Monoethyl Phthalate Research Articles

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.

Biodegradation of dibutyl phthalate and diethyl phthalate by indigenous isolate Bacillus sp. MY156: Characterization, stoichiometry, enzyme activity, and physiological response to cell surface

An indigenous bacterial strain, Bacillus sp. MY156, was isolated from a local wastewater treatment plant and utilized for degradation of dibutyl phthalate (DBP) and diethyl phthalate (DEP). The isolate showed a substrate preference of DBP to DEP. The optimal biodegradation conditions were pH 7, 30 °C, 0.2 (in terms of OD600) inoculum size, and 2 % (v v−1) bacterial load. The biodegradation of DBP and DEP as sole carbon source was comprehensively investigated via degradation kinetics and mass balance analysis. The isolate achieved complete degradation and over 80 % removal of 300 mg L−1 DBP within 60 h and 200 mg L−1 DEP in 5 days. The biodegradation of DBP and DEP fitted the inhibitory kinetic model, and the maximum degradation rates for DBP and DEP were 183.34 and 66.90 mg L−1 day−1, respectively. The cell surface responses to biodegradation were investigated by analyses of morphology, Fourier transform-infrared, and extracellular polymeric substance. The potential intermediates were mono-n-butyl phthalate, mono-ethyl phthalate, phthalic acid, and protocatechuic acid by β-oxidation, hydrolysis, and decarboxylation. The esterase and dehydrogenase activities reached the highest at the initial and middle phases during biodegradation. The docking studies also elucidated the relevant enzyme preferred DBP to DEP via binding energy and bond distance.

Phthalates exposure and pubertal development in a 15-year follow-up birth cohort study in Taiwan.

Phthalates are ubiquitous endocrine disruptors that can affect pubertal development in children. The association of fetal and childhood levels of phthalates with pubertal development were explored. We conduct a population-based birth cohort study to investigate the association between prenatal and childhood exposure to phthalates and pubertal development. Initially, a total of 445 children were recruited from 2000 to 2001, of which 90 children were followed for 15 years which measurements of urine and development assessed at 2, 5, 8, 11, and 14 years. We defined higher Tanner stage as the 14-year-old Tanner stage ≥ 4 and 5 for boys and girls, respectively. A logistic regression analysis was conducted to estimate the crude and adjusted odds ratio of a higher Tanner stage at 14 years old. The Pearson correlation coefficient and multiple linear regression were used to estimate the association of testicular volume, uterine volume, ovarian volume, and blood hormones at 14 years of age with the log-transformed concentration of phthalates at 2, 5, 8, 11, and 14 years. In boys, a significantly different geometric mean of mono-benzyl phthalate (MBzP) was observed in 11-year-olds; 6.82 and 2.96 in the lower Tanner stage group and higher Tanner stage group. In girls, a significant difference in the geometric mean of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in 11-year-olds and mono-ethyl phthalate (MEP) in 2-year-olds was observed; MEHHP was 32.97 and 18.13 in the lower Tanner stage group and higher Tanner stage group, and MEP was 26.54 and 65.74 in the lower Tanner stage group and higher Tanner stage group, respectively. Uterine volume at 14 years old was negatively associated with several phthalate metabolites (MEHP at 8 years old, MnBP at 8 years old, MBzP at 14 years old, MMP prenatally, MMP at 8 years old, and MEP at 8 years old) after adjusting for covariates. However, no significant correlations were found between phthalate metabolites and ovarian or testicular volume. Phthalate exposure at certain time points may influence the reproductive development of children during puberty; however, further studies should be conducted to determine the causal nature of this association.

Supporting legislative action: Urinary levels of phthalates and phenols among influencers in the ‘Plastics in the spotlight’ advocacy initiative

BackgroundSociety-wide initiatives to prevent human exposure to plastic residues include laws and policies. Such measures require citizens’ support, which can be increased by honest advocacy and pedagogic projects. These efforts must have a scientific basis. ObjectiveTo assist the ‘Plastics in the spotlight’ advocacy initiative raise awareness among the general public of the presence of plastic residues in the human body, and to increase citizens' support for legislation on plastic control in the European Union. MethodsSpot urine samples of 69 volunteers with cultural and political influence from Spain, Portugal, Latvia, Slovenia, Belgium, and Bulgaria were collected. Concentrations of 30 phthalate metabolites and phenols were determined through a high-performance liquid chromatography with tandem mass spectrometry and ultra-high-performance liquid chromatography with tandem mass spectrometry, respectively. ResultsAt least 18 compounds were detected in all urine samples. The maximum number of compounds detected per participant was 23, and the mean, 20.5. Phthalates were detected more frequently than phenols. Median concentrations were highest for monoethyl phthalate (41.6 ng/mL, adjusted for specific gravity), and maximum concentrations were highest for mono-iso-butyl phthalate (1345.1 ng/mL), oxybenzone (1915.1 ng/mL), and triclosan (949.6 ng/mL). Most reference values were not exceeded. Women had higher concentrations of the 14 phthalate metabolites and oxybenzone than men. Urinary concentrations were not correlated with age. DiscussionThe study had three main limitations: method of subject selection (volunteers), small sample size, and limited data on determinants of exposure. Studies on volunteers do not pretend to be representative of the general population and are no substitute for biomonitoring studies in representative samples of the populations of interest. Studies as ours can only illustrate the existence and some aspects of the problem, and can raise awareness among citizens concerned by the evidence that the studies provide in a group of subjects who are humanly appealing. ConclusionsThe results illustrate that human exposure to phthalates and phenols is widespread. All countries appeared to be similarly exposed to these contaminants, with higher levels in females. Most concentrations did not exceed reference values. The effects of this study on the objectives of the ‘Plastics in the spotlight’ advocacy initiative deserve a specific analysis from policy science.

Urinary phthalate metabolites and heart rate variability: A panel study

Phthalates exposure is linked with cardiovascular disease. Decreased heart rate variability (HRV) is an early indicator of cardiac autonomic imbalance. We conducted a longitudinal panel study in 127 Chinese adults with 3 repeated visits to explore the associations of individual and mixtures of phthalates exposure with HRV. We quantified 10 urinary phthalate metabolites by gas chromatograph-tandem mass spectrometer (GC-MS/MS) and 6 HRV indices by 3-channel digital Holter monitors. Linear mixed-effect (LME) models and Bayesian kernel machine regression (BKMR) models were separately implemented to evaluate the associations. After multivariate adjustments, we found that urinary mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MBP) at lag 0 day were inversely associated with low-frequency power (LF) or total power (TP) (all P-FDR <0.05). In mixture analysis, we observed negative overall associations of phthalate mixtures at lag 0 day with LF or TP, and MiBP was the major contributor. Moreover, stratified analysis suggested that the inverse relationships of MiBP at lag 0 day with LF and TP were more prominent in subjects aged >50 years (all Pinteraction < 0.01). Our findings revealed that exposure to individual and mixtures of phthalates, especially MiBP, were related to decreased HRV.

Phthalates and phthalate metabolites in urine from Tianjin and implications for platelet mitochondrial DNA methylation.

Phthalates (PAEs) are important synthetic substances in plastics, attracting much attention due to their potential effects on the cardiovascular system. In this study, urine and blood samples from 39 individuals were collected in Tianjin, China. Phthalates and phthalate metabolites (mPAEs) were analyzed using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. The polymerase chain reaction (PCR) products from bisulfite-treated mitochondrial DNA (mtDNA) samples were analyzed using pyrosequencing technology. The detection frequencies for 9 PAEs varied from 2.56 to 92.31%, and those for 10 mPAEs varied from 30.77 to 100%. The estimated daily intakes (EDIs) and cumulative risk of PAEs were calculated based on the experimental statistics of urinary PAEs and mPAEs. For PAEs, the HIRfD (hazard index corresponding to reference doses) values of 10.26% of participants and the HITDI (hazard index corresponding to tolerable daily intake) values of 30.77% of participants were estimated to exceed 1, suggesting a relatively high exposure risk. The mtDNA methylation levels in the MT-ATP8 and MT-ND5 were observed to be lower than in the MT-ATP6. Mono-ethyl phthalate (MEP) and MT-ATP8 were positively correlated with triglyceride levels (p < 0.05). Based on the association of PAEs, mtDNA methylation, and triglycerides, the mediating role of mtDNA methylation between PAEs and cardiovascular diseases (CVDs) was analyzed in this study, but no mediated effect was observed. The effects of PAE exposure on cardiovascular diseases (CVDs) should be investigated further.

Dysregulation of steroid metabolome in follicular fluid links phthalate exposure to diminished ovarian reserve of childbearing-age women

The widespread use of phthalates (PAEs) has drawn increasing attention due to their endocrine disruption and reproductive toxicity, while the steroid metabolome is essential for follicular development. However, the mechanism by which PAE exposure affects ovarian reserve through the steroid metabolome remains unclear. This study recruited 264 childbearing-age women in Tianjin (China) from April 2019 to August 2020 in a cross-sectional design. Target metabolome analysis of 16 steroids was performed in follicular fluid (FF) to compare diminished ovarian reserve (DOR) against normal ovarian reserve (NOR) women and differential steroids were identified using binary logistic analyses. Further analysis of eleven PAE metabolites (mPAEs) in FF was conducted, and the retrieved oocyte number (RON) representing ovarian reserve was counted. Multiple linear regression and quantile-based g-computation (qgcomp) models were used to associate individual mPAEs and mPAE mixture with the DOR-related differential steroids in FF. Mediation analysis was used to discuss the mediating effect of DOR-related steroids on the association between mPAEs and RON. Androstenedione (A4), corticosterone (CORT), cortisol (COR) and cortisone were significantly down-regulated in FF from women with DOR. Nine mPAEs with detection frequencies greater than 60% and median concentrations of 0.02–4.86 ng/mL were incorporated into statistical models. Negative associations with COR and CORT were found for mono-ethyl phthalate (mEP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and mono-2-ethylhexyl phthalate (mEHP). A positive association with cortisone was found for mEOHP, mEHP, monobutyl phthalate (mBP), and mono (2-isobutyl) phthalate (miBP). The qgcomp and mediation analyses revealed that mEP and mEOHP not only significantly contributed to the decline of COR and CORT in the mixed exposure but also indirectly reduced RON through the mediating effects of COR and CORT. In conclusion, PAE exposure may decrease ovarian reserve by downregulating COR and CORT.

Risk assessment of phthalate metabolites accumulated in fish to the Indo-Pacific humpback dolphins from their largest habitat

Food has consistently been shown to be an important source of exposure to environmental pollutants, drawing attention to the health risks of pollutants in marine mammals with high daily food intake. Here, the dietary exposure risks posed to the Indo-Pacific humpback dolphins from the Pearl River Estuary (PRE), China, by fourteen phthalate metabolites (mPAEs) were evaluated for the first time. On the basis of liquid chromatography-mass spectrometry (LC-MS/MS) analysis, the levels of ∑14mPAEs in ten main species of prey fish (n = 120) of dolphins ranged from 103.0 to 444.5 ng/g wet weight (ww), among which Bombay duck contained a significantly higher body burden of ∑14mPAEs than other prey species. Phthalic acid (PA), monooctyl phthalate (MnOP), monononyl phthalate (MNP), monoethyl phthalate (MEP), monoethylhexyl phthalate (MEHP), mono (5-carboxy-2-ethylpentyl) phthalate (MECPP), monobutyl phthalate (MBP), and monoisobutyl phthalate (MiBP) all had a trophic magnification factor (TMF) greater than unity, indicating the biomagnification potential of these mPAEs in the marine ecosystem of the PRE. A dietary exposure assessment based on the adjusted reference dose values of phthalates (PAEs) showed that bis (2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) may pose a high (HQ > 1) and medium (0.01 < HQ < 1) risk to the dolphin adults and juveniles, respectively. Our results highlight the potential health risks of mPAEs to marine mammals through dietary routes.

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.

Associations of early life phthalate exposures with adolescent lipid levels and insulin resistance: The HOME Study.

Early-life phthalate exposures may disrupt metabolic processes; however few prospective studies have assessed whether these associations extend to cardiometabolic outcomes during adolescence. Among 183 mother-adolescent pairs in a prospective cohort study that enrolled pregnant women in Cincinnati, OH (2003-2006), we quantified nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children. At age 12 years, we assessed triglycerides, high-density (HDL) and low-density (LDL) lipoprotein cholesterol, insulin, and glucose from fasting serum samples and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Using multiple informant models, we estimated covariate-adjusted associations between urinary phthalate concentrations at each time period and cardiometabolic biomarkers at age 12 years, including modification by child sex. Although most associations were weak or null, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and monobenzyl phthalate (MBzP) concentrations were generally associated with lower LDL at age 12 years. A 10-fold increase in 4- and 12-year MEP was associated with -15.3mg/dL (95% CI: 27.5, -3.13mg/dL) and -11.8mg/dL (-22.0, -1.51mg/dL) lower LDL, respectively. Discrepant associations were observed in females versus males: a 10-fold increase in 3-year MEP concentrations was associated with 12.0mg/dL (95% CI: 7.11, 31.1mg/dL) higher LDL levels in males and -30.4mg/dL (95% CI: 50.9, -9.8mg/dL) lower LDL levels in females. Some urinary phthalate concentrations were cross-sectionally associated with HOMA-IR. Early-life phthalate biomarker concentrations may be inversely associated with LDL during early adolescence in an exposure-period and sex-dependent manner.

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.

Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children.

The mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential mechanism of hypertension in children. Serum samples from 29 control children, 38 children with normal body mass index and simple hypertension (NBp), 8 children overweight with simple hypertension (OBp), 37 children with normal body mass index and H-type hypertension (NH) and 19 children overweight with H-type hypertension (OH) were analyzed by non-targeted metabolomics. A total of 1235 differential metabolites were identified between children with hypertension and normal controls, of which 193 metabolites including various lipids were significantly expressed. Compared with the control group, 3-dehydroepiandrosterone sulfate, oleic acid and linoleic acid were up-regulated, and gamma-muricholic acid was down-regulated in the NBp group; 3-dehydroepiandrosterone sulfate, 4-acetamidobutanoate and 1-hexadecanoyl-2-octadecadienoyl-sn-glyero-3-phosphocholine were up-regulated in the OBp group, whereas adenosine and 1-myristoyl-sn-glyero-3-phosphocholine were down-regulated; in the NH group, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, phenol and 3-methoxytyramine were up-regulated, while pentadecanoic acid was down-regulated; in the OH group, NG,NG-dimethyl-L-arginine, 1-palmitoyl-sn-glycero-3-phosphocholine and monoethyl phthalate were up-regulated, while phloretin and glycine were down-regulated. The results showed that the children with hypertension had obvious disorders of lipid metabolism (especially in the overweight hypertension group), which led to the occurrence of hypertension. Additionally, the concentration of NO production-related NG, NG-dimethyl-L-arginine, was significantly increased, which may play an important role in H-type hypertension in children.

Associations between exposure to phthalates and subclinical hypothyroidism in pregnant women during early pregnancy: A pilot case-control study in China

Phthalates are environmental endocrine disruptors with thyroid-disrupting properties; however, the association between phthalate exposure and subclinical hypothyroidism (SCH) during pregnancy is unknown. We recruited a study population from a cohort of pregnant women in Beijing, China, and conducted the present pilot case-control study of 42 SCH cases and 84 non-SCH controls matched with age and body mass index (BMI). Serum levels of thyroid peroxidase antibody, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and urinary levels of ten phthalate metabolites during early pregnancy were measured. Urinary monoethyl phthalate (MEP) levels in SCH cases were observably higher than those in controls (p = 0.01). Conditional logistic regression analysis revealed that mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), MEP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and di-(2-ethylhexyl) phthalate (ΣDEHP) were significantly associated with a higher risk of SCH during early pregnancy (adjusted odds ratios = 1.89, 1.42, 1.81, and 1.92, respectively). Concomitantly, multiple linear regression analysis showed that MECPP, MEOHP, and ΣDEHP were positively associated with TSH and FT4 × TSH in the entire study population. Bayesian kernel machine regression analysis and stratified analysis by BMI revealed upward tendencies in the serum levels of TSH and FT4 × TSH. In summary, exposure to phthalates, especially DEHP, may be associated with a higher risk of SCH during early pregnancy, and a possible mechanism is the disruption of the hypothalamus-pituitary-thyroid axis.

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.

Do phthalates and their metabolites cause poor semen quality? A systematic review and meta-analysis of epidemiological studies on risk of decline in sperm quality.

A systematic review and meta-analysis were conducted to understand the association of phthalates and their metabolites with sperm quality in humans. By June 30, 2022, relevant literature on the effects of phthalates and their metabolites on sperm quality were searched and collected using three English-language databases including PubMed, EMbase, and Web of Science. Two researchers independently screened literature, extracted data, and assessed risk of bias. Stata 11 and RevMan 5.3 were used to conduct meta-analysis, test publication bias, and sensitivity analysis. A total of 12 literature were included for meta-analysis, excluding literature with different effect sizes. The results of meta-analysis indicated that monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP) in urine were negatively correlated with semen concentration, and the results were statistically significant (MBP, pooled odds ratio (OR), 95% confidence interval (CI): 2.186 (1.471, 3.248), P < 0.05) and (MBzP, pooled OR (95%CI): 1.882 (1.471, 3.248), P < 0.05). Furthermore, the level of Di-(2-ethylhexyl) phthalate (DEHP) in semen was negatively correlated with semen concentration and the combined effect size was (pooled correlation coefficients (r) (95%CI): -0.225 (-0.319, -0.192), P < 0.05). However, the associations between MBP and MBzP with sperm motility and sperm morphology were not statistically significant (P > 0.05). And there was also no significant correlation between monoethyl phthalate (MEP), monomethyl phthalate (MMP), and mono-2-ethylhexyl phthalate (MEHP) and semen parameters, including semen concentration, sperm motility, and sperm morphology (P > 0.05). In summary, this current study provides moderate-certainty evidence for the data demonstrated that is a negative correlation between urine MBP levels, urine MBzP levels, and semen DEHP levels with semen concentration. In the future, more longitudinal cohort studies are needed to help elucidate the overall association.

The association of phthalate metabolites with childhood waist circumference and abdominal obesity.

The detection rate of PAEs metabolites is common, and the exposure level of PAEs metabolites was associated with the risk of abdominal obesity in Chinese students aged 7-10years. •The prevalence of childhood abdominal obesity had increased sharply from 4.9% in 1993 to 17.5% in 2014 in China. More than 80% of the Chinese children and adolescents have measurable level of several PAEs metabolites in the urine. Previous studies with limited sample had explored the association between DEHP metabolites exposure and childhood abdominal obesity risk, however, the association were inconsistent. •The detection rate of PAEs metabolites is common among Chinese children aged 7-10 years. Boys had higher concentrations of PAEs metabolites than girls (P < 0.05), except for monoethyl phthalate. Compared with the Q1 group of PAEs metabolites, the risk of childhood abdominal obesity increased to 429% and 273% for the Q4 group of monoethyl phthalate and monoisobutyl phthalate, respectively.

Exposure to a mixture of personal care product and plasticizing chemicals in relation to reproductive hormones and menarche timing among 12-19 years old girls in NHANES 2013-2016.

The effects of co-exposure to personal care product and plasticizing chemicals (PCPPCs) on reproductive hormones and menarche timing has rarely been studied. We used Bayesian kernel machine regression (BKMR), adaptive least absolute shrinkage and selection operator (adaptive LASSO), and generalized linear model (GLM) to explore the mixture effects of 16 PCPPCs on reproductive hormones and early menarche among 297 girls aged 12-19 years in the National Health and Nutrition Examination Survey (NHANES) 2013-2016. In the BKMR, the mixture of PCPPCs was negatively and positively associated with testosterone (TT) and sex hormone-binding globulin (SHBG), respectively. In the adaptive LASSO, 2,5-dichlorophenol (2, 5-DCP), Mono (carboxyisoctyl) phthalate (MCOP), and Mono-benzyl phthalate (MBzP) were positively associated with estrogen (E2), whereas Mono-ethyl phthalate (MEP), Monoisobutyl phthalate (MiBP) and Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were inversely associated with E2. Bisphenol A (BPA) and MBzP were positively associated with SHBG, whereas Mono (carboxyisonony) phthalate (MCNP) and Mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) were inversely associated with SHBG. In GLM, Benzophenone-3 (BZP) and MECPP were negatively associated with TT, whereas 2,4-dichlorophenol (2,4-DCP) revealed a positive association with early menarche onset. In conclusion, PCPPCs in the mixture and individually are associated with reproductive hormones and early menarche onset in girls.

Maternal urine phthalate metabolite exposure and miscarriage risk: a nested case-control study of the Zunyi Birth Cohort.

Phthalates (PAEs) are widespread persistent organic pollutants and endocrine disruptors. However, the associations between PAE exposure and the risk of miscarriage in humans are unclear, and an insufficient number of studies have evaluated the possible threshold or dose-dependent effects of first trimester PAE exposure on miscarriage risk. Our research measured the levels of mono-methyl phthalate (MMP), mono-ethyl phthalate, mono-isobutyl phthalate, MiBP mono-butyl phthalate (MBP), mono-octyl phthalate, mono-benzyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in maternal urine collected in early gestation between 150 pregnancies ending in miscarriage and 150 pregnancies with live birth. We also estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PAE as a continuous variable or quartile. A restrictive cubic splines was used to assess dose-dependent effects after controlling for maternal characteristics (e.g., age, educational level). we identified monotonically increasing dose-dependent effects of MEHHP and MMP on the risk of miscarriage. The largest effect estimates were approximately threefold higher for the highest MBP (OR = 2.57; 95% CI = 1.32-5.01) or MMP quartile (OR = 3.57; 95% CI = 1.82-7.00) and two-fold higher for the highest MEHHP quartile (OR = 2.12; 95% CI = 1.10-4.11). Our research preliminarily obtained possible thresholds of MBP, MEHHP, and MMP which were 18.07, 2.38, and 0.80µg/g Cr for the risk of miscarriage, respectively. First-trimester exposure to MBP, MEHHP, and MMP exceeding certain thresholds increases the risk of miscarriage.

Phthalate Metabolites in Urine of Chinese Children and Their Association with Asthma and Allergic Symptoms.

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.

Exposure to phthalates, potential endocrine disruptors, in an infant cohort in Modena, Italy

Abstract Phthalates are pollutants ubiquitous in the environment. Human exposure to phthalates and their endocrine disrupting effects have been widely studied. Therefore, the European Union forbids phthalates in toys, cosmetic and kitchenware manufacturing. However, phthalate metabolites can still be found in human biological matrices. The purpose of this study is to investigate phthalate exposure over time in a group of Italian healthy newborns. In a prospective cohort study, we enlisted 187 women who gave birth in the University Hospital of Modena, Italy, between January 2019 and May 2020. Urine samples from women after delivery and from their infants at birth, 3 and 6 months were collected and 8 metabolites of 6 phthalates were analysed. Descriptive statistics were calculated and preliminary correlation coefficients tests were performed. Monoethylphthalate (MEP) was always detectable in urine samples. MEP, monomethylphthalate and diethylhexylphthalate metabolites showed an increasing trend over time, while monobutylphthalate and monobenzylphthalate showed decreasing levels over time. Associations between levels of phthalates metabolites in mother and infant pairs at birth were found for a few metabolites, while metabolites in infant samples at 3 and 6 months appeared often significantly associated. Infants’ phthalate exposure in Modena is still high and prolonged over time, even to those more toxic and strictly regulated. As phthalates presence in indoor environment can be a risk factor especially for the most fragile groups of population, such as children, public Health campaigns addressing childbearing age women should stress about the risk posed by these substances and how to avoid their exposure. Moreover, regulatory actions and a stricter legislation should be considered. Key messages • In Italy infant exposure to phthalates, including those strictly forbidden, appears still high and continuous over time. • Public heath intervention and stricter regulatory actions should be considered.