Concentrations of phthalates in bottled water under common storage conditions: Do they pose a health risk to children?

Of recent concern is the migration of phthalates from plastic products such as Polyethylene Terephthalate (PET) bottles into the water contain. These concerns should be addressed, especially considering the steady growth of the consumption of bottled water and the toxicological effects of phthalates. In this regard, special attention should be paid to children's consumption because of their particular susceptibility to the effects of phthalates.The aim of this study was to determine the concentrations of phthalates, including dibutyl phthalate (DBP), butyl benzyl phthalate (BBP) and bis(2-ethylhexyl) phthalate (DEHP), in bottled water and to estimate the health risk of endocrine disrupting chemicals due to water intake in children for the first time.Migration of phthalates was investigated in PET-bottled water under various storage conditions using gas chromatography–mass spectroscopy. A phthalate exposure assessment was performed to characterize their risk to the children's health via a calculated hazard quotient (HQ).It seems that increase in the temperature and the duration of storage affect phthalate migration, but the level of DEHP in bottled water was always very low and does not exceed 26.83% of the U.S. EPA maximum concentration limit (MCL). In particular, phthalate migration was not substantial at low temperatures (< 25 °C) and freezing conditions and the most abundant phthalate (DEHP) was not more than 10.6% MCL.The estimated child intake ranged from 0.01 μg/kg/day for BBP to 0.24 μg/kg/day for DEHP. Estimated phthalate intakes are generally in the safe range and exposure decreased with increasing age. Toxicological risk assessment of the maximum concentrations measured revealed a maximum HQ of 0.012 in the worst condition. Furthermore, a negligible carcinogenic risk of 6.5 × 10^− 7 for DEHP was observed. Consequently, risk evaluation showed that bottled water is safe for consumption by children.     

Phthalate Esters in Foods: Sources,Occurrence, and Analytical Methods

ABSTRACT: Phthalates are a group of diesters of ortho‐phthalic acid (dialkyl or alkyl aryl esters of 1,2‐benzenedicarboxylic acid). Higher‐molecular‐weight phthalates, such as di‐2‐ethylhexyl phthalate (DEHP), are primarily used as plasticizers to soften polyvinyl chloride (PVC) products, while the lower‐molecular‐weight phthalates, such as diethyl phthalate (DEP), di‐n‐butyl phthalate (DBP), and butyl benzyl phthalate (BBzP), are widely used as solvents to hold color and scent in various consumer and personal care products. Phthalates have become ubiquitous environmental contaminants due to volatilization and leaching from their widespread applications, and thus contamination of the environment has become another important source for phthalates in foods in addition to migration from packaging materials. Human exposure to phthalates has been an increased concern due to the findings from toxicology studies in animals. DEHP, one of the important and widely used phthalates, is a rodent liver carcinogen. DEHP, DBP, BBzP, and several phthalate metabolites, such as monobutyl phthalate, monobenzyl phthalate, and mono‐(2‐ethylhexyl) phthalate, are teratogenic in animals. Since foods are the major source of exposure to phthalates, information on levels of phthalates in foods is important for human exposure assessment. The objective of this review is to identify the knowledge gaps for future investigations by reviewing levels of a wide range of phthalates in a variety of foods, such as bottled water, soft drinks, infant formula, human milk, total diet foods, and others, migration of phthalates from various food‐packaging materials, and traditional and new methodologies for the determination of phthalates in foods.     

Occurrence of phthalate metabolites in human urine from several Asian countries

The occurrence of 14 phthalate metabolites was found in human urine samples collected from seven Asian countries: China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam. Phthalate metabolites were found in all samples, indicating widespread exposure of humans to phthalates in these Asian countries. The highest total (the sum of 14 phthalates) phthalate metabolite concentrations were found in samples collected from Kuwait (median: 1050 ng/mL), followed in decreasing order by samples from India (389 ng/mL), China (234 ng/mL), Vietnam (133 ng/mL), Japan (120 ng/mL), Korea (117 ng/mL), and Malaysia (94.9 ng/mL). The creatinine-adjusted median concentrations of total phthalates for urine samples from Kuwait, India, China, Vietnam, Japan, Korea, and Malaysia were 692, 506, 289, 119, 103, 104, and 169 μg/g creatinine, respectively. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono (2-isobutyl phthalate) (miBP), mono-n-butyl phthalate (mBP), and metabolites of di-(2-ethylhexyl) phthalate (DEHP) were the dominant compounds, collectively accounting for >95% of the total concentrations in the samples from the seven countries. The profiles of urinary phthalate metabolite concentrations varied among the samples collected from the seven countries. Urine samples from Kuwait contained the highest concentrations of mEP (median: 391 ng/mL), mBP (94.1 ng/mL), and the metabolites of DEHP (202 ng/mL), whereas samples from China and Japan contained the highest concentrations of miBP (50.8 ng/mL) and mMP (17.5 ng/mL), respectively. mEP was the predominant metabolite in urine samples from India and Kuwait (accounting for 49% of the total), mBP and miBP were the predominant compounds in samples from China (52%), and DEHP metabolites were the predominant compounds in samples from Korea (46%) and Vietnam (52%). Based on the urinary concentrations of mEP, mBP, miBP, and DEHP metabolites of the samples from the seven Asian countries, we estimated daily intake rates of diethyl phthalate (DEP), dibutyl phthalate (DBP), and DEHP. The results indicated that people in the seven Asian countries are exposed to DEP, DBP, and DEHP at levels well below the reference doses (RfD) suggested as unsafe by the U.S. Environmental Protection Agency (EPA). The estimated exposure doses to DEHP in Kuwait, however, were above the RfD recommended by the EPA.     

Development and application of a method for analysis of phthalates in ham sausages by solid-phase extraction and gas chromatography–mass spectrometry

A gas chromatography-mass spectrometry assay was developed and successfully applied for the determination of phthalates in ham sausage migrated from packaging film. The phthalates studied were dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), benzylbutyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP) , with dibutyl adipate (DBA) as internal standard. The sample pre-treatments included extraction with n-hexane, solvent evaporation and reconstitution with acetonitrile before and after solid-phase extraction (SPE). The extraction and cleaning up procedure was carried out with cartridges containing dimethyl butylamine groups, which showed extraction efficiencies over 87.3%. The calibration curves obtained were linear with correlation coefficients greater than 0.99. The method proved to be accurate and precise for the six phthalates used. It was successfully applied to a study on the migration of phthalates from packaging PVC film into ham sausage.     

Determination of Phthalate Residues in Different Types of Yogurt by Gas Chromatography-Mass Spectrometry and Estimation of Yogurt-Related Intake of Phthalates

Phthalates are potential endocrine-disrupting chemicals, found widely in the environment, and commonly used to make plastics softer and more flexible. Little information is available about the presence of phthalates in yogurt products sold on the world market. This study aimed to develop a sensitive GC-MS method for the determination of selected phthalates in yogurt and residue levels in fruit yogurts together with the packaging materials and to estimate a yogurt-related exposure to phthalates in the Turkish population. Acetonitrile extraction followed by cleanup procedures using different adsorbents yielded relatively clean extracts. The presence as the percent of selected phthalates tested—dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP), dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-octyl phthalate (DNOP), and benzyl butyl phthalate (BBP)—were determined as 76, 70, 70, 54, 20, and 8% of the samples, respectively, for the phthalates, ranging from <LOQ to 1640 μg/kg. The highest concentrations were found in cherry yogurt among the fruit yogurts, while banana and pineapple yogurts contained the least. The results indicate that the estimated daily intakes for phthalates were below tolerable daily intakes.     

Comparative assessment of human exposure to phthalate esters from house dust in China and the United States

Because of volatilization and leaching from their application in consumer and personal care products, phthalate esters are ubiquitous contaminants in the indoor environment. In this study, we measured concentrations and profiles of 9 phthalate esters in indoor dust samples collected from six cities in China (n = 75). For comparison, we also analyzed samples collected from Albany, New York, USA (n = 33). The results indicated that concentrations, except for dicyclohexyl phthalate (DCHP) and bis(2-ethylhexyl) phthalate (DEHP), and profiles of phthalate esters varied significantly between the two countries. Concentrations of diethyl phthalate (DEP), di-n-hexyl phthalate (DNHP), and benzyl butyl phthalate (BzBP) were 5 to 10 times higher in dust samples collected from Albany than those from the Chinese cities. In contrast, concentrations of di-iso-butyl phthalate (DIBP) in dust samples from Albany were 5 times lower than those from the Chinese cities. We estimated the daily intake (DI) of phthalate esters through the routes of dust ingestion and dermal dust absorption. The extent of contribution of indoor dust to human exposures varied, depending on the type of phthalate esters. The contribution of dust to DEHP exposure was 2-5% and 10-58% of the estimated total DIs in China and the USA, respectively. On the basis of the estimates of total DIs of phthalates, extrapolated from urinary metabolite concentrations, the contributions of inhalation, dermal absorption, and dietary intake to total DIs were estimated. The results indicated that dietary intake is the main source of exposure to DEHP (especially in China), whereas dermal exposure was a major source for DEP. This is the first study to elucidate sources of human exposure to phthalates among the general population in China.     

Quantitative identification of unknown exposure pathways of phthalates based on measuring their metabolites in human urine

Humans are exposed to ubiquitous phthalates via multiple pathways. Exposures to phthalates have been estimated in some previous risk assessments in Japan based on point-of-contact measurement or scenario evaluation approaches. While the Japanese national government has regulated the use of di(2-ethylhexyl)phthalate (DEHP) and excluded several other phthalates from its regulation based on some of them, it is unclear whether such past exposure assessment studies fully assessed total human exposure to phthalates. In the present study, we measured their urinary metabolites, which show direct evidence of human exposure to phthalates. We recruited voluntary participants (N = 36) who agreed to donate urine samples, and measured the urinary concentrations of phthalate metabolites using enzymatic deconjugation, solid-phase extraction, and high-performance liquid-chromatography isotope-dilution tandem mass spectrometry. We then derived the daily intakes of their respective phthalates based on steady state assumption and finally compared them with the corresponding estimated daily intakes of each phthalate via diet and air derived from previous exposure or risk assessments in Japan. These comparisons showed that exposures to dimethyl phthalate, diethyl phthalate, and di-n-butyl phthalate via diet and air accounted for less than half of their respective total exposures. On the other hand, it appears that dietary intake was more predictive for the total exposure to n-butyl-benzyl phthalate and DEHP. The probabilities that the log normal distribution of each phthalate daily intake estimated from the present study exceeds the corresponding tolerable daily intake were estimated to be less than 10(-4).     

Contamination of wines and spirits by phthalates: types of contaminants present,contamination sources and means of prevention

This research determines the concentrations of various phthalates in French wines and grape spirits marketed in Europe or intended for export. Dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP) were the most frequently detected compounds in the wines analysed. While only 15% of the samples examined contained quantifiable concentrations (> 0.010 mg kg^–1) of DEHP and BBP, 59% of the wines contained significant quantities of DBP, with a median value as high as 0.0587 mg kg^–1. Only 17% of the samples did not contain any detectable quantity of at least one of the phthalates and 19% contained only non-quantifiable traces. In the spirits analysed, DBP (median = 0.105 mg kg^–1) and DEHP (median = 0.353 mg kg^–1) were the substances measured at the highest concentrations, as well as the most frequently detected (90% of samples). BBP was present in 40% of the samples at an average concentration of 0.026 mg kg^–1. Di-isobutyl phthalate (DiBP), which is not permitted in contact with food, was found in 25% of the spirits tested. According to the specific migration limits (SML) for materials in contact with food, slightly more than 11% of the wines analysed were non-compliant, as they exceeded the SML for DBP (0.3 mg kg^–1); just under 4% were close to the SML for DEHP. Concerning spirits, 19% of the samples analysed were considered non-compliant to the SML for DBP and nearly 7% were close to the SML for DEHP. The aged grape spirits analysed were often excessively contaminated with DiBP, which is not permitted to be used in contact with food (> 0.01 mg kg^–1). A study of various materials frequently present in wineries revealed that a relatively large number of polymers sometimes contained high concentrations of phthalates. However, the epoxy resin coatings used on vats represented the major source of contamination.     

Metabolism of phthalates in humans

Phthalates are synthetic compounds widely used as plasticisers, solvents and additives in many consumer products. Several animal studies have shown that some phthalates possess endocrine disrupting effects. Some of the effects of phthalates seen in rats are due to testosterone lowering effects on the foetal testis and they are similar to those seen in humans with testicular dysgenesis syndrome. Therefore, exposure of the human foetus and infants to phthalates via maternal exposure is a matter of concern. The metabolic pathways of phthalate metabolites excreted in human urine are partly known for some phthalates, but our knowledge about metabolic distribution in the body and other biological fluids, including breast milk, is limited. Compared to urine, human breast milk contains relatively more of the hydrophobic phthalates, such as di-n-butyl phthalate and the longer-branched, di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP); and their monoester metabolites. Urine, however, contains relatively more of the secondary metabolites of DEHP and DiNP, as well as the monoester phthalates of the more short-branched phthalates. This differential distribution is of special concern as, in particular, the hydrophobic phthalates and their metabolites are shown to have adverse effects following in utero and lactational exposures in animal studies.     

Occurrence and air-sea exchange of phthalates in the Arctic

Air and seawater samples were taken simultaneously to investigate the distribution and air-sea gas exchange of phthalates in the Arctic onboard the German Research Ship FS Polarstern. Samples were collected on expeditions ARK XX1&2 from the North Sea to the high Arctic (60 degrees N-85 degrees N) in the summer of 2004. The concentration of sigma6 phthalates (dimethyl phthalate (DMP), diethyl phthalate (DEP), di-i-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBP), and diethylhexyl phthalate (DEHP)) ranged from 30 to 5030 pg L(-1) in the aqueous dissolved phase and from 1110 to 3090 pg m(-3) in the atmospheric gas phase. A decreasing latitudinal trend was present in the seawater and to a lesser degree in the atmosphere from the Norwegian coast to the high Arctic. Overall, deposition dominated the air-sea gas exchange for DEHP, while volatilization from seawater took place in the near-coast environment. The estimated net gas deposition of DEHP was 5, 30, and 190 t year(-1) for the Norwegian Sea, the Greenland Sea, and the Arctic, respectively. This suggests that atmospheric transport and deposition of phthalates is a significant process for their occurrence in the remote Atlantic and Arctic Ocean.