Levels Of Di-(2-ethylhexyl) Phthalate Research Articles

Environmental monitoring of phthalic acid esters in northwest Persian Gulf estuary: Concentrations, distribution, and risk assessment

The present study investigates the concentration level, distribution, and risk assessment of six high-priority phthalic acid esters (PAEs) in seawaters and sediments of the Musa estuary, northwest of the Persian Gulf, Iran. Additionally, the industrial and urban effluents terminating in this estuary were also analyzed. The overall variations of Σ6PAEs were 10.65–164.80 µg/L in seawaters, 0.53–26.18 µg/g in sediments, and 181.09–764.57 µg/L in effluent samples. Di–n–butyl phthalate (DnBP) and di(2–ethylhexyl) phthalate (DEHP), together accounted for 57.2 %–99.5 % and 59 %–100 % of the Σ6PAEs concentrations in seawaters and sediments, respectively. A relatively similar trend was also detected in the effluent waters. While industrial runoffs exhibited greater shares and concentrations compared to urban areas, the levels of PAEs were higher in waters and sediments near urban regions due to restricted water circulation. A significant correlation was found (r = 0.8385) between Σ6PAEs in seawater and sediment. Given its consistent detection frequency of 100 % across all stations, DEHP can be served as a reliable indicator for PAE contamination. In nearly all stations, the pollution levels of DnBP and DEHP exceeded the environmental risk level (ERL). The ecological risk quotient (RQ) for at least two PAEs appeared at medium to high levels in both seawaters and sediments. Establishing baseline data on PAEs in the Musa estuary will guide future strategies for pollutant control across the Persian Gulf network.

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.

Reduced ovarian cholesterol and steroid biosynthesis along with increased inflammation are associated with high DEHP metabolite levels in human ovarian follicular fluids

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is known to have endocrine-disrupting properties mediated by its many metabolites that form upon exposure in biological systems. In a previous study, we reported an inverse association between DEHP metabolites in the human ovarian follicular fluid (FF) and the responsiveness of the follicles to controlled ovarian stimulation during in vitro fertilization (IVF) treatments. Here, we explored this association further through molecular analysis of the ovarian FF samples.Ninety-six IVF patients from Swedish (N = 48) and Estonian (N = 48) infertility clinics were selected from the previous cohort (N = 333) based on the molar sum of DEHP metabolites in their FF samples to arrive at “high” (mean 7.7 ± SD 2.3 nM, N = 48) and “low” (0.8 ± 0.4 nM, N = 48) exposure groups. Extracellular miRNA levels and concentrations of 15 steroid hormones were measured across FF samples. In addition, FF somatic cells, available for the Estonian patients, were used for RNA sequencing.Differential expression (DE) and interactions between miRNA and mRNA networks revealed that the expression levels of genes in the cholesterol biosynthesis and steroidogenesis pathways were significantly decreased in the high compared to the low DEHP group. In addition, the DE miRNAs were predicted to target key enzymes within these pathways (FDR < 0.05). A decreased 17-OH-progesterone to progesterone ratio was observed in the FF of the high DEHP group (p < 0.05). Additionally, the expression levels of genes associated with inflammatory processes were elevated in the FF somatic cells, and a computational cell-type deconvolution analysis suggested an increased immune cell infiltration into the high DEHP follicles (p < 0.05).In conclusion, elevated DEHP levels in FF were associated with a significantly altered follicular milieu within human ovaries, involving a pro-inflammatory environment and reduced cholesterol metabolism, including steroid synthesis. These results contribute to our understanding of the molecular mechanisms of female reprotoxic effects of DEHP.

The relationship between bisphenol A and phthalates with precocious puberty in Vietnamese children.

This study is aimed to explore the correlation between bisphenol A (BPA) and phthalates, including diethylhexylphthalate (DEHP) and dibutylphthalate (DBP), and precocious puberty (PP). A case-control study was conducted in Ho Chi Minh City, Vietnam, from November 2021 to April 2022, involving 250 children, with 124 of them diagnosed with PP and 126 serving as controls. We assessed the levels of urinary BPA, DEHP, and DBP in all participants and examined their association with the risk of PP. BPA was detected in 11.3 % of PP cases but was not found in any individuals in the control group (p<0.001). Diethylhexylphthalate metabolite (MEHP) was not detected in any of the samples. Positive urinary results for dibutylphthalate metabolite (MBP) were observed in 8.1 % of PP cases and 2.4 % in the control group, with an odds ratio of 3.6 (95 % confidence interval: 0.97-13.4, p=0.03). The PP group exhibited a higher prevalence of positive urinary BPA and DBP levels compared to the control group.

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

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

Microbial Mechanisms of Removal of Phthalic Acid Esters in Purple Soils Revealed Using Metagenomic Analysis

The removal mechanisms of phthalic acid esters (PAEs) have attracted much attention because of their endocrine-disrupting properties and persistence in environmental media. In order to reveal the removal mechanism of PAEs and involved keystone taxa and functional genes, purple soils were polluted by di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), respectively, along a gradient of 0, 5, 10, and 20 mg·kg-1 and cultured for 90 days in the dark. The results showed that the degradation dynamics of DBP and DEHP were well-fitted by the first-order kinetic model, and the half-life of DBP and DEHP ranged from 17.0 to 38.2 days. The degradation rate of DBP (5 mg·kg-1) was the fastest, and that of DEHP (20 mg·kg-1) was the slowest. The soil samples of the seventh day and the fifteenth day were analyzed using metagenomic sequencing. NMDS and cluster analysis showed that there was a significant difference between the bacterial community structure of soil samples from the seventh day and the fifteenth day. The relative abundance of Actinobacteria increased from the seventh day to the fifteenth day. The smaller the half-life of DBP or DEHP, the higher the relative abundance of Actinobacteria in the different treatments. In addition, Streptomyces was the dominant genus in all polluted soils. Co-occurrence network analysis elucidated that Pandoraea was a keystone genus of the soil bacterial communities, which could be used to indicate the pollution levels of DBP and DEHP. The results of KEGG annotation demonstrated that Pandoraea was responsible for benzoate degradation, quorum sensing, ABC transporters, and the two-component system and could promote the intercellular communications and the microbial growth and proliferation and maintain the stability of the community structure. Therefore, the degradation rate of DBP and DEHP in purple soils depended on their initial content and their own properties. Actinobacteria played an important role in the PAEs degradation, and Pandoraea played a major part in promoting PAEs degradation and regulating the stability of the structure and function of degrading bacterial communities.

Evaluation of precopulatory pairing behaviour and male fertility in a marine amphipod exposed to plastic additives

Plastics contain a mixture of chemical additives that can leach into the environment and potentially cause harmful effects on reproduction and the endocrine system. Two of these chemicals, N-butyl benzenesulfonamide (NBBS) and triphenyl phosphate (TPHP), are among the top 30 organic chemicals detected in surface and groundwater and are currently placed on international watchlist for evaluation. Although bans have been placed on legacy pollutants such as diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP), their persistence remains a concern. This study aimed to examine the impact of plastic additives, including NBBS, TPHP, DBP, and DEHP, on the reproductive behaviour and male fertility of the marine amphipod Echinogammarus marinus. Twenty precopulatory pairs of E. marinus were exposed to varying concentrations of the four test chemicals to assess their pairing behaviour. A high-throughput methodology was developed and optimised to record the contact time and re-pair time within 15 min and additional point observations for 96 h. The study found that low levels of NBBS, TPHP, and DEHP prolonged the contact and re-pairing time of amphipods and the proportion of pairs reduced drastically with re-pairing success ranging from 75% to 100% in the control group and 0%–85% in the exposed groups at 96 h. Sperm count declined by 40% and 60% in the 50 μg/l and 500 μg/l DBP groups, respectively, whereas TPHP resulted in significantly lower sperms in 50 μg/l exposed group. Animals exposed to NBBS and DEHP showed high interindividual variability in all exposed groups. Overall, this study provides evidence that plastic additives can disrupt the reproductive mechanisms and sperm counts of amphipods at environmentally relevant concentrations. Our research also demonstrated the usefulness of the precopulatory pairing mechanism as a sensitive endpoint in ecotoxicity assessments to proactively mitigate population-level effects in the aquatic environment.

Di-(2-Ethylhexyl) Phthalate (DEHP) in House Dust in Canadian Homes: Behaviors and Associations with Housing Characteristics and Consumer Products

Background. Di-(2-ethylhexyl) phthalate (DEHP), which is ubiquitous in indoor environments, was the predominant phthalate measured in house dust in the Canadian CHILD Cohort and was found to be associated with a large increased risk of childhood asthma. Objective. To inform interventions by identifying sources of DEHP in dust and assessing behaviors related to DEHP concentrations in house dust. Methods. DEHP levels were measured in 726 dust samples collected at ~3 months of age in CHILD as well as in ~50 homes at two time points (June and November) in the CHILD pilot study. DEHP metabolites were measured in urine for a subset of the ~3-month-old infants. Housing characteristics were assessed at the time of dust and urine collection. Numerous factors from these surveys were investigated as potential sources of DEHP using univariate analyses and multivariable regressions. Correlations between DEHP in dust and urinary metabolites and between repeat dust samples were examined to study the relationship between dust measurement and DEHP exposure. Results. Overall, DEHP dust concentrations were higher for lower-income families. Homes with vinyl flooring in the kitchen and bathroom showed higher levels of DEHP than those without vinyl flooring. The quantity of vinyl furniture and the presence of mold were associated with higher DEHP concentrations, while the use of mattress covers reduced concentration. No other significant associations were found. DEHP concentrations in dust were consistent over 6 months, although the correlation between dust and DEHP metabolites in urine was low. Conclusion. DEHP in house dust persisted over multiple months, contributed to infant internal exposure, and was associated with specific housing characteristics. These findings may inform the public on their choice of building materials and products, as well as future policies, aimed at reducing the health risk associated with exposures in the indoor environment especially for children.

Phthalate exposure and risk of ovarian dysfunction in endometriosis: human and animal data.

Objective: We aimed to explore the correlations between and possible mechanisms of common environmental endocrine disruptors, phthalates, and ovarian dysfunction in endometriosis. Methods: Subjects were included in the case group (n = 107) who were diagnosed with endometriosis by postoperative pathology in Fujian Maternal and Child Hospital from February 2018 to February 2021, and the women who were excluded from endometriosis by surgery were as the control group (n = 70). The demographic information of the subjects were evaluated by questionnaire, and the clinical characteristics were evaluated by medical records and 3-year follow-up results. Gas chromatography‒mass spectrometry was used to quantify 10 metabolites of phthalates, including dimethyl ortho-phthalate (DMP), mono-n-methyl phthalate (MMP), dioctyl ortho-phthalate (DEP), mono-ethyl phthalate (MEP), di-n-butyl ortho-phthalate (DBP), mono-butyl phthalate (MBP), benzylbutyl phthalate (BBzP), mono-benzyl; phthalate (MBzP), diethylhexyl phthalate (DEHP) and mono-ethylhexyl phthalate (MEHP), in the urine samples of the subjects. Furthermore, a total of 54 SD rats were exposed to DEHP 0, 5, 50, 100, 250, 500, 1,000, 2000, and 3,000mg/kg/day for 2weeks. The SD rats' body weight, oestrus cycle changes, and serum anti-mullerian hormone (AMH) levels were evaluated. After sacrifice, the mass index of the rat uterus and bilateral ovaries were calculated. Finally, bioinformatics analysis of rat ovarian tissues was performed to explore the possible mechanism. SPSS 24.0 (IBM, United States) was used for data analysis. p-value <0.05 was considered statistically significant. Results: The human urinary levels of DMP (p < 0.001), MMP (p = 0.001), DEP (p = 0.003), MEP (p = 0.002), DBP (p = 0.041), MBP (p < 0.001), BBzP (p = 0.009), DEHP (p < 0.001), and MEHP (p < 0.001) were significantly higher in women with endometriosis than in controls. Notably, DEHP was a significant risk factor for endometriosis (OR: 11.0, 95% CI: 5.4-22.6). The area under the ROC curve increased when multiple phthalates were diagnosed jointly, reaching 0.974 as the highest value, which was helpful for the diagnosis of endometriosis. In vivo experiments showed that after DEHP exposure in rats, the mass index of the ovary and uterus decreased in a dose-dependent manner; the oestrus cycle of SD rats was irregularly prolonged and disordered; and the serum AMH level was negatively correlated with the DEHP exposure dose (Rho = -0.8, p < 0.001). Bioinformatics analysis of rat ovarian tissues showed that seven genes involved in the steroid biosynthesis pathway were upregulated and may play a negative role in ovarian function. Conclusion: Exposure to phthalates, especially DEHP, is associated with the occurrence of endometriosis and affects women's reproductive prognosis and ovarian function. The steroid biosynthesis pathway may be related to ovarian dysfunction. The detection of phthalate in urine may become a new biological target for the diagnosis of endometriosis.

P-673 Women exposed to higher levels of DEHP display altered microRNA expression profile in the pre-ovulatory follicular fluid

Abstract Study question Can higher concentrations of di-2-ethylhexyl phthalate (DEHP) in follicular fluid (FF) lead to an altered microRNA expression profile? Summary answer The present study indicates the upregulation of miR-203a-3p, miR-150-5p and miR-28-3p in the follicular fluid of women with higher DEHP concentrations (FDR&amp;lt;0.05). What is known already Women are exposed daily to endocrine-disrupting chemicals (EDCs) such as phthalates which can be found in hundreds of personal care products and plastic items. In studies of rodents exposed to certain phthalates, high doses have been shown to change hormone levels, disrupt folliculogenesis and cause birth defects. Recently, we reported a strong inverse association between DEHP metabolites and ovarian sensitivity index (OSI) in females undergoing ART treatment. Several mechanisms have been proposed to explain the association between DEHP and fertility in rodents, however not much is known about the mechanisms in humans. Study design, size, duration FF was collected from 96 women undergoing IVF treatment after controlled ovarian stimulation during ovarian puncture. 48 participants from Estonia were recruited at Nova Vita Clinic AS in Tallinn, Estonia in 2019 and 48 participants from Sweden were recruited at Carl von Linnekliniken in Uppsala, Sweden in 2016. In both cohorts, patients signed a written informed consent form. Both cohorts were matched for age, BMI, parity and the number of previous IVF treatments. Participants/materials, setting, methods DEHP metabolite concentrations in the FF samples were measured in our earlier study by LC-MS/MS. Cell free RNA was extracted from FF samples with Qiagen miRNeasy Micro kit, sequencing libraries were prepared with QIAseq miRNA library kit and sequenced on Illumina NextSeq 550 instrument. Differential miRNA expression analysis was performed with the DESeq2 package. Pathway enrichment analysis for differentially expressed miRNA targets was conducted with the miEAA tool integrated with WikiPathways. Main results and the role of chance In total, 465 miRNAs were observed at least twice in ≥ 24 samples. Differential expression analysis was conducted between DEHP-high and DEHP-low groups in combined cohorts using the cohort as a covariate. 16 miRNAs were found to be differentially expressed between DEHP groups with FDR&amp;lt;0.1. Three miRNAs: miR-203a-3p, miR-150-5p and miR-28-3p, were differentially expressed with FDR&amp;lt;0.05 and were more abundant in women with high DEHP-levels in both cohorts. Of these, miR-203a-3p was negatively correlated with OSI (Pearson R = -0.27, p = 0.0089). Six miRNAs (miR-10b-5p, miR-112-5p, miR-132-5p, miR-203-3p, miR-205-5p and miR-27-3p) were found to have predicted targets in the androgen receptor signalling pathway. Limitations, reasons for caution The miRNAs found in this study need to be validated in a larger set of patients as a cohort-dependent difference in the results was observed. There is a need for further functional studies to investigate miRNAs as possible mediators of the association between DEHP and ovarian sensitivity index. Wider implications of the findings The current study presents evidence that DEHP exposure alters the expression of FF miRNAs which are associated with androgen receptor signalling. These results provide novel evidence of the potential influence of endocrine-disrupting chemicals on female reproduction. Trial registration number NA

Remediation of di(2-ethylhexyl) phthalate (DEHP) contaminated black soil by freeze-thaw aging biochar

Di(2-ethylhexyl) phthalate (DEHP), a complex structure with high toxicity, is a common organic pollutant. This study investigated the effects of fresh biochar (FBC), and freeze-thaw cycled aged biochar (FTC-BC) on DEHP-contaminated soils using a pot experiment. The specific surface area of FBC increased from 145.20 to 303.50 m2/g, and oxygen-containing functional groups increased from 1.26 to 1.48 mol/g after freeze-thaw cycles, greatly enhancing the adsorption of DEHP by biochar in the soil. The comprehensive radar chart evaluation showed that FBC and FTC-BC reduced DEHP growth stress and improved the soil properties. Compared with FBC, FTC-BC performed better in protecting the normal growth of pakchoi and improving soil properties. In addition, the application of biochar increased the diversity and abundance of bacteria in the DEHP-contaminated soil and changed the composition of the soil bacterial community. The partial least squares path model (PLS-PM) showed that adding biochar as a soil remediation agent significantly positively impacted soil nutrients and indirectly reduced the DEHP levels in soil and plants by increasing soil microbial diversity. Compared with FBC, FTC-BC creates a more satisfactory living environment for microorganisms and has a better effect on the degradation of DEHP in the soil. This study provides a theoretical basis for future biochar remediation of DEHP-contaminated soils in cold high-latitude regions.

Early-life exposure to di (2-ethyl-hexyl) phthalate: Role in children with endocrine disorders.

Di (2-ethyl-hexyl) phthalate (DEHP), one of endocrine-disrupting chemicals (EDCs), has widespread concern due to its serious health hazards. Exposure to DEHP in the early stage of life affects fetal metabolic and endocrine function, which even would cause genetic lesions. To date, it is widely believed that the increasing incidence of childhood obesity and diabetes in adolescents is related to the impact of DEHP on glucose and lipid homeostasis in children. However, there remains a knowledge gap to recognize these adverse effects. Thus, in this review, besides the exposure routes and levels of DEHP, we further outline the effects of early-life exposure to DEHP on children and potential mechanisms, focusing on the aspect of metabolic and endocrine homeostasis.

Determination and Traceability Analysis of Phthalic Acid Esters in Garlic (Allium stivum L.) from Jiangsu Province, China

Phthalic acid esters (PAEs) are ubiquitous environmental pollutants and are recognized as a threat to the environment and agricultural product safety across the world. In order to investigate the level of PAEs in garlic, soils, and agricultural films from Pizhou City, Jiangsu province, China, 11 garlic samples, 106 soil samples, and 4 agricultural film samples were collected and analyzed using GC-MS. In addition, the uptake and transport characteristics of six PAEs compounds classified as priority pollutants by the United States Environmental Protection Agency (EPA) in the garlic cultivar Daqingke were investigated under hydroponic conditions. The results indicated that dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were the dominant PAEs species in garlic cloves of the different garlic varieties from Pizhou City. The average contents of DBP and DEHP in garlic cloves were 0.611 mg·kg-1 and 0.167 mg·kg-1, respectively, which were significantly higher than those of the commercial varieties of garlic. The concentrations of DBP and DEHP differed in three tissues of garlic bulbs, ordered as the skin of garlic bulb>skin of garlic clove>garlic clove. Dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), DBP, and DEHP were the main PAEs species and were detected in all the surface soils collected from Pizhou City. Compared with the soil allowable concentrations of the six PAEs in the United States, the DMP and DBP concentrations in approximately 100% and 63.2% of soil samples exceeded the recommended allowable concentrations set by the EPA. However, the levels of DEP, DIBP, and DEHP in the soils were below the maximum allowable concentrations set by the EPA. Nevertheless, the average content of DEHP in soils was 486 μg·kg-1 and was found to be much higher than that in the other four PAEs. Six PAEs, including DMP, DEP, DIBP, DBP, butyl benzyl phthalate (BBP), and DEHP, were detected in all the agricultural film samples. Among them, the contents of DBP and DEHP in the agricultural films were the highest, accounting for 53.7%-63.2% of the total PAEs. The amount of PAEs present in the residual film was significantly lower than that in the new film, and all six PAEs were detected in garlic or soil samples, suggesting that agricultural film can be an important source of PAEs in garlic farming soils and garlic. Furthermore, the garlic plants absorbed DMP and DEP efficiently from the substrate and showed higher translocation factors (TFs) for DMP and DEP than those for DBP, BBP, DEHP, and di-n-octyl phthalate (DnOP), resulting in a higher accumulation of DMP and DEP in the over-ground parts of garlic. In contrast, DBP and BBP in roots of garlic displayed higher bioconcentration factors (57.4 and 81.5, respectively) compared to those of the other four PAEs, whereas the TFs of DBP and BBP were lower; this may have contributed to the high accumulation of DBP in garlic bulbs. The BCFs and TFs of DEHP and DnOP in garlic were relatively lower, but the DEHP had been detected in all garlic cloves, which may be a result of the higher DEHP contents in soils.

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.

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

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

M6A contributes to a pro-survival state in GC-2 cells by facilitating DNA damage repair: Novel perspectives on the mechanism underlying DEHP genotoxicity in male germ cells

Di(2-ethyl-hexyl) phthalate (DEHP), an environmental endocrine disruptor, can destroy the sperm genomic integrity and impairs spermatogenesis. N6-methyladenosine (m6A) is involved in the cellular effects of DEHP. However, the genotoxic effect of DEHP on spermatocytes and the possible role of m6A in this process remain unclear. This study demonstrated that m6A alleviates DEHP genotoxicity in GC-2 cells. In DEHP-treated mice, DNA double-strand breaks (DSBs) were induced in the testis and spermatocytes. To further explore the molecular mechanism of DEHP genotoxicity on spermatocytes, GC-2 cells were exposed to DEHP. DEHP produced distinct genotoxicity and caused DSBs, which led to the inhibition of DNA synthesis and cell cycle arrest. The DNA damage response (DDR) was initiated to repair the DSBs induced by environmentally relevant levels of DEHP (100 μM and 200 μM). During this process, METTL3 upregulated m6A, which facilitated the DDR via stabilizing the DNA damage repair factors (Rad51 and Xrcc5) mRNA to maintain the pro-survival state. Moreover, Mettl3 knockdown partially inhibited DDR. Interestingly, high-dose DEHP (400 μM and 600 μM) directly induced apoptosis rather than the pro-survival state. Altogether: METTL3-mediated m6A participates in maintaining the pro-survival state by upregulating DDR, providing guidance for mitigating the genotoxicity of environment-related level DEHP exposure.

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.

Benchmark dose in the presence of coexposure to melamine and diethylhexyl phthalate and urinary renal injury markers in pregnant women

Environmental exposures to mixtures of toxic chemicals have potential interaction effects that may lead to hazard index values exceeding one. However, current regulation levels, such as tolerable daily intake (TDI), are mostly based on experimental studies conducted with a single chemical compound. In this study, we assessed the relationships between melamine and di-(2-ethylhexyl) phthalate (DEHP) exposure and their coexposure with the early renal injury markers N-acetyl -D-glucosaminidase (NAG), albumin/creatinine ratio (ACR), and microalbuminuria in 1236 pregnant women. Various generalized linear models with interaction terms and Bayesian kernel machine regression models were used for the (co-)exposure response associations. We derived the benchmark dose (BMD) and the corresponding one-sided 95% confidence bound BMDL based on the estimated (covariate-adjusted) average daily intake of melamine and DEHP metabolites measured in spot urine of the women collected during the third trimester. Given a benchmark response of 0.1, the BMDL level of melamine (DEHP) exposure on NAG (ACR, microalbuminuria) was 2.67 (11.20, 4.45) μg/kg_bw/day, and it decreased to as low as 1.46 (3.83, 2.73) μg/kg_bw/day when considering coexposure to DEHP (melamine) up to the 90th percentile. Both the exposure threshold levels of melamine and DEHP for early renal injuries in pregnant women were several-fold to one order lower than the current recommended TDIs by the WHO and the US FDA and EPA and were even lower considering coexposure. Because of concurrent exposures in real-world environments, more stringent regulation levels are recommended in susceptible populations, such as pregnant women, due to potential synergistic mixture effects.

Sensitive detection of di-(2-ethylhexyl) phthalate using a liquid crystal-based aptasensor

ABSTRACT We report a di-(2-ethylhexyl) phthalate (DEHP) aptasensor based on liquid crystal (LC), 4-cyano-4′-pentylbiphenyl (5CB). This optical sensor is made up of an aptamer that interacts with DEHP and cetrimonium bromide (CTAB) at the aqueous/LCs interface. The cationic surfactants, CTAB, trigger the homeotropic state of 5CB and control its local anchoring depending on the extent to which they interact with the aptamers. When the aptamers are electrostatically attracted to CTAB, the orientation of 5CB is disturbed. The conformational changes of the aptamers contribute to a change in the ordering of 5CB from a tilted to homeotropic state due to the formation of the DEHP-aptamer complexes. The ordering of the LCs is influenced by the biomolecular interactions at the CTAB-filled aqueous/5CB interface. We analysed the orientational ordering of 5CB according to the DEHP concentrations. An orientational transition from homeotropic to tilted alignment was observed with decreasing DEHP concentration. We determined the detection limit to be approximately 0.651 pg/mL in phosphate-buffered saline. We interpreted the greyscale intensity data that measured the intensity of polarised light, which penetrated the LCs, to quantify the polarised image. Our results demonstrate the potential method for simply monitoring the DEHP levels in various environmental parameters.

Lactic acid bacteria alleviate di-(2-ethylhexyl) phthalate-induced liver and testis toxicity via their bio-binding capacity, antioxidant capacity and regulation of the gut microbiota

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticiser that, if absorbed into the human body, can cause various adverse effects including reproductive toxicity, liver toxicity and gut microbiota dysbiosis. So far, some studies have proved that the toxicity of DEHP can be reduced by using antioxidants. However, these candidates all show potential side effects and cannot prevent the accumulation of DEHP in the body, making them unable to be used as a daily dietary supplement to relieve the toxic effects of DEHP. Lactic acid bacteria (LAB) have antioxidant capacity and the ability to adsorb harmful substances. Herein, we investigated the protective effects of five strains of LAB, selected based on our in vitro assessments on antioxidant capacities or bio-binding capacities, against the adverse effects of DEHP exposure in rats. Our results showed that LAB strains with outstanding DEHP/MEHP binding capacities, Lactococcus lactis subsp. lactis CCFM1018 and Lactobacillus plantarum CCFM1019, possess the ability to facilitate the elimination of DEHP and its metabolite mono-(2-ethylhexyl) phthalate (MEHP) with the faeces, decrease DEHP and MEHP level in serum further. Meanwhile, DEHP-induced liver and testicular injuries were effectively alleviated by CCFM1018 and CCFM1019. In addition, CCFM1018 effectively alleviated the DEHP-induced oxidative stress with its strong antioxidant ability. Furthermore, both CCFM1018 and CCFM1019 modulated the gut microbiota, which in turn increased the concentrations of faecal propionate and butyrate and regulated the pathways related to host metabolism. Correlation analysis indicate that DEHP/MEHP bio-binding capacity of LAB plays a crucial role in protecting the body from DEHP exposure, and its antioxidant capacity and the ability to alleviate the gut microbiota dysbiosis are also involved in the alleviation of damage. Thus, LAB with powerful bio-binding capacity of DEHP and MEHP can be considered as a potential therapeutic dietary strategy against DEHP exposure.