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.     

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.     

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.     

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.     

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.     

Personal care product use and urinary levels of phthalate metabolites in Mexican women

Sources of phthalates other than Polyvinyl chloride (PVC) related products are scarcely documented in Mexico. The objective of our study was to explore the association between urinary levels of nine phthalate metabolites and the use of personal care products. Subjects included 108 women who participated as controls in an ongoing population-based case-control study of environmental factors and genetic susceptibility to breast cancer in northern Mexico. Direct interviews were performed to inquire about sociodemographic characteristics, reproductive history, use of personal care products, and diet. Phthalate metabolites measured in urine by high performance liquid chromatography-isotope dilution tandem mass spectrometry were monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-3-carboxypropyl phthalate (MCPP) as well as mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP) that are metabolites of di-ethylhexyl phthalate (DEHP). Detectable urinary concentrations of phthalate metabolites varied from 75% (MEHP) to 100% (MEP, MBP, MEOHP, MEHHP and MECPP). Medians of urinary concentrations of some phthalate metabolites were significantly higher among users of the following personal care products compared to nonusers: body lotion (MEHHP, MECPP and sum of DEHP metabolites (ΣDEHP)), deodorant (MEHP and ΣDEHP), perfume (MiBP), anti-aging facial cream (MEP, MBP and MCPP) and bottled water (MCPP, MEHHP and MEOHP). Urinary concentrations of MEP showed a positive relationship with the number of personal care products used. Our results suggest that the use of some personal care products contributes to phthalate body burden that deserves attention due to its potential health impact.     

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.     

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.     

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.     

Correcting serum concentrations of organochlorine compounds by lipids: Alternatives to the organochlorine/total lipids ratio

IntroductionWhen studying the effects of organochlorine compounds (OCs) on human health it is common to correct serum concentrations of OC by total lipids (TL). However, the relationship between serum OCs and serum TL is far from established in many diseases, including several cancers. Our aim was to analyze the relationship between serum OC and TL in patients with pancreatic ductal adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid correction.MethodsIncident cases of PDA were interviewed and had blood drawn soon around hospital admission (n = 144). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection.ResultsMost patients with high TL had moderate or low concentrations of OCs. By contrast, the variability of OC values among patients with normal TL was large. Correlations were of a similar magnitude between OC and TL and between OC and total cholesterol; while these correlations were weak (all Spearman's ρ < 0.3 and R² < 0.11), no OC were significantly correlated with triglycerides. Although all alternatives to the OC/TL linear ratio were statistically significant for at least one OC, their R² was always below 10%.ConclusionsIn patients with severe diseases as PDA, linear correction of OC by TL as commonly performed in epidemiologic studies may be inappropriate. Results contribute to the scant literature on the rationale to correct serum concentrations of OC by lipids. They suggest that it is unwarranted to routinely correct OC by TL, offer ways to assess such need, and present alternatives as no TL correction, correction by total cholesterol only or use of different statistical models.     

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.     

Ambient air pollution and children's lung function in China

ObjectiveTo describe the correlations between ambient air pollutants (TSP, SO₂, NO_x) and the level of children's lung function (FVC, FEV₁, MMEF) in China.MethodsWe collected the research articles on ambient air pollution and children's lung function published from 1985 to 2006 and selected 11 articles finally according to the following criteria: (1) Children between the age of 7 and 15 as objects; (2) Local air quality monitoring results were reported; (3) Strict quality control was taken when testing children's lung function; (4) The results were expressed by the average of measured value. Then we analyzed the correlation relationship between the level of ambient air pollutants and children's lung function and compared the effects of ambient air pollutants on children's lung function of boy and girl.ResultsThe selected articles included the results of 7 cities in China. Among them, the results of 6 cities' studies revealed that the levels of children's lung function were significantly lower in the areas with heavy ambient air pollution than those in the areas with light ambient air pollution. According to the articles, the average levels of TSP were at the range of 0.084 mg/m³–0.835 mg/m³, SO₂ were 0.013 mg/m³–0.929 mg/m³, NO_x were 0.044 mg/m³–0.229 mg/m³. Correlation analysis showed significant negative correlation between the levels of TSP and SO₂ and children's FVC and FEV₁, as well as the levels of NO_x and children's MMEF. The correlation coefficient was ? 0.797 (t = ? 4.384, P = 0.001) between TSP and FVC, ? 0.693 (t = ? 4.190, P < 0.001) between Ln (SO₂) and FVC, ? 0.886 (t = ? 5.392, P = 0.001) and ? 0.685 (t = ? 4.101, P = 0.001) between FEV₁ and TSP and Ln (SO₂), and ? 0.973 (t = ? 5.993, P = 0.027) between NO_xNO_x and MMEF, respectively. The results also suggested that the decreases of lung function for girl with the increasing of ambient air pollution were significantly greater for boy.ConclusionThe levels of ambient air TSP and SO₂ correlated with the damage of the big airway function of children, while NO_xNO_x affected the small airway function chiefly. Furthermore, lung function of girl was more susceptible to ambient air pollutants than boy.     

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.     

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.     

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.     

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.     

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.     

Number of persistent organic pollutants detected at high concentrations in a general population

BackgroundSurveys of human exposure to environmental chemicals do not integrate the number of compounds detected per person and the concentration of each compound. This leaves untested relevant exposure scenarios, such as whether individuals with low concentrations of some compounds have high concentrations of the other compounds.ObjectiveTo analyze the number of persistent organic pollutants (POPs) detected at high concentrations.MethodsSerum concentrations of 19 POPs were analyzed by gas chromatography with electron-capture detection in a representative sample of the general population of Catalonia, Spain (N = 919).ResultsOver 58% of participants had concentrations in the top quartile of ≥ 1 of the eight most prevalent POPs, and 34% of ≥ 3 POPs. 83% of women 60 to 74 years old had concentrations of ≥ 3 POPs in the top quartile; 56% of women 60 to 74 years had p,p′-DDE, HCB and β-HCH all in their respective top quartiles, and 48% had concentrations of ≥ 6 POPs in the top quartile. Over 30% of subjects had concentrations in the top decile of 1 to 5 of the eight most prevalent POPs. Half of the population had levels of 1 to 5 POPs > 500 ng/g. Less than 4% had all eight POPs in the lowest quartile.ConclusionsMore than half of the study population had concentrations in the top quartile of ≥ 1 POPs. Significant subgroups of the population accumulate POP mixtures at high concentrations. POP concentrations appear low in most of the population only when each individual compound is looked at separately.     

Determinants of plasma concentrations of perfluoroalkyl substances in pregnant Norwegian women

BackgroundPerfluoroalkyl substances (PFASs) are widespread pollutants that have been associated with adverse health effects although not on a consistent basis. Diet has been considered the main source of exposure. The aim of the present study was to identify determinants of four plasma PFASs in pregnant Norwegian women.MethodsThis study is based in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Our sample included 487 women who enrolled in MoBa from 2003 to 2004. A questionnaire regarding sociodemographic, medical, and reproductive history was completed at 17 weeks of gestation and a dietary questionnaire was completed at 22 weeks of gestation. Maternal plasma samples were obtained around 17 weeks of gestation. Plasma concentrations of four PFASs (perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA)) were examined in relation to demographic, lifestyle, dietary, and pregnancy-related covariates. Predictors were identified by optimizing multiple linear regression models using Akaike's information criterion (AIC).ResultsParity was the determinant with the largest influence on plasma PFAS concentrations, with r² between 0.09 and 0.32 in simple regression models. In optimal multivariate models, when compared to nulliparous women, parous women had 46%, 70%, 19%, and 62% lower concentrations of PFOS, PFOA, PFHxS, and PFNA respectively (p < 0.001 except for PFHxS, p < 0.01). In all these models, duration of breastfeeding was associated with reduced PFAS levels. PFOA showed the largest reduction from breastfeeding, with a 2–3% reduction per month of breastfeeding in typical cases. Levels of PFOS, PFOA, and PFNA increased with time since most recent pregnancy. While pregnancy-related factors were the most important predictors, diet was a significant factor explaining up to 4% of the variance. One quartile increase in estimated dietary PFAS intake was associated with plasma PFOS, PFOA, PFHxS, and PFNA concentration increases of 7.2%, 3.3%, 5.8% and 9.8%, respectively, resulting in small, although non-trivial absolute changes in PFAS concentrations.ConclusionPrevious pregnancies and breastfeeding duration were the most important determinants of PFASs in this sample of pregnant women.     

Novel exposure biomarkers of N,N-diethyl-m-toluamide (DEET): Data from the 2007–2010 National Health and Nutrition Examination Survey

BackgroundN,N-diethyl-m-toluamide (DEET) is a widely used insect repellent in the United States.ObjectivesTo assess exposure to DEET in a representative sample of persons 6 years and older in the U.S. general population from the 2007–2010 National Health and Nutrition Examination Survey.MethodsWe analyzed 5348 urine samples by using online solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. We used regression models to examine associations of various demographic parameters with urinary concentrations of DEET biomarkers.ResultsWe detected DEET in ~ 3% of samples and at concentration ranges (> 0.08 μg/L–45.1 μg/L) much lower than those of 3-(diethylcarbamoyl)benzoic acid (DCBA) (> 0.48 μg/L–30,400 μg/L) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB) (> 0.09 μg/L–332 μg/L). DCBA was the most frequently detected metabolite (~ 84%). Regardless of survey cycle and the person's race/ethnicity or income, adjusted geometric mean concentrations of DCBA were higher in May–Sep than in Oct–Apr. Furthermore, non-Hispanic whites in the warm season were more likely than in the colder months [adjusted odds ratio (OR) = 10.83; 95% confidence interval (CI), 3.28–35.79] and more likely than non-Hispanic blacks (OR = 3.45; 95% CI, 1.51–7.87) to have DCBA concentrations above the 95th percentile.ConclusionsThe general U.S. population, including school-age children, is exposed to DEET. However, reliance on DEET as the sole urinary biomarker would likely underestimate the prevalence of exposure. Instead, oxidative metabolites of DEET are the most adequate exposure biomarkers. Differences by season of the year based on demographic variables including race/ethnicity likely reflect different lifestyle uses of DEET-containing products.