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.

Extracellular Vesicles as a potential source of biomarkers for endocrine disruptors in MASLD: a short review on the case of DEHP.

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is a chronic disease with increasing prevalence and for which non-invasive biomarkers are needed. Environmental endocrine disruptors (EDs) are known to be involved in the onset and progression of MASLD and assays to monitor their impact on the liver are being developed. Extracellular vesicles (EVs) mediate cell communication and their content reflects the pathophysiological state of the cells from which they are released. They can thus serve as biomarkers of the pathological state of the liver and of exposure to EDs. In this review, we present the relationships between DEHP (Di(2-ethylhexyl) phthalate) and MASLD and highlight the potential of EVs as biomarkers of DEHP exposure and the resulting progression of MASLD.

Di-(2-ethylhexyl) phthalate exposure induces ferroptosis by regulating the Nrf2-mediated signaling pathway in mouse ovaries.

Di-(2-ethylhexyl) phthalate (DEHP), an endocrine-disrupting chemical present in plasticized products, exerts strong modulation on the anatomy and function of the female reproductive system. However, the potential mechanisms underlying DEHP-induced regulation of prepubertal female reproductive toxicity have not yet been elucidated. Therefore, this study was designed to elucidate the molecular mechanism of ovarian injury induced by DEHP exposure in mice. Elevated serum mono-2-ethylhexyl phthalate (MEHP) concentrations, decreased levels of ovarian hormones (E2 and P4), and observed ovarian injury were found after DEHP exposure. Ovarian transcriptome analysis revealed significant alterations in ferroptosis-associated gene expression, with potential regulation by Nrf2. Subsequent analysis of ferrous iron, malondialdehyde (MDA), Western blotting, and immunofluorescence of the ovaries confirmed the RNA-seq findings. Transcriptome analysis of granulosa cells revealed a direct or indirect regulatory relationship between Nrf2 and downstream ferroptosis-related proteins following MEHP exposure. Further experiments demonstrated that ferrostatin-1 attenuated MEHP-induced ferroptosis in granulosa cells. Additionally, Nrf2 stabilization and accumulation in the nucleus of granulosa cells were observed following MEHP treatment. RNAi-mediated knockdown of Nrf2 exacerbated MEHP-induced ferroptosis in granulosa cells. This evidence indicates that DEHP exposure induces ferroptosis through regulation of the Nrf2-mediated signaling pathway in mouse ovaries, laying the groundwork for future studies aiming to develop therapeutic strategies against DEHP toxicity.

DEHP regulates ferritinophagy to promote testicular ferroptosis via suppressing SIRT1/PGC-1α pathway.

To increase elasticity and flexibility, di-2-ethylhexyl phthalate (DEHP) is used in a variety of industrial products, but excessive exposure to it can pose a threat to human health. In epidemiological studies of population exposure to DEHP, attention has been paid to damage to the male reproductive system. However, the toxicological mechanism of DEHP regarding testicular injury is not well understood. We used Western blot analysis, transmission electron microscopy, fluorescence staining, transient transfection and assay kit to detect relevant indicators, and the results were as follows: After DEHP exposure, the expression levels of ACSL4, COX2, TF, FTH1, LC3, AMPK, p-AMPK, ULK1, p-ULK1, serum iron, tissue iron and MDA in the exposure group were significantly increased. The expression levels of GPX4, NCOA4, p62, SIRT1, and PGC-1α, as well as the contents of GSH and ATP, decreased. Electron microscopy showed that more autophagosomes were observed. Our findings suggest that exposure to DEHP induced ferritinophagy and ferroptosis in the testis. In vitro, the promoting effect of ferritinophagy on ferroptosis was verified by applying the autophagy inhibitor (3-MA) and si-NCOA4. Moreover, Mono-(2-ethylhexyl) phthalate (MEHP) inhibited the mitochondrial regulatory protein SIRT1/PGC-1α, leading to mitochondrial dysfunction. Changes in mitochondrial reactive oxygen species (MtROS) and energy over-activated AMPK/ULK1 autophagy pathway, and then promoted ferritinophagy, which increased the sensitivity of TM4 cells to ferroptosis. This research offers a theoretical framework for the prevention and management of DEHP-induced harm.

Di-(2-ethylhexyl) phthalate induces prepubertal testicular injury through MAM-related mitochondrial calcium overload in Leydig and Sertoli cell apoptosis.

As one of the most prevalent environmental endocrine disruptors, di-(2-ethylhexyl) phthalate (DEHP) is known for its significant developmental toxicity to the male reproductive system in humans and mice. Prepubertal exposure to DEHP has been shown to cause testicular damage, but the underlying mechanisms require further investigation. To investigate this effect, prepubertal mice were exposed to 100, 250 or 500 mg/kg body weight (bw) of DEHP for 14 days, which resulted in impaired histological structure and increased apoptosis of the testes. RNA sequencing (RNA-seq) of testicular tissue suggested that DEHP led to injury in Leydig and Sertoli cells. To further elucidate these mechanisms, we conducted experiments using immature mouse Leydig (TM3) and Sertoli (TM4) cells, and exposed them to 200 µM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP, for 24 h. We found that MEHP exposure induced oxidative stress injury and promoted cell apoptosis, and that cotreatment with N-acetylcysteine partially reversed these injuries. Given the close association between oxidative stress and mitochondrial calcium levels, we demonstrated that MEHP exposure disrupted mitochondria and increased mitochondrial calcium levels. In addition, MEHP exposure facilitated the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs), upregulated protein expression and enhanced the interactions of the IP3R3-Grp75-VDAC1 complex. Furthermore, inhibition of calcium transfer in the IP3R3-Grp75-VDAC1-MCU axis relieved MEHP-induced mitochondrial injury, oxidative stress and apoptosis in TM3 and TM4 cells. This study highlights the importance of MAM-mediated mitochondrial calcium overload and the subsequent apoptosis of Leydig and Sertoli cells as pivotal factors contributing to testicular injury induced by prepubertal exposure to DEHP.

Calcium homeostasis imbalance mediates DEHP induced mitochondrial damage in cerebellum and the antagonistic effect of lycopene.

Phthalates (PAEs), especially di (2-ethylhexyl) phthalate (DEHP), are generally considered to have adverse impact on nervous system. The residue of DEHP in the environment has gradually become a widely concerned environmental problem due to its widespread use in plastic items. Lycopene (LYC) as the readily available natural antioxidant is considered to have the potential to alleviate exogenous poisons-induced nerve damage. However, there is currently a lack of strategies to alleviate the neurotoxicity caused by DEHP, and it is also unknown whether LYC can alleviate the neurotoxicity caused by DEHP. The experiment demonstrated that LYC had the potential to mitigate DEHP-induced mitochondrial damage in cerebellum. DEHP induced the disorder of Ca2+ transport in cerebellum, thereby resulting in the imbalance of protein homeostasis. Such disruption in protein homeostasis further results in the overactivation of mitochondrial unfolded protein response (UPRmt) and mitochondrial injury. Mechanistically, LYC could alleviate the imbalance of calcium homeostasis and protein homeostasis induced by DEHP via regulating inositol 1, 4, 5-trisphosphate receptor type1 (IP3R1) and sarco/endoplasmic reticulum Ca (2+)-ATPase 2 (SERCA2), further alleviating mitochondrial damage in cerebellum. Subsequently, the present study suggested the mechanism of cerebellar injury induced by DEHP, and provided a novel approach to treating DEHP-induced neurotoxicity.

Polystyrene microplastics and di-2-ethylhexyl phthalate co-exposure: Implications for female reproductive health.

Microplastics and phthalates are prevalent and emerging pollutants that pose a potential impact on human health. Previous studies suggest that both microplastics and phthalates can adversely affect the reproductive systems of humans and mammals. However, the combined impact of these pollutants on the female reproductive system remains unclear. Here we show the impacts of exposure to polystyrene microplastics (PS-MPs) and di-2-ethylhexyl phthalate (DEHP) on female Sprague-Dawley rats' reproductive systems. We find that co-exposure to PS-MPs and DEHP results in a marked increase in cystic and atretic follicles, oxidative stress, fibrosis, and dysregulation of serum sex hormone homeostasis in the ovaries of the rats. Proteomic analysis identified differentially expressed proteins that were predominantly enriched in signaling pathways related to fatty acid metabolism and tight junctions, regulated by transforming growth factor ß1 (TGF-ß1). We further confirm that co-exposure to DEHP and PS-MPs activates the TGF-ß1/Smad3 signaling pathway, and inhibiting this pathway alleviates oxidative stress, hormonal dysregulation, and ovarian fibrosis. These results indicate that exposure to the combination of microplastics and phthalates leads to a significant increase in atretic follicles and may increase the risk of polycystic ovary syndrome (PCOS). Our study provides new insights into the reproductive toxicity effects of microplastics and DEHP exposure on female mammals, highlighting the potential link between environmental pollutants and the occurrence of PCOS. These findings highlight the need for comprehensive assessments of the reproductive health risks posed by microplastic pollution to women and contribute to the scientific basis for evaluating such risks.

Occurrence of plastic additives in coral-reef invertebrates on natural and plastic substrates.

Numerous studies have investigated the occurrence of plastic additives in marine biota. Yet, their main vector of transfer into organisms tissues remains unknown. We explored seven common additives in benthic coral reef invertebrates residing on natural/plastic substrates in a protected marine reserve versus an unprotected reef to ascertain whether additives transfer by substrate leaching. Samples of three coral-reef species were extracted and analyzed by GCMS and HPLC. Of the seven chemical additives investigated, dibenzylamine and bis(2-ethylhexyl) phthalate were detected. No significant association was found between additives and substrate type, possibly because these plastics have been submerged for years, and the majority of additives within them have leached. The marine reserve had fewer samples with additives, highlighting the importance of active management. Understanding the transfer vectors of plastic additives into biota is essential for assessing the risk they pose and devising effective management tools for protecting coral reefs.

Exposure to environmental doses of DEHP causes phenotypes of polycystic ovary syndrome.

Globally, approximately 6-20% of women who are of reproductive age suffer from polycystic ovary syndrome (PCOS), with environmental factors believed to be significant contributors. Di-2-ethylhexyl phthalate (DEHP) is known to be an endocrine disruptor, and is also suspected of being associated with the occurrence of PCOS, but in vivo studies to verify this association are lacking. In this study, female SD rats were exposed to DEHP at levels of 0.1, 1.0, and 10mg/kg/d, which are comparable to daily human exposure, to explore its potential role in the development of PCOS. The findings indicated that DEHP exposure reduced ovarian and uterine coefficients, decreased accumulation of primordial follicles, increased the prevalence of atretic and cystic follicles and fibrosis in ovarian tissues, altered serum hormone levels, elevated blood glucose levels and insulin resistance, disrupted the endocrine system and resulted in significant oxidative damage in the ovarian tissues. These results imply that DEHP exposure may cause lesions resembling PCOS to develop. By analyzing the differential expression of the proteome, and using GO and KEGG enrichment analyses, we found they were mainly enriched in the metabolic pathway and in the PPAR signaling pathway. We confirmed that activation of the PPARγ signaling pathway caused by DEHP exposure, is related to the emergence of PCOS-like lesions. This research provides direct in vivo experimental evidence for the association between DEHP exposure and PCOS.

Novel Insight into the mechanism of di (2-ethylhexyl) phthalate (DEHP) impairing early follicle development.

Di (2-ethylhexyl) phthalate (DEHP), an artificially synthetic plasticizer, is a widespread environmental endocrine disruptor, which has raised substantial concern among the public about its potential reproductive toxicity effects. Taking large amounts of DEHP disrupts the normal functioning of the ovaries, however, the toxicological effects and the mechanisms by which DEHP impairs fetal folliculogenesis remain poorly understood. Our research aims to elucidate the associations between utero exposure to DEHP and fetal folliculogenesis in offspring. In this research, we monitored the spatiotemporal and expression levels of GDF9-Hedgehog (Hh) pathway-related genes during postnatal days 3-14, confirming initially the potential associations between defects in theca cell development and the downregulation of GDF9-Hh signaling. Moreover, utilizing an ovarian organ in vitro culture model, rescue validation experiments demonstrated that the addition of recombinant GDF9 protein effectively alleviate the theca cell damage caused by DEHP, thus supporting the aforementioned associations. In conclusion, our findings validate the significant role of the GDF9-Hh pathway in the enduring reproductive toxicity resulting from prenatal exposure to DEHP.

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.

Interspecies synergistic interactions mediated by cofactor exchange enhance stress tolerance by inducing biofilm formation.

Metabolic exchange plays a crucial role in shaping microbial community interactions and functions, including the exchange of small molecules such as cofactors. Cofactors are fundamental to enzyme catalytic activities; however, the role of cofactors in microbial stress tolerance is unclear. Here, we constructed a synergistic consortium containing two strains that could efficiently mineralize di-(2-ethylhexyl) phthalate under hyperosmotic stress. Integration of transcriptomic analysis, metabolic profiling, and a genome-scale metabolic model (GEM) facilitated the discovery of the potential mechanism of microbial interactions. Multi-omics analysis revealed that the vitamin B12-dependent methionine-folate cycle could be a key pathway for enhancing the hyperosmotic stress tolerance of synergistic consortium. Further GEM simulations revealed interspecies exchange of S-adenosyl-L-methionine and riboflavin, cofactors needed for vitamin B12 biosynthesis, which was confirmed by in vitro experiments. Overall, we proposed a new mechanism of bacterial hyperosmotic stress tolerance: bacteria might promote the production of vitamin B12 to enhance biofilm formation, and the species collaborate with each other by exchanging cofactors to improve consortium hyperosmotic stress tolerance. These findings offer new insights into the role of cofactors in microbial interactions and stress tolerance and are potentially exploitable for environmental remediation. IMPORTANCE: Metabolic interactions (also known as cross-feeding) are thought to be ubiquitous in microbial communities. Cross-feeding is the basis for many positive interactions (e.g., mutualism) and is a primary driver of microbial community assembly. In this study, a combination of multi-omics analysis and metabolic modeling simulation was used to reveal the metabolic interactions of a synthetic consortium under hyperosmotic stress. Interspecies cofactor exchange was found to promote biofilm formation under hyperosmotic stress. This provides a new perspective for understanding the role of metabolic interactions in microbial communities to enhance environmental adaptation, which is significant for improving the efficiency of production activities and environmental bioremediation.

Reduced ovarian cholesterol and steroid biosynthesis along with increased inflammation are associated with high DEHP metabolite levels in human ovarian follicular fluids.

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is known to have endocrine-disrupting properties mediated by its many metabolites that form upon exposure in biological systems. In a previous study, we reported an inverse association between DEHP metabolites in the human ovarian follicular fluid (FF) and the responsiveness of the follicles to controlled ovarian stimulation during in vitro fertilization (IVF) treatments. Here, we explored this association further through molecular analysis of the ovarian FF samples. Ninety-six IVF patients from Swedish (N = 48) and Estonian (N = 48) infertility clinics were selected from the previous cohort (N = 333) based on the molar sum of DEHP metabolites in their FF samples to arrive at "high" (mean 7.7 ± SD 2.3 nM, N = 48) and "low" (0.8 ± 0.4 nM, N = 48) exposure groups. Extracellular miRNA levels and concentrations of 15 steroid hormones were measured across FF samples. In addition, FF somatic cells, available for the Estonian patients, were used for RNA sequencing. Differential expression (DE) and interactions between miRNA and mRNA networks revealed that the expression levels of genes in the cholesterol biosynthesis and steroidogenesis pathways were significantly decreased in the high compared to the low DEHP group. In addition, the DE miRNAs were predicted to target key enzymes within these pathways (FDR < 0.05). A decreased 17-OH-progesterone to progesterone ratio was observed in the FF of the high DEHP group (p < 0.05). Additionally, the expression levels of genes associated with inflammatory processes were elevated in the FF somatic cells, and a computational cell-type deconvolution analysis suggested an increased immune cell infiltration into the high DEHP follicles (p < 0.05). In conclusion, elevated DEHP levels in FF were associated with a significantly altered follicular milieu within human ovaries, involving a pro-inflammatory environment and reduced cholesterol metabolism, including steroid synthesis. These results contribute to our understanding of the molecular mechanisms of female reprotoxic effects of DEHP.

In vitro Evaluation of DINCH-Plasticized Blood Bags for Red Blood Cell Storage with CPDA-1 Anticoagulant.

Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in blood bags. Despite its protective effects on red blood cell (RBC) storage, concerns about its reproductive toxicity exist. This study investigated the in vitro quality of RBC concentrates stored in bags using di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) as an alternative plasticizer. Methods: Using a pool-and-split study design, we produced 20 matched homogenous quintets of RBC concentrates in two DINCH bags and three DEHP bags with citrate phosphate dextrose adenine (CPDA-1) anticoagulant. RBC storage quality was assessed weekly for 35 days. Results: On day 35, the median hemolysis levels in the DINCH bags (0.297-0.342%) were marginally higher (p < 0.05) than the DEHP bags (0.204-0.240%). All DINCH bags showed <0.8% hemolysis. RBCs in the DINCH bags showed increased mean corpuscular volume and decreased eosin 5' maleimide binding than in the DEHP bags. Higher pO2 and lower pCO2 levels in the DINCH bags indicated better gas permeability than in DEHP bags. Other metabolic parameters were comparable in both bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Conclusion: The quality of RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for nonleukoreduced RBC storage even without the use of next-generation additive solutions to improve RBC preservation quality.

A plasticizer is a chemical substance added to plastic to increase its flexibility. DEHP is a plasticizer that has been widely used in many products including plastic tubing and bags of medical devices. However, concerns about DEHP-related toxicity have been debated for many years. DEHP has been replaced with other plasticizers in many products, but it is still being used in blood bags due to its protective effect on RBC preservation. DINCH is an alternative plasticizer with a low toxicology profile. This study investigated the quality of RBC concentrates stored in blood bags using DINCH. Twenty sets of five RBC concentrates were produced using two DINCH bags and three DEHP bags with CPDA-1 anticoagulant, and the storage quality was assessed weekly for 35 days. On day 35, the median hemolysis levels in the DINCH bags (0.297­0.342%) were slightly increased than the DEHP bags (0.204­0.240%). However, all DINCH bags showed hemolysis lower than the regulatory limit of 0.8%. DINCH bags exhibited better gas permeability than DEHP bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Most of the other metabolic parameters were comparable in both bags. The quality of nonleukocyte-reduced RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for RBC storage, even without the use of next-generation additive solutions to improve RBC preservation quality.

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.

Di-(2-ethylhexyl) phthalate and its metabolites research trend: a bibliometric analysis.

Di-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers. Many studies focus on the impact of continuous exposure to DEHP on humans and ecosystems. In this study, the bibliometric analysis of DEHP and its metabolites research was conducted to assess the research performances, hotspot issues, and trends in this field. The data was retrieved from a Web of Science Core Collection online database. VOSviewer 1.6.18 was used to analyze. A total of 4672 publications were collected from 1975 to 2022 October 21. The number of publications and citations increased annually in the last decades. China had the largest number of publications, and the USA had the highest co-authorship score. The most productive and most frequently cited institutions were the Chinese Academy of Sciences and the Centers for Disease Control & Prevention (USA), respectively. The journal with the most publications was the Science of Total Environment, and the most cited one was the Environmental Health Perspectives. The most productive and cited author was Calafat A. M. (USA). The most cited reference was "Phthalates: toxicology and exposure." Four hotspot issues were as follows: influences of DEHP on the organisms and its possible mechanisms, assessment of DEHP exposure to the human and its metabolism, dynamics of DEHP in external environments, and indoor exposure of DEHP and health outcomes. The research trends were DNOP, preterm birth, gut microbiota, microplastics, lycopene, hypertension, and thyroid hormones. This study can provide researchers with new ideas and decision-makers with reference basis to formulate relevant policies.

Evaluation of the Effects of Di-(2-ethylhexyl) phthalate (DEHP) on Caenorhabditis elegans Survival and Fertility.

Di-2-ethylhexyl (DEHP), which is widely used in industrial products, is produced annually in excess of 2 million tons worldwide. DEHP is an endocrine disruptor and one of the major environmental pollutant chemicals (EDCs) in nature. There is some information about the effects of these products, which provide great advantages in every respect, on human health and the environment. In this study, C. elegans organism was used to evaluate the health and environmental risks of DEHP. The survival and fertility effects of DEHP on the C. elegans organism were examined and the results were evaluated. In the study, it was determined that DEHP not only shortened the survival time of C. elegans but also caused a decrease in fertility. DEHP (0.625 mM and 10 mM) caused a 23.2-30.6% decrease in fertility. Additionally, the LC50 (50% lethal concentration) value of DEHP was found to be 321 µg/mL.

Di(2-ethylexyl) phthalate and chromosomal damage: Insight on aneugenicity from the cytochalasin-block micronucleus assay.

Bis(2-ethylhexyl) phthalate is the most abundant phthalate used as plasticizer to soften plastics and polymers included in medical devices. Human and environmental exposure may occur because DEHP is not chemically bound to plastics and can easily leach out of the materials. This phthalate is classified as reproductive toxicant and possible carcinogen to humans. The genotoxic potential has still to be clarified, but there are indications suggesting that DEHP may have aneugenic effects. To further investigate DEHP genotoxicity, the cytochalasin-block micronucleus assay was applied and combined with the CREST staining to characterise micronucleus content and gain insights on its genotoxic mode of action. Chromosomal damage was also analysed in metaphase and ana-telophase cells and the morphology of the mitotic spindle was investigated to evaluate the possible involvement of this cellular apparatus as a target of DEHP. Our findings indicated that DEHP induced a statistically significant increase in the frequency of micronuclei as well as in the frequency of CREST-positive micronuclei. Consistently, disturbance of chromosome segregation and induction of numerical chromosome changes were observed together with changes in spindle morphology, formation of multipolar spindles and alteration of the microtubule network. Experiments performed without metabolic activation demonstrated a direct action of DEHP on chromosome segregation not mediated by its metabolites. In conclusion, there is consistent evidence for an aneugenic activity of DEHP. A thresholded genotoxic activity was identified for DEHP, disclosing possible implications for risk assessment.

Exposure to endocrine disruptor DEHP promotes the progression and radiotherapy resistance of pancreatic cancer cells by increasing BMI1 expression and properties of cancer stem cells.

Most patients diagnosed with pancreatic cancer are initially at an advanced stage, and radiotherapy resistance impact the effectiveness of treatment. This study aims to investigate the effects of endocrine disruptor Di-(2-ethylhexyl) phthalate (DEHP) on various biological behaviors and the radiotherapy sensitivity of pancreatic cancer cells, as well as its potential mechanisms. Our findings indicate that exposure to DEHP promotes the proliferation of various cancer cells, including those from the lung, breast, pancreas, and liver, in a time- and concentration-dependent manner. Furthermore, DEHP exposure could influence several biological behaviors of pancreatic cancer cells in vivo and vitro. These effects include reducing cell apoptosis, causing G0/G1 phase arrest, increasing migration capacity, enhancing tumorigenicity, elevating the proportion of cancer stem cells (CSCs), and upregulating expression levels of CSCs markers such as CD133 and BMI1. DEHP exposure can also increase radiation resistance, which can be reversed by downregulating BMI1 expression. In summary our research suggests that DEHP exposure can lead to pancreatic cancer progression and radiotherapy resistance, and the mechanism may be related to the upregulation of BMI1 expression, which leads to the increase of CSCs properties.

Fluorescent MnO2@DEHP Nanoprobe for Rapid and Selective Detection of Fe(III) ions.

Particle extraction via the liquid-liquid interface (PELLI) method has been utilized to produce Di-(2-ethylhexyl) phosphate (DEHP) coated MnO2 fluorescent nanoprobe denoted as MnO2@DEHP for the selective detection of Fe3+ ions. The synthesized MnO2@DEHP nanoprobe was characterized by various instrumental techniques such as FT-IR, PXRD, TEM, EDAX, HRTEM, DLS, and XPS. Since the high concentration of Fe3+ in waste water leads to water pollution, which in turn affects the ecosystem, and causes severe health hazards. Therefore, accurate detection of Fe3+ ions in the aqueous systems is essential as they are involved in various chemical and biological processes in living things. Here, the synthesized MnO2@DEHP nanoprobe selectively detects Fe3+ ions in the presence of various metal ions in an aqueous media by fluorescence quenching (turn-off) mechanism. The limit of detection (LOD) of MnO2@DEHP nanoprobe for Fe3+ was found to be 0.49 µM. The test-strip method and real water sample analysis were also used to demonstrate the viability of MnO2@DEHP as a fluorescent nanoprobe to detect Fe3+ ions visually and in environment monitoring applications.