Di(isononyl)cyclohexane-1,2-dicarboxylate Research Articles

Addressing Data Gaps in Toxicity of Food Additive Chemicals using High-throughput Screening Technology

Background: More than 8,000 chemical additives are permitted in food in the United States, however, most lack adequate health and safety information. High-throughput screening tools, such as Toxicity Forecaster (ToxCast), provide opportunities to quickly assess and prioritize thousands of food additives for further investigation. Given the significant lack of in vivo data for most chemicals, we aimed to characterize the toxicity data available for chemical food additives using ToxCast.Methods: We developed an up-to-date inventory of chemical food additives utilizing information from the U.S. Food and Drug Administration, the Environmental Protection Agency, and private manufacturers. We quantified the number of chemicals with ToxCast data available, and conducted a preliminary analysis of toxicity data for selected phthalates and phthalate alternatives (di(2-ethylhexyl) phthalate (DEHP), diisononyl cyclohexane-1,2-dicarboxylate (DINCH), N,N-Diethylhydroxylamine (DEHA), and bis (2-ethylhexyl) terephthalate (DEHT)).Results: Our updated inventory indicates that there are more than 9,000 chemicals allowed in contact with food, including direct and indirect additives, food packaging chemicals, pesticide residues, and substances generally recognized as safe. Preliminary analyses suggest that approximately 23% of these have ToxCast data available. Comparing bioassay data in ToxCast for selected phthalates and phthalate alternatives, we found DEHP to be the most toxic chemical, with 40 active endpoints related to cell morphology, DNA binding, and nuclear receptors. DEHT had seven bioactive endpoints, followed by DINCH and DEHA each with 3 active endpoints. DEHA was the only plasticizer with no bioactivity for nuclear receptor assays, one important biological pathway for toxicity in humans.Conclusions: ToxCast may be a useful tool for characterizing the toxicity of chemical food additives. Future analyses will focus on more diverse biological endpoints and compare ToxCast results to available in vivo data. These analyses will help advance understanding on the appropriateness of ToxCast for regulatory decision-making.

Sorption of Benzene, Toluene, and Ethylbenzene by Poly(ethyl methacrylate) and Plasticized Poly(ethyl methacrylate) at 298.15 K Using a Quartz Crystal Microbalance

Solubilities of benzene, toluene, and ethylbenzene (BTEX compounds, together with xylene) in poly(ethyl methacrylate) (PEMA) and plasticized PEMA at 298.15 K were measured using a quartz crystal microbalance and are reported in the form of solvent activity versus solvent weight fraction. Two plasticizers, diisononyl cyclohexane-1,2-dicarboxylate (DINCH) and diisooctyl azelate (DIOA), were studied, each at three different concentration levels in the polymer. The presence of a plasticizer increases the solubility of all three compounds. Data were interpreted using a pseudobinary Flory–Huggins model in which the plasticized polymer is considered to be a single pseudocomponent.

Between- and within-individual variability of urinary phthalate and alternative plasticizer metabolites in spot, morning void and 24-h pooled urine samples

Due to international regulations, commonly used phthalates such as di(2-ethylhexyl) phthalate (DEHP) are being replaced by other phthalates, such as di-isononyl phthalate (DINP), and di-isodecyl phthalate (DIDP) and by alternative plasticizers (APs) with similar chemical characteristics, like di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), or di-(2-ethylhexyl) adipate (DEHA). Urinary concentrations of metabolites are frequently used in the exposure assessment of non-persistent chemicals and for biomonitoring purposes, the intra- and inter-day variability of the metabolites should be known. However, the short-term variability of AP and several phthalate biomarkers has not been investigated yet. In this study, we collected all spot samples from 10 healthy adults for 5 consecutive days and 24h pooled urine on one additional day to investigate the short-term variability of 22 biomarkers of phthalates and APs. Metabolites of DEP, DEHP, DiBP, DnBP, DBzP, DINP and DIDP were found in high detection frequencies, while metabolites of most APs were found in approximately 50% of the samples. The short-term reproducibility of metabolites with diet as primary source (DEHP, DINP, DIDP) was poor (intraclass correlation coefficient – ICC < 0.4), whereas biomarkers of DEP, DnBP, DiBP and BBzP showed good consistency, most likely due to more continuous sources resulting in less between-day variance. ICC values of AP metabolites were similar to those of DEHP, but more studies are required to confirm these findings. Overall, reproducibility improved considerably when values were corrected for urinary dilution and when only morning voids samples were considered. Levels in morning voids samples were consistent for 5 days and comparable to 24-h pooled urine for all metabolites except for OH-MEHTP, sum DINP and sum DIDP, which supports the use of morning voids in human biomonitoring studies.

Biomonitoring of emerging DINCH metabolites in pregnant women in charleston, SC: 2011–2014

Due to the mounting evidence that phthalates, specifically di-2-ethylhexyl phthalate and dibutyl phthalate, produce adverse endocrine effects in humans and wildlife, the use of other chemicals as replacements has increased. One of the most commonly encountered phthalate replacements is di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH). Currently, little is known about the prevalence of human exposure, bioactivity, and endocrine disrupting potential of DINCH. We sampled urine from 100 pregnant women during the second trimester of pregnancy living in Charleston, SC between 2011 and 2014 and measured the following DINCH metabolites by LC-MS/MS: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (OH-MINCH), cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester (oxo-MINCH), and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (cx-MINCH). These metabolites were also tested on human estrogen receptor alpha and progesterone receptor beta transactivation assays in vitro. OH-MINCH was detected in 98% of urine samples. The specific gravity-adjusted median (interquartile range) OH-MINCH concentration was 0.20 (0.25) ng/mL, and concentrations were significantly higher in African American women compared to Caucasian women (p = 0.01). DINCH metabolite concentrations were consistent between years, and they did not exhibit estrogenic or progestogenic activity in vitro. Human exposure to these emerging compounds should continue to be monitored, especially in vulnerable populations, to ensure the replacement of phthalates by DINCH is not a case of regrettable substitution.

Temporal Trends of Exposure to Phthalates and Phthalate Alternatives in California Pregnant Women during 2007–2013: Comparison with Other Populations

Phthalates with potential adverse health effects are being replaced by other phthalates or phthalate alternatives. Little is known about temporal trends of phthalate exposure in pregnant women in the United States. We quantified 16 metabolites of eight phthalates and di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) in 656 urine samples collected from 192 California pregnant women in 2007-2013 during their second and third trimesters of pregnancy who participated in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. We used multiple regression to estimate least squares geometric means of phthalate biomarker concentrations and annual percent changes over the study period. Biomarker concentrations of diethyl phthalate (DEP) and three phthalates with known toxicity and adverse health effects (i.e., butyl benzyl phthalate [BBzP], dibutyl phthalate [DBP], di(2-ethylhexyl) phthalate [DEHP]) decreased, while those of di-isobutyl phthalate [DiBP], di-isononyl phthalate [DiNP], and di-n-octyl phthalate [DOP] increased in California pregnant women during our study period. To understand broad social forces that may influence temporal trends and geographic variations in phthalate exposure across countries, we compared our phthalate biomarker concentrations with those of other populations. We observed over a factor of 2 differences in exposure across countries for some phthalate biomarkers and between pregnant and nonpregnant women for DEP.

Exposure to organophosphate esters, phthalates, and alternative plasticizers in association with uterine fibroids

Exposure to endocrine disrupting chemicals is suggested to be responsible for the development or progression of uterine fibroids. However, little is known about risks related to emerging chemicals, such as organophosphate esters (OPEs) and alternative plasticizers (APs). A case-control study was conducted to investigate whether exposures to OPEs, APs, and phthalates, were associated with uterine fibroids in women of reproductive age. For this purpose, the cases (n = 32) and the matching controls (n = 79) were chosen based on the results of gynecologic ultrasonography among premenopausal adult women in Korea and measured for metabolites of several OPEs, APs, and major phthalates. Logistic regression models were employed to assess the associations between chemical exposure and disease status. Factor analysis was conducted for multiple chemical exposure assessments as a secondary analysis. Among OPE metabolites, diphenyl phosphate (DPHP), 2-ethylhexyl phenyl phosphate (EHPHP), and 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) were detected in >80% of the subjects. Among APs, metabolites of di-isononyl phthalate (DINP) and di(2-propylheptyl) phthalate (DPrHpP) were detected in >75% of the urine samples. The odds ratios (ORs) of uterine fibroids were significantly higher among the women with higher exposures to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-butoxyethyl) phosphate (TBOEP), di(2-ethylhexyl) terephthalate (DEHTP), DPrHpP, and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH). In addition, urinary concentrations of mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), a sum of five di(2-ethylhexyl) phthalate metabolites (∑5DEHP), and mono(4-methyl-7-hydroxyoctyl) phthalate (OH-MINP) were significantly higher in the cases. In factor analysis, a factor heavily loaded with DPrHpP and DEHP was significantly associated with uterine fibroids, supporting the observation from the single chemical regression model. We found for the first time that several metabolites of OPEs and APs are associated with increased risks of uterine fibroids among pre-menopausal women. Further epidemiological and mechanistic studies are warranted to validate the associations observed in the present study.

Plastic toys and child care articles as a source of children exposure to phthalates and other plasticisers in Saudi Arabia

ABSTRACT Phthalates are chemical compounds added to plastic materials to provide flexibility. They are used in numerous consumer products including children’s toys and child care articles. Exposure to phthalates is linked to reproductive and developmental disorders in addition to endocrine disruption effects. This study is the first to investigate the presence and levels of phthalates and other plasticisers in children’s toys and child care articles sold in the Saudi market. Twenty-seven products were obtained from local marketplaces and analysed by GC-MS for the levels of the six regulated phthalates dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), di-(2-ethylhexl) phthalate (DEHP), di-n-octyl phthalate (DnOP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP). Other plasticisers and plastic additives were investigated qualitatively for potential risks. Overall, 19% of products tested were found to have one or more regulated phthalates exceeding the 0.1% w/w regulatory limit. All noncompliant items were made of polyvinyl chloride (PVC). In contrast, the 16 non-PVC items tested were compliant with regulations. Among the 11 PVC items tested, 45% were noncompliant. DEHP was detected in all 11 PVC products, with concentrations ranging from <LOQ-32.2% w/w, and with concentrations exceeding regulatory levels in 4 of 11 PVC products (36%). The other regulated phthalates detected in PVC products were DBP and DINP with amounts that ranged from <LOQ-0.275 and 0.218–14.2% w/w, respectively. Plasticisers other than the regulated ones were present in a number of products; including dioctyl isophthalate (DOIP), di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), methyl stearate, acetyl tributyl citrate (ATBC) and diisobutyl phthalate (DIBP). Inexpensive children’s toys were found to be less complying with the regulations of toys safety regarding phthalates content, which may pose more risk to children.

Trends for plasticizers in German freshwater environments – Evidence for the substitution of DEHP with emerging phthalate and non-phthalate alternatives

Plasticizers are marketed in high volumes and Di(2-ethylhexyl) phthalate (DEHP) is frequently detected in the environment and human populations. Industry had largely relied on DEHP until regulation started to restrict its marketing in 1999 due to environmental and human health concerns. The aim of this study was to obtain spatial-temporal trends for DEHP and its substitutes in German rivers. We have investigated suspended particulate matter (SPM) samples from the German Environmental Specimen Bank (ESB) for the presence of 23 plasticizers, i.e. 17 phthalates and 6 non-phthalates. The samples were collected in the last 10 years at 13 sites in large river basins in Germany such as the Rhine, Elbe and Danube. A decrease in DEHP concentrations was observed at all sampling sites between the mid-2000s and 2017. The maximum concentration for DEHP was determined in 2006 in samples from Rehlingen/Saar (6720 ng/g dry weight (dw)). By 2017, the DEHP concentration in Rehlingen had dropped to 2080 ng/g dw. Currently, Diisononyl phthalate (DINP) is the plasticizer with the highest levels in the SPM samples (maximum value 4150 ng/g dw in Rehlingen/Saar). Our results show that novel plasticizers such as Diisononylcyclohexane-1,2-dicarboxylate (DINCH) spread rapidly in surface waters after their market introduction. We have found several plasticizers of emerging concern in the environmental samples, the further use of which is currently under review under the EU chemicals regulation (REACH, registration, evaluation, authorisation and restriction of chemicals). In particular for Di(2-propylheptyl) phthalate (DPHP) a significant increase in concentration was observed at almost all sites between the mid-2000s and 2017, for example in Prossen/Elbe from 24 ng/g dw (2005) to 1380 ng/g dw (2017).

Simultaneous determination of di(2-ethylhexyl) phthalate and diisononylcyclohexane-1,2-dicarboxylate and their monoester metabolites in four labile blood products by liquid chromatography tandem mass spectrometry

Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer that is largely used for PVC blood bags. The migration of DEHP from medical devices into labile blood products (LBP) is a well-known situation. While DEHP has beneficial effects on the storage of red blood cells, it can have toxicological impact due to its potential reprotoxic effects (classified group 1B). Since July 1st, 2015, the French law prohibits the use of tubing made in DEHP-plasticized PVC in paediatric, neonatal and maternity wards. This provision, which could extend in several years more widely to medical devices used for drugs infusion, dialysis, feeding and blood bags, has led manufacturers to replace DEHP to alternative plasticizers such as diisononylcyclohexane-1,2-dicarboxylate (DINCH). In this paper, a liquid chromatography-tandem mass spectrometry (LCMS/MS) method has been developed and validated for the determination of DEHP, DINCH and their corresponding monoester metabolites (MEHP and MINCH) in four labile blood products (LBP): whole blood (WB), red cells concentrate (RCC), plasma and platelet concentrate (PC). Due to strong contamination of blank LBP by DEHP because of its ubiquitous presence in working environment and despite the attention paid to avoid contamination of solvents and glassware, a trap chromatographic column was implemented between the solvent mixing chamber and the injector of the LC system. This set-up permitted to discriminate DEHP present in the sample to DEHP brought by the environmental contamination. In the optimized conditions, all compounds were separated in less than 10 min. The analytes were extracted from LBP samples using a liquid-liquid extraction. After optimization, recoveries were ranged from 47 to 96 %, depending on the analytes and the nature of LBP. Except for DEHP which exhibited RSD values of intermediate precision higher than 20 % at a concentration of 25 nM, all the precision results (repeatability and intermediate precision) were lower than 16 % and trueness values ranged from -16.2–19.8%. Using the validated method, the leachability of DEHP and DINCH from corresponding PVC-blood bags was investigated and the concentrations of their corresponding metabolites, MEHP and MINCH, were determined in whole blood, red cells concentrate, plasma and platelet concentrate.

Urinary levels of phthalates and DINCH metabolites in Korean and Thai pregnant women across three trimesters

Phthalates are anti-androgenic chemicals and may cause long-lasting adverse effects on growing fetuses. Understanding their exposure profile during pregnancy, therefore, is of public health importance. Because both behavioral and physiological changes of pregnant women are expected to be substantial, the amount of phthalate exposure is expected to vary significantly over the course of pregnancy. Temporal trend of phthalate exposure during pregnancy, however, is largely unknown, especially in Asian women. The purpose of this study is to investigate the urinary concentrations of metabolites for major phthalates and alternative plasticizers over the course of pregnancy among Korean (n = 81) and Thai women (n = 102). Twenty-four metabolites from 15 plasticizers, such as dimethyl phthalate (DMP), diethyl phthalate (DEP), di-isobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), benzyl butyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), dioctyl phthalate (DnOP), diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di(2-ethylhexyl) terephthalate (DEHTP), and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH), were measured in urine samples collected in each trimester from pregnant women. While the levels of several phthalate metabolites were significantly different by trimester among Korean women, those of Thai women were relatively consistent. Urinary metabolites of DEP and DnOP were higher in Thai pregnant women compared to Korean pregnant women. The detection frequencies of the DINCH metabolite were 67.4% and 44.9% among Korean and Thai pregnant women, respectively. However, the ratio of DINCH to DEHP metabolites was significantly higher in Thai women. According to risk assessment, 11.9% of Korean and 5.3% of Thai women were considered at risk due to phthalate exposure, and DEHP, DnBP and DiBP were identified as major risk drivers. Considering the vulnerability of growing fetuses, further studies are warranted to identify major sources of exposure to these plasticizers during pregnancy.

Changes in urinary excretion of phthalates, phthalate substitutes, bisphenols and other polychlorinated and phenolic substances in young Danish men; 2009-2017.

During the past two decades human exposure to bisphenol A (BPA) and phthalates such as di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP) and di-(2-ethyl-hexyl) phthalate (DEHP) has received substantial interest due to widespread population exposures and potential endocrine disrupting effects. Therefore, these chemicals have gradually been restricted and phased out through legislation. However, humans are still exposed to a wide range of other less studied phthalates, phthalate substitutes and BPA analogues as well as other polychlorinated and phenolic substances. In this study, we investigated human exposure to these chemicals over the past decade. Three hundred urine samples collected in 2009, 2013 and 2017 (100 samples each year) from young Danish men of the general population, participating in a large on-going cross-sectional study, were selected for the present time trend study. The urinary concentration of metabolites of 15 phthalates, di-2-ethylhexyl terephthalate (DEHTP) and di-iso-nonyl-cyclohexane-1,2-dicarboxylate (DINCH), seven bisphenols including BPA, bisphenol S (BPS) and bisphenol F (BPF), as well as triclosan, triclocarban, benzophenone-3, three chlorophenols and two phenylphenols were analyzed by two new sensitive LC-MS/MS methods developed and validated for the present study. A significant decrease in urinary concentrations over time was observed for the majority of the chemicals. Median concentrations of BPA and the metabolites of DiBP, DnBP, BBzP and DEHP were more than halved from 2009 to 2017. Similar decreases were observed for triclosan and the chloro- and phenylphenols. In contrast, metabolites of the two phthalate substitutes DEHTP and DINCH increased more than 20 and 2 times, respectively. The potential BPA substitutes; BPS and BPF also increased, but only slightly. Despite these new exposure patterns, the exposure to the old well-known chemicals, such as DiBP, DnBP, BBzP, DEHP and BPA was still higher in 2017 compared to the exposure level of the new substitutes such as DEHTP, DINCH, BPS and BPF. A significant decrease in internal exposure to most of the common phthalates and BPA over the past decade was observed, reflecting market changes and regulatory measures implemented in EU. Despite increasing exposures to some of the known phthalate substitutes and BPA analogues, the total amount of each measured chemical group (original and substitute analytes combined) was lower in the more recently collected samples. This indicates only partial direct substitution or substitution by chemicals not covered in this approach, or a general decline in the exposure to these chemical/product groups over the last decade.

Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico.

Background:As a result of evidence suggesting phthalate toxicity, their use has decreased in recent years. However, new phthalates and non-phthalate replacements have emerged in their place, with unknown potential impacts on health.Methods:We measured 15 phthalate, two di(2-ethylhexyl)terephthalate (DEHTP), and two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) urinary metabolites, collected up to three times during pregnancy from 994 women in Northern Puerto Rico (2011-2017). We used tests of linear trend to asses changes in concentrations over time and linear mixed models to identify predictors of exposure (sociodemographic characteristics, drinking water sources, diet, product use).Results:Several phthalate metabolites decreased over the study period indicating decreased exposure, while the geometric mean of DEHTP metabolites (molecular sum) increased 3-fold between 2014-2017. Intraclass correlations revealed low to moderate reproducibility of these biomarkers across pregnancy. Several metabolites were associated with maternal age, income, education, pre-pregnancy BMI, drinking public water, use of cleaning and personal care products and ice cream consumption. DINCH metabolite concentrations remained low throughout the study period.Conclusion:Although exposure to some phthalates may be decreasing, exposure to replacements, such as DEHTP, is increasing. Additional studies are needed to further characterize sources of phthalate replacement chemicals and potential exposure-related health effects among vulnerable populations.

Occurrence and emission of phthalates and non-phthalate plasticizers in sludge from wastewater treatment plants in Korea.

Phthalates are endocrine-disrupting chemicals that cause adverse health effects in wildlife and humans. Due to domestic and global regulations of phthalates in commercial products, non-phthalate plasticizers (NPPs) have been introduced into industrial markets. Few studies have been conducted on the occurrence of phthalates and NPPs in sludge from wastewater treatment plants (WWTPs). In this study, sludge samples were collected from 40 WWTPs in Korea to investigate the occurrence, compositional profiles, and emission flux of phthalates and NPPs. Total concentrations of phthalates and NPPs in sludge ranged from 4.7 to 1400 (mean: 110) μg/g dry weight and from 0.17 to 780 (mean: 28.0) μg/g dry weight, respectively. Di(2-ethylhexyl)phthalate (DEHP) was a predominant compound, suggesting widespread consumption in Korea. Di(2-ethylhexyl)terephthalate (DEHT) was dominant in industrial sludge samples, whereas di-isononyl cyclohexane-1,2-dicarboxylate (DINCH) and trioctyl trimellitate (TOTM) were dominant in domestic sludge. This implies different consumption patterns of phthalate alternatives by industry and domestic activities. Concentrations of NPPs were significantly correlated with those of high-molecular-weight (HMW) phthalates, indicating that HMW phthalates were preferentially replaced by NPPs. The emission fluxes of phthalates via domestic WWTP activities were higher than those measured for industrial WWTPs, while the emission fluxes of NPPs via industrial WWTPs were higher than those found for domestic and industrial WWTPs. This indicates that phthalate emissions are associated with household activities, while NPP emissions are associated with industrial activities.

In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells

ABSTRACTPlasticizers are currently present in many consumer products, particularly food packaging, children’s toys, and medical devices. There are concerns regarding potential leaching to environment or food, thus increasing the risk of human exposure by inhalation, ingestion and/or dermal absorption potentially leading to adverse health consequences. Hexamoll diisononyl cyclohexane-1,2-dicarboxylate (Hexamoll® DINCH®), a non-phthalate plasticizer, has been used as a safer alternative to hazardous phthalates. In contrast to phthalates, evidence indicates that DINCH did not produce endocrine disruption, reproductive dysfunctions, genotoxicity or mutagenicity. However, there are limited data available regarding safety assessment, especially with respect to genotoxicity in human cells. The aim of this study was to assess DINCH cytotoxic and genotoxic effects in human liver and kidney cell lines following several exposure periods. For this purpose, the MTT cell viability, micronucleus, conventional and formamidopyrimidine DNA glycosylase (FPG)-modified comet assays were employed to detect cell death and genotoxicity, respectively. Data demonstrated that DINCH induced cytotoxicity in kidney cells exposed for 48hr, but not in liver cells. No marked chromosomal damage was noted after short-term or longer following treatment of both cell lines. However, DINCH produced oxidative DNA damage in liver cells exposed for 3 h, which decreased after a more prolonged incubation period. The occurrence of oxidative lesions, even transiently, indicates that mutation fixation may occur leading to adverse effects in liver. Therefore, these findings suggest that DINCH may be hazardous to humans and that further investigation is necessary to warrant its safety.

Effects of Cooling Ways on the Structure of Polypropylene Hollow Fiber Membranes Prepared by Stretching

Abstract Air, water, and DINCH (Di-isononyl-cyclohexane-1,2-dicarboxylate) were selected as the cooling media to prepare polypropylene hollow fiber membranes by melt spinning. The effects of various cooling ways with different cooling rates on the row-nucleated lamellar crystallization were investigated. The crystallinity, orientation and arrangement of the crystals were examined by differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and small-angle X-ray scattering (SAXS). Membrane morphology was observed by SEM. The less uniform pores, a layer of amorphous phase, and only a small part of slit-shaped pores were observed on the surface of samples when water and DINCH were used as the heat transfer medium because the fast cooling rate froze the surface molecules and decreased the crystallinity and orientation. However, when air was used as the cooling medium, the higher crystallinity and the better orientation of the annealed hollow fibers were obtained mainly due to the slow cooling rate. Corresponding hollow fiber membranes prepared by stretching had better interconnectivity of pores and larger pure water flux. Thus this study explains why air was selected as the cooling medium to prepare polypropylene hollow fiber membranes which can have larger pure water flux. Also, it provides new insights into the structure control of polypropylene hollow fiber membranes by stretching in order to prepare membranes with high strength.

Urinary metabolites of phthalates and di-iso-nonyl cyclohexane-1,2-dicarboxylate (DINCH)–Czech mothers' and newborns' exposure biomarkers

To assess human exposure to hazardous diesters of phthalic acid and their substitute di-iso-nonyl cyclohexane-1,2-dicarboxylate (DINCH), concentrations of their metabolites in urine should be determined. For the purpose of this biomonitoring study, a quick and easy sample preparation procedure for the simultaneous determination of eight phthalate and four DINCH metabolites in urine has been implemented and validated. Following the enzymatic hydrolysis and dilution with methanol, the sample is ready for the analysis by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The limits of quantification of this method ranged from 0.15 to 0.4 ng/mL urine with recoveries of 60–126% and repeatability in the range of 1–11%. The validated method was subsequently used for the analysis of urine samples collected from mothers and their newborn children living in two localities of the Czech Republic (Karvina and Ceske Budejovice, 2013–2014). Median concentrations of all measured metabolites (∑metabolites) were slightly lower in the urine samples collected from children (77.7 ng/mL urine) compared to their mothers (115.3 ng/mL urine), but no correlation was found between the concentrations of target compounds in children's and mothers' urine samples. The analyte with the highest concentration was monobutyl phthalate (MBP), with the median concentration of 32.1 ng/mL urine in the urine samples collected from mothers and 17.2 ng/mL urine in the samples collected from their children. This compound was also found in almost all of the measured samples. On the other hand, mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH) was not found in any urine sample. The most contaminated samples were collected from children living in the Karvina locality (median ∑metabolites 103.2 ng/mL urine), where the mono (2-ethyl-5-carboxypentyl) phthalate (cx-MEHP) compound contributed 43% to the total content of phthalate metabolites in newborns' urine. The results from our study are comparable with concentrations of the target compounds from Norway and Germany and lower compared to the results concluded in Sweden.

Development and validation of a bioanalytical assay based on liquid chromatography-tandem mass spectrometry for measuring biomarkers of exposure of alternative plasticizers in human urine and serum

Alternative plasticizers (APs) have been increasingly used in the last decade to replace conventional phthalate esters, in particular di(2-ethylhexyl) phthalate (DEHP), due to the toxicity of the latter. However, there is currently very little data about the toxicity of and exposure to APs. No method exists so far for the analysis of multiple exposure biomarkers. The objective of this work consisted in developing a simple bioanalytical procedure for the analysis of multiple exposure biomarkers of APs in human urine and serum. Focus was set on metabolites of di(2-propylheptyl) phthalate (DPrHpP), di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP) and di-2-ethylhexyl adipate (DEHA). A sample preparation protocol was developed and optimized using Oasis HLB solid-phase extraction (SPE) cartridges. Subsequently, an instrumental method based on liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS) was optimized. Following established guidelines, the sample preparation and instrumental methods were validated in terms of recovery, matrix effects, carry-over, linearity, limits of quantification, within- and between-run precision and trueness. Obtained results were satisfactory for all compounds except for one of the metabolites of DEHA (i.e., mono(2-ethylhexyl) adipate (MEHA)). A pilot biomonitoring study was carried out to assess the method's ability to detect and quantify target analytes in human urine and serum. In urine, most analytes could be detected with frequencies ranging from 8% for mono(2-ethyl-5-hydroxyhexyl) adipate (OH-MEHA) and cyclohexane-1,2-dicarboxylic mono hydroxyisononyl ester (OH-MINCH) to 92% for mono(2-ethyl-5-oxohexyl) adipate (oxo-MEHA), whilst most compounds could not be detected in serum, except for mono(2-ethylhexyl) terephthalate (MEHTP) and mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPrHpP) which were detected in all samples. The obtained results show that the developed method can be used to simultaneously analyse multiple exposure biomarkers to APs in human urine and serum.

Hair as an alternative matrix to monitor human exposure to plasticizers – Development of a liquid chromatography - tandem mass spectrometry method

The application and production of alternative plasticizers (APs) has been increasing in the last decade in replacement of conventional phthalates due to their toxicity. This calls for the development of non-invasive monitoring approaches to assess human exposure to APs. A method for the simultaneous measurement of exposure biomarkers of di(2‑propylheptyl) phthalate (DPHP), di(isononyl)cyclohexane‑1,2‑dicarboxylate (DINCH), di(2‑ethylhexyl) terephthalate (DEHTP) and di‑2‑ethylhexyl adipate (DEHA) in hair samples was developed and validated in this study. Prior to the analysis, the hair samples were washed in acetone and ultrapure water and pulverized to powder. Further, a solid-liquid and solid-phase extraction, followed by quantification using liquid chromatography - tandem mass spectrometry (LC-MS/MS) was performed. The method was validated in terms of recovery, matrix effects, carry-over, linearity, limits of quantification, within- and between-run precision and trueness. Satisfying results were obtained for all targeted compounds, except for mono(2‑ethylhexyl) adipate (MEHA), which was monitored only qualitatively. The optimized method was implemented in a pilot biomonitoring study with hair samples from 9 healthy volunteers. Detection frequencies of seven metabolites ranged from 11% to 100%. Mono(2‑ethylhexyl) terephthalate (MEHTP) and mono(2‑ethyl‑5‑oxohexyl) adipate (oxo-MEHA) were found in all hair samples. More hydrophobic monoester metabolites were found to be incorporated in hair to a greater extent compared to their oxidized counterparts. Obtained results show that the developed method can detect AP metabolites in hair, supporting the use of this alternative matrix in human biomonitoring.

Inflammation Differentiated from Oxidative Stress in Relation to Environmental Phthalate Exposure: Evidence from Human and Animal Studies

Exposure to phthalates has been linked to many adverse birth outcomes including preterm birth and preeclampsia. One mechanism behind these associations may be oxidative stress, which is best estimated using biomarkers such as 8-iso-prostaglandin F2&amp;#945;(8-iso-PGF2&amp;#945;). Previously observed associations with 8-iso-PGF2&amp;#945;may be confounded due to simultaneous generation of this marker by an inflammation-driven mechanism. In this study, we reexamined the association between phthalate exposure and elevated oxidative stress using the ratio between 8-iso-PGF2&amp;#945;and PGF2&amp;#945;, which allows for the quantitative distinction of the two sources of 8-iso-PGF2&amp;#945;, i.e., oxidative stress or inflammation,and thus clarifies the true mechanism of the association. We investigated the association between phthalate metabolites and oxidative stress vs. inflammation in The Infant Development and the Environment Study. In 761 urine specimens collected during the 3rdtrimester we analyzed phthalate metabolites as well 8-iso-PGF2&amp;#945; and PGF2&amp;#945; using mass spectrometry. Most phthalates were associated with increased oxidative stress. For example, an interquartile range difference in mono-n-butyl phthalate was associated with a 22% (95% confidence interval&amp;#61;14, 31) increase in the oxidative stress pathway in covariate-adjusted models. Detection of phthalate replacement metabolites such as di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) was associated with an increase in the inflammation pathway. We also examined these associations in an animal model, in which adult rats were administered di-butyl phthalate (DBP) or di-2-ethylhexyl phthalate (DEHP) and urine samples collected 7 hours after dosing were analyzed by mass spectrometry for the same biomarkers. We observed a similar increase in the oxidative stress pathway in response to DBP exposure. These findings have important implications for developing interventions to prevent adverse birth outcomes when intervening on exposure is difficult or impossible.

Temporal trends of phthalate exposures during 2007-2010 in Swedish pregnant women.

The general population is exposed to phthalates, a group of chemicals with strong evidence for endocrine disrupting properties, commonly used in a large number of consumer products. Based on published research and evidence compiled by environmental agencies, certain phthalate applications and products have become restricted, leading to an increasing number of "new generation compounds" coming onto the market during recent years replacing older phthalates. Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2-dicarboxylate (DiNCH). In order to evaluate temporal trends in phthalate exposure, first trimester urinary biomarkers of phthalates were measured in the Swedish SELMA study over a period of 2.5 years (2007-2010). We collected first morning void urine samples around week 10 of pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate metabolites and one phthalate replacement and least square geometric mean (LSGM) levels of the metabolites were compared between the sampling years when adjusted for potential confounders. All 14 metabolites were detectable in more than 99% of the SELMA subjects. The levels were generally comparable to other studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP) metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP), and DiNCH metabolites levels increased during the sampling period. Urinary metabolite levels of the older phthalates and more recently introduced phthalate replacement compound changed during the short sampling period in this Swedish pregnancy cohort. Our results indicate that replacement of phthalates can make an impact on human exposure to these chemicals. During this particularly vulnerable stage of life, phthalate exposures are of particular concern as the impacts, though not immediately noticeable, may increase the risk for health effects later in life.