Plasticizers levels in four fish species from the Ligurian Sea and Central Adriatic Sea (Mediterranean Sea) and potential risk for human consumption.

Plastic materials contain additives such as plasticizers and flame retardants, which are not covalently bound to plastic polymers and can therefore be unintentionally released into the marine environment. This study investigated three families of compounds, phthalates (PAEs), organophosphate esters (OPEs), and non-phthalate plasticizers (NPPs) currently used as plastic additives, in 48 muscle samples of bogue (Boops boops), European hake (Merluccius merluccius), red mullet (Mullus barbatus), and European pilchard (Sardina pilchardus) sampled in the Central Adriatic and the Ligurian Seas. The additional goal of this study is to assess the potential risk to human health from fish consumption with the objective of determining whether the detected levels might potentially pose a concern. PAEs represent the majority of the plastic additives detected in the selected species, with ubiquitous distribution across the study areas, whereas for OPEs and NPPs, there is a more pronounced difference between the two study areas, suggesting that these compounds may represent different exposure levels in the two seas. Among PAEs, bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and diisobutyl phthalate (DIBP) were the most abundant compounds, reaching levels up to 455 ng/g ww. OPEs were detected at higher concentrations in samples from the Ligurian Sea, and triethyl phosphate (TEP) was the most abundant compound. Among the NPPs, acetyl tributyl citrate (ATBC) was most frequently detected. From the results obtained, fish consumption may not pose a risk to human health (Hazard Quotient<1) but needs to be considered in future studies. Given the limited number of studies on PAEs, OPEs and NPPs in the Mediterranean Sea, further research is necessary to understand their potential bioaccumulation in marine organisms.

Di (2-ethyl hexyl) phthalate and its metabolite-induced metabolic syndrome: a review of molecular mechanisms.

OBJECTIVES: Metabolic disorders, as multifactorial disorders, are induced by genetic susceptibility and exposure to environmental chemicals. Di (2-ethyl hexyl) phthalate (DEHP), a ubiquitous plasticizer, is well known as an endocrine-disrupting chemical in living organisms. In recent decades, researchers have focused on the potential of DEHP and its main metabolite (Mono (2-ethylhexyl) phthalate) (MEHP) to induce metabolic disorders. In the present review, we aimed to summarize studies regarding DEHP and MEHP-induced Metabolic syndrome (MetS) as well as address the involved mechanisms. METHODS: A search has been carried out in Google Scholar, PubMed, Scopus, and Web of Science databases using appropriate keywords including 'Metabolic syndrome' or 'Metabolic disorder' or 'Obesity' or 'Hyperglycemia' or 'Hyperlipidemia' or 'Hypertension' or 'Non-alcoholic fatty liver disease' and 'DEHP' or 'Di (2-ethyl hexyl) phthalate' or 'Bis(2-ethylhexyl) phthalate' or 'MEHP' or 'Mono (2-ethylhexyl) phthalate'. Studies were chosen based on inclusion and exclusion criteria. Inclusion criteria are in vitro, in vivo, epidemiological studies, and English-written studies. Exclusion criteria are lack of access to the full text of studies, editorial articles, review articles, and conference articles. RESULTS: Animal studies indicate that DEHP and MEHP disrupt insulin hemostasis, increase glucose content, and induce hyperlipidemia and hypertension as well as obesity, which could lead to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). DEHP and its metabolite induce such effects directly through influence on nuclear receptors such as peroxisome proliferator-activated receptors (PPARs) or indirectly through reactive oxygen species (ROS) production. Both events led to the disruption of several molecular signaling pathways and subsequently metabolic syndrome (MetS). Furthermore, epidemiological studies showed that there was a correlation between DEHP metabolites levels and obesity, hyperglycemia, and hypertension. CONCLUSIONS: According to studies, DEHP and its main metabolite have the potential to induce MetS by involving various molecular mechanisms. Epidemiological studies concerning the association of DEHP and MetS in humans are not sufficient. Therefore, more studies are needed in this regard.

Characterization and mechanism of phthalic acid esters bioaccumulation in dominant mangrove fish at different habitats in the mangrove ecosystem of Dongzhai Harbor, China.

With the wide application of phthalic acid esters (PAEs) in the manufacturing of plastic products, a large number of PAEs were discharged into marine ecosystem and accumulated in fish, which has posed a serious threat to marine ecological environment and fishery resources. However, the bioaccumulation of PAEs in fish in mangrove ecosystem, the most productive marine ecosystem, has not been well characterized. In this study, dominant fish and their potential food sources (including particulate organic matter (POM), sedimentary organic matter (SOM), Metapenaeus ensis (Shrimp) and Oreochromis (Ore) were collected from Dongzhai Harbor, a typical mangrove ecosystem. The concentrations of nine PAEs in fish and their potential food sources were determined. Then stable nitrogen and carbon isotope analysis, combined with a new Bayesian mixing model (MixSIMMR) was used to quantify the diet compositions of fish and elucidate the effect of dietary habit on PAEs bioaccumulation in fish. The results indicated that the median concentration of ∑9PAEs in fish was 1119 µg/kg ww, positioning it at a moderate to low level in comparison to other regions. di-n-butyl phthalate (DBP) and diisononyl ortho-phthalate (DINP) were the dominant PAEs in fish. The PAEs concentration in demersal fish was significantly higher than that of pelagic fish, which may be attributed to the substantial contributions of shrimp (28.5 %) and POM (25.3 %) to the diet of demersal fish. This study provided new insights on the bioaccumulation of PAEs in dominant mangrove fish and confirmed that habitat preferences and food sources could significantly influence the bioaccumulation of PAEs in fish.

Di-2-ethylhexyl phthalate (DEHP) exposure increase female infertility.

This study explores the relationship between Di-2-ethylhexyl phthalate (DEHP) exposure and female infertility. The analysis included 998 female participants aged between 18 and 44 years. We analyzed data from the National Health and Nutrition Examination Survey (2013-2018) using multiple logistic regression and generalized linear models to assess the impact of DEHP on infertility. Additionally, we employed curve fitting and two-piecewise linear regression models to investigate potential nonlinear correlations, conducting subgroup analyses based on age, BMI, alcohol consumption, smoking status, hypertension, and diabetes. Our results, after adjusting for confounders, revealed a positive association between DEHP exposure and infertility. This association was significant whether DEHP was treated as a continuous variable (odds ratio OR = 1.28, 95 % confidence interval CI: 1.08-1.52, P = 0.0072) or as a categorical variable (P for trend = 0.0038). A non-linear relationship was identified, with an inflection point at - 3.35 (∑DEHP = 0.0981 × 10-9 mol/mg creatinine). Effect sizes were 1.55 (1.01-2.36) on the left side of the inflection point and 0.73 (0.43-1.23) on the right side. Subgroup analysis indicated that the correlation was consistent across stratified variables. In conclusion, our findings suggest a non-linear association between DEHP exposure and female infertility, with a positive correlation within a specific dose range, but no further increase in risk beyond a certain threshold.

Prenatal co-exposure to phthalate metabolites and bisphenols among non-syndromic cleft lip and/or palate in offspring.

Phthalate metabolites and bisphenols can cause adverse pregnancy outcomes. However, there is no study to evaluate the associations of prenatal exposure to phthalate metabolites and bisphenols with non-syndromic cleft lip and/or palate (NSCL/P) risk in offspring. A population-based case-control study was conducted in a multicenter setting from 2005 to 2021, enrolling 448 pregnant women. Seven phthalate metabolites and six bisphenols were quantified in placenta using liquid chromatography-tandem mass spectrometry. In the logistic regression analysis, high levels of mono-ethyl phthalate, mono-cyclohexyl phthalate, mono-octyl phthalate, bisphenol A, bisphenol AF, bisphenol AP, and fluorene-9-bisphenol were associated with increased NSCL/P risk with odds ratios (95% confidence intervals) of 1.86(1.07,3.25), 6.56(3.47,12.39), 8.49(4.44,16.24), 8.34(4.32,16.08), 3.19(1.81,5.62), 2.78(1.59,4.86), and 5.16(2.82,9.44). The Bayesian kernel machine regression model revealed that co-exposure to phthalate metabolites and bisphenols was associated with increased NSCL/P risk. Similarly, quantile-based g-computation analysis indicated that each quantile increase in mixture concentration was positively related to higher risk for NSCL/P [odds ratio (95% confidence interval) = 2.98(1.97,4.51)]. This study provides novel evidence that prenatal single and co-exposure to phthalate metabolites and bisphenols were associated with increased NSCL/P risk, suggesting that exposure to phthalate metabolites and bisphenols during pregnancy should be minimized to reduce the incidence of NSCL/P in offspring.

In-silico characterization of a hypothetical protein of Sulfobacillus sp. hq2 for degradation of phthalate diesters.

Phthalate plasticizers are hazardous compounds capable of causing endocrine disruption, cancers, and developmental disorders. Phthalate diesters are commonly used plasticizers in plastic products (PVC pipes) that leach out into the environment due to changes in temperature, pressure, and pH, posing harmful effects on different life forms. Bioremediation of phthalate diesters utilizing bacterial esterase has been recognized as an efficient approach but few effective esterases capable of degrading a wide range of phthalate diesters have been identified. Further, the thermostability of these esterases is a highly desirable property for their applications in diverse in-situ conditions. In this present in-silico study a hypothetical protein (POB10642.1) as a high-potential esterase from a thermostable strain of Sulfobacillus sp. hq2 has been characterized. Analysis revealed significant sequence identity of 42.67 % and structural similarity (RMSD 0.557) with known phthalate diester degrading EstS1 esterase and a high Tm range of 55-66 °C. Structural analysis revealed the presence of two cavities on the surface mediating toward the catalytic site forming a catalytic tunnel. The enzyme POB10642.1 has significant molecular docking binding energies in the range of -5.4 to -7.5 kcal/mol with several phthalate diesters, including Diethyl phthalate, Dipropyl phthalate, Dibutyl phthalate, Dipentyl phthalate, Dihexyl phthalate, Benzyl butyl phthalate, Dicyclohexyl phthalate, and Bis(2-ethylhexyl) phthalate. High stability of binding during 100 ns molecular dynamics simulations revealed efficient and stable binding of the enzyme with a wide range of phthalate diesters at its active site, demonstrating the ability of the identified esterase to interact with and degrade diverse phthalate diesters. Therefore, POB10642.1 esterase can be an efficient candidate to be utilized in the development of enzyme-based bioremediation technologies to reduce the toxic levels of phthalate diesters.

Effect of Bis (methyl glycol) Phthalate on Endoplasmic Reticulum Stress in Endothelial Cells.

Phthalate-based polymeric plasticizers are widely used for their durability, transparency, and odorless nature, resulting in human exposure through inhalation, ingestion, or contaminated water. Epidemiological studies have identified bis-phthalate as a potential cardiovascular disease risk factor, though its mechanisms remain unclear. This study investigates the effects of bis-phthalate on endothelial dysfunction (ED), an early event in cardiovascular complications, with a focus on Endoplasmic Reticulum (ER) stress pathways. We observed dose- and time-dependent cytotoxicity in endothelial cells exposed to bis-phthalate, accompanied by elevated expression of ER stress markers (GRP78, IRE-1α, CHOP) and oxidative stress markers (TXNIP, P22phox), as measured by qPCR. Reactive oxygen species (ROS) levels also increased dose-dependently, as determined by H2DCFDA using flow cytometry. These findings suggest that bis-phthalate exposure induces both oxidative and ER stress, leading to the development of ED, providing insights into its potential role in cardiovascular disease progression.

The Impact of Dibutyl Phthalate on Insulin Signaling in Human Skeletal Muscle Cells.

BACKGROUND: In China, the environmental concern of Dibutyl Phthalate (DBP) exposure significantly endangers human health by inducing insulin resistance (IR). Skeletal muscle tissue plays a critical role in this process. However, the precise molecular mechanisms through which DBP interferes with the insulin signaling pathway remain to be fully elucidated. This study aims to explore the molecular mechanisms by which DBP induces IR in skeletal muscle, focusing on the phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT)-glucose transporter 4 (GLUT4) signaling pathway. METHODS: To investigate the molecular mechanisms underlying DBP-induced IR, an experimental study was established on a human skeletal muscle cell line (HSkMC). Expression levels of mRNA and proteins associated with key signaling genes within the insulin receptor (INSR)-insulin receptor substrate (IRS)-PI3K-AKT-GLUT4 pathway were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot techniques. Additionally, this study explored the effects of DBP alone and in combination with a PI3K inhibitor (BKM120) or phosphatase and tensin homolog (PTEN) overexpression lentivirus on these signaling components. RESULTS: Results from this study demonstrated that DBP exposure significantly decreased mRNA levels of INSR, IRS1, PI3K, AKT2, and GLUT4 in HSkMC cells compared to untreated control cells. This reduction was exacerbated when DBP was combined with BKM120 or PTEN overexpression lentivirus, suggesting a synergistic effect. Furthermore, DBP treatment reduced the expression and phosphorylation of AKT2, indicating a disruption in the insulin signaling pathway. CONCLUSIONS: This study elucidates a molecular mechanism by which DBP induces IR in skeletal muscle cells, primarily through the deregulation of the PI3K-dependent insulin signaling pathway. These insights enhance comprehension of the pathophysiological changes associated with IR caused by environmental pollutants like DBP, potentially guiding future strategies for prevention and intervention.

Toxicity of Dibutyl phthalate (DBP) toward isolated human blood lymphocytes: Apoptosis initiated from intracellular calcium enhancement and mitochondrial/lysosomal cross talk.

Dibutyl phthalate (DBP) is a phthalate ester with wide application in industrial products, so human exposure can happen in workplaces and environment. Conflicting results have been acquired in researches which measured the influences of phthalates contact on immune responses in laboratory animals. Nevertheless, the straight influence of DBP on human lymphocytes and entire mechanisms of its effect against these cells continue to be unexplored. The major purpose of present research was to evaluate the mechanisms which lead to the DBP toxicity on human lymphocytes using accelerated cytotoxicity mechanisms screening (ACMS) technique. Cell viability was determined following12h incubation of lymphocytes with 0.05-1 mM DBP, and mechanistic parameters were assessed after 2, 4 and 6 h of lymphocyte treatment with ½ the IC5012h (0.3 mM), the IC5012h (0.6 mM) and twice the IC5012h (1.2 mM) of DBP. The IC5012 h of a chemical/toxicant is defined as concentration that kills 50 % of cells after 12 h of exposure. The results indicate that DBP exerts toxic effects on isolated human lymphocytes, probably through mitochondrial and lysosomal damage induced by glutathione depletion and oxidative stress. In this study, suppression of cytokines (IL2, INF-gamma and TNF-alpha) production and increase in intracellular calcium were also related to DBP induced lymphocyte toxicity.

Recent advancements in the extraction and analysis of phthalate acid esters in food samples.

Phthalate acid esters (PAEs) are ubiquitous environmental pollutants present in food samples, necessitating accurate detection for risk assessment and remediation efforts. This review provides an updated overview of the recent progress on the PAEs analysis regarding sample pretreatment techniques and analytical methodologies over the latest decade. Advances in sample preparation include solid-based extraction techniques replacing conventional liquid-liquid extraction, with solid sorbents emerging as promising alternatives due to their minimal solvent consumption and enhanced selectivity. Although techniques like the microextraction methods offer versatility and reduced solvent reliance, there is a need for more efficient and environmentally friendly techniques enabling on-site portable detection. High-resolution mass spectrometry is increasingly utilized for its enhanced sensitivity and reduced contamination risks. However, challenges persist in developing in situ analytical techniques for trace PAEs in complex food samples. Future research should prioritize novel analytical techniques with superior sensitivity and selectivity, addressing current limitations to meet the demand for precise PAEs detection in diverse food matrices.

Phthalate exposure as a hidden risk factor for uterine leiomyoma in adult women: Accumulated evidence from observational studies.

BACKGROUND: There is evidence that exposure to phthalate in women may increase the risk of uterine leiomyomas. Whereas, the association between exposure to phthalate and the incidence of uterine leiomyoma remained inconclusive. METHODS: A meta-analysis was performed to evaluate their relationship. Literature eligible for inclusion was found in PubMed, EMBASE, Web of Science, and WanFang Medical Database. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to assess the risk for effect estimate for each phthalate. RESULTS: A total of fourteen observational studies with 5777 subjects of adult women were included in this study. In the pooled analysis, we found an elevated risk of uterine leiomyoma among women who were exposed to higher levels of di-2-ethylhexyl phthalate (DEHP) (OR 1.61, 95 % CI: 1.18-2.20), as estimated indirectly from the molar summation of its urinary metabolite concentrations. In addition, a positive association was observed between the occurrence of uterine leiomyoma and exposure to low molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.00-1.15), as well as high molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.01-1.15), as quantified by integrating the effect estimates of individual metabolite from each study. Urinary levels of DEHP metabolites, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, monoethyl phthalate, and monomethyl phthalate were not appreciably correlated with the risk of uterine leiomyoma. CONCLUSION: Our results indicated that exposure to DEHP, and co-exposure to high or low molecular weight phthalate mixture might be potential risk factors for uterine leiomyoma in adult women. Owing to the indirect estimation of association, when interpreting these findings, cautions should be taken.

Occurrence, distribution and risk assessment of phthalate esters in dust deposited in the outdoor environment of Yazd industrial park using Monte Carlo simulation.

In this study, the distribution of eight phthalate esters (PAEs), namely (dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP), bis (2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP)) were examined across fifteen sampling stations in Yazd industrial Park. All the PAEs in dust deposited in the outdoor environment were analyzed using a Gas-mass chromatography (GC-MS/MS) device. Both probabilistic and deterministic approaches were utilized to assess the non-carcinogenic and carcinogenic health risks for adult occupational population groups. These risks were associated with three exposure pathways: inhalation, ingestion, and dermal exposure to six phthalates in the dust samples. The findings revealed, among the fifteen sampling stations, highest and lowest concentrations of the PAEs in dust deposited in the outdoor environment were observed in S8 and S6, with BEHP (326.21 ± 4.35) µg/g and DMP (0.00 ± 0.02) µg/g, respectively. The total hazard index (HI) values were below one in all samples, indicating that the combined non-carcinogenic health risk from exposure to phthalates via inhalation, ingestion, and dermal pathways is within acceptable levels in each studied area. The total cancer risk (CR) values for BBP across all exposure routes were consistently low, with magnitudes ranging from 10- x 10-15to 10 x 10-11. The order of cancer risk from phthalate exposure in outdoor environments was ingestion > dermal > inhalation. The sensitivity analysis (SA) results indicated that the influential parameters in the carcinogenic risk in adult occupational population groups were concentration for inhalation and dermal pathways, as well as ingestion rate for the ingestion pathway. The result of this study provides new insight in to PAEs pollution and risk assessments related to the dust deposited in the outdoor environment of industrial Park. Furthermore, this finding is beneficial to the controlling the exposure and promoting steps to reduce PAEs contamination and manage health in the industrial area.

Synthesis and functional mechanism evaluation of Novel Polymer-Graphene Oxide-Biochar Nanocomposite for Efficient Removal of Diethyl Phthalate.

Phthalates, categorized as a main constituent of endocrine-disrupting chemicals (EDCs), are present in polymeric products. These substances can enter the environment through several pathways, including improper handling, which leads to their presence in toilet water, floor washings, surface runoff, and landfill leachate. This study focuses on the performance analysis of nanocomposite materials made of polymer (polypyrrole), quasi-metal (graphene oxide), and biochar (from palmyra seed) for the elimination of diethyl phthalates (DEP) from aqueous environments. Scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) were used to describe the nanocomposite characteristics. The experimental results supported a chemisorption process by agreeing well with the pseudo-second order. The Langmuir isotherm explained the DEP sorption data, which aligned to monolayer DEP adsorption on the nanocomposite surface. With a binding affinity of -13.36 (kcal/mol) and the highest docking score, Diethyl phthalates and graphene oxide interaction is validated. The produced nanocomposite is suggested as a possible alternative for the sorption of DEP. Future applications could benefit from the higher adsorption capacity, and environmental friendliness of nanocomposites.

Review of toxicity and global distribution of phthalate acid esters in fish.

Organic additives are incorporated during the manufacturing of plastics, and these additives are gradually released into the environment from plastic debris. Among these, phthalate acid esters (PAEs) are the most prevalent. PAEs can be found in the atmosphere, aquatic ecosystems, terrestrial regions, soil, and within animal and human bodies. They are released from industrial activities and have a significant impact on the natural environment. This study reviews research on PAEs from various regions worldwide, with about 47.8 % of the studies published between 2020 and 2024. The highest concentrations of PAEs were detected in fish samples from rivers in Taiwan, ranging from 13.6 to 70.0 mg/kg dry weight. PAEs tend to accumulate more in benthic organisms and sediments. DEHP was the most prevalent PAE in fish samples, showing the highest levels and detection frequency among the analyzed PAEs. Some studies found a strong correlation (r2 = 0.85) between PAEs concentrations in fish and water. The findings of this study can help in assessing the fate and behavior of PAEs in the environment and provide a basis for developing future management strategies to control phthalate acid esters pollution in aquatic environments.

Association Between Phthalates Exposure and All-Cause Mortality Among Diabetic Cases: A Prospective Study.

The aim of this study was to explore the association between phthalates (PAEs) exposure and all-cause mortality among diabetic cases, and potential molecular mechanisms of the effect. We followed 2806 diabetes cases from 2008 to the end of 2018 based on the Dongfeng-Tongji study, of which 446 cases died. We measured serum levels of six PAEs (DMP, DEP, DiBP, DnBP, BBP, and DEHP). Cox models were used to investigate the associations between PAEs and all-cause mortality. Genes related to PAEs are obtained from the Comparative Toxicogenomics Database. We constructed polygenic scores for sex hormone-binding globulin (SHBG) and testosterone, and functional SNPs for IL-6, PPARG, and GPX1 from genotyping data, and further analyzed the environment-gene interactions. The positive associations of PAEs (DMP, DiBP, DnBP, DEHP) with mortality were only observed in males but not in females. Comparing with the extreme quartile 1, the HRs (95% CI) for quartile 4 were 1.63 (.17, 2.26) for DMP, 1.82 (1.29, 2.56) for DiBP, 1.68 (1.18, 2.40) for DnBP, 1.66 (1.17, 2.36) for DEHP. Enrichment analysis showed that PAEs-related genes were mainly associated with hormones and IL-6-related pathways. Genetic variants of SHBG, testosterone, and IL-6 modified the association between PAEs mixture and all-cause mortality. PAEs exposure are associated with all-cause mortality among diabetic cases, and PAE exposure increases the risk of all-cause mortality only in males. Effects on the hormonal system and IL6-related pathways may be potential mechanisms.

In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Phthalates Alters Hypothalamic Gene Expression and Sexual Preference in Rats.

Several phthalates, mainly used as plasticizers, are known for their adverse effects on the male genital system. Previously, we demonstrated that an environmentally relevant mixture of six antiandrogenic phthalates (PMix), derived from a biomonitoring study in pregnant Brazilian women, was able to disrupt the reproductive development in male rats. Experimental groups (control, 0.1, 0.5, and 500 mg PMix/kg/day) were established starting from the extrapolated human dose (0.1 mg/kg/day), followed by doses 5 times and 5000 times higher. Pregnant rats received daily oral gavage administration of either vehicle (control) or PMix from gestational day 13 to postnatal day 10. Here, we examined male and female offspring regarding changes in gene expression of key reproductive factors in the hypothalamus and pituitary gland at adulthood and conducted a battery of behavioral tests in males, including partner preference, sexual behavior, and male attractiveness tests. PMix induced some changes in mating-related behavior in males, as demonstrated by the absence of preference for females against males and a higher number of penetrations up to ejaculation in the 0.5 dose group. PMix decreased Esr2 expression in the male hypothalamus across all three doses, and in females at mid and high doses in both the hypothalamus and pituitary. In male hypothalamus, we also observed decreased Kiss1 transcripts in these groups and a reduction in AR at the 0.5 dose group. In summary, our results provide further evidence that phthalates in a mixture, even at low doses, may exert cumulative effects on the structures underlying sexual behavior, which seems to be more sensitive than reproductive endpoints for the same experimental design.

Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model.

Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body's metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20-30 g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30 days. In contrast, group 2 (DiNP group), received 50 mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (P < 0.05) activities of the enzymes of glycolysis, tricyclic acid cycle, and electron transport chain except the hexokinase and succinate dehydrogenase activity which were upregulate relative to control. Also, oxidative distress markers (GSH, CAT, and MDA and SOD) were also perturbed. Biomarkers of inflammation (MPO and NO) were considerably higher (P < 0.05) in the heart of DiNP-induced asthma mice as compared with the control group. Furthermore, DiNP-induced asthma group has an increased cardiac caspase-3, Bax, c-Myc and K-ras, and p53 while the Bcl2 decreased when compared with control. Overall, the findings indicate that DiNP-induced asthma impairs cardiac functions by induction of key cardiac oncogenes, downregulation of cardiac energy, transduction of enzymes, and promotion of oxidative stress and cellular death.

Environmental pollutant Di-(2-ethylhexyl) phthalate induces asthenozoospermia: new insights from network toxicology.

The global decline in sperm quality in men is closely associated with environmental exposure to the plasticizer Di-(2-ethylhexyl) phthalate (DEHP), but the molecular mechanisms underlying its induction of asthenozoospermia (AZS) remain incompletely understood. By integrating the toxicological targets of DEHP and differential genes in AZS patients, and combining machine learning, molecular docking, and dynamics simulations, this study successfully identified hub genes and signaling pathways induced by DEHP in AZS, aiming to provide new strategies for the prevention and treatment of this disease. A total of 26 toxicological targets were identified, with FGFR1, MMP7, and ST14 clearly defined as playing crucial regulatory roles in DEHP-induced AZS. This study also reveals that DEHP may induce reproductive system inflammation, affecting the proliferation and survival of reproductive cells, and subsequently impacting sperm vitality, possibly through regulating the mTORC1 pathway, TNF-α signaling via the NF-κB pathway, and MYC targets v1 pathway. Furthermore, changes in the immune microenvironment revealed the significant impact of immune status on testicular function. In conclusion, this study provides important scientific evidence for understanding the molecular mechanisms of AZS and developing prevention and treatment strategies based on toxicological targets.

Association between phthalate exposure and risk of allergic rhinitis in children: A systematic review and meta-analysis.

Phthalates are ubiquitous in diverse environments and have been linked to a myriad of detrimental health outcomes. However, the association between phthalate exposure and allergic rhinitis (AR) remains unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to comprehensively evaluate the relationship between phthalate exposure and childhood AR risk. We searched the Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, and PubMed to collect relevant studies and estimated pooled odds ratios (OR) and 95% confidence intervals (CI) for risk estimation. Ultimately, 18 articles, including seven cross-sectional, seven case-control, and four prospective cohort studies, were selected for our systematic review and meta-analysis. Our pooled data revealed a significant association between di-2-ethylhexyl phthalate (DEHP) exposure in children's urine and AR risk (OR = 1.188; 95% CI = 1.016-1.389). Additionally, prenatal exposure to combined phthalates and their metabolites in maternal urine was significantly associated with the risk of childhood AR (OR = 1.041; 95% CI = 1.003-1.081), although specific types of phthalates and their metabolites were not significant. Furthermore, we examined environmental phthalate exposure in household dust and found no significant association with AR risk (OR = 1.021; 95% CI = 0.980-1.065). Our findings underscore the potential hazardous effects of phthalates on childhood AR and offer valuable insights into its pathogenesis and prevention.

Micro-injection as a tool to detect the effects of bisphenol A, diethyl phthalate, and 17ß-estradiol on ontogenesis of zebrafish (Danio rerio).

Diethyl phthalate (DEP), bisphenol A (BPA), and external estradiol 17ß-estradiol (E2) all are endocrine disrupting chemicals (EDCs). Our previous study has found that the development of ceratohyal cartilage (CH) in embryos could be disrupted when the maternal generation was exposed with 8.06 µM DEP, 2.86 µM BPA, and 1.11 µM E2. However, it is still unknown how doses of the residual EDCs in eggs cause abnormal CH development in their offspring. Microinjection is used at the 2-cell stage of embryos to mimic the maternal effect and to observe the toxicities of EDCs in embryos. Results shown that the amounts of DEP, BPA, and E2 were 1.3 × 10-6 ng, 4.7 × 10-7 ng, and 1.4 × 10-7 ng, respectively, inducing the CH angles to become bigger than the control. However, related genes to the migratory pathways of neural crest cells (NCCs) were not influenced upon BPA and E2 treatments. Both sox10 and smad3 gene expressions were up-regulated upon DEP treatment. On the other hand, the CH angles were smaller than the control upon 1.3 × 10-5, 9.4 × 10-6, and 1.4 × 10-6 ng of DEP, BPA, and E2 microinjection, respectively. Furthermore, genes related to migratory NCCs were significantly influenced upon 10-5 ng of BPA, and 10-4 ng of DEP treatments on embryos. According to the data, we suggested that 10-5-10-7 ng of EDCs in eggs could disrupt CH development as well as significantly increase the mortality on their embryos. The present study raises concern that the responses were highly sensitive in embryos through maternal effects.