ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Di(2-ethylhexyl) phthalate (DEHP) is a widely recognized environmental endocrine disruptor that potentially impacts female reproductive function, although the specific mechanisms leading to such impairment remain unclear. A growing body of research has revealed that the endoplasmic reticulum and mitochondrial function significantly influence oocyte quality. The structure of mitochondria-associated endoplasmic reticulum membranes (MAMs) is crucial for facilitating the exchange of Ca2+, lipids, and metabolites. This study aimed to investigate the alterations in the composition and function of MAMs after DEHP exposure and to elucidate the underlying mechanisms of ovarian toxicity. The female mice were exposed to DEHP at doses of 5 and 500â¯mg/kg/day for one month. The results revealed that DEHP exposure led to reduced serum anti-Müllerian hormone levels and increased atretic follicles in mice. DEHP induced endoplasmic reticulum stress and disrupted calcium homeostasis in oocytes. Furthermore, DEHP impaired the mitochondrial function of oocytes and reduced their membrane potential, and promoting apoptosis. Similar results were observed in human granulosa cells after exposure to mono-(2-ethylhexyl) phthalate (MEHP, metabolites of DEHP) in vitro. Proteomic analysis and transmission electron microscopy revealed modifications in the functional proteins and structure of the MAMs, and the suppression of oxidative phosphorylation pathways. The findings of this investigation provide a new perspective on the mechanism underlying the reproductive toxicity of DEHP in females.
Subject(s)
Diethylhexyl Phthalate , Endocrine Disruptors , Endoplasmic Reticulum , Mitochondria , Ovary , Female , Animals , Diethylhexyl Phthalate/toxicity , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/ultrastructure , Mice , Mitochondria/drug effects , Mitochondria/ultrastructure , Ovary/drug effects , Endocrine Disruptors/toxicity , Oocytes/drug effects , Granulosa Cells/drug effects , Reproduction/drug effects , Calcium/metabolism , Apoptosis/drug effects , Endoplasmic Reticulum Stress/drug effects , Humans , Anti-Mullerian Hormone/metabolismABSTRACT
Autism spectrum disorder (ASD), also known as autism, is a common, highly hereditary and heterogeneous neurodevelopmental disorder. The global prevalence of ASD among children continues to rise significantly, which is partially attributed to environmental pollution. It has been reported that pre- or post-natal exposure to di-(2-ethylhexyl) phthalate (DEHP) or bisphenol A (BPA), two prevalent environmental endocrine disruptors, increases the risk of ASD in offspring. Yet, the joint action mode linking DEHP and BPA with ASD is incompletely understood. This study aims to unravel the joint action mode of DEHP and BPA co-exposure on the development of ASD. An adverse outcome pathway (AOP) framework was employed to integrate data from multiple public database and construct chemical-gene-phenotype-disease networks (CGPDN) for DEHP- and BPA-related ASD. Topological analysis and comprehensive literature exploration of the CGPDN were performed to build the AOP. By analysis of shared key events (KEs) or phenotypes within the AOP or the CGPDN, we uncovered two AOPs, decreased N-methyl-D-aspartate receptor (NMDAR) and estrogen antagonism that were likely linked to ASD, both with moderate confidence. Our analysis further predicted that the joint action mode of DEHP and BPA related ASD was possibly an additive or synergistic action. Thus, we propose that the co-exposure to BPA and DEHP perhaps additively or synergistically increases the risk of ASD.
ABSTRACT
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.
ABSTRACT
Plasticizers are considered as newly emerged contaminants. They are added to plastics to increase their flexibility and softness. Phthalate plasticizers including the Di-2-ethylhexyl phthalates (DEHP) are toxic and induce adverse effects on the different organization levels of the environment. In the current study, we investigated the potential toxicity of DEHP using Zebrafish as a biological model. Five ascending concentrations of DEHP were tested in embryos throughout 96 hpf: 0.0086, 0.086, 0.86, 8.6, and 86 mg/L. Embryotoxicity assessments revealed limited lethal effects on DEHP-exposed embryos, yet notable anticipation of the hatching process was observed at 48 hpf. Although DEHP showed negligible influence on the length and pericardial area of exposed embryos, it led to multiple bodily deformities. Gene expression analyses of key cardiogenic and inflammatory genes evidenced alterations in tbx20, bcl2, and il1b expression in Zebrafish embryos at 96 h post-fertilization. Results from the cardiac function analysis displayed that DEHP significantly affected the arterial pulse and linear velocity within the Posterior Cardinal Vein (PCV) of exposed fish. These findings strongly advance that even at low concentrations, DEHP can be considered as potential toxic agent, capable of inducing cardiotoxic effects.
Subject(s)
Diethylhexyl Phthalate , Embryo, Nonmammalian , Plasticizers , Zebrafish , Animals , Zebrafish/embryology , Diethylhexyl Phthalate/toxicity , Embryo, Nonmammalian/drug effects , Plasticizers/toxicity , Cardiotoxicity , Gene Expression Regulation, Developmental/drug effects , Water Pollutants, Chemical/toxicity , Heart/drug effects , Heart/embryologyABSTRACT
Owing to growing concerns about the adverse effects of phthalate plasticizers, non-phthalate plasticizers are being increasingly used as their replacement. However, information on the residual environmental concentrations and ecological risks posed by these plasticizers is limited. In this study, we analyzed the environmental contamination of 11 phthalates and 5 non-phthalate plasticizers in Class A and B rivers in Japan. In the considered river water samples, phthalates and non-phthalates were detected in the following order of detection frequency: phthalates (DEHP > DMP > DMEP > BBP > DNPP > DNP > DEEP > DBEP = DNOP) and non-phthalates (ATBC > DEHS > DEHA > TOTM = DIBA). Phthalate plasticizers were the most abundant and included DEHP (157-859 ng/L), DMP (Subject(s)
Environmental Monitoring
, Estuaries
, Phthalic Acids
, Plasticizers
, Rivers
, Water Pollutants, Chemical
, Plasticizers/analysis
, Japan
, Rivers/chemistry
, Risk Assessment
, Water Pollutants, Chemical/analysis
, Phthalic Acids/analysis
ABSTRACT
Psoriasis is classified as an autoimmune disorder characterized by abnormal immune response leading to the development of chronic dermal inflammation. Most individuals have a genetic vulnerability that may be further influenced by epigenetic changes occurring due to multiple variables such as pollutant exposure. Epigenetic modifications such as DNA methylation possess a dynamic nature, enabling cellular differentiation and adaptation by controlling gene expression. Di(2-ethylhexyl) phthalate (DEHP) and psoriatic inflammation are known to cause modification of DNA methylation via DNA methyltransferase (DNMT). However, it is not known whether DEHP, a ubiquitous plasticizer affects psoriatic inflammation via DNMT modulation. Therefore, this study investigated the effect of DNMT inhibitor, 5-aza-2'-deoxycytidine (AZA) on DEHP-induced changes in the expression of DNMT1, global DNA methylation, and anti-/inflammatory parameters (p-STAT3, IL-17A, IL-6, iNOS, IL-10, Foxp3, Nrf2, HO-1) in the skin and the peripheral adaptive/ myeloid immune cells (CD4+ T cells/CD11b+ cells) in imiquimod (IMQ) model of psoriasiform inflammation. Further, psoriasis-associated clinical/histopathological features (ear thickness, ear weight, ear PASI score, MPO activity, and H&E staining of the ear and the back skin) were also analyzed in IMQ model. Our data show that IMQ-treated mice with DEHP exposure had increased DNMT1 expression and DNA methylation which was associated with elevated inflammatory (p-STAT3, IL-17A, IL-6, iNOS) and downregulated anti-inflammatory mediators (IL-10, Foxp3, Nrf2, HO-1) in the peripheral immune cells (CD4+ T cells/CD11b+ cells) and the skin as compared to IMQ-treated mice. Treatment with DNMT1 inhibitor caused reduction in inflammatory and elevation in anti-inflammatory parameters with significant improvement in clinical/histopathological symptoms in both IMQ-treated and DEHP-exposed IMQ-treated mice. In conclusion, our study shows strong evidence indicating that DNMT1 plays an important role in DEHP-induced exacerbation of psoriasiform inflammation in mice through hypermethylation of DNA.
Subject(s)
DNA (Cytosine-5-)-Methyltransferase 1 , DNA Methylation , Decitabine , Diethylhexyl Phthalate , Psoriasis , Skin , Animals , DNA Methylation/drug effects , Psoriasis/chemically induced , Psoriasis/drug therapy , Psoriasis/immunology , Psoriasis/pathology , Decitabine/pharmacology , Decitabine/therapeutic use , DNA (Cytosine-5-)-Methyltransferase 1/antagonists & inhibitors , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , Skin/pathology , Skin/drug effects , Skin/immunology , Diethylhexyl Phthalate/toxicity , Mice , Male , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Cytokines/metabolism , Disease Models, Animal , Mice, Inbred BALB C , FemaleABSTRACT
Phthalates are extensively employed plasticizers crucial for conferring flexibility and plasticity to polyvinyl chloride. Phthalates, including DEHP (di(2-ethylhexyl)phthalate), present in diverse products, have been identified in fine dust and are capable of infiltrating the body, potentially posing health hazards. Importantly, melanocytes, existing at the basal layer of the epidermis, are susceptible to toxic substances. In our study, we employed the 3D human pigmented epidermis model, MelanoDerm™, along with the B16F10 murine melanoma cell line, to examine the influence of DEHP exposure on melanocytes. The exposure to low concentrations of DEHP (~ 5 µM), resulted in the extension of melanocyte dendrites, indicating the stimulation of melanocytes. Analysis of gene expression and protein profiles unveiled the up-regulation of MITF, Arpc2, and TRP1 genes subsequent to DEHP exposure, indicating alterations in cytoskeletal and melanosome-related genetic and protein components in melanocytes. Notably, increased pigmentation was observed in MelanoDerm™ following DEHP exposure. DEHP-stimulated reactive oxygen species generation appeared to be involved in these events since the antioxidant, ascorbic acid attenuated ROS generation and MITF upregulation. Collectively, our study demonstrated that DEHP exposure can induce cytoskeletal disturbance and skin pigmentation through oxidative stress.
ABSTRACT
As the COVID-19 pandemic has progressed, increasing evidences suggest that the gut microbiota may play a crucial role in the effectiveness of SARS-CoV-2 vaccine. Thus, this study was aimed at investigating the influence of SARS-CoV-2 vaccine on the gut microbiota and short-chain fatty acids (SCFAs) of organisms exposed to environmental contaminants, i.e., plasticizers: phthalate esters. We found that in mice, exposure to dioctyl terephthalate (DOTP) and bis -2-ethylhexyl phthalate (DEHP) decreased the blood glucose level and white fat weight, induced inflammatory responses, caused damage to liver and intestinal tissues, and disrupted the gut microbiota composition and SCFAs metabolism. Specifically, the Bacteroidetes phylum was positively correlated with BBIBP-CorV vaccine, while acetic acid was negatively associated with the vaccine. Interestingly, the BBIBP-CorV vaccine somewhat alleviated tissue inflammation and reduced the contents of acetic acid and propionic acid in mice exposed to DEHP and DOTP. These findings were confirmed by a fecal microbiota transplantation assay. Overall, this study revealed that exposure to DEHP and DOTP adversely affects the gut microbiota and SCFAs, while the BBIBP-CorV vaccine can protect mice against these effects. This work highlighted the relationship between BBIBP-CorV vaccination, gut microbiome composition, and responses to plasticizers, which may facilitate the development and risk assessment of SARS-CoV-2 vaccines and environmental contaminants on microbiota health.
ABSTRACT
Di-(2-ethylhexyl) phthalic acid (DEHP) pollutes the environment, and posing a significant risk to human and animal health. Consequently, a successful preventative strategy against DEHP-induced liver toxicity needs to be investigated. Morin hydrate (MH), a flavanol compound, possesses toxic preventive attributes against various environmental pollutants. However, the effects of MH have not been investigated against DEHP-induced liver toxicity. Female Swiss albino mice were divided into four groups: control, DEHP (orally administered with 500 mg/kg, DEHP plus MH 10 mg/kg, and DEHP plus MH 100 mg/kg for 14 days. The results showed that the MH treatment ameliorated the DEHP-induced liver dysfunctions by decreasing the alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin, liver histoarchitecture, fibrosis, and markers of oxidative stress. Furthermore, DEHP increased apoptosis, increased active caspase 3 and decreased B cell lymphoma-2 (Bcl-2) expression. However, the MH treatment showed a differential effect on these proteins; a lower dose increased, and a higher dose decreased the expression. Thus, a lower dose of MH could be involved in the disposal of damaged hepatocytes. Expression of Estrogen receptors alpha (ERα) also showed a similar trend with active caspase 3. Furthermore, the expression of Tumor necrosis factor alpha (TNF-α) and Nuclear factor-κß (NF-κß) were up-regulated by DEHP treatment, and MH treatment down-regulated the expression of these two inflammatory markers. Since this down-regulation of TNF-α and NF-κß coincides with improved liver functions against DEHP-induced toxicity, it can be concluded that MH-mediated liver function involves the singling of TNF-α and NF-κß.
ABSTRACT
Because of the significant environmental and health hazards imposed by di(2-ethylhexyl) phthalate (DEHP), a common plasticizer, developing safe and green techniques to degrade DEHP plasticizer is of huge scientific significance. It has been observed that environmental contamination of DEHP may also induce serious food safety problems because crops raised in plasticizers contaminated soils would transfer the plasticizer into foods, such as Baijiu. Additionally, when plastic packaging or vessels are used during Baijiu fermentation and processing, plasticizer compounds frequently migrate and contaminate the product. In this study, hairpin-like structured peptides with catalytically active sites containing serine, histidine and aspartic acid were found to degrade DEHP. Furthermore, after incorporating caffeic acid molecules at the N-terminus, the peptides could be attached onto foam titanium (Ti) surfaces via enediol-metal interactions to create an enzyme-mimicking flow reactor for the degradation of DEHP in Baijiu. The structure and catalytic activity of peptides, their interaction with DEHP substrate and the hydrolysis mechanism of DEHP were discussed in this work. The stability and reusability of the peptide-modified foam Ti flow reactor were also investigated. This approach provides an effective technique for the degradation of plasticizer compounds.
Subject(s)
Diethylhexyl Phthalate , Peptides , Plasticizers , Titanium , Diethylhexyl Phthalate/chemistry , Diethylhexyl Phthalate/metabolism , Plasticizers/chemistry , Titanium/chemistry , Peptides/chemistry , Peptides/metabolism , HydrolysisABSTRACT
Di-(2-ethylhexyl)-phthalate (DEHP), as distinctive endocrine disrupting chemicals, has become a global environmental pollutant harmful to human and animal health. However, the impacts on offspring and mothers with maternal DEHP exposure are largely unknown and the mechanism remains elusive. We established DEHP-exposed maternal mice to investigate the impacts on mother and offspring and illustrate the mechanism from multiple perspectives. Pregnant mice were administered with different doses of DEHP, respectively. Metagenomic sequencing used fecal and transcriptome sequencing using placentas and livers from offspring have been performed, respectively. The results of the histopathology perspective demonstrated that DEHP exposure could disrupt the function of islets impact placentas and fetus development for maternal mice, and cause the disorder of glucose and lipid metabolism for immature offspring mice, resulting in hyperglycemia. The results of the metagenome of gut microbial communities indicated that the dysbiosis of gut microbiota in mother and offspring mice and the dominant phyla transformed through vertical transmission. Transcriptome analysis found DEHP exposure induced mutations of Ahcy and Gstp3, which can damage liver cells and affect the metabolism of the host. DEHP exposure harms pregnant mice and offspring by affecting gene expression and altering metabolism. Our results suggested that exposure of pregnant mice to DEHP during pregnancy and lactation increased the risk of metabolic disorders by altering key genes in liver and gut microbiota, and these results provided new insights into the potential long-term harms of DEHP.
Subject(s)
Diethylhexyl Phthalate , Energy Metabolism , Hyperglycemia , Maternal Exposure , Female , Animals , Pregnancy , Diethylhexyl Phthalate/toxicity , Mice , Hyperglycemia/chemically induced , Energy Metabolism/drug effects , Maternal Exposure/adverse effects , Endocrine Disruptors/toxicity , Prenatal Exposure Delayed Effects/chemically induced , Gastrointestinal Microbiome/drug effects , Environmental Pollutants/toxicity , Placenta/drug effects , Liver/drug effectsABSTRACT
Phthalate esters (PAEs) have become one of the most concerned emerging organic pollutants in the world, due to the toxicity to human health, and hard to remove it efficiently. In this study, the degradation performance of DBP and DEHP in the soil by water bath heating activated sodium persulfate (PS) method under different factors were studied, in which the degradation rate of DBP and DEHP were improved with the increasing of temperature, PS concentration and water/soil ratio, and higher diffusion efficiency treatments methods, due to the improved mass transfer from organic phase to aqueous media. However, the degradation rate of DEHP was much lower than that of DBP, because DEHP in the soil was more difficult to contact with SO4â¢- for reaction on soil surface, and the degradation rate of PAEs in soil was significantly lower than that in water. Redundancy analysis of degradation rate of DBP and DEHP in water demonstrated that the key factors that determine the degradation rate is time for DBP, and cosolvent dosage for DEHP, indicating that the solubility and diffusion rate of PAEs from soil to aqueous are predominance function. This study provides comprehensive scenes in PAEs degradation with persulfate oxidation activated by thermal in soil, reveal the difference of degradation between DBP and DEHP is structure-dependent. So that we provide fundamental understanding and theoretical operation for subsequent filed treatment of various structural emerging pollutants PAEs contaminated soil with thermal activated persulfate.
Subject(s)
Oxidation-Reduction , Phthalic Acids , Soil Pollutants , Soil , Sulfates , Sulfates/chemistry , Phthalic Acids/chemistry , Soil Pollutants/chemistry , Soil/chemistry , Esters/chemistry , Sodium Compounds/chemistry , Hot TemperatureABSTRACT
Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), two common types of phthalates, are known to cause reproductive and developmental toxicity in animals and humans. The reference doses (RfD) of DBP and DEHP should be determined by sensitive endpoints. We here aimed to identify sensitive endpoints for DBP- and DEHP-induced such toxicity using published literatures. By examining the impacts of maternal exposure to DBP or DEHP on anogenital distance (AGD) and semen quality of offspring, we discovered that DBP or DEHP caused AGD decline in boys but increase in girls with DBP being more potent and the first 14weeks of pregnancy being more susceptible, suggesting a chemical- and time-dependent phenomenon. We also identified AGD shortening and total sperm count reduction as two sensitive endpoints for DBP- or DEHP-induced reproductive and developmental toxicity, respectively. Based upon these two endpoints and the employment of the Bayesian benchmark dose approach with an uncertainty factor of 3,000, we estimated the RfD values of DBP and DEHP were 15 µg/kg/day and 36 µg/kg/day, respectively. Thus, we uncover previously unrecognized phenomena of DBP- or DEHP-induced reproductive and developmental toxicity and establish new and comparable or more conservative RfDs for the risk assessment of phthalates exposure in humans.
Subject(s)
Dibutyl Phthalate , Reproduction , Male , Humans , Reproduction/drug effects , Female , Animals , Dibutyl Phthalate/toxicity , Pregnancy , Diethylhexyl Phthalate/toxicity , Phthalic Acids/toxicity , Maternal Exposure/adverse effectsABSTRACT
Sickle cell disease (SCD) is a hereditary hemoglobinopathy, caused by a mutation at position 6 of the ß-globin chain and patients are frequently exposed to several blood transfusions in order to maintain physiological function. Transfusion blood bags are composed of PVC and phthalates (as DEHP) are often introduced to the material in order to confer malleability. In this sense, DEHP can easily elute to the blood and cause harmful effects. This study aimed to unravel DEHP effect on SCD patient's hemoglobin function. We found that HbS polymerization using whole erythrocytes is decreased by DEHP in ex vivo experiments and this effect might be mediated by the DEHP-VAL6 interaction, evaluated in silico. Isolated HbS exhibited less polymerization at low DEHP concentrations and increased polymerization rate at higher concentration. When analyzing the propensity to aggregate, HbS is more inclined to aggregate when compared to HbA due to the residue 6 mutation. Circular dichroism showed characteristic hemoglobin peaks for oxygenated HbS that are lost when oxygen is sequestered, and DEHP at higher concentration mildly recovers a peak close to the second hemoglobin one. Finally, by transmission electron microscopy we demonstrated that high DEHP concentration increased polymer formation with a more organized structure. These findings show for the first-time the beneficial effect of low-dose DEHP on HbS polymerization.
Subject(s)
Anemia, Sickle Cell , Diethylhexyl Phthalate , Erythrocytes , Hemoglobin, Sickle , Polymerization , Humans , Anemia, Sickle Cell/genetics , Anemia, Sickle Cell/metabolism , Hemoglobin, Sickle/genetics , Hemoglobin, Sickle/metabolism , Erythrocytes/drug effects , Erythrocytes/metabolism , Diethylhexyl Phthalate/toxicity , Computer SimulationABSTRACT
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.
ABSTRACT
Background: Epidemiologic studies suggested the association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and disorders of sex development (DSD), adult male disorders, and reproductive aging. Inhibiting testosterone synthesis by interfering with steroidogenic gene expression induces testicular toxicity, however, whether prenatal DEHP exposure induces testicular toxicity through this mechanism remains uncertain. Methods: C57BL/6JGpt male mice underwent different doses (0, 100, 500, 1,000 mg/kg) of prenatal DEHP exposure during gestational day 10 to delivery day, the testicular toxicity (genital development, testosterone, semen quality, and morphology of testis tissue) in the neonatal, post-puberal and middle-aged stages was observed, and the steroidogenic gene (Lhcgr, Star, Cyp11a1, Cyp17a1, Hsd17b3, and Hsd3b2) expression was analyzed by quantitative polymerase chain reaction (qPCR) and Western blot (WB). The interference of steroidogenic gene expression in TM3 cells after mono-(2-ethylhexyl) phthalate (MEHP) exposure was also explored for verification. Results: Prenatal DEHP exposure induced immediate testicular injury in the neonatal stage [reduced anogenital distance (AGD) and intratesticular testosterone], DSD in the post-puberal stage (poor genital development), and reproductive aging in the middle-aged stage (obesity, reduced testosterone and semen quality, and atrophic seminiferous tubules), especially in the high dose. Prenatal DEHP exposure continuously interfered with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. MEHP inhibited testosterone synthesis of TM3 cells by interfering with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. Conclusions: Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression, thus indicating the association between prenatal exposure and DSD, adult male disorders, and reproductive aging.
ABSTRACT
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.