Di-(2-ethylhexyl) Phthalate Concentrations Research Articles

Content and Health Risks of Microplastics and Phthalate Esters in Bottled Water

To study the content and health risks of microplastics （MPs） and phthalate esters （PAEs） in bottled water, a quantitative analysis of MPs was conducted by using Rose Bengal staining and stereomicroscopy. Seven PAEs were quantified by using gas chromatography-triple quadrupole tandem mass spectrometry （GC-MS/MS）. The daily intake of MPs was estimated and the carcinogenic and non-carcinogenic risks of PAEs were evaluated through a health risk assessment model. The results showed that the abundance of MPs in 21 bottled waters ranged from 48 n·L-1 to 216 n·L-1 （with the median abundance of 88 n·L-1）. The majority （72.1%） of MPs were fibrous in shape, and fragments accounted for only 27.9%. The average proportion of small-sized （10-50 μm） MPs was 33.9%, and that of large-sized MPs （>500 μm） was 4.3%. Most MPs were blue. The ∑(PAEs) in bottled water was 1.15-2.47 μg·L-1 （average 1.62 μg·L-1）. PAEs detected with high frequencies （100%） included dimethyl phthalate （DMP）, diethyl phthalate （DEP）, diisobutyl phthalate （DIBP）, di-n-butyl phthalate （DBP）, and di（2-ethylhexyl） phthalate （DEHP）, while the detection frequencies of butylbenzyl phthalate （BBP） and di-n-octyl phthalate （DNOP） were relatively low. The concentrations of DBP, DEHP, and DEP were all below the standard limits for drinking water in China. The ∑(PAEs) in the migration experiments was 0.61-2.04 μg·L-1 （average 1.33 μg·L-1）. The migration amounts of DBP and DEHP were also within the allowable range under the condition of 60℃ for 10 days. Seven PAEs were detected in both the bottles and caps, and the average content of DEHP in bottles was the highest, while DBP had the highest content in caps. The estimated intake of MPs （EDI） by drinking bottled water in different age groups of humans was 2.87 n·（kg·d）-1 for adults, 3.87 n·（kg·d）-1 for children, and 5.85 n·（kg·d）-1 for infants. The carcinogenic risks of DEHP in 21 bottled water samples and the migration test were less than the maximum acceptable risk level （1×10-6）, and the non-carcinogenic risk indices （HIs） of PAEs were all less than 1, indicating no non-carcinogenic risk to humans； however, the risk value of infants and children was higher than that of adults and should not be ignored.

Producción de esterasa por Fusarium culmorum crecido en presencia de diferentes concentraciones di(2-etilhexil) ftalato y de ion calcio en fermentación sumergida

Phthalates are plastic additives used as plasticizers in the manufacture of flexible plastic materials. These compounds, such as di(2-ethylhexyl) phthalate (DEHP) are toxic substances to the environment and human health, and have been detected as environmental pollutants. In this study, the activity of esterase produced by Fusarium culmorum grown in media supplemented with different concentrations of DEHP (1.5, 3 and 4 g/L) and calcium ion (0.1 and 0.5 g/L) in submerged fermentation was characterized by biochemical tests and polyacrylamide gel electrophoresis. The greatest esterase activity was observed in cultures grown in media added with 3 g of DEHP/L and 0.5 g of calcium ion/L, followed by those cultures grown in media containing 1.5 g of DEHP/L. Whereas cultures grown on 4 g of DEHP/L had the lowest esterase activity. In general, cultures added with 0.5 g of calcium ion/L had the maximum enzymatic activity and the highest enzymatic productivity in the media tested. High concentration of DEHP were used as the sole source of carbon and energy by F. culmorum. It is suggested that the calcium ion favored the esterase production during the DEHP biodegradation. However, further studies are needed to understand the relationship between calcium ion, fungal growth, and enzyme production to provide the appropriate concentration of this ion in the culture medium.

Increasing the Recycling of PVC Flooring Requires Phthalate Removal for Ensuring Consumers' Safety: A Cross-Checked Substance Flow Analysis of Plasticizers for Switzerland.

As our planet grapples with the severe repercussions of plastic pollution, mechanical recycling has been proposed as a potential remedy. However, increasing mechanical recycling may have unintended negative consequences. For example, recycling of PVC flooring containing hazardous plasticizers that were used in the past may lead to continued exposure. Here we propose measures to increase recycling while circumventing adverse health impacts caused by legacy additives. For this, we conduct a dynamic substance flow analysis for Switzerland and the time period from 1950 to 2100, focusing on three plasticizers: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), and di(2-ethylhexyl) terephthalate (DEHT). We quantify the uncertainty of results, check their plausibility against measured concentrations in samples representative for the Swiss market, and compare them with modeled substance flows in Germany. Based on the cross-checked model, future average concentrations of DEHP in PVC flooring on the Swiss market are expected to be above the legal limit of 0.1 wt % for several decades if increased recycling rates are implemented without additional measures. Phasing out the potentially concerning DiNP, too, and preventing phthalates from entering recycling would lower their average market concentrations to values below 0.1 wt % and enable increasing recycling rates without compromising product safety. Analogous measures could help achieve this goal across other European countries and product groups.

Metabolic Stress Responses in Labeo rohita Subjected to Di (2-ethylhexyl) Phthalate (DEHP), Dibutyl Phthalate (DBP), and Diethyl Phthalate (DEP)

This study investigates the stress response of glucose and cholesterol levels in Labeo rohita (Rohu) upon exposure to three widely used phthalates: Di(2-ethylhexyl) phthalate (DEHP), Dibutyl phthalate (DBP), and Diethyl phthalate (DEP). Phthalates, recognized for their endocrine-disrupting properties, are prevalent environmental contaminants. Specimens of Labeo rohita were subjected to environmentally relevant concentrations of DEHP, DBP, and DEP over a controlled period. Blood samples were collected periodically to measure fluctuations in glucose and cholesterol levels, serving as biomarkers of metabolic stress. The results indicate significant alterations in both glucose and cholesterol concentrations, with each phthalate demonstrating a distinct impact on these metabolic parameters. DEHP and DBP elicited more pronounced disruptions compared to DEP, underscoring their higher toxicity. These findings highlight the differential metabolic responses of Labeo rohita to various phthalates and underscore the ecological risks associated with phthalate contamination. The study advocates for stricter regulatory measures to mitigate phthalate pollution and protect aquatic ecosystems. This research enhances our understanding of the biochemical pathways affected by phthalate exposure and lays the groundwork for future investigations into the mechanisms underlying phthalate-induced stress in fish.

Rapid effects of plastic pollution on coastal sediment metabolism in nature

While extensive research has explored the effects of plastic pollution, ecosystem responses remain poorly quantified, especially in field experiments. In this study, we investigated the impact of polyester pollution, a prevalent plastic type, on coastal sediment ecosystem function. Strips of polyester netting were buried into intertidal sediments, and effects on sediment oxygen consumption and polyester additive concentrations were monitored over 72-days. Our results revealed a rapid reduction in the magnitude and variability of sediment oxygen consumption, a crucial ecosystem process, potentially attributed to the loss of the additive di(2-ethylhexyl) phthalate (DEHP) from the polyester material. DEHP concentrations declined by 89% within the first seven days of deployment. However, effects on SOC dissipated after 22 days, indicating a short-term impact and a quick recovery by the ecosystem. Our study provides critical insights into the immediate consequences of plastic pollution on ecosystem metabolism in coastal sediments, contributing to a nuanced understanding of the temporal variation of plastic pollution’s multifaceted impacts. Additionally, our research sheds light on the urgent need for comprehensive mitigation strategies to preserve marine ecosystem functionality from plastic pollution impacts.

Determination of phthalate esters contents in different types of cheese produced and consumed in Saudi Arabia

Background: Phthalates’ esters are commonly incorporated into plastic materials to enhance their elasticity, thereby facilitating their migration into food items. Aims: To evaluate the levels of phthalate esters in six distinct varieties of locally produced cheese and sold in Saudi Arabia, at the time of purchase (t=0) and after storage for one and two months. Methods: Six types of local cheeses (Cheddar, Mozzarella, Feta, Cheeseburger slices, Haloumi and Kashkaval) were purchased and analyzed at three different intervals: at the time of purchase (t=0), after one month, and after two months of storage. The Phthalate ester concentrations were determined using indirect gas chromatography with results expressed in mg/kg of cheese. Results: Among the cheese samples analyzed, di(2-ethylhexyl) phthalate (DEHP) was found to be the most prevalent. Halloumi cheese exhibited the highest average concentration of DEHP (4.29 ± 0.51 mg/kg) followed by Mozzarella cheese (3.65 ± 0.46 mg/kg). After two months of storage, more than two-thirds (n=13) of the samples exceeded the permissible limits content of DEHP content while one-third (n=6) and more than half (n=9) exceeded the limits for dibutyl phthalate (DBP) and di-n-octyl phthalate (DNOP), respectively. The levels of phthalates in all cheese types increased with prolonged storage duration with Cheddar cheese exhibiting the highest rate of increase, exceeding fivefold (from 0.34 to 2.29 mg/kg). Conclusion: This study confirms the presence of phthalate in cheese samples, with concentrations varying depending on the cheese type, specific phthalate compound, and storage duration. Heightened consumer awareness regarding cheese storage practices is imperative to mitigate potential health risks associated with phthalate consumption. Keywords: Phthalate, cheese, chemical analysis, content, Saudi Arabia.

Modulating responses of indicator genes in cellular homeostasis, immune defense and apoptotic process in the Macrophthalmus japonicus exposed to di(2-ethylhexyl) phthalate as a plastic additive

Di(2-ethylhexyl) phthalate (DEHP), have been increasingly used as plasticizers to manufacture soft and flexible materials and ubiquitously found in water and sediments in the aquatic ecosystem. The aim of the present study was to evaluate the effect of DEHP exposure on cellular homeostasis (HSF1 and seven HSPs), immune responses (ILF), and apoptotic responses (p53, BAX, Bcl-2). DEHP exposure upregulated the expression of HSF1 and ILF. Moreover, it altered the expression levels of HSPs (upregulation of HSP70, HSP90, HSP40, HSP83, and HSP67B2 and downregulation of HSP60 and HSP21) in conjunction with HSF1 and ILF in the gills and hepatopancreas of M. japonicus exposed to DEHP. At the protein level, DEHP exposure changed apoptotic signals in both tissues of M. japonicus. These findings indicate that chronic exposures to several DEHP concentrations could disturb cellular balance, damage the inflammatory and immune systems, and induce apoptotic cell death, thereby affecting the survival of M. japonicus.

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

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

Di (2-ethylhexyl) phthalate effects on the growth, development, and reproduction of Moina macrocopa (Crustacea: Cladocera)

Di (2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in plastics. The effects of DEHP on terrestrial vertebrates have been extensively reported but the effects of DEHP contamination on aquatic ecosystems have not been thoroughly studied. Since water bodies are one of the main mediums through which DEHP is released worldwide, the impacts of DEHP contamination should be manifested in water fleas. Therefore, maternal Moina macrocopa were exposed to 1, 10, 100, and 1000 μg/L concentrations of DEHP. Changes in growth and reproduction were evaluated. The findings demonstrated that DEHP exposure did not have a negative impact on growth or the ability to reproduce. An analysis of the ovary yolk body (YB) demonstrated that the average size and number of yolk bodies (YBs) produced by M. macrocopa exposed to 1000 μg/L DEHP were not significantly different to the average size and number of YBs produced in blank control and solvent control conditions. These outcomes support the cellular pathology data gathered by other researchers. Nevertheless, when M. macrocopa was exposed to 1000 μg/L DEHP for five days, a significant increase in YB numbers was observed with changes in YB morphology. The critical cellular pathology of YB showed morphological abnormalities, including rod-shaped YBs, and YB density was higher than in the blank and solvent controls. Even though these results suggest that antioxidative stress can be induced by DEHP exposure, growth, and reproduction were not significantly different among exposed water fleas compared to fleas in the blank and solvent controls. The result was attributed to the antioxidant response of the water flea. In conclusion, the present study enhances our understanding of previous findings from risk assessments of DEHP contamination in aquatic ecosystems.

Biotoxicity responses of zebrafish in environmentally relevant concentration of di (2-ethylhexyl) phthalate

As an emerging environmental contaminant, di (2-ethylhexyl) phthalate (DEHP) is widely present in the aquatic environment, however, the effects and underlying mechanisms of DEHP on the aquatic organisms are poorly understood. This study systematically investigated the ecotoxicity induced by chronic exposure to environmental relevant concentrations of DEHP (0.03 mg/L, 0.1 mg/L, and 0.3 mg/L) on zebrafish brain. Results indicated that DEHP exposure significantly increased the levels of ROS and disturbance of the antioxidant enzymes activities in the brain, which may further enhance lipid peroxidation and DNA damage. Furthermore, acetylcholinesterase activity was first stimulated and inhibited by exposure to DEHP, and the antioxidant and apoptosis related genes were mainly upregulated. Risk assessment indicated that the ecotoxicity of DEHP on the zebrafish showed an “enhancement-reduction” trend as the exposure time was prolonged. Overall, these results provided new insights and useful information to ecological risk assessment and environmental management of DEHP pollution.

Exposure to di-2-ethylhexyl phthalate and breast neoplasm incidence: A cohort study

BackgroundPhthalates are ubiquitous environmental endocrine disruptors. As the predominant phthalate, di-2-ethylhexyl phthalate (DEHP) has been considered possibly carcinogenic to humans but large-scale longitudinal evidence is needed to further clarify its carcinogenicity. ObjectivesTo examine the association between DEHP exposure and incidence of breast malignant neoplasm, carcinoma in situ and benign neoplasm. MethodsA total of 273,295 women from UK Biobank cohort were followed up for a median of 13.5 years. Disease information was collected from National Health Service Cancer Registry and National Death Index. Baseline and yearly-average level of DEHP exposure were estimated for each individual by linking chemical monitoring record of European Environment Agency with home address of the participants by Kriging interpolation model. Cox proportional hazard model was employed to estimate the association between DEHP exposure and breast neoplasms. ResultsThe median (IQR) of baseline and yearly-average DEHP concentration were 8000.25 (interquartile range: 6657.85–11,948.83) and 8000.25 (interquartile range: 1819.93–11,359.55) μg/L. The highest quartile of baseline DEHP was associated with 1.11 fold risk of carcinoma in situ (95 % CI, 1.00, 1.23, p < 0.001) and 1.27 fold risk of benign neoplasm (95 % CI, 1.05, 1.54, p < 0.001). As for yearly-average exposure, each quartile of DEHP was positively associated with higher risk of malignant neoplasm (HR, 1.05; 95 % CI, 1.03, 1.07, p < 0.001), carcinoma in situ (HR, 1.08; 95 % CI, 1.04, 1.11, p < 0.001) and benign neoplasm (HR, 1.13; 95 % CI, 1.07, 1.20, p < 0.001). Stratification analysis showed no significant modification effects on the DEHP-neoplasm relationship by menopausal status or ethnicity but a suggestive higher risk in younger women and those who underwent oral contraceptive pill therapy. In sensitivity analysis, the associations remained when excluding the cases diagnosed within 2 years post baseline. ConclusionsReal-world level of DEHP exposure was associated with higher risk of breast neoplasms. Because of the health risks associated with DEHP, its release to the environment should be managed.

Levels of Phthalate Acid Esters in Carbonated Soft Drinks Bottled in Polyethylene Terephthalate (PET) Bottles Kept under Various Storage Conditions in Mwanza City, Tanzania

Background: Carbonated soft drinks (CSD), packaged in PET (polyethylene terephthalate) bottles, are among the most widely consumed non-alcoholic beverage globally. People of all ages enjoy CSDs for their flavour, mouthfeel, crispness, freshness, and capacity to both quench thirst and provide mental refreshment. Terephthalic acid, ethylene glycol, and other additives such as phthalates are the materials used to make these PET bottles. Several studies have demonstrated that phthalates may migrate into packaged goods and, when consumed, can cause several ill-health conditions to humans. Type II diabetes, obesity, asthma, male and female reproductive disorders, tumours (including breast cancer), pituitary, hypothalamic, and peripheral hormone disorders, behavioral issues, and neurodevelopmental disorders are among the health issues reported to be associated with phthalates. Objective: This study aimed to ascertain the presence and concentration of phthalates in PET bottled carbonated soft drinks produced in Mwanza City, and to examine the effects of various storage conditions on the migration of these contaminants into the product. Methods: Liquid-liquid extraction, clean-up techniques, and chromatographic analysis were used as the methods of determination to identify and quantify the specific phthalates compounds. Results: The findings demonstrated that after being stored outdoors for four to six months, the migration, especially for dibutyl phthalate (DBP) and di [2-ethylhexyl] phthalate (DEHP), became more apparent. After two, four, and six months of indoor storage, there was no appreciable change in the mean concentrations of DMP (dimethyl phthalate), DEP (diethyl phthalate), DBP (dibutyl phthalate), and DEHP for either brand in this study. Compared to indoor storage, the DBP and DEHP migration increased by up to 24-fold when the two brands were kept outdoors for four and six months. Thus, the safety and quality of carbonated soft drinks were seriously compromised by the phthalate compounds from the PET bottles that these companies were using. Conclusion: The study's conclusions show that PET packaging, which is influenced by the bottle manufacturing process and raw material formulations for packages of the studied CSDs, are responsible for the migration of phthalates into the products. The storage conditions and time are established to be the primary causes of phthalates migration in bottled carbonated soft drinks. Though the migration figures in this study are lower than those of the other studies from different locations that were compared, it is important to remember that these compounds may interfere with hormones even in small quantities.

Endocrine-disrupting chemicals and hormonal profiles in PCOS women: A comparative study between urban and rural environment

Polycystic Ovary Syndrome (PCOS), a multifaceted endocrine disorder, affects a significant proportion of women globally, with its etiology rooted in both genetic and environmental factors. This study delves into the environmental aspect, particularly focusing on the role of endocrine-disrupting chemicals (EDCs) in the context of urbanization and industrialization. This research examines the impact of endocrine-disrupting chemicals (EDCs) — Bisphenol A (BPA), Mono-ethyl Hexyl Phthalate (MEHP), and Di-ethyl Hexyl Phthalate (DEHP) — on 40 women with Polycystic Ovary Syndrome (PCOS) across urban and rural Gujarat. Employing High-Performance Liquid Chromatography (HPLC) and chemiluminescence, we analyzed their blood samples for EDCs levels and hormonal parameters. Urban individuals displayed significantly higher BPA and DEHP concentrations, highlighting the environmental exposure differences. Notably, urban exposure to MEHP and DEHP correlated with a marked decrease in estradiol levels, while rural DEHP exposure was associated with an increase in estradiol but a decrease in prolactin and DHEAS levels. These findings illuminate the variable effects of EDC exposure on hormonal profiles in PCOS, influenced by geographical and environmental contexts. The study underscores the critical need for tailored environmental health policies to mitigate the diverse impacts of EDCs, advocating for a nuanced approach to PCOS management that considers environmental exposures. Our insights contribute to the understanding of PCOS’s hormonal dynamics, emphasizing the significance of addressing EDC exposure in different settings.

Pollution characteristics, sources, and health risks of phthalate esters in ambient air: A daily continuous monitoring study in the central Chinese city of Nanchang

In recent years, the atmospheric pollution caused by phthalate esters (PAEs) has been increasing due to the widespread use of PAE-containing materials. Existing research on atmospheric PAEs lacks long-term continuous observation and samples from cities in central China. To investigate the pollution characteristics, sources, and health risks of PAEs in the ambient air of a typical city in central China, daily PM2.5 samples were collected in Nanchang from November 2020 to October 2021. In this study, the detection and quantification of six significant PAE contaminants, namely diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DIBP), Di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DnOP), and diisodecyl phthalate (DIDP), were accomplished using gas chromatography and mass spectrometry. The results revealed that the concentrations of DEP, DnBP, DEHP, and DnOP were relatively high. Higher temperatures promote the volatilization of PAEs, leading to an increase in the gaseous and particulate PAE concentrations in warm seasons and winter pollution scenarios. The results of principal component analysis show that PAEs mainly come from volatile products and polyvinylchloride plastics. Using positive matrix factorization analysis, it is shown that these two sources contribute 67.0% and 33.0% in atmosphere PAEs, respectively. Seasonally, the contribution of volatile products to both gaseous and particulate PAEs substantially increases during warm seasons. The residents in Nanchang exposed to PAEs have a negligible non-cancer risk and a potential low cancer risk. During the warm seasons, more PAEs are emitted into the air, which will increase the toxicity of PAEs and their impact on human health.

Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011–2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.

Effects of D-allulose on di (2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP)-induced toxicity in rats

Background: Oral exposure to high concentrations of DEHP and DBP causes testicular and hepatotoxicity in rodents. Phthalate metabolites such as mono (2-ethylhexyl) phthalate (MEHP) and mono-n-butyl phthalate (MBP) stimulate peroxisome proliferator-activated receptors and disrupts carbohydrate and lipid metabolism. The oxidative stress generated may be closely related to these toxicities. Method: To clarify the effects of the rare sugar D-allulose, a potent free radical scavenger, on testicular and hepatotoxicity induced by DEHP and DBP, rats were fed DEHP or DBP containing diet and D-allulose water. Result: Dietary exposure to DEHP and DBP induced a significant decrease in testicular weight and significant increase in liver weight. D-allulose treatment significantly inhibited the testicular weight loss. But D-allulose treatment did not significantly suppress the increase in liver weight. Plasma glucose levels were significantly lower in the DEHP- or DBP-only treated groups compared to controls, but were improved by D-allulose treatment. This suggests that D-allulose blocks DEHP- and DBP-induced glycemic suppression. Plasma lipid-related markers such as total cholesterol, high-density lipoprotein cholesterol, and triglycerides were lower than controls in all treatment groups on the DEHP and DBP diets, but showed a slight trend toward improvement with D-allulose. Conclusion: D-allulose reduced DEHP- and DBP-induced testicular toxicity and blood glucose suppression in rats, but did not improve liver hypertrophy. This effect may be due to the strong oxidant scavenging ability of D-allulose.

Regulation of BTB (POZ) Structural Domain 6b by MicroRNA-222b in Zebrafish Embryos after Exposure to Di(2-ethylhexyl)phthalate at Low Concentrations.

Di-(2-ethylhexyl) phthalate (DEHP) is a sort of endocrine disruptor that induces abnormal physiological and biochemical activities such as epigenetic alterations, apoptosis, and oxidative stress. MicroRNAs (miRNAs) are a class of short noncoding RNAs that may regulate the expression of many protein-coding genes when organisms are exposed to environmental chemicals. miR-222b is a differentially expressed miRNA after DEHP exposure. miRNA-mRNA prediction suggested that BTB (POZ) structural domain 6b (BTBD6B) might be a target mRNA of miR-222b, and DEHP exposure altered its expression. However, the correlation between miR-222b and BTBD6B has not been experimentally confirmed. The aim of this study was to investigate the regulation of BTBD6B by miR-222b in zebrafish embryos under the effect of low concentration of DEHP. Dual fluorescent protein assays and dual luciferase reporter gene assays confirmed the interaction between miR-222b and the 3'-untranslated region (3'-UTR) of BTBD6B. Ectopic expression assays showed that miR-222b could negatively regulate BTBD6B in ZF4 cells. However, the relative expression of miR-222b and BTBD6B was significantly higher at both transcriptional and post-transcriptional levels in zebrafish embryos exposed to low concentrations of DEHP. The results of this study improved our understanding of the molecular mechanism of DEHP exposure toxicity. It identified that the aberrant expression of miR-222b/BTBD6B may be one of the mechanisms of DEHP toxicity, which can provide a theoretical reference and scientific basis for environmental management and biological health risk assessment.

Genistein prevents the production of hypospadias induced by Di-(2-ethylhexyl) phthalate through androgen signaling and antioxidant response in rats

Environmental estrogen exposure has increased dramatically over the past 50 years. In particular, prenatal exposure to estrogen causes many congenital diseases, among which reproductive system development disorders are extremely serious. In this study, the molecular mechanism of hypospadias and the therapeutic effect of genistein (GEN) were investigated through in vivo models prepared by Di-(2-ethylhexyl) phthalate (DEHP) exposure between 12 and 19 days of gestation. With increased DEHP concentrations, the incidence of hypospadias increased gradually. DEHP inhibited the key enzymes involved in steroid synthesis, resulting in decreasing testosterone synthesis. At the same time, DEHP increased reactive oxygen species (ROS) and produced inflammatory factors via NADPH oxidase-1 (NOX1) and NADPH oxidase-4 (NOX4) pathways. It also inhibited Steroid 5 α Reductase 2 (Srd5α2) and decreased dihydrotestosterone (DHT) synthesis. Additionally, DEHP inhibited the androgen receptor (AR), resulting in reduced DHT binding to the AR that ultimately retarded the development of the external reproductive system. GEN, a phytoestrogen, competes with DEHP for binding to estrogen receptor β (ERβ). This competition, along with GEN's antiestrogen and antioxidant properties, could potentially reverse impairments. The findings of this study provide valuable insights into the role of phytoestrogens in alleviating environmental estrogen-induced congenital diseases.

A novel and efficient strategy for the biodegradation of di(2-ethylhexyl) phthalate by Fusarium culmorum.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is used worldwide and raises concerns because of its prevalence in the environment and potential toxicity. Herein, the capability of Fusarium culmorum to degrade a high concentration (3 g/L) of DEHP as the sole carbon and energy source in solid-state fermentation (SSF) was studied. Cultures grown on glucose were used as controls. The biodegradation of DEHP by F. culmorum reached 96.9% within 312 h. This fungus produced a 3-fold higher esterase activity in DEHP-supplemented cultures than in control cultures (1288.9 and 443.2 U/L, respectively). In DEHP-supplemented cultures, nine bands with esterase activity (24.6, 31.2, 34.2, 39.5, 42.8, 62.1, 74.5, 134.5, and 214.5 kDa) were observed by zymography, which were different from those in control cultures and from those previously reported for cultures grown in submerged fermentation. This is the first study to report the DEHP biodegradation pathway by a microorganism grown in SSF. The study findings uncovered a novel biodegradation strategy by which high concentrations of DEHP could be biodegraded using two alternative pathways simultaneously. F. culmorum has an outstanding capability to efficiently degrade DEHP by inducing esterase production, representing an ecologically promising alternative for the development of environmental biotechnologies, which might help mitigate the negative impacts of environmental contamination by this phthalate. KEY POINTS: •F. culmorum has potential to tolerate and remove di(2-ethylhexyl) phthalate (DEHP) •Solid-state fermentation is an efficient system for DEHP degradation by F. culmorum •High concentrations of DEHP induce high levels of esterase production by F. culmorum.

Evaluating the risk of phthalate and non-phthalate plasticizers in dust samples from 100 Japanese houses

Phthalates are widely used as plasticizer and associated with various health issues. Recently, non-phthalate plasticizers are replacing phthalates; however, the exposure to these substances and the risk in Japan is unclear. In this study, we assessed the concentrations of phthalates, non-phthalate plasticizers, and phthalate degradation products in house dust and determined their respective exposure risks via oral and dermal routes. Twelve phthalates, seven non-phthalate plasticizers, and two degradation products were determined in the house dust obtained from 100 Japanese homes. The median concentration of di(2-ethylhexyl) phthalate (DEHP), accounting for 85 % of the total concentration of phthalates and non-phthalate plasticizers detected in this study, was 2.1 × 103 μg/g of dust. Apart from DEHP, diisononyl phthalate (DINP) and di(2-ethylhexyl) terephthalate (DEHT) were the most abundant in the house dust, accounting for 6.2 % (median: 1.7 × 102 μg/g of dust) and 6.1 % (median: 1.7 × 102 μg/g of dust) of the total concentrations, respectively. DEHP and DEHT concentrations in house dust were higher in apartment and small houses (floor area: ≤30 m2 or 31–60 m2 for DEHP and 31–60 m2 for DEHT) than in detached and large houses (floor area: ≥121 m2). Conversely, di-n-butyl phthalate (DnBP) concentrations were significantly higher in detached and large houses (floor area: ≥121 m2) than in apartment and small houses (floor area: ≤30 m2). The total hazard quotient (HQ), using the maximum concentration in house dust, revealed that oral and dermal exposure to house dust was 1.3 × 10-6–0.11 for adults (all substances) and 1.6 × 10-5–2.2 × 10-2 for preschool children (except for DnBP and DEHP), suggesting no risk. The HQs for DnBP and DEHP exposure via house dust for preschool children using the maximum values were 0.46 and 1.2, and 6.0 × 10-3 and 0.18 using the median values, indicating that risk of DEHP exposure should be exhaustively determined by considering other exposure routes that were not evaluated in this study, such as diet.