Mono-(2-ethylhexyl) Phthalate Levels Research Articles

Evaluation of Exposure to Bisphenol A, Bisphenol F, and Phthalates in Patients with Phenylketonuria and Its Differences According to Dietary Status.

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. 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. 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). 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.

Endocrine-Disrupting Chemicals Exposure and Neurocognitive Function in the General Population: A Community-Based Study.

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. 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. 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. Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

Long-term impacts of endocrine-disrupting chemicals exposure on kidney function: A community-based cohort study

This study explores the extended renal effects of endocrine-disrupting chemicals (EDCs) exposure, a linkage already established with adverse health outcomes, notably chronic kidney disease. To delve deeper, the Chang Gung Community Research Center conducted a longitudinal study with 887 participants. Among them, 120 individuals were scrutinized based on EDC scores, analyzing 17 urinary EDCs and renal function. Findings revealed elevated mono-(2-ethylhexyl) phthalate (MEHP) and bisphenol A levels in higher EDC exposure cases. MEHP notably correlated with increased urinary albumin-to-creatinine ratio (UACR), predicting a > 15% decline in estimated glomerular filtration rate. Higher MEHP levels also hinted at declining renal function. UACR escalation linked significantly with specific EDCs: MEHP, methylparaben, nonylphenol, and 4-tert-octylphenol. This research underscores enduring renal hazards tied to environmental EDC exposure, particularly MEHP, emphasizing the urgent call for robust preventive public health strategies.

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.

Associations between phthalate metabolites and cytokines in the follicular fluid of women undergoing in vitro fertilization

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

BackgroundAdiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood.MethodsThis study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12–30 from Taiwan.ResultsResults showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (− 0.095 vs. − 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG.ConclusionsIn this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Toxicoproteomics of Mono(2-ethylhexyl) phthalate and Perfluorooctanesulfonic Acid in Models of Prostatic Diseases.

Benign and malignant prostatic diseases are common, costly, and burdensome; moreover, they share fundamental underlying molecular processes. Several ubiquitous contaminants may perturb these processes, possibly via peroxisome proliferator-activated receptor (PPAR) signaling, but the role of environmental exposures─particularly mixtures─in prostatic diseases is undefined. In the present study, nontumorigenic prostate stromal cells and metastatic prostate epithelial cells were exposed to ubiquitous exogenous PPAR ligands under different dosing paradigms, including a mixture, and effects were assessed via mass spectrometry-based global proteomics. In prostate stromal cells, environmentally relevant levels of mono(2-ethylhexyl) phthalate (MEHP), alone and in combination with perfluorooctanesulfonic acid, led to significant changes in proteins involved in key processes underlying prostatic diseases: oxidative stress defense, proteostasis, damage-associated molecular pattern signaling, and innate immune response signaling. A follow-up experiment in metastatic prostate epithelial cells showed that the occupationally relevant levels of MEHP perturbed similar processes, including lipid, cholesterol, steroid, and alcohol metabolism; apoptosis and coagulation regulation; wound response; and aging. This work shows that environmental exposures may contribute to prostatic diseases by perturbing key processes of a proposed adverse outcome pathway, including lipid metabolism, oxidative stress, and inflammation. Future in vivo research will investigate the role of contaminants in prostatic diseases and in preventative agents.

Plasma bisphenol a and phthalate levels in children with cerebral palsy: a case-control study

ABSTRACT The case-control study aimed to evaluate potential sources of exposure and the plasma concentrations of bisphenol A (BPA) and phthalates in prepubertal children having cerebral palsy (CP) and healthy control. Blood samples of 68 CP and 70 controls were analyzed for BPA, di-(2-ethylhexyl)-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and dibutyl phthalate (DBP). BPA and DBP levels were similar in groups. The median DEHP and MEHP levels of the children with CP were significantly lower than those of the controls (p = 0.035, p < 0.001, respectively). Exposure to plastic food containers/bags, personal care hygiene products, household cleaners, wood/coal stove heating, and city water supplies were associated with increased odds of higher BPA and phthalate levels in children with CP. In conclusion, potential exposure sources for BPA and phthalates differ in children with CP and healthy controls, and children with CP are not exposed to higher levels of BPA and phthalates.

The Potential Biomarker of Di(2-ethylhexyl) Phthalate Exposure during Catheterization.

Di(2-ethylhexyl) phthalate (DEHP) may produce toxicity, posing a risk to human health. Medical devices composed of DEHP are frequently used in catheterization, but few studies have investigated DEHP exposure during catheterization. The aim of this prospective series was to characterize the exposure pattern of DEHP during catheterization. We enrolled 16 patients with congenital heart disease undergoing catheterization. Collection of urine was done to measure DEHP metabolites on hospitalization, before catheterization, after catheterization, and at discharge. The following DEHP metabolites were measured: mono-(2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and the ratio of MEHP to overall metabolites (MEHP%) was determined. DEHP exposure from polyvinyl chloride (PVC)-containing catheter and infusion systems were recorded in detail. Differences in DEHP levels before and after catheterization were analyzed. Urinary levels of MEHP, MEHHP, and MEOHP significantly decreased from before catheterization to after catheterization (all p < 0.01), but did not change significantly from initial hospitalization to before catheterization. Urinary MEHP% significantly decreased from initial hospitalization to before catheterization (p < 0.001), then increased after catheterization (p < 0.001), and decreased gradually at discharge (p = 0.03). Urinary MEHP% after catheterization and at discharge was significantly positively related to the duration of using PVC-containing catheter systems. There was a significant positive correlation between urinary MEHP% and the duration of using PVC-containing infusion system before catheterization, and a borderline significant correlation at both post-catheterization time slots. Our results demonstrated that urinary MEHP% may be a potential biomarker of DEHP contamination from the use of PVC-containing catheters or infusion systems.

Association of Phthalate Exposure with Endometriosis and Idiopathic Infertility in Egyptian Women

BACKGROUND: Phthalates are compounds found in medical supplies, cellophane wraps, beverage containers, metal can linings, and other products. They have the potential to be significant endocrine disruptors. In experimental animals, thereby affecting their reproductive capacity. Endometriosis is a gynecological condition defined by ectopic endometrial glands and stromal development. Exposure to phthalates has been linked to the development of endometriosis in numerous studies. The dangers of phthalates to women’s reproductive health and fertility have been widely reported. AIM: So far, the relationship between phthalates and infertility is not proven so we decided to see if there was a link between the urine phthalate metabolite levels and endometriosis or idiopathic infertility in Egyptian women. METHODS: Our research was carried out at the infertility outpatient clinic of the Faculty of Medicine of Cairo University. It included 100 female subjects aged 18−40-years-old. Group A (idiopathic infertility; n = 40), Group B (endometriosis; n = 40), and Group C (control; n = 20) were the three age-matched groups that were studied. Using high-performance liquid chromatography (HPLC), the urine levels of mono-2-ethylhexyl phthalate (MEHP) were quantified. RESULTS: The comparison between the study groups has revealed statistically significant differences regarding the urine MEHP levels between Groups A and B. An analysis of the urine MEHP levels in the study Groups A and B has also revealed that the significantly higher urinary MEHP levels are correlated with the use of dietary plastic containers, the use of cosmetics, and the patients’ estrogen levels. Moreover, the urinary MEHP levels of Group A were associated with a history of abortions. CONCLUSIONS: Higher levels of urinary MEHP are positively associated with female reproductive disorders, specifically endometriosis, idiopathic infertility, and abortion.

Targeting the Macrophage: Immune Cells May Be the Key to Phthalate-Induced Liver Toxicity.

Targeting the Macrophage: Immune Cells May Be the Key to Phthalate-Induced Liver Toxicity.

Chronic inflammation as a potential mediator between phthalate exposure and depressive symptoms

BackgroundA few studies have reported phthalate exposure as a risk factor for depressive symptoms, but the results have been inconsistent. Whether chronic inflammation mediates the relationship between phthalates (PAEs) and depressive symptoms remains unclear. In this study, we establish mediating models of inflammatory factors and explore the mediating role of chronic inflammation in the association between PAEs exposure and depressive symptoms. MethodsThe sample included 989 participants from the Study on Health and Environment of the Elderly in Lu'an City, Anhui Province. Geriatric depression scale (GDS-30) was used to screen depressive symptoms of the elderly. The levels of seven kinds of PAEs in urine samples and four inflammatory factors in serum of the elderly were measured. To establish the mediating effect of inflammatory factors to explore the potential effect of PAEs exposure on the increased odds of depressive symptoms. ResultsAdjusted for multiple variables, the highest tertiles of Mono (2-ethylhexyl) phthalate (MEHP) (95%CI = 1.051–2.112), Mono benzyl phthalate (MBzP) (95%CI = 1.016–2.082) and Mono butyl phthalate (MBP) (95%CI = 1.102–2.262) were positively correlated with depressive symptoms. The mediating effect of IL-6 and generalized inflammation factor between MEHP exposure and depressive symptoms were 15.96% (95%CI=0.0288–0.1971) and 14.25% (95%CI = 0.0167–0.1899). ConclusionsHigh levels of MEHP, MBzP and MBP increased the odds of depressive symptoms in the elderly, and chronic inflammation had a partial mediating effect on the increased odds of depressive symptoms due to MEHP exposure.

Urinary Phthalate Levels in Relation to Obesity among a Sample of Egyptian Children

BACKGROUND: Childhood obesity is considered a risk factor for chronic diseases later in life. Phthalates (phthalate acid esters), predominant constituents of plasticizers, are well-thought-out global environmental contaminants. AIM: This study aims to investigate the relationship between obesity and urinary phthalates in Egyptian children. MATERIALS AND METHODS: This cross-sectional study included 210 children; 71 children were obese. Age ranged between 8.8 and 16 years with a mean of 12.93 ± 1.29 years. Sociodemographic data were collected. Clinical examination included measuring body weight, height, waist and hip circumferences (WC and HC), and calculation of body mass index (BMI). The lipid profile was analyzed. Urine samples were tested for phthalates levels using high-performance liquid chromatography. RESULTS: Urinary phthalates metabolites mono benzyl (MBzP), monobutyl (MBP), monoethyl (MEP), and mono (2ethylhexyl) phthalate (MEHP) were detected in all urinary samples with varying levels. The median concentrations of MBzP, MEHP, MBP, and MEP were 1.4, 54.5, 29.9, and 490 (ng/ml), respectively. In obese children, urinary MBP, MEP, and MEHP demonstrated significantly higher mean levels than in non-obese children. Physical indicators of obesity as body weight, BMI, WC, and HC were significantly positively correlated with urinary levels of MEHP and MEP, while urinary MBzP demonstrated a significant positive association with serum triglycerides levels. CONCLUSION: The present study suggests an association between phthalates exposure and childhood and adolescent adiposity.

Associations between maternal mono-(2-ethylhexyl) phthalate levels, nuclear receptor gene polymorphisms, and fatty acid levels in pregnant Japanese women in the Hokkaido study

We assessed how the interaction between mono-(2-ethylhexyl) phthalate (MEHP) in maternal sera and the maternal genotypes associated with nuclear receptors affect fatty acid levels in a prospective birth cohort study of pregnant Japanese individuals (n = 437) recruited in Sapporo between 2002 and 2005. We analyzed MEHP and fatty acids using gas chromatography-mass spectrometry. Thirteen single nucleotide polymorphisms of peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma (PPARG), PPARG coactivator 1A (PPARGC1A), PPAR delta, constitutive androstane receptor, liver X receptor (LXR) alpha, and LXR beta (LXRB) were analyzed using real-time PCR. Multiple linear regression models were used to confirm the influence of log10-transformed MEHP levels and maternal genotypes on log10-transformed fatty acid levels. When the effects of the interaction between MEHP levels and the maternal PPARGC1A (rs8192678) genotype on oleic acid levels were evaluated, the estimated changes (95 % confidence intervals) in oleic acid levels against MEHP levels, maternal PPARGC1A (rs8192678)-GA/AA genotype, and the interaction between them showed a mean reduction of 0.200 (0.079, 0.322), mean reduction of 0.141 (0.000, 0.283), and mean increase of 0.145 (0.010, 0.281), respectively, after adjusting for the perfluorooctanesulfonate level. The effects of the interaction between MEHP levels and maternal LXRB (rs2303044) genotype on linoleic acid levels was also significant (pint = 0.010). In conclusion, the interaction between MEHP and the maternal genotypes PPARGC1A (rs8192678) and LXRB (rs2303044) decreased fatty acid levels. Further, the interaction between MEHP and PPARGC1A (rs8192678) may have a greater effect on fatty acid levels than the interaction between PFOS and PPARGC1A.

Does heated erythrocyte suspension transfusion with medical devices containing phthalates increase DEHP and MEHP levels?

It is commonly known that stored blood and blood products are heated before transfusion to prevent hypothermia, which leads to increased di-(2-ethylhexyl) phthalate (DEHP) content leaching into the blood and blood products and thereby causes greater conversion of DEHP to mono (2-ethylhexyl) phthalate (MEHP). However, there has been no study in the literature reporting on the amount of toxic phthalates in blood following the erythrocyte suspension (ES) transfused via warming. In this study, we aimed to investigate the DEHP and MEHP content in blood following the heated ES transfusions administered by DEHP-containing and DEHP-free infusion sets. The study included 30 patients that were randomly divided into two groups with 15 patients each: group I underwent ES transfusion via DEHP-containing infusion sets warmed with blood-fluid warmers, and group II underwent ES transfusion via DEHP-free infusion sets warmed with blood-fluid warmers. DEHP and MEHP levels were measured both before and after transfusion. DEHP-free infusion sets led to no increase in the phthalate content, whereas DEHP-containing infusion sets significantly increased the DEHP and MEHP, where the DEHP level increased almost four times (P=.001). DEHP-containing products lead to toxicity. Therefore, using DEHP-free medical devices may prevent toxicity in patients undergoing ES transfusion.

Phthalate Exposure Pattern in Breast Milk within a Six-Month Postpartum Time in Southern Taiwan.

Di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, has been detected in breast milk in many countries; however, whether phthalate metabolite concentration and the detection rate in breast milk change postpartum is still unknown. We measured phthalate metabolite concentrations in breast milk in the first 6 months postpartum in women enrolled in the E-Da hospital from January to July 2017. A total of 56 breastfeeding mothers and 66 samples were included in this study. We analyzed the samples’ concentration of eight phthalate metabolites using liquid chromatography mass spectrometry. The concentration of mono-2-ethylhexyl phthalate (MEHP) was significantly higher in the first month, and then decreased over time. The detection rate of ono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MBP) was low in the first month and then increased over time. Compared with a previous study published in 2011, the levels of MEHP and MiBP in breast milk were much lower in the present study, suggesting an increased awareness of the health risks of phthalate exposure after a food scandal occurred in Taiwan. This study provides information for evaluating newborns’ exposure to different kinds of phthalate through human milk in the postpartum period.

Xenoestrogen exposure and kidney function in the general population: Results of a community-based study by laboratory tests and questionnaire-based interviewing

BackgroundChronic kidney disease (CKD) is a growing concern worldwide. Exposure to xenoestrogens (XEs), such as phthalates, parabens, and phenols, lead to CKD. However, kidney function and its complex relationship with XEs, lifestyle, and dietary habits are not well understood. MethodsIn the present cross-sectional community-based cohort study, we enrolled 887 subjects for a questionnaire-based interview and laboratory tests. XE exposure concerning lifestyle/dietary habits were evaluated using questionnaires. Urinary levels of 17XE metabolites were measured in 60 subjects with high exposure risk scores and 60 subjects with low exposure risk scores. ResultsUnivariate and multivariate linear regression showed that a high exposure score (β ± SE: 4.226 ± 1.830, P = 0.021) was independently negatively associated with eGFR in 887 subjects. Univariate and multivariate linear regression to urinary XEs and urine albumin creatinine excretion ratio (UACR) in 120 subjects indicated that ethylparaben (EP) (β: 1.934, 95% CI: 0.135–3.733, P = 0.035) was significantly associated with increased UACR. Multivariate regression analyses of the CKD subgroup (n = 38), after adjusting for age, showed that higher levels of mono-(2-ethylhexyl) phthalate (MEHP), EP, nonylphenol (NP), and benzophenone-3 (BP-3) were significantly associated with lower estimated glomerular filtration rate (eGFR). Higher urinary levels of MEHP (OR: 3.037, 95% CI: 1.274–7.241) were more likely associated with high exposure scores (>5 points), after adjusting for diabetes, gender, eGFR, age, Na, Ca, albumin, vitamin D, systolic blood pressure (SBP), white blood cell count, total bilirubin, aspartate transaminase, and heart rate. MEHP (β ± SE: 0.033 ± 0.009, P < 0.001) was also significantly positively associated with total exposure scores after applying multivariate linear regression analyses. ConclusionXE exposure scores obtained from the questionnaires were negatively associated with kidney function. Urinary metabolites of XEs, including EP, NP, BP-3, and MEHP, are potential risk factors for microalbuminuria and decline in kidney function. MEHP seemed to have the strongest correlation with high exposure scores and decline in kidney function.

Effect of prenatal exposure to phthalates on epigenome-wide DNA methylations in cord blood and implications for fetal growth: The Hokkaido Study on Environment and Children's Health

Prenatal exposure to phthalates negatively affects the offspring's health. In particular, epigenetic alterations, such as DNA methylation, may connect phthalate exposure with health outcomes. Here, we evaluated the association of di-2-ethylhexyl phthalate (DEHP) exposure in utero with cord blood epigenome-wide DNA methylation in 203 mother-child pairs enrolled in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analysis demonstrated the predominant positive associations between the levels of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), in maternal blood and DNA methylation levels in cord blood. The genes annotated to the CpGs positively associated with MEHP levels were enriched for pathways related to metabolism, the endocrine system, and signal transduction. Among them, methylation levels of CpGs involved in metabolism were inversely associated with the offspring's ponderal index (PI). Further, clustering and mediation analyses suggested that multiple increased methylation changes may jointly mediate the association of DEHP exposure in utero with the offspring's PI at birth. Although further studies are required to assess the impact of these changes, this study suggests that differential DNA methylation may link phthalate exposure in utero to fetal growth and further imply that DNA methylation has predictive value for the offspring's obesity.

Potential health risks of maternal phthalate exposure during the first trimester - The Saudi Early Autism and Environment Study (SEAES)

Phthalates are the most ubiquitous contaminants that we are exposed to daily due to their wide use as plasticizers in various consumer products. A few studies have suggested that in utero exposure to phthalates can disturb fetal growth and development in humans, because phthalates can interfere with endocrine function. We collected spot urine samples from 291 pregnant women in their first trimester (9.8 ± 2.3 gestational weeks) recruited in an ongoing prospective cohort study in Saudi Arabia. A second urine sample was collected within 1–7 d after enrollment. The aims of this study were to: (1) assess the extent of exposure to phthalates during the first trimester and (2) estimate the risk from single and cumulative exposures to phthalates. Most phthalate metabolites' urinary levels were high, several-fold higher than those reported in relevant studies from other countries. The highest median levels of monoethyl phthalate, mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), and mono-(2-ethylhexyl) phthalate (MEHP) in μg/l (μg/g creatinine) were 245.62 (197.23), 114.26 (99.45), 39.59 (34.02), and 23.51 (19.92), respectively. The MEHP levels were highest among three di (2-ethylhexyl) phthalate (DEHP) metabolites. %MEHP4, the ratio of MEHP to four di (2-ethylhexyl) phthalate metabolites (∑4DEHP), was 44%, indicating interindividual differences in metabolism and excretion. The hazard quotient (HQ) of individual phthalates estimated based on the reference dose (RfD) of the U.S. Environmental Protection Agency indicated that 58% (volume-based) and 37% (creatinine-based) of the women were at risk of exposure to ∑4DEHP (HQ > 1). Based on the tolerable daily intake (TDI) from the European Food Safety Authority, 35/12% (volume-/creatinine-based data) of the women were at risk of exposure to two dibutyl phthalate (∑DBP) metabolites (MiBP and MnBP). The cumulative risk was assessed using the hazard index (HI), the sum of HQs of all phthalates. The percentages of women (volume-/creatinine-based data) at health risks with an HI > 1 were 64/40% and 42/22% based on RfD and TDI, respectively. In view of these indices for assessing risk, our results for the anti-androgenic effects of exposing pregnant women to ∑4DEHP and ∑DBP early during pregnancy are alarming.

Urinary di(2-ethylhexyl)phthalate metabolite ratios in obese children of South Korea.

Phthalate exposure has been reported to be more associated with obesity in children than in adults. The concentration of di(2-ethylhexyl)phthalate (DEHP) was high temporal variability in spot urine, so additional tools of assessing DEHP exposure were required. Therefore, we used relative metabolite ratios (RMRs) as well as concentrations, and RMRs did not need to be corrected to the creatinine concentration. We aimed to evaluate the levels of urinary DEHP metabolites and their RMRs in obese children in South Korea, and to investigate the potential of RMRs for assessing the risks for childhood obesity. We analyzed the four urinary DEHP metabolites (mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)) in 240 children aged 5-16 years, using isotope dilution GC-MS/MS. The children were placed into three groups ("normal weight," "overweight," and "obese") according to body mass index (BMI) percentiles. We statistically compared the concentrations and RMRs of DEHP metabolites among these groups. The obese group had lower MEHP levels, and higher secondary metabolite (MEHHP, MEOHP, and MECPP) levels, than the normal weight group. DEHP metabolite levels did not differ significantly between the normal weight and obese groups, whereas RMRA2 (as the ratio of the molar concentrations of MEOHP to MEHHP) was found to be negatively associated with BMI percentile (β= -0.236, p <0.01) and weight percentile (β= -0.282, p<0.001). Therefore, we suggest that RMRs are an additional tool for assessing the health risks of DEHP.