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Comparing the potency in vivo of PFAS alternatives and their predecessors
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
(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 [en]
PFOS, PFOA, PFAS alternatives, toxicokinetic model, potency, toxicity
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
URN: urn:nbn:se:su:diva-141082OAI: oai:DiVA.org:su-141082DiVA: diva2:1085755
Available from: 2017-03-30 Created: 2017-03-30 Last updated: 2017-03-31Bibliographically approved
In thesis
1. From emission sources to human tissues: modelling the exposure to per- and polyfluoroalkyl substances
Open this publication in new window or tab >>From emission sources to human tissues: modelling the exposure to per- and polyfluoroalkyl substances
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
PFAAs, PFOA, PFOS, fluorinated alternatives, human exposure, pharmacokinetic modelling, hazard assessment
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-141034 (URN)978-91-7649-712-8 (ISBN)978-91-7649-713-5 (ISBN)
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: 2017-04-03Bibliographically approved

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