RESUMO
Although phthalate exposure has been linked with multiple adverse pregnancy outcomes, their underlying biological mechanisms are not fully understood. We examined associations between biomarkers of phthalate exposures and metabolic alterations using untargeted metabolomics in 99 pregnant women and 86 newborns [mean (SD) gestational age = 39.5 (1.5) weeks] in the PROTECT cohort. Maternal urinary phthalate metabolites were quantified using isotope dilution high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), while metabolic profiles in maternal and cord blood plasma were characterized via reversed-phase LC-MS. Multivariable linear regression was used in metabolome-wide association studies (MWAS) to identify individual metabolic features associated with elevated phthalate levels, while clustering and correlation network analyses were used to discern the interconnectedness of biologically relevant features. In the MWAS adjusted for maternal age and prepregnancy BMI, we observed significant associations between specific phthalates, namely, di(2-ethylhexyl) phthalate (DEHP) and mono(3-carboxypropyl) phthalate (MCPP), and 34 maternal plasma metabolic features. These associations predominantly included upregulation of fatty acids, amino acids, purines, or their derivatives and downregulation of ceramides and sphingomyelins. In contrast, fewer significant associations were observed with metabolic features in cord blood. Correlation network analysis highlighted the overlap of features associated with phthalates and those identified as differentiating markers for preterm birth in a previous study. Overall, our findings underscore the complex impact of phthalate exposures on maternal and fetal metabolism, highlighting metabolomics as a tool for understanding associated biological processes. Future research should focus on expanding the sample size, exploring the effects of phthalate mixtures, and validating identified metabolic features in larger, more diverse populations.
Assuntos
Metabolômica , Ácidos Ftálicos , Humanos , Feminino , Ácidos Ftálicos/urina , Gravidez , Adulto , Porto Rico , Exposição Materna , Recém-Nascido , Sangue Fetal/química , Sangue Fetal/metabolismo , Biomarcadores/sangue , Metaboloma , Exposição AmbientalRESUMO
Phthalates, such as di-n-butyl phthalate (DBP) and di-isopentyl phthalate (DiPeP), are pollutants with a high potential for endocrine disruption. This study aimed to evaluate parameters of endocrine disruption in specimens of the Neotropical fish Rhamdia quelen exposed to DBP and DiPeP through their food. After 30 days of exposure, the fish were anesthetized and then euthanized, and blood, hypothalamus, liver, and gonads were collected. DBP caused statistically significant alterations in the serotoninergic system of males (5 and 25 ng/g) and females (5 ng/g) of R. quelen and it increased testosterone levels in females (25 ng/g). DiPeP significantly altered the dopaminergic system in females, reduced plasma estradiol levels (125 ng/g) and hepatic vitellogenin expression (25 ng/g), and changed the antioxidant system in gonads (125 ng/g). The results suggest that DBP and DiPeP may have different response patterns in females, with the former being androgenic and the latter being anti-estrogenic. These findings provide additional evidence regarding the molecular events involving DBP and DiPeP in the endocrine disruption potential in juvenile specimens of Rhamdia quelen.
Assuntos
Antioxidantes , Peixes-Gato , Dibutilftalato , Disruptores Endócrinos , Neurotransmissores , Vitelogeninas , Animais , Vitelogeninas/metabolismo , Vitelogeninas/sangue , Dibutilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Feminino , Antioxidantes/metabolismo , Masculino , Neurotransmissores/metabolismo , Poluentes Químicos da Água/toxicidade , Ácidos Ftálicos/toxicidade , Gônadas/efeitos dos fármacosRESUMO
Dienelactone hydrolase (DLH) is one of numerous hydrolytic enzymes with an α/ß-hydrolase fold, which catalyze the hydrolysis of dienelactone to maleylacetate. The DLHs share remarkably similar tertiary structures and a conserved arrangement of catalytic residues. This study presents the crystal structure and comprehensive functional characterization of a novel thermostable DLH from the bacterium Hydrogenobacter thermophilus (HtDLH). The crystal structure of the HtDLH, solved at a resolution of about 1.67â¯Å, exhibits a canonical α/ß-hydrolase fold formed by eight ß-sheet strands in the core, with one buried α-helix and six others exposed to the solvent. The structure also confirmed the conserved catalytic triad of DHLs formed by Cys121, Asp170, and His202 residues. The HtDLH forms stable homodimers in solution. Functional studies showed that HtDLH has the expected esterase activity over esters with short carbon chains, such as p-nitrophenyl acetate, reaching optimal activity at pH 7.5 and 70⯰C. Furthermore, HtDLH maintains more than 50â¯% of its activity even after incubation at 90⯰C for 16â¯h. Interestingly, HtDLH exhibits catalytic activity towards polyethylene terephthalate (PET) monomers, including bis-1,2-hydroxyethyl terephthalate (BHET) and 1-(2-hydroxyethyl) 4-methyl terephthalate, as well as other aliphatic and aromatic esters. These findings associated with the lack of activity on amorphous PET indicate that HtDLH has characteristic of a BHET-degrading enzyme. This work expands our understanding of enzyme families involved in PET degradation, providing novel insights for plastic biorecycling through protein engineering, which could lead to eco-friendly solutions to reduce the accumulation of plastic in landfills and natural environments.
Assuntos
Hidrolases de Éster Carboxílico , Estabilidade Enzimática , Especificidade por Substrato , Cristalografia por Raios X , Hidrolases de Éster Carboxílico/metabolismo , Hidrolases de Éster Carboxílico/química , Hidrolases de Éster Carboxílico/genética , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/química , Ésteres/metabolismo , Ésteres/química , Modelos Moleculares , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Conformação Proteica , Concentração de Íons de Hidrogênio , Cinética , Hidrólise , Domínio Catalítico , TemperaturaRESUMO
Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children's lung function was evaluated at ages 8-13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV1 (ß = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (ß = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV1, ß = -0.017, 95 %CI: -0.066, 0.026; FVC, ß = -0.014, 95 %CI: -0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner.
Assuntos
Pulmão , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Ácidos Ftálicos/urina , Ácidos Ftálicos/toxicidade , Feminino , Criança , México , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adolescente , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Exposição Materna/efeitos adversos , Poluentes Ambientais/urina , Poluentes Ambientais/toxicidade , Testes de Função RespiratóriaRESUMO
The concerning of plastic pollution in different ecosystems has been worsened by the widespread presence. Phthalate esters (PAEs), plasticizers found in everyday products, can migrate into the environment, especially into the oceans. Researches on their effects on cetaceans are still rare. Metabolomics helps assess perturbations induced by exposure to PAEs, which act as persistent endocrine disruptors. Four PAEs (dimethyl phthalate - DMP, diethyl phthalate - DEP, dibutyl phthalate - DBP, and di(2-ethylhexyl phthalate - DEHP) were analyzed, along with cholesterol and fatty acid profiles of P. blainvillei's blubber samples collected in southern Brazil. The study reveals pervasive contamination by PAEs - especially DEHP, present in all samples - with positive correlations between DEP content and animal size and weight, as well as between the DEHP amount and the C17:1 fatty acid. These findings will be relevant to conservation efforts aimed at this threatened species and overall marine ecosystems.
Assuntos
Golfinhos , Monitoramento Ambiental , Ésteres , Metaboloma , Ácidos Ftálicos , Poluentes Químicos da Água , Animais , Brasil , Ácidos Ftálicos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/análise , Ésteres/análise , Ésteres/metabolismo , Golfinhos/metabolismo , Tecido Adiposo/metabolismo , Dietilexilftalato/metabolismo , Plastificantes , Disruptores Endócrinos/análise , Masculino , Feminino , DibutilftalatoRESUMO
Diisopentyl phthalate (DiPeP) is primarily used as a plasticizer or additive within the production of polyvinyl chloride (PVC), and has many additional industrial applications. Its metabolites were recently found in urinary samples of pregnant women; thus, this substance is of concern as relates to human exposure. Depending upon the nature of the alcohol used in its synthesis, DiPeP may exist either as a mixture consisting of several branched positional isomers, or as a single defined structure. This article investigates the skin sensitization potential and immunomodulatory effects of DiPeP CAS No. 84777-06-0, which is currently marketed and classified as a UVCB substance, by in silico and in vitro methods. Our findings showed an immunomodulatory effect for DiPeP in LPS-induced THP-1 activation assay (increased CD54 expression). In silico predictions using QSAR TOOLBOX 4.5, ToxTree, and VEGA did not identify DiPeP, in the form of a discrete compound, as a skin sensitizer. The keratinocyte activation (Key Event 2 (KE2) of the adverse outcome pathway (AOP) for skin sensitization) was evaluated by two different test methods (HaCaT assay and RHE assay), and results were discordant. While the HaCaT assay showed that DiPeP can activate keratinocytes (increased levels of IL-6, IL-8, IL-1α, and ILA gene expression), in the RHE assay, DiPeP slightly increased IL-6 release. Although inconclusive for KE2, the role of DiPeP in KE3 (dendritic cell activation) was demonstrated by the increased levels of CD54 and IL-8 and TNF-α in THP-1 cells (THP-1 activation assay). Altogether, findings were inconclusive regarding the skin sensitization potential of the UVCB DiPeP-disagreeing with the results of DiPeP in the form of discrete compound (skin sensitizer by the LLNA assay). Additional studies are needed to elucidate the differences between DiPeP isomer forms, and to better understand the applicability domains of non-animal methods in identifying skin sensitization hazards of UVCB substances.
Assuntos
Simulação por Computador , Queratinócitos , Ácidos Ftálicos , Humanos , Queratinócitos/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Células HaCaT , Pele/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Relação Quantitativa Estrutura-Atividade , Plastificantes/toxicidade , Células THP-1 , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Linhagem CelularRESUMO
The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile accessibility to the population. New drug delivery systems (DDS) are necessary to overcome the bioavailability and toxicity related to NSAIDs. In this context, UiO-66(Zr) metal-organic framework (MOF) shows high porosity, stability, and load capacity, thus being a promising DDS. However, the adsorption and release capability for different NSAIDs is scarcely described. In this work, the biocompatible UiO-66(Zr) MOF was used to study the adsorption and release conditions of ibuprofen, naproxen, and diclofenac using a theoretical and experimental approximation. DFT results showed that the MOF-drug interaction was due to an intermolecular hydrogen bond between protons of the groups in the defect sites, (µ3 - OH, and - OH2) and a lone pair of oxygen carboxyl functional group of the NSAIDs. Also, the experimental results suggest that the solvent where the drug is dissolved affects the adsorption process. The adsorption kinetics are similar between the drugs, but the maximum load capacity differs for each drug. The release kinetics assay showed a solvent dependence kinetics whose maximum liberation capacity is affected by the interaction between the drug and the material. Finally, the biological assays show that none of the systems studied are cytotoxic for HMVEC. Additionally, the wound healing assay suggests that the UiO-66(Zr) material has potential application on the wound healing process. However, further studies should be done.
Assuntos
Anti-Inflamatórios não Esteroides , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estruturas Metalorgânicas , Naproxeno , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/química , Estruturas Metalorgânicas/química , Naproxeno/administração & dosagem , Naproxeno/química , Naproxeno/farmacocinética , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Ibuprofeno/farmacocinética , Humanos , Adsorção , Portadores de Fármacos/química , Diclofenaco/administração & dosagem , Diclofenaco/química , Diclofenaco/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Ácidos FtálicosRESUMO
Phthalic acid esters (PAEs) are byproducts released from various sources, including microplastics, cosmetics, personal care products, pharmaceuticals, waxes, inks, detergents, and insecticides. This review article provides an overview of the literature on PAEs in landfill leachates, exploring their identification, occurrence, characteristics, fate, and transport in landfills across different countries. The study emphasizes the influence of these substances on the environment, especially on water and soil. Various analytical techniques, such as GC-MS, GC-FID, and HPLC, are commonly employed to quantify concentrations of PAEs. Studies show significant variations in levels of PAEs among different countries, with the highest concentration observed in landfill leachates in Brazil, followed by Iran. Among the different types of PAE, the survey highlights DEHP as the most concentrated PAE in the leachate, with a concentration of 89.6 µg/L. The review also discusses the levels of other types of PAEs. The data shows that DBP has the highest concentration at 6.8 mg/kg, while DOP has the lowest concentration (0.04 mg/kg). The concentration of PAEs typically decreases as the depth in the soil profile increases. In older landfills, concentrations of PAE decrease significantly, possibly due to long-term degradation and conversion of PAE into other chemical compounds. Future research should prioritize evaluating the effectiveness of landfill liners and waste management practices in preventing the release of PAE and other pollutants into the environment. It is also possible to focus on developing efficient physical, biological, and chemical methods for removing PAEs from landfill leachates. Additionally, the effectiveness of existing treatment processes in removing PAEs from landfill leachates and the necessity for new treatment processes can be considered.
Assuntos
Monitoramento Ambiental , Ésteres , Ácidos Ftálicos , Instalações de Eliminação de Resíduos , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Ácidos Ftálicos/análise , Ésteres/análise , Poluentes do Solo/análise , Brasil , Solo/químicaRESUMO
A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno-miR-184 and rno-miR-141-3p in the ventral prostate (VP) of offspring. Here, rno-miR-184 and rno-miR-141-3 expressions were obtained by RT-qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets. VP samples from rats exposed to a mixture of phthalates maternally during pregnancy and lactation (GD10 to PND21-F1) and VP from offspring (F2) were examined. The phthalate mixture at both concentrations (20 µg and 200 mg/kg/day) increased the expression of both miRNAs in the F1 (PND22 and 120) and F2 (descendants of F1-treated males) prostate. Target prediction analysis revealed that both microRNAs are responsible for modulating the expression and synthesis of 40 common targets. A phthalate target association analysis and the HPA database showed an interesting relationship among these possible miRNAs modulated targets with prostate adenocarcinoma and other oncogenic processes. Western blots showed alteration in P63, P53, WNT5, and STAT3 expression, which are targeted by the miRNAs, in the VP of F1/F2 males. The data draw attention to the epigenetic modulation in the prostate of descendants exposed to phthalates and adds to one of the few currently found in the literature to point to microRNAs signature as biomarkers of exposure to plasticizers.
Assuntos
MicroRNAs , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Neoplasias da Próstata , MicroRNAs/genética , MicroRNAs/metabolismo , Masculino , Animais , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Feminino , Ácidos Ftálicos/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Exposição Materna/efeitos adversos , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos Wistar , Ratos , Simulação por ComputadorRESUMO
Phthalates are synthetic plasticizers present in the daily lives of humans, as part of the composition of different products, such as food packaging, water bottles, and toys. These compounds can migrate from plastic materials to the environment changing biological systems. Although diisopentyl phthalate (DiPeP) is largely used in Brazil, there is a lack of information on the possible toxic effects of this compound. This research aims to evaluate the toxicity of DiPeP in the Vero renal cells. These cells were exposed to the 1-1000 µM of DiPeP for 24 and 72 h and subsequently, the cytotoxicity, apoptosis and necrosis-inducing potential, and antioxidant system (SOD, GPx, and GST) were investigated. DiPeP neither caused cytotoxicity nor altered SOD and GPx activity, although GST has been increased at 100 or 1 µM (24 and 72 h, respectively). However, cell death by apoptosis and necrosis was observed. These results indicate that DiPeP caused cell death by a non-oxidative stress-mediated mechanism, which shows the relevance of investigate other process in further researches.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Humanos , Plastificantes/toxicidade , Ácidos Ftálicos/toxicidade , Necrose/induzido quimicamente , Superóxido Dismutase , Linhagem CelularRESUMO
Phthalates or phthalic acid esters (PAE) and bis(2-ethylhexyl)adipate (DEHA) are ubiquitous chemicals often used as plasticisers and additives in many industrial products and are classified as both persistent organic pollutants (POPs) and new emerging pollutants (NEPs). Exposure to these chemicals, especially through inhalation, is linked to a wide range of negative health effects, including endocrine disruption. Air particulate matter (PM) with an aerodynamic diameter ≤ 2.5 µm can be enriched with PAEs and DEHA and if inhaled can cause multi-system human toxicity. Therefore, proper monitoring of PAEs and DEHA in PM is required to assess human exposure to these pollutants. In this work, we developed and validated a new and sensitive gas-chromatography high-resolution mass spectrometry (GC-HRMS) method for targeted analysis of PAEs including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), bis(2-ethylhexyl)adipate (DEHA), bis(2-ethylhexyl)phthalate (DEHP), di-n-octyl phthalate (DOP), in PM. Analytical aspects including sample preparation steps and GC-HRMS parameters, e.g., quadrupole isolation window, to enhance method sensitivity have been assessed. The estimated limit of detection (LODs) of target PAEs and DEHA ranged from 5.5 to 17 pg µL-1, allowing their trace-level detection in PM. Extraction efficiencies of 78-101% were obtained for the target compounds. Low DMP and DEP extraction efficiencies from the spiked filter substrates indicated that significant losses of higher volatility PAEs can occur during the sample collection when filter-based techniques are used. This work is the first targeted method based on GC-Orbitrap MS for PAEs and DEHA in environmental samples. The validated method was successfully applied for the targeted analysis of PAEs and DEHA in PM2.5 samples from the eighth most populous city in Brazil, Curitiba. This work is the first to report DBP, DEHA, DEHP, and DOP in urban PM from Brazil. The observed concentrations of PAEs (up to 29 ng m-3) in PM2.5 from Curitiba may not represent the extent of pollution by these toxic compounds since the analysed samples were collected during a COVID-19 restriction when anthropogenic activities were reduced.
Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Humanos , Material Particulado/análise , Dietilexilftalato/análise , Ésteres/análise , Brasil , Ácidos Ftálicos/análise , Dibutilftalato/análise , Adipatos/análise , Poluentes Ambientais/análiseRESUMO
Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is used worldwide and raises concerns because of its prevalence in the environment and potential toxicity. Herein, the capability of Fusarium culmorum to degrade a high concentration (3 g/L) of DEHP as the sole carbon and energy source in solid-state fermentation (SSF) was studied. Cultures grown on glucose were used as controls. The biodegradation of DEHP by F. culmorum reached 96.9% within 312 h. This fungus produced a 3-fold higher esterase activity in DEHP-supplemented cultures than in control cultures (1288.9 and 443.2 U/L, respectively). In DEHP-supplemented cultures, nine bands with esterase activity (24.6, 31.2, 34.2, 39.5, 42.8, 62.1, 74.5, 134.5, and 214.5 kDa) were observed by zymography, which were different from those in control cultures and from those previously reported for cultures grown in submerged fermentation. This is the first study to report the DEHP biodegradation pathway by a microorganism grown in SSF. The study findings uncovered a novel biodegradation strategy by which high concentrations of DEHP could be biodegraded using two alternative pathways simultaneously. F. culmorum has an outstanding capability to efficiently degrade DEHP by inducing esterase production, representing an ecologically promising alternative for the development of environmental biotechnologies, which might help mitigate the negative impacts of environmental contamination by this phthalate. KEY POINTS: ⢠F. culmorum has potential to tolerate and remove di(2-ethylhexyl) phthalate (DEHP) ⢠Solid-state fermentation is an efficient system for DEHP degradation by F. culmorum ⢠High concentrations of DEHP induce high levels of esterase production by F. culmorum.
Assuntos
Dietilexilftalato , Fusarium , Ácidos Ftálicos , Dietilexilftalato/metabolismo , Biodegradação Ambiental , Esterases/metabolismoRESUMO
A new class of lanthanide mixed-carboxylate ligands compounds with formula {[Ln2 (phthgly)4 (bdc)(H2 O)6 ]·(H2 O)4 }∞ , labelled as Ln3+ : Eu (1) and Gd (2) coordination polymers (CP) were synthesized under mild reaction conditions between lanthanide nitrate salts and a solution of N-phthaloylglycine (phthgly) and terephthalic (bdc) ligands. The (1) and (2) coordination polymers were formed by symmetric binuclear units, in which phthgly and bdc carboxylate ligands are coordinated to the lanthanide ions by different coordination modes. Surprisingly, all organic ligands participate in hydrogen bonding interactions, forming an extremally rigid crystalline structure. The red narrow emission bands from the 5 D0 â7 FJ transitions of the Eu3+ ion show a high colour purity. The intramolecular energy transfer process from LâEu3+ ion has been discussed. The experimental intensity parameters (Ω2,4 ) reflect lower angular distortion and polarizability of the chemical environment around the metal ion compared with other Eu3+ compounds reported in the literature. This novel class of coordination polymer offers a more attractive platform for developing luminescent functional materials for different applications.
Assuntos
Elementos da Série dos Lantanídeos , Compostos Organometálicos , Ácidos Ftálicos , Elementos da Série dos Lantanídeos/química , Compostos Organometálicos/química , Polímeros/química , Modelos Moleculares , Cristalografia por Raios X , Ligantes , Ácidos CarboxílicosRESUMO
OBJECTIVES: Narrative review evaluating food contamination by endocrine disruptors present in food packaging. DATA SOURCE: The terms "endocrine disruptors" and "food packaging" were used in combination in the PubMed, MEDLINE and SciELO databases, evaluating studies, in humans, published in Portuguese, English, French and Spanish between 1990 and 2023. DATA SYNTHESIS: Packaging, especially those made from plastic or recycled material, is an important source of food contamination by endocrine disruptors. Bisphenols and phthalates are the endocrine disruptors most frequently associated with food contamination from packaging. However, many unknown substances and even those legally authorized can cause harm to health when exposure is prolonged or when substances with additive effects are mixed. Furthermore, the discarding of packaging can cause contamination to continue into the environment. CONCLUSION: Although packaging materials are essential for the transport and storage of food, many of them are associated with chemical contamination. As it is not possible to exclude them from our routine, it is important to develop research aimed at identifying the endocrine disruptors present in them, including the effects of chronic exposure; and that regulatory agencies and industry come together to reduce or prevent this risk. Additionally, consumers must be instructed on how to purchase products, handle them and prepare them to reduce the migration of chemical substances into food.
Assuntos
Disruptores Endócrinos , Ácidos Ftálicos , Humanos , Embalagem de Alimentos , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/análise , Disruptores Endócrinos/química , Alimentos , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Ácidos Ftálicos/efeitos adversosRESUMO
Phthalates and bisphenol A (BPA) are compounds widely used as raw materials in the production of plastics, making them ubiquitous in our daily lives. This results in widespread human exposure and human health hazards. Although efforts have been conducted to evaluate the risk of these compounds in diverse regions around the world, data scattering may mask important trends that could be useful for updating current guidelines and regulations. This study offers a comprehensive global assessment of human exposure levels to these chemicals, considering dietary and nondietary ingestion, and evaluates the associated risk. Overall, the exposure daily intake (EDI) values of phthalates and BPA reported worldwide ranged from 1.11 × 10-7 to 3 700 µg kg bw-1 d-1 and from 3.00 × 10-5 to 6.56 µg kg bw-1 d-1, respectively. Nevertheless, the dose-additive effect of phthalates has been shown to increase the EDI up to 5 100 µg kg bw-1 d-1, representing a high risk in terms of noncarcinogenic (HQ) and carcinogenic (CR) effects. The worldwide HQ values of phthalates and BPA ranged from 2.25 × 10-7 to 3.66 and from 2.74 × 10-7 to 9.72 × 10-2, respectively. Meanwhile, a significant number of studies exhibit high CR values for benzyl butyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP). Moreover, DEHP has shown the highest maximum mean CR values for humans in numerous studies, up to 179-fold higher than BBP. Despite mounting evidence of the harmful effects of these chemicals at low-dose exposure on animals and humans, most regulations have not been updated. Thus, this article emphasizes the need for updating guidelines and public policies considering compelling evidence for the adverse effects of low-dose exposure, and it cautions against the use of alternative plasticizers as substitutes for phthalates and BPA because of the significant gaps in their safety.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Animais , Humanos , Exposição Ambiental/efeitos adversos , Medição de RiscoRESUMO
This rodent (Wistar rats) study examined reproductive effects of in utero/lactational exposure to a mixture of 6 antiandrogenic phthalates (PMix): diisobutyl phthalate, di-n-butyl phthalate, diisopentyl phthalate, butylbenzyl phthalate, di-2-ethylhexyl phthalate, and diisononyl phthalate. The PMix was defined based on exposure data from pregnant women in Brazil. Experimental groups were established by extrapolating the estimated human dose to rats (0.1 mg/kg/day), followed by up to 3 additional doses corresponding to 5, 1000, and 5000 times the starting rat dose: 0 (control), 0.1, 0.5, 100, and 500 mg/kg/day. The fetal experiment assessed gestational exposure effects on fetal gonads, whereas the postnatal experiment evaluated reproductive parameters in males and females after in utero and lactational exposure. Prenatal exposure decreased fetal testicular testosterone production at 0.5 and 500 mg/kg/day. PMix 500 also reduced mRNA expression of steroidogenesis-related genes, upregulated transcript expression of the retinoic acid-degrading enzyme Cyp26b1, and increased multinucleated gonocytes incidence in fetal testes. Postnatal assessment revealed antiandrogenic effects at the highest dose, including reduced anogenital distance, nipple retention, and decreased weight of reproductive organs. Early puberty onset (preputial separation) was observed at the lowest dose in males. In contrast, females did not show significant changes in fetal and adult endpoints. Overall, the PMix recapitulated early and late male rat phthalate syndrome phenotypes at the highest dose, but also induced some subtle changes at lower doses, which warrant confirmation and mechanistic assessments. Our data support the use of epidemiologically defined mixtures for exposure risk assessments over traditional toxicological approaches.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Adulto , Ratos , Gravidez , Masculino , Feminino , Animais , Ratos Wistar , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Reprodução , Testosterona/metabolismo , Testículo , Dietilexilftalato/toxicidade , Dibutilftalato/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
INTRODUCTION: High mammographic density is among the strongest and most established predictors for breast cancer risk. Puberty, the period during which breasts undergo exponential mammary growth, is considered one of the critical stages of breast development for environmental exposures. Benzylbutyl phthalate (BBP) and perfluorooctanoic acid (PFOA) are pervasive endocrine disrupting chemicals that may increase hormone-sensitive cancers. Evaluating the potential impact of BBP and PFOA exposure on pubertal breast density is important to our understanding of early-life environmental influences on breast cancer etiology. OBJECTIVE: To prospectively assess the effect of biomarker concentrations of monobenzyl phthalate (MBzP) and PFOA at specific pubertal window of susceptibility (WOS) on adolescent breast density. METHOD: This study included 376 Chilean girls from the Growth and Obesity Cohort Study with data collection at four timepoints: Tanner breast stages 1 (B1) and 4 (B4), 1- year post- menarche (1YPM) and 2-years post-menarche (2YPM). Dual-energy X-ray absorptiometry was used to assess the absolute fibroglandular volume (FGV) and percent breast density (%FGV) at 2YPM. We used concentrations of PFOA in serum and MBzP in urine as an index of exposure to PFOA and BBP, respectively. Parametric G-formula was used to estimate the time-specific effects of MBzP and PFOA on breast density. The models included body fat percentage as a time-varying confounder and age, birthweight, age at menarche, and maternal education as fixed covariates. RESULTS: A doubling of serum PFOA concentration at B4 resulted in a non-significant increase in absolute FGV (ß:11.25, 95% confidence interval (CI): -0.28, 23.49)), while a doubling of PFOA concentration at 1YPM resulted in a decrease in % FGV (ß:-4.61, 95% CI: -7.45, -1.78). We observed no associations between urine MBzP and breast density measures. CONCLUSION: In this cohort of Latina girls, PFOA serum concentrations corresponded to a decrease in % FGV. No effect was observed between MBzP and breast density measures across pubertal WOS.
Assuntos
Neoplasias da Mama , Ácidos Ftálicos , Feminino , Humanos , Adolescente , Densidade da Mama , Estudos de Coortes , Chile , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/urinaRESUMO
Schistosomiasis affects about 260â million people worldwide and the search for new schistosomicidal compounds is urgent. In this study we evaluated the inâ vitro effect of barbatic acid against schistosomulae and young worms of Schistosoma mansoni. The barbatic acid was evaluated through the bioassay of motility and mortality, cellular viability and ultrastructural analysis of juvenile stages through Scanning Electron Microscopy. Barbatic acid showed a schistosomicidal effect against schistosomulae and young worms of S. mansoni after 3â h of exposure. At the end of 24â h, barbatic acid showed 100 %, 89.5 %, 52 % and 28.5 % of lethality for schistosomulae at the concentrations of 200, 100, 50 and 25â µM, respectively. For young worms, barbatic acid showed 100 % and 31.7 % of lethality at the concentrations of 200 and 100â µM, respectively. Motility changes were observed at all sublethal concentrations. There was a significant reduction in the viability of young worms after exposure to barbatic acid at 50, 100 and 200â µM. Extensive damage to the schistosomulae and young worm's tegument, was observed from 50â µM. This report provides data showing the schistosomicidal effect of barbatic acid on schistosomulae and young worms of S.â mansoni, causing death, motility changes and ultrastructural damage to worms.
Assuntos
Anti-Helmínticos , Ácidos Ftálicos , Esquistossomicidas , Animais , Schistosoma mansoni , Anti-Helmínticos/farmacologia , Ácidos Ftálicos/farmacologia , Esquistossomicidas/farmacologia , Microscopia Eletrônica de VarreduraRESUMO
BACKGROUND: Epidemiological studies on children and adults have linked toxicants from plastics and personal care products to metabolic disruption. Yet, the impact of endocrine-disrupting chemicals (EDCs) on adolescent metabolic syndrome (MetS) risk during early and mid-adolescence is unclear. METHODS: To examine the links between exposure to EDCs and MetS risk and its components, cross-sectional data from 344 Mexican youth in early-to-mid adolescence (10-17 years) were analyzed. Urinary biomarker concentrations of phthalates, phenol, and paraben analytes were measured from a single spot urine sample collected in 2015; study personnel obtained anthropometric and metabolic measures. We examined associations between summary phthalates and metabolites, phenol, and paraben analytes with MetS risk z-scores using linear regression, adjusted for specific gravity, sex, age, pubertal status, smoking, alcohol intake, physical activity level, and screen time. As a secondary aim, mediation analysis was conducted to evaluate the role of hormones in the association between summary phthalates with lipids and MetS risk z-scores. RESULTS: The mean (SD) age was 13.2 (1.9) years, and 50.9% were female. Sex-stratified analyses revealed associations between summary phthalates and lipids ratio z-scores, including Σ DEHP [ß = 0.21 (95% CI: 0.04, 0.37; p < 0.01)], phthalates from plastic sources (Σ Plastic) [ß = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], anti-androgenic phthalates (Σ AA) [ß = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], and individual phthalate metabolites (MEHHP, MEOHP, and MECPP) among males. Among females, BPA [ß = 0.24 (95% CI: 0.03, 0.44; p < 0.05)] was positively associated with lipids ratio z-score and one phenol (2,5 DCP) [ß = 0.09 (95% CI: 0.01, 0.18); p < 0.05)] was associated with increased waist circumference z-score. Results showed no evidence of mediation by hormone concentrations in the association between summary phthalates with lipids ratio or MetS risk z-scores. CONCLUSION: Higher EDC exposure was positively associated with serum lipids during adolescence, particularly among males.
Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Síndrome Metabólica , Ácidos Ftálicos , Masculino , Adulto , Criança , Humanos , Adolescente , Feminino , Parabenos/análise , Fenóis/urina , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/epidemiologia , Estudos Transversais , Ácidos Ftálicos/urina , Fenol , Disruptores Endócrinos/toxicidade , Disruptores Endócrinos/urina , Lipídeos , Poluentes Ambientais/metabolismo , Exposição Ambiental/análiseRESUMO
Endocrine-disrupting chemicals (EDCs) may impact sleep during the menopausal transition by altering sex hormones. However, these studies are scarce among Latin American women. This investigation utilized cross-sectional and retrospective data from midlife women enrolled in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study to examine associations between exposure to EDCs (phthalates, phenols, and parabens) and sleep health measures. For cross-sectional analyses, single spot urine samples were collected between 2017-2019 from a pilot sample of women (N = 91) of midlife age to estimate the urinary concentration of individual phthalates, phenols, and parabens and to calculate the summary concentration of phthalate mixtures. Seven-day nightly sleep duration, midpoint, and fragmentation were obtained from wrist-actigraphy devices and estimated from the actigraphy data using a pruned dynamic programming algorithm. Self-reported poor sleep quality was assessed by one item from the Pittsburgh Sleep Quality Index (PSQI). We examined associations between urinary summary phthalate mixtures, phthalate metabolites, phenol, and paraben analytes with each sleep measure using linear or logistic (to compute odds of poor sleep quality only) regression models adjusted for specific gravity, age, and socioeconomic status. We ran similar regression models for retrospective analyses (N = 74), except that urine exposure biomarker data were collected in 2008 when women were 24-50 years old. At the 2017-2019 midlife visit, 38% reported poor sleep quality. Cross-sectionally, EDCs were associated with longer sleep duration, earlier sleep timing, and more fragmented sleep. For example, every 1-unit IQR increase in the phenol triclosan was associated with a 26.3 min per night (95% CI: 10.5, 42.2; P < 0.05) longer sleep duration and marginally associated with 0.2 decimal hours (95% CI: -0.4, 0.0; P < 0.10) earlier sleep midpoint; while every 1-unit IQR increase in the phthalate metabolite MEHP was associated with 1.1% higher sleep fragmentation (95% CI: 0.1, 2.1; P < 0.05). Retrospective study results generally mirrored cross-sectional results such that EDCs were linked to longer sleep duration, earlier sleep timing, and more fragmented sleep. EDCs were not significantly associated with odds of self-reported poor sleep quality. Results from cross-sectional and retrospective analyses revealed that higher exposure to EDCs was predictive of longer sleep duration, earlier sleep timing, and more fragmented sleep among midlife women.