Harmful beauty - Temporal profile of urinary phthalate metabolites in tattooed volunteers from Slovakia.

BACKGROUND AND AIM: Low molecular weight (LMW) and high molecular weight (HMW) phthalates are used in multiple everyday products, many of which are bioavailable to children. Evidence concerning the effects of these phthalates on child adiposity remain inconsistent. METHODS: Analyses included 540 racial/ethnically diverse children ages 4-8 in the Environmental Influences on Child Health Outcomes (ECHO) study, a follow-up of the NICHD Fetal Growth Studies. Urinary oxidative metabolites of three LMW and eleven HMW phthalates were determined using liquid chromatography tandem-mass spectrometry. Values were divided by molecular weight and summed to obtain composite LMW and HMW group values (nmol/ml) and natural log transformed. Outcomes were child’s body mass index (BMI) z-score, waist circumference z-score, and percent body fat. Linear regression models were adjusted for urine specific gravity, gender, age, race/ethnicity, birth weight, prolonged exclusive breastfeeding, physical activity, fast-food consumption, smoke exposure, neighborhood traffic, mother’s education and pre-pregnancy BMI. RESULTS:All children had LMW and HMW phthalate group levels at or above the limit of detection. LMW levels were not associated with BMI z-score (β [95% CI]: 0.010 [-0.037. 0.057]), waist circumference z-score (β [95% CI]: -0.002 [-0.046, 0.042]) or percent body fat (β [95% CI]: -0.009 [-0.025, -0.007]). There was evidence of a possible interaction with race (p=0.09), with increased LMW levels in Black children being positively associated with percent body fat (β [95% CI]: 0.005 [0.001, 0.010]). HMW levels were not associated with BMI z-score (β [95% CI]: -0.003 [-0.084, 0.078]), waist circumference z-score (β [95% CI]: 0.021 [-0.055, 0.097]) or percent body fat (β [95% CI]: 0.0003 [-0.008, 0.008]). CONCLUSIONS:In this largely null cross-sectional analysis only LMW phthalates in Black children were associated with percent body fat. Additional research is needed to identify possible interactions between LMW phthalates, HMW phthalates and joint exposure to related chemicals. KEYWORDS: Phthalates, Obesity and metabolic disorders, Children's environmental health

Levels of phthalate metabolites in urine among mother–child-pairs – Results from the Duisburg birth cohort study, Germany

The relationship between phthalates, a group of chemical pollutants classified as endocrine disruptors, and oxidative stress is not fully understood. The aim of the present hospital-based study was to explore the associations between circulating levels of 10 phthalate metabolites and 8 biomarkers of oxidative stress in adipose tissue. The study population (n = 143) was recruited in two hospitals in the province of Granada (Spain). Phthalate metabolite concentrations were analyzed by isotope diluted online-TurboFlow-LC-MS/MS in serum samples, while oxidative stress markers were measured by commercially available kits in adipose tissue collected during routine surgery. Statistical analyses were performed by MM estimators' robust linear regression and weighted quantile sum regression. Mainly, positive associations were observed of monomethyl phthalate (MMP), monoiso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) (all low molecular weight phthalates) with glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS), while an inverse association was found between monoiso-nonyl phthalate (MiNP) (high molecular weight phthalate) and the same biomarkers. WQS analyses showed significant effects of the phthalate mixture on GSH (β = -30.089; p-value = 0.025) and GSSG levels (β = -19.591; p-value = 0.030). Despite the limitations inherent to the cross-sectional design, our novel study underlines the potential influence of phthalate exposure on redox homeostasis, which warrants confirmation in further research.

Despite increasing attention to the occupational risk of firefighters, little is known about phthalate exposure. In our study, we detected mono-isobutyl phthalate (MiBP), mono-n-buthyl phthalate (MnBP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MECPP), and mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) in each urine sample. We detected positive association between MnBP, MiBP, mono-2-ethylhexyl phthalate (MEHP), 5OH-MEHP, 5oxo-MEHP, 5cx-MECPP, mono-isononyl phthalate (MiNP), the sum of low (∑LMWP) and high molecular-weight phthalates (∑HMWP). and Tiffeneau–Pinelli index (the ratio of forced expiratory volume in 1/ forced vital capacity; FEV1/FVC; p = 0.001−0.04) and the percent predicted value (%PV) of FEV1/FVC (p = 0.005−0.05) and negative association between MiNP and peak expiratory flow (PEF; r = −0.31; p = 0.084). We observed a positive association between phthalate metabolites (MnBP, 5OH-MEHP, 5oxo-MEHP, 5cx-MECPP, 2cx-MMHP, ∑LMWP, and ∑HMWP) and waist-to-hip ratio (WHR; p = 0.003−0.09) and body shape index (ABSI; p = 0.039−0.09) and a negative association between MnBP, ∑LMWP, and hip circumference (p = 0.005−0.02). We detected association between concentrations of 5OH-MEHP, 5cx-MECPP, 5oxo-MEHP, and MnBP and consumption of food heating in plastic material in microwave (p = 0.02−0.04) and between probands who ate margarines and vegetable fat packed in plastic containers and concentration of MMP (p = 0.03). Results of multivariate regression indicated that exposure to phthalates could be linked with changing body structure, which subsequently affects values of pulmonary functions in firefighters.

Use of stored serum in the study of time trends and geographical differences in exposure of pregnant women to phthalates

Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen metabolites were determined in samples from 60 young Danish men. Metabolites of common di-ester phthalates were detected in most urine samples. Summed di-(2-ethylhexyl) phthalate (DEHP) metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL), followed by monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and finally summed di-isononyl phthalate (DiNP) metabolites. All these metabolite levels correlated significantly, indicating that when a participant was highly exposed to one phthalate he was also highly exposed to other phthalates. Several metabolites were also detectable in serum and in seminal plasma, although in much lower levels. Significant correlations between MEP and MiBP levels in serum and urine were observed, showing that serum levels could be used as biomarkers of human exposure. For DEHP and DiNP metabolites, correlations between urine and serum levels were only observed for mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(4-methyl-7-carboxyheptyl) phthalate (MCiOP), indicating that these secondary carboxylated metabolites were better serum markers than primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-iso-nonyl phthalate (MiNP)]. In seminal plasma, only MEP levels correlated significantly to levels in urine and in serum.

Phthalate exposure and the metabolic syndrome: A systematic review and meta-analysis

BACKGROUND AND AIM: Exposure to Endocrine Disrupting Chemicals (EDC) may increase liver injury, but few studies have examined these associations in children and most focused on a single chemical group. We evaluated the associations between a wide range of prenatal EDC exposures and child liver injury. METHODS: We studied 1108 healthy children from the Human Early-Life Exposome (HELIX) project, a collaborative network of six established longitudinal population-based birth cohort studies in Europe. Thirty lipophilic EDCs (including 3 organochlorine pesticides, 5 polychlorinated-biphenyl, 2 polybrominated-diphenyl-ethers [PBDEs], 5 high molecular weight phthalates (HMWP), 5 low molecular weight phthalates, 6 phenols and 4 organophosphate pesticides) were measured in maternal pregnancy blood or urine. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and cytokeratin 18 (CK18) were measured in child serum at follow-up between age 6-11 years. Liver injury was defined as having any liver enzyme (ALT, AST or GGT) above the 90th percentile. We used Bayesian generalized linear mixed regressions (Bglmr) to estimate associations of individual chemicals, Bayesian Weighted Quantile Sum (BWQS) and Bayesian Kernel Machine Regression (BKMR) to assess the overall association of each chemical group with liver injury and CK18, adjusting for confounders. RESULTS:BWQS results indicated that organochlorine pesticides and PBDEs were associated with increased odds of liver injury (OR[95%CI] by chemical mixture quartile increase=1.44[1.23, 1.72] and 1.59[1.37, 1.90], respectively); whereas HMWP were associated with decreased odds of liver injury (OR[95%CI]=0.71[0.59, 0.85]). A quartile increase of PBDEs was positively associated with CK18 (Estimate[95%CI]=5.33 Units/Liter [2.52,8.16]). Bglmr and BKMR showed associations in same direction as the BWQS results. There was evidence of effect heterogeneity by sex for organochlorine pesticides and HMWPs with liver injury status. CONCLUSIONS:Using multiple chemical mixture approaches we found that prenatal exposures to persistent pollutants, especially to organochlorine compounds, and PBDEs, may be associated with increased risk for liver injury in childhood. KEYWORDS: Chemical exposures, Endocrine disrupting chemicals, Mixtures analysis, Modeling, Environmental epidemiology

The impact of first trimester phthalate and phenol exposure on IGF2/H19 genomic imprinting and birth outcomes

Background/Aim: Phthalates are implicated as reproductive toxicants in experimental and observational studies. We examined associations between potential exposure sources and urinary phthalate concentrations among infertile couples.Methods: Women (n=56) and their male partners (n=43) undergoing in vitro fertilization (IVF) were enrolled in a prospective cohort investigation of environmental chemicals and IVF outcomes. On the day of oocyte retrieval, women (fasting) and their male partners provided urine samples and completed questionnaires detailing use of personal care products (PCPs), consumption of medications, and foods/beverages in the preceding 24-hours. Urine was analyzed for monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-n-pentyl phthalate (MPP), mono-n-hexyl phthalate (MHxP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isononyl phthalate (MiNP), mono-isodecyl phthalate (MiDP), monocyclohexyl phthalate (MCHP), and monobenzyl phthalate (MBzP) via liquid chromatography-tandem mass spectrometry (Agilent LC 1260-AB Sciex 5500). We employed principal component analysis (PCA) to summarize questionnaire responses as patterns of exposure and entered factors into linear regression models to evaluate associations with urinary phthalate concentrations, adjusted for specific gravity, age, BMI (for women), history of smoking, and race. Results: Among women, recent application of moisturizers, cleansers, and nail polish was associated with greater urinary MBP [β=0.08 (95% CI: 0.02-0.14)] and the molar sum of diethylhexyl phthalate (DEHP) metabolites [β=0.23 (95% CI: 0.16-0.29)]. Among men, recent supplement and allergy medication intake was positively associated with the sum of DEHP metabolites [β=0.12 (95% CI: 0.02-0.21)]. Women with a tubal factor or polycystic ovarysyndrome infertility diagnosis had higher urinary phthalate concentrations than women with other infertility diagnoses.Conclusions: Among women, recent PCP use predicted urinary phthalate concentrations, whereas in men, supplements/medications were important contributors to phthalate exposure. This difference in exposure sources among couples will be useful for developing strategies to limit phthalate exposure as part of a comprehensive strategy to help improve IVF outcomes.

The associations between endocrine disrupting chemicals and markers of inflammation and immune responses: A systematic review and meta-analysis

ObjectivesTo investigate the rates of depressive symptoms in college students, explore the relationship between urinary phthalate metabolites and depressive symptoms and their gender differences, and further explore the moderating role of insomnia in this association.MethodsA total of 1 179 college students were recruited from 2 universities in Hefei and Shangrao cities from April to May 2019. The depressive symptoms and insomnia of college students were investigated by the Patient Health Questionnaire 9 and Insomnia Severity Index. The high-performance liquid chromatography-tandem mass spectrometry was adapted to determine the concentration of urinary phthalate metabolites. The generalized linear model was used to analyze the relationship of phthalate metabolites with depressive symptoms. Moderating analysis was used to examine whether insomnia moderated the relationship of phthalate metabolites with depressive symptoms.ResultsThe rates of mild depression, and moderate depression and above in college students were 31.9% and 9.2%, respectively. The phthalate metabolites exhibited a median and mean concentration spanning from 2.98 ∼ 156.55 ng/mL and 6.12 ∼ 205.53 ng/mL. The generalized linear model results showed that monobutyl phthalate (MBP) (β = 1.160, 95%CI: 0.423 ∼ 1.896) and low molecular weight phthalate (LMWP) (β = 1.230, 95%CI: 0.348 ∼ 2.113) were positively correlated with depressive symptoms, and MBP (β = 1.320, 95%CI: 0.453 ∼ 2.187) and LMWP (β = 1.396, 95%CI: 0.351 ∼ 2.440) were positively correlated with depressive symptoms only in female college students after stratified by gender. Furthermore, insomnia has a positive moderating role between MBP, LMWP, and depressive symptoms and has a sex-based difference.ConclusionsThis study suggests that there is a positive association of phthalate metabolites with depressive symptoms among Chinese college students, as well as insomnia plays a positive moderating role in this association.

Human biomonitoring reference values and characteristics of Phthalate exposure in the general population of Taiwan: Taiwan Environmental Survey for Toxicants 2013-2016.

Phthalate monoesters act through peroxisome proliferator-activated receptors in the mouse ovary

Association between Phthalate exposure and Reproductive Health in Patients Undergoing Assisted Reproductive Treatment: A Systematic Review and Meta-Analysis.