Department of Materials and Environmental Chemistry, Environmental Chemistry Unit, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
The knowledge about fetal exposure to acrylamide/glycidamide from the maternal exposure through food is limited. Acrylamide, glycidamide, and ethylene oxide are electrophiles and form adducts with hemoglobin (Hb), which could be used for in vivo dose measurement. In this study, a method for analysis of Hb adducts by liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27-0.86) for acrylamide, 0.38 (range 0.20-0.73) for glycidamide, and 0.43 (range 0.17-1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together, these results indicate a similar life span of fetal and maternal erythrocytes. The results showed that the in vivo dose in fetal and maternal blood is about the same and that the placenta gives negligible protection of the fetus to exposure from the investigated compounds. A trend of higher levels of the measured adducts in cord blood with gestational age was observed, which may reflect the gestational age-related change of the cord blood Hb composition toward a higher content of adult Hb. The results suggest that the Hb adduct levels measured in cord blood reflect the exposure to the fetus during the third trimester. The evaluation of the new analytical method showed that it is suitable for monitoring of background exposures of the investigated electrophilic compounds in large population studies.
Polychlorinated biphenyls (PCBs) are ubiquitously present in the environment and are suspected of carcinogenic, neurotoxic and immunotoxic effects. Significantly higher plasma concentrations of the congener PCB 28 occur in children compared to adults. Exposure in schools may contribute to this difference.
To determine whether increased blood plasma concentrations of PCB 28 in Danish school children and mothers are associated with living in homes or attending schools constructed in the PCB period (1959-1977).
PCB 28 was analyzed in plasma samples from 116 children aged 6-11years and 143 mothers living in an urban and a rural area in Denmark and participating in the European pilot project DEMOCOPHES (Demonstration of a study to COordinate and Perform Human Biomonitoring on a European Scale). In Denmark, PCBs were used in construction in the period 1950-1977, and year of construction or renovation of the homes and schools was used as a proxy for indoor PCB exposure. Linear regression models were used to assess the association between potential PCB exposure from building materials and lipid adjusted concentrations of PCB 28 in plasma, with and without adjustment for potential confounders.
Among the 116 children and 143 mothers, we were able to specify home construction period in all but 4 children and 5 mothers leaving 111 children and 138 mothers for our analyses. The median lipid adjusted plasma PCB 28 concentration was 3 (range: 1-28) ng/g lipid in the children and 2 (range: 1-8) ng/g lipid in the mothers. Children living in homes built in the PCB period had significantly higher lipid adjusted plasma PCB 28 concentrations compared to children living in homes built before or after the PCB period. Following adjustment for covariates, PCB 28 concentrations in children were 40 (95% CI: 13; 68) percent higher than concentrations of children living in homes constructed at other times. Furthermore, children attending schools built or substantially refurbished in the PCB period also had significantly higher (46%, 95% CI: 22; 70) PCB 28 concentrations compared to children attending schools constructed before or after the PCB period, while their mothers had similar concentrations. Adjustment for the most prevalent congener, PCB 153, did not change this effect of home or school construction. When both home and school construction year were included in the models, the increase in lipid adjusted plasma PCB 28 for children living in or attending schools from the PCB period was no longer statistically significant. The individual effect of home and school construction periods could not be evaluated further with the available data.
Our results suggest that PCB exposure in the indoor environment in schools and homes constructed during the PCB period may contribute significantly to children's plasma PCB 28 concentration. Efforts to minimize PCB exposure in indoor environments should be considered.
The Danish contribution to the European DEMOCOPHES project: A description of cadmium, cotinine and mercury levels in Danish mother-child pairs and the perspectives of supplementary sampling and measurements.
Human biomonitoring (HBM) is an important tool, increasingly used for measuring true levels of the body burdens of environmental chemicals in the general population. In Europe, a harmonized HBM program was needed to open the possibility to compare levels across borders. To explore the prospect of a harmonized European HBM project, DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) was completed in 17 European countries. The basic measurements performed in all implemented countries of DEMOCOPHES included cadmium, cotinine and phthalate metabolites in urine and mercury in hair. In the Danish participants, significant correlations between mothers and children for mercury in hair and cotinine in urine were found. Mercury in hair was further significantly associated with intake of fish and area of residence. Cadmium was positively associated with BMI in mothers and an association between cadmium and cotinine was also found. As expected high cotinine levels were found in smoking mothers. For both mercury and cadmium significantly higher concentrations were found in the mothers compared to their children. In Denmark, the DEMOCOPHES project was co-financed by the Danish ministries of health, environment and food safety. The co-financing ministries agreed to finance a number of supplementary measurements of substances of current toxicological, public and regulatory interest. This also included blood sampling from the participants. The collected urine and blood samples were analyzed for a range of other persistent and non-persistent environmental chemicals as well as two biomarkers of effect. The variety of supplementary measurements gives the researchers further information on the exposure status of the participants and creates a basis for valuable knowledge on the pattern of exposure to various chemicals.
This study aimed to analyze if adverse psychosocial working conditions, defined by the model of effort-reward imbalance (ERI), increase the risk of sleep disturbances in the Danish workforce.
Analyses were conducted both cross-sectionally and prospectively in a representative sample of Danish employees. The cross-sectional sample included 2614 participants (50% women) aged 18-59 years, of whom 263 had sleep disturbances. Of the 2351 participants initially free of sleep disturbances, 304 (12.9%) developed sleep disturbances during the 5-year follow-up. Data were analyzed with gender-stratified, multivariate logistic and linear regression analyses, adjusted for numerous covariates.
Cross-sectionally, a 1 S.D. increase in the ERI ratio was associated with sleep disturbances among both men [odds ratio (OR)=1.65, 95% confidence interval (CI)=1.20-2.27] and women (OR=1.82, 95% CI=1.46-2.28). In the prospective analysis, a 1 S.D. increase of the ERI ratio at baseline predicted the onset of sleep disturbances among men (OR=1.39, 95% CI=1.03-1.87) but not among women (OR=0.97, 95% CI=0.76-1.24).
Among men, ERI is a risk factor for the development of sleep disturbances in the Danish workforce. Among women, an association between ERI and sleep disturbances was restricted to the cross-sectional sample. Improving psychosocial working conditions might reduce the risk of sleep disturbances and subsequently also help to prevent clinical disorders related to sleep disturbances.
Maternal diet can result in exposure to environmental contaminants including dioxins which may influence foetal growth. We investigated the association between maternal diet and birth outcomes by defining a dioxin-rich diet. We used validated food frequency questionnaires to assess the diet of pregnant women from Greece, Spain, United Kingdom, Denmark and Norway and estimated plasma dioxin-like activity by the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR-CALUX®) bioassay in 604 maternal blood samples collected at delivery. We applied reduced rank regression to identify a dioxin-rich dietary pattern based on dioxin-like activity (DR-CALUX®) levels in maternal plasma, and calculated a dioxin-diet score as an estimate of adherence to this dietary pattern. In the five country population, dioxin-diet score was characterised by high consumption of red and white meat, lean and fatty fish, low-fat dairy and low consumption of salty snacks and high-fat cheese, during pregnancy. The upper tertile of the dioxin-diet score was associated with a change in birth weight of -121g (95% confidence intervals: -232, -10g) compared to the lower tertile after adjustment for confounders. A small non-significant reduction in gestational age was also observed (-1.4days, 95% CI: -3.8, 1.0days). Our results suggest that maternal diet might contribute to the exposure of the foetus to dioxins and dioxin-like compounds and may be related to reduced birth weight. More studies are needed to develop updated dietary guidelines for women of reproductive age, aiming to the reduction of dietary exposure to persistent organic pollutants as dioxins and dioxin-like compounds.
Micronucleus (MN) frequency is a biomarker for early genetic effects which is often used in human biomonitoring studies. Increased frequency of micronuclei has been associated with high levels of traffic exposure. Further high MN frequency was found predictive for cancer development in several studies of adults. In the present study, the MN frequency in blood samples from the Danish participants of the European pilot project DEMOCOPHES was analysed and related to the area of residence, self-reported and calculated exposure to road traffic as well as to mercury in hair and blood concentrations of persistent organic pollutants and dioxin-like activity measured in the same participants. The MN frequency analysis was performed with the cytokinesis-block micronucleus (CBMN) assay and included 100 children and 119 mothers. We found a significant correlation between mothers and children in the levels of micronuclei in 1000 binucleated T lymphocytes (‰MNBN) and in the proliferation index. Further the levels of ‰MNBN were significantly higher in mothers compared with their children. No significant associations were found for ‰MNBN for traffic related exposure in neither children nor their mothers. In children, a 2.5 times higher micronuclei in mononuclear T lymphocytes were found in children living within 50 m of a busy road, however, this was not found in mothers or in MNBN and the effect of exposure to road traffic on MN frequency needs further investigation. No significant associations were found between MN frequencies and the other biomarkers measured in the same participants.
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.
OBJECTIVE: We examined the association between outdoor work and the risks of non-melanoma skin cancer, cutaneous malignant melanoma, and lip cancer in a population-based case-control study. METHODS: Among all male wage earners in Denmark, 42,542 cases of non-melanoma skin cancer, 7,690 cases of cutaneous malignant melanoma, and 2,341 cases of lip cancer were identified in the nationwide Danish Cancer Registry. Population controls matched on sex and year of birth were selected at random among wage earners by incidence density sampling. Conditional logistic regression models were used to calculate odds ratios for risks of non-melanoma skin cancer, malignant melanoma, and lip cancer in relation to outdoor work after adjusting for covariates. RESULTS: For outdoor workers employed more than 10 years, the adjusted odds ratios were 0.83 (95% confidence interval (CI) 0.77-0.88) for non-melanoma skin cancer and 1.67 (95% CI 1.38-2.03) for lip cancer. Significantly reduced risk of basal cell cancers on the head, trunk, upper, or lower extremities were observed (range of odds ratios, 0.36 to 0.86). CONCLUSIONS: The results support the hypothesis of a decreased risk of non-melanoma skin cancer and an increased risk of lip cancer among outdoor workers in the Northern Hemisphere.
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.
Epidemiological studies have found negative associations between human health and particulate matter in urban air. In most studies outdoor monitoring of urban background has been used to assess exposure. In a field study, personal exposure as well as bedroom, front door and background concentrations of PM(2.5), black smoke (BS), and nitrogen dioxide (NO(2)) were measured during 2-day periods in 30 subjects (20-33 years old) living and studying in central parts of Copenhagen. The measurements were repeated in the four seasons. Information on indoor exposure sources such as environmental tobacco smoke (ETS) and burning of candles was collected by questionnaires. The personal exposure, the bedroom concentration and the front door concentration was set as outcome variable in separate models and analysed by mixed effect model regression methodology, regarding subject levels as a random factor. Seasons were defined as a dichotomised grouping of outdoor temperature (above and below 8 degrees C). For NO(2) there was a significant association between personal exposure and both the bedroom, the front door and the background concentrations, whereas for PM(2.5) and BS only the bedroom and the front door concentrations, and not the background concentration, were significantly associated to the personal exposure. The bedroom concentration was the strongest predictor of all three pollution measurements. The association between the bedroom and front door concentrations was significant for all three measurements, and the association between the front door and the background concentrations was significant for PM(2.5) and NO(2), but not for BS, indicating greater spatial variation for BS than for PM(2.5) and NO(2). For NO(2), the relationship between the personal exposure and the front door concentration was dependent upon the "season", with a stronger association in the warm season compared with the cold season, and for PM(2.5) and BS the same tendency was seen. Time exposed to burning of candles was a significant predictor of personal PM(2.5), BS and NO(2) exposure, and time exposed to ETS only associated with personal PM(2.5) exposure. These findings imply that the personal exposure to PM(2.5), BS and NO(2) depends on many factors besides the outdoor levels, and that information on, for example, time of season or outdoor temperature and residence exposure, could improve the accuracy of the personal exposure estimation.
