Marie Frederiksen

Human internal and external exposure to PBDEs - a review of levels and sources.

This paper reviews the existing literature on human exposure to polybrominated diphenyl ethers (PBDEs), with particular focus on external exposure routes (e.g. dust, diet, and air) and the resulting internal exposure to PBDEs (e.g. breast milk and blood). Being lipophilic and persistent organic compounds, PBDEs accumulate in lipid-rich tissues. Consequently, food items like fish from high trophic levels or lipid-rich oils have been found to contain relatively high concentrations of PBDEs, thus presenting an important exposure pathway to humans. The presence of PBDEs in various products of everyday use may lead to some additional exposure in the home environment. Dust seem to be an aggregate of the indoor source, and the ingestion of dust conveys the highest intake of BDE-209 of all sources, possibly also of other PBDE congeners. The PBDE exposure through dust is significant for toddlers who ingest more dust than adults. Infants are also exposed to PBDEs via breast milk. Internal human exposure has generally been found to be one order of magnitude larger in North America than in Europe and Asia. These differences cannot solely be explained by the dietary intake as meat products are the only food group where some differences has been observed. However, indoor air and dust concentrations have been found to be approximately one order of magnitude higher in North America than in Europe, possibly a result of different fire safety standards. Within Europe, higher PBDE concentrations in dust were found in the UK than in continental Europe. Recent studies have shown that BDE-209 also accumulates in humans. A shift in congener composition from maternal to umbilical cord blood has been observed in several cases. A shift has also been observed for BDE-209, which is present in larger ratios in umbilical cord blood and in particular in placenta than in maternal blood.

Polybrominated diphenyl ethers (PBDEs) in the indoor environment and associations with prenatal exposure

As part of a larger exposure study, samples of dust and indoor air were collected in the homes of 43 pregnant women living in the Copenhagen area (Denmark) and analysed for 12 polybrominated diphenyl ethers using GC-MS. A second dust sample collected after delivery was analysed for BDE-183 and BDE-209, which were highly correlated with the pre-delivery samples, but did not reproduce the actual values. Concentrations as high as 80 μg/g were measured for the dominant BDE congener BDE-209, with median concentrations of 332 and 432 ng/g, respectively, in pre- and post-delivery dust samples. In 12% of the dust samples, the concentration of BDE-209 was lower than that of the summed concentration of PentaBDE congeners. The median concentrations of BDE-47 and BDE-99 in dust were 16.9 and 13.6 ng/g, respectively. The dust concentrations were in line with other European studies and confirmed previously established geographical differences between continental Europe and North America. Additional octa- and nonaBDE congeners (BDE-197, BDE-203, BDE-206, BDE-207, and BDE-208) were analysed in dust and analytical issues were discussed as these congeners also can be a product of thermal degradation of BDE-209 in gas chromatographic analysis. BDE-206 was the dominating nonaBDE, with median and maximum concentrations of 12.8 and 2217 ng/g, respectively, but the ratio of nonaBDEs to the sum of nona- and decaBDEs was relatively constant, despite a large range in absolute dust concentrations. While the congeners of the PentaBDE mixture were highly inter-correlated for both dust and air, no correlation was found with BDE-209 in either matrix. Air concentrations were relatively high in an international context, with median concentrations of 134, 63.7 and 119 pg/m³ for BDE-47, BDE-99 and BDE-209, respectively, and not correlated with dust concentrations. Additional placenta data were available for the study group and found to correlate significantly with dust concentrations for some PentaBDE congeners, but not BDE-209, indicating that dust may be an important exposure pathway for PentaBDE congeners. While BDE-209 also was present in placenta, it did not exceed the other congeners by the same factors as in dust. This might be caused by a combination of the compounds physical-chemical properties affecting bioavailability, uptake, partitioning and metabolisation, and other sources of exposure, but was not investigated further in this study. For all matrices, the PBDE profile resembled that of the technical product Bromkal 70-5DE, but air contained higher percentages of the lower brominated congeners and placenta tissue was dominated by BDE-153. The predominance of BDE-153 has been described in other studies on human samples and related to the highest retention in the body, but further research into toxicokinetics will be required to clarify mechanisms.

Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

BackgroundPolybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants in consumer products. PBDEs may affect thyroid hormone homeostasis, which can result in irreversible damage of cognitive performance, motor skills and altered behaviour. Thus, in utero exposure is of very high concern due to critical windows in fetal development.MethodsA human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored in the maternal and fetal compartments. In addition, the perfused cotyledon, the surrounding placental tissue as well as pre-perfusion placental tissue and umbilical cord plasma were also analysed. The PBDE analysis included Soxhlet extraction, clean-up by adsorption chromatography and GC-MS analysis.Results and DiscussionPlacental transfer of BDE-47 was faster and more extensive than for BDE-99. The fetal-maternal ratios (FM-ratio) after four hours of perfusion were 0.47 and 0.25 for BDE-47 and BDE-99, respectively, while the indicative permeability coefficient (IPC) measured after 60 minutes of perfusion was 0.26 h-1 and 0.10 h-1, respectively. The transport of BDE-209 seemed to be limited. These differences between the congeners may be related to the degree of bromination. Significant accumulation was observed for all congeners in the perfused cotyledon as well as in the surrounding placental tissue.ConclusionThe transport of BDE-47 and BDE-99 indicates in utero exposure to these congeners. Although the transport of BDE-209 was limited, however, possible metabolic debromination may lead to products which are both more toxic and transportable. Our study demonstrates fetal exposure to PBDEs, which should be included in risk assessment of PBDE exposure of women of child-bearing age.

Patterns and concentration levels of polybrominated diphenyl ethers (PBDEs) in placental tissue of women in Denmark

The levels and congener patterns of PBDEs were investigated in human placental samples in Denmark. The median concentrations of sigmaPBDE(tri-hepta) and BDE-209 in the 50 samples were 1.22 and 1.14 ng g(-1) lw, respectively, with the total sum ranging from 0.51 to 17.1 ng g(-1) lw, which is similar to previous placental studies. The PBDE content in placental tissue was dominated by BDE-209, which accounted for approximately 50% of the total amount of PBDEs. BDE-47, -99, and -153 were detected in all samples. Approximately equal amounts of BDE-47 and BDE-153 were observed in the placental tissue, which is in agreement with previous European studies of human serum. Principal Component Analysis (PCA) was performed to analyze congener patterns within and between mothers. The loading plot showed groupings of the measured PBDE variables in three groups, representative of Penta-, Octa- and Deca-BDE technical mixtures. Congeners representing the individual technical mixtures were close to orthogonal or inversely correlated, indicating variation in the congener patterns of internal exposure corresponding to the patterns of technical mixtures used in products. Visualisation of the participant objects according to body mass index (BMI), revealed inherent congener patterns (19% X-variance) showing increased frequency for participants within the highest BMI group to have elevated concentrations of BDE-209 in the placental tissue.

Sampling, extraction and measurement of bacteria, endotoxin, fungi and inflammatory potential of settling indoor dust

Selection of sampling device, sampling location and period are important first steps in the measurement of exposure to bioaerosols in indoor air. The steps following the sampling include treatment of samples and laboratory analysis. In this study, settling bacteria, endotoxin, fungi and serine protease have been measured in Danish homes using Electrostatic Dust Fall Collectors (EDCs). The effects of the presence of occupants, sampling on open surfaces versus in bookcases and treatment of samples have been studied. Concentrations of bacteria and endotoxin were significantly higher when occupants were at home than when they were absent. Across homes, higher concentrations of fungi were found in spring than in winter, as was the total inflammatory potential, while higher concentrations of protease were found in winter than in spring. The placement of the EDCs in bookcases versus on an open surface significantly affected the measured concentrations of bacteria and endotoxin. Direct extraction of EDC cloths caused a higher measured concentration of bacteria, fungi and serine protease than if EDC cloths were extracted post-storage at -20 °C. Extraction of EDC cloths caused an average of 51% and 58% extraction of bacteria and fungi respectively. In conclusion, EDCs should be placed on open surfaces during the sampling, how much occupants are present in their home during sampling and sampling season should be considered, EDC cloths should not be stored in a freezer before extraction of microorganisms, but extraction suspensions can be stored at -80 °C without affecting the number of microorganisms significantly.

Polychlorinated biphenyls (PCBs) in indoor air originating from sealants in contaminated and uncontaminated apartments within the same housing estate

Twenty-four congeners of polychlorinated biphenyls (PCBs) were measured in 83 air samples and 20 elastic sealants samples of apartments with PCB-containing sealants. In addition, PCBs were measured in 21 air samples from reference apartments located in an uncontaminated section of the same estate. The PCB(tot) levels in the air of the contaminated section were 168-3843 ng m(-3) (mean: 1030 ng m(-3)), while the mean levels in the reference apartments were 6.03 ng m(-3). The sum of the 24 measured PCB congeners in sealants from the contaminated section was 187-221680 mg kg(-1). Principal component analysis revealed four groups among the sealant samples with different congener compositions, only two of which were clearly similar to known PCB mixtures, while two were not. Significant correlations and intercorrelations were observed between the lower chlorinated congeners in air and sealant, e.g. for PCB 28(air) and 28(seal) (p=0.04) and for PCB 28(air) and 52(air), 52(seal). However, no correlation was observed between the lower chlorinated congeners and the sums of PCB (∑PCB(6) or ∑PCB(24)) or the higher chlorinated congeners. Analysis of air concentrations in relation to questionnaire data indicated that the indoor air levels could be reduced by increased cleaning and airing frequencies.

Method development for simultaneous analysis of HBCD, TBBPA, and dimethyl-TBBPA in marine biota from Greenland and the Faroe Islands

The brominated flame retardants hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are high-production-volume chemicals. In recent years, their presence has been reported in sediment and biota from the marine environment. In this study, an analytical method was developed for the simultaneous determination of HBCD, TBBPA, and the possible metabolite dimethyl-TBBPA. The method was applied in a preliminary screening of egg, liver, and adipose tissue of marine biota from Greenland and the Faroe Islands. α-HBCD was detected in 35 of 36 analysed samples from the Arctic, indicating a ubiquitous presence of α-HBCD in the environment. β- and γ-HBCD were found in 10 and 14 samples, respectively. TBBPA and dimethyl-TBBPA were not detected in any of the samples indicating limited or no transport of these compounds to remote areas.

Plasma polychlorinated biphenyls in residents of 91 PCB-contaminated and 108 non-contaminated dwellings-an exposure study.

BACKGROUND In the1950s-1970s polychlorinated biphenyls (PCBs) were used in several countries as plasticizers in elastic sealants in buildings. OBJECTIVE The primary objective was to study whether residents of PCB-contaminated dwellings had higher plasma levels of PCBs than their neighbours in non-contaminated dwellings. The secondary objective was to study possible associations between concentrations of PCBs in the indoor air and in the plasma of residents. METHODS Stratified cross-sectional study of residents of a housing estate with four sections, of which only one section had PCB-containing sealants. The determination of 27 PCB congeners in plasma was performed among 134 exposed and 139 non-exposed residents. Air measurements were conducted in 104 flats. RESULTS Significant differences in plasma PCBs between exposed versus non-exposed were found for most of the lower chlorinated and many of the higher chlorinated congeners. The median of sum of 27 PCBs was approximately four times higher in exposed compared with non-exposed residents. The elevated PCB concentrations persisted in multivariable analyses controlling for relevant cofactors. We found significant correlations between PCB indoor air concentrations and the PCB concentration in the plasma of the residents for ten of the lower chlorinated congeners. CONCLUSION Our study confirms that indoor air exposure to PCBs from PCB containing sealants may result in a considerable internal PCBs exposure of the residents. For the first time we were able to demonstrate that the internal exposure to low chlorinated PCBs is significantly associated with the indoor air concentration of these congeners.

Indoor and outdoor exposure to ultrafine, fine and microbiologically derived particulate matter related to cardiovascular and respiratory effects in a panel of elderly urban citizens.

To explore associations of exposure to ambient and indoor air particulate and bio-aerosol pollutants with cardiovascular and respiratory disease markers, we utilized seven repeated measurements from 48 elderly subjects participating in a 4-week home air filtration study. Microvascular function (MVF), lung function, blood leukocyte counts, monocyte adhesion molecule expression, C-reactive protein, Clara cell protein (CC16) and surfactant protein-D (SPD) were examined in relation to exposure preceding each measurement. Exposure assessment included 48-h urban background monitoring of PM10, PM2.5 and particle number concentration (PNC), weekly measurements of PM2.5 in living- and bedroom, 24-h measurements of indoor PNC three times, and bio-aerosol components in settled dust on a 2-week basis. Statistically significant inverse associations included: MVF with outdoor PNC; granulocyte counts with PM2.5; CD31 expression with dust fungi; SPD with dust endotoxin. Significant positive associations included: MVF with dust bacteria; monocyte expression of CD11 with PM2.5 in the bedroom and dust bacteria and endotoxin, CD31 expression with dust serine protease; serum CC16 with dust NAGase. Multiple comparisons demand cautious interpretation of results, which suggest that outdoor PNC have adverse effects on MVF, and outdoor and indoor PM2.5 and bio-aerosols are associated with markers of inflammation and lung cell integrity.

Modelling of human transplacental transport as performed in Copenhagen, Denmark

Placenta perfusion models are very effective when studying the placental mechanisms in order to extrapolate to real-life situations. The models are most often used to investigate the transport of substances between mother and foetus, including the potential metabolism of these. We have studied the relationships between maternal and foetal exposures to various compounds including pollutants such as polychlorinated biphenyls, polybrominated flame retardants, nanoparticles as well as recombinant human antibodies. The compounds have been studied in the human placenta perfusion model and to some extent in vitro with an established human monolayer trophoblast cell culture model. Results from our studies distinguish placental transport of substances by physicochemical properties, adsorption to placental tissue, binding to transport and receptor proteins and metabolism. We have collected data from different classes of chemicals and nanoparticles for comparisons across chemical structures as well as different test systems. Our test systems are based on human material to bypass the extrapolation from animal data. By combining data from our two test systems, we are able to rank and compare the transport of different classes of substances according to their transport ability. Ultimately, human data including measurements in cord blood contribute to the study of placental transport.