Diethylhexyl Phthalate Research Articles

The mechanism of DEHP-induced lipid accumulation in liver of female zebrafish

Diethylhexyl phthalate (DEHP) is a typical environmental pollutant and poses a potential threat to organisms by disrupting the lipid metabolism. This study found that DEHP at environmental concentrations, led to lipid accumulation in female zebrafish, as indicated by significant increases in the content of total cholesterol, triglycerides and the lipid droplets, in a concentration-dependent manner. However, how DEHP induces the lipid accumulation remains poorly understood. Our results demonstrated that DEHP up-regulated the expression of fat synthesis related-genes fas, acc, acs, elvol6, scd and dgat1, and increased the enzymatic activity of fatty acid synthase and acetyl-CoA carboxylase. Furthermore, the expression of several key transcription factors that regulate fat synthesis was detected, among which active sterol regulatory element-binding protein-1 (SREBP-1) was significantly increased. When active SREBP-1 was inhibited with specific inhibitor or knocked down by transient transfection, the expression of lipid synthesis-related genes was significantly decreased in DEHP group, indicating that DEHP disrupted the lipid synthesis via SREBP-1 pathway. Additionally, molecular docking revealed direct interaction sites between DEHP and SREBP-1. Our findings revealed that DEHP could directly activate SREBP-1-mediated lipid synthesis, providing theoretical basis for DEHP threatening biological health.

Assessing male reproductive toxicity of environmental pollutant di-ethylhexyl phthalate with network toxicology and molecular docking strategy

Environmental pollutants, especially endocrine-disrupting chemicals (EDCs) like di-ethylhexyl phthalate (DEHP), pose serious threats to human health, with DEHP widely implicated in male reproductive toxicity. However, the complex molecular interactions remain unknown. We employed a network toxicology approach combined with molecular docking analysis to identify potential targets and mechanisms of DEHP's toxic effects. Databases such as ChEMBL, STITCH, OMIM, and GeneCards were utilized to gather data, and Cytoscape software was used to construct protein-protein interaction networks. A total of 51 potential targets were identified, with eight core targets, including PTGS2, CASP3, and ESR1, highlighted for their roles in oxidative stress, apoptosis, and hormonal dysregulation. KEGG pathway enrichment analysis revealed significant associations with pathways in cancer, cytokine-mediated signaling, and the hypothalamic-pituitary-gonadal axis. Additionally, gene expression datasets from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes overlapped with DEHP targets in testicular diseases. Molecular docking results confirmed strong binding affinities between DEHP and the core target proteins, suggesting a robust interaction mechanism. This study underscores the need for further investigation into DEHP's toxic mechanisms and its combined effects with other environmental pollutants, paving the way for comprehensive risk assessments and the development of targeted intervention strategies.

Diethylhexyl phthalate induces immune dysregulation and is an environmental immune disruptor

Diethylhexyl phthalate (DEHP) is the most abundant phthalate compound in the environment, and has been linked with multiple human diseases. The immune system is closely associated with the occurrence and progression of various diseases. However, minimal research has addressed the impact of DEHP on the immune system. In this study, single-cell RNA sequencing was performed using spleen tissue of mice to comprehensively determine alterations of the immune system in response to DEHP. The results showed that DEHP exposure reduced the absolute number of peripheral white blood cells (WBCs), including lymphocytes, monocytes, eosinophils, basophils, and neutrophils in mice. In addition, scRNA-seq analyses showed that inflammatory signaling and the expression of heat shock proteins (HSPs) were reduced in all peripheral immune cell populations. Furthermore, we established a mice cecal ligation and puncture (CLP) model, and showed that DEHP exacerbated sepsis-induced immunosuppression and organ damage. These results suggest that DEHP is an environmental immune disruptor that undermines the immune system, exacerbating acute infections and organ damage. Our findings offer a novel perspective on the hazards of DEHP to human health.

Determining personal exposure to high production volume chemicals (HPVCs) and polycyclic aromatic hydrocarbons (PAHs) with silicone wristbands: A pilot study

High production volume chemicals (HPVCs) and polycyclic aromatic hydrocarbons (PAHs) are semi-volatile organic compounds (semi-VOCs) of great environmental concern because of their presence worldwide and health problems resulting from long-term exposure to some of them. It is essential to have robust analytical methods to monitor the concentrations of these compounds not only in environmental samples but also individual exposure. In this pilot study we develop and validate a multiresidue analytical method based on ultrasound-assisted extraction and gas-chromatography mass spectrometry for the simultaneous determination of 56 semi-VOCs using silicone wristbands (SWBs) as personal passive samplers. The developed method provided recoveries between 43% and 114% on sampled SWBs and method detection and quantification limits in the range of 0.1–35 ng/g and 0.3–119 ng/g, respectively. A preliminary study was performed with a small group of adults living in the industrial city of Tarragona (north-eastern Spain) to evaluate the applicability of SWBs for monitoring individual exposure to the studied HPVCs and PAHs. Benzothiazoles, benzenesulfonamides, UV stabilisers and phenolic antioxidants were determined for the first time in SWBs. Phthalates (PAEs), stood out above the rest, accounting for 52% of the total concentrations. Diethylhexyl phthalate was the compound found at the highest concentrations with values between 1.1 and 82 μg/g. Carcinogenic and non-carcinogenic dermal risk assessment was performed for adults and considering two scenarios (low and high). PAHs were the compounds with the highest carcinogenic and non-carcinogenic dermal risk regardless of the exposure scenario. The second family of compounds that contributed the most to the total risk were PAEs but high punctual concentrations of these compounds caused significant differences between exposure scenarios.

Bioaccessibility of plastic-related compounds from polymeric particles in marine settings: Are microplastics the principal vector of phthalate ester congeners and bisphenol A towards marine vertebrates?

Marine vertebrates are known to ingest significant amounts of microplastics (MPs). Once ingested, MPs might cause gastrointestinal injuries and serve as a path of harmful plastic components, such as phthalate esters (PAEs) and bisphenol A (BPA) in the food chain. However, there is a lack of standardized in-vitro methods capable of simulating fish uptake of chemicals from MPs in the environment as potential vectors of such contaminants. In this work, leaching and in-vitro oral bioaccessibility testing of PAEs and BPA from MPs were conducted batchwise using artificial seawater and gut fluids mimicking gastric, intestinal, and gastrointestinal compartments of marine vertebrates at physiological temperature. The environmental and physiologically relevant extraction tests were applied to medium-density polyethylene (PE) and polyvinyl chloride (PVC) certified reference materials containing eight PAEs of varying hydrophobicity, namely, dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate, benzylbutyl phthalate, diethylhexyl phthalate, di-n-octyl phthalate, diisononyl phthalate and diisodecyl phthalate, and BPA (only in PE) as MP surrogates with realistic analyte concentrations of additives for primary MPs. The analysis of the leachates/gut fluid extracts was performed via dilute-and-shoot by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Only the most hydrophilic compounds, i.e. DMP, DEP and BPA, were found to get released significantly in saline waters, and exhibited the highest oral bioaccessibility rates (34–83 %). Based on our results, a dual-compartment physiologically relevant gastrointestinal test is recommended for appropriate estimation of fish bioaccessibility. The fish daily intakes of DMP, DEP and BPA from MPs, and seawater ingestion as well were estimated using several contamination scenarios (10th percentile as the low level, 50th percentile as the medium level and 90th percentile as the high level) based on probabilistic distributions and cumulative probability curves of measured environmental concentrations of (i) MPs in seawater throughout the world, (ii) DMP, DEP and BPA in beached MPs and those sampled in the open ocean (including both incurred and adsorbed contaminants), and (iii) DMP, DEP and BPA in seawater as reported in recent literature. Under a medium-level concentration scenario (50th percentile) in marine settings, and taking the gastrointestinal bioaccessibility factor into account, the daily intake of DMP, DEP and BPA from MPs accounted for a mere 0.02 % of the waterborne contribution. Hence, the ingestion of MPs should not be considered the primary route of fish exposure to BPA and the most polar PAEs in marine environments. However, more studies on the local and the global scales for mass concentrations of MPs and additives in marine settings are needed for further confirmation of our findings.

Impact of Skin Care Products on Phthalates and Phthalate Replacements in Children: the ECHO-FGS.

Phthalates and their replacements have been implicated as developmental toxicants. Young children may be exposed to phthalates/replacements when using skin care products (SCPs). Our objective is to assess the associations between use of SCPs and children's urinary phthalate/replacement metabolite concentrations. Children (4-8 years old) from the Environmental Influences on Child Health Outcomes-Fetal Growth Study (ECHO-FGS) cohort provided spot urine samples from 2017 to 2019, and mothers were queried about children's SCP use in the past 24 h (). Concentrations of 16 urinary phthalate/replacement metabolites were determined by liquid chromatography-tandem mass spectrometry (). We used linear regression to estimate the child's use of different SCPs as individual predictors of urinary phthalate/replacement metabolites, adjusted for urinary specific gravity, age, sex assigned at birth, body mass index, and self-reported race/ethnic identity, as well as maternal education, and season of specimen collection. We created self-organizing maps (SOM) to group children into "exposure profiles" that reflect discovered patterns of use for multiple SCPs. Children had lotions applied (43.0%) frequently, but "2-in-1" hair-care products (7.5%), sunscreens (5.9%), and oils (4.3%) infrequently. Use of lotions was associated with 1.17-fold [95% confidence interval (CI): 1.00, 1.34] greater mono-benzyl phthalate and oils with 2.86-fold (95% CI: 1.89, 4.31) greater monoethyl phthalate (MEP), 1.43-fold (95% CI: 1.09, 1.90) greater monobutyl phthalate (MBP), and 1.40-fold (95% CI: 1.22, 1.61) greater low-molecular-weight phthalates (LMW). Use of 2-in-1 haircare products was associated with 0.84-fold (95% CI: 0.72, 0.97) and 0.78-fold (95% CI: 0.62, 0.98) lesser mono(3-carboxypropyl) phthalate (MCPP) and MBP, respectively. Child's race/ethnic identity modified the associations of lotions with LMW, oils with MEP and LMW, sunscreen with MCPP, ointments with MEP, and hair conditioner with MCPP. SOM identified four distinct SCP-use exposure scenarios (i.e., profiles) within our population that predicted 1.09-fold (95% CI: 1.03, 1.15) greater mono-carboxy isononyl phthalate, 1.31-fold (95% CI: 0.98, 1.77) greater mono-2-ethyl-5-hydroxyhexyl terephthalate, 1.13-fold (95% CI: 0.99, 1.29) greater monoethylhexyl phthalate, and 1.04-fold (95% CI: 1.00, 1.09) greater diethylhexyl phthalate. We found that reported SCP use was associated with urinary phthalate/replacement metabolites in young children. These results may inform policymakers, clinicians, and parents to help limit children's exposure to developmental toxicants. https://doi.org/10.1289/EHP13937.

Application of solvent-based dissolution for the recycling of polyvinylchloride flooring waste containing restricted phthalate plasticizers

The applicability of a new recycling method for extracting contaminants from polymers, dissolution-based recycling, was tested on a polyvinylchloride equipped with diethylhexyl phthalate, benzylbutyl phthalate, di-isobutyl phthalate, di-n‑butyl phthalate, originating from post-consumer flooring waste. Due to European restrictions on these ortho-phthalate diester-based plasticizers, the mechanical recycling of plasticized polyvinylchloride is no longer feasible. In this study, we have shown that dissolution and consecutive purification of the polymer eliminate 99.9 % of diethylhexyl phthalate's initial concentration at the laboratory scale. The impact of different process parameters, e.g., temperature, agitation, and extraction kinetics, have been tested. The findings were transferred to a technical scale of 5 kg/d, using a multi-step extraction in counter-flow mode. An elimination of 99.4 % of diethylhexyl phthalate initial concentration has been achieved, which fulfills legal requirements. These promising results showed the technical feasibility and served as a preliminary stage for further up-scaling to technical readiness level 6.

A low-temperature co-treatment of diethylhexyl phthalate-rich polyvinyl chloride and waste copper catalyst by subcritical water (hydrothermal treatment): Dechlorination, recovery of diethylhexyl phthalate and copper

As one of the most widespread plastics in the world, the recycling of diethylhexyl phthalate-rich polyvinyl chloride (DEHP-rich PVC) faces great challenges because of the high levels of Cl and plasticizers. On the other hand, waste copper catalyst (WCC) discharged from various industrial processes is not effectively recycled. In this study, a significant synergistic effect between the DEHP-rich PVC and WCC was found in a subcritical water (SubCW) medium, and a co-treatment of the DEHP-rich PVC and WCC was developed by the SubCW process. The introduction of WCC significantly improved the dechlorination efficiency of the DEHP-rich PVC to 96.03 % at a low temperature of 250 °C. Under the optimal conditions, the leaching of copper from WCC reached a maximum of 81.08 %. Oil products included DEHP (55.7 %, GC peak area%), 3-methyl-3-heptene (37.3 %, GC peak area%), and 2-ethyl-1-hexanol (7.0 %, GC peak area%). The dechlorination pathways of the DEHP-rich PVC included hydroxyl substitution and direct dechlorination. HCl released from the DEHP-rich PVC led to a decrease in the pH of the system and significant copper leaching from the WCC. DEHP was decomposed by hydrolysis, dehydration, and rearrangement reaction by the SubCW co-treatment process. The enhancement mechanism of the WCC for the dechlorination of the DEHP-rich PVC was based on that the conversion of copper species in the SubCW promoted the formation of hydroxyl radicals and the hydroxyl substitution for chlorine in PVC molecular chain. The proposed SubCW low-temperature co-treatment could be a prospective strategy for the low-energy and synchronous recovery of the two different wastes of the DEHP-rich PVC and WCC.

Portulaca Oleracea L. Phenolic Amide Methyl (3,4,5-Trimethoxybenzoyl) Valylprolinate Attenuates Diethylhexyl Phthalate-Induced Human Umbilical Vein Endothelial Cells' Inflammation Through NLRP3 and NF-κB Pathways.

Twelve polyphenol derivatives were obtained in a protective activity-guided isolation from the Portulaca oleracea L. extract on a cell model of human umbilical vein endothelial cells (HUVECs) under diethylhexyl phthalate (DEHP) exposure. Among them, methyl (3,4,5-trimethoxybenzoyl) valylprolinate (PP-10) performed the most protective activity and inhibited DEHP exposure-induced HUVECs' apoptosis. PP-10 also inhibited the DEHP-induced inflammatory cytokines (TNF-α, IL-6, IL-1β, and IL-8) and adhesion molecule (ICAM-1 andVCAM-1) overexpression. Furthermore, DEHP-induced NLRP3 inflammasomes' and NF-κB signaling pathway activation was significantly inhibited after the PP-10 treatments. Of note, the current results suggest the potential application of Portulaca oleracea L. and PP-10 in the prevention of DEHP-induced inflammatory damages in HUVECs.

Prenatal Exposure to Bisphenol A and/or Diethylhexyl Phthalate Impacts Brain Monoamine Levels in Rat Offspring.

This study examines the sex-specific effects of gestational exposure (days 6-21) to endocrine-disrupting chemicals such as bisphenol A (BPA), diethylhexyl phthalate (DEHP), or their combination on brain monoamine levels that play an important role in regulating behavior. Pregnant Sprague-Dawley rats were orally administered saline, low doses (5 µg/kg BW/day) of BPA or DEHP, and their combination or a high dose (7.5 mg/kg BW/day) of DEHP alone or in combination with BPA during pregnancy. The offspring were subjected to a behavioral test and sacrificed in adulthood, and the brains were analyzed for neurotransmitter levels. In the paraventricular nucleus, there was a marked reduction in dopamine levels (p < 0.01) in male offspring from the BPA, DEHP, and B + D (HD) groups, which correlated well with their shock probe defensive burying times. Neurotransmitter changes in all brain regions examined were significant in female offspring, with DEHP (HD) females being affected the most, followed by the B + D groups. BPA and/or DEHP (LD) increased monoamine turnover in a region-specific manner in male offspring (p < 0.05). Overall, prenatal exposure to BPA, DEHP, or their combination alters monoamine levels in a brain region-specific, sex-specific, and dose-dependent manner, which could have implications for their behavioral and neuroendocrine effects.

An insight into carcinogenic activity and molecular mechanisms of Bis(2-ethylhexyl) phthalate.

Di(ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant to which humans are exposed via multiple routes. Human health risk assessments for this substance have recently been updated, focusing on reproductive toxicity, including DEHP, in the list of chemicals classified as carcinogenic, mutagenic, or toxic to reproduction (CMR). Moreover, DEHP has also been defined as probably and possibly carcinogenic to humans based on its carcinogenicity in rodents. However, the mechanism of action of DEHP and its relevance in humans remain unclear. Rodent data suggests that DEHP induces cancer through non-genotoxic mechanisms related to multiple molecular signals, including PPARα activation, perturbation of fatty acid metabolism, induction of cell proliferation, decreased apoptosis, production of reactive oxygen species, and oxidative stress. According to the DEHP toxicological dataset, several in vitro cell transformation assays have been performed using different protocols and cellular models to produce different results. This study aimed to evaluate the carcinogenic potential of DEHP by using the A31-1-1 BALB/c-3T3 cell line in a standard cell transformation assay. Additionally, transcriptomic analysis was performed to explore the molecular responses and identify the affected toxicological pathways. Although DEHP treatment did not induce transformation in BALB/c-3T3 cells, the transcriptomic results revealed significant modulation of several pathways associated with DEHP metabolism, tissue-specific functions related to systemic metabolism, and basal cellular signaling with pleiotropic outcomes. Among these signaling pathways, modulation of cell-regulating signaling pathways, such as Notch, Wnt, and TGF-β, can be highlighted. More specific modulation of such genes and pathways with double functions in metabolism and neurophysiology underlies the well-known crosstalk that may be crucial for the mechanism of action of DEHP. Our findings offer evidence to support the notion that these models are effective in minimizing the use of animal testing for toxicity assessment.

Endocrine disruption and male reproductive disorders: unanswered questions.

Maternal exposure to endocrine-disrupting chemicals (EDCs) in human pregnancy is widely considered as an important cause of adverse changes in male reproductive health due to impaired foetal androgen production/action. However, the epidemiological evidence supporting this view is equivocal, except for certain phthalates, notably diethyl hexyl phthalate (DEHP). Maternal phthalate exposure levels associated with adverse reproductive changes in epidemiological studies are several thousand-fold lower than those needed to suppress foetal androgen production in rats, and direct studies using human foetal testis tissue show no effect of high phthalate exposure on androgen production. This conundrum is unexplained and raises fundamental questions. Human DEHP exposure is predominantly via food with highest exposure associated with consumption of a Western style (unhealthy) diet. This diet is also associated with increased exposure to the most common EDCs, whether persistent (chlorinated or fluorinated chemicals) or non-persistent (phthalates, bisphenols) compounds, which are found at highest levels in fatty and processed foods. Consequently, epidemiological studies associating EDC exposure and male reproductive health disorders are confounded by potential dietary effects, and vice versa. A Western diet/lifestyle in young adulthood is also associated with low sperm counts. Disentangling EDC and dietary effects in epidemiological studies is challenging. In pregnancy, a Western diet, EDC exposure, and maternal living in proximity to industrial sites are all associated with impaired foetal growth/development due to placental dysfunction, which predisposes to congenital male reproductive disorders (cryptorchidism, hypospadias). While the latter are considered to reflect impaired foetal androgen production, effects resulting from foetal growth impairment (FGI) are likely indirect. As FGI has numerous life-long health consequences, and is affected by maternal lifestyle, research into the origins of male reproductive disorders should take more account of this. Additionally, potential effects on foetal growth/foetal testis from the increasing use of medications in pregnancy deserves more research attention.

Maternal phthalate exposure and BMI trajectory in children-an 18-year birth cohort follow-up study.

Obesity is a major health concern worldwide. Previous studies have suggested that phthalate plasticizers are obesogens. However, the relationship between early-life phthalate exposure and long-term obesity development remains unknown. We investigated the association between prenatal phthalate exposure and children's body mass index (BMI) patterns in an 18-year birth cohort follow-up study in Taiwan. Our analytical lab quantified seven phthalate metabolites in maternal urine during pregnancy using quantitative liquid chromatography-tandem mass spectrometry. In addition, we calculated BMI z scores for participated children at each follow-up, utilized trajectory analysis to describe children's BMI z-score patterns at 2-18 years of age, and adopted generalized estimating equations (GEE) and multivariate logistic regression models to assess the association between prenatal phthalate exposure and BMI z scores in children. A total of 208 mother-child pairs were included in the analysis. Maternal urinary diethyl phthalate (DEP) metabolites were associated with the increase of BMI z scores in children aged 2-18 years in the GEE model. Doubled maternal urinary ∑mDEHP (3 mono hexyl-metabolites of di-ethyl-hexyl phthalate (DEHP) increased the risk of children being in the stable-high BMI trajectory group until the age of eighteen. We observed that BMI trajectories of children remained stable after the age of 5 years. During each follow-up, a higher frequency of overweight or obese was observed in children, ranging from 15.9% to 35.6% for girls and 15.2-32.0% for boys, respectively. Prenatal phthalate exposure was associated with increasing BMI z scores in children. Prenatal DEHP exposure was associated with a stable-high BMI trajectory in children up to the age of 18 years.

Extralong hot-spots sensor for SERS sensitive detection of phthalate plasticizers in biological tear and serum fluids.

Phthalate plasticizers (PAEs) illegally used in food pose a great threat to human health. A new and efficient sensing platform for the sensitive detection of the PAE residues in biological fluids needs to be designed and developed. Here, we report a simple and reliable surface-enhanced Raman spectroscopy (SERS) active platform with extralong hot spots of Au nanobipyramids@Ag nanorods (Au NBPs@Ag NRs) for the rapid and sensitive detection of PAEs in biological fluids. To achieve high activity, Au NBPs@Ag NRs with different shell lengths were fabricated by controlling the synthesis conditions, and the corresponding SERS properties were investigated by using crystal violet (CryV) and butyl benzyl phthalate (BBP). The experimental results showed that a longer shell length correlated to greater Raman activity, which was confirmed by finite-difference time-domain (FDTD) electromagnetic simulation. More importantly, the extralong hot spots of the Au NBPs@Ag NR SERS-active substrate showed excellent homogeneity and reproducibility for the CryV probe molecules (6.21%), and the detection limit was 10-9M for both BBP and diethylhexyl phthalate (DEHP). Furthermore, through the standard addition method, an extralong hot spots SERS substrate could achieve highly sensitive detection of BBP and DEHP in serum and tears fluids, and the detection limit was as low as 3.52 10-8M and 2.82 10-8M. Therefore, the Au NBPs@Ag NR substrate with an extraordinarily long surface is efficient and versatile, and can potentially be used for high-efficiency sensing analysis in complex biological fluids.

The relationship between bisphenol A and phthalates with precocious puberty in Vietnamese children.

This study is aimed to explore the correlation between bisphenol A (BPA) and phthalates, including diethylhexylphthalate (DEHP) and dibutylphthalate (DBP), and precocious puberty (PP). A case-control study was conducted in Ho Chi Minh City, Vietnam, from November 2021 to April 2022, involving 250 children, with 124 of them diagnosed with PP and 126 serving as controls. We assessed the levels of urinary BPA, DEHP, and DBP in all participants and examined their association with the risk of PP. BPA was detected in 11.3 % of PP cases but was not found in any individuals in the control group (p<0.001). Diethylhexylphthalate metabolite (MEHP) was not detected in any of the samples. Positive urinary results for dibutylphthalate metabolite (MBP) were observed in 8.1 % of PP cases and 2.4 % in the control group, with an odds ratio of 3.6 (95 % confidence interval: 0.97-13.4, p=0.03). The PP group exhibited a higher prevalence of positive urinary BPA and DBP levels compared to the control group.

Fabrication of Magnetic Molecularly Imprinted Polymers for Selective Extraction of Dibutyl Phthalates in Food Matrices.

In this study, a novel magnetic molecularly imprinted polymeric material (Fe3O4@MOF@MIP-160) with a metal-organic backbone (Fe3O4@MOF) carrier was prepared using dibutyl phthalate (DBP) as a template. The material can be used for the efficient, rapid, and selective extraction of trace amounts of phthalic acid esters (PAEs) in food and can detect them via gas chromatography-mass spectrometry (GC-MS). The synthesis conditions of the materials were optimized to prepare the Fe3O4@MOF@MIP160 with the highest adsorption performance. Transmission electron microscopy (TEM), Fourier Transform Infrared Spectra (FT-IR), Vibration Sample Magnetic (VSM), and the Brunauer-Emmett-Teller (BET) method were used to characterize the materials. Compared with Fe3O4@MOF and the magnetic non-imprinted polymeric material (Fe3O4@MOF@NIP), Fe3O4@MOF@MIP-160 possesses the advantages of easy and rapid manipulation of magnetic materials, the advantages of high specific surface area and the stability of metal-organic frameworks, and the advantages of high selectivity of molecularly imprinted polymers. Fe3O4@MOF@MIP-160 has good recognition and adsorption capacity for di-butyl phthalate (DBP) and diethylhexyl phthalate (DEHP): the adsorption capacity for DBP and DEHP is 260 mg·g-1 and 240.2 mg·g-1, and the adsorption rate is fast (reaching equilibrium in about 20 min). Additionally, Fe3O4@MOF@MIP160 could be recycled six times, making it cost-effective, easy to operate, and time-saving as compared to traditional solid-phase extraction materials. The phthalate ester content in drinking water, fruit juice, and white wine was analyzed, with recoveries ranging from 70.3% to 100.7%. This proved that Fe3O4@MOF@MIP160 was suitable for detecting and removing PAEs from food matrices.

Prenatal diethylhexylphthalate exposure disturbs adult Leydig cell function via epigenetic downregulation of METTL4 expression in male rats

Prenatal exposure to diethylhexyl phthalate (DEHP) has been linked with a decline in testosterone levels in adult male rats, but the underlying mechanism remains unclear. We investigated the potential epigenetic regulation, particularly focusing on N6-methyladenosine (m6A) modification, as a possible mechanism. Dams were gavaged with DEHP (0, 10, 100, and 750 mg/kg/day) from gestational day 14 to day 21. The male offspring were examined at the age of 56 days. Prenatal DEHP administration at 750 mg/kg/day caused a decline in testosterone concentrations, an elevation in follicle-stimulating hormone, a downregulated expression of CYP11A1 HSD3B2, without affecting Leydig cell numbers. Interestingly, Methyltransferase Like 4 (METTL4), an m6A methyltransferase, was downregulated, while there were no changes in METTL3 and METTL14. Moreover, CYP11A1 showed m6A reduction in response to prenatal DEHP exposure. Additionally, METTL4 expression increased postnatally, peaking in adulthood. Knockdown of METTL4 resulted in the downregulation of CYP11A1 and HSD3B2 and an increase in SCARB1 expression. Furthermore, the increase in autophagy protection in adult Leydig cells induced by prenatal DEHP exposure was not affected by 3-methyladenosine (3MA) treatment, indicating a potential protective role of autophagy in response to DEHP exposure. In conclusion, prenatal DEHP exposure reduces testosterone by downregulating CYP11A1 and HSD3B2 via m6A epigenetic regulation and induction of autophagy protection in adult Leydig cells as a response to DEHP exposure.

Effects of Lactobacillus salivarius ssp. salicinius SA-03 Supplementation on Reversing Phthalate-Induced Asthma in Mice.

Probiotics may protect against asthma. We want to investigate whether probiotics can reverse the adverse effects of phthalate exposure on asthma. We selected the female offspring of BALB/c mice, born from pregnant female mice fed with diethylhexyl phthalate (DEHP). They were continuously administrated DEHP and Lactobacillus salivarius ssp. salicinius SA-03 when they were 5 weeks old, and ovalbumin (OVA) for asthma induction started at 6 weeks for 32 days. The mice were divided into four groups (n = 6/group): 1. control group (C), 2. OVA/DEHP group (OD), 3. OVA/DEHP/probiotics low-dose group (ODP-1X), and OVA/DEHP/probiotics high-dose group (ODP-5X). We found that the administration of probiotics significantly reduced the asthma severity of the mice, as well as serum IgE and IL-5. In the ODP-5X group, the proportion of CD4+ cells in the lung was reduced, whereas IL-10 in serum and CD8+ cells in BALF were increased. In histopathology, the ODP group showed reduced infiltration of inflammatory cells, bronchial epithelial cell hyperplasia, and tracheal mucus secretion. These results might indicate that high-dose probiotics may affect anti-inflammatory cytokines and reduce asthma-relative indicators. The above results may provide evidence that high-dose probiotics supplementation might play a modulating role in DEHP causes of allergic asthma in the pediatric animal model.

Sex toys for pleasure, but there are risks: In silico toxicity studies of leached Micro/Nanoplastics and phthalates

The widespread use of sex toys has sparked concerns about potential health risks associated with the leaching of micro/nanoplastics (M/NPs) and phthalates. In this in silico toxicity analysis, we investigated the immunotoxicity potential of compounds mechanically produced from sex toys. The research focuses on understanding their interactions with critical human cytochrome P450 enzymes (CYP34A and CYP2D6), which are central to drug metabolism and immune function. Four types of M/NPs (polyethylene terephthalate - PET, polyvinyl chloride - PVC, polydimethylsiloxane - PDMS, polyisoprene) and eight phthalates (Diethyl phthalate - DEP, Bis(4-methyl-2-pentyl) phthalate, Bis(2-methoxyethyl) phthalate, Benzyl butyl phthalate - BBP, Dibutyl Phthalate - DBP, Diethylhexyl phthalate - DEHP, Dinonyl phthalate - DNP, Di-n-octyl phthalate - DnOP) from sex toys were analyzed. Molecular dynamics and docking simulations were conducted to assess the binding affinity of these compounds to the enzymes. PET exhibited the highest toxicity, with a binding affinity of -8.3 kcal/mol and -8.9 kcal/mol for CYP3A4 and CYP2D6, respectively, surpassing control values (-7.8 kcal/mol and -6.3 kcal/mol). BBP showed considerable toxicity, binding strongly to CYP3A4 (-7.8 kcal/mol) and CYP2D6 (-9.1 kcal/mol). PDMS and DEP were the lowest toxic compounds in both groups. Molecular interactions revealed hydrogen bonds, pi interactions, and unfavorable donor-donor effects between compounds and specific amino acid residues within the enzymes. While these in silico findings provide insights, they underscore the need for comprehensive chemical analyses and absorption studies to validate health risks. This research emphasizes the necessity of evaluating the toxicity of M/NPs and phthalates from sex toys, promoting further investigations to protect individuals' health during product use.

Basin scale monitoring of microplastics and phthalates in sediments from the Persian Gulf and the Gulf of Makran using GIS-based algorithms: Insights towards spatial variation and potential risk assessment

Information on sedimentary microplastics and phthalates has been restricted to the coastal regions of the Persian Gulf and the Gulf of Makran. Our basin-wide study monitored their levels, spatial behaviors, and potential risks using GIS-based techniques. Microplastics and phthalates ranged from 5 to 75 particles/kg d.w and 0.004–1.219 μg g−1 d.w, respectively. Microplastics were in the size category of 100 μm to 3 mm, and black microfibers (< 1 mm) and high-density polymers were dominant. The total number of microplastics was between 356.333 × 1012 and 469.075 × 1012 particles in the surface sediments of the studied regions (confidence interval = 99 %). Diethylhexyl phthalate (DEHP) and Di-isobutyl phthalate contributed 88 % of detected phthalates. Significant correlations among microplastic abundance, total phthalates, and DEHP were distinguished (p < 0.05). Overall, the findings reiterated the widespread presence of microplastics and a potential link between phthalates and microplastics. Semi-variogram, cluster Voronoi polygons, and Trend analysis identified spatial outliers and major deposition sites of microplastics and phthalates and consequently outlined the localities where upcoming studies should be concentrated. A hotspot of potential risks was marked using Fuzzy logic and GIS-based algorithms in the Sea of Makran, covering an area equal to 342. 99 km2.