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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 -
Environmental Science and Pollution... Jun 2022This review aims to understand the impacts of plasticizers on the thyroid system of animals and humans. The thyroid gland is one of the earliest endocrine glands that... (Review)
Review
This review aims to understand the impacts of plasticizers on the thyroid system of animals and humans. The thyroid gland is one of the earliest endocrine glands that appear during embryogenesis. The thyroid gland synthesizes thyroid hormones (TH), triiodothyronine (T3), and thyroxine (T4) that are important in the regulation of body homeostasis. TH plays critical roles in regulating different physiological functions, including metabolism, cell growth, circadian rhythm, and nervous system development. Alteration in thyroid function can lead to different medical problems. In recent years, thyroid-related medical problems have increased and this could be due to rising environmental pollutants. Plasticizers are one such group of a pollutant that impacts thyroid function. Plasticizers are man-made chemicals used in a wide range of products, such as children's toys, food packaging items, building materials, medical devices, cosmetics, and ink. The increased use of plasticizers has resulted in their detection in the environment, animals, and humans. Studies indicated that plasticizers could alter thyroid function in both animals and humans at different levels. Several studies demonstrated a positive and/or negative correlation between plasticizers and serum T4 and T3 levels. Plasticizers could also change the expression of various TH-related genes and proteins, including thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), and transporters. Histological analyses demonstrated thyroid follicular cell hypertrophy and hyperplasia in response to several plasticizers. In conclusion, plasticizers could disrupt TH homeostasis and the mechanisms of toxicity could be diverse.
Topics: Animals; Humans; Plasticizers; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine
PubMed: 35303231
DOI: 10.1007/s11356-022-19594-0 -
Current Environmental Health Reports Dec 2019Organophosphate esters (OPEs) are applied to a variety of consumer products, primarily as flame retardants and plasticizers. OPEs can leach out of products over time and... (Review)
Review
PURPOSE OF REVIEW
Organophosphate esters (OPEs) are applied to a variety of consumer products, primarily as flame retardants and plasticizers. OPEs can leach out of products over time and are consequently prevalent in the environment and frequently detected in human biomonitoring studies. Exposure during pregnancy is of particular concern as OPEs have recently been detected in placental tissues, suggesting they may be transferred to the developing infant. Also, studies have now shown that children typically experience higher exposure to several OPEs compared with adults, indicating they may be disproportionately impacted by these compounds. This review summarizes the current literature on reproductive and child health outcomes of OPE exposures and highlights areas for future research.
RECENT FINDINGS
Experimental animal studies demonstrate potential for OPEs to adversely impact health, and a limited number of epidemiologic studies conducted in adult cohorts suggest that OPEs may interfere with the endocrine system. Neurodevelopment is perhaps the most well studied of children's health endpoints, and several studies indicate that prenatal and early life OPE exposures impact both cognitive and behavioral development. Associations have also been reported with reproductive outcomes (e.g., fertilization and pregnancy loss) and with the timing of parturition and preterm birth. Cross-sectional studies also demonstrate associations between OPEs and respiratory health outcomes, allergic disease, and measures of adiposity. An expanding body of research demonstrates that OPEs are associated with adverse reproductive health and birth outcomes, asthma and allergic disease, early growth and adiposity, and neurodevelopment. Still, additional research is urgently needed to elucidate the full impact of OPEs on children's health.
Topics: Adult; Child; Cross-Sectional Studies; Environmental Exposure; Environmental Monitoring; Esters; Female; Flame Retardants; Humans; Maternal Exposure; Organophosphates; Plasticizers; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 31755035
DOI: 10.1007/s40572-019-00258-0 -
Food and Chemical Toxicology : An... Jun 2022Several non-ortho phthalate plasticizers, including ATBC, DEHA, DINCH, DOTP, and ESBO, are currently used in flexible PVC applications for food packaging and processing.... (Review)
Review
Several non-ortho phthalate plasticizers, including ATBC, DEHA, DINCH, DOTP, and ESBO, are currently used in flexible PVC applications for food packaging and processing. The aim of this review is to summarize the available toxicity, migration, and human biomonitoring data. Available assessments from US CPSC, EFSA, other governmental and non-governmental organizations, and published toxicology studies were used to show that these plasticizers are generally well-studied and demonstrate low toxicity with a focus on potential carcinogenicity, reproductive, developmental, and endocrine related adverse effects as well as biodegradation, aquatic toxicity, and bioaccumulation. Seven other plasticizers, 2EHESBO, ASE, COMGHA, DBT, DEHCH, PETV, and TOTM, have at least some recent but limited food contact clearances; assessments from CPSC, EFSA, and robust summaries in the REACH dossiers were reviewed for these products. Data gaps were found for some of these; however, there were no concerns raised by the existing data, and they for now have limited use in food contact applications. Migration of ASE, COMGHA, DINCH, DOTP, DEHCH, and TOTM in simulants for aqueous and low alcohol foods ranged from <0.02 to 0.165 mg/kg, which showed they are below established migration limits and well-suited for these applications. Human biomonitoring data are available for DINCH, DOTP, DEHA, DINA, and TOTM, and are essential for determining exposure from all uses.
Topics: Biological Monitoring; Food Packaging; Humans; Phthalic Acids; Plasticizers
PubMed: 35452769
DOI: 10.1016/j.fct.2022.112984 -
Basic & Clinical Pharmacology &... Sep 2017Phthalates are known endocrine disruptors. Not commonly recognized, phthalates are used as excipients in a number of drug formulations. We aimed to describe the sale of... (Comparative Study)
Comparative Study
Phthalates are known endocrine disruptors. Not commonly recognized, phthalates are used as excipients in a number of drug formulations. We aimed to describe the sale of phthalate-containing drugs in Denmark from 2004 to 2015. National data on annual sale of medications (tablets only) were accessed from medstat.dk. Data from the Danish Medicines Agency on phthalate content per tablet were merged with data on total sale for each active substance and drug formulation. We used the 'defined daily dose' (DDD) as the unit of sale and calculated the total amount of phthalate (mg) dispensed per 1000 inhabitants. Specific tablet content was compared with the maximum daily exposure limits defined by regulatory agencies for diethyl phthalate (DEP) and dibutyl phthalate (DBP) of 4.0 and 0.01 mg/kg/day, respectively. Use of phthalate-containing drugs in Denmark was common. We found 154 drug products containing five different phthalates. Two low-molecular-weight phthalates and three high-molecular-weight phthalates were identified, with a total sale of 59.4 and 112 DDD per 1000 inhabitants per day during the study period, respectively. The highest amount of DBP was found in multi-enzymes (24.6-32.8 mg per DDD) and mesalazine (12.5-26.4 mg per DDD). Budesonide, lithium and bisacodyl also exceeded the DBP exposure limit of 0.01 mg/kg/day. Other drugs had high levels of DEP, although not exceeding the exposure limit. Sales of phthalate-containing drugs in Denmark from 2004 to 2015 were substantial, and phthalate exposure from several products exceeded the regulatory exposure limit introduced in 2014.
Topics: Adult; Databases, Factual; Denmark; Dibutyl Phthalate; Drug Contamination; Endocrine Disruptors; Environmental Exposure; Excipients; Humans; Legislation, Drug; Molecular Weight; Pharmaceutical Preparations; Phthalic Acids; Plasticizers; Tablets
PubMed: 28371296
DOI: 10.1111/bcpt.12781 -
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 -
Environmental Pollution (Barking, Essex... Aug 2023Human membrane drug transporters are recognized as major actors of pharmacokinetics; they also handle endogenous compounds, including hormones and metabolites. Chemical... (Review)
Review
Human membrane drug transporters are recognized as major actors of pharmacokinetics; they also handle endogenous compounds, including hormones and metabolites. Chemical additives present in plastics interact with human drug transporters, which may have consequences for the toxicokinetics and toxicity of these widely-distributed environmental and/or dietary pollutants, to which humans are highly exposed. The present review summarizes key findings about this topic. In vitro assays have demonstrated that various plastic additives, including bisphenols, phthalates, brominated flame retardants, poly-alkyl phenols and per- and poly-fluoroalkyl substances, can inhibit the activities of solute carrier uptake transporters and/or ATP-binding cassette efflux pumps. Some are substrates for transporters or can regulate their expression. The relatively low human concentration of plastic additives from environmental or dietary exposure is a key parameter to consider to appreciate the in vivo relevance of plasticizer-transporter interactions and their consequences for human toxicokinetics and toxicity of plastic additives, although even low concentrations of pollutants (in the nM range) may have clinical effects. Existing data about interactions of plastic additives with drug transporters remain somewhat sparse and incomplete. A more systematic characterization of plasticizer-transporter relationships is needed. The potential effects of chemical additive mixtures towards transporter activities and the identification of transporter substrates among plasticizers, as well as their interactions with transporters of emerging relevance deserve particular attention. A better understanding of the human toxicokinetics of plastic additives may help to fully integrate the possible contribution of transporters to the absorption, distribution, metabolism and excretion of plastics-related chemicals, as well as to their deleterious effects towards human health.
Topics: Humans; Plastics; Toxicokinetics; Plasticizers; Membrane Transport Proteins; Environmental Pollutants; Drug Interactions
PubMed: 37236587
DOI: 10.1016/j.envpol.2023.121882 -
Marine Pollution Bulletin Apr 2022This review summarizes the current state of knowledge regarding the risk assessment of plastic-associated residual additives, i.e. residual monomers, degradation... (Review)
Review
This review summarizes the current state of knowledge regarding the risk assessment of plastic-associated residual additives, i.e. residual monomers, degradation products and additives, in the marine environment, also considering effects of weathering and bioavailability. Experimental studies have found a number of organic and metal additive compounds in leachates from plastics, and the analysis of weathered plastic particles, such as polyethylene, polypropylene and polystyrene particles sampled on beaches and shorelines, has identified residual additives, such as flame retardants, plasticizers, UV stabilizers and antioxidants. While the transfer of e.g. PBDEs to organisms upon ingestion has been demonstrated, studies on uptake and bioaccumulation of plastic-associated chemicals are inconclusive. Studies on hazard and risk assessments are few, and focus on monomers and/or a limited number of high concentration additives, such as phthalates and flame retardants. The risk assessment results vary between low, moderate and high risks of specific additives, and are not necessarily consistent for the same compound. Given the large number of chemicals potentially introduced into the marine environment with plastic particles and the challenges associated with the correct quantification of exposure concentrations and toxicity thresholds, the question arises whether new risk assessment concepts may be needed.
Topics: Flame Retardants; Microplastics; Plastics; Risk Assessment; Water Pollutants, Chemical
PubMed: 35314391
DOI: 10.1016/j.marpolbul.2022.113467 -
Environment International Feb 2019Increasingly diverse chemicals are used in consumer products, while our understanding of their exposure pathways and associated human health risks still lags behind.... (Review)
Review
Increasingly diverse chemicals are used in consumer products, while our understanding of their exposure pathways and associated human health risks still lags behind. This paper aims to identify the dominant patterns of exposure pathways and associated health risks of chemicals used in consumer products reported in the peer-reviewed literature. We analyzed 342 articles covering 202 unique chemicals, and distilled the information on the functional uses, product applications, exposure routes, exposure pathways, toxicity endpoints and their combinations. We found that the volume of the literature addressing human health risks of chemicals in consumer products is increasing. Among others, phthalates, bisphenol-A, and polybrominated diphenyl ethers were the most frequently discussed chemical groups in the literature reviewed. Emerged from our review were a number of frequently reported functional use/product application combinations, including plasticizers, polymers/monomers, and flame retardants used in food contact products, personal care products, cosmetics, furniture, flooring, and electronics. We also observed a strong tendency that the number of publications on a chemical surges following major regulatory changes or exposure incidents associated with the chemical. We highlight the need to develop the capacity and the mechanism through which human health risks of chemicals in consumer products can be identified prior to their releases.
Topics: Benzhydryl Compounds; Consumer Product Safety; Cosmetics; Environmental Exposure; Flame Retardants; Halogenated Diphenyl Ethers; Household Products; Humans; Phenols; Phthalic Acids; Plasticizers
PubMed: 30622082
DOI: 10.1016/j.envint.2018.12.033 -
Environmental Toxicology and... Jun 2023The plastic accumulation and its degradation into microplastics is an environmental issue not only for their ubiquity, but also for the release of intrinsic chemicals,...
The plastic accumulation and its degradation into microplastics is an environmental issue not only for their ubiquity, but also for the release of intrinsic chemicals, such as phthalates (PAEs), non-phthalate plasticizers (NPPs), and bisphenols (BPs), which may reach body organs and tissues, and act as endocrine disruptors. Monitoring plastic additives in biological matrices, such as blood, may help in deriving relationships between human exposure and health outcomes. In this work, the profile of PAEs, NPPs and BPs was determined in Sicilian women's blood with different ages (20-60 years) and interpreted by chemometrics. PAEs (DiBP and DEPH), NPPs (DEHT and DEHA), BPA and BPS were at higher frequencies and greater levels in women's blood and varied in relation to age. According to statistical analysis, younger females' blood had higher contents of plasticizers than older women, probably due to a more frequent use of higher quantities of plastic products in daily life.
Topics: Humans; Female; Aged; Plasticizers; Plastics; Phthalic Acids
PubMed: 37268242
DOI: 10.1016/j.etap.2023.104166