Low Molecular Weight Phthalates Research Articles

Serum Phthalate Concentrations and Biomarkers of Oxidative Stress in Adipose Tissue in a Spanish Adult Cohort.

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.

Income inequalities in exposure to endocrine disrupting chemicals among pregnant women in Taiwan

BackgroundExposure to endocrine disrupting chemicals (EDCs) is being rigorously studied in associations with various health outcomes, however less attention has been paid to its socio-economic determinants. This study investigated how EDCs exposure levels in pregnant women could differ on individual- and area- level income in Taiwan. MethodsUrinary measurements of phthalates, nonylphenol, bisphenol A, parabens and individual socio-economic variables (income, education, etc.) of pregnant women from Taiwan Maternal and Infant Cohort Study (TMICS) were linked via residence to area-level average annual household income. EDCs concentrations were compared between the four main Taiwan regions (North, Central, South and East) and between individual income groups. Lorenz curves were plotted to describe inequalities in EDCs exposure, and EDCs exposure related to income. Concentration indexes (CIx) were calculated and compared between the four regions. ResultsNo significant differences between EDCs concentrations adjusted for molar mass and creatinine across individual-level income groups were detected. Exposure inequalities were highest for parabens (CIx = 73.6 %), BPA (CIx = 73.6) and low molecular weight (LMW) phthalates (CIx = 63.3 %). Lorenz curve for LMW phthalates distribution across area-level income was significantly above the equality line (CIx = -21.9 %, p-value < 0.05). Stratification showed significant differences in inequality (p = 0.046) in LMW phthalates exposure across area-level income between South (CIx = -23.1 %), East (CIx = -35.3 %), North (CIx = -3.3 %) and Central (CIx = -6.5 %) regions. ConclusionInequalities in LMW phthalates exposure related to area-level income in East and South regions suggest target areas for public health interventions in terms of environmental regulations and health promotion. Using Lorenz curves and CIx to describe inequalities can be useful in case of inadequate sample sizes in costly human biomonitoring studies, however this method needs to be further developed and validated using human biomonitoring datasets in more diverse populations with larger socio-economic inequalities.

Long-term exposure to exogenous phthalate, masculinity and femininity trait, and gender identity in children: a Chinese 3-year longitudinal cohort study

BackgroundPhthalate esters (PAEs) are known to have hormone-like properties, and there is a growing trend of children expressing a gender identity different from assigned sex. However, there has been limited research in the potential links between PAEs exposure and gender identity.MethodsA total of 571 children (278 boys) completed the follow-up from Oct 2017 to Oct 2020 in Childhood Blood Pressure and Environmental Factors (CBPEF) cohort in Xiamen, China. Urinary PAE metabolites were measured at three time of visits using ultraperformance liquid chromatography-tandem mass spectrometry. The Children’s Sex Role Inventory scale was used to assess gender identity (masculinity, femininity, androgyny and undifferentiated), and Tanner definition was used to define puberty timing. Generalized linear models and log-binomial regression were used to assess the relationships between PAEs exposure, gender trait scores and gender identity.ResultsOverall, the concentration of most PAEs in more than 90% of participants was above the limit of detection values. In visit 1, there were 10.1% boys with femininity and 11.3% girls with masculinity; while these figures increased to 10.8% and 12.3% during follow-up, respectively. Early puberty onset accounted for 24.8% and 25.6% among boys and girls. Long-term exposure to mono-2-ethylhexyl phthalate (MEHP) (β = 1.20, 95%CI = 0.13, 2.28), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (β = 1.25, 95%CI = 0.22, 2.28) and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 1.40, 95%CI = 0.24, 2.56) was associated with the increased differences of femininity trait scores in boys who enter puberty earlier, prolonged exposure to di(2-ethylhexyl) phthalate (DEHP) might also have such a positive impact (β = 1.38, 95%CI = 0.36, 2.41). For gender identity, persistent exposure to low molecular weight phthalates (LMWP) was negatively associated with undifferentiated type among boys entering puberty earlier (RR = 0.18, 95%CI = 0.05, 0.75, P < 0.05), and most of the PAE metabolites exposures showed risk ratios > 1 for their femininity.ConclusionLong-term exposure to PAEs increase the femininity trait scores in boys with early onset of puberty. Although the mechanisms remain to be determined, environmental pollution might have subtle, yet measurable effects on childhood gender identity. Reducing these chemicals exposure has important public implications on gender development.

Biodegradation of low, medium and high molecular weight phthalate by Gordonia sp. in a batch system: Kinetics and phytotoxicity analyses

ABSTRACTPhthalic acid esters (PAEs) are highly toxic compounds and can disrupt the hormonal balance of human, animal, and aquatic organisms. Due to the hazardous nature of such compounds, their removal from constituent wastewater before discharging into the environment is mandatory. This study focused on the biodegradation of dimethyl phthalates (DMP), di-n-butyl phthalates (DBP), and di-n-octyl phthalates (DnOP) by Gordonia sp. in a batch system. Initially, five different concentrations of DBP, DMP, and DnOP (200–1000 mg/L) were chosen individually as the sole carbon source to examine their effect on the biodegradation and biomass growth of Gordonia sp. Complete degradation of DBP and DMP was achieved up to 1000 mg/L initial concentration within 96 h, whereas in case of DnOP, the degradation value was only 83.5% at 120 h for the same initial concentration. The experimental data were fitted into various substrate inhibition kinetic models, and accurate predicted values of degradation of all the three PAEs were obtained using the Tiesser model in comparison with other models, which yielded the highest and lowest R2 and SSE values of 0.99 and 0.02 × 10−4, respectively. In addition, the phytotoxicity of PAEs degraded samples was assessed and more than 50% germination index value was observed for DMP and DBP degraded sample which established the treatment efficiency of Gordonia sp. in degrading DMP and DBP. Hence, high DMP and DEP degradation and phytotoxicity removal efficiency of Gordonia sp. demonstrate its potential for the treatment of PAEs contaminated wastewater.

Associating phthalate exposure during pregnancy with preschooler's FMI, ABSI and BRI trajectories via putative mechanism pathways

Phthalates are well-known obesogens, but a few studies have explored their impacts on the childhood fat mass index (FMI), body shape index (ABSI) and body roundness index (BRI). Information from 2950 participants recruited in the Ma'anshan Birth Cohort was analyzed. The relationships between six maternal phthalate metabolites and their mixture and childhood FMI, ABSI and BRI were investigated. FMI, ABSI and BRI in children aged 3.5 y, 4.0 y, 4.5 y, 5.0 y, 5.5 y and 6.0 y were calculated. The latent class trajectory modeling categorized the FMI trajectories into “rapidly increasing FMI” (4.71%) and “stable FMI” (95.29%) groups; ABSI trajectories were categorized as “decreasing ABSI” (32.74%), “stable ABSI” (46.55%), “slowly increasing ABSI” (13.26%), “moderately increasing ABSI” (5.27%) and “rapidly increasing ABSI” (2.18%) groups; BRI trajectories were categorized as “increasing BRI” (2.82%), “stable BRI” (19.85%), and “decreasing BRI” (77.34%) groups. Prenatal MEP exposure was associated with repeated measurements of FMI (β = 0.111, 95% CI = 0.002–0.221), ABSI (β = 0.145, 95% CI = 0.023–0.268) and BRI (β = 0.046, 95% CI = −0.005–0.097). Compared with each stable trajectory group, prenatal MEP (OR = 0.650, 95% CI = 0.502–0.844) and MBP (OR = 0.717, 95% CI = 0.984–1.015) were linked to a decreased risk of “decreasing BRI” in children; there was a negative relationship between MBP and the “decreasing ABSI” group (OR = 0.667, 95% CI = 0.487–0.914), and MEP increased the risks of “slowly increasing ABSI” (OR = 1.668, 95% CI = 1.210–2.299) and “rapidly increasing ABSI” (OR = 2.522, 95% CI = 1.266–5.024) in children. Phthalate mixture during pregnancy showed significant relationships with all anthropometric indicator trajectories, with MEP and MBP always being of the largest importance. In conclusion, this study suggested that prenatal phthalate coexposure increased the childhood probability of being in higher ABSI and BRI trajectory groups. That is, children were more likely to be obese when they were exposed to higher levels of some phthalate metabolites and their mixture. The low-molecular weight phthalates, including MEP and MBP, contributed the greatest weights.

A novel hybrid system for continuous biodegradation and toxicity removal of low molecular weight phthalates

Dimethyl phthalate (DMP) and diethyl phthalate (DEP) are environmental toxicants that can interfere with the endocrine system and cause adverse health impacts by mimicking the natural hormone activity. The present study focused on the biodegradation of DMP and DEP mixture by Cellulosimicrobium bacteria in a bioreactor under batch, fed-batch, continuous and continuous with biomass recycle modes. Biomass recycling was done followed by microfiltration using an indigenous low-cost tubular ceramic membrane. Under the batch mode of operation, maximum degradation values of 85 % and 58 % were observed at 1000 and 2000 mg/L initial concentrations of DMP and DEP, respectively, in mixture, whereas, complete degradation was achieved in the fed-batch system at the same initial concentrations. In continuous operation mode at 24 h hydraulic retention time, complete degradation was achieved for all inlet DMP and DEP concentrations. The biomass recycle operation mode was found to be the best strategy owing to complete degradation of the phthalates, even at very high inlet concentrations and at a short hydraulic retention time (HRT) of 16 h. A high germination index (GI) value of 91.86 % and 0 % brine shrimp mortality further demonstrated the potential of the biomass recycle system for the treatment of phthalate containing wastewater.

Urine phthalate levels were associated with skin barrier dysfunction and atopic sensitization in children.

Phthalates can cause immunological disorders and aggravate allergic diseases. Thus, we investigated the relationship between urinary phthalate, skin barrier function, and atopic sensitization in children. In total, 448 school children [334 with severe allergic disease; and 123 with severe atopic dermatitis (AD)] aged 10-12 years were enrolled in this study between June and July 2017. Four high-molecular-weight phthalates (HMWP) [Σ4HMWP] and three low-molecular-weight phthalates (LMWP) [Σ3LMWP] metabolites in urine samples, specific immunoglobulin E (IgE), and total eosinophil count were measured. Four-part trans epidermal water loss (TEWL) (cheek, leg, and upper/lower arm; Σ4TEWL) was measured to evaluate the skin barrier function. After adjusting for confounding variables, Σ4TEWL was significantly associated with the quartiles of urinary Σ4HMWP [adjusted β=7.897, 95% confidence interval (CI): 0.636-15.158, p=0.033] and Σ3LMWP (adjusted β=9.670, 95% CI: 2.422-16.919, p=0.009). The adjusted analyses revealed that the quartiles of urinary Σ4HMWP and Σ3LMWP were not significantly associated with total eosinophil count, atopic sensitization, and severe AD (p>0.05). According to the quartiles of urinary Σ4HMWP and Σ3LMWP, there were significant differences in the TEWL of the lower arm and leg (p<0.05) but not in cheek and upper arm. Exposure to HMWPs and LMWPs was significantly associated with skin barrier dysfunction but not with atopic sensitization. These results suggest that children exposed to phthalates may be more susceptible to fragile skin barrier function.

The association of prenatal phthalates, organophosphorous pesticides, and organophosphate esters with early child language ability in Norway

BackgroundPrenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides have been associated with neurodevelopmental deficits including language ability, however, few studies consider the effect of exposure mixtures and the potential longitudinal detriments over time. ObjectiveThis study examines the influence of prenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides, on children's language ability from toddlerhood to the preschool period. MethodsThis study includes 299 mother-child dyads from Norway in the Norwegian Mother, Father and Child Cohort Study (MoBa). Prenatal exposure to chemicals were assessed at 17 weeks’ gestation, and child language skills were assessed at 18 months using the Ages and Stages Questionnaire communication subscale and at preschool age using the Child Development Inventory. We ran two structural equation models to examine the simultaneous influences of chemical exposures on parent-reported and teacher-reported child language ability. ResultsPrenatal organophosphorous pesticides were negatively associated with preschool language ability through language ability at 18 months. Additionally, there was a negative association between low molecular weight phthalates and teacher-reported preschool language ability. There was no effect of prenatal organophosphate esters on child language ability at either 18 months or preschool age. ConclusionsThis study adds to the literature on prenatal exposure to chemicals and neurodevelopment and highlights the importance of developmental pathways in early childhood.

Dimethyl phthalate removal from aqueous system using a photocatalytic membrane reactor with suspended photocatalyst

Dimethyl phthalate is low molecular weight phthalate used on a wide scale within industry for manufacture of plastics, solvents, adhesives, lubricants, coatings and due to its poor biodegradability is not removed by classic wastewater treatment processes. It was proved that it affects the endocrine system, presenting carcinogenic, teratogenic and mutagenic effects on upon living organisms. Therefore, there is a need for more advanced treatment methods such as advanced oxidation processes for dimethyl phthalate removal from aqueous systems. A hybrid process consisting from photo catalysis and membrane based processes was investigated and the optimum parameters for dimethyl phthalate removal were established. In respect to photocatalytic process the influence of photo catalyst dose, pH, irradiation time were studied and process kinetics were set up using a synthetic dimethyl phthalate solution. In order to recover and reuse the photocatalyst a membrane process was used and optimum working pressure was determined. In the case of real wastewater matrix the addition of hydrogen peroxide was needed, in the photocatalytic stage, in order to improve process efficiency. Four treatment cycles, using real wastewater spiked with dimethyl phthalate, were performed with the reuse of photo catalyst proving that the use of photocatalytic membrane reactor with suspended photo catalyst represents a promising method for phthalates removal from aqueous systems.

Effects of Prenatal Phthalate Exposure on Early Childhood Expressive Language Development Trajectories

BACKGROUND AND AIM: Phthalates are common endocrine disruptors that can impair neurodevelopment. We investigated potential links between prenatal exposure to phthalates and child language development trajectories given prior inconsistent evidence across individual phthalates. METHODS: We investigated fourteen urinary phthalate metabolites, measured in maternal urine during pregnancy, and child expressive language scores from the Mullen Scales of Early Learning (MSEL) at 6, 12, 24, and 36 months in 231 children from an enhanced autism-risk cohort (19% with autism): Early Autism Risk Longitudinal Investigation (EARLI), born 2009 - 2013 from California, Maryland, and Pennsylvania. We used multiple imputation to handle missingness in MSEL (~37%) and phthalates (~9%), and assigned children to six distinct expressive language trajectories after selecting the latent class growth analysis model with best goodness-of-fit measures. We estimated relative risk ratios (RRR) of being in different language trajectories (&amp;#x22;high growth” as reference) associated with two-fold change in creatinine adjusted phthalates using multinomial logistic regression with Firth correction, adjusting for child sex, birth season, income, and maternal age, race, and education. RESULTS: Some low molecular weight phthalates were associated with sub-optimal language trajectories, e.g. RRRs of 1.33 or higher for mono-2-hydroxy-iso-butyl phthalate, peaking at 1.51 (1.02, 2.24) for the delayed growth low trajectory. In contrast, some high molecular weight phthalates exhibited protective effects for delayed growth trajectories but adverse effects for plateau and tracking trajectories: e.g. mono-isononyl phthalate with RRR 0.72 (0.59, 0.89) with delayed growth low but 1.29 (1.08, 1.53) with the tracking low trajectory. Some phthalates exhibited null patterns. CONCLUSIONS: Prenatal phthalate exposure may impact the trajectory of expressive language development in early childhood, with differences by individual phthalates, perhaps by molecular weight group. We observed adverse and protective influences of phthalates that may be influenced by small numbers in each trajectory class. KEYWORDS: phthalates, language development, trajectory analysis

Urinary metabolites and handwipe phthalate levels among adults and children in southern China: Implication for dermal exposure

Paired handwipe and urine samples were collected from adult (n = 130) and child (n = 82) residents of a typical urban community in southern China to examine relationships between external and internal exposure as well as the contribution of dermal absorption to the exposure of phthalates. The concentrations and composition profiles of phthalates were similar in handwipes from both adults and children, and contained mainly di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP) and di-iso-butyl phthalate (DiBP), consistent with profiles of phthalates in air and dust. The major metabolites of these phthalates, i.e., mono-n-butyl phthalate (mnBP) from DnBP, mono-iso-butyl phthalate (miBP) from DiBP and three metabolites of DEHP (namely mEHP, mEHHP and mEOHP) were widely detected in paired urine samples. Positive correlations were found between contamination levels of DiBP and DnBP in handwipes and their corresponding urinary metabolites, whereas no significant correlation was observed for DEHP. This suggests that dermal absorption might be an important exposure pathway particularly for low molecular weight phthalates. Our study shows that dermal absorption is a non-negligible exposure pathway for phthalates, to which children are particularly sensitive since the contribution of dermal uptake to the internal exposure of phthalates was higher in children than adults.

Personal care product use and lifestyle affect phthalate and DINCH metabolite levels in teenagers and young adults

Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12–17) and 300 from young adults (aged 18–37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 μg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 μg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5–6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2–3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites.

Phthalate exposure and DNA oxidative damage in young people of takeaway food lovers.

Numerous studies have demonstrated the ubiquitous of phthalates in materials of food and food packaging, and the effects of regular eating takeaway food for a long time on human health and phthalate exposure levels were not fully investigated. A total of 288 college students who love eating takeaway food were recruited to explore phthalate exposure and oxidative stress, by measuring metabolites of traditional or alternative phthalates and 8-hydroxydeoxyguanosine (8-OHdG, a biomarker of DNA oxidative damage) in their urine samples. Both traditional and alternative phthalates were highly detected. Based on weekly frequency of takeaway eating collecting from questionnaire, the students were divided into four groups including level 1 (L1, < 3 times), level 2 (L2, 3-7 times), level 3 (L3, 8-12 times) and level 4 (L4, > 12 times). The total concentrations of all phthalate metabolites were 42.5-893ng/mL in all students, which were significantly different among four groups, with the lowest level in L1 (p < 0.05). Checking with the generalized linear model (L1 as the reference), the concentrations of most phthalate metabolites increased 12.0-144% in L2 and L3 compared with those in L1. For each group increase, the concentrations of total metabolites, and metabolites of high and low molecular weight phthalates will increase by 0.156%, 0.128%, and 0.142%, respectively. Besides, levels of 8-OHdG (0.639-33.7ng/mL) were positively correlated with phthalate daily exposure doses. The each increase of a percentage unit of daily exposure of phthalates, the concentrations of 8-OHdG will increase by 0.258-0.405%. However, levels of 8-OHdG were not significantly different among the four groups. The alternative phthalates have already entered the body of Chinese young people. Our results indicated the regular consumption of takeaway food (e.g., more than three times per week) may increase the chance of exposure to certain phthalates, and may not significantly increase the levels of DNA oxidative damage, unless exposed to other pollutants such as phthalates.

Diverging trends of plasticizers (phthalates and non-phthalates) in indoor and freshwater environments—why?

BackgroundEuropean chemicals management aims to protect human health and the environment from legacy and emerging contaminants. The plasticizer market changed in response to the restriction of low molecular weight (LMW) phthalate plasticizers such as Di (2-ethylhexyl) phthalate (DEHP) due to their hazardous properties. We investigated patterns and trends of 19 regulated and emerging plasticizers in house dust from German homes and in suspended particulate matter (SPM) from major German rivers. The samples were used from the mid-2000s and late 2010s from two governmental long-term monitoring programs in Germany.ResultsWhile the sum of the respective plasticizer levels hardly changed over the study period, we observed a significant decrease of LMW phthalates in both house dust (2003/06, 80% of the ∑plasticizer concentration; 2014/17, 31%) and SPM (2005, 48%; 2017, 28%). This was accompanied by their substitution with high molecular weight (HMW) phthalates and non-phthalates. HMW phthalates increased from 19% of the ∑plasticizer concentration to 46% between the mid-2000s and the late 2010s in house dust, and from 50% to 63% in SPM samples. Diisononyl phthalate (DINP) replaced DEHP as the dominant plasticizer in both compartments. A significant tenfold increase (p < 0.05) was observed in SPM samples for Di (2-propylheptyl) phthalate (DPHP) (1–13%), compared to low levels in house dust (2014/17, 1%). Non-phthalates increased to 23% of the ∑plasticizer concentration in house dust but only to 9% in SPM (mid-2000s: house dust, < 1%; SPM, 1.5%). In recent house dust samples, Di (2-ethylhexyl) terephthalate (DEHT) had the third highest concentration of all plasticizers and contributed 18% to the total load, whereas Tris (2-ethylhexyl) trimellitate (TOTM) was one of the major non-phthalates in SPM samples.ConclusionsUnlike in the indoor environment, the substitution of LMW phthalates in the aquatic environment was characterized by a significant shift towards plasticizers with potentially hazardous properties. DPHP and TOTM were identified by European chemical regulation as potentially endocrine disrupting compounds and persistent, bioaccumulative and toxic compounds. Our data document the need for integrated chemicals management to safeguard the transition to a non-toxic environment.

Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study.

Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood. Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs). Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n=74) or BECs (n=78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders. One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs. Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.

Phthalate biomarkers and associations with respiratory symptoms and healthcare utilization among low-income urban children with asthma

BackgroundPhthalates are synthetic chemicals present in building materials, personal care products and other consumer goods. Limited studies link phthalates to pediatric asthma incidence; however, their effects on respiratory-related outcomes among those with pre-existing asthma remains unclear. ObjectiveWe examined associations between phthalates and asthma symptoms, healthcare use, lung function, and lung inflammation among children with asthma. MethodsWe collected repeated measures of urinary biomarkers for select phthalates and phthalate replacements (MBzP, MCINP, MCIOP, MCPP, MECPTP, MEHHTP, molar sum of DEHP biomarkers [MECPP, MEHHP, MEHP, MEOHP], MEP, MiBP, MnBP) and asthma symptoms, healthcare utilization, lung function, and inflammation among 148 predominantly low-income Black children (5–17 years) with persistent asthma every 3 months for one year. We used generalized estimating equations to assess associations between biomarker concentrations and asthma-related measures adjusting for age, sex, race/ethnicity, caregiver's education level, presence of smokers in the home, and season. We also considered co-exposures to other contaminants previously associated with asthma morbidity. ResultsWe observed consistent positive associations with individual DEHP biomarkers, the molar sum of DEHP, and BBzP with increased odds of asthma symptoms and with healthcare utilization (adjusted Odds Ratio for general asthma symptoms: ΣDEHP:1.49,95% Confidence Interval, CI:1.08–2.07; BBzP:1.34, CI:1.04–1.73). We observed similar associations between the DEHP phthalate replacement biomarker MEHHTP and most asthma symptoms evaluated; and with select low molecular weight phthalates (DiBP, DBP) and healthcare utilization. Results were similar when controlling for other environmental exposures (e.g., PM2.5, BPA). No associations were observed with lung function or inflammation, and overall, we did not observe consistent evidence of sexually dimorphic effects. ConclusionIn the present study, we found evidence to suggest that exposure to select phthalates may be associated with asthma symptoms and healthcare utilization. These findings warrant confirmation given the high asthma burden and widespread and disparate phthalate exposures reported among select populations of color.

Determinants of phthalate exposures in pregnant women in New York City

Previous studies have provided data on determinants of phthalates in pregnant women, but results were disparate across regions. We aimed to identify the food groups and demographic factors that predict phthalate exposure in an urban contemporary pregnancy cohort in the US. The study included 450 pregnant women from the New York University Children's Health and Environment Study in New York City. Urinary concentrations of 22 phthalate metabolites, including metabolites of di-2-ethylhexylphthalate (DEHP), were determined at three time points across pregnancy by liquid chromatography coupled with tandem mass spectrometry. The Diet History Questionnaire II was completed by pregnant women at mid-pregnancy to assess dietary information. Linear mixed models were fitted to examine determinants of urinary phthalate metabolite concentrations. Using partial-linear single-index (PLSI) models, we assessed the major contributors, among ten food groups, to phthalate exposure. Metabolites of DEHP and its ortho-phthalate replacement, diisononyl phthalate (DiNP), were found in >90% of the samples. The sum of creatinine-adjusted DiNP metabolite concentrations was higher in older and single women and in samples collected in summer. Hispanic and non-Hispanic Black women had lower urinary concentrations of summed metabolites of di-n-octyl phthalate (DnOP), but higher concentrations of low molecular weight phthalates compared with non-Hispanic White women. Each doubling of grain products consumed was associated with a 20.9% increase in ∑DiNP concentrations (95%CI: 4.5, 39.9). PLSI models revealed that intake of dried beans and peas was the main dietary factor contributing to urinary ∑DEHP, ∑DiNP, and ∑DnOP levels, with contribution proportions of 76.3%, 35.8%, and 27.4%, respectively. Urinary metabolite levels of phthalates in pregnant women in NYC varied by age, marital status, seasonality, race/ethnicity, and diet. These results lend insight into the major determinants of phthalates levels, and may be used to identify exposure sources and guide interventions to reduce exposures in susceptible populations.

The association between maternal urinary phthalate metabolites concentrations and pregnancy induced hypertension: Results from the EDEN Mother-Child Cohort

BackgroundStudies have suggested that exposure to endocrine disruptors such as phthalates that are widely used in our daily life (food wrapping, cosmetics, toys, medical devices, polyvinyl chloride flooring, and building materials) might be related to raised blood pressure and increased risk of cardiovascular diseases. Phthalates might induce a pro-inflammatory response and increased oxidative stress and may be a cause of pregnancy induced hypertension. MethodsWe evaluated the association between maternal exposure to phthalates during pregnancy and pregnancy induced hypertension. 604 pregnant women were included and eleven phthalate metabolites were quantified in spot maternal urine samples collected between the 23rd and 28th week of gestation in a French EDEN mother-child cohort. The associations were assessed by applying multiple logistic regression analysis. ResultsTwenty nine (4,8%) mothers developed pregnancy induced hypertension. Two low molecular weight phthalate metabolites: Monoethyl phthalate (MEP) and Mono-n‑butyl phthalate (MBP) were positively associated with pregnancy induced hypertension in crude (Odds Ratio: 1.43, 95% Confidence Interval: 1.04–1.96, p-value = 0.02 and 1.48, 1.10–2.01, p-value =0.01) and in adjusted (1.47, 1.01–2.14, p-value = 0.04 and 1.66, 1.11–2.47, p-value = 0.01) models respectively. ConclusionOur data suggest that prenatal exposure to some phthalates, including MEP and MBP, might play a role in pregnancy induced hypertension.

Low and high molecular weight metabolite concentrations in relationship to adiposity in a multi-site, multi-racial cohort of children

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

Exposure to phthalates in relation to sleep duration and social jetlag among adolescent boys and girls in Mexico City

BACKGROUND AND AIM: Emerging research has demonstrated the importance of environmental toxicants, such as phthalates, for sleep health, as they may disrupt neuronal sleep regulation circuitry. However, the impact of high-molecular-weight (HMW) versus low-molecular-weight (LMW) phthalates remains unknown. Among Mexican adolescents, we evaluated the association between exposure to HMW and LMW phthalates with sleep duration and social jetlag (a circadian marker that measures the discrepancy between weekend and weekday sleep duration). METHODS: Participants included 413 adolescents from the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) study. In 2015, urinary concentrations of 13 phthalates were measured from spot urine samples, and sleep duration was assessed with wrist-actigraph devices over 7consecutive days. We examined associations between phthalates with mean weekday and weekend sleep duration and social jetlag using linear regression models, adjusted for specific-gravity, sex, age, BMI z-score, total energy intake, caffeine intake, and physical activity. RESULTS:The mean (SD) age was 15.6 (2.0) years; 53.5% were girls. The mean (SD) sleep duration was 8.4 (1.2) hr/night on weekdays and 9.0 (1.3) hr/night on weekends. In adjusted models, each IQR increase in the HMW phthalate, mono-(2-ethyl-5-oxohexyl) phthalate was associated with a 13.3 minute (95%CI: -26.3, -0.41; p 0.05) lower social jetlag, and each IQR increase in mono-benzyl phthalate was associated with an 8.0 minute (95% CI: -16.8, -0.72; p 0.05) shorter sleep duration on weekends. Among LMW phthalates, we found that each IQR increase in monoethyl phthalate was associated with an 8.6 minute (95% CI: -17.9, -0.63; p 0.05) shorter sleep duration on weekends and a 15.3 minute (95% CI: -29.0, -1.6; p 0.05) lower social jetlag. CONCLUSIONS:In contrast to other literature, higher phthalate exposure was related to shorter weekend sleep duration and lower social jetlag among Mexican adolescents, sleep characteristics that may be indicative of better sleep health. KEYWORDS: phthalates; environmental epidemiology; adolescent sleep health; social jetlag, sleep duration, wrist-actigraphy