Mono-n-butyl Phthalate Concentrations Research Articles

Associations of urinary phthalate metabolites with household environments among mothers and their preschool-age children

Phthalates have become a matter of public health concern due to their extensive use worldwide and negative health effects. The evaluation of potential sources of phthalate exposure is crucial to design prevention strategies, especially for vulnerable populations. This study included 528 mother-child pairs in the Taiwan Mother Infant Cohort Study who were followed up at ages 3–6 years between 2016 and 2020. Each mother was interviewed by using a structured questionnaire containing questions on demographic characteristics and household environment factors, such as the use of plastic food packaging, residential visible mold, insecticide sprays, and electric mosquito repellents. Eleven phthalate metabolites were analyzed in urine samples simultaneously collected from the mother-child pairs. The phthalate metabolite urinary concentrations were higher among the children than among their mothers, except those of mono-ethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Multiple linear regression analyses showed that urine samples collected during the summer showed higher concentrations of phthalate metabolites than those collected during the winter. Family income levels had negative associations with the concentrations of MnBP and metabolites of di-2-ethylhexyl phthalate (DEHP) in children. The use of plastic food packaging was positively associated with mono-n-butyl phthalate (MnBP) and metabolites of DEHP in mothers. Residential visible mold or mold stains were significantly associated with higher MnBP and DEHP metabolite concentrations in children. The use of insecticide sprays was positively associated with MnBP concentrations in children. Significant associations between household environmental factors and phthalate exposure were mostly found in children, potentially indicating different exposure pathways between mothers and their children. Findings from this study provide additional information for the design of prevention strategies to protect the health of children and women.

Urinary phthalate concentrations and mortality risk: A population-based study

Phthalates are widely used as plasticizers. Laboratory-based mechanistic and epidemiological studies suggest that phthalates are detrimental to human health. Here, we present prospective analyses on phthalate exposure and all-cause, as well as cause-specific, mortality from the National Health and Nutrition Examination Survey (NHANES), a population-based cohort. Between 1999 and 2018, urinary concentrations of 12 phthalate metabolites were measured by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in spot urine samples of 10,881 adults aged 40–85 years, of which 2382 died over a median duration of 8.9 years after sample provision. Multivariable Cox regression analyses adjusted for a wide range of lifestyle factors and comorbidities showed that higher concentrations of mono-benzyl phthalate (MBzP) and Mono-n-butyl phthalate (MnBP) were associated with increased mortality. The hazard ratios for participants in the highest quartiles of MBzP and MnBP concentrations were at 1.27 [95% confidence interval: 1.08, 1.49; p linear trend = 0.002] and 1.35 [1.13, 1.62; p linear trend = 0.005). These findings reinforce the need for monitoring of phthalate exposure in relation to health outcomes.

Personal care product use and lifestyle affect phthalate and DINCH metabolite levels in teenagers and young adults

Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12–17) and 300 from young adults (aged 18–37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 μg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 μg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5–6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2–3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites.

Effect of childhood phthalates exposure on the risk of overweight and obesity: A nested case-control study in China.

There was growing interest in endocrine disrupting chemicals that might have effect on the obesity epidemic, but few studies on the association of phthalates (PAEs) with childhood overweight and obesity in China based on longitudinal cohort study were available, which was the purpose of the present study. A nested case-control study was conducted in a prospective cohort of 2298 children aged 7-13years from October 2017 to October 2020 with five waves visits in Xiamen city, China. A total of 829 children remained in the first wave of follow up with collection of urine for measuring seven PAEs metabolites, including mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate (MiBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), utilizing ultra high performance liquid chromatography-triple quadrupole mass spectrometry. Overweight and obesity, defined by WHO classifications, were allocated to the cases group, and those of all normal weight and matched cases with normal weight in each wave of follow-up as two control groups. Logistic regression models after adjusting for confounders were utilized to analyze the effect of PAEs on overweight and obesity in children with divided four groups based on the quartile distribution of each and total PAEs concentration. The detection rates of children for each PAEs metabolite were 99.4% for MMP, 99.4% for MEP, 99.8% for MBP, 54.5% for MEHP, 84.4% for MEOHP, 99.9% for MEHHP, and 97.2% for MiBP. The geometric mean of concentrations of PAEs, MMP, MEP, MBP, MEHP, MEHHP, and MiBP were 310.085, 34.658, 9.127, 166.347, 7.043, 3.400, 18.571, and 24.093 (ng/ml), respectively. The total PAEs and seven metabolites concentrations were positively associated with childhood BMI Z-Scores with statistically significant slope rates and correlation coefficients, and were higher in the cases group than those in two controls groups in each wave of follow-up. The PAEs concentrations in the cases group was 5.90 (95%CI: 5.79, 6.01) ng/ml in the first wave of survey, which was higher than those normal controls group (5.68 (95%CI: 5.61, 5.75) ng/ml, P<0.001) and matched controls group (5.72 (95%CI: 5.61, 5.84) ng/ml, P=0.018). The prevalence and ORs of overweight and obesity increased with quartile group of each and total PAEs concentrations accompanying a dose-response relationship. Compared with the quartile1 reference group with lowest total PAEs concentrations, the ORs of overweight and obesity in quartile2, quartile3 and quartile4 group increased gradually and reached at 1.20 (0.74-1.95), 1.49 (0.93-2.38) and 2.22 (1.41-3.48), respectively (Ptrend<0.001). The strength of the associations between PAEs and overweight and obesity was sex-specific in children. Children in China were extensively exposed to PAEs, and the exposure to PAEs during childhood could significantly increase the risk of overweight and obesity with a dose-response relationship, particularly in girls. While limiting the exposure of PAEs products, the determination of exposure limit of plasticizer should be further strengthened.

The sex-specific association of prenatal phthalate exposure with low birth weight and small for gestational age: A nationwide survey by the Taiwan Maternal and Infant Cohort Study (TMICS)

The Taiwan Maternal and Infant Cohort Study (TMICS) was launched with the aim to assess the effects of prenatal exposure to phthalic acid esters (PAEs) on infant health. A total of 1102 pregnant women were enrolled in this study from 2012 to 2015. All participants completed a structured questionnaire, and provided urine specimens. The urinary concentrations of PAE metabolites in the third trimester were measured using liquid chromatography-electrospray ionization tandem mass spectrometry. Generalized additive model-penalized regression splines and logistic regression models were employed to determine the risk for low birth weight (LBW) or small for gestational age (SGA) among pregnant women exposed to PAEs. After adjustments for other covariates, each incremental unit of ln-transformed mono-n-butyl phthalate (MnBP) for pregnant women increased the odds of SGA in male neonates by 1.44 (95% CI: 0.92–2.23). An inverse association between SGA and maternal MnBP exposure level was observed in female neonates. An increase in one ln-transformed MnBP concentration unit decreased the risk of female SGA to 0.50 (95% CI: 0.24–0.97). In the penalized regression splines, increased risks of LBW/SGA in male neonates were presented while pregnant women exposed to increased MnBP levels. However, an association in the opposite direction was observed between maternal MnBP and LBW or SGA for male and female neonates.This study indicated that high maternal MnBP exposure in the third trimester was associated with LBW or SGA for male infants. Adverse effects on susceptible populations exposed to high levels of PAEs should be of concern.

Urinary phthalate metabolites among workers in plastic greenhouses in western China

Agricultural plastic greenhouse (PG) production can extend the growing season of crops to satisfy domestic consumption in countries such as China. Workers in PGs have potential higher phthalate exposure risks than the general population as phthalate accumulation has been observed in greenhouse soil, air, and crops. To date, biomonitoring tests of phthalates for the working population have not been carried out. To address this shortage, we conducted a pilot study in Shaanxi Province, China, among 35 healthy PG workers by follow-up recording their seasonal dietary habits and work activities and urine sample collection and measurement between 2018 and 2019. The objectives were to uncover the association between phthalate metabolites and the population characteristics, seasonal and diurnal variations and causes, and to estimate exposure risks and contributions of exposure pathways from PG production systems. A total of 13 phthalate metabolite concentrations (Σ13 phthalate metabolites) ranged from 102 to 781 (5th-95th) ng/mL (median: 300 ng/mL). Mono-n-butyl phthalate (MNBP) made up 51.3% of Σ13 phthalate metabolites, followed by the sum of four di-2-ethylhexyl phthalate (DEHP) metabolites (24.2%), mono-2-isobutyl phthalate (MIBP) (13.4%), and mono-ethyl phthalate (MEP) (9.8%). The concentrations of MNBP and MIBP in summer were significantly higher than the levels in winter (p < 0.0001). A total of 62.3% of the PG worker population was shown to have exposure risks, and the proportion was as high as 79.4% in summer. Phthalate exposure of the workers from PG production systems constituted over 20% of the total creatinine-based daily intake, and consuming vegetables and fruit planted in PGs and inhalation in PGs were the two largest exposure pathways. Our findings demonstrate that it is important to protect workers in PGs from phthalate exposure risks, and phasing out the use of plastic materials containing phthalates in PGs is imperative, to guarantee food safety in PGs.

Urinary specific gravity measures in the U.S. population: Implications for the adjustment of non-persistent chemical urinary biomarker data.

Urinary biomarkers are often corrected for sample dilution using creatinine, which is influenced by sociodemographic factors and certain health conditions. It is unknown whether these factors similarly influence specific gravity. To identify predictors of specific gravity and creatinine and compare methods for correcting estimated chemical concentrations for sample dilution using these measures. We assessed predictors of urinary specific gravity and creatinine among NHANES 2007-2008 participants (n=7257). We corrected concentrations of mono-n-butyl phthalate (MnBP) for dilution using two methods, each applied to both specific gravity and creatinine: correction using a sample mean of the dilution indicator (i.e., specific gravity or creatinine) and covariate-adjusted standardization. We compared distributions and assessed the agreement of uncorrected or corrected concentrations visually using Bland-Altman plots and statistically by Kendall's τa. We stratified all analyses by age category (i.e., 6-19 or 20+years of age). Gender, race/ethnicity, body mass index, and height were associated with urinary specific gravity and creatinine. Distributions of corrected MnBP concentrations were comparable for both methods and dilution indicators, but agreement between methods was greater for specific gravity. Additionally, specific gravity- and creatinine-corrected MnBP concentrations had slightly greater agreement with each other when corrected using a covariate-adjusted standardization method. Specific gravity, like creatinine, is associated with sociodemographic and body composition variables. Accounting for these factors as part of the dilution correction method may be important to minimize bias.

Associations between medication use and phthalate metabolites in urine and follicular fluid among women undergoing in vitro fertilization

BackgroundPhthalates, which are used as excipients of drugs, have been related to adverse reproductive outcomes. However, the relationships between medication use and phthalate exposure among women undergoing in vitro fertilization (IVF) have not been studied. ObjectiveTo investigate the associations between the medication intake and phthalate metabolites in urine and follicular fluid (FF). MethodEight phthalate metabolites were measured in urine and FF samples from 274 women undergoing IVF using liquid chromatography-tandem mass spectrometry. Information on recent medication intake was obtained via interview by trained staff. We constructed generalized linear regression models to examine the associations of medication intake with phthalate metabolite concentrations and dose-response relationships between the number of medicines used and metabolite concentrations in two matrices. ResultsFour of 10 drugs were used by more than 10% of the participants, including vitamins (23.0%), traditional Chinese medicine (TCM, 22.3%), antioxidants (12.4%) and amoxicillin (10.2%). Participants who had used TCM had 26.0% (95% CI: 0.0, 58.8%), 32.6% (95% CI: 4.2, 68.8%) and 32.3% (95% CI: 2.6, 70.6%) higher urinary mono-n-butyl phthalate (MBP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) concentrations, respectively, than those who had not. Antioxidant intake was associated with a 30.6% (95% CI: −48.5, −6.6%) decrease in the urinary MBP concentration. Compared with non-users, women who reported the use of medicines had 53.2% (95% CI: 2.7, 128.5%) higher concentrations of MMP and a 37.7% (95% CI: −60.7, −1.5%) lower level of MBP in FF, respectively. ConclusionOur data suggest that the intake of some medications may increase phthalate exposure among women undergoing IVF.

Urinary Concentrations of Phthalate Metabolite Mixtures in Relation to Serum Biomarkers of Thyroid Function and Autoimmunity among Women from a Fertility Center.

Background:Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women.Objective:We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity.Methods:This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005–2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (, ) and triiodothyronine (, ), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores.Results:We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of , , , and [absolute difference: ; 95% confidence interval (CI): , ; ; absolute difference: ; 95% CI: , ; ; absolute difference: ; 95% CI: 0.54, ; ; and absolute difference: ; 95% CI: , ; , respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb.Conclusions:Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740

Exposure to Mono-n-Butyl Phthalate in Women with Endometriosis and Its Association with the Biological Effects on Human Granulosa Cells.

To study the association between urinary phthalate metabolite levels, endometriosis, and their effects on human granulosa cells, we recruited patients who underwent laparoscopy to confirm endometriosis (n = 123) and control patients (n = 78). Liquid chromatography–tandem mass spectrometry was used to measure the following five urinary phthalate metabolites: mono-n-butyl phthalate (MnBP), mono(2-ethylhexyl) phthalate, monobenzyl phthalate, mono(2-ethyl-5-oxo-hexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate. Urinary MnBP levels were higher in patients with endometriosis than in controls after multivariable logistic regression including the number of deliveries, body mass index, and use of medicine as covariables. MnBP correlates with other phthalate metabolites. Previous studies found that endometriosis was a detrimental condition for granulosa cells. In our study, we observed whether MnBP affected granulosa cells. MnBP treatment altered the gene expression of BIRC5, BUB1B, CDC20, cyclin B1, IL-1β, TNF-α, inhibin-B, StAR, and P450ssc and attenuated the ratio of the mitochondrial membrane potential in human granulosa cells. Moreover, MnBP decreased the expression of the anti-Mullerian hormone. These findings suggest that MnBP concentration is associated with endometriosis and may affect the health and steroidogenesis of human granulosa cells.

The associations of urinary phthalate metabolites with the intermediate and pregnancy outcomes of women receiving IVF/ICSI treatments: A prospective single-center study

BackgroundPhthalate exposure was reported to induce defects in ovarian function, and further influence embryo development and pregnancy outcomes. However, the data about the associations of phthalates with intermediate and pregnancy outcomes of in vitro fertilization (IVF) cycles are scarce in the Chinese population. MethodsA total of 663 women receiving IVF/intracytoplasmic sperm injection (ICSI) treatments in our center were enrolled in this analysis. They provided one urine sample on the day of oocyte retrieval. We measured urinary concentrations of eight phthalate metabolites. Generalized linear models were used to analyze the associations of urinary phthalate metabolites with ovarian response, fertilization, early embryo development, and pregnancy outcomes. ResultsAmong all the phthalate metabolites, mono-n-butyl phthalate (MBP) had the highest urinary concentration with a median level of 101.51 μg/g creatinine (Cr). MBP concentration was inversely associated with normal fertilization odds (overall P-trend < 0.01). There was a significant correlation of monoethyl phthalate (MEP) with decreased odds of normal fertilization in medium-concentration group compared to low-concentration group (overall P-trend = 0.02). No significant associations of metabolite concentrations with the odds of good-quality embryos on day 3 or blastocyst formation were found. Monomethyl phthalate (MMP) and MEP in medium-concentration group reduced 22.4% (95% CI: 0.64–0.94, overall P-trend = 0.04) and 21.9% (95% CI: 0.64–0.95, overall P-trend = 0.05) of the odds to gain good-quality blastocyst compared to low-concentration group. The eight phthalate metabolites were not correlated to clinical pregnancy rate, live birth rate, or early miscarriage rate. There was no significant association of di (2-ethylhexyl) phthalate (DEHP) metabolites observed with any clinical outcomes in the total population. After excluding male infertility, mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in medium-concentration group turned to be associated with a higher number of retrieved oocytes (overall P-trend = 0.04), whereas mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) in medium-concentration group was associated with a lower odds of normal fertilization compared to low-concentration group (overall P-trend = 0.02). ConclusionsUrinary MBP concentration was much higher compared to other phthalate metabolites in this cohort of Chinese IVF/ICSI women, and also higher than it was reported by studies in other countries. MBP showed adverse impacts on fertilization. MMP and MEP could affect blastocyst quality, but not embryo quality on day 3. DEHP metabolites didn’t show consistent reproductive toxicities as demonstrated in previous studies.

Unhealthy Levels of Phthalates and Bisphenol A in Mexican Pregnant Women with Gestational Diabetes and Its Association to Altered Expression of miRNAs Involved with Metabolic Disease.

Several studies indicate that bisphenol A (BPA) and phthalates may have a role in the development of metabolic diseases using different molecular pathways, including epigenetic regulatory mechanisms. However, it is unclear whether exposure to these chemicals modifies serum levels of miRNAs associated with gestational diabetes mellitus (GDM) risk. In the present study, we evaluated the serum levels of miRNAs associated with GDM (miR-9-5p, miR-16-5p, miR-29a-3p and miR-330-3p) and urinary levels of phthalate metabolites (mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono(2-ethyl hexyl) phthalate (MEHP)) and bisphenol A in GDM patients and women without GDM during the second trimester of gestation. We observed higher levels of miR-9-5p, miR-29a-3p and miR-330-3p in sera of patients with GDM compared to non-diabetic subjects. Phthalates were detected in 97–100% of urine samples, while BPA only in 40%. Urinary MEHP and BPA concentrations were remarkably higher in both study groups compared to previously reported data. Unadjusted MEHP levels and adjusted BPA levels were higher in non-diabetics than in GDM patients (p = 0.03, p = 0.02). We found positive correlations between adjusted urinary MBzP levels and miR-16-5p expression levels (p < 0.05), adjusted MEHP concentrations and miR-29a-3p expression levels (p < 0.05). We also found negative correlations between unadjusted and adjusted MBP concentrations and miR-29a-3p expression levels (p < 0.0001, p < 0.05), unadjusted MiBP concentrations and miR-29a-3p expression levels (p < 0.01). Urinary MEHP levels reflect a striking exposure to di(2-ethylhexyl) phthalate (DEHP) in pregnant Mexican women. This study highlights the need for a regulatory strategy in the manufacture of several items containing endocrine disruptors in order to avoid involuntary ingestion of these compounds in the Mexican population.

Racial disparity in maternal phthalates exposure; Association with racial disparity in fetal growth and birth outcomes

Experimental and observational data implicate phthalates as developmental toxicants. However, few data are available to assess the maternal risks of gestational exposure by race and infant sex. To begin to address this data gap, we characterized associations between maternal urinary phthalate metabolites and birth outcomes among African American and white mothers from a southeastern U.S. population. We enrolled pregnant African American (n = 152) and white (n = 158) women with singleton live births between 18 and 22 weeks gestation. We measured phthalate metabolites (mono-n-butyl phthalate (MBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), monoethyl phthalate (MEP), monomethyl phthalate (MMP), and the sums of DEHP (ΣDEHP) and DBP (ΣDBP) metabolites) in up to two gestational urine specimens from mothers, and evaluated confounder-adjusted associations per natural log unit greater concentration with birth weight for gestational age z-score, small for gestational age (SGA; <10th %tile), preterm birth (PTB; <37 weeks gestation), and low birth weight (LBW; <2500 g). We also tested for interactions by maternal race and infant sex. We found that lower z-scores were associated with greater MiBP (β = −0.28; 95% CI: −0.54, −0.02) and MMP (β = −0.30; 95% CI: −0.52, −0.09) concentrations, while MEP interacted with race (p = 0.04), indicating an association among whites (β = −0.14; 95% CI: −0.28, 0.001) but not among African Americans (β = 0.05; 95% CI = −0.09, 0.19). Greater MiBP (OR = 2.82; 95% CI: 1.21, 6.56) and MEOHP (OR = 2.80; 95% CI: 1.05, 7.42) were associated with an overall higher SGA risk, greater MEHP was associated with higher SGA risk (p = 0.10) in whites (OR = 3.26 95% CI: 0.64, 16.56) but not in African Americans (OR = 0.71 95% CI: 0.07, 7.17), and the associations for MiBP (p = 0.02) and ΣDBP (p = 0.02) varied by infant sex. We detected interactions for PTB in which African Americans were at higher risk than whites for greater MiBP (p = 0.08) and MEP (p = 0.02) although lower risk for greater MEHP (p = 0.09). Greater MEP was associated with an overall higher LBW risk (OR = 1.33; 95% CI: 0.95, 1.86), and males were at higher risk than females with greater MBP (p = 0.002), MiBP (p = 0.02), MBzP (p = 0.01), MEP (p = 0.002), MMP (p = 0.09), and ΣDBP (p = 0.01) concentrations. Overall, our results suggest that gestational phthalate exposure is associated with adverse maternal birth outcomes, and that the effects vary by maternal race and infant sex.

Binding ability of phthalate monoesters by Saccharomyces cerevisiae strains in vitro

The objective of the present study was to evaluate the capability of four food associated Saccharomyces cerevisiae strains to remove phthalate monoesters (PMEs), major metabolites produced in the gastrointestinal tract before absorption once phthalates being ingested, from aqueous solution by taking mono-n-butyl phthalate (MBP) as the representative. Consequently, all these four S. cerevisiae strains were able to remove four categories of common PMEs compounds from the aqueous solution. However, the binding capability is strain-specific; S. cerevisiae strains Y50-7 and YS102 presented higher removal capability of around 60% binding rate at the 50 mg/L of MBP. The removal capability depends on both initial MBP and yeast cell concentrations. In addition, the binding is a fast process with 15 min achieving a considerable removal level and 4 h reaching equilibrium, and strongly depends on pH (pH 3.0 is best for removal process) and temperature. The investigation for stability of yeast/MBP complexes showed that lower percentage of released MBP was detected after wash treatment using water and pH 3.0 buffer, compared with pH 7.0 buffer. Under simulated gastrointestinal conditions, the binding capability also showed strain specificity; among all S. cerevisiae strains Y50-7 showed significantly higher removal capability. Hence, our results allow us to predict that S. ceresiviae Y50-7 is a good candidate for future studies to detoxify and reduce the bioavailability of phthalates and their respective metabolites, PMEs in the human diet and animal feed.

Association between urinary phthalate metabolites and obesity in adult Korean population: Korean National Environmental Health Survey (KoNEHS), 2012-2014.

BackgroundPhthalate is a chemical that is commonly used as a plasticizer in processing plastic products and as a solvent in personal care products. Although previous experimental studies have reported that phthalate metabolites are associated with obesity, epidemiological study results have been inconsistent and insufficient. The objective of the present study was to investigate the association between urinary phthalate metabolites and obesity in adult Korean population.MethodsThe present study selected 4,752 Korean adults aged 19 years or older from the 2012–2014 Korean National Environmental Health Survey data. The concentrations of urinary di-(2-ethyl-5-carboxypentyl) phthalate (DEHP) metabolites—i.e., mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-carboxypentyl) phthalate—mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP) were adjusted using the urinary creatinine. We used logistic regression analysis to investigate the association between urinary phthalate metabolite concentration and body mass index (BMI) with respect to sex and age.ResultsAmong women, urinary MEHHP and DEHP concentrations were found to have statistically significantly positive associations with obesity (Q4 versus Q1; odds ratio (OR): 1.72, 95% confidence interval (CI): 1.19–2.49 for MEHHP and OR: 1.52, 95% CI: 1.04–2.21 for DEHP). Among men, urinary MnBP concentration was found to have statistically significantly negative association with obesity (Q4 versus Q1; OR: 0.71, 95% CI: 0.50–0.99). In the analysis stratified by sex and age, women aged ≥ 50 years showed statistically significantly positive associations between the concentrations of urinary DEHP metabolites, DEHP, MBzP, and obesity (Q4 versus Q1; OR: 1.94, 95% CI: 1.28–2.94 for MEHHP, OR: 1.88, 95% CI: 1.21–2.94 for MEOHP, OR: 2.04, 95% CI: 1.31–3.18 for DEHP, and Q3 versus Q1; OR: 1.45, 95% CI: 1.02–2.05 for MBzP). Meanwhile, men aged ≥ 50 years showed no significant associations between urinary phthalate concentrations and obesity.ConclusionsIn the present study, we found differences in the associations between urinary phthalate metabolites and BMI according to sex and age. However, because the present study was cross-sectional in nature, additional support through prospective studies is needed to estimate the causal associations.

Effects of two environmental endocrine disruptors di-n-butyl phthalate (DBP) and mono-n-butyl phthalate (MBP) on human sperm functions in vitro

Di-n-butyl phthalate (DBP), a plastic-derived, endocrine-disrupting chemical, is regarded as a male reproductive toxicant. In this study, we investigated the in vitro actions of DBP and mono-n-butyl phthalate (MBP, the main metabolite of DBP) on human sperm functions. Human sperm were treated with DBP (2 nM-6 μM), MBP (1 nM-3 μM), and a mixture of DBP and MBP in vitro. The results showed that only DBP at 6 μM, a dose reported in semen of infertile men, MBP at 3 μM (three times of the reported maximum MBP concentration in semen), and their mixture, had obvious adverse effects on sperm motility, penetration ability and capacitation. In addition, these doses of phthalates suppressed human sperm tyrosine phosphorylation, a key signaling pathway that regulates sperm functions. Our findings indicate that DBP and MBP may compromise human sperm functions by inhibiting sperm tyrosine phosphorylation once they accumulate in semen at high levels.

Urinary phthalate metabolites and metabolic syndrome in U.S. adolescents: Cross-sectional results from the National Health and Nutrition Examination Survey (2003-2014) data.

There is limited research on the association between phthalates and metabolic syndrome (MetS). Among adolescents, phthalate exposure, which can occur from multiple sources, has been linked to several risk factors for MetS. The objective was to investigate the association between urinary phthalate metabolite concentrations (i.e., mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), mono-(3-carboxylpropyl) phthalate (MCPP), and di(2-ethylhexyl phthalate (DEHP)) and MetS in adolescents aged 12-19 years using the National Health and Nutrition Examination Survey (NHANES) data (2003-2014). A secondary aim was to assess if observed associations varied by a measure of socioeconomic status, economic adversity, which was defined using parental income and educational attainment as well as household food security. We used NHANES data which included physical examination, laboratory urinalysis and fasting blood profiles, and self-reported health characteristics and demographics. Physical examination and laboratory data were used to obtain values of MetS components and urinary phthalate metabolites. We created age-, sex-, and survey year-specific tertiles of creatinine-corrected urinary phthalate metabolites. Analysis was performed using appropriate weighting procedures that accounted for NHANES' complex sampling design. After univariate and bivariate analyses, we performed adjusted logistic regressions to test for associations between individual phthalate metabolites and MetS as well as MetS components and number of MetS components, separately, using the lowest tertile as the reference category. A cross-product term (phthalate metabolite*economic adversity) was subsequently added to adjusted models. Among 918 participants (mean age 16 years, 45% female, 18% with economic adversity), the prevalence of MetS was 5.3%. Prior to adjustment, adolescents with MetS had marginally higher concentrations of phthalate metabolites than adolescents without MetS. There was a suggestive positive association between intermediate concentrations of MnBP and odds of MetS after adjustment (T2: Odds Ratio (OR) = 2.66 (95% confidence interval: 0.98-7.24); T3: OR = 2.11 (0.71-6.27)). Males with higher MnBP concentrations had higher odds of dyslipidemia; however, associations were mostly non-significant for females. Relationships between MiBP concentrations and odds of MetS varied by sex. Males with higher concentrations of MnBP and MiBP had greater odds of having a higher number of MetS components. Relationships between phthalate metabolites and MetS did not vary by economic adversity. There was a suggestive positive association between MnBP and MetS among adolescents. Associations between phthalate metabolites and MetS as well as MetS components may vary by sex, but may not vary by economic adversity. Further research of the relationships between phthalate exposures, MetS, and potential interactions with socioeconomic factors is warranted.

Early Life Phthalate Exposure and Cognition at Age 8 Years: Identifying Windows of Heightened Vulnerability

Background: Early-life phthalate exposures may adversely affect children&amp;#8217;s neurodevelopment by disrupting thyroid function, reducing gonadal hormone levels, or altering concentrations of fatty acids in the brain. We attempted to identify windows of heightened vulnerability to phthalate exposures during fetal period and early childhood.Methods: We used data from 204 mother-child pairs in the HOME Study (Cincinnati, Ohio), a longitudinal pregnancy-birth cohort. We quantified phthalate biomarkers in urine samples collected up to twice at gestational visits and up to 6 times during childhood visits at ages 1-8 years. We assessed children&amp;#8217;s intelligence (IQ) at age 8 years using the Wechsler Intelligence Scale for Children-IV. We estimated covariate-adjusted associations between log10-transformed biomarker concentrations and children&amp;#8217;s IQ at each visit, and tested for differences in these associations across visits using multiple informants models.Results: The associations between phthalate biomarker concentrations and IQ varied by visit (biomarker*visit interaction p-values&amp;lt;0.2). Concentrations of monobenzyl phthalate, mono(3-carboxypropyl) phthalate, and monoethyl phthalate at ages 2 and 3 years, and di(2-ethylhexyl) phthalate (&amp;#931;DEHP) metabolites at age 3 years were inversely associated with children&amp;#8217;s full-scale IQ. For example, each 10-fold increase in urine &amp;#931;DEHP concentrations at age 3 was associated with a 4.9-point decrease in full-scale IQ (95% confidence interval [CI]: -8.8, -1.1). Concentrations of mono-n-butyl phthalate (MnBP) at age 4 years and mono-isobutyl phthalate at gestation and age 4 years were positively associated with children&amp;#8217;s IQ. For instance, each 10-fold increase in urine MnBP concentrations at age 4 years was associated with a 5.0-point increase in full-scale IQ (95% CI: 0.8, 9.2).Conclusion: In this cohort, associations of gestational and childhood urinary phthalate biomarker concentrations with IQ scores depended on the timing of exposure.

Phthalate exposure and odds of bacterial vaginosis among U.S. reproductive-aged women, NHANES 2001–2004

Endocrine-disrupting chemicals, such as phthalates, are an unexamined potential risk factor for bacterial vaginosis (BV) and warrant investigation because hormones affect BV. We examined the association between phthalate exposure and BV in the National Health and Nutrition Examination Survey, 2001–2004. BV outcomes were defined as intermediate (Nugent score of 4–6) and positive (7–10). Phthalate metabolites, including monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), and di(2-ethylhexyl) phthalate (DEHP) metabolites, were measured in urine. Among 854 women with complete data, multinomial logistic regression revealed that concentrations of MnBP (Q4 vs. Q1 OR = 3.01, 95% CI 1.76–5.15, p-trend <0.001) and ΣDEHP metabolites (Q4 OR = 2.55, 95% CI 1.45–4.47, p-trend = 0.03) were associated with Nugent-score BV, although only MnBP was significant after adjustment for confounders. Associations were null after adjustment for urinary creatinine (MnBP Q4 OR = 1.11, 95% CI 0.63–1.96; ΣDEHP Q4 OR = 0.72, 95% CI 0.37–1.39). Future work should further examine these relationships using direct measurements of intravaginal phthalates exposures.

Screening of lactic acid bacteria strains for their ability to bind phthalate monoesters in vitro and the binding characteristics

In the present study, thirty lactic acid bacteria (LAB) strains were first screened for their ability to remove mono-n-butyl phthalate (MBP) in vitro, one representative of phthalate monoesters (PMEs), from the aqueous solution. Three Lactobacillus plantarum and two L. fermentum strains removed more than 25% MBP and were selected for further investigation of the binding characteristics. Consequently, five LAB strains were resistant to MBP, and the binding ability depends on initial MBP and bacterial cell concentrations. In particular, the removal was a fast and reversible process, and pH plays a major role in the binding capability. Both heat-treated and acid-treated bacteria were capable of removing the MBP, indicating the binding, not metabolism, is the mechanism by which MBP is removed from the aqueous solution. Acid treatment can increase the binding ability of LAB and also enhance the stability of MBP-LAB complex. In addition, these LAB strains could remove different percentages of other several common PMEs from the aqueous solution, especially exhibiting high binding capability on monoethylhexyl phthalate. These findings indicate that some specific LAB strains are able to detoxify phthalate monoesters and may be useful to protect humans and/or animals from the adverse health effects of PAEs.