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The plasticizer di(2-ethylhexyl) phthalate (DEHP) is known to have endocrine-disrupting properties mediated by its many metabolites that form upon exposure in biological systems. In a previous study, we reported an inverse association between DEHP metabolites in the human ovarian follicular fluid (FF) and the responsiveness of the follicles to controlled ovarian stimulation during in vitro fertilization (IVF) treatments. Here, we explored this association further through molecular analysis of the ovarian FF samples. Ninety-six IVF patients from Swedish (N = 48) and Estonian (N = 48) infertility clinics were selected from the previous cohort (N = 333) based on the molar sum of DEHP metabolites in their FF samples to arrive at "high" (mean 7.7 ± SD 2.3 nM, N = 48) and "low" (0.8 ± 0.4 nM, N = 48) exposure groups. Extracellular miRNA levels and concentrations of 15 steroid hormones were measured across FF samples. In addition, FF somatic cells, available for the Estonian patients, were used for RNA sequencing. Differential expression (DE) and interactions between miRNA and mRNA networks revealed that the expression levels of genes in the cholesterol biosynthesis and steroidogenesis pathways were significantly decreased in the high compared to the low DEHP group. In addition, the DE miRNAs were predicted to target key enzymes within these pathways (FDR < 0.05). A decreased 17-OH-progesterone to progesterone ratio was observed in the FF of the high DEHP group (p < 0.05). Additionally, the expression levels of genes associated with inflammatory processes were elevated in the FF somatic cells, and a computational cell-type deconvolution analysis suggested an increased immune cell infiltration into the high DEHP follicles (p < 0.05). In conclusion, elevated DEHP levels in FF were associated with a significantly altered follicular milieu within human ovaries, involving a pro-inflammatory environment and reduced cholesterol metabolism, including steroid synthesis. These results contribute to our understanding of the molecular mechanisms of female reprotoxic effects of DEHP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Poly(vinyl chloride) (PVC) is one of the most widely used plastics. However, a major challenge in recycling PVC is that there is no economical method to separate and remove its toxic phthalate plasticizers. This research made a breakthrough by extracting PVC with liquefied dimethyl ether (DME) and successfully separating the plasticizer components. Nearly all (97.1 %) of the di(2-ethylhexyl) phthalate plasticizer was extracted within 30 min by passing liquefied DME (285 g) through PVC at 25 °C. The compatibility of PVC with organic solvents, including liquefied DME, was derived theoretically from their Hansen solubility parameters (HSP), and actual dissolution experiments were conducted to determine the optimal PVC solvents. A liquefied DME mixture was used to dissolve PVC, and the extract was diluted with ethanol to precipitate the dissolved PVC. We demonstrated that liquefied DME is a promising method for producing high quality recycled products and that the process retains the fundamental properties of plasticizers and PVC without inducing degradation or depolymerization. Because of its low boiling point, DME can be easily separated from the solute after extraction, allowing for efficient reuse of the solvent, extracted plasticizer, and PVC. DME does not require heat and produces little harmful wastewater, which significantly reduces the energy consumption of the plasticizer additive separation process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sediments are important sinks for di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, and thus, maintaining the sediment quality is essential for eliminating plasticizers in aqueous environments and recovering the sediment ecological functions. To mitigate the potential risks of endocrine-disrupting compounds, identifying an effective and eco-friendly degradation process of organic pollutants from sediments is important. However, sustainable and efficient utilization of slow pyrolysis for converting shark fishbone to generate shark fishbone biochar (SFBC) has rarely been explored. Herein, SFBC biomass was firstly produced by externally incorporating heteroatoms or iron oxide onto its surface in conjunction with peroxymonosulfate (PMS) to promote DEHP degradation and explore the associated benthic bacterial community composition from the sediment in the water column using the Fe-N-SFBC/PMS system. SFBC was pyrolyzed at 300-900 °C in aqueous sediment using a carbon-advanced oxidation process (CAOP) system based on PMS. SFBC was rationally modified via N or Fe-N doping as a radical precursor in the presence of PMS (1 × 10 -5  M) for DEHP removal. The innovative SFBC/PMS, N-SFBC/PMS, and Fe-N-SFBC/PMS systems could remove 82%, 65%, and 90% of the DEHP at pH 3 in 60 min, respectively. The functionalized Fe 3 O 4 and heteroatom (N) co-doped SFBC composite catalysts within a hydroxyapatite-based structure demonstrated the efficient action of PMS compared to pristine SFBC, which was attributed to its synergistic behavior, generating reactive radicals (SO 4 •- , HO•, and O 2 •- ) and non-radicals ( 1 O 2 ) involved in DEHP decontamination. DEHP was significantly removed using the combined Fe-N-SFBC/PMS system, revealing that indigenous benthic microorganisms enhance their performance in DEHP-containing sediments. Further, DEHP-induced perturbation was particularly related to the Proteobacteria phylum, whereas Sulfurovum genus and Sulfurovum lithotrophicum species were observed. This study presents a sustainable method for practical, green marine sediment remediation via PMS-CAOP-induced processes using a novel Fe-N-SFBC composite material and biodegradation synergy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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

Plastic additives, represented by plasticizers, are important components of plastic pollution. Biofilms inevitably form on plastic surfaces when plastic enters the aqueous environment. However, little is known about the effect of biofilms on plastic surfaces on the release of additives therein. In this study, PVC plastics with different levels of di(2-ethylhexyl)phthalate (DEHP) content were investigated to study the effect of biofilm growth on DEHP release. The presence of biofilms promoted the migration of DEHP from PVC plastics to the external environment. Relative to biofilm-free controls, although the presence of surface biofilm resulted in 0.8 to 11.6 times lower DEHP concentrations in water, the concentrations of the degradation product, monoethylhexyl phthalate (MEHP) in water, were 2.3 to 57.3 times higher. When the total release amounts of DEHP in the biofilm and in the water were combined, they were increased by 0.6-73 times after biofilm growth. However, most of the released DEHP was adsorbed in the biofilms and was subsequently degraded. The results of this study suggest that the biofilm as a new interface between plastics and the surrounding environment can affect the transport and transformation of plastic additives in the environment through barrier, adsorption, and degradation. Future research endeavors should aim to explore the transport dynamics and fate of plastic additives under various biofilm compositions as well as evaluate the ecological risks associated with their enrichment by biofilms.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

An LC-MS based analytical method was developed and validated for the simultaneous targeted analysis and suspect screening of plastic-related contaminants in e-waste impacted soils. Satisfactory recoveries (97 ± 13 %) were achieved using ultrasound-assisted extraction for 14/15 of the targeted analytes (7 bisphenols and 8 plasticizers) in a range of agricultural and non-agricultural soils. The method was applied to 53 soil samples collected in May 2015 in the region of Agbogbloshie (Ghana) at e-waste facilities (incl. Dump, trade, and burn sites), neighboring non-agricultural (incl. upstream, downstream, and community) and agricultural fields, and at two control agricultural sites away from e-waste recycling facilities. Bisphenol A (BPA) and bis(2-ethylhexyl) phthalate (DEHP) were the two dominant contaminants in e-waste soil (with concentrations up to 48.7 and 184 μg g -1 , respectively), especially at the trade site, where e-waste was sorted and dismantled. The non-targeted workflow was successfully applied to identify additional plastic-related contaminants previously unreported in e-waste impacted soils, including bis(2-propylheptyl) phthalate, diisononyl phthalate, trioctyl trimellitate, 4-dodecylbenzenesulfonic acid, perfluorooctanesulfonic acid, perfluorobutanesulfonic acid, diphenyl phosphate, and triethylene glycol monobutyl ether. The agricultural soils surrounding the e-waste sites were also contaminated by plastic-related chemicals (especially DEHP), highlighting the impact of e-waste activities on the surrounding agricultural system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Plasticizers such as phthalate esters (PAEs) are commonly used in various consumer and industrial products. This widespread use raises valid concerns regarding their ubiquity in the environment and potential negative impacts. The present study investigates the distribution of eight common plasticizers in the largest European lagoon (Curonian Lagoon) located in the SE Baltic Sea. The concentration levels of plasticizers in the water column, containing both the dissolved and particulate-bound phases, and in sediments were evaluated to reveal seasonal patterns in distribution and potential effects on the lagoon ecosystem. A total of 24 water samples and 48 sediment samples were collected across all four seasons from the two dominant sedimentary areas within the lagoon. The average concentration of total PAEs in the water column ranged from 1 to 21 μg L -1 , whereas sediment concentration varied from 5.0 to 250 ng g -1 . The distribution of plasticizers was influenced by the patterns in hydrodynamics and water circulation within the lagoon. The confined south-central area contained a higher amount of PAEs in sediments, accounting for most of the lagoon's plasticizer accumulation. More than 7 tons of plasticizers are stored in the 5 upper centimetres of sediment, with over 3 tons persisting for more than five years. Di(2-ethylhexyl) phthalate (DEHP), Diisobutyl phthalate (DiBP), and Dibutyl phthalate (DnBP) were the most abundant PAE congeners, with DEHP posing the highest risk quotient to algae, based on water column concentration. Several other congeners demonstrated medium to high-risk levels for organisms living in the lagoon., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Priority water pollutants comprising six plasticizers, 18 volatile organic compounds (VOCs), total petroleum hydrocarbon (TPH), 1,4-dioxane, epichlorohydrin, formaldehyde, acrylamide, and cyanides were determined in surface river sediments to assess their distribution patterns and ecological risks. Among these, di (2-ethylhexyl) phthalate (DEHP), toluene, TPH, and acrylamide were frequently found in sediments. The industrial sites had higher concentrations of ∑plasticizers (median 628 ng/g dry weight (dw)), ∑VOCs (median 3.35 ng/g dw), acrylamide (median 0.966 ng/g dw), and TPH (median 152 μg/g dw) in sediments than the mixed and non-industrial areas. The other pollutants did not show the significant differences in levels according to site types because of their relatively low detection frequencies. Volatile and soluble substances as well as hydrophobic pollutants were predominantly detected in surface sediments from industrial areas. Sediment contamination patterns were affected by the size and composition of the industrial zones around the sampling sites. The ecological risks determined using the sediment quality guidelines (DEHP, VOCs, and TPH) and the mean probable effect level quotients (DEHP) were mostly acceptable. However, the two most representative industrial regions (the largest industrial area and the first industrial city) showed risks of concern for DEHP and TPH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This paper presents the phthalate esters (PAEs), nonylphenol (NPs), and microplastics (MPs) in river sediments. Results showed that sediments near residential areas were mainly composed of fine particles, potentially influencing the adsorption of PAEs and NPs in the area. The concentrations of Σ10 PAEs in the sediments ranged between 2448 and 63,457 μg/kg dw, dominated by DEHP and DnOP. Microplastics were detected in all samples, with higher abundances found in sediments near residential areas dominated by polypropylene. Toxicological risk assessment indicated potential risks to sensitive aquatic organisms exposed to the sediments. Correlations between MPs, PAEs, and NPs suggest that MPs may serve as possible sources of PAEs in the sediments. Principal component analysis explained 95.4 % of the pollutant variability in the sediments. Overall, this study emphasizes the significance of monitoring and understanding the presence and interactions of PAEs and MPs in river sediments to assess their potential impacts on aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Di-(2-ethylhexyl) phthalate (DEHP), a phthalate plasticizer, is widely spread in the environment, presenting hazards to human health and food safety. Hence, this study examined the probable preventive role of coenzyme10 (CQ10) (10 mg/kg.b.wt) against DEHP (500 mg/kg.wt) - induced neurotoxic and neurobehavioral impacts in juvenile (34 ± 1.01g and 3 weeks old) male Sprague Dawley rats in 35-days oral dosing trial. The results indicated that CQ10 significantly protected against DEHP-induced memory impairment, anxiety, depression, spatial learning disorders, and repetitive/stereotypic-like behavior. Besides, the DEHP-induced depletion in dopamine and gamma amino butyric acid levels was significantly restored by CQ10. Moreover, CQ10 significantly protected against the exhaustion of CAT, GPx, SOD, GSH, and GSH/GSSG ratio, as well as the increase in malondialdehyde, Caspas-3, interleukin-6, and tumor necrosis factor-alpha brain content accompanying with DEHP exposure. Furthermore, CQ10 significantly protected the brain from the DEHP-induced neurodegenerative alterations. Also, the increased immunoexpression of brain-derived neurotrophic factor, not glial fibrillary acidic protein, in the cerebral, hippocampal, and cerebellar brain tissues due to DEHP exposure was alleviated with CQ10. This study's findings provide conclusive evidence that CQ10 has the potential to be used as an efficient natural protective agent against the neurobehavioral and neurotoxic consequences of DEHP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hazardous chemicals in building and construction plastics can lead to health risks due to indoor exposure and may contaminate recycled materials. We systematically sampled new polyvinyl chloride floorings on the Swiss market ( n = 151). We performed elemental analysis by X-ray fluorescence, targeted and suspect gas chromatography-mass spectrometry analysis of ortho -phthalates and alternative plasticizers, and bioassay tests for cytotoxicity and oxidative stress, and endocrine, mutagenic, and genotoxic activities (for selected samples). Surprisingly, 16% of the samples contained regulated chemicals above 0.1 wt %, mainly lead and bis(2-ethylhexyl) phthalate (DEHP). Their presence is likely related to the use of recycled PVC in new flooring, highlighting that uncontrolled recycling can delay the phase-out of hazardous chemicals. Besides DEHP, 29% of the samples contained other ortho -phthalates (mainly diisononyl and diisodecyl phthalates, DiNP and DiDP) above 0.1 wt %, and 17% of the samples indicated a potential to cause biological effects. Considering some overlap between these groups, they together make up an additional 35% of the samples of potential concern. Moreover, both suspect screening and bioassay results indicate the presence of additional potentially hazardous substances. Overall, our study highlights the urgent need to accelerate the phase-out of hazardous substances, increase the transparency of chemical compositions in plastics to protect human and ecosystem health, and enable the transition to a safe and sustainable circular economy.

Workers involved in the processing of electronic waste (e-waste) are potentially exposed to toxic chemicals, including phthalates and alternative plasticizers (APs). Dismantling and shredding of e-waste may lead to the production of dust that contains these plasticizers. The aim of this study, which was part of the European Human Biomonitoring Initiative (HBM4EU), was to assess the exposure to phthalates (e.g. di-(2-ethylhexyl) phthalate (DEHP), diethyl phthalate (DEP), di-butyl phthalate (DBP), butyl-benzyl phthalate (BBzP), di-isononyl phthalate (DiNP), di-isodecyl phthalate (DiDP) and cyclohexane-1,2-dicarboxylic di-isononyl ester (DINCH) in e-waste workers from ten European companies. This was achieved by (i) analysing urine samples from 106 e-waste workers collected at the beginning and at the end of the work week, (ii) comparing these with urine samples from 63 non-occupationally exposed controls, and (iii) analysing settled floor dust collected in e-waste premises. Significantly higher urinary concentrations of seven out of thirteen phthalates and DINCH metabolites were found in the e-waste workers compared to the control population. However, no significant differences were found between pre- and post-shift concentrations in the e-waste workers. Concentrations of DBP, DEHP and DiDP in dust were weakly to moderately positively correlated with their corresponding urinary metabolite concentrations in the e-waste workers (Spearman's ρ = 0.4, 0.3 and 0.2, respectively). Additionally, significantly lower urinary concentrations of nine phthalates and DINCH metabolites were found in e-waste workers using respiratory protective equipment (RPE) during their work activities, reflecting the potential benefits of RPE to prevent occupational exposure to phthalates and DINCH. The estimated daily intake (EDI) values obtained in this study were lower than the corresponding tolerable daily intake (TDI) adopted by the European Food Safety Authority (EFSA) for the general population, suggesting that the risk for negative health consequences in this population of e-waste workers from exposure to phthalates and DINCH is expected to be low. This was confirmed by the urinary metabolite concentrations of all workers being lower than the HBM4EU guidance values derived for the occupational exposed and general population. This study is one of the first to address the occupational exposure to phthalates and DINCH in Europe in e-waste dismantling workers, combining a human biomonitoring approach with analysis of settled indoor dust., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Di-2-ethylhexyl phthalate (DEHP) is used as a plasticizer in making plastics and released from landfills. This study attempted to degrade DEHP using microbial isolates. Isolates of Bacillus spp. were tested for their efficacy in degrading DEHP. Degradation was assessed using liquid chromatography-mass spectrometry (LC-MS). The most efficient DEHP degradation was achieved by Bacillus firmus MP04, which has been identified as Bacillus firmus MP04. This strain was found to use DEHP as the sole source of carbon without carbon source supplementation. Full factorial design was used to optimize the conditions for DEHP degradation which revealed the suitability of pH 7, 5% salt concentration, 20 to 37 °C temperature, and yeast extract as a nitrogen source. LC-MS elucidated the possible degradation mechanism via benzoic acid formation. However, prolonged incubation formed a typical compound denatonium benzoate due to reactions with other compounds. As maximum degradation was achieved in 4 days, prolonged incubation is not suggested. It can be concluded that new strain Bacillus firmus MP04 is the most efficient strain among all the tested strains for DEHP degradation., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Considering the ubiquitous occurrences and ecotoxicity of phthalates (PAEs), it is essential to understand their sources, distribution, and associated ecological risks of PAEs in sediments to assess the environmental health of estuaries and support effective management practices. This study provides the first comprehensive dataset on the occurrence, spatial variation, inventory, and potential ecological risk assessment of PAEs in surface sediments of commercially and ecologically significant estuaries in the southeastern United States, Mobile Bay and adjoining eastern Mississippi Sound. Fifteen PAEs were widely detected in the sediments of the study region, with total concentrations varying between 0.02 and 3.37 μg/g. The dominance of low-molecular-weight (LMW) PAEs (DEP, DBP and DiBP) relative to high-molecular-weight (HMW) PAEs (DEHP, DOP, DNP) indicates that residential activities have stronger impacts than industrial activities on PAE distributions. The total PAE concentrations displayed an overall decreasing trend with increasing bottom water salinity, with the maximum concentrations occurring near river mouths. These observations suggest that river inputs were an important pathway by which PAEs were transported to the estuary. Linear regression models identified sediment adsorption (measured by total organic carbon and median grain size) and riverine inputs (measured by bottom water salinity) as significant predictors for the concentrations of LMW and HMW PAEs. Estimated 5-year total inventories of sedimentary PAEs in Mobile Bay and the eastern Mississippi Sound were 13.82 tons and 1.16 tons, respectively. Risk assessment calculations suggest that LMW PAEs posed a medium-to-high risk to sensitive aquatic organisms, and DEHP posed a low or negligible risk to the aquatic organisms. The results of this study provide important information needed for establishing and implementing effective practices for monitoring and regulating plasticizer pollutants in estuaries., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine., Hypothesis: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers., Methods: We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP., Results: (1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends., Conclusion: ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Stein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Being an essential component in the plastics industry, phthalates are ubiquitous in the environment and in everyday life. They are considered environmental contaminants that have been classified as endocrine-disrupting compounds. Despite di-2-ethylhexyl phthalate (DEHP) being the most common plasticizer and the most studied to date, there are many others that, in addition to being widely used in the plastic, are also applied in the medical and pharmaceutical industries and cosmetics. Due to their wide use, phthalates are easily absorbed by the human body where they can disrupt the endocrine system by binding to molecular targets and interfering with hormonal homeostasis. Thus, phthalates exposure has been implicated in the development of several diseases in different age groups. Collecting information from the most recent available literature, this review aims to relate human phthalates' exposure with the development of cardiovascular diseases throughout all ages. Overall, most of the studies presented demonstrated an association between phthalates and several cardiovascular diseases, either from prenatal or postnatal exposure, affecting foetuses, infants, children, young and older adults. However, the mechanisms underlying these effects remain poorly explored. Thus, considering the cardiovascular diseases incidence worldwide and the constant human exposure to phthalates, this topic should be extensively studied to understand the mechanisms involved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Endocrine disrupting chemicals (EDCs) were defined as "an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects". These compounds are mainly eliminated by the renal route. However, patients with end-stage kidney disease treated by dialysis (ESKDD) can no longer eliminate these EDCs efficiently. Furthermore, EDCs exposure could occur via leaching from medical devices used in dialysis therapy. As a result, ESKDD patients are overexposed to EDCs. The aims of this study were to summarize EDCs exposure of ESKDD patients and to evaluate the factors at the origin of this exposure. To handle these objectives, we performed a literature review. An electronic search on PubMed, Embase and Web of science databases was performed. Twenty-six studies were finally included. The EDCs reported in these studies were Bisphenol A (BPA), Bisphenol S (BPS), Bisphenol B (BPB), Nonylphenol, Di(2-ethylhexyl) phthalate (DEHP), Di-n-butyl phthalate (DBP), and Butylbenzyl phthalate (BBP). Regarding the environment of dialysis patients, BPA, BPB, BPS, DEHP, DBP and nonylphenol have been found. Environmental exposure affects EDCs blood levels in ESKDD patients who are overexposed to BPA, BPS, BPB and DEHP. For ESKDD patients, dialyzers with housing in polycarbonate and fibers in polysulfone seem to overexpose them to BPA. Regarding dialysis therapy, peritoneal dialysis seems to decrease patient exposure vs hemodialysis therapy, and hemodiafiltration therapy seems to reduce this exposure vs hemodialysis therapy. Regarding DEHP, levels tend to increase during dialysis and when DEHP plasticizer is used in PVC devices. Finally, in the European Union a regulation on medical devices was adopted on 5 April 2017 and has been applied recently. This regulation will regulate EDCs in medical devices and thereby contribute to reconsideration of their conceptions and, finally, to reduction of ESKDD patients' exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of bis (2-ethylhexyl) phthalate (DEHP), 2,2'4,4'-tetrabromodiphenyl ether (BDE47), and bisphenol A (BPA), as plasticizers, flame retardants, and epoxy resins, respectively, has been regulated due to their endocrine disrupting activities. Replacements for these chemicals are found in human matrices, yet the endocrine disrupting potential of these emerging contaminants is poorly characterized. We compared the effects of legacy chemicals with those of their replacements using fetal rat testis organ culture. Fetal testes sampled at gestation day 15 were grown ex vivo, and the impact was evaluated after a 3-day exposure to 10 μM of each legacy chemical; two BPA analogs (bisphenol M and bisphenol TMC); three replacements for DEHP/MEHP (2,2,4-trimethyl-1,3-pentanediol diisobutyrate, diisononyl-phthalate, and diisodecyl adipate); or two replacements for BDE47 (tributoxyethyl phosphate and isopropylated triphenyl phosphate). We showed that only BPA and MEHP significantly decrease testosterone secretions after 24 h, while BPM and BPTMC have the opposite effect. Luteinizing hormone-stimulated testosterone was reduced by BPA and MEHP but was increased by BPTMC. After exposure, testes were used for immunofluorescent staining of germ cells, Sertoli cells, and Leydig cells. Interestingly, exposures to BPM or BPTMC induced a significant increase in the Leydig cell density and surface area. A decrease in germ cell density was observed only after treatment with MEHP or BDE47. MEHP also significantly decreased Sertoli cell proliferation. These studies show that some replacement chemicals can affect testicular function, while others appear to show little toxicity in this model. These findings provide essential information regarding the need for their regulation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This systematic review aimed to investigate the occurrence of phthalates (phthalic acid esters [PAEs]) in different food matrices, as well as report the main sources of PAEs in food, the potential risks to the population, and the factors that influence its migration from food contact materials (FCMs) to food. Nineteen PAEs were identified, including di-(2-ehtylhexyl) phthalate (DEHP), dibutyl-phthalate (DBP), benzylbutyl phthalate (BBP), diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP) in fruits and vegetables, milk and dairy products, cereals, meat, fish, fat and oils, snacks, condiments and sauces, miscellaneous, and baby food. Fifty-seven values of PAEs were above the legal limits of countries. DEHP is the PAE with the highest incidence, with maximum concentrations above the specific migration limit (SML) for milk and dairy products, oils and fats, fish, cereals, condiments and sauces, meat, and fruits and vegetables. The risk of exceeding the tolerable daily intake (TDI) was high for DEHP and DBP in fish, fat and oils, cereals, and milk and dairy products for children and adults. Fat and oils are the most critical food for DEHP, DBP, BBP, and DINP. Comparing the estimated daily intake (EDI) with the TDI, there was a risk for "milk and dairy products" in adults and for "cereal and cereal products" in children concerning DEHP. "Cereal and cereal products" presented a risk in children and adults concerning DBP. The "fat and oils" category presented a risk in children and adults about DBP and DINP. Temperature, contact time between food and the FCM, fat percent, and acidity positively correlate with the PAE's migration. The contamination occurs in many steps of the production chain., (© 2023 Institute of Food Technologists®.)

Di-(2-ethylhexyl) phthalate (DEHP) is among the most widely used plasticizers in plastic production, which has been detected in various environments. However, DEHP safety remains poorly known. Using zebrafish models, the effects of DEHP on the angiogenesis and hematopoiesis, and the underlying mechanism, were studied. Transgenic zebrafish embryos with specific fluorescence of vascular endothelial cells, myeloid cells, or hematopoietic stem cells were exposed to 0, 100, 150, 200, or 250 nM of DEHP for 22, 46 or 70 h, followed by fluorescence observation, endogenous alkaline phosphatase activity measurement, erythrocyte staining, and gene expression analysis by quantitative PCR and whole mount in situ hybridization. High DEHP concentrations decreased the sprouting rate, average diameter, and length, and the expansion area of the vessels lowered the EAP activity and suppressed the vascular endothelial growth factor (vegf) and hematopoietic marker genes, including c-myb, hbae1, hbbe1, and lyz expressions. DEHP treatment also decreased the number of hematopoietic stem cells, erythrocytes, and myeloid cells at 24 and 72 hpf. These DEHP-induced angiogenetic and hematopoietic defects might be alleviated by vegf overexpression. Our results reveal a plausible mechanistic link between DEHP exposure-induced embryonic angiogenetic defect and hematopoietic impairment., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Several plasticizing chemicals induce endocrine disrupting effects in humans, and the indoor environment is suggested to be a source of exposure. As children are particularly vulnerable to the effects from exposure to endocrine disrupting chemicals (EDCs), it is essential to monitor exposure to EDCs such as phthalates and non-phthalate plasticizers in indoor environments intended for use by children. The aim of this study was to assess everyday plasticizer exposure among preschool-aged children in Sweden by measuring urinary plasticizer metabolite concentrations. In addition, it was investigated whether the concentrations would be altered as a result of the children spending part of the day at preschool, in comparison with weekend exposure, when they may spend more time in home environments or engage in various weekend and leisure activities. For this purpose, fourteen metabolites from eight phthalates (di-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP; di-isobutyl phthalate, DiBP; butyl-benzyl phthalate, BBzP; di-iso-nonyl phthalate, DiNP; di-propylheptyl phthalate, DPHP; di-iso-decyl phthalate, DiDP; and di-ethyl phthalate, DEP) and one non-phthalate plasticizer (di-isononyl cyclohexane 1,2-dicarboxylate, DiNCH) were measured in 206 urine samples collected at four occasions, i.e. twice during the winter and twice during the spring from 54 children (mean 5.1 years, SD 0.94) enrolled at eight preschools in Sweden. A detection frequency (DF) of 99.9% for the 14 metabolites indicates a widespread exposure to plasticizers among children in Sweden. Compared to previous Swedish and international studies performed during approximately the same time period, high urinary concentrations of monobenzyl phthalate (MBzP), a metabolite from the strictly regulated BBzP, were measured in this study (median 17 ng/mL). Overall, high urinary phthalate metabolite concentrations were observed in this study compared to the US CDC-NHANES from the same time period and similar age-group. Compared to European studies, however, similar concentrations were observed for most metabolites and the urinary concentrations from few participating children exceeded the human biomonitoring guidance values (HBM-GV) for children. After days with preschool attendance, lower urinary concentrations of metabolites originating from DEP and phthalates that are strictly regulated within the EU REACH legislation (DEHP, DnBP, and DiBP) and higher concentrations of metabolites originating from DiNP, DPHP, and DiDP, i.e. less or non-regulated phthalates were found compared the urinary concentrations of these metabolites in weekends. This may indicate that factors in the indoor environment itself are important for the extent of the plasticizer exposure. All the analyzed metabolites were measured in lower concentrations in urine collected from children attending preschools built or renovated after the year 2000, while no seasonal differences were observed in this study., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

We recently showed that chronic exposure of adult male mice to environmental doses of DEHP alone or in a phthalate mixture altered blood brain barrier integrity and induced an inflammatory profile in the hippocampus. Here, we investigate whether such exposure alters hippocampus-dependent behavior and underlying cellular mechanisms. Adult C57BL/6 J male mice were continuously exposed orally to the vehicle or DEHP alone (5 or 50 μg/kg/d) or to DEHP (5 μg/kg/d) in a phthalate mixture. In the Morris water maze, males showed reduced latencies across days to find the platform in the cue and spatial reference memory tasks, regardless of their treatment group. In the probe test, DEHP-50 exposed males displayed a higher latency to find the platform quadrant. In the temporal order memory test, males exposed to DEHP alone or in a phthalate mixture were unable to discriminate between the most recently and previously seen objects. They also displayed reduced ability to show a preference for the new object in the novel object recognition test. These behavioral alterations were associated with a lowered dendritic spine density and protein levels of glutamate receptors and postsynaptic markers, and increased protein levels of the presynaptic synaptophysin in the hippocampus. Metabolomic analysis of the hippocampus indicated changes in amino acid levels including reduced tryptophan and L-kynurenine and elevated NAD + levels, respectively, a precursor, intermediate and endproduct of the kynurenine pathway of tryptophan metabolism. Interestingly, the protein amounts of the xenobiotic aryl hydrocarbon receptor, a target of this metabolic pathway, were elevated in the CA1 area. These data indicate that chronic exposure of adult male mice to environmental doses of DEHP alone or in a phthalate mixture impacted hippocampal function and structure, associated with modifications in amino acid metabolites with a potential involvement of the kynurenine pathway of tryptophan metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bis(2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been massively used since the second part of the twentieth century by the plastic industry to provide softness properties to PVC. This chemical is considered as toxic to reproduction and endocrine disrupting, and a wide range of uses are now forbidden by the EU. Despite these regulations, DEHP is still found to be a widespread contaminant in watersheds in the EU. In this study, we calculate retrospective and prospective scenarios of past and future emissions of DEHP in the environment (water, soil, air) in the EU 28, taking into account the entire lifecycle of the substance, from its production and its inclusion in polymer (mainly PVC) and non-polymer products (adhesive and sealant, ceramic and printing ink) to the recycling and end of life of these products. We develop a stock and flow model based on dynamically estimating the stocks of DEHP present in products on the market. Our results show that the introduction of recent regulations to limit the use of DEHP (that bring a 70% reduction of DEHP contained in products placed on the market in 2020 and 75% in 2040) will not reduce significantly future emissions. This persistence of emissions is explained by the high stocks built in the economy and the long-term presence of soft PVC waste in landfills. Our results suggest that DEHP will remain a cause of environmental contamination many decades after uses have declined and even ceased, and it appears to be too late for market regulation at the market stage to offset the effect of past stock buildup and landfilling. It is likely that several chemicals that are not considered as persistent and therefore not the focus of international regulations could exhibit the same characteristics. Regulations should avoid possible use patterns that make hazardous chemicals persistent in products, because they have the potential to create long-term and almost irreversible environmental pollution and impacts., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: DEHP, di(2-ethylhexyl) phthalate, is the most common member of the class of ortho-phthalates, which are used as plasticizers. The Medical Device Regulation has restricted the use of phthalates in medical devices. Also DEHP has been added to the Annex XIV of REACH, "Registration, Evaluation, Authorisation and Restriction of Chemicals" due to its endocrine disrupting properties to the environment. As such, the sunset date for commercialisation of DEHP-containing blood bags is May 27 th 2025. There are major concerns in meeting this deadline as these systems have not yet been fully validated and/or CE-marked. Also, since DEHP is known to affect red cell quality during storage, it is imperative to transit to non-DEHP without affecting blood product quality. Here, EBA members aim to establish common grounds on the evaluation and assessment of blood components collected, prepared and stored in non-DEHP devices., Materials and Methods: Based on data as well as the input of relevant stakeholders a rationale for the validation of each component was composed., Results: The red cell components will require the most extensive validation as their quality is directly affected by the absence of DEHP, as opposed to platelet and plasma components., Conclusion: Studies in the scope of evaluating the quality of blood products obtained with non-DEHP devices, under the condition that they are carried out according to these recommendations, could be used by all members of the EBA to serve as scientific support in the authorization process specific to their jurisdiction or for their internal validation use., (© 2022 International Society of Blood Transfusion.)

Di (2-ethylhexyl) phthalate (DEHP), di-ethyl phthalate (DEP) and di-isononyl phthalate (DINP) are all endocrine disrupting chemicals (EDCs) for organisms. However, little research has been done on the effects of long-term EDC exposure. The present study found that the zebrafish barely grew during the 7 months of DINP exposure. The fecundity rate (%) of female spawning was lower in the DEHP treatment by 4 months compared to other exposure groups. Zebrafish treated with 12.5-25.0 ppm of DEP for 4 months presented no spawning. Gonadal-somatic index (GSI) levels significantly decreased, and there were more oocytes in the atresia and peri-nucleus stage compared to the control group. In addition, the hatching rate of embryos were 71.02%, 56.92%, and 21.70% for females treated with DINP, DEHP and DEP, respectively. There were also abnormal craniofacial chondrogenesis development on 72 hpf embryos upon females treated with the three EDCs. In conclusion, long term exposure of DEHP, DINP, and DEP did not only affect the reproductive capacity of female zebrafish, but the 3 plasticizers also influence craniofacial cartilage development of its offspring., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices (PMDs), was restricted in PMDs due to adverse health effects, being gradually replaced by alternative plasticizers (APs). Parenteral nutrition (PN), essential in the care for premature neonates in the neonatal intensive care unit, is stored in plastic storage bags and administered intravenously through plastic infusion circuits. We investigated to which extent PN contributes to current phthalate and AP exposure in premature neonates. First, we showed that DEHP and several APs are present in relevant amounts in PMDs used for neonatal PN administration. Secondly, ex vivo experiments mimicking clinical PN administration showed that lipid emulsions contained significant concentrations of DEHP and several APs (ATBC, TOTM, DEHT & DEHA), while hardly any plasticizers were detected in non-lipid solutions. ATBC leached from infusion circuits, while lipid emulsions were the major source for DEHP, TOTM, DEHT, and DEHA. PN administration resulted in estimated daily exposures of 13.9 µg/kg/d DEHP and 95.7 µg/kg/d ATBC in premature neonates, below their respective reference doses. Our data indicate that premature neonates requiring PN are still exposed to DEHP, as well as to a range of APs, making it a target for reduction of harmful plasticizer exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

It is difficult to dispose diethylhexyl phthalate-rich polyvinyl chloride (DEHP-rich PVC) waste due to the high level of chlorine and plasticizer. On the other hand, the denitrification of urine wastewater with high nitrogen content also faces great challenges. In this study, a synergistic treatment strategy was developed for the DEHP-rich PVC waste and urine wastewater by a subcritical water process. Subcritical urine wastewater (SUW) was used as a reaction medium in the synergistic treatment. PVC dechlorination, DEHP decomposition, and denitrification of urine wastewater were synchronously achieved in the one pot SUW. Under the optimal conditions (300 °C, 15 min, 1:5 g/mL), the PVC dechlorination ratio, urine wastewater denitrification ratio and DEHP decomposition ratio could reach 98.4%, 64.9%, and 99.2%, respectively. The decomposition of DEHP mainly included hydrolysis, nucleophilic substitution, and acylation. DEHP could be converted into phthalic acid crystal at 220 °C with a yield of 66.25% due to the efficient hydrolysis action of SUW. All the removed Cl was transferred from PVC matrix to aqueous phase. Hydroxyl nucleophilic substitution is the principal dechlorination path of PVC. The reactions between N-containing species and DEHP in SUW resulted in the high-efficiency denitrification of urine wastewater, and the N element was fixed in solid residue or transferred to oil phase as amides compounds. It is believed that the proposed SUW process is a promising technology for the synergistic treatment of DEHP-rich PVC waste and urine wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Di-(2-ethylhexyl) phthalate (DEHP) is an extensively used and toxic phthalate plasticizer that is widely reported in marine environments. Degradation of DEHP by bacteria from several environments have been studied, but little is known about marine sediment bacteria that can degrade DEHP and other phthalate plasticizers. Therefore, in this study, we enriched a bacterial consortium C10 that can degrade four phthalate plasticizers of varying alkyl chain lengths (DEHP, dibutyl phthalate, diethyl phthalate, and dimethyl phthalate) from marine sediment. The major bacterial genera in C10 during degradation of the phthalate plasticizers were Glutamicibacter, Ochrobactrum, Pseudomonas, Bacillus, Stenotrophomonas, and Methylophaga. Growth of C10 on DEHP intermediates (mono-ethylhexyl phthalate, 2-ethylhexanol, phthalic acid, and protocatechuic acid) was studied and these intermediates enhanced the Brevibacterium, Ochrobactrum, Achromobacter, Bacillus, Sporosarcina, and Microbacterium populations. Using a network-based approach, we predicted that Bacillus, Stenotrophomonas, and Microbacterium interacted cooperatively and were the main degraders of phthalate plasticizers. Through selective isolation techniques, we obtained twenty isolates belonging to Bacillus, Microbacterium, Sporosarcina, Micrococcus, Ochrobactrum, Stenotrophomonas, Alcaligenes, and Cytobacillus. The best DEHP-degraders were Stenotrophomonas acidaminiphila OR13, Microbacterium esteraromaticum OR16, Sporosarcina sp. OR19, and Cytobacillus firmus OR20 (83.68%, 59.1%, 43.4%, and 40.6% degradation of 100 mg/L DEHP in 8 d), which agrees with the prediction of key degraders. This is the first report of DEHP degradation by all four bacteria and, thus, our findings reveal as yet unknown PAE-degradation capabilities of marine sediment bacteria. This study provides insights into how bacterial communities adapt to degrade or resist the toxicities of different PAEs and demonstrates a simple approach for the prediction and isolation of potential pollutant degraders from complex and dynamic bacterial communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Plastic ingestion is a problem for seabirds worldwide. In addition to direct health effects such as obstruction or perforation of the gastrointestinal tract, plastic ingestion can also lead to indirect health effects through the release of chemicals that may be absorbed and cause systemic and chronic toxicity. Among chemicals that can be released by plastics are phthalate esters, a group of chemicals widely used as plasticizers or additives to change the physical characteristics of plastics. In this study, three phthalate esters, dimethyl phthalate (DMP), dibuthyl phthalate (DBP), and diethylhexyl phthalate (DEHP), were quantified in the uropygial gland of 48 seabirds from 16 species collected ashore in a tropical region, the coast of Espírito Santo, Eastern Brazil. Including trace levels, DMP was detected in 16 birds (33%) from 10 species, with an average concentration of 0.014 ± 0.005 ng/µl (mean ± SD for individuals with concentrations above the practical level of detection of 0.01 ng/µl). DBP was detected in 15 birds (31%) from 11 species, with an average concentration of 0.049 ± 0.032 ng/µl. DEHP was detected in 21 birds (44%) from 11 species, with an average concentration of 0.115 ± 0.105 ng/µl. DMP concentration in the uropygial gland was positively associated with the presence, number, and mass of plastic items in the upper digestive tract. However, no such relationship was noted for DBP nor DEHP, suggesting the concentration of phthalate compounds in the uropygial gland might not always serve as a reliable proxy for plastic ingestion. In spite of relatively high frequencies of detection, the low concentrations of phthalates detected in this study suggest levels of exposure below known toxicity thresholds. Further studies on the potential adverse effects of phthalate exposure in seabirds are necessary, especially on the reproductive development of embryos and chicks.

Plasticizers containing phthalates have the potential to alter endocrine function in vertebrates. While non-phthalate plasticizers were previously considered to be environmentally friendly and safe, our research team discovered that bis-(2-ethylhexyl) adipate (DEHA) and acetyl tributyl citrate (ATBC) disrupt thyroid hormones in Japanese medaka ( Oryzias latipes ). We assessed reproductive- and estrogen-responsive gene expression patterns in Japanese medaka to determine whether the phthalate plasticizers bis-(2-ethylhexyl) phthalate (DEHP, positive control) and the non-phthalate plasticizers DEHA and ATBC disrupt endocrine signaling. The results showed that the levels of choriogenin H ( chgH ) and vitellogenin ( vtg ) genes increased after exposure to DEHP and ATBC, suggesting that these plasticizers may have estrogenic activity. Exposure to DEHP and DEHA resulted in the upregulation of kisspeptin ( kiss ), gonadotropin-releasing hormone ( gnrh ), and follicle-stimulating hormone beta ( fshβ ) genes, suggesting that these plasticizers may interfere with reproductive function. To the best of our knowledge, this is the first study to demonstrate that the non-phthalate plasticizers DEHA and ATBC can disrupt reproduction-related hormonal activity in fish.

Phthalates are organic pollutants frequently detected in the environment. The effects of these substances on male reproduction have been extensively studied but their potential impact on female reproductive behaviors in particular at environmental doses still remains to be documented. In the present study, we examined the effects of chronic exposure to di (2-ethylhexyl) phthalate (DEHP) alone at 5 or 50 μg/kg/d, or in an environmental phthalate mixture on maternal behavior of lactating female mice after a first (primiparous) and a second gestation (multiparous). Exposure of DEHP alone or in a phthalate mixture reduced pup-directed behaviors, increased self-care and forced nursing behaviors and altered nest quality for both primiparous and multiparous dams. In pup-retrieval test, primiparous and multiparous dams exposed to DEHP alone or in a phthalate mixture retrieved their pups more rapidly, probably due to a higher emission of ultrasonic vocalizations by the pups. At lactational day 2 following the third and last gestational period, the neural circuitry of maternal behavior was analyzed. A lower number of oxytocin-immunoreactive neurons in the paraventricular and anterior commissural nuclei was found in dams exposed to DEHP alone or in a phthalate mixture, while no changes were observed in the number of arginine-vasopressin immunoreactive cells. In the medial preoptic area, exposure to DEHP alone or in a phthalate mixture reduced ERα-immunoreactive cell number. Dendritic spine density assessed for DEHP at 5 μg/kg/d was also reduced. Thus, exposure to DEHP alone or in a phthalate mixture altered maternal behavior probably through a neuroendocrine mode of action involving oxytocin and estrogen through ERα, key pathways necessary for neuroplasticity and behavioral processing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Microplastic (MP) ingestion, along with accumulated plasticizers such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and phthalates represented by diethyl phthalate (DEP), dibutyl phthalate (DBP) and bis (2-ethylhexyl) phthalate (DEHP), were quantified in bivalves, fish, and holothurians collected from a coastal pristine area at the western Mediterranean Sea. MP ingestion in sediment-feeders holothurians (mean value 12.67 ± 7.31 MPs/individual) was statistically higher than ingestion in bivalves and fish (mean 4.83 ± 5.35 and 3 ± 4.44 MPs/individual, respectively). The main ingested polymers were polyethylene, polypropylene, and polystyrene. The levels of BPS, BPF, and DEHP were highest in bivalves' soft tissue; BPA and DBP had the highest levels in the holothurians' muscle. In addition, the levels of all plasticizers assessed were lowest in fish muscle; only BPA levels in fish were higher than in bivalves, with intermediate values between those of bivalves and holothurians. This study provides data on exposure to MPs and plasticizers of different species inhabiting Cabrera Marine Protected Area (MPA) and highlights the differences in MP ingestion and levels of plasticizers between species with different ecological characteristics and feeding strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Phthalate esters (PEs) one of the widely used plasticizers, and are known for their environmental contamination and endocrine disruption. Hence, it is important to study their distribution in a riverine environment. This study was aimed to determine the Spatio-temporal trends of 16 PEs in surface water, sediment and fish from rivers in southern India, and to assess their environmental health risks. Phthalates were quantified in all matrices with the mean concentrations (∑ 16 PEs) in water, sediment and fish as 35.6 μg/L, 1.25 μg/kg and 17.0 μg/kg, respectively. The Kaveri River is highly loaded with PEs compared to the Thamiraparani and Vellar Rivers. PEs such as DBP, DEHP, DCHP and DiBP were most frequently detected in all matrices, and at elevated concentrations in the dry season. The risk quotient (RQ < 1) suggests that the health risk of PEs from river water and fish to humans is negligible. However, DBP and DEHP from the Kaveri River pose some risk to aquatic organisms (HQ > 1). DEHP from the Vellar River may pose risks to algae and crustaceans. Non-priority phthalate (DiBP) may pose risks to Kaveri and Vellar River fish. The bioaccumulation factor of DCHP and DEHP was found to be very high in Sardinella longiceps and in Centropristis striata, and also exceeded the threshold limit of 5000 suggesting that PEs in the riverine environment may pose some health concerns. This is the first study to assess the spatio-temporal distribution, riverine flux and potential ecological effects of 16 PEs from the southern Indian Rivers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Phthalate esters (PAEs) are fat soluble synthetic chemicals, usually regarded as plasticizers for being added in numerous plastic products. Thus, environmental and health hazards of PAEs are associated with increasing plastic pollution. In this study, PAEs from sludge samples collected from water, sewage, and industrial treatment plants (N = 17) were analyzed using Gas Chromatography/Mass Spectrometry. Microplastics (MPs) were also quantified and correlated with PAEs. Results showed the highest average PAE concentrations in sewage treatment plants. The greatest ΣPAEs concentration were found in sewage treatment plant (STP4) with 32,414 μg/kg dw, while the lowest found in water treatment plant (WTP3) with 2062 μg/kg dw. Among different PAEs, di-(2-ethyl hexyl) phthalate (DEHP) contributes the highest. Similarly, DEHP, di-n-octyl phthalate (DnOP) and diisononyl phthalate (DiNP) significantly correlated with the total PAEs indicating their large contribution to sludge contamination. The abundance of microplastics in sludge ranged between 1 and 7 MP/g, highest at ITP6, but not detected in some stations. While microplastics may potentially increase PAEs, there was no significant relationship between ΣPAEs and MP abundance. The estimated human daily intake of DEHP and di-n-butyl phthalate (DnBP) when contaminated sludge be used showed low toxicological risks to exposed adults. This research presents the sludge characteristics, PAEs, and microplastic concentrations in different wastewater treatment plants in Taiwan. PAE contamination was highly contributed by domestic and industrial wastes shown by their significant amounts in STP and ITP. Results further provide evidence for potential sludge recycling (WTP sludge) and application to soil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pollution of water bodies with plasticizers is a serious environmental problem worldwide. In this study, we investigated the effects of plasticizers bis-(2-ethylhexyl) phthalate (DEHP) and bis-(2-ethylhexyl) adipate (DEHA) in Japanese medaka (Oryzias latipes). DEHP significantly increased the expression of all the genes tested: thyroid stimulating hormone beta subunit (tshβ-like), tshβ, deiodinase 1 (dio1), deiodinase 2 (dio2), and thyroid hormone receptor alpha (trα) and beta (trβ). However, DEHA only significantly increased tshβ at 7.4 µg/L but significantly decreased dio2 expression at 25.8, 111.1, and 412.6 4 µg/L, while other genes were not significantly affected. Both chemicals reduced eye size and total body length, but did not affect embryo development, hatching time and rate, and swimming performance. DEHA alone affected swim bladder inflation and not DEHP. This is the first report that not only DEHP but also DEHA disrupt thyroid hormone activity in fish. DEHP contamination (13.2 μg/L) was detected in tap water from Kobe, Japan; thus, tap water itself may disrupt thyroid hormone activity in Japanese medaka. Importantly, the effective concentration of DEHP for thyroid hormone-related gene expression and growth was close to or lower than DEHP concentrations reported in surface water elsewhere, indicating that DEHP contamination is a serious aquatic pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

The incidence of thyroid cancer (TC) has increased considerably in the last few decades. Environmental factors, including plasticizers, are recognized as potential risks leading to thyroid cancer in humans. In this study, we used a transcriptome-metabolome-wide association study to find the unidentified carcinogenic mechanism of di-2-ethylhexyl phthalate (DEHP) in thyroid and biomarkers for non-invasive diagnosis. Rats were treated with different doses of DEHP (0, 0.3, 3, 30, 150 mg DEHP/kg bw/day) for 13 weeks. Then, the thyroids were processed for Ki67 staining and RNA-seq. Also, 17-h urine samples were collected for high-resolution metabolomics analysis. After a high dose of DEHP exposure, the terminal body weights and the thyroid and parathyroid glands weights were not altered. However, the liver weights and numbers of Ki67-positive cells were increased. Further, multivariate statistical analysis revealed that metabolic shifts were considerably altered above 30 mg DEHP/kg bw/day. In RNA-seq analysis, some cancer-related genes were altered, including 18 upregulated and 9 downregulated transcripts. These cancer transcripts and whole metabolome data were integrated to uncover thyroid cancer-related metabolic pathways, which revealed that cancer-related transcripts had a network structure linked to eicosanoids such as leukotriene D4 and prostaglandin. In brief, our study demonstrated that DEHP can induce thyroid hyperplasia through the eicosanoid-associated pathway, providing further insight into the mechanism of DEHP-associated thyroid cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Plastics are widely used as packaging and engineering materials in feed processing, which leads to the potential contamination of plasticizers and microplastics (MPs) in animal feeds. In this study, the concentrations of two typical MPs, i.e., polyethylene terephthalate (PET) and polycarbonate (PC), and seven phthalates (PAEs) as well as their corresponding monoester metabolites (mPAEs) in 45 pig feed samples in China were analyzed by mass spectrometers. Among PAEs, dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) were detected in all samples, and DEHP showed the highest concentrations of 8.26-2464 μg/kg, which accounted for 65.6% of the total detected PAEs. PET MPs (

Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12-17) and 300 from young adults (aged 18-37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 μg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 μg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5-6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2-3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Di-ethyl-hexyl-phthalate (DEHP) is currently the main plasticizer used for whole blood collection systems. However, in Europe, after May 2025, DEHP may no longer be used above 0.1% (w/w) in medical devices. DEHP stabilizes red cell membranes, thereby suppressing haemolysis during storage. Here we compared in vitro quality parameters of red cell concentrates (RCCs) collected and stored in DEHP-, DINCH- or DINCH/BTHC-PVC hybrid blood bags with saline-adenine-glucose-mannitol (SAGM) or phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) storage solution. Last, we performed haemovigilance surveillance for RCC collected in DINCH-PVC and stored in PAGGSM/BTHC-PVC., Materials and Methods: In vitro quality parameters of RCC were determined during 42 days of storage. Haemovigilance surveillance was conducted to compare the frequency and type of transfusion reaction., Results: Haemolysis levels were increased in SAGM/BTHC-PVC as compared to SAGM/DEHP-PVC (0.66% ± 0.18% vs. 0.36% ± 0.17%). PAGGSM storage solution was able to adequately suppress haemolysis to levels observed during storage in SAGM/DEHP-PVC, both in BTHC-PVC (0.38% ± 0.12%), and to a slightly lesser extent in DINCH-PVC (0.48% ± 0.17%). A total of 1650 PAGGSM/BTHC-PVC and 5662 SAGM/DEHP-PVC RCC were transfused yielding a transfusion reaction frequency of 0.24% (95% CI 0.0000-0.0048) and 0.44% (95% CI 0.0027-0.0061) respectively., Conclusion: The in vitro quality of RCC stored in PAGGSM/BTHC-PVC and SAGM/DEHP-PVC is comparable. There is no indication that transfusion of erythrocytes stored in PAGGSM/BTHC-PVC results in increased transfusion reaction frequency. These initial results provide a basis for further clinical evaluation to narrow down the confidence interval of transfusion reaction frequency., (© 2022 International Society of Blood Transfusion.)

Background: Phthalates are widespread, anti-androgenic chemicals known to alter early development, with possible impact on puberty timing., Aim: To investigate the association of prenatal phthalate exposure with pubertal development in boys and girls., Methods: Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP) and non-phthalate plasticizer DINCH® were quantified in two urine samples collected during pregnancy from mothers participating in the INMA Spanish cohort study. Pubertal assessment of their children at age 7-10 years (409 boys, 379 girls) was conducted using the parent-reported Pubertal Development Scale. Modified Poisson and Weighted Quantile Sum (WQS) regression was employed to examine associations between prenatal phthalates and risk of puberty onset, adrenarche, and gonadarche. Effect modification by child weight status was explored by stratified analysis., Results: Prenatal exposure to DEHP was associated with higher risk of puberty onset (relative risk [RR] = 1.32, 95% CI = 1.09-1.59 per each log-unit increase in concentrations) and gonadarche (RR = 1.23, 95% CI = 1.00-1.50) in boys and higher risk of adrenarche (RR = 1.25, 95% CI = 1.03-1.51) in girls at age 7-10 years. In boys, prenatal exposure to DEP, DnBP, and DEHP was also associated with higher risk of adrenarche or gonadarche (RRs = 1.49-1.80) in those with normal weight, and BBzP and DINCH® exposure with lower risk of adrenarche (RR = 0.49, 95% CI = 0.27-0.89 and RR = 0.47, 95% CI = 0.24-0.90, respectively) in those with overweight/obesity. In girls, DiBP, DnBP, and DINCH® were associated with slightly higher risk of gonadarche (RRs = 1.14-1.19) in those with overweight/obesity. In the WQS model, the phthalate mixture was not associated with puberty in boys or girls., Conclusion: Prenatal exposure to certain phthalates was associated with pubertal development at age 7-10 years, especially earlier puberty in boys with normal weight and girls with overweight/obesity. However, there was no evidence of effect of the phthalate mixture on advancing or delaying puberty in boys or girls., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The occurrence of thirty-nine contaminants including plasticizers, bisphenols, and flame retardants in potable water from Montreal and South Africa was analyzed to determine their presence and concentrations in different water sources. In Montreal, five bottled water (BW) brands and three drinking water treatment plants (DWTP) were included. In South Africa, water was sampled from one urban DWTP located in Pretoria, Gauteng, and one rural DWTP located in Vhembe, along with water from the same rural DWTP which had been stored in small and large plastic containers. A combination of legacy compounds, typically with proven toxic effects, and replacement compounds was investigated. Bisphenols, Dechlorane-602, Dechlorane-603, and s-dechlorane plus (s-DP) were not detected in any water samples, and a-dechlorane plus (a-DP) was only detected in one sample from Pretoria at a concentration of 1.09 ng/L. Lower brominated polybrominated diphenyl ethers (PBDE)s were detected more frequently than higher brominated PBDEs, always at low concentrations of <2 ng/L, and total PBDE levels were statistically higher in South Africa than in Montreal. Replacement flame retardants, organophosphate esters (OPEs), were detected at statistically higher concentrations in Montreal's BW (68.56 ng/L), drinking water (DW) (421.45 ng/L) and Vhembe (198.33 ng/L) than legacy PBDEs. Total OPE concentrations did not demonstrate any geographical trend; however, levels were statistically higher in Montreal's DW than Montreal's BW. Plasticizers were frequently detected in all samples, with legacy compounds DEHP, DBP, and replacement DINCH being detected in 100 % of samples with average concentrations ranging from 6.89 ng/L for DEHP in Pretoria to 175.04 ng/L for DINCH in Montreal's DW. Total plasticizer concentrations were higher in Montreal than in South Africa. The replacement plasticizers (DINCH, DINP, DIDA, and DEHA) were detected at similar frequencies and concentrations as legacy plasticizers (DEHP, DEP, DBP, MEHP). For the compounds reported in earlier studies, the concentrations detected in the present study were similar to other locations. These compounds are not currently regulated in drinking water but their frequent detection, especially OPEs and plasticizers, and the presence of replacement compounds at similar or higher levels than their legacy compounds demonstrate the importance of further investigating the prevalence and the ecological or human health effects of these compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe substitutes gained importance. Focusing on the master regulator of adipogenesis and adipose tissue functionality, the peroxisome proliferator-activated receptor gamma (PPARγ), we evaluated 20 alternative plasticizers as well as their metabolites for binding to and activation of PPARγ and assessed effects on adipocyte lipid accumulation. Among several compounds that showed interaction with PPARγ, the metabolites MINCH, MHINP, and OH-MPHP of the plasticizers DINCH, DINP, and DPHP exerted the highest adipogenic potential in human adipocytes. These metabolites and their parent plasticizers were further analyzed in human preadipocytes and mature adipocytes using cellular assays and global proteomics. In preadipocytes, the plasticizer metabolites significantly increased lipid accumulation, enhanced leptin and adipsin secretion, and upregulated adipogenesis-associated markers and pathways, in a similar pattern to the PPARγ agonist rosiglitazone. Proteomics of mature adipocytes revealed that both, the plasticizers and their metabolites, induced oxidative stress, disturbed lipid storage, impaired metabolic homeostasis, and led to proinflammatory and insulin resistance promoting adipokine secretion. In conclusion, the plasticizer metabolites enhanced preadipocyte differentiation, at least partly mediated by PPARγ activation and, together with their parent plasticizers, affected the functionality of mature adipocytes similar to reported effects of a high-fat diet. This highlights the need to further investigate the currently used plasticizer alternatives for potential associations with obesity and the metabolic syndrome., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Di(2-ethylhexyl) phthalate (DEHP) must be removed from blood bag sets in Europe by 27 May 2025. DEHP is known to interact with the red blood cell (RBC) membrane, resulting in reduced haemolysis and thus prolonging shelf-life. Current non-DEHP alternatives result in increased haemolysis requiring reconsideration of the RBC shelf-life. Although the immediate impact of eliminating DEHP is to the European community, the non-DEHP movement could affect blood bag set availability globally. The purpose of this survey is to understand blood centre readiness regarding the transition to non-DEHP blood collection and storage systems., Materials and Methods: A 24-question on-line survey was completed by members of the Biomedical Excellence for Safer Transfusion Collaborative research network., Results: Responses were obtained from 16 blood collection or processing institutions. A majority of respondents (12/16) indicated that both shelf-life and haemolysis were equally important in selecting non-DEHP blood bag sets. Six respondents would accept a lower RBC product shelf-life compared to current practice. Respondents were not clear on the best non-DEHP vinyl material or RBC storage solution. Three European blood centres indicated they have developed non-DEHP transition plans. One challenge identified regarding the transition to non-DEHP is the extensive validation testing that will be required., Conclusion: Blood centres in Europe are concerned with meeting the sunset date for DEHP, considering that limited non-DEHP blood bag and RBC storage solutions are currently available. Banning DEHP in Europe, which may have global ramifications, represents a major challenge not yet fully understood by the transfusion medicine community., (© 2022 International Society of Blood Transfusion.)

Background: Fast food consumption is associated with biomarkers of ortho-phthalates exposures. However, the chemical content of fast food is unknown; certain ortho-phthalates (i.e., di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP)) have been phased out and replaced with other plasticizers (e.g., dioctyl terephthalate (DEHT))., Objective: We conducted a preliminary study to examine ortho-phthalate and replacement plasticizer concentrations in foods and food handling gloves from U.S. fast food restaurants., Methods: We obtained hamburgers, fries, chicken nuggets, chicken burritos, cheese pizza (n = 64 food samples) and gloves (n = 3) from restaurants and analyzed them for 11 chemicals using gas chromatography mass spectrometry., Results: We found DEHT at the highest concentrations in both foods (n = 19; median = 2510 µg/kg; max = 12,400 µg/kg) and gloves (n = 3; range: 28-37% by weight). We detected DnBP and DEHP in 81% and 70% of food samples, respectively. Median DEHT concentrations were significantly higher in burritos than hamburgers (6000 µg/kg vs. 2200 µg/kg; p < 0.0001); DEHT was not detected in fries. Cheese pizza had the lowest levels of most chemicals., Significance: To our knowledge, these are the first measurements of DEHT in food. Our preliminary findings suggest that ortho-phthalates remain ubiquitous and replacement plasticizers may be abundant in fast food meals., Impact Statement: A selection of popular fast food items sampled in this study contain detectable levels of replacement plasticizers and concerning ortho-phthalates. In addition, food handling gloves contain replacement plasticizers, which may be a source of food contamination. These results, if confirmed, may inform individual and regulatory exposure reduction strategies., (© 2021. The Author(s).)

Background and Objectives: Di(2-ethylhexyl) phthalate (DEHP) is a toxic plasticizer that is commonly used in the manufacture of polyvinyl chloride (PVC) blood bags. It is well known that DEHP can migrate from a medical device into the blood plasma. For safety reasons, pathogens in plasma must be inactivated; however, this process may increase DEHP migration. Here, we assessed the impact of illumination-based pathogen inactivation on the migration of DEHP from PVC bags into plasma., Materials and Methods: Pairs of native PVC-DEHP plasma bags were pooled. Each pool was then split into a pathogen-inactivated bag and a control bag. After illumination, the plasma concentrations of DEHP and its main metabolite (mono(2-ethylhexyl) phthalate, MEHP) in each bag were assayed and compared using liquid chromatography-tandem mass spectrometry. Concentrations were evaluated in repeated-measures, two-way analyses of variance., Results: The MEHP concentration was significantly associated with storage but not with illumination (p = 0.0001). The DEHP concentration stayed constant throughout the storage period. The DEHP equivalent concentration (corresponding to the overall plasticizer migration rate into plasma) was not significantly associated with illumination (p = 0.3) or storage (p = 0.09; mean ± standard deviation of the mean DEHP concentration for all conditions: 147.9 ± 11.3 μg/ml)., Conclusion: Illumination-based inactivation of pathogens in plasma did not increase the DEHP equivalent concentration, relative to control (non-inactivated) plasma., (© 2022 International Society of Blood Transfusion.)