Search Results (50)

Early-life exposure to organic chemicals (OCs) may influence childhood obesity and associated cardiometabolic risk. These conditions have been shown to disproportionately affect minority populations such as Mexican Americans (MAs). However, information on the impact of organic chemicals on cardiometabolic risk in MA children is limited. Therefore, we conducted a pilot study to assess the extent to which exposure to organic chemicals influences cardiometabolic traits (CMTs) in MA children. We recalled 25 children from a previous study and collected 25 primary teeth from them. Chemical analyses of the teeth were performed using established protocols. Target analytes included acetaminophen (APAP); 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), diethyl phosphate (DEP), N,N-diethyl-m-toluamide (DEET), tris(2-butoxyethyl) phosphate (TBOEP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). The organic chemicals most frequently detected in the teeth were APAP; the insect repellent DEET; plasticizers MnBP and MiBP; and the plasticizer-derived metabolite MEHP. These five analytes were included in association analyses with selected CMTs. After adjusting for covariate (age, sex, tooth-type) effects, we found significant (p < 0.05) positive correlations between MiBP and the following CMTs: fat mass, fasting insulin, and the homeostasis model of assessment-insulin resistance (HOMA-IR). Both MnBP and MEHP exhibited negative correlation with blood pressure measures and triglycerides, respectively. In addition, APAP showed a strong negative correlation with HDL-C (p = 0.009) and positive association with triglycerides (p < 0.10). These findings suggest a potential role for early-life exposures to organic chemicals in influencing cardiometabolic risk in MA children. Full article

Mono(2-ethylhexyl) phthalate (MEHP), a bioactive metabolite of di(2-ethylhexyl) phthalate (DEHP), has been detected in the placenta and urine of pregnant women and is linked to adverse pregnancy outcomes. However, its effects on mitochondrial homeostasis in trophoblast cells remain incompletely understood. This study examined the impact of MEHP (0.5–200 µM) on mitochondrial function, dynamics, and biogenesis in human HTR-8/SVneo trophoblast cells. MEHP (≥5 µM) reduced MTT conversion without compromising membrane integrity, suggesting early metabolic or redox imbalance. A dose-dependent loss of mitochondrial membrane potential was observed, with increased reactive oxygen species (ROS) generation only at 200 µM. MEHP modulated the expression of mitochondrial dynamics genes, with a more pronounced mitofusin 1 (MFN1) induction at low doses and increased mitochondrial DNA content, suggesting a compensatory response to mild stress. Conversely, high doses more strongly induced fission and mitochondrial 1 (FIS1) expression, suggesting mitochondrial fragmentation. Both concentrations induced the expression of the mitochondrial biogenesis regulators peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear factor erythroid 2–related factor 2 (Nrf2), while sirtuin 1 (SIRT1) expression and activity declined progressively with dose. These results demonstrate that MEHP disrupts mitochondrial homeostasis in trophoblast cells at concentrations spanning the estimated human exposure range. The dose-dependent effects, from adaptive responses to overt dysfunction, may help explain the associations between MEHP exposure and placental pathology observed in epidemiological studies. Full article

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

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

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

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

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

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

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

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

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

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

Plasticizers give flexibility to a wide range of consumer and medical plastic products. Among them, phthalate esters are recognized as endocrine disruptors that target male reproductive functions. With this notion, past studies designed and produced alternative plasticizers that could replace phthalates with limited toxicity to the environment and to male reproductive functions. Here, we focused on one reproductive cell type that was not investigated in past studies—spermatogonial stem cells (SSCs)—and examined in vitro the effects on 22 compounds (seven plasticizers currently in use and 15 newly synthesized potential alternative plasticizers) for their effects on SSCs. Our in vitro compound screening analyses showed that a majority of the compounds examined had a limited level of toxicity to SSCs. Yet, some commercial plasticizers and their derivatives, such as DEHP (di-(2-ethylhexyl) phthalate) and MEHP (mono-(2-ethylhexyl) phthalate), were detrimental at 10⁻⁵ to 10⁻⁴ M. Among new compounds, some of maleate- and fumarate-derivatives showed toxic effects. In contrast, no detrimental effects were detected with two new compounds, BDDB (1,4 butanediol dibenzoate) and DOS (dioctyl succinate). Furthermore, SSCs that were exposed to BDDB and DOS in vitro successfully established spermatogenic colonies in testes of recipient mice after transplantation. These results demonstrate that SSC culture acts as an effective platform for toxicological tests on SSC function and provide novel information that two new compounds, BDDB and DOS, are alternative plasticizers that do not have significant negative impacts on SSC integrity. Full article

Phthalate metabolites are detectable within the majority of the population. Evidence suggests that a prenatal exposure to phthalates may be associated with the subsequent risks of obesity and elevated blood pressure. We hypothesised that a prenatal exposure to phthalates would lead to an increase in adverse cardiometabolic parameters through childhood and adulthood. The maternal serum phthalate measurements from the stored samples taken from Gen1 mothers at 18 and 34 weeks gestation were examined in relation to the cardiometabolic measures in 387 male offspring from the Raine Study. Data from the Gen2 follow-ups between 3 and 27 years were used. The primary outcomes were analysed longitudinally using linear mixed models for the repeated measures. Non-alcoholic fatty liver disease (NAFLD) was assessed at 17 years using logistic regression. A consistent positive relationship was observed between a prenatal exposure to mono-carboxy-iso-octyl phthalate (MCiOP) through adolescence into adulthood with systolic blood pressure. There were no other consistent cardiovascular associations. Mid-levels of prenatal exposures to Mono-n-butyl phthalate (MnBP) were associated with a greater incidence of NAFLD. Detectable Mono-3-carboxypropyl phthalate (MCPP) was associated with a lower serum HDL-C through late childhood into adulthood, while a higher prenatal exposure to mono-iso-butyl phthalate (MiBP), was associated with a higher LDL-C at 22 years of age. A mid-level prenatal exposure to mono-2-ethylhexyl phthalate (MEHP) metabolites was associated with higher insulin in adulthood, while a higher prenatal exposure to the sum of the Di-(2-ethyl-hexyl) phthalate (DEHP) and Di-iso-nonyl phthalate (DiNP) metabolites was associated with higher fasting serum glucose in adulthood. In conclusion, our study demonstrated that higher prenatal phthalate exposures to some phthalate metabolites was associated with some adverse metabolic profiles through adolescence into adulthood, although the consistent themes were limited to a few metabolites and the outcomes of systolic blood pressure, fasting insulin and glucose. Full article

Phthalates are ubiquitous ‘modern’ chemical compounds with potential negative impacts on children’s health. A nested case–control study was designed to investigate associations of phthalate exposure with children’s asthma and allergic symptoms. We collected 243 first morning urine samples from 4–8-year-old children in Tianjin, China. Eight metabolites (i.e., mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP) and mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-carboxylpentyl) phthalate (MECPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) of five phthalates were analyzed using HPLC-MS. MiBP, MnBP and MECPP were the dominant phthalate metabolites in urine of children in Tianjin with median concentrations of 31.6 μg/L, 26.24 μg/L and 46.12 μg/L, respectively. We found significantly positive associations of diagnosed asthma with MnBP (adjusted odds ratios (AOR): 1.96; 95% confidence intervals (CIs): 1.07–3.61), MEHHP (AOR: 2.00; 95% CI: 1.08–3.71) and MEOHP (AOR: 2.09; 95% CI: 1.06–4.10). Our study indicates that phthalate exposure in childhood, especially to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP), may be a risk factor for children’s asthma. Full article