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.     

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.     

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.     

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.     

Respiratory hospital admissions in young children living near metal smelters,pulp mills and oil refineries in two Canadian provinces

BackgroundIndustrial plants emit air pollutants like fine particles (PM2.5), sulfur dioxide (SO2) and nitrogen dioxide (NO2) that may affect the health of individuals living nearby.ObjectiveTo assess the effects of community exposure to air emissions of PM2.5, SO2, and NO2 from pulp mills, oil refineries, metal smelters, on respiratory hospital admissions in young children in Quebec (QC) and British Columbia (BC), Canada.MethodsWe assessed QC, BC and pooled associations between the following estimates of exposure and hospital admissions for asthma and bronchiolitis in children aged 2–4 years for the years 2002–2010: i) Crude emission exposures at the residential postal codes of children, calculated by multiplying estimated daily emissions of PM2.5, SO2, or NO2 from all nearby (< 7.5 km) pulp mills, oil refineries, metal smelters emitting yearly ≥ 50 t and their total emissions, by the percent of the day each postal code was downwind; ii) Daily levels of these pollutants at central ambient monitoring stations nearby the industries and the children's residences.ResultsSeventy-one major industries were selected between QC and BC, with a total of 2868 cases included in our analyses. More cases were exposed to emissions from major industries in QC than in BC (e.g. 2505 admissions near SO2 industrial emitters in QC vs 334 in BC), although air pollutant levels were similar. Odds ratios (ORs) for crude refinery and smelter emissions were positive in QC but more variable in BC. For example with PM2.5 in QC, ORs were 1.13 per 0.15 t/day (95% CI: 1.00–1.27) and 1.03 (95% CI: 0.99–1.07) for refinery and smelter emissions, respectively. Pooled results of QC and BC for crude total SO2 emissions from all sources indicated a 1% increase (0–3%) in odds of hospital admissions per 1.50 t/day increase in exposure. Associations with measured pollutant levels were only seen in BC, with SO2 and NO2.ConclusionHospital admissions for wheezing diseases in young children were associated with community exposure to industrial air pollutant emissions. Future work is needed to better assess the risk of exposure to complex mixture of air pollutants from multiple industrial sources.     

Circulating levels of environmental contaminants are associated with dietary patterns in older adults

BackgroundFood intake contributes substantially to our exposure to environmental contaminants. Still, little is known about our dietary habits' contribution to exposure variability.ObjectiveThe aim of this study was to assess circulating levels of environmental contaminants in relation to predefined dietary patterns in an elderly Swedish population.MethodsDietary data and serum concentrations of environmental contaminants were obtained from 844 70-year-old Swedish subjects (50% women) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Dietary data from 7-day food records was used to assess adherence to a Mediterranean-like diet, a low carbohydrate–high protein diet and the WHO dietary recommendations. Circulating levels of 6 polychlorinated biphenyl markers, 3 organochlorine pesticides, 1 dioxin and 1 polybrominated diphenyl ether, the metals cadmium, lead, mercury and aluminum and serum levels of bisphenol A and 4 phthalate metabolites were investigated in relation to dietary patterns in multivariate linear regression models.ResultsA Mediterranean-like diet was positively associated with levels of several polychlorinated biphenyls (118, 126, 153, and 209), trans-nonachlor and mercury. A low carbohydrate–high protein diet was positively associated with polychlorinated biphenyls 118 and 153, trans-nonachlor, hexachlorobenzene and p, p′-dichlorodiphenyldichloroethylene, mercury and lead. The WHO recommended diet was negatively related to levels of dioxin and lead, and borderline positively to polychlorinated biphenyl 118 and trans-nonachlor.ConclusionDietary patterns were associated in diverse manners with circulating levels of environmental contaminants in this elderly Swedish population. Following the WHO dietary recommendations seems to be associated with a lower burden of environmental contaminants.     

Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction in men — A population-based prospective cohort study

BackgroundMajor food contaminants such as polychlorinated biphenyls (PCBs) are proposed to play a role in the etiology of cardiovascular disease (CVD), but to date the impact of PCBs on cardiovascular health need to be explored.Methods and resultsWe assessed the association between validated food frequency questionnaire-based estimates of dietary PCB exposure and risk of myocardial infarction, ascertained through register-linkage, among 36,759 men from the population-based Swedish Cohort of Men, free of cardiovascular disease, diabetes and cancer at baseline (1997). Relative risks were adjusted for known cardiovascular risk factors, long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) and methyl mercury exposure. During 12 years of follow-up (433,243 person-years), we ascertained 3005 incident cases of myocardial infarction (654 fatal). Compared with the lowest quintile of dietary PCB exposure (median 113 ng/day), men in the highest quintile (median 436 ng/day) had multivariable-adjusted relative risks of 1.74 (95% confidence interval [CI], 1.30–2.33; p-trend < 0.001) for total and 1.97 (95% CI 1.42–2.75; p-trend < 0.001) for non-fatal myocardial infarction. In mutually adjusted models, dietary PCB exposure was associated with an increased risk of myocardial infarction, while the intake of long-chain omega-3 fish fatty acids was associated with a decreased risk. We also observed an effect modification by adiposity on the association between of dietary PCB exposure and myocardial infarction, with higher risk among lean men (p value for interaction = 0.03).ConclusionsExposure to PCBs via diet was associated with increased risk of myocardial infarction in men.     

Phthalate exposure and reproductive parameters in young men from the general Swedish population

BackgroundIn animals, exposure to certain phthalates negatively affects the male reproductive function. Human results are conflicting and mostly based on subfertile males, in whom the association between exposure and reproductive function may differ from the general population.ObjectivesTo study if levels of phthalate metabolites were associated with semen quality and reproductive hormones in general Swedish men.MethodsWe recruited 314 young men delivering semen, urine and blood samples at the same visit. We analyzed reproductive hormones and several semen parameters including progressive motility and high DNA stainability (HDS)—a marker for sperm immaturity. In urine, we analyzed metabolites of phthalates, including diethylhexyl phthalate (DEHP). We studied associations between urinary levels of the metabolites and seminal as well as serum reproductive parameters, accounting for potential confounders.ResultsDEHP metabolite levels, particularly urinary mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), were negatively associated with progressive sperm motility, which was 11 (95% CI: 5.0–17) percentage points lower in the highest quartile of MECPP than in the lowest. Further, men in the highest quartile of the DEHP metabolite monoethylhexyl phthalate had 27% (95% CI: 5.5%–53%) higher HDS than men in the lowest quartile.ConclusionsDEHP metabolite levels seemed negatively associated with sperm motility and maturation.     

Exposure to multiple sources of polycyclic aromatic hydrocarbons and breast cancer incidence

BackgroundDespite studies having consistently linked exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to breast cancer, it is unclear whether single sources or specific groups of PAH sources should be targeted for breast cancer risk reduction.ObjectivesThis study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures.MethodsIn a population-based case-control study conducted on Long Island, New York (N = 1508 breast cancer cases/1556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake.ResultsMost women were exposed to PAHs from multiple sources, and the most common included active/passive smoking and grilled/smoked food intake. In multiple-PAH source models, breast cancer incidence was associated with residential ETS from a spouse (OR = 1.20, 95%CrI = 1.03, 1.40) and synthetic firelog burning (OR = 1.29, 95%CrI = 1.06, 1.57); these estimates are similar, but slightly attenuated, to those from single-source models. Additionally when we considered PAH exposure groups, the most pronounced significant associations included total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR = 1.45, 95%CrI = 1.02, 2.04).ConclusionsGroups of PAH sources, particularly indoor sources, were associated with a 30–50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor.     

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.     

The internal exposure of Taiwanese to phthalate--an evidence of intensive use of plastic materials

Phthalates are widely used in industry and consumer products. Di-(2-ethylhexyl) phthalate (DEHP) and di-n-butylphthalate (DBP) show the greatest potency of reproductive toxicants among phthalates. The purposes of this study are to examine the migration level of phthalate from PVC films by simulating food handling and to reveal the body burden of phthalate for Taiwanese. In order to estimate a worst-case of phthalate migration, food was covered with polyvinyl chloride (PVC) films and then microwave heated. Results show that DEHP level in food increased significantly after heating for 3 min. Under the heating condition, the calculated intake of phthalate and the percentage of the tolerable daily intake (TDI, based on body weight of 60 kg) from eating one 400-g meal were 1705.6 microg and 92.2% for DEHP. Determination of urinary metabolites from 60 subjects reveals more than 90% of samples were detectable for mono-methyl phthalate (MMP), mono-butyl phthalate (MBP) and mono-ethylhexyl phthalate (MEHP). Notably, the median value of estimated daily intake of DEHP had reached 91.6% of TDI established by the European Union Scientific Committee for Toxicity, Ecotoxicity and the Environment (CSTEE) (1998). Thirty-seven percent of the study population exceeded the TDI and 85% exceeded the reference dose (RfD) of the US EPA. We conclude that the body burden of DEHP for Taiwanese reflects the intensives use of plastic materials in the region. The regulation of PVC for food preparation is necessary.     

Dietary benzo(a)pyrene intake during pregnancy and birth weight: Associations modified by vitamin C intakes in the Norwegian Mother and Child Cohort Study (MoBa)

BackgroundMaternal exposure to polycyclic aromatic hydrocarbons (PAH) during pregnancy has been associated with reduced fetal growth. However, the role of diet, the main source of PAH exposure among non-smokers, remains uncertain.ObjectiveTo assess associations between maternal exposure to dietary intake of the genotoxic PAH benzo(a)pyrene [B(a)P] during pregnancy and birth weight, exploring potential effect modification by dietary intakes of vitamins C, E and A, hypothesized to influence PAH metabolism.MethodsThis study included 50,651 women in the Norwegian Mother and Child Cohort Study (MoBa). Dietary B(a)P and nutrient intakes were estimated based on total consumption obtained from a food frequency questionnaire (FFQ) and estimated based on food composition data. Data on infant birth weight were obtained from the Medical Birth Registry of Norway (MBRN). Multivariate regression was used to assess associations between dietary B(a)P and birth weight, evaluating potential interactions with candidate nutrients.ResultsThe multivariate-adjusted coefficient (95%CI) for birth weight associated with maternal energy-adjusted B(a)P intake was − 20.5 g (− 31.1, − 10.0) in women in the third compared with the first tertile of B(a)P intake. Results were similar after excluding smokers. Significant interactions were found between elevated intakes of vitamin C (> 85 mg/day) and dietary B(a)P during pregnancy for birth weight (P < 0.05), but no interactions were found with other vitamins. The multivariate-adjusted coefficients (95%CI) for birth weight in women in the third compared with the first tertile of B(a)P intake were − 44.4 g (− 76.5, − 12.3) in the group with low vitamin C intakes vs. − 17.6 g (− 29.0, − 6.1) in the high vitamin C intake group.ConclusionThe results suggest that higher prenatal exposure to dietary B(a)P may reduce birth weight. Lowering maternal intake of B(a)P and increasing dietary vitamin C intake during pregnancy may help to reduce any adverse effects of B(a)P on birth weight.     

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 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.     

Mechanistic polychlorinated biphenyl exposure modeling of mothers in the Canadian Arctic: the challenge of reliably establishing dietary composition

BackgroundTraditional food (TF) consumption represents the main route of persistent organic pollutant (POP) exposure for indigenous Arctic Canadians. Ongoing dietary transitions away from TFs and toward imported foods (IFs) may contribute to decreasing POP exposures observed in these groups.MethodsTo explore this issue, we combined the global fate and transport model GloboPOP and the human food chain bioaccumulation model ACC-Human Arctic to simulate polychlorinated biphenyl (PCB) exposure in two indigenous Arctic Canadian communities from the Inuvik region, Northwest Territories and Baffin region, Nunavut. Using dietary survey information from initial (1996–98) and follow-up (2005–07) biomonitoring campaigns in Inuvik and Baffin, we simulated PCB exposures (PCB-118, -138, -153, and -180) for each individual study participant and also whole study populations.ResultsTF intake rates, particularly of marine mammals (MMs), were the most important predictors of modeled PCB exposure, while TF consumption did not associate consistently with measured PCB exposures. Further, reported mean TF intake increased from baseline to follow-up in both Inuvik (from 8 to 183 g d^− 1) and Baffin (from 60 to 134 g d^− 1), opposing both the expected dietary transition direction and the observed decrease in human PCB exposures in these communities (ΣPCB Inuvik: from 43 to 29 ng g lipid^− 1, ΣPCB Baffin: from 213 to 82 ng g lipid^− 1). However dietary questionnaire data are frequently subject to numerous biases (e.g., recall, recency, confirmation), and thus casts doubt on the usefulness of these data.ConclusionsUltimately, our model's capability to reproduce historic PCB exposure data in these two groups was highly sensitive to TF intake, further underscoring the importance of accurate TF consumption reporting, and clarification of the role of dietary transitions in future POP biomonitoring of indigenous Arctic populations.     

Antibiotics detected in urines and adipogenesis in school children

BackgroundAlthough antibiotic use during early life has been demonstrated to be related to the altered adipogenesis in later life, limited data are available for the effect of antibiotic exposure in school children on adiposity from various sources, including from the use or contaminated food or drinking water.ObjectiveTo explore the association between the internal exposure of antibiotics from various sources and adipogenesis in school children using the biomonitoring of urinary antibiotics.MethodsAfter 586 school children aged 8–11 years were selected from Shanghai in 2013, total urinary concentrations (free and conjugated) of 21 common antibiotics from six categories (macrolides, β-lactams, tetracyclines, fluoroquinolones, sulfonamides, and phenicols), including five human antibiotics (HAs), two antibiotics preferred as HA, four veterinary antibiotics (VAs), and ten antibiotics preferred as VA, were measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Creatinine-corrected urinary concentrations of antibiotics were used to assess their exposure. Overweight or obesity was determined by the body mass index or waist circumference-based criteria deriving from national data.ResultsAll 21 antibiotics were found in urines with the overall detection frequency of 79.6%. The multinomial logistic regression analyses showed the significant associations of overweight and obesity with the exposure to VAs and antibiotics preferred as VA, but not with HAs or antibiotics preferred as HA. After adjusted for a number of obesity-relevant variables, the odds ratios (95% confidence interval) of BMI-based obesity risk of tertiles 2 and 3 of urinary concentrations relative to tertile 1 were respectively 2.54 (1.27, 5.07) and 2.92 (1.45, 5.87) for florfenicol, 0.57 (0.12, 2.63) and 3.63 (1.41, 9.32) for trimethoprim, and 3.00 (1.56, 5.76) and 1.99 (0.99, 4.01) for sum of veterinary antibiotics. Similar results were found when the outcome used WC-based obesity risk. The associations were sex related and mainly observed in boys.ConclusionsSome types of antibiotic exposure, which were mainly from food or drinking water, were associated with an increased risk of obesity in school children. Due to the cross-sectional design, more longitudinal and experimental studies are warranted to further test these findings.     

Predictors of exposure to organophosphate pesticides in schoolchildren in the Province of Talca,Chile

BackgroundFew data exist in Latin America concerning the association between organophosphate (OP) urinary metabolites and the consumption of fruits and vegetables and other exposure risk variables in schoolchildren.MethodsWe collected samples of urine from 190 Chilean children aged 6–12 years, fruits and vegetables, water and soil from schools and homes, and sociodemographic data through a questionnaire. We measured urinary dialkylphosphate (DAP) OP metabolites and OP pesticide residues in food consumed by these 190 children during two seasons: December 2010 (summer) and May 2011 (fall). We analyzed the relationship between urinary DAP concentrations and pesticide residues in food, home pesticide use, and residential location.ResultsDiethylalkylphosphates (DEAP) and dimethylalkylphosphates (DMAP) were detected in urine in 76% and 27% of the samples, respectively. Factors associated with urinary DEAP included chlorpyrifos in consumed fruits (p < 0.0001), urinary creatinine (p < 0.0001), rural residence (p = 0.02) and age less than 9 years (p = 0.004). Factors associated with urinary DMAP included the presence of phosmet residues in fruits (p < 0.0001), close proximity to a farm (p = 0.002), home fenitrothion use (p = 0.009), and season (p < 0.0001).ConclusionsUrinary DAP levels in Chilean school children were high compared to previously reported studies. The presence of chlorpyrifos and phosmet residues in fruits was the major factor predicting urinary DAP metabolite concentrations in children.     

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.     

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.