Intake Of Di(2-ethylhexyl) Phthalate Research Articles

Occurrence and distribution of phthalate esters and microplastics in wastewater treatment plants in Taiwan and their toxicological risks

Phthalate esters (PAEs) are fat soluble synthetic chemicals, usually regarded as plasticizers for being added in numerous plastic products. Thus, environmental and health hazards of PAEs are associated with increasing plastic pollution. In this study, PAEs from sludge samples collected from water, sewage, and industrial treatment plants (N = 17) were analyzed using Gas Chromatography/Mass Spectrometry. Microplastics (MPs) were also quantified and correlated with PAEs. Results showed the highest average PAE concentrations in sewage treatment plants. The greatest ΣPAEs concentration were found in sewage treatment plant (STP4) with 32,414 μg/kg dw, while the lowest found in water treatment plant (WTP3) with 2062 μg/kg dw. Among different PAEs, di-(2-ethyl hexyl) phthalate (DEHP) contributes the highest. Similarly, DEHP, di-n-octyl phthalate (DnOP) and diisononyl phthalate (DiNP) significantly correlated with the total PAEs indicating their large contribution to sludge contamination. The abundance of microplastics in sludge ranged between 1 and 7 MP/g, highest at ITP6, but not detected in some stations. While microplastics may potentially increase PAEs, there was no significant relationship between ΣPAEs and MP abundance. The estimated human daily intake of DEHP and di-n-butyl phthalate (DnBP) when contaminated sludge be used showed low toxicological risks to exposed adults. This research presents the sludge characteristics, PAEs, and microplastic concentrations in different wastewater treatment plants in Taiwan. PAE contamination was highly contributed by domestic and industrial wastes shown by their significant amounts in STP and ITP. Results further provide evidence for potential sludge recycling (WTP sludge) and application to soil.

Exposure to di (2-ethylhexyl) phthalate causes locomotor increase and anxiety-like behavior via induction of oxidative stress in brain

Di (2-ethylhexyl) phthalate (DEHP) is the most prevalent exposure scenario in the daily life. A growing number of significant studies showed that DEHP could exhibit long-term adverse health effects for the human body, particularly in the liver, kidneys, heart and reproductive systems. However, the impact of oral intake of DEHP on nervous system is extremely limited. In the present study, the adult C57BL/6J male mice were intragastric administered with two dosages DEHP for 35 days. The behavioral parameters were assessed using the elevated plus maze and open-field test. The mRNA expression levels of neuropeptides and the oxidative stress-associated proteins were detected by qPCR and western blot severally. The histopathologic alterations of brain were also observed by H&E and Nissl staining. The results demonstrated that oral DEHP exposure could result in neurobehavioral impairments such as locomotor increase and anxiety-like behavior. Furthermore, the pathological damages were clearly observed in cerebral cortex and hippocampus, accompanied by a decrease in neuropeptides and an increase in oxidative stress, which were all positively correlated with the dose of DEHP. Together, these findings provide valuable clues into the DEHP-induced neurotoxicity.

Levels of phthalates and bisphenol in toys from Brazilian markets: Migration rate into children's saliva and daily exposure

Bisphenols (BPs) and phthalate esters (PAEs) are extensively used in toys and childcare products. Therefore, children may be exposed to these compounds, causing potential adverse effects. Despite the strict control of the levels of these contaminants in toys by some nations, routine testing in Brazil is very scarce. The present study was aimed at determining the concentrations of PAEs and BPs in toys commercialized in Brazil, employing GC–MS and LC-MS/MS, respectively. Furthermore, the migration capacity of PAEs into saliva and the daily intake (EDI) were also estimated. Di-2-ethylhexyl phthalate (DEHP) was the PAE with the highest detection rate (93%) and migration rate (0.26 μg/min). Moreover, the levels of DEHP in some samples were above the threshold values set by the European Commission and the Brazilian Institute of Metrology, Standardization, and Industrial Quality. Among the BPs analogs, BPA and BPS presented the highest positive detection rates (72% and 30%, respectively). However, their levels were below the permitted values in all analyzed samples. A daily intake of DEHP was estimated at 29.8 μg/kg bw/day, being this exposure similar to those found in other countries and below the EFSA acceptable intake limit (50 μg/kg bw/day). However, our data are referred to exposure through oral contact with the analyzed toys, while the contribution of other potential sources, such as food consumption, were not here considered. To the best of our knowledge, this is the first study estimating the exposure of Brazilian children to PAEs and BPs, considering toys as the exposure source. These preliminary data may become a valuable guide for the control of EDC levels in toys commercialized in Brazil, as well as for future studies regarding estimation of exposure to EDCs by children taking into account multiple potential sources.

Comparison of the exposure assessment of di(2-ethylhexyl) phthalate between the PBPK model-based reverse dosimetry and scenario-based analysis: A Korean general population study

Di (2-ethylhexyl) phthalate (DEHP), classified as a reproductive toxicant, is a ubiquitous pollutant in foodstuffs, dust, and commercial products. In this study, to provide a useful cross-check on the accuracy of the exposure assessment, the estimated daily intake of DEHP was compared using reverse dosimetry with a physiologically-based pharmacokinetic (PBPK) model and a scenario-based probabilistic estimation model for six subpopulations in Korea. For reverse dosimetry analysis, the concentrations of urinary DEHP metabolites, namely mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl)phthalate (MEOHP), from three human biomonitoring program datasets were used. For the scenario-based model, we evaluated the various exposure sources of DEHP, including diet, air, indoor dust, soil, and personal care products (PCPs), and also determined its levels based on the literature review and measurements of indoor dust. The DEHP exposure doses using both exposure assessment approaches were similar in all cases, except for the 95th percentile exposure doses in toddlers (1–2 years) and young children (3–6 years). The PBPK-reverse dosimetry estimated daily intakes at the 95th percentile ranged between 22.53 and 29.90 μg/kg/day for toddlers and young children. These exceeded the reference dose (RfD) of 20 μg/kg bw/day of the US Environmental Protection Agency (EPA) based on the increased relative liver weight. Although, food was considered the primary source of DEHP, contributing to a total exposure of 50.8–75.1%, the effect of exposure to indoor dust should not be overlooked. The occurrence of high levels of DEHP in indoor dust collected from Korean homes suggests the use of a wide variety of consumer products containing DEHP. Furthermore, more attention should be paid to the high exposure levels of DEHP, especially in young children. Therefore, it is necessary to perform continuous monitoring of the indoor dust, consumer products, and the body burden of children.

Longitudinal changes in oxidative stress and early renal injury in children exposed to DEHP and melamine in the 2011 Taiwan food scandal.

In 2011, phthalates, mainly di-(2-ethylhexyl) phthalate (DEHP), were found to have been added to a variety of foods in Taiwan, increasing the risk of microalbuminuria in children. Exposure to melamine perhaps modifies that risk. This prospective cohort study investigates whether renal injury resulting from exposure to DEHP-tainted foods from the 2011 Taiwan Food Scandal is reversed over time. The temporal and interactive effects of past daily DEHP intake, current daily DEHP intake, and urinary melamine levels on oxidative stress and renal injury were also examined. Two hundred possibly DEHP-affected children (aged<18years) were enrolled in the first survey wave (August 2012-January 2013), with 170 and 159 children in the second (July 2014-February 2015) and third waves (May 2016-October 2016), respectively. The first wave comprised questionnaires that were used to collect information about possible past daily DEHP intake from DEHP-tainted foods. One-spot first morning urine samples were collected to measure melamine levels, phthalate metabolites, and markers indicating oxidative stress (malondialdehyde and 8-oxo-2'-deoxyguanosine), and renal injury (albumin/creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase) in all three waves. Generalized estimating equation (GEE) modeling revealed that both past daily DEHP intake and time might affect urinary ACR. However, most interactions were negative and significant correlation was observed only during the second wave (P for interaction=0.014) in the group with the highest past daily DEHP intake (>50μg/kg/day). Urinary melamine levels were found to correlate significantly with both urinary ACR and oxidative stress markers. The highest impact associated with exposure to DEHP-tainted foods in increasing urinary ACR of children was observed during the first wave, and the effect may partially diminish over time. These results suggest that continuous monitoring of renal health and other long-term health consequences is required in individuals who were affected by the scandal in 2011.

Development of di(2-ethylhexyl) phthalate-containing thioglycolic acid immobilized chitosan mucoadhesive gel as an alternative hormone therapy for menopausal syndrome.

Menopausal syndrome includes the symptoms that most women experience owing to hormone changes after menopause. Although hormone replacement therapy is a common treatment for menopausal syndrome, there are still many side effects and challenges hindering research. In this study, thioglycolic acid (TGA)‐immobilized chitosan mucoadhesive gel was synthesized by a new method of low concentration of 1,4‐butanediol diglycidyl ether (BDDE) would encapsulate di(2‐ethylhexyl) phthalate (DEHP) as an alternative hormone replacement therapy for menopausal syndrome. The efficacies of the DEHP‐containing TGA‐chitosan gel (CT‐D) were confirmed and evaluated by materials characterization and in vitro study. Results showed that CT‐D was not cytotoxic and had better mucoadhesive ability than chitosan. The animal model was constructed 1 month after bilateral ovariectomy in SD rats. CT‐D was administered intravaginally every 3 days. Bodyweight, wet weight of the uterus and vagina, vaginal smears, histology, blood element analysis, and serological analysis was used to assess the ability of the material to relieve menopausal syndrome. The results indicated that the combination of the sustained release of DEHP and mucoadhesive TGA‐immobilized chitosan allows the developed CT‐D to relieve the menopausal syndrome through low concentrations of DEHP, which falls in the safety level of the tolerable daily intake of DEHP.

Promotion effects of DEHP on hepatocellular carcinoma models: up-regulation of PD-L1 by activating the JAK2/STAT3 pathway.

Di(2-ethylhexyl) phthalate (DEHP), as an endocrine disruptor, is often used as a plasticizer in various polyvinyl chloride plastic products and medical consumables. Epidemiological studies have shown that long-term large intake of DEHP may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and aggravates the progression of chronic liver injury. However, the effects of DEHP on hepatocellular carcinoma (HCC) are rarely studied. In this study, we sought to determine the effects of DEHP on HCC induced by carbon tetrachloride combined with diethylnitrosamine, and further study its molecular mechanism. It was found that DEHP exposure significantly promotes tumor immune escape and activates signaling pathways involved in related protein expression of tumor immune escape, including PD-L1, JAK2, and STAT3. In addition, the trends observed in the HepG2 cells assay are consistent with vivo conditions. In summary, DEHP may play a tumor-promoting role in HCC mice and IFN-γ stimulated HepG2 cells, which may be related to the JAK2/STAT3 signaling pathway.

Characteristics of dust-phase phthalates in dormitory, classroom, and home and non-dietary exposure in Beijing, China.

The phthalate concentrations in dust from undergraduate dormitories, classrooms, and homes in Beijing, China, were measured in April 2017. We analyzed the characteristics of phthalates in dust from three environments. In addition, we estimated the daily intake of phthalates via three pathways using Monte Carlo simulations. The detection frequency of eight phthalates in dust ranges from 74.5 to 100%. Di (2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP) are the most abundant phthalates. The median proportion of DEHP in dust is the highest, ranging from 67.1 to 72.9%. The PMF results indicated that two, four, and three types of phthalate sources exist in home, dormitory, and classroom, respectively. The differences in the phthalate concentrations between sunny and shaded rooms and urban and suburban classrooms are insignificant, whereas that between male and female dormitories is significant. The total daily intake of DEHP, DnBP, and DiBP ranges from 97.3 to 336 ng/ (kg·day). The oral intake for DEHP in classrooms and the dermal intake of DnBP and DiBP in homes are the highest. The carcinogenic risk of DEHP to university students is the highest in classrooms and the total carcinogenic risk of the three environments is 4.70 × 10-6.

Association between two common environmental toxicants (phthalates and melamine) and urinary markers of renal injury in the third trimester of pregnant women: The Taiwan Maternal and Infant Cohort Study (TMICS)

BackgroundExposure to either melamine or phthalate, two common toxicants, during pregnancy may cause adverse health effects, including kidney damage. ObjectivesWe investigated the independent and interactive effect of exposure to melamine and phthalates, particularly di-(2-ethylhexyl) phthalate (DEHP), on markers of early renal injury in women their third trimester of pregnancy in one nationwide birth cohort, the Taiwan Maternal and Infant Cohort Study (TMICS). MethodsBetween October, 2012 and May, 2015, participants were administered questionnaires, physical examinations, and blood and urine tests during their third trimester. One-spot overnight urine specimens were used to simultaneously measure melamine, 11 phthalate metabolites, and two markers of renal injury, microalbumin and N-acetyl-beta-D-glucosaminidas (NAG). Estimated daily DEHP intake was calculated based on measurement of three urinary DEHP metabolites. Microalbuminuria was defined as having a urinary albumin/creatinine ratio (ACR) higher than 3.5 mg/mmol. ResultsTotal 1433 pregnant women were analyzed. The median value for urinary melamine was 0.63 μg/mmol Cr and estimated DEHP intake was 1.84 μg/kg/day. We found subjects in the highest quartile of estimated DEHP intake to have significantly higher urinary ACR (β = 0.095, p = 0.043) and the prevalence of microalbuminuria (adjusted OR = 1.752, 95% confidence interval = 1.118–2.746), compared to those in the lowest quartile. In addition, there was a significant interactive effect between urinary melamine and estimated DEHP intake on urinary ACR and NAG. ConclusionOur results suggest these two ubiquitous chemicals together may be associated with markers of early kidney injury in pregnant women.

A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children

Prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD). Our aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children. A total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL). Associations of maternal DEHP exposure (median 4.54μg/kg_bw/day) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) μg/kg_bw/dayfor an integrated CBCL score. The current TDI (RfD) of 50 (20) μg/kg_bw/day for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.

Health risk of phthalates in water environment: Occurrence in water resources, bottled water, and tap water, and burden of disease from exposure through drinking water in tehran, Iran

Occurrence of phthalates in water resources, bottled water, and tap water, and health risk of exposure to the phthalates through drinking water in Tehran, Iran, 2018 were studied. The six phthalates with the most health and environmental concerns, including di-(2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP), diethyl phthalate (DEP), dimethyl phthalate (DMP), and di-n-octyl phthalate (DNOP) were monitored in drinking water and water resources. The average levels (±standard deviation: SD) of the total phthalates in drinking water from the water distribution system, bottled water, surface waters, and ground waters were determined to be 0.76 ± 0.19, 0.96 ± 0.10, 1.06 ± 0.23, and 0.77 ± 0.06 μg/L, respectively. The dominant compounds in the phthalates were DMP and DEHP causing a contribution to the total phthalate levels higher than 60% in all the water sources. The phthalate levels of drinking water significantly increased by contact of hot water with disposable plastic and paper cups and by sunlight exposure of bottled water (p value < 0.05). The hazard quotients (HQs) of DEHP, BBP, DBP, and DEP for all ages both sexes combined were determined to be 1.56 × 10−4, 1.01 × 10−5, 1.80 × 10−5, and 1.29 × 10−6, respectively that were much lower than the boundary value of 1.0. The disability-adjusted life years (DALYs) and DALY rate (per 100,000 people) attributable to DEHP intake through drinking water for all ages both sexes combined were estimated to be 6.385 (uncertainty interval: UI 95% 1.892 to 22.133), and 0.073 (0.022–0.255), respectively. The proportion of mortality in the attributable DALYs was over 96%. The attributable DALY rate exhibited no significant difference by sex, but was considerably affected by age in a manner that the DALY rates ranged from 0.052 (0.015–0.175) in the age group 65 y plus to 0.099 (0.026–0.304) in the age group 5 to 9 y. Both the carcinogenic and non-carcinogenic health risks of the phthalates in drinking water were considered to be very low. The results can also be of importance in terms of developing frameworks to expand the domain of burden of disease study to the other environmental risks.

Di(2-ethylhexyl) phthalate promotes hepatic fibrosis by regulation of oxidative stress and inflammation responses in rats

Di(2-ethylhexyl) phthalate (DEHP) is an environmental pollutant that is widely used in medical and consumer products. An epidemiological study has suggested that a large daily intake of DEHP from phthalate-contaminated food may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and exacerbates the progression of chronic liver injury. However, the effect of DEHP on hepatic fibrosis is rarely studied. In the present study, we sought to determine the effect of DEHP on carbon tetrachloride (CCl4)-induced liver fibrosis, and to further examine the molecular mechanisms. We found that DEHP exposure remarkably promoted liver inflammation, necrosis and fibrosis, and increased expression of the protein associated with liver inflammation and fibrogenesis, including α-SMA, COL-Ⅰ, COL-Ⅲ, TGF-β1, P-Smad2, P-Smad3, P-p38 and P-p65. The similar trend was observed in the LX-2 cells. Furthermore, DEHP exposure induced oxidative stress and inflammatory cytokine production. Taken together, DEHP might play a fibrotic role in hepatic fibrosis rats and TGF-β1-stimulated LX-2 cells in vitro which was related to TGF-β1/Smad and p38MAPK/NF-κB signal pathway.

Plasticizer Di-(2-Ethylhexyl)Phthalate Induces Epithelial-to-Mesenchymal Transition and Renal Fibrosis In Vitro and In Vivo.

Plasticizer di-(2-ethylhexyl)phthalate (DEHP) is known as an endocrine disruptor and a peroxisome proliferator. A currently epidemiological study has suggested that daily high DEHP intake from phthalate-tainted foods in children may be a risk factor for renal dysfunction. DEHP can leach from medical devices such as blood storage bags and the tubing. Long-term exposure to DEHP is associated with nephropathy and exacerbates chronic kidney diseases (CKDs) progression. However, the detailed effects and molecular mechanisms remain unclear. Here, we hypothesized that DEHP and its major metabolite mono-(2-ethylhexyl)phthalate (MEHP) incited epithelial-to-mesenchymal transition (EMT) and lead to aggravate renal fibrosis progression. Treatment with low-cytotoxic concentration DEHP, but not MEHP, for 72 h obviously induced the morphological and phenotypic changes and EMT markers induction in normal rat renal tubular epithelial cells (NRK-52E). AKT inhibitor MK-2206 inhibited DEHP-induced EMT features and signals of AKT phosphorylation and downstream NF-κB and GSK3β. DEHP did not affect the expression of transforming growth factor-β1 mRNA. DEHP down-regulated the peroxisome proliferator-activated receptor (PPAR)α and PPARγ protein expressions. PPARγ agonist pioglitazone partially and significantly inhibited DEHP-induced EMT induction. In vivo DEHP exposure for 6 weeks enhanced the renal dysfunction and renal fibrosis and mortality rate, but decreased the PPARα and PPARγ protein expressions, in a folic acid-induced kidney fibrosis mouse model. Taken together, these results demonstrate for the first time that DEHP arouses EMT induction and renal fibrosis progression in renal tubular cells and is associated with PPARs downregulation. DEHP exposure potentially exacerbated renal fibrosis/nephropathy in a kidney disease condition.

Excretion of Di-2-ethylhexyl phthalate (DEHP) metabolites in urine is related to body mass index because of higher energy intake in the overweight and obese

A higher body mass index (BMI) has been positively associated with the rate of excretion of di-2-ethylhexyl phthalate (DEHP) metabolites in urine in data from the National Health and Nutrition Examination Survey (NHANES), suggesting an association between DEHP exposure and BMI. The association, however, may be due to the association between body mass maintenance and higher energy intake, with higher energy intake being accompanied by a higher intake of DEHP. To examine this hypothesis, we ran a Monte Carlo simulation with a DEHP physiologically-based pharmacokinetic (PBPK) model for adult humans. A realistic exposure sub-model was used, which included the relation of body weight to energy intake and of energy intake to DEHP intake. The model simulation output, when compared with urinary metabolite data from NHANES, supported good model validity. The distribution of BMI in the simulated population closely resembled that in the NHANES population. This indicated that the simulated subjects and DEHP exposure model were closely aligned with the NHANES population of interest. In the simulated population, the ordinary least squares regression coefficient for log(BMI) as a function of log(DEHP nmol/min) was 0.048 (SE 0.001), as compared with the reported value of 0.019 (SE 0.005). In other words, given our model structure, the higher energy intake in the overweight and obese, and the concomitant higher DEHP exposure, describes the reported relationship between BMI and DEHP.

Prenatal exposure estimation of BPA and DEHP using integrated external and internal dosimetry: A case study

Prenatal exposure to Endocrine disruptors (EDs), such as Bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP), has been associated with obesity and diabetes diseases in childhood, as well as reproductive, behavioral and neurodevelopment problems. The aim of this study was to estimate the prenatal exposure to BPA and DEHP through food consumption for pregnant women living in Tarragona County (Spain). Probabilistic calculations of prenatal exposure were estimated by integrated external and internal dosimetry modelling, physiologically based pharmacokinetic (PBPK) model, using a Monte-Carlo simulation. Physical characteristic data from the cohort, along with food intake information from the questionnaires (concentrations of BPA and DEHP in different food categories and the range of the different food ratios), were used to estimate the value of the total dietary intake for the Tarragona pregnancy cohort. The major contributors to the total dietary intake of BPA were canned fruits and vegetables, followed by canned meat and meat products. In turn, milk and dairy products, followed by ready to eat food (including canned dinners), were the most important contributors to the total dietary intake of DEHP. Despite the dietary variations among the participants, the intakes of both chemicals were considerably lower than their respective current tolerable daily intake (TDI) values established by the European Food Safety Authority (EFSA). Internal dosimetry estimates suggest that the plasma concentrations of free BPA and the most important DEHP metabolite, mono (2-ethylhexyl) phthalate (MEHP), in pregnant women were characterized by transient peaks (associated with meals) and short half-lives (< 2 h). In contrast, fetal exposure was characterized by a low and sustained basal BPA and MEHP concentration due to a lack of metabolic activity in the fetus. Therefore, EDs may have a greater effect on developing organs in young children or in the unborn child.

Using exposure prediction tools to link exposure and dosimetry for risk-based decisions: A case study with phthalates

A few different exposure prediction tools were evaluated for use in the new in vitro-based safety assessment paradigm using di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DnBP) as case compounds. Daily intake of each phthalate was estimated using both high-throughput (HT) prediction models such as the HT Stochastic Human Exposure and Dose Simulation model (SHEDS-HT) and the ExpoCast heuristic model and non-HT approaches based on chemical specific exposure estimations in the environment in conjunction with human exposure factors. Reverse dosimetry was performed using a published physiologically based pharmacokinetic (PBPK) model for phthalates and their metabolites to provide a comparison point. Daily intakes of DEHP and DnBP were estimated based on the urinary concentrations of their respective monoesters, mono-2-ethylhexyl phthalate (MEHP) and monobutyl phthalate (MnBP), reported in NHANES (2011–2012). The PBPK-reverse dosimetry estimated daily intakes at the 50th and 95th percentiles were 0.68 and 9.58 μg/kg/d and 0.089 and 0.68 μg/kg/d for DEHP and DnBP, respectively. For DEHP, the estimated median from PBPK-reverse dosimetry was about 3.6-fold higher than the ExpoCast estimate (0.68 and 0.18 μg/kg/d, respectively). For DnBP, the estimated median was similar to that predicted by ExpoCast (0.089 and 0.094 μg/kg/d, respectively). The SHEDS-HT prediction of DnBP intake from consumer product pathways alone was higher at 0.67 μg/kg/d. The PBPK-reverse dosimetry-estimated median intake of DEHP and DnBP was comparable to values previously reported for US populations. These comparisons provide insights into establishing criteria for selecting appropriate exposure prediction tools for use in an integrated modeling platform to link exposure to health effects.

Dietary exposure and human risk assessment of phthalate esters based on total diet study in Cambodia

Phthalate esters are used in a wide variety of consumer products, and human exposure to this class of compounds is widespread. Nevertheless, studies on dietary exposure of human to phthalates are limited. In this study, to assess the daily intakes of phthalate esters and the possible adverse health impacts, different food samples were collected from three areas of Cambodia, one of the poorest countries in the world. The ∑phthalate ester concentrations in Kampong Cham, Kratie and Kandal provinces ranged from 0.05 to 2.34 (median 0.88) μgg−1, 0.19–1.65 (median 0.86) μgg−1 and 0.24–3.05 (median 0.59) μgg−1 wet weight (ww), respectively. Di-2-Ethylhexyl phthalate (DEHP) and diisobutyl phthalate (DiBP) were the predominant compounds among all foodstuffs. The estimated daily intake (EDI) of phthalate esters for the general population in Kampong Cham, Kratie and Kandal was 34.3, 35.6 and 35.8μgkg−1 bw d−1, respectively. The dietary daily intake of DEHP, benzylbutyl phthalate (BBP) and di-n-butyl phthalate (DBP) in Kampong Cham, Kratie and Kandal were below the tolerable daily intakes (TDI) imposed by the European Food Safety Authority (EFSA) and reference doses (RfD) imposed by The United States Environmental Protection Agency (USEPA). Rice contributed the greatest quantity of DEHP to the daily intake in Cambodia so may deserve further exploration. To our knowledge, this is the first study to investigate the occurrence and the daily intakes of phthalate esters in Cambodia.

Effects of high di(2-ethylhexyl) phthalate (DEHP) exposure due to tainted food intake on pre-pubertal growth characteristics in a Taiwanese population

On May 23, 2011, a major scandal involving the illegal use of phthalates as clouding agents in food products was reported. Specifically, di(2-ethylhexyl) phthalate (DEHP) was purposefully added to foods as a substitute emulsifier. The purpose of this study was to examine the effects of DEHP exposure on the growth characteristics of the child victims of this scandal. Eighty-eight victims, originating from northern, central, and southern Taiwan and ranging in age from 6.0 to 10.5 years, were invited to participate in this study during clinic visits. The participants underwent follow-up health examinations from August 2012 to February 2013. We collected information on each participant's history of exposure to tainted food products using a questionnaire, and we analyzed their urinary concentrations of DEHP metabolites using high-performance liquid chromatography/tandem mass spectrometry. These data were then used to estimate their daily DEHP intake (DIAll) during the scandal. We also measured physical development parameters (height, weight, and bone age) and hormone levels (thyroid, sex and growth hormones) to evaluate their overall growth characteristics. The average (SD) duration of DEHP intake from tainted nutrition supplements was 1.39 (1.01) years. The median DIAll values were 19.93 and 20.69μg/kg bw/day for boys and girls, respectively. Among the enrolled children, the DIAll values of 46.9% of boys and 51.3% of girls exceeded the reference dose (RfD) of 20μg/kg bw/day established by the US Environmental Protection Agency. Our results demonstrate that DIAll is negatively associated with the height percentile, weight percentile, bone age/chronological age, and insulin-like growth factor 1 (IGF-1) levels but not with IGF binding protein 3 (IGF-BP3) level, IGF-1/IGF-BP3, sex hormones, or thyroid hormone levels. The DEHP DIAll value exceeded the RfD at high rates among children of both genders. Our results suggest that high levels of DEHP exposure due to the consumption of tainted food products are negatively associated with body weight, height, bone age, and IGF-1 levels in children. The likelihood of delayed puberty among the affected children is therefore a reasonable concern, and further follow-up is required.

Determination of phthalates in plum spirit and their occurrence during plum spirit production

Phthalates are ubiquitous environmental contaminants that, due to their lipophilicity, migrate more readily into beverages with higher ethanol content. The aim of this work was to study the occurrence of phthalates in samples during the plum spirit production and in the final product, plum spirit manufactured by registered producers from five European countries, using gas chromatography-mass spectrometry (GC-MS). A decreasing trend of mean values was observed for diethyl phthalate (DEP), di-iso-butyl phthalate (DiBP), and di-n-butyl phthalate (DBP) as the distillation process went on. Levels of benzyl-butyl phthalate (BBP) and di-(2-ethylhexyl) phthalate (DEHP) increased in the distillation phase compared to concentrations in the preceding phases. In commercial plum spirits, DEHP and DiBP were detected in the highest concentrations. Results also indicated that a moderate daily consumption of plum spirit does not pose a health risk regarding the Tolerable Daily Intake of BBP, DEHP, and DBP

Intake of phthalate-tainted foods and microalbuminuria in children: The 2011 Taiwan food scandal

BackgroundA major threat to public health involving phthalate-tainted foodstuffs occurred in Taiwan in 2011. Phthalates, mainly di-(2-ethylhexyl) phthalate (DEHP), were intentionally added to several categories of food commonly consumed by children. This study investigated the relationship between intake of the phthalate-tainted foods and renal function in children. MethodsChildren aged ≤10years with possible phthalate exposure were enrolled in this study between August 2012 and January 2013. Questionnaires were used to collect details of exposure to phthalate-tainted foodstuffs, and blood and urine samples were collected for clinical biochemical workup. The clinical biomarkers of renal injury, including urinary microalbumin, N-acetyl-beta-d-glucosaminidase (NAG), and β2-microglobulin were measured. Exposure was categorized based on recommended tolerable daily intake level defined by the U.S. Environmental Protection Agency (0.02mg/kg/day) and the European Food Safety Authority (0.05mg/kg/day). ResultsWe analyzed intake and renal function of 184 children whose intake of DEHP-tainted foods was known. Higher DEHP exposure to DEHP-tainted foods was significantly associated with increase of urine albumin/creatinine ratio (ACR). Children in the high-exposed group (daily DEHP intake (DDI)>0.05mg/kg/day) had 10.395 times the risk of microalbuminuria than the low-exposed group (DDI≤0.02 and >0mg/kg/day) and no-exposed group combined after adjustment (95% CI=1.096–98.580, P=0.04). ConclusionIntake of DEHP from phthalate-tainted foods may be a potential risk factor for microalbuminuria, a marker of glomerular injury in children.