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Radiosynthesis of Perfluoroalkyl Substances: Chemical analysis, uptake, distribution, and partitioning studies
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). (Enheten för miljökemi)
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Perfluoroalkyl substances (PFASs) are widely utilized manmade chemicals. Their properties have made them highly appreciated in a variety of industrial and consumer product applications, including fire-fighting foams, hydraulic fluids, as well as in cookware and food contact papers.

However, some of the PFASs are highly persistent in the environment and their toxicological profiles are of concern. Voluntary and regulatory efforts have been taken to reduce the environmental levels of PFASs. These actions have resulted in a reduction of PFASs in human milk from Stockholm as presented in this thesis.

The radiosyntheses of 35S-PFOS, 35S-PFBS, and 14C-PFOA presented herein were applied for distribution studies in mice but also for solubility and adhesion experiments of common laboratory solvents and buffers. The radiosynthesis employed reactive Grignard reagents, perfluoroalkyliodides, and 35S-sulfur dioxide or 14C-carbon dioxide. The distribution studies were performed with 35S-PFOS on both pregnant mice and their offspring as well as on male mice. The mice were subjected to whole-body autoradiography and the tissues were analyzed by liquid scintillation counting. Liver and lungs were the target organs for 35S-PFOS in the dams. The fetuses and pups had remarkable high levels of 35S-PFOS in their lungs as well as in the brain. The male mice were given a high dose and a more environmental relevant dose of 35S-PFOS. PFOS was transferred from the blood to the tissues as the dose increased.

In another study the distribution pattern of the shorter homologue PFBS was compared to PFOS. 35S-PFBS was utilized and demonstrated a 5-40 fold lower tissue levels in comparison to PFOS.

The pharmacokinetic parameters determined for PFHxS in mice, rats, and monkeys will provide valuable insight in establishing a proper risk assessment for this compound. The study confirms the common species differences in serum elimination half-life that are associated with PFASs.

Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry (MMK), Stockholm University , 2012. , 65 p.
Keyword [en]
PFOS, PFOA, PFBS
National Category
Organic Chemistry
Research subject
Environmental Chemistry
Identifiers
URN: urn:nbn:se:su:diva-81061ISBN: 978-91-7447-579-1 (print)OAI: oai:DiVA.org:su-81061DiVA: diva2:559260
Public defence
2012-11-16, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 6: Manuscript.

Available from: 2012-10-25 Created: 2012-10-08 Last updated: 2012-10-12Bibliographically approved
List of papers
1. Radiosynthesis of perfluorooctanesulfonate (PFOS) and perfluorobutanesulfonate (PFBS), including solubility, partition and adhesion studies
Open this publication in new window or tab >>Radiosynthesis of perfluorooctanesulfonate (PFOS) and perfluorobutanesulfonate (PFBS), including solubility, partition and adhesion studies
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2012 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 87, no 8, 865-871 p.Article in journal (Refereed) Published
Abstract [en]

Here, we describe for the first time the synthesis of [S-35] PFOS and [S-35] PFBS with sulfur-35 enriched sulfur dioxide as the radiolabelled reagent, resulting in 2.5 and 2.3 mCi of product, respectively. Basic information concerning the physicochemical properties of perfluorooctanesulfonate (PFOS), perfluorobutanesulfonate (PFBS) and perfluorooctanoic acid (PFOA) are still limited. Hence, we utilized these radiolabelled perfluoroalkanesulfonates (PFSAs), as well as carbon-14 labelled perfluorooctanoic acid a, ([C-14] PFOA) to determine some basic characteristics of physiological and experimental significance. The solubility of PFOS in buffered aqueous solutions at pH 7.4 was found to be severely reduced in the presence of potassium and sodium ions, which, however, did not reduce the solubility of PFOA or PFBS. PFOS was found to adhere to a small extent to polypropylene and polystyrene, whereas no such adhesion of PFOA or PFBS was detected. The extents of adhesion of PFOS and PFOA to glass were found to be 20% and 10%, respectively. For the first time, the partition coefficients for PFOS, PFBS and PFOA between n-octanol and water were determined experimentally, to be -0.7, -0.3, and 1.4, respectively, reflecting the difference in the amphiphilic natures of these molecules.

Keyword
Perfluorooctanoic acid (PFOA), Perfluoroalkyl derivatives, PFAS, Radiolabelled, Partition, Solubility
National Category
Environmental Sciences Ecology
Identifiers
urn:nbn:se:su:diva-80763 (URN)10.1016/j.chemosphere.2012.01.027 (DOI)000302988100006 ()
Note

AuthorCount:9;

Available from: 2012-09-28 Created: 2012-09-27 Last updated: 2017-12-07Bibliographically approved
2. A temporal trend study (1972-2008) of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in pooled human milk samples from Stockholm, Sweden
Open this publication in new window or tab >>A temporal trend study (1972-2008) of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in pooled human milk samples from Stockholm, Sweden
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2010 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 37, no 1, 178-83 p.Article in journal (Refereed) Published
Abstract [en]

The widespread presence of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) in human general populations and their slow elimination profiles have led to renewed interest in understanding the potential human neonatal exposures of perfluoroalkyls (PFAs) from consumption of human milk. The objective of this study was to evaluate the concentrations of PFOS, PFHxS, and PFOA in pooled human milk samples obtained in Sweden between 1972 and 2008 (a period representing the most significant period of PFA production) and to see whether the time trend of these analytes parallels that indicated in human serum. Chemical analysis of PFOS, PFHxS, and PFOA was performed on pooled Swedish human milk samples from 1972 to 2008 after methodological refinements. The 20 samples which formed the 2007 pool were also analyzed individually to evaluate sample variations. Analyses were performed by HPLC-MS/MS. Due to the complexities of the human milk matrix and the requirement to accurately quantitate low pg/mL concentrations, meticulous attention must be paid to background contamination if accurate results are to be obtained. PFOS was the predominant analyte present in the pools and all three analytes showed statistically significant increasing trends from 1972 to 2000, with concentrations reaching a plateau in the 1990s. PFOA and PFOS showed statistically significant decreasing trends during 2001-2008. At the end of the study, in 2008, the measured concentrations of PFOS, PFHxS, and PFOA in pooled human milk were 75 pg/mL, 14 pg/mL, and 74 pg/mL, respectively. The temporal concentration trends of PFOS, PFHxS, and PFOA observed in human milk are parallel to those reported in the general population serum concentrations.

 

National Category
Environmental Sciences Ecology
Identifiers
urn:nbn:se:su:diva-53031 (URN)10.1016/j.envint.2010.08.014 (DOI)000285662600023 ()
Note
authorCount :7 Även konferensbidrag (Dioxin 2010, Organohalogen Compounds) Available from: 2011-01-19 Created: 2011-01-19 Last updated: 2012-10-09Bibliographically approved
3. Tissue distribution of S-35-labelled perfluorooctane sulfonate (PFOS) in C57Bl/6 mice following late gestational exposure
Open this publication in new window or tab >>Tissue distribution of S-35-labelled perfluorooctane sulfonate (PFOS) in C57Bl/6 mice following late gestational exposure
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2010 (English)In: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 30, no 4, 558-565 p.Article in journal (Refereed) Published
Abstract [en]

Exposure of rodents in utero to perfluorooctane sulfonate (PFOS) impairs perinatal development and survival Following intravenous or gavage exposure of C57Bl/6 mouse dams on gestational day (GD) 16 to S-35-PFOS (12 5 mg/kg) we determined the distribution in dams fetuses (GD18 and GD20) and pups (postnatal day 1 PND1) employing whole-body autoradiography and liquid scintillation counting In dams levels were highest in liver and lungs After placental transfer S-35-PFOS was present on GD18 at 2-3 times higher levels in lungs liver and kidneys than in maternal blood In PND1 pups levels in lungs were significantly higher than in GD18 fetuses A heterogeneous distribution of S-35-PFOS was observed in brains of fetuses and pups with levels higher than in maternal brain This first demonstration of substantial localization of PFOS to both perinatal and adult lungs is consistent with evidence describing the lung as a target for the toxicity of PFOS at these ages.

Keyword
Perfluorooctane sulfonate (PFOS), Perfluoroalkylated compounds (PFCs), Autoradiography, Liquid scintillation counting, Perinatal, Tissue distribution, C57Bl/6 mouse
National Category
Biological Sciences Pharmacology and Toxicology
Research subject
Toxicology
Identifiers
urn:nbn:se:su:diva-51259 (URN)10.1016/j.reprotox.2010.07.004 (DOI)000285036300007 ()
Note

authorCount :9

Available from: 2011-01-11 Created: 2011-01-10 Last updated: 2012-10-10Bibliographically approved
4. Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose
Open this publication in new window or tab >>Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose
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2011 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 284, no 1-3, 54-62 p.Article in journal (Refereed) Published
Abstract [en]

The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g., hepatotoxicity, immunotoxicity and developmental toxicity. However, detailed information on the tissue distribution of PFOS in mammals is scarce and, in particular, the lack of available information regarding environmentally relevant exposure levels limits our understanding of how mammals (including humans) may be affected. Accordingly, we characterized the tissue distribution of this compound in mice, an important experimental animal for studying PFOS toxicity. Following dietary exposure of adult male C57/BL6 mice for 1-5 days to an environmentally relevant (0.031 mg/kg/day) or a 750-fold higher experimentally relevant dose (23 mg/kg/day) of (35)S-PFOS, most of the radioactivity administered was recovered in liver, bone (bone marrow), blood, skin and muscle, with the highest levels detected in liver, lung, blood, kidney and bone (bone marrow). Following high daily dose exposure, PFOS exhibited a different distribution profile than with low daily dose exposure, which indicated a shift in distribution from the blood to the tissues with increasing dose. Both scintillation counting (with correction for the blood present in the tissues) and whole-body autoradiography revealed the presence of PFOS in all 19 tissues examined, with identification of thymus as a novel site for localization for PFOS and bone (bone marrow), skin and muscle as significant body compartments for PFOS. These findings demonstrate that PFOS leaves the bloodstream and enters most tissues in a dose-dependent manner.

Keyword
PFOS, Distribution, Hemoglobin, Scintillation, Autoradiography, Adult mice
National Category
Biological Sciences Chemical Sciences
Identifiers
urn:nbn:se:su:diva-67584 (URN)10.1016/j.tox.2011.03.014 (DOI)000291140300008 ()
Note
authorCount :10Available from: 2011-12-29 Created: 2011-12-29 Last updated: 2017-12-08Bibliographically approved
5. Comparative pharmacokinetics of perfluorohexanesulfonate (PFHxS) in rats, mice, and monkeys
Open this publication in new window or tab >>Comparative pharmacokinetics of perfluorohexanesulfonate (PFHxS) in rats, mice, and monkeys
Show others...
2012 (English)In: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 33, no 4, 441-451 p.Article in journal (Refereed) Published
Abstract [en]

Perfluorohexanesulfonate (PFHxS) has been found in biological samples from wildlife and humans. The human geometric mean serum PFHxS elimination half-life has been estimated to be 2665 days. A series of studies was undertaken to establish pharmacokinetic parameters for PFHxS in rats, mice, and monkeys after single administration with pharmacokinetic parameters determined by WinNonlin (R) software. Rats and mice appeared to be more effective at eliminating PFHxS than monkeys. With the exception of female rats, which had serum PFHxS elimination half-life of approximately 2 days, the serum elimination half-lives in the rodent species and monkeys approximated 1 month and 4 months, respectively, when followed over extended time periods (10-24 weeks). Collectively, these studies provide valuable insight for human health risk assessment regarding the potential for accumulation of PFHxS in humans.

Keyword
Perfluorohexanesulfonate, PFHxS, Pharmacokinetics, Rats, Monkeys, Mice
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-80032 (URN)10.1016/j.reprotox.2011.07.004 (DOI)000305303100005 ()
Note

AuthorCount:8;

Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2017-12-07Bibliographically approved
6. Tissue distribution of 35S-labelled perfluorobutane sulfonic acid in adult mice following dietary exposure for 1-5 days
Open this publication in new window or tab >>Tissue distribution of 35S-labelled perfluorobutane sulfonic acid in adult mice following dietary exposure for 1-5 days
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Other Chemistry Topics
Identifiers
urn:nbn:se:su:diva-81056 (URN)
Available from: 2012-10-08 Created: 2012-10-08 Last updated: 2012-10-10Bibliographically approved

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Citation style
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  • modern-language-association-8th-edition
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  • nn-NO
  • nn-NB
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  • Other locale
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Output format
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