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Pediatric Nephrology (Berlin, Germany) Aug 2019Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for... (Observational Study)
Observational Study
BACKGROUND
Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern.
METHODS
We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11β-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index.
RESULTS
Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 ± 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures (p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants (p < 0.05). SBP index was related to DEHP exposure from IV fluid (p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index (p < 0.05). Sodium transporter/channel expression was also related to SBP index (p < 0.05).
CONCLUSIONS
Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11β-HSD2.
Topics: 11-beta-Hydroxysteroid Dehydrogenases; Administration, Intravenous; Airway Management; Blood Pressure; Diethylhexyl Phthalate; Female; Humans; Hypertension; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Plasticizers; Prospective Studies; Receptors, Mineralocorticoid; Signal Transduction
PubMed: 31028470
DOI: 10.1007/s00467-019-04244-4 -
Biomolecules Jul 2020Dual-functioning additives with plasticizing and antibacterial functions were designed by exploiting the natural aromatic compound eugenol and green platform chemical...
Dual-functioning additives with plasticizing and antibacterial functions were designed by exploiting the natural aromatic compound eugenol and green platform chemical levulinic acid or valeric acid that can be produced from biobased resources. One-pot synthesis methodology was utilized to create three ester-rich plasticizers. The plasticizers were thoroughly characterized by several nuclear magnetic resonance techniques (H NMR, C NMR, P NMR, HSQC, COSY, HMBC) and by electrospray ionization-mass spectrometry (ESI-MS) and their performances, as plasticizers for polylactide (PLA), were evaluated. The eugenyl valerate was equipped with a strong capability to depress the glass transition temperature () of PLA. Incorporating 30 wt% plasticizer led to a reduction of the by 43 °C. This was also reflected by a remarkable change in mechanical properties, illustrated by a strain at break of 560%, almost 110 times the strain for the breaking of neat PLA. The two eugenyl levulinates also led to PLA with significantly increased strain at breaking. The eugenyl levulinates portrayed higher thermal stabilities than eugenyl valerate, both neat and in PLA blends. The different concentrations of phenol, carboxyl and alcohol functional groups in the three plasticizers caused different bactericidal activities. The eugenyl levulinate with the highest phenol-, carboxyl- and alcohol group content significantly inhibited the growth of and , while the other two plasticizers could only inhibit the growth of . Thus, the utilization of eugenol as a building block in plasticizer design for PLA illustrated an interesting potential for production of additives with dual functions, being both plasticizers and antibacterial agents.
Topics: Anti-Bacterial Agents; Calorimetry, Differential Scanning; Escherichia coli; Eugenol; Green Chemistry Technology; Levulinic Acids; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Pentanoic Acids; Plasticizers; Polyesters; Spectrometry, Mass, Electrospray Ionization; Staphylococcus aureus; Thermodynamics
PubMed: 32698323
DOI: 10.3390/biom10071077 -
PloS One 2020The pollution of the natural environment, especially the world's oceans, with conventional plastic is of major concern. Biodegradable plastics are an emerging market...
The pollution of the natural environment, especially the world's oceans, with conventional plastic is of major concern. Biodegradable plastics are an emerging market bringing along potential chances and risks. The fate of these materials in the environment and their possible effects on organisms and ecosystems has rarely been studied systematically and is not well understood. For the marine environment, reliable field test methods and standards for assessing and certifying biodegradation to bridge laboratory respirometric data are lacking. In this work we present newly developed field tests to assess the performance of (biodegradable) plastics under natural marine conditions. These methods were successfully applied and validated in three coastal habitats (eulittoral, benthic and pelagic) and two climate zones (Mediterranean Sea and tropical Southeast Asia). Additionally, a stand-alone mesocosm test system which integrated all three habitats in one technical system at 400-L scale independent from running seawater is presented as a methodological bridge. Films of polyhydroxyalkanoate copolymer (PHA) and low density polyethylene (LD-PE) were used to validate the tests. While LD-PE remained intact, PHA disintegrated to a varying degree depending on the habitat and the climate zone. Together with the existing laboratory standard test methods, the field and mesocosm test systems presented in this work provide a 3-tier testing scheme for the reliable assessment of the biodegradation of (biodegradable) plastic in the marine environment. This toolset of tests can be adapted to other aquatic ecosystems.
Topics: Biodegradation, Environmental; Environment, Controlled; Food Chain; Geologic Sediments; Oceans and Seas; Plastics; Seawater; Temperature
PubMed: 32735596
DOI: 10.1371/journal.pone.0236579 -
Environmental Research Apr 2020Phthalate esters and phosphate flame retardants and plasticizers (PFRs) are both used as plasticizers and are commonly detected in indoor environments. Although both...
BACKGROUND
Phthalate esters and phosphate flame retardants and plasticizers (PFRs) are both used as plasticizers and are commonly detected in indoor environments. Although both phthalates and PFRs are known to be associated with children's wheeze and allergic symptoms, there have been no previous studies examining the effects of mixtures of these exposures.
OBJECTIVES
To investigate the association between exposure to mixtures of phthalate esters and PFRs, and wheeze and allergic symptoms among school-aged children.
METHODS
A total of 128 elementary school-aged children were enrolled. Metabolites of 3 phthalate esters and 7 PFRs were measured in urine samples. Parent-reported symptoms of wheeze, rhinoconjunctivitis, and eczema were evaluated using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. In the primary model, we created a phthalate ester and PFR mixture exposure index, and estimated odds ratios (ORs) using weighted quantile sum (WQS) regression and quantile g (qg)-computation. The two highest chemicals according to qg-computation weight %s were combined to create a combination high × high exposure estimate, with ORs calculated using the "low × low" exposure group as the reference category. Concentrations of each metabolite were corrected by multiplying this value by the sex- and body size-Standardised creatinine concentration and dividing by the observed creatinine value. All models were adjusted for sex, grade, dampness index and annual house income.
RESULTS
The odds ratio of rhinoconjunctivitis for the association between exposure to chemical mixtures according to the WQS index positive models was; OR = 2.60 (95% confidence interval [CI]: 1.38-5.14). However, wheeze and eczema of the WQS index positive model, none of the WQS index negative models or qg-computation result yielded statistically significant results. Combined exposure to the two highest WQS weight %s of "high-high" ΣTCIPP and ΣTPHP was associated with an increased prevalence of rhino-conjunctivitis, OR = 5.78 (1.81-18.43) to the "low × low" group.
CONCLUSIONS
Significant associations of mixed exposures to phthalates and PFRs and increased prevalence of rhinoconjunctivitis was found among elementary school-aged children in the WQS positive model. Mixed exposures were not associated with any of allergic symptoms in the WQS negative model or qg-computation approach. However, the combined effects of exposure to two PFRs suggested an additive and/or multiplicative interaction, potentially increasing the prevalence of rhinoconjunctivitis. A further study with a larger sample size is needed to confirm these results.
Topics: Child; Environmental Exposure; Esters; Flame Retardants; Humans; Hypersensitivity; Phosphates; Phthalic Acids; Plasticizers; Respiratory Sounds
PubMed: 32058144
DOI: 10.1016/j.envres.2020.109212 -
Environmental Science and Pollution... Jun 2018Phthalates are a group of chemical compounds used as plasticizers in the manufacture of plastic materials. They can be present in many commonly used products. There...
Phthalates are a group of chemical compounds used as plasticizers in the manufacture of plastic materials. They can be present in many commonly used products. There seems to be a relationship between exposure to phthalates and the occurrence of metabolic dysfunctions, such as a decrease in glucose tolerance, oxidative stress, loss of beta cells, and a decrease in insulin synthesis. As beta cells play a key role in the onset of type 1 diabetes mellitus (T1DM), we sought to investigate the relationship between exposure to phthalates and the diagnosis of T1DM in prepubertal children. Design concentrations of phthalate metabolites were compared in the urine of a population of prepubertal children with new-onset diabetes, patients with T1DM diagnosed more than 6 months previously, and healthy control children. Although the concentrations of DBP and DiBP metabolites were statistically identical in the new-onset diabetes, diabetes, and control groups, there was a clear trend for higher levels of DiBP metabolites in the children with new-onset diabetes. In our sample, there was a trend for higher levels of DiBP metabolites in children with new-onset diabetes.
Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Humans; Insulin-Secreting Cells; Oxidative Stress; Phthalic Acids; Plasticizers; Plastics
PubMed: 29680886
DOI: 10.1007/s11356-018-1997-z -
International Journal of Environmental... Dec 2022Male infertility is a serious concern for public health, and the possible role of exposure to plasticizers such as phthalates and bisphenol A in contributing to the...
Male infertility is a serious concern for public health, and the possible role of exposure to plasticizers such as phthalates and bisphenol A in contributing to the condition is widely debated. We have herein enrolled 155 infertility cases attending an infertility center and 211 controls (fathers of a spontaneously conceived newborn) to investigate this issue. The urinary levels of seven phthalates and BPA were analyzed through HPLC/MS/MS. All data were statistically elaborated considering information about clinical situation, life habits, occupational activity, and, for cases, semen parameters (volume, sperm concentration, total count of spermatozoa, and sperm motility). Results showed significantly higher urinary concentrations for all the phthalates in cases compared to controls, except for monoethylphthalate and BPA. In total, 90.07% of cases had sperm motility lower than the WHO reference value (2010), while 53.69%, 46.31%, and 16.56% had sperm total number, concentration, and volume, respectively, out of the reference range. Regarding the possible source of exposure, the use of scents seems to be a significant source of DEP (diethylphthalate). When considering occupational settings, industrial workers, dental technicians, artisans, and farmers using chemicals showed higher risk (OR = 2.766, 95% CI 1.236-6.185), particularly in relation to DnBP (di--butyl phthalate) and DEHP (di-ethyl-hexyl phthalate) exposure. No clear quantitative correlation between specific plasticizers and sperm parameters could be demonstrated but these findings call for future studies about the risks associated with exposure to their mixture.
Topics: Infant, Newborn; Male; Humans; Plasticizers; Case-Control Studies; Tandem Mass Spectrometry; Sperm Motility; Semen; Phthalic Acids; Infertility; Fertility; Environmental Exposure; Environmental Pollutants
PubMed: 36612557
DOI: 10.3390/ijerph20010235 -
Environment International Oct 2020Indoor dust has been extensively used for assessment of indoor contamination, especially for semi-volatile organic compounds (SVOCs). In the present study, the...
Indoor dust has been extensively used for assessment of indoor contamination, especially for semi-volatile organic compounds (SVOCs). In the present study, the occurrence of four groups of SVOCs, i.e. organophosphorus flame retardants (PFRs), emerging PFRs (ePFRs), legacy phthalates (LPs), and alternative plasticizers (APs), was investigated in the indoor dust and air collected from floors, table surfaces, windows, and air conditioner (A/C) filters in bedrooms and offices in Guangzhou, South China. In bedrooms, A/C filter dust showed the highest median concentrations of PFRs (4670 ng/g) and ePFRs (586 ng/g), whilst the highest median concentrations of LPs and APs were found in floor (240,880 ng/g) and window dust (157,160 ng/g), respectively. In offices, A/C filter dust showed the highest median concentrations for PFRs (6750 ng/g) and APs (504,520 ng/g), while the highest ePFR median level was found in PC table dust (5810 ng/g) and LPs in floor dust (296,270 ng/g). Median air concentrations of PFRs, ePFRs, LPs, and APs were measured at 4.6, 0.12, 399, and 25 ng/m in bedrooms, and at 8.0, 0.05, 332, and 43 ng/m in offices, respectively. Tris(1-chloro-iso-propyl) phosphate (TCIPP) was the predominant PFRs/ePFRs in both dust and air. Di(2-ethylhexyl) phthalate (DEHP), di-iso-decyl phthalate (DIDP) and di-iso-nonyl phthalate (DINP) were the main LP/AP compounds in dust, whilst di-iso-butyl phthalate (DIBP) and di-n-butyl phthalate (DNBP) were the most abundant LPs/APs in air. A significant correlation (p < 0.05) was found between dust and air levels for chemicals with log K < 14, indicating that equilibrium was achieved for these chemicals but not for those with log K > 14. Among the investigated human exposure pathways (i.e. dust ingestion, dermal absorption, and air inhalation), dust ingestion was the predominant one for all chemicals. Human exposures of this magnitude to these chemicals through the investigated pathways was unlikely to present a health risk in the present study.
Topics: Air Pollution, Indoor; China; Dust; Environmental Exposure; Flame Retardants; Humans; Organophosphorus Compounds; Plasticizers
PubMed: 32707272
DOI: 10.1016/j.envint.2020.105972 -
Environment International Nov 2023The global production and use of plastic materials has increased dramatically since the 1960s and there is increasing evidence of human health impacts related to...
BACKGROUND
The global production and use of plastic materials has increased dramatically since the 1960s and there is increasing evidence of human health impacts related to exposure to plastic-associated chemicals. There is, however, no comprehensive, regulatory, post-market monitoring for human health effects of plastic-associated chemicals or particles and it is unclear how many of these have been investigated for effects in humans, and therefore what the knowledge gaps are.
OBJECTIVE
To create a systematic evidence map of peer-reviewed human studies investigating the potential effects of exposure to plastic-associated particles/chemicals on health to identify research gaps and provide recommendations for future research and regulation policy.
METHODS
Medline and Embase databases were used to identify peer-reviewed primary human studies published in English from Jan 1960 - Jan 2022 that investigated relationships between exposures to included plastic-associated particles/chemicals measured and detected in bio-samples and human health outcomes. Plastic-associated particles/chemicals included are: micro and nanoplastics, due to their widespread occurrence and potential for human exposure; polymers, the main building blocks of plastic; plasticizers and flame retardants, the two most common types of plastic additives with the highest concentration ranges in plastic materials; and bisphenols and per- or polyfluoroalkyl substances, two chemical classes of known health concern that are common in plastics. We extracted metadata on the population and study characteristics (country, intergenerational, sex, age, general/special exposure risk status, study design), exposure (plastic-associated particle/chemical, multiple exposures), and health outcome measures (biochemical, physiological, and/or clinical), from which we produced the interactive database 'Plastic Health Map' and a narrative summary.
RESULTS
We identified 100,949 unique articles, of which 3,587 met our inclusion criteria and were used to create a systematic evidence map. The Plastic Health Map with extracted metadata from included studies are freely available at https://osf.io/fhw7d/ and summary tables, plots and overall observations are included in this report.
CONCLUSIONS
We present the first evidence map compiling human health research on a wide range of plastic-associated chemicals from several different chemical classes, in order to provide stakeholders, including researchers, regulators, and concerned individuals, with an efficient way to access published literature on the matter and determine knowledge gaps. We also provide examples of data clusters to facilitate systematic reviews and research gaps to help direct future research efforts. Extensive gaps are identified in the breadth of populations, exposures and outcomes addressed in studies of potential human health effects of plastic-associated chemicals. No studies of the human health effects of micro and/or nanoplastics were found, and no studies were found for 26/1,202 additives included in our search that are of known hazard concern and confirmed to be in active production. Few studies have addressed recent "substitution" chemicals for restricted additives such as organophosphate flame retardants, phthalate substitutes, and bisphenol analogues. We call for a paradigm shift in chemical regulation whereby new plastic chemicals are rigorously tested for safety before being introduced in consumer products, with ongoing post-introduction biomonitoring of their levels in humans and health effects throughout individuals' life span, including in old age and across generations.
Topics: Humans; Flame Retardants; Microplastics; Plasticizers
PubMed: 37948868
DOI: 10.1016/j.envint.2023.108225 -
Shokuhin Eiseigaku Zasshi. Journal of... 2023We determined the fifteen types of plasticizers, including four kinds of phthalic acid esters (PAEs) used in 220 polyvinyl chloride (PVC) toys on Japanese market from...
We determined the fifteen types of plasticizers, including four kinds of phthalic acid esters (PAEs) used in 220 polyvinyl chloride (PVC) toys on Japanese market from 2019 to 2020. Three kinds of previously undetected types of PAEs were also detected, but not identified in this study. Di (2-ethylhexyl) terephthalate (DEHTP) was the highest detection rate in 209 soft PVC toys out of 220 toys, with 71.2% for designated toys and 88.9% for not-designated toys, respectively, showing a gradual increase from the previous reports in 2009 and 2014. On the other hand, the usages of o-acetyl tributyl citrate and adipic acid esters decreased, but the six types of PAEs prohibited to use for the designated toys in Japan were not detected in them, the usage of diisobutyl phthalate were increased. In contrast, four types of PAEs were detected in not-designated toys. Among them, the detection ratio of di (2-ethyhexyl) phthalate decreased to about 1/10. The content levels of plasticizers in per each sample were continued to keep low level from the report five years ago. These results showed that the main plasticizer used in PVC toys is DEHTP, and that the usage of other plasticizers was decreased.
Topics: Plasticizers; Polyvinyl Chloride; Esters; Japan
PubMed: 37673604
DOI: 10.3358/shokueishi.64.145 -
Environment International Mar 2023Di-2-ethylhexyl phthalate (DEHP) and its substitute 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) are widely used as plasticizers but may have adverse...
Di-2-ethylhexyl phthalate (DEHP) and its substitute 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) are widely used as plasticizers but may have adverse health effects. Via hydrolysis of one of the two ester bonds in the human body, DEHP and DINCH form the monoesters MEHP and MINCH, respectively. Previous studies demonstrated binding of these metabolites to PPARγ and the induction of adipogenesis via this pathway. Detailed structural understanding of how these metabolites interact with PPARγ and thereby affect human health is lacking until now. We therefore characterized the binding modes of MINCH and MEHP to the ligand binding domain of PPARγ by X-ray crystallography and molecular dynamics (MD) simulations. Both compounds bind to the activating function-2 (AF-2) binding site via an interaction of the free carboxylates with the histidines 323 and 449, tyrosine 473 and serine 289. The alkyl chains form hydrophobic interactions with the tunnel next to cysteine 285. These binding modes are generally stable as demonstrated by the MD simulations and they resemble the complexation of fatty acids and their metabolites to the AF-2 site of PPARγ. Similar to the situation for these natural PPARγ agonists, the interaction of the free carboxylate groups of MEHP and MINCH with tyrosine 473 and surrounding residues stabilizes the AF-2 helix in the upward conformation. This state promotes binding of coactivator proteins and thus formation of the active complex for transcription of the specific target genes. Moreover, a comparison of the residues involved in binding of the plasticizer metabolites in vertebrate PPARγ orthologs shows that these compounds likely have similar effects in other species.
Topics: Humans; Plasticizers; Diethylhexyl Phthalate; PPAR gamma; Furylfuramide; Phthalic Acids
PubMed: 36841188
DOI: 10.1016/j.envint.2023.107822