Gabriel Bekö

Children's Phthalate Intakes and Resultant Cumulative Exposures Estimated from Urine Compared with Estimates from Dust Ingestion, Inhalation and Dermal Absorption in Their Homes and Daycare Centers

Total daily intakes of diethyl phthalate (DEP), di(n-butyl) phthalate (DnBP), di(isobutyl) phthalate (DiBP), butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) were calculated from phthalate metabolite levels measured in the urine of 431 Danish children between 3 and 6 years of age. For each child the intake attributable to exposures in the indoor environment via dust ingestion, inhalation and dermal absorption were estimated from the phthalate levels in the dust collected from the child’s home and daycare center. Based on the urine samples, DEHP had the highest total daily intake (median: 4.42 µg/d/kg-bw) and BBzP the lowest (median: 0.49 µg/d/kg-bw). For DEP, DnBP and DiBP, exposures to air and dust in the indoor environment accounted for approximately 100%, 15% and 50% of the total intake, respectively, with dermal absorption from the gas-phase being the major exposure pathway. More than 90% of the total intake of BBzP and DEHP came from sources other than indoor air and dust. Daily intake of DnBP and DiBP from all exposure pathways, based on levels of metabolites in urine samples, exceeded the Tolerable Daily Intake (TDI) for 22 and 23 children, respectively. Indoor exposures resulted in an average daily DiBP intake that exceeded the TDI for 14 children. Using the concept of relative cumulative Tolerable Daily Intake (TDIcum), which is applicable for phthalates that have established TDIs based on the same health endpoint, we examined the cumulative total exposure to DnBP, DiBP and DEHP from all pathways; it exceeded the tolerable levels for 30% of the children. From the three indoor pathways alone, several children had a cumulative intake that exceeded TDIcum. Exposures to phthalates present in the air and dust indoors meaningfully contribute to a child’s total intake of certain phthalates. Such exposures, by themselves, may lead to intakes exceeding current limit values.

Seasonal Variations of Indoor Microbial Exposures and Their Relation to Temperature, Relative Humidity, and Air Exchange Rate

ABSTRACT Indoor microbial exposure has been related to adverse pulmonary health effects. Exposure assessment is not standardized, and various factors may affect the measured exposure. The aim of this study was to investigate the seasonal variation of selected microbial exposures and their associations with temperature, relative humidity, and air exchange rates in Danish homes. Airborne inhalable dust was sampled in five Danish homes throughout the four seasons of 1 year (indoors, n = 127; outdoors, n = 37). Measurements included culturable fungi and bacteria, endotoxin, N-acetyl-beta-d-glucosaminidase, total inflammatory potential, particles (0.75 to 15 μm), temperature, relative humidity, and air exchange rates. Significant seasonal variation was found for all indoor microbial exposures, excluding endotoxin. Indoor fungi peaked in summer (median, 235 CFU/m3) and were lowest in winter (median, 26 CFU/m3). Indoor bacteria peaked in spring (median, 2,165 CFU/m3) and were lowest in summer (median, 240 CFU/m3). Concentrations of fungi were predominately higher outdoors than indoors, whereas bacteria, endotoxin, and inhalable dust concentrations were highest indoors. Bacteria and endotoxin correlated with the mass of inhalable dust and number of particles. Temperature and air exchange rates were positively associated with fungi and N-acetyl-beta-d-glucosaminidase and negatively with bacteria and the total inflammatory potential. Although temperature, relative humidity, and air exchange rates were significantly associated with several indoor microbial exposures, they could not fully explain the observed seasonal variations when tested in a mixed statistical model. In conclusion, the season significantly affects indoor microbial exposures, which are influenced by temperature, relative humidity, and air exchange rates.

Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: Experimental verification

Background Fundamental considerations indicate that, for certain phthalate esters, dermal absorption from air is an uptake pathway that is comparable to or greater than inhalation. Yet this pathway has not been experimentally evaluated and has been largely overlooked when assessing uptake of phthalate esters. Objectives This study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. Methods In a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air concentrations of DEP and DnBP. The participants either wore a hood and breathed air with phthalate concentrations substantially below those in the chamber or did not wear a hood and breathed chamber air. All urinations were collected from initiation of exposure until 54 hr later. Metabolites of DEP and DnBP were measured in these samples and extrapolated to parent phthalate intakes, corrected for background and hood air exposures. Results For DEP, the median dermal uptake directly from air was 4.0 μg/(μg/m3 in air) compared with an inhalation intake of 3.8 μg/(μg/m3 in air). For DnBP, the median dermal uptake from air was 3.1 μg/(μg/m3 in air) compared with an inhalation intake of 3.9 μg/(μg/m3 in air). Conclusions This study shows that dermal uptake directly from air can be a meaningful exposure pathway for DEP and DnBP. For other semivolatile organic compounds (SVOCs) whose molecular weight and lipid/air partition coefficient are in the appropriate range, direct absorption from air is also anticipated to be significant. Citation Weschler CJ, Bekö G, Koch HM, Salthammer T, Schripp T, Toftum J, Clausen G. 2015. Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: experimental verification. Environ Health Perspect 123:928–934; http://dx.doi.org/10.1289/ehp.1409151

Ultrafine Particles: Exposure and Source Apportionment in 56 Danish Homes

Particle number (PN) concentrations (10-300 nm in size) were continuously measured over a period of ~45 h in 56 residences of nonsmokers in Copenhagen, Denmark. The highest concentrations were measured when occupants were present and awake (geometric mean, GM: 22.3 × 10(3) cm(-3)), the lowest when the homes were vacant (GM: 6.1 × 10(3) cm(-3)) or the occupants were asleep (GM: 5.1 × 10(3) cm(-3)). Diary entries regarding occupancy and particle related activities were used to identify source events and apportion the daily integrated exposure among sources. Source events clearly resulted in increased PN concentrations and decreased average particle diameter. For a given event, elevated particle concentrations persisted for several hours after the emission of fresh particles ceased. The residential daily integrated PN exposure in the 56 homes ranged between 37 × 10(3) and 6.0 × 10(6) particles per cm(3)·h/day (GM: 3.3 × 10(5) cm(-3)·h/day). On average, ~90% of this exposure occurred outside of the period from midnight to 6 a.m. Source events, especially candle burning, cooking, toasting, and unknown activities, were responsible on average for ~65% of the residential integrated exposure (51% without the unknown activities). Candle burning occurred in half of the homes where, on average, it was responsible for almost 60% of the integrated exposure.

Cardiovascular and lung function in relation to outdoor and indoor exposure to fine and ultrafine particulate matter in middle-aged subjects

This cross-sectional study investigated the relationship between exposure to airborne indoor and outdoor particulate matter (PM) and cardiovascular and respiratory health in a population-based sample of 58 residences in Copenhagen, Denmark. Over a 2-day period indoor particle number concentrations (PNC, 10-300 nm) and PM2.5 (aerodynamic diameter<2.5 μm) were monitored for each of the residences in the living room, and outdoor PNC (10-280 nm), PM2.5 and PM10 (aerodynamic diameter<10 μm) were monitored at an urban background station in Copenhagen. In the morning, after the 2-day monitoring period, we measured microvascular function (MVF) and lung function and collected blood samples for biomarkers related to inflammation, in 78 middle-aged residents. Bacteria, endotoxin and fungi were analyzed in material from electrostatic dust fall collectors placed in the residences for 4 weeks. Data were analyzed using linear regression with the generalized estimating equation approach. Statistically significant associations were found between indoor PNC, dominated by indoor use of candles, and lower lung function, the prediabetic marker HbA1c and systemic inflammatory markers observed as changes in leukocyte differential count and expression of adhesion markers on monocytes, whereas C-reactive protein was significantly associated with indoor PM2.5. The presence of indoor endotoxin was associated with lower lung function and expression of adhesion markers on monocytes. An inverse association between outdoor PNC and MVF was also statistically significant. The study suggests that PNC in the outdoor environment may be associated with decreased MVF, while PNC, mainly driven by candle burning, and bioaerosols in the indoor environment may have a negative effect on lung function and markers of systemic inflammation and diabetes.

Role of clothing in both accelerating and impeding dermal absorption of airborne SVOCs

To assess the influence of clothing on dermal uptake of semi-volatile organic compounds (SVOCs), we measured uptake of selected airborne phthalates for an individual wearing clean clothes or air-exposed clothes and compared these results with dermal uptake for bare-skinned individuals under otherwise identical experimental conditions. Using a breathing hood to isolate dermal from inhalation uptake, we measured urinary metabolites of diethylphthalate (DEP) and di-n-butylphthalate (DnBP) from an individual exposed to known concentrations of these compounds for 6 h in an experimental chamber. The individual wore either clean (fresh) cotton clothes or cotton clothes that had been exposed to the same chamber air concentrations for 9 days. For a 6-h exposure, the net amounts of DEP and DnBP absorbed when wearing fresh clothes were, respectively, 0.017 and 0.007 μg/kg/(μg/m3); for exposed clothes the results were 0.178 and 0.261 μg/kg/(μg/m3), respectively (values normalized by air concentration and body mass). When compared against the average results for bare-skinned participants, clean clothes were protective, whereas exposed clothes increased dermal uptake for DEP and DnBP by factors of 3.3 and 6.5, respectively. Even for non-occupational environments, wearing clothing that has adsorbed/absorbed indoor air pollutants can increase dermal uptake of SVOCs by substantial amounts relative to bare skin.

Phthalate exposure through different pathways and allergic sensitization in preschool children with asthma, allergic rhinoconjunctivitis and atopic dermatitis.

Studies in rodents indicate that phthalates can function as adjuvants, increasing the potency of allergens. Meanwhile, epidemiological studies have produced inconsistent findings regarding relationships between phthalate exposures and allergic disease in humans. The present study examined phthalate exposure and allergic sensitization in a large group of 3-5 year old children: 300 random controls and 200 cases with asthma, rhinoconjunctivitis or atopic dermatitis as reported in questionnaires. The children were clinically examined to confirm their health status. Blood samples were analyzed for IgE sensitization to 20 allergens. Adjusted logistic regressions were used to look for associations between phthalate exposure indicators (mass fractions in dust from childrens homes and daycares, metabolites in urine, and estimated daily indoor intakes from dust ingestion, inhalation and dermal absorption) and sensitization and allergic disease. No direct associations were found between phthalate exposures and asthma, rhinoconjunctivitis or atopic dermatitis. However, among children with these diseases, there were significant associations between non-dietary exposures to DnBP, BBzP and DEHP in the indoor environment (mass fractions in dust or daily indoor intakes from dust ingestion, inhalation and dermal absorption) and allergic sensitization. Some exposure pathways were more strongly associated with sensitization than others, although the results are not conclusive and require confirmation. A number of the associations depended on accounting for a childs exposure in more than one environment (i.e., daycare facility as well as home). Significant associations were not observed between phthalate metabolites in urine, which reflected exposure from diet as well as indoor pathways, and allergic sensitization.

Squalene and Cholesterol in Dust from Danish Homes and Daycare Centers

Given the rate at which humans shed their skin (desquamation), skin flakes that contain squalene and cholesterol are anticipated to be major constituents of indoor dust. These compounds have been detected in more than 97% of the dust samples collected from 500 bedrooms and 151 daycare centers of young children living in Odense, Denmark. The mass fractions of squalene in dust were approximately log-normally distributed (homes: GM = 32 μg/g, GSD = 4.3; daycare centers: GM = 11.5 μg/g, GSD = 4.3); those of cholesterol displayed a poorer fit to such a distribution (homes: GM = 625 μg/g, GSD = 3.4; daycare centers: GM = 220 μg/g, GSD = 4.0). Correlations between squalene and cholesterol were weak (r = 0.22). Furthermore, the median squalene-to-cholesterol ratio in dust (~0.05) was more than an order of magnitude smaller than that in skin oil. This implies sources in addition to desquamation (e.g., cholesterol from cooking) coupled, perhaps, with a shorter indoor lifetime for squalene. Estimated values of squalenes vapor pressure, while uncertain, suggest meaningful redistribution from dust to other indoor compartments. We estimate that dust containing squalene at 60 μg/g would contribute about 4% to overall ozone removal by indoor surfaces. This is roughly comparable to the fraction of ozone removal that can be ascribed to reactions with indoor terpenes. Squalene containing dust is anticipated to contribute to the scavenging of ozone in all settings occupied by humans.

Vascular and lung function related to ultrafine and fine particles exposure assessed by personal and indoor monitoring: a cross-sectional study

BackgroundExposure to ambient air particulate matter (PM) has been linked to decline in pulmonary function and cardiovascular events possibly through inflammation. Little is known about individual exposure to ultrafine particles (UFP) inside and outside modern homes and associated health-related effects.MethodsAssociations between vascular and lung function, inflammation markers and exposure in terms of particle number concentration (PNC; d = 10-300 nm) were studied in a cross-sectional design with personal and home indoor monitoring in the Western Copenhagen Area, Denmark. During 48-h, PNC and PM2.5 were monitored in living rooms of 60 homes with 81 non-smoking subjects (30-75 years old), 59 of whom carried personal monitors both when at home and away from home. We measured lung function in terms of the FEV1/FVC ratio, microvascular function (MVF) and pulse amplitude by digital artery tonometry, blood pressure and biomarkers of inflammation including C-reactive protein, and leukocyte counts with subdivision in neutrophils, eosinophils, monocytes, and lymphocytes in blood.ResultsPNC from personal and stationary home monitoring showed weak correlation (r = 0.15, p = 0.24). Personal UFP exposure away from home was significantly inversely associated with MVF (1.3% decline per interquartile range, 95% confidence interval: 0.1-2.5%) and pulse amplitude and positively associated with leukocyte and neutrophil counts. The leukocyte and neutrophil counts were also positively and pulse amplitude negatively associated with total personal PNC. Indoor PNC and PM2.5 showed positive association with blood pressure and inverse association with eosinophil counts.ConclusionsThe inverse association between personal exposure away from home and MVF is consistent with adverse health effects of UFP from sources outside the home and might be related to increased inflammation indicated by leukocyte counts, whereas UFP from sources in the home could have less effect.

Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects

To better understand the dermal exposure pathway, we enhance an existing mechanistic model of transdermal uptake by including skin surface lipids (SSL) and consider the impact of clothing. Addition of SSL increases the overall resistance to uptake of SVOCs from air but also allows for rapid transfer of SVOCs to sinks like clothing or clean air. We test the model by simulating di-ethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) exposures of six bare-skinned (Weschler et al. 2015, Environ. Health Perspect., 123, 928) and one clothed participant (Morrison et al. 2016, J. Expo. Sci. Environ. Epidemiol., 26, 113). The model predicts total uptake values that are consistent with the measured values. For bare-skinned participants, the model predicts a normalized mass uptake of DEP of 3.1 (μg/m2 )/(μg/m3 ), whereas the experimental results range from 1.0 to 4.3 (μg/m2 )/(μg/m3 ); uptake of DnBP is somewhat overpredicted: 4.6 (μg/m2 )/(μg/m3 ) vs. the experimental range of 0.5-3.2 (μg/m2 )/(μg/m3 ). For the clothed participant, the model predicts higher than observed uptake for both species. Uncertainty in model inputs, including convective mass transfer coefficients, partition coefficients, and diffusion coefficients, could account for overpredictions. Simulations that include transfer of skin oil to clothing improve model predictions. A dynamic model that includes SSL is more sensitive to changes that impact external mass transfer such as putting on and removing clothes and bathing.