Comprehensive risk assessment of the inhalation of plasticizers from the use of face masks.

Disposable masks, formed mainly from polymers, often incorporate various chemical additives to enhance their performance. These additives, which include plasticizers, may be released during mask usage, presenting a novel source of human exposure to these compounds. In this study, the presence of 16 organophosphate esters (OPEs), 11 phthalates, and four alternative plasticizers, in four various types of face masks, were studied, as well as their release during simulated mask use (artificial laboratory conditions). Total plasticizer concentrations exhibited minimal variation across different mask types, with mean values of 7.27 µg/face mask for surgical, 8.61 µg/face mask for reusable, 11.0 µg/face mask for KN-95, and 13.9 µg/face mask for FFP2 masks. To explore plasticizer release behavior, inhalation experiments were conducted under different conditions. The findings revealed a significant temperature-dependent enhancement in plasticizer release from masks, subsequently increasing human inhalation exposure. The inhalation experiments showed variation in the release percentages, ranging from 0.1 to 95 %, depending on the specific compound and mask type. Notably, OPEs exhibited a mean release percentage of 1.0 %, similar to phthalates, which showed a 1.2 % release. Although alternative plasticizers were less frequently released, they still presented a notable percentage of release of 4.1 %. Daily intake estimations via inhalation ranged from 0.01 to 9.04 ng/kg body weight (bw)/day for these additives. Using these estimations, carcinogenic and non-carcinogenic risks associated with this exposure to these compounds were evaluated. All calculated values for the specific compounds studied in this paper remained below the established threshold limits. However, they do represent an additional exposure pathway that, when considered alongside other more predominant routes such as indoor/outdoor inhalation, dermal absorption, and dietary intake, makes the total exposure worthy of consideration.

Mixtures of phthalates disrupt expression of genes related to lipid metabolism and peroxisome proliferator-activated receptor signaling in mouse granulosa cells.

Phthalates are a class of known endocrine disrupting chemicals that are found in common everyday products. Several studies associate phthalate exposure with detrimental effects on ovarian function, including growth and development of the follicle and production of steroid hormones. We hypothesized that dysregulation of the ovary by phthalates may be mediated by phthalate toxicity towards granulosa cells, a major cell type in ovarian follicles responsible for key steps of hormone production and nourishing the developing oocyte. To test the hypothesis that phthalates target granulosa cells, we harvested granulosa cells from adult CD-1 mouse ovaries and cultured them for 96 hours in vehicle control, a phthalate mixture, or a phthalate metabolite mixture (0.1-100 µg/mL). After culture, we measured metabolism of the phthalate mixture into monoester metabolites by the granulosa cells, finding that granulosa cells do not significantly contribute to ovarian metabolism of phthalates. Immunohistochemistry of phthalate metabolizing enzymes in whole ovaries confirmed that these enzymes are not strongly expressed in granulosa cells of antral follicles and that ovarian metabolism of phthalates likely occurs primarily in the stroma. RNA sequencing of treated granulosa cells identified 407 differentially expressed genes, with overrepresentation of genes from lipid metabolic processes, cholesterol metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Expression of significantly differentially expressed genes related to these pathways was confirmed using qPCR. Our results agree with previous findings that phthalates and phthalate metabolites have different effects on the ovary, but both interfere with PPAR signaling in granulosa cells.

Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age.

Background: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations. Methods: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors. Findings: In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) µg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05). Interpretation: We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve. Funding: This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.

Associations of Urinary Biomarkers of Phthalates, Phenols, Parabens, and Organophosphate Esters with Glycemic Traits in Pregnancy: The Healthy Start Study.

BACKGROUND: Certain endocrine-disrupting chemicals (EDCs) are widespread in consumer products and may alter glucose metabolism. However, the impact of EDC exposures on glucose and insulin regulation during pregnancy is incompletely understood, despite potential adverse consequences for maternal and infant health. We estimated associations between 37 urinary biomarkers of EDCs and glucose-insulin traits among pregnant women. METHODS: Seventeen phthalate or phthalate substitute metabolites, six environmental phenols, four parabens, and ten organophosphate ester metabolites were quantified in mid-pregnancy urine from 298 participants in the Healthy Start Study. Fasting blood glucose, insulin, and hemoglobin A1c were assessed concurrently, and Homeostasis Model Assessment 2-Insulin Resistance (HOMA2-IR) was calculated. Gestational diabetes diagnoses and screening results were obtained from medical records for a subset of participants. We estimated associations between each EDC and outcome separately using linear and robust Poisson regression models and analyzed EDC mixture effects. RESULTS: The EDC mixture was positively associated with glucose, insulin, and HOMA2-IR, although overall associations were attenuated after adjustment for maternal BMI. Two mixture approaches identified di(2-ethylhexyl) phthalate (DEHP) metabolites as top contributors to the mixture's positive associations. In single-pollutant models, DEHP metabolites were positively associated with fasting glucose, fasting insulin, and HOMA2-IR even after adjustment for maternal BMI. For example, each interquartile range increase in log2-transformed mono(2-ethyl-5-oxohexyl) phthalate was associated with 2.4 mg/dL (95% confidence interval (CI): 1.1, 3.6) higher fasting glucose, 11.8% (95%CI: 3.6, 20.5) higher fasting insulin, and 12.3% (95%CI: 4.2, 21.1) higher HOMA2-IR. Few EDCs were associated with hemoglobin A1c or with a combined outcome of impaired glucose tolerance or gestational diabetes. DISCUSSION: Exposures to phthalates and particularly DEHP during pregnancy are associated with altered glucose-insulin regulation. Disruptions in maternal glucose metabolism during pregnancy may contribute to adverse pregnancy outcomes including gestational diabetes and fetal macrosomia, and associated long-term consequences for maternal and child health.

Associations of environmental chemical exposures measured in personal silicone wristbands with sociodemographic factors, COVID-19 restrictions, and child respiratory health.

BACKGROUND: Although human biomonitoring of environmental chemicals has been considered a gold standard, these methods can be costly, burdensome, and prone to unwanted sources of variability that may cause confounding. Silicone wristbands have recently emerged as innovative passive samplers for measuring personal exposures. METHODS: In a pilot study from 2019 to 2021 involving 55 children aged 5-9 years in Seattle and Yakima, Washington, we utilized silicone wristbands to explore associations of sociodemographic variables and COVID-19-related restrictions, including school closures, with exposures to numerous chemicals including brominated and organophosphate ester (OPE) flame retardants, polychlorinated biphenyls, polycyclic aromatic hydrocarbons (PAHs), phthalates, and pesticides. We additionally conducted the first analysis testing silicone wristband chemicals as predictors of child wheeze, individually and in mixtures via logistic weighted quantile sum regression (WQS). RESULTS: Among 109 semi-volatile organic compounds measured, we detected 40 in >60% of wristbands worn by children continuously for an average of 5 days. Chemicals were generally positively correlated, especially within the same class. Male sex and increasing age were linked with higher exposures across several chemical classes; Hispanic/Latino ethnicity was linked with higher exposures to some phthalates and OPEs. COVID-19 restrictions were associated with lower wristband concentrations of brominated and triaryl OPE flame retardants. Each one-decile higher WQS exposure index was suggestively associated with 2.11-fold [95% CI: 0.93-4.80] higher odds of child wheeze. Risk of child wheeze was higher per 10-fold increase in the PAH chrysene (RR = 1.93[1.07-3.49]), the pesticide cis-permethrin (3.31[1.23-8.91]), and di-isononyl phthalate (DINP) (5.40[1.22-24.0]) CONCLUSIONS: Our identification of demographic factors including sex, age, and ethnicity associated with chemical exposures may aid efforts to mitigate exposure disparities. Lower exposures to flame retardants during pandemic restrictions corroborates prior evidence of higher levels of these chemicals in school versus home environments. Future research in larger cohorts is needed to validate these findings.

Occurrence of specific pollutants in a mixture of sewage and rainwater from an urbanized area.

Urban runoff appears to be a pathway for transferring new emerging pollutants from land-based sources to the aquatic environment. This paper aimed to identify and describe the groups of pollutants present in rainwater surface runoff as well as their mixture with wastewater in the combined sewer system from urbanized catchments and to determine the correlations between these pollutants. Four leading groups of new emerging pollutants have been identified that may be present in rainwater and municipal wastewater mixtures. The samples were tested for microplastics, phthalic acid esters, pesticides, and polycyclic aromatic hydrocarbons as well as basic parameters. The pilot site was Slupsk (northwestern Poland). We conducted nine sampling campaigns at three points. The results of the present study revealed that (i) polycyclic aromatic hydrocarbons were not present in the tested samples; (ii) the selected organochlorine pesticides were detected during one campaign in the dry season and therefore were not of critical importance; (iii) out of the 11 analyzed phthalic acid esters, five selected substances released from commonly used plastic products were present; and (iv) the number of microplastics contained in the tested samples ranged from 1,400 to 14,036 pcs/L and even occurred during pure rainfall.

Association between phthalate exposure and sleep quality in pregnant women: Results from the Korean Children's Environmental Health Study with repeated assessment of exposure.

Background: Evidence linking environmental toxicants to sleep quality is growing; however, these associations during pregnancy remain unclear. We examined the associations of repeated measures of urinary phthalates in early and late pregnancy with multiple markers of sleep quality among pregnant women. Methods: The study population included 2324 pregnant women from the Korean Children's Environmental Health Study. We analyzed spot urine samples collected at two time points during pregnancy for exposure biomarkers of eight phthalate metabolites. We investigated associations between four summary phthalates (all phthalates: ∑Phthalates; di-(2-ethylhexyl) phthalate: ∑DEHP; phthalates from plastic sources: ∑Plastic; and antiandrogenic phthalates: ∑AA) and eight individual phthalates and self-reported sleep measures using generalized ordinal logistic regression and generalized estimating equations models that accounted for repeated exposure measurements. The models were adjusted for age, body mass index, education, gestational age, income, physical activity, smoking, occupation, chronic diseases, depression, and urinary cotinine levels. Results: Multiple individual phthalates and summary measures of phthalate mixtures, including ∑Plastic, ∑DEHP, ∑AA, and ∑Phthalates, were associated with lower sleep efficiency. To illustrate, every 1-unit log increase in ∑AA was associated with a reduction of sleep efficiency by 1.37 % (95% confidence interval [CI] = -2.41, -0.32). ∑AA and ∑Phthalates were also associated with shorter sleep duration and longer sleep latency. Associations between summary phthalate measures and sleep efficiency differed by urinary cotinine levels (P for subgroup difference < 0.05). Conclusions: Findings suggest that higher phthalate exposure may be related to lower sleep efficiency, shorter sleep duration, and prolonged sleep latency during pregnancy.

Investigating the modulation of the endocannabinoid system by probiotic Lactiplantibacillus plantarum IMC513 in a zebrafish model of di-n-hexyl phthalate exposure.

Environmental pollutants used as plasticizers in food packaging and in thousands of everyday products have become harmful for their impact on human health. Among them, phthalates, recognized as emerging endocrine disruptors (EDs) can induce toxic effects leading to different health disorders. Only few studies evaluated the effects of di-n-hexyl phthalate (DnHP) in in vivo models and no studies have been conducted to investigate the effect of DnHP on the endocannabinoid system (ECS), one of the majors signaling pathways involved in the microbiota-gut-brain axis. Due to the current relevance of probiotic bacteria as beneficial dietary interventions, the present study was aimed at evaluating the potential neuroprotective impact of daily administration of Lactiplantibacillus (Lpb.) plantarum IMC513 on zebrafish adults exposed to DnHP, with a focus on ECS modulation. Gene expression analysis revealed a promising protective role of probiotic through the restoration of ECS genes expression to the control level, in the brain of zebrafish daily exposed to DnHP. In addition, the levels of main endocannabinoids were also modulated. These findings confirm the potential ability of probiotics to interact at central level by modulating the ECS, suggesting the use of probiotics as innovative dietary strategy to counteract alterations by EDs exposure.

Di(2-ethylexyl) phthalate and chromosomal damage: Insight on aneugenicity from the cytochalasin-block micronucleus assay.

Bis(2-ethylhexyl) phthalate is the most abundant phthalate used as plasticizer to soften plastics and polymers included in medical devices. Human and environmental exposure may occur because DEHP is not chemically bound to plastics and can easily leach out of the materials. This phthalate is classified as reproductive toxicant and possible carcinogen to humans. The genotoxic potential has still to be clarified, but there are indications suggesting that DEHP may have aneugenic effects. To further investigate DEHP genotoxicity, the cytochalasin-block micronucleus assay was applied and combined with the CREST staining to characterise micronucleus content and gain insights on its genotoxic mode of action. Chromosomal damage was also analysed in metaphase and ana-telophase cells and the morphology of the mitotic spindle was investigated to evaluate the possible involvement of this cellular apparatus as a target of DEHP. Our findings indicated that DEHP induced a statistically significant increase in the frequency of micronuclei as well as in the frequency of CREST-positive micronuclei. Consistently, disturbance of chromosome segregation and induction of numerical chromosome changes were observed together with changes in spindle morphology, formation of multipolar spindles and alteration of the microtubule network. Experiments performed without metabolic activation demonstrated a direct action of DEHP on chromosome segregation not mediated by its metabolites. In conclusion, there is consistent evidence for an aneugenic activity of DEHP. A thresholded genotoxic activity was identified for DEHP, disclosing possible implications for risk assessment.

Effect of combined exposure to phthalates and polycyclic aromatic hydrocarbons during early pregnancy on gestational age and neonatal size: A prospective cohort study.

Many studies have indicated that individual exposure to phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affects pregnancy outcomes. However, combined exposure to PAEs and PAHs presents a more realistic situation, and research on the combined effects of PAEs and PAHs on gestational age and newborn size is still limited. This study aimed to assess the effects of combined exposure to PAEs and PAHs on neonatal gestational age and birth size. Levels of 9 PAE and 10 PAH metabolites were measured from the urine samples of 1030 women during early pregnancy from the Zunyi Birth Cohort in China. Various statistical models, including linear regression, restricted cubic spline, Bayesian kernel machine regression, and quantile g-computation, were used to study the individual effects, dose-response relationships, and combined effects, respectively. The results of this prospective study revealed that each ten-fold increase in the concentration of monoethyl phthalate (MEP), 2-hydroxynaphthalene (2-OHNap), 2-hydroxyphenanthrene (2-OHPhe), and 1-hydroxypyrene (1-OHPyr) decreased gestational age by 1.033 days (95 % CI: -1.748, -0.319), 0.647 days (95 % CI: -1.076, -0.219), 0.845 days (95 % CI: -1.430, -0.260), and 0.888 days (95 % CI: -1.398, -0.378), respectively. Moreover, when the concentrations of MEP, 2-OHNap, 2-OHPhe, and 1-OHPyr exceeded 0.528, 0.039, 0.012, and 0.002 µg/g Cr, respectively, gestational age decreased in a dose-response manner. Upon analyzing the selected PAE and PAH metabolites as a mixture, we found that they were significantly negatively associated with gestational age, birth weight, and the ponderal index, with 1-OHPyr being the most important contributor. These findings highlight the adverse effects of single and combined exposure to PAEs and PAHs on gestational age. Therefore, future longitudinal cohort studies with larger sample sizes should be conducted across different geographic regions and ethnic groups to confirm the impact of combined exposure to PAEs and PAHs on birth outcomes.

Identification of organic constituents on atmospheric particulate matter in the East Asian background air of free troposphere by GC×GC-TOFMS.

The presence of organic compounds on the particulate matter (PM) or aerosols can arise from the condensation of gaseous organic compounds on the existing aerosols, or from organic precursors to form secondary organic aerosols (SOA) through photochemistry. The objective of this study is to characterize organic constituents on aerosols relevant to their emission sources and the key compounds revealing the evolution of aerosols with the use of a novel analytical technique. A time-of-flight mass spectrometry (TOFMS) coupled with comprehensive two-dimensional gas chromatography (GC×GC) was developed using a flow type of modulator instead of a thermal type as a prelude to field applications without the need for cryogen. The methodology of GC×GC-TOFMS is discussed in this study in detail. Since the coarse PM (PM10-2.5) may exhibit with a relatively high OC content compared to PM2.5, the GC×GC results have been obtained by analyzing PM10 samples collected in parallel with OC/EC analysis of PM2.5 samples at the Lulin Atmospheric Background Station (LABS, 23.47°N, 120.87°E, 2,862 m ASL) as the high-mountain background site in East Asia. We found that the organic analytes were in a majority in the range of 12 - 30 carbon numbers falling in the category of semi-volatile organic compounds (SVOCs) with 43 compounds of alcohol, aldehyde, ketone, and ester varieties if excluding alkanes. Intriguingly, trace amounts of plasticizers and phosphorus flame retardants such as phthalates (PAEs) and triphenyl phosphate (TPP) were also found, likely originating from regions involved in open burning of household solid waste in Southeast Asia or e-waste recycling in southern China and along the long-range transport route. Compounds such as these are unique to the specific sources, demonstrating the wide spread of these hazardous compounds in the environment.

Epidemiologically relevant phthalates affect human endometrial cells in vitro through cell specific gene expression changes related to the cytoskeleton and mitochondria.

Phthalates are endocrine disrupting chemicals (EDCs) found in common consumer products such as soft plastics and cosmetics. Although the knowledge regarding the adverse effects of phthalates on female fertility are accumulating, information on the hormone sensitive endometrium is still scarce. Here, we studied the effects of phthalates on endometrial cell proliferation and gene expression. Human endometrial primary epithelial and stromal cells were isolated from healthy fertile-aged women (n=3), and were compared to endometrial cell lines T-HESC and Ishikawa. Three different epidemiologically relevant phthalate mixtures were used, defined by urine samples in the Midlife Women Health Study (MWHS) cohort. Mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was used as a single phthalate control. Cells were harvested for proliferation testing and transcriptomic analyses after 24 h exposure. Even though all cell models responded differently to the phthalate exposures, many overlapping differentially expressed genes (DEGs, FDR<0.1), related to cell adhesion, cytoskeleton and mitochondria were found in all cell types. The qPCR analysis confirmed that MEHHP significantly affected cell adhesion gene vinculin (VCL) and NADH:ubiquinone oxidoreductase subunit B7 (NDUFB7), important for oxidative phosphorylation. Benchmark dose modelling showed that MEHHP had significant concentration-dependent effects on cytoskeleton gene actin-beta (ACTB). In conclusion, short 24 h phthalate exposures significantly altered gene expression cell-specifically in human endometrial cells, with six shared DEGs. The mixture effects were similar to those of MEHHP, suggesting MEHHP could be the main driver in the mixture. Impact of phthalate exposures on endometrial functions including receptivity should be addressed.

Exploring associations between the Phthalate Environmental Reproductive Health Literacy (PERHL) scale & biomarkers of phthalate exposure: A pilot study.

BACKGROUND: Perinatal exposure to phthalates is associated with adverse health impacts for parents and children. The field of environmental health literacy seeks to measure how environmental health information is conceptualized and used to inform behaviors. We assessed whether scores on the validated Phthalate Environmental Reproductive Health Literacy (PERHL) scale were associated with biomarkers of phthalate exposure. METHODS: 42 members of the Environmental Reproductive and Glucose Outcomes (ERGO) cohort completed the PERHL scale and provided spot urine samples. Phthalate summary measures for model outcomes were created by calculating molar sums of specific gravity-corrected metabolite concentrations representing exposure to parent phthalate, Di(2-ethylhexyl)phthalate (DEHP), personal care product (PCP)-associated phthalates, and parent butyl-phthalates. Linear regression models were used to estimate the associations of the PERHL scale scores with phthalate summary measures, controlling for educational attainment (college degree or higher vs. no college degree), age (years), and race and ethnicity (non-Hispanic White vs. non-White). RESULTS: Higher scores on the PERHL Scale and subscales were generally associated with lower ΣDEHP, Σbutyl, and ΣPCP metabolite concentrations. A one-point increase in the 'Protective Behavior/Risk Control' subscale score was significantly associated with a -30.3% (95% CI: -50.1, -2.6) decrease in ΣDEHP, and a -30.6% (95% CI: -51.5, -0.63) decrease in Σbutyl metabolite concentrations.

Association between phthalates exposure and myocardial damage in the general population: A cross-sectional study.

BACKGROUND: Cardiovascular consequences of phthalates exposure have been given increasing attention, but the association of phthalates with subclinical cardiovascular disease (CVD) was unknown. Accordingly, this study aimed to investigate the association between phthalates exposure and high-sensitivity cardiac troponin I (hs-cTnI), a marker of myocardial injury, which was detectable in the subclinical stage of CVD. METHODS: Participants aged 6 years or older with available urinary phthalates metabolites and serum hs-cTnI concentrations were included in the National Health and Nutrition Examination Survey 2003-2004 cycle. Multivariable linear regression and weighted quantiles sum (WQS) regression were used to assess the association of hs-cTnI with individual phthalates and their co-exposure. Di-2-ethylhexylphthalate (ΣDEHP), high-molecular-weight phthalate (ΣHMWP), and low-molecular-weight phthalate (ΣLMWP) were defined as the molecular sum of phthalates metabolites in urine. RESULTS: 2241 participants were finally included. The percent change of serum hs-cTnI concentrations related to per 1-standard deviation increase of logarithmic urinary phthalates concentrations was 3.4% (0.1-6.7, P = 0.04) for ΣDEHP, 3.6% (0.3-6.9, P = 0.03) for ΣHMWP, and 3.5% (0.2-6.8, P = 0.04) for ΣLMWP. Co-exposure to phthalates metabolites expressed as the WQS index also demonstrated a positive association with hs-cTnI. A similar association pattern was found in the population with no prior CVD. CONCLUSIONS: This study indicated the potential of phthalates to myocardial injury which may occur even before clinically apparent CVD was identified, emphasizing the significance of reducing phthalates in the prevention of CVD.

Association between prenatal phthalate exposure and ano-genital indices among offsprings in an Israeli cohort.

Background: In-utero phthalate exposure was shown to be associated with shortened anogenital distance (AGD) in male newborns, but findings among female are inconsistent. While phthalate exposure among pregnant women in Israel is widespread, no study has examined the association with offspring AGD. The objective of the current study was to investigate the association between maternal phthalates urinary concentration and offspring AGD at time of delivery among a birth cohort in Israel. Methods: We measured spot urinary concentration of monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) among women presenting to the delivery room at Shamir Medical Center in Israel. Birthweight, length and AGD were measured in all newborns using a standardized protocol. Each AGD measurement was adjusted to weight (ano-genital index). Confounders included socio-demographic characteristics, comorbidities and obstetrical history. Univariate and multivariate analyses assessed the associations between phthalates, confounders and AGD. Results: Overall, 193 mother and infant were analyzed. All newborns were born at term and had normal Apgar scores. Mean maternal age was 32 ± 4.7 years old. Mean birth weight and pregnancy week were 3183 ± 498 g and 39 ± 1.3, respectively. Median (IQR) urinary phthalate concentration adjusted to creatinine (ug/g) were 3.96 (2.2-6.6), 1.22 (0.7-2), 10.84 (7-20.4), 6.36 (3.3-11.2) and 0.64 (0.4-1.1) for MBP, MBzP, MECPP, MEHHP and MEOHP, respectively. Univariate comparison showed a significant association between higher than median MBzP concentration, higher Ano-Fourchetal index (AFI: 4.4 vs. 4.1, p = 0.037) and Ano-clitoral index (ACI: 11.5 vs. 10.4, p = 0.032) in infants. Total urinary phthalates concentration ≥26.25 µg/g was significantly associated with smaller penile width index (3.5 vs. 3.7, p = 0.022), higher ACI (11.6 vs. 10.3, p = 0.013) and a trend towards significance for higher AFI (4.3 vs. 4.1, p = 0.055). Following multivariate linear regression only PWI remained significantly associated with total phthalate urinary concentration. Conclusions: Maternal urinary phthalates concentration at delivery were not associated with female AGD, but total urinary phthalate concentration were inversely associated with penile width.

A Personalized Intervention to Increase Environmental Health Literacy and Readiness to Change in a Northern Nevada Population: Effects of Environmental Chemical Exposure Report-Back.

BACKGROUND: Interventions are needed to help people reduce exposure to harmful chemicals from everyday products and lifestyle habits. Report-back of individual exposures is a potential pathway to increasing environmental health literacy (EHL) and readiness to reduce exposures. OBJECTIVES: Our objective was to determine if report-back of endocrine-disrupting chemicals (EDCs) can reduce EDC exposure, increase EHL, and increase readiness to change (i.e., to implement EDC exposure-reduction behaviors). METHODS: Participants in the Healthy Nevada Project completed EHL and readiness-to-change surveys before (n = 424) and after (n = 174) a report-back intervention. Participants used mail-in kits to measure urinary biomarkers of EDCs. The report-back of results included urinary levels, information about health effects, sources of exposure, and personalized recommendations to reduce exposure. RESULTS: EHL was generally very high at baseline, especially for questions related to the general pollution. For questions related to chemical exposures, responses varied across several demographics. Statistically reliable improvements in EHL responses were seen after report-back. For readiness to change, 72% were already or planning to change their behaviors. Post-intervention, women increased their readiness (p = 0.053), while men decreased (p = 0.007). When asked what challenges they faced in reducing exposure, 79% cited not knowing what to do. This dropped to 35% after report-back. Participants with higher propylparaben were younger (p = 0.03) and women and participants who rated themselves in better health had higher levels of some phthalates (p = 0.02-0.003 and p = 0.001-0.003, respectively). After report-back, monobutyl phthalate decreased among the 48 participants who had valid urine tests before and after the intervention (p < 0.001). CONCLUSIONS: The report-back intervention was successful as evidenced by increased EHL behaviors, increased readiness to change among women, and a decrease in monobutyl phthalate. An EHL questionnaire more sensitive to chemical exposures would help differentiate high and low literacy. Future research will focus on understanding why men decreased their readiness to change and how the intervention can be improved for all participants.

Phthalate Acid Esters (PAEs) in Indoor Dust from Decoration Material Stores: Occurrence, Sources, and Health Risks.

Phthalate acid esters (PAEs) are one of the most widely used plasticizers globally, extensively employed in various decoration materials. However, studies on the impact of these materials on indoor environmental PAE pollution and their effects on human health are limited. In this study, forty dust samples were collected from four types of stores specializing in decoration materials (flooring, furniture boards, wall coverings, and household articles). The levels, sources, exposure doses, and potential health risks of PAEs in dust from decoration material stores were assessed. The total concentrations of Σ9PAE (the sum of nine PAEs) in dust from all decoration-material stores ranged from 46,100 ng/g to 695,000 ng/g, with a median concentration of 146,000 ng/g. DMP, DEP, DBP, and DEHP were identified as the predominant components. Among all stores, furniture board stores exhibited the highest Σ9PAE (159,000 ng/g, median value), while flooring stores exhibited the lowest (95,300 ng/g). Principal component analysis (PCA) showed that decoration materials are important sources of PAEs in the indoor environment. The estimated daily intakes of PAEs through non-dietary dust ingestion and dermal-absorption pathways among staff in various decoration-material stores were 60.0 and 0.470 ng/kg-bw/day (flooring stores), 113 and 0.780 ng/kg-bw/day (furniture board stores), 102 and 0.510 ng/kg-bw/day (wall covering stores), and 114 and 0.710 ng/kg-bw/day (household article stores). Particularly, staff in wall-covering and furniture-board stores exhibited relatively higher exposure doses of DEHP. Risk assessment indicated that although certain PAEs posed potential health risks, the exposure levels for staff in decoration material stores were within acceptable limits. However, staff in wall covering stores exhibited relatively higher risks, necessitating targeted risk-management strategies. This study provides new insights into understanding the risk associated with PAEs in indoor environments.

Prenatal exposure to environmental phenols and phthalates and altered patterns of DNA methylation in childhood.

INTRODUCTION: Epigenetic marks are key biomarkers linking the prenatal environment to health and development. However, DNA methylation associations and persistence of marks for prenatal exposure to multiple Endocrine Disrupting Chemicals (EDCs) in human populations have not been examined in great detail. METHODS: We measured Bisphenol-A (BPA), triclosan, benzophenone-3 (BP3), methyl-paraben, propyl-paraben, and butyl-paraben, as well as 11 phthalate metabolites, in two pregnancy urine samples, at approximately 13 and 26 weeks of gestation in participants of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (N = 309). DNA methylation of cord blood at birth and child peripheral blood at ages 9 and 14 years was measured with 450K and EPIC arrays. Robust linear regression was used to identify differentially methylated probes (DMPs), and comb-p was used to identify differentially methylated regions (DMRs) in association with pregnancy-averaged EDC concentrations. Quantile g-computation was used to assess associations of the whole phenol/phthalate mixture with DMPs and DMRs. RESULTS: Prenatal BPA exposure was associated with 1 CpG among males and Parabens were associated with 10 CpGs among females at Bonferroni-level significance in cord blood. Other suggestive DMPs (unadjusted p-value < 1 × 10-6) and several DMRs associated with the individual phenols and whole mixture were also identified. A total of 10 CpG sites at least suggestively associated with BPA, Triclosan, BP3, Parabens, and the whole mixture in cord blood were found to persist into adolescence in peripheral blood. CONCLUSIONS: We found sex-specific associations between prenatal phenol exposure and DNA methylation, particularly with BPA in males and Parabens in females. Additionally, we found several DMPs that maintained significant associations with prenatal EDC exposures at age 9 and age 14 years.

Possible associations between prenatal exposure to environmental pollutants and neurodevelopmental outcome in children.

This study aimed to evaluate associations between prenatal and childhood exposure to phthalates and prenatal exposure to polychlorinated biphenyls (PCBs) and the development of 4-year-old children. Urinary metabolites of five phthalates were measured in women upon delivery, as well as serum concentrations of four PCB congeners. Postnatal phthalate metabolites were measured from children's urine obtained at the time of developmental assessment. The primary outcome was cognitive function as evaluated by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) administered at 4 years. Secondary outcomes were motor function and response to sensory stimuli as evaluated by the Developmental Coordination Disorder Questionnaire (DCDQ) and Short Sensory Profile (SSP) that the mothers filled out, respectively. The study included 57 mother-child pairs. Higher maternal phthalate metabolite concentrations were inversely associated with WPPSI-III scores among boys and not among girls. After using linear regression models and controlling for confounding variables, we found that higher levels of monobenzyl phthalate (MBzP) were the ones associated with lower WPPSI-III scores (p=0.004, 95 %CI [-14.18; -3.16]), lower DCDQ scores (p=0.007, 95 %CI [-6.08; -1.17] and lower SSP scores (p=0.004, 95 %CI [-7.47; -1.79]). No association was found between child urinary phthalate metabolite concentrations or maternal PCB blood concentrations and developmental function. These findings indicate that higher prenatal phthalate metabolite levels may be associated with deficits in neurologic development of young boys.

Prenatal exposure to an environmentally relevant phthalate mixture alters serum cytokine levels and inflammatory markers in the F1 mouse ovary.

Phthalates are used as plasticizers and solvents in consumer products. Virtually 100% of the U.S. population has measurable exposure levels to phthalates, however, the mechanisms by which prenatal exposure to phthalate mixtures affects reproductive health in the offspring remain unclear. Thus, this study tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture promotes inflammation in F1 ovarian tissue. Pregnant CD-1 dams were dosed orally with vehicle control (corn oil) or phthalate mixture (20 µg/kg/day, 200 µg/kg/day, 200 mg/kg/day, 500 mg/kg/day). Pregnant dams delivered pups naturally and ovaries and sera from the F1 females were collected at postnatal day (PND) 21, PND 60, 3 months, and 6 months. Sera were used to measure levels of C-reactive protein (CRP). Ovaries and sera were used for cytokine array analysis. RNA was isolated from F1 ovaries and used to quantify expression of selected cytokine genes. Prenatal exposure to the mixture significantly increased the levels of CRP at 200 µg/kg/day on PND 21 compared to controls. The mixture altered 6 immune factors in sera at PND 21 and 33 immune factors in the ovary and sera at 6 months compared to controls. The mixture increased ovarian expression of cytokines at PND 21 and decreased ovarian expression of cytokines at 6 months compared to controls. These data suggest that prenatal exposure to a phthalate mixture interferes with the immune response in F1 female mice long after initial exposure.