Phthalic Acid Diesters Research Articles

Phthalate Exposure and Pediatric Asthma: A Case Control Study Among Egyptian Children

Background: Phthalates, which are diesters of phthalic acid, are commonly used as plasticizers and additives in various consumer products. Several phthalates have been identified as substances of high concern. Exposure to phthalate esters (PAEs) has been linked to asthma in children, but the specific impacts of PAEs on asthmatic children were not well understood. Objective: The objective of this study was to compare urinary phthalate concentrations in asthmatic and non-asthmatic children and to identify potential sources of exposure as risk factors for asthma. Methods: A case control study was conducted for 100 Egyptian children aged 8-16 years (50 asthmatics and 50 healthy controls). Asthma was identified using GINA guidelines. Socio-demographic and probable risk factors were assessed, in addition to measuring phthalate levels in urine samples using high-performance liquid chromatography. Results and conclusion: Mean urinary Mono-methyl as well as Mono-benzyl levels were highly significant in asthmatic children compared to control group (895.26ng/ mL vs 548.55 ng/mL and 13.5 ng/mL vs 2.07 ng/mL respectively) (p= 0.001). The number of asthmatic children living in houses painted with non-plastic paint was significantly lower (P<0.05) than children living in houses painted with other paints. No association between floor type and asthma was reported. The frequent use of personal care products and plastic painting of walls were identified by multiple logistic regression analysis as the highly significant predictors of asthma in the studied subjects. The declared higher levels of urinary phthalate metabolites (Mono-methyl and Mono-benzyl) in Egyptian asthmatic children may reveal the probable risk of phthalate exposure in triggering bronchial asthma.

Study on determination of PAEs in water samples by using solid phase extraction combined with gas chromatography-mass spectrometry

Phthalic acid diesters (PAEs) are industrial chemicals used as plasticizers in a variety of commercial products. Due to wide usage, PAEs have been found in various environments and their human exposure risks have also attracted a lot of concerns. However, little information about the distributions of PAEs in the water samples collected from Vietnam was reported. In this study, the method for the determination of nine typical PAEs in water samples by using the solid phase extraction (SPE) combined with gas chromatography-mass spectrometry (GC-MS) technique was optimized. The method detection limits (MDLs) and method quantitation limits (MQLs) of PAEs in water samples were in ranges of 0.2–0.4 ng/L and (0.6-1.2) ng/L, respectively. The recoveries of surrogate compounds in blank and real samples ranged from (74.8 to 93.9) %, with RSD < 9.2 %. The calibration curve for all standards was linear over a concentration range of (1.0-1,000) ng/mL (with R2 ≥ 0.998). The total concentrations of PAEs measured in bottled water of six brands were ranged from 10.0 ng/L to 6,690 ng/L. Among the studied PAEs, di-(2-ethylhexyl) phthalate (DEHP) was found at the highest frequencies and concentrations. Overall, the distribution of PAEs in plastic bottled water is significantly lower than the permitted regulations (only with DEHP) in drinking water by the Ministry of Health of Vietnam in 2011. ® 2023 Journal of Science and Technology - NTTU

Study on determination of PAEs in water samples by using solid phase extraction combined with gas chromatography-mass spectrometry

Phthalic acid diesters (PAEs) are industrial chemicals used as plasticizers in a variety of commercial products. Due to wide usage, PAEs have been found in various environments and their human exposure risks have also attracted a lot of concerns. However, little information about the distributions of PAEs in the water samples collected from Vietnam was reported. In this study, the method for the determination of nine typical PAEs in water samples by using the solid phase extraction (SPE) combined with gas chromatography-mass spectrometry (GC-MS) technique was optimized. The method detection limits (MDLs) and method quantitation limits (MQLs) of PAEs in water samples were in ranges of 0.2–0.4 ng/L and (0.6-1.2) ng/L, respectively. The recoveries of surrogate compounds in blank and real samples ranged from (74.8 to 93.9) %, with RSD < 9.2 %. The calibration curve for all standards was linear over a concentration range of (1.0-1,000) ng/mL (with R2 ≥ 0.998). The total concentrations of PAEs measured in bottled water of six brands were ranged from 10.0 ng/L to 6,690 ng/L. Among the studied PAEs, di-(2-ethylhexyl) phthalate (DEHP) was found at the highest frequencies and concentrations. Overall, the distribution of PAEs in plastic bottled water is significantly lower than the permitted regulations (only with DEHP) in drinking water by the Ministry of Health of Vietnam in 2011.
 ® 2023 Journal of Science and Technology - NTTU

Co-occurrence of phthalic acid esters (PAEs) and cyclic volatile methylsiloxanes (cVMSs) in fine particulate matter (PM0.5 and PM0.1) collected from an industrial area in Vietnam

Distribution patterns of 10 phthalic acid diesters (PAEs) and four cyclic volatile methylsiloxanes (cVMSs) were investigated in fine particulate matter (PM0.1 and PM0.5) collected from Bac Ninh, an industrial province in Vietnam during September–October in 2021. Total concentrations of PAEs found in PM0.1 and PM0.5 were in the ranges of 1.76–372 (median: 34.0 ng/m3) and 2.23–895 ng/m3 (median: 15.4 ng/m3), respectively. Among PAEs, di-n-butyl phthalate (DBP) was the most abundant compound found in PM0.1, whereas, di-2-(ethyl)hexyl phthalate (DEHP) was measured at the highest concentration in PM0.5. Total concentrations of cVMSs measured in PM0.1 and PM0.5 were in the ranges of method quantification limit (MQL)–203 (median: 2.10 ng/m3) and MQL–537 ng/m3 (median: 0.389 ng/m3), respectively. Among cVMSs, decamethylcyclopentasiloxane (D5) was found at the highest concentration in both PM0.1 and PM0.5 fractions of particulate matter. The concentration ratios between PAEs and cVMSs in PM0.1/PM0.5 were greater than 1 (except di-n-octyl phthalate: DnOP), suggesting that these chemicals tend to sorb to PM0.1 more preferentially than PM0.5. Among sampling locations, high concentrations of PAEs and cVMSs were found at traffic intersections (Que Vo district) and a craft village (Tu Son city). Relatively stronger correlations existed between cVMSs pairs in PM0.1 and PM0.5 (correlation coefficient: 0.73–1) than those of PAEs (−0.83–0.90). The human exposure doses to PAEs and cVMSs through inhalation of particulate matter were estimated based on the measured concentrations in PM0.1 and PM0.5 fractions. The estimated exposure doses of PAEs and cVMSs for infants (7.1 ng/kg-bw/d and 2.5 ng/kg-bw/d) were higher than those for adults (2.6 ng/kg-bw/d and 0.9 ng/kg-bw/d).

Evaluation and identification of chemical migrants leached from baby food pouch packaging

Multilayer plastic pouch (MLPP) has an estimated 9% annual increase of market growth. However, the migrants it can introduce to food has not yet been systematically studied. A total of 79 MLPPs for baby food were purchased from major retail outlets in Australia. The methodology for testing chemical migration followed the design of previous studies using four types of selected simulants according to the European Committee Regulation No. 10/2011 method. Four bisphenols and five phthalic acid diesters (PAEs) were detected, including the ones known for endocrine disrupting effect in human. Three intentionally added and 23 non-intentionally added substances (NIAS) were tentatively identified through a suspect screening procedure. Out of the 23 NIAS, neopentyl glycol – phthalic acid – 1,6-hexanediol – phthalic acid oligomer was identified for the first time with MLPP. A further two NIAS were detected for the first time in baby food related products. For 40% of the pouches where adipic acid - diethylene glycol was detected, the estimated exposure from consuming one pouch of food per day may exceed the threshold of toxicological concern established based on the Cramer classification.

Phthalate diester occurrence in marine feed and food (Mediterranean Sea).

Organic contaminants such as diesters of phthalic acid (PAEs) can be conveyed by microplastics in aquatic environment and constitute a relevant risk to marine organisms and humans that consume them. A method was developed for the identification and quantitative detection of 6 dimethyl phthalate (DMP), di-ethyl phthalate (DEP), di-n-butyl phthalate (DNBP), butyl benzyl phthalate (BBP), di-2-ethylesyl phthalate (DHEP), and di-n-octyl phthalate (DnOP). PAEs were then quantified in mesozooplankton, mollusk bivalves, and fish from the north-western Mediterranean Sea. Among all PAEs, DEHP was found in all zooplankton samples, in 30% of fish samples, and in 10% of bivalve samples. DBP was instead recovered in only 4% of samples (plankton and fish).

Species-Specific Activation of Transient Receptor Potential Ankyrin 1 by Phthalic Acid Monoesters.

Phthalic acid (PA) diesters are widely used in consumer products, as plasticizers, and are ubiquitous environmental pollutants. There is a growing concern about their adjuvant effect on allergic diseases. Although its precise mechanism remains unknown, possible involvement of transient receptor potential ankyrin 1 (TRPA1) has been suggested. Hence, in this study, the activation of human and mouse TRPA1s by a series of PA di- and monoesters was investigated using a heterologous expression system in vitro. Consequently, it was found that monoesters activated human TRPA1, where EC50 values were in the order of mono-hexyl > mono-heptyl > mono-n-octyl > mono-2-ethylhexyl > mono-isononyl and mono-isodecyl esters. Significant species differences in TRPA1 activation by PA monoesters were also discovered; PA monoesters activated human TRPA1 but not mouse TRPA1 in a concentration-dependent manner up to 50 µM. These findings suggest that PA esters may exert TRPA1-dependent adverse effects on humans, which have never been demonstrated in experimental animals.

Hazards of phthalate exposure on fish reproduction – a review

Phthalates (diesters of phthalic acid) are widely used as plasticizers and additives in many consumer products. Laboratory animal studies have reported the endocrine-disrupting and reproductive effects of phthalates and human exposure to this class of chemicals is a concern. Several phthalates including DEHP, BBP, DBP and etc. have been recognized as substances of high concern. This study aims to systematically review the literature on effects of exposure to phthalates including ovarian effects, testicular effects, effects on reproductive hormonal level as well as gene level and effects on breeding performances in fishes. Related literature search was done through Scopus, Google Scholar, Pub-Med and the reference lists of previous review articles to identify relevant articles published in each subject area. The inclusion criteria were original research, cross-sectional studies, case-control studies, interventional studies and review articles. The search was limited to English language papers. Finally, this review paper provides all current information on the hazards of various phthalate exposures on fish reproduction. The available data demonstrate that phthalate exposure is associated with reproductive disorders in both male and female fishes. Exposure of phthalates causes alteration in reproductive gene expression level as well hormonal level, changes in gamete quality parameters and also has impacts on spawning performances in both sexes.

Exposure estimates of phthalates and DINCH from foods and personal care products in comparison with biomonitoring data in 24-hour urine from the Norwegian EuroMix biomonitoring study

Phthalates are diesters of phthalic acid and have been widely used as plasticizers in polyvinyl chloride (PVC) plastics. Phthalates are also used as excipients in pharmaceuticals and personal care products (PCPs). Phthalates can migrate from the plastic into the air, water and food, and humans can be exposed via multiple pathways such as dermal, oral and inhalation. There is evidence that phthalates can induce reproductive and developmental toxicity not only in experimental animals but also in humans through disruption of estrogenic activity. The aim of this study was to collect concentration data on five phthalates in foods and PCPs from the scientific literature and combine these with food consumption data and PCP use frequency data from the EuroMix biomonitoring (BM) study in order to assess exposure. Probabilistic exposure assessments of phthalates were performed from foods and PCPs. Due to the very limited data available in the literature for DINCH, an exposure assessment was not carried out for this compound. The food groups with the highest contribution to phthalates exposure were: beverages, dairy, bread and meat products. The exposure estimates were compared with the measured phthalate metabolite levels from 24-hour urine samples. Regarding the oral route, measured phthalate exposure was between the lower bound (LB) and medium bound (MB) estimated exposure for all phthalates, except for DEP. The measured exposure from urine correlated with the estimated exposure from food for DEHP and DBP, while for BBP and DEP it correlated with the exposure estimates from PCPs. There were no significant differences between the BM data and the estimated exposure, except for DINP for males (p = 0.01). The LB and MB phthalate exposures estimated from foods and PCPs and the measured exposure from the urine were considerably lower than their respective tolerable daily intake (TDI) values established by the European Food Safety Authority (EFSA) and the World Health Organization (WHO). For the upper bound (UB), the exposure estimates are approximately double the TDI; however, this is regarded as a worst-case estimate and has low correlation with the measured exposure.

Risk assessment of phthalates based on aggregated exposure from foods and personal care products and comparison with biomonitoring data.

Phthalates are a group of diesters of phthalic acid and have been widely used by the industry as plasticisers giving flexibility and durability to polyvinyl chloride (PVC) plastics. Commonly their uses vary from plasticisers in food contact materials and toys to emulsifying agents in personal care products. Phthalates are not covalently bound to PVC, thus they can migrate into the air, skin, water, food and the environment. The omnipresence of phthalates results in human exposure via multiple pathways such as dermal, oral and inhalation for prolonged periods. There is evidence that phthalates can induce disruption in oestrogenic activity, reproductive, developmental and liver toxicity both in experimental animals and potentially in humans. The aim of this technical report is to summarise the activities of the fellow performed at the Norwegian Institute of Public Health (NIPH). The goals of the work programme were collecting concentration levels on five specific phthalates from the scientific literature and combining them with consumption/use data reported in a biomonitoring study part of a Horizon 2020 project (EuroMix), and finally, estimate the aggregate phthalate exposure from food and personal care products and compare them with the measured phthalate levels in urine samples collected in the biomonitoring study.

Transformation of phthalic acid diesters in an anaerobic/anoxic/oxic leachate treatment process

Abstract Transformations of di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) have been investigated in anaerobic/anoxic/oxic (A/A/O) leachate treatment processes. Although the DBP removal processes are different when the DBP initial concentration is different, the overall system DBP removal efficiencies are high (> 94%). DEHP is much more difficult to remove than DBP. The removal efficiency of DEHP is approximately 75%–78%. The results of mass balance calculations indicate that approximately 33.7%–50.7% of the DBP is degraded by the activated sludge, 48.9%–64.9% accumulates in the system, and 0.4%–1.4% is contained in the final effluent. Approximately 15.0%–19.0% of the DEHP is degraded by activated microcosms, 75.8%–79.0% accumulates in the system, and 5.2%–6.0% is contained in the final effluent. Biodegradation and adsorption to the activated sludge are the main mechanisms for DBP removal and adsorption to the activated sludge is the main mechanism for DEHP removal. The different removal mechanisms of the two PAEs may be related to their different molecular structures. However, PAEs are not really removed when they adsorb onto the sludge. Therefore, methods for decreasing PAEs adsorption and increasing the biodegradation efficiencies of the leachate treatment processes should be further investigated.

A Review of Biomonitoring of Phthalate Exposures.

Phthalates (diesters of phthalic acid) are widely used as plasticizers and additives in many consumer products. Laboratory animal studies have reported the endocrine-disrupting and reproductive effects of phthalates, and human exposure to this class of chemicals is a concern. Several phthalates have been recognized as substances of high concern. Human exposure to phthalates occurs mainly via dietary sources, dermal absorption, and air inhalation. Phthalates are excreted as conjugated monoesters in urine, and some phthalates, such as di-2-ethylhexyl phthalate (DEHP), undergo secondary metabolism, including oxidative transformation, prior to urinary excretion. The occurrence of phthalates and their metabolites in urine, serum, breast milk, and semen has been widely reported. Urine has been the preferred matrix in human biomonitoring studies, and concentrations on the order of several tens to hundreds of nanograms per milliliter have been reported for several phthalate metabolites. Metabolites of diethyl phthalate (DEP), dibutyl- (DBP) and diisobutyl- (DiBP) phthalates, and DEHP were the most abundant compounds measured in urine. Temporal trends in phthalate exposures varied among countries. In the United States (US), DEHP exposure has declined since 2005, whereas DiNP exposure has increased. In China, DEHP exposure has increased since 2000. For many phthalates, exposures in children are higher than those in adults. Human epidemiological studies have shown a significant association between phthalate exposures and adverse reproductive outcomes in women and men, type II diabetes and insulin resistance, overweight/obesity, allergy, and asthma. This review compiles biomonitoring studies of phthalates and exposure doses to assess health risks from phthalate exposures in populations across the globe.

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.

Removal of phthalic acid diesters through a municipal solid waste landfill leachate treatment process

We studied the removal of two phthalic acid diesters (PAEs), di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), from leachates of a municipal solid waste landfill treatment facility. The leachates originated from the adjusting unit, the anaerobic unit, the aerobic unit, the ultrafiltration membrane unit, and the reverse osmosis membrane unit. The initial concentrations of DBP and DEHP were 225.8 and 260.9 µg/L, respectively, which were reduced to 5.8 and 3.2 µg/L in the effluent, representing 97.4% removal of DBP and 98.8% removal of DEHP. DBP was removed stepwise during the process, mainly via degradation by microorganisms. Approximately, 70.1% of the DEHP was removed by the membrane processes, owing to physical retention of the compound by the membranes. The dissolved organic carbon occurred mostly in the 1–100 kDa molecular weight fraction. The positive correlation between dissolved organic carbon and DBP/DEHP concentrations in raw leachate and in effluents from each treatment unit showed that the interaction between dissolved organic matter and PAEs facilitated the removal of organic pollutants. Large amounts of PAEs can accumulate over long periods of time in the concentrated leachate product, which may make further leachate treatment more difficult and may lead to adverse impacts on the environment.

Characterization of estrogenic and androgenic activity of phthalates by the XenoScreen YES/YAS in vitro assay

The presented study investigates and compares the estrogenic and androgenic activities of commonly used diesters of phthalic acid (phthalates) using the XenoScreen YES/YAS assay. Phthalates are commonly used plasticizers in polymers dedicated for i.e. food and drug containers. Since phthalates are not chemically bonded to the polymer, they can leach or migrate from the polymer. Therefore, phthalates are identified as contaminants in a variety of consumer products. Investigation of estrogenic and androgenic activities of phthalates (DEP, DBP, BBP, DEHP and DINP) showed no significant effect of tested substances either on hERα or hAR receptors. Phthalates exhibited strong anti-estrogenic (IC50 for BBP=8.66μM, IC50 for DEHP=3.61μM and IC50 for DINP=0.065μM) and anti-androgenic (IC50 for BBP=5.30μM, IC50 for DEHP=2.87μM and IC50 for DINP=0.068μM) activities.

Design and Characterization of 4,5‐Bis(diarylamino)phthalic Acid Diesters as a New Class of Fluorophores Exhibiting Efficient Blue Emission in the Solid State

AbstractWe developed 4,5‐bis(diarylamino)phthalic acid diesters as blue fluorophores exhibiting efficient photoluminescence in powder and in a thin film of pol(methyl methacrylate). Increasing the electron‐donating nature of the substituents in the para positions of the diarylamino moieties in the dimethyl esters increased the redshift in the fluorescence spectrum. Replacing the methoxycarbonyl groups with aryloxylcarbonyl groups also induced a bathochromic shift in the fluorescence spectrum. Thus, the color of the emission was finely tuned by simple molecular modification. Single‐crystal X‐ray analysis revealed a twisted conformation with loose packing in the crystal. Density functional theory calculations suggested that the excitation process was governed by intramolecular charge transfer from the diarylamino moieties to the alkoxycarbonyl groups.

Biotin–streptavidin-amplified real-time immune-PCR assay for detecting dimethyl phthalate in beverage and drinking water samples

Dimethyl phthalate (DMP), one family of the phthalic acid diesters (PAEs), is an increasing widely used plasticizer. A sensitive and high-throughput direct competitive biotin-streptavidin-amplified system based on real-time immune-PCR (BA-rt-IPCR) techniques was developed for detecting DMP in beverage and drinking water samples. In our assay, we selected dimethyl 4-aminophthalate as the optimal DMP hapten to prepare high titer of rabbit polyclonal anti-DMP antibodies (pAb-DMP). Under the optimized conditions, the proposed method was used to detect DMP with a linearity range from 10 to 100ngL(-1), and the limit of detection (LOD) was 1.98pgL(-1). Finally, the results about DMP in beverage and drinking water samples were consistent with those using gas chromatography-mass spectrometry (GC-MS), which proved that the proposed immunoassay for detecting DMP in the environment was accurate, reliably rapid, and receptive.

Asymmetric phthalates—A special case for risk assessment

Phthalic acid diesters are ubiquitously present in the environment due to their intensive use as plasticizers. Human exposure to these contaminants has been proved by determining phthalates and their metabolites in human urine and blood. Particular phthalates with ester chain lengths of C4-C6 possess reprotoxic properties [T. Lovekamp-Swan & B. J. Davis, Environmental Health Perspectives 111 (2003) 139–145]. Asymmetric phthalic acid diesters with “critical” C4–C6 chain lengths have been pre-registered in REACH but information on their human metabolism is scarce. Theoretically, two different monoesters with either “critical” or “uncritical” ester moieties may be formed. Thus, for an adequate assessment of possible health risks of asymmetric phthalic acid esters it is essential to know, which of the monoesters are preferably formed by human metabolism. In order to gain insight into the metabolism of asymmetric phthalates, conversion of 11 asymmetric phthalic acid diesters was investigated by in vitro hydrolysis experiments using rat and human liver S9 homogenates. All asymmetric phthalates were fast hydrolysed into mixtures of both possible monoesters and as consequence; organisms are exposed to mixtures of phthalic acid monoesters. Based on these results, the risk assessment of asymmetric phthalic acid diesters seems to be more complex than that of symmetric phthalates because two different monoesters can be formed. This has implications for the risk assessment and the exposure assessment, as in case of asymmetric phthalic acid diesters with a critical chain length, the same metabolites can be formed which are responsible for the reprotoxic effects of already classified reprotoxic phthalates

Determination of phthalic acid diesters in human milk at low ppb levels

Phthalic acid diesters (PAE) are omnipresent in the human environment and food is a major contributor to the overall human exposure towards these chemicals. Due to developmental effects, PAE infants’ exposure via human milk has been subjected to a number of analytical studies. These previous studies, however, revealed that normal laboratory blank values are in the range of or even higher than human milk levels due to the presence of PAE in laboratory environments. In order to provide more reliable data on PAE exposure via human milk, the aim of this study was to develop and validate a robust and sensitive analytical method. This should be capable of removing matrix components efficiently and guarantee limits of quantification in the low ppb range. The method development took into account liquid–liquid extraction and selective pressurised fluid extraction (sPFE) as well as chromatography-based clean-up steps. The final method consisted of a liquid–liquid extraction followed by an automated chromatographic clean-up by an sPFE device. After volume reduction the cleaned extracts were analysed by quadrupole GC/MS. Quantification was based on internal standards. An extensive quality assurance and method test programme demonstrated conservatively determined limits of detection and quantification from 0.3 to 10 ng g−1 in human milk, with recoveries of internal standards from 50% to 101%. Thus, the method allowed the quality-assured detection of di-isobutyl phthalate (DiBP), di-n-butyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), di-allyl phthalate (DAP), benzylbutyl phthalate (BBP) and di-cyclohexyl phthalate (DcHP) in 30 human milk samples provided by 30 volunteers from southern Germany. DiBP, DBP and DEHP were the most commonly detected PAE, with median levels of 1.0, 0.6 and 2.3 ng g−1, respectively.

PHTHALATE EXPOSURE AND BREAST-CANCER RISK ACCORDING TO PPARγ AND PPARGC1B GENOTYPES

Background and Aims: Some phthalic acid diesters (phthalates) have recently been associated with breast cancer (BC). In this study we evaluated if that association is modified according to PPARγ and PPARGC1B genotypes. Methods: 208 BC cases were age-matched with 220 population controls from the north of Mexico. Urine concentrations of nine phthalate metabolites were determined by isotope dilution/high-performance liquid chromatography and mass spectrometry. Genotyping of variant Pro12Ala (rs1801281) of the PPARγ gene and variants Ala203Pro (rs7732671) and Val279Ile (rs17572019) of the PPARGC1B gene were carried out by traditional PCR with TaqMan probes. Results: The three polymorphisms under study were in Hardy-Weinberg equilibrium, with a minor allele frequency of 0.11, 0.14, and 0.14 for the Pro12Ala, Ala203Pro, and Val279Ile variants respectively. Only the association between the higher levels of urinary mono-(2-ethylhexyl) phthalate (MEHP) concentration with BC was modified after the stratification by the PPARγ gene Pro12Ala polymorphism alleles (for G carriers: OR=0.59 CI95%=0.25-1.39; for C carriers: OR=1.50 CI95%=1.08-2.08); and the association between the mono-iso-butyl phthalate (MiBP) with BC in women with higher urinary concentrations was modified after the stratification by the PPARGC1B gene Ala203Pro polymorphism alleles (for C carriers OR=1.12 CI95%=0.55-2.27; for G carriers OR=0.67 CI95%=0.44-1.01). Conclusions: Our results suggest the presence of a gene-environment interaction influencing BC risk that could be determined by the magnitude of exposure.