Phthalates exposure of Chinese reproductive age couples and its effect on male semen quality,a primary study

Phthalates are suspected of having adverse effects on androgen-regulated reproductive development in animals and may be toxic for human sperm. The purposes of our study were to investigate the general exposure of a Chinese reproductive age cohort to these ubiquitous pollutants and to assess their potential effect on semen quality.Six phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) were measured in spot urines of 150 individuals recruited from a Chongqing, China, reproductive institute. The questionnaire and clinical data were evaluated, and the correlations of phthalate exposure and semen qualities like semen volume, sperm concentration, motility and sperm motion parameters, were determined by multiple logistic regression analysis.The creatinine adjusted average concentrations for MMP, MEP, MBP, MBzP, MEHP and MEOHP were 41.3, 300, 41.0, 0.78, 2.99 and 3.90 μg/g, respectively. After adjustment for age, body mass index (BMI), abstinence, smoking, drinking, and education, there was a borderline-significant dose–response relationship between MBP and sperm concentration, with odd ratios (ORs) 1.0, 6.8 and 12.0 for increasing exposure tertiles (p = 0.05). Although the dose–response relationships for MMP and MEP versus sperm concentration were not significant, a significant positive correlation between MEP and straight-line velocity of sperm motion was observed.The present data may imply some effects of phthalate exposure on semen. However, due to the small sample size, our finding needs to be confirmed on a larger population.     

Morphology,spatial distribution,and concentration of flame retardants in consumer products and environmental dusts using scanning electron microscopy and Raman micro-spectroscopy

We characterized flame retardant (FR) morphologies and spatial distributions in 7 consumer products and 7 environmental dusts to determine their implications for transfer mechanisms, human exposure, and the reproducibility of gas chromatography–mass spectrometry (GC–MS) dust measurements. We characterized individual particles using scanning electron microscopy/energy dispersive x-ray spectroscopy (SEM/EDS) and Raman micro-spectroscopy (RMS). Samples were screened for the presence of 3 FR constituents (bromine, phosphorous, non-salt chlorine) and 2 metal synergists (antimony and bismuth). Subsequent analyses of select samples by RMS enabled molecular identification of the FR compounds and matrix materials. The consumer products and dust samples possessed FR elemental weight percents of up to 36% and 31%, respectively. We identified 24 FR-containing particles in the dust samples and classified them into 9 types based on morphology and composition. We observed a broad range of morphologies for these FR-containing particles, suggesting FR transfer to dust via multiple mechanisms. We developed an equation to describe the heterogeneity of FR-containing particles in environmental dust samples. The number of individual FR-containing particles expected in a 1-mg dust sample with a FR concentration of 100 ppm ranged from < 1 to > 1000 particles. The presence of rare, high-concentration bromine particles was correlated with decabromodiphenyl ether concentrations obtained via GC–MS. When FRs are distributed heterogeneously in highly concentrated dust particles, human exposure to FRs may be characterized by high transient exposures interspersed by periods of low exposure, and GC–MS FR concentrations may exhibit large variability in replicate subsamples. Current limitations of this SEM/EDS technique include potential false negatives for volatile and chlorinated FRs and greater quantitation uncertainty for brominated FR in aluminum-rich matrices.     

Increased levels of phthalates in very low birth weight infants with septicemia and bronchopulmonary dysplasia

Very low birth weight infants (VLBW; birth weight < 1500 g) are exposed to potentially harmful phthalates from medical devices during their hospital stay. We measured urinary phthalate concentrations among hospitalized VLBW infants participating in a nutritional study. Possible associations between different phthalates and birth weight (BW), septicemia and bronchopulmonary dysplasia (BPD) were evaluated. Forty-six VLBW infants were enrolled in this randomized controlled nutritional study. The intervention group (n = 24) received increased quantities of energy, protein, fat, essential fatty acids and vitamin A, as compared to the control group (n = 22). The concentrations of 12 urinary phthalate metabolites were measured, using high-performance liquid chromatography coupled to tandem mass spectrometry, at 3 time points during the first 5 weeks of life. During this study, the levels of di (2-ethylhexyl) phthalate (DEHP) metabolites decreased, whereas an increasing trend was seen regarding metabolites of di-iso-nonyl phthalate (DiNP). Significantly higher levels of phthalate metabolites were seen in infants with lower BW and those diagnosed with late onset septicemia or BPD. A significant positive correlation between the duration of respiratory support and DEHP metabolites was observed (p ≤ 0.01) at 2.9 weeks of age. Birth weight was negatively associated with urinary phthalate metabolite concentrations. Infants with lower BW and those diagnosed with septicemia or BPD experienced prolonged exposure from medical equipment containing phthalates, with subsequent higher levels of phthalate metabolites detected. Clinical Trial Registration no.: NCT01103219.     

Predictors and long-term reproducibility of urinary phthalate metabolites in middle-aged men and women living in urban Shanghai

Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997–2000 and 2002–2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤ 0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl) phthalate, had a Spearman rank correlation coefficient ≥ 0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population.     

Lactational exposure to phthalates in Southern Italy

BackgroundPhthalates, reproductive toxicants in animals, are synthetic chemicals with ubiquitous human exposures because of their extensive use, with potential detrimental health effects. Infants are considered to represent a population at increased risk, as they are exposed early in life to several different sources of exposure to phthalates.Objectives and methodsLittle information exists on phthalate exposure through breast milk from different geographic areas. By means of a LC/LC–MS/MS method we tested the presence of several different phthalate metabolites in breast milk from 62 healthy mothers living in Southern Italy.ResultsThe simple monoesters mono-isobutyl phthalate (MiBP) (median 18.8 μg/l) and mono(2-ethylhexyl) phthalate (MEHP) (median 8.4 μg/l) were present in all milk samples, whereas mono-n-butyl phthalate (MnBP) (median 1.5 μg/l) and mono-benzyl phthalate (MBzP) (median < 0.3 μg/l) were found in 64.5% and 43.5% of the samples, respectively. Among the oxidative metabolites of DEHP and DiNP only mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and monoisononyl phthalate with one hydroxyl group (OH-MiNP) were detectable in one and 13 samples (21%), respectively.ConclusionsThese findings indicate that exposure to phthalates through breast milk in Southern Italian infants is comparable to that of other countries, thus confirming that human milk may represent an additional potential source of phthalate exposure in a population at increased risk. However, different milk concentrations of MiBP may suggest a different pattern of usage of di-iso-butyl phthalate in Europe, as compared to USA, whereas for the first time, we detected an oxidative DiNP metabolite, whose significance remains unclear.     

Phthalates in house dust

The main objective of this study was to generate a fast analytical method to determine the five phthalates benzylbutylphthalate (BBP), dibutylphthalate (DBP), di-(2-ethylhexyl)-phthalate (DEHP), di-isodecylphthalate (DIDP), and di-isononylphthalate (DINP) in house dust. To achieve this liquid chromatography electrospray tandem mass spectrometry (LC–ESI–MS/MS) was used for measurement. The risk of lab- and cross-contamination was nearly eliminated completely as a very short and fast sample preparation including a sieving step and an ultrasonic extraction for the analytes from the dust samples was used. Quantification through internal standard calibration resulted in low limits of determination (DEHP 4 mg kg^? 1 to DBP 14 mg kg^? 1). A potential interaction between the analytes DIDP and DINP during chromatographic measurement could be excluded while performing a two level factorial design. Furthermore it was examined to what extend carpet and plastic materials respectively have influence on the total amount of phthalates in dust. It could be shown that apartments in which a minimum of both of these sources appeared revealed the lowest total amount of sum of phthalates in dust (median 362 mg kg^? 1).     

Phthalates dietary exposure and food sources for Belgian preschool children and adults

Numerous studies have indicated that for phthalates, the intake of contaminated foods is the most important exposure pathway for the general population. Up to now, data on dietary phthalate intake are scarce and – to the authors' knowledge – not available for the Belgian population. Therefore, the purpose of this study was: (1) to assess the long-term intake of the Belgian population for eight phthalates considering different exposure scenarios (benzylbutyl phthalate (BBP); di-n-butyl phthalate (DnBP); dicyclohexyl phthalate (DCHP); di(2-ethylhexyl) phthalate (DEHP); diethyl phthalate (DEP); diisobutyl phthalate (DiBP); dimethyl phthalate (DMP), di-n-octyl phthalate (DnOP)); (2) to evaluate the intake of BBP, DnBP, DEP and DEHP against tolerable daily intake (TDI) values; and (3) to assess the contribution of the different food groups to the phthalate intake. The intake assessment was performed using two Belgian food consumption databases, one with consumption data of preschool children (2.5 to 6.5 years old) and another of adults (≥ 15 years old), combined with a database of phthalate concentrations measured in over 550 food products sold on the Belgian market. Phthalate intake was calculated using the ‘Monte Carlo Risk Assessment’ programme (MCRA 7.0). The intake of DEHP was the highest, followed by DiBP. The intake of BBP, DnBP and DEP was far below the TDI for both children and adults. However, for DEHP, the 99th percentile of the intake distribution of preschoolers in the worst case exposure scenario was equal to 80% of the TDI, respectively. This is not negligible, since other exposure routes of DEHP exist for children as well (e.g. mouthing of toys). Bread was the most important contributor to the DEHP intake and this may deserve further exploration, since the origin of this phthalate in bread remains unclear.     

Could exposure to phthalates speed up or delay pubertal onset and development? A 1.5-year follow-up of a school-based population

PurposePhthalates may interfere with the timing of pubertal development in adolescence and existing studies have shown inconsistent results. This study aims to assess the associations of pubertal onset and progression with urinary concentrations of phthalate metabolites in school-aged boys and girls.MethodsUsing isotope-dilution liquid chromatography tandem mass spectrometry, we analyzed 6 phthalate metabolites in urine samples of 430 children (222 boys and 208 girls) aged 9.7 ± 2.2 years (age range 6.1 to 13.8 years) at baseline and 18 months of follow-up. The associations of exposures to phthalates with pubertal development such as the testis, breast and pubic hair were evaluated using ordered logistic regression models, adjusting for baseline development stage, current chronological age, current body fat composition, and parental education.ResultsUrinary mono-n-butyl phthalate (MnBP) was associated with a 39% increase in the odds of presenting lower pubic hair development stages in boys, and mono (2-ethylhexyl) phthalate (MEHP) (p < 0.10), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were associated with 54%–65% increase in the odds of presenting higher breast development stages in girls (p < 0.05), while MEHHP and MEOHP were also associated with a 70% increase in the odds of menarche onset (p < 0.05). After adjusting for potential confounding variables, the associations of girls' pubertal onset with MnBP, MMP, MEP and MEHP were significant. The odds of girls' breast onset were 4 to 10 times higher in high MnBP, MMP, MEP or MEHP exposure group than in low exposure group.ConclusionsOur findings suggest subtle effects of phthalate metabolites associated with pubertal onset and progression. MnBP exposure may be associated with delayed pubic hair development in boys, while MnBP, MMP, MEP, and MEHP exposures may be associated with breast onset, and MEHP metabolites associated with speedup in breast development progression and earlier menarche onset in girls.     

ATR-FTIR spectroscopy reveals polycyclic aromatic hydrocarbon contamination despite relatively pristine site characteristics: Results of a field study in the Niger Delta

Fourier-transform infrared (FTIR) spectroscopy is an emerging technique to detect biochemical alterations in biological tissues, particularly changes due to sub-lethal exposures to environmental contaminants. We have previously shown the potential of attenuated total reflection FTIR (ATR-FTIR) spectroscopy to detect real-time exposure to contaminants in sentinel organisms as well as the potential to relate spectral alterations to the presence of specific environmental agents. In this study based in the Niger Delta (Nigeria), changes occurring in fish tissues as a result of polycyclic aromatic hydrocarbon (PAH) exposure at contaminated sites are compared to the infrared (IR) spectra of the tissues obtained from a relatively pristine site. Multivariate analysis revealed that PAH contamination could be occurring at the pristine site, based on the IR spectra and significant (P < 0.0001) differences between sites. The study provides evidence of the IR spectroscopy techniques' sensitivity and supports their potential application in environmental biomonitoring.     

Organic micropollutants in coastal waters from NW Mediterranean Sea: Sources distribution and potential risk

This study provides a first estimation on the sources, distribution and risk of organic micropollutants (OMPs) in coastal waters from NW Mediterranean Sea. Polycyclic aromatic hydrocarbons, polychlorinated biphenyls, organochlorinated pesticides, polybrominated diphenyl ethers, phthalates and alkylphenols were analyzed by solid phase extraction and gas chromatography coupled to tandem mass spectrometry (SPE–GC–EI-MS/MS). River waters and wastewater treatment plant effluents discharging to the sea were identified as the main sources of OMPs to coastal waters, with an estimated input amount of around of 25,800 g d^− 1. The concentration of ΣOMPs in coastal areas ranged from 17.4 to 8442 ng L^− 1, and was the highest in port waters, followed by coastal and river mouth seawaters. A summarized overview of the patterns and sources of OMP contamination on the investigated coastal sea waters of NW Mediterranean Sea, as well as of their geographical distribution was obtained by Principal Component Analysis of the complete data set after its adequate pretreatment. Alkylphenols, bisphenol A and phthalates were the main contributors to ΣOMPs and produced an estimated significant pollution risk for fish, algae and the sensitive mysid shrimp organisms in seawater samples. The combination of GC-MS/MS, chemometrics and risk analysis is proven to be useful for a better control and management of OMP discharges.     

Elevated childhood exposure to arsenic despite reduced drinking water concentrations — A longitudinal cohort study in rural Bangladesh

ObjectivesThe aim of this study was to evaluate the massive efforts to lower water arsenic concentrations in Bangladesh.MethodsIn our large mother–child cohort in rural Matlab, we measured the arsenic concentrations (and other elements) in drinking water and evaluated the actual exposure (urinary arsenic), from early gestation to 10 years of age (n = 1017).ResultsMedian drinking water arsenic decreased from 23 (2002–2003) to < 2 μg/L (2013), and the fraction of wells exceeding the national standard (50 μg/L) decreased from 58 to 27%. Still, some children had higher water arsenic at 10 years than earlier. Installation of deeper wells (> 50 m) explained much of the lower water arsenic concentrations, but increased the manganese concentrations. The highest manganese concentrations (~ 900 μg/L) appeared in 50–100 m wells. Low arsenic and manganese concentrations (17% of the children) occurred mainly in > 100 m wells. The decrease in urinary arsenic concentrations over time was less apparent, from 82 to 58 μg/L, indicating remaining sources of exposure, probably through food (mean 133 μg/kg in rice).ConclusionDespite decreased water arsenic concentrations in rural Bangladesh, the children still have elevated exposure, largely from food. Considering the known risks of severe health effects in children, additional mitigation strategies are needed.     

Phthalate exposure among pregnant women in Jerusalem, Israel: results of a pilot study

BackgroundPhthalates can disrupt endocrine function and induce reproductive and developmental toxicity in laboratory animals. Few studies have evaluated exposure to phthalates in pregnant women, despite the potential sensitivity of the developing fetus to adverse effects of phthalates.MethodsWe measured urinary concentrations of 11 phthalate metabolites in 19 pregnant women, recruited in Jerusalem, Israel in 2006, and collected questionnaire data on demographic factors and consumer habits from these women. We compared geometric mean concentrations in subgroups and used the Mann–Whitney U-test for independent samples to determine significant differences between groups.ResultsNine metabolites were detected in at least 95% of the samples: mono(2-ethyl-5-carboxypentyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(n-butyl) phthalate, monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), mono(2-ethylhexyl) phthalate and monoisobutyl phthalate. Phthalate metabolite concentrations in these pregnant women were remarkably similar to those in the general United States female population. MBzP geometric mean concentrations were higher in women living in buildings existing 40 years or more (P = 0.04). In women who used four or more personal care products (perfume, deodorant, lipstick, nail polish, or hand/face cream) in the 48 h prior to providing the urine sample, geometric mean MEP concentrations were more than 4 times higher than concentrations in women using only two or three of the aforementioned products (P = 0.07).ConclusionsPregnant women in Jerusalem are exposed to a wide range of phthalates. Building materials used in old constructions may be a source of exposure to benzylbutyl phthalate, the parent compound of MBzP. Personal care products may be sources of exposure to diethyl phthalate, the parent compound of MEP.     

Phthalates in German daycare centers: Occurrence in air and dust and the excretion of their metabolites by children (LUPE 3)

Phthalates have been used for decades in large quantities, leading to the ubiquitous exposure of the population.In an investigation of 63 German daycare centers, indoor air and dust samples were analyzed for the presence of 10 phthalate diesters. Moreover, 10 primary and secondary phthalate metabolites were quantified in urine samples from 663 children attending these facilities. In addition, the urine specimens of 150 children were collected after the weekend and before they went to daycare centers.Di-isobutyl phthalate (DiBP), dibutyl phthalate (DnBP), and di-2-ethylhexyl phthalate (DEHP) were found in the indoor air, with median values of 468, 227, and 194 ng/m³, respectively. In the dust, median values of 888 mg/kg for DEHP and 302 mg/kg for di-isononyl phthalate (DiNP) were observed. DnBP and DiBP were together responsible for 55% of the total phthalate concentration in the indoor air, whereas DEHP and DiNP were responsible for 70% and 24% of the total phthalate concentration in the dust.Median concentrations in the urine specimens were 44.7 μg/l for the DiBP monoester, 32.4 μg/l for the DnBP monoester, and 16.5 μg/l and 17.9 μg/l for the two secondary DEHP metabolites. For some phthalates, we observed significant correlations between their concentrations in the indoor air and dust and their corresponding metabolites in the urine specimens using bivariate analyses. In multivariate analyses, the concentrations in dust were not associated with urinary metabolite excretion after controlling for the concentrations in the indoor air.The total daily “high” intake levels based on the 95th percentiles calculated from the biomonitoring data were 14.1 μg/kg b.w. for DiNP and 11.9 μg/kg b.w. for DEHP. Compared with tolerable daily intake (TDI) values, our “high” intake was 62% of the TDI value for DiBP, 49% for DnBP, 24% for DEHP, and 9% for DiNP. For DiBP, the total daily intake exceeded the TDI value for 2.4% of the individuals. Using a cumulative risk-assessment approach for the sum of DEHP, DnBP, and DiBP, 20% of the children had concentrations exceeding the hazard index of one. Therefore, a further reduction of the phthalate exposure of children is needed.     

Intake of phthalates and di(2-ethylhexyl)adipate: results of the Integrated Exposure Assessment Survey based on duplicate diet samples and biomonitoring data

Phthalates are ubiquitous environmental chemicals with potential detrimental health effects. The purpose of our study was to quantify dietary intake of phthalates and of DEHA (Di-ethylhexyl adipate) using duplicate diet samples and to compare these data with the calculated data based on urinary levels of primary and secondary phthalate metabolites. 27 female and 23 male healthy subjects aged 14-60 years collected daily duplicate diet samples over 7 consecutive days. Overall, 11 phthalates were measured in the duplicates by GC/MS and LC/MS methods. Urinary levels of primary and secondary phthalate metabolites are also available. The median (95th percentile) daily intake via food was 2.4 (4.0) microg/kg b.w. (Di-2-ethylhexyl phthalate, DEHP), 0.3 (1.4) microg/kg b.w. (Di-n-butyl phthalate, DnBP), 0.6 (2.1) microg/kg b.w. (Di-isobutyl phthalate, DiBP) and 0.7 (2.2) microg/kg b.w. for DEHA. MEPH (Mono-2-ethylhexyl phthalate) was detectable only in minor concentrations in the samples, thus conversion of DEHP to MEHP and dietary intake of MEHP were negligible. When comparing back-calculated intake data of the DEHP metabolites with dietary DEHP intake from the day before significant correlations were observed for most of the metabolites. No correlation was found for DnBP and only a weak but significant correlation for DiBP. The median and 95th percentile daily dietary intake of all target analytes did not exceed the recommended tolerable daily intake. Our data indicated that food was the predominant intake source of DEHP, whilst other sources considerably contributed to the daily intake of DnBP and DiBP in an adult population.     

Exposure to endocrine disrupting chemicals among residents of a rural vegetarian/vegan community

Background & AimsEndocrine-disrupting chemicals (EDCs) are increasingly thought to be involved in the rising prevalence of disorders such as obesity, diabetes, and some hormone-dependent cancers. Several lines of evidence have indicated that vegetarian and vegan diets may offer some protection from such diseases. We hypothesized that exposure to selected EDCs among residents of the unique vegetarian/vegan community of Amirim would be lower than what has recently been reported for the omnivorous population in the first Israel Biomonitoring Study (IBMS).MethodsWe studied 42 Amirim residents (29 vegetarians/13 vegans; 24 women/18men, aged 50.7 ± 13.7 y). Subjects answered detailed lifestyle, and multipass, memory-based 24-hr dietary recall questionnaires. Concentrations of bisphenol A (BPA), 11 phthalate metabolites, and the isoflavone phytoestrogens (genistein and daidzein) were determined by GC or LC tandem mass-spectrometry on a spot urine sample. The results were compared to those obtained following the same methodology in the Jewish subgroup of the IBMS (n = 184).ResultsWhile a vegetarian/vegan nutritional pattern had no effect on exposure to BPA, it seemed to confer a modest protection (~ 21%) from exposure to high molecular weight phthalates. Furthermore, the summed metabolites of the high molecular weight phthalate DiNP were 36% lower in vegans compared to vegetarians (P < 0.05). In contrast, Amirim residents exhibited a level of exposure to isoflavone phytoestrogens about an order of magnitude higher than in the IBMS (P < 0.001).ConclusionsIn Israel, a country whose inhabitants demonstrate exposure to EDCs comparable to that of the US and Canada, a voluntary lifestyle of vegetarianism and preference for organic food has a modest, but possibly valuable, impact on exposure to phthalates, while it is associated with a very steep increase in the exposure to phytoestrogens. Major reduction in exposure to EDCs will require regulatory actions.     

Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults

Di-(2-ethylhexyl) phthalate (DEHP) has been used worldwide in various products for many years. In vitro studies have shown that exposure to DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) induces endothelial cell apoptosis. Moreover, exposure to DEHP had been linked to cardiovascular risk factors and cardiovascular diseases in epidemiological studies. Circulating microparticles have been known to be indicators of vascular injury. However, whether DEHP or its metabolites are independently associated with microparticles in humans remains unknown. From 2006 to 2008, we recruited 793 subjects (12–30 years) from a population-based sample to participate in this cardiovascular disease prevention examination. Each participant was subjected to interviews and biological sample collection to determine the relationship between concentrations of DEHP metabolites MEHP, mono(ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethly-5-oxoheyl) phthalate in urine and concentrations of endothelial microparticles (CD62E and CD31 +/CD42a −), platelet microparticles (CD62P and CD31 +/CD42a +), and CD14 in serum. Multiple linear regression analysis revealed that an ln-unit increase in MEHP concentration in urine was positively associated with an increase in serum microparticle counts/μL of 0.132 (± 0.016) in CD31 +/CD42a − (endothelial apoptosis marker), 0.117 (± 0.023) in CD31 +/CD42a + (platelet apoptosis marker), and 0.026 (± 0.007) in CD14 (monocyte, macrophage, and neutrophil activation marker). There was no association between DEHP metabolite concentration and CD62E or CD62P. In conclusion, a higher MEHP concentration in urine was associated with an increase in endothelial and platelet microparticles in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to DEHP and atherosclerosis.     

Exposure assessment issues in epidemiology studies of phthalates

PurposeThe purpose of this paper is to review exposure assessment issues that need to be addressed in designing and interpreting epidemiology studies of phthalates, a class of chemicals commonly used in consumer and personal care products. Specific issues include population trends in exposure, temporal reliability of a urinary metabolite measurement, and how well a single urine sample may represent longer-term exposure. The focus of this review is on seven specific phthalates: diethyl phthalate (DEP); di-n-butyl phthalate (DBP); diisobutyl phthalate (DiBP); butyl benzyl phthalate (BBzP); di(2-ethylhexyl) phthalate (DEHP); diisononyl phthalate (DiNP); and diisodecyl phthalate (DiDP).MethodsComprehensive literature search using multiple search strategies.ResultsSince 2001, declines in population exposure to DEP, BBzP, DBP, and DEHP have been reported in the United States and Germany, but DEHP exposure has increased in China. Although the half-lives of various phthalate metabolites are relatively short (3 to 18 h), the intraclass correlation coefficients (ICCs) for phthalate metabolites, based on spot and first morning urine samples collected over a week to several months, range from weak to moderate, with a tendency toward higher ICCs (greater temporal stability) for metabolites of the shorter-chained (DEP, DBP, DiBP and BBzP, ICCs generally 0.3 to 0.6) compared with those of the longer-chained (DEHP, DiNP, DiDP, ICCs generally 0.1 to 0.3) phthalates. Additional research on optimal approaches to addressing the issue of urine dilution in studies of associations between biomarkers and different type of health effects is needed.ConclusionsIn conclusion, the measurement of urinary metabolite concentrations in urine could serve as a valuable approach to estimating exposure to phthalates in environmental epidemiology studies. Careful consideration of the strengths and limitations of this approach when interpreting study results is required.     

Phthalate exposure,flavonoid consumption and breast cancer risk among Mexican women

ObjectiveTo evaluate if selected phthalate exposure and flavonoid intake interact on breast cancer (BC) risk.Material and methodsInterviews and urine samples were obtained from 233 women with histologically confirmed BC and 221 healthy controls matched by age and place of residence, from various states of northern Mexico. Urinary metabolites concentrations of diethyl phthalate (DEP), butyl benzyl phthalate (BBzP) and dioctyl phthalate (DOP) were determined by solid-phase extraction coupled with high-performance liquid chromatography/isotope dilution/tandem mass spectrometry. Using a semiquantitative food frequency questionnaire, consumption of five types of flavonoids (anthocyanidins, flavan-3-ols, flavanones, flavones and flavonols) was estimated according to three food groups: vegetables, fruits and legumes-oil seeds.ResultsA higher intake of anthocyanidins and flavan-3-ols (from vegetables), synergistically increased the negative association between BBzP and BC. No other significant flavonoid-phthalate multiplicative interactions on the risk for BC were found.ConclusionThe consumption of some flavonoids may interact with exposure to phthalates on the risk of BC. Epidemiological and underlying mechanisms information is still insufficient and requires further investigations.     

Thyroid hormone disrupting activities associated with phthalate esters in water sources from Yangtze River Delta

Thyroid hormone disrupting compounds in water sources is a concern. Thyroid hormone (TH) agonist and antagonist activities of water sources from the Yangtze River, Huaihe River, Taihu Lake and ground water in the Yangtze River Delta region were evaluated by use of a TH reporter gene assay based on the green monkey kidney fibroblast (CV-1). While weak TH receptor (TR) agonist potency was observed in only one of 15 water sources, antagonist potency was present in most of the water sources. TR antagonist equivalents could be explained by the presence of dibutyl phthalate (DBP), with concentrations ranging from 2.8 × 10¹ to 1.6 × 10³ μg DBP /L (ATR-EQ₅₀s). None of the ground waters exhibited TH agonist potencies while all of the samples from Taihu Lake displayed notable TR antagonist potencies. To identify the responsible thyroid active compounds, instrumental analysis was conducted to measure a list of potential thyroid-disrupting chemicals, including organochlorine (OC) pesticides and phthalate esters. Combining the results of the instrumental analysis with those of the bioassay, DBP was determined to account for 17% to 144% of ATR-EQ₅₀s in water sources. Furthermore, ATR-EQ_20–80 ranges for TR antagonist activities indicated that samples from locations WX-1 and WX-2 posed the greatest health concern and the associated uncertainty may warrant further investigation.     

Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring

There is a growing need in the field of exposure science for monitoring methods that rapidly screen environmental media for suspect contaminants. Measurement and analysis platforms, based on high resolution mass spectrometry (HRMS), now exist to meet this need. Here we describe results of a study that links HRMS data with exposure predictions from the U.S. EPA's ExpoCast™ program and in vitro bioassay data from the U.S. interagency Tox21 consortium. Vacuum dust samples were collected from 56 households across the U.S. as part of the American Healthy Homes Survey (AHHS). Sample extracts were analyzed using liquid chromatography time-of-flight mass spectrometry (LC–TOF/MS) with electrospray ionization. On average, approximately 2000 molecular features were identified per sample (based on accurate mass) in negative ion mode, and 3000 in positive ion mode. Exact mass, isotope distribution, and isotope spacing were used to match molecular features with a unique listing of chemical formulas extracted from EPA's Distributed Structure-Searchable Toxicity (DSSTox) database. A total of 978 DSSTox formulas were consistent with the dust LC–TOF/molecular feature data (match score ≥ 90); these formulas mapped to 3228 possible chemicals in the database. Correct assignment of a unique chemical to a given formula required additional validation steps. Each suspect chemical was prioritized for follow-up confirmation using abundance and detection frequency results, along with exposure and bioactivity estimates from ExpoCast and Tox21, respectively. Chemicals with elevated exposure and/or toxicity potential were further examined using a mixture of 100 chemical standards. A total of 33 chemicals were confirmed present in the dust samples by formula and retention time match; nearly half of these do not appear to have been associated with house dust in the published literature. Chemical matches found in at least 10 of the 56 dust samples include Piperine, N,N-Diethyl-m-toluamide (DEET), Triclocarban, Diethyl phthalate (DEP), Propylparaben, Methylparaben, Tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and Nicotine. This study demonstrates a novel suspect screening methodology to prioritize chemicals of interest for subsequent targeted analysis. The methods described here rely on strategic integration of available public resources and should be considered in future non-targeted and suspect screening assessments of environmental and biological media.