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.     

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.     

Considerable exposure to the endocrine disrupting chemicals phthalates and bisphenol-A in intensive care unit (ICU) patients

Critical care medicine has largely benefited from plastic-containing medical devices. However, bisphenol-A (BPA) and phthalates present in the plastics can leach from such devices. We hypothesized that intensive care unit (ICU) patients are exposed to BPA and phthalates through (plastic) medical devices. Serum (n = 118) and urine (n = 102) samples of adult ICU patients (n = 35) were analyzed for total BPA and phthalate metabolites (PMs). Our results showed that adult ICU patients are continuously exposed to phthalates, such as di(2-ethylhexyl)phthalate (DEHP), as well as to BPA, albeit to a lesser extent. This exposure resulted in detectable high serum and urinary levels in almost every patient and at every studied time point. Moreover, these levels were significantly higher than in controls or compared to referenced literature. The chronology of exposure was demonstrated: pre-operative urinary and serum levels of the DEHP metabolites were often below the detection limit. Plastic-containing medical devices were the main source of DEHP exposure: post-operative patients on hemofiltration, extracorporeal membrane oxygenation or both showed serum levels 100-or 1000-fold higher than the levels in the general population reported in the literature. The serum and some of the urinary levels of the DEHP metabolites are the highest ever reported in humans; some at biologically highly relevant concentrations of ≥ 10–50 μM. Despite the continuously tightening regulations, BPA and DEHP appear to be still present in (some) medical devices. Because patient safety is a concern in the ICU, further research into the (possibly toxic and clinical) effects of these chemicals released from medical devices is imperiously necessary.     

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.     

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.     

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.     

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.     

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.     

Development and application of simple pharmacokinetic models to study human exposure to di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP)

In a published controlled dosing experiment, a single individual consumed 5 mg each of labeled di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) on separate occasions and tracked metabolites in his blood and urine over 48 h. Data from this study were used to structure and calibrate simple pharmacokinetic (PK) models for these two phthalates, which predict urine and blood metabolite concentrations with a given phthalate intake scenario (times and quantities). The calibrated models were applied to a second published experiment in which 5 individuals fasted over the course of a 48-h weekend (bottled water only), and their full urine voids were captured and measured for DnBP and DiBP metabolites. One goal of this model application was to confirm the validity of the calibrated models — their validity would be demonstrated if a profile of intakes could be found which adequately duplicated the metabolite concentrations measured in the urine. A second goal was to study patterns of exposure for this group. It was found that all metabolites could be duplicated very well with individual-specific “best-fit” intake scenarios, with one exception. It appears that the model predicted much lower concentrations of the metabolite, 3carboxy-mono-propylphthalate (MCPP), than were observed in all individuals. Modeled as a metabolite of DnBP, this suggests that DnBP was not the major source of MCPP in the urine. For all 5 individuals, the reconstructed dose profiles of the two phthalates were similar: about 6 small bolus doses per day and an intake of about 0.5 μg/kg-day. The intakes did not appear to be associated with diary-reported activities (personal hygiene and medication) of the participants. The modeled frequent intakes suggested one (or both) of two possibilities: ongoing exposures such as an inhalation exposure, or no exposure but rather an ongoing release of body stores of the phthalate metabolites from past exposures.     

Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth

Growth of the fetus is highly sensitive to environmental perturbations, and disruption can lead to problems in pregnancy as well as later in life. This study investigates the relationship between maternal exposure to common plasticizers in pregnancy and fetal growth. Participants from a longitudinal birth cohort in Boston were recruited early in gestation and followed until delivery. Urine samples were collected at up to four time points and analyzed for concentrations of phthalate metabolites and bisphenol A (BPA). Ultrasound scans were performed at four time points during pregnancy for estimation of growth parameters, and birthweight was recorded at delivery. Growth measures were standardized to a larger population. For the present analysis we examined cross-sectional and repeated measures associations between exposure biomarkers and growth estimates in 482 non-anomalous singleton pregnancies. Cross-sectional associations between urinary phthalate metabolites or BPA and growth indices were imprecise. However, in repeated measures models, we observed significant inverse associations between di-2-ethylhexyl phthalate (DEHP) metabolites and estimated or actual fetal weight. An interquartile range increase in summed DEHP metabolites was associated with a 0.13 standard deviation decrease in estimated or actual fetal weight (95% confidence interval = − 0.23, − 0.03). Associations were consistent across different growth parameters (e.g., head circumference, femur length), and by fetal sex. No consistent associations were observed for other phthalate metabolites or BPA. Maternal exposure to DEHP during pregnancy was associated with decreased fetal growth, which could have repercussive effects.     

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.     

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.     

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).     

Daily intake of bisphenol A and triclosan and their association with anthropometric data,thyroid hormones and weight loss in overweight and obese individuals

Bisphenol A (BPA) and triclosan (TCS) were determined in urine of Belgian overweight and obese (n = 151) and lean (n = 43) individuals. After the first urine collection (0 M), obese patients started a diet program or have undergone bariatric surgery. Hereafter, three additional urine samples from obese patients were collected after 3 (3 M), 6 (6 M) and 12 (12 M) months. Both compounds were detected in > 99% of the samples. BPA had median concentrations of 1.7 and 1.2 ng/mL in obese and lean groups, respectively, while TCS had median concentrations of 1.5 and 0.9 ng/mL in the obese and lean groups, respectively. The obese group had higher urinary concentrations (ng/mL) of BPA (p < 0.5), while no significant differences were found for TCS between the obese and lean groups. No time trends between the different collection moments were observed. The BPA concentrations in the obese group were negatively associated with age, while no gender difference or relationship with body mass index was observed. For TCS, no relationships with gender, BMI, or age were found. The temporal variability of BPA and TCS was assessed with calculation of the intraclass correlation coefficient, Spearman rank correlation coefficients, and surrogate category analysis. We observed evidence that single spot urine samples might be predictive of exposure over a longer period of time. Dietary intakes of BPA and TCS did not differ significantly among the time points considered after obese individuals started losing weight (6 and 12 months). Multiple linear regression analyses after adjusting for age and weight loss revealed negative associations between urinary TCS and serum FT4 in the 0 M and 3 M female obese individuals and positive associations between urinary BPA and serum TSH in the lean group.     

The influence of resource strategies on childhood phthalate exposure—The role of REACH in a zero waste society

The present study aims to investigate how resource strategies, which intend to reduce waste and increase recycling, influence on human exposure to hazardous chemicals from material recycling. In order to examine the flows of hazardous chemicals in recycled material, a mass flow analysis of plastics and paper at European level, including the flow of phthalates, i.e. di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and benzyl-butyl phthalate (BBP), has been performed. The result for the year 2012 shows that 26% of plastic wastes and 60% of paper consumed in Europe were recycled. This corresponds to the finding that approximately 4% of DEHP and BBP and 18% of DBP annual demands in Europe as raw material re-enter the product cycle with recycled plastics and paper. To examine the potential contribution of the phthalate exposure through recycled plastics and paper, a case study assessing the childhood exposures to phthalates from foods packed in recycled paper and plastics has been performed for 2-year-old children in Denmark. The result verifies that an increase in recycled paperboard and PET bottles in food packaging material causes a significant increase in childhood exposure to DBP corresponding to an additional exposure of 0.116–0.355 μg/kg bw/day; up to 18% of the total DBP exposure in Danish 2-year-olds. While most of the DEHP exposure can be explained, more than 50% of DBP and 70% of BBP exposure sources still remain to be identified. Finally, a conceptual framework for a circular economy based on sustainable and clean resource flows is proposed in order to increase material recycling without increasing adverse health effects.     

Exposure to phthalates,bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC study

BackgroundStudies from several countries report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Exposure to environmental chemicals could contribute to this trend.ObjectivesTo determine the associations between plasticisers and metals measured in early pregnancy with impaired glucose tolerance (IGT) and GDM in a Canadian pregnancy cohort.MethodsWomen enrolled in the Maternal–Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Eleven phthalate metabolites and total bisphenol A (BPA) were measured in first-trimester urine samples, and four metals (lead, cadmium, mercury and arsenic) were measured in first-trimester blood samples. IGT and GDM were assessed in accordance with standard guidelines by chart review. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for maternal age, race, pre-pregnancy BMI, and education. Restricted cubic spline analysis was performed to help assess linearity and nature of any dose–response relationships.ResultsOf 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome data and biomonitoring data measured for at least one of the chemicals we examined. Elevated odds of GDM were observed in the highest quartile of arsenic exposure (OR = 3.7, 95% CI = 1.4–9.6) in the adjusted analyses. A significant dose–response relationship was observed in a cubic spline model between arsenic and odds of GDM (p < 0.01). No statistically significant associations were observed between phthalates or BPA or other metals with IGT or GDM.ConclusionsOur findings add to the growing body of evidence supporting the role of maternal arsenic exposure as a risk factor for gestational diabetes.     

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 ≤ 10 years 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 (0.02 mg/kg/day) and the European Food Safety Authority (0.05 mg/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) > 0.05 mg/kg/day) had 10.395 times the risk of microalbuminuria than the low-exposed group (DDI ≤ 0.02 and > 0 mg/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.     

Human exposure to endocrine disrupting chemicals and fertility: A case–control study in male subfertility patients

BackgroundDioxins, PCBs, chlorinated pesticides, brominated flame retardants, bisphenol A, triclosan, perfluorinated compounds and phthalates are known as endocrine disrupting chemicals (EDCs).ObjectivesThe aim of our study was to investigate whether higher exposure to EDCs is associated with increased subfertility in men.MethodsWe measured biomarkers of exposure in 163 men, recruited through four fertility clinics. According to WHO guidelines, we used a total motility count (TMC) of 20 million as cut-off value. We assigned patients to the case group when two semen samples – collected at least one week apart – had a TMC < 20 and to the control group when both samples had a TMC ≥ 20. To estimate the risk of subfertility and alteration in sex hormone concentrations we used multivariable-adjusted analysis, using logistic and linear regressions, respectively.ResultsFor an IQR increase in serum oxychlordane, the odds ratio for subfertility was 1.98 (95% CI: 1.07; 3.69). Furthermore, men with serum levels of BDE209 above the quantification limit had an odds of 7.22 (1.03; 50.6) for subfertility compared with those having values below the LOQ. Urinary levels of phthalates and triclosan were negatively associated with inhibin B and positively with LH. Urinary bisphenol A correlated negatively with testosterone levels.ConclusionsOur study in men showed that internal body concentrations of endocrine disrupting chemicals are associated with an increased risk of subfertility together with alterations in hormone levels. The results emphasize the importance to reduce chemicals in the environment in order to safeguard male fertility.     

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.     

Measurement of flame retardants and triclosan in municipal sewage sludge and biosolids

As polybrominated diphenyl ethers (PBDEs) face increasing restrictions worldwide, several alternate flame retardants are expected to see increased use as replacement compounds in consumer products. Chemical analysis of biosolids collected from wastewater treatment plants (WWTPs) can help determine whether these flame retardants are migrating from the indoor environment to the outdoor environment, where little is known about their ultimate fate and effects. The objective of this study was to measure concentrations of a suite of flame retardants, and the antimicrobial compound triclosan, in opportunistic samples of municipal biosolids and the domestic sludge Standard Reference Material (SRM) 2781. Grab samples of biosolids were collected from two WWTPs in North Carolina and two in California. Biosolids samples were also obtained during three subsequent collection events at one of the North Carolina WWTPs to evaluate fluctuations in contaminant levels within a given facility over a period of three years. The biosolids and SRM 2781 were analyzed for PBDEs, hexabromobenzene (HBB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB), di(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), the chlorinated flame retardant Dechlorane Plus (syn- and anti-isomers), and the antimicrobial agent 5-chloro-2-(2,4-dichlorophenoxy)phenol (triclosan). PBDEs were detected in every sample analyzed, and ΣPBDE concentrations ranged from 1750 to 6358 ng/g dry weight. Additionally, the PBDE replacement chemicals TBB and TBPH were detected at concentrations ranging from 120 to 3749 ng/g dry weight and from 206 to 1631 ng/g dry weight, respectively. Triclosan concentrations ranged from 490 to 13,866 ng/g dry weight. The detection of these contaminants of emerging concern in biosolids suggests that these chemicals have the potential to migrate out of consumer products and enter the outdoor environment.