Occurrence of phthalate esters in the yellow and Yangtze rivers of china: Risk assessment and source apportionment.

Phthalate esters (PAEs), recognized as endocrine disruptors, are released into the environment during usage, thereby exerting adverse ecological effects. This study investigates the occurrence, sources, and risk assessment of PAEs in surface water obtained from 36 sampling points within the Yellow River and Yangtze River basins. The total concentration of PAEs in the Yellow River spans from 124.5 to 836.5 ng/L, with Dimethyl phthalate (DMP) (75.4 ± 102.7 ng/L) and Diisobutyl phthalate (DiBP) (263.4 ± 103.1 ng/L) emerging as the predominant types. Concentrations exhibit a pattern of upstream (512.9 ± 202.1 ng/L) > midstream (344.5 ± 135.3 ng/L) > downstream (177.8 ± 46.7 ng/L). In the Yangtze River, the total concentration ranges from 81.9 to 441.6 ng/L, with DMP (46.1 ± 23.4 ng/L), Diethyl phthalate (DEP) (93.3 ± 45.2 ng/L), and DiBP (174.2 ± 67.6 ng/L) as the primary components. Concentration levels follow a midstream (324.8 ± 107.3 ng/L) > upstream (200.8 ± 51.8 ng/L) > downstream (165.8 ± 71.6 ng/L) pattern. Attention should be directed towards the moderate ecological risks of DiBP in the upstream of HH, and both the upstream and midstream of CJ need consideration for the moderate ecological risks associated with Di-n-octyl phthalate (DNOP). Conversely, in other regions, the associated risk with PAEs is either low or negligible. The main source of PAEs in Yellow River is attributed to the release of construction land, while in the Yangtze River Basin, it stems from the accumulation of pollutants in lakes and forests discharged into the river. These findings are instrumental for pinpointing sources of PAEs pollution and formulating control strategies in the Yellow and Yangtze Rivers, providing valuable insights for global PAEs research in other major rivers.

Association of phthalates exposure and sex steroid hormones with late-onset preeclampsia: a case-control study.

BACKGROUND: This study aimed to investigate the relationship between phthalates exposure and estrogen and progesterone levels, as well as their role in late-onset preeclampsia. METHODS: A total of 60 pregnant women who met the inclusion and exclusion criteria were recruited. Based on the diagnosis of preeclampsia, participants were divided into two groups: normotensive pregnant women (n = 30) and pregnant women with late-onset preeclampsia (n = 30). The major metabolites of phthalates (MMP, MEP, MiBP, MBP, MEHP, MEOHP, MEHHP) and sex steroid hormones (estrogen and progesterone) were quantified in urine samples of the participants. RESULTS: No significant differences were observed in the levels of MMP, MEP, MiBP, MBP, MEHP, MEOHP, and MEHHP between women with preeclampsia and normotensive pregnant women (P > 0.05). The urinary estrogen showed a negative correlation with systolic blood pressure (rs= -0.46, P < 0.001) and diastolic blood pressure (rs= -0.47, P < 0.001). Additionally, the urinary estrogen and progesterone levels were lower in women with preeclampsia compared to those in normotensive pregnant women (P < 0.05). After adjusting for confounding factors, we observed a significant association between reduced urinary estrogen levels and an increased risk of preeclampsia (aOR = 0.09, 95%CI = 0.02-0.46). Notably, in our decision tree model, urinary estrogen emerged as the most crucial variable for identifying pregnant women at a high risk of developing preeclampsia. A positive correlation was observed between urinary progesterone and MEHP (rs = 0.36, P < 0.05) in normotensive pregnant women. A negative correlation was observed between urinary estrogen and MEP in pregnant women with preeclampsia (rs= -0.42, P < 0.05). CONCLUSIONS: Phthalates exposure was similar in normotensive pregnant women and those with late-onset preeclampsia within the same region. Pregnant women with preeclampsia had lower levels of estrogen and progesterone in their urine, while maternal urinary estrogen was negatively correlated with the risk of preeclampsia and phthalate metabolites (MEP). TRIAL REGISTRATION: Registration ID in Clinical Trials: NCT04369313; registration date: 30/04/2020.

Endocrine disrupting chemicals and obesity prevention: scoping review.

INTRODUCTION: Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of natural hormones in the body. The aim of this review article is to highlight the knowledge about EDCs and obesity. METHODS: A scoping review of the electronic literature was performed using PubMed platform for studies on EDCs and obesity published between the years 2013-2023. A total of 10 systematic reviews and meta-analysis studies met our inclusion criteria on more prominent EDCs focusing mainly on bisphenols, including parabens, triclosan, and phthalates, and their association with obesity. DESIGN: Scoping review. RESULTS: EDCs, mostly bisphenols and phthalates, are related to health effects, while there is less information on the impact of parabens and triclosan. A series of negative physiological effects involving obesogenic, diabetogenic, carcinogenic, and inflammatory mechanisms as well as epigenetic and microbiota modulations was related to a prolonged EDCs exposure. A more profound research of particular pollutants is required to illuminate the accelerating effects of particular EDCs, mixtures or their metabolites on the mechanism of the development of obesity. CONCLUSION: Considering the characteristics of EDCs and the heterogeneity of studies, it is necessary to design specific studies of effect tracking and, in particular, education about daily preventive exposure to EDCs for the preservation of long-term public health.

Toxic effects of dibutyl phthalate on testes of adult zebrafish: evaluation of oxidative stress parameters and histopathology.

Dibutyl phthalate (DBP) is a phthalic compound and is most commonly used as a plasticizer in the polymer industry. It affects the hypothalamus-pituitary-gonadal axis and produces infertility in exposed animals. A total of 366 adult male zebrafish were used to evaluate the toxicological effects of DBP in testes following continuous exposure for 28 days. To evaluate histological changes during phase I of the study, 30 zebrafish were equally divided into five groups viz., control (RO water), vehicle control (0.01% DMSO), T0 (250 µg/L of water), T1 (500 µg/L of water), and T2 group (1000 µg/L of water). The protocol for phase II of the study was decided based on the results of phase I of the study. During phase II, for evaluation of oxidative stress parameters and gene expression profile, a total of 336 fish were equally divided into four groups viz., control, vehicle control, T1 (500 µg/L of water), and T2 (1000 µg/L of water). The activity of SOD, CAT, and TAC was significantly lower in zebrafish from the T2 group; however, a significantly increased level of MDA in the T2 group was recorded as compared to control groups. mRNA expression profile of sod, cat, and nrf2 genes was significantly downregulated in the T2 group as compared to the control group. Histopathology and proliferating cell nuclear antigen immunostaining revealed a reduction in spermatozoa with increased spermatocytes and spermatogonia in testes from T1 and T2 groups. The result indicated that DBP can induce oxidative stress and affect spermatogenesis in zebrafish testes.

Whole-cell biocatalysis for phthalate esters biodegradation in wastewater by a saline soil bacteria SSB-consortium.

Phthalic acid esters (PAE) are widely used as plasticizers and have been classified as ubiquitous environmental contaminants of primary concern. PAE have accumulated intensively in surface water, groundwater, and wastewaters; thus, PAE degradation is essential. In the present study, the ability of a saline soil bacteria (SSB)-consortium to degrade synthetic wastewater-phthalates with alkyl chains of different lengths, such as diethyl phthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), and di (2-ethylhexyl) phthalate (DEHP) was characterized. A central composite design-response surface methodology was applied to optimize the degradation of each phthalate, where the independent variables were temperature (21-41 °C), pH (5.3-8.6) and PAE concentration (79.5-920.4 mg L-1), and Gas Chromatography-Mass Spectrometry was used to identify the metabolites generated during phthalate degradation. Optimal conditions were 31 °C, pH 7.0, and an initial PAE concentration of 500 mg L-1, where the SSB-consortium removed 84.9%, 98.47%, 99.09% and 98.25% of initial DEP, DBP, BBP, and DEHP, respectively, in 168h. A first-order kinetic model explained - the biodegradation progression, while the half-life of PAE degradation ranged from 12.8 to 29.8 h. Genera distribution of the SSB-consortium was determined by bacterial meta-taxonomic analysis. Serratia, Methylobacillus, Acrhomobacter, and Pseudomonas were the predominant genera; however, the type of phthalate directly affected their distribution. Scanning electron microscopy analysis showed that high concentrations (1000 mg L-1) of phthalates induced morphological alterations in the bacterial SSB-consortium. The metabolite profiling showed that DEP, DBP, BBP, and DEHP could be fully metabolized through the de-esterification and ß-oxidation pathways. Therefore, the SSB-consortium can be considered a potential candidate for bioremediation of complex phthalate-contaminated water resources.

Assessing the fate, toxicity, and ecological risk of mixtures of di(2-ethylhexyl)phthalate and di-n-butylphthalate using aquatic and terrestrial microcosms.

Di(2-ethylhexyl)phthalate (DEHP) and di-n-butylphthalate (DBP) frequently coexist in different environmental compartments. Thus, in this study, model aquatic and terrestrial microcosms were prepared to analyze the combined effect of DEHP and DBP on their fate, toxicity, and ecological risk. In the aquatic microcosms, with the addition of the same amount of DEHP and DBP, a higher total amount of DEHP was detected in water, suspended particles, and sediment than DBP due to the higher Kow and half-life of DEHP than DBP. Sediment was the major sink of both phthalates, as the highest percentages of DEHP (90.0 % ~ 95.6 %) and DBP (68.7 % ~ 78.1 %) were found in the sediment. The results of the whole sediment toxicity test showed that DBP (LC50/LC10: 6.75/1.171 µg/g dw) was more toxic than DEHP (LC50/LC10: 158.75/27.25 µg/g dw) to the tubificid oligochaete Monopylephorus limosus, with a synergistic toxic effect of the mixture of DEHP and DBP (LC50/LC10: 100.3/4.6 µg/g dw). The mobility of DEHP and DBP in soil was low during irrigation, with the release of 0.054 % ~ 2.29 % DEHP and 0.097 % ~ 1.86 % DBP. The bioconcentration factors/biota-sediment accumulation factors for DEHP (70.8-145 L/kg/0.093-0.359) in the muscle of the fish Carassius auratus were lower than those for DBP (82.2-300 L/kg/0.514-1.625). The bioaccumulation factors of DEHP and DBP for earthworms were 0.373 and 0.682, respectively. The levels of DEHP and DBP in the water and sediment of aquatic systems and in the soil of terrestrial systems might pose high ecological risks to some fish species, M. limosus and earthworms, according to the risk quotient values. These data provide valuable insights for the development of government control strategies to minimize the ecological risks of DEHP and DBP.

Antioxidants in Mitigating Phthalate-Induced Male Reproductive Toxicity: A Comprehensive Review.

Phthalates, widely used as plasticizers, have been increasingly linked to male reproductive toxicity through mechanisms including oxidative stress, endocrine disruption, inflammation, and apoptosis. This comprehensive review evaluates the protective role of various antioxidants in mitigating the detrimental effects of phthalates such as di-(2-ethylhexyl) phthalate (DEHP), di-butyl phthalate (DBP), mono-(2-ethylhexyl) phthalate (MEHP), and monobutyl phthalate (MBP) on male reproductive health. Antioxidants such as lycopene, ellagic acid, genistein, and selenium compounds exhibit significant efficacy in counteracting phthalate-induced damage by neutralizing reactive oxygen species (ROS), enhancing endogenous antioxidant defenses, reducing inflammatory responses, and preventing apoptosis. Lycopene demonstrates broad-spectrum protective effects, particularly through its high ROS-scavenging capacity and ability to preserve mitochondrial function. Ellagic acid effectively ameliorates oxidative stress and inflammation, while genistein enhances the Nuclear factor erythroid-derived 2 (Nrf2) pathway and restores hormonal balance, offering robust protection against reproductive toxicity. Selenium compounds improve antioxidant enzyme activities, providing essential support against oxidative damage. These findings underscore the potential of antioxidants as therapeutic agents against phthalate-induced male reproductive dysfunction. Future research should focus on optimizing antioxidant combinations, understanding dose-response relationships, and assessing long-term efficacy and safety to develop effective interventions for safeguarding male reproductive health.

Maternal symptoms of depression and anxiety as modifiers of the relationship between prenatal phthalate exposure and infant neurodevelopment in the Atlanta African American maternal-child cohort.

Background: Prenatal exposure to phthalates, a group of synthetic chemicals widely used in consumer products, has previously been associated with adverse infant and child development. Studies also suggest that maternal depression and anxiety, may amplify the harmful effects of phthalates on infant and child neurodevelopment. Study design: Our analysis included a subset of dyads enrolled in the Atlanta African American Maternal-Child Cohort (N = 81). We measured eight phthalate metabolites in first and second trimester (8-14 weeks and 24-32 weeks gestation) maternal urine samples to estimate prenatal exposures. Phthalate metabolite concentrations were averaged across visits and natural log-transformed for analysis. Maternal symptoms of depression and anxiety were assessed using validated questionnaires (Edinberg Postnatal Depression Scale and State Trait Anxiety Inventory, respectively) and the total score on each scale was averaged across study visits. The NICU Network Neurobehavioral Scale (NNNS) was administered at two weeks of age. Our primary outcomes included two composite NNNS scores reflecting newborn attention and arousal. Linear regression was used to estimate associations between individual phthalate exposures and newborn attention and arousal. We assessed effect modification by maternal depression and anxiety. Results: Higher levels of urinary phthalate metabolites were not associated with higher levels of infant attention and arousal, but true associations may still exist given the limited power of this analysis. In models examining effect modification by maternal depression, we observed that an interquartile range increase in mono (2-ethlyhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with a significant increase in newborn arousal only among those with high depressive symptoms (MEHP: ß = 0.71, 95% confidence interval [CI] = 0.10, 1.32 for high, ß = -0.30, 95% CI = -0.73, 0.12 for low; MEOHP: ß = 0.60, 95% CI = -0.03, 1.23 for high, ß = -0.12, 95% CI = -0.58, 0.33 for low; MEHHP: ß = 0.54, 95% CI = -0.04, 1.11 for high, ß = -0.11, 95% CI = -0.54, 0.32 for low). Similar patterns were observed in models stratified by maternal anxiety, although CIs were wide. Conclusion: Our results suggest maternal anxiety and depression symptoms may exacerbate the effect of phthalates on infant neurodevelopment. Future studies are needed to determine the optimal levels of attention and arousal in early infancy.

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.

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.

Association between the Exposure to Phthalates and the Risk of Endometriosis: An Updated Review.

Endometriosis is a chronic gynecological disease, primarily associated with pelvic pain and infertility, that affects approximately 10% of the women of reproductive age. Estrogen plays a central role in endometriosis, and there is growing evidence that endocrine disruptors, such as phthalates, may contribute to its development. This review aimed to determine whether there is a causal relationship between phthalate exposure and the development of endometriosis, as well as the possible effects of phthalates on fertility, by analyzing epidemiological data. After a literature search with a combination of specific terms on this topic, we found that although there are limitations to the current studies, there is a clear association between phthalate exposure and endometriosis. Phthalates can interfere with the cellular processes of the endometrium; specifically, they can bind to PPAR and ER-α and activate TGF-ß, promoting different signaling cascades that regulate the expression of specific target genes. This may lead to inflammation, invasion, cytokine alteration, increased oxidative stress, and impaired cell viability and proliferation, culminating in endometriosis. Nevertheless, future research is important to curb the progression and development of endometriosis, and strategies for prevention, diagnosis, and treatment are a priority. In this regard, public policies and recommendations to reduce exposure to phthalates and other endocrine disruptors should be promptly implemented.

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.

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.

Phthalate and DINCH metabolites in the urine of Hungarian schoolchildren: Cumulative risk assessment and exposure determinants.

A human biomonitoring study was conducted to assess the exposure of Hungarian children aged 8-11 years to ten phthalate esters (PEs) and DINCH between 2017 and 2018. In addition to collecting urine samples from 262 participants, a questionnaire was completed by the parents or legal guardians to identify potential determinants of exposure. The highest geometric mean concentration was observed for MiBP, followed by MBP, cx- MEHP, OH-MEHP and MEP. Three out of the four DINCH metabolites were detected in more than 90% of the samples. The comparison of the urinary concentrations measured in this study with those observed in the DEMOCOPHES study revealed a significant decreasing trend in all PE metabolites investigated in both studies between 2011/2012 and 2017/2018. Different approaches were used to assess the health risks associated with the exposure to PEs and DINCH. Our results highlighted that the hazard index (HI) values were higher than 1 in 17.6% of the children when the human biomonitoring guidance values were applied. In contrast, less than 3% of the children had HI values exceeding 1 when other sources of reference values were used. By applying a safety factor of 10 for the risk assessment, 17.6-91.6% of the children were characterized by HI values higher than 0.1, indicating the need for risk reduction measures. Overall, DnBP, DiBP and DEHP were identified as the main drivers of the mixture risk. Although PEs and DINCH are ubiquitous contaminants, there are still inconsistencies and gaps in our understanding of the determinants of exposure. The results of the multivariate regression analysis showed significant associations between PE or DINCH metabolite concentrations and certain individual characteristics, use of personal care products, home and school environment and food and beverages consumption 24 h prior to sample collection.

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.

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.

Evaluating Phthalates and Bisphenol in Foods: Risks for Precocious Puberty and Early-Onset Obesity.

Recent scientific results indicate that diet is the primary source of exposure to endocrine-disrupting chemicals (EDCs) due to their use in food processing, pesticides, fertilizers, and migration from packaging to food, particularly in plastic or canned foods. Although EDCs are not listed on nutrition labels, their migration from packaging to food could inadvertently lead to food contamination, affecting individuals by inhalation, ingestion, and direct contact. The aim of our narrative review is to investigate the role of phthalates and bisphenol A (BPA) in foods, assessing their risks for precocious puberty (PP) and early-onset obesity, which are two clinical entities that are often associated and that share common pathogenetic mechanisms. The diverse outcomes observed across different studies highlight the complexity of phthalates and BPA effects on the human body, both in terms of early puberty, particularly in girls, and obesity with its metabolic disruptions. Moreover, obesity, which is independently linked to early puberty, might confound the relationship between exposure to these EDCs and pubertal timing. Given the potential public health implications, it is crucial to adopt a precautionary approach, minimizing exposure to these EDCs, especially in vulnerable populations such as children.

Primary alcohol-induced coacervation in alkyl polyglucoside micellar solution for supramolecular solvent-based microextraction and chromatographic determination of phthalates in baby food.

This study reports for the first time the phenomenon of supramolecular solvent formation based on alkyl polyglucoside as an amphiphile and primary alcohol as a coacervation agent. The physical properties (density, kinematic viscosity, phase diagram for ternary system) of the supramolecular solvent were investigated, and a mechanism for its formation was proposed. A green and simple microextraction procedure for preconcentration and determination of phthalates in baby foods packaged in plastic packaging was developed as proof-of-concept example. The microextraction procedure assumed separation of analytes from solid phase sample in micellar solution of decyl glucoside and in situ formation of supramolecular solvent for analytes preconcentration after addition of n-heptanol. The determination of phthalates in obtained extracts was implemented by high-performance liquid chromatography with UV-Vis detection. The limits of detection, calculated from a blank test based on 3σ, were determined to be 10 µg kg-1 for dimethyl phthalate, diethyl phthalate, di-n-butyl phthalate, and di-n-octyl phthalate. The developed procedure did not require filtration of sample suspension, and assumed the use of green and biodegradable substances for the supramolecular solvent formation across a wide pH range.

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.

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.