Association of phthalate metabolites with periodontitis: a population-based study.

BACKGROUND: Widespread exposure to phthalates may raise the probability of various diseases. However, the association of phthalate metabolites with periodontitis remains unclear. METHODS: Totally 3402 participants from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2014 cycles were enrolled in the cross-sectional investigation. We utilized weighted logistic regression to evaluate the association of ten phthalate metabolites with periodontitis. Restricted cubic spline analysis was applied to investigate potential nonlinear relationships. RESULTS: The weighted prevalence of periodontitis in the study was 42.37%. A one standard deviation (SD) rise in log-transformed levels of mono-2-ethyl-5-carboxypenty phthalate (MECPP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-isobutyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-benzyl phthalate (MBzP) was associated with higher odds of periodontitis, with odds ratios (95% confidence intervals) of 1.08 (1.02-1.14), 1.07 (1.02-1.11), 1.10 (1.05-1.15), 1.05 (1.01-1.09), 1.09 (1.04-1.14), and 1.08 (1.03-1.13), respectively. Individuals with the highest quartile concentrations of MECPP, MnBP, MEHHP, MEOHP, and MBzP were associated with 32%, 20%, 30%, 25%, and 26% increased odds of periodontitis, respectively, compared to those with the lowest quartile. Additionally, mono-(3-carboxypropyl) phthalate (MCPP) demonstrated an interesting inverted J-shaped relationship with periodontitis. CONCLUSIONS: The findings indicate an association of certain phthalate metabolites with periodontitis among US adults.

Fetal and Infancy Exposure to Phenols, Parabens, and Phthalates and Anthropometric Measurements up to 36 Months, in the Longitudinal SEPAGES Cohort.

BACKGROUND: Endocrine-disrupting chemicals may play a role in adiposity development during childhood. Until now literature in this scope suffers from methodologic limitations in exposure assessment using one or few urine samples and missing assessment during the infancy period. OBJECTIVES: We investigated the associations between early-life exposure to quickly metabolized chemicals and post-natal growth, relying on repeated within-subject urine collections over pregnancy and infancy. METHODS: We studied the associations of four phenols, four parabens, seven phthalates, and one nonphthalate plasticizer from weekly pooled urine samples collected from the mother during second and third trimesters (median 18 and 34 gestational weeks, respectively) and infant at 2 and 12 months of age, and child growth until 36 months. We relied on repeated measures of height, weight and head circumference from study visits and the child health booklet to predict growth outcomes at 3 and 36 months using the Jenss-Bayley nonlinear mixed model. We assessed associations with individual chemicals using adjusted linear regression and mixtures of chemicals using a Bayesian kernel machine regression model. RESULTS: The unipollutant analysis revealed few associations. Bisphenol S (BPS) at second trimester was positively associated with all infant growth parameters at 3 and 36 months, with similar patterns between exposure at third trimester and all infant growth parameters at 3 months. Mono-n-butyl phthalate (MnBP) at 12 months was positively associated with body mass index (BMI), weight, and head circumference at 36 months. Mixture analysis revealed positive associations between exposure at 12 months and BMI and weight at 36 months, with MnBP showing the highest effect size within the mixture. CONCLUSIONS: This study suggests that exposure in early infancy may be associated with increased weight and BMI in early childhood, which are risk factors of obesity in later life. Furthermore, this study highlighted the impact of BPS, a compound replacing bisphenol A, which has never been studied in this context. https://doi.org/10.1289/EHP13644.

Biodegradation of DEP, DIBP, and BBP by a psychrotolerant Sphingobium yanoikuyae strain P4: Degradation potentiality and mechanism study.

Phthalic acid esters (PAEs) are human made chemicals widely used as plasticizers to enhance the flexibility of plastic products. Due to the lack of chemical bonding between phthalates and plastics, these materials can easily enter the environment. Deleterious effects caused by this chemo-pollutant have drawn the attention of the scientific community to remediate them from different ecosystem. In this context, many bacterial strains have been reported across different habitats and Sphingobium yanoikuyae strain P4 is among the few psychrotolerant bacterial species reported to biodegrade simple and complex phthalates. In the present study, biodegradation of three structurally different PAEs viz., diethyl phthalate (DEP), di-isobutyl phthalate (DIBP), and butyl benzyl phthalate (BBP) have been investigated by the strain P4. Quantitative analyses through High-performance liquid chromatography (HPLC) revealed that the bacterium completely degraded 1 g/L of DEP, DIBP, and BBP supplemented individually in minimal media pH 7.0 within 72, 54, and 120 h of incubation, respectively, at 28 °C and under shake culture condition (180 rpm). In addition, the strain could grow in minimal media supplemented individually with up to 3 g/L of DEP and 10.0 g/L of DIBP and BBP at 28 °C and pH 7.0. The strain also could grow in metabolites resulting from biodegradation of DEP, DIBP, and BBP, viz. n-butanol, isobutanol, butyric acid, ethanol, benzyl alcohol, benzoic acid, phthalic acid, and protocatechuic acid. Furthermore, phthalic acid and protocatechuic acid were also detected as degradation pathway metabolites of DEP and DIBP by HPLC, which gave an initial idea about the biodegradation pathway(s) of these phthalates.

Vitamin D Deficiency Exacerbates Poor Sleep Outcomes with Endocrine-Disrupting Chemicals Exposure: A Large American Population Study.

Phthalates and bisphenol A are recognized as the predominant endocrine-disrupting substances (EDCs) in the environment, but their impact on sleep health remains unclear. Vitamin D has often been reported to play a role in sleep health and may be affected by endocrine-disrupting compounds. The study utilized data from 5476 individuals in the NHANES project to investigate the correlation between combined exposure to environmental EDCs and sleep duration through modeling various exposures. Furthermore, it emphasizes the importance of vitamin D in the present scenario. Preliminary analyses suggested that vitamin D-deficient individuals generally slept shorter than individuals with normal vitamin D (p < 0.05). Exposure to Mono-ethyl phthalate (MEP), triclosan (TRS), and Mono-benzyl phthalate (MZP), either alone or in combination, was associated with reduced sleep duration and a greater risk of vitamin D deficiency. Individuals with low vitamin D levels exposed to TRS experienced shorter sleep duration than those with normal vitamin D levels (p < 0.05). TRS and MZP were identified as crucial factors in patient outcomes when evaluating mixed exposures (p < 0.05). The results provide new data supporting a link between exposure to EDCs and insufficient sleep length. Additionally, they imply that a vitamin D shortage may worsen the sleep problems induced by EDCs.

Association of Di(2-ethylhexyl) Terephthalate and Its Metabolites with Nonalcoholic Fatty Liver Disease: An Epidemiology and Toxicology Study.

As an alternative plasticizer to conventional phthalates, di(2-ethylhexyl) terephthalate (DEHTP) has attracted considerable concerns, given its widespread detection in the environment and humans. However, the potential toxicity, especially liver toxicity, posed by DEHTP remains unclear. In this study, based on the 2017-2018 National Health and Nutrition Examination Survey, two metabolites of DEHTP, i.e., mono(2-ethyl-5-hydroxyhexyl) terephthalate (MEHHTP) and mono(2-ethyl-5-carboxypentyl) terephthalate (MECPTP), were found to be present in the urine samples of nearly all representative U.S. adults. Moreover, a positive linear correlation was observed between the concentrations of the two metabolites and the risk of nonalcoholic fatty liver disease (NAFLD) in the population. Results of weighted quantile sum and Bayesian kernel machine regression indicated that MEHHTP contributed a greater weight to the risk of NAFLD in comparison with 12 conventional phthalate metabolites. In vitro experiments with hepatocyte HepG2 revealed that MEHHTP exposure could increase lipogenic gene programs, thereby promoting a dose-dependent hepatic lipid accumulation. Activation of liver X receptor α may be an important regulator of MEHHTP-induced hepatic lipid disorders. These findings provide new insights into the liver lipid metabolism toxicity potential of DEHTP exposure in the population.

Cu-BTC Derived Mesoporous CuS Nanomaterial as Nanozyme for Colorimetric Detection of Glutathione.

In this paper, Cu-BTC derived mesoporous CuS nanomaterial (m-CuS) was synthesized via a two-step process involving carbonization and sulfidation of Cu-BTC for colorimetric glutathione detection. The Cu-BTC was constructed by 1,3,5-benzenetri-carboxylic acid (H3BTC) and Cu2+ ions. The obtained m-CuS showed a large specific surface area (55.751 m2/g), pore volume (0.153 cm3/g), and pore diameter (15.380 nm). In addition, the synthesized m-CuS exhibited high peroxidase-like activity and could catalyze oxidation of the colorless substrate 3,3',5,5'-tetramethylbenzidine to a blue product. Peroxidase-like activity mechanism studies using terephthalic acid as a fluorescent probe proved that m-CuS assists H2O2 decomposition to reactive oxygen species, which are responsible for TMB oxidation. However, the catalytic activity of m-CuS for the oxidation of TMB by H2O2 could be potently inhibited in the presence of glutathione. Based on this phenomenon, the colorimetric detection of glutathione was demonstrated with good selectivity and high sensitivity. The linear range was 1-20 µM and 20-300 µM with a detection limit of 0.1 µM. The m-CuS showing good stability and robust peroxidase catalytic activity was applied for the detection of glutathione in human urine samples.

Extracellular Vesicles in Environmental Toxicological Studies: Association between Urinary Concentrations of Phthalate Metabolites and Exosomal miRNA Expression Profiles.

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers.

The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

Prevalence and clinical implications of heightened plastic chemical exposure in pediatric patients undergoing cardiopulmonary bypass.

BACKGROUND: Phthalate chemicals are used to manufacture plastic medical products, including many components of cardiopulmonary bypass (CPB) circuits. We aimed to quantify iatrogenic phthalate exposure in pediatric patients undergoing cardiac surgery and examine the link between phthalate exposure and postoperative outcomes. STUDY DESIGN AND METHODS: The study included pediatric patients undergoing (n=122) unique cardiac surgeries at Children's National Hospital. For each patient, a single plasma sample was collected preoperatively and two additional samples were collected postoperatively upon return from the operating room and the morning after surgery. Concentrations of di(2-ethylhexyl) phthalate (DEHP) and its metabolites were quantified using ultra high-pressure liquid chromatography coupled to mass spectrometry. RESULTS: Patients were subdivided into three groups, according to surgical procedure: (1) cardiac surgery not requiring CPB support, (2) cardiac surgery requiring CPB with a crystalloid prime, and (3) cardiac surgery requiring CPB with red blood cells (RBCs) to prime the circuit. Phthalate metabolites were detected in all patients, and postoperative phthalate levels were highest in patients undergoing CPB with an RBC-based prime. Age-matched (<1 year) CPB patients with elevated phthalate exposure were more likely to experience postoperative complications. RBC washing was an effective strategy to reduce phthalate levels in CPB prime. DISCUSSION: Pediatric cardiac surgery patients are exposed to phthalate chemicals from plastic medical products, and the degree of exposure increases in the context of CPB with an RBC-based prime. Additional studies are warranted to measure the direct effect of phthalates on patient health outcomes and investigate mitigation strategies to reduce exposure.

A systematic review of global distribution, sources and exposure risk of phthalate esters (PAEs) in indoor dust.

Phthalate esters (PAEs) are a class of plasticizers that are readily released from plastic products, posing a potential exposure risk to human body. At present, much attention is paid on PAE concentrations in indoor dust with the understanding of PAEs toxicity. This study collected 8187 data on 10 PAEs concentrations in indoor dusts from 26 countries and comprehensively reviewed the worldwide distribution, influencing factors, and health risks of PAEs. Di-(2-ethylhexyl) phthalate (DEHP) is the predominant PAE with a median concentration of 316 µg·g-1 in indoor dust. Polyvinyl chloride wallpaper and flooring and personal care products are the main sources of PAEs indoor dust. The dust concentrations of DEHP show a downward trend over the past two decades, while high dust concentrations of DiNP are found from 2011 to 2016. The median dust contents of 8 PAEs in public places are higher than those in households. Moreover, the concentrations of 9 PAEs in indoor dusts from high-income countries are higher than those from upper-middle-income countries. DEHP in 69.8% and 77.8% of the dust samples may pose a potential carcinogenic risk for adults and children, respectively. Besides, DEHP in 16.9% of the dust samples may pose a non-carcinogenic risk to children. Nevertheless, a negligible risk was found for other PAEs in indoor dust worldwide. This review contributes to an in-depth understanding of the global distribution, sources and health risks of PAEs in indoor dust.

Chemical uptake into silicone wristbands over a five day period.

Silicone wristbands are a noninvasive personal exposure assessment tool. However, despite their utility, questions remain about the rate at which chemicals accumulate on wristbands when worn, as validation studies utilizing wristbands worn by human participants are limited. This study evaluated the chemical uptake rates of 113 organic pollutants from several chemical classes (i.e., polychlorinated biphenyls (PCB), organophosphate esters (OPEs), alkyl OPEs, polybrominated diphenyl ethers (PBDEs), brominated flame retardants (BFR), phthalates, pesticides, and polycyclic aromatic hydrocarbons (PAHs) over a five-day period. Adult participants (n = 10) were asked to wear five silicone wristbands and then remove one wristband each day. Several compounds were detected in all participants' wristbands after only one day. The number of chemicals detected frequently (i.e. in at least seven participants wristbands) increased from 20% of target compounds to 26% after three days and more substantially increased to 34% of target compounds after four days of wear. Chemicals detected in at least seven participants' day five wristbands (n = 24 chemicals) underwent further statistical analysis, including estimating the chemical uptake rates over time. Some chemicals, including pesticides and phthalates, had postive and significant correlations between concentrations on wristbands worn five days and concentrations of wristbands worn fewer days suggesting chronic exposure. For 23 of the 24 compounds evaluated there was a statistically significant and positive linear association between the length of time wristbands were worn and chemical concentrations in wristbands. Despite the differences that exist between laboratory studies using polydimethylsiloxane (PDMS) environmental samplers and worn wristbands, these results indicate that worn wristbands are primarily acting as first-order kinetic samplers. These results suggest that studies using different deployment lengths should be comparable when results are normalized to the length of the deployment period. In addition, a shorter deployment period could be utilized for compounds that were commonly detected in as little as one day.

In-situ growth of metal-organic frameworks on cellulose nanofiber aerogels for rapid adsorption of heterocyclic aromatic amines.

Heterocyclic aromatic amines (HAAs) are the main carcinogens produced during thermal processing of protein-rich foods. In this paper, a composite aerogel (TOCNFCa) with a stabilized dual-network structure was prepared via a template for the in-situ synthesis of UiO-66 on cellulose for the adsorption of HAAs in food. The dual-network structure of TOCNFCa provides the composite aerogel with excellent wet strength, maintaining excellent compressive properties. With the in-situ grown UiO-66 content up to 71.89 wt%, the hierarchical porosity endowed TOCNFCa@UiO-66 with the ability to rapidly adsorb HAAs molecules with high capacity (1.44-5.82 µmol/g). Based on excellent thermal stability, adsorption capacity and anti-interference, TOCNFCa@UiO-66 achieved satisfactory recoveries of HAAs in the boiled marinade, which is faster and more economical than the conventional SPE method. Moreover, TOCNFCa@UiO-66 could maintain 84.55 % of the initial adsorption capacity after 5 times of reuse.

Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies.

BACKGROUND: Exposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated. OBJECTIVE: To investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies. METHODS: In 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry. Serum kisspeptin (kiss54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were measured by immunosorbent assays. Free Androgen Index (FAI) was calculated as a proxy of free testosterone. Adjusted sex-stratified linear regression models for individual studies, mixed effect models (LME) accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the phthalate/DINCH mixture were performed. RESULTS: The LME suggested that each IQR increase in ln-transformed levels of several phthalates was associated with lower kisspeptin [MnBP: %change (95%CI): -2.8 (-4.2;-0.4); MEHP: -1.4 (-3.4,0.2)] and higher FSH [∑DINP: 11.8 (-0.6;25.1)] levels in females from pooled studies. G-computation showed that the phthalates/DINCH mixture was associated with lower kisspeptin [-4.28 (-8.07;-0.34)] and higher FSH [22.13 (0.5;48.4)] also in females; BKMR showed similar although non-significant pattern. In males, higher phthalates metabolites [MEHP: -12.22 (-21.09;-1.18); oxo-MEHP: -12.73 (-22.34;-1.93)] were associated with lower TT and FAI, although higher DINCH [OH-MINCH: 16.31 (6.23;27.35), cx-MINCH: 16.80 (7.03;27.46), ∑DINCH: 17.37 (7.26;29.74)] were associated with higher TT levels. No mixture associations were found in males. CONCLUSION: We observed sex-specific associations between urinary concentrations of phthalate/DINCH metabolites and the panel of selected effect biomarkers (kisspeptin and reproductive hormones). This suggests that exposure to phthalates would be associated with changes in kisspeptin levels, which would affect the HPG axis and thus influence reproductive health. However, further research is needed, particularly for phthalate replacements such as DINCH.

Relationship between phthalates exposures and metabolic dysfunction-associated fatty liver disease in United States adults.

As a new definition for the evidence of hepatic steatosis and metabolic dysfunctions, the relationship between phthalates (PAEs) and metabolic dysfunction-associated fatty liver disease (MAFLD) remains virtually unexplored. This study included 3,137 adults from the National Health and Nutrition Examination Survey spanning 2007-2018. The diagnosis of MAFLD depended on the US Fatty Liver Index (US FLI) and evidence of metabolic dysregulation. Eleven metabolites of PAEs were included in the study. Poisson regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were used to assess the associations between phthalate metabolites and MAFLD. After adjusting for potential confounders, Poisson regression analysis showed that mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate were generally significant positively associated with MAFLD (P<0.05). Furthermore, the WQS index constructed for the eleven phthalates was significantly related to MAFLD (OR:1.43; 95%CI: 1.20, 1.70), MEHHP (33.30%), MEP (20.84%), MECPP (15.43%), and mono-isobutyl phthalate (11.78%) contributing the most. This study suggests that exposure to phthalates, individually or in combination, may be associated with an increased risk of MAFLD.

Intra-Articular Injection of PLGA/Polydopamine Core-Shell Nanoparticle Attenuates Osteoarthritis Progression.

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration. Unfortunately, currently available clinical drugs are mainly analgesics and cannot alleviate the development of OA. Kartogenin (KGN) has been found to promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes for the treatment of cartilage damage in early OA. However, KGN, as a small hydrophobic molecule, is rapidly cleared from the synovial fluid after intra-articular injection. This study synthesized a KGN-loaded nanocarrier based on PLGA/polydopamine core/shell structure to treat OA. The fluorescence signal of KGN@PLGA/PDA-PEG-E7 nanoparticles lasted for 4 weeks, ensuring long-term sustained release of KGN from a single intra-articular injection. In addition, the polyphenolic structure of PDA enables it to effectively scavenge reactive oxygen species, and the BMSC-targeting peptide E7 (EPLQLKM) endows KGN@PLGA/PDA-PEG-E7 NPs with an effective affinity for BMSCs. As a result, the KGN@PLGA/PDA-PEG-E7 nanoparticles could effectively induce cartilage in vitro and protect the cartilage and subchondral bone in a rat ACLT model. This therapeutic strategy could also be extended to the delivery of other drugs, targeting other tissues to treat joint diseases.

Toxic mechanism in Daphnia magna due to phthalic acid esters and CuO nanoparticles co-exposure: The insight of physiological, microbiomic and metabolomic profiles.

Various phthalic acid esters (PAEs) such as dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) co-exist with nanopollutants in aquatic environment. In this study, Daphnia magna was exposed to nano-CuO and DBP or BBP at environmental relevant concentrations for 21-days to investigate these combined toxic effects. Acute EC50 values (48 h) of nano-CuO, DBP, and BBP were 12.572 mg/L, 8.978 mg/L, and 4.785 mg/L, respectively. Results showed that co-exposure with nano-CuO (500 µg/L) for 21 days significantly enhanced the toxicity of DBP (100 µg/L) and BBP (100 µg/L) to Daphnia magna by 18.37% and 18.11%, respectively. The activities of superoxide dismutase, catalase, and glutathione S-transferase were enhanced by 10.95% and 14.07%, 25.63% and 25.91%, and 39.93% and 35.01% in nano-CuO+DBP and nano-CuO+BBP treatments as compared to the individual exposure groups, verifying that antioxidative defense responses were activated. Furthermore, the co-exposure of nano-CuO and PAEs decreased the population richness and diversity microbiota, and changed the microbial community composition in Daphnia magna. Metabolomic analysis elucidated that nano-CuO + PAEs exposure induced stronger disturbance on metabolic network and molecular function, including amino acid, nucleotides, and lipid metabolism-related metabolic pathways, as comparison to PAEs single exposure treatments. In summary, the integration of physiological, microflora, and untargeted metabolomics analysis offers a fresh perspective into the potential ecological risk associated with nanopollutants and phthalate pollution in aquatic ecosystems.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

A Noninvasive Quantitative Method for Evaluating Intestinal Exposure to Microplastics Based on the Excretion and Metabolism Patterns of Microplastics and Their Additives.

Microplastics (MPs) pose potential health risks to the intestinal tract and gut microbiota, a topic that has garnered significant attention. However, the absence of quantitative assessment methods for human gut MP exposure impedes related health risk assessments. Here, we performed long-term continuous exposure experiments on mice using MPs that mimic actual human exposure characteristics. The daily excretion of fecal MPs and the concentrations of phthalates (PAEs) and their metabolites (mPAEs) in serum and urine were detected. The cumulative excretion rate of fecal MPs remains stable at about 93%. A significant linear correlation was observed between MP exposure and concentration of mPAEs in urine for both low MP (LMP; 150 µg of MPs/d) (R2 = 0.90) and high MP (HMP; 360 µg of MPs/d) groups (R2 = 0.97). Moreover, a strong correlation was found between daily PAEs exposure and total MP-associated PAEs exposure in both LMP (R2 = 0.77) and HMP (R2 = 0.88) groups. Based on these findings, we established a noninvasive model and evaluated multiple MP exposure parameters in the human gut across 6 continents, 30 countries, and 133 individuals. This study offers novel insights for the quantitative assessment of in vivo MP exposure and provides technical support for assessing the health risks of MPs.

Nanoparticles for Augmenting Therapeutic Potential and Alleviating the Effect of Di(2-ethylhexyl) Phthalate on Gastric Cancer.

Changes in diet culture and modern lifestyle contributed to a higher incidence of gastrointestinal-related diseases, including gastritis, implicated in the pathogenesis of gastric cancer. This observation raised concerns regarding exposure to di(2-ethylhexyl) phthalate (DEHP), which is linked to adverse health effects, including reproductive and developmental problems, inflammatory response, and invasive adenocarcinoma. Research on the direct link between DEHP and gastric cancer is ongoing, and further studies are required to establish a conclusive association. In our study, extremely low concentrations of DEHP exerted significant effects on cell migration by promoting the epithelial-mesenchymal transition in gastric cancer cells. This effect was mediated by the modulation of the PI3K/AKT/mTOR and Smad2 signaling pathways. To address the DEHP challenges, our initial design of TPGS-conjugated fucoidan, delivered via pH-responsive nanoparticles, successfully demonstrated binding to the P-selectin protein. This achievement has not only enhanced the antigastric tumor efficacy but has also led to a significant reduction in the expression of malignant proteins associated with the condition. These findings underscore the promising clinical therapeutic potential of our approach.

Development of a Phthalate Environmental Reproductive Health Literacy (PERHL) Scale.

BACKGROUND: Substantial evidence exists linking phthalate exposure to adverse reproductive health outcomes. Current US federal regulations of consumer product chemicals place the onus on individuals to mitigate their exposure to phthalates, with assumptions of sufficient environmental health literacy (EHL). Few validated scales for people of reproductive age exist to evaluate phthalate-specific EHL. OBJECTIVES: Our objective is to develop a multidimensional scale characterizing latent factors of phthalate knowledge, risk perception, and self-efficacy to inform individual-level interventions for reducing phthalate exposure. METHODS: We distributed a survey with 31 items to 117 participants in the Environmental Reproductive and Glucose Outcomes (ERGO) cohort who gave birth within the last 5 years. Exploratory factor analysis (EFA) was used to identify underlying latent factors. Internal reliability was assessed via omega hierarchical coefficient. Average sum scores for each latent factor and the overall Phthalate Environmental Reproductive Health Literacy (PERHL) score were calculated. Associations between latent factors, overall PERHL score, and sociodemographic characteristics were explored using linear models. RESULTS: Six latent factors were identified as follows: "Awareness of Phthalate Reproductive Health Impacts," "Uncertainty," "Protective Behavior/Risk Control," "Regulatory Interest," "Awareness of Phthalate Exposure Pathways," and "General Phthalate Knowledge." Each factor demonstrated acceptable to strong internal reliability, with coefficients ranging between 0.63 and 0.93. Non-white participants had lower scores for the "Awareness of Phthalate Reproductive Health Impacts" [ß: -0.35, 95% confidence interval (CI): -0.63, -0.07], "Awareness of Phthalate Exposure Pathways" (ß: -0.32, 95% CI: -0.57, -0.07), and "General Phthalate Knowledge" (ß: -0.36, 95% CI: -0.66, -0.06), but no significant difference in scores on "Uncertainty" (ß: 0.17, 95% CI: -0.16, 0.50), "Protective Behavior/Risk Control" (ß: -0.04, 95% CI: -0.36, 0.28), or "Regulatory Interest" (ß: -0.21, 95% CI: -0.51, 0.09). No associations were seen for age or educational attainment and latent or sum factors. DISCUSSION: Six latent factors were identified for the PERHL scale. Non-white race and ethnicity was associated with lower scores for knowledge-related scale factors. https://doi.org/10.1289/EHP13128.