Diisononyl Phthalate Research Articles

Simultaneous targeted and non-targeted analysis of plastic-related contaminants in e-waste impacted soil in Agbogbloshie, Ghana

An LC-MS based analytical method was developed and validated for the simultaneous targeted analysis and suspect screening of plastic-related contaminants in e-waste impacted soils. Satisfactory recoveries (97 ± 13 %) were achieved using ultrasound-assisted extraction for 14/15 of the targeted analytes (7 bisphenols and 8 plasticizers) in a range of agricultural and non-agricultural soils. The method was applied to 53 soil samples collected in May 2015 in the region of Agbogbloshie (Ghana) at e-waste facilities (incl. Dump, trade, and burn sites), neighboring non-agricultural (incl. upstream, downstream, and community) and agricultural fields, and at two control agricultural sites away from e-waste recycling facilities. Bisphenol A (BPA) and bis(2-ethylhexyl) phthalate (DEHP) were the two dominant contaminants in e-waste soil (with concentrations up to 48.7 and 184 μg g−1, respectively), especially at the trade site, where e-waste was sorted and dismantled. The non-targeted workflow was successfully applied to identify additional plastic-related contaminants previously unreported in e-waste impacted soils, including bis(2-propylheptyl) phthalate, diisononyl phthalate, trioctyl trimellitate, 4-dodecylbenzenesulfonic acid, perfluorooctanesulfonic acid, perfluorobutanesulfonic acid, diphenyl phosphate, and triethylene glycol monobutyl ether. The agricultural soils surrounding the e-waste sites were also contaminated by plastic-related chemicals (especially DEHP), highlighting the impact of e-waste activities on the surrounding agricultural system.

Legacy and Emerging Plasticizers and Stabilizers in PVC Floorings and Implications for Recycling.

Hazardous chemicals in building and construction plastics can lead to health risks due to indoor exposure and may contaminate recycled materials. We systematically sampled new polyvinyl chloride floorings on the Swiss market (n = 151). We performed elemental analysis by X-ray fluorescence, targeted and suspect gas chromatography-mass spectrometry analysis of ortho-phthalates and alternative plasticizers, and bioassay tests for cytotoxicity and oxidative stress, and endocrine, mutagenic, and genotoxic activities (for selected samples). Surprisingly, 16% of the samples contained regulated chemicals above 0.1 wt %, mainly lead and bis(2-ethylhexyl) phthalate (DEHP). Their presence is likely related to the use of recycled PVC in new flooring, highlighting that uncontrolled recycling can delay the phase-out of hazardous chemicals. Besides DEHP, 29% of the samples contained other ortho-phthalates (mainly diisononyl and diisodecyl phthalates, DiNP and DiDP) above 0.1 wt %, and 17% of the samples indicated a potential to cause biological effects. Considering some overlap between these groups, they together make up an additional 35% of the samples of potential concern. Moreover, both suspect screening and bioassay results indicate the presence of additional potentially hazardous substances. Overall, our study highlights the urgent need to accelerate the phase-out of hazardous substances, increase the transparency of chemical compositions in plastics to protect human and ecosystem health, and enable the transition to a safe and sustainable circular economy.

The impact of follicular fluid phthalate metabolites on the ovarian reserve and ovarian function in Indian women undergoing intracytoplasmic sperm injection

To investigate the adverse effects of phthalate-induced ovarian toxicity on the ovarian reserve and ovarian function. To assess whether the accumulation of higher levels of selected phthalate metabolites in the follicular fluid (FF) of Indian women undergoing intracytoplasmic sperm injection (ICSI) was associated with a decline in their antral follicle count (AFC) and/or serum antimüllerian hormone (AMH) levels, suggesting a negative impact on the ovarian reserve. To evaluate the effects of follicular phthalate metabolites on peak serum estradiol (E2) levels and the total number of oocytes and mature metaphase II (MII) stage oocytes retrieved to assess the impact of phthalate toxicity on ovarian function. A subanalysis of an ongoing prospective cohort study was conducted to examine the association between the levels of six phthalate metabolites, namely, mono-n-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-isononyl phthalate (MiNP), mono-isodecyl phthalate (MiDP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate, in the FF of Indian women undergoing ICSI and their ovarian reserve markers (AFC and serum AMH levels). To investigate the association of these follicular phthalate metabolite levels with the peak E2 levels and the total number of oocytes and number of MII stage oocytes retrieved. Invitro fertilization center in a referral hospital in India. A total of 245 consenting Indian women who had undergone oocyte retrieval between April 2017 and mid-March 2020 were included. Each woman contributed one FF sample to the study. This was screened for six phthalate metabolites. The samples were collected before the coronavirus disease 2019 pandemic. Using liquid chromatography-tandem mass spectrometry, the total levels of six phthalate metabolites were quantified in the FF of 245 women. Using linear regression models that were unadjusted and adjusted for maternal age and body mass index (BMI), we evaluated the association between the follicular metabolites in these women and their AFC, serum AMH levels, peak E2 levels, total number of oocytes, and MII stage oocytes. To evaluate the impact of phthalate-induced ovarian toxicity on the ovarian reserve and ovarian function in Indian women undergoing ICSI by studying their accumulated levels in their FF. For MiNP (a metabolite of di-isononyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MiNP, there was a significant trend in the decrease in mean AFC (P-trend = 0.023) and a suggestive trend in the decrease in mean serum AMH levels (P-trend = 0.077). For MiDP (a metabolite of di-isodecyl phthalate), in the unadjusted regression model, we found that with increasing quartiles of follicular MiDP, there was a significant trend in the decrease in mean serum AMH levels (P-trend = 0.045). For MBP (a metabolite of dibutyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MBP, there were significant trends in the decrease in the mean number of total oocytes retrieved (P-trend = 0.003), a decrease in the mean number of MII stage oocytes retrieved, (P-trend = 0.003) and a decrease in the mean peak E2 levels (P-trend = 0.016). Although we found that with increasing quartiles of follicular mono(2-ethyl-5-oxohexyl) phthalate there was a decrease in the mean number of total and MII stage oocytes retrieved and higher follicular MEP levels were negatively associated with the mean AFC and serum AMH levels, neither trend was statistically significant. We also found that although follicular MEP levels did not show an adverse impact on ovarian function, follicular mono(2-ethyl-5-hydroxyhexyl) phthalate levels did not show an adverse impact on both the ovarian reserve and function. In this study of 245 Indian women, higher accumulated FF levels of MiNP and MiDP were negatively associated with AFC and serum AMH levels, suggesting an adverse effect on the ovarian reserve. Higher accumulated FF levels of MBP were negatively associated with the total number of oocytes, MII stage oocytes, and peak E2 values, suggesting a negative impact on ovarian function. Although we found that phthalate-induced ovarian toxicity was statistically significant for selected phthalate metabolites, the role of the cumulative effect of multiple phthalates in the ovarian microenvironment cannot be ruled out and needs to be investigated further.

Prevention of surface defects in calendered poly(vinyl chloride) sheets using a succinate‐capped poly(caprolactone) additive

AbstractSurface defects known as “gas checks” often mar the surfaces of poly(vinyl chloride) (PVC) calendered films. These defects are typically prevented through changes in the calender operating parameters, a costly exercise which also limits the sheet thickness and the production rate. Adding a low concentration of poly(caprolactone) (PCL)‐based star‐shaped compound can eliminate gas check defects in PVC calendering. The effects of a triheptylsuccinate‐terminated PCL with a PCL triol core and number average molecular weight of 540 g/mol (i.e., PCL540‐[(succ)‐C7]3) has been investigated on the material, thermal, and processing properties of PVC blends containing diisononyl phthalate (DINP) as a primary plasticizer and PCL540‐[(succ)‐C7]3 in low quantities (i.e., 0, 5, or 10 parts per hundred rubber (phr)) as a secondary plasticizer and processing aid. The most significant differences between PVC blends containing PCL540‐[(succ)‐C7]3 and those without are in the rheological properties of the PVC blends at higher temperatures and lower angular frequencies. Under these conditions, PVC blends containing 10 phr of PCL540‐[(succ)‐C7]3 have a complex viscosity nearly three times higher than those containing only DINP. PVC/PCL540‐[(succ)‐C7]3 blends had comparable tensile properties to those containing only DINP, with no significant change in maximum elongation and a small but significant increase of 28% in maximum stress. The addition of PCL540‐[(succ)‐C7]3 made it possible to produce calendered films without gas checks that were twice as thick as those produced in its absence. In addition to reduced wastage of marred films, the increased calender operating range for PVC films containing PCL540‐[(succ)‐C7]3 has the potential to significantly reduce energy costs for the calendering of thick PVC films.

Comprehensive survey on the use of plastic additives in toy products used in Japan.

Plastic additives have adverse effects on human health. Children frequently use toys that contain various substances found in paints, plasticizers, and other materials, which heighten the risk of specific chemical exposure. Infants are particularly prone to chemical exposure through the "mouthing" behavior because of the possibility of placing toys in their mouths. Thus, this vulnerability should be considered during risk assessments of chemical exposure. This study performed a comprehensive analysis of the chemical components in various 84 plastic toys including "designated toys" (toys that may be harmful to infant health if in contact with their mouths: Article 78 of the Enforcement Regulations of the Food Sanitation Law by the Minister of Health, Labor and Welfare) such as dolls, balls, blocks, bathing toys, toy vehicles, pacifiers, and household items, purchased in the Japanese market by nontargeted and targeted analysis. Plasticizers, flame retardants, and fragrances were the main compounds in almost all the toy products. The results showed that plastic products made in China tended to contain high levels of phthalate esters. In particular, hazardous plasticizers, such as diisodecyl, di-n-octyl, and diisononyl phthalates were detected above the regulatory limit (0.1%) in used products manufactured before regulations were passed in Japan. Furthermore, we detected alternative plasticizers, such as acetyl tributyl citrate (ATBC; 52%), diisononyl adipate (DINA; 50%), and di(2-ethylhexyl) terephthalate (DEHT; 40%). ATBC was detected at high concentrations in numerous toy products. Thus, infants with free access to indoor plastic toys might be exposed to these chemicals. This study observed that the chemical profiles of toy products were dependent on the year of manufacture. Furthermore, the detection of currently regulated plasticizers in secondhand products manufactured before regulations were enforced, along with the increasing trend of using alternative substances to regulated phthalate esters in products, suggests the potential exposure of infants to these plasticizers through the use of toys. Therefore, regular fact-finding surveys should continue to be conducted for the risk assessment and safety management of domestic toy products.

Characterizing Chemical Exposure Trends from NHANES Urinary Biomonitoring Data.

Xenobiotic metabolites are widely present in human urine and can indicate recent exposure to environmental chemicals. Proper inference of which chemicals contribute to these metabolites can inform human exposure and risk. Furthermore, longitudinal biomonitoring studies provide insight into how chemical exposures change over time. We constructed an exposure landscape for as many human-exposure relevant chemicals over as large a time span as possible to characterize exposure trends across demographic groups and chemical types. We analyzed urine data of nine 2-y cohorts (1999-2016) from the National Health and Nutrition Examination Survey (NHANES). Chemical daily intake rates (in milligrams per kilogram bodyweight per day) were inferred, using the R package bayesmarker, from metabolite concentrations in each cohort individually to identify exposure trends. Trends for metabolites and parents were clustered to find chemicals with similar exposure patterns. Exposure variation by age, gender, and body mass index were also assessed. Intake rates for 179 parent chemicals were inferred from 151 metabolites (96 measured in five or more cohorts). Seventeen metabolites and 44 parent chemicals exhibited fold-changes between any two cohorts (deltamethrin, di--octyl phthalate, and di-isononyl phthalate had the greatest exposure increases). Di-2-ethylhexyl phthalate intake began decreasing in 2007, whereas both di-isobutyl and di-isononyl phthalate began increasing shortly before. Intake for four parabens was markedly higher in females, especially reproductive-age females, compared with males and children. Cadmium and arsenobetaine exhibited higher exposure for individuals years of age and lower for individuals years of age. With appropriate analysis, NHANES indicates trends in chemical exposures over the past two decades. Decreases in exposure are observable as the result of regulatory action, with some being accompanied by increases in replacement chemicals. Age- and gender-specific variations in exposure were observed for multiple chemicals. Continued estimation of demographic-specific exposures is needed to both monitor and identify potential vulnerable populations. https://doi.org/10.1289/EHP12188.

Using targeted fetal rat testis genomic and endocrine alterations to predict the effects of a phthalate mixture on the male reproductive tract

Administration of phthalates in utero disrupts gene expression and hormone levels in the fetal rat testis, which are key events in an Adverse Outcome Pathway (AOP) for the Phthalate Syndrome. These measures can be used to predict the postnatal adverse effects of phthalate esters (PEs) on male rat sexual differentiation. Here, pregnant rats were exposed to dibutyl (DBP)- and diisononyl (DINP) phthalate on gestational days 14 to 18 individually and as a mixture (DBP,250 mg/kg/d; DINP, 750 mg/kg/d; and DBP 250 mg/kg/d plus DINP 750 mg/kg/d). We found that each PE reduced testosterone production (T Prod) and related gene transcripts by about 50 % and that they acted in a dose additive manner, reducing T Prod and gene expression by 75 % as a mixture. Based upon effects on T Prod, DINP was 0.33 times as potent as DBP and thus the DBP + DINP mixture was predicted to be equivalent to 500 mg DBP/kg/d.Logistic regression models of T Prod predicted that the adverse effects of the DBP + DINP mixture group versus the DBP and DINP individual treatments would reduce anogenital distance (AGD) by 27 % versus 10 %, increase hypospadias in 18 % versus < 1 %, induce epididymal agenesis in 46 % versus 10 %, and increase areolae/nipples in 4.8 % versus < 0.1 % of the, respectively. These predictions were highly consistent with effects from previously published dose response studies on the male reproductive effects of DBP. In summary, these results support the use of this New Approach Method to predict the detrimental effects of PEs and PE mixtures, replacing or reducing the need to run long-term, resource and animal use intensive extended one-generation reproduction studies for this class of chemicals.

The IL-31/TRPV1 pathway mediates allergic asthma exacerbated by DINP dermal exposure in OVA-sensitized Balb/c mice

BackgroundThe potential role of dermal exposure diisononyl phthalate (DINP) as an adjuvant in allergic inflammation and asthma has been suggested. However, the current findings do not provide enough evidence to support this claim. ObjectivesThe purpose of this investigation was to examine the impact and mechanisms of allergic asthma exacerbation through the dermal exposure to DINP. MethodsThe study was undertaken using OVA-sensitized mice. Lung histopathology and airway hyperreactivity (AHR) were assessed. Expression levels of immunoglobulins (t-IgE, OVA-IgE and OVA-IgG1), cytokines (IL-31, IL-4, IL-5, IL-6, IL-13 and INF-γ), and TRPV1 were measured. To investigate the mechanism by which allergic asthma worsens due to dermal exposure to DINP, the blockade analysis using the IL-31 antagonist SB-431542 and the TRPV1 antagonist capsazepine (CZP) were performed. ResultsThe findings of the study revealed that the simultaneous exposure to DINP and OVA resulted in an increase in inspiratory resistance (Ri) and expiratory resistance (Re), a decrease in the minimum value of lung dynamic compliance (Cldyn), and worsened airway remodeling. Additionally, it was found that this exposure led to an increase in the levels of IL-31 and TRPV1, which are biomarkers of Th2 cytokines (IL-4, IL-5, IL-6, and IL-13), as well as immunoglobulins (Total IgE, OVA-lgE, and OVA-IgG1), while decreasing the biomarker of Th1 cytokines (IFN-γ). However, these impairments showed improvement after the administration of SB-431542 or CZP. ConclusionThe findings of this research indicate that the IL-31/TRPV1 pathway plays a moderating function in OVA-induced allergic asthma worsened by dermal exposure to DINP.

Presence of Phthalates in Vacuum Packaged Kashar Cheeses Sold Retails in Türkiye

Phthalate esters (PAEs) are synthetic compounds, commonly used as plasticizers and softeners in plastic material production, and they are recognized as endocrine-disrupting chemicals. This study was focused on monitoring the extent of PAEs migration in vacuum-packaged Kashar cheeses and plastic materials used in their packaging. A total of fifteen cheese samples were tested for PAEs, including benzyl butyl phthalate (BBP), dibutyl phthalate (DBP), diisononyl phthalate (DiNP), di-2-ethylhexyl phthalate (DEHP), and diisodecyl phthalate (DiDP). The quantification (LOQ) and detection (LOD) limits varied between 0.197 to 0.619 µg/mL and 0.059 to 0.185 µg/mL for all analytes, respectively. All phthalate ester concentrations in both of the cheese samples and their packaging materials were below the detectable level LOQ of the analytical method. FTIR spectra also confirmed that the packaging materials which consisted of polypropylene and polyethylene.

Phthalate contamination in marine mammals off the Norwegian coast

Phthalates are used in plastics, found throughout the marine environment and have the potential to cause adverse health effects. In the present study, we quantified blubber concentrations of 11 phthalates in 16 samples from stranded and/or free-living marine mammals from the Norwegian coast: the killer whale (Orcinus orca), sperm whale (Physeter macrocephalus), long-finned pilot whale (Globicephala melas), white-beaked dolphin (Lagenorhynchus albirostris), harbour porpoise (Phocoena phocoena), and harbour seal (Phoca vitulina). Five compounds were detected across all samples: benzyl butyl phthalate (BBP; in 50 % of samples), bis(2-ethylhexyl) phthalate (DEHP; 33 %), diisononyl phthalate (DiNP; 33 %), diisobutyl phthalate (DiBP; 19 %), and dioctyl phthalate (DOP; 13 %). Overall, the most contaminated individual was the white-beaked dolphin, whilst the lowest concentrations were measured in the killer whale, sperm whale and long-finned pilot whale. We found no phthalates in the neonate killer whale. The present study is important for future monitoring and management of these toxic compounds.

Evaluating the risk of phthalate and non-phthalate plasticizers in dust samples from 100 Japanese houses

Phthalates are widely used as plasticizer and associated with various health issues. Recently, non-phthalate plasticizers are replacing phthalates; however, the exposure to these substances and the risk in Japan is unclear. In this study, we assessed the concentrations of phthalates, non-phthalate plasticizers, and phthalate degradation products in house dust and determined their respective exposure risks via oral and dermal routes. Twelve phthalates, seven non-phthalate plasticizers, and two degradation products were determined in the house dust obtained from 100 Japanese homes. The median concentration of di(2-ethylhexyl) phthalate (DEHP), accounting for 85 % of the total concentration of phthalates and non-phthalate plasticizers detected in this study, was 2.1 × 103 μg/g of dust. Apart from DEHP, diisononyl phthalate (DINP) and di(2-ethylhexyl) terephthalate (DEHT) were the most abundant in the house dust, accounting for 6.2 % (median: 1.7 × 102 μg/g of dust) and 6.1 % (median: 1.7 × 102 μg/g of dust) of the total concentrations, respectively. DEHP and DEHT concentrations in house dust were higher in apartment and small houses (floor area: ≤30 m2 or 31–60 m2 for DEHP and 31–60 m2 for DEHT) than in detached and large houses (floor area: ≥121 m2). Conversely, di-n-butyl phthalate (DnBP) concentrations were significantly higher in detached and large houses (floor area: ≥121 m2) than in apartment and small houses (floor area: ≤30 m2). The total hazard quotient (HQ), using the maximum concentration in house dust, revealed that oral and dermal exposure to house dust was 1.3 × 10-6–0.11 for adults (all substances) and 1.6 × 10-5–2.2 × 10-2 for preschool children (except for DnBP and DEHP), suggesting no risk. The HQs for DnBP and DEHP exposure via house dust for preschool children using the maximum values were 0.46 and 1.2, and 6.0 × 10-3 and 0.18 using the median values, indicating that risk of DEHP exposure should be exhaustively determined by considering other exposure routes that were not evaluated in this study, such as diet.

Human Health Risk Assessment of Phthalate Esters and Antimony Levels in Beverages Packaged in Polyethylene Terephthalate under Different Storage Conditions

The main objective of this study was to examine how common storage conditions affect the migration of phthalate esters (PAEs) and antimony (Sb) from polyethylene terephthalate (PET) bottles into bottled drinks. The drinks were collected from local supermarkets in Turkey, including different types such as bottled drinking water (DW), mineral water (MW), cola (C), orange flavored carbonated drink (OFCD), fermented turnip drink (FTD), and lemonade (L). Additionally, a deterministic model was utilized to evaluate the potential risk to human health associated with this migration process. The performance and optimization of the LC-MS/MS and ICP-MS instruments for the analysis of PAEs and Sb were also evaluated. The limits of detection (LODs) for PAEs and Sb ranged from 0.004 to 1.88ng/mL, while the limits of quantification (LOQs) ranged from 0.013 to 6.27ng/mL. The analysis results revealed the presence of PAEs at varying concentrations. Di-isodecyl phthalate (DIDP) and di-isononyl phthalate (DINP) exhibited the highest level of migration to drink samples. The type of beverage also affected the migration of PAEs and Sb. The highest migration levels were detected in MWs. Storage temperature (4 °C, 25 °C, and 40 °C) and storage duration (365 days) had an impact on the release of PAEs and Sb into beverages from PET bottles. The Hazard Quotients (HQs) calculated for PAEs and Sb were significantly lower than 1 in all scenarios, indicating that no adverse health effects are anticipated due to exposure to PAEs and Sb through beverage consumption.

DEHP and DINP accelerate aging effects in male and female of Drosophila melanogaster depend on AKT/FOXO pathway

Phthalates are commonly used as plasticizers. Numerous studies have focused on endocrine, reproductive, and developmental toxicity of phthalates exposure to male organisms. In recent years, some studies looking into the aging effects of phthalates exposure in D. melanogaster showed discrepant results. In this study, we compared the different concentrations of Di(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP) for acute and chronic treatment for different gender D. melanogaster and explored the potential mechanism of DEHP and DINP exposure. The results showed that acute exposure to DEHP or DINP at a high dose significantly decreased the lifespan of female and male D. melanogaster under HFD stress. Chronic exposure significantly decreased the lifespan of flies in all exposure groups except for the low-dose DINP exposure female group. Among them, in the normal feeding group, we found that female flies seemed to be more resistant to DEHP or DINP exposure. Meanwhile, the locomotion ability and fertility of flies exhibited a dose-dependent decline. Furthermore, phthalates did not significantly reduce the lifespan or health status of akt and foxo mutant flies in the mutant fly assays, and real-time quantitative-PCR (q-PCR) data revealed akt and foxo significant change with 10 μM DEHP or DINP treatment. This suggests that akt and foxo played a role in the process by which DEHP and DINP caused age-related declines in D. melanogaster.

DDIT4 is essential for DINP-induced autophagy of ovarian granulosa cells

As one of the most important phthalates, di-isononyl phthalate (DINP) has been widely used as a common plasticizer in the food and personal care products sectors. In our previous study, we found that DINP can induce autophagy of ovarian granulosa cells; while the underlying mechanism is unclear. In the study, we showed that DINP exposure could induce autophagy of ovarian granulosa cells and KGN cells, accompanied with the increase in the mRNA and protein level of DDIT4. Furthermore, overexpression of DDIT4 were shown to induce autophagy of KGN cells; while knockdown of DDIT4 inhibited DINP-induced autophagy, implying that DDIT4 played an important role in DINP-induced autophagy of ovarian granulosa cells. There were three putative binding sites of transcription factor ATF4 in the promoter region of DDIT4 gene, suggesting that DDIT4 might be regulated by ATF4. Herein, we found that overexpression of ATF4 could upregulate the expression of DDIT4 in KGN cells, while knockdown of ATF4 inhibited its expression. Subsequently, ATF4 was identified to bind to the promoter region of DDIT4 gene and promote its transcription. The expression of ATF4 was also increased in the DINP-exposed granulosa cells, and ATF4 overexpression promoted autophagy of KGN cells; whereas knockdown of ATF4 alleviated DINP-induced upregulation of DDIT4 and autophagy of the cells. Taken together, DINP triggered autophagy of ovarian granulosa cells through activating ATF4/DDIT4 signals.

HBM4EU e-waste study: Occupational exposure of electronic waste workers to phthalates and DINCH in Europe

Workers involved in the processing of electronic waste (e-waste) are potentially exposed to toxic chemicals, including phthalates and alternative plasticizers (APs). Dismantling and shredding of e-waste may lead to the production of dust that contains these plasticizers. The aim of this study, which was part of the European Human Biomonitoring Initiative (HBM4EU), was to assess the exposure to phthalates (e.g. di-(2-ethylhexyl) phthalate (DEHP), diethyl phthalate (DEP), di-butyl phthalate (DBP), butyl-benzyl phthalate (BBzP), di-isononyl phthalate (DiNP), di-isodecyl phthalate (DiDP) and cyclohexane-1,2-dicarboxylic di-isononyl ester (DINCH) in e-waste workers from ten European companies. This was achieved by (i) analysing urine samples from 106 e-waste workers collected at the beginning and at the end of the work week, (ii) comparing these with urine samples from 63 non-occupationally exposed controls, and (iii) analysing settled floor dust collected in e-waste premises. Significantly higher urinary concentrations of seven out of thirteen phthalates and DINCH metabolites were found in the e-waste workers compared to the control population. However, no significant differences were found between pre- and post-shift concentrations in the e-waste workers. Concentrations of DBP, DEHP and DiDP in dust were weakly to moderately positively correlated with their corresponding urinary metabolite concentrations in the e-waste workers (Spearman's ρ = 0.4, 0.3 and 0.2, respectively). Additionally, significantly lower urinary concentrations of nine phthalates and DINCH metabolites were found in e-waste workers using respiratory protective equipment (RPE) during their work activities, reflecting the potential benefits of RPE to prevent occupational exposure to phthalates and DINCH. The estimated daily intake (EDI) values obtained in this study were lower than the corresponding tolerable daily intake (TDI) adopted by the European Food Safety Authority (EFSA) for the general population, suggesting that the risk for negative health consequences in this population of e-waste workers from exposure to phthalates and DINCH is expected to be low. This was confirmed by the urinary metabolite concentrations of all workers being lower than the HBM4EU guidance values derived for the occupational exposed and general population. This study is one of the first to address the occupational exposure to phthalates and DINCH in Europe in e-waste dismantling workers, combining a human biomonitoring approach with analysis of settled indoor dust.

Longitudinal Associations between Prenatal Exposure to Phthalates and Steroid Hormones in Maternal Hair Samples from the SEPAGES Cohort.

We assessed phthalate-hormone associations in 382 pregnant women of the new-generation SEPAGES cohort (2014-2017, France) using improved exposure and outcome assessments. Metabolites from seven phthalate compounds and the replacement di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) were measured in within-subject pools of repeated urine samples collected at the second and third pregnancy trimesters (≈21 samples/trimester). Metabolites from five steroid hormones were measured in maternal hair samples collected at delivery, reflecting cumulative levels over the previous weeks to months. Adjusted linear regression and Bayesian weighted quantile sum (BWQS) mixture models were performed. Each doubling in third-trimester urinary mono-benzyl phthalate (MBzP) concentrations was associated with an average increase of 13.3% (95% CI: 2.65, 24.9) for ∑cortisol, 10.0% (95% CI: 0.26, 20.7) for ∑cortisone, 17.3% (95% CI: 1.67, 35.4) for 11-dehydrocorticosterone, and 16.2% (95% CI: 2.20, 32.1) for testosterone, together with a suggestive 10.5% (95% CI: -1.57, 24.1) increase in progesterone levels. Each doubling in second-trimester urinary di-isononyl phthalate (DiNP) concentrations was inversely associated with testosterone levels (-11.6%; 95% CI: -21.6, -0.31). For most hormones, a nonsignificant trend toward a positive phthalate mixture effect was observed in the third but not in the second trimester. Our study showed that exposure to some phthalate metabolites, especially MBzP, may affect adrenal and reproductive hormone levels during pregnancy.

Comparative analysis of diisononyl phthalate and di(isononyl)cyclohexane-1,2 dicarboxylate plasticizers in regulation of lipid metabolism in 3T3-L1 cells.

Diisononyl phthalate (DINP) and di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) are plasticizers introduced to replace previously used phthalate plasticizers in polymeric products. Exposure to DINP and DINCH has been shown to impact lipid metabolism. However, there are limited studies that address the mechanisms of toxicity of these two plasticizers. Here, a comparative toxicity analysis has been performed to evaluate the impacts of DINP and DINCH on 3T3-L1 cells. The preadipocyte 3T3-L1 cells were exposed to 1, 10, and 100 μM of DINP or DINCH for 10 days and assessed for lipid accumulation, gene expression, and protein analysis. Lipid staining showed that higher concentrations of DINP and DINCH can induce adipogenesis. The gene expression analysis demonstrated that both DINP and DINCH could alter the expression of lipid-related genes involved in adipogenesis. DINP and DINCH upregulated Pparγ, Pparα, C/EBPα Fabp4, and Fabp5, while both compounds significantly downregulated Fasn and Gata2. Protein analysis showed that both DINP and DINCH repressed the expression of FASN. Additionally, we analyzed an independent transcriptome dataset encompassing temporal data on lipid differentiation within 3T3-L1 cells. Subsequently, we derived a gene set that accurately portrays significant pathways involved in lipid differentiation, which we subsequently subjected to experimental validation through quantitative polymerase chain reaction. In addition, we extended our analysis to encompass a thorough assessment of the expression profiles of this identical gene set across 40 discrete transcriptome datasets that have linked to diverse pathological conditions to foreseen any potential association with DINP and DINCH exposure. Comparative analysis indicated that DINP could be more effective in regulating lipid metabolism.

Unveiling the Nexus the link between water quality index and phthalic acid ester concentrations in Tigris River

Monitoring water quality in an aquatic system is a crucial objective in pursuing sustainable development, despite the challenges posed by water scarcity and the impact of climate change. The objective of the present study was to examine the water quality of the Tigris River along its course from the point of entry into Baghdad city to its exit, particularly in the presence of Phthalic Acid Esters (PAEs). In both dry and wet seasons and from five sites of the river, nine environmental factors (Turbidity, Total dissolved solids, pH, dissolved oxygen, Chloride, nitrate, phosphate, sulfate, and Biological oxygen demand) and three PAEs (di-n-butyl phthalate (DBP), di-isononyl phthalate (DiNP), and di-2-ethyl hexyl phthalate (DEHP)) were investigated. Results revealed that the river has high levels of turbidity and Total dissolved solids, slightly alkaline, and well-aerated (dissolved oxygen >7 mg/L). Chloride, nitrate, phosphate, and sulfate values varied between seasons, as high values were recorded in the wet season. Biochemical oxygen demand levels were higher during the dry season. The highest value of total PAEs (2.20 μg/L) was observed during the dry season, and the lowest value was in the wet season (1.16 μg/L). The HQ results revealed that the river was ranked as a moderate risk area. However the water quality index and environmental risk index classified the water quality as a poor category, with a high-risk score in the study sites within Baghdad city. Therefore, despite the acceptable limit of PAEs in the river's water (<3 μg/L), its presence is an early alarm to withdraw attention to its environmental risk. These findings highlight the need for appropriate measures to control and remove pollutants to ensure a safe and healthy water supply in the Tigris River.

Accurate determination of 11 representative phthalates and di(2-ethylhexyl) terephthalate in polyvinyl chloride using isotope dilution-gas chromatography/mass spectrometry

Phthalates are mainly used as plasticizers in polyvinyl chloride (PVC). However, prolonged exposure to phthalates poses considerable risks to human health. Consequently, the utilization of phthalates in consumer products is subject to regulations, with a defined threshold of 0.1 %. In this study, we developed an accurate and simultaneous method for determination of 11 representative phthalates and a non-phthalate plasticizer (di(2-ethylhexyl) terephthalate, DEHT) in PVC as a higher-order reference method. Homogeneously prepared PVC samples, each containing approximately 0.1 % of the target plasticizer compounds, were analyzed using gas chromatography-mass spectrometry (GC–MS) with deuterium-labeled phthalates and DEHT. The developed method could effectively separate and quantify all target plasticizers without interference with each other and potential overlap between the isomeric forms of phthalates, di-isodecyl phthalate, and di-isononyl phthalate. The developed method has high-order metrological quality, exhibiting exceptional selectivity, accuracy, repeatability (≤ 2.17 %), reproducibility (≤ 2.16 %), and relative expanded uncertainty (≤ 5.6 %). This analytical method is thus suitable for accurately assessing the target plasticizer levels in PVC products for ensuring compliance with the established 0.1 % threshold. This method was successfully applied to quantify twelve distinct plasticizers in PVC products obtained from the Korean market, validating its effectiveness and reliability in real-world scenarios.

The effects of short-term and long-term phthalate exposures on ovarian follicle growth dynamics and hormone levels in female mice†.

Di(2-ethylhexyl) phthalate and diisononyl phthalate are widely used as plasticizers in polyvinyl chloride products. Short-term exposures to phthalates affect hormone levels, ovarian follicle populations, and ovarian gene expression. However, limited data exist regarding the effects of long-term exposure to phthalates on reproductive functions. Thus, this study tested the hypothesis that short-term and long-term exposure to di(2-ethylhexyl) phthalate or diisononyl phthalate disrupts follicle dynamics, ovarian and pituitary gene expression, and hormone levels in female mice. Adult CD-1 female mice were exposed to vehicle, di(2-ethylhexyl) phthalate, or diisononyl phthalate (0.15ppm, 1.5ppm, or 1500ppm) via the chow for 1 or 6months. Short-term exposure to di(2-ethylhexyl) phthalate (0.15ppm) and diisononyl phthalate (1.5ppm) decreased serum follicle-stimulating hormone levels compared to control. Long-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate (1500 ppm) increased the percentage of primordial follicles and decreased the percentages of preantral and antral follicles compared to control. Both phthalates increased follicle-stimulating hormone levels (di(2-ethylhexyl) phthalate at 1500ppm; diisononyl phthalate at 1.5ppm) and decreased luteinizing hormone levels (di(2-ethylhexyl) phthalate at 0.15 and 1.5ppm; diisononyl phthalate at 1.5ppm and 1500ppm) compared to control. Furthermore, both phthalates altered the expression of pituitary gonadotropin subunit genes (Cga, Fshb, and Lhb) and a transcription factor (Nr5a1) that regulates gonadotropin synthesis. These data indicate that long-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate alters follicle growth dynamics in the ovary and the expression of gonadotropin subunit genes in the pituitary and consequently luteinizing hormone and follicle-stimulating hormone synthesis.