the population was 11.34 (2.55) years and no significant difference existed in terms of age (p-value = 0.374). MBzP, MBP, MMP were observed in urine samples of all subjects, and MEHP, MEOHP, and MEHHP were observed in 99.6, 95.87, and 96.28% of the subjects, respectively. Of the total participants, 15.2% (n = 37) were obese and 37.7% (n = 92) were overweight. According to the logistic regression analysis, except MEOHP, all other pollutants were significantly associated with obesity (OR adjusted >1, p-value ≤ 0.002). A significant association existed between MBP and elevated blood pressure [OR crude in tertile3 = 4.87 (CI: 1.02-23.32), p-value = 0.024]. MBzP and MEHP were significantly associated with obesity, elevated levels of triglyceride and blood pressure. Increase in MBzP metabolite in the 3rd tertile resulted to about 2.5-fold increase in triglyceride levels than the first tertile [OR multivariate adjusted = 2.7 (CI: 1.23-6.22)]. The findings of this study clearly showed the association between phthalate metabolites with obesity, cardiometabolic risk factors in children and adolescents, however further longitudinal studies are necessary to evaluate the clinical effects of this finding.

Association of urinary phthalate metabolites concentrations with body mass index and waist circumference.

This study aims to investigate the association of urinary concentration of phthalate metabolites with body mass index (BMI) and waist circumference (WC) in 2016 on 242 children and adolescents, aged 6-18 years living in Isfahan, Iran. Urinary concentration of mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-methyl phthalate (MMP), mono (2-ethyl-5-exohexyl) phthalate (MEOHP), and mono (2-ethyl-5hydroxyhexyl) phthalate (MEHHP) metabolites were determined. For comparison of means, t test and to evaluate the association of analytes in different groups according to weight ANOVA was used. The correlation was applied to determine the association between phthalate metabolites with age, sex, WC, BMI, and BMI z-score. The univariate and multivariate regression models were used to determine the association of metabolites concentration with BMI z-score and WC. Mean (SD) BMI, BMI z-score and WC were 23.89 (4.41) kg/m2, 1.37 (1.3), and 82.37 (12.71) cm, respectively. There was a significant correlation between boys' age with BMI z-score (p value = 0.03) and WC (p value = 0.01), while the corresponding figures were not statistically significant in girls (p value = 0.48, and 0.4, respectively). Of the total population, 37 participants (15.3%) were obese. MMP, MBP, and MBzP metabolites were observed in all samples while MEHP, MEOHP, and MEHHP in 99.6, 95.86, and 96.28% of the studied population. Mean concentration of MMP (64.38 µg/L) and MBzP (268 µg/L) had the lowest and highest concentrations of metabolites, respectively. A significant relationship was observed among all studied metabolites and weight groups (p value ≤ 0.02). After adjustment for potential confounders, all metabolites (except MMP) showed a low-to-moderate positive and significant relationship with BMI z-score (ß = 0.17-0.3). A weak to moderate positive and significant relationship was observed between all phthalate metabolites and WC (ß = 0.14-0.39). The concentration of phthalate metabolites was much higher in the population living in Isfahan-Iran than in some other populations, indicating a high exposure to contaminants. Therefore, further studies and preventive measures are required for improving the environmental health.