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BioMed Research International 2018Di-2-ethylhexyl phthalate (DEHP) is extensively used as a plasticizer in many products, especially medical devices, furniture materials, cosmetics, and personal care... (Review)
Review
Di-2-ethylhexyl phthalate (DEHP) is extensively used as a plasticizer in many products, especially medical devices, furniture materials, cosmetics, and personal care products. DEHP is noncovalently bound to plastics, and therefore, it will leach out of these products after repeated use, heating, and/or cleaning of the products. Due to the overuse of DEHP in many products, it enters and pollutes the environment through release from industrial settings and plastic waste disposal sites. DEHP can enter the body through inhalation, ingestion, and dermal contact on a daily basis, which has raised some concerns about its safety and its potential effects on human health. The main aim of this review is to give an overview of the endocrine, testicular, ovarian, neural, hepatotoxic, and cardiotoxic effects of DEHP on animal models and humans and .
Topics: Animals; Diethylhexyl Phthalate; Environmental Exposure; Humans; Plasticizers; Plastics
PubMed: 29682520
DOI: 10.1155/2018/1750368 -
Proceedings of the National Academy of... Nov 2022Uterine leiomyoma is the most common tumor in women and causes severe morbidity in 15 to 30% of reproductive-age women. Epidemiological studies consistently indicate a...
Uterine leiomyoma is the most common tumor in women and causes severe morbidity in 15 to 30% of reproductive-age women. Epidemiological studies consistently indicate a correlation between leiomyoma development and exposure to endocrine-disrupting chemical phthalates, especially di-(2-ethylhexyl) phthalate (DEHP); however, the underlying mechanisms are unknown. Here, among the most commonly encountered phthalate metabolites, we found the strongest association between the urine levels of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), the principal DEHP metabolite, and the risk of uterine leiomyoma diagnosis ( = 712 patients). The treatment of primary leiomyoma and smooth muscle cells ( = 29) with various mixtures of phthalate metabolites, at concentrations equivalent to those detected in urine samples, significantly increased cell viability and decreased apoptosis. MEHHP had the strongest effects on both cell viability and apoptosis. MEHHP increased cellular tryptophan and kynurenine levels strikingly and induced the expression of the tryptophan transporters SLC7A5 and SLC7A8, as well as, tryptophan 2,3-dioxygenase (TDO2), the key enzyme catalyzing the conversion of tryptophan to kynurenine that is the endogenous ligand of aryl hydrocarbon receptor (AHR). MEHHP stimulated nuclear localization of AHR and up-regulated the expression of CYP1A1 and CYP1B1, two prototype targets of AHR. siRNA knockdown or pharmacological inhibition of SLC7A5/SLC7A8, TDO2, or AHR abolished MEHHP-mediated effects on leiomyoma cell survival. These findings indicate that MEHHP promotes leiomyoma cell survival by activating the tryptophan-kynurenine-AHR pathway. This study pinpoints MEHHP exposure as a high-risk factor for leiomyoma growth, uncovers a mechanism by which exposure to environmental phthalate impacts leiomyoma pathogenesis, and may lead to the development of novel druggable targets.
Topics: Humans; Female; Diethylhexyl Phthalate; Kynurenine; Tryptophan; Cell Survival; Receptors, Aryl Hydrocarbon; Large Neutral Amino Acid-Transporter 1; Environmental Exposure; Phthalic Acids; Leiomyoma; Environmental Pollutants
PubMed: 36375056
DOI: 10.1073/pnas.2208886119 -
Frontiers in Endocrinology 202130% of men suffer from benign prostatic hyperplasia (BPH) worldwide. As one of the most important members of Phthalate esters, previous studies suggested ubiquitous...
30% of men suffer from benign prostatic hyperplasia (BPH) worldwide. As one of the most important members of Phthalate esters, previous studies suggested ubiquitous Di-(2-ethylhexyl) phthalate (DEHP) exposure is associated with such male disorders by interfering with endocrine system, however, little is known about the association between DEHP exposure and BPH. The objective of this study was to study the potential association by the 2001-2008 National Health and Nutrition Examination Survey (NHANES) data. The data was collected, and multiple logistic regression was adapted to measure the association. The concentrations of DEHP (∑DEHP) were calculated by each metabolite and split into quartiles for analysis. Results showed that the odds ratio (OR) decreased with increased ∑DEHP concentration. In the crude model, the OR for the second quartile (OR = 1.60, 95%CI [1.24, 2.07]) was obviously higher compared with the lowest quartile. However, the OR for the highest quartile (OR = 0.55, 95%CI [0.44,0.69]) was lower than that for the third quartile (OR = 0.77, 95%CI [0.61, 0.97]), and the OR for the third and the highest quartile were significantly lower than that of the lowest quartile, which suggested biphasic effects of DEHP based on concentration. The results showed the same trend after adjusting confounding factors. The study suggested that the DEHP exposure is associated with DEHP, and the results adds limited evidence to study this topic, however, further researches are needed to determine if the status of BPH can be changed by controlling DEHP exposure.
Topics: Aged; Cross-Sectional Studies; Diethylhexyl Phthalate; Environmental Exposure; Environmental Pollutants; Humans; Male; Nutrition Surveys; Odds Ratio; Phthalic Acids; Prostatic Hyperplasia
PubMed: 35095770
DOI: 10.3389/fendo.2021.804457 -
Toxins Jul 2021Phthalic acid esters (PAEs) are a class of lipophilic chemicals widely used as plasticizers and additives to improve various products' mechanical extensibility and... (Review)
Review
Phthalic acid esters (PAEs) are a class of lipophilic chemicals widely used as plasticizers and additives to improve various products' mechanical extensibility and flexibility. At present, synthesized PAEs, which are considered to cause potential hazards to ecosystem functioning and public health, have been easily detected in the atmosphere, water, soil, and sediments; PAEs are also frequently discovered in plant and microorganism sources, suggesting the possibility that they might be biosynthesized in nature. In this review, we summarize that PAEs have not only been identified in the organic solvent extracts, root exudates, and essential oils of a large number of different plant species, but also isolated and purified from various algae, bacteria, and fungi. Dominant PAEs identified from natural sources generally include di--butyl phthalate, diethyl phthalate, dimethyl phthalate, di(2-ethylhexyl) phthalate, diisobutyl phthalate, diisooctyl phthalate, etc. Further studies reveal that PAEs can be biosynthesized by at least several algae. PAEs are reported to possess allelopathic, antimicrobial, insecticidal, and other biological activities, which might enhance the competitiveness of plants, algae, and microorganisms to better accommodate biotic and abiotic stress. These findings suggest that PAEs should not be treated solely as a "human-made pollutant" simply because they have been extensively synthesized and utilized; on the other hand, synthesized PAEs entering the ecosystem might disrupt the metabolic process of certain plant, algal, and microbial communities. Therefore, further studies are required to elucidate the relevant mechanisms and ecological consequences.
Topics: Agriculture; China; Dibutyl Phthalate; Diethylhexyl Phthalate; Ecosystem; Environmental Pollutants; Esters; Humans; Phthalic Acids; Plasticizers; Soil; Soil Pollutants
PubMed: 34357967
DOI: 10.3390/toxins13070495 -
Archivum Immunologiae Et Therapiae... Jun 2018Di(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer, mainly serves as an additive to render polyvinyl chloride (PVC) soft and flexible. PVC plastics have become... (Review)
Review
Di(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer, mainly serves as an additive to render polyvinyl chloride (PVC) soft and flexible. PVC plastics have become ubiquitous in our modern society. Yet, the leaching of DEHP from PVC-based consumables ultimately results in the deposition in certain tissues via inadvertent applications. Health risks for human populations exposed to DEHP has been assumed by studies on rodents and other species, including the DEHP-induced developmental dysregulation, reproductive impairments, tumorigenesis, and diseases in a transgenerational manner. In this review, we comprehensively summarize the accumulated literature regarding the multifaceted roles of DEHP in the activation of the nuclear receptors, the alteration of the redox homeostasis, epigenetic modifications and the acquisition of chemoresistance.
Topics: Animals; Antineoplastic Agents; Carcinogenesis; Diethylhexyl Phthalate; Drug Resistance, Neoplasm; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Homeostasis; Humans; Neoplasms; Oxidation-Reduction; Phthalic Acids; Plasticizers; Polyvinyl Chloride; Receptors, Cytoplasmic and Nuclear
PubMed: 29209738
DOI: 10.1007/s00005-017-0494-2 -
IARC Monographs on the Evaluation of... 2000
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Cricetinae; Diethylhexyl Phthalate; Disease Models, Animal; Environmental Exposure; Humans; Maximum Allowable Concentration; Mice; Neoplasms; Rats; Reproduction
PubMed: 11100399
DOI: No ID Found -
International Journal of Environmental... Jul 2016Children's exposure assessment is a key input into epidemiology studies, risk assessment and source apportionment. The goals of this article are to describe a... (Review)
Review
Children's exposure assessment is a key input into epidemiology studies, risk assessment and source apportionment. The goals of this article are to describe a methodology for children's exposure assessment that can be used for these purposes and to apply the methodology to source apportionment for the case study chemical, diethylhexylphthalate (DEHP). A key feature is the comparison of total (aggregate) exposure calculated via a pathways approach to that derived from a biomonitoring approach. The 4-step methodology and its results for DEHP are: (1) Prioritization of life stages and exposure pathways, with pregnancy, breast-fed infants, and toddlers the focus of the case study and pathways selected that are relevant to these groups; (2) Estimation of pathway-specific exposures by life stage wherein diet was found to be the largest contributor for pregnant women, breast milk and mouthing behavior for the nursing infant and diet, house dust, and mouthing for toddlers; (3) Comparison of aggregate exposure by pathways vs biomonitoring-based approaches wherein good concordance was found for toddlers and pregnant women providing confidence in the exposure assessment; (4) Source apportionment in which DEHP presence in foods, children's products, consumer products and the built environment are discussed with respect to early life mouthing, house dust and dietary exposure. A potential fifth step of the method involves the calculation of exposure doses for risk assessment which is described but outside the scope for the current case study. In summary, the methodology has been used to synthesize the available information to identify key sources of early life exposure to DEHP.
Topics: Child, Preschool; Diet; Diethylhexyl Phthalate; Dust; Environmental Exposure; Environmental Monitoring; Female; Humans; Infant; Milk, Human; Pregnancy; Risk Assessment
PubMed: 27376320
DOI: 10.3390/ijerph13070670 -
Environmental Health and Preventive... Jul 2019The plasticizer di(2-ethylhexyl) phthalate (DEHP) has been widely used in the manufacture of polyvinyl chloride-containing products such as medical and consumer goods.... (Review)
Review
The plasticizer di(2-ethylhexyl) phthalate (DEHP) has been widely used in the manufacture of polyvinyl chloride-containing products such as medical and consumer goods. Humans can easily be exposed to it because DEHP is ubiquitous in the environment. Recent research on the adverse effects of DEHP has focused on reproductive and developmental toxicity in rodents and/or humans. DEHP is a representative of the peroxisome proliferators. Therefore, peroxisome proliferator-activated receptor alpha (PPARα)-dependent pathways are the expected mode of action of several kinds of DEHP-induced toxicities. In this review, we summarize DEHP kinetics and its mechanisms of carcinogenicity and reproductive and developmental toxicity in relation to PPARα. Additionally, we give an overview of the impacts of science policy on exposure sources.
Topics: Animals; Diethylhexyl Phthalate; Environmental Pollutants; Haplorhini; Humans; Mice; PPAR alpha; Plasticizers; Rats
PubMed: 31279339
DOI: 10.1186/s12199-019-0802-z -
The Turkish Journal of Pediatrics 2022Phthalates are ubiquitous in the environment and they can penetrate the human body via multiple routes. However, the impact of phthalates on human male reproductive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phthalates are ubiquitous in the environment and they can penetrate the human body via multiple routes. However, the impact of phthalates on human male reproductive disorders remains unclear.
METHODS
A critical review of published studies was conducted to clarify the association of phthalates and male reproductive disorders and to highlight future research needs. PubMed, Cochrane Library, and Web of Science Database were systematically searched for relevant articles written in English, independent of region and time period. If more than one paper overlapped in study design or participants included, the most recent manuscript was included in our review. Due to limited homogeneous statistical data, observed trends were summarized to draw approximate conclusions.
RESULTS
Nineteen manuscripts were included in our final analysis. Exposure to di-(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), diethyl phthalate (DEP), and/or benzyl butyl phthalate (BBP) is associated with a shorter anogenital distance (AGD). Meanwhile, exposure to DEHP and/or di-isodecyl phthalate (DIDP) is associated with higher risks for cryptorchidism and hypospadias.
CONCLUSIONS
Generic exposure to phthalates has an adverse effect on human reproductive development, especially exposure to DEHP, DBP, DEP, BBP, and DIDP. A critical time for exposure sensitivity is during early pregnancy. Due to the lack of significant statistical power in this study, the conclusions drawn should be cautiously interpreted and they remain to be validated. Thus, additional well-designed studies, as well as propaganda and education regarding phthalate exposure and safer substitutes for these compounds, are greatly needed.
Topics: Diethylhexyl Phthalate; Female; Humans; Male; Maternal Exposure; Phthalic Acids; Pregnancy
PubMed: 35611408
DOI: 10.24953/turkjped.2020.2060 -
Cardiovascular Toxicology Dec 2014The ubiquitous nature of plastics has raised concerns pertaining to continuous exposure to plastic polymers and human health risks. Of particular concern is the use of... (Review)
Review
The ubiquitous nature of plastics has raised concerns pertaining to continuous exposure to plastic polymers and human health risks. Of particular concern is the use of endocrine-disrupting chemicals in plastic production, including di(2-ethylhexyl)phthalate (DEHP) and bisphenol A (BPA). Widespread and continuous exposure to DEHP and BPA occurs through dietary intake, inhalation, dermal and intravenous exposure via consumer products and medical devices. This article reviews the literature examining the relationship between DEHP and BPA exposure and cardiac toxicity. In vitro and in vivo experimental reports are outlined, as well as epidemiological studies which examine the association between these chemicals and cardiovascular outcomes. Gaps in our current knowledge are also discussed, along with future investigative endeavors that may help resolve whether DEHP and/or BPA exposure has a negative impact on cardiovascular physiology.
Topics: Benzhydryl Compounds; Cardiotoxicity; Child; Child, Preschool; Diethylhexyl Phthalate; Endocrine Disruptors; Environmental Exposure; Estrogens, Non-Steroidal; Humans; Infant; Infant, Newborn; Phenols; Plasticizers; Plastics
PubMed: 24811950
DOI: 10.1007/s12012-014-9258-y