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.

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.

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.

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 2019-2021 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.

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 Słupsk (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.

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.

The ubiquitous presence of phthalate compounds in cosmetics, personal care products and plastics commonly used in toys, food packaging or household products, results in human exposure with adverse effects on reproductive health and fetal development. Following the PRISMA methodology, this systematic review analyzes the effect of prenatal phthalate exposure on major pregnancy complications, such as gestational diabetes, pregnancy-induced hypertension, fetal growth restriction and preterm birth, and its role in fetal neurodevelopment. This review includes >100 articles published in the last 10 years, showing an association between maternal exposure to phthalates and the risk of developing pregnancy complications. Phthalates are negatively associated with motor skills and memory, and also increase the risk of delayed language acquisition, autism spectrum disorder traits, and behavioral deficits, such as attention deficit hyperactivity disorder in children prenatally exposed to phthalates. Di (2-ethylhexyl) phthalate and its metabolites (mono(2-ethylhexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate) are the main compounds associated with the above-mentioned pregnancy complications and fetal neurodevelopmental disorders. In addition, this review discusses the molecular mechanisms responsible for various pregnancy complications and neurodevelopmental disorders, and the critical window of exposure, in order to clarify these aspects. Globally, the most common molecular mechanisms involved in the effects of phthalates are endocrine disruption, oxidative stress induction, intrauterine inflammation, and DNA methylation disorders. In general, the critical window of exposure varies depending on the pathophysiology of the complication being studied, although the first trimester is considered an important period because some of the most vulnerable processes (embryogenesis and placentation) begin early in pregnancy. Future research should aim to understand the specific mechanism of the disruptive effect of each component and to establish the toxic dose of phthalates, as well as to elucidate the most critical period of pregnancy for exposure and the long-term consequences for human health.

Beeswaxes are used as a coating agent or as a wrapping material for food products making them potentially ingested by consumers. There is no regulation yet in Europe giving maximum levels of contaminants in this type of product. Nevertheless, being a natural product, they are exposed to environmental pollution, thus it appears necessary to establish their contamination rate in order to evaluate potential human exposure. In this study, a method of extraction of different environmental contaminants including pesticides, phthalates, PAHs and phenols was developed. Based on a hot Soxhlet extraction, followed by cleaning steps, the method was validated for the quantitation of the cited contaminants by LC-MS/MS and GC-(MS)/MS. Three different types of waxes were analyzed including typical white waxes (Cera Alba) and yellow waxes (Cera Flava). It was shown that all waxes had the presence of at least one contaminant and that phthalates, in particular DEHP, was present in all beeswax samples. Insecticides were found in majority among all the classes of pesticides screened. The yellow waxes were found to be contaminated with the highest rates of PAHs (60%), pesticides (75%) and phenols (40%). The detection frequency of PAHs, in contrast to phthalates, was the lowest for all the types of waxes combined.

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.
OBJECTIVE: 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.