Monomethyl Phthalate Research Articles

Phthalate exposure as a hidden risk factor for uterine leiomyoma in adult women: Accumulated evidence from observational studies

BackgroundThere is evidence that exposure to phthalate in women may increase the risk of uterine leiomyomas. Whereas, the association between exposure to phthalate and the incidence of uterine leiomyoma remained inconclusive. MethodsA meta-analysis was performed to evaluate their relationship. Literature eligible for inclusion was found in PubMed, EMBASE, Web of Science, and WanFang Medical Database. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to assess the risk for effect estimate for each phthalate. ResultsA total of fourteen observational studies with 5777 subjects of adult women were included in this study. In the pooled analysis, we found an elevated risk of uterine leiomyoma among women who were exposed to higher levels of di-2-ethylhexyl phthalate (DEHP) (OR 1.61, 95 % CI: 1.18–2.20), as estimated indirectly from the molar summation of its urinary metabolite concentrations. In addition, a positive association was observed between the occurrence of uterine leiomyoma and exposure to low molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.00–1.15), as well as high molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.01–1.15), as quantified by integrating the effect estimates of individual metabolite from each study. Urinary levels of DEHP metabolites, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, monoethyl phthalate, and monomethyl phthalate were not appreciably correlated with the risk of uterine leiomyoma. ConclusionOur results indicated that exposure to DEHP, and co-exposure to high or low molecular weight phthalate mixture might be potential risk factors for uterine leiomyoma in adult women. Owing to the indirect estimation of association, when interpreting these findings, cautions should be taken.

The effect of endocrine-disrupting chemicals in follicular fluid: The insights from oocyte to fertilization

Endocrine-disrupting chemicals (EDCs) exhibited the detriment in female reproductive health. Our objective was to investigate the individual and mixture effects of EDCs present in follicular fluid, the environment in which oocytes grow and develop, on early reproductive outcomes. We recruited 188 women seeking reproduction examination from the Study of Exposure and Reproductive Health (SEARCH) cohort between December 2020 and November 2021. We assessed the concentrations of 7 categories of 64 EDCs in follicular fluid, and measured early reproductive outcomes, including retrieved oocytes, mature oocytes, normal fertilized oocytes, and high-quality embryos. In this study Monomethyl phthalate (MMP) (2.17 ng/ml) were the compounds found in the highest median concentrations in follicular fluid. After adjusting for multiple testing, multivariate regression showed that multiple EDCs were significantly negatively associated with early assisted reproduction outcomes. For example, MMP showed a significant negative correlation with the number of high quality embryos (β: −0.1, 95 % CI: −0.15, −0.04). Specifically, eight types of EDCs were significantly negatively associated with four early assisted reproductive outcomes (β range: −0.2 ∼ -0.03). In the mixed exposure model, we found that mixtures of EDC were significantly negatively correlated with all four outcomes. In the quantile g-computation (QGCOMP) model, for each interquartile range increase in the concentration of EDC mixtures, the number of oocytes retrieved, mature oocytes, normally fertilized oocytes, and high-quality embryos decreased by 0.46, 0.52, 0.77, and 1.2, respectively. Moreover, we identified that phthalates (PAEs) predominantly contributed to the negative effects. Future research should validate our findings.

Concentration levels of phthalate metabolites in wild boar hair samples

Phthalates used in the industry penetrate the environment and negatively affect humans and animals. Hair samples seem to be the best matrix for studies on long-term exposure to phthalates, but till now they were used only in investigations on humans. Moreover, the knowledge of the wild terrestrial animal exposure to phthalates is extremely limited. This study aimed to establish of concentration levels of selected phthalate metabolites (i.e. monomethyl phthalate—MMP, monoethyl phthalate—MEP, mono-isobutyl phthalate—MiBP, monobutyl phthalate—MBP, monobenzyl phthalate—MBzP, mono-cyclohexyl phthalate—MCHP, mono(2-ethylhexyl) phthalate—MEHP and mono-n-octyl phthalate—MOP) in wild boar hair samples using liquid chromatography with mass spectrometry (LC–MS) analysis. MEHP was noted in 90.7% of samples with mean 66.17 ± 58.69 pg/mg (median 49.35 pg/mg), MMP in 59.3% with mean 145.1 ± 310.6 pg/mg (median 64.45 pg/mg), MiBP in 37.0% with mean 56.96 ± 119.4 pg/mg (median < limit of detection—LOD), MBP in 35.2% with mean 19.97 ± 34.38 pg/mg (median < LOD) and MBzP in 1.9% with concentration below limit of quantification. MEP, MCHP, and MOP have not been found in wild boar hair samples during this study. The results have shown that wild boars are exposed to phthalates and hair samples may be used as a matrix during studies on levels of phthalate metabolites in wild animals.

Serum Phthalate Concentrations and Biomarkers of Oxidative Stress in Adipose Tissue in a Spanish Adult Cohort.

The relationship between phthalates, a group of chemical pollutants classified as endocrine disruptors, and oxidative stress is not fully understood. The aim of the present hospital-based study was to explore the associations between circulating levels of 10 phthalate metabolites and 8 biomarkers of oxidative stress in adipose tissue. The study population (n = 143) was recruited in two hospitals in the province of Granada (Spain). Phthalate metabolite concentrations were analyzed by isotope diluted online-TurboFlow-LC-MS/MS in serum samples, while oxidative stress markers were measured by commercially available kits in adipose tissue collected during routine surgery. Statistical analyses were performed by MM estimators' robust linear regression and weighted quantile sum regression. Mainly, positive associations were observed of monomethyl phthalate (MMP), monoiso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) (all low molecular weight phthalates) with glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS), while an inverse association was found between monoiso-nonyl phthalate (MiNP) (high molecular weight phthalate) and the same biomarkers. WQS analyses showed significant effects of the phthalate mixture on GSH (β = -30.089; p-value = 0.025) and GSSG levels (β = -19.591; p-value = 0.030). Despite the limitations inherent to the cross-sectional design, our novel study underlines the potential influence of phthalate exposure on redox homeostasis, which warrants confirmation in further research.

Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study.

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.

Prenatal phthalate exposure and sex steroid hormones in newborns: Taiwan Maternal and Infant Cohort Study.

Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear. This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD). In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD. Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs. Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure.

Relationship between phthalates exposure, risk of decreased ovarian reserve, and oxidative stress levels.

Phthalates (PAEs), a group of environmental endocrine disruptors, are associated with oxidative stress and have adverse effects on female ovarian reserves. However, this association has been poorly investigated, particularly with respect to clinical evidence. In this study, we provided clinical evidence of a relationship between exposure levels of PAEs, oxidative stress and decreased ovarian reserve (DOR). Firstly, the urinary concentrations of metabolites of PAEs were measured by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), and the biomarkers of oxidative stress, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), were determined. Finally, statistical analyses were conducted to describe the relationship between the PAEs exposure, oxidative stress and DOR. We found that the levels of monomethyl phthalate (MMP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), and mono-(2-ethyl-5-hydroxypentyl) phthalate (MECPP) in the DOR group were significantly higher than those in the control group. There was a significant negative association between AMH and MMP, MiBP levels. and a significant positive association between FSH and MMP levels. PAEs exposure was also associated with a significant increase in MDA levels and decrease in SOD levels. In conclusion, the exposure of PAEs was closely associated with DOR, potentially mediated by oxidative stress pathways; however, small sample size was a limitation in this study.

Association of co-exposure to polycyclic aromatic hydrocarbons and phthalates with oxidative stress and inflammation

Exposure to multiple environmental pollutants is ubiquitous and inevitable, but studies investigating their exposure effects on oxidative stress or inflammation have mainly been restricted to single-pollutant models. This study investigated the association of co-exposure to polycyclic aromatic hydrocarbons and phthalates with oxidative stress and inflammation. Using a cross-sectional study in adults, we measured urinary concentrations of metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) and phthalates (mPAEs), urinary oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine, and 9 inflammatory biomarkers in paired blood samples. The associations of urinary OH-PAHs and mPAEs with oxidative stress and inflammation biomarkers were evaluated by different statistical models. The Bayesian kernel machine regression and quantile g-computation was used to examine the joint effects, and increased levels of urinary concentrations of OH-PAHs and mPAEs were associated with elevated 8-hydroxy-2′-deoxyguanosine level and white blood cell counts. Exposure to polycyclic aromatic hydrocarbons contributed more significantly to inflammation, while exposure to phthalates contributed more to oxidative stress. Monoisobutyl phthalate was identified as the most significant metabolite contributing to elevated oxidative stress levels. 1-Hydroxypyrene was negatively associated with platelet, and monomethyl phthalate was significantly positively associated with interleukin 6 in multivariate linear regression. The restricted cubic spline analysis revealed non-linear patterns of 3-hydroxyfluorene with white blood cell, lymphocyte, neutrophil, and C-reactive protein. The results indicated significant associations between increased co-exposure to polycyclic aromatic hydrocarbons and phthalates with elevated oxidative stress and inflammation. Further investigation is needed to elucidate the underlying biological mechanisms and to determine the potential public health implications.

Phthalate metabolites in breast milk from mothers in Southern China: Occurrence, temporal trends, daily intake, and risk assessment

The extensive production and use of phthalates means that these compounds are now ubiquitous in the environment and various biota, which raises concerns about potential harmful health effects. In this study, phthalate metabolites (mPAEs) were measured in breast milk (n = 100) collected from mothers of southern China between 2014 − 2022. Of the nine target mPAEs, five were detected in all of the samples, including mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP). The total levels of mPAEs in breast milk ranged from 4.76 to 51.6 ng/mL, with MiBP and MnBP being the predominant isomers (MiBP + MnBP > 48.3%). Increasing trends were observed in MMP (5.7%/year) and MEHP (7.1%/year) levels during the study period, while a decreasing trend were observed in MiBP (−6.6%/year); no clear temporal trends were found for the other metabolites and total mPAE levels. The results indicate that exposure to phthalates is still prevalent in southern China. Breastfeeding was found to contribute to estimated daily phthalate intakes of 0.383–6.95 μg/kg-bw/day, suggesting insignificant health risks to infants based on dietary exposure. However, the increasing exposure to MMP and MEHP calls for more research into the possible sources and potential risks.

Monomethyl Phthalate Causes Early Embryo Development Delay, Apoptosis, and Energy Metabolism Disruptions Through Inducing Redox Imbalance.

Phthalates are a class of environmental endocrine disrupting chemicals which can cause reproductive system damages. However, data about reproductive toxicity spectrum of phthalate metabolites among Chinese women undergoing in vitro fertilization (IVF) treatments are scarce yet. Previous studies regarding underlying embryo toxicities focused on oxidative stress and apoptosis, while energy metabolism abnormality might be another key cause for embryo developmental disruptions. Here, we found that among the measured eight phthalate metabolites, monomethyl phthalate (MMP) had the second highest urinary concentration in women receiving IVF. Compare to the lowest exposure level group, MMP in tertile 3 was associated with fewer counts of oocyte retrieved and good-quality embryos, and MMP in tertile 2 was correlated with reduced good-quality embryo rate. The direct embryo toxicities of MMP were studied using mouse 2-cell embryos. Consistent to results found in human populations, exposure to MMP induced mouse early embryo developmental delay. Furthermore, MMP exposure led to excessive reactive oxygen species production in early embryos, and antioxidant can partially rescue the early embryo development slow down. Embryo apoptosis could also be caused by oxidative stress. To be noted, elevated apoptosis level was not found in live "slow" embryos but dead embryos, which suggested that apoptosis was not related to early embryo developmental delay. Additionally, MMP exposure depleted adenosine triphosphate (ATP) synthesis of early embryos, which could be reversed by antioxidant. In conclusion, MMP, as the newly found embryonic toxicant in Chinese women, resulted in early embryo development delay, apoptosis, and energy metabolism disruptions via inducing redox imbalance.

Associations between the chemical exposome and pregnancy induced hypertension

Exposure to environmental chemicals has been linked to an increased risk of pregnancy-induced hypertension (PIH). This prospective cohort study examined the associations between PIH and maternal chemical exposure to four classes of chemicals (i.e., phthalates, bisphenols, perfluoroalkyl acids, non-essential metals and trace minerals). Participants included 420 pregnant women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort who had data available on diagnosed PIH and environmental chemical exposure. Twelve phthalate metabolites, two bisphenols, eight perfluoroalkyl acids and eleven non-essential metals or trace minerals were quantified in maternal urine or blood samples collected in the second trimester of pregnancy. Associations between the urinary and blood concentrations of these chemicals and PIH were assessed using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. Thirty-five (8.3%) participants were diagnosed with PIH. In single chemical exposure models, two phthalate metabolites, mono-methyl phthalate (MMP) and monoethyl phthalate (MEP), three perfluoroalkyl acids, perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), and one metal, manganese, were associated with increased odds of PIH. The metabolites of di (2-ethylhexyl) phthalate (DEHP) and the molar sum of these metabolites, as well as antimony, displayed trend associations (p < 0.10). In multi-chemical exposure models using LASSO penalized regressions and double-LASSO regressions, MEP (AOR: 1.43, 95% CI: 1.09–1.88, p = 0.009) and PFNA (AOR: 2.03, 95% CI: 1.01–4.07, p = 0.04) were selected as the chemicals most highly associated with PIH. These findings suggest that maternal levels of phthalates and perfluoroalkyl acids may be associated with the diagnosis on PIH. Future research should consider both individual and multi-chemical exposures when examining predictors of PIH and other maternal cardiometabolic health disorders, such as preeclampsia, eclampsia, HELLP syndrome, and gestational diabetes.

Underlying Degradation of Phthalates via Microbials in Dust from Different Microenvironments.

Phthalate monoesters (me-PAEs) have been used as biomarkers for assessing human exposure to phthalate esters (PAEs) for a long time, and studies on the sources and distribution of me-PAEs in the environment are limited. In this study, dust samples from microenvironments were collected to measure the occurrence of PAEs and me-PAEs, as well as the bacterial diversity. The results indicated that me-PAEs coexisted with PAEs in different microenvironmental dust samples, with concentrations of nine PAEs and 16 me-PAEs ranging from 108 to 1450 μg/g (median range) and 6.00 to 21.6 μg/g, respectively. The concentrations of several low molecular weight me-PAEs (e.g., monomethyl phthalate and monoethyl phthalate) in dust were even significantly higher than those of their parents. The bacteria in the dust were mainly predominant with Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes (total abundance >90%). Bacteria from bus and air conditioning dust samples had the highest species richness and species diversity. Seven genes of suspected enzymes with the ability to degrade PAEs were selected, and the concentration of me-PAEs increased with increasing abundance of enzyme function. Our findings will provide useful information on the profiles of me-PAEs and their potential sources in indoor dusts, which will benefit the accurate estimation of human exposure.

Distribution of phthalate metabolites, benzophenone-type ultraviolet filters, parabens, triclosan and triclocarban in paired human hair, nail and urine samples

In this study, the distribution of nineteen ingredients of personal care product (PCPs), including seven metabolites of phthalates (mPAEs), five benzophenone-type ultraviolet filters (BPs), and seven antimicrobial agents (AAs), were investigated in paired human hair, nail and urine samples. The median concentrations of ΣmPAEs, ΣBPs and ΣAAs were 135, 2.76 and 179 ng/g in hair, 37.3, 2.95 and 297 ng/g in nails, and 345, 4.03 and 50.1 ng/mL in urine, respectively. Mono-methyl phthalate (49%), 2,4-dihydroxybenzophenone (45%) and triclosan (71%) were the most abundant mPAE, BP and AA in hair samples, respectively, and had similar abundance in nail samples. In contrast, mono-n-butyl phthalate (45%), 4-hydroxy benzophenone (29%) and methyl paraben (54%) were the predominant mPAE, BP and AA in urine samples, respectively. Significant differences in the concentrations of some target compounds were observed between male and female but inconsistent across different matrices. Moreover, most compounds with significant correlations had quite different correlation coefficients in each matrix. No significant correlations were found between hair, nail and urine samples for most of the target analytes. These results suggest these analytes have matrix-specific distribution, and it is necessary to use multiple matrices to comprehensively assess the risk of ingredients of PCPs to human health.

Oxidative stress mediates the associations between phthalate exposures and thyroid cancer/benign nodule risk

Epidemiological studies have suggested that phthalate exposures are associated with increased risks of thyroid cancer and benign nodule, while the underlying mechanisms are largely unknown. Here, we explored the mediation effects of oxidative stress (OS) biomarkers in the associations between phthalate exposures and the risks of thyroid cancer and benign nodule. Urine samples collected from 143 thyroid cancer, 136 nodule patients, and 141 healthy controls were analyzed for 8 phthalate metabolites and 3 OS biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), and 8-iso-prostaglandin F2α (8-isoPGF2α)]. Multivariable linear or logistic regression models were used to explore the associations of OS biomarkers with phthalate metabolite concentrations and the risks of thyroid cancer and nodule. The mediation role of OS biomarkers was also investigated. Urinary monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethylhexyl) phthalate (MEHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were positively associated with at least 2 OS biomarkers (all P-values<0.01), and part of these positive associations varied in different subgroups. All 3 OS biomarkers were positively associated with the risks of thyroid nodule and cancer (P-values<0.001). The mediation analysis showed that OS biomarkers significantly mediated the associations between urinary MEHOP concentration and nodule, as well as between urinary MMP, MEHP, and MEHHP concentrations and cancer and nodule, with the estimated proportions of mediation ranging from 15.8% to 85.6%. Our results suggest that OS is a potential mediating mechanism through which phthalate exposures induce thyroid carcinogenesis and nodular formation.

Process optimization and kinetic study of biodegradation of dimethyl phthalate by KS2, a novel strain of Micrococcus sp.

The present study elucidates identification and characterization of dimethyl phthalate (DMP) degrading novel bacterial strain, Micrococcus sp. KS2, isolated from soil contaminated with municipal wastewater. Statistical designs were exercised to achieve optimum values of process parameters for DMP degradation by Micrococcus sp. KS2. The screening of the ten important parameters was performed by applying Plackett–Burman design, and it delivered three significant factors (pH, temperature, and DMP concentration). Further, response surface methodology involving central composite design (CCD) was implemented to examine mutual interactions among variables and achieve their optimal response. The predicted response indicated that maximum DMP degradation (99.67%) could be attained at pH 7.05, temperature 31.5 °C and DMP 289.19 mg/l. The strain KS2 was capable of degrading up to 1250 mg/l of DMP in batch mode and it was observed that oxygen was limiting factor in the DMP degradation. Kinetic modeling of DMP biodegradation indicated that Haldane model fitted well with the experimental data. During DMP degradation, monomethyl phthalate (MMP) and phthalic acid (PA) were identified as degradation metabolites. This study provides insight into DMP biodegradation process and proposes that Micrococcus sp. KS2 is a potential bacterial candidate to treat effluent containing DMP.

Phthalates exposure as environmental risk factor for type 2 diabetes mellitus

Phthalates exposure occurs in all areas, such as foods' plastic packaging, cosmetics, and others. Previous studies showed that phthalates are associated with the prevalence of T2DM. Type 2 Diabetes Mellitus (T2DM) is caused by a combination of defective insulin secretion by pancreatic β-cells and the insulin-resistance. This study aimed to investigate whether phthalate exposure is an environmental risk factor for T2DM. A case-control study was conducted among residents in the South Tangerang district from June 2020 to February 2021 using a purposive sampling technique. The cases were the patients diagnosed T2DM with HbA1c&lt;span style="text-decoration: underline;"&gt;&amp;gt;&lt;/span&gt;6.5% random blood sugar&lt;span style="text-decoration: underline;"&gt;&amp;gt;&lt;/span&gt;200 mg/dL, with history T2DM treatment. The respondents' urines were collected and evaluated using liquid chromatography/mass spectrometry (LC/MS). A total of 47 cases and 47 controls were recruited in the study. The lowest monomethyl phthalate (MEP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were 5.37 µg/L and 2.02 µg/L, respectively. On multivariable regression analysis, the high urinary MEP level (&amp;gt;131.91 µg/L) was independently associated with T2DM (OR: 3.754, 95% CI: 1.559–8.811, p-value: 0.002). MEP is an environmental risk factor for T2DM and likely has a significant impact on human health than MEHHP.

Daphnia magna sub-lethal exposure to phthalate pollutants elicits disruptions in amino acid and energy metabolism

Phthalic acid esters (PAEs) are a class of chemicals that are usually incorporated as additives in the manufacturing of plastics. PAEs are not covalently bound to the material matrix and can, consequently, be leached into the environment. PAEs have been reported to act as endocrine disruptors, neurotoxins, metabolic stressors, and immunotoxins to aquatic organisms but there is a lack of information regarding the impact of sub-lethal concentrations to target organisms. The freshwater crustacean Daphnia magna, a commonly used model organism in aquatic toxicity, was exposed to four phthalate pollutants: dimethyl phthalate (DMP), diethyl phthalate (DEP), monomethyl phthalate (MMP), and monoethyl phthalate (MEP). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in a targeted metabolomic approach to quantify polar metabolites extracted from a single Daphnia body. Individual metabolite percent changes and hierarchical clustering heatmap analysis showed unique metabolic profiles for each phthalate pollutant. Metabolite percent changes were mostly downregulated or presented opposing responses for the low and high concentrations tested. Meanwhile, pathway analyses suggest the disruption of related and unique pathways, mostly connected with amino acid and energy metabolism. The pathways aminoacyl-tRNA biosynthesis, arginine biosynthesis, and glutathione metabolism were disrupted by most selected PAEs. Overall, this study indicates that although phthalate pollutants can elicit distinct metabolic perturbations to each PAE, they still impacted related biochemical pathways. These chemical-class based responses could be associated with a common toxic mechanism of action. The reported findings show how targeted metabolomic approaches can lead to a better understanding of sub-lethal exposure to pollutants, revealing metabolomic endpoints do not hold a close relationship with traditional acute toxicity endpoints.

Role of inflammatory lipid and fatty acid metabolic abnormalities induced by plastic additives exposure in childhood asthma

Lipid metabolism play an essential role in occurrence and development of asthma, and it can be disturbed by phthalate esters (PAEs) and organophosphate flame retardants (OPFRs). As a chronic inflammatory respiratory disease, the occurrence risk of childhood asthma is increased by PAEs and OPFRs exposure, but it remains not entirely clear how PAEs and OPFRs contribute the onset and progress of the disease. We have profiled the serum levels of PAEs and OPFRs congeners by liquid chromatography coupled with mass spectrometry, and its relationships with the dysregulation of lipid metabolism in asthmatic, bronchitic (acute inflammation) and healthy (non-inflammation) children. Eight PAEs and nine OPFRs congeners were found in the serum of children (1 – 5 years old) from Shenzhen, and their total median levels were 615.16 ng/mL and 17.06 ng/mL, respectively. Moreover, the serum levels of mono-methyl phthalate (MMP), tri-propyl phosphate (TPP) and tri-n-butyl phosphate (TNBP) were significant higher in asthmatic children than in healthy and bronchitic children as control. Thirty-one characteristic lipids and fatty acids of asthma were screened by machine-learning random forest model based on serum lipidome data, and the alterations of inflammatory characteristic lipids and fatty acids including palmitic acids, 12,13-DiHODE, 14,21-DiHDHA, prostaglandin D2 and LysoPA(18:2) showed significant correlated with high serum levels of MMP, TPP and TNBP. These results imply PAEs and OPFRs promote the occurrence of childhood asthma via disrupting inflammatory lipid and fatty acid metabolism, and provide a novel sight for better understanding the effects of plastic additives on childhood asthma.

Phthalate metabolites in loggerhead marine turtles (Caretta caretta) from the Mediterranean Sea (East Spain region)

The exposure of marine reptiles to phthalates has received considerable attention due to the ubiquitous occurrence of these contaminants in the marine environment. The occurrence of phthalate metabolites is established in human populations and marine mammals, but data is scarce for marine reptiles. In this study, concentrations of 18 phthalate metabolites were determined in liver samples from 79 loggerhead marine turtle (Caretta caretta) samples collected between 2016 and 2021 in the limits of the Valencian Community (East Spain). For this purpose, the phthalate metabolites were purified from the livers by solid phase extraction and were quantified by UPLC-MS/MS. Fifteen phthalate metabolites were detected in the samples. Monoethyl phthalate (mEP), monomethyl phthalate (mMP), mono-n-butyl phthalate (mBP), phthalic acid (PA) and mono-n-hexyl phthalate (mHxP) were the most abundant metabolites, accounting for detection rates >85%. The highest median concentrations were found for PA (24.2 ng/g dry weight, d.w.) and mHxP (20.3 ng/g d.w.) followed by mMP (12.0 ng/g d.w.), mEP (5.76 ng/g d.w.) and mBP (4.26 ng/g d.w.). The sum of the medians of these five phthalate metabolites (Σ5PhMet) indicated that concentrations were higher for turtles during year 2020, while a negative association was found between [Σ5PhMet] and the turtle size. To our knowledge, this is the first study on the biomonitoring of 18 phthalate metabolites in loggerhead marine turtles, and results show that western Mediterranean loggerhead turtles are usually exposed to these contaminants.

Associations between maternal phthalate exposure and neonatal neurobehaviors: The Taiwan maternal and infant cohort study (TMICS)

Previous studies have shown associations between prenatal phthalate exposure and neurobehavioral changes in children. However, few studies have focused on neonatal neurobehavioral development. This study aimed to examine the associations between prenatal phthalate exposure and neonatal neurobehavioral development in the early days of life after birth.This cohort study included 283 mother-infant pairs who participated in the Taiwan Mother Infant Cohort Study during 2012–2015. Each mother was interviewed, and urine samples were collected during the third trimester of pregnancy (weeks 29–40). Eleven common phthalate metabolites in maternal urine were analyzed. The Chinese version of the Neonatal Neurobehavioral Examination was used to evaluate early infant neurobehavioral development within five days of birth. We performed multiple linear regressions to explore the associations between phthalate exposure and neonatal neurobehavioral development. Sex differences in the association between phthalate metabolites and neonatal neurobehaviors were noted. Among girls, tertiles of phthalate metabolite concentrations were associated with worse behavioral responses and tone and motor patterns in the high-molecular-weight phthalate (HMW) and low-molecular-weight phthalate (LMW) groups. Girls in the highest tertile of di-2-ethylhexyl phthalate (DEHP) and mono-isobutyl phthalate (MiBP) had a negative association with tone and motor patterns. Girls in the highest tertile of mono-n-butyl phthalate (MnBP) and MiBP showed a negative association with behavioral responses. In contrast, tertiles of phthalate metabolite exposure were associated with improved neurobehaviors in mono-methyl phthalate (MMP) among boys. The highest tertile of MMP was positively associated with behavioral responses, primitive reflexes, and tone and motor patterns. Our findings suggest that maternal phthalate exposure affects neonatal neurobehavioral development in a sex-specific manner. Despite the relatively small sample size, our findings add to the existing research linking maternal phthalate exposure to neonatal neurobehavioral development. Additional research is needed to determine the potential long-term effects of prenatal phthalate exposure on children.