Phthalate Diesters Research Articles

In-silico characterization of a hypothetical protein of Sulfobacillus sp. hq2 for degradation of phthalate diesters

Phthalate plasticizers are hazardous compounds capable of causing endocrine disruption, cancers, and developmental disorders. Phthalate diesters are commonly used plasticizers in plastic products (PVC pipes) that leach out into the environment due to changes in temperature, pressure, and pH, posing harmful effects on different life forms. Bioremediation of phthalate diesters utilizing bacterial esterase has been recognized as an efficient approach but few effective esterases capable of degrading a wide range of phthalate diesters have been identified. Further, the thermostability of these esterases is a highly desirable property for their applications in diverse in-situ conditions. In this present in-silico study a hypothetical protein (POB10642.1) as a high-potential esterase from a thermostable strain of Sulfobacillus sp. hq2 has been characterized. Analysis revealed a significant sequence identity of 42.67 % and structural similarity (RMSD 0.557) with known phthalate diester degrading EstS1 esterase and a high Tm range of 55–66 °C. Structural analysis revealed the presence of two cavities on the surface mediating toward the catalytic site forming a catalytic tunnel. The enzyme POB10642.1 has significant molecular docking binding energies in the range of −5.4 to −7.5 kcal/mol with several phthalate diesters, including Diethyl phthalate, Dipropyl phthalate, Dibutyl phthalate, Dipentyl phthalate, Dihexyl phthalate, Benzyl butyl phthalate, Dicyclohexyl phthalate, and Bis(2-ethylhexyl) phthalate. High stability of binding during 100 ns molecular dynamics simulations revealed efficient and stable binding of the enzyme with a wide range of phthalate diesters at its active site, demonstrating the ability of the identified esterase to interact with and degrade diverse phthalate diesters. Therefore, POB10642.1 esterase can be an efficient candidate to be utilized in the development of enzyme-based bioremediation technologies to reduce the toxic levels of phthalate diesters.

Mixtures of urinary concentrations of phenols and phthalate biomarkers in relation to the ovarian reserve among women attending a fertility clinic

Although prior studies have found associations of the ovarian reserve with urinary concentrations of some individual phenols and phthalate metabolites, little is known about the potential associations of these chemicals as a mixture with the ovarian reserve. We investigated whether mixtures of four urinary phenols (bisphenol A, butylparaben, methylparaben, propylparaben) and eight metabolites of five phthalate diesters including di(2-ethylhexyl) phthalate were associated with markers of the ovarian reserve among 271 women attending a fertility center who enrolled in the Environment and Reproductive Health study (2004–2017). The analysis was restricted to one outcome per study participant using the earliest outcome after the last exposure assessment. Ovarian reserve markers included lower antral follicle count (AFC) defined as AFC < 7, circulating serum levels of day 3 follicle stimulating hormone (FSH) assessed by immunoassays, and diminished ovarian reserve (DOR) defined as either AFC < 7, FSH > 10 UI/L or primary infertility diagnosis of DOR. We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation to estimate the joint associations and assess the interactions between chemical exposure biomarkers on the markers of the ovarian reserve while adjusting for confounders. Among all 271 women, 738 urine samples were collected. In quantile g-computation models, a quartile increase in the exposure biomarkers mixture was not significantly associated with lower AFC (OR = 1.10, 95 % CI = 0.52, 2.30), day 3 FSH levels (Beta = 0.30, 95 % CI = −0.32, 0.93) or DOR (OR = 1.02, 95 % CI = 0.52, 2.05). Similarly, BKMR did not show any evidence of associations between the mixture and any of the studied outcomes, or interactions between chemicals. Despite the lack of associations, these results need to be explored among women in other study cohorts.

Evaluation of distinct molecular architectures and coordinated regulation of the catabolic pathways of oestrogenic dioctyl phthalate isomers in Gordonia sp.

Bacterial strain GONU, belonging to the genus Gordonia, was isolated from a municipal waste-contaminated soil sample and was capable of utilizing an array of endocrine-disrupting phthalate diesters, including di-n-octyl phthalate (DnOP) and its isomer di(2-ethylhexyl) phthalate (DEHP), as the sole carbon and energy sources. The biochemical pathways of the degradation of DnOP and DEHP were evaluated in strain GONU by using a combination of various chromatographic, spectrometric and enzymatic analyses. Further, the upregulation of three different esterases (estG2, estG3 and estG5), a phthalic acid (PA)-metabolizing pht operon and a protocatechuic acid (PCA)-metabolizing pca operon were revealed based on de novo whole genome sequence information and substrate-induced protein profiling by LC-ESI-MS/MS analysis followed by differential gene expression by real-time PCR. Subsequently, functional characterization of the differentially upregulated esterases on the inducible hydrolytic metabolism of DnOP and DEHP revealed that EstG5 is involved in the hydrolysis of DnOP to PA, whereas EstG2 and EstG3 are involved in the metabolism of DEHP to PA. Finally, gene knockout experiments further validated the role of EstG2 and EstG5, and the present study deciphered the inducible regulation of the specific genes and operons in the assimilation of DOP isomers.

Biochemical and Multi-Omics Approaches To Obtain Molecular Insights into the Catabolism of the Plasticizer Benzyl Butyl Phthalate in Rhodococcus sp. Strain PAE-6.

Phthalate diesters are extensively used as plasticizers in manufacturing plastic materials; however, because of their estrogenic properties, these chemicals have emerged as a global threat to human health. The present study investigated the course of degradation of a widely used plasticizer, benzyl butyl phthalate (BBP), by the bacterium PAE-6, belonging to the genus Rhodococcus. The metabolism of BBP, possessing structurally dissimilar side chains, was evaluated biochemically using a combination of respirometric, chromatographic, enzymatic, and mass-spectrometric analyses, depicting pathways of degradation. Consequently, the biochemical observations were corroborated by identifying possible catabolic genes from whole-genome analysis, and the involvement of inducible specific esterases and other degradative enzymes was validated by transcriptomic, reverse transcription-quantitative PCR (RT-qPCR) and proteomic analyses. Nonetheless, phthalic acid (PA), an intermediate of BBP, could not be efficiently metabolized by strain PAE-6, although the genome contains a PA-degrading gene cluster. This deficiency of complete degradation of BBP by strain PAE-6 was effectively managed by using a coculture of strains PAE-6 and PAE-2. The latter was identified as a Paenarthrobacter strain which can efficiently utilize PA. Based on sequence analysis of the PA-degrading gene cluster in strain PAE-6, it appeared that the alpha subunit of the multicomponent phthalate 3,4-dioxygenase harbors a number of altered residues in the multiple sequence alignment of homologous subunits, which may play a role(s) in poor turnover of PA. IMPORTANCE Benzyl butyl phthalate (BBP), an estrogenic, high-molecular-weight phthalic acid diester, is an extensively used plasticizer throughout the world. Due to its structural rigidity and hydrophobic nature, BBP gets adsorbed on sediments and largely escapes the biotic and abiotic degradative processes of the ecosystem. In the present study, a potent BBP-degrading bacterial strain belonging to the genus Rhodococcus was isolated that can also assimilate a number of other phthalate diesters of environmental concern. Various biochemical and multi-omics analyses revealed that the strain harbors all the required catabolic machinery for the degradation of the plasticizer and elucidated the inducible regulation of the associated catabolic genes and gene clusters.

Molecular evaluation of the metabolism of estrogenic di(2-ethylhexyl) phthalate in Mycolicibacterium sp.

BackgroundDi(2-ethylhexyl) phthalate (DEHP) is a widely detected plasticizer and a priority pollutant of utmost concern for its adverse impact on humans, wildlife and the environment. To eliminate such toxic burden, biological processes are the most promising ways to combat rampant environmental insults under eco-friendly conditions. The present study investigated the biochemical and molecular assessment of the catabolic potential of Mycolicibacterium sp. strain MBM in the assimilation of estrogenic DEHP.ResultsA detailed biochemical study revealed an initial hydrolytic pathway of degradation for DEHP followed by the assimilation of hydrolyzed phthalic acid and 2-ethylhexanol to TCA cycle intermediates. Besides the inducible nature of DEHP-catabolic enzymes, strain MBM can efficiently utilize various low- and high-molecular-weight phthalate diesters and can grow under moderately halotolerant conditions. Whole genome sequence analysis exhibited a genome size of 6.2 Mb with a GC content of 66.51% containing 6,878 coding sequences, including multiple genes, annotated as relevant to the catabolism of phthalic acid esters (PAEs). Substantiating the annotated genes through transcriptome assessment followed by RT-qPCR analysis, the possible roles of upregulated genes/gene clusters in the metabolism of DEHP were revealed, reinforcing the biochemical pathway of degradation at the molecular level.ConclusionsA detailed co-relation of biochemical, genomic, transcriptomic and RT-qPCR analyses highlights the PAE-degrading catabolic machineries in strain MBM. Further, due to functional attributes in the salinity range of both freshwater and seawater, strain MBM may find use as a suitable candidate in the bioremediation of PAEs.

Phthalates in the environment: Their toxicology and associated risk to humans

Abstract This review describes the presence of phthalate diesters (PAEs) in various products and elements of the environment, their toxicology, and possible risk is presented as reported in the scientific literature. PAEs have been detected in a variety of environmental elements, including air, soils, sediments, and landfill leachate, as well as in ground, surface, and drinking water, which makes them a common environmental contaminant. The most common and detectable phthalate in all elements of the environment is di(2-ethylhexyl) phthalate (DEHP). When added up, the amounts of human exposure to all sources of phthalates can be significant and pose an equally significant health risk to humans and other living organisms. Several PAEs, including DEHP, di-n-butyl phthalate (DBP), di-isobutylphthalate (DIBP), and butyl benzyl phthalate (BBP) are classified as toxic to reproduction and have endocrine-disrupting properties. Despite the introduction of strict regulations and restrictions on PAEs worldwide, long-term monitoring of human exposure is needed to reduce the potential risk to humans and other living organisms.

Wide substrate range for a candidate bioremediation enzyme isolated from Nocardioides sp. strain SG-4G.

Narrow substrate ranges can impact heavily on the range of applications and hence commercial viability of candidate bioremediation enzymes. Here we show that an ester hydrolase from Nocardioides strain SG-4G has potential as a bioremediation agent against various pollutants which can be detoxified by hydrolytic cleavage of some carboxylester, carbamate or amide linkages. Previously we showed that a radiation-killed, freeze-dried preparation (ZimA) of this strain can rapidly degrade the benzimidazole fungicide carbendazim due to the activity of a specific ester hydrolase, MheI. Here, we report that ZimA also has substantial hydrolytic activity against phthalate diesters (dimethyl, dibutyl and dioctyl phthalate) and anilide (propanil and monalide) and carbamate ester (chlorpropham) herbicides under laboratory conditions. The reaction products are substantially less toxic, or inactive as herbicides, than the parent compounds. Tests of strain SG-4G and Escherichia coli expressing MheI found they were also able to hydrolyse dimethyl phthalate, propanil and chlorpropham, indicating that MheI is principally responsible for the above activities.

Co-occurrence of light microplastics and phthalate esters in soils of China

The terrestrial environment is both a critical source and sink for microplastics (MPs). However, further efforts into the risk assessment, management, and mitigation activities of MPs in the terrestrial environment were limited by the scant data on their occurrence. In this study, we investigated the co-occurrence and correlations of light MPs and phthalate esters (PAEs) in the soils of China's hotspots and non-hotspot regions. Light MPs and PAEs were detected in all agricultural and urban soils (n = 125). In soils from hotspots (Shihezi, Xinjiang) where intense plastic mulching was used, the concentrations of MPs and phthalate diesters (di-PAEs) were 650–36,450 pcs kg−1 and 55.60–1236.64 μg kg−1, respectively. In hotspots but not in non-hotspot regions of China, a positive correlation between MPs and PAEs was established, suggesting PAEs may serve as an indicator of MP contamination in hotspots. High quantities of MPs (1143–5911 pcs kg−1) and PAEs (67.3–1236.64 μg kg−1) were also detected in urban park soils, demonstrating a need for future research on MP in urban soils. In addition, the ubiquitous co-occurrence of MPs and PAEs in all 125 investigated soils revealed that potential joint toxicity, co-transformation, and co-transportation of MPs and PAEs should not be disregarded.

Phthalates in dormitory dust and human urine: A study of exposure characteristics and risk assessments of university students

Phthalate diesters (PAEs) are prevalent and potentially toxic to human health. The university dormitory represents a typical and relatively uniform indoor environment. This study evaluated the concentrations of phthalate monoesters (mPAEs) in urine samples from 101 residents of university status, and the concentrations of PAEs in dust collected from 36 corresponding dormitories. Di-(2-ethylhexyl) phthalate (DEHP, median: 68.0 μg/g) was the major PAE in dust, and mono-ethyl phthalate (47.9 %) was the most abundant mPAE in urine. The levels of both PAEs in dormitory dust and mPAEs in urine were higher in females than in males, indicating higher PAE exposure in females. Differences in lifestyles (dormitory time and plastic product use frequency) may also affect human exposure to PAEs. Moreover, there were significant positive correlations between the estimated daily intakes of PAEs calculated by using concentrations of PAEs in dust (EDID) and mPAEs in urine (EDIU), suggesting that PAEs in dust could be a significant source of human exposure to PAEs. The value of EDID/EDIU for low molecular weight PAEs (3–6 carbon atoms in their backbone) was lower than that of high molecular weight PAEs. The contribution rate of various pathways to PAE exposure illustrated that non-dietary ingestion (87.8 %) was the major pathway of human exposure to PAEs in dust. Approximately 4.95 % of university students' hazard quotients of DEHP were >1, indicating that there may be some health risks associated with DEHP exposure among PAEs. Furthermore, it is recommended that some measures be taken to reduce the production and application of DEHP.

Association of prenatal phthalate exposure with pubertal development in Spanish boys and girls

BackgroundPhthalates are widespread, anti-androgenic chemicals known to alter early development, with possible impact on puberty timing. AimTo investigate the association of prenatal phthalate exposure with pubertal development in boys and girls. MethodsUrinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP) and non-phthalate plasticizer DINCH® were quantified in two urine samples collected during pregnancy from mothers participating in the INMA Spanish cohort study. Pubertal assessment of their children at age 7–10 years (409 boys, 379 girls) was conducted using the parent-reported Pubertal Development Scale. Modified Poisson and Weighted Quantile Sum (WQS) regression was employed to examine associations between prenatal phthalates and risk of puberty onset, adrenarche, and gonadarche. Effect modification by child weight status was explored by stratified analysis. ResultsPrenatal exposure to DEHP was associated with higher risk of puberty onset (relative risk [RR] = 1.32, 95% CI = 1.09–1.59 per each log-unit increase in concentrations) and gonadarche (RR = 1.23, 95% CI = 1.00–1.50) in boys and higher risk of adrenarche (RR = 1.25, 95% CI = 1.03–1.51) in girls at age 7–10 years. In boys, prenatal exposure to DEP, DnBP, and DEHP was also associated with higher risk of adrenarche or gonadarche (RRs = 1.49–1.80) in those with normal weight, and BBzP and DINCH® exposure with lower risk of adrenarche (RR = 0.49, 95% CI = 0.27–0.89 and RR = 0.47, 95% CI = 0.24–0.90, respectively) in those with overweight/obesity. In girls, DiBP, DnBP, and DINCH® were associated with slightly higher risk of gonadarche (RRs = 1.14–1.19) in those with overweight/obesity. In the WQS model, the phthalate mixture was not associated with puberty in boys or girls. ConclusionPrenatal exposure to certain phthalates was associated with pubertal development at age 7–10 years, especially earlier puberty in boys with normal weight and girls with overweight/obesity. However, there was no evidence of effect of the phthalate mixture on advancing or delaying puberty in boys or girls.

Toxicokinetic assessment of inhalatory absorption of Diisobutyl phthalate (DiBP) using a novel thermal desorption-GC-MS method to determine phthalate diesters in blood plasma

Phthalates are endocrine disrupting compounds that have been found in outdoor and indoor air. However, little is known about their inhalatory absorption. Although measurement of urinary metabolites is the current standard, complex and convergent metabolism of phthalates poses the necessity for alternative methodologies such as the quantitation of parental compounds in plasma. We determined the inhalatory absorption of Diisobutyl phthalate (DiBP) using a novel method based on a thermal desorption probe (TSP)–gas chromatography–mass spectrometry developed for the detection and quantitation of nine phthalate diesters in blood plasma, which fulfilled the acceptance criteria suggested by FDA guidelines regarding specificity, matrix effect, recovery, linearity, sensitivity, accuracy, and precision. After inhalation, plasma concentration of DiBP exhibited two peaks, suggesting a first, rapid absorption event, followed by a second, delayed one and a first order elimination stage. Half-life was calculated as 62 min and bioavailability, compared to IV route, was 15%.

Presence of parabens, phenols and phthalates in paired maternal serum, urine and amniotic fluid

ObjectiveTo examine whether selected endocrine disrupting chemicals were present in pregnant women and passed through the placental barrier to amniotic fluid, potentially exposing the developing fetus. MethodsPaired samples of maternal serum, urine and amniotic fluid were concurrently collected (<1 h) from 200 pregnant women (age >18 years) with a singleton pregnancy and undergoing amniocentesis between gestational weeks 12 – 36. The concentration of six different parabens, seven phenols, 31 metabolites from 15 phthalate diesters and the polychlorinated substance triclocarban were analyzed by isotope diluted TurboFlow-liquid chromatography-tandem mass spectrometry. ResultsConcentrations of all included compounds were highest in maternal urine followed by serum, and lowest in amniotic fluid. Of the six parabens measured in amniotic fluid, methylparaben (MeP) and ethylparaben (EtP) were detectable most often (87% and 33% of the samples, respectively). Of the seven phenols measured, three (2,4-dichlorphenol, 2,5-dichlorphenol, 2-propylphenol) were detectable in the range of 14–21% of the amniotic fluid samples, at low concentrations (<0.12 ng/ml). Two secondary phthalates metabolites, mono-(2-carboxymethyl-hexyl) phthalate and mono-carboxy-iso-octyl phthalate were each present in ≤15% of the amniotic fluid samples at concentrations 2–5 times lower than in maternal serum and 20–100 times lower than in maternal urine. A modest statistically significant correlation between the levels of MeP and EtP was detected in paired maternal urine-amniotic fluid samples was detected (Spearman rMeP: 0.246; rEtP: 0.364). Likewise, the concentration of mono-ethyl phthalate (MEP) in paired maternal urine and amniotic fluid samples indicated a modest statistically significant correlation (Spearman rMEP: 0.264), driven by detectable levels of MEP in only 3% of the amniotic fluid samples. ConclusionsIn general, the included parabens, phenols and phthalates were effectively metabolized and excreted via the urine, which was the matrix that reflected the highest detectable levels. The detectable levels of several included parabens and phthalates in human amniotic fluid calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of individual and multiple endocrine disruptors in order to better assess the risk to the developing fetus.

Widespread occurrence of phthalate and non-phthalate plasticizers in single-use facemasks collected in the United States

Single-use or disposable facemasks have been widely used by the public for personal protection against the spread of COVID-19. The majority of disposable facemasks are made of synthetic polymers such as polypropylene, polyethylene terephthalate (as polyester), and polystyrene, and could therefore be a source of human exposure to plasticizers that are incorporated into these polymers during production. Little is known, however, about the occurrence of plasticizers in facemasks. In this study, we determined the concentrations of nine phthalate diesters and six non-phthalate plasticizers in 66 facemasks purchased in the United States. Among phthalate diesters, dibutyl phthalate, di(2-ethylhexyl)phthalate, di-iso-butyl phthalate, and butyl benzyl phthalate were found in all facemask samples, at median concentrations of 486, 397, 254, and 92 ng/g, respectively. Among non-phthalate plasticizers, dibutyl sebacate (median: 3390 ng/g) and di(2-ethylhexyl)adipate (352 ng/g) were found at notable concentrations. Inhalation exposure to select phthalate and non-phthalate plasticizers from the use of facemasks was estimated to range from 0.1 to 3.1 and 3.5 to 151 ng/kg-bw/d, respectively. To our knowledge, this is the first study to report the occurrence of phthalate and non-phthalate plasticizers in facemasks collected from the United States.

Fast determination of phthalates in mussel samples by micro-matrix solid-phase dispersion (micro-MSPD) coupled with GC\u2013MS/MS

A fast, effective and low cost sample preparation method based on miniaturized matrix solid-phase dispersion (micro-MSPD) combined with gas chromatography coupled to tandem triple-quadrupole-mass spectrometry (GC–MS/MS) has been developed for the determination of six phthalate diesters (DMP, DEP, DBP, BzBP, DEHP and DnOP) in mussel samples. The six target compounds have been included in the list of priority pollutants by United States Environmental Protection Agency. The extraction step was optimized on real spiked mussel coming from Galician Rías by means of a factorial design. The final procedure involved the use of 0.45 g of sample, 0.5 g of dispersant agent (Florisil) and 3 mL of organic solvent (ethyl acetate). The optimized method was validated giving satisfactory analytical performance, low detection limits (0.09 to 6.73 ng g−1 dw) and high recoveries (93 and 114%). The validated method was applied to four real mussel samples coming from Galician Rías.

Composition and structure characteristics of soluble organic matter from Naomaohu lignite by sequential extraction and thermal conversion performance of the corresponding residue

Carbon disulfide (CDS), methanol, acetone and isometric carbon disulfide/acetone mixture (IMCDSAM) were used as solvents to sequentially extract Naomaohu lignite (NL) via ultrasonic-assisted extraction to obtain extracts (E1–E4) and final extraction residue (ER). Composition and structure of E1–E4 were analyzed by GC-MS. It is found that the main compounds in E1 are alkanes, aromatics, alcohols and esters. Alkanes, alcohols and esters are the main compounds in E2. Alcohols, phenolics and esters are the main components in E3, and esters are mainly phthalic diester compounds. Affected by synergistic effect of the two solvents CDS and acetone, the relative content of alkenes in E4 is relatively high. FT-IR was used to characterize functional groups in NL, E1–E4 and ER. The results show that the ultrasonic extraction process only extracts free small compounds from macromolecular skeleton of the NL and some other molecules, which connect the macromolecular skeleton by weak covalent bonds, and the process does not destroy the macromolecular skeleton structure. In addition, peak fitting results from FT-IR show that types of infrared absorption peaks in ER do not change after ultrasonic extraction, while intensity of the peaks varies. TG-DTG profiles of NL and ER indicate that after ultrasonic extraction weight loss of NL increases from 47.09% to 51.04%, and peak of the maximum weight loss rate is advanced from 450 to 430°C. Pyrolysis kinetic analysis of NL and ER based on Coats-Redfern model show that after ultrasonic extraction activation energy of ER in rapid pyrolysis stage is lower than that of NL, and the pyrolysis process is easier to proceed.

Association of phthalate replacement DINCH metabolite concentrations with adiposity in a multi-site, multi-racial cohort of children

BACKGROUND AND AIM: 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) is a recent plasticizer replacing high molecular weight phthalate diesters in items such as toys, medical devices, and food packaging. Little is known regarding the association of DINCH exposure and adiposity in children. METHODS: Analyses included 629 racial/ethnically diverse children ages 4-8 in the Environmental Influences on Child Health Outcomes (ECHO) study, a follow-up of the NICHD Fetal Growth Studies at 10 US sites. Urinary oxidative metabolites of DINCH (cyclohexane-1,2-dicarboxylic acid mono carboxyisooctyl [MCOCH] and cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl [MHNCH] esters) were determined using liquid chromatography tandem-mass spectrometry (UPLC-ESI-MS/MS). Values were divided by molecular weight and summed to obtain a composite DINCH value (nmol/ml). Outcomes were child’s body mass index (BMI) z-score, waist circumference z-score, percent body fat, and categorized BMI percentiles (85, 85 to 95, ≥95). Multivariable linear and logistic regression models adjusted for urine specific gravity, gender, age, race/ethnicity, birth weight, prolonged exclusive breastfeeding, reported physical activity level, frequency of fast-food consumption, cigarette smoke exposure, neighborhood traffic, mother’s education and pre-pregnancy BMI were used to analyze the association between natural log transformed DINCH levels and outcomes. RESULTS:88% of children had DINCH levels at or above the limit of detection. For each unit increase in natural log transformed DINCH there was a significant decrease in BMI z-score (β [95% CI]: -0.103 [-0.180, -0.026]), waist circumference z-score (β [95% CI]: -0.126 [-0.198, -0.054]) and percent body fat (β [95% CI]: -0.022 [-0.035, -0.009]). DINCH levels were not associated with overweight [OR=0.82 (95% CI: 0.66, 1.02)] or obese [OR=0.88 (95% CI: 0.69, 1.12)] versus normal BMI percentile categories. CONCLUSIONS:In this cross-sectional analysis there were significant inverse associations between children’s DINCH exposure levels and adiposity measures. Additional research is needed to confirm this association and identify possible interactions between DINCH and joint exposure to other related chemicals. KEYWORDS: Phthalates, Obesity and metabolic disorders, Children's environmental health

Sociodemographic and dietary predictors of urinary concentrations of phthalates and their alternatives in children in the Project Viva cohort

BACKGROUND AND AIM: Although phthalates are still widely used, phthalate alternatives are replacing their use in food packaging, toys, and personal care products. However, data on sociodemographic and dietary predictors of concentrations of phthalate alternatives in children are limited. METHODS: We studied 830 children ages 6-10 years from 2007-2010 in Project Viva, a Boston-area cohort. We measured urinary phthalate metabolites and summed metabolites to calculate concentrations of ten parent phthalate diesters and alternatives. We determined average daily intake of 12 food groups over the prior month via a PrimeScreen questionnaire. We used linear regression to examine mutually adjusted associations of sociodemographics and diet with individual phthalates and alternatives, accounting for specific gravity. We used logistic regression to examine predictors of 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) detectability. RESULTS:Participants were mean (SD) 7.8 (0.8) years; 67% had college-educated mothers. We detected at least one DINCH metabolite in 35% of samples and at least one metabolite of all other phthalates in ≥ 94% of samples. Sociodemographics and diet explained 25% (for di-isodecyl phthalate) to 48% (for di-n-butyl phthalate) of phthalate variability. The phthalate alternative di-2-ethylhexyl terephthalate was higher in girls (18.7% [95% CI: 0.7, 39.9]), children who consumed more meat and dairy (e.g. 36.9% higher [95% CI: 3.8, 80.6] for ≥ daily vs daily meat consumption), and samples from later years (e.g., 373.4% higher [95% CI: 220.9, 598.4] for 2010 vs. 2007). DINCH was more likely to be detectable in girls (odds ratio [OR] 2.1 [95% CI: 1.5, 3.0]) and samples from later years (e.g., OR 8.5 [95% CI: 3.6, 21.2] for 2010 vs. 2007). CONCLUSIONS:Sociodemographics and diet explained moderate variability of phthalate and alternative concentrations in children. We found higher concentrations of phthalate alternatives in girls and in samples from later years. Future studies should continue to investigate health effects of phthalate alternatives. KEYWORDS: Phthalates, Children's environmental health, Endocrine disrupting chemicals

Associations between Prenatal Exposure to Phthalates and Timing of Menarche and Growth and Adiposity into Adulthood: A Twenty-Years Birth Cohort Study.

Phthalates are ubiquitous environmental chemicals with endocrine disrupting properties and potentially obesogenic effects. We hypothesised that antenatal phthalate exposure may influence growth and adiposity patterns in girls through childhood into adolescence. Among 1342 Raine Study singleton females, 462 had maternal serum and at least one outcome available up to 20 years of age. Individuals’ maternal serum collected at 18 and 34 weeks gestation was pooled and analyzed for concentrations of 32 metabolites of 15 phthalate diesters. Cox regression and linear models were used to determine associations between maternal phthalate levels and age at menarche, change in height and weight z-scores between birth and two years, height from birth to 20 years, BMI from two to 20 years, deviation from mid-parental height at age 20 and DEXA scan measures at age 20. Weak negative associations were detected with some phthalate metabolites and change in height and weight z-score during infancy. Weak positive associations between some of the high molecular weight phthalate metabolites and height z-score were detected during childhood. While still within the normal range, age at menarche was slightly delayed in girls with higher prenatal exposure to the higher molecular weight phthalate metabolites. We derived some associations between prenatal phthalate exposure with early growth patterns and age at menarche.

Secular trends of urinary phthalate metabolites in 7-year old children and association with building characteristics: Hokkaido study on environment and children's health

The widespread commercial production and use of phthalates as plasticizers in consumer products have led to significant human exposure. Some phthalates are known to disrupt the endocrine system and result in adverse health outcomes. As such, they have been regulated in materials used for children's items and food packages. In this study, we examined the secular trend of urinary phthalate metabolites in children and the association between metabolites and building characteristics. In total, 400 first-morning spot urine samples of 7 years old children collected from 2012 to 2017 from an ongoing birth cohort study were examined. Parents provided information on demographics and building questionnaires. We analyzed 10 urinary phthalate metabolites from five phthalate diesters using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS): MiBP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MECPP, MiNP, OH-MiNP, and cx-MiNP. A multivariable regression model with creatinine-corrected metabolite levels was applied to assess secular trends during 2012-2017. The association between metabolite levels and building characteristics was investigated using a mutual-adjusted linear regression. The metabolites MnBP, MEHP, MEOHP, MEHHP, MECPP, and OH-MiNP were detected in all samples. The highest median concentration was for MECPP 37.4ng/mL, followed by MnBP and MEHHP at concentrations of 36.8 and 25.8ng/mL, respectively. Overall, DBP, BBzP, and DINP metabolite concentrations in this study were comparable to or lower than those in previous studies from Japan and other countries in a similar study period. Higher concentrations of DEHP metabolites were observed in this study than in children from the USA and Germany, as per previous reports. Despite updated phthalate regulations and reports of production volume change in Japan, all the measured metabolites showed a stable trend between 2012 and 2017. Higher phthalate metabolite levels were observed among children from households with low annual income, those who lived in old buildings, and those with window opening habits of ≥1h than ≤1h. In contrast, children in houses that vacuumed 4 or more days/week showed a lower level of MnBP than those in houses that vacuumed ≤3 days/week. This study demonstrates that the internal exposure level of phthalates in Japanese children was stable from 2012 to 2017. Our findings suggest that phthalate exposure in children is consistent. Thus, improvements in the indoor environment, such as frequent vacuuming, may reduce exposure. Biomonitoring of phthalates is critical for elucidating their possible health effects and developing mitigation strategies.

Maternal Food and Beverage Consumption Behaviors and Discrepant Phthalate Exposure by Race.

Background: Differential exposure to endocrine-disrupting chemicals, including phthalate diesters, may contribute to persistent racial/ethnic disparities in women’s reproductive health outcomes. We sought to characterize sources of gestational exposure to these agents that may differ according to maternal race. Methods: We enrolled pregnant Black (n = 198), including African American, and White (n = 197) women during the second trimester, and measured eight phthalate monoester metabolites in urine. We assessed confounder-adjusted associations between multiple food and beverage consumption habits, summarized using a principal component analysis, as predictors of maternal urinary phthalate metabolite levels, stratified by race. Results: Whites reported significantly greater unprocessed food consumption (42.5% vs. 32.0%; p < 0.001) and storage of food in clear unbreakable plastic containers (66.5% vs. 49.3%; p < 0.001) than Blacks, while Blacks consumed more canned fruits and vegetables (23.5% vs. 12.2%; p < 0.001) than Whites. Using plastics for food storage, microwaving in plastic containers, and using hard plastic water bottles was associated with urinary phthalate concentrations, especially DEHP metabolites (e.g., mean difference = 5.13%; 95% CI: 3.05, 7.25). These associations were driven primarily by Black pregnant women. Conclusions: Targeted interventions to reduce maternal exposure to phthalates need to be designed with specific attention to differences in food and beverage consumption behaviors among Black and White women.