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- Kärrman, Anna
(författare)
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Analysis and human levels of persistent perfluorinated chemicals
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An extensive use of perfluorinated chemicals (PFCs) in the last 50 years has resulted in a worldwide spread of these persistent chemicals. Human populations are subjected to a large number of PFCs in ways that are not yet fully explained. The aims of this thesis are to develop and assure the quality of analytical methods in order to collect information on human levels and to facilitate the assessment of human exposure of PFCs. Solid-phase extraction (SPE) methods for human blood and milk using two sorbents, octadecyl (C18) and a weak anion exchange polymer (WAX), were developed. Perfluorinated alkyl sulfonates (PFSAs) and perfluorinated alkyl carboxylic acids (PFCAs) with carbon chain lengths between four and fourteen together with perfluorooctane sulfonamide (PFOSA) could be extracted from human matrices. These extraction procedures enable selective and sensitive analysis of PFCs in human matrices using single quadrupole mass spectrometry (SQMS). The accuracy and reliability of the methods are discussed in the context of intralaboratory as well as interlaboratory quality assurance. Further improvements of the analysis are discussed including the evaluation of ultra performance liquid chromatography (UPLC). Human whole blood, plasma and serum from Sweden, Australia and the United Kingdom have been analysed. The blood matrix selection in the assessment and comparisons of human exposure to PFCs is crucial. Human plasma contains a high percentage of PFSAs and PFCAs. On the contrary, only about 20% of the total PFOSA content is present in plasma after removal of the red blood cells. Up to eleven persistent PFCs are detected in human blood, with detection levels between 0.1-0.5 ng/mL. A gender difference with higher serum levels for males is apparent. An age trend was observed for perfluorooctane sulfonate (PFOS) levels in serum from Australia. The levels found in Australian serum indicate that emissions from the PFC production facilities are of less importance for human exposure. Matched human milk and serum samples from Sweden show that milk levels of PFCs are about 1% of the maternal serum level. Up to five persistent PFCs are found in human milk from Sweden, with detection limits between 0.005-0.1 ng/mL, and the levels in Swedish pooled milk samples have remained constant between 1996 and 2004. A linear relationship between the maternal serum level and milk level was seen for PFOS and its shorter homologue perfluorohexane sulfonate (PFHxS). The daily intake of PFOS for a nursing infant in Sweden is estimated to be 121 ng/day if the maternal serum level is 20 ng/mL. Lactation is therefore a major exposure source for breast-fed infants. Monomethyl- and dimethyl-branched isomers of PFOS could be separated in human blood using high performance liquid chromatography (HPLC). Human plasma contains a smaller percentage of the linear PFOS compared to commercially available PFOS standard materials, which indicate isomer specific uptake and/or elimination. A difference in the isomer composition is also seen between the countries studied. Human blood from the UK and Australia have significantly lower amount of linear PFOS (59-60%) compared to Swedish blood (68%). This geographical variation suggests different human exposure sources and pathways.
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| 2. |
- Söderqvist, Fredrik
(författare)
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Health symptoms and potential effects on the blood-brain and blood-cerebrospinal fluid barriers associated with use of wireless telephones
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Recent years have seen a rapid increase in the use of wireless telephones, yet little systematic data exist on the actual use of such devices in the general population. Mobile and cordless telephones emit radiofrequency fields (RF) raising concern about possible adverse health effects. As children and teenagers might be more vulnerable and have longer expected lifetime exposures to RF from these devices than adults, who started to use them later in life, they are a group of special concern. The aims of papers I and II in this thesis were to increase our knowledge of use of wireless telephones in the age group of 7-19 years, to study what factors could explain such use; and furthermore, whether the use among the 15-19 year group was associated with self-reported health symptoms and well-being. For collection of data a posted questionnaire was used. Among the 7-14 group (n=1423) nearly all had access to a mobile telephone, a cordless telephone or both, although the percentage of regular users was rather low, totally. Use of wireless telephones increased with age and was more common among girls than boys, especially among the 15-19 year group (n=1269). Relatively few regular users of mobile telephones reported to use a handsfree. Besides age and gender the probability of using either a mobile or cordless telephone was associated mainly with watching TV extensively and below average household income. Regular users more often had health symptoms and reported poorer perceived health than did non-regular users. However, the latter should be interpreted with caution since bias and chance findings due to multiple testing might have influenced the results. Methodologically more sophisticated studies are needed to confirm these results and also investigate directions of possible associations. The aim of papers III-V was to investigate the potential effects of wireless telephone emissions on the integrity of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) using biomarkers. In paper III – an observational study on adults (n=314) – use of mobile and cordless telephones combined was not associated with serum levels of S100B as a marker of BBB disruption. Analyzing the different telephone types separately yielded a weak association of decreasing concentrations with minutes since last use of cordless telephone on the day of leaving blood and a statistically significant association of higher concentrations the more years since first use of a 3G-telephone. However, the latter is probably a result of chance or confounding. Paper IV comprised the same data set as in paper III using serum transthyretin (TTR) as a marker of BCSFB dysfunction. The main finding was that the number of years since first use of mobile and cordless telephones combined was statistically significantly associated with higher serum levels of TTR regardless of how much each telephone type had been used. However, extra-cerebral sources of TTR might have confounded the results, if associated with exposure. Paper V was an experimental study investigating a possible short-term effect of an 890-megahertz mobile phone-like exposure on the BBB and the BCSFB of 41 volunteers. Repeated blood sampling before and after the provocation showed no statistically significant increase in the serum levels of S100B, while for TTR a small but statistically significant increase was seen in the final blood sample 60 minutes after the end of the provocation as compared to the prior sample taken immediately after provocation. The possible clinical significance of this finding is unknown. Larger randomized studies that employ use of additional more brain-specific markers and multiple exposure conditions are needed.
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| 3. |
- Dreifaldt, Ann Charlotte, 1964-
(författare)
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Epidemiological aspects on malignant diseases in childhood
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The trends of malignant diseases in children aged 0 to 14 years, reported to the Swedish Cancer Registry 1960–1998 (n=9 298) were analyzed. The most common diagnoses were leukemia, 29.7%, tumors of the central nervous system (CNS), 27.6%, and lymphomas, 10.2%. The average annual incidence rate of childhood malignant diseases 1990–1998 was 16.19/100 000 person-years. Average annual change in incidence rate of all childhood cancer was +1.01% (95% confidence interval (CI)=0.80-1.22). Statistically significant increase was seen for leukemia +0.85% (95% CI=0.42–1.28), lymphomas +1.87% (95% CI=1.17–2.58), CNS tumors +1.45% (95% CI=1.02–1.88), sympathetic nervous system tumors +1.61% (95% CI=0.79–2.44), hepatic tumors +2.62% (95% CI=2.02–3.21), and germ cell and gonadal tumors +1.21% (95% CI=0.23–2.19). Children are exposed to persistent organic pollutants (POPs) during fetal life and breast-feeding. In a case-control study including cases of childhood cancer reported to the Cancer Registry 1988–1991 (n=962) we used breastfeeding duration as a surrogate for exposure to POPs. One matched control per case was used. Information on breast-feeding, vaccinations and chronic illness was collected from copies of the children’s Child Health Center records. Overall, breast-feeding did not affect the risk of childhood cancer, OR=1.0 (95% CI=0.7–1.3) using breast-feeding up to one month as reference. For non-Hodgkin lymphoma (NHL) OR for breast-feeding for >1 month yielded OR=5.0 (95% CI=1.1–23). No association was seen between preschool vaccinations and childhood cancer except for lymphomas and measles/measles-mumps-rubella vaccination, OR=0.2 (95% CI=0.1–0.6). Increased risk of all cancer was found for congenital malformations, OR=1.7 (95% CI=0.97–2.9), especially of leukemia, OR=3.0 (95% CI=1.5–5.8). Children with disorders of brain function had an increased risk of all cancer, OR=6.0 (95% CI=1.3–27), especially of brain tumors, OR=10 (95% CI=1.3–78). A childhood population expected to be more exposed to POPs is children of fishermen. In a register-based study, the cancer incidence rates in a cohort of fishermen children (at age 0-19 years) were compared to the rates of referent children. A modestly increased incidence rate ratio (IRR) of childhood cancer was found, IRR=1.38 (95% CI=0.96–2.00) and an increased IRR for acute lymphoid leukemia, IRR=2.65 (95% CI=1.005–6.97). In west coast fishermen children, an increased IRR was observed for NHL, IRR=3.19 (95% CI=0.98–10.4).
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| 4. |
- Tondel, Martin, 1962-
(författare)
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Malignancies in Sweden after the Chernobyl accident in 1986
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- On 26 April 1986 an accident occurred in the Chernobyl nuclear power plant resulting in the release of large amount of radionuclides. Almost five percent of the total released caesium-137 was deposited in Sweden. The incidence of malignancies in the most affected counties in Sweden was investigated in three epidemiological studies.In the first study the incidence of malignancies in children and adolescents was studied for the period 1978-1992. The parishes and their inhabitants were classified according to the ground deposition of caesium-137 on an analogue map provided be the Swedish Radiological Protection Authority. A continuous increase of brain tumour incidence observed during the time of the study had no clear relationship to the Chernobyl fallout. A somewhat decreased relative risk of ALL was observed in areas with increased deposition. Other malignancies showed no changes in incidence over time or with regard to the exposure of caesium-137. In study II and III we enlarged the study base by including adults. We improved the methodology by defining a cohort of subjects who lived in the same parish from 31 December 1985 to 31 December 1987. The inhabitants from seven counties were included. Parishes were classified the same way as in study I. Due to the large number of individuals six exposure categories could be created; <3, 3–29, 30–39, 40–59, 60–79, and 80–120 kBq caesium-137/m2. The inhabitants of the 117 non-affected parishes (<3 kBq/m2) served as reference. During the 1988-1996 followup, 22,409 malignancies were recorded. The MH-IRR in the fully adjusted model was 1.00 (reference), 1.05, 1.03, 1.08, 1.10 and 1.21, respectively. ERR was 0.11 per 100 kBq/m2 (95% CL 0.03;0.20). A more advanced method was used in Study III by ignoring the exposure classification for parishes, and instead matching the dwelling coordinate to a digital map of deposition of casesium-137. In spite of a more valid exposure classification the risk estimates were similar in study II and III. Also, the ERR during the longer follow-up of 1988-1999 was almost identical, 0.10 per 100 kBq/m2 (95% CL 0.00;0.23). The strongest dose-response relationship was seen in the first four years (1988-1991). No obvious excess for leukaemia or thyroid cancer was recognised in either study II or III. The estimated number of exposure related cases was calculated to 849 in study II and 1,278 in study III. Our interpretation is that we have shown an increased incidence of total malignancies with dose-response relationship for caesium-137, only a few years after the Chernobyl accident. In study IV we compared the two different ways of classifying the exposure in study II and III. Out of the 450 parishes 111 got a different classification. The similar risk estimates in study II and III could probably be explained by relatively homogenous exposure in the parishes making the intra-parish difference less influential, especially when included in categories. In study V we examined the urinary excretion of 8-OHdG in Belarussian children from areas with high and low fallout of caesium-137, respectively. We found significantly lower urinary 8-OHdG levels in children from rural contaminated areas compared to urban uncontaminated areas, suggesting an urban, rather than a radiation related, risk factor.Using the Hill criteria for causality there is support for a causal inference between the fallout of caesium-137 from the Chernobyl accident and the increased incidence in total malignancies in Northern Sweden.
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