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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
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
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2011 (Engelska)Ingår i: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 284, nr 1-3, s. 54-62Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2011. Vol. 284, nr 1-3, s. 54-62
Nyckelord [en]
PFOS, Distribution, Hemoglobin, Scintillation, Autoradiography, Adult mice
Nationell ämneskategori
Biologiska vetenskaper Kemi
Identifikatorer
URN: urn:nbn:se:su:diva-67584DOI: 10.1016/j.tox.2011.03.014ISI: 000291140300008OAI: oai:DiVA.org:su-67584DiVA, id: diva2:470530
Anmärkning
authorCount :10Tillgänglig från: 2011-12-29 Skapad: 2011-12-29 Senast uppdaterad: 2022-02-28Bibliografiskt granskad
Ingår i avhandling
1. Radiosynthesis of Perfluoroalkyl Substances: Chemical analysis, uptake, distribution, and partitioning studies
Öppna denna publikation i ny flik eller fönster >>Radiosynthesis of Perfluoroalkyl Substances: Chemical analysis, uptake, distribution, and partitioning studies
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Stockholm: Department of Materials and Environmental Chemistry (MMK), Stockholm University, 2012. s. 65
Nyckelord
PFOS, PFOA, PFBS
Nationell ämneskategori
Organisk kemi
Forskningsämne
miljökemi
Identifikatorer
urn:nbn:se:su:diva-81061 (URN)978-91-7447-579-1 (ISBN)
Disputation
2012-11-16, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (Engelska)
Opponent
Handledare
Anmärkning

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 6: Manuscript.

Tillgänglig från: 2012-10-25 Skapad: 2012-10-08 Senast uppdaterad: 2022-02-24Bibliografiskt granskad

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Sundström, MariaAbedi-Valugerdi, ManuchehrBergman, ÅkeNelson, BuckDePierre, JosephNobel, Stefan

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Sundström, MariaAbedi-Valugerdi, ManuchehrBergman, ÅkeNelson, BuckDePierre, JosephNobel, Stefan
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