Marianne Thomsen

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.

Phthalates and nonylphenols in profiles of differently dressed soils

The concentrations of nonylphenols and phthalates in depth profiles of eight differently dressed, fertilised and cultured fields were investigated. The fields were typical for Danish agriculture and comprised an uncultured location, two manured fields, an artificially fertilised field and three fields amended with different amounts of sewage sludge. In addition, a location receiving run-off from a sewage sludge storage facility were investigated. At each location, two 50 cm vertical soil cores were taken, divided into sections of 10 cm each and analysed for nonylphenols and phthalates by high-resolution mass spectrometry. Di-(2-ethylhexyl)-phthalate (DEHP) was the most abundant phthalate in all samples whereas Di-(n-butyl)-phthalate (DBP) played a minor role. Nonylphenols occurred in significant concentrations only in soil samples exposed to high amounts of sludge and at the run-off location. A close relationship was found between the concentrations of contaminants in the soil samples and the method of dressing. The concentrations were low at comparable levels in the soil samples from the artificially fertilised field and in the fields amended with low amounts of sludge, as well as in the manured fields. Remarkably, these concentrations did not differ significantly from the level in an uncultured recreational preserved area, which was used as a reference. In contrast, much higher levels of contaminants were found in the soil samples from fields exposed to high amounts of sludge. We must conclude that sludge amendment below a certain limit does not lead to elevated levels of nonylphenols and phthalates in the soils, whereas heavy sludge amendment leads to the accumulation of these contaminants. For the vertical distribution of substances in the soils, an influence of soil characteristics on the concentration profile was noted. Thus, in soils with visible clay in the upper layers, a DEHP maximum occurred at a depth of 10-20 cm, whereas in most sandy soils no such maximum was observed. A 2-year time trend study of the highly sludge amended soil showed no measurable reduction in the substances during this period. The time study further suggested a downward movement of the DEHP maximum of approximately 10 cm per year.

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.

Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action.

Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile a comprehensive database based on OECDs standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68% of the pharmaceuticals have a non-specific MOA. Additionally, the acute-to-chronic ratio (ACR) for 70% of the analyzed pharmaceuticals was below 25 further suggesting a non-specific MOA. Sub-lethal receptor-mediated effects may however have a more specific MOA.

Characterisation of humic materials of different origin: A multivariate approach for quantifying the latent properties of dissolved organic matter

The inherent chemical properties of eight different dissolved organic matters (DOMs) originating from soil, surface and groundwater have been analysed. The samples consist of isolated fulvic acids (FA), humic acids (HA), and humic substances (HS), i.e. natural mixtures containing a humic and a fulvic fraction. The humic substances have been characterised by elemental analysis, size exclusion chromatography, E2/E3 and E4/E6 UV absorption ratios, and liquid-state 13C-NMR spectroscopy. The information contents of the different analytical methods have been investigated by pattern recognition, i.e. cluster analysis and principal component analysis (PCA). A comparative study of the information contents of DOM descriptors derived from different analytical methods is presented. Through extraction of information content of the individual analytical methods the inherent properties of DOM are quantified. Pattern recognition revealed significant quantitative differences in the inherent properties of DOM of different origin and type. PCA based on the NMR descriptors showed highest explained variance. However, all models showed low robustness due to the limited number of samples. The supervised pattern recognition, i.e. PCA, indicates a classification of DOMs into groups of similar properties by an increase in the number of samples. Furthermore that the number of groups may be higher and more continuously distributed than the conventional classification into fulvic acids, humic acids or humic substances.

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.

Environmental Hazards of Sea-Dumped Chemical Weapons

Does the post-WWII burial at sea of chemical weapons still pose a human and environmental risk?

Long-term human exposure to lead from different media and intake pathways.

Lead (Pb) is well known as an environmental pollutant: it can accumulate in various media, so actual lead exposure reflects both historical and present contaminations. Two main challenges then emerge: obtaining updated information to gain an overall picture of the sources of exposure, and predicting the resulting internal body exposure levels and effects that occur under long-term exposure conditions. In this paper, a modeling approach is used to meet these challenges with reference to Danish exposure conditions. Levels of lead content in various media have been coupled with data for lead intake and absorption in the human body, for both children and adults. An age-dependent biokinetic model allows then for determination of the blood lead levels resulting from chronic exposure. The study shows that the actual intake of lead is up to 27% of the Provisional Tolerable Daily Intake (PTDI) for children and around 8% for adults. It is confirmed that the critical route of exposure is via ingestion, accounting for 99% of total lead intake, while inhalation contributes only to 1% of total lead intake. The resulting lead levels in the blood after 2 years of exposure to actual contamination conditions have been estimated as up to 2.2μg/dl in children and almost 1μg/dl in adults. Impacts from lead can occur even at such levels. The role of historical and present sources to lead in the environment is discussed, and, for specific child and adult exposure scenarios, external-internal concentration relationships for the direct linkage between lead in environmental media and resulting concentrations of lead in blood are then presented.

The Use of Hasse Diagrams as a Potential Approach for Inverse QSAR

Abstract Quantitative structure-activity relationships are often based on standard multidimensional statistical analyses and sophisticated local and global molecular descriptors. Here, the aim is to develop a tool helpful to define a molecule or a class of molecules which fulfills pre-described properties, i.e., an Inverse QSAR approach. If highly sophisticated descriptors are used in QSAR, the structure and then the synthesis recipe may be hard to derive. Thus, descriptors, from which the synthesis recipe can be easily derived, seem appropriate to be included within this study. However, if descriptors simple enough to be useful for defining syntheses recipes of chemicals were used, the accuracy of a numeric expression may fail. This paper suggests a method, based on very simple elements of the theory of partially ordered sets, to find a qualitative basis for the relationship between such fairly simple descriptors on the one side and a series of ecotoxicological properties, on the other side. The partial order ranking method assumes neither linearity nor certain statistical distribution properties. Therefore the method may be more general compared to many standard statistical techniques. A series of chlorinated aliphatic compounds has been used as an illustrative example and a comparison with more sophisticated descriptors derived from quantum chemistry and graph theory is given. Among the results, it was disclosed that only for algae lethal concentration, as one of the four ecotoxicological properties, the synthesis specific predictors seem to be good estimators. For all other ecotoxicological properties quantum chemical descriptors appear as the more suitable estimators.

The influence on partial order ranking from input parameter uncertainty. Definition of a robustness parameter.

The method of partial order ranking has been used within the environmental area for a variety of purposes as an attractive way of handling complex information. However, the environmental data are often associated with a significant degree of uncertainty. In this investigation the general nature of the influence from data uncertainty on the partial order ranking is analyzed. A Monte Carlo type analysis is performed in which a series of randomly formed data are used to test the influence of data uncertainty. The partial order ranking is interpreted, where the results are transferred to a one-dimensional ranking scale taking into account that not all elements are ranked with the same certainty. A simple general robustness parameter (E) in form of the expected number of comparisons for each ranking element is defined and correlated to the uncertainty analysis results. A simple equation relates E to the number of elements and the number of parameters, respectively. The magnitude of the ranking uncertainty is shown to increase rapidly when the E value decreases below 4-5 comparisons per element. When the E value exceeds 5 the ranking uncertainty becomes nearly constant and independent on the actual E value.