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From emission sources to human tissues: modelling the exposure to per- and polyfluoroalkyl substances
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Produced since the 1950’s, per- and polyfluoroalkyl (PFASs) substances are persistent, bioaccumulative and toxic compounds that are ubiquitous in the environment. Being proteinophilic with a tendency to partition to protein-rich tissues, PFASs have been found in human serum worldwide and in wildlife with a predominance of long-chain perfluoroalkyl carboxilic acids (C7-C14 PFCAs) and perfluoroalkyl sulfonic acids (C6-C9 PFSAs). Due to rising concern regarding their hazardous properties, several regulatory actions and voluntary industrial phase-outs have been conducted since early 2000s, shifting the production towards other fluorinated alternatives. This thesis explores the human exposure to long-chain PFASs and their alternatives using different modelling methods and aims to 1) link comprehensively the past and current industrial production with the human body burden and 2) assess the potential hazardous properties of legacy PFASs replacements, on which information is very limited. In Paper I, the historical daily intakes in Australia and USA were reconstructed from cross-sectional biomonitoring data of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA) andperfluorohexanesulfonic acid (PFHxS). The results indicate that humans experienced similar exposure levels and trends to PFOS and PFOA in both regions, suggesting a common historical exposure possibly dominated by consumer products. The model could not be fitted to PFHxS concentration in serum. In Paper II, the relative contribution of indirect (i.e. subsequent metabolism of precursors into legacy PFASs) versus direct exposure was evaluated on occupationally exposed ski wax technicians. The indirect exposure contributed by up to 45% to the total body burden of PFOA. In Paper III, the physicochemical properties, the persistence and the long-range transport of fluorinated alternatives were predicted using different in silico tools. Findings suggest that fluorinated alternatives are likely similar to their predecessors, in terms of physicochemical properties and environmental fate. Finally, Paper IV compares the toxic potency of PFOS, PFOA and their alternatives as a function of external and internal dose. While alternatives are less potent than their predecessors when considering the administered dose, they become similarly potent when the assessment is based on levels in the target tissue. This thesis demonstrates that pharmacokinetic models are effective tools to comprehensively reconnect the body burden to the exposure of phased-out chemicals. More importantly, the studies on fluorinated alternatives raise the necessity to provide more information and data on the potential hazard of these novel and emerging products.

Place, publisher, year, edition, pages
Stockholm: Department of Environmental Science and Analytical Chemistry, Stockholm University , 2017. , 42 p.
Keyword [en]
PFAAs, PFOA, PFOS, fluorinated alternatives, human exposure, pharmacokinetic modelling, hazard assessment
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
URN: urn:nbn:se:su:diva-141034ISBN: 978-91-7649-712-8 (print)ISBN: 978-91-7649-713-5 (electronic)OAI: oai:DiVA.org:su-141034DiVA: diva2:1085404
Public defence
2017-05-12, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 4: Manuscript.

Available from: 2017-04-19 Created: 2017-03-29 Last updated: 2017-11-29Bibliographically approved
List of papers
1. Historical human exposure to perfluoroalkyl acids in the United States and Australia reconstructed from biomonitoring data using population-based pharmacokinetic modelling
Open this publication in new window or tab >>Historical human exposure to perfluoroalkyl acids in the United States and Australia reconstructed from biomonitoring data using population-based pharmacokinetic modelling
Show others...
2017 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 108, 92-102 p.Article in journal (Refereed) Published
Abstract [en]

Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) are found in the blood of humans and wildlife worldwide. Since the beginning of the 21st century, a downward trend in the human body burden, especially for PFOS and PFOA, has been observed while there is no clear temporal trend in wildlife. The inconsistency between the concentration decline in human serum and in wildlife could be indicative of a historical exposure pathway for humans linked to consumer products that has been reduced or eliminated. In this study, we reconstruct the past human exposure trends in two different regions, USA and Australia, by inferring the historical intake from cross-sectional biomonitoring data of PFOS, PFOA and PFHxS using a population-based pharmacokinetic model. For PFOS in the USA, the reconstructed daily intake peaked at 4.5 ng/kg-bw/day between 1988 and 1999 while in Australia it peaked at 4.0 ng/kg-bw/day between 1984 and 1996. For PFOA in the USA and Australia, the peak reconstructed daily intake was 1.1 ng/kg-bw/day in 1995 and 3.6 ng/kg-bw/day in 1992, respectively, and started to decline in 2000 and 1995, respectively. The model could not be satisfactorily fitted to the biomonitoring data for PFHxS within reasonable boundaries for its intrinsic elimination half-life, and thus reconstructing intakes of PFHxS was not possible. Our results indicate that humans experienced similar exposure levels and trends to PFOS and PFOA in the USA and Australia. Our findings support the hypothesis that near-field consumer product exposure pathways were likely dominant prior to the phase-out in industrialized countries. The intrinsic elimination half-life, which represents elimination processes that are common for all humans, and elimination processes unique to women (i.e., menstruation, cord-blood transfer and breastfeeding) were also investigated. The intrinsic elimination half-lives for PFOS and PFOA derived from model fitting for men were 3.8 and 2.4 years, respectively, for the USA, and 4.9 and 2 years respectively for Australia. Our results show that menstruation is a depuration pathway for PFOA for women, similarly but to a lesser extent compared to previous reports for PFOS. However menstruation, cord-blood transfer and breastfeeding together do not fully explain the apparently more rapid elimination of PFOA and PFOS by women compared to men; the intrinsic elimination half-lives in women were up to 13% lower for PFOS and up to 12% lower for PFOA compared to the corresponding half-lives in men.

National Category
Earth and Related Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-147834 (URN)10.1016/j.envint.2017.08.002 (DOI)000411604400010 ()28818713 (PubMedID)
Available from: 2017-11-02 Created: 2017-11-02 Last updated: 2017-11-29Bibliographically approved
2. Contribution of Direct and Indirect Exposure to Human Serum Concentrations of Perfluorooctanoic Acid in an Occupationally Exposed Group of Ski Waxers
Open this publication in new window or tab >>Contribution of Direct and Indirect Exposure to Human Serum Concentrations of Perfluorooctanoic Acid in an Occupationally Exposed Group of Ski Waxers
2016 (English)In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 50, no 13, 7037-7046 p.Article in journal (Refereed) Published
Abstract [en]

The contribution of direct (i.e., uptake of perfluorooctanoic acid (PFOA) itself) and indirect (i.e., uptake of 8:2 fluorotelomer alcohol (FTOH) and metabolism to PFOA) exposure to PFOA serum concentrations was investigated using a dynamic one compartment pharmacokinetic (PK) model. The PK model was applied to six occupationally exposed ski waxers for whom direct and indirect exposures via inhalation were characterized using multiple measurements with personal air sampling devices. The model was able to predict the diverging individual temporal trends of PFOA in serum with correlation coefficients of 0.82-0.94. For the four technicians with high initial concentrations of PFOA in serum (250-1050 ng/mL), the ongoing occupational exposure (both direct and indirect) was of minor importance and net depuration of PFOA was observed throughout the ski season. An estimated average intrinsic elimination half-life of 2.4 years (1.8-3.1 years accounting for variation between technicians and model uncertainty) was derived for these technicians. The remaining two technicians, who had much lower initial serum concentrations (10-17 ng/mL), were strongly influenced by exposure during the ski season with indirect exposure contributing to 45% of PFOA serum concentrations. On the basis of these model simulations, an average metabolism yield of 0.003 (molar concentration basis; uncertainty range of 0.0006-0.01) was derived for transformation of 8:2 FTOH to PFOA. An uncertainty analysis was performed, and it was determined that the input parameters quantifying the intake of PFOA were mainly responsible for the uncertainty of the metabolism yield and the initial concentration of PFOA in serum was mainly contributing to the uncertainty of estimated serum half-lives.

National Category
Environmental Sciences Environmental Engineering
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-132534 (URN)10.1021/acs.est.6b01477 (DOI)000379366300053 ()27304840 (PubMedID)
Available from: 2016-08-25 Created: 2016-08-15 Last updated: 2017-11-28Bibliographically approved
3. A modeling assessment of the physicochemical properties and environmental fate of emerging and novel per- and polyfluoroalkyl substances
Open this publication in new window or tab >>A modeling assessment of the physicochemical properties and environmental fate of emerging and novel per- and polyfluoroalkyl substances
2015 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 505, 981-991 p.Article in journal (Refereed) Published
Abstract [en]

Long-chain perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkane sulfonic acids (PFSAs) are persistent, bioaccumulative, and toxic contaminants that are globally present in the environment, wildlife and humans. Phase-out actions and use restrictions to reduce the environmental release of long-chain PFCAs, PFSAs and their precursors have been taken since 2000. In particular, long-chain poly- and perfluoroalkyl substances (PFASs) are being replaced with shorter-chain homologues or other fluorinated or non-fluorinated alternatives. A key question is: are these alternatives, particularly the structurally similar fluorinated alternatives, less hazardous to humans and the environment than the substances they replace? Several fluorinated alternatives including perfluoroether carboxylic acids (PFECAs) and perfluoroether sulfonic adds (PFESAs) have beet recently identified. However, the scarcity of experimental data prevents hazard and risk assessments for these substances. In this study, we use state-of-the-art in silico tools to estimate key properties of these newly identified fluorinated alternatives. [i] COSMOtherm and SPARC ate used to estimate physicochemical properties. The US EPA EPISuite software package is used to predict degradation half-lives in air, water and soil. [ii] In combination with estimated chemical properties, a fugacity-based multimedia mass-balance unit-world model the OECD Overall Persistence (Pov) and Long-Range Transport Potential (LRTP) Screening Tool is used to assess the likely environmental fate of these alternatives. Even though the fluorinated alternatives contain some structural differences, their physicochemical properties are not significantly different from those of their predecessors. Furthermore, most of the alternatives are estimated to be similarly persistent and mobile in the environment as the long-chain PFASs. The models therefore predict that the fluorinated alternatives will become globally distributed in the environment similar to their predecessors. Although such in silico methods are coupled with uncertainties, this preliminary assessment provides enough cause for concern to warrant experimental work to better determine the properties of these fluorinated alternatives.

Keyword
Hazard assessment, Environmental fate, Fluorinated alternative, In silico tool, PFOS, PFOA
National Category
Earth and Related Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-114232 (URN)10.1016/j.scitotenv.2014.10.062 (DOI)000347654900096 ()25461098 (PubMedID)
Note

AuthorCount:4;

Available from: 2015-03-20 Created: 2015-02-25 Last updated: 2017-12-04Bibliographically approved
4. Comparing the potency in vivo of PFAS alternatives and their predecessors
Open this publication in new window or tab >>Comparing the potency in vivo of PFAS alternatives and their predecessors
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Since the year 2000, a number of per- and polyfluoroalkyl substances (PFASs) have been introduced onto the market to replace long-chain perfluoroalkyl acids (e.g. perfluoroctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)) and their respective precursors. The main rationale for this industrial transition is that the PFAS alternatives are less bioaccumulative and toxic than their predecessors. Here, we evaluated to what extent differences in toxicological effect thresholds for PFASs, expressed as an administered dose, were confounded by differences in their distribution and elimination kinetics. Increased liver weight was selected as the investigated endpoint based on the availability of sufficient toxicological and toxicokinetic data to enable a comparison of sub-chronic effects. Converting administered doses into equivalent serum and liver concentrations significantly reduced the variability in the dose-response curves for perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononaoic acid (PFNA) and ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (GenX). The toxicity ranking using serum (PFNA>GenX>PFOA>PFHxA>PFBA) and liver (GenX>PFNA≈PFOA≈PFHxA≈PFBA) concentrations also indicated that some PFAS alternatives may have a higher toxic potency than their predecessors when correcting for differences in toxicokinetics. For PFOS and perfluorobutane sulfonic acid (PFBS) the conversion from administered dose to serum concentration equivalents did not change the toxicity ranking which, however, could be due to the internal dose of PFBS being too low to allow a correct comparison. This study illustrates the importance of taking toxicokinetics/internal dose into account in substitution of hazardous chemicals for independent evaluation of bioaccumulation and toxicity criteria.

Keyword
PFOS, PFOA, PFAS alternatives, toxicokinetic model, potency, toxicity
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-141082 (URN)
Available from: 2017-03-30 Created: 2017-03-30 Last updated: 2017-03-31Bibliographically approved

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Citation style
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  • modern-language-association-8th-edition
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Output format
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