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Keywords = Mono-2-ethylhexyl phthalate

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13 pages, 529 KiB  
Article
Emerging Pollutants in Chinstrap Penguins and Krill from Deception Island (South Shetland Islands, Antarctica)
by Miguel Motas, Silvia Jerez-Rodríguez, José Manuel Veiga-del-Baño, Juan José Ramos, José Oliva, Miguel Ángel Cámara, Pedro Andreo-Martínez and Simonetta Corsolini
Toxics 2025, 13(7), 549; https://doi.org/10.3390/toxics13070549 - 29 Jun 2025
Viewed by 352
Abstract
This study aimed to evaluate the presence of emerging pollutants [perfluorinated compounds, phthalates and bisphenol A (BPA)] in chinstrap penguins (Pygoscelis antarctica) and krill (Euphausia superba) from Deception Island (South Shetland Islands, Antarctica) to provide data on the occurrence [...] Read more.
This study aimed to evaluate the presence of emerging pollutants [perfluorinated compounds, phthalates and bisphenol A (BPA)] in chinstrap penguins (Pygoscelis antarctica) and krill (Euphausia superba) from Deception Island (South Shetland Islands, Antarctica) to provide data on the occurrence of emerging pollutants in Antarctica. For this purpose, thirty-four samples were studied, including four samples of adult tissue and six samples of chick tissue, as well as krill samples from the area. The selected samples were subjected to extraction processes and subsequent analytical determination of perfluorooctane sulfonate, perfluorooctanoic acid, di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate and BPA using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry. Our results highlight that the analyzed organic pollutants, except for BPA, are clearly present in Pygoscelis antarctica and Euphausia superba from Deception Island. Full article
(This article belongs to the Special Issue Environmental Toxicology and Risk Assessment of Priority Substances)
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16 pages, 789 KiB  
Article
Phthalate Metabolites and Their Relationship with Abdominal and General Obesity: Evidence from the Aragon Workers’ Health Study (AWHS)
by Jordan Akritidis, Diana María Mérida, Carolina Torrijo-Belanche, Belén Moreno-Franco, Sofía Gimeno-Ruiz, Jimena Rey-García, María Morales-Suarez-Varela and Pilar Guallar-Castillón
Nutrients 2025, 17(11), 1869; https://doi.org/10.3390/nu17111869 - 30 May 2025
Viewed by 594
Abstract
Background/Objectives: Phthalates are endocrine-disrupting chemicals that are commonly used in plastic consumer products and food packaging, with growing evidence suggesting that they have a potential role in obesity. This study aimed to investigate the association between urinary concentrations of phthalate metabolites and both [...] Read more.
Background/Objectives: Phthalates are endocrine-disrupting chemicals that are commonly used in plastic consumer products and food packaging, with growing evidence suggesting that they have a potential role in obesity. This study aimed to investigate the association between urinary concentrations of phthalate metabolites and both general and abdominal obesity among adult males in Spain. Methods: We analysed data from 1124 male participants of the Aragon Workers’ Health Study (AWHS) collected between 2011 and 2014 in Zaragoza, Spain. Eleven urinary phthalate metabolites were measured and adjusted for creatinine levels. Multivariate logistic regression models were used to evaluate associations between phthalate exposure and general and abdominal obesity, controlling for dietary and lifestyle factors. Dose–response relationships were explored using restricted cubic spline models. Results: Higher urinary concentrations of di(2-ethylhexyl) phthalate (∑DEHP) and two of its metabolites—mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)—were significantly associated with general obesity. The adjusted odds ratios were: ∑DEHP [OR = 1.26; 95% CI: 1.01, 1.58], MEOHP [OR = 1.24; 95% CI: 1.00, 1.53], and MEHHP [OR = 1.26; 95% CI: 1.03, 1.55]. In contrast, mono-isobutyl phthalate (MiBP) was inversely associated with abdominal obesity [OR = 0.73; 95% CI: 0.57, 0.93]. Conclusions: These findings suggest a positive association between exposure to DEHP and its metabolites and general obesity. This highlights the potential importance of environmental exposures as modifiable factors in obesity prevention and supports the need for further investigation in nutritional and public health contexts. Full article
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14 pages, 294 KiB  
Article
Evidence About the Possible Role of Phthalates and Bisphenol A in Recurrent Pregnancy Loss and Endocrine Dysfunctions: A Case–Control Study
by Lidia Caporossi, Paola Viganò, Enrico Paci, Silvia Capanna, Alessandra Alteri, Mariangela De Rosa, Daniela Pigini, Elisa Partenzi and Bruno Papaleo
Environments 2025, 12(2), 38; https://doi.org/10.3390/environments12020038 - 24 Jan 2025
Viewed by 1308
Abstract
Objectives. A case–control study was conducted to investigate the exposure levels to some specific chemicals, in women with infertility issues, compared with fertile women. Methods. A total of 186 cases and 196 controls were recruited. Each participant provided a urine sample for the [...] Read more.
Objectives. A case–control study was conducted to investigate the exposure levels to some specific chemicals, in women with infertility issues, compared with fertile women. Methods. A total of 186 cases and 196 controls were recruited. Each participant provided a urine sample for the determination of six phthalate metabolites (mono-ethyl phthalate, MEP; mono-n-butyl phthalate, MnBP; mono-n-ottyl phthalate, MnOP; monobenzyl phthalate, MBzP; and two metabolites of the diethyl-hexyl phthalate (DEHP): mono(2-ethyl-5-hydroxyhexyl) phthalate, MEHHP and mono(2-ethylhexyl) phthalate, MEHP) in addition to bisphenol A, BPA. Each woman also completed a questionnaire. The urine samples were analyzed using HPLC/MS/MS methods. Results. The analysis revealed significantly higher metabolite concentrations in cases than in controls for all metabolites, except MnOP. Stratification based on infertility factors, showed a significant association of MnBP, MBzP, BPA and DEHP with ovulatory and endocrine dysfunctions. Furthermore, higher mean concentrations of MEP and DEHP were observed in women with recurrent pregnancy loss (RPL) and idiopathic infertility, respectively. Conclusion. These findings suggest that some of the analyzed chemicals may play a role in female infertility. Exposure to DEP (diethyl phthalate) and DEHP appears to be associated with RPL and idiopathic infertility. Further investigation is required to explore potential sources of these risks. Full article
16 pages, 805 KiB  
Article
Distinct Impacts of Prenatal and Postnatal Phthalate Exposure on Behavioral and Emotional Development in Children Aged 1.5 to 3 Years
by Yi-Siang Huang, Pi-Lien Hung, Liang-Jen Wang, Chih-Min Tsai, Chang-Ku Tsai, Mao-Meng Tiao and Hong-Ren Yu
Toxics 2024, 12(11), 795; https://doi.org/10.3390/toxics12110795 - 31 Oct 2024
Cited by 1 | Viewed by 1791
Abstract
Development is a continuous process, but few studies have assessed the simultaneous impact of prenatal and postnatal phthalate exposure on children’s behavioral and emotional development. A total of 491 mother–child pairs from the general population in southern Taiwan were studied from 2021 to [...] Read more.
Development is a continuous process, but few studies have assessed the simultaneous impact of prenatal and postnatal phthalate exposure on children’s behavioral and emotional development. A total of 491 mother–child pairs from the general population in southern Taiwan were studied from 2021 to 2022. Urinary concentrations of bisphenol A (BPA) and phthalate metabolites—mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and mono-2-ethylhexyl phthalate (MEHP)—were measured in pregnant mothers during the second trimester and in their corresponding children aged 1.5 to 3 years. Behavioral symptoms in children were evaluated using the Child Behavior Checklist (CBCL). Odds ratios (ORs) represent a 1-unit increase in log10-transformed creatinine-corrected maternal urine concentrations. Prenatal maternal urinary MnBP levels were associated with total problems (OR = 19.32, 95% CI: 1.80–43.13, p = 0.04), anxiety (OR = 33.58, 95% CI: 2.16–521.18, p = 0.01), and sleep problems (OR = 41.34, 95% CI: 1.04–1632.84, p = 0.04) in children. Additionally, urinary MnBP levels in children correlated with total problems (OR = 7.06, 95% CI: 1.01–49.05, p = 0.04) and internalizing problems (OR = 11.04, 95% CI: 1.27–95.72, p = 0.01). These findings suggest that prenatal and postnatal exposure to dibutyl phthalate (DBP), metabolized as MnBP, distinctly affects children’s behavioral development. Full article
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19 pages, 8961 KiB  
Article
Novel Insights into Ethanol-Soluble Oyster Peptide–Zinc-Chelating Agents: Structural Characterization, Chelation Mechanism, and Potential Protection on MEHP-Induced Leydig Cells
by Zhen Lu, Qianqian Huang, Xiaoming Qin, Fujia Chen, Enzhong Li and Haisheng Lin
Mar. Drugs 2024, 22(10), 465; https://doi.org/10.3390/md22100465 - 10 Oct 2024
Viewed by 2081
Abstract
Numerous studies have reported that mono-(2-ethylhexyl) phthalate (MEHP) (bioactive metabolite of Di(2-ethylhexyl) phthalate) has inhibitory effects on Leydig cells. This study aims to prepare an oyster peptide–zinc complex (PEP-Zn) to alleviate MEHP-induced damage in Leydig cells. Zinc-binding peptides were obtained through the following [...] Read more.
Numerous studies have reported that mono-(2-ethylhexyl) phthalate (MEHP) (bioactive metabolite of Di(2-ethylhexyl) phthalate) has inhibitory effects on Leydig cells. This study aims to prepare an oyster peptide–zinc complex (PEP-Zn) to alleviate MEHP-induced damage in Leydig cells. Zinc-binding peptides were obtained through the following processes: zinc-immobilized affinity chromatography (IMAC-Zn2+), liquid chromatography–mass spectrometry technology (LC-MS/MS) analysis, molecular docking, molecular dynamic simulation, and structural characterization. Then, the Zn-binding peptide (PEP) named Glu—His—Ala—Pro—Asn—His—Asp—Asn—Pro—Gly—Asp—Leu (EHAPNHDNPGDL) was identified. EHAPNHDNPGDL showed the highest zinc-chelating ability of 49.74 ± 1.44%, which was higher than that of the ethanol-soluble oyster peptides (27.50 ± 0.41%). In the EHAPNHDNPGDL-Zn complex, Asn-5, Asp-7, Asn-8, His-2, and Asp-11 played an important role in binding to the zinc ion. Additionally, EHAPNHDNPGDL-Zn was found to increase the cell viability, significantly increase the relative activity of antioxidant enzymes and testosterone content, and decrease malondialdehyde (MDA) content in MEHP-induced TM3 cells. The results also indicated that EHAPNHDNPGDL-Zn could alleviate MEHP-induced apoptosis by reducing the protein level of p53, p21, and Bax, and increasing the protein level of Bcl-2. These results indicate that the zinc-chelating peptides derived from oyster peptides could be used as a potential dietary zinc supplement. Full article
(This article belongs to the Special Issue The Bioactive Potential of Marine-Derived Peptides and Proteins)
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17 pages, 289 KiB  
Article
Evaluation of Exposure to Bisphenol A, Bisphenol F, and Phthalates in Patients with Phenylketonuria and Its Differences According to Dietary Status
by İzzet Erdal, Yılmaz Yıldız, Sıddıka Songül Yalçın, Anıl Yirün, Göksun Demirel and Pınar Erkekoğlu
Nutrients 2024, 16(18), 3213; https://doi.org/10.3390/nu16183213 - 23 Sep 2024
Cited by 2 | Viewed by 1803
Abstract
Background: Phenylketonuria (PKU) is the most common amino acid metabolism disorder. Patients with blood phenylalanine (Phe) levels of ≥6 mg/dL require treatment, and the most definitive treatment is the Phe-restricted diet. Bisphenols and phthalates are widely used endocrine-disrupting chemicals (EDCs) found in personal [...] Read more.
Background: Phenylketonuria (PKU) is the most common amino acid metabolism disorder. Patients with blood phenylalanine (Phe) levels of ≥6 mg/dL require treatment, and the most definitive treatment is the Phe-restricted diet. Bisphenols and phthalates are widely used endocrine-disrupting chemicals (EDCs) found in personal care products, baby bottles, and food packaging. Methods: In this study, we evaluated the possible routes of exposure to these EDCs in patients diagnosed with PKU (n = 105, 2–6 years of age) and determined the relationship between the plasma levels of bisphenol A (BPA), bisphenol F (BPF), di-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), mono-(2ethylhexyl) phthalate (MEHP), and dietary regimens. Participant characteristics and exposure routes were evaluated according to their dietary treatment status. Results: Thirty-four of these patients were on a Phe-restricted diet, while the remaining 71 had no dietary restrictions. DBP and DEHP levels were higher in those using plastic tablecloths (p = 0.049 and p = 0.04, respectively). In addition, plasma DBP levels were higher in those who used bottled water (p = 0.01). Being under 4 years of age, using plastic food containers, and using plastic shower curtains were characteristics associated with higher MEHP levels (p = 0.027, p = 0.019, and p = 0.014, respectively). After adjustment for baseline characteristics (Model 1), the odds of having a plasma BPA level in the upper tertile were 3.34 times higher in the free-diet group (95% CI = 1.09–10.25). When we additionally adjusted for plastic exposure (Model 2), the odds ratio was found to be 18.64 (95% CI = 2.09–166.42) for BPA. In the free-diet group, the probability of having plasma DEHP levels in the upper tertile was increased by a relative risk of 3.01 (p = 0.039, 95% CI = 1.06–8.60). Conclusion: Our results indicate that exposure to bisphenols and phthalates varies with dietary treatment. The difference in sources of exposure to EDCs between the diet and non-diet groups indicates that diet plays an important role in EDC exposure. Full article
(This article belongs to the Section Nutrition and Public Health)
22 pages, 1724 KiB  
Article
Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies
by Elena Salamanca-Fernández, Lydia Espín-Moreno, Alicia Olivas-Martínez, Ainhoa Pérez-Cantero, José L. Martín-Rodríguez, Rafael M. Poyatos, Fabio Barbone, Valentina Rosolen, Marika Mariuz, Luca Ronfani, Ľubica Palkovičová Murínová, Lucia Fábelová, Tamás Szigeti, Réka Kakucs, Amrit K. Sakhi, Line S. Haug, Birgitte Lindeman, Janja Snoj Tratnik, Tina Kosjek, Griet Jacobs, Stefan Voorspoels, Helena Jurdáková, Renáta Górová, Ida Petrovičová, Branislav Kolena, Marta Esteban, Susana Pedraza-Díaz, Marike Kolossa-Gehring, Sylvie Remy, Eva Govarts, Greet Schoeters, Mariana F. Fernández and Vicente Mustielesadd Show full author list remove Hide full author list
Toxics 2024, 12(9), 642; https://doi.org/10.3390/toxics12090642 - 31 Aug 2024
Cited by 1 | Viewed by 2298
Abstract
Based on toxicological evidence, children’s exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels [...] Read more.
Based on toxicological evidence, children’s exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6–12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children’s total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS—IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: −8.8%; 95% CI: −16.7, −0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children’s exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a “urine concentration bias” that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations. Full article
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16 pages, 1750 KiB  
Article
Endocrine-Disrupting Chemicals Exposure and Neurocognitive Function in the General Population: A Community-Based Study
by Feng-Chieh Su, Yi-Chia Wei, Chiao-Yin Sun, Heng-Jung Hsu, Chin-Chan Lee, Yih-Ting Chen, Heng-Chih Pan, Cheng-Kai Hsu, Yun-An Liu and Chun-Yu Chen
Toxics 2024, 12(7), 514; https://doi.org/10.3390/toxics12070514 - 17 Jul 2024
Cited by 3 | Viewed by 2891
Abstract
Background: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. Methods: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. [...] Read more.
Background: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. Methods: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. Results: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (β ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. Conclusion: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults. Full article
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13 pages, 2406 KiB  
Article
Extracellular Vesicles in Environmental Toxicological Studies: Association between Urinary Concentrations of Phthalate Metabolites and Exosomal miRNA Expression Profiles
by Paolo Cocci, Danilo Bondi, Carmen Santangelo, Tiziana Pietrangelo, Vittore Verratti, Angelo Cichelli, Giovanni Caprioli, Franks Kamgang Nzekoue, Manuella Lesly Kouamo Nguefang, Gianni Sagratini, Gilberto Mosconi and Francesco Alessandro Palermo
Int. J. Mol. Sci. 2024, 25(9), 4876; https://doi.org/10.3390/ijms25094876 - 30 Apr 2024
Cited by 2 | Viewed by 1631
Abstract
Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to [...] Read more.
Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers. Full article
(This article belongs to the Special Issue Toxicity Mechanism of Emerging Pollutants)
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17 pages, 523 KiB  
Article
PFAS and Phthalate/DINCH Exposure in Association with Age at Menarche in Teenagers of the HBM4EU Aligned Studies
by Bianca Cox, Natasha Wauters, Andrea Rodríguez-Carrillo, Lützen Portengen, Antje Gerofke, Marike Kolossa-Gehring, Sanna Lignell, Anna Karin Lindroos, Lucia Fabelova, Lubica Palkovicova Murinova, Anteneh Desalegn, Nina Iszatt, Tessa Schillemans, Agneta Åkesson, Ann Colles, Elly Den Hond, Gudrun Koppen, Nicolas Van Larebeke, Greet Schoeters, Eva Govarts and Sylvie Remyadd Show full author list remove Hide full author list
Toxics 2023, 11(8), 711; https://doi.org/10.3390/toxics11080711 - 18 Aug 2023
Cited by 4 | Viewed by 3723
Abstract
Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). [...] Read more.
Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). Evidence for the association between PFAS and phthalate exposure and menarche onset, however, is inconsistent. We studied the association between PFAS and phthalate/DINCH exposure and age at menarche using data of 514 teenagers (12 to 18 years) from four aligned studies of the Human Biomonitoring for Europe initiative (HBM4EU): Riksmaten Adolescents 2016–2017 (Sweden), PCB cohort (follow-up; Slovakia), GerES V-sub (Germany), and FLEHS IV (Belgium). PFAS concentrations were measured in blood, and phthalate/DINCH concentrations in urine. We assessed the role of each individual pollutant within the context of the others, by using different multi-pollutant approaches, adjusting for age, age- and sex-standardized body mass index z-score and household educational level. Exposure to di(2-ethylhexyl) phthalate (DEHP), especially mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), was associated with an earlier age at menarche, with estimates per interquartile fold change in 5OH-MEHP ranging from −0.34 to −0.12 years in the different models. Findings from this study indicated associations between age at menarche and some specific EDCs at concentrations detected in the general European population, but due to the study design (menarche onset preceded the chemical measurements), caution is needed in the interpretation of causality. Full article
(This article belongs to the Section Reproductive and Developmental Toxicity)
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12 pages, 540 KiB  
Article
A Study of the Relationship between Phthalate Exposure and the Occurrence of Adult Asthma in Taiwan
by Tsai-Hui Duh, Chih-Jen Yang, Chien-Hung Lee and Ying-Chin Ko
Molecules 2023, 28(13), 5230; https://doi.org/10.3390/molecules28135230 - 5 Jul 2023
Cited by 5 | Viewed by 1632
Abstract
Although phthalate esters contribute to airway remodeling by increasing bronchial cells’ migration and proliferation, the relationship between human exposure to phthalates and asthma is not understood. We measured phthalate exposure in the human body and evaluated its effect on asthma. Asthma (n [...] Read more.
Although phthalate esters contribute to airway remodeling by increasing bronchial cells’ migration and proliferation, the relationship between human exposure to phthalates and asthma is not understood. We measured phthalate exposure in the human body and evaluated its effect on asthma. Asthma (n = 123) and asthma-free (n = 139) participants were, respectively, recruited from an asthma clinic and the community in Taiwan. The urine levels of six phthalate metabolites were determined by liquid chromatography tandem mass spectrometry. Compared with the controls, male asthma patients had higher means of mono-(2-ethylhexyl) phthalate (MEHP) (116.3 nmol/g), monobutyl phthalate (MBP) (850.3 nmol/g) and monoethyl phthalate (MEP) (965.8 nmol/g), and female patients had greater MBP (2902.4 nmol/g). Each 10-fold increase in the level of these phthalate metabolites was correspondingly associated with a 5.0-, 5.8-, 4.2- and 5.3-fold risk of contracting asthma. Male asthma patients were identified to have a higher proportion of MEHP exposure (32.5%) than the controls (25.3%). In asthma patients, an increase in urine MEHP levels and the total phthalate metabolite concentration were notably linked to increased risks of emergency room visits and being hospitalized. For the occurrence and acute clinical events of adult asthma, phthalate exposures and MEHP retention may contribute to higher risks of contracting this respiratory disorder. Full article
(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)
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16 pages, 526 KiB  
Systematic Review
The Association between Maternal Urinary Phthalate Concentrations and Blood Pressure in Pregnancy: A Systematic Review and Meta-Analysis
by Mengyue Zhang, Jianchao Qiao, Pinpeng Xie, Zhuoyan Li, Chengyang Hu and Fei Li
Metabolites 2023, 13(7), 812; https://doi.org/10.3390/metabo13070812 - 30 Jun 2023
Cited by 7 | Viewed by 1705
Abstract
Phthalates are commonly found in a wide range of environments and have been linked to several negative health outcomes. While earlier research indicated a potential connection between phthalate exposure and blood pressure (BP) during pregnancy, the results of these studies remain inconclusive. The [...] Read more.
Phthalates are commonly found in a wide range of environments and have been linked to several negative health outcomes. While earlier research indicated a potential connection between phthalate exposure and blood pressure (BP) during pregnancy, the results of these studies remain inconclusive. The objective of this meta-analysis was to elucidate the relationship between phthalate exposure and BP in pregnancy. A comprehensive literature search was carried out with PubMed, EMBASE, and Web of Science, and pertinent studies published up until 5 March 2023 were reviewed. Random-effects models were utilized to consolidate the findings of continuous outcomes, such as diastolic and systolic BP, as well as the binary outcomes of hypertensive disorders of pregnancy (HDP). The present study included a total of 10 studies. First-trimester MBP exposure exhibited a positive association with mean systolic and diastolic BP during both the second and third trimesters (β = 1.05, 95% CI: 0.27, 1.83, I2 = 93%; β = 0.40, 95% CI: 0.05, 0.74, I2 = 71%, respectively). Second-trimester monobenzyl phthalate (MBzP) exposure was positively associated with systolic and diastolic BP in the third trimester (β = 0.57, 95% CI: 0.01, 1.13, I2 = 0; β = 0.70, 95% CI: 0.27, 1.13, I2 = 0, respectively). Conversely, first-trimester mono-2-ethylhexyl phthalate (MEHP) exposure demonstrated a negative association with mean systolic and diastolic BP during the second and third trimesters (β = −0.32, 95% CI: −0.60, −0.05, I2 = 0; β = −0.32, 95% CI: −0.60, −0.05, I2 = 0, respectively). Additionally, monoethyl phthalate (MEP) exposure was found to be associated with an increased risk of HDP (OR = 1.12, 95% CI: 1.02, 1.23, I2 = 26%). Our study found that several phthalate metabolites were associated with increased systolic and diastolic BP, as well as the risk of HDP across pregnancies. Nevertheless, given the limited number of studies analyzed, additional research is essential to corroborate these findings and elucidate the molecular mechanisms linking phthalates to BP changes during pregnancy. Full article
(This article belongs to the Special Issue Environmental Exposures and Cardiovascular Disease)
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14 pages, 2195 KiB  
Article
Mono-(2-ethylhexyl) Phthalate (MEHP)-Induced Telomere Structure and Function Disorder Mediates Cell Cycle Dysregulation and Apoptosis via c-Myc and Its Upstream Transcription Factors in a Mouse Spermatogonia-Derived (GC-1) Cell Line
by Fangji Zhou, Chengwei Guo, Lingqiao Wang, Guowei Zhang, Jia Wang, Weiyan Chen, Ke Cui, Yao Tan and Ziyuan Zhou
Toxics 2023, 11(5), 448; https://doi.org/10.3390/toxics11050448 - 10 May 2023
Cited by 15 | Viewed by 2622
Abstract
As a typical environmental endocrine disrupting chemical (EDC), di-(2-ethylhexyl) phthalate (DEHP) is thought to be related to reproductive disorders, especially in males. Growing evidence suggests that various EDCs may result in an impaired telomere structure and function, which is associated with male infertility. [...] Read more.
As a typical environmental endocrine disrupting chemical (EDC), di-(2-ethylhexyl) phthalate (DEHP) is thought to be related to reproductive disorders, especially in males. Growing evidence suggests that various EDCs may result in an impaired telomere structure and function, which is associated with male infertility. However, the adverse effect of DEHP on telomeres in male reproductive cells has rarely been studied, and the related mechanisms remain unclear. In this study, we tested the effects of mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP, on telomere dysfunction in mouse spermatogonia-derived cells (GC-1) and the potential role of TERT and c-Myc in MEHP-induced spermatogenic cell damage. Results showed that MEHP induced cell viability inhibition, G0/G1 phase cell cycle arrest, and apoptosis in GC-1 cells in a dose-dependent manner. Shortened telomeres, reduced telomerase activity, and decreased expression of TERT, c-Myc, and upstream transcription factors of c-Myc were also observed in the MEHP-treated cells. In conclusion, it can be concluded that TERT-mediated telomere dysfunction may contribute to MEHP-induced G0/G1 phase cell cycle arrest and apoptosis in GC-1 cells through the impairment of c-Myc and its upstream transcription factors. Full article
(This article belongs to the Special Issue Cellular, Molecular and Genetic Toxicity of Endocrine Disruptors)
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16 pages, 13609 KiB  
Article
Distribution of Micro-Nano PS, DEHP, and/or MEHP in Mice and Nerve Cell Models In Vitro after Exposure to Micro-Nano PS and DEHP
by Jie Han, Jun Yan, Kang Li, Bencheng Lin, Wenqing Lai, Liping Bian, Rui Jia, Xiaohua Liu and Zhuge Xi
Toxics 2023, 11(5), 441; https://doi.org/10.3390/toxics11050441 - 7 May 2023
Cited by 16 | Viewed by 3243
Abstract
Polystyrene (PS) and di-(2-ethylhexyl) phthalate (DEHP) exist widely in the environment. However, their distribution in organisms remains unclear. We used three sizes (50 nm, 500 nm, and 5 μm) of PS and DEHP to study the distribution and accumulation of PS, DEHP, and [...] Read more.
Polystyrene (PS) and di-(2-ethylhexyl) phthalate (DEHP) exist widely in the environment. However, their distribution in organisms remains unclear. We used three sizes (50 nm, 500 nm, and 5 μm) of PS and DEHP to study the distribution and accumulation of PS, DEHP, and mono(2-ethylhexyl) phthalate (MEHP) in mice and nerve cell models (HT22 and BV2 cells) and their potential toxicity. Results showed that PS entered the blood of mice, and the distribution of different particle sizes in different tissues was different. After the combined exposure to PS and DEHP, PS carried DEHP, which significantly increased the DEHP content and MEHP content and the highest content of MEHP was in the brain. With the decrease in PS particle size, the contents of PS, DEHP, and MEHP in the body increased. The levels of inflammatory factors were increased in the serum of the PS or/and DEHP group. In addition, 50 nm polystyrene can carry MEHP into nerve cells. These results suggest for the first time that PS and DEHP combined exposure can induce systemic inflammation, and the brain is an important target organ of PS and DEHP combined exposure. This study may serve as a reference for further evaluation of the neurotoxicity induced by combined exposure to PS and DEHP. Full article
(This article belongs to the Section Neurotoxicity)
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18 pages, 5446 KiB  
Article
Gestational Exposure to Phthalates and Phthalate Replacements in Relation to Neurodevelopmental Delays in Early Childhood
by Seonyoung Park, Emily Zimmerman, Gredia Huerta-Montañez, Zaira Rosario-Pabón, Carmen M. Vélez-Vega, José F. Cordero, Akram Alshwabekah, John D. Meeker and Deborah J. Watkins
Toxics 2023, 11(1), 65; https://doi.org/10.3390/toxics11010065 - 11 Jan 2023
Cited by 15 | Viewed by 3360
Abstract
Phthalates have been linked to changes in child neurodevelopment. However, sex-specificity has been reported inconsistently, and little is known about the impact of recent phthalate replacement chemicals. Our analysis included mother–child pairs (N = 274) from the PROTECT birth cohort in Puerto Rico. [...] Read more.
Phthalates have been linked to changes in child neurodevelopment. However, sex-specificity has been reported inconsistently, and little is known about the impact of recent phthalate replacement chemicals. Our analysis included mother–child pairs (N = 274) from the PROTECT birth cohort in Puerto Rico. Phthalate metabolites were measured in multiple maternal urine collected during pregnancy. Neurodevelopment was measured at 6, 12, and 24 months of age using the Battelle Developmental Inventory-2nd edition (BDI), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. Multivariable linear regression was used to examine associations between phthalate metabolite concentrations and BDI scores, adjusting for maternal age, maternal education, child age, and specific gravity. Sex-specificity was assessed with sex X exposure interaction terms and stratified models. Results show that all five domains were significantly associated with mono-3-carboxypropyl phthalate (MCPP) at age 24 months, suggesting a holistic developmental delay related to this metabolite. Sex-specificity existed for all timepoints (p-interaction < 0.2), in general, showing stronger associations among boys. For example, metabolites of a recent phthalate replacement, di-2-ethylhexyl terephthalate (DEHTP), were differentially associated with the adaptive domain (boys −7.53%/IQR, 95% CI: −14.58, −0.48 vs. girls −0.85%/IQR, 95% CI: −5.08, 3.37), and the cognitive domain (boys −6.05%/IQR, 95% CI: −10.88, −1.22 vs. girls −1.93%/IQR, 95%CI: −4.14, 0.28) at 6 months. To conclude, gestational exposure to phthalates and phthalate replacements was associated with neurodevelopmental delay across multiple domains, with differences by sex and child age. Full article
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